X National Congress of Digestive Disease Italian Federation of Digestive Disease Turin,27-31 March 2004

Digestive and Liver Disease 36 (Suppl. 2) (2004) S129–S331

Abstracts

X National Congress of Digestive Diseases Italian Federation of Digestive Diseases Turin, 27–31 March 2004

SELECTED COMMUNICATIONS CS01 PREDICTIVE ROLE OF MELD SCORE AND PRESENCE OF HCC IN SHORT-TERM SURVIVAL IN CIRRHOTIC PATIENTS WITH VARICEAL BLEEDING L. Amitrano, M.A. Guardascione, R. Bennato, F. Manguso, E. Riccio, A. Balzano Gastroenterology Unit, A. Cardarelli Hospital, Naples, Italy Background. MELD is a validated score to predict short-term survival in patients with liver cirrhosis undergoing liver transplantation or TIPS. No data are available about the MELD score in patients bleeding from oesophageal varices. The role of hepatocellular carcinoma (HCC) as risk factor of short-term mortality in these patients is not clearly established. Aim. The aim of our study was to evaluate if MELD score and HCC are predictors of short-term mortality in cirrhotic patients bleeding from oesophageal varices. Material and methods. From February 2002 to August 2003, 257 patients with liver cirrhosis were admitted to our unit because of gastrointestinal bleeding. Fifty-nine (23%) patients bled from non-variceal sources; 26 (10%) were not eligible because of missing data regarding cause of bleeding, HCC status or MELD score. The remaining 172 patients received medical therapy (somatostatin or octreotide) plus sclerotherapy or band ligation. MELD was calculated from data taken within 24 h from the variceal bleed. Patients’ survival was evaluated at 6 weeks and 3 months. The better cut-off (MELD score 15) in sensitivity and specificity was calculated with ROC curve analysis, and odds ratio using binary logistic regression. Results. In 172 patients (M/F = 108/64, mean age ± S.D. = 61.3 ± 11.4 years) the overall mortality was 21.5 and 30.2% at 6 weeks and 3 months, respectively. Data about the risk of mortality according to MELD score and presence of HCC at 6 weeks and 3 months are summarised in the table.

Number 6 Weeks of patients Deaths, Odds ratio n (%) (CI 95%) MELD ≤15 and HCC−a MELD ≤15 and HCC+ MELD >15 and HCC− MELD >15 and HCC+ a

76

4 (5.2)

29

4 (13.8)

– 2.9 (0.7–12.4)

3 Months P-value Deaths, n (%) –

6 (7.9)

0.16

9 (31)

42

16 (38.1) 11.8 (3.4–36.2) <0.001 18 (42.8)

25

13 (52)

Reference category.

19.5 (5.4–69.9) <0.001 19 (76)

Odds ratio (CI 95%) –

P-value

–

5.3 (1.7–16.5)

<0.05

8.8 (3.1–24.6)

<0.001

36.9 (10.7–127.6) <0.001

Conclusions. Both MELD score >15 and presence of HCC increase the mortality risk after variceal bleeding in cirrhotic patients. MELD score seems to be more effective in predicting death at 6 weeks, whereas the presence of HCC influences mainly the 3 months mortality. In particular, taken together MELD and presence of HCC is the worst short-term prognosis in cirrhotic patients with variceal bleeding. CS02 ANAL ULTRASOUND (AUS) IN EVALUATING ACTIVITY OF PERIANAL CROHN’S DISEASE (CD) G. Basiliscoa , A. Loscoa , F. Capriolia , D. Contea , P. Biondettib a Gastroenterology

Unit, Department of Medical Sciences, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy b Radiology Unit, Department of Medical Sciences, University of Milan, IRCCS Ospedale Maggiore, Milan, Italy

Background. Both magnetic resonance imaging (MRI) and AUS accurately detect and classify perianal fistulas in CD patients, but MRI is still the gold standard for evaluating fistula track activity. Active fistulas are characterised by hyperintensity in MRI T2-weighted sequences; AUS shows hypoechogenicity with multiple internal hyperechoic spots. Aim. To assess the relationships between AUS findings and MRI T2-hyperintensity and the Perianal Disease Activity Index (PDAI) score. Material and methods. Fourteen consecutive CD patients (11 male, 3 female; mean age 39 years) with draining perianal fistulas underwent pelvic MRI, AUS and PDAI assessment. Areas of interest corresponding to the same fistula track were selected from the digitalised MRI and AUS images, and their mean grey-scale tone was measured using dedicated software and a numeric scale ranging from 0 (black) to 255 (white). The presence of AUS hyperechoic spots was also evaluated dichotomously (present/absent). The data are given as mean values + S.D. (range). Results. AUS hypoechogenicity and the presence of hyperechoic spots were both associated with MRI T2-hyperintensity: there was an inverse correlation between the mean grey-scale tone of the corresponding MRI and AUS images of fistula tracks (Spearman: P = 0.047), and the patients with hyperechoic spots showed significantly greater MRI T2 hyperintensity (U-test: 223 + 12 (210–239) versus 178 + 45 (131–219); P = 0.018). There was also an inverse correlation between AUS hypoechogenicity and the PDAI score (P < 0.0001), particularly in relation to pain/interference with daily activities, restricted sexual activity and the degree of perianal induration (P < 0.001 for all items). The patients with hyperechoic spots were characterised by a significantly higher PDAI score than those without (11.1 + 2.5 (7–15) versus 4.9 + 2.2 (2–10), P < 0.0001). Conclusions. AUS is useful for quantifying fistula track activity in CD patients, and this quantitative assessment is related to the clinical evaluation of perianal disease activity.

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Abstracts

CS03 EFFECTIVENESS OF MAGNIFYING CHROMO-ENDOSCOPY IN PREDICTING HISTOPATHOLOGIC FINDINGS AND DEPTH OF INVASION OF NON-POLYPOID COLORECTAL LESIONS M.A. Biancoa , G. Rotondanoa , M.L. Garofanoa , R. Marmoa , A.M. Salvatib , L. Orsinia , L. Cipollettaa a U.O.

Gastroenterologia, ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy b UO Anatomia ed Istologia Patologica, ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy Background. The development of magnifying chromo-endoscopy has facilitated the observation of mucosal pit patterns. We investigated the value of this technology in predicting the histologic findings of non-polypoid colorectal lesions. Methods. From December 2002 through October 2003, a total of 54 colorectal lesions were included. Macroscopically, lesions could be classified as type IIa (superficially elevated, 30), type IIb (flat, 5), type IIc (depressed, 3), type IIa + IIc (10) and type IIc + IIa (6). After identifying the lesions at colonoscopy, 0.4% indigo carmine solution was sprayed and then the zoom apparatus (Olympus CF-Q160Z) was switched to make a magnified view of the stained crypt orifice at a maximum of 150 times magnification. The observed pit patterns were classified into six categories (I, II, IIIL, IIIS, IV, and V) according to modified Kudo’s classification. Types I and II were designated as non-neoplastic patterns whereas other types were neoplastic. Correlation of the pit pattern with the findings of histologic examinations of resected lesions was performed. Results. There were 11 non-neoplastic lesions (20.3%) and 43 neoplastic lesions (79.7%), including 39 adenomas and 4 carcinomas. When comparing histologically confirmed neoplastic lesions to non-neoplastic lesions, prediction of neoplastic lesions by endoscopists based on magnifying chromoendoscopy had a sensitivity of 90.8%, a specificity of 72.7%, a positive predictive value of 90.4%, a negative predictive value of 73.6%, and an overall accuracy of 86.1%. Conclusions. Characteristic pit patterns obtained by magnifying chromoendoscopy allows differentiation between hyperplastic and adenomatous lesions which may have consequences with regard to the endoscopic interventions needed. CS04 MAGNIFYING ENDOSCOPY AND HISTOLOGY FOR SURVEILLANCE OF ACUTE REJECTION IN ISOLATED SMALL BOWEL AND MULTIVISCERAL TRANSPLANTATION V. Boarinoa , A. Merighia , A. Bagnib , A. Scarcellia , M. Del Buonoa , A. Bertania , F. Schepisa , N. Cauteroc , G.P. Rigoa , A. Pinnac , E. Villaa

a Gastroenterologia,

Università degli Studi, Az. Osp. Policlinico, Modena, Italy b A. Patologica, Università degli Studi, Az. Osp. Policlinico, Modena, Italy c Centro Trapianti Multiviscerale, Università degli Studi, Az. Osp. Policlinico, Modena, Italy Background and aim. Small bowel transplantation (SBTx) is indicated in patients with irreversible intestinal failure. As patient and graft survival is related to grade of acute rejection (AR), rapid diagnosis is essential to improve the outcome. The aim of this study is to evaluate endoscopic surveillance of AR in patients with SBTx to analyse endoscopic findings in comparison with istological features. Materials and methods. Eighteen SBTx were performed at our institution between 31 December 2000 and 30 September 2003: 14 isolated small bowel, 4 multivisceral. Indications were: intestinal pseudo-obstruction (six), short bowel syndrome (eight), Gardner’s syndrome (two), intestinal atresia (one), angiodysplasia (one). Patients underwent ileoscopies with zoom videoendoscope (ZVE). Biopsies were obtained for istological examination.

Results. Mean follow-up was 17 months (range 1–33); three patients died (two for sepsis and one for AR) and one graft was removed for AR. Patients and graft survival were 83.3 and 77.7%, respectively. A total of 603 ileoscopies were performed, 445 by ZVE. Rejection was diagnosed by histology in 106/445 examinations and its severity grade was indeterminate in 64, mild in 27, moderate in 7 and severe in 8. AR was found in early (<90 days) and late period after transplantation: most moderate and severe cases in later period. ZVE revealed abnormalities in 65/106 cases and was normal in 224/339 negative istological examinations: sensitivity 61.3%, specificity 66.1%, positive predictive value 36.1%, negative predictive value (NPV) 84.9%; not considering indeterminate grade of rejection, sensibility was 80.9% and NPV 96.5%. We did not observe one or more endoscopic findings correlated to a specific grade of rejection. Conclusions. Combined endoscopic and histological surveillance allows early detection of AR and must be continued in time; absence of endoscopic abnormalities is indicative of normal histology especially not considering indeterminate grade of rejection. CS05 THERAPEUTIC EFFICACY OF BLOCKING Smad7 IN TNBSINDUCED COLITIS M. Boirivanta , F. Palloneb , I. Monteleoneb , C. Di Giacintoa , M. Marinaroa , T.T. MacDonaldc , G. Monteleoneb a Laboratorio

di Immunologia, Istituto Superiore di Sanitá, Rome, Italy di Medicina Interna, Università Tor Vergata di Roma,

b Dipartimento

Rome, Italy c Division of Infection, Inflammation and Repair, University of Southampton, UK Background and aims. In Crohn’s disease (CD) there is defective TGF-␤1-mediated negative regulation of ongoing inflammation, associated with high local expression of Smad7, an inhibitory Smad which interacts with TGF-b receptor type I and suppresses the TGF-b1 signalling cascade. The aim of this study was to determine if blocking Smad7 is of therapeutic benefit in vivo. We have therefore analysed TGF-␤1-associated signalling and Smad7 expression in TNBS-induced colitis, a mouse model of CD, and then determined if blocking Smad7 limits ongoing mucosal inflammation. Methods. Whole colonic mucosal and lamina propria mononuclear cell (LPMC) samples were obtained from mice with established TNBS-induced colitis. Whole mucosal samples were analysed for the content of activated TGF-beta1 by ELISA, and Smad3 and Smad7 were assessed both in whole mucosal and LPMC samples by Western blotting. Smad7 antisense or control sense oligonucleotides were administered into mice with established colitis by oral gauvage (250 ␮g per mouse) at day 2 after TNBS. At day 5, mice were weighted, and then sacrificed. Colonic tissues were removed, analysed for the macroscopic degree of inflammation, and then stored at −80 ◦ C for further analysis. Results. Activated TGFb1 was produced at a higher level in the colonic mucosa of mice with TNBS colitis than ethanol and controls. Despite this, whole mucosal and isolated LPMC samples from mice with TNBS-colitis exhibit defective TGFb1-associated Smad3 phosphorylation, which was associated with high Smad7. In vivo administration of Smad7 anti-sense oligonucleotides into mice with established colitis restored TGFb1 signalling with the down-stream effect of reducing the synthesis of interferon-g and interleukin-12 and dampening the ongoing mucosal inflammation. Conclusions. These data support further the notion that defective TGF-beta1 signalling occurs in chronic intestinal inflammation, and suggest that blocking Smad7 is a new and promising therapeutical approach in CD.

Abstracts CS06 PREGNANCY IN WOMEN WITH ULCERATIVE COLITIS AND CROHN’S DISEASE: MULTICENTRE PROSPECTIVE CASE– CONTROL ITALIAN STUDY Aurora Bortoli On Behalf Of IG-IBD (Italian Group of Inflammatory Bowel Disease) Gastroenterology Unit, Rho Hospital. Rho (MI), Italy Background. Many women with inflammatory bowel disease (IBD) are of reproductive age and are concerned about the impact that IBD may have on pregnancy. Aim. The aim is to evaluate the outcome of pregnancy and the disease course in a group of Italian pregnant women with IBD. Methods. Patients with ulcerative colitis (UC) and Crohn’s disease (CD) were followed-up during gestation and interviewed regarding IBD activity, therapy and outcome of pregnancy (live births, abortions, preterm delivery, birth weight, congenital abnormalities). Two control matched pregnancies, for each study of pregnancy, were collected. Results. Two hundred and seventy-five pregnancies from IBD patients (160 UC, 115 CD) were compared to 554 pregnancies in control group. We found a similar rate of live births (85.4% versus 86.6%, P = 0.72) and of spontaneous abortions (9.1% versus 10.1%, P = 0.73) in IBD and controls, respectively, while the therapeutic abortions rate was higher in IBD patients (3.3% versus 0.4%, P = 0.001). Mean birth weight was lower in IBD patients (3046 g versus 3211 g, P < 0.001) and the number of low birth babies (<2500 g) was higher in IBD group (10.6% versus 2.5%, P < 0.001). The preterm delivery was more frequent in IBD than in controls, but the difference was not statistically significant (10.2% versus 6.04%, P = 0.67). The rate of congenital abnormalities was higher in IBD patients than controls (2.2% versus 0.2%, P = 0.007). Only two out of six abnormalities were clinically severe (cardiac disease and renal agenesia). With regard to disease course we found that 82.3% of the IBD patients were in remission at conception. In 3.3% of the pregnant women, the first appearance of the disease (UC > CD) was during gestation. During pregnancy, 14.9% of the UC and 7.3% of the CD patients relapsed. In post-partum period (6 months) the rate of recurrence was higher in UC patients (UC 24.6% versus CD 20.2%). About therapy: 78.7% of patients were under treatment at conception and 71.8% during gestation. Furthermore, we evaluated all the items of the pregnancy outcome with regard to treatment and course of the disease. We found that in IBD patients the activity of the disease influences both preterm delivery and birth weight. Conclusion. IBD influences the outcome of pregnancy with regard to birth weight and congenital abnormalities. But only the last one, with the occurrence of two severe abnormalities in our IBD group, is clinically relevant. The disease activity appeared to influence the rate of preterm delivery and the birth weight. The pregnancy in IBD patients should not be discouraged but closely monitored. CS07 ENDOSCOPIC MUCOSAL RESECTION FOR HIGH-GRADE DYSPLASIA AND INTRAMUCOSAL CARCINOMA OCCURRING IN BARRETT’S OESOPHAGUS M. Conioa , A. Repicib , R. Cestaric , S. Blanchia , G. Missalec , L. Lapertosad , G. Calandria , R. Filibertia a Istituto

Nazionale Ricerca Cancro, Genoa, Italy Ospedale Molinette, Università di Genova, Genoa,

b Gastroenterologia

Italy c Spedali Civili di Brescia, Università di Genova, Genoa, Italy d Anatomia Patologica, Università di Genova, Genoa, Italy Introduction. Patients with Barrett’s oesophagus (BE) are at an increased risk of developing oesophageal adenocarcinoma (AC). High-grade dysplasia (HGD) is considered the final step towards AC, and oesophagec-

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tomy is advised. Endoscopic mucosal resection (EMR) could become an alternative to surgery. The limited available data are encouraging. Aim. To evaluate the effectiveness and safety of selective EMR in patients with HGD and/or intramucosal cancer (IMC) occurring in BE patients. Methods. Between October 1998 and July 2003, 38 consecutive patients (mean age 62.5 ± 1.5 years) with HGD (34) and/or IMC (4) in BE underwent EMR. All patients had endoscopically detectable mucosal abnormalities. Long segment BE (>30 mm, LSBE) was present in 18 patients. In three patients with short segment BE (SSBE: 15%), HGD was detected in a normal appearing BE. The latter patients were included with the aim of completely removing BE. EUS was performed to assess the depth of the lesion and the status of mediastinal lymph nodes. The median diameter of lesions was 13.5 mm (range 3–40). EMR was carried out by using the cap method (EMRC), after submucosal injection of a diluted epinephrine solution (1:60.000). During the EMR, patients were sedated with propofol. Follow-up was scheduled at 3 and 6 months, and then every 6 months thereafter. Results. The average size of EMR was 20.0 ± 9.5 × 14.0 ± 6.4 mm. The results of the histopathologic assessment post-EMR were: 5 LGD (13.2%), 26 HGD (68.4%), 2 IMC (5.3%), and 5 AC with submucosal infiltration (13.2%). EMR changed the pre-treatment diagnosis in 10 patients (26.3%). Three patients with invasive AC underwent surgery, but the histopathologic assessment of the surgical specimen did not show residual disease and lymph node involvement. The remaining two patients with AC are cancer free at 8 and 10 months. Among the 26 HGD, one recurrence occurred after 19 months, and a new EMR was performed. Three months later, a further control was negative. Post-EMR bleeding occurred in four patients (10.5%), and haemoclips were placed in two of them. After a median follow-up of 14.2 months (range 3–55.8), all patients remained in remission. Conclusions. EMRC is effective and safe to treat HGD and/or IMC within BE. Moreover, it is a valuable staging method. EMRC can completely remove BE in patients with SSBE. The complication rate is negligible even in large resections. Careful surveillance is recommended for early detection of residual and metachronous lesions. CS08 HIGH FREQUENCY US MINIPROBES IN THE COLON: EXTENDING ENDOSCOPIC ULTRASOUND (EUS) INDICATIONS ABOVE THE RECTUM C. De Angelis, P. Carucci, A. Repici, S. Konstantinidou, F. Curri, M. Bruno, G. Saracco, M. Rizzetto SCDU Gastroenterologia Epatologia, ASO S. Giovanni Battista, Turin, Italy Background and aim. As local staging of suprarectal colon carcinoma has little or no influence on treatment decisions, colon EUS failed to demonstrate a clinical usefulness in everyday practice, so that a dedicated echoendoscope is no more commercially available. Furthermore colonoscopy by this instrument was a demanding and time-consuming procedure. High frequency US miniprobes allows us to easily perform EUS in every GI district accessible to an endoscope. We reviewed our experience of more than 360 transcanalar endoscopic ultrasounds (TEUS) in the last 2 years to evaluate clinical applications of EUS miniprobes in suprarectal colon diseases. Materials and methods. Between the end of 2001 and November 2003 we performed colonoscopy with TEUS in 34 patients (mean age 58.2; males 20). In 24 patients miniprobes were used to assist endoscopic mucosal resection (EMR) (8 lesions in the right colon, 10 in the left and 6 in the trasverse;11 flat lesions). Furthermore we performed 10 suprarectal TEUSs for parietal mass (four patients), infiltration (three patients) and vascular malformation (one patient) suspected by other imaging exams, rectal bleeding (one patient) and treated polypoid lymphoma (one patient). Results. TEUS was difficult to perform in four patients for the position of the lesion or presence of faeces and/or air and EMR was based mainly

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Abstracts

on the lifting sign. In the other cases TEUS demonstrated integrity of the submucosa, but could not differentiate adenomas with high-grade dysplasia (HDG) from T1m carcinoma. Histology on the resected specimens demonstrated HGD in 14 patients, HGD + intramucosal cancer in three patients and HGD + submucosal cancer in one patient; low-grade dyslasia in six patients. In 10 patients TEUS diagnosed: septate ovarian cyst compressing the caecum (one), lipoma (one), GIST or leiomyoma (one), endometriosis into the serosal and muscular layers of the wall (three), vascular malformation of the submucosa and pericolonic tissue (one), acute intestinal ischaemia (one) and infiltrative lymphoma (two). All these results were confirmed by surgery (two), endoscopic resection/biopsies (two), instrumental or clinical follow-up (six). Conclusions. In our experience suprarectal TEUS demonstrated to be of clinical value in selected patients with different colon diseases. CS09 LIVER TRANSPLANTATION (OLT), COMPARED TO PERCUTANEOUS ETHANOL INJECTION (PEI), ASSURES BETTER SURVIVAL IN PATIENTS WITH “EARLY HCC”: A CONTROLLED, MULTICENTRE STUDY I. de Sioa , A. Andriullib , L. Solmic , V. Festab , E. Caturellib , A. Casinid , A. Burroughsd , R. Troisie , B. De Hemptinnee , L. De Carlisf , F. Perrib a Division

of Gastroenterology, Naples, Italy of Gastroenterology, San Giovanni Rotondo, Italy c Division of Gastroenterology, Bologna, Italy d Liver Transplantation Unit, London, UK e Liver Transplantation Unit, Ghent, Belgium f Liver Transplantation Unit, Milan, Italy b Division

Background and aims. For patients with single HCC <5 cm or three nodules <3 cm (“early HCC”) surgical resection, OLT and PEI are assumed to improve the natural history of the disease. As there are no RCTs comparing these options, each centre has established the best treatment approach for the patients. We retrospectively evaluated the outcome of 662 patients with early HCC, derived from two consecutive series: the first series refers to 452 patients treated by PEI at three centres in Italy because OLT was unavailable locally, and the second series refers to 201 patients who underwent OLT for early HCC at three transplantation centres. HCCs, incidentally discovered at pathological examination of explanted livers, were excluded. Study population. Six hundred and sixty-two patients with HCC (78% males), with a mean age at diagnosis of 61.3 ± 10.9 years (range 25–87); all but two with pre-existing cirrhosis, secondary to HCV infection in 64% of them. Cirrhosis was in child A, B and C classes in 51.1, 34.6 and 14.3% of the cases, respectively. The majority of patients (74.5%) had single HCC. At baseline, OLT treated patients were significantly younger, had higher ␣-fetoprotein levels, and higher Child–Pugh score than those PEI treated. Results. After a mean follow-up of 36 ± 30 months, HCC recurred in 264 patients (58.4%) after PEI versus 29 (13.8%) after OLT (P < 0.0001). Disease-free interval was significantly shorter after PEI (16.4 ± 14.2 months) than OLT (23.4 ± 20.9 months) (P < 0.0001). At the end of follow-up, 56.6% of PEI treated patients had died versus 36.7% of OLT patients (P < 0.0001). Mean survival time was 55.1 ± 2.9 months after PEI, and 88.3 ± 6.3 months after OLT (P < 0.0001). Cumulative percentage of survivors at 5 and 10 years were 61.3 and 45.1% for the OLT group, and 34.9 and 14.7% for the PEI group. At multivariate Cox regression analysis, high Child–Pugh score, high ␣-fetoprotein levels, and PEI were significantly associated with the worst prognosis. Conclusions. Despite the more severe impairment of the underlying liver and the longer waiting period between diagnosis and treatment in transplanted patients, OLT provided a survival benefit for patients with early HCC, and should be considered as the primary therapeutic option.

CS10 PREPARATION FOR COLONOSCOPY: A RANDOMISED, BLIND, PROSPECTIVE STUDY COMPARING TOLERABILITY AND EFFECTIVENESS OF 4ltPEG, NaP AND 2ltPEG + LAXATIVE M. Dinellia , A. Lomazzia , S. Paterlinib , F. Milesic , P. Ceasrib , A. Redaellia , F. Buffolib , L. Berettaa , D. Fossatia , M. Loverab , F. Rolfib , M.R. Peregoa , F. Salvionia a Endoscopia

Digestiva, Az. Osp. S. Gerardo, Monza, Italy Digestiva, Polimabulanza, Brescia, Italy c Endoscopia Digestiva, Az. Osp. Treviglio, Italy b Endoscopia

Background. PEG- and NaP-based solutions are both effective in bowel cleansing for colonoscopy. Low volume (2lt) PEG + laxative has been published to reduce discomfort associated with large volume lavage, maintaining effectiveness for cleansing. Design of the study. Outpatients consecutively scheduled for colonoscopy (excluding patients previously submitted to colonoscopy or colon surgery, patients with significant renal or cardiac or hepatic diseases, patients with known IBD or complicated diverticular disease and suspected bowel occlusion) were randomly assigned to 4lt standard PEG regimen (ISO4) (#144) or NaP (#156) or low volume 2lt PEG plus senna, two tablets before and two tablet after PEG (ISOLAX) (#137). Endoscopists were blinded with regard to the solutions administered and scored bowel cleansing “1–5” or “no liquid” to “solid stools”, both for left and right colon, considering “1 + 2” rate “optimal” for colonoscopy; before examination nurses interviewed patients on easiness to complete preparation (scored “1–5” or “easy” or “impossible” to complete) and subjective complaints during preparation (scored “1–5” or “no complaints” or “complaints severe enough to stop preparation”). Statistics (c2) applied compared proportions. Results. Caecum was reached in 100% of patients both in ISO4 and NaP patients while only 53% (73/137) in ISOLAX patients (P < 0.005). Scores “1 + 2” for right colon cleansing were 90.9% for ISO4 patients and 82.7% for NaP patients (P = 0.06, NS) versus 38.3% for ISOLAX patients (P < 0.005), and for left colon cleansing were 89% for ISO4 patients and 85.2% for NaP patients (P = 0.4, NS) versus 76% for ISOLAX patients (P < 0.005 versus ISO4 and P = 0.06 versus NaP, NS). In 95% of ISOLAX and 93% of NaP patients easiness to complete preparation was scored “1 + 2” (P = 0.6, NS) versus 80% in ISO4 patients (P < 0.005). ISOLAX was also the best tolerated regimen, as scored “1 + 2” in 94% of patients versus 92% in NaP patients (P = 0.7, NS) and 85.4% in ISO4 patients (P < 0.005 versus ISOLAX; P = 0.09 versus NaP). Conclusions. Both low volume PEG + laxative and NaP were the best tolerated and “easy to complete” options. Left colon cleansing was optimal in >85% patients prepared with ISO4 or NaP and suboptimal in 24% of ISOLAX patients while right colon cleansing was optimal in about 90% of ISO4 patients and about 80% of NaP patients: ISOLAX produces optimal rates in less than 40% of patients. There seems to be no advantage in using low volume PEG regimens with laxative. Standard 4lt PEG regimen showed a positive trend in optimally cleaning right colon and should be used if caecum has to be reached. CS11 COMPARISON OF TUBELESS TESTS AND DYNAMIC RM CHOLANGIOPANCREATOGRAPHY (CWRM) AFTER SECRETIN STIMULATION IN THE ASSESSMENT OF EXOCRINE PANCREATIC FUNCTION IN PATIENTS SUFFERING FROM CHRONIC PANCREATITIS (CP) L. Frulloni, S. Biasin, B. Ferri, L. Bernardoni, E. Coato, K. Faitini, A. Katsotourchi, F. Patrizi, P. Bovo, B. Vaona, G. Cavallini Department of Surgical and Gastroenterological Sciences, University of Verona, Italy Background. Tubeless tests, in particular faecal elastase-1, have been proposed to evaluate exocrine pancreatic function. Duodenal filling detected

Abstracts at CWRM after secretin stimulation (CWRM-S) may quantify pancreatic function test in patients suffering from pancreatitis. The aim of this study was to compare tubeless tests and CWRM-S. Patients and methods. We studied 15 healthy subjects (C) (seven males, eight females, mean age 36 ± 15.6 years), 15 patients suffering from acute recurrent pancreatitis (ARP) (eight males, seven females, mean age 45 ± 10.8 years) and 18 patients suffering from chronic pancreatitis (CP) (12 males, 6 females, mean age 52 ± 13 years). Faecal fat output, faecal chimotrypsin and faecal elastase-1, pancreo-lauryl test were tested in all patients, whereas only CP patients underwent CWRM-S. Duodenal filling were classified as grade 1 (liquid limited to duodenal cap), grade 2 (up to genu inferior) and grade 3 (beyond the genu inferior). Results. Elastase-1 was the best test for the diagnosis of CP (see table).

Test

Elastase-1 Chimotrypsin Pancreo-lauryl test Faecal fat output

Sensitivity (%) 83 57 70 28

Specificity PPV (%) (%) 100 87 92 100

100 80 87 100

PNV Diagnostic (%) accuracy (%) 83 68 79 54

91 72 82 61

All patients with grade 1 of duodenal filling at CWRM-S had pathologic pancreatic function tests (see table).

Tubeless test (pathologic) Elastase-1 Chimotrypsin Pancreo-lauryl test Faecal fat output

Duodenal (%)

Filling (%)

At CWRM-S (%)

Grade 1

Grade 2

Grade 3

100 100 100 50

75 0 50 0

60 0 0 0

We found steatorrhoea only in CP patients with grade 1 of duodenal filling at CWRM. Conclusions. Faecal elastase-1 is the best sensitive test for the diagnosis of chronic pancreatitis. There is a good correlation between tubeless test and CWRM-S. Faecal fat output may quantify only in patients with grade 1 of duodenal filling at CWRM-S grade 1 of duodenal filling at CWRM. CS12 INCREASED EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTOR IN HEPATOCELLULAR CARCINOMA AND EXTRA-TUMOURAL CIRRHOTIC TISSUES M. Iavarone, P. Lampertico, E. Arosio, M.F. Donato, A. Sangiovanni, E. Del Ninno, M. Colombo Division of Hepatology, IRCCS Maggiore Hospital, University of Milan, Milan, Italy To investigate whether vascular endothelial growth factor (VEGF)/VEGF receptor (KDR) expression has any relation to HCC development and progression, VEGF-165, VEGF-189 and KDR mRNA were assessed by a semi-quantitative RT-PCR method in 56 liver biopsy specimens: 21 HCC and 35 chronic liver disease tissues (CLD) (9 extra-tumoural cirrhotic tissues, 11 cirrhosis, 15 chronic hepatitis). Results were expressed as mean ± S.D. of ratio between target gene and beta-actin expression. Results. VEGF-165, VEGF-189 and KDR were more significantly expressed in 21 HCC than in 35 CLD tissues (1.46±0.93 versus 0.58±0.48, P < 0.0001; 1.02 ± 0.64 versus 0.57 ± 0.53, P = 0.005; 1.27 ± 1.15 versus 0.65 ± 0.70, P = 0.014). VEGF-165 mRNA correlated with KDR expression in both HCC and CLD tissues (r = 0.8 and 0.6). VEGF-165 was more expressed in HCC than in the corresponding extra-tumoural

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tissues (1.46 ± 0.33 versus 1.09 ± 0.26, P = 0.04). VEGF-165 and VEGF-189 mRNA were higher in cirrhotic tissues than in chronic hepatitis (0.74 ± 0.48 versus 0.33 ± 0.37, P = 0.01 and 0.77 ± 0.57 versus 0.26 ± 0.31, P = 0.004). VEGF-165, VEGF-189 and KDR were more expressed in nine extra-tumoural cirrhotic tissues than in 11 cirrhotics (1.01±0.26 versus 0.45±0.45, P = 0.001; 1.21±0.27 versus 0.41±0.48, P = 0.0003; 1.14 ± 0.89 versus 0.30 ± 0.42, P = 0.01). VEGF-189 mRNA was higher in five multifocal poorly-differentiated HCCs than in six single well-differentiated small HCCs (1.49 ± 0.5 versus 0.78 ± 0.42, P = 0.03). VEGF/KDR expression did not correlate either with liver cell proliferation in 21 HCC, or with the necro-inflammatory activity in 35 CLDs. Conclusions. VEGF/KDR was increasingly expressed from chronic hepatitis to more aggressive HCCs, suggesting that it is a regulator of neoplastic transformation and angiogenesis, and a possible marker of tumour aggressiveness. CS13 ACTIVITY OF THE CENTRE FOR SURVEILLANCE AND CONTROL OF COELIAC DISEASE (CCD) OF BRESCIA PROVINCE: INCIDENCE, PREVALENCE AND CLINICAL PRESENTATION OF THE DISEASE A. Lanzini, F. Donato, F. Lanzarotto, N. Pillan, V. Villanacci, F. Pirali, M. Amato, F. Benini, A. Mora, A. Indelicato, C. Scarcella Medicine 1m, Hygene, Pathology, Paediatrics, Spedali Civili and Medical School, A.S.L. Brescia, Italy Though the prevalence of coeliac disease (CD) is as high as nearly 1/100, underdiagnosed in the primary care is very common mainly because of heterogeneous clinical presentation. A centre for surveillance and control of CD (CCD) has been instituted on June 2000 in the province of Brescia in Northern Italy (1,016,426 residents in the year 2001 census) with the aim to improve awareness of CD, to implement diagnostic criteria, and to monitor incidence and prevalence of the disease. We report here demographic characteristics, histologic pattern and clinical presentation of CD patients identified as a result of CCD activity. One thousand four hundred and thirty-seven CD patients have been identified by CCD, 508 of them diagnosed after June 2000 (M/F 2/1). At present the annual incidence of CD diagnosis is 0.17/1000 and is raised from 0.13/1000 as it was on the year preceding CCD activity. Mean age at diagnosis increased from 20.2+17.7 years to 27.2+19.3 years (P < 0.0001) and the proportion of patients diagnosed at an age more than 15 years increased from 55 to 68%, before and after CCD start of activity. The proportion of asymptomatic patients also increased from 8 to 15%. After CCD start of activity the proportion of patients with types 1, 2, 3A, 3B and 3C lesion at duodenal biopsy (Marsh–Hoberhuber classification) was 6, 2, 11, 17 and 64%, respectively. The histological severity declined with age, and type 3C lesion represented 82% in patients younger than 4 years and 52% in those older than 55 years. The positivity of antiendomisial and transglutaminase antibodies was significantly associated with the severity of duodenal lesions (P < 0.001) and increased from 50 and 50% in type 1 to 89 and 86% in type 3C lesion, respectively. Our results indicate that increased awareness of CD as achieved by the activity of CCD results in large increase in annual incidence rate for newly diagnosed CD, and that this increase is mainly due to diagnosis in adult patients. The majority of patients have severe atrophic disease particularly among paediatric patients, and histological severity of CD is mirrored by increased prevalence of autoantibodies.

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Abstracts

CS14 HEPATITS C VIRUS RNA LOAD DECLINE DURING THERAPY: COMPARISON BETWEEN RELAPSED AND LONG-RESPONDING PATIENTS A. Mancaa , S. Ungarib , R. Bonardic , A. Antinozzib , S. Orsinib , S. Riberob , A. Mattaliaa , R. Ferrarisa , M. Rizzettoc a Gastroenterology

Unit, Cuneo, Italy Biology Laboratory, S. Croce e Carle Hospital, Cuneo, Italy c UOADU Gastro-Hepatology Molinette Hospital, Turin, Italy b Molecular

Background. Recent studies have demonstrated that in chronic hepatitis C virus infection an early viremic response to therapy is predictive for a sustained virologic response (SR). We analysed the viral load decline and the loss of detectable HCV–RNA during the early weeks of treatment, with the purpose of identifying different behaviours between patients who relapsed (R) and those who maintained a SR. Methods. We studied 99 consecutive patients treated with different Interferon-based regimens (IFN or PEG-IFN plus ribavirine): 60 of them (42 genotype non-1 and 18 genotype 1) had SR (confirmed by undetectable HCV–RNA at the end of the initial treatment and again at 24 weeks post-treatment), 23 (13 genotype 1 and 10 genotype non-1) relapsed and 16 were non-responders (NR). HCV–RNA levels were determined using a quantitative semi-automated method (COBAS Amplicor-Roche) at 15 day intervals until HCV–RNA level became undetectable. Results. At the end of the 12th week 96% of SR and 71% of R patients showed undetectable levels of HCV–RNA. SR had a more rapid decline of viral load than R: HCV–RNA was undetectable in 38% at 4 weeks and in 83% at 8 weeks versus 9% at 4 weeks and 40% at 8 weeks, respectively. In the SR group, genotype non-1 showed a more consistent drop than genotype 1: HCV–RNA was undetectable in 45% at 4 weeks and in 93% at 8 weeks versus 22% at 4 weeks and 61% at 8 weeks, respectively. HCV–RNA disappeared after 6 weeks in all SR patients with genotype 3 (100%). Conclusion. Previous data reporting 12 weeks as the time point to estimate a viral load decline in order to predict a sustained virological response were not confirmed in this study. Our data suggest that an earlier evaluation of the viral decline at week 8 is preferable in order to distinguish SR from R. The rapid identification of patients who are unlikely to achieve a sustained virological response may help to stop useless and costly therapy. CS15 WIRELESS CAPSULE ENDOSCOPY versus SMALL BOWEL ENTEROCLYSIS IN THE DETECTION OF ILEAL INVOLVEMENT IN CROHN’S DISEASE: A PROSPECTIVE CONTROLLED TRIAL R. Marmoa , G. Rotondanob , M. Antonia Biancob , A. Sianic , R. Piscopob , L. Cipollettab a UOC

Gastroenterologia, ASL SA3, Ospedale “L. Curto”, Polla (SA), Italy b UOC Gastroenterologia, ASL NA 5, Ospedale “A. Maresca”, Torre Del Greco (NA), Italy c Dipartimento di Radiologia, ASL NA 2, Ospedale di Pozzuoli (NA), Italy

Background. Small bowel enteroclysis (SBE) is considered the gold standard for demonstration of small bowel ulcerations. Wireless capsule endoscopy (WCE) (M2A Capsule, Given Imaging, Yoqneam, Israel) is a new method of imaging the entire small bowel. Crohn’s disease (CD) represents the main ulcerating disease affecting small bowel. Aim. To compare the diagnostic yield of both procedures in patients with newly diagnosed CD. Methods. Patients with newly diagnosed CD consecutively observed from 1 January 2002 to 1 October 2003 were included. Patients with stenosing or fistulising disease, pregnancy, implanted electromedical devices, previous small bowel surgery, lack of ability to swallow, suspected small bowel obstruction, HIV positive, FANS intake within 1 week were excluded.

CD was endoscopically and histologically proven in all cases. Patients underwent first SBE and then WCE. The physicians were unaware of the reciprocal results. If a fistulising and/or stenosing disease was observed on radiographs, the patient was withdrawn from the study. Results. Nineteen patients (12 male, 7 female) with newly diagnosed CD were recruited. Mean age was 42.1 years (S.D. 14.8) (range 15–66). Mean CDAI score was 170 (S.D. 27) points. Small bowel lesions were detected in 14/19 patients with WCE and only in 4/19 with SBE. Two patients had negative findings with both techniques. In only one patient both methods agreed on the presence of ileal disease. A significantly higher number of ileal lesions were detected with WCE as compared to SBE (P = 0.021). Enteroclysis WCE total lesions absent, lesions present, lesions absent 2 (13.3%), 13 (86.7%), 15 lesions present, 3 (75%), 1 (25.0%), 4 total; 5, 14, 19 McNemar test exact significance (two-sided) P = 0.021 by ITT. Conclusions. Given M2A capsule successfully imaged and provided good views of the gastrointestinal tract from the mouth to the colon. As compared to SBE, WCE indicated a more diffuse small bowel involvement with a diagnostic gain of about 60%, providing a more correct evaluation of the extension of CD in patients understaged with standard diagnostic procedures. WCE might be proposed as the new gold standard for diagnosing small bowel involvement in patients with CD. CS16 OESTROGEN ADMINISTRATION PROTECTS FROM THE BILE DUCT VANISHING INDUCED BY BILIARY-DIGESTIVE DIVERSION IN THE BDL RAT M. Marzionia , R. Ghisellia , G. Svegliati Baronia , D. Alvarob , F. Mocchegiania , S. Saccomannoa , V. Sistia , L. Ugilia , F. Orlandoa , V. Sabaa , G. Alpinic , A. Benedettia a Università

Politecnica delle Marche, Ancona, Italy “La Sapienza”, Rome, Italy c Texas A&M University, Temple, TX, USA b Università

The biliary tree is the target of chronic cholestatic diseases (cholangiopathies), characterised by increased death of cholangiocytes not counteracted by adequate proliferation. After bile duct ligation (BDL) cholangiocyte proliferation is markedly increased, with a parallel enhancement of the functional activity. In contrast, it has been shown that when a biliary-digestive diversion (BDD) follows the BDL, there is a loss of bile ducts, with marked reduction of cholangiocyte proliferation and increased apoptosis. We have previously demonstrated that oestrogens exert a major role by the activation of the MAP-kinase intracellular pathway. Aim. To evaluate whether oestrogen administration protects from the bile duct loss induced by BDD. Methods. After 4 weeks of BDL, rats were subjected to biliary-digestive diversion for 7 or 14 days. Simultaneously, they were also treated with daily IP injections of 17␤-estradiol (100 ␮g/kg body weight). Cholangiocyte apoptosis was evaluated by TUNEL assay in liver sections. The changes in cholangiocyte proliferation were measured by: (i) immunohistochemistry for PCNA and (ii) estimating the bile duct mass by the morphometrical analysis of the gamma-glutamyl-transpeptidase staining. We also studied by immunohistochemistry and immunoblots the changes on ERK1/2 phosphorylation (pERK). Results. Both after 7 and 14 days from the BDD a marked increase of the number of apoptotic cholangiocytes was observed by TUNEL. In contrast, 17␤-estradiol significantly reduced cholangiocyte apoptosis. 17␤-estradiol also increased the number of PCNA-positive cholangiocytes and the bile duct mass, strikingly reduced by BDD. Both immunoblots and immunohistocemistry showed a very high ERK1/2 phopsphorylation after BDL. BDD determined a marked reduction of pERK, that was reversed by the administration of 17␤-estradiol. Summary/conclusions. Oestrogens prevent the increase of cholangiocyte apoptosis and loss of cholagiocyte proliferation induced by BDD in the BDL rat. In parallel, 17␤-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by BDD. These novel findings suggest

Abstracts that oestrogens may play a major role in preventing liver injury associated with vanishing of bile ducts. CS17 PREDICTIVE FACTORS OF OUTCOME AFTER LIVER TRANSPLANTATION IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA G. Nicolinia , M. Merlia , F. Gerrtilia , G. Indrioa , M. Iappellib , M. Rossia , P. Berlocob , U. Di Tondoc , A. Onetti Mudac , S. Gianni Corradinia , F. Nudob , O. Riggioa , A.F. Attilia a II

Gastroenterologia, Dipartimento di Medicina Clinica, Italy di Chirurgia Generale II, Italy c Istituto di Anatomia Patologica Università di Roma “La Sapienza”, Rome, Italy b Dipartimento

Background. Available studies to define the optimal upper limits of tumour size and number as predictors for outcome after orthotopic liver transplantation (OLT) have given conflicted results. Aims. We retrospectively analysed the outcome of 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 10-year period. Possible predictive factors and survival according to the Milan [1] and UCSF [2] criteria of transplantation were also examined. Patients and methods. Our cohort included 60 males and 12 females with mean age of 54 ± 8 years and mean follow-up of 22 ± 26 months. Sixty percent of patients underwent loco-regional therapy before OLT. Origin of cirrhosis was post-viral in 71%, Child class was B or C in 90%. Diagnosis of HCC was always confirmed at histology after OLT and. HCC was multifocal in 57%, 68% of HCC had micro or macro-vascular involvement and 70% had positive nodes. Cumulative size of lesion was 0–3 cm in 38% of cases, 0–5 cm in 54% and >5 cm in 33%. Sixty percent of patients met the Milan criteria and 67% met the UCSF criteria of selection for OLT. Results. During follow-up, 23 patients died and in 52% of cases the cause of death was the tumour’s recurrence. At multivariate analysis, only the presence of positive nodes was significant predictors of survival and tumour size >8 cm in maximum diameter was predictive of death due to the tumour’s recurrence. The 1- and 2-year survival were 87 and 64% for patients who met the Milan criteria versus 41 and 35% for patients exceeding these limits (P = 0.01). Among patients who met the UCSF criteria, the 1- and 2-year survival were 86 and 67% compared with 31 and 23% for patients exceeding the criteria (P = 0.0008). Conclusions. Our analysis suggests that the Milan criteria for selection of patients with cirrhosis and HCC might be revalued and UCSF criteria may be adopted. References [1] N Engl J Med 1996;334:693–9. [2] Hepatology 2001;33:1394–403. CS18 PROGNOSTIC FACTORS AND SURVIVAL IN PATIENTS WITH DIGESTIVE NEUROENDOCRINE TUMOURS F. Panzutoa , S. Nasonia , M.S. Cattaruzzab , M. Milionec , S. Cassettaa , V. Tornatorea , M. Di Fonzoa , G. Capursoa , V.D. Corletoa , C. Bordic , G. Delle Favea a Department

of Digestive and Liver Disease, II School of Medicine, University “La Sapienza”, Rome, Italy b Department of Public Health, II School of Medicine, University “La Sapienza”, Rome, Italy c Department of Pathology, University of Parma, Rome, Italy

Background. Due to their rarity and their biological heterogeneity, natural history of digestive neuroendocrine tumours (dNETs) is not well known. Aim. To determine prognostic factors and survival in dNETs.

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Patients and methods. One hundred and forty-four consecutive patients with dNETs were enrolled (68 male, median age 51 years, range 10– 78) and observed during a median follow-up of 36 months (range 3– 239). Univariate and multivariate analysis (Cox regression model) was performed to identify prognostic factors. Survival rates were assessed by Kaplan–Meier curves and log-rank test. Results. Tumour was non-functioning (NF) in 89 patients (62%). Primary tumour was located in the pancreas in 60 patients (41.7%). At diagnosis, 34.5% of patients had no metastases, and 12% had local involvement; 53.5% of patients had distant metastases (40.1% liver, and 13.4% also distant non-liver). Tumour cells degree of differentiation was good in 87.2%. Ki67 was >2% in 43% of patients. Primary tumour size was >3 cm in 50% of patients. Positive Octreoscan was found in 91.7% of the patients. At univariate analysis, the negative prognostic factors were: pancreatic site of the primary tumour (risk 4.4, z = 3.58), poor degree of cells differentiation (risk 4.3, z = 2.82), primary tumour size >3 cm (risk 4.3, z = 2.93), presence of metastases (local: risk 4.19, z = 1.56; liver: risk 5.68, z = 2.29; distant non-liver: risk 12.6, z = 3.23). The pancreatic site of the tumour and the presence of distant metastases were confirmed to be negative prognostic factors by multivariate analysis also. Overall 5-year survival rate was 77.4%. Different 5-year survival rates were observed in relationship to: primary tumour site (62.5% pancreatic versus 89% of non-pancreatic, P = 0.0003) and size (68% >3 cm versus 88% <3 cm, P = 0.001), degree of differentiation (good 83% versus poor 0%, P = 0.001), ki 67% (>2, 59% versus <2, 87%, P = 0.04), metastases (absent 96%, local 75%, liver 72%, distant non-hepatic 54%). Conclusion. Even if 53.5% of dNETs have distant metastases at the time of diagnosis, the 5-year overall survival rate is relatively high (77.4%). The pancreatic site of the primary tumour and the presence of distant metastases are the major negative prognostic factors. CS19 SERIAL US MEASUREMENT OF BOWEL WALL THICKNESS AFTER CONSERVATIVE SURGERY IS HIGHLY PREDICTIVE OF CLINICAL OR SURGICAL RECURRENCE IN PATIENTS WITH CROHN’S DISEASE F. Parentea , M. Moltenia , G. Sampietrob , S. Grecoa , C. Spositoa , G. Maconia , P.G. Danellib , G. Bianchi Porroa a Department

of Gastroenterology, L. Sacco University Hospital, Milan, Italy b Department of General Surgery, L. Sacco University Hospital, Milan, Italy Background and aim. Clinical or surgical recurrences after conventional or conservative surgery for Crohn’s disease (CD) are frequent and often unpredictable. To date, post-operative follow-up of CD patients has mainly relied on clinical and biochemical parameters although preliminary reports have suggested a potential role for bowel US on this regard. The aim of this study has been to assess whether a systematic US follow-up of CD patients after conservative surgery may predict clinical or surgical recurrence. Material and methods. One hundred and two consecutive patients (65 males) have undergone conservative surgery for complicated or therapy-refractory CD were followed-up by regular bowel US examinations at 3, 6 and 12 months after surgery for the first year, then every 6 months. All patients received long-term oral 5-ASA compounds as postoperative adjuvant therapy. CD recurrences were sought by clinical and laboratory evaluation at 6-month intervals for a median follow-up of 41.2 months. Clinical recurrence was defined as the presence of CD-related abdominal symptoms, variably associated with X-ray, endoscopic and laboratory findings, needing therapy with medium–high dose of steroids; surgical recurrence was defined as the presence of therapy-refractory disease or CD-related complications requiring a new surgical procedure. Cumulative probability of clinical and surgical recurrences was estimated by the time-to-event Kaplan and Meier’s method.

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Results. Bowel wall thickness normalised within 3–12 months from conservative surgery in 28% of patients. The estimated 10 years cumulative clinical and surgical recurrence rates were 43 and 27%, respectively. Patients with bowel wall thickness more than 7 mm at 6–12 months after surgery had a significantly higher risk of either clinical or surgical recurrence compared with those with normalised or slightly increased bowel wall thickness (<5 mm). Conclusions. Systematic US follow-up is strongly advisable in CD patients after conservative surgery as it allows the early identification of those at high risk of clinical or surgical recurrence. This may dictate the choice of the most appropriate postoperative prophylactic treatment. CS20 CLINICAL OUTCOME OF PATIENTS WITH OBSCURE GASTROINTESTINAL BLEEDING AFTER CAPSULE ENDOSCOPY: REPORT OF 100 CONSECUTIVE CASES M. Pennazioa , E. Rondonottib , C. Abbiatib , C. Signorellib , F.P. Rossinia , R. de Franchisb a Division

of Gastroenterology 2, Department of Oncology, S. Giovanni AS Hospital, Turin, Italy b Gastroenterology and Gastrointestinal Endoscopy Service, Department of Internal Medicine, University of Milan, IRCCS Maggiore Policlinico Hospital, Milan, Italy

Background. Previous studies have reported on diagnostic yield of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB). Data on patient outcome are however lacking. Aims and methods. We report on 100 consecutive patients who underwent CE for OGIB. The aims were: (1) to evaluate the yield and to determine sensitivity and specificity of CE; (2) to assess the impact of CE on the clinical outcome. Indications were: ongoing obscure-overt bleeding in 26 patients, previous obscure-overt bleeding in 31 and, obscure-occult bleeding in 43. Results of CE were classified as: true positive: (a) verification of CE diagnosis by surgery, endoscopy or other alternative means. True negative: negative CE study and bleeding problem resolved with no further treatment, or (b) extra-intestinal lesions found and treated with resolution of the bleeding. False positive: positive CE study with a different small bowel lesion found on subsequent work-up. False negative: negative CE study with small bowel lesion diagnosed by different means and treated with resolution of the bleeding. Unknown: in any other case. Clinical outcome after CE was assessed by collecting the following information: use of medical, endoscopic or surgical treatment, further bleeding episodes, results of faecal occult blood testing, presence or absence of iron deficiency anaemia. Results. The yield of positive diagnostic findings on CE was: overall 47%; patients with ongoing overt bleeding: 92%; patients with occult bleeding: 44.2%; patients with previous overt bleeding: 12.9% (P < 0.0001). The overall accuracy, sensitivity, specificity, predictive positive and negative values of CE were: 91, 89, 95, 97 and 82%, respectively. Follow-up (f/u) data were obtained for 91 patients: 23 with ongoing obscure-overt bleeding, 29 with previous obscure-overt bleeding, 39 with obscure-occult bleeding. The mean f/u after CE was 18 months (5–25). In patients with ongoing overt bleeding, the subsequent management dictated by CE findings led to complete resolution of the bleeding during f/u in 86.9% of these patients. The corresponding figures for patients with occult bleeding or with previous overt bleeding were 69.2 and 41.4% (P = 0.002). Conclusion. CE is a highly specific tool for the detection of small bowel lesions in patients with OGIB. The best candidates for the procedure are those with ongoing bleeding. CE contributes to definitive treatment in a relevant proportion of patients over medium-term f/u. The clinical outcome appears to be better if the patient undergoes CE while actively bleeding.

CS21 TARGET CONTROLLED INFUSION (TCI) OF PROPOFOL FOR OUTPATIENT COLONOSCOPY: RESULTS ON 500 PROCEDURES N. Polimenia , F. Bovaa , A. Lauriaa , A. Luveràa , F. Furfarob , A. Posterinob , A. Musitanob , F. Polimenia a Unit

of Gastroenterology, Unit of Anesthesiology, Italy Hospital, Reggio Calabria, Italy

b “Bianchi–Melacrino–Morelli”

Background and aims. The use of controlled sedation (CS) with propofol in performing endoscopic procedures is increased in the last years, especially regarding colonoscopy. Target controlled infusion (TCI) is used in anaesthetic practice to achieve and maintain a selected target blood propofol concentration. The aim of this study was to evaluate efficacy and safety of CS with TCI of propofol for outpatient colonoscopy. Methods. Data from 500 outpatients’ colonoscopies performed with the assistance of dedicated anaesthetists were reviewed retrospectively. Midazolam (0.02 mg/kg) and Fentanyl (1.5 ␮g/kg) were given by intravenous bolus injection as induction and then propofol was delivered by a Terumo Infusor Pump. All patients were given supplemental oxygen with a nasal cannula or Vent mask and were monitored with continuous pulse oxymetry for heart rate, blood pressure, SaO2 and electrocardiograph by automated sphygmomanometry at intervals of 5 min. Results. Table shows the results. Variable Number of patients Sex; age ASA class Propofol target blood concentration Propofol total dose Delay in starting procedure Complete examination

491 317 male–183 female; 15–92 years (range) I–III (range) 2–4 ␮g/ml 60–300 mg (range) 3–5 min 487 patients (97.4%)

Complications related to CS: in our series we had only one case of respiratory failure resolved with assisted ventilation; transient desaturation below 90% and hypotension in no case required intervention. Conclusions. CS with TCI of propofol for outpatient colonoscopy is a safe and efficacy technique; the use of Meperidine and Fentanyl as induction can reduce the dosage of propofol. CS22 COMPARISON OF THE LARGE SOFT CAP VERSUS STANDARD HARD CAP FOR EMR OF DYSPLASTIC LESIONS OR EARLY CANCER IN THE OESOPHAGUS, STOMACH AND COLON A. Repici, M. Conio, A. Sapino, C. De Angelis, S. Caronna, M. Goss, A. De Lio, R. Nicita, A. Musso, M. Rizzetto, G. Saracco Background and aims. Cap-assisted mucosectomy is a therapeutic option for endoscopic treatment of preneoplastic and neoplastic lesions of the GI tract. The effectiveness and safety of a larger and soft cap was compared in this study with the conventional oblique hard cap. Methods. Nine patients with Barrett’s oesophagus containing multifocal high-grade intraepithelial neoplasia or intramucosal cancer larger than 3 cm and 11 patients with gastric and colonic adenoma were included. For each patient’s resection of a large specimen with the soft cap was initially done. Thereafter, removal of residual areas of the lesions was performed with the oblique, hard cap. Diameter, resection specimen depth and rate of complications were analysed. Results. Twenty patients (12 male and 8 female, mean age 68.8 years) underwent EMR of HGD on BE (nine patients), large gastric adenoma (five patients) and flat colonic adenoma (six patients) using both caps in a single session. Mean diameter of specimens resected with the soft cap

Abstracts was larger: 19.1 (±0.6) versus 14.6 (±0.3) mm (P < 0.001). Soft cap specimens were also thicker: 2.8 (±0.8) versus 1.5 (±0.11) (P < 0.001). Muscolaris propria layer (circular, inner layer) was present in soft cap specimens of four patients with BE, one patient with gastric lesions and two patients with colonic lesions. The medial total area of mucosa in resected specimens was 3.9 cm2 . No early or late complications were recorded except two cases of post-procedural bleeding controlled by clips placement. Conclusion. Soft cap EMR in the oesophagus, stomach and colon provides thicker and larger resection of neoplastic specimens compared with the standard oblique hard cap. In several cases the muscolaris propria is reached thus increasing the risk of wall perforation. A modification of the technique (injection of larger volume of saline or injection of substances different than saline) could be required for a safe use of the soft cap in the EMR of the GI tract. CS23 EARLY AN LATE OUTCOME OF PATIENTS WITH OBSTRUCTING COLORECTAL CANCER TREATED BY STENTING AND ELECTIVE SURGERY. A COMPARISON WITH EMERGENCY SURGERY AND PATIENTS OPERATED WITHOUT OBSTRUCTIVE SYMPTOMS A. Repicia , M. Coniob , M. Gossa , C. Caronnaa , C. De Angelisa , C. Dalla Costaa , M. Morinoc , A. Focoa , P. Miolic , L. Petruzzellic , M. Rizzettoa , G. Saraccoa a Department

of Gastroenterology, Molinette Hospital, Turin, Italy Cancer Institute, Genoa, Italy c Emergency Surgery, Molinette Hospital, Turin, Italy b National

Background. SEMS have been developed to treat acute malignant colorectal obstruction (AMCO). Nobody knows if the SEMS placement can be associated with tumour cell spreading and increased risk of tumour recurrence compared with emergently and electively operated patients. The aim of this study was the evaluation of early and late outcome of the use of SEMS as a bridge to surgery for AMCO. Methods. Between March 1999 and December 2000, 28 (18 male/10 female, mean age 72.4 years) patients admitted with left-sided AMCO were treated by SEMS placement followed by elective surgery (group 1). The early and late outcome of these patients were compared, by retrospective analysis, with 25 unselected patients with AMCO managed by surgical decompression (group 2) and 24 who underwent elective surgery for left-sided colorectal cancer (group 3). Results. Primary stenting success rate was 92.8 (26/28). Perforation occurred in one case (3.5%), failure of stenting in one patient. After a median of 3.7 days, one-stage resection was performed in 89.2% of patients (25/28) compared with 28% (7/25) of group 2 and 95.8 (23/24) of group 3. Complication rate was 10.7% (two leakages, one wound infection) in group 1, 25% (four leakages, one pulmonary embolism, one bleeding) in group 2 and 8.3% in group 3 (one leakage, one acute renal failure). The 30-day mortality was 0% in group 1, 8% in group 2 and 0% in group 3. Three patients of group 2 treated by Hartmann’s resection never underwent colostomy closure because of high surgical risk. Eight out 28 patients (28.5%) underwent chemotherapy after surgical resection compared with 24% in group 2 and 33.3% (8/24) in group 3. At 3-year follow-up 18 patients (64.2%) were alive and disease-free, four patients were alive but with tumour progression and six patients have died due to tumour progression in group 1. In group 2, 15 patients were alive and disease-free, two patients were alive but with tumour progression, two patients have died of unrelated cause, and six patients have died due to tumour progression.

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CS24 SPORADIC COLORECTAL CANCERS LACKING HMLH1 AND WITH MICROSATELLITE INSTABILITY SHOW FUNCTIONAL P53 AND HIGH EXPRESSION OF THYMIDILATE SYNTHASE: IMPLICATIONS FOR CLINICAL SETTINGS AND CHEMOTHERAPEUTIC STRATEGIES L. Ricciardielloa,b,1 , C. Ceccarellia,b,1 , G. Angiolinia,b , G.N. Martinellia,b , E. Rodaa,b , F. Bazzolia,b a Department

of Internal Medicine and Gastroenterology, University of Bologna, Italy b Center for Applied Biomedical Research (CRBA), S. Orsola-Malpighi Hospital, Bologna, Italy 1 Both authors equally contributed to this work. Microsatellite instability (MSI) is due to failure of the DNA mismatch repair (MMR) system. Colon cancers with MSI, although pathologically more aggressive, are clinically less aggressive since they tend not to metastasise, and, on the other hand, do not respond to 5-FU. The reasons why MSI tumours are clinically less aggressive and do not respond to 5-FU-based therapies, have not been fully elucidated. Aim. We investigated biomolecular markers that could explain the different clinical behaviours and chemotherapeutic responses of MSI and non-MSI CRCs. Methods. One hundred and forty-three consecutive CRCs, were tested for microsatellite instability with BAT25 and BAT26. MSI-H tumours were defined by having both markers mutated; those with a single marker unstable were considered MSI-low (MSI-L) and those with no mutations were stable (MSS). Samples were stained for p53, MDM2, ␤-catenin, p21, thymidylate synthase (TS), hMLH1, hMSH2 and hMSH6. The function of the p53 system (Fp53) was considered for samples having concomitant negative staining of p53 and high expression of MDM2 and p21. Results. Fifty-three CRCs (37.1%) were located in the right colon and 90 (62.9%) were in the left. Nineteen cases (13.3%) were MSI-H, 40 (28.0%) were MSI-L and 84 (58.7%) MSS. Of the MSI-H CRCs, 14 were located in the right colon while five were in the left (26.4% versus 5.6%, P = 0.0018). Of the 53 CRCs located in the right colon 14 lacked hMLH1 versus 1/90 in the left colon (P < 0.0001). Cases (10/143) had reduced hMSH2 expression (7.0%) and 1/143 cases had loss of hMSH6 (0.7%). No differences were found for ␤-catenin. MSI-H cases (13/19) lacked hMLH1 expression (68.4%), compared to 1/40 (2.5%) and 1/84 (1.2%) for MSI-L and MSS cases, respectively (P < 0.0001 and <0.0001). CRCs (12/15) lacking hMLH1 had Fp53 compared to 23/126 hMLH1 positive cases (80% versus 18.3%, P < 0.0001). Finally, the 13 CRCs with MSI-H and loss of hMLH1 showed higher expression of TS compared to MSS or MSI-L CRC (P < 0.0001 and <0.0001). Conclusions. About 10% of CRCs are hMLH1 defective with MSI. These tumours are located on the right side, retain fully functional p53 system and have high expression of TS. Taken together, these data: (1) explain why sporadic hMLH1 defective CRC are clinically less aggressive (retention of p53 regulation) and often do not respond to 5-FU (high expression of TS); and (2) suggest the use of these markers in diagnostic settings and eventually for the choice of chemotherapeutic strategies. CS25 THE ROLE OF DIGESTIVE ENDOSCOPY IN TRANSMITTING HEPATITIS C VIRUS INFECTION: RESULTS OF A PROSPECTIVE MULTICENTRE STUDY G. Saracco, A. Ciancio, S. Caronna, A. Morgando, P. Manzini, P. Reynaudo, G. Ciccone, C. Barletti, P. Carucci, W. De Bernardi Venon, C. De Angelis, A. Musso, A. Repici, S. Peyre, M. Ballarè, M. Del Piano, M. Rizzetto Background. The potential role of digestive endoscopy as a mode of iatrogenic transmission of hepatitis C virus (HCV) has been largely de-

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bated. Reviews of endoscopic procedures have revealed that inappropriate cleaning and disinfection of the endoscopic instruments were probably responsible for the rare reported cases of HCV transmission. Aim. To evaluate the role of digestive endoscopy in transmitting HCV infection, we performed a prospective study on 8260 outpatients consecutively recruited in three Italian Endoscopic Units who underwent upper digestive endoscopy between 1999 and 2002. Patients and methods. Of 9188 patients who gave their written consent to participate into the study, 8260 (90%) anti-HCV-negative patients were re-tested for anti-HCV 6 months after the endoscopic procedure. As controls, we considered 51,230 blood donors consecutively admitted to blood donation in two Italian Blood Banks in the same period; all of them were anti-HCV-negative at baseline. Blood donors (38,280, 75%) were tested again 6 months after the first blood donation. The two populations were well matched for gender and age. Results. Anti-HCV was negative 6 months after endoscopy in all subjects (1 year cumulative incidence = 0%; 95% confidence interval = 0–1.17%). In the non-exposed group, seven became anti-HCV and HCV–RNA positive (1 year cumulative incidence = 0.018%; 95% confidence interval = 0.006–0.043%; P = 0.88). In five out of the seven positive subjects, a history of minor surgery 2–4 months before the second test was detected. Conclusions. These findings suggest that digestive endoscopy does not play a major role in transmitting HCV infection if appropriate guidelines of cleaning and disinfection are observed. CS26 USEFULNESS OF MULTIPLE RAPID SWALLOWING (MRS) IN THE EVALUATION OF LOWER OESOPHAGEAL SPHINCTER (LES) MOTOR FUNCTION D. Savojardo, M. Mangano, P. Cantù, S. Carmagnola, R. Penagini Cattedra di Gastroenterologia, IRCCS Ospedale Maggiore di Milano, Milan, Italy Background. Occurrence of simultaneous repetitive pressure waves in the oesophageal body may theoretically interfere with assessment of lower oesophageal sphincter (LES) relaxation in response to single swallows (SS), especially when using a sleeve sensor. Multiple rapid swallowing (MRS) inhibits motility in the oesophageal body of healthy subjects; it is also anecdotally reported to help bolus progression in achalasia patients and induces complete LES relaxation in a pharmacological human model of achalasia [1]. Aim and methods. In order to assess usefulness of MRS during oesophageal motility testing we have compared the response of the oesophageal body and LES to SS (5 ml of water) and MRS (five swallows in 10 s, 2 ml of water/swallow) in 20 consecutive patients with untreated idiopathic achalasia (10 men, aged 23–81 years) and in 20 control patients (nine men, aged 31–71 years), using sleeve manometry. Results. A total of 277 SS and 85 MRS were analysed. Achalasia patients showed incomplete LES relaxation (see table) and higher (P < 0.001) LES nadir pressure in response to SS when compared with controls, however, the simultaneous waves in the oesophageal body occurred 2.1 + 0.2 s (mean + S.E.M.) after SS, i.e. before completion of LES relaxation (3.9 + 0.1 s), as assessed in controls.

Achalasia patients Control patients

LES pressure (mmHg)

LES relaxation SS (%)

LES relaxation MRS (%)

MRS with body inhibition (%)

29 ± 1.1∗ 13 ± 0.6

41 ± 2∗ 94 ± 1

52 ± 5∗,# 99 ± 0.5#

49∗ 97.5

∗ P < 0.001 vs. control patients. # P < 0.05 vs. SS.

MRS completely inhibited motor activity in the distal oesophageal body of achalasia patients on 49% of the occasions, delayed (P < 0.001) occurrence on the remaining occasions (4.0 + 0.8 s), and increased (P <

0.05) LES relaxation when compared with SS. Furthermore in three of the achalasia patients LES relaxation was complete (90–96%) after MRS versus 59–65% after SS. In conclusion, MRS during oesophageal motility testing: (1) may allow a more accurate assessment of LES motor function in patients with simultaneous waves in the oesophageal body; (2) induces complete LES relaxation in a subset of achalasia patients who may have only partial damage of inhibitory neural pathways and benefit from MRS in everyday life to help with bolus progression. Reference [1] Gastroenterology 1997;113:409–14. CS27 M2A® PATENCY CAPSULE PRIOR TO VIDEO CAPSULE ENDOSCOPY IN PATIENTS WITH MORPHOLOGICAL SMALL BOWEL STRICTURES C. Spadoa , G. Speraa , M.E. Riccionia , A. Tringalia , P. Familiaria , L. Petruzzielloa , L. Bianconeb , F. Palloneb , G. Costamagnaa a Digestive

Endoscopy Unit, Catholic University, Rome, Italy University of “Tor Vergata”, Rome, Italy

b Gastroenterology,

Background. Wireless video capsule endoscopy (VCE) (Given Imaging Limited, Yoqneam, Israel) provides excellent visualisation of the small intestine. However, one major contra-indication is intestinal obstruction. Availability of non-radiological methods able to exclude significant small bowel strictures prior to VCE would be desirable. Aim. To evaluate the safety of VCE in patients with known small bowel stricture previously tested by M2A® Patency Capsule, a new swallowing, biodegradable capsule, similar to standard VCE in dimension. Patients and methods. Eleven patients (six female, five male; mean age 44 years, R 21–83) with a diagnosis of Crohn’s disease (n = 10) (CDAI < 150) and suspected ischaemic enteritis (n = 1), were prospectively studied. In all cases a small bowel barium X-ray detected ileal strictures involving the ileo-caecal valve in two cases. The M2A® Patency Capsule was ingested. If the M2A® Patency Capsule was excreted intact within 72 h after the ingestion and adverse events were not observed, patients underwent a standard VCE. Results. All patients swallowed the M2A® Patency Capsule smoothly. One patient (9%) did not retrieve the M2A® Patency Capsule in the stools and one withdrew the consent. Two out of nine patients (22.2%) (one with suspected ischaemic enteritis and one with Crohn’s disease) excreted the M2A® Patency Capsule 241 and 96 h after ingestion, respectively, and were not eligible for VCE. The remaining seven patients (77.8%) excreted the M2A® Patency Capsule intact after a mean transit time of 26.4 h (range 5–60 h) and swallowed the VCE. In all cases the VCE passed through the small bowel stricture and was retrieved in the stools after a mean transit time of 33.5 h (range 6–72 h). The VCE showed the presence of ulcers (n = 7), cobblestone pattern (n = 3), mucosal erosions (n = 3) and substenotic area (n = 1). No adverse events occurred. Conclusions. These preliminary results show that the M2A® Patency Capsule may indicate functional bowel patency even in cases with known morphological intestinal strictures. When the M2A® Patency Capsule is excreted intact, within 72 h, without adverse events, the VCE can pass uneventfully. A discrepancy between the radiological features and intestinal patency was observed.

Abstracts

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CS28

CS29

ASSOCIATION STUDY OF THE CARD15 AND CD14 VARIANTS IN IBD; AN UPDATE FROM ‘GRUPPO DI STUDIO PIEMONTESE SULLE MALATTIE INFIAMMATORIE CRONICHE INTESTINALI’

RESCUE TREATMENT WITH ADEFOVIR-DIPIVO- XIL IN LAMIVUDINE RESISTANT PATIENTS WITH CHRONIC HEPATITIS B

Duista ,

Giachinoa ,

Regazzonia ,

Saponeb ,

Salaconec ,

M.M. van D. S. N. P. A. Sambataroc , M. Dapernod , R. Sostegnid , D. Gregorie , M. Astegianob , E. Gaiac , A. Perad , M. De Marchia a Department

of Clinical and Biological Science, University of Turin, ASO San Luigi Orbassano, Turin, Italy b Department of Gastroenterology, ASO San Giovanni Battista, Turin, Italy c Department of Gastroenterology, ASO San Luigi Orbassano, Italy d Department of Gastroenterology, Ospedale Mauriziano, Turin, Italy e Department of Public Health and Microbiology, University of Turin, Turin, Italy

Linkage studies identified several IBD susceptibility loci, but only CARD15 in IBD1 on chr 16 has been identified as the responsible gene. This finding opened new understanding and supported the pathogenetic role of an altered natural immunity in Crohn disease (CD). A cluster of cytokine genes in IBD5 on chr 5, such as IL4, IL4R, IL5, IL12, have been considered good candidates, based on their function. However, association studies did not support their role. Another candidate gene located of the same IBD5 locus is CD14, which encodes for the TLR4 co-receptor. As recently reported by our group, all the three recurrent CARD15 variants show increased frequencies in CD, while no significant association was found in ulcerative colitis (UC). Within our ongoing study, we update here the results of an association study of CARD15 and CD14 common variants, in which 233 CD and 111 UC patients have been retrospectively enrolled. DNA samples of 177 medical students were used as controls. Analysing this larger sample, association significance of the three CARD15 variants increased: R702W OR 1.7, CI 0.9–3.0, G908R OR 3.4, CI 1.3–9.3, L1007fs OR 2.2, CI 1.0–5.1. CARD15 genotypes with a more severe defect are expected to confer a greater susceptibility, and show stronger disease association, than those with only a partially defective protein function, whose associated risk is indeed weaker. In accordance with other studies, we grouped the three recurrent variants in a mutated M-allele, of which the frequency results in 20.3% in CD, 11.7% in UC and 9.6% in controls. The homozygous genotype MM was more strongly associated with CD (OR 17.7, CI 2.3–133.6) than the heterozygous MW genotype (OR 1.7, CI 1.1–2.8). The observed frequencies of the three genotypes M/M, M/wt and wt/wt resulted in close accordance with the expected frequency within the control group, but a clear increase of homozygotes among CD patients was seen (χ2 = 13.3, P = 0.001). As described by Regazzoni et al. (this congress), the CD14-159 promoter SNP showed a weaker association with CD. The CD14 TT genotype frequency do not show significant difference among CD (n = 74, 31.9%) and controls (n = 43, 24.4%). Also considering the TT genotype only within the CARD15 negative or positive, it does not reach a significant association. These results do not support an interaction between CD14 and CARD15. Research funded in part by ‘Fondazione per la Ricerca Scientifica e per la Cura delle Malattie Infiammatorie Croniche Intestinali’.

M. Viganòa,b , P. Lamperticoa,b , M. Iavaronea,b , G. Lunghia,b , G. Coluccia,b , E. Del Ninnoa,b , M. Colomboa,b a Division

of Hepatology, Department of Hygene, IRCCS Maggiore Hospital, University of Milan, Italy b Roche Molecular Systems, Rotkreutz, Switzerland

Background and aim. Patients with chronic hepatitis B developing lamivudine resistance are at high risk of disease progression and death. To assess the efficacy and safety of adefovir-dipivoxil (Gilead Sciences, Foster City, CA), 46 patients with lamivudine resistance (43 men, 53 years, 42 HBeAg negative, 37 cirrhotics, 89% with HBV-DNA >6 log10 copies/ml by HBV Roche Amplicor Monitor) were also given adefovir-dipivoxil 10 mg daily for 5–30 months (median 7). Results. At month 5, HBV-DNA levels decreased from a median of 7.6 (range 3.8–9.3) to 3.7 log10 copies/ml. HBV-DNA was <2.3 log10 copies/ml in 21 (46%) patients, between 2.3 and 5.3 in 12 (26%) and >5.3 log in 13 (28%). Twenty-nine (63%) patients had normal ALT. Patients with undetectable serum HBV-DNA at month 5 had pre-treatment lower HBV-DNA and higher levels of ALT than those with detectable HBV-DNA (6.7 log versus 8.2 log, P = 0.011; 174 U/l versus 74 U/l, P = 0.045). None of the patients showed a >1 log rebound of serum HBV-DNA. In two patients who had >4 log HBV-DNA despite 12 months of therapy, the adefovir-resistance associated rtN236T and rtA181V mutations were not identified. Child–Pugh score improved by at least two points in 9 out of 13 Child–Pugh B/C patients. None of the patients had significant changes of renal function. Conclusions. Adefovir-dipivoxil resulted in a significant reduction of serum HBV DNA in 72% of patients with lamivudine resistant HBV after 5 months of therapy. High ALT and low HBV-DNA predicted a faster response to treatment. CS30 PREVALENCE OF INTERLEUKIN 1 GENETIC POLYMORPHISMS IN SUBJECTS WITH AND WITHOUT POSITIVE FAMILY HISTORY OF GASTRIC CANCER R.M. Zagaria,1 , L. Ricciardielloa,1 , M. Baglionia , C. Bonvicinib , V. Lunedeia , L. Fuccioa , C. Martuzzia , E. Rodaa , F. Bazzolia a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Genetics Unit, IRCCS “Centro San Giovanni di Dio” Fatebenefratelli, Brescia, Italy 1 Both authors equally contributed to this work.

Background. Family history (FH) of gastric cancer (GC) is known to increase the risk for GC development. It has been reported that the carriers of interleukin (IL)-1 genetic polymorphisms (IL-1␤-511 T/T, IL-1␤-31 C/C and IL-1RN 2/2 genotypes) have higher mucosal levels of IL-1␤, a potent proinflammatory cytokine and inhibitor of gastric acid secretion, and higher risk for GC. The information about the prevalence of IL-1 genetic polymorphisms stratified in the general population according to FH for GC is lacking. Aim. To evaluate the prevalence of IL-1␤-511, IL-1␤-31 and IL-1RN genetic polymorphisms in subjects with and without positive FH of GC in a representative sample of general population. Methods. In the frame of the Loiano–Monghidoro Project [1], buffy coats are also obtained from the blood of a sample of subjects, representative of the general population. We considered Genomic DNA extracted from buffy coats of 60 subjects (33 males, 27 females, mean age 59 years) with and 299 (151 males, 148 females, mean age 55 years) without positive FH of GC, using the QIAmp Blood Extraction kit (QIAgen). All samples were

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genotyped for the polymorphisms of the IL-1␤ (IL-31 C and IL-511 T) and the IL-1RN. The IL-1␤-31 and IL-1␤-511 polymorphisms were genotyped by PCR and RFLP analysis. Statistical analysis: the Hardy–Weinberg equilibrium and the haplotype frequencies estimation calculated from the observed genotypes were tested by using the Arlequin softwares version 2.0. For the genetic comparisons, differences in genotype frequencies were evaluated by using the chi-square (χ2 ) method (significance set at P < 0.05) calculated by SPSS (version 10.0). The odds ratio (OR) and the 95% confidence interval (CI) were calculated to evaluate the genotype effects. Results. The table shows the results. Genotypes

Family history of gastric cancer

P-value

Odds ratio (95% CI)

Positive (%)

Negative (%)

IL-1␤-511 C/C C/T T/T

20 (33.3) 27 (45.0) 13 (21.7)

72 (24.1) 187 (62.5) 40 (13.4)

ns 0.012 ns

– 0.49 (0.27–0.8) –

IL-1␤-31 C/C C/T T/T

11 (18.3) 31 (51.7) 18 (30.0)

57 (19.1) 178 (59.5) 64 (21.4)

ns ns ns

– – –

147 118 12 11 7 3 1

ns ns ns 0.035 ns ns ns

– – – 2.9 (1.03–8.2) – – –

IL-1RN (IL-86bp)n 1/1 27 1/2 25 1/3, 4, 5 2 2/2 6 2/3, 4, 5 0 3/3 0 4/4 0 Total

60

(45.0) (41.7) (3.3) (10)

(49.2) (39.5) (4.0) (3.7) (2.3) (1.0) (0.3)

299

Conclusions. Family history for gastric cancer is significantly associated with IL-1RN 2/2, one of the IL-1 genetic polymorphisms associated with gastric cancer. Reference [1] APT 2001;15:1001–7.

Abstracts ORAL COMMUNICATIONS CO001 INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) AND OESTROGENS MODULATE NEOPLASTIC CELL GROWTH IN HUMAN CHOLANGIOCARCINOMA D. Alvaroa,b , B. Barbaroa,b , A. Franchittoa,b , P. Onoria,b , L. Maruccia,b , M. Marzionia,b , V. Drudi-Metallia,b , A. Augelloa,b , V. Cardinalea,b , A.F. Attilia,b , A. Benedettia,b , E. Gaudioa,b a Division

of Gastroenterology, Department of Anatomy, University of Rome, La Sapienza, Italy a Department of Gastroenterology, University of Ancona, Ancona, Italy

Oestrogens and insulin-like growth factor 1 (IGF-1) play a key role in promoting cell growth and tumour progression in neoplastic cells expressing specific receptors. Human cholangiocarcinoma is a cancer with a bad prognosis and poor response to current therapies but, the expression of oestrogen (ER) and IGF1 (IGF1-R) receptors is unknown. The aims of this study were to investigate the expression of ER and IGF1-R in human cholangiocarcinoma and cell lines and to evaluate the role of oestrogens and IGF1 in the modulation of neoplastic cell growth. Methods. The expression of ER and IGF1-R was investigated by immunohistochemistry, RT-PCR and immunoblotting in biopsies of human cholangiocarcinoma (n = 8) and in three different human cholangiocarcinoma cell lines (HuH-28, TFK-1, Mz-ChA-1). The effect of 17beta-estradiol, IGF1, and receptor antagonists on the growth of HuH-28 cell line was investigated by PCNA or H3-histone protein expression. Results. A marked immunohistochemical positivity for ER-alpha, ER-beta and IGF1-R was found in all (8/8) biopsies of human cholangiocarcinoma. As far as cell lines is concerned, only HuH-28 was positive for ER-alpha, with a protein expression lower than MCF7 breast cancer cell line. In contrast, ER-beta was expressed in the three different cell lines examined (P < 0.02 versus MCF7 breast cancer). IGF1-R was similarly expressed in the three cell lines. IGF1 (10 ng/ml) or 17beta-estradiol (10 ␮M) markedly stimulate cell proliferation in HuH-28 cell line, inhibit apoptosis and exert additive effects. In contrast, ER selective antagonist Ici 182,780 or IGF1-R antagonist (AB-1) markedly inhibits cell proliferation and activate apoptosis. Conclusions. Human cholangiocarcinoma express ER and IGF1 receptors which co-operate in the modulation of cell growth and apoptosis. Modulation of ER and IGF1-R could represent a future therapeutic strategy for the management of cholangiocarcinoma. CO002 MUTATIONS OF NOD2 /CARD15 GENE ARE ASSOCIATED WITH A MORE AGGRESSIVE CLINICAL COURSE OF CROHN’S DISEASE. AN IG-IBD STUDY V. Annese, G. Lombardi, F. Perri, R. D’Incà, S. Ardizzone, G. Riegler, S. Giaccari, M. Vecchi, F. Castiglione, P. Gionchetti, A. Latiano, O. Palmieri, A. Andreoli, M. Astegiano, M. Cottone, S. Cucchiara, C. Papi, D. Valpiani, G. Iaquinto, G. Frieri, G. Leandro, W. Fries, M. Mastronardi, P. Fortina, A. Andriulli Italian Group for IBD, CSS-IRCCS Hospital, San Giovanni, Rotondo, Italy Background. Three major variants of CARD15 gene confers an increased susceptibility to Crohn’s disease; (CD) whether they are correlated with specific clinical features is under evaluation. Aim. We investigated the possible association of CARD15 variants with specific clinical characteristics, included the presence of ASCA and ANCA, in a large cohort of IBD patients and unaffected relatives. Materials and methods. A total number of 316 CD patients (156 with family history), 408 ulcerative colitis (UC) patients (206 with family history), 588 unaffected relatives (173 trios), and 205 unrelated healthy

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controls (HC), were included in the study. The polymorphism of SNPs 8, 12, and 13 of CARD15 gene were investigated; after amplification of genomic DNA, sequence products were analysed by pyrosequencing. Clinical features investigated were: age at diagnosis, gender, family history, localisation, extra-intestinal manifestations (EIM), previous resective surgery, and stenosing/fistulising pattern. For each subject, ANCA and ASCA were also tested. Results. In CD patients, the allele frequencies of all the three mutations was significantly increased compared to HC (SNP 8 = 8.7% versus 4.1%, P < 0.002) (SNP 12 = 7.3% versus 2.7%, P < 0.003) (SNP 13 = 9.3% versus 0.7%, P < 0.000001). At least one risk allele was found in 38.2% (P = 0.0000001), 13.7 and 15.1% of CD, UC and HC, respectively. An increased frequency of the SNP 13 risk allele was also found in healthy familial relatives (5%, P = 0.0003), trios relatives (6%, P = 0.000009), and UC patients (2.1%, P = 0.07), as compared to HC (0.7%). Sixteen relatives, carriers of two risk alleles, were asymptomatic. At the multivariate analysis, an excess of CARD15 variants was found in CD patients ASCA-positive (OR = 1.94), with ileal localisation (OR = 1.76), and previous resective surgery (OR = 1.52). No difference between familial and sporadic cases of CD was found. UC patient carriers of the SNP 13 risk alleles had arthropathy more frequently (P = 0.046). Conclusions. In our population, both familial and sporadic CD patient carriers of the major variants of CARD15 , showed a more aggressive clinical course. Some CARD15 variants might also influence the UC phenotype. CO003 A FOLLOW-UP PROGRAMME FOR THE EVALUATION OF THE RISK OF NEOPLASTIC LESIONS IN PATIENTS WITH ATROPHIC BODY GASTRITIS (ABG): RESULTS AT 6 YEARS B. Annibalea , E. Lahnera , G. D’Ambraa , G. Capursoa , E. Di Giulioa , M. Milioneb , C. Bordib , G. Delle Favea a Digestive

and Liver Disease Unit, II Medical School, University “La Sapienza”, Rome, Italy b Department of Pathology, University of Parma, Parma, Italy

Background. ABG is considered a definite risk factor for gastric cancer and carcinoids. Helicobacter pylori is involved in the induction of ABG and included among class I carcinogens for gastric cancer. The effect of H. pylori eradication on atrophy and intestinal metaplasia is unclear and it is still debated whether cure of infection can ameliorate histological changes and eventually reduce the risk of neoplastic and preneoplastic lesions. Aim. To evaluate the incidence of macroscopical lesions and histological alterations in ABG patients included in a long-term follow-up programme investigating the risk of gastric neoplastic lesions. Materials and methods. Ninety-five ABG patients (28 male, 67 female, median age 56 years) were included. All patients had gastroscopy with antral (n = 3) and corporal (n = 3) biopsies for histology at baseline and follow-up. Gastritis was scored according to the updated Sydney system. Twenty-nine patients (group A, H. pylori positive at histology and/or serology) were cured of infection (bismuth-based regimens), 66 patients (group B, H. pylori negative and/or positive at serology) were not treated. Median follow-up time was 74 months (range 48–123) in both groups. Results. Macroscopical lesions: In group A, one (3.4%) patient developed gastric cancer and one (3.4%) a body hyperplastic/dysplastic polyp. In group B, one (1.5%) patient developed a gastric carcinoid, one (1.5%) a mild dyplastic adenoma, one (1.5%) a body hyperplastic/dysplastic polyp, and eight (12.1%) hyperplastic polyps (five body and three antrum). Histological findings: three (10.3%) group A patients developed mild antral dysplasia versus one (1.5%) group B patient (P = 0.08). In group A, body atrophy score did not change, whereas body intestinal metaplasia increased (1.12 versus 1.42, P = 0.057). In group B patients, both body atrophy and intestinal metaplasia did not change.

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Conclusions. At long-term follow-up, the degree of body atrophy is unchanged, whereas body intestinal metaplasia increases only in H. pylori-cured patients. The incidence of neoplastic (2.1%) and dysplastic lesions (6.3%) was similar among patients treated for active H. pylori infection and those without H. pylori infection. The present results confirm the risk of neoplastic and preneoplastic lesions in ABG patients who should be followed-up irrespective of successful H. pylori cure.

Conclusions. AZA and Pentasa are equally effective in reducing clinical and surgical recurrence. Taking into account its efficacy and safety, we believe that Pentasa should be considered as the first choice treatment for prevention of postoperative recurrence, while AZA should be considered in patients with more intestinal resections and with a risk of short bowel syndrome. CO005

CO004 CONTROLLED TRIAL OF AZATHIOPRINE AND MESALAMINE IN PREVENTING RECURRENCE AFTER CONSERVATIVE SURGERY FOR CROHN’S DISEASE

A FOUR-YEAR FOLLOW-UP OF SELF EXPANDABLE METAL STENTS IN THE ENDOSCOPIC PALLIATION OF LONG-TERM SURVIVORS WITH UNRESECTABLE MALIGNANT BILIARY STRICTURES

S. Ardizzonea , G. Maconia , A. Russob , E. Radicea , E. Colomboa , M. Moltenia , G. Sampietroa,b , P.G. Danellia,b , G. Bianchi Porroa

M. Ayoubi, E. Solerio, F. Rosina, L. Pace, S. Bosco, A. Antonelli, L. Bonardi

a “L.

Divisione di Gastroenterologia ed Epatologia, Unità di Endoscopia Digestiva, Presidio Sanitario Gradenigo, Turin, Italy

Sacco” University Hospital, Italy Unit, Local Health Authority, Milan, Italy

b Epidemiology

Background and aims. Crohn’s disease (CD) frequently recurs after surgical resection, and the risk of re-operation is very high. Therefore, new “bowel-sparing” techniques have been proposed. However, long-term clinical and surgical recurrence rates for these techniques are comparable to those observed after conventional surgical resection. We designed a prospective, randomised study to compare the long-term efficacy and safety of azathioprine (AZA) and mesalamine (Pentasa aˆ ) in preventing clinical and surgical relapses in patients who had undergone conservative surgery for CD. Methods. One hundred and forty-two patients (41 female, 101 male, mean age 34 years) who underwent bowel sparing surgery, were prospectively randomised to receive AZA (n = 71) 2 mg/kg per day or Pentasa (n = 71) 3 g per day. The study lasted for 60 months. At entry, the disease had to be clinically quiescent, defined as a Crohn’s Disease Activity Index (CDAI) of £150. The primary outcome parameters were clinical and surgical disease recurrence after 24 months of therapy. Clinical recurrence was defined as the presence of symptoms related to CD, with a CDAI higher than 200, that were severe enough to warrant treatment with a medium–high dose of systemic steroid. Surgical recurrence was defined as the presence of symptoms that were refractory to medical treatment or complications requiring a new surgical procedure. The following secondary outcome parameters were considered: (1) cumulative proportion of clinical and surgical relapse with two treatment regimens at 60 months; (2) efficacy of both treatments in decreasing the recurrence risk in relation to presence/absence of internal fistulas at surgery, previous surgical resections, and smoking habit after surgical therapy; (3) identification of prognostic factors for clinical recurrence. Results. Using intention-to-treat analysis, there were 12/69 clinical recurrences in the AZA group compared with 20/71 in the Pentasa group (17% versus 28%, P = 0.2, OR 2.04, 95% CI 0.89–4.67). On a per protocol basis, 17/50 patients taking AZA and 28/61 in the Pentasa group relapsed (34% versus 46%, P = 0.2, OR 1.79, 95% CI 0.80–3.97). No statistically significant difference in the surgical relapse rate was observed between the two treatment groups, both at intention-to-treat analysis (AZA 4/69 (6%), Pentasa 7/71 (10%), P = 0.5) and on a per protocol analysis (AZA 5/50 (10%), Pentasa 11/61 (19%), P = 0.2). At 60 months, the difference in clinical and surgical recurrence rates for the two treatment regimens was not statistically significant. A subgroup analysis showed that AZA was significantly more effective than Pentasa in preventing clinical recurrence in patients with more than one CD operation (AZA 5/39 (13%), Pentasa 14/39 (36%), P = 0.03). Moreover, in this subgroup of patients, the clinical relapse risk was significantly higher among patients treated with Pentasa (OR 4.83, 95% CI 1.47–15.8). The stepwise logistic regression predicted that the probability of clinical recurrence increases in patients with colonic disease (OR 10.4, 95% CI 2.1–51.5, P = 0.006) and in the Pentasa group (OR 2.6, 95% CI 1.1–6.5, P = 0.03). More patients treated with AZA withdrew from treatment due to adverse events than those taking Pentasa (AZA 15/69 (22%), Pentasa 6/71 (8%), P = 0.04).

Background. The patients with inoperable malignant biliary obstruction have a poor prognosis. Endoscopic stent insertion is the treatment of choice for these patients. Effective palliation of malignanat biliary obstruction with conventional plastic endoprostheses is limited by stent occlusion, which typically occurs 3–4 months after insertion. Aims. To assess the long-term efficacy and complications of metal stents in the treatment of patients with unresectable malignant biliary strictures. Methods. Between January 1999 and January 2003, self-expandable metallic stent (wallstent) were inserted in 21 patients (7 female and 14 male, median age 83 years, range 48–94) with unresectable malignant biliary obstruction. Bile duct obstruction was secondary to pancreatic carcinoma in 11 patients, ampulla carcinoma in five patients, colangiocarcinoma in five patients. The mean tumour size/length was 24 mm (range 10–40) and was obtained in all patients from abdominal ultrasound scans and ERCP, and in some patients also with CT. The median time from diagnosis of malignant bile duct obstruction to insertion of a metal stent was 107 days (range 8–600 days), and in this period every patient had one 10 Fr plastic stent. Results. Biliary drainage was successful in all patients. The median follow-up was 9.81 months (range 1.0–35.0). The median period of stent patency for 21 patients was 7.57 months (range 1.0–29.5). The median survival was 9.85 months (range 1.0–35.0). By the end of study: • Three patients (14.28%) are still alive with their initial metal stent in situ and they are free of jaundice or cholangitis. • Eighteen patients (85.71%) had died and all but one death were related to the primary malignancy. This patient died from cardiac failure. Eleven of these patients (52.3%) had died with their initial metal stent in situ and they remained free of jaundice or cholangitis. Another seven of these patients (33.33%) developed symptomatic metal stent occlusion as evidenced clinically by jaundice or cholangitis, or both at a median of 9.32 months (3–20). There were no complications during and after stent placement. Conclusion. The stent was easily inserted, expanded well, was flexible and well tolerated by the patients. Metal stent give prolonged palliation and superior results compared with plastic stent in patients with inoperable malignant biliary obstruction. To optimise cost-effectiveness, it is essential that subgroup patients surviving for more than 4–5 months are selected for this form of treatment.

Abstracts CO006 MRP2 IS UP-REGULATED BY UDCA IN CHOLESTASIS OF PREGNANCY

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Conclusion. IBS patients have an enhanced perceptual sensitivity to rectal distensions. Response bias does not seem to influence their perceptual response.

F. Azzaroli, V. Feletti, C. Mazzeo, P. Simoni, S. Giovanelli, A. Miracolo, G. Nigro, F. Lodato, A. Roda, E. Roda, G. Mazzella

CO008

Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy

TECHNETIUM-99m LABELLED LEUKOCYTE SINGLE PHOTON EMISSION COMPUTERISED TOMOGRAPHY (SPECT) FOR CROHN’S DISEASE ASSESSMENT

Introduction. Increased bile acids (BA) in the foetal compartment is one of the factors involved in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP), a disease that may be harmful for the foetus. Recently, the presence of BA transporters in the placenta was found, among which MRP2, has been described. The treatment of choice is UDCA whose effects on human placenta are still undefined. The aim of our study was to evaluate whether UDCA could induce MRP2 expression in the placenta. Materials and methods. Thirty pregnant women were enrolled. Ten were controls with physiologic pregnancies and 20 with ICP. The latter were divided in two groups: (1) UDCA (20 mg/kg per day); (2) untreated. Routine liver test and BA in serum, cord blood and amniotic fluid were determined in each subject. Placentas were collected at the time of delivery for subsequent evaluation, by immunoblotting and immunofluorescence, of MRP2 protein expression. Statistical differences between groups were calculated with t-test for paired and unpaired data. Results. UDCA induced a significant improvement in transaminases and serum BA compared to untreated patients with ICP as well as a reduction in bile acids in all compartments. No significant difference was observed between controls and untreated ICP with regard to MRP2 protein expression in the placenta. In patients with ICP who received UDCA a significant increase in MRP2 expression was observed (P < 0.03). Conclusions. MRP2 protein expression is induced by the administration of UDCA in ICP. This may account, at least partially, for the efficacy of UDCA in ICP. CO007 APPLICATION OF THE SIGNAL DETECTION TECHNIQUE DURING RECTAL DISTENSION IN IRRITABLE BOWEL SYNDROME (IBS) G. Basilisco, M. Corsetti, C. Ogliari, B. Cesana Unità di Gastroenterologia, Dipartimento di Scienze Mediche, Università degli Studi di Milano, IRCCS, Ospedale Maggiore di Milan, Italy Reduced rectal distension thresholds characterise about two-thirds of IBS patients, but it is still debated whether they reflect altered perceptual sensitivity or the patient’s psychological eagerness to report the presence of a stimulus (response bias). The signal detection technique (SDT) allows these two components to be distinguished. Aim. To assess the perceptual sensitivity (d ) and response bias (Lx) to rectal distension using the SDT in IBS patients and healthy subjects (HS). Methods. Nine HS (four men; mean age 29 + 10 years) and nine IBS patients (six men; mean age 34 + 8 years) underwent fifteen 10 s rectal distensions. The SDT was used to calculate d and Lx in discriminating low (100 ml) or high (200 ml) intensity stimuli and periods of simulated distension. The subjects reported their perception of distension by means of an electronic keypad choosing between first perception, a desire to defaecate or urgency. The data are given as mean value + S.D. Results. The frequency of perceived distensions was similar during simulated distensions in HS and IBS (24 + 29% versus 26 + 36%, P = 0.88), but greater in IBS than HS during the 100 ml distensions (68+42% versus 28 + 34%, P = 0.04). The frequency of the perceived 200-ml distensions was similar in HS and IBS (100 + 0% versus 95 + 13%, P = 0.88). d

was higher in IBS than in HS during the 100 ml distensions (2.3 + 1.9 versus 0.5 + 0.6, P = 0.02), but did not differ during the 200 ml distensions (3.4 + 1.4 versus 3.1 + 1.1, P = 0.66). Lx was similar in the two groups at both 100 ml (1.7 + 3.1 versus 0.9 + 0.2, P = 0.43) and 200 ml (0.5 + 0.4 versus 0.4 + 0.4, P = 0.65).

L. Bianconea , F. Capoccettib , A. Geremiaa , C. Petruzzielloa , D. Finaa , R.M. Bozzia , G. Simonettib , O. Schillacib , F. Pallonea a Cattedra

di Gastroenterologia, Dipartimento di Medicina Interna, Università di Roma “Tor Vergata”, Rome, Italy b Cattedra di Radiologia e Diagnostica per Immagini, Dipartimento di Medicina Interna, Università di Roma “Tor Vergata”, Rome, Italy

Background. Scintigraphy using radiolabelled leucocytes is a useful non-invasive technique for assessing neutrophils infiltration in Inflammatory Bowel disease (IBD) gut. However, planar images show overlapping activity in other organs, including the liver, spleen and bone marrow. Aims. To assess whether 99mTc-HMPAO labelled leucocyte SPECT (single photon emission computerised tomography) shows a higher sensitivity and specificity than conventional scintigraphy in assessing the presence, site and extent of IBD lesions. Methods. Twenty-two IBD patients (19 Crohn’s disease, CD; 3 ulcerative colitis, UC) were enrolled. Disease extent was assessed within the last 6 months by endoscopy and radiology. Leucocytes were labelled with 99mTc-HMPAO. Planar and SPECT images were acquired at 20 min and 3 h. Bowel uptake was quantitated in nine abdominal regions (0: no labelling; 1: less than bone marrow; 2: equal to bone marrow; 3: more than bone marrow). Results. No patients showed adverse events. Both SPECT and planar images detected a negative scintigraphy (score 0) in one UC (1/22 IBD) with ileal pouch and no pouchitis (true negative). Positive scintigraphy (score 1–3) was detected by both techniques in 21 IBD (21/22) (21 true positives). SPECT detected a higher global score than planar images (0.73±0.08 versus 0.34±0.05, P < 0.001), while only in the hypogastric region the SPECT score was higher than planar images (1.27±0.28 versus 0.55 ± 0.17, P = 0.032). SPECT provided a better visualisation of the lesions than planar images as it differentiated between uptake in the bowel and in other sites, particularly sigmoid colon, rectum and perianal areas. SPECT images also visualised perianal disease (two CD), entero-vesical fistula (one CD) and ileal dilatation (one CD). Conclusions. 99mTc-HMPAO labelled leucocyte SPECT provides a more detailed visualisation of IBD lesions than planar scintigraphic images. This technique may discriminate between intestinal and bone marrow uptake, being particularly useful for assessing IBD lesions in the pelvic floor. CO009 ROFECOXIB AND EARLY RELAPSE OF INFLAMMATORY BOWEL DISEASE PATIENTS WITH ASSOCIATED ARTHRALGIAS: AN OPEN-LABEL TRIAL L. Biancone, C. Tosti, S. Emerenziani, F. De Nigris, C. Petruzziello, A. Geremia, R.M. Bozzi, F. Pallone Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università di Roma “Tor Vergata”, Rome, Italy Background. The safety and efficacy of selective cyclo-oxygenase-2 inhibitors in inflammatory bowel disease (IBD) is under investigation. Aims. To assess, in a prospective open-label trial, the efficacy and safety of rofecoxib in IBD and controls. Methods. Thirty-eight inactive IBD patients (23 Crohn’s disease, CD; 15 ulcerative colitis, UC) with associated arthralgias were enrolled. Controls (C) included 20 dyspeptic patients. The efficacy and safety of rofecoxib (12.5 mg per day; 3 days to 3 months) was recorded.

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Results. In IBD, 8/38 (21%) patients dropped out due to side-effects. Arthralgias relief was complete in 6/38 (16%), partial in 19/38 (50%), while no benefit was reported by 13/38 (34%). In CD group, 5/23 (22%) patients dropped out due to diarrhoea (n = 1) or abdominal pain (n = 4), subsiding at drug discontinuation. Arthralgias relief was complete in 5/23 (22%), partial in 12/23 (52%) (four drop out), while no benefit was reported by 6/23 (26%) (one drop out) CD patients. In UC group, 3/15 (20%) patients dropped out due to bloody diarrhoea. Arthralgias relief was complete in 1 (6%), partial in 7/15 (47%) (one drop out), while 7/15 patients (47%) (two drop out) referred no benefit. No C dropped out to side-effects, although 2/20 (10%) subjects referred epigastric pain subsiding after PPI treatment. In group C, arthralgias relief was complete in 4/20 (20%), partial in 10/20 (50%), while 6/20 subjects (30%) referred no benefit. Conclusions. Rofecoxib appears to control arthralgias in two/thirds of IBD patients. Side-effects requiring drug discontinuation is however observed in about one-fourth of patients. CO010 ENDOSCOPIC LIGATION OF OESOPHAGO-GASVARICES WITH A NEW MULTIPLE BAND LIGATOR

TRIC

P. Billi, A. Grilli, C. Mwangemi, D. Baroncini, C. Fabbri, V. Cennamo, D. Lo Cuoco, L. De Luca, S. Stanzani, M. Jachelli, N. D’Imperio U.O. di Gastroenterologia ed Endoscopia Digestiva, P.O. Bellaria-Maggiore, Bologna, Italy Endoscopic ligation of oesophageal varices is a well-documented technique for haemostasis and prevention of re-bleeding, with similar results to sclerotherapy but with fewer complications. Furthermore, there is limited data concerning its use in the treatment of gastric varices. The oesophago-gastric varices, GOV 1 and 2 according to Sarin’s classification, account for more than 90% of all gastric varices. The aim of our study was to evaluate the efficacy of endoscopic ligation of oesophago-gastric varices in retro flexion using a new multiple band ligator (Speedband Superview Super 7, Microvasive, Boston Scientific). Seven male patients (mean age 64 years, range 53–78) were treated electively in the Digestive Endoscopy Unit of our department. All patients had experienced a previous episode of variceal haemorrhage due to portal hypertension (virus-related cirrhosis in six patients, portal vein thrombosis in one); all patients had oesophago-gastric varices, GOV 1 in four and GOV 2 in three patients. Endoscopic variceal ligation was performed using a new multiple band ligator on the tip of a modified endoscope introduced into the stomach and then retroflexed; bands were applied circumferentially at the cardias junction in the gastric cavity in all visible varices and ligation was continued in the lower third of the oesophagus. The mean number of bands per session were 9 (range 4–14), the mean number of sessions were 2.5 (range 2–4) and the total number of bands applied per patient were 18 (range 9–36) to achieve eradication. One patient re-bled 10 days after the first session, and was treated conservatively. Our preliminary data demonstrate the technical feasibility of endoscopic elective treatment of oesophago-gastric varices using the new multiple band ligators, in retro-flexion. CO011 PROPOFOL SEDATION FOR UPPER GASTROINTESTINAL ENDOSCOPY (UGE) IN CHILDREN G. Bonannoa , M. Astutob , N. Dismab , P. Nasoa , G. Aprilea , C. Barberaa , A. Russoa a Cattedra

di Gastroenterologia, Università di Catania, Dir. A. Russo, Italy Specialità Medico-Chirurgiche, Sez. Anestesia, Italy

b Dipartimento

Background. Conscious and deep sedation are the two commonly used methods to perform diagnostic procedures in children. A variety of anaesthetic techniques have been described, including intravenous or inhala-

tional anaesthesia with or without tracheal intubation. A standard ideal sedation protocol does not exist to perform UGE in children. The aims of our study were to investigate both the safety and tolerance of propofol sedation, used alone and in combination with either fentanyl or midazolam, for UGE in children. Methods. In 120 children, ASA physical status I and II, aged 3–12 years, we performed a diagnostic UGE. A randomised, prospective, three-study-group design was used. The patients were randomly allocated to one of the three study groups to receive propofol alone (41 patients, group P) or propofol with fentanyl (1 ␮g kg−1 ) (39 patients, group PF) or with midazolam (0.1 mg kg−1 ) (40 patients, group PM). If further administration of propofol was necessary this was recorded for the study as well as the sum of all medications given during the procedure. Adequacy of sedation and endoscopist’s evaluation (score: 0–1–2–3) were made; the endoscopist did not know which drugs were used. The UGEs were performed in the endoscopic unit by the same endoscopist, with 15 years’ experience of paediatric endoscopy, using Olympus GIF-140 videoendoscopes. Results. All the procedures were carried out successfully and propofol was well tolerated in all patients. Mean propofol doses were: 4.7 (1.2) mg for group P versus 3.3 mg (0.8) for PF and 3.4 mg for PM group (P < 0.05). Rescue propofol was necessary in 39% of patients in group P, in 12.5% of group PF and in 18% of group PM. Duration of procedure and recovery period were comparable in the three groups. PF and PM groups had lower incidence of side-effects during endoscopy (25% P group, 5% PF group, 8% PM group; P < 0.05) and a better endoscopist’s evaluation (score 3: 63.4% group P, 84.6% group PF and 87.5 group PM; P < 0.5). Adverse events (desaturation, cough, bradycardia, apnoea) were recorded in 29.2% of patients in group P, 7.5% patients in group PF and 5.1% in group PM (P < 0.05). Conclusion. We conclude that propofol given with fentanyl or midazolam allows a better sedation and endoscopy condition when compared with propofol alone. CO012 NOD2 MUTATION AND TNF PROMOTER POLYMORPHISMS IN ITALIAN IBD PATIENTS F. Bressoa,b , T. Skoogc , M. Astegianoa , B. Demarchia , P. Gionchettid , M. Rizzettoa , S. Petterssonb , M. D’Amatob a SC

Gastroepatologia, Molinette Hospital, Turin, Italy and Tumour Biology Center, Karolinska Institute, Stockholm, Sweden c Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden d Department of Internal Medicine, University of Bologna, Bologna, Italy b Microbiology

Introduction. The frameshift mutation 3020insC in the NOD2 gene was found associated with susceptibility to Crohn’s disease (CD), in particular characterised by early age of onset, ileal location and fibrostenosing behaviour. The TNF␣ gene has been considered a candidate gene for CD, in particular two of the TNF␣ promoter polymorphisms (863 C/A and 857 C/T), placed in the binding sites of NF-␬B and OCT1, respectively, are associated with inflammatory bowel disease (IBD) and modulate gene expression. Aim. To evaluate the role of NOD2 3020insC mutation and of TNF␣ promoter polymorphisms in conferring susceptibility to CD in an Italian population and the possible genotype–phenotype relation. Materials and methods. Two hundred and thirty-six CD patients, 144 ulcerative colitis and 166 controls were included in the study population. All the patients gave their informed consent. The diagnosis of inflammatory bowel disease was obtained in accordance to the commonly accepted diagnostic criteria. Phenotypic characteristics, such as the age at diagnosis, disease location, disease behaviour and steroid-dependency, were also recorded and correlated with the genetic results. After extraction of DNA and amplification of NOD2 gene and TNF␣ promoter region, the mutation

Abstracts and the polymorphisms have been identified by digestion with restriction enzymes. The data have been analysed by multiple logistic regression. Results. CD was significantly associated with the NOD2 3020insC, P = 0.011 (RR = 13.68, 95% CI = 1.8–102.8). Although some trend could be observed, neither CD, nor ulcerative colitis were significantly associated with TNF␣ promoter polymorphisms or haplotypes, not even after stratification for NOD2. However, in the ulcerative colitis group a significant association between TNF␣ promoter polymorphisms and steroid-dependency was observed in female patients only (P = 0.011, RR = 6.63, 95% CI = 1.54–28.56). Conclusion. The NOD2 3020insC variant was confirmed to be associated with Crohn’s disease in the Italian population, even if its frequency was lower than previously reported in other populations. In ulcerative colitis a pharmacogenetic effect was observed for the TNF␣ promoter polymorphism-857, which conferred a higher risk of steroid-dependency in female patients. The biological significance of this finding might reside in sex-specific effect of steroids on the binding of OCT-1 to OCT-857 T/C and is currently under investigation. CO013 ENDOSCOPIC ULTRASONOGRAPHY (EUS) OR ENDOSCOPIC SPHINCTEROTOMY (EST) IN SUSPECTED BILIARY ACUTE PANCREATITIS? PRELIMINARY DATA FROM A PROSPECTIVE CONTROLLED STUDY E. Buscarini, F. De Grazia, G. Brambilla, F. Menozzi, G. Lupinacci, L. La Mantia, C. Londoni, A. Zambelli U.O. Gastroenterologia ed Endoscopia Digestiva, ASL Ospedale Maggiore, Crema, Italy Background/aims. A prospective controlled study was started in patients with suspected biliary acute pancreatitis comparing a strategy using EUS to select patients for EST with a strategy using EST. The aim of this study was to evaluate patients’ outcomes. Material and methods. A consecutive series of patients with suspected biliary pancreatitis on the basis of historical, clinical, biochemical, and imaging (US or CT) data were referred for EUS; in case of contraindications to cholecystectomy, or absence of EUS examiner, patients were directly addressed to EST. The results of positive EUS were controlled by sphincterotomy. The results of negative EUS were controlled by follow-up. The EUS result was considered true negative if the patient was confirmed symptom-free and with normal tests on a follow-up at least 6 months later. Outcomes were studied in relation to the presence of stones, complications, recurrence of pancreatitis or biliary symptoms. Results. Fifteen males, 16 females, mean age 64.3 years, range 32–90 underwent EUS and/or EST 2–16 (mean 5.6) days after an acute pancreatitis of suspected biliary aetiology. At US 20 patients had gallstones, two a normal gallbladder, nine had been previously cholecystectomised. US showed a normal sized common bile duct in 11 patients, dilated in 20 (6–18 mm). Mean values at admission of: amylase 1312.2, lipase 2066.4, bilirubin 4.1, AST 252.2, ALT 317.8, alkaline phosphatase 326.5, gammaglutamiltranspept. 432; mean values at EUS or EST of: amylase 154.3, lipase 159.3, bilirubin 1.9, AST 48.2, ALT 105.7, alkaline phosphatase 155.2, gammaglutamiltranspept. 161.3. EUS, performed in 22 patients, diagnosed choledocholithiasis in 4/22 patients (18%); absence of stones in 18 (with Wirsung stones in one case). EUS was not performed in nine patients who were directly addressed to EST; choledocholithiasis was found in 2/9 (22%). EUS had no complications. A EST-related complication occurred in a patient directly addressed to EST, with negative results: a moderate increase, remitting in 48 h, of amylase and lipase level. Recurrence of acute pancreatitis occurred in one patient 5 days after EST (performed without previous EUS and proved negative). Conclusions. A substantial proportion of patients with acute biliary pancreatitis may have negative common bile duct exams; advantages offered by a non-invasive and effective EUS selection for EST are highlighted.

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CO014 PNUT1l (SEPTIN 5): A NOVEL MARKER OF ISLET CELLS AND OF PANCREATIC ENDOCRINE TUMOURS G. Capursoa , T. Crnogorac-Jurcevicb , F. Panzutoa , R. Gangeswaranb , N. Campaninic , M. Milionec , C. Bordic , G. Delle Favea , N. Lemoineb a Department

of Digestive and Liver Disease, II School of Medicine, University “La Sapienza”, Rome, Italy b Cancer Research UK, Molecular Oncology Unit, Imperial College School of Medicine, London, UK c Department of Pathology, University of Parma, Parma, Italy

Introduction. PNUT1l (CDCrel1, septin 5) is a member of a family of highly conserved GTPases called septins, and has been demonstrated to coimmunoprecipitate with synaptophysin in human brain. PNUT1l is believed to play a role in exocytosis by regulating vesicle dynamics. Since PNUTl1 is also involved in serotonin-release in platelets and expressed in secretory organs such as prostate, ovary and testis, its expression and role in normal and neoplastic pancreatic endocrine cells are of interest. Aim. To investigate the expression pattern of PNUT1l in normal pancreas and in pancreatic neuroendocrine tumours (PNETs). Methods. IHC with an anti-PNUT1l monoclonal antibody (BD transduction laboratories) was performed on paraffin embedded tissue sections of normal pancreas of eight PNETs (five primary, three liver metastases) and on a 280 cancer cores tissue microarray from Ambion (LandMark High Density Cancer Tissue MicroArray). RT-PCR, qPCR and western blot (WB) were performed on RNA and proteins extracted from 15 samples (nine primary lesions, six liver metastases) from 11 individual NF PNETs patients, from normal pancreata, isolated normal human pancreatic islets, and from 3 human PNET cell lines (QGP-1, BON, CM). Results. Both WB and RT-PCR suggested preferential expression of PNUT1l in islets in normal pancreas. IHC demonstrated staining of all islet cells without specific co-localisation in one cell type. A weaker staining was detected in acinar cells and none in ducts. PNUTl1 expression resulted increase in PNETs (15/15) compared to isolated islets on RNA level (median increase at qPCR 18.5 times, range 4–100), but this difference was not evident at a protein level on WB. PNET cell lines express lower level of PNUT1l rna and protein compared to islets. At IHC, all PNET samples showed strong positivity without significant difference related to differentiation, functioning status or site (primary/metastasis). On the Cancer Tissue MicroArray PNUT1l staining was associated with “endocrine” tumours other than pancreatic (prostate, parotid). Conclusion. PNUT1l seems a promising marker of both normal and transformed endocrine cells of the human pancreas. Evaluation of its expression in normal and transformed endocrine cells of the GI tract and of relationship between PNUT1l and other endocrine markers staining (chromogranin-a, synaptophysin) is currently being performed to assess its potential utility in clinical practice. CO015 COMPUTERISED TOMOGRAPHY–COLONOGRA- PHY (CTC) AS A SCREENING TEST IN SUBJECTS AT INCREASED RISK OF COLORECTAL CANCER: PRELIMINARY RESULTS A. Carlinoa , T.M. Gallob , M. Fracchiaa , D. Reggeb , A. Peraa , G. Corraoa,b , G. Galatolaa a Institute

for Cancer Research and Treatment, Gastroenterology Unit, Candiolo, Italy b Institute for Cancer Research and Treatment, Radiology Unit, Candiolo, Italy Background. Relatives (aged >40 years) of patients affected by colonic advanced adenomas or cancer diagnosed before 65 years are at an increased risk of developing colorectal cancer. It is not known what is the best screening procedure in these subjects.

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Aim. We designed a randomised prospective controlled study comparing the efficacy of CTC versus colonoscopy (CS) and versus faecal occult blood test (FOBT). The end point was polyp detection rate. Methods. Two hundred and forty-one index cases generated 1065 relatives: 182 of them accepted randomisation to FOBT (n = 115) or to CTC followed by CS (n = 67), performed on the same day. Results. Seventy-one CTC + CS have been performed, including 11 FOBT+ patients. Thirty-three polyps were found at CS in 21 subjects: four had multiple polyps. At per-patient analysis, there were 17 adenomas (24% prevalence): 10 were advanced (14% prevalence); six polyps were ≥10 mm (all adenomas); five 6–9 mm (all adenomas, two advanced) and ten ≤5 mm (four hyperplastic, six adenomas, two advanced). CTC identified polyps ≥10 mm in 4/6 cases and polyps >5 mm in 6/11 cases; only 1/10 polyps ≤5 mm was identified by CTC. Overall CTC sensitivity for polyp detection was 33%, but it was 67% when considering only polyps ≥10 mm. In 50 subjects CS was negative: in seven of them CTC identified polyps, six of them were ≤5 mm, which were excluded by CS. Thus, overall specificity was 86%, but it was 98% if polyps ≤5 mm were not considered. Evaluation of tolerance: CS was judged worst in 66% of the cases, CTC in 8%, 26% of subjects considered them similar; CS would be preferred as a future test in 28% and CTC in 51%; 5% would rather not repeat any test and 13% did not express a preference. The level of discomfort caused by CS was significantly higher than for CTC (P < 0.05, paired t-test) whereas preparation caused a similar level of discomfort to either procedure (NS versus either CS or CTC). Conclusion. The preliminary results of CTC for screening subjects at increased risk indicate high specificity, but sensitivity may not yet be enough to grant its use outside controlled studies. CTC is better accepted than CS but colon preparation is still a problem.

Results. AET was in the normal range in the asymptomatic controls (mean (95% confidence interval), 1.50% (1.3–1.7)) and in six patients (1.55% (1.4–1.7)) (NERD pH-negative), it was abnormal in seven patients (11.4% (10–12.8)) (NERD pH positive). Mean intercellular space diameter was 0.81 = B5m (0.78–0.85) in controls, 1.45 (1.38–1.52) in NERD pH negative (P < 0.001 versus controls) and 1.4 (1.33–1.46) in NERD pH positive patients. No correlation was found between AET and intercellular spaces in the patient groups. Conclusions. Presence of DIS is a feature of NERD patients, irrespective of oesophageal acid exposure. If this finding will be confirmed in larger series, defective oesophageal mucosal resistance to small amounts of acid refluxate would play a relevant role in the pathophysiology of GERD. Reference

CO016

Background and aim. Coeliac disease (CD) can be associated with a variety of neurological diseases. Recent evidence indicates that neuronal antibodies (NA) can be identified in CD patients with neurological impairment. The pathogenetic mechanisms underlying neuronal dysfunction in this subset of CD patients are still undefined. We tested the pro-apoptotic effect evoked by sera of CD patients with neurological diseases in a neuroblastoma cell line and investigated the intracellular pathways involved in apoptosis. Methods. Sera containing central and enteric nervous system NA from seven CD patients with (6F; three patients with cerebellar ataxia; two with attention/memory impairment syndrome, one with epilepsy and one with multiple sclerosis) and without (n = 6, 5F) neurological disorders were studied. SH-Sy5Y neuroblasts were exposed to sera from both groups and foetal calf serum (FCS). Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) technique, and caspase-3 and apaf-1 immunofluorescence. Also, cleaved caspase-8 was assessed by western blot. Mitochondrial fraction from neuroblasts was processed for respiratory chain complexes (NADH-ubiquinone oxidoreductase, succinate dehydrogenase, rotenone-insensitive NADH-cytochrome c reductase, cytochrome oxidase) and citrate synthase specific activities. Results. After 6, 12 and 24 h of exposure to NA+ve sera (18.3 ± 3; 31.7 ± 2.3; 33.8 ± 3.8), the percentage of TUNEL+ve neuroblasts was significantly greater than that of control sera (12.8 ± 1.3; 10.1 ± 2; 8.8 ± 2.4) or FCS (11.8 ± 1.6; 8.7 ± 1.4; 4.7 ± 0.8). Apaf-1 and caspase-3 immunolabelling showed an intense cytoplasmic staining in a greater proportion of cells exposed to NA+ve sera compared to controls, whereas western blot analysis was negative for cleaved caspase-8 in NA+ve sera and controls. Citrate synthase, succinate dehydrogenase and cytochrome oxidase specific activities were significantly higher in cells exposed to NA+ve sera at 6 h than in controls. These specific activities were lower in cells exposed to NA+ve sera at 12 than 6 h. Conclusions. Our findings show that NA+ve sera evoke neuronal apoptosis, which is dependent upon mitochondrial pathway activation as indicated by the absence of cleaved caspase-8 and by the progressive impairment of enzymatic activities. We postulate that these mechanisms contribute to neuronal dysfunction observed in CD-related neurological diseases.

DILATED INTERCELLULAR SPACES IN NON-EROSIVE REFLUX DISEASE PATIENTS WITH PHYSIOLOGICAL OESOPHAGEAL ACID EXPOSURE R. Cavigliaa , M. Ribolsia , A. Gabbriellia , N. Maggianob , S. Emerenziania , M. Pier Luca Guarinoa , S. Carottia , C. Rabittic , M. Cicalaa a Dipartimento

Malattie dell’Apparato Digerente, Università Campus Bio Medico, Rome, Italy b Dipartimento di Anatomia Patologica Università Cattolica del Sacro Cuore, Rome, Italy c Dipartimento Anatomia Patologica, Università Campus Bio Medico, Rome, Italy Background. The link between typical gastro-oesophageal reflux disease (GERD) symptoms and oesophageal acid exposure is poorly understood, particularly in non-erosive reflux disease (NERD) patients with a 24 h pH test in the normal range. Dilation of intercellular spaces (DIS) of oesophageal epithelium is a morphological marker of tissue damage and has been shown in erosive and non-erosive GERD patients with a pathological pH profile. Aim. To evaluate the relation between ultrastructural changes, acid exposure and GERD symptoms, the presence of DIS has been assessed in NERD patients with and without abnormal pH profile. Methods. After 14 days of pharmacological wash-out, consecutive GERD patients were recruited: of these, 13 were NERD patients (F9, mean age 46 years). Two biopsy specimens were taken within the lower 5 cm of oesophagus from each patient. One specimen was selected for traditional histology and one has been processed by trasmission electron microscopy (TEM). Intercellular space diameter was measured from TEM photomicrographs using a previously reported method [1]. Twenty-four-hour pH monitoring was performed 3–8 days after endoscopy. Acid exposure time (AET) was considered pathologic if exceeding 5% of total recording time. Six asymptomatic volunteers (F4, mean age 32 years) underwent the same protocol.

[1] Tobey NA, et al. Gastroenterology 1999.

CO017 SERA OF PATIENTS WITH COELIAC DISEASE AND NEUROLOGICAL DISORDERS EVOKE A MITOCHONDRIALDEPENDENT APOPTOSIS IN A NEUROBLASTOMA CELL LINE E. Cervioa,b , R. De Giorgioa,b , U. Voltaa,b , M. Verria,b , F. Boschia,b , O. Pastorisa,b , R. Vicinia,b , A. Agazzia,b , G. Barbaraa,b , G. Sarnellia,b , F. De Pontia,b , V. Stanghellinia,b , R. Corinaldesia,b , M. Toninia,b a Department

of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy b Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy

Abstracts CO018 COLORECTAL CANCER SCREENING PROGR- AMME BY COLONOSCOPY IN 55-YEAR-OLD SUBJECTS F. Chilovi, A. Bertozzo, S. Amplatz, S. Benvenuti, M. Comberlato, F. Di Fede, A. De’Guelmi, P. Farris, M. Felder, T. Grasso, S. Hauer, L. Piazzi, L. Zancanella Divisione di Gastroenterologia Ospedale Regionale di Bolzano, Italy Background. Indirect evidence suggests that the colonoscopy is almost certainly a highly effective screening test. However, a colonoscopy screening programme extended to all medium-risk individuals over the age of 50 years is greatly limited by the lack of resources and specialised personnel. Screening project. The multi-year screening project financed by the “Provincia di Bolzano” allows for the city of Bolzano residents (the city has about 100,000 residents) who turn 55 every year (in 2002 those born in 1947, in 2003 those born in 1948, etc.) to be invited to have a colonoscopy. The primary objective of this project is to reduce the incidence and mortality of colorectal cancer. Aim. To evaluate at the end of the first year of the screening project the compliance and the incidence of colon pathologies in residents born in 1947 in order to determinate the feasibility of the project. Methods and procedures. Following a sensitising media campaign, an invitation to undergo a free colonoscopy screening was mailed to 1340 Bolzano residents born in 1947. The endoscopic procedures were then performed on the project volunteers at the Division of Gastroenterology of the Bolzano Hospital by 10 different endoscopists with varying degrees of experience who practice at this same facility. Results. Compliance: 336/1.116, eligible residents 30.1%, number of colonoscopies 336 (163 men, 48.5%) (173 women, 51.5%). Completed colonoscopies: 312 (92.8%), complications: 0, negative colonoscopies: 160 (51.5%). Patients. Haemorrhoids 29: 9.2% (prevalent pathology), diverticula 22: 7.0%, adenomatous polyps 58: 18.5%, hyperplastic polyps 31: 9.9%, cancer 3: 0.9%, other 6: 2.2%. Conclusions. (a) The colonoscopies were successfully performed on 93% of the subjects without complications. (b) The 30% compliance is unsatisfactory but likely to be improved with a larger sensitising campaign. (c) The percentage of colonic pathologies—including minor ones–in the 55-year-old age group is 50%. (d) The percentage of lesions at high risk for malignant transformation is 12% and it justifies the expansion of the project to other geographic areas. CO019 RETREATMENT WITH COMBINATION THERAPY (IFN-␣2b + RIBAVIRIN) OF HCV POSITIVE NON-RESPONDER PATIENTS TO INTERFERON MONOTHERAPY: RESULTS OF LONG-TERM FOLLOW-UP OF SUSTAINED RESPONDERS A. Ciancio, A. Olivero, S. Carenzi, A. Smedile, C. Colletta, G. Croce, L. Roffi, G. Cariti, A. Macor, A. Di Napoli, G.F. Tappero, A. Biglino, M. Andreoni, P.G. Orsi, A. Manca, G. Calleri, M. Rizzetto, G. Saracco Background. Long-term follow-up studies of HCV+ patients who respond to IFN are scarce and usually regarded as naive patients. Aims. To evaluate the virological relapse rate during long-term follow-up of non-responders to IFN monotherapy who were successfully retreated with various schedules of IFN-␣2b and Ribavirin. Methods. We performed a prospective long-term biochemical and virological follow-up of 87 previous non-responders to IFN monotherapy included in a randomised four-arm multicentre study of IFN-␣2b and Ribavirin who achieved a sustained response (HCV−ve 6 months after therapy withdrawal). Seven out of 87 were lost to follow-up (8%); after a mean follow-up of 42 months (range 39–72), serum HCV–RNA remained undetectable in 69/80 patients (86%): all of them had normal ALT value. Virological relapse among the remaining 11 patients

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occurred usually after 1 year (mean 13.6 months, range 5–21). Three (27%) of 11 relapsers showed persistently normal ALT levels. Most of them were males (10/11, 91%), showed genotype 1 or 4 (9/11, 82%) and had advanced liver disease at baseline (5/11, 45%). In the previous study 30 patients were biochemical sustained responders (HCV–RNA persistently positive); four were lost during follow-up. Twenty-one of 26 (81%) showed an ALT relapse during the follow-up (mean 14.7 months, range 5–24) confirming the poor value of biochemical response as endpoint. Conclusions. Previous non-responders to IFN monotherapy who are HCV–RNA negative 6 months after a successful course of combination therapy deserve a stringent long-term follow-up since a significant proportion of them (14%) will show a viremic reappearance. CO020 STUDY OF THE EXPRESSION AND LOCALISATION OF THE MAIN MOLECULAR COMPONENTS OF EPITHELIAL TIGHT JUNCTIONS IN COELIAC DUODENAL MUCOSA R. Ciccocioppoa,b,c,d , A. Di Sabatinoa,b,c,d , C. Araa,b,c,d , A. Finamorea,b,c,d , M. Brucchia,b,c,d , R. Lucantonia,b,c,d , F. Biagia,b,c,d , G. Roberto Corazzaa,b,c,d a Department

of Internal Medicine, University of L’Aquila, L’Aquila, Italy Unit, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy c National Institute for the Study of Foods and Nutrition, Rome, Italy d Division of General Surgery, Hospital G. Mazzini of Teramo, Italy b Gastroenterology

Background and aim. Changes of the intestinal mucosal barrier are considered to play a role in the pathogenesis of coeliac disease (CD). A correct assembly and functionality of the molecular components of tight junctions is needed for the maintenance of barrier integrity. Therefore, we aimed to study the expression and localisation of the two main junctional components, i.e. occludin and zonula occludens (ZO)-1, in CD together with the level of tyrosine phosphorylation, a phenomenon known to affect their distribution. Patients and methods. Snap-frozen and OCT-embedded duodenal biopsies from 10 untreated, 11 treated adult coeliac patients and 12 biopsied controls were used for immunoprecipitation and Western blot experiments, such as for immunolocalisation analysis at confocal scanning laser microscope SARASTRO 2000 (Molecular Dynamics). Anti-occludin, anti-ZO-1, and anti-phosphotyrosine antibodies (all from Zymed Laboratories, San Francisco, CA) were used. Bands were quantified by scanning densitometry using an LKB Ultrascan XL Laser Densitometer (Kodak Ltd., Hemel Hempstead, UK). Results. The immunoprecipitation and blotting of mucosal samples with the anti-ZO-1 antibody revealed the presence of similar amounts of protein within the three groups, whereas the blotting of these immunoprecipitates with the anti-occludin and anti-phosphotyrosine antibodies revealed the absence of the corresponding bands in untreated CD. These results were mirrored by those at confocal microscopy showing that in normal and treated CD mucosa, ZO-1 and occludin were co-localised at the apical portion of the lateral cellular membrane. In untreated CD, the ZO-1 fluorescence was less intense and more diffuse in comparison to normal condition, whilst that corresponding to occludin was almost completely absent. Double staining evidenced a lack of co-localisation of the two molecules. Conclusions. Our data suggest that the lack of tyrosine phosphorylation of ZO-1 may cause its inability to migrate apically along the enterocyte lateral membrane to joint occludin leading to the well known disruption of intestinal barrier observed in CD. Whether this phenomenon is a primary or secondary event remains to be elucitated.

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CO021

CO022

DELIVERY OF RADIOFREQUENCY ENERGY TO THE GASTRO-OESOPHAGEAL JUNCTION (STRETTA PROCEDURE) FOR THE TREATMENT OF GERD: THE ITALIAN EXPERIENCE

A PROSPECTIVE, RANDOMISED STUDY COMPARING TWO SELF-EXPANDING STENTS IN THE PALLIATION OF PATIENTS WITH DYSPHAGIA DUE TO INOPERABLE OESOPHAGEAL CANCER

L. Cipollettaa , A. Repicib , G. Rotondanoa , L. Dugherac , M.A. Biancoa , C. De Angelisb , A.M. Vingiania , E. Battagliac a UOC

Gastroenterologia, ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy b Dip. Gastro-Epatologia, A.O. San Giovanni Battista, Turin, Italy c Dip. Fisiopatologia Clinica, A.O. San Giovanni Battista, Turin, Italy

Background. Radiofrequency energy (RF) treatment to the lower oesophageal sphincter (LES) and gastric cardia is increasingly offered as first-line therapy before surgery for selected GERD patients. Aim. To assess efficacy and safety of RF treatment and patient satisfaction. Methods. Thirty-two patients (20 males, age range 24–71 years) undergoing the Stretta procedure between June 2001 and October 2003 were prospectively evaluated. All patients were on daily PPIs. At baseline endoscopy, 12 had small (<2 cm) hiatal hernia, 9 had grade A and 1 grade B oesophagitis. Most patients had breakthrough symptoms while on drugs or were not willing to take drugs for a lifetime and refused laparoscopic antireflux surgery. Under an IRB-approved protocol, patients were studied preoperatively and postoperatively with upper endoscopy, oesophageal manometry, 24 h pH testing, SF-36 surveys, and GERD-specific questionnaires (GERD-HRQL). Results. All procedures were performed on an outpatient basis (17 conscious sedation, 15 general anaesthesia). Significant clinical improvement was observed in 91% of patients (29/32). Mean heartburn score decreased from 3.4 to 1.6 (P = 0.001). The quality of life scores were significantly improved: mean GERD-HRQL score decreased from 28 to 16 (P = 0.003), mental SF-36 increased from 43 to 56 (P = 0.001) and physical SF-36 increased from 40 to 49 (P = 0.05). Twenty-one patients were available for 24 h pH testing, endoscopy and manometry at a mean follow-up of 18 ± 6 months (range 12–30). Median oesophageal acid exposure decreased (11.7–8.4%, P = 0.79), and was normalised in eight patients. Median LES pressure was unchanged (15–23 mmHg, P = 0.72). Oesophagitis healed in 8/10 patients, but two patients with non-erosive disease developed an asymptomatic grade A oesophagitis during follow-up. At 12 months 7/20 patients (35%) were off PPIs, yet another 5/20 (25%) substantially reduced medication use. Fever and retrosternal pain were the most frequent complaints, always resolved within 48 h. The only major complication related to Stretta was a case of severe gastroparesis 10 days post-operatively that resolved after 4 months. Conclusions. RF significantly improves symptoms and quality of life in GERD patients. Stretta might be a new option for selected (endoscopy-negative or low-grade oesophagitis) patients who are intolerant of, or desire an alternative to, traditional medical therapies.

M. Conioa , A. Repicib , G. Battagliac , G. De Pretisd , J.F. Demarquaye , M. Bittingerf , H. Messmannf , L. Ghezzog , S. Blanchia , R. Conigliaroh , A. Cartac , P. Bocusc , G. Calandria , R. Filibertia a Istituto

Nazionale Ricerca Cancro, Genoa, Italy Molinette, Turin, Italy c Università di Padova, Padua, Italy d Ospedale di Trento, Trento, Italy e Università di Nice, Francia, Italy f Ospedale di Aufburg, Germania, Italy g Ospedale di Cuneo, Italy h Ospedale di Reggio Emilia, Italy b Ospedale

Introduction. Oesophageal cancer (EC) is rarely a curable disease. Most patients require palliative treatment. Self-expanding stents (SES) are used to restore swallowing. The major drawback of marketed metal stents is the high cost. A less expensive, new expandable plastic stent has been developed. Aim. To compare two different SES in terms of relief of dysphagia (D), complications, and survival. Methods. Seventy-eight consecutive patients (65 males, 13 females; mean age 71.9 ± 10.5 years) with unresectable EC were randomised to insertion of a covered SES (Ultraflex, 23 mm × 28 mm) (U), or a new type of covered SES made of polyester netting, embedded in silicone (polyflex, 18 mm × 23 mm) (P). The primary end point was relief of D (D score: 0, no D; 1, some solid food; 2, semisolids only; 3, liquids only; 4, complete D). Secondary endpoints were: complications and survival. Results. Stents were successfully inserted in all patients: 42 had U, 36 P. At 7 days, D was relieved in 60/78 (76.9%) patients, and in 50/78 (64.1%) at 1 month. Following SES placement, the median D score improved from 3 to 1 at 7 days, and was 2 at 30 days, in the U group; and improved from 3 to 1 at 7 days, and was 1 at 30 days in the P group (P = n.s.). Twenty-seven patients received previous radiotherapy (31% U and 38.9% P). The complication rate in U and P groups was 41.5 and 55.6%, respectively (P = n.s.). In the U group complications were: migration (1), and pain (13). In the P group complications were: migration (1), pain (15), and perforation (1) (P = n.s.). Stent related mortality was two patients (4.8%) in the U group and one (2.8%) in the P group. Recurrent D due to tumour overgrowth occurred in four (9.5%) U, and eight (22.2%) P, after a median follow-up of 3 months (P = n.s.). Dysphagia due to hyperplastic overgrowth was diagnosed in four patients treated with U, and in four in the P group (P = n.s.). Endoscopic reintervention was required in 10 (23.8%) U patients, and 14 (38.9%) P patients (P = n.s.). In the U group relief of D was obtained with a further SES in four (9.5%) patients. Thermal therapy was used in six (14.3%) patients. In the P group relief of D was obtained with a second stent in five (13.9%). Thermal therapy was used in six (16.7%) patients. Median survival was 8.4 months in U group and 13.5 months in P (P = n.s.). Median length of hospital stay was 4 days in the U patients, as compared to three in the P group (P = n.s.). Conclusions. The metal and the plastic SES were similarly effective in relieving malignant D in patients with EC. The complication rate was also similar in both the groups. A non-significant trend to longer survival was noted in the P group. An advantage of the P stent is its lower cost.

Abstracts CO023 ACID SUPPRESSION IMPROVES CARDIAC SYMPTOMS IN A SUBGROUP OF GERD PATIENTS WITH IDIOPATHIC ARRHYTMIAS AND ALTERED NEUROCARDIAC FUNCTION R. Cuomoa , F. De Giorgia , G. Sarnellia , L. Adinolfib , D. Iannuzzob , C. Verdea , G. Budillona a Gastroenterologia,

Dip. di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Naples, Italy b Dip. di Medicina Interna, Università degli Studi di Napoli “Federico II”, Naples, Italy

Background. We previously reported a link between acid reflux and cardiac autonomic reflexes in a subgroup of patients with idiopathic supraventricular arrhythmias and gastro-oesophageal (GER) symptoms. However, whether acid suppression is able to modify cardiac symptoms in these patients remains to be elucidated. Aim. To evaluate the effect of acid suppression on cardiac symptoms in patients with idiopathic supraventricular arrhythmias and symptoms of GERD. Subjects and methods. Thirty-one patients (19 males, aged 20–69 years), with idiopathic supraventricular arrhythmias and GERD symptoms, underwent simultaneous 24 h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV), with its low frequency (LF, influenced by sympathetic modulation) and high frequency (HF, influenced by vagal modulation) components, was obtained and LF/HF ratio calculated. Total time with oesophageal pH < 4 and mean pH were considered during pH-monitoring, and compared with PSHRV data. A 4 months full-dosage PPI therapy was prescribed to each patient. Results. In 18 out of 31 patients (58%), a significant correlation between mean oesophageal pH and LF/HF ratio was observed (P < 0.05). In 12 of these patients the pH decrease was positively correlated with a decreased ratio (r = 0.53 ± 0.08), which was dependent on the HF component increase. Conversely, in the remaining six cases, a negative correlation (r = −0.57 ± 0.12), with an increase in ratio dependent on the LF increase was observed. Furthermore, time with oesophageal pH < 4 was higher in the 18 acid responsive patients than in non-responsive subjects (6.3 ± 1.7% of time with pH < 4 versus 4.8 ± 1.6; P = ns), although the difference was not statistically significant. The PPI therapy significantly reduced GERD symptoms in the 22 patients who complied with treatment (there were nine drop-outs). However, a significant reduction of cardiac symptoms as palpitations was observed only in the subgroup of patients who experienced a significant correlation between mean oesophageal pH and LF/HF ratio (12/15 versus 1/7, P < 0.01). Conclusions. This study identified a subgroup of patients with idiopathic supraventricular arrhythmias and cardiac autonomic reflexes elicited by the acid stimulus in the oesophagus. In this subset of patients, acid suppression improved GERD and cardiac symptoms. CO024 DOES RECTAL SENSORIMOTOR FUNCTION IN PATIENTS WITH IRRITABLE BOWEL SYNDROME VARY ACCORDING TO PREVAILING SYMPTOMS? R. Cuomo, M. Flavia Savarese, G. Sarnelli, R. Grasso, P. Ciamarra, G. Budillon Gastroenterologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Naples, Italy Background. Patients with irritable bowel syndrome (IBS) mainly complain of symptoms such as diarrhoea, constipation and/or bloating, although the hallmark of IBS is rectal hypersensitivity. Aims. To investigate whether sensitivity, compliance and tone of the rectum differ among patients according to whether diarrhoea, constipation or bloating is the prevailing symptom.

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Methods. Thirty patients who fulfilled the Rome II Criteria for IBS were enrolled; 11 patients (six males; 19–34 years) with predominant diarrhoea (IBS-D; more than three bowel movements a day) and 10 patients (four males; 24–43 years) with predominant constipation (IBS-C; fewer than three bowel movements a week), nine patients (five males; 23–35 years) with predominant bloating (IBS-B; bloating relieved with defaecation and with normal stool frequency) were selected to undergo a rectal barostat study. After bag placement, minimal distending pressure (MDP) was measured as the pressure enabling the detection of respiratory movements. Over a 30 min period, rectal adaptation was measured as difference in average bag volume at MDP + 2 between the last five and the first 5 min. Rectal compliance and sensitivity were then assessed by isobaric distension with stepwise pressure increasing from 0 to 30 mmHg. During distension, subjects were asked to report: first perception, feeling of stool and urgency to defaecate. Data are expressed as mean ± S.E.M. Results. Rectal volumes that induced feeling of stool and urgency to defaecate were significantly lower in IBS-D patients than in IBS-Cs (93.6 ± 20.9 ml versus 208.4 ± 29.6 ml, P < 0.01 and 157.2 ± 32.2 ml versus 304.3±46.9 ml, P < 0.05, respectively) whereas in IBS-B patients, only rectal volumes that induced feeling of stool were significantly lower than in IBS-C patients (111.2±18.3 ml versus 208.4±29.6 ml, P < 0.05). No significant difference was observed when sensitivity was expressed as pressure levels. Rectal compliance was also significantly lower in IBS-D patients than in IBS-Cs (5.6 ± 0.6 ml/mmHg versus 9.0 ± 1.2 ml/mmHg, P < 0.05). Rectal adaptation was significantly higher in IBS-D than in IBS-B patients (15.8 ± 3.3 ml versus 6.4 ± 3.0 ml, P < 0.05). Conclusion. IBS patients with predominant bloating seem to have intermediate rectal hypersensitivity ranging between IBS patients with prevalence of diarrhoea and those with prevalent constipation. In addition, rectal adaptation seems to be rather mild in these patients. Barostat rectal studies could help identify IBS subtypes and address therapeutic choices. CO025 INCREASED NEOANGIOGENESIS IN THE MUCOSA OF INFLAMMATORY BOWEL DISEASE PATIENTS S. Danesea,c , M. Sansa , C. de la Motteb , A. Gasbarrinic , C. Fiocchia a Division

of Gastroenterology, University Hospitals of Cleveland Case Western Reserve University School of Medicine, Cleveland, OH 44195, USA b Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA c Università Cattolica del S. Cuore, Rome, Italy

Background. Neoangiogenesis is a critical component in neoplastic growth. It also plays a key pathogenic role in a variety of chronic inflammatory disorders. At present, there is no information on whether neoangiogenesis also occurs in inflammatory bowel disease (IBD). Aims. To explore the presence of neoangiogenesis in Crohn’s disease (CD) and ulcerative colitis (UC) mucosa by assessing its vascularisation state, investigate the expression of the angiogenic marker integrin ␣V␤3 by mucosal endothelial cells, and determine whether gene expression patterns of IBD-derived human intestinal microvascular endothelial cells (HIMEC) display a pro-angiogenic profile. Methods. Control and IBD colonic tissue was immunostained for endothelial-specific proteins (CD31 and von Willebrand) and vessel quantitative analysis was performed by computerised morphometry. Confocal microscopy was used to assess integrin ␣V␤3 expression in vivo, and flow cytometry evaluated the presence of ␣V␤3 by resting HIMEC and after stimulation with bFGF, VEGF and TNF-␣. Gene microarray (Affimetrix) appraised HIMEC gene expression. Results. Compared to normal controls, both actively involved CD and UC mucosa displayed a significantly (P < 0.05) higher microvascular density, percentage vascular section area, and larger diameter. ␣V␤3 expression was essentially absent in the microvasculature of histologically normal mucosa, but was significantly up-regulated in IBD microvasculature, where it colocalised with CD31. bFGF and TNF-␣, but not VEGF,

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markedly up-regulated HIMEC ␣V␤3 expression. Microarray gene expression profiles in HIMEC isolated from IBD subjects revealed a robust increase in multiple genes known to be involved in neoangiogenesis. Conclusions. Our results are the first objective evidence for the existence of neoangiogenesis in IBD, which provides the basis for novel anti-angiogenic therapeutic strategies, as currently considered for autoimmune disorders. CO026 KERATINOCYTE TRANSGLUTAMINASE IN NORMAL COLON AND ULCERATIVE COLITIS: A POTENTIAL ROLE IN CELL ADHESION G. D’Argenioa , N. Della Vallea , M. Calvanib , V. Cosenzac , G. Di Matteod , P. Giorgiod , S. Margaruccie , O. Petillof , F.P. Jorig , G. Pelusof a Gasatroenterologia,

Università Federico II di Napoli, Naples, Italy Scientifico Sigma-Tau, Pomezia, Rome, Italy c Divisione di Medicina, Ospedale di Sorrento, Naples, Italy d Endoscopia Digestiva, IRCCS S. De Bellis, Castellana Grotte, Bari, Italy e IBP CNR Naples, Italy f INT Fondazione G. Pascale, Naples, Italy g Seconda Università di Napoli, Naples, Italy b Dipartimento

Background and aims. The mechanisms underlying damage and impaired healing in ulcerative colitis (UC) have yet to be defined. Transglutaminases (TG) are a family of enzymes which catalyse protein cross-linking and are associated with increased tissue stabilisation and wound healing. Expression of keratinocyte transglutaminase (TGk), resulting in cross-linked protein envelopes in cornified epidermal cells, is required for barrier function in terminally differentiating stratified squamous epithelia. In this study, we looked at a possible role of this isoenzyme in intestinal mucosa integrity in UC patients. Patients and methods. Endoscopic and histologic indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 normal controls undergoing colonoscopy. TGk protein content and mRNA expression in the colon were evaluated by Western blot analysis and semiquantitative RT-PCR, respectively. The colonic location of TGk was evaluated by immunohistochemistry using specific monoclonal antibody. Results. We showed for the first time, the presence of TGk in normal colonic mucosa. In control subjects, an increasing number of epithelial cells positive for TGk were observed by immunohistochemistry from the base to the upper crypt; the staining was less pronounced in inactive patients and surprisingly absent in active UC. In keeping with these results, Western blot and RT-PCR showed that protein level and gene expression of TGk were down-regulated in active UC compared to inactive disease and controls. Conclusions. We demonstrate for the first time the presence of the keratinocyte form of transglutaminase in human normal colonocytes, whereas it is not expressed in active colitis. This result suggests that, similarly to the role played in the epidermis, keratinocyte transglutaminase may promote cell cohesion in the colon epithelium. Our finding that damaged epithelium with increased permeability to bacterial and luminal antigenic components shows an impaired TGk expression as a marker of reduced cell adhesion remains of considerable interest.

CO027 ASSESSMENT OF COLORECTAL LESIONS USING MAGNIFYING COLONOSCOPY AND MUCOSAL DYE SPRAYING: CORRELATION BETWEEN MUCOSAL CRYPT PATTERNS AND HISTOLOGICAL FINDINGS D. De Palma Giovanni, M. Rega, P. Ciamarra, F. Patrone, L. Mastantuono, I. Simeoli, V. Pilone, G. Persico Settore di Diagnostica e Terapia Endoscopica Dipartimento di Chirurgia Generale e Tecnologie Avanzate Università Federico II di Napoli Facoltà di Medicina e Chirurgia, Naples, Italy Background and study aims. Assessing the nature of lesions at the time of colonoscopy is important, and magnifying colonoscopy allows examination of mucosal crypt patterns. In this study, we assessed mucosal crypt patterns to see whether we could predict the histological findings. Patients and methods. This prospective study of total colonoscopy using magnifying colonoscopy involved 75 patients between January and December 2003. The mucosal crypt patterns of 102 lesions were observed under magnifying colonoscopy with 0.2% indigo carmine solution, and classified according to a modified Kudo classification (types I–V). After endoscopic or surgical resection (71 and 4 cases, respectively), histopathological examination was performed. Results. The diagnostic accuracy of magnifying endoscopy for non-neoplastic lesions was 73% (8/11), for adenomatous polyps it was 92% (65/60), and for invasive carcinomas it was 75% (3/4). Conclusions. The combination of magnifying colonoscopy and dye spraying is helpful in determining the nature of colonic lesions as non-neoplastic, adenomas, or invasive carcinomas. Therefore, it may be possible to determine, at the time of colonoscopy, which lesions require no treatment, which can be removed endoscopically, and which should be removed by surgery. CO028 CHARACTERISATION OF FOCAL LIVER LESIONS WITH CONTRAST TUNE IMAGING: A PROSPECTIVE STUDY VERSUS SPIRAL TC, MRI AND US-GUIDED FNB I. de Sio, B. Palmentieri, A. Federico, L. Tibullo, M. Persico, R. Torella, C. Del Vecchio-Blanco, L. Castellano Dipartimento di Medicina Interna e Gastroenterologia, Seconda Università di Napoli, Naples, Italy Introduction. Contrast tune imaging (CnTi) is a new ultrasound technique with a low mechanical index (MI) and continuous scanning useful in assessing real time perfusion of focal liver lesions by means of second generation contrast agents (SonoVue® ). Aim. To characterise focal liver lesions by CnTi and SonoVue® (sulphur hexafluoride) comparing the results with the diagnosis obtained by the gold standard (spiral CT scan, MRI, US-guided FNB). Materials and methods. Evaluation by CnTi (Esatune, Esaote, 3.5 MHz transducer) and SonoVue® (Bracco) of 48 patients (27 male–21 female; age range 18–78 years; mean 57) with focal liver lesions (1.2–12 cm, mean 3.5 cm): 13 hepatocellular carcinoma (HCC); 11 metastases (six colorectal carcinoma, one breast cancer, two pancreatic carcinoma, one neuroendocrine tumour, one non-defined) seven hemangiomas, six focal nodular hyperplasia (FNH), five adenomatous hyperplasia (RN), two colangiocarcinoma, one hepatic lymphoma, one biliary cistoadenoma, one abscess, one necrotic solitary nodule. Contrast agent was administered intravenously (4.8 ml followed by 5–10 ml normal saline flush). Focal liver lesions enhancement was evaluated in arterial, portal and late phases. The enhancement patterns were classified according to Kim et al. [1]. Results. Contrast enhanced ultrasound was not diagnostic in 2%; sensitivity, specificity, diagnostic accuracy, positive and negative predictive value for diagnosis of liver malignancy were, respectively, 100, 85.7, 93.6, 89 and 100%. Three patients with benign lesions (abscess, necrotic solitary

Abstracts nodule and biliary cistoadenoma) were diagnosed as having malignancy; one patient with neuroendocrine metastasis and one with hepatic lymphoma were diagnosed as having HCC; two patients with colangiocarcinoma were diagnosed as having liver metastasis. Conclusions. CnTi + SonoVue® may be helpful to characterise focal liver lesions. Typical patterns of enhancement are present in FNH, haemangiomas and HCC with high diagnostic accuracy for these lesions. Diagnostic accuracy for malignancy is high (93.6%); however in about 15% of cases (7/47) a definitive diagnosis cannot be achieved with an inappropriate diagnosis of focal liver lesion nature. Reference [1] Kim, et al. Radiology 2000.

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as confined in damaged epithelial cells showing either loss of mucus production and nuclear polarity as well as polymorphonuclear/lymphocytic infiltration. This pattern was directly related to apoptotic index (P < 0.05, Pearson’s correlation test between tTG and PARP LI). Additionally, tTG was overexpressed in stromal cells of inflammed mucosa when compared to normal (LI: 31.3 ± 4.8 versus 9.1 ± 3.4, P < 0.001, Student’s t-test for unpaired data). After eradication, tTG remained expressed in residual few epithelial damaged cells as well as in stromal cells without changes in LI despite bacterium and active inflammation disappearance. Finally, an increased tTG extracellular staining was observed in the lamina propria. Conclusions. Our results confirm, even in gastric epithelium, a strong relationship between apoptosis and tTG in HP positive gastritis. Moreover, the lack of TG activity increase despite tTG immunohistochemical overexpression may be due to the enzyme entrapment in the gastric mucosa in order to repair HP induced tissue damage.

CO029 TISSUE TRANGLUTAMINASE (tTG) IN Helicobacter pylori (HP) CHRONIC ACTIVE GASTRITIS: RELATIONSHIP WITH EPITHELIAL APOPTOSIS AND TISSUE REPAIR N. Della Vallea , E. Ierardia , V. De Francescob , V. Cosenzac , S. Marangid , M. Romanoe , C. Panellaa , G. D’Argeniof a Gastroenterology

Section, Department of Medical Sciences, University of Foggia, Foggia, Italy b Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy c Divisione di Medicina Ospedale di Sorrento (NA), Italy d Gatroenterology Section, Department Emergency and Organ Transpl University of Bari, Bari, Italy e Gastrointestinal Unit 2nd University of Napoli, Naples, Italy f Gastrointestinal Unit, Department of Clinical and Experimental Medicine, University Federico II of Napoli, Naples, Italy Background. Transglutaminases (TG), a calcium dependent enzyme family, play a relevant role in the repair of mucosal lesions of the gastrointestinal tract both in experimental and clinical conditions. Moreover, tTG involvement in the final step of epithelial apoptosis (cross-linking of membrane with extracellular matrix proteins and formation and stabilisation of apoptotic bodies) has been clearly demonstrated. In the stomach, tTG has been reported to be involved in the healing of gastric ulcer and stress-induced gastric erosions in an experimental model. No data are available about tTG expression and location in human disorders of the stomach. Aim. On these bases, we have studied the pattern of tTG in a mucosal lesion of the stomach, i.e. HP-related chronic active gastritis, in which the increase of epithelial apoptosis is known. Patients. Forty-one consecutive patients undergoing upper endoscopy and gastric (body and antrum) biopsies for dyspeptic symptoms were enrolled. Methods. Histological examination was performed on haematoxylin–eosin and Gram stained sections for both histological picture and HP status evaluation. Gastritis was assessed according to updated Sydney system. HP positive patients were treated with sequential therapy and underwent a second endoscopy/histology 2 months after the end of therapy. TG activity was assessed in gastric mucosa homogenate using a radioenzymatic method which evaluates 14C-putrescine incorporation into dimethylcasein. Additionally, immunohistochemistry was performed to identify the location of tTG in the gastric mucosa using a specific monoclonal antibody (CUB 7402, NeoMarkers, CA, USA) and of apoptotic cells by PARP staining in epithelium (Promega Corp., Madison WI, USA). The labelling index (LI: percentage of positive cells) was evaluated for both these stains. Results. Twenty-one patients showed HP positive chronic active gastritis and 20 HP-negative histologically normal stomach. In 8/21 HP positive patients endoscopic/histological examination was performed after therapy and bacterium eradication assessed in all. No difference was observed in TG activity among HP negative and positive patients and this parameter was not related to the activity of HP gastritis. At immunohistochemistry, tTG was not expressed in normal epithelium, whilst it was detected

CO030 ENDOSCOPIC DILATION OF BENIGN STRICTURES FOLLOWING LOW ANTERIOR RESECTION: A COMPARISON OF TWO KINDS OF BALLOONS P. Di Giorgio, L. De Luca, G. Rivellini, E. D’Amore, E. Sorrentino, B. De Luca Regione Campania, ASL Na 1 Ospedale dei Pellegrini, Napoli UOC di Gastroenterologia, Naples, Italy Background. Benign strictures occurs in 5.8–20% of colorectal anastomoses. Endoscopic dilation has proven to be a valid and a safe therapy. A variety of endoscopic techniques have been proposed but there is a lack of controlled prospective trials. The aim of this study was to compare dilation of this kind of strictures using an achalasia over the wire (OTW) balloon with through the scope (TTS) balloon dilation. Methods. Thirty patients with a benign colorectal anastomotic stricture were randomised to two different treatments: TTS balloon dilation (group A, 15 patients) and OTW achalasia balloon dilation (group B, 15 patients). All patients were symptomatic. Successful treatment was defined as a wide anastomotic lumen to allow passage of a standard colonscope with the disappearance of symptoms. We considered the success of dilation, the number of sessions required, complications and time of maintenance of the dilation. Follow-up period was 24 months. Results. Dilation was successful in all patients with no technique related complications. The mean number of session required was 2.6 (0.98) in TTS group and 1.6 (0.77) in OTW. This difference was statistically significant. We also found a longer maintenance time of dilation in the group treated with the achalasia device. Conclusions. Both TTS and OTW dilation techniques are effective and safe in treating benign colorectal anastomotic strictures. Using greater diameter achalasia balloons, reduces the number of dilation sessions required and permits a longer maintenance time of dilation. CO031 HIGH RELEASE OF IL-15 BY EPITHELIAL CELLS REGULATES PERFORIN-DEPENDENT CYTOTOXICITY BY INTESTINAL INTRAEPITHELIAL LYMPHOCYTES (IELs) IN COELIAC DISEASE (CD) A. Di Sabatinoa,b , R. Ciccocioppoa,b , B. Cinquea,b , F. Cupellia,b , M.G. Cifonea,b , G.R. Corazzaa,b a Gastroenterology

Unit, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy b Department of Internal and Experimental Medicine, University of L’Aquila, Rome, Italy Background and aims. The discovery that IL-15 may be produced by intestinal epithelial cells and that its signals via IL-15Ra are critical for the development, activation and/or survival of IELs focused the attention in

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mucosal immunity on the role of IL-15 in the intranet between enterocytes and IELs. On this basis, our aim was to verify whether IL-15, which has been reported to enhance the cytotoxicity of murine IELs against epithelial cell line, might support the cytotoxicity of IELs against enterocytes in active CD. Methods. Endoscopic biopsies were obtained from the duodenum of 10 untreated CD patients and 10 biopsied controls. IELs and enterocytes were isolated by mechanical/chemical disruption of the epithelial layer and discontinuous Percoll gradient centrifugation. Detection of IL-15 on enterocytes and of IL-15Ra on IELs was assessed by Western Blotting on cell lysates. IL-15 release by enterocytes was measured in culture supernatants by ELISA assay. To examine the influence of exogenous IL-15 on IEL cytotoxicity, control IELs were cultured in the absence or presence of 5 ng/ml recombinant IL-15 (rIL-15). To determine the role of endogenous IL-15, coeliac IELs were cultured in the absence or presence of 10 ␮g/ml anti-IL-15 blocking antibody (Ab). To assess cytotoxicity, a 51Cr release assay was performed by incubating unstimulated and stimulated IELs with Caco-2 cells as target, labelled with 30 ␮Ci of 51 Cr, at different effector/target ratios (E/T). Perforin-dependent cytotoxicity was blocked by preincubation of IELs with increasing concentrations of chloroquine (10, 50 and 100 ␮g/ml), known to block perforin-dependent cytotoxicity. Results. An increased expression of IL-15 and IL-15Ra was, respectively, found on enterocytes and IELs in untreated coeliacs in comparison to controls. Coeliac enterocytes showed a higher secretion of IL-15 when compared to that of controls. In controls, at each E/T, the killing activity of rIL-15-pretreated IELs was significantly higher (P < 0.001) than that observed in unstimulated IELs and was blocked by chloroquine in a dose-dependent manner. In untreated CD, IEL cytotoxicity was inhibited by anti-IL-15 blocking Ab, and was blocked when IELs were pretreated with chloroquine. Conclusions. Our results suggest that in active CD IL-15, which is highly released by enterocytes, may be available to neighbouring IL-15Ra-expressing IELs, thus activating their cytotoxicity against epithelial cells via a perforin-dependent pathway. CO032 LAMINA PROPRIA CD4+ CD25+ REGULATORY T CELLS ARE DECREASED IN PATIENTS WITH COELIAC DISEASE A. Di Sabatinoa,b , R. Ciccocioppoa,b , R. Carsettia,b , M.M. Rosadoa,b , F. Cupellia,b , M. Rossia,b , P. Morettia,b , G.R. Corazzaa,b a Gastroenterology

Unit, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy b Department of Internal Medicine, University of L’Aquila; Research Center Ospedale Bambino Gesù, Rome, Italy Background and aims. Regulatory T cells are produced by the thymus as a functionally mature T-cell subpopulation and coexpress CD4 and the IL-2R alpha-chain (CD25). They play a pivotal role in the maintenance of immune tolerance by down-regulating the response to foreign or self antigens. Since depletion of CD4+ CD25+ regulatory T cells has been shown to lead to the development of various autoimmune disorders, such as type 1 diabetes, autoimmune gastritis, experimental autoimmune encephalitis and inflammatory bowel disease, we aimed to explore whether CD4+ CD25+ regulatory T cells were changed in coeliac duodenal mucosa. Methods. Lamina propria lymphocytes were isolated from duodenal biopsies of seven untreated and eight treated coeliac patients, and eight biopsied controls, by removing the epithelial layer with EDTA and DDT. After continuous agitation for 1 h, the supernatant was removed and the remaining tissue was treated with type 1A collagenase for 1 h with continuous agitation. The crude cell suspension was allowed to stand for 5 min to permit sedimentation of debris. Cells from the supernatant were layered on Ficoll–Hypaque solution to isolate lamina propria lymphocytes by a density gradient method. Purified cell suspensions were used for two-colour cell surface labelling with FITC-conjugated (anti-CD4)

and PE-conjugated (anti-CD25) MoAb. Labelled cells were washed and analysed by FACSCalibur flow cytometer (Becton Dickinson). Results. Median percentage of lamina propria CD4+ CD25 + regulatory T cells was significantly (P < 0.0001) lower in patients with untreated (0.8%, range 0.1–1.8) and treated coeliac disease (1.0%, range 0.2–1.9) when compared to biopsied controls (11.2%, range 7.1– 14.8). No significant difference was found between untreated and treated coeliac patients. Conclusions. Our data provide the first evidence for CD4+ CD25+ regulatory T cell depletion in the duodenal mucosa of coeliac patients. It is likely that the lack of the powerful suppressive activity of CD4+ CD25+ regulatory T cells may favour the loss of tolerance to gluten or to self-antigens, thus predisposing coeliac patients to the generation of an abnormal immune response. The observation that this depletion is not reverted by gluten-free diet (GFD) gives evidence for a primary defect of regulatory T-cells in coeliac disease. Strategies of manipulating the numbers or the activation status of CD4+ CD25+ regulatory T cells may offer potential therapeutic alternatives to GFD in this condition. CO033 HIGHER PREVALENCE OF FUNCTIONAL HYPOSPLENISM IN COELIAC PATIENTS WITH AUTOIMMUNE DISORDERS A. Di Sabatino, P. Cazzola, R. Ciccocioppo, L. Ricevuti, F. Biagi, J. Campanella, R. Morera, M. Bruni, G.R. Corazza Gastroenterology Unit, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy Background and aims. It is known that anatomical or functional asplenia may lead to autoimmunity and that anti-nuclear and anti-smooth muscle antibodies develop within months from splenectomy. Since coeliac disease (CD) is thought to be the commonest cause of non-surgical asplenia and is frequently associated with autoimmune diseases, we investigated whether the prevalence of functional hyposplenism was higher in CD patients with autoimmune disorders. Methods. Peripheral blood samples were obtained from 36 CD patients on a gluten-free diet for at least 12 months, 16 of them with associated autoimmune disorders (mean age 38.8 years, range 32–57) and 20 of them without autoimmune disorders (mean age 41.4 years, range 30–63), from 20 healthy volunteers (mean age 39.2 years, range 34–65) and from 22 patients who had had an elective splenectomy (mean age 37.7 years, range 21–74). Among the 16 CD patients with autoimmune disorders, 3 were affected by insulin-dependent diabetes mellitus, 5 by Hashimoto’s thyroiditis, four by dermatitis herpetiform, and 4 by connective tissue diseases. Splenic function was assessed by counting pitted red cells (PRC), which are red cells bearing membrane abnormalities as so-called pits. One drop of fresh venous blood was mixed with 1.5 ml 3% buffered-glutaraldehyde solution, pH 7.4. One thousand red cells were examined in a wet preparation (magnification 1000×) with a direct-interference contrast microscope equipped with Nomarsky optics. The percentage of PRC was calculated and taken as a measure of splenic function (upper limit of normal = 4%). Results. In CD patients with autoimmune disorders the median percentage of PRC (4.7%, range 2.1–12.0) was significantly higher when compared to that of CD patients without autoimmune disorders (3.1%, range 1.2– 5.2, P < 0.005) and healthy controls (0.5%, range 0–2.9, P < 0.0001). A significant difference was found between CD patients without autoimmune disorders and healthy controls (P < 0.0001). Ten of the 16 CD patients with autoimmune disorders (62.5%) and 4 of the 20 non-autoimmune CD patients (20.0%) had PRC values >4.0% and were considered to be hyposplenic. The median percentage of PRC in splenectomised patients was 15.1% (range 7.4–38.8). Conclusions. On the basis of our data, showing a higher prevalence of hyposplenism in CD associated with autoimmune disorders, it is possible to speculate that an impaired splenic function may predispose CD patients to an increased risk to develop autoimmunity.

Abstracts CO034 IMPAIRED SPLENIC FUNCTION IS ASSOCIATED WITH IMMUNOGLOBULIN M (IgM) MEMORY B CELL DEPLETION IN CROHN’S DISEASE A. Di Sabatino, R. Carsetti, P. Cazzola, R. Ciccocioppo, M.M. Rosado, R. Morera, L. Ricevuti, M. Bruni, G.R. Corazza Gastroenterology Unit, IRCCS Policlinico S. Matteo, Research Center Ospedale Bambino Gesù, University of Pavia, Rome, Italy Background and aims. IgM memory B cells, which are responsible for the protection against infections by encapsulated bacteria, require the spleen for their generation and survival. Since the association between inflammatory bowel disease, functional hyposplenism and the risk of overwhelming infection is well described, our aim was to verify whether circulating IgM memory B cells mirror the reduction of functional splenic tissue in Crohn’s disease. Methods. Peripheral blood samples were obtained from 31 patients with a firm diagnosis of Crohn’s disease, 29 healthy volunteers, and 20 patients who had had an elective splenectomy, all sex- and age-matched. Splenic function was assessed by counting pitted red cells (PRC), which are red cells bearing membrane abnormalities as so-called pits. Briefly, one drop of fresh venous blood was mixed with 1.5 ml 3% buffered-glutaraldehyde solution, pH 7.4. One thousand red cells were examined in a wet preparation (magnification 1000×) with a direct-interference contrast microscope equipped with Nomarsky optics. The percentage of PRC was calculated and taken as a measure of splenic function (upper limit of normal = 4%). For the phenotypic analysis of B cells, isolated mononuclear cells were stained with the appropriate antibody combinations of fluorescein, phycoerythrin, APC, cychrome, or biotin-labelled antibodies followed by streptavidin-cychrome and streptavidin-APC, and analysed on a FACSCalibur (Becton Dickinson). Results. In Crohn’s disease patients the median percentage of PRC (5.0%, range 1.4–14.8) was significantly (P < 0.001) higher than that of controls (0.9%, range 0.12–3.9) and lower than that of splenectomised patients (32.6%, range 21.3–45.7). Thirteen of 31 Crohn’s disease patients (41.9%) had PRC values >4.0% and were considered to be hyposplenic. IgM memory B cells were 45.9% of the B cells in the control group, but were significantly (P < 0.001) lower in hyposplenic Crohn’s disease patients (12.9%) and splenectomised patients (7.1%). Memory B cells showed no significant difference in eusplenic Crohn’s disease patients in comparison to controls. Conclusions. Our findings show that splenic hypofunction is closely associated with IgM memory B cell depletion in Crohn’s disease. Since IgM memory B cell defect causes a higher susceptibility to Streptococcus pneumoniae, detection of circulating IgM memory B cells could be used to discriminate between Crohn’s disease patients with a higher or lower risk of infection. CO035 SELECTIVE INHIBITION OF THE Na+ /H+ EXCHANGER AND OF THE Na+ -DEPENDENT Cl− / HCO3 − EXCHANGER REDUCES PROLIFERATION AND INDUCE APOPTOSIS IN CHOLANGYOCARCINOMA CELLS (HUH-28 CELLS) A. Di Sarioa , E. Bendiaa , A. Omenettia , M. Marzionia , S. De Minicisa , C. Candelaresia , H.W. Kleemannb , U. Schindlerb , A. Benedettia a Department

of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy b Aventis Pharma Deutschland GmbH, Frankfurt, Germany

Background/aim. Cells within the acidic extracellular environment of solid tumours maintain their intracellular pH (pHi) through the activity of membrane exchange mechanisms, such as the Na+ /H+ exchanger and the Na+ -dependent Cl− /HCO3 − exchanger. If these mechanisms are inhibited, the pHi of cells might be expected to establish equilibrium with

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the extracellular pH (pHe) with a consequent inhibition of growth. In this study, we evaluated, by means of spectrofluorimentry, the activity of the Na+ /H+ exchanger and of the Na+ -dependent Cl− /HCO3 − exchanger in a cholangyocarcinoma cell line (HUH-28 cells), and the effect of two novel and selective inhibitors (cariporide and S3705) on cell proliferation and apoptosis as a function of pHe (7.4 and 6.8). Methods/results. Cariporide and S3705 were able to inhibit their respective pHi regulatory mechanism (Na+ /H+ exchanger and the Na+ -dependent Cl− /HCO3 − exchanger, respectively). When HUH-28 cells were incubated for 24 h at pHe 7.4 or 6.8 in the absence of inhibitors they maintained pHi at physiological level. On the contrary, incubation with cariporide and S3705 at either pHe caused the pHi of the cells to drop. The ability of cariporide and S3705 to inhibit proliferation of HUH-28 cells was assessed by evaluating growth rate at different pHe (7.4 and 6.8) in the absence and presence of the agents, by measuring bromodeoxyuridine incorporation. As pHe decreased, HUH-28 cells showed decreased growth rate. At pHe 7.4, cariporide and S3705 alone were able to significantly reduce cell proliferation starting at a concentration of 50 mmol/l, with a maximal effect at 100 mmol/l. This effect was greater when cells were incubated with both inhibitors at the maximal concentration (70% inhibition). At pHe 6.8, the inhibitory effect of cariporide and S3705 alone on cell proliferation was evident already at a concentration of 10 mmol/l (25% inhibition) and reached the maximal effect at a concentration of 100 mmol/l (60% inhibition). When cells were incubated with both agents, the inhibition was 40% at 10 mmol/l and 80% at 100 mmol/l. Incubation of HUH-28 cells for 5 h with both cariporide and S3705 at pHe 7.4 was able to induce apoptosis, evaluated by Annessin-V staining, in a dose-dependent manner, with a maximal effect at a concentration of 100 mmol/l (22% apoptotic cells). The pro-apoptotic effect of the two inhibitors was more evident at pHe 6.8 (40% apoptotic cells). Conclusion. These results indicate that cariporide and S3705 are selective cytostatic and pro-apoptotic agents under in vitro conditions which reflect the acidic microenvironment found in solid tumours. CO036 REPEATED ACID EXPOSURE OF DISTAL OESOPHAGUS PROGRESSIVELY REDUCES THE EFFICACY OF OESOPHAGEAL CLEARANCE IN PATIENTS WITH GASTRO-OESOPHAGEAL REFLUX DISEASE (GERD): THE ROLE OF OESOPHAGEAL PERISTALSIS M. Di Stefano, S. Mazzocchi, A. Missanelli, E. Miceli, G.R. Corazza Gastroenterology Unit, IRCCS “S. Matteo” Hospital, University of Pavia, Pavia, Italy Background. Oesophageal clearance is an important protective factor against reflux-induced damage and impaired clearance is present in 50% of GERD patients. The 5-HT1A receptor agonist buspirone enhances oesophageal peristalsis. The aim of this study was to investigate the effect of repeated acid exposure of the distal oesophagus on efficacy of oesophageal clearance and the effect of increased peristalsis induced by buspirone. Methods. Twelve GERD patients and five HV underwent oesophageal manometry and distal oesophageal pH-monitoring in upright position. The manometric and pH catheters were inserted through the nostril and, through a perfusion channel positioned 5 cm above LES, 10 perfusions of 5 cm3 of water followed by a further 10 perfusions of 5 cm3 of acid 0.1 N were performed. Oesophageal waves were detected at 3, 8, 13, 18 cm from LES and pH values 3 cm above LES. Then buspirone 10 mg was given orally and perfusions were repeated. Acid clearance time was calculated as time needed to return to pre-infusion pH values. The number of spontaneous swallows was also monitored. Results. In HV, the 10th exposure time did not differ from the 1st (162 ± 90 versus 174 ± 88). In GERD patients, acid clearance time prolonged progressively with increasing number of perfusions. The 10th

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exposure time was significantly longer than the first (333 ± 206 s versus 188 ± 126 s, P < 0.003), and the average clearance time was significantly longer in GERD compared to HV (264 ± 134 s versus 185 ± 105 s; P < 0.05). Peristaltic wave amplitude and duration showed no significant difference between GERD and HV (78±30 mmHg versus 116±19 mmHg; 6 ± 2 s versus 5 ± 3 s), but the mean number of swallows after each perfusion did not differ between GERD and HV (6 ± 3 versus 5 ± 5) and the total number of swallows/min was significantly lower in GERD than in HV (1.0 ± 0.8 swallows/min versus 1.9 ± 0.6 swallows/min; P < 0.05). Buspirone significantly increased wave amplitude both in GERD (103± 33 mmHg; P < 0.05) and in HV (145 ± 90; P < 0.05) but did not affect acid exposure time (140 ± 28 s versus 185 ± 21 s in HV and 277 ± 102 s versus 256 ± 131 s at the 10th perfusion in GERD). Conclusions. In GERD, repeated acid exposure of the distal oesophagus induces a progressively slower acid clearance. Swallowing frequency seemed a major determinant of clearance and, consequently, an increase in peristaltic amplitude by buspirone failed to improve acid clearance. CO037 THE ROLE OF HYPERSENSITIVITY TO COLONIC GAS IN THE PATHOPHYSIOLOGY OF SYMPTOMS IN FUNCTIONAL PATIENTS M. Di Stefano, E. Miceli, A. Missanelli, S. Mazzocchi, G.R. Corazza Gastroenterology Unit, IRCCS “S. Matteo” Hospital, University of Pavia, Pavia, Italy Background and aims. Colonic fermentation has been shown to affect upper GI motility. A relaxation of the gastric fundus occurs when lactulose is fermented at colonic level. The existence of long reflexes is also known since both duodenal and jejunal distension induces gastric relaxation. On the contrary, no data are available on the effect of colonic fermentation on sensitivity. As functional patients show gas related symptoms without excessive gas production, we tested whether hypersensitivity to gas is present in these patients. Patients and methods. Five patients (one female II criteria) and five matched healthy volunteers (HV), all hydrogen (H2 ) producers, underwent two rectal barostat tests. After minimal distension pressure (MDP) determination, rectal distensions (2 mmHg steps for 2 min) were performed and perception and discomfort threshold were calculated. A 250 ml solution containing 10 g of lactulose (Lact), a non-absorbable carbohydrate fermented by colonic flora, or a 250 ml non-absorbable iso-osmotic electrolyte solution (ES) were then administered in random order. When a sustained increase of breath H2 excretion was detected, distensions were repeated. In the control test, 10 g of barium were added to the ES and distensions started after the arrival of the barium in the caecum at X-ray. Symptoms (abdominal pain, bloating, borborygmi, nausea) were monitored by VAS. Results. In HV, basal and post-solution thresholds for perception and discomfort were not altered by ES (11 ± 7 versus 9 ± 7; 25 ± 4 versus 24 ± 5, respectively) or Lact (4 ± 3 versus 2 ± 1; 28 ± 17 versus 24 ± 14, respectively). In patients, both ES (6.75 ± 4 mmHg + MDP versus 3.5 ± 2 mmHg+MDP, P < 0.05) and Lact (6±4 versus 2±2, P < 0.05) tended to induce a reduction in thresholds for perception, which did not differ between both solutions. Basal and post-solution discomfort thresholds were not altered by ES (17±11 versus 16.5±6), but significantly lowered by Lact (16 ± 8 versus 9.5 ± 6, P < 0.05). The extent of the decrease was significantly higher after Lact (0.5±0.5 versus 6.5±3, P < 0.05). Severity of bloating at perception or discomfort threshold was significantly higher in patients after Lact (3 ± 1 versus 3.5 ± 1 and 5 ± 1 versus 5.5 ± 1, respectively) compared to ES (1 ± 1 versus 1.5 ± 1 and 2 ± 1 versus 2.5±1, respectively, all P < 0.05) while no difference was present in HV. Conclusion. Patients with functional bloating are characterised by rectal hypersensitivity during colonic gas fermentation.

CO038 EFFECT OF BUSPIRONE, A 5HT1A RECEPTOR AGONIST, ON OESOPHAGEAL PERISTALSIS AND LOWER OESOPHAGEAL SPHINCTER FUNCTION IN HEALTHY VOLUNTEERS M. Di Stefano, R. Vos, D. Sifrim, J. Janssens, J. Tack Center for Gastroenterological Research, K.U. Leuven, Belgium Background. In the enteric nervous system, 5HT1A receptors mediate both pre-synaptic and post-synaptic neuronal inhibition. Recent data suggest that 5-HT1A receptor activation in man alters both gastric and small intestinal motility in man, but the effect on oesophageal motility has not been studied. The aim of the present study was to investigate the influence of the 5-HT1A receptor buspirone on oesophageal peristalsis and lower oesophageal sphincter (LES) function in man. Methods. Oesophageal motor activity was studied in 20 healthy volunteers (mean age 26 ± 4 years) using a water-perfused manometric catheter with four axial channels at 5 cm intervals proximal to a 6-cm sleeve sensor. After an overnight fast, the manometric catheter was introduced through the mouth and positioned with the sleeve straddling the LES. After a basal series of 10 swallows of 5 cm3 of water, placebo or buspirone 20 mg (n = 10 each) was administered orally and another 3 series of wet swallows were performed after 10, 30 and 60 min. Mean distal oesophageal peristaltic wave amplitude and duration, as well as LES pressure, LES pressure decrease and residual pressure during swallowing were calculated. Data were compared using ANOVA. Results. The protocol and drug administration were well tolerated. Placebo had no significant effect on motility parameters. Buspirone significantly increased mean oesophageal body wave amplitude (145.7 ± 49 mmHg versus 120.3 ± 49 mmHg, P < 0.05) and duration (7.7 ± 0.3 s versus 8.0 ± 0.3 s; P < 0.05). Buspirone increased basal LES pressure (26 ± 5 mmHg versus 21 ± 5 mmHg, P = 0.04) and mean residual pressure (6.99 ± 1.0 mmHg versus 2.06 ± 0.3 mmHg, P < 0.0001). Buspirone reduced mean percent pressure decrease during relaxation (74.8 ± 3.5% versus 89.3±1.7%, P < 0.0001) and mean duration of relaxation (7.7±1.5 versus 8.0 ± 1.4, P < 0.02). Conclusions. The 5-HT1A receptor agonist buspirone increases oesophageal peristalsis and LES pressure and reduces the duration and the extent of LES relaxation. These observations suggest a potential for 5-HT1A receptor agonists in the treatment of impaired oesophageal motility. CO039 THE STROMAL EXPRESSION OF C-KIT POSITIVE INTERSTITIAL CELLS OF CAJAL IN GERD: A POSSIBLE RELEVANT PHYSIOPATHOLOGICAL ROLE L. Dugheraa , D. Tibaudia , E. Battagliaa , A. Repicib , A. Serraa , M. Navinoa , A. Sapinoc , G. Bassottid , G. Bellonea , G. Emanuellia a Department

of Clinical Physiopathology, University of Turin, Turin, Italy of Gastroenterology, University of Turin, Turin, Italy c Department of Pathology, University of Turin, Turin, Italy d Department of Gastroenterology, Univerity of Perugia, Perugia, Italy b Department

Interstitial cells of Cajal (ICC) plays an important role in the control of gastrointestinal motility: generating electrical slow waves, the ICC are intercalated between the intramural neurons and the effector smooth muscle cells within the submucosa and muscle layers to form the gastroenteric pacemaker system. It has been found that both increase or decrease of ICC is associated with dysmotility symptoms in several gastroenteric disorders; moreover, tissue inflammation suppresses phasic contractile activity in vivo and this could be in part due to specific structural alterations or distribution of ICC. Since ICC express on their surface the tyrosine kinase receptor Kit, c-Kit immunochemistry appears to be an excellent technique for their labelling in the gastrointestinal tract. The aim of this study was to examine the presence and distribution of c-Kit immunoreac-

Abstracts tivity in oesophageal mucosa of patients affected by gastro-oesophageal acid disease (GERD). Material and methods. Sixty patients with clinical history of GERD underwent upper endoscopy and oesophageal manometry; in all subjects tissue samples were obtained, both in absence and in presence of oesophagitis and/or intestinal metaplasia by a jumbo forceps and ICC were identified by c-Kit positive immunoreactivity and the absence of alpha-actin immunostaining. Results. At endoscopy and histology 30 patients showed mild to severe oesophagitis, 20 intestinal metaplasia and 8 metaplasia with dysplasia. According to our previous findings, most of patients with oesophagitis or intestinal metaplasia showed manometric dysmotility patterns, mainly depicted as ineffective oesophageal motility (IEM). The c-Kit immunoreactivity has been identified mainly in the squamous epithelial stroma in oesophagitis specimens, both in epithelial and in glandular stroma in metaplasia and, rarely, into muscolaris mucosa in both. The c-Kit expression was stronger in specimens with oesophagitis and/or metaplasia compared to those of normal subjects; moreover, a positive correlation was also found between immunohistochemical c-Kit expression and IEM at manometric examination. This is the first study describing c-Kit positive ICC within the epithelial stroma and these finding might suggest a pathogenic role for inflammation in the ICC dysregulation that finally lead to well-defined dysmotility patterns associated to GERD. CO040 GLIADIN-INDUCED OXIDATIVE STRESS THREE-DIMENSIONAL CELL CULTURES

IN

TWO-

AND

L. Ellia,b , E. Dolfinib , L. Roncoronia,b , M.P. Colleonic , B. Costad , S. Ramponie , V. Lorussoe , M.L. Falinif , A. Varnierb , M.T. Bardellaa a IRCCS

Ospedale Maggiore, University of Milan, Milan, Italy of Biology and Genetics for Health Sciences, University of Milan, Milan, Italy c Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy d Department of Biotechnology and Bioscience, University of Milan-Bicocca, Milan, Italy e Milan Research Centre, Bracco spa, Milan, Italy f Department of Agrifood Molecular Science, University of Milan, Milan, Italy b Department

Background and aim. It is known that gliadin has direct cytotoxic effects on different cell lines. The mechanism of the damage is not completely understood but previous in vitro studies suggested an over-production of free radicals and disruption of the redox equilibrium. Our aim is to evaluate the oxidative stress in the “in vivo-like” three-dimensional cell cultures (multicellular spheroids, MCS) in comparison with the conventional two-dimensional cultures. Materials and methods. Two- and three-dimensionally grown Lovo cell lines (colic adenocarcinoma) have been cultured without (controls) and with peptic-tryptic digested bread wheat gliadin at a concentration of 500 ␮g/ml. Cell viability (colony-forming assay), cell concentrations (in two-dimensional cultures), diameters and volumes of spheroids (in MCS), LDH release, reduced glutathione (GSH) cytosolic content and activity of glutathione-related enzymes (peroxidase GPOX, S-transferase GST, and reductase GSR) were evaluated in untreated and treated cultures. Results. In comparison with controls the gliadin-treated cultures showed a significantly (P < 0.05) inhibited cell viability (range 20–80%) in both the systems. MCS did not change in diameters and volumes. LDH concentration was two-fold increased in the medium from treated cultures. GSH content was decreased in both two- and three-dimensional systems (34 and 21% versus controls, respectively). The activity of glutathione-related enzymes was significantly inhibited in MCS (GPOX of about 31%, GST of 31%, GSR 47% versus control) and in two-dimensional cultures (GPOX 29%, GST 39%, GSR 30% versus control) (Fig. 1).

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Conclusions. In both cell cultures systems, two- and three-dimensional, a gliadin-induced oxidative damage has been observed. These data pinpoint the role of cytotoxic effects directly induced by gliadin on epithelial cells and support the hypothesis that gliadin-enterocytes interaction could play an important role in the initial steps of pathogenic mechanism of gluten intolerance. CO041 ROLE OF HIATUS HERNIA AND OF PERISTALTIC DYSFUNCTION ON INTRAOESOPHAGEAL DISTRIBUTION OF REFLUXED ACID IN GERD PATIENTS S. Emerenziania , F.I. Habibb , M. Ribolsia , M.P.L. Guarinoa , R. Cavigliaa , T. Petittia , M. Cicalaa a Dipartimento

Malattie Apparato Digerente, Università Campus Bio Medico, Italy b Dipartimento Scienze Cliniche, Università La Sapienza, Rome, Italy

Proximal oesophageal spread of acid is a major determinant of reflux perception both in erosive (EE) and non-erosive (NERD) GERD patients [1]. GERD patients with hiatus hernia (HH) show a wider opening of the relaxed oesophagogastric junction [2]. To assess the role of HH and ineffective oesophageal motility (IEM) [3] on dynamic characteristics of acid reflux, 41 consecutive GERD patients (24 NERD, 17 EE) underwent manometry, multisensor 24 h pH test and videofluoroscopy. Based upon manometry, the four pH sensors were placed at gastric level, 5 cm above LES, 10 and 3 cm below UES. Propagated (proximal) reflux is defined elsewhere [1]. Acid exposure time (AET) at 5 cm above LES >4.5% of total recording time, at 10 and 3 cm below UES >95th percentile values (0.9 and 0.8%) of 15 asymptomatic controls were considered abnormal. Multivariate logistic regression and ANOVA were used for statistical analysis. Results. Fluoroscopy confirmed the presence of HH (>2 cm) in 11 patients (five NERD, six EE). Reflux events (4732) were analysed. Hypotensive LES was not significantly associated with a pathological, distal and proximal, AET. IEM, found in 14/41 patients, was associated (odds ratio 16.2, P < 0.02) with a pathological AET of the distal oesophagus only. Presence of HH perfectly predicted a pathological distal AET and was associated to higher percentage of proximal reflux (25% versus 14%, P < 0.05). Overall risk of proximal reflux, controlled for reflux duration (OR) was 1.8 (1.5–2.3) in HH patients. Figure shows the occurrence of proximal reflux, in HH and non-HH patients, according to reflux duration at 5 cm below LES. Short-lasting refluxes were highly propagated. Symptom-reflux association (SAP) was not significantly different between groups (HH, IEM, EE). The effect of HH on proximal reflux did not differ in NERD and EE. Conclusions. Of the considered variables, HH has the greater impact on the proximal distribution of acid refluxate, irrespective of the presence of EE. If this finding is confirmed in larger series, presence of HH would have relevant implications in the treatment strategies for GERD symptoms. References [1] Cicala, et al. Aliment Pharmacol Ther 2003. [2] Pandolfino, et al. Gastroenterology 2003. [3] Leite, et al. Dig Dis Sci 1997.

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CO042 PROGNOSTIC VALUE OF A SINGLE HEPATIC VENOUS PRESSURE GRADIENT MEASUREMENT IN CIRRHOTIC PATIENTS F.M. Fabris, A. Dell’Era, R. de Franchis, F. Salerno, A. Sangiovanni, G. Borroni, S. Visentin, A. Nicolini, G. Meregaglia, F. Iannuzzi, M. Primignani Department of Internal Medicine and Radiology Service, IRCCS Ospedale Maggiore of Milan, Milan, Italy Background and aims. Although high HVPG values have been associated with an increased risk of death and/or bleeding, the usefulness of HVPG measurement in clinical practice is still controversial. We assessed whether a single HVPG measurement can predict death or bleeding in cirrhotic patients or improve the efficiency of other, non-invasive, prognostic indexes such as the Child–Pugh classification (for survival) or the NIEC score (for bleeding). Patients and methods. Eighty-eight cirrhotic patients with portal hypertension, without recent bleeding (<6 weeks) or HCC (55 males, mean age 58±10 years; Child–Pugh class: 37A, 39B, 12C) submitted to HVPG measurement from October 1992 to June 2003 were evaluated. Actuarial probability of survival was assessed by Kaplan–Meier plots. Independent predictors of death were identified by Cox’s regression model. Results. During a median follow-up of 455 days (range 27–2350), death occurred in 17 of 88 patients (19%). Child–Pugh score (9.2 ± 1.5 versus 6.8 ± 1.6, P = 0.0001) and HVPG (22.9 ± 5.3 mmHg versus 17.5 ± 6.3 mmHg, P = 0.003) were higher in non-survivors as compared to survivors. At univariate analysis, Child–Pugh score (P < 0.0001), ascites (P = 0.0002) and HVPG (P < 0.0001) were the only variables predicting death. At multivariate analysis, only Child–Pugh score (P = 0.004) and HVPG (P = 0.004) maintained independent prognostic significance. Death occurred only among Child–Pugh B and C patients with HVPG ≥16 mmHg. Bleeding occurred in six patients (Child–Pugh class: 2A, 3B, 1C; bleeding risk, according to NIEC index: 10–56% in 1 year) all with HVPG ≥16 mmHg. The small number of bleeding events precluded statistical evaluation. Conclusions. The severity of cirrhosis and of portal hypertension (respectively, assessed by the Child–Pugh score and the HVPG value) are the only independent predictors for death. Death and bleeding occurred only in patients with HVPG ≥16 mmHg. A single HVPG measurement can improve the predictive efficiency of other prognostic indexes such as the Child–Pugh classification or the NIEC score. CO043 NATURAL HISTORY OF GALLSTONE DISEASE: EXPECTANT MANAGEMENT OR ACTIVE TREATMENT? RESULTS FROM A POPULATION-BASED COHORT STUDY (THE MULTICENTRE ITALIAN STUDY OF CHOLELITHIASIS, MICOL) D. Festia , A. Colecchiaa , E. Rodaa , A.F. Attilib , P. Loriac , N. Carullic , S. Capodicasad , F. Romanod a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Department of Gastroenterology, University of Rome, Rome, Italy c Department of Internal Medicine, University of Modena, Modena, Italy d Department of Medicine and Aging, University of Chieti, Chieti, Italy

Background. Cholecystectomy represents the gold standard for most of the symptomatic gallstones; according to several guidelines. However, an increased cholecystectomy rate has been recently documented, suggesting the presence of an unjustified extension of the indications for this procedure. Aim. To evaluate the natural history (frequency and characteristics of symptoms and clinical outcome) of gallstone disease (GS) in a population-based cohort study.

Methods. Subjects (11,229) (6610 males, 4619 females, age range 29–69 years, mean age: 48 years) were studied by five different operative units. At ultrasonography, GS were present in 793 (338 males, 455 females) out of 11,229 (7.1%,) subjects. GS were followed at 4 year interval by means of a questionnaire inquiring the presence and characteristics of specific biliary symptoms: according to a previous study [1], symptoms were defined as: mild, when pain was present only at right hypocondrium/epigastrium, not forcing to rest, and severe when pain forced to rest. Results. At enrolment, 580 (73.1%) patients were without, 94 (11.8%) with mild and 119 (15.0%) with severe symptoms. GS patients were followed up for a mean time of 6.8 years. Patients (183, 23%) were cholecystectomised. The table shows the percentage of variations in symptom severity and cholecystectomy rate (% CC).

Enrolment

Follow-up No symptoms (% GS)

Mild symptoms

(% CC) (% GS)

No symptoms (n = 580) 78.1 10.7 Mild symptoms (n = 94) 58.0, 23.5 Severe symptoms (n = 119) 51.8, 27.9

Severe symptoms

(% CC) (% GS) (% CC)

10.5 33.8 17.0 46.7 16.9, 28.6

11.4 25.0 31.3

56.3 90.9 53.8

Distribution of the 183 cholecystectomies by GS severity was: 41.5% in asymptomatic,18.0% in mild and 40.5% in severe symptoms. Conclusions. This study indicates that: (a) asymptomatic and symptomatic GS have a benign natural history; (b) most of the GS with severe or mild symptoms will no more experience biliary pain; (c) most of the cholecystectomies were performed in asymptomatic GS. Therefore, expectant management still represents a valid therapeutic approach in most of the GS patients. Reference [1] Hepatology 1999;30:839–46.

CO044 OUTCOME OF LAPAROSCOPIC VERSUS LAPAROTOMIC CHOLECYSTECTOMY: A POPULATION-BASED MORTALITY COHORT STUDY D. Festia , A. Vestitoa , A. Colecchiaa , M.P. Fantinib , M. Bossob , M. Clob , D. Fuscoc , C.A. Peruccic a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Department of Medicine and Public Health, University of Bologna, Bologna, Italy c Department of Epidemiology, ASL RM E, Rome, Italy Background. Cholecystectomy (laparoscopic, LC or open, OC) is the preferred treatment in patients with symptomatic gallstones. Few controlled studies compare LC and OC in terms of efficacy. Aim. To compare LC and OC by a population-based mortality cohort study. Methods. Discharge records, Emilia Romagna Regional Health System (Italy), 1998–2002, including individual information on patient discharged from public or private hospitals, coded according to ICDIX-CM. Inclusion criteria. OL and LC (51.22–23), cholelithiasis (574), age <18, and residence in the region. Exclusion criteria: diagnosis of tumours (140– 239), pregnancy and new-borns (MDC 14, 15), trauma (800–999), surgical procedures associated with incidental secondary cholelithiasis. Comorbidity included diagnoses of chronic diseases during index and previous (12 months preceding cholecystectomy) hospital admissions. Severity of cholelithiasis also included. Outcome: 30-day mortality, ascertained by linking hospital records with death certificate registry. Logistic regression and multilevel models to adjust for confounding and to detect interac-

Abstracts tion by demographic characteristics, comorbidity, and severity of disease. Study population: 16,526 LC and 7457 OC, in 83 hospitals. Results. Procedure-specific mortality risk: 0.01 for OC and 0.0011 for LC. Crude OR = 0.09 (95% CI, 0.05–0.15) for LC versus OC. Risk adjustment evaluated fitting logistic regression models to the observed data, selecting significant variables by stepwise method based on the Akaike Information Criterion. The final general risk adjustment model includes: gender, severe non-ischaemic heart disease, chronic renal disease, other chronic diseases (liver, pancreatic), and severity of cholelithiasis. Age acts as an effect modifier. Therefore, risk adjusted ORs for LC versus OC were estimated separately for age strata. Adjusted OR for LC versus OC ranged from OR = 0.11 (95% CI, 0.04–0.25) for age <70 to OR = 0.28 (95% CI, 0.12–0.66) for age over 70. Conclusion. LC is associated with a lower mortality compared with OC. The strong crude protective effect was significantly reduced by adjusting for comorbidities and severity of disease. The advantage of LC seems greater for age <70. Although the results support the hypothesis that LC is more effective than OC, the outcome of this study cannot exclude that the observed lower mortality after LC is actually due to selective patient characteristics that cannot be detected by available hospital discharge forms. Given the limited evidence of efficacy for LC versus OC from RCTs, results from observational outcome studies provide the best possible evidence of effectiveness. CO045 CELECOXIB INHIBITS ACETHYLATED COX-2 IN THE GASTRIC MUCOSA AND ENHANCES GASTRIC INJURY CAUSED BY ASPIRIN IN ARTHRITIC RATS. EVIDENCE FOR A PROTECTIVE ROLE OF NO-RELEASING ASPIRIN (NCX-4016) S. Fiorucci, A.R. Di Lorenzo, E. Antonelli, E. Distrutti, M. Baldoni, A. Morelli Gatsroenterologia, University of Perugia, Via E dal Pozzo 06122, Perugia, Italy Background. Aspirin acetylates COX-2, enabling the conversion of arachidonic acid to 15(R)-epi-lipoxin A4, or aspirin triggered lipoxin (ATL). Selective COX-2 inhibitors block ATL formation and exacerbate mucosal injury in aspirin taking volunteers. NCX-4016 is a NO-releasing aspirin that exerts anti-platelet effects without causing gastric damage. Aims. To investigate gastric safety, ATL generation and anti-inflammatory activity of NCX-4016 and aspirin administered in combination with celecoxib in a rodent model of arthritis. Methods. Arthritis was induced in male Lewis rats by s.c. injection of Freund’s complete adjuvant (FCA). Rats were administered orally with aspirin (30 mg/kg) and NCX-4016 (45 mg/kg) alone or in combination with celecoxib (30 mg/kg), from days 7 to 21. Arthritis activity was assessed by scoring the hindpaw oedema, the number of tail nodules, animal weight and plasma concentration of IL-1beta. The gastric mucosa was examined for macroscopic lesions and MPO activity. COX-1 and COX-2 expression was assessed by RT-PCR and Western blot analyses and gastric PGE2 and ATL levels and plasma concentrations of TXB2 measured. Results. Aspirin and NCX-4016, alone or in combination with celecoxib, but not aspirin, reduced the plasma levels of IL-1beta and tail nodules (P < 0.01 versus arthritic). Only co-administration of aspirin or NCX-4016 with celecoxib was effective in reducing hindpaw oedema (P < 0.01). In contrast to aspirin, NCX-4016 slightly down-regulated gastric COX-2 expression, but it was still effective in triggering ATL synthesis (82 ± 14 pg/mg versus 11 ± 4 pg/mg of protein by arthritic, P < 0.05). Administration of celecoxib in combination with aspirin increased the severity of gastric damage induced by aspirin from 7.2 ± 1.8 mm to 20.8 ± 2 mm versus (P < 0.01). In contrast, no damage was seen in animals treated with NCX-4016 plus celecoxib (1.1 ± 0.5 mm) respect to aspirin plus celecoxib (20.8 ± 2.0 mm, P < 0.01). Both aspirin and NCX-4016, alone or in combination with celecoxib, inhibited gastric PGE2 (P < 0.001 versus arthritic, N = 6/group) and TXB2 (P < 0.01 versus arthritic/group).

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Conclusions. These studies support the notion that NCX-4016 might represent an alternative to aspirin for cardioprotection in arthritic patients taking selective COX-2 inhibitors. CO046 GASTROINTESTINAL SAFETY AND ANTI-INFLA- MMATORY ACTIVITY OF HCT-1026, NO-RELEA- SING FLURBIPROFEN, IN HEALTHY HUMANS VOLUNTEERS: A PROOF OF THE CONCEPT THAT NO-RELEASING NSAIDS SPARE THE STOMACH WHILE INHIBIT CYCLO-OXYGENASE 1 AND 2 S. Fioruccia,b , L. Santuccia,b , A. Mencarellia,b , A. Franzionic , E. Distruttia,b , M. Baldonia,b , P. del Soldatod , A. Morellia,b a Clinica

di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Via E. Dal Pozzo, I-06126 Perugia, Italy b Divisione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna, Università di Perugia, Via E. Dal Pozzo, I-06126 Perugia, Italy c CroAlliance, Lugano, Switzerland d Nicox SA, Espace Gaia II, Batiment I BP 313, Sophia Antipolis, France Background. HCT-1026 is a nitric oxide (NO)-releasing derivative of flurbiprofen. Aims. To investigate the effect of HCT-1026 on gastrointestinal mucosa and COX-1 and COX-2 activity in healthy human volunteers. Methods. We enrolled in a parallel-group, double-blind, placebo controlled study, 32 healthy subjects were randomly allocated to receive 7 days treatment with HCT-1026 (100 and 150 mg b.i.d.), flurbiprofen (100 mg b.i.d.) or placebo. Upper endoscopies were performed before and at the end of treatment period and gastroduodenal lesions assessed using a pre-specified scoring system. Basal and post-treatment platelet aggregation in response to arachidonic acid (AA), TXB2 plasma levels and ex vivo generation of PGE2 and IL-6 in response to endotoxin were assessed. Results. Flurbiprofen administration caused gastric and duodenal damage (total mean endoscopic score of 17.6 ± 2.0, P < 0.001 versus placebo). Administration of HCT-1026 resulted in a significant attenuation of gastrointestinal damage: mean endoscopic score were 7.0±1.9 and 8.0±11.7 with 150 mg/bid (i.e. equimolar to 100 mg/bid flurbiprofen) and 100 mg bid HCT-1026, respectively. Flurbiprofen and HCT-1026, 150 and 100 mg bid, caused 96, 95 and 96% inhibition of platelet aggregation induced by AA and >99% inhibition of in vivo TXB2 formation and >85% reduction of urinary 11-DH-TXB2 excretion. All drugs inhibited ex vivo generation of PGE2 as well as gastric PGE2 and 6-K-PGF1. Finally, HCT-1026, 100 mg/bid but not flurbiprofen, inhibited endotoxin-induced IL-6 release from isolated granulocytes. Conclusions. HCT-1026 is a potent COX-1 and COX-2 inhibitor. In comparison with flurbiprofen HCT-1026 causes 80–100% reduction of gastric/duodenal ulcers. This data confirm that addition of an NO-releasing moiety to NSAIDs is an effective strategy to reduce gastrointestinal damage in humans. CO047 HEPATIC CHIMERISM IN PATIENTS WITH GENDERMISMATCH LIVER TRANSPLANTATION S. Gaiaa,b , S. Cappiaa,b , E. Bacilloa,b , E. Gaiaa,b , A. Smedilea,b , A. Marzanoa,b , A. Oliveroa,b , M.L. Abatia,b , L. Gubittaa,b , M. Rizzettoa,b a Department b Department

of Gastroenterology, Molinette Hospital, Turin, Italy of Anatomy Pathology, San Luigi Hospital, Orbassano, Italy

Background and aims. Haematopoietic stem-cells can trans-differentiate into hepatocytes. Liver biopsies (LBs) from males transplanted with liver from female donors were analysed in order to characterise hepatic chimerism (Y-positive hepatocytes in XY recipients of XX donors) in different clinical situations.

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Material and methods. Twelve needle LBs (performed after whole or split LT in five male recipients and two not-transplanted controls), were analysed. Hepatocytes identification was obtained through epithelial cytokeratines (AE1-AE3clone, DakoCytomation, Denmark) immunohistochemical staining, Y-chromosome presence through FISH. Probes for X-chromosomes were conjugated to fluorescein and Y-chromosomes to rhodamine. Slides were counterstained with DAPI for nucleus staining. Contemporary fluorescent and optical light of the confocal microscope was used by two independent operators to identify and assess the degree of hepatic chimerism. Results. In male and female controls a clear Y-chromosome signal in hepatocytes was detected in 67% (correction factor) and 0, respectively. In 9 (90%) of the XY recipients’ biopsies, Y-positive hepatocytes were founded. Their percentage ranged between 2.3 and 25‰ of hepatocytes (table). They were identified as isolated single cells in nine biopsies and in a small groups of three cells one specimen. No correlation was found between grade of inflammation and number of Y-positive hepatocytes. LBs from split liver seems to have a higher rate than whole LT. Conclusions. This work confirms that in humans, stem cell derived from recipient can occur and differentiate into hepatocytes in liver graft. The degree of intra-graft tissue chimerism of extra-hepatic origin cells is 2.3– 25‰ of all hepatocytes. They are isolated and scattered through the hepatic lobules and rarely observed in groups (cluster-like) of side by side cells. CO048 EFFECTS OF MODIFIED SHAM FEEDING ON GHRELIN LEVELS IN HEALTHY HUMAN SUBJECTS C. Gebbiaa , M. Arosiob , D. Contea , C. Vescarellia , C. Ronchib , P. Beck-Peccozb , M. Peracchia a Gastroenterology

Unit, Department of Medical Sciences, University of Milan, IRCCS-Ospedale Maggiore, Milan, Italy b Institute of Endocrine Sciences, University of Milan, IRCCS-Ospedale Maggiore, Milan, Italy

Background and aim. Ghrelin is a gut-brain hormone with orexigenic, gastro-entero-pancreatic and endocrine effects. Pre-prandial rises and post-prandial falls in circulating ghrelin levels have been described in humans. Several studies have confirmed that feeding decreases ghrelin concentrations, but the mechanisms involved in these modifications are yet unknown. Many hormonal and metabolic responses to nutrient intake begin during the cephalic, or preabsorptive phase, mostly mediated by vagal activation. The aim of the present study was to investigate, in healthy subjects, the effect on ghrelin secretion of cephalic phase stimulation, achieved by modified sham feeding (MSF), in which foods are smelled, chewed and tasted but not swallowed. Plasma pancreatic polypeptide (PP) response to MSF was also assayed as indicator of successful cephalic-vagal stimulation. Material and methods. Seven healthy volunteers (four male and three female, aged 23–35 years, mean 29, with normal BMI) were studied after an overnight fasting. Blood samples for ghrelin, PP, insulin and glucose assays, were taken at times −30, 0, 15, 30, 45, 60, 90 and 120 min. Statistical analysis was carried out by repeated measures of ANOVA followed by Student–Newman–Keuls test. Results. Ghrelin levels increased from time −30 min to time 0 (from 226±38.4 to 260±26.6 pmol/l, P < 0.05), and then significantly decreased reaching a nadir of 148±27.3 pmol/l at 30 min (P < 0.001). As expected, PP concentrations promptly increased after MSF from 17 ± 2.6 to 31 ± 1.5 pmol/l (P < 0.01). Both insulin and glucose levels did not significantly change from baseline. Conclusions. This study demonstrates for the first time in humans that circulating ghrelin concentration are decreased by MSF. These findings underline the importance of cephalic response to nutrients intake, thus the role of vagal activity, in the ghrelin secretion control.

CO049 EARLY EVALUATION OF HCC TREATED WITH RFTA: CONTRAST-US TO PREDICT LOCAL RECURRENCE F. Giangregorio, M. Di Stasi, M.G. Marinone, G. Sbolli, P. Tansini, F. Fornari Divisione di Gastroenterologia, Ospedale “G. da Saliceto”, Piacenza, Italy Aim. To assess the efficacy of the contrast-enhanced harmonic ultrasonography (CEUS) as early predictor of local regrowth of HCC nodules with complete necrosis after percutaneous-radiofrequency-thermal-ablation (RFTA). Material and methods. One hundred and twenty-seven consecutive cirrhotic patients (M/F: 74/53; mean age 77.5; child A/B: 121/6; 91.1% HCV-positive) affected from HCC were submitted to RFTA. Pre-treatment-US identified 139 lesions. CEUS was performed using a suspension of sulphur hexafluoride in sterile saline (SonoVue, Bracco), as contrast agent, and two machines (Esatune and Technos-MPX, Esaote) with a new harmonic sonography (called CnTI). Positive enhancement in the early arterial phase was interpreted as residual viable tumour after treatment. US and CT-follow-up were performed every 3 months. During the arterial phase of the CEUS after treatment we studied the following features of the hyperechoic peripheral rim: margin regularity, mean thickness, and its persistence in the later phases. We correlated these data with the HCC vascular pre-treatment patterns and with the time of local regrowth of the tumour during the follow-up. Results. The post-treatment evaluation of the 139 nodules showed an incomplete necrosis in 17 nodules and a complete necrosis in 122 nodules. During the follow-up (mean time: 12 months), 21/122 nodules (17.2%), efficaciously treated, showed a local recurrence. In all these cases either a thickness (>4 mm) or irregular margins of the hyperchoic rim were observed 24 h after RFTA. Conclusion. An early evaluation of HCC treated with RFTA using CEUS may predict an early local recurrence by visualising a thickened and irregular hyperechoic rim. CO050 THE ANIONIC POLYPEPTIDE FRACTION IS PRESENT ON THE GALLBLADDER APICAL EPITHELIUM AND FAVOURS BILIARY CHOLESTEROL ABSORPTION S. Ginanni Corradinia , F. Liguoria , N. Domingob , G. Tebalac , C. Ripania , R. De Marcoa , M. Sicilianoa , M.A. Meinic , P. Lechˆene dela Porteb , D. Laironb , H. Lafontb , A.F. Attilia a Div.

Gastro., Dip. Clin. Med., Univ. La Sapienza, Italy Unité 476, Marseille, France c Dip. Chir., Aurelia Hosp., Rome, Italy b Inserm

Background. The anionic polypeptide fraction (APF) favours free cholesterol (Ch) transport in bile, is one of the most abundant biliary proteins and regulates in vitro Ch absorption by the brush border membrane vescicles of the intestinal epithelium [1]. Gallbladder absorption of biliary Ch could be of physiologyical relevance to Ch haemostasis and involved in gallstone pathogenesis [2]. Aims. We investigated in vivo the absorbtion/secretion patterns by the gallbladder of APF, total proteins and Ch. Methods. Female pigs were anaesthetised, a soft catheter was inserted through the cystic duct and secured. The native bile was substituted with a standard pig natural bile, previously radiolabelled with 14 C-Ch. Two series of experiments were performed using the same standard pig bile with different dilutions and with or without addition of non-radiolabelled Ch: group A (n = 3; 4.4 mM Ch; CSI 1.6); group B (n = 3; 0.2 mM Ch; CSI 1.7). Bile volume, Ch, total proteins (BCA method) and APF (ELISA) concentrations in bile were measured at time 0 and at the end of the experiments after 360 min. The cellular distribution of APF

Abstracts in the gallbladder tissue was determined by immunohistochemistry. In addition, the localisation in the gallbladder tissue of the APF and of the radiolabelled Ch was determined with a fluorophoshoimager. Results. The table shows the differences between time 360 and time 0 of the amounts of Ch, APF and total proteins present in gallbladder bile.

Group A Group B

Ch (␮mol/cm2 )

APF (␮g/cm2 )

Total proteins (mg/cm2 )

−4440 ± 106 −38 ± 6

−67 ± 54 −34 ± 18

+5.4 ± 2.9 −1.2 ± 1.1

APF was absorbed (−) by the gallbladder in both groups, while total proteins were secreted (+) in group A and absorbed in group B. The amount of Ch absorbed by the gallbladder positively correlated with the amount of APF absorbed (P < 0.05) in group B experiments. APF localised mainly in the gallbladder apical epithelium, showing the same localisation of radiolabelled Ch absorbed from bile. Conclusion. APF contributes to Ch absorption by the gallbladder epithelium. References [1] BBRC 2002;292:390–5. [2] Gastroenterology 2000;1118:912–20.

CO051 DIAGNOSTIC YIELD OF VIDEO CAPSULE ENDOSCOPY IN SMALL BOWEL DISEASE. AN ANALYSIS OF 101 CASES C.M. Girelli, F. Barzaghi, V. Malacrida, C. Mirata, F. Rocca U.O. Medicina 1, Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale di Busto Arsizio, Italy Aim. To assess the diagnostic yield of video capsule endoscopy (VCE) in the diagnosis of suspected small bowel disorders. Patients and methods. From September 2001 to November 2003, we undertook 113 VCE examinations for various indications. One hundred and one patients (52 males, 55 ± 21 years old) were available for analysis. Indications for VCE were as follows: 75 obscure gastrointestinal bleeding (OGB) (39 of the overt type, 23 of which evaluated within 72 h from bleeding); the remainder (n = 26) for non-haemorrhagic indications (10 clinical and radiological suspicion of Crohn’s disease; 5 staging of familial polyposis syndrome (FPS); 3 non-responder coeliac disease; 3 unexplained chronic diarrhoea and 5 miscellaneous reasons). Lesions compatible with the clinical picture and/or blood in the lumen were defined positive finding. Chi-square was used for percentages’ comparison. Results. In patients with overt OGB, the cumulative diagnostic yield was 66.6%; however it was 95.6 and 37.5% in those evaluated within or after 72 h from bleeding, respectively (P = 0.005); five patients (12.8%) had lesions missed at previous panendoscopy. In patients with occult OGB (n = 36) the diagnostic yield was 72.3% with three lesions (8.3%) missed at previous panendoscopy. Overall, in OGB 54 lesions were identified: 55.5% vascular (angiodysplasia, angioma, varices, Dieulafoy); 24.2% inflammatory (ulcer, erosion, IBD-like picture); 18.5% neoplastic (polyp, adenocarcinoma, lymphoma, GIST); 1.8% Meckel’s diverticulum. In non-haemorrhagic patients, the cumulative yield was 42%. Five out of 10 patients had confirmation of suspected Crohn’s disease; four out of five with FPS had small bowel polyps; one out of three non-responder coeliac disease had jejunal adenocarcinoma and none of unexplained chronic diarrhoea had pathological findings. Of patients with miscellaneous indications (lung metastasis of unknown origin; chronic abdominal pain; positive faecal occult blood without anaemia; unexplained vomiting; malabsorption) only the patient with malabsorption had a picture of jejunal atrophy with a subsequent histological confirmation of coeliac disease, missed at first evaluation.

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Conclusion. In suspected small bowel disease, VCE has a satisfactory diagnostic yield that is very high in patients with overt OGB evaluated within 72 h from bleeding. In OGB, the rate of missed lesions at panendoscopy is consistent with that reported by others; conversely, we found a higher prevalence of neoplastic and inflammatory lesions in comparison with other series published before the advent of VCE. In non-haemorrhagic indications, in selected patients with suspected Crohn’s disease and polyposis syndrome the yield may be higher than for other ill-defined conditions, but our data are very limited and no firm conclusions can be drawn. CO052 THE USEFULNESS OF CHROMO-MAGNIFYING ENDOSCOPY IN THE DETECTION OF COLORECTAL DYSPLASIA IN LONG-STANDING ULCERATIVE COLITIS G.C. Gizzi, R. Pezzilli, M.A. Pantaleo, V. Villani, B. Misitano, G. Epifanio, G. Biasco, R. Corinaldesi Internal Medicine and Gastroenterology, Department of Hematology and Oncology, University of Bologna, Bologna, Italy Introduction. Patients with long-standing ulcerative colitis (LSCU) have an increased risk for developing malignancy through a dysplasia-carcinoma sequence. Dysplasia in ulcerative colitis (UC), categorised as either flat or dysplasia associated lesion or mass (DALM), is usually difficult to detect by means of conventional colonoscopic (CC) surveillance. Furthermore, polypoid dysplastic lesions (adenoma-like mass, ALM) may occur in these patients within the colitis mucosa and they need to be distinguished from inflammatory or hyperplastic polyps occurring along the inflamed mucosa and from coincidental adenomas (CA) arising in the colonic mucosa free of the disease. Aims and methods. To evaluate the characteristics of polypoid lesions in patients affected by LSUC by means of magnifying plus dye spraying colonoscopy (CMC) and to compare these findings with the histological findings. Fifty patients (30 males, 20 females, mean age 48 years, range 28–65) with extensive LSCU were examined. The duration of the disease was 13.5 ± 2.5 years (mean ± S.D.). All patients underwent magnifying colonoscopy (Olympus CF Q160ZI, providing up to 140×) plus dye spraying with methylene blue (CMC). The size of the polyps was estimated by placing an open biopsy forceps (7 mm diameter) close to the lesion and measuring the lesion exactly by means of an electronic system which also provided the storage of colorectal photos (Casti Imaging System, Italy). In all patients, the time to reach the caecum was 7.1±2.3 min (mean±S.D.); the mean (±S.D.) duration of the examination was 43 ± 11.2 min (range 36–51). Irregular or polypoid lesions, occurring along the inflamed colonic mucosa or in the not-involved mucosa, were coloured with MB 0.2%, evaluated with magnification, assessed with the pit pattern of Kudo’s classification system and resected or biopsied. Results. A total of 65 polyps were detected at endoscopy in 22 patients. Chromo-magnifying colonoscopy identified 24 flat lesions (histology: hyperplastic in 6, inflammatory in 9, CA in 2, ALM in 7), 29 sessile lesions (histology: hyperplastic in 8, inflammatory in 5, CA in 9, ALM in 4 and DALM in 3, and 12 pedunculated lesions (histology: hyperplastic in 5, inflammatory in 6, CA in 1). Conclusion. In patients with LSCU, CMC permits an accurate detection of neoplastic lesions; it is also able to distinguish neoplastic from non-neoplastic polyps.

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Abstracts

CO053 ACUTE EFFECT OF CAPSAICIN ON OESOPHA- GEAL MOTOR ACTIVITY IN GERD PATIENTS WITH INEFFECTIVE OESOPHAGEAL MOTILITY L. Grossi, G. Cappello, M. Spezzaferro, L. Marzio G. d’Annunzio University of Chieti, c/o Medicine I Ospedale Spirito Santo Pescara, Italy Background and aim. Ineffective oesophageal motility (IEM) is a motor disorder present in about 50% of patients with gastro-oesophageal reflux disease (GERD). We previously found that its frequency seems reduced in patients chronically assuming red chilly pepper in their diet. Capsaicin, the active compound of red pepper, actually exerts a prokinetic effect on oesophageal motility, by increasing the amplitude of body waves but to date its action has been documented only in healthy subjects [1]. The aim of this study has been, therefore, to test the effect of an acute administration of capsaicin on oesophageal motility during an ambulatory manometry in a group of GERD patients affected by IEM. Methods. Twenty-five patients with oesophageal pH-metry positive for GERD underwent a stationary oesophageal water-perfused manometry. If motor characteristics of IEM were identified (<30% of waves with an amplitude <30 mmHg and/or non-transmitted) patients received the administration of a mixture of red chilly pepper/olive oil and an infusion of olive oil alone as a control. The two administrations were performed through one manometric channel placed at the middle oesophagus and were given in a random order during the same manometric session. The motor response was analysed for 45 min following the stimulus and compared to the baseline period. Results. Twelve patients showed IEM and were included in the protocol. The amplitude of oesophageal body waves was significantly increased as compared to baseline after the red pepper oil infusion (45.9 ± 3.7 mmHg versus 38.4 ± 3.1 mmHg, respectively, P = 0.03) whereas the administration of olive oil alone did not elicit any modification (amplitude 39.3 ± 3.5 mmHg, P = 0.2 versus baseline). The velocity of propagation of oesophageal body waves and the LES basal tone resulted unaltered in both groups. Summary and conclusions. The acute administration of capsaicin in GERD patients with IEM determines an increase in the amplitude of oesophageal body waves. Such a condition may lead to a more effective oesophageal clearing of the acid content. Whether these findings could affect the natural history of GERD and represent a novel therapeutic approach for such disease needs to be elucidated. Reference [1] Dig Dis Sci 1998;43:1165–71.

CO054 PROLONGED EFFECT OF BACLOFEN ON OESOPHAGEAL MOTILITY: A 48-H MANOMETRIC STUDY IN HEALTHY SUBJECTS L. Grossi, G. Cappello, M. Spezzaferro, L. Marzio G. d’Annunzio University, Italy Background. The GABAb agonist baclofen seems to have a potential beneficial role in treating gastro-oesophageal reflux disease (GERD). The drug, in fact, is able to reduce the amount of refluxes mainly by lowering the frequency of transient lower oesophageal sphincter relaxations (TLESRs). Such an effect, however, has been so far studied only for a few hours and a prolonged 24 h manometric evaluation is still lacking. The aim of this study has been, therefore, to investigate the oesophageal motility in a group of healthy subjects, 24 h before and after the administration of multiple doses of baclofen.

Materials and methods. Five healthy subjects were studied. They underwent a 48 h oesophageal manometry performed with an electronic device with two single sites recording the swallowing pattern and the oesophageal body motility; a sphinctometer served for monitoring the LES activity. During the second 24 h period patients received baclofen per dose at the dose of 10 mg four times a day. Results. During the 24 h with baclofen, the LES basal tone result increased as compared to the period without (42.2 ± 18.46 versus 39.9 ± 18.7, mean ± S.E.M., P = 0.017), with a concomitant reduction in the amount of TLESRs (13.3 ± 2 versus 23.6 ± 3.2, P = 0.045). Moreover, the administration of baclofen induced a decrease in the number of the swallowings (1387 ± 239 basal versus 1690 ± 279 basal, P = 0.04). A trend towards a reduced number of primary oesophageal body waves was detected (baclofen: 1228 ± 166; basal 1379 ± 296, P = 0.09) without any changes in the amplitude (baclofen: 43.7 ± 6.9 mmHg; basal: 49.4 ± 9.6 mmHg, P = 0.15). One patient experienced moderate headache, no other significant side-effects were reported with baclofen in the other subjects examined. Summary and conclusions. Our data show that multiple doses of baclofen determine a reduction in the amount of swallowings and TLESRs and an increase in the LES tone throughout the 24 h. All these effects may contribute to the reduction of gastro-oesophageal refluxes already shown in normal subjects and GERD patients. CO055 ABDOMINAL OBESITY IS AN INDEPENDENT RISK FACTOR FOR THE SEVERITY OF EROSIVE OESOPHAGITIS G. Iacopini, A. Vitale, G. Villotti, S. Frontespezi, L. d’Alba, A. De Cesare, F. Iacopini U.O.C. Gastroenterologia ed Endoscopia, Ospedale S. GiovanniAddolorata-Calvary, Rome, Italy Background. There is a widespread notion that obesity leads to gastro-oesophageal reflux disease (GERD), but conflicting evidences have been found using the body mass index. Aim. To investigate whether there is a relationship between the severity of erosive oesophagitis (EE) with abdominal obesity rather than with obesity per se. Methods. All consecutive patients with GERD undergoing an upper GI endoscopy, with erosive oesophagitis (EE) diagnosed by the Los Angeles classification, were enrolled in the study. Patients were categorised in three groups for BMI (kg/m2 ): <25, normal; 25–30, overweight; >30 obese, and for abdominal obesity measured by waist circumference (cm): <80 and <94, normal; 80–88 and 94–102, action level 1 (AL1); >88 and >102, action level 2 (AL2), for females and males, respectively, according to the WHO classification. Hiatal hernia was diagnosed when the gastro-oesophageal junction was at least 2 cm above the diaphragmatic hiatus. Results. EE was diagnosed in 328 patients: as A in 158 (48%), B in 127 (39%), C in 36 (11%) and D in 7 (2%). Patients with EE were overweight in 35% and obese in 28%, but when classified by WC resulted at AL1 in 24% and at AL2 in 47%. Prevalence of severe EE (grades C and D) resulted similar in each BMI category (P = 0.07), but appeared significantly higher in AL1 (P = 0.04) and even more in AL2 (P < 0.001) (see table).

Abstracts

Severe EE (grades C and D) n (total)

n (%)

OR (95% CI)

BMI Normal Overweight Obesity

121 115 92

11 (9) 16 (14) 16 (17)

1 1.61 (0.71–3.64) 2.10 (0.92–4.78)

WC Normal Action level 1 Action level 2

95 80 153

2 (2) 8 (10) 33 (22)

1 5.16 (1.06–25.08) 12.78 (2.99–54.68)

Odd risk for severe EE of AL2 was independent of hiatal hernia (OR 11.82, P = 0.0001). Conclusions. Waist circumference, and not BMI, seems to be directly correlated to the severity of erosive oesophagitis. Evaluation of the adipose tissue in the abdomen, rather than of obesity per se, could be useful to identify those patients at higher risk of severe erosive oesophagitis, probably due to an increased intra-abdominal pressure. CO056 A “2 WEEK” WAITING TIME, PREFERENTIAL LANE, FOR THE ENDOSCOPICAL EVALUATION OF PATIENTS WITH ALARM SYMPTOMS: A PROSPECTIVE STUDY G. Iacopini, A. Di Marzio, A.M. Vitale, A. De Cesare, G. Villotti, L. d’Alba, S. Frontespezi, F. Iacopini Gastroenterology and Digestive Endoscopy Unit, S. Giovanni-AddolorataCalvary Hospital, Rome, Italy Introduction. The presence of alarm symptoms (AS) is believed to discriminate between gastrointestinal functional disorders and organic lesions. In our Endoscopic Service, a 2-week waiting time, preferential lane (PL), for the endoscopical investigations of patients with “alarm” symptoms was introduced to reduce waiting list and increase diagnostic results of organic diseases, without variation of resources and costs and proportionally the open accesses endoscopy. Aim. To evaluate the impact of a PL on the total direct access endoscopy workload evaluating the different prevalences of endoscopic lesions (EL) and negative endoscopies between selected rapid access and routine open direct access investigations. Methods. Referrals for the inclusion in the PL were made using a referral form indicating the presence of one or more of the standard alarm features. Endoscopic diagnosis were recorded prospectively. The presence of major EL was defined by at least one of the following findings: oesophagitis, gastric and duodenal ulcers, erosive duodenitis, colitis, diverticular disease and neoplasms. Statistical analysis were performed using chi-square test. Results. Among 1290 subjects endoscopically evaluated during the period from April 2003 to October 2003, 540 (41.8%) were referred to the PL (mean age 62 ± 7 years), and 750 to the open access (mean age 53 ± 9 years). Colonoscopies were the 33 and 40% of the overall number of endoscopies in the PL and open access, respectively. Demographic features and endoscopic lesions found in both groups of patients are shown in the table.

Over 55 years Males Major lesions Cancer

Open access, n (%)

Preferential lane, n (%)

OR (95% CI)

P-value

413 353 354 5

351 302 352 18

1.5 1.4 2.1 5.1

0.0004 0.0004 0.0001 0.0004

(55) (47) (47) (1)

(65) (56) (65) (3)

(1.2–1.9) (1.1–1.8) (1.7–2.6) (1.9–13.9)

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Conclusions. The introduction of the 2-week preferential lane for patients with alarm features, is a possible and very useful option as an optimal cost-effective management measure to increase the health efficacy of an Endoscopic Service, obtaining a significative increase of the diagnosis of malignancies (OR 5.1) and major endoscopic lesions (OR 2.1). CO057 MOLECULAR SCREENING FOR HEREDITARY NONPOLYPOSIS COLORECTAL CANCER (HNPCC) T. Labellaa , E. Ricciob , A. Menchiseb , A. Lettieria , E. Crafab , F. Rossoc , A. Balzanob a IBP

(CNR), Naples, Italy Cardarelli, Naples, Italy c II Università di Medicina, Naples, Italy b Ospedale

HNPCC is an autosomal-dominant disease accounting for approximately 1–3% of all colorectal cancer cases. As many as 70% of colorectal tumours in HNPCC occur proximal to the splenic flexure. The genetic mutation involves proteins of a specialised DNA repair system, the mismatch-repair (MMR). Defects in the MMR increase the risk for specific types of cancer because of instability in microsatellite DNA sequences (MSI). MMR may improve identification of such families previously diagnosed by family history alone. MSI of DNA is a hall mark of HNPCC and as many as 15–20% of cases of sporadic coloretal cancer also displays MSI. Furthermore, MSI can also be detected in other tumours which are part of the HNPCC tumour spectrum (e.g. gastric, ovarian, and endometrial carcinomas). Colon cancers with MSI+ seem to be associated with a favourable prognosis. Aims. To assess MSI frequency within a population of colorectal cancer patients (CRC) and to evaluate in MSI+ patients, the presence of mutation of two DNA mismatch repair genes (MSH2 and MLH1) are needed. Patients and methods. Both blood and tumour tissues were collected from CRC patients subjected to colonscopy in Cardarelli Hospital from October 2002 and September 2003. Heighty-height CRC cases (86.3% of samples of the incident cases) were screened for microsatellite instability (MSI) with the five mono- and dinucleotide markers of the reference panel (BAT25, BAT26, D2S123, D5S346, D17S250; Boland et al., 1998). The set of microsatellite markers was amplified by PCR followed by gel or capillary electrophoresis to separate PCR amplicons. Results. Seventeen cases (19.3% of the total) showed MSI. The male/female (11/6) ratio was the same compared to total patients (52/36). Surprisingly, only two MSI positives showed a cancer proximal to the splenic flexure. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunochemistry (data not yet available). Conclusions. Although this may appear to be a small number (19%), the positivity of MSI is important in order to alert the clinician of the possibility of an unrecognised diagnosis of HNPCC. CO058 THE LONG-TERM OUTCOME OF HBEAG-NEGATIVE PATIENTS WITH CIRRHOSIS TREATED WITH LAMIVUDINE MONOTHERAPY: A 5-YEAR PROSPECTIVE COHORT STUDY P. Lamperticoa , M. Viganòa , M. Iavaronea , G. Lunghib , R. Romeoa , G. Coluccic , A. Morabitod , E. del Ninnoa , M. Colomboa a Division

of Hepatology, Division of Hygiene, IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy b Division of Hygiene, IRCCS Maggiore Policlinico Hospital, University of Milan, Milan, Italy c Roche Molecular Systems, Rotkreutz, Switzerland d Division of Statistics, Department of Medicine, Surgery and Dentistry, University of Milan, Milan, Italy

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To assess the impact of long-term continuous lamivudine treatment in HBeAg-negative cirrhosis, 44 consecutive patients were treated with 100 mg daily for 52 (5–84) months (89% men, 82% genotype D, 39% decompensated cirrhosis and 36% oesophageal varices). HBV-DNA was tested by bDNA (<700.000 eq/ml, Bayer) and Cobas Amplicor HBV Monitor (<200 cp/ml, Roche). Lamivudine resistance was confirmed by INNO-LiPA assay (Innogenetics, Belgium). Results. After 5 years of treatment, 21 (48%) patients maintained undetectable serum HBV-DNA by non-PCR assay and normal ALT whereas 22 (52%) developed lamivudine resistance. One patient (2%) never achieved a virological response. The 5-year cumulative probability of developing lamivudine resistance was 63% but only 10% of patients had undetectable HBV DNA by PCR assay. Clinical decompensation occurred in none of responders but in seven lamivudine-resistant cirrhotics (0% versus 32%, P < 0.001) whereas hepatocellular carcinoma occurred in both groups at similar rates (28 and 41%). Later complications (>12 months of treatment) included both HCC (n = 7) and liver decompensation (n = 7) and occurred only in lamivudine-resistant cirrhotics (13/14, 93%). Overall, liver-related complications occurred less frequently in responders than in lamivudine-resistant cirrhotics (28% versus 64%, P < 0.01). The 5-year patient survival was 74%, similar in responders and lamivudine-resistant cirrhotics, but five patients with lamivudine resistance and clinical decompensation were rescued by another antiviral drug. Conclusions. Five-year administration of lamivudine monotherapy led to prolonged control of viral replication in approximately one third of HBeAg-negative cirrhotics, but complete suppression in only 10%. Lamivudine resistance was associated to increased risk of liver-related complications, particularly HCC. CO059 LONG-TERM RIBAVIRIN MONOTHERAPY SIGNIFICANTLY DELAYS FIBROSIS PROGRESSION IN OLT RECIPIENTS WITH RECURRENT HEPATITIS C R. Lionetti, G. Palmieri, S. Battista, A. Petrolati, D. Di Paolo, C. Ciceroni, L. De Luca, G. Tisone, M. Angelico Gastroenterology and Liver Transplantation Center, Tor Vergata University, Italy Background. Recurrent hepatitis C after OLT is associated with rapid fibrosis progression. HCV eradication with antivirals is difficult in this setting. Aim. To assess whether long-term ribavirin (RBV) monotherapy affects liver inflammation and fibrosis progression. Methods. Fifteen OLT recipients with HCV recurrent disease and a follow-up >4 years without any treatment received RBV monotherapy, up to the maximum tolerated dose, for 3 years. In each patient 6 yearly biopsies were assessed for grading and staging (Ishak), three before and three during treatment. Variations of >2 points for grading and of >1 point for staging in the last pre-treatment biopsy versus that after 3 years of RBV (end-of-treatment) were considered as significant histological changes (improvement/deterio- ration). Results. Mean ribavirin dose was 353 + 74 mg per day. Mean grading score was 5.2 + 1.9 before and 4.3 + 1.4 after RBV (P < 0.07). Fibrosis score improved in 2 patients, was unchanged in 10 and increased in 3. Consequently, mean fibrosis score before and after 3 years RBV did not differ (2.27 + 1.1 versus 2.47 + 1.1, ns). The yearly fibrosis progression rate during the 3 years prior to treatment (excluding year 1 after OLT) was significantly greater than that observed during the 3 years of RBV therapy (0.51 + 0.31 versus 0.07 + 0.26 points per year, P < 0.002). Conclusions. Long-term administration of low-dose ribavirin monotherapy is well tolerated in OLT recipients with recurrent HCV disease and associated with a significant delay in fibrosis progression compared to a similar pre-treatment period. Extended studies are needed to assess the potential of RBV monotherapy in stabilising liver disease in these difficult-to-treat patients.

CO060 A NEW NON-INVASIVE TECHNIQUE IN PRIMARY SCLEROSING CHOLANGITIS (PSC): A CASE–CONTROL STUDY V. Macchia,b,c , E. Bezzona , A. Floreanib , R. Pasinia , P. Marchesia , G.P. Feltrina , R. De Caroc , D. Miottoa a Department

of Medical-Diagnostic Sciences and Special Therapies, Section of Radiology, University of Padua, Padua, Italy b Department of Surgical and Gastroenterological Sciences, Section of Anatomy, University of Padua, Padua, Italy c Department Human Anatomy and Physiology, Section of Anatomy, University of Padua, Padua, Italy Magnetic resonance cholangiography is a non-invasive technique that has already gained a role in the diagnosis of PSC. Computerised tomographic cholangiography (CTC) is a new imaging technique, which has been used in assessing anatomy and pathology of the biliary tree, but has never been utilised in PSC. Aim. To determinate the accuracy of CTC for detection and localisation of PSC. Methods. A prospective case-control study has been performed; 32 patients (16 with PSC established with ERCP and 16 with hepatobiliary diseases other than PSC) were enrolled. The CTC images were obtained after the i.v. injection of contrast medium (meglumine iotraxate) with a single slice CT scan. The CTC data set was transferred to a workstation to obtain 3D reconstructions. CTC images were independently analysed blind by two radiologists to assess the PSC involvement in the first-, second-, third-, and fourth-order intrahepatic bile ducts, in the extrahepatic bile ducts, and in the gallbladder. Imaging findings were recorded with the use of a five-point rating system. Results. Sensitivity, specificity, PPV, NPV, detection of PSC 94, 94, 94 and 94%; localisation of extrahepatic disease 81, 100, 100 and 84%; localisation of intrahepatic disease 88, 94, 93 and 88%; where PPV, positive predictive value; NPV, negative predictive value. CTC offered dynamic information on biliary excretion. Conclusions. CTC enables an accurate detection and localisation of PSC. Since it offers additional information about biliary excretion, it may be proposed as an integrative technique in the diagnosis and in the follow-up of patients with PSC. CO061 TIMING OF ANTIBIOTIC PROPHYLAXIS OF SEPTIC COMPLICATIONS IN ACUTE PANCREATITIS: A CONTROLLED RANDOMISED STUDY WITH MEROPENEM G. Manes, G. Uomo, P.G. Rabitti, R. Martino, A. Menchise, E. Crafa, S. Picascia, A. Balzano Dipartimenti di Gastroenterologia e Medicina Interna, Ospedale Cardarelli, Naples, Italy Background and aim. Antibiotic (AB) prophylaxis with carbapenem reduces the incidence of septic complications and mortality in necrotising acute pancreatitis (AP). Although pancreatic sepsis is not an early event, bacterial translocation from the gut is likely to occur in the first hours of AP. An earlier AB therapy is, thus, crucial to achieve the maximal effect. Methods. One hundred and seventy-five patients with AP were considered. Patients were randomised to group A, who started AB therapy (meropenem 500 mg tid) at admission, and group B who received AB after the demonstration of necrosis at contrast-enhanced CT. CT was performed in both groups at least after 48 h of hospitalisation and patients without necrosis were not further evaluated. The clinical course of the disease was compared in the two groups. Results. The two groups (A25 and B23) were matched for demographic, severity of pancreatitis (CT score and CrP), aetiology of disease and concomitant diseases. AB treatment was started after 4.7+1.4 days (range 2–6) from hospitalisation in group B and after 1.04 + 0.7 (range 0–2) in

Abstracts group A (P < 0.001). Group surgery days infections in hospital Pancreas Extra A (25): 2 (8%), 18.4 + 11.3; 3 (12%), 4 (16%); B (23): 8 (42.1%), 30.4 + 17.7;7 (30.4%), 11 (47.8%), P < 0.05, <0.01, ns (P = 0.1), P < 0.03. Conclusions. An earlier AB treatment is associated with a significant improvement in the prognosis of necrotising AP. Maximal effort is, thus, needed to early recognise or suspect the presence of necrosis in AP patients and start AB treatment as soon as possible. CO062 OESTROGEN RECEPTOR ALPHA (ER␣) AND BETA (ER␤) EXPRESSION IN NORMAL COLON AND ADENOMAS OF LARGE BOWEL S. Marangia , E. Ierardib , D. Piscitellic , L. Troiania , G.L. Rizzoa , O. Burattinia , A. Di Leoa , A. Francavillaa a Section

of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), Italy b Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Foggia, Italy c Institute of Pathology, University of Bari, Bari, Italy

Background and aim. Several epidemiological studies have demonstrated that colorectal cancer incidence and mortality rates are lower in women than in men. It is well known that oestrogen replacement therapy (ERT) reduces colorectal cancer risk in the 33% of postmenopausal women. Our previous study demonstrated that ER-negative human colorectal carcinomas have higher levels of polyamines, which are associated with fast proliferating cells. ER␤ expression is significantly lower in colon adenocarcinoma cells versus normal colon epithelial cells; these data suggest a central role of ER␤ in preventing neoplastic transformation of colon epithelial cells. Until now, there are no studies of ER␣ and ER␤ expression in preneoplastic lesions. The aim of this study was to demonstrate epithelial ER␣ and ER␤ expression in colorectal adenomas, compared with normal colon expression. Moreover, we have studied the relationship between proliferative and apoptosis activities and ER expression in intestinal adenomas. Patients. We studied samples from seven patients with adenomas of the large bowel and seven patients with irritable bowel syndrome (homogeneous for sex and age) as control. Serial 3 ␮m sections of paraffined biopsies were used for immunohistochemistry. Methods. We performed ER␣ and ER␤ immunohistochemical detection, using a diluted 1:50 primary mouse monoclonal anti ER␤ antibody and primary rabbit polyclonal antibody. Labelling indices (LI) of receptor was indicated by the percentage of positive epithelial cells and evaluated by the count on at least 10 well-oriented crypts. Additionally, the percentage of proliferating cells (PCNA LI) and of apoptotic cells (PARP LI) in normal and adenomatous mucosa have been evaluated. Results. ER␤ LI (mean ± S.D.: 10.14 ± 5.58 versus 21.75 ± 9.7, P = 0.03; Student’s t-test for unpaired data) was significantly lower in polyps compared to controls, while PCNA LI confirmed a higher proliferative rate in adenomas (mean ± S.D.: 59.29 ± 7.16) when compared to control (mean ± S.D.: 18.5 ± 8.8, P = 0.0001). Furthermore, we found an inverse correlation between ER␤ expression and proliferative activity in adenomas (r = −0.81, P = 0.002; Pearson’s test). There was no difference in ER␣ expression between normal and adenomatous tissues. Conclusion. We demonstrated a statistically significant reduction in colorectal adenoma ER␤ expression when compared to normal colonic mucosa. No difference for ER␣ expression was found. Our preliminary data confirm that ER␤ could exert a protective role against colorectal carcinogenesis.

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CO063 ANTIREFLUX SURGERY DOES NOR PREVENT THE PROGRESSION OF BARRETT’S INTESTINAL METAPLASIA TO HIGH GRADE DYSPLASIA AND CANCER: A SYSTEMATIC REVIEW R. Marmo, G. Rotondano, M.A. Biano, R. Piscopo, L. Cipolletta UO Gastroenterologia ASL SA3, Ospedale Curto, Polla (SA), Italy UO Gastroenterologia ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy Background. Patients with specialised intestinal metaplasia of the Barrett’s oesophagus (BE) are at an increased risk of developing oesophageal adenocarcinoma. Both medical therapy and antireflux surgery (ARS) aim at effectively controlling symptoms, induce healing of oesophagitis and promote regression of BE metaplasia, with the ultimate goal of preventing progression of metaplasia to high-grade dysplasia (HGD) and cancer. Nonetheless, the impact of either treatment on these important outcomes is still contradictory. Aim. A meta-analysis was performed to assess the relative efficacy and safety of medical therapy and ARS in patients with BE. Methods. A systematic review of randomised controlled trials on the efficacy and safety of medical therapy versus ARS for the treatment of BE, published between 1970 and 2003. Five original studies were selected according to predefined criteria. Pooled risk estimates and number needed to treat were calculated for each treatment. Heterogeneity of effects was tested. Results. A total of 736 patients (580 males) treated were evaluated with a mean follow-up of 48 months (range 36–136). Mean age was similar in both groups. Medical therapy included antacids, H2-RA or PPI. Surgical operation was open fundoplication. After pooling of data, both treatments were equally effective in controlling symptoms, but surgical therapy was significantly more effective in healing erosive oesophagitis (ARR 14.8 (95% CI, 10.7, 18.9), OR 0.36 (95% CI, 0.21, 0.61), P < 0.001). When only PPI treated patients were evaluated, such differences completely disappeared. Overall length of BE metaplasia was not affected by either treatment and, most importantly, ARS was no better than medical therapy in preventing progression of BE to HGD/cancer with a pooled difference of 1.1% (95% CI, 1.8, 4.8). Medical therapy was significantly safer than ARS, whose morbidity was as high as 45%. Conclusions. ARS is effective in controlling reflux symptoms and healing erosive oesophagitis, but has no effect in preventing the progression of BE metaplasia to HGD and cancer. It does not obviate the need for long-term high-dose PPi therapy and should not be proposed as a cancer-presenting strategy. CO064 COLONOSCOPY SURVEILLANCE IN ASYMPTOMATIC SUBJECTS WITH INCREASED RISK FOR COLORECTAL CANCER: A CLINICAL EVALUATION AND COST-EFFECTIVENESS ANALYSIS OF “FERRARA PROJECT” V. Matarese, A. Pezzoli, M. Brancaleoni, L. Simone, S. Gullini Azienda Ospedaliera-Universitaria, S. Anna Ferrara, Italy Background. Colorectal cancer (CRC) represents the second leading cause of cancer deaths in Western countries with elevated costs for health service. Literature data show that approximately 25% of adenomatous polyps evolve into CRC in 10 years. It is necessary to develop screening and surveillance programmes for CRC prevention with “cost-effective” means. Aim. In this study, we present a surveillance programme with colonoscopy, focused on first-degree relatives of CRC patients and a comparison of the costs of this Plan with the costs of CRC, stages C and D, in our Province. Materials and methods. Five hundred and eighty-five subjects at risk were interviewed from June 2000 to October 2003; 575 joined a surveillance programme. Indeed, 544 accepted colonoscopy (93%), 21 barium

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enema (3.6%), 10 FOBT (1.7%); 10 (1.7%) refused whatever method of surveillance was used. Results. Four hundred and thirty-nine colonoscopies were executed until October 2003. Colonscopy was normal in 330 subjects. In 109 subjects, 144 lesions were found (71% in the left colon, 29% in the right bowel, beyond the splenic flexure): 35 hyperplastic polyps (24.3%), 68 tubular adenomas (47.2%), 24 tubulo-villous adenomas (16.6%), 9 adenomas with severe dysplasia (6.3%) and 8 adenocarcinoma Dukes A (5.6%). The total cost for this plan was 46,914.67 per year. In Ferrara, the cost of a single CRC stages C and D (50% of total CRC in our Province), is approximately 10,000.00. Now, supposing 50% of the adenomas with severe dysplasia, 50% of the adenocarcinomas Dukes A and 25% of the adenomas that we diagnosed were not diagnosed preventively, we could say that they would have evolved into CRC, stages C and D, totalling a cost of 100,833.00 per year. The amount of money saved, would sum up to 53,918.33. Conclusions. Our study has demonstrated the feasibility and validity of a Surveillance Plan aimed at those asymptomatic subjects at a greater risk of CRC and its cost-effectiveness. It would be useful to confront our data with a study of the feasibility aimed at the general population. CO065 BODY COMPOSITION AND NUTRIENT UTILISATION IN PATIENTS WITH NON-ALCOHOLIC STEATO-HEPATITIS (NASH) L. Miele, E. Capristo, A. Forgione, V. Vero, M. Diana, G. Mingrone, A.V. Greco, A. Grieco, G. Gasbarrini Institute of Internal Medicine, Catholic University, Rome, Italy Background and aim. Metabolic alterations are a common feature in patients affected by non-alcoholic steato-hepatitis (NASH). A dietary treatment, with consequent body weight reduction, represents a fundamental tool in disease management of these patients. The aim of the present study was to evaluate body composition, energy expenditure and substrate utilisation in male patients with NASH, comparing them with patients affected by chronic hepatitis related to HCV infection (HCV) and a group of healthy subjects. Methods. Twenty male outpatients with NASH (age: 41 ± 11 years; BMI: 26.2 ± 2.1 kg/m2 ) and 14 HCV male patients (age 44.6 ± 13 years; BMI: 24.8 ± 2.8 kg/m2 ) were enrolled in the study. A group of 20 healthy male subjects (age: 39 ± 10 years; BMI: 23.3 ± 1.1 kg/m2 ) were studied as controls. Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry; resting metabolic rate and nutrient oxidation by indirect calorimetry. A 7-day food diary was collected. The main biochemical parameters were measured using standardised laboratory techniques. Results. Body weight was higher in NASH patients with respect to HCV patients and control subjects (respectively, 75.2 ± 8.9 kg versus 68.5 ± 9.4 kg and versus 67.0 ± 8.0 kg, P < 0.01) and this was essentially due to fat mass (FM) increase (29.8 ± 4.8% versus 26.8 ± 5.0%, P < 0.05). A reduction in fat-free mass (FFM) was found in HCV patients with respect to both NASH and control subjects. Patients with NASH had a significantly higher waist circumference (104 ± 6 cm, P < 0.01) with respect to HCV (95 ± 6 cm) and control subjects (92 ± 5 cm). After adjustment for age and body composition, resting metabolic rate (RMR) was lower in NASH compared to HCV and control subjects, while HCV patients showed an increase in RMR and in lipid utilisation with respect to the other two groups (P < 0.01 both). Energy intake was significantly higher in NASH patients (2210±840 kcal per day, P < 0.01) compared to both HCV (1980±760 kcal per day) and control subjects (1880±570 kcal per day). Conclusions. NASH patients showed an increase in body weight, fat mass and visceral fat accumulation with respect to HCV and control subjects. The reduction in RMR, coupled with increase energy intake may explain the body composition alterations found in these patients. An accurate nutritional and metabolic evaluation of these patients may

allow to optimise their dietary treatment and to identify those patients at a higher risk of metabolic complications, such as diabetes, dyslipidaemia and cardio-vascular disease. CO066 ASSOCIATION BETWEEN POLYMORPHISMS PPAR-ALPHA GENE AND GALLSTONE DISEASE

OF

THE

M. Montagnani, E. Ravaioli, R. Aldini, A. Morganti, A. Roda, M. Letizia Bacchi-Reggiani, F. Minni, E. Roda Dipartimento di Medicina Interna e Gastroenterologia, CRBA, Università di Bologna, Bologna, Italy Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a nuclear receptor which regulates the transcription of genes responsible for fatty acid uptake and oxidation, bile acid and lipid metabolism, and inflammation. Human studies showed that fibrates, hypolipidemic drugs that bind and activate PPAR-alpha, reduce the activity of cholesterol 7alpha-hydroxylase. A relatively common polymorphism of the PPAR-alpha gene (PPARA), is due to a functional missense mutation which causes a leucine to valine substitution (L162V). An even more frequent PPARA polymorphism is the G to C transversion in intron 7, which is in allelic association with the L162V polymorphism. In order to investigate the role of PPAR-alpha in human gallstone formation, we determined the prevalence of the exon 5 and intron 7 polymorphisms in a control population and in gallstone patients. Methods. Fifty-six patients (20 males, 36 females) admitted to the hospital for either elective cholecystectomy for gallstone disease, or endoscopic treatment for choledocolithiasis, were screened for the presence of both the exon 5 (L162V) and the intron 7 polymorphism. The control population was composed of 95 hospital workers and university students who volunteered to participate in the study. Both groups were composed of Italian Caucasian subjects. DNA was extracted from peripheral blood leukocytes by the salting out procedure. PCR amplification of exon 5 and intron 7 was carried out by polymerase chain reaction (PCR) followed by denaturing-high performance liquid chromatography (D-HPLC) and automated sequencing. Statistical analysis was performed using the chi-square test. Results. In the control population, the carrier frequency for the exon 5 L162V polymorphism was 10%, while in male and female lithiasic patients it was 15 and 17%, respectively (P = 0.58). In the control population, the carrier frequency for intron 7 polymorphism was 26%, while in male and female lithiasic patients it was 55 and 31%, respectively (P = 0.04). Conclusion. Carrier frequency of PPARA polymorphisms was higher in lithiasic patients in comparison to a control population. Significantly higher prevalence was found for the intron 7 variant, mainly due to its higher frequency in male gallstone patients. Studies on polymorphism prevalence and the association with changes in biliary lipid composition will be performed in order to elucidate the real importance of PPAR-alpha in gallstone disease. CO067 INTERLEUKIN-21 (IL-21) ENHANCES TH1 CELL SIGNALLING AND INTERFERON-GAMMA PRODUCTION IN CROHN’S DISEASE G. Monteleonea , I. Monteleonea , D. Finaa , P. Vavassoria , G. Del Vecchio Blancoa , T.T. MacDonaldb , F. Pallonea a Dipartimento

di Medicina Interna, Università Tor Vergata di Roma, Rome, Italy b Division of Infection, Inflammation and Repair, University of Southampton, Southampton, UK Background and aim. Activated Th1 cells play a central role in the pathogenesis of tissue damage in Crohn’s disease (CD). There is evidence that IL-12/STAT4 signalling promotes Th1 cell commitment in CD, but

Abstracts other cytokines are needed to maintain activated Th1 cells in the mucosa. We have previously shown that mucosal IL-12-induced Th1 responses can be enhanced by cytokines which signal through the common ␥-chain receptor. IL-21 is a newly described cytokine produced by activated T cells which signals through the ␥-chain receptor. In this study, we therefore examined the expression and role of IL-21 in CD. Methods. Whole intestinal mucosa, lamina propria mononuclear cells (LPMC) and LP CD3+ T lymphocytes (LPL) were obtained from CD and ulcerative colitis (UC) patients and normal controls. Additional biopsies were taken from patients with Helicobacter pylori-associated gastritis and controls. To investigate mechanisms underlying the induction of IL-21, normal T-LPL were stimulated with anti-CD3 antibody in the presence or absence of IL-12, and CD LPMC were cultured with or without a neutralising IL-12 antibody. To examine if IL-21 regulates mucosal Th1 cell responses, CD LPMC were pre-treated with a recombinant human IL-21 receptor/Fc fusion protein for 12 h and then stimulated with anti-CD3 for further 24 h. IFN-␥ was then measured in the culture supernatants by ELISA, whereas phosphorylated STAT4 (p-STAT4), T-bet, GATA-3 and IL-21 were examined by Western blotting. Results. IL-21 was detected in all samples, but its expression was higher at the site of disease in CD in comparison to UC and controls. Enhanced IL-21 was seen in both small bowel and colonic CD and was not associated with any CD phenotype, such as structuring disease. IL-21 expression was moreover up-regulated in UC inflamed areas in comparison to controls. IL-12 enhanced IL-21 in normal TLPL through an IFN-gamma-independent mechanism, and blocking IL-12 in CD LPMC reduced anti-CD3-stimulated IL-21 expression. Neutralisation of IL-21 in CD LPMC cultures reduced anti-CD3-stimulated p-STAT4 and T-bet expression thereby inhibiting IFN-gamma production. Finally we provide evidence that IL-21 is up-regulated in Helicobacter pylori-induced gastritis, another IL-12-associated Th1 gastrointestinal diseases. Conclusions. This is the first study to show an up-regulation of IL-21 in human inflammatory diseases. Our data suggest that IL-21 contributes to the ongoing Th1 mucosal response in CD. CO068 REGULATION OF Smad7 EXPRESSION IN CROHN’S DISEASE MUCOSA G. Monteleonea , G. Del Vecchio Blancoa , S. Ballerinia , P. Vavassoria , I. Monteleonea , D. Finaa , S. Bernardinia , T.T. MacDonaldb , F. Pallonea a Dipartimento

di Medicina Interna, Università Tor Vergata di Roma, Rome, Italy b Division of Infection, Inflammation and Repair, University of Southampton, Southampton, UK Background and aims. Defective TGF-beta1 signalling is associated with high Smad7 in the mucosa of patients with Crohn’s disease (CD), and enhanced Smad7 contributes to maintaining mucosal inflammation. In this study we have examined the molecular mechanisms underlying the induction of Smad7 in human intestine. Methods. Whole intestinal mucosal and lamina propria mononuclear cell (LPMC) samples were obtained from CD patients and controls and analysed for Smad7 RNA and protein by real time light cycler RT-PCR and Western blotting. Smad7 acetylation and interaction with the intrinsic histone acetyltransferase, p300, were examined by immunoprecipitation and Western blotting. To determine if Smad7 expression requires de novo protein synthesis, CD LPMC were treated with cycloheximide (CHX) for 1 up to 6 h, and analysed for Smad7, Ikba, and beta-actin by Western blotting. Finally, to determine if acetylation enhances Smad7 expression, normal LPMC were treated with trichostatin, a histone deacetylase inhibitor, for 1 up to 24 h. Results. Smad7 protein expression was increased in all CD samples in comparison to controls. In contrast, controls exhibit higher levels of Smad7 RNA than CD, suggesting that Smad7 is regulated at the post-transcriptional level in CD. Indeed, inhibition of de novo protein syn-

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thesis with CHX reduced Ikba (a protein with a very short half-life), but not Smad7 expression, raising the possibility that high Smad7 is caused by enhanced protein stability. To address this issue, we first examined if Smad7 is acetylated in CD mucosa, given that acetylation is one of the dynamic post-translational mechanisms, which enhance protein stability. Co-immunoprecipitation assays revealed that Smad7 was acetylated on lysine residues and interacted with p300. Importantly, inhibition of histone deacetylase by trichostatin enhanced Smad7 protein but not RNA expression in normal LPMC. Conclusions. These data indicate that, in CD mucosa, high cellular levels of Smad7 are sustained by dynamic post-transcriptional mechanisms, and suggest that acetylation of Smad7 on lysine residues can enhance Smad7 protein expression by making the protein resistant to ubiquitination and degradation. CO069 ENHANCED EXPRESSION OF THE FAS PATHWAY INHIBITOR, FLIP, IN THE MUCOSA OF PATIENTS WITH CROHN’S DISEASE I. Monteleonea , L. Franchib , L. Bianconea , F. Pallonea , G. Monteleonea a Cattedra

di Gastroenterologia, Dipartimento Medicina Interna, Università “Tor Vergata”, Rome, Italy b Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università “Tor Vergata”, Rome, Italy Background and aim. In Crohn’s disease (CD) mucosa, lamina propria T lymphocytes (LPL) express high levels of Fas but are resistant to Fas-mediated apoptosis. The molecular mechanism underlying the resistance of CD LPL to FAS-mediated apoptosis still remains unclear. The aim of the present study was to examine the expression and the role of FLICE-inhibitory protein (Flip), an inhibitor of the Fas signalling pathway, in CD. Materials and methods. Whole intestinal mucosa, lamina propria mononuclear cells (LPMC) and LP CD3+ T lymphocytes (LPL) were obtained from CD and ulcerative colitis (UC) patients and normal controls and analysed for the expression of Flip by Western blotting, using a monoclonal antibody that recognises both the full-length and short form of Flip. To investigate mechanisms underlying the induction of Flip, normal LPMC were cultured in the presence of anti-CD3 with or without the addition of IL-12, a cytokine which is produced in excess in CD mucosa and able to enhance resistance of T cells to Fas-mediated apoptosis. Results. The full-length form of Flip was constitutively detected in all samples, but its expression was higher in whole biopsies and mucosal cells from CD patients in comparison to UC and normal controls. In addition, CD samples exhibit higher levels of the short form of Flip, which negatively regulates the activity of initiator caspases. Treatment of normal LPL with IL-12 enhanced anti-CD3-induced Flip expression, thus suggesting a role for this cytokine in inducing Flip in CD mucosa. Discussion. Data suggest that high Flip expression contributes to confer resistance of mucosal T cells to Fas-mediated apoptosis in CD. CO070 CORRELATION BETWEEN THE DIAMETER OF ASPIRATION CHANNEL AND ASPIRATION TIME IN THREE DIFFERENT VIDEOENDOSCOPES F. Montino, M. Ballare’, M. Orsello, E. Garello, P. Occhipinti, M. Del Piano U.O.A Gastroenterologia, Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy Background. In GI bleedings a rapid aspiration of blood is crucial. The aspiration channel diameter of an endoscope is a critical factor but the real advantage of its increase has never been calculated. Theoretically the

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relation between aspiration channel diameter and aspiration time could be calculated by the Bernoulli equation: P = Ph + Pa + Pm + Pfd + Pfc . However, some of these variables cannot be calculated in a complex model such as an endoscopic system. Aim. The aim of this study was to experimentally define the relation between the aspiration channel diameter and the aspiration time. Methods. Three endoscopes with aspiration channel diameter of 2.8, 3.7, and 6 mm were tested in suction of a fixed volume (1 l) of water, fluid and coagulated blood using a 85 kPa vacuum pump. Aspiration times were plotted in a time/diameter curve. Results. The aspiration times were 101, 51, and 13 s with water and 177, 77, and 17 s with blood using the 2.8, 3.7, and 6 mm endoscope, respectively. Coagulated blood was completely aspirated by the 6 mm endoscope but not by the other ones. The time/diameter interpolate curves were represented on the graphic. The 6 mm channel endoscope aspirated water 8.16 times and blood 11.59 times faster than the 2.8 mm channel instrument. Conclusions. Our experimental findings show that the increase of the diameter produces a reduction of the aspiration time higher than expected. This is probably due to the interaction between the viscosity of fluids and the characteristics of the endoscopes. Thus, the recently marketed 6 mm aspiration channel endoscope provides the best performances needed in GI bleeding emergencies.

therapy. Outcomes: crude rates of responders (minimal or no symptoms at the end of the follow-up) and rates of drop-out for side-effects, assessed by three independent observers on the basis of the intention-to-treat principle. Pooling: Der Simonian e Laird (DL) methods was used, considering rate difference (RD); heterogeneity was evaluated using Q statistic. Results. Two hundred and eighty-six articles were identified, 10 full RCTs have been admitted, 6 studies reported the number of patients with minimal or no symptoms at the end of the follow-up and only 7 studies reported sufficient information on side-effects of eradication. The RD for treatment success in NUD with HP eradication therapy compared with control therapy was 6.02% (95% CI, 0.92–11.1%). However, significant heterogeneity (P = 0.09) calls the validity of aggregating the data into question. Heterogeneity resolved with the seclusion of one study (RD% 3.9 (95% CI, 0.2–8.1%), P = 0.4). The RD for discontinuation of therapy for side-effects in NUD with HP eradication therapy compared with control therapy was 2.7% (95% CI, 0.3–5%), NNH = 37. Conclusion. This m-a, updated to October 2003, does not suggest any effect of eradication on symptoms. Every 37 patients with HP+ NUD are treated with HP eradication therapy. But, one stops therapy for side-effects. CO072 STAT3 SIGNALLING PATHWAY: A CRUCIAL MEDIATOR OF INFLAMMATORY BOWEL DISEASE (IBD) AND OTHER FORMS OF INTESTINAL INFLAMMATION A. Mussoa , P. Dentellib , A. Carlinob , L. Chiusac , A. Repicia , A. Sturmd , C. Fiocchid , M. Rizzettoa , L. Pegorarob , C. Sategna-Guidettib , M.F. Brizzib a Divisione

di Gastroenterologia, Ospedale San Giovanni Battista, Università di Torino, Turin, Italy b Dipartimento di Medicina Interna, Università di Torino, Turin, Italy c Dipartimento di Scienze Biomediche ed Oncologia Umana, Anatomia Patologica, Università di Torino, Turin, Italy d Case Western Reserve University, Cleveland, OH, USA

CO071 EFFICACY AND SAFETY OF Helicobacter pylori ERADICATION THERAPY IN PATIENTS WITH NON-ULCER DYSPEPSIA: A META-ANALYSIS, UPDATED TO OCTOBER 2003 A. Moretti, C. Papi, M. Bianchi, M. Tarquini, M. Koch, L. Capurso U.O.C. di Gastroenterologia, A.C.O. San Filippo Neri, Rome, Italy Background and aim. The evidence for association between HP and non-ulcer dyspepsia (NUD) in more uncertain. Many trials evaluating the efficacy of HP eradication treatment for NUD have been poorly designed and have given conflicting results. Previous meta-analysis (m-a), methodologically unsound, concluded in favour of the potential advantage of eradication, or suggest no effect. However, consensus statements in North America and Europe have been supporting a strategy of “test and treat HP”. Aim. Assess if HP eradication relives symptoms in the long-term (12 months), and is still an option for NUD. Material and method. Search strategy: Medline and references of randomised trial (RCTs) and reviews. Inclusion criteria: RCTs of HP eradication versus control in NUD; evaluation of symptoms >12 months, after

Background and aim. Crohn’s disease (CD) and ulcerative colitis (UC) are characterised by abnormal mucosal immune activation driven by a cytokine imbalance. Several cytokines involved in IBD pathogenesis, such as IL-10 and IL-6, act through activation of signal transducers and activators of transcription (STATs) family. In animal models, conditional deletion of STAT3 gene in macrophages and neutrophils results in chronic enterocolitis and constitutive activation of STAT3 has been reported in intestinal and peripheral T cells from CD patients. To evaluate whether STAT3 activation is a systemic alteration specific for IBD, we investigated the activation of STAT3 in CD, UC mucosa and in other types of intestinal inflammation. Materials and methods. Total and phosphorylated STAT3 levels were assessed by Western blot in mucosal biopsies, in lamina propria (LPMC) and peripheral blood mononuclear cells (PBMC) obtained from 18 CD, 18 UC, 4 coeliac disease, one acute self-limiting colitis, and 13 healthy controls. Immunofluorescence staining of mucosal biopsies was performed to characterise cell populations expressing activated STAT3. Results. Using Western blot and immunofluorescence, activated STAT3 was exclusively detected in mucosal samples obtained from CD and UC patients, but not from normal controls. Similarly, STAT3 activation was found in LPMC isolated from CD and UC tissues, not from controls. No phosphorylated STAT3 was detected in lysates of PBMC from IBD patients. When paired autologous mucosal samples obtained from macroscopically involved or uninvolved bowel areas were analysed, STAT3 activation was found only in microscopically inflamed tissues. Double immunostaining identified mucosal CD68+ macrophages and CD3+ lymphocytes, but not neutrophils, as cellular sources of activated STAT3. Finally, immunoblotting and immunofluorescence of coeliac disease and acute self-limiting colitis mucosal samples revealed activated STAT3 also in these forms of intestinal inflammation.

Abstracts Conclusions. Local activation of STAT3 signalling occurs in both CD and UC, it is strictly confined to actively inflamed intestinal mucosa and is limited to infiltrating macrophages and T cells. STAT3 is also activated in other acute and chronic intestinal inflammatory conditions, characterised by different aetiology and pathogenesis. These data suggest that, rather than a specific feature of IBD, this signalling pathway is critically involved in multiple forms of gut inflammation.

CO074 AMINOPYRINE AND METHACETIN 13C-BREATH TESTS TO ASSESS HEPATIC FUNCTION IN HCV-RELATED CHRONIC LIVER DISEASE E.C. Nista, I.A. Cazzato, A. Armuzzi, L. Fini, M. Candelli, M.A. Zocco, L. Zileri dal Verme, R. Finizio, G. Gasbarrini, A. Gasbarrini Internal Medicine Department, Catholic University, Gemelli Hospital, Rome, Italy

CO073 GASTRO-DUODENAL LESIONS, DYSPEPTIC SCORE SYMPTOMS, AND Helicobacter pylori INFECTION IN PATIENTS WITH CHRONIC RENAL FAILURE G. Nardonea , A. Roccoa , M. Fiorillob , M. Del Pezzoc , G. Autieroa , A. Lambiasec , G. Budillona , B. Cianciarusob a Department

of Clinical and Experimental Medicine, Gastroenterology Unit, University “Federico II”, Naples, Italy b Nephrology Unit, University “Federico II”, Naples, Italy c Department of Cellular and Molecular Biology and Pathology “L. Califano”, University “Federico II”, Naples, Italy

Patients with chronic renal failure (CRF) may frequently develop peptic diseases or digestive disorders leading sometimes to severe gastrointestinal complications. Aim. To evaluate the incidence of upper gastroduodenal lesions and the related symptoms in uremic patients. Secondary aim of this study was to evaluate whether uremic status may affect the diagnostic efficiency of 13C-urea breath test (13C-UBT), a non-invasive test routinely used in the diagnosis of H. pylori infection. Patients and methods. Fifty patients with chronic renal failure (39 non-dialysed CRF and 11 dialysed HD) and 93 dyspeptic patients were consecutively enrolled. All patients underwent an oriented and validated questionnaire scoring dyspeptic symptoms, upper endoscopy with multiple bioptic specimens for rapid urease test and histological examination, 13C-UBT and H. pylori stool antigen (HpSA) test, an other non-invasive test routinely used in the diagnosis of H. pylori infection. Results. Mild or even total absent symptoms score (4 ± 3), but a higher frequency of gastro-duodenal peptic lesions (overall 77%) were observed in uremic patients (non-dialysed and dialysed) versus dyspeptic controls (symptom’s mean score 8 ± 5; prevalence of peptic diseases 10%) in spite of H. pylori infection. The diagnostic accuracy of 13C-UBT was greater than HpSA in all studied groups (see table). 13 C-UBT

Controls CRF HD

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Sensitivity (%)

Specificity (%)

DA (%)

Sensitivity (%)

Specificity (%)

DA (%)

96 95 86

98 95 100

97 95 93

90 81 71

98 94 75

94 88 73

Background and aim. Aminopyrine (ABT) and methacetin (MBT) breath tests have been shown to be sensitive tools to assess hepatic residual functional microsomal mass. The aim of this study is to compare ABT and MBT results in patients with HCV-related chronic liver disease and healthy subjects and to evaluate their reliability to discriminate among progressive stages of liver disease. Methods. Forty patients affected by HCV-related chronic liver disease (20 chronic hepatitis (CH), 30 liver cirrhosis (LC)) and 20 healthy subjects (HS) were studied. The severity of cirrhosis was also assessed according to the Child–Pugh score. After ingestion of 13C-aminopyrine (2 mg/kg body weight), subjects’ breath was continuously sampled for 2 h and 13CO2 /12CO2 ratio was simultaneously analysed by means of a novel breath system device (Oridion BreathID, Jerusalem, Israel). At the same time, breath samples were taken at baseline and every 15 min thereafter for 2 h and then analysed by IRMS. Forty-eight hours later, test was repeated after 13C-methacetin (75 mg) ingestion. ABT and MBT results were expressed as cumulative percentage of the administered 13C-dose recovered in breath during 2 h (cPDR). Results. ABT and MBT cPDR values were significantly different among the three groups (BreathID cPDR values, ABT: HS 15.6 ± 3.3, CH 11.1 ± 3.1, LC 3.8 ± 2.1, P < 0.05; MBT: HS 35.2 ± 3.1, CH 29.7 ± 3.8, LC 9.7 ± 6.4, P < 0.05) Moreover, only ABT was significantly different (P < 0.05) among Child–Pugh status. BreathID and IRMS showed similar cPDR values. Conclusion. Both ABT and MBT were able to discriminate among healthy subjects, patients with HCV-related chronic hepatitis and patients with HCV-related liver cirrhosis. Conversely, only ABT was significantly related to Child–Pugh status, thus being potentially useful to assess prognosis of cirrhotic patients. CO075 INFLIXIMAB IN THE TREATMENT OF STEROID RESISTANT/ DEPENDANT AND FISTULATING CROHN’S DISEASE: A MULTIVARIABLE ANALYSIS OF PREDICTORS OF RESPONSE IN AN ITALIAN MULTICENTRIC OPEN STUDY IN 366 PATIENTS A. Orlandoa , E. Colombob , A. Kohnc , L. Bianconed , A. Viscidoe , M. Dapernof , F. Mocciaroa , V. Criscuolia a Ist.

di Medicina Generale Università di Palermo Osp. V. Cervello, Italy Osp. L. Sacco, Milan, Italy c Div. Gastroenterologia, Osp. Forlanini Roma, Rome, Italy d Gastroenterologia Università Roma Tor Vergata, Rome, Italy e Gastroenterologia Università Roma La Sapienza, Rome, Italy f Div. Gastroenterologia, Osp. Mauriziano Umberto I, Turin, Italy b Gastroenterologia

In conclusion, in our study (1) patients with chronic renal failure in respect to dyspeptic patients had a mild or even absence of upper gastrointestinal symptoms but a high prevalence of severe gastroduodenal peptic lesions irrespective of H. pylori infection and (2) the uremic status of patients with CRF did not affect the diagnostic accuracy of 13C-UBT. Therefore, upper endoscopy is suggested in patients with chronic renal failure even in the absence of specific symptoms to avoid several upper GI complications.

Aim. To evaluate the role of infliximab in a large series of patients with acute steroid resistant Crohn’s disease or fistulating disease looking at the predictors of response. Patients and methods. Three hundred and sixty-six (201 men and 165 women) with steroid dependent/resistant moderate severe Crohn’s disease (CDAI > 220–400) (217 patients) or with fistulating disease (149 patients: enterocutaneous 23%, perianal 77% in six Italian referral centres were treated with a dose of 5 mg per kg of body weight. In dependant/resistant steroid disease one single or three infusions were given whereas in fistulating disease three infusions (at 0, 2, 6 weeks) were given. Primary endpoints were: (a) clinical response, defined as a reduction of 70 or more

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points in the score on the Crohn’s disease activity index at 12 weeks after first infusion and clinical remission, defined as CDAI < 150 in patients with steroid/dependant patients; (b) reduction of at least 50% of the number of fistulas or complete closure of fistulas in patients with fistulating disease. The following variables were evaluated in a multivariable model (logistic regression: sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies. Results. (a) Steroid dependant/resistant disease: 36 patients (16%) had a clinical response and 145 patients (66.8%) reached clinical remission. (b) Fistulating disease: 48 patients (28.9%) had a reduction of 50% of the number of fistulas and in 69 patients (41.5%) a total closure of fistulas was observed. At multivariable analysis, previous surgery was associated with a reduced response in steroid resistant/dependant patients whereas no variable predictive of response was identified in patients with fistulating disease. Conclusions. Infliximab is effective in steroid dependant/resistant patients and in fistulating disease. Previous surgery predicts a worse response in steroid dependant/resistant inflammatory disease. CO076 IDENTIFICATION OF VARIABLES RELATED TO COMPLICATIONS AND DIABETES IN PATIENTS AFFECTED BY CHRONIC PANCREATITIS BY ARTIFICIAL NEURAL NETWORKS (ANNs) N. Paganoa , M. Buscemab , E. Grossic , M. Intraligib , G. Massinib , P. Salaconea , E. Gaiaa a Gastroenterology

Unit, S. Luigi Hospital, Orbassano, Turin, Italy Research Center, Rome, Italy c Bracco Imaging, Milan, Italy b Semeion

Artificial neural networks have been used to identify the variables predictive of the complications (pseudocyst, fluid collections, inflammatory masses, segmentary portal hypertension), or diabetes in patients suffering from chronic pancreatitis (CP) that was diagnosed by clinical history, imaging and functional pattern. Materials. The analysed data base consisted of 92 patients, 36 of which were female, in age between 20 and 83 years. The considered variables were 26: male, female, age, family history, determined illness onset, undetermined illness onset, alcohol consumption, smoking, gallstone disease, dislipidaemia, dispepsia, pain, seric enzymes rise at the time of pain, calcifications, esocrine insufficiency, other pathologies, genetic mutations (CFTR, PSTI, 5T polymorphism, no mutations found in studied genes), abdominal ultrasound alterations, CT alterations, ERCP alterations, direct X-ray abdomen scan alterations, complications, diabetes mellitus. The last two variables represented the targets to be predicted, the remaining 24 have been used as neural networks’ input. Methods. Three research protocols were used, all based on supervised neural networks: (1) random research protocol implemented by utilisation of back propagation neural networks and linear statistical model; (2) optimised protocol with “artificial organisms” training and testing (T&T) and input selection (IS) (Semeion); (3) euristic protocol based on the variables most frequently selected by IS. Results. The best classification was achieved by the euristic protocol with the 93.23% of accuracy for what concerns the variable complications and with the 92.63% for the variable diabetes. The variables that resulted in association with the complications were: alcohol consumption, smoking, gallstone disease, dislipidaemia, pain, calcifications, esocrine insufficiency, other pathologies, genetic mutations, abdominal ultrasound alterations, CT alterations. The variables which resulted predictive of diabetes were: age, family history, alcohol, other pathologies, genetic mutations, CT alterations, ERCP alterations. Conclusions. Artificial neural network provides an important help in clinical practice. Their use has permitted to identify with an accuracy higher than 92% of the variables that significantly predicted the onset of complications and diabetes in chronic pancreatitis patients.

CO077 PREVALENCE OF THE K469E POLYMORPHISM OF INTERCELLULAR ADHESION MOLECULE 1 GENE IN ITALIAN PATIENTS WITH INFLAMMATORY BOWEL DISEASE A. Papa, A. Flex, R. Pola, E. Gaetani, A. Armuzzi, A. Grillo, R. Urgesi, S. Guglielmo, I. Roberto, B. De Pascalis, P. Fedeli, L. Guidi, I. De Vitis, G. Fedeli, G. Gasbarrini, P. Pola, A. Gasbarrini. Istituto di Medicina Interna, Università Cattolica, Rome, Italy Background and aim. Intercellular adhesion molecule 1 plays an important role in the recruitment of leukocytes at the sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene, has been identified. The aim of this study was to assess the potential association of this polymorphism with inflammatory bowel disease. Patients and methods. A total of 165 inflammatory bowel disease patients, 75 with Crohn’s disease and 90 with ulcerative colitis and 187 controls were studied. The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by χ2 test. Results. In inflammatory bowel disease the distribution of intercellular adhesion molecule 1 genotypes was: 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly increased in inflammatory bowel disease than controls. The prevalence of the E469 allele was higher in inflammatory bowel disease than controls. Conclusions. We identified an association of inflammatory bowel disease with the allele E469 of intercellular adhesion molecule 1 gene and E/E genotype. However, further studies are needed to confirm our findings. CO078 COLORECTAL LATERAL SPREADING TUMOURS: CLINICOPATHOLOGIC FEATURES M. Pellegrini, M. Marini, M. Nardi, R. Macchiarelli, R. Chieca, S. Rentini, G. Frosini GI Unit, Post-Graduate School of Gastroenterology, University of Siena, Siena, Italy Background and aim. Lesions over 10 mm in diameter that extend superficially over the colorectal mucosa are known as lateral spreading tumours (LST). These lesions have been recognised as important precursors of advanced colorectal carcinoma. The aim of our study was to assess the clinicopathologic features and the efficacy and safety of endoscopic mucosal resection (EMR) of these large tumours. Materials and methods. Seventy-two lesions were studied, divided into two macroscopic types: F-type composed of LST with a flat and smooth surface and G-type composed of lesions with a granulonodular surface. Tumour features were analysed using chromoendoscopy with indigo-carmin dye. EMR was performed with en bloc or piecemeal technique, with saline solution injection under the lesion. Results. The size of lesions ranged from 1 to 5 cm. Of the 72 LST, 34 tumours were of F-type and 38 of G-type. Flat and smooth lesions (mean± S.D., 21.4±8.5 mm) were significantly smaller than granulonodular lesions (mean ± S.D., 34.6 ± 14.2 mm). Flat-LST were preferentially located in the ascending and transverse colon; G-type were most frequently located in the caecum and rectum. Endoscopic resection was performed in one segment in 40 of 72 cases; in the remaining 32 lesions piecemeal resection was done. Lateral spreading tumours consisted of 35 adenomas and 37 adenocarcinomas; Flat lesions showed a more aggressive phenotype (62%) than Granulonodular type (39%). Local recurrence was found in 12 cases (five F-type and seven G-type), during an average follow-up period of 5 years. All recurrent lesions were small size adenomas and were treated

Abstracts endoscopically. Complications included five cases of procedural bleeding, easily treated with endoscopic thermal methods. Conclusions. Our study confirms that, despite their smaller size, F-type LST have a more important role as a precursor of colorectal carcinoma than G-type. These lesions can be treated effectively and safely with endoscopic mucosal resection. CO079 BILIRUBIN INCREASES BILE SALT-DETERGENT ACTIVITY: RELEVANCE FOR GASTROINTESTINAL AND BILIARY TOXICITY IN CHOLESTASIS P. Portincasa, A. Moschetta, M. Petruzzelli, M. Vacca, M. Krawczyk, G. Palasciano Section of Internal Medicine, Department of Internal and Public Medicine (DIMIMP), University Medical School, Bari, Italy Background. Bile salts and bilirubin are key bile components, both potentially toxic. Bile salt detergent activity is prevented by micellar incorporation of phospholipids in bile [1]. Whereas intracellular bilirubin can be toxic, little is known on combination of bilirubin plus bile salts and/or phospholipids on cellular membrane. Aims. To study the effect of bilirubin and phosphatidilcholine—the main human bile phospholipid—combined with different BS on cellular osmotic resistance. Methods. Osmotic resistance and haemolysis were evaluated in red blood cells (RBCs) from control subjects and patients with extrahepatic cholestasis and upon incubation with different concentrations of bilirubin, phosphatidylcholine and bile salts (taurodeoxycholate (TDC), hydrophobic— highly detergent; taurocholate (TC), intermediate hydrophobicity; taurodeoxycholate (TUDC), hydrophilic: not detergent). Results. Control RBCs showed 50% haemolysis (E50 ) with 55% H2 O/45% NaCl. Pre-incubation with bilirubin 50 and 100 ␮M increased osmotic resistance (E50 : 65% H2 O/35% NaCl and 75% H2 O/25% NaCl, respectively). Cholestatic RBCs showed increased osmotic resistance (similar to that of control RBCs preincubated with 100 ␮M bilirubin). Bilirubin + bile salt incubation yielded increased haemolysis compared to bile salts alone. Bilirubin at 0, 50 and 100 ␮M dose-dependently increased haemolysis by TDC (E50 = 2.1, 1.8 and 1.4 mM, respectively) and TC (E50 = 36, 26 and 21 mM), while TUDC was poorly toxic with 100 ␮M bilirubin (E50 = 90 mM). Concentration of micellar phosphatidylcholine which is able to prevent bile salt toxicity increased in the presence of bilirubin 100 ␮M (phosphatidylcholine/bile salt ratios from 0.41 to 0.52 for TDC and from 0.28 to 0.42 for TC). Conclusions. Bilirubin causes plasma membrane osmotic resistance. The presence of bilirubin further increases bile salt-detergent effect with more micellar phospholipids needed for protection. Our data offer insights into mechanisms of apical membrane toxicity in the gastrointestinal and biliary tract during cholestasis and are relevant to assess in vitro protection models. Reference

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CO080 SYNDECAN 1 (SY-1) AND TUMOUR NECROSIS FACTOR ALPHA (TNF␣) IN COLONIC MUCOSA OF PATIENTS WITH CROHN’S DISEASE (CD): A DOWN-REGULATION OF ADHESION MOLECULES BY CYTOKINES? M. Principia , R. Dayb , S. Marangic , O. Burattinic , M. Margiottac , V. De Francescoa , E. Ierardid , C. Panellad , A. Francavillac , A. Forbesb a Gastroenterology

Unit, Ospedali Riuniti, Foggia, Italy Mark’s Hospital, London, UK c Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy d Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Foggia, Italy b St.

Background. It is known that a key role in the inflammation which characterises CD is linked to TNF␣ release in intestinal mucosa. Moreover, SY-1 is a cell adhesion molecule, which mediates the maintenance of mucosal integrity and, in the case of damage, stimulates tissue repair. A recent evidence demonstrates that SY-1 expression is suppressed by TNF␣ in endothelial cells. Aim. To evaluate and correlate the simultaneous expression of TNF␣ and SY-1 in biopsy samples of patients affected by CD of the large bowel in an active phase. Patients. The study was performed on biopsies from 10 patients with active CD of large bowel. Samples from an equal number of subjects (homogeneous for sex and age) with irritable bowel syndrome were used as control. Methods. Immunohistochemical detection of both TNF␣ (PromoCell, Heidelberg, Germany) and SY-1 (MCA 681, clone B-B4, Serotec, Kidlington, UK) were performed on successive serial sections according to previously described methods [1,2]. Overall labelling indices (OLI) of both molecules in the lamina propria was indicated by the percentage of positive stromal cells and evaluated by the count of at least 1000 cells in randomised fields. Additionally, a simultaneous evaluation of TNF␣ and SY-1 expression in a same single selected field of each specimen (SLI) was performed. Results. Both TNF␣ (34.7 ± 7.4 versus 15.0 ± 3.8, P < 0.001; Mann– Whitney U-test); and SY-1 (40.8 ± 5.2 versus 19.8 ± 5.2, P < 0.001; Mann–Whitney U-test) OLI were significantly higher in CD compared to controls. Nevertheless, SLI evaluation showed that TNF␣ overexpression was associated to SY-1 underestimation in CD (r = −0.68, P < 0.03; Spearman’s R-test), while this inverse relationship was not observed in controls. Conclusions. Both TNF␣ and SY-1 are totally increased in intestinal mucosa of patients with CD thus suggesting a general simultaneous presence of damage and repair phenomena. Nevertheless, these two processes are inversely related when a single field is considered, so indicating a patchy predominancy of only one of them. Finally, our data seem to confirm the possibility of a down-regulation between adhesion molecules and cytokines in CD. References

[1] JLR 2000;41:916–24. [1] Ierardi E, et al. J Clin Pathol 2001;54:774. [2] Day R, et al. Dig Dis Sci 1999;44:2508.

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CO081 PROSPECTIVE COMPARISON OF ENDOSCOPIC ULTRASONOGRAPHY (EUS) AND ENDOSCOPIC RETROGRADE CHOLANGIO-PANCREATOGRAPHY (ERCP) IN THE DIAGNOSIS OF COMMON BILE DUCT STONES A. Prisco, M.A. Bianco, T. De Simone, G. Rotondano, C. Meucci, L. Cipolletta UO Gastroenterologia, ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy Aim. To compare the diagnostic accuracy of EUS and ERCP in the diagnosis of CBD stones. Methods. From January 2001 to September 2003, a total of 585 consecutive patients were referred to our division for ERCP. Indication for cholangiography was the suspect of CBD stones in 450 (77%). Ninety patients (20%) presented with jaundice or acute pancreatitis or acute cholangitis or had stones visualised during abdominal ultrasound or CT scan. They were submitted to ERCP and sphincterotomy for duct clearance. One hundred and forty (31%) presented with CBD dilation (≤7 mm) or mild elevation of serum liver enzyme tests or a recent past of acute pancreatitis. They were considered as moderate-risk patients for the presence of CBD stones and were included in the study. They were all submitted to standard bilio-pancreatic radial EUS (GF-UM20; Olympus) under conscious sedation. If the test was positive for the presence of CBD stones, ERCP followed immediately and the radiological images interpreted in a blind fashion. Sphincterotomy and sweeping of the CBD were the next step irrespective of the interpretation of the ERC images. If EUS showed no stones, ERCP was immediately done, and if stones were detected, sphincterotomy was performed. If both tests proved negative for CBD stones, the patient was sent for surgery when appropriate. In patients with CBD stones, the duct was cleared after sphincterotomy and the largest stone was removed for measurement. Results. The diagnosis of CBD stones were confirmed in 32 patients (47%). The sensitivity, specificity and accuracy of EUS and ERC were, respectively, 96% versus 69% (P = 0.028), 100% versus 100%; 98.5% versus 78%. For microlithiasis (stones < 3.0 mm), the sensitivity of EUS and ERCP was 96% versus 19% (P = 0.0013). The diameter of the bile duct (< or >6.0 mm) or the size of the stone (< or >3.0 mm) did not influence the efficacy of EUS. Conclusions. EUS is superior to ERCP in the diagnosis of choledocholithiasis, especially for microlithiasis. Its accuracy approaches 100% irrespective of the diameter of the CBD or the size of the stone. CO082 IS COLONOSCOPY A SUITABLE INVESTIGATION IN THE PREOPERATIVE STAGING OF OVARIAN CANCER PATIENTS? D. Ravizza, G. Fiori, C. Trovato, P. Maisonneuve, A. Maggioni, C. Crosta European Institute of Oncology, Italy Background. During debulking surgery for ovarian cancer, resection of the colon/rectum may be required. In our institution preoperative colonoscopy is usually performed to assess such visceral involvement. The aim of this study is to evaluate the ability of endoscopic findings to predict the infiltration of the colon/rectum in a series of ovarian cancer patients. Moreover, we undertook to observe the prevalence of adenomas in this population. Methods. The study involved 144 consecutive patients with a suspected primary ovarian cancer (physical examination, CT scan, dosage of blood Ca 125, CEA and Ca 19–9) who underwent colonoscopy before debulking laparotomy. Mucosal infiltration, bowel wall elasticity, bowel fixity and extrinsic bowel compression were used to predict colon/rectal infiltration. Colonoscopy findings were compared with the pathologic evaluation of the surgical specimens. All the observed polyps were removed.

Results. Six patients (4.2%) were excluded from the study because of a misdiagnosed primary colorectal cancer metastatic to the ovary. On the basis of the endoscopic findings, 8 (5.8%) patients were considered to have a bowel infiltration, 8 (5.8%) an uncertain infiltration and in the remaining 122 (88.4%) no signs of bowel infiltration were observed. On pathological examination of the surgical specimens, bowel infiltration was histologically confirmed in the eight patients identified during endoscopy. Two infiltrations were histologically confirmed in the group of patients with uncertain infiltration and eight in the group of patients with no evidence of infiltration at endoscopy. Colonoscopy had a low sensitivity (44%) to correctly identify bowel infiltration. Specificity was 100%, positive predictive value 100% and negative predictive value 92%. The overall accuracy was approximately 90%. Thirty-six adenomas were removed in 26 (19%) women. Conclusions. Our study underlines the value of preoperative colonoscopy for patients with supposed primary ovarian cancer in avoiding misdiagnosis with colorectal cancer. Moreover, in the setting of primary ovarian cancer, it accurately identifies a significant number of patients requiring bowel resection, allowing an appropriate planning of the surgical approach. Finally, even though we did not observe any higher prevalence of adenomas in our population, colonoscopy permits their removal and colorectal cancer screening in a population with some evidence of an increased risk for this malignancy. CO083 LACK OF SOMATIC FRAMESHIFT MUTATIONS OF THE hMBD4 GENE IN SPORADIC COLORECTAL CANCERS WITH MICROSATELLITE INSTABILITY L. Ricciardielloa,b,c,1 , C. Ceccarellia,b,c,1 , G. Angiolinia,b,c , A. Goela,b,c , G.N. Martinellia,b,c , C.R. Bolanda,b,c , E. Rodaa,b,c , F. Bazzolia,b,c a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Center for Applied Biomedical Research (CRBA), S. Orsola-Malpighi Hospital Bologna, Bologna, Italy c Baylor University Medical Center, Dallas, TX, USA 1 Both authors equally contributed to this work. Background. Microsatellite instability (MSI) is characterised by insertions, deletions or mutations of single or multiple nucleotides at highly repetitive-short sequences. This phenomenon is due to the lack of function of the DNA mismatch repair (MMR) system. In recent years the hMBD4 gene has been discovered that encodes a methyl-CpG binding endonuclease-1 and interacts with hMLH1. Studies investigating the role of hMBD4 mutations in sporadic colorectal tumours reported diverse (25–90%) mutation rates, and these mutations have been shown to be exclusively associated with MSI-H colorectal tumours. We believe that this large discordance is partially due to the analysis of very small number of cases, but more importantly to the criteria used to define the MSI phenotype. Aim. To determine the correlation between the frequency of hMBD4 gene mutations and microsatellite instability (MSI), using accepted criteria for MSI, and sporadic consecutive colorectal cancers (CRCs). Methods. One hundred and forty-three consecutive sporadic CRCs were tested for microsatellite instability with BAT25 and BAT26. MSI-H tumours were defined by having both markers mutated, those with a single marker unstable were considered as MSI-low (MSI-L) and those negative were stable (MSS). The frequency of somatic mutations in the exonic sequence of hMBD4 (codons 310–313) was determined by PCR followed by fragment analysis using an automated sequencer. DNA from the HCT116 cell line was the positive control. Samples were also stained for protein expression of hMLH1, hMSH2 and hMSH6. Nuclear immunostaining for proteins was quantified by image cytometry. Results. Nineteen cases (13.3%) were MSI-H, 40 (28.0%) were MSI-L and 84 (58.7%) MSS. Thirteen out of 19 MSI-H cases lacked hMLH1

Abstracts expression (68.4%), compared to 1/40 (2.5%) and 1/84 (1.2%) for MSI-L and MSS cases, respectively (P < 0.0001 and <0.0001). hMBD4 was mutated in just 3 cases out of 143 (2%), with two cases being MSI-H and one MSS tumour. We also found 10/143 cases with reduced hMSH2 expression (7.0%) and 1/143 cases with loss of hMSH6 (0.7%). Of the MSI-H CRC, 14 were located in the right colon while 5 were in the left (26.4% versus 5.6%, P = 0.0018). Of the 53 CRC located in the right colon 14 were lacking hMLH1 versus one out of 90 in the left colon (P < 0.0001). Conclusions. hMBD4 is rarely mutated in sporadic colorectal cancers featuring microsatellite instability. The mutation of the gene might be a concomitant feature of hMLH1 mutation in HNPCC. CO084 APPLE POLYPHENOL EXTRACTS PREVENT OXIDATIVE DAMAGE TO HUMAN GASTRIC EPITHELIAL CELLS IN VITRO M. Romanoa,b , G. Graziania,b , C. Tuccilloa,b , V. Foglianoa,b , C. Loguercioa,b , A. Ritienia,b , N. Caporasoa,b , C. Del Vecchio Blancoa,b a Dipartimento

di Scienza degli Alimenti, Università di Napoli, “Federico II” Parco Gussone, Ed. 84-80055 Portici (NA), Italy b Centro Interuniversitario di Ricerche su Alimenti, Nutrizione ed Apparato Digerente (CIRANAD) and Dipartimento Medico Chirurgico di Internistica Clinica e Sperimentale, Cattedra di Gastroenterologia, Seconda Università di Napoli, Naples, Italy

Background and aims. Generation of reactive oxygen species is harmful to the gastric mucosa. Fresh fruit and vegetables exert multiple biological effects on the mucosa of the gastrointestinal tract due to their anti-oxidants content. Whether apple polyphenol extracts (APE) prevent reactive oxygen species-related damage to gastric cells is unknown. This study was designed (1) to assess whether APE counteract oxidative damage to gastric epithelial cells in vitro and (2) to evaluate the mechanism of any such effect. Methods. We used MKN 28 gastric epithelial cells derived from a human well differentiated gastric adenocarcinoma. APE were obtained from freeze dried apple flesh of “Annurca” variety following extraction with methanol. Oxidative stress was induced by incubating cells with xanthine oxidase (XO) (50 mU/ml) in the presence of xanthine (X) (1 mM). Cell damage was assessed by LDH release and by MTT. Intracellular anti-oxidant activity was determined using the 2,2 -azinobis (3-ethylbenzothiazolin-6-sulphonate (ABTS)) method. Malondialdheyde intracellular concentration, an index of lipid peroxidation, was determined by HPLC with fluorometric detection. Results. (1) X-XO dose-dependently and significantly damaged gastric cells. (2) Preincubation with APE significantly prevented X-XO-induced injury decreasing cell damage by over 50% (P < 0.05). (3) Pure catechin or chlorogenic acid (the main polyphenol components of APE) were as effective as APE in preventing oxidative injury to gastric cells. (4) Pre-treatment with APE increased the intracellular concentration of catechin, chlorogenic acid and epicatechin. (5) Pre-treatment with APE caused a four-fold increase in the intracellular anti-oxidant activity and significantly prevented its drop induced by X-XO. (6) Pre-treatment with APE counteracted X-XO-induced increase in malondialdhyde formation. Conclusions. (1) APE significantly protects gastric epithelial cells in vitro against damage brought about by reactive oxygen species. (2) Catechin and chlorogenic acid seem to greatly contribute to APE-related protective effect. (3) APE increases the intracellular anti-oxidant activity and prevent lipid peroxidation induced by reactive oxygen species. (4) MKN 28 cells are a suitable in vitro system for screening vegetable compounds with anti-oxidant properties and for elucidating their mechanism of action. (5) We postulate that a diet enriched with apple polyphenols might exert a beneficial effect in gastric pathological conditions related to generation of reactive oxygen species.

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CO085 REACHING THE ILEO-CAECAL VALVE DURING CAPSULE ENTEROSCOPY (CE) IS INDIPENDENT BOTH FROM INTESTINAL PREPARATION WITH LAXATIVES AND FROM THE USE OF PROKINETIC DRUGS PRIOR TO THE EXAM E. Rondonotti, C. Abbiati, C. Signorelli, G. Beccari, R. de Franchis IRCCS Ospedale Maggiore Policlinico Milano, Dipartimento di Medicina Interna, Servizio di Gastroenterologia ed Endoscopia Digestiva, Università degli Studi di Milano, Milan, Italy Background. CE is a diagnostic tool for the endoscopic study of the entire small bowel. Aims. To assess causes of incomplete small bowel evaluation by CE, and whether the incompleteness of CE decreases the diagnostic yield of the procedure. Patients and methods. One hundred and forty-two CE were performed in 138 patients (mean age ± S.D.: 59.7 ± 18.0 years). Indications were: obscure GI bleeding (80.2%), refractory coeliac disease (4.9%), diarrhoea (4.2%), known or suspected Crohn’s disease (2.1%), other (8.4%). Patients (77.9%) were given laxatives the day before CE; metoclopramide (10 mg i.v., 15 min before the exam) was used in 5.8%. CE was performed according to the standard procedure. Results. Overall mean gastric transit time (GTT) and mean small bowel transit time (SBTT) were 42 ± 54 (range 1–254), and 254 ± 79 (range 101 –532 ), respectively. CE results were positive in 35.2% of cases, negative in 36.7% and uncertain in 28.1%. The ileo-caecal valve (ICV) was reached during the recording time in 100 cases (70.4%, group A): in this group the mean GTT and mean SBTT were 32 ± 32 (range 1–177) and 254 ± 80 (range 101–532). In 36 cases (25.3%) the ICV was not reached during the exam (group B): a cause of this could be identified in six cases (16.6%, group B1); while in 30 (83.3%, group B2) there was no apparent reason. Laxatives had been administered in 81% of cases in group A versus 93.1% in group B2 (P = 0.204). The i.v. metoclopramide had been administered in 7.0% of cases in group A versus 6.8% in group B2 (P = 0.794). Mean GTT was 32 ± 32

in group A and 71 ± 85 in group B2 (P = 0.023). CE results were: group A, positive in 30.8% of cases, uncertain in 27.8% and negative in 41.4%; group B, positive in 51.5% of cases, uncertain in 30.9% and negative in 18.2% (P = 0.0094). In 14.2% (3/21) of patients in group B, further exams showed lesions beyond the point reached by the capsule. Conclusions. CE enables a complete study of the small bowel in about 3/4 of cases. Failure to reach the ICV during video recording appears to be related to the GTT, but does not depend on intestinal preparation, or on the administration of prokinetic drugs before the exam. The diagnostic yield of CE in complete exams was similar to that of the exams in which the ICV was not reached, although, in about 15% of the latter, further diagnostic techniques identified some lesions in small bowel segments beyond the point reached during capsule recording.

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CO086 FREQUENT DNA HYPERMETHYLATION IN GASTROINTESTINAL TUMOURS: AN EARLY TUMOUR SPECIFIC LESION THAT CAN BE DETECTED IN PERIPHERAL BLOOD S. Sabbionia , A. Pezzolib , E. Miottoa,c , A. Veronesec , E. Sattind , R. Gafàa , G. Lanzaa , C. Feod , A. Libonid , S. Gullinib , M. Negrinia,c,e a Dipartimento

di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy b Unità Operativa di Gastroenterologia, Azienda Ospedaliera Universitaria di Ferrara, Ferrara, Italy c Istituto Oncologico Veneto, International Cancer Center, Molecular Biology Laboratories, Rovigo, Italy d Dipartimento di Scienze Chirurgiche, Anestesiologiche e Radiologiche, Università di Ferrara, Ferrara, Italy e Centro Interdipartimentale per la Ricerca sul Cancro, Università di Ferrara, Ferrara, Italy Introduction. Identification of frequently hypermethylated tumour markers, that by becoming methylated in early or preneoplastic lesions, may be useful for early disease detection. Materials and methods. Analysis of methylation status at eight loci in 89 primary tumour samples of the gastrointestinal tract, and in early or pre-neoplastic lesions of the colon and the liver, was carried out using a methylation-specific PCR assay (MSP). Analysis of the most informative markers was also performed on DNA from colon washings and peripheral blood of patients undergoing surgery for colorectal carcinoma and individuals undergoing colonscopy for clinical conditions not associated with tumours. Results. Analysis of methylation status of DNA revealed that in tumour samples the DNA is frequently abnormally methylated at different loci. Methylation was found in 95% of colorectal carcinomas, 100% of gastric carcinomas and 86% of hepatocellular carcinomas. These alterations were also detected in colon adenomas and surrounding tissues, indicating that hypermethylation at these loci occurs early in tumour progression. The same alterations were detected in colon washings and peripheral blood of colorectal tumour patients and patients with early or pre-neoplastic lesions, but not in healthy volunteers. Conclusions. A limited panel of loci frequently hypermethylated in colorectal tumour patients and patients with early or pre-neoplastic lesions was identified. Their detection in colon washings and peripheral blood, could allow their use for the follow-up of cancer patients or the screening of individuals at the risk of developing cancer using a non-invasive approach. CO087 CHANGE OF ENDOTHELIAL PROTEIN C RECEPTOR (EPCR) AND THROMBOMODULIN EXPRESSION IN THE INTESTINAL MUCOSA OF PATIENTS WITH INFLAMMATORY BOWEL DISEASES S. Saibenia , E.M. Faionib , S. Ferreroc , G. Fontanab , U. Gianellic , M. Ciullad , E. Biguzzie , N. Cordanic , F. Franchie , S. Bosaric , M. Cattaneob , M. Vecchif

a University

of Milano, Milan, Italy and Thrombosis Unit, Ospedale San Paolo, San Paolo, Italy c Pathology Unit, Ospedale San Paolo and IRCCS Ospedale Maggiore Policlinico, San Paolo, Italy d Laboratory of Clinical Informatics and Cardiovascular Imaging, Institute of Clinical Medicine and Therapy, IRCCS Ospedale Maggiore Policlinico, San Paolo, Italy e Haemophilia and Thrombosis Center, IRCCS Ospedale Maggiore Policlinico, San Paolo, Italy f Gastroenterology and Gastrointestinal Endoscopy Service, Hepatology Unit, IRCCS Ospedale Maggiore Policlinico, San Paolo, Italy b Hematology

Background and aim. The protein C is a potent natural anti-thrombotic and anti-inflammatory substance, whose activation is regulated by the endothelial expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR). Inflammatory bowel diseases are characterised by chronic inflammation and an increase prevalence of thrombosis. The aim of the present study was to evaluate the expression of EPCR and TM in intestinal resection or mucosal biopsy specimens from patients with inflammatory bowel diseases and controls. The soluble forms of the receptors were also measured in plasma. Materials and methods. Resection specimens from 36 patients with ulcerative colitis, 38 with Crohn’s disease were studied by immunohistochemistry and immunofluorescence. Thirty-eight peritumoural tissue specimens from patients with colon cancer and 32 resection specimens from patients with diverticulitis were used as controls. RNA from 12 frozen tissues from IBD and controls undergoing colonoscopy was extracted for RT-PCR. Soluble receptors were measured in the plasma of 52 IBD patients and 52 controls. Statistical analysis was performed by means of non-parametric tests. Results. Endothelial protein C receptor and thrombomodulin were expressed on mucosal endothelium of normal specimens, while the intensity of the signal decreased in inflammatory bowel diseases. Surprisingly, EPCR was also expressed by dendritic-like cells, which also stained positive for CD21. Co-localisation was verified by immunofluorescence. The number of EPCR+/CD21+ dendritic-like cells was decreased in ulcerative colitis patients compared to controls (12.0 ± 3.6 cells per high power field versus 23.8 ± 10.4, P = 0.03), while this decrease was less evident in sections from Crohn’s disease patients. Messenger RNA for EPCR paralleled protein expression. Median soluble thrombomodulin and EPCR plasma levels were higher in IBD patients than in controls: 41.5 versus 26.0 ug/ml (P < 0.0001) and 141 versus 130 ng/ml (P < 0.05), respectively. Conclusions. EPCR expression on dendritic-like cells which bear the key complement receptor CD21 suggests a role for EPCR in innate immunity. In IBD, the reduced mucosal expression of TM and EPCR as well as the high soluble TM and EPCR plasma levels suggest a derangement of protein C activation, possibly leading to decreased anti-thrombotic activity of this pathway. CO088 INAPPROPRIATELY LOW ANGIOTENSIN-CON- VERTING ENZYME (ACE) PLASMA LEVELS: A FACTOR WORSENING KIDNEY FUNCTION AND SURVIVAL RATE IN SUBSETS OF PATIENTS WITH DECOMPENSATED CIRRHOSIS G. Sansoéa , S. Silvanob , G. Mengozzic , L. Todrosb , A. Smedileb , G. Touscozb , F. Rosinaa , M. Rizzettob a Gastroenterology b Department

Unit, Gradenigo Hospital, Turin, Italy of Gastroenterology, Molinette Hospital, University of Turin,

Turin, Italy c Institute of General Pathology, Molinette Hospital, Turin, Italy Angiotensin II is the main mediator in the glomerular vas efferens vasoconstriction, which maintains glomerular perfusion pressure and glomerular filtration rate (GFR) in renal hypoperfusion. This study explores the hypothesis that depressed angiotensin II generation, due to reduced angiotensinogen production or low angiotensin-converting enzyme (ACE) levels, could impair kidney function in advanced cirrhosis. We studied and prospectively followed up 21 diuretic-free ascitic cirrhotic patients, through these determinations: systemic plasma levels of active renin (AR), renin activity (PRA), angiotensin II (Ang II), angiotensin-converting enzyme (ACE) and aldosterone; renal clearances of sodium, insulin and para-aminohippurate; antipyrine clearance and plasma half-life. Fifteen healthy subjects were also studied. GFR distribution was bimodal: 10 patients had low GFR values (l-GFR group) and 11 had normal GFR values (n-GFR group) (below and above 105 ml/min/1.73 m2 b.s.a., respectively). Antipyrine clearance and Child–Pugh score did not differ

Abstracts in the two patient groups. Compared with the n-GFR group, the l-GFR group had significantly higher AR and PRA values (all P < 0.01), significantly lower levels of plasma ACE (P < 0.03) and a significantly higher AR/Angiotensin II ratio (1.66 ± 0.97 versus 0.48 ± 0.38, P < 0.003). Compared with controls all 21 patients showed markedly increased values of the AR/PRA ratio (P < 0.03), i.e. reduced renin substrate circulating levels. The respective 18-month survival rates of l-GFR and n-GFR groups were 20 and 81% (P < 0.02). In conclusion, Low-GFR cirrhotic patients had a worse survival rate associated with more severe contraction of the effective arterial blood volume, higher AR/Angiotensin II ratio and lower ACE levels. CO089 TYPE 1 VANILLOID RECEPTOR (VR-1) MEDIATES THE CAPSAICIN-INDUCED [Ca2+ ]i INCREASE IN MYENTERIC PLEXUS OF GUINEA PIG’S SMALL INTESTINE G. Sarnelli, R. Bischoops, P. Rayemakers, R. Cuomo, J. Tack Centre for Gastroenterological Research, KUL, Leuven, Belgium Background. Capsaicin activates extrinsic afferent nerves in the gastrointestinal tract through the non-selective cation channel type 1 vanilloid receptor (VR-1) receptor. Recently, VR1 immunoreactivity has also been reported in intrinsic neurons in the myenteric plexus of guinea pig (Anavi-Goffer, 2002; 2003). Our aim was to study the effect of capsaicin on [Ca2+ ]i in myenteric plexus and in cultured myenteric neurons. Methods. We used confocal calcium imaging to study neuronal responses to capsaicin (10−7 to 10−5 M) in the myenteric plexus in situ from guinea pig’s small intestine. Capsaicin selective antagonist and agonist capsazepine (10−6 M) and resiniferotoxin (RTX) were, respectively, used to characterise whether capsaicin induced responses were mediated by VR1. Also sets of experiments were performed in cultured myenteric neurons. Results. In the myenteric plexus, capsaicin produced a concentrationdependent increase in [Ca2+ ]i , with 9, 13 and 24% of neurons responding, respectively, to 10−7 , 10−6 and 10−5 M (n = 33, 102 and 160, respectively). Capsaicin-induced [Ca2+ ]i rises depended on the presence of extracellular Ca2+ (no neuron responding out of 107) and they were inhibited by pre-treatment with the VR-1 antagonist capsazepine (1 neuron responding out of the 118). Administration of the selective VR-1 agonist resiniferatoxin (10−6 M) induced similar [Ca2+ ]i rises, confirming specificity of the excitatory responses (37% of responses, n = 59). In cultured myenteric neurons capsaicin failed to induce any significant response (n > 100). Conclusions. In in situ myenteric plexus capsaicin induces a [Ca2+ ]i rise in a subset of neurons via influx of extracellular calcium which is mediated by the VR-1 receptor. In cultured myenteric neurons capsaicin has no effect on neuronal excitation. Although the lack of effect of capsaicin in cultured myenteric neurons may reflect phenotypic variations our results are likely to suggest that capsaicin-induced myenteric responses involves type 1 vanilloid receptor that are located on extrinsic fibres projecting to myenteric plexus. CO090 INADEQUATE USE OF ACID-SUPPRESSIVE THERAPY IN HOSPITALISED PATIENTS AND ITS IMPLICATIONS FOR GENERAL PRACTICE R. Scagliarini, E. Magnani, A. Zelante, R. Bocchini, A. Praticò, P. Pazzi Dipartimento di Medicina, Interna Ospedale “M. Bufalini” Cesena, Italy Acid-suppressive therapy (AST) is largely prescribed in both hospital setting and general practice. Only scanty data are available on AST use in hospitalised patients and its influence on general practice prescription. Our aims were to evaluate the appropriateness of AST in hospitalised patients and to determine the fall-out of hospital prescription in general practice. AST use was assessed in 834 patients consecutively admitted to

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an internal medicine department of an urban, community hospital. Clinical charts were reviewed to determine the type of medication and timing of prescription, and indication for use was jointly assessed by two consultant gastroenterologists, according to widely accepted clinical guidelines. Prescriptions were rated as indicated, acceptable or not indicated. A total of 834 patients were evaluated: 58.7% of them received AST, mainly proton pump inhibitors (97.8%). Overall, 50.1% of prescriptions were rated as indicated, 6.5% as acceptable, 41.5% as not-indicated, unclassifiable in nine cases (1.9%) due to incomplete clinical chart. The main reason for inappropriate prescription was ulcer prophylaxis in low-risk patients (64.8%), particularly in patients on corticosteroids, oral anticoagulation or episodic NSAID use. At the time of admission, 112 patients (13.4%) were already on AST: the prescription was appropriated in 52.6%, acceptable in 8.9%, inappropriate in 35.7%, non-valuable in 2.7%. Among patients on AST during hospitalisation, 320 were discharged on therapy: indications were appropriated in 52.8%, acceptable in 5.9%, inappropriate in 36.9%, non-valuable in 4.4%. Again, the main reason for inappropriate use was prophylaxis in low-risk patients (66.1%). Although a trend for higher inappropriate rate was observed during hospitalisation, no significant difference was observed when comparing the proportion of inappropriate use at the admission, during hospitalisation and at the discharge. Interestingly, in 64 inpatients (7.7%) AST was judged as necessary (i.e. necessity of prescription), but they were not put on therapy (under-use): in 95.3% there was a need of ulcer-prophylaxis. In conclusion, AST is over-used in both hospital setting and general practice, mainly because of over prescription for prophylaxis in low-risk patients. The inappropriate use in hospitalised patients seems also to induce inappropriate prescription in general practice. In a small but not negligible proportion of patients, albeit is recommendable, AST is not prescribed. CO091 INTERLEUKIN 17 INDUCES THE ACTIVATION OF AP-1 AND NF-␬B IN HUMAN GASTRIC EPITHELIAL CELLS LEADING TO IL-8 TRANSCRIPTION L. Sebkova, A. Pellicanò, G. Monteleone, B. Grazioli, G. Guarnieri, M. Imeneo, F. Pallone, F. Luzza Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro “Magna Graecia”, Italy Background. IL-17, a potent inducer of IL-8 in epithelial cells, is up-regulated in Helicobacter pylori (HP)-colonised gastric mucosa. The promoter region of the gene encoding IL-8 includes binding sites for the transcription factors activator protein-1 (AP-1), nuclear factor-kappa B (NF-␬B), and NF-IL-6. Aim. To investigate the transcriptional activation of IL-17-induced IL-8 synthesis in gastric epithelial cells. Methods. Human gastric cancer cell line MKN 28 was cultivated in complete medium at a concentration of 3 × 1,000,000 cells/ml until they reach confluence. After that, MKN 28 cells were serum deprived for 12 h and stimulated with recombinant IL-17 (1 ng/ml) up to 30 min at intervals of 5 min. Finally, nuclear proteins were extracted from MKN 28 cells. Also mRNA was extracted at 0, 15, and 30 min time points. IL-8 levels were measured by semiquantitative RT-PCR. The activation of AP-1, NF-␬B, and NF-IL-6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Results. IL-17 rapidly induced an increase in AP-1 and NF-␬B DNA-binding activity in MKN 28 cells within 5 min. No changes were found in NF-IL-6 DNA-binding activity at any time point. The activation of AP-1 sites persisted up to 15 min and then slightly declined, while NF-␬B DNA-binding activity declined immediately after 5 min. Transcription of IL-8 significantly increased at 30 min, while no changes were seen at 15 min. Conclusion. Transcriptional activation of the IL-8 promoter induced by IL-17 in gastric epithelial cells involves AP-1 and NF-␬B. This pathway may be relevant in HP-colonised gastric mucosa.

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CO092

CO093

COLONOSCOPY SCREENING FOR COLORECTAL CANCER. A COMPARATIVE STUDY OF DIFFERENT STRATEGIES

SENSITIVITY AND SPECIFICITY OF THE “RED BLOOD IDENTIFICATION SYSTEM (RBIs)” IN VIDEO CAPSULE ENTEROSCOPY

N. Segnana , L. Bisantib , G. Castiglionec , C. Crostad , A. Ederlee , A. Fantine , A. Ferrarif , S. Gasperonig , G. Malfitanah , A. Perai , S. Recchiaj , M. Rizzettok , C. Senorea , P. Turcol a CPO

Piemonte, Turin, Italy Unit, ASL “Citta’ di Milano”, Milan, Italy c Gastroenterology Unit, CSPO, Firenze, Italy d Gastroenterology Unit, European Institute Gastroenterology Unit, Italy e Manani Hospital, USSL 20 Verona, Italy f Gastroenterology Unit, Maria Vittoria Hospital, Turin, Italy g Gastroenterology Unit, Infermi Hospital, AUSL Rimini, Rimini, Italy h Gastroenterology Unit, Infermi Hospital, ASL 12 Biella, Italy i Gastroenterology Unit, Mauriziano “Umberto I” Hospital, Turin, Italy j Gastroenterology Unit, S. Giovanni Bosco Hospital, Turin, Italy k Gastroenterology Unit, S. Giovanni Battista-Molinette Hospital, Turin, Italy l Citopathology Unit, CSPO, Firenze, Italy b Epidemiology

Background and aims. Colonoscopy (TC) has been proposed as a screening method for colorectal cancer (CRC), but comparative data concerning performance and acceptability of the test are lacking. The study aims to estimate the coverage and the detection rate (DR) achievable through different strategies. Methods. We conducted a multicentre randomised trial comparing: (1) biennial immunological faecal occult blood test (FOBT); (2) “once only” sigmoidoscopy (FS); (3) “once only” TC. A random sample of men and women, aged 55–64 years, was drawn from general practitioners (GP) lists in six Italian cities. GPs were asked to exclude patients with a history of CRC, adenomas, inflammatory bowel disease, recent (2 years) colorectal endoscopy or FOBT, or two first degree relatives with CRC. Eligible subjects were randomised, within GP, and were mailed a personal invitation, signed by GP. We will send a second invitation at 12 months to non-responders in groups 2–3. The use of sedation during TC was negotiated with the patient. Screenees with “high risk” (villous component, severe dysplasia, CRC, size 10 mm, or >2 adenomas) distal polyps at FS and those with positive FOBT were referred for TC. Results. Attendance to the first invitation was: 29.3% (1625/5546) for FOBT (range 19.6–56.4%); 27.4% (1380/5043) for FS (range 19.2– 48.4%); 21.9% (1103/5041) for TC (range 12.2–43.6%). Positivity rate of FOBT was 4.3%. The positive predictive value for advanced neoplasia (villous component, severe dysplasia, CRC, size 10 mm) was 33.3%: 2 patients were detected with CRC (1.3 = 89) and 16 with advanced adenomas (1.0%). FS was completed to the distal descending colon in 90.4% of the cases; 90 (6.8%) patients were referred for TC. Six patients (4.3 = 89) harboured a CRC and 61 (4.4%) an advanced adenoma. Completion rate of TC was 86.2%. Sedation was used in 30.5% of the exams (range 14.3–77.0%). Prevalence of advanced neoplasia was 5.2% in the rectum and sigmoid and 2.2% in the proximal colon. FS would have detected 25.9% of the proximal advanced neoplasms detected at TC. Minor self-limited complications occurred in 0.2% of patients following FS and in 1.2% following TC. Conclusions. Attendance was significantly higher in the FOBT group (FOBT versus FS, P ≤ 0.027; FOBT versus TC, P < 0.000). FS was associated with a four-fold increase in the DR of advanced neoplasia compared to FOBT. The increase in DR of proximal neoplasia with TC compared to FS was associated with a 20% reduction in the attendance.

C. Signorelli, C. Abbiati, E. Rondonotti, G. Beccari, R. de Franchis Università degli Studi di Milano, Dipartimento di Medicina Interna, Servizio di Gastroenterologia ed Endoscopia Digestiva, IRCCS Ospedale Maggiore Policlinico Milano, Milan, Italy Introduction. Capsule enteroscopy (CE), a recently introduced diagnostic tool for the endoscopic study for the small bowel, has given very good results in patients with obscure GI bleeding (OGIB). In order to make the analysis of video recordings quicker in these patients, a specific software has been implemented which can recognise the frames containing “red spots” (red blood identification system, RBIs). Aim of the study. To assess the sensitivity and specificity of the RBIs in a group of consecutive patients undergoing CE. Patients and methods. Between February and October 2003, 54 patients (mean age ± S.D.: 62.4 ± 19.1 years; M/F: 28/26) were submitted to CE for the following indications: OGIB (41/54 patients; 76%), known or suspected Crohn’s disease (3/54; 5.5%); other (10/54; 18.5%). Small bowel visualisation was obtained in 50/54 cases (one patient could not swallow the capsule, and in three cases the capsule remained in the stomach for the entire recording time). The diagnostic yield of CE, according to the physician’s interpretation, was 30% (positive results: 15/50, suspicious: 14/50 and negative 21/50). Results. In the 50 video recordings of the small bowel, the physician could identify 135 frames with “red spots”: 57 artero-venous malformations (AVM), 36 hyperaemic areas, 21 images of red blood, 4 aphtoid lesions, 4 hyperaemic and hypertrophic folds, 3 hyperaemic polyps, 1 ulcerated polyp, 4 trace amounts of red blood, 3 erosions and 2 ulcers. The RBIs could identify 29/135 (21.5%) red spots in the same video recordings, that is: 10/21 (48%) images of red blood, 10/57 (17.5%) AVM, 4/4 (100%) hyperaemic and hypertrophic folds, 3/3 (100%) hyperaemic polyps, 1/1 (100%) ulcerated polyp, 1/36 (2.8%) hyperaemic areas. The sensitivity of the RBIs, calculated on the number of findings (number of positive findings detected by the system/total number of positive findings) was 21.5%. In 10 out of the 50 exams neither the physician, nor the RBIs could identify any lesion (true negative), while on 14 exams the RBIs selected as ‘red’ at least one area which corresponded to normal mucosa (false positive). The specificity of the RBIs, calculated on the number of exams (true negative/true negative + false positive), was 41.6%. Conclusions. The RBIs has low sensitivity and specificity, and cannot replace the viewer’s evaluation. Further studies are needed to clarify whether the RBIs can shorten the review time of the recordings. CO094 BLEEDING AND ISCHAEMIA: MYOCARDIAL DAMAGE DURING GASTROINTESTINAL BLEEDING E. Silverja , T. Mancusoa , A. Catib , F. Bellottob , M. Plebanic , M. Zaninottoc , A. Paveib , M. Senzoloa , R. Naccaratoa , G.C. Sturnioloa , S. Fagiuolia a Department

of Surgical and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy b Department of Cardiology, University Hospital of Padua, Padua, Italy c Laboratory Medicine, University Hospital of Padua, Padua, Italy

Introduction. Patients with gastrointestinal bleeding and acute anaemia may present myocardial ischaemic injury. Gold standard for the diagnosis of myocardial ischaemia (MIS) is a Troponine I (TrI) elevation >0.15 (␮g/l). Aims. Define the prevalence and risk factors of MIS during acute GI bleeding in patients without evidence of coronary artery disease at admission.

Abstracts Material and methods. Patients admitted to the GI Department for GI bleeding (hematemesis and/or melena), with anaemia (Hb < 12 g/dl for female and Hb < 14 g/dl for male patients). A Troponine I curve with sampling within 1 h from admission and thereafter every 8 h for 24 h was obtained, together with ECG recording (ECG alterations was analysed utilising the “Minnesota code”. Results. From November 2002 to September 2003, 227 patients have been enrolled, 145 male, 82 female (mean age 68.7, range 19–97). Concomitant diseases were: cirrhosis (32.2%), cardiovalscular disease (27.3%). Drug-related risk factors for GI bleeding were: anticoagulation/antiaggregation (31%), chronic use of NSAIDS (3%), sporadic use of NSAIDS (12%). TrI was elevated in 8.4% of patients (MIS); (TrI was elevated in 35.3% in patients of age between 60 and 80 years, with a mean level of 0.8 ␮g/l. Thirty-three percent of the patients with abnormal TrI showed ECG alterations. ECG showed alterations in 29% of patients (in 13.6% an elevation of TrI was present). Acute myocardial infarction (MI) was clinically diagnosed in 8/227 (3.5%). In this group the mean age was 72.8 years, mean level of TrI was 3.8 ␮g/l, the mean level of Hb was 8.4 g/dl; 5/8 patients with MI showed EEG alteration. There was no statistical difference between maximal and mean level of TrI between patients with MIS and patients with MI. Minimal value of Hb was significantly different between patients with and without MIS (P = 0.03). This was confirmed by the Multivariate analysis. Sub-grouping the patients according to alcohol intake (no intake, <40, >40 g per day), patients with moderate alcohol consumption showed a significantly lower prevalence of TrI alteration (the prevalence of cirrhosis was 21.7% in alcohol consumer, compared with 36.7% in non-consumer). Upon sub-grouping in quartiles of Hb a cut-off limit of 8.2 g/dl was identified, which strictly correlated with higher risk of MIS (P < 0.05; RR 2 (95% CI, 0,9–4.5]) was identified. Conclusions. In patients with acute GI bleeding: 1. 2. 3. 4.

the prevalence of elevated TrI is 8.4%; MI was diagnosed in 3.5% of the cases; ECG findings are non-specific in identifying patients with MIS; and Hb levels <8.2 g/dl and age over 60 years can identify patients at higher risk of MIS, which require prompt cardiologic evaluation prior to perform the endoscopic procedure.

CO095 CARD15, IL-10 AND CTLA4 POLYMORPHISMS AS MODULATORS OF IBD SUSCEPTIBILITY AND PHENOTYPE E. Solerioa,b,c , M. Ayoubia,b,c , G. Tapperoa,b,c , M. Cicilanoa,b,c , G. Fornaciaria,b,c , G. Matulloa,b,c , A. Parzialea,b,c , A. Mattaliaa,b,c , L. Iannacea,b,c , S. Boscoa,b,c , M. Chiriottoa,b,c , F. Rosinaa,b,c

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controls of Italian Caucasian origin. DNA was extracted from whole blood, amplified by PCR and assayed by RFLP using the restriction enzyme BbvI for the CTLA4 A + 49G; NlaIV for CARD15 3020insC; RsaII, MaeIII and MnlI, respectively, for IL10: A − 592C, T − 819C and G − 1082A polymorphisms. Results UC. A significant correlation was found between UC risk and IL10 A − 592C (P = 0.013 (OR for A/A or A/G = 2.107 (CI 1.270– 3.496)) and IL10 T − 819C (P = 0.007 (OR for T/T or T/C = 2.161 (CI 1.302–3.587)) polymorphisms. A significant correlation was found between UC severity and CTLA4 A+49G polymorphism (P = 0.031 (OR for G/G or A/G = 3.198 (CI 1.089–9.391)) CD: a significant correlation was found between CD risk and IL10 G−1082A (P = 0.045 (OR for G/G or G/A = 1.646 (CI 1.005–2.698)) and CARD15 3020insC (P = 0.007 (OR for wild-type/insC = 3.644 (CI 1.345–9.870)) polymorphisms. Conclusions. Production modifying IL10-promoter polymorphisms modulate IBDs susceptibility. Frameshift mutation CARD15 3020insC, impairing activation of NF-␬B, increases susceptibility to CD. G allele at CTLA4-exon 1 + 49, affecting the CTLA4-driven down-regulation of T-cell activation, represents a risk factor for a severe course of UC. Genotype distribution among healthy controls and ulcerative colitis patients. HC (%), n = 234

UC (%), n = 84

IL10 A − 592C A/A A/C C/C

11 (5) 77 (33) 146 (62)

4 (5) 43 (51) 37 (44)

IL10 T − 819C T/T T/C C/C

14 (6) 78 (33) 142 (61)

5 (6) 44 (52) 35 (42)

Genotype distribution among patients with mild or severe ulcerative colitis.

CTLA4 A+49G A/A A/G G/G

Background and aims. Inflammatory bowel diseases (IBDs) are regarded as multifactorial disorders involving environmental factors and polygenic defects. IBDs are characterised by chronic intestinal inflammation as a result of an exaggerated T-cell response. Genetically driven variations in cytokines production may alter the balance between stimulatory and inhibitory pathways perpetuating the mucosal inflammatory state. Aim. The aim of our study was to evaluate if and how IBDs susceptibility and phenotype is modulated by the following gene polymorphisms (SNPs): CARD15: 3020insC; CTLA-4: A + 49G; IL10: A − 592C; T − 819C; G − 1082A. Patients and methods. We studied 84 unrelated patients with ulcerative colitis (UC), 99 patients with Crohn’s disease (CD) and 234 healthy

Severe (%), n = 20

37 (58) 24 (37) 3 (5)

6 (30) 14 (70) 0 (0)

Genotype distribution among healthy controls and Crohn disease patients.

a Divisione

di Gastroenterologia ed Epatologia, Laboratorio di Biologia Molecolare, Presidio Sanitario Gradenigo, Turin, Italy b Divisione di Gastroenterologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy c Divisione di Gastroenterologia, Ospedale Santa Croce, Cuneo and Dipartimento di Genetica, Biologia e Biochimica, Università degli Studi di Torino, Turin, Italy

Mild (%), n = 64

HC (%), n = 234

CD (%), n = 99

IL10 G − 1082A G/G G/A A/A

31 (13) 100 (43) 103 (44)

22 (22) 45 (46) 32 (32)

CARD15 insC C/C C/W W/Wa

14 (6) 78 (33) 142 (61)

0 (0) 10 (10) 89 (90)

a

Wild-type.

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Abstracts

CO096 M2A PATENCY CAPSULE IN PATIENT WITH INTESTINAL STRICTURES: RESULTS OF THE ITALIAN STUDY GROUP C. Spadaa , S. Gianlucaa , M.E. Riccionia , P. Familiaria , A. Tringalia , M. Marchesea , V. Perria , L. Bianconeb , F. Palloneb , G. Costamagnaa a Digestive

Endoscopy Unit, Department of Surgical Sciences, Catholic University, Rome, Italy b Gastroenterology, University of “Tor Vergata”, Rome, Italy

Background. Small bowel strictures present a clinically difficult diagnostic problem. The radiology offers some options: plain abdominal X-ray, small bowel enteroclysis, small bowel follow-through, magnetic resonance imaging and helical computed tomography. However, false negative examination results can occur in patients with obstruction mainly when it occurs intermittently or it is “only” a partial obstruction. In these cases the obstruction can be discovered only after the ingestion of solids. Aim. To assess the ability of the M2A® Patency Capsule to detect intestinal strictures and the safety of the M2A® Patency System (M2A® Patency Capsule and M2A® Patency Reader) during its use in patients with known or suspected strictures. Material and method. The M2A Patency capsule is a new swallowing, biodegradable capsule, made of an entirely biodegradable (in 100 h) external lactose shaft containing a 3 mm long, radiopaque, metallic tag. The M2A Patency capsule dimensions are similar to those of a regular VCE. Twenty-six patients (10 female, 16 male; mean age 43.2 years) (23 with Crohn’s disease, 2 with adhesive syndrome and 1 with a suspect of ischaemic enteritis) with small bowel strictures (25 cases) or delayed transit time (1 case) depicted by barium X-ray were studied. Previous small bowel resection had been performed in 12 out of 26 patients. Patients were followed with an external reader (M2A® Patency Reader) and fluoroscopy. Results. All M2A Patency capsules but three (11.5%) were retrieved in the stools after mean time of 54.9 h (range 5–391). One patient withdrew the consent during the protocol and stopped to look at the capsule in the stools. Capsule was retrieved intact from the stools in 13 out of 22, with a mean transit time of 16.9 h (range 5–40), in nine patients was retrieved dissolved with a mean transit time of 109.7 h (range 10–391). Statistical correlation was found between the two groups (P < 0.05). Four patients (15.4%) complained of abdominal pain resolved within 24 h after ingestion. No correlation was found between transit time and pain occurrence (Pearson’s correlation test). In two patients the M2A® Patency Reader malfunctioned and it was not able to detect the M2A Patency capsule. Conclusion. M2A Patency capsule could give direct indication of functional patency even in cases where small bowel barium X-ray suggests the presence of a stricture. It seems to be a simple, safe and minimally-invasive.

Material and methods. Familial clustering of CRC and other neoplasms and correspondence to Amsterdam criteria for HNPCC was investigated in 1520 consecutive CRC patients with a family history of CRC. HNPCC families were identified and individuals at risk were advised to take part in a surveillance programme, based on colonoscopy, oesophagogastroduodenoscopy, ultrasonography and other examinations performed at 2-year intervals, starting from 25 years. Results. Twenty-two HNPCC families, with 435 at risk individuals (104 deceased and 331 alive), were identified. None of these families was previously classified as HNPCC. The overall prevalence of CRC was 27.8% (121/435), decreasing from 59.4% in the I evaluable generation, to 24.4 and 8% in the II and III generations, respectively. Multiple CRC were reported in 29 patients. Thirty-four patients with EC were recorded in 12 out of 22 families (Lynch II families). One hundred and ninety-nine patients out of 331 at risk individuals accepted surveillance, the remaining ones were traced at the end of the study. The mean follow-up duration was 48 + 32 months (range 12–84 months). The overall incidence of CRC was 6/199 (3%) in surveyed patients and 5/132 (3.7%) in unsurveyed patients (P = ns). The mean annual incidence was 0.89% subjects at risk. Four surveyed individuals had CRC detected at first surveillance colonoscopy; in two of them CRC were metacronous appearing 7 and 11 years after a previous CRC. Two individuals developed CRC during follow-up, after a previous negative surveillance colonscopy. CRC detected in surveyed patients were significantly less advanced than those diagnosed in symptomatic, unsurveyed patients. Seven surveyed and six unsurveyed individuals, all belonging to the 12 Lynch II families, had EC during the study period (endometrium, small bowel, thyroid, central nervous system). Moreover, anterior pituitary adenoma was found in two unrelated patients. Twenty-two adenomas in 11 surveyed individuals were found. Tubulo-villous adenomas with high grade dysplasia was removed in one patient. All patients with CRC detected by surveillance are alive. One of the CRC patient in the group of those who refused surveillance died 18 months after the diagnosis. Conclusions. Family history collection in each patient with colorectal cancer leads to identification of often misdiagnosed HNPCC families which, otherwise, could escape an adequate surveillance policy. CRC incidence in at risk subjects was 20 times greater than the incidence reported in our region. Data support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at risk members. Longer follow-up is required to assess the efficacy of surveillance for EC. CO098 TX 527, A NOVEL VITAMIN D ANALOGUE WITH IMMUNOMODULATORY CAPACITY, EXERTS ITS EFFECTS ON PERIPHERAL BLOOD MONONUCLEAR CELLS OF HEALTHY CONTROLS AND IBD PATIENTS M. Stio, M. Martinesi, S. Bruni, C. Treves, G. d’Albasio, S. Bagnoli, A.G. Bonanomi

CO097 CLINICAL IDENTIFICATION AND LONG-TERM SURVEILLANCE IN 22 HEREDITARY NON-POLYP- OSIS COLON CANCER (HNPCC) ITALIAN FAMILIES Sprujevnika,b ,

Arrigonia,b ,

Pennazioa,b ,

Spandrea,b ,

T. A. M. M. M. Cavalleroa,b , A. Bertonea,b , A. Focoa,b , A. Rossia,b , V. Alvisia,b , G. Riccia,b , F.P. Rossinia,b a Division

of Gastroenterology, Department of Oncology, S. Giovanni A.S. Hospital, Turin, Italy b Postgraduate School of Gastroenterology, University of Ferrara, Ferrara, Italy Background and aim. HNPCC is an autosomal dominant cancer susceptibility syndrome characterised by an increased incidence of colorectal (CRC) and extracolonic cancer (EC). The aim of this study was to assess the efficacy of a HNPCC identification and surveillance policy over 8 years.

Department of Biochemical Sciences of the University and Gastroenterology Units of Careggi and Castelfiorentino, Florence, Italy Background and aim. We previously reported that 1,25-dihydroxy Vitamin D and two Vitamin D analogues, EB 1089 and KH 1060, significantly inhibited the proliferation of peripheral blood mononuclear cells (PBMC) of either healthy controls or Crohn’s disease (CD) or ulcerative colitis (UC) patients and that KH 1060 exerted an anti-TNF effect in vitro. The aim of this study was to test a new Vitamin D analogue, named TX 527, which shows a reduced calcemic activity associated with enhanced in vitro and in vivo immunomodulating capacity in comparison with the mother-molecule. Materials and methods. PBMC were cultured for 3 or 5 days with 10 ␮g/ml PHA in the absence or in the presence of 0.01, 0.1, 1 nM TX 527. The studies on NF-␬B levels were carried out in cells treated for 2 h with 50 ng/ml TNF-alpha. Cell proliferation was measured by tritiated thymidine incorporation. TNF-alpha was assayed by ELISA.

Abstracts Vitamin D receptor (VDR), NF-␬B and related proteins were determined by Western blot analysis. NF-␬B levels were also measured using an enzyme immunoassay. Results. The proliferation of PBMC obtained from healthy subjects and IBD patients significantly decreased, when cell cultures were treated for 5 days with TX 527. This decrease was dose-dependent and much more accentuated in UC patients in comparison with the other two groups. After 3-day treatment the effect exerted by TX527 on PBMC proliferation was less remarkable. VDR in PBMC significantly increased in consequence of TX 527 stimulation, indicating that this Vitamin D analogue exerts its action interacting with its nuclear receptor. Moreover, TX 527 significantly decreased TNF-alpha levels in PBMC incubated with 1 ␮g/ml LPS for 24 h. In order to verify whether this anti-TNF effect could be mediated by inhibition of NF-␬B activation, NF-␬B protein levels were determined in nuclear extracts of PBMC treated with either TNF-alpha or TX 527 or the combination. In the presence of TNF-alpha, NF-␬B levels significantly increased, as expected, while the contemporaneous treatment of the cells with TNF and TX 527 induced a decrease in NF-␬B compared to the treatment with TNF-alpha alone. Conclusions. These preliminary results indicate that TX 527 should be taken into account as useful therapeutic support in IBD diseases. This study was supported by a donation of the Cassa di Risparmio di Firenze. CO099 POLYURETHANE GASTROSTOMY TUBE DETERIORATION AND FUNGAL COLONISATION L. Trevisania , A. Pezzolia , S. Sartoria , G. Mataresea , V. Abbascianoa , R. Rossib , R. Bovolentac , M. Scoponid , S. Gullinia a U.O.

di Gastroenterologia, Azienda Ospedaliera “S. Anna”, Ferrara, Italy b Servizio di Microbiologia, Azienda Ospedaliera “S. Anna”, Ferrara, Italy c Centro di Microscopia Elettronica, Università degli Studi, Ferrara, Italy d Centro ISOF-CNR, Dipartimento di Chimica, Università degli Studi, Ferrara, Italy

Background and aims. Percutaneous endoscopic gastrostomy (PEG) is the most commonly used route for long-term enteral access. Longevity of PEG devices is of great clinical and economic interest. Fungal colonisation seems to play a role in the deterioration of these devices. This study was planned to evaluate the degree of polyurethane PEG catheters deterioration in relation to the duration of their use, and the role played by fungal colonisation. Methods. The inner surface of 20 polyurethane PEG tubes removed were brushed with sterile cytology brush. The brushing end was cut and put into Saburaud broth, and incubated for 7 days. When fungal growth was observed, subcultures were performed and yeast species were identified. Three of the 20 PEG tubes, previously used for 12 weeks (sample 2), 17 weeks (sample 3) and 96 weeks (sample 4), and two new PEG tubes were cut longitudinally to produce several equal halves. Six samples from the new PEG tubes were used as a control sample (sample 1), seven were incubated in Saburaud broth for 4 weeks (sample 5), and seven were incubated in the broth added with C. albicans (sample 6). All used and new samples underwent differential scanning calorimetry measurements (DSC): for each sample, glass transition temperature (Tg ), melting temperature (Tm ) and melting enthalpy (H) were determined. Moreover, morphological examination was carried out by transmission electron microscopy and scanning electron microscopy. Results. All tubes had fungal colonisation. C. tropicalis was the most frequent species; and in two cases two species were cultured. DSC analysis showed that Tg progressively increased, and Tm and H decreased, according to the duration of the tubes use. Incubation of the new tubes in Saburaud broth for 4 weeks induced the same effects, whereas adding C. albicans to the broth had no additional effects. Sample 1’s inner surface had regular pattern at morphological examinations, and the cryogenically fractured surface was smooth, without holes and crevices. Samples 2–4 had the

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inner surfaces covered with a thick biofilm, and their cryogenically fractured surfaces had crevices and holes generating strong disuniformity. The more the PEG tubes had been used for a long time, the more the changes were severe. Samples 5 and 6 had no significant changes in the inner surface, but their cryogenically fractured surfaces showed holes and crevices. Conclusions. Our results indicate that a deterioration occurs in polyurethane used tubes. It is already demonstrable just after 3 months of use, and increases with PEG age. Fungi constantly colonise PEG tubes. In our opinion, yeasts can contribute to polyurethane deterioration. We think that biomaterials for PEG devices should be improved to become more resistant to fungal colonisation. The impairment of the new tubes incubated in Saburaud broth, shown by DSC analysis, suggests that other factors also play an important role in polyurethane deterioration. CO100 Mt 21-42: AN INNOVATIVE DEVICE FOR THE ENDOSCOPIC DIAGNOSIS OF Helicobacter pylori INFECTION AND ATROPHIC GASTRITIS A. Tuccia,b , P. Tuccia,b , A. Marchegiania,b , G. Papadopolia,b , P. Fusarolia,b , M. Biscegliaa,b , A. Spadaa,b , L. Polia,b , M.F. Minennaa,b , A. Villania,b , M. Buccia,b , M. Marinellia,b , G. Calettia,b a GI

Unit, University of Bologna, AUSL of Imola, Castel S. Pietro Terme Hospital, Bologna, Italy b Endoscopic Unit, Teresa Masselli Hospital, San Severo (FG), Italy Background. Gastric juice is usually aspirated and thrown away during upper GI endoscopy. Indeed, this organic fluid may represent a source of precious clinico-pathological information if properly analysed. Aim. We evaluated reliability and clinical validity of an innovative medical device (Mt 21-42) that, analysing gastric juice, allows to identify Helicobacter pylori infection and atrophic gastritis of the oxyntic mucosa (AGOM) “during” endoscopy. Materials and methods. Mt 21-42 is an innovative device developed and realised by two of the investigators. It has the following main characteristics: (1) automatic working modality; (2) easy operating approach (only three buttons to press); (3) vocal synthesis interaction (with the endoscopist); (4) low uses and maintenance costs (< 0.4 per test). The device was tested in 150 consecutive outpatients (68 male; 82 female; 47.3±17.4 years, mean±S.D.) undergoing diagnostic upper GI endoscopy. In the meantime of endoscopic examinations, Mt 21-42 analysed gastric juice and communicated the H. pylori status and the presence/absence of AGOM. Additional tests were also performed in each patient to compare the results of the device. Specifically, urease test, routine histology, IgG to H. pylori, and urea breath test (UBT), for H. pylori-status; routine histology, serum gastrin, pepsinogen, intrinsic factor autoantibodies (IFA), parietal cell autoantibodies (PCA), and Vitamin B12, for AGOM. Results are reported in the tables.

H. pylori

Sensitivity Specificity

Mt 21-42 (%)

IgG to HP (%)

Urease test (%)

97 94

87 89

79a 99

UBT (%) 91 93

Histology (%) 94 76a

Atrophic gastritis of oxyntic mucosa (AGOM)

Sensitivity Specificity a b

Mt 21-42 (%)

Gastrin (%)

PCA (%)

IFA (%)

95 85

42b 99

32b 94

5b 100

P < 0.001 vs. Mt 21-42. P < 0.001 vs. Mt 21-42 (χ2 test).

B12 (%) 11b 100

Histology (%) 32b 98

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Abstracts

Conclusions. Mt-21-42 is a reliable and sensitive instrument, suitable for the perendoscopic diagnosis of H. pylori infection and AGOM. In particular, it resulted to be the most accurate method for the detection of AGOM. The good diagnostic performance and its particular characteristics (rapid analysis, automatic operating mode, vocal synthesis interaction, low use and maintenance costs), make this device an attractive and useful component for endoscopy. CO101 DISAPPEARANCE OF GASTRIC MUCOSA-ASSO- CIATED LYMPHOID TISSUE IN HCV-POSITIVE PATIENTS AFTER ANTI-HCV THERAPY A. Tursia , G. Brandimarteb , G. Laforgiac , W. Eliseib , V. Annunziatab , M. Torellod a Digestive

Endoscopy Unit, “L. Bonomo” Hospital, Andria (BA), Italy b Department of Internal Medicine, Division of Gastroenterology, “Cristo Re” Hospital, Rome, Italy c Division of Gastroenterology, “Sarcone” Hospital, Terlizzi (BA), Italy d Research Department, Shriners Hospital for Children and Department of Medical Genetic, Oregon Health and Science University, Portland, OR, USA Background. Mucosa-associated lymphoid tissue (MALT), which has a follicular structure closely resembling Peyer’s patches, is absent in the normal gastric mucosa but it can develop in several chronic conditions. Aims. Since we recently detected HCV–RNA in gastric MALT of patients with chronic hepatitis C, we tried to treat HCV infection to evaluate the effect of antiviral therapy on gastric MALT. Methods. Eighteen patients (12 male and 6 female; mean age 52 years; range 33–71 years) affected by chronic HCV-hepatitis and with gastric MALT were enrolled. We enrolled only HCV-positive, MALT-positive and H. pylori-negative patients (eight patients) or HCV-positive patients in whom anti-H. pylori therapy did not obtain disappearance of gastric MALT (10 patients). HCV-hepatitis was evaluated by hepatic biopsy with histological evaluation and serological examination; Gastric MALT was scored using Wotherspoon’s score. All patients were treated with recombinant leukocyte IFN-alpha-2b plus oral ribavirin for 6 months. The HCV–RNA was assayed at entry and 3 months after stopping treatment. Virological response was defined as undetectable levels of serum HCV– RNA 3 months after stopping treatment; oesophago-gastro-duodenoscopy was repeated at this time to evaluate the effect of anti-HCV therapy on acquired gastric MALT. Results. Two (11.11%) patients were withdrawn from the study. HCV cure was obtained in 11/16 patients (68.75%), and in all of them we obtained disappearance of gastric MALT (P < 0.01). HCV infection persisted, but with very lower levels, in 5/16 patients (31.25%): in 3 patients gastric MALT persisted (but in two it decreased from grades 3 to 2), while in 2 it disappeared. Conclusions. We showed clearly that there is a strict correlation between HCV infection and acquired, obtaining the disappearance of this acquired immunological acquired gastric tissue curing HCV infection. However, further studies are needed to clarify there is the same correlation between HCV infection and gastric MALT lymphomas in HCV-positive patients.

CO102 ANTI-PROTHROMBIN ANTIBODIES AND THROMBOTIC COMPLICATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE M. Vecchia , S. Daneseb , S. Saibenia , M. Sansc , D. Tassiesd , J.C. Reverterd , J.M. Piquéc , J. Panésc , A. Gasbarrinib a Gastroenterology

Service, Hepatology Unit, IRCCS Maggiore Hospital and University of Milan, Milan, Italy b Department of Internal Medicine, Catholic University, Rome, Italy c Department of Gastroenterology, Department of Hemostasis, Hospital Cl´ınic, Barcelona, Spain d Department of Hemostasis, Hospital Cl´ınic, Barcelona, Spain

Background and aims. Inflammatory bowel disease (IBD) is characterised by a hypercoagulability state and an increased risk of thrombotic complications, whose causative agents are still poorly understood. The association between anti-prothrombin antibodies (APA) and development of thrombosis in patients with several autoimmune disorders has been recently described. However, the role of APA in thrombosis complicating the course of IBD has not been assessed. Aims. (1) To study the prevalence of APA in IBD patients with thrombosis. (2) To analyse the relationship existing between APA, development of thrombosis and other clinical characteristics. Methods. This is a retrospective, case–control study. Thirty-three IBD patients with a recent or previous episode of thrombosis (IBD cases) were identified in two referral hospitals. Seventeen of them had ulcerative colitis (UC), 15 had Crohn’s disease (CD), and 1 had indeterminate colitis (IC). For each IBD case, one IBD control (with the same type of IBD and without history of thrombosis) and two healthy controls were paired for sex and age. Patient records were reviewed and the presence of IgG and IgM APA was assessed in plasma samples. Results. Thirty-four thrombotic events were found in 33 cases, including 24 venous thromboses (17 deep venous thromboses, 2 portal thromboses, 2 axillary thromboses, 1 jugular thrombosis, 2 Budd-Chiari syndromes) and 10 arterial thromboses (5 myocardial infarctions, 3 cerebral strokes, 2 retinal thromboses). APA were present in three IBD cases (9.1%), four IBD controls (12.1%), and three healthy controls (4.5%, P = 0.39). Among the three APA+ IBD cases, one was IgG+, one was IgM+, and the third was both IgG+ and IgM+. All APA+ IBD cases were UC patients with a history of deep venous thrombosis. Among APA+ IBD controls, one was IgG+, one IgM+, and two were both IgG+ and IgM+. There was no association between APA positivity and patient clinical characteristics. Conclusions. Although the prevalence of APA is slightly increased in IBD patients compared to normal controls, the presence of plasma APA in IBD patients does not appear associated with an increased risk of thrombotic complications. CO103 CARD15 GENOTYPES IN ITALIAN PATIENTS WITH CROHN’S DISEASE M. Vecchia , L. Laghib,c , S. Costad , S. Saibenia , P. Bianchic , A. Carrarad , L. Spinaa , S. Ferreroe , E. Contessini Avesanid , M. Vecchia , R. de Franchisa , A. Malescib a Servizio

di Gastroenterologia, Unità di Epatologia, IRCCS Ospedale Maggiore e Università degli Studi di Milano, Milan, Italy b U.O. Gastroenterologia ed Endoscopia Digestiva, Istituto Clinico Humanitas, Milan, Italy c Laboratorio di Ricerca, Istituto Clinico Humanitas, Milan, Italy d Dipartimento di Scienze Chirurgiche, U.O. Chirurgia Generale II, IRCCS Ospedale Maggiore e Università degli Studi di Milano, Milan, Italy e Dipartimento di Anatomia Patologica e Medicina di Laboratorio, Ospedale San Paolo e Università degli Studi di Milano, Milan, Italy Background and aim. Variant CARD15 genotypes (R702W, G908R and 1007fs) are known to confer familial susceptibility to Crohn’s disease (CD)

Abstracts and to increase the relative risk for the sporadic form of the disease in the Western population. Preliminary data appear to confirm this association among Italian CD patients. It remains unclear whether CARD15 genotype can influence CD phenotype. The aim of this study was to investigate the relationship between CARD15 genotype and phenotype in a large series of Italian CD patients. Methods. We retrospectively determined the CARD15, R702W, G908R, and 1007fs haplotypes in 217 CD patients referred to the involved GI Units. To perform genotype–phenotype correlation, the clinical records of all patients were reviewed. CD phenotypes were defined according to the Vienna classification. Results. A total of 76 (35%) patients carried at least one of the investigated CARD15 variants. The allelic frequencies of R702W, G908R and 1007fs were: 10.1, 5.3, and 8%, respectively. Fourteen of 23 (61%) patients with a positive family history carried a CARD15 variant versus only 62 out of 194 (32%; P = 0.006) patients with sporadic disease; R702W and G908R variants accounted for this difference (P = 0.0362, and 0.0013, respectively). A higher prevalence of CARD15 variants was observed in patients with a history of surgery (70/179, 39%) compared with those without it (6/38, 15.8%) (P = 0.004); the mean follow-up time of these groups was similar (11.8 years versus 11.0 years). The CARD15 genotype was not associated with an age younger than 40 years at the time of diagnosis. However, the median age at diagnosis of patients with homozygous or compound heterozygous CARD15 haplotypes (25 years; range 16–60) was significantly lower (P = 0.04, Mann–Whitney U-test) than that of patients with other haplotypes (33 years; 10–77). Disease location (L1, L2, L3, L4) was not associated with CARD15 genotype. Penetrating disease behaviour (B3) was significantly more frequent in patients with genotype variants (42/76; 55%) than in wild-type patients (57/141; 40%) (P = 0.03). Conclusions. In our series, CARD15 variants were associated with a positive family history, an earlier age at diagnosis, a higher frequency of penetrating phenotype and a more frequent need for surgery. CO104 5-HT7 RECEPTORS ARE INVOLVED IN THE ACCOMMODATION OF THE CIRCULAR MUSCLE DURING PERISTALSIS IN THE GUINEA-PIG ILEUM R. Vicinia,b,c , E. Cervioa,b,c , A. Agazzia,b,c , R. De Giorgioa,b,c , G. Barbaraa,b,c , F. De Pontia,b,c , M. Toninia,b,c a Department

of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy b Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy c Department of Pharmacology, University of Bologna, Bologna, Italy

Background and aim. 5-HT7 receptor is the most recently identified member of the serotonin receptor family. In the gastrointestinal tract, this receptor physiologically mediates 5-HT-induced smooth muscle relaxation. The aim of the present study is to evaluate the functional role of 5-HT7 receptor activation by endogenous 5-HT in the peristaltic reflex. Material and methods. Peristalsis was induced by delivering a physiological solution into the oral end of an isolated guinea-pig ileum segment (n = 8). Longitudinal muscle reflex contraction, pressure and volume thresholds to trigger peristalsis, accommodation of the intestinal wall during the preparatory phase of peristalsis, which is partly due to activation of descending inhibitory pathways, and the maximal ejection pressure during the emptying phase were measured in 10 min duration cycles of peristaltic activity. The effect of the 5-HT7 receptor selective antagonist SB-269970 (100 nM) was evaluated at 30, 60 and 90 min of contact.

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Results. SB-269970 significantly increased the threshold pressure of peristalsis by 33.3 ± 2.2% (P < 0.001) and by 27.2 ± 1.6% (P < 0.05) at 60 and 90 min, respectively. As a consequence, the compliance of the intestinal wall (V/P at threshold) significantly decreased by 27.5% (P < 0.05) at 60 and 90 min, respectively. The other parameters of peristalsis were not affected by SB-269970. Conclusions. In the guinea-pig ileum, the blockade of 5-HT7 receptors by SB-269970 is responsible for the decrease of accommodation of the circular muscle during the preparatory phase of peristalsis. This suggests that endogenous 5-HT, mainly secreted by enterochromaffin cells, is pharmacologically involved in the modulation of circular muscle compliance via the activation of 5-HT7 receptors expressed by smooth muscle cells. Since a neuronal source of 5-HT is located on some interneurones mediating the descending inhibitory reflex, studies are needed to establish the role of 5-HT7 receptors at the neuronal level, which may contribute to the accommodation process of peristalsis. CO105 EPIDEMIOLOGY OF GASTRO-OESOPHAGEAL REFLUX DISEASE SYMPTOMS AND ENDOSCOPIC FINDINGS IN THE GENERAL POPULATION R. Maurizio Zagari, C. Martuzzi, L. Fuccio, L. Ricciardiello, S. Maltoni, M. Di Marco, E. Roda, F. Bazzoli Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy Gastro-oesophageal reflux disease (GERD), which includes erosive oesophagitis (EE) and non-erosive reflux disease (NERD) is a very common condition, however little is known about its epidemiology. In fact, endoscopic-based clinical studies depend on small series of patients and population studies, that can rely on large samples of subjects, are based on symptom questionnaires and lack endoscopic information. In the frame of the Loiano–Monghidoro population study [1] both upper GI symptoms (by a validated questionnaire) and endoscopic evaluation are obtained in a large and representative sample of the general population. We report the prevalence of EE as well as of typical and atypical oesophageal symptoms in a sample of 966 (494 males, 472 females, age range 18–86 years, mean age 56 years) inhabitants representative of the population of Loiano and Monghidoro commons. Results. The prevalence of GERD was 43.9% (424/966): NERD 30.5% (295/966), EE 13.4% (129/966). The severity of EE (Savary–Miller modified classification) was as follows: grade I 80.6% (104/129), grade II 8.5% (11/129), grade III 2.3% (3/129), grade IV 0.8% (1/129), grade V (Barrett’s oesophagus) 7.8% (10/129). The prevalence of Hiatus Hernia was 37% in non-GERD subjects, 73.6% in subjects with EE (P < 0.001) and 40% of those with NERD. Subjects (19.4%, 25/129) with EE reported no symptoms; of these 88% (22/25) had grade I, 4% (1/25) grade II and 8% (2/25) grade V; all subjects with EE grades III and IV were symptomatic. Conclusions. Almost half of the general population suffer from GERD. NERD is the most frequent manifestation. However, also asymptomatic EE frequently occurs. Reference [1] APT 2001;15:1001–7.

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Abstracts

CO106 Helicobacter pylori INFECTION AND CHRONIC CORPUS GASTRITIS RELATED IN GASTRO-OESOPHA- GEAL REFLUX DISEASE R. Maurizio Zagaria , S. Casanovab , C. Martuzzia , L. Fuccioa , M. Di Marcoa , S. Maltonia , L. Ricciardielloa , A. D’Erricob , W. Grigionib , R. Fioccac , E. Rodaa , F. Bazzolia a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Pathology Unit of the Addarii Institute of Oncology, University of Bologna, Bologna, Italy c Department of Human Pathology, University of Genoa, Genoa, Italy

Background. The role of Helicobacter pylori infection in the pathogenesis of gastro-oesophageal reflux disease (GERD) is still controversial. It has been proposed that H. pylori-related corpus gastritis can result in decreased acid output and therefore protect against GERD. Aim. To evaluate the prevalence of H. pylori infection and corpus gastritis in subjects with and without GERD in a sample representative of the general population. Methods. In the frame of the Loiano–Monghidoro project [1], the inhabitants of Loiano and Monghidoro commons were re-invited to undergo upper gastrointestinal (UGI) endoscopy and 13C-Urea Breath Test. During endoscopy three biopsy specimens were taken from antrum and three from corpus-fundus and stained with haematoxylin/eosin and GIEMSA for the detection of gastritis and H. pylori infection. The presence and severity of gastritis were classified according to a modified updated Sidney System. Two biopsy specimens were taken from antrum and corpus for rapid urease test and culture. Upper GI symptoms were evaluated by a validated dyspepsia questionnaire. Results. Eight hundred and ninety-two inhabitants (452 male, 440 female, age range 18–86 years, mean age 56) were evaluated. The prevalence of H. pylori infection was 52.9% (262/495) in non-GERD subjects, 57.7% (71/123) in subjects with erosive oesophagitis and 57.3% (157/274) in those with non-erosive-reflux disease (NERD) (P = ns). In H. pylori positive subjects non-atrophic corpus gastritis was found in 93.5% (245/262) without GERD, in 93%(66/71) with erosive oesophagitis and in 93% (146/157) with NERD (P = ns). However, out of 11 subjects with severe atrophic corpus gastritis, notably, none had erosive oesophagitis. Conclusions. In the general population, the prevalence of H. pylori infection and non-atrophic corpus gastritis is similar in both GERD and non-GERD subjects. Only severe atrophic corpus gastritis seem to protect against erosive oesophagitis. Reference [1] APT 2001;15:1001–7.

and higher risk for gastric cancer. However, the frequency of these IL-1 genetic polymorphisms in the general population is unknown. Aim. To evaluate the prevalence of IL-1␤-511, IL-1␤-31 and IL-1RN genetic polymorphism in a representative sample of general population. Methods. In the frame of the Loiano–Monghidoro project [1], also buffy coats are obtained from blood of a sample of subjects representative of the general population. Genomic DNA was extracted from buffy coats of the first consecutive 866 subjects (441 male, 425 female; mean age 56 years) enrolled, using the QIAmp Blood Extraction kit (QIAgen). All samples were genotyped for the polymorphisms of the IL-1␤ (IL-31 C and IL-511 T) and the IL-1RN. The IL-1␤-31 and IL-1␤-511 polymorphisms were genotyped by PCR and RFLP analysis. Statistical analysis: the Hardy–Weinberg equilibrium and the haplotype frequency estimation calculated from the observed genotypes were tested by using the Arlequin software version 2.0. For the genetic comparisons, differences in genotype frequencies were evaluated by using the chi-square (χ2 ) method (significance set at P < 0.05) calculated by SPSS (version 10.0). Results. Table shows the results.

Genotype

Carrier Total (%)

Female (%)

Male (%)

IL-1␤-511 C/C C/T T/T∗

216 (24.9) 522 (60.3) 128 (14.8)

101 (23.6) 257 (60.8) 67 (15.6)

115 (26.1) 265 (60.1) 61 (13.8)

IL-1␤-31 C/C∗ C/T T/T

177 (20.4) 504 (58.2) 185 (21.4)

86 (20.2) 258 (60.7) 81 (19.1)

91 (20.6) 246 (55.8) 104 (23.6)

IL-1RN (86 bp)n 1/1 1/2 1/3, 4, 5 2/2∗ 2/3, 4, 5 3/3 4/4

446 320 39 37 19 4 1

218 155 22 19 10 1 0

228 165 17 18 9 3 1

Total

866

(51.5) (37) (4.5) (4.3) (2.2) (0.4) (0.1)

(51.2) (36.5) (5.2) (4.5) (2.4) (0.2) (0)

425

(51.7) (37.4) (3.9) (4.1) (2.0) (0.7) (0.2)

441

Conclusions. The genetic polymorphisms of IL-1, for which an association with gastric cancer has been reported, are present in 5–15% of the general population. Reference

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[1] APT 2001;15:1001–7.

EPIDEMIOLOGY OF INTERLEUKIN 1 GENETIC POLYMORPHISMS IN THE GENERAL POPULATION

CO108

R. Maurizio Zagaria,1 , L. Ricciardielloa,1 , M. Baglionia , C. Bonvicinib , V. Lunedeia , L. Fuccioa , C. Martuzzia , E. Rodaa , F. Bazzolia

EFFICACY AND SAFETY OF ARGON PLASMA COAGULATION IN TREATING WATERMELON STOMACH

a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Genetics Unit, IRCCS “Centro San Giovanni di Dio” Fatebenefratelli, Brescia, Italy 1 Both authors equally contributed to this work. Background. Proinflammatory interleukin (IL)-1 genetic polymorphisms seems to be involved in Helicobacter pylori-related gastric carcinogenesis. It has been reported that subject carriers of the IL-1␤-511 T/T, IL-1␤-31 C/C and IL-1RN 2/2 genotypes have higher mucosal levels of IL-1␤, a potent proinflammatory cytokine and inhibitor of gastric acid secretion,

R. Maurizio Zagari, L. Fuccio, E. Roda, F. Bazzoli Department of Internal Medicine and Gastroenterology, University of Bologna, Italy Background and aims. Watermelon stomach (WS) or gastric antral vascular ectasia is an uncommon but important and often misdiagnosed cause of gastrointestinal bleeding. Recently, argon plasma coagulation (APC), a new non-contact electrocoagulation technique, has been proposed as an endoscopic treatment of Watermelon stomach; however, until now, there are only few cases of such condition treated with APC reported in the

Abstracts literature. The aim of this study was to evaluate efficacy and safety of APC in the treatment of Watermelon stomach. Patients and methods. Seven patients (M:F = 5:2; mean age 60 years; range 46–75) with transfusion dependent gastrointestinal (GI) bleeding with a mean transfusion requirement of 4.5 units (range 0.5–15) per month, were treated with APC. In all patients the endoscopic diagnosis of WS was histologically confirmed and other causes of bleeding were excluded by both upper and lower GI endoscopy. Endoscopic treatment with APC was done using a 2.3 mm diameter probe with a heat-resistant ceramic tip (ERBE probe; ERBE Electromedizin, Tuebingen, Germany). An argon plasma coagulation unit, including a high-frequency electrosurgical generator (ERBE ICC 200) and an argon delivery unit (ERBE APC 300) was used. The argon gas flow was set at 2.0 l/min and 60 W power was used. Treatment was applied using a “spot and stripe” technique. Results. A mean of six treatment sessions (range 3–10) per patient was performed. Transfusion dependence was abolished in five patients in whom a mean haemoglobin rise of 2.52 g/dl (range 1.4–5.9) was also obtained. Moreover, in these five patients endoscopic eradication of vascular lesions was fully achieved. In the remaining two patients treatment is ongoing, however partial endoscopic response obtained at this time point has been paralleled by the 50% decrease transfusion requirement. In all these seven patients, WS treatment by APC was well tolerated and no complication was observed. Conclusions. These preliminary results show that APC is a safe and efficacious endoscopic treatment of Watermelon stomach. CO109 ULTRASONOGRAPHIC ASSESSMENT OF SMALL BOWEL CROHN’S DISEASE AFTER ORAL ADMINISTRATION OF CONTRAST G. Zirizzotti, C. Ciarletti, G. Ditrapani, C.A. Gervasi, A. Gioieni, F. Goffredo, C. Giannelli Unit of Digestive Diseases and Gastrointestinal Rehabilitation Background and aim. Bowel ultrasound is an useful tool in the diagnosis on inflammatory bowel diseases (IBD) revealing the wall thickness, narrowed and/or dilated lumen and stenosis. In spite of these results, small bowel enemas is still the gold standard for the assessment of small bowel Crohn’s disease (CD). In the last years the ultrasonography of small bowel has improved his sensitivity and specificity after oral administration of anechoic solution of polyethyleneglycol (PEG) distending intestinal loops. The aim of this experience was to evaluate the efficacy of contrast ultrasonography to localise CD lesions, to define their extent and to reveal luminal and extraluminal complications. Material and method. Forty-eight patients with Crohn’s disease (30 after surgical resection of distal ileum and right colon, 18 without surgery) were studied by small bowel enema and US before and after oral administration of 500–750 cm3 of PEG (Macrogol 4000) and by barium enema. The ultrasound examinations were performed by the same physician, unaware of CD localisation and kind of surgery. The examinations were carried out using a real time scanner Aloka SS550, second harmonic, with a convex 3.5 and 7.5 MHz transducers. Results. After oral administration of PEG a good distension of intestinal lumen was obtained in all patients. No side-effects were observed. The

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mean time of rich distal lumen was 45 min (S.D. 8.3). The sensitivity in revealing CD lesions before and after oral contrast was 91.5 and 98.2%, respectively. Sensitivity for strictures was 74% before and 91% after oral contrast. The surgical anastomosis was correctly identified in all patients. The sensitivity in detecting extraluminal complications was 70% before and 92% after PEG, respectively. Conclusions. The ultrasonography after oral administration of PEG is superior to conventional US in defining the wall structure and extension of small bowel CD, in detecting the narrowed lumen and stenosis and in revealing extraluminal complications. For all these reasons, it can be regarded as the first imaging procedure in diagnosis and in follow-up of small bowel CD. CO110 DIFFERENTIAL GENE EXPRESSION IN KUPFFER CELLS STIMULATED WITH IFN ALPHA AND GAMMA M.A. Zoccoa,b , E. Carlonia,b , M. Pescatoria,b , M.C. Santoroa,b , E.C. Nistaa,b , G. Gasbarrinia,b , G. Ramadoria,b , A. Gasbarrinia,b a Department

of Internal Medicine, Catholic University, Rome, Italy of Gastroenterology and Endocrinology, Georg-AugustUniversity, Göttingen, Germany b Department

Background. Kupffer cells (KC), like other components of the mononuclear phagocyte system, secrete potent mediators of the inflammatory response and thus control the early phase of the inflammation, playing an important role in the innate immune defense and in preventing the tumour’s development of malignant. Both IFN alpha and gamma are involved in the regulation of a large number of genes and are crucial for the macrophage activation. Aim. To evaluate KC gene expression in basal condition and after stimulation with IFN alpha and gamma. Methods. Rat KC isolated by collagenase perfusion and centrifugal elutriation were cultured for 24 h and divided into three different groups: (1) unstimulated; (2) stimulated with IFN alpha (1000 UI/ml); (3) stimulated with IFN gamma (1000 UI/ml). After an 8 h incubation period total RNA was extracted and hybridised on R34A microarray gene set. Data analyses was performed using MAS 5.0 software. Genes showing remarkably different expression in microarray analysis were selected and confirmed by real time PCR. Results. Nearly 4000 out of the 8800 genes represented in the array were expressed by KC. Among these, IFN alpha up-regulates 183 genes by over twofold and down-regulates 125 genes by 50% or more. Up-regulated genes belong to a broad range of functional pathways and include effector proteins with strong antiviral activities, genes involved in antigen processing and presentation and tumour suppressor/proapoptotic genes. IFN gamma up-regulates over twofold 188 genes, and down-regulates 264 genes by 50% or more. Most of the genes are commonly induced by IFN alpha and IFN gamma. Among down-regulated genes there are genes involved in cytoskeletal regulation like EB1 and markers of proliferation like cyclin D1. Real time PCR confirms the array results. Conclusion. This study shows that IFNs directly target rat KC and are involved in the regulation of a wide variety of genes. The analysis of their expression profile shed light onto molecular mechanism of KC activation in specific pathways such as antiviral and antitumour processes.

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Abstracts cavity and ligation then proceeded normally in the lower third of the oesophagus. The video will demonstrate the feasibility of the described technique.

VIDEOTAPES VT01 D-PEJ PLACEMENT IN CASES OF FAILURE OF PEG INSERTION M. Ballarè, M. Orsello, E. Garello, F. Montino, P. Occhipinti, M. Del Piano

VT03 PANCREATIC PSEUDOCYST DRAINAGE: THE EUS-GUIDED ONE-STEP PROCEDURE C. De Angelis, A. Repici, P. Carucci, A. Foco, A. Isabello, M. Rizzetto

U.O.A Gastroenterologia, Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy

Department of Gastroenterology, ASO S. Giovanni Battista, Turin, Italy

P. Billi, V. Cennamo, C. Fabbri, D. Baroncini, P. Bergonzoni, P. Landi, S. De Vito, P. Zobbi, A. Grilli, C. Mwangemi, L. De Luca, F. Biolchini, E. Jovine, N. D’Imperio

Background and aim. Pancreatic pseudocysts (PP) of various aetiology can have a spontaneous resolution in a significant number of patients even if very large, but if symptoms worsen and/or size increases, a drainage procedure is indicated. We can drain a PP by surgery or percutaneously under US or CT guidance, but today endoscopic and endosonographic procedures are more widely employed and accepted. Endoscopic transmural drainage can have some obvious limitation, due to its relatively blind approach, with high morbidity (15.6%) and mortality (3.1%) rates. Especially these complications have prompted the opportunity for high resolution imaging right before (EUS-assisted drainage) or during the procedure (EUS-guided drainage). Today there is general agreement that a diagnostic EUS is mandatory before endoscopic treatment of PP. Interventional EUS can offer some advantages and new possibilities (drainage of non-bulging cysts and abscesses), but literature data are still scarce. The advent of new big channel convex echoendoscopes allows us to perform all the drainage procedure in one step with the same instrument. Materials and methods. In this video we demonstrate the one-step approach to PP under EUS guidance in two patients with large PP. In the first case we performed the drainage with the one-step procedure so-called of endoscopic type (the needle–knife technique); in the second patient we used the entirely EUS-guided one-step procedure (the so-called Seldinger technique). We used the same convex echoendoscope, Olympus GF-UCT 140 AL5, with an operative channel of 3.7 mm, which allows to advance in the PP up to a 10 French stent. Results. In the first case (MT) we performed the cystogastrostomy by placing two double pig-tail plastic stents of 7 and 10 Fr. In the second (BB) we drained the PP with one 10 Fr double pig-tail stent. At 2 months follow-up both the cysts resolved. No early or late complications were observed. Both patients underwent broad-spectrum antibiotic prophylaxis. Conclusions. In our experience the one-step EUS-guided drainage of PP with a big-channel echoendoscope is feasible, safe and effective. Whether this new technique will completely replace the current standard approach (diagnostic radial EUS + endoscopic drainage with a therapeutic duodenoscope) is an open question today.

U.O. di Gastroenterologia ed Endoscopia Digestiva, P.O. Bellaria-Maggiore, Bologna, Italy

VT04

Background. In some cases PEG is not feasible because of technical difficulties such as gastric herniation, organ interposition, or gastroparesis. In these cases, surgical gastrostomy or jejunostomy are the possible alternatives. More recently, direct percutaneous endoscopic jejunostomy (D-PEJ) has been proposed to avoid surgical intervention. Aim of the study. To evaluate technical feasibility of DPEJ in patients with technical obstacles to PEG placement or contraindications (e.g. severe gastro-oesophageal reflux disease). Methods. A variable stiffness paediatric videocolonscope was used to reach the jejunum, then D-PEJ was performed with the same technique and materials as PEG. Results. In a 6-month period, 45 patients were proposed for PEG placement; in four of them PEG could not be inserted for technical reasons in three (gastric herniation in one, organ interposition in two) and gastroparesis in one. The time of the endoscopic procedure was slightly longer in D-PEJ (mean 20 min versus 15 min). This was mainly due to the time needed to reach the jejunum. No complication related to the endoscopy procedure was observed in D-PEJ patients. Conclusions. In our preliminary experience, PEG was not feasible or contraindicated in about 10% of patients proposed for. In these patients, D-PEJ was placed: the procedure resulted to be feasible and safe with the use of a paediatric videocolonscope to easily reach the jejunum. Given that jejunum is a smaller cavity than stomach, we suggest that D-PEJ should be performed by endoscopists well trained in PEG placement. The insertion of D-PEJ did not change the nutritional management of enteral feeding. However, long-term effects or complications remain to be evaluated in larger studies. VT02 ENDOSCOPIC LIGATION OF OESOPHAGO-GASVARICES: THE RETROFLEXION TECHNIQUE

TRIC

Endoscopic variceal ligation has recently been used to replace sclerotherapy as the treatment of choice for the prevention of rebleeding of oesophageal varices, due to similar results in terms of haemostasis and eradication, but with less complications. In our sclerotherapy technique, the first injections were performed intra- and peri-variceally, beginning at the cardias in retro flexion in the gastric cavity. This is an effective way to treat the junctional varices first which are the more frequent and the most dramatic cause of bleeding. The recent availability of new multiple band ligators with better vision, a renewed system of band delivery which are easy to handle in retro flexion, induced us to apply the same technique to ligation. We will present a short film showing endoscopic ligation of oesophago-gastric varices in retro flexion, using a new multiple band ligator (Speedband Superview Super 7, Microvasive, Boston Scientific). We applied the multiple band ligator to the tip of a modified endoscope introduced into the stomach and then retro flexed. The bands were applied circumferentially in all visible varices at the cardias junction in the gastric

ROLE OF ENDOSCOPIC ULTRASOUND STAGING (EUS) IN ENDOSCOPIC SNARE RESECTION (ESR) OF AMPULLARY TUMOURS: VIDEO PRESENTATION OF A CLINICAL CASE T. Federici, G. De Maio, A. Iacobellis, D. Facciorusso, F. Spirito, R. Forlano, G. Antonio, A. Andriulli U.O. Gastroenterologia ed Endoscopia Digestiva IRCCS Casa Sollievo Della Sofferenza S. Giovanni Rotondo (FG) Background and aim. The standard of care for ampullary tumours has been surgical resection. In the era of ERCP, endoscopic resection (ESR) of ampullary tumours is becoming more and more common, although not universally accepted. Endoscopic ultrasound staging (EUS) can play an important role in differentiating T1m from T1sm with good accuracy, as demonstrated in some studies. We report a video presentation on a similar clinical case. Patients and methods (video). An 83-year-old man was referred to our Gastrointestinal Unit, in September 2003, because of the persistence of

Abstracts jaundice and dark urine for 1 month, without fever, abdominal pain and a recent history of drug use. Two months earlier, he underwent a laparotomic resection of the sigma for an adenocarcinoma T2-N0 and a cholecystectomy for cholelithiasis. Biochemical parameters, at the time of admission to hospital, were: bilirubin 6.03 (D 4.13); alkaline phosphatase 2504; gamma-glutamyl transpeptidase 1275; aspartate aminotransferase 243; alanine aminotransferase 175. Upper abdominal ultrasound shows: ∅ main biliary tract (MBT) 9 mm + slight dilation of left intrahepatic biliary tract (IBT), without lithiasis. EGDS: papilla of Vater swelling; ERCP + endoscopic sphincterotomy (ES) + biopsies of papilla: no lithiasis. Suspicion of ampulloma; MBT dilation. Histology: severe dysplasia of epithelium. EUS (GF-UM 160, Olympus): ampullary neoplasia T1-N0. ESR of the ampulloma was performed after infiltration with saline. Histological evaluation on the anatomical sample of endoscopic resection: well differentiated adenocarcinoma, involving muscolaris mucosae, completely removed. Results. Two months after ESR, EGDS complete scar formation in the site of excision; normal choleastatic parameters. Restaging EUS + IDUS (intraductal ultrasonography with UM-G20-29R Olympus) results in the absence of neoplastic residue remaining, both in duodenum and in the MBT, no lymphoadenomegaly. Conclusions. In our experience, according to the data in literature, early EUS can select early ampullary tumours (T1m) for curative ESR. A combination of EUS and IDUS is safe and more accurate in the staging of ampullary tumours. VT05 BAND LIGATION WITHOUT CAP BY USING LARGE CHANNEL (6 mm) ENDOSCOPE M. Orsello, M. Ballarè, E. Garello, F. Montino, P. Occhipinti, M. Del Piano U.O.A Gastroenterologia, Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy Background. Band ligation is widely used in the treatment of oesophageal varices and haemorrhoids. Nonetheless, its use in bleeding emergencies requires the removal of the instrument after the endoscopic diagnosis of the bleeding source, to place the banding unit over the tip of the endoscope. Besides, in oesophageal varices the amount of bleeding not always allows the use of the banding unit which further limit the visualisation of the bleeding source. Aim of the study. To test the use of a large (6 mm) endoscope in aspirating the gastrointestinal mucosa and bleeding vessels and placing a single band without the use of an aspiration cap. Methods. A single elastic band is placed on the tip of a large (6 mm) videoendoscope (Olympus GIFXTQ160). The gastrointestinal mucosa (or bleeding vessel) is aspirated by the large channel of the endoscopic, and the band is shooted by a silk wire attached to another elastic band. Results. Our preliminary experiments has showed the successful positioning of the band on the gastric mucosa. Conclusions. The single band device without aspiration cap could be proposed for the treatment of bleeding emergencies such as varices or Dieaulafoy’s lesions. It has the advantage of not requiring the removal of the endoscope to place the banding unit, and the absence of a cap permits an optimal visualisation of the bleeding lesion. Further studies are needed to test the device extensively. VT06 OCCULT INTESTINAL HAEMORRHAGE DUE TO BLEEDING LIPOMA OF THE JEJUNUM DIAGNOSED BY CAPSULE ENDOSCOPY AND ENTEROSCOPY. A CASE REPORT A. Pezzoli, C. Rizzo, S. Boccia, L. Simone, L. Trevisani, V. Matarese, S. Gullini Department of Gastroenterology, Sant’Anna Hospital, Ferrara, Italy

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Submucosal lipoma of the upper gastrointestinal tract is a rare benign tumour. In general the patients were asymptomatic and the lesions were discovered incidentally. We report a case of occult GI haemorrhage from jejunum lipoma diagnosed with capsule endoscopy and enteroscopy. Case report. A 64-year-old man was admitted to our unit because of anaemia and a positive faecal occult blood test. The patient had no melena. His medical history showed diabetes and an IMA 10 years before. Laboratory tests included the following: haemoglobin 8.8 mg/dl, haematocrit 29%, iron 33 ng/dl, urea nitrogen 101 mg/dl, creatinine 1.6 mg/dl. Abdominal ultrasound examination (US) was normal. At upper GI endoscopy only a mild gastritis was revealed. A colonoscopy did not show any lesions. Finally an X-ray enteroclysma was performed with a negative result. We decided to perform a capsule endoscopy examination that revealed a minimal amount of fresh blood near an undefined mass. So the patient underwent an enteroscopy that showed a large peduncolated polypoid mass measuring about 4 cm with a superficial ulcer at the tip. Bioptic samples were taken but the histological examination was inconclusive. The patient was referred to the surgical department to remove the lesion. The final histopathologic diagnosis was a lipoma covered with normal duodenal mucosa with superficial ulceration. No further bleeding or anaemia was observed in the following 6 months. Discussion. Lipomas although rare are the commonest mesenchymal benign tumours that can be found throughout the GI tract; anaemia and haemorrhage are rare complications and few cases are described in the literature. In our patients, capsule endoscopy provided orientative elements for diagnosis but the lesion was best visualised with enteroscopy probably because of its unusual morphologic shape. Since lipoma is a submucosal lesion the biopsy was not useful for the diagnosis and surgical extirpation was necessary to stop the bleeding and establish the nature of the polyp accurately. In patients with occult bleeding, the correct chronological sequence of capsule endoscopy and enteroscopy is still controversial. VT07 ENDOSCOPIC TREATMENT OF ZENKER’S DIVERTICULUM IN ELDERLY PATIENTS NOT SUITABLE FOR STANDARD DIVERTICULECTOMY A. Repici, C. De Angelis, S. Caronna, M. Goss, M. Bruno, C. Dalla Costa, A. Musso, A. De Lio, M. Rizzetto, G. Saracco Dipartimento di Gastroenterologia, Ospedale Molinette, Turin, Italy Background and aim. Zenker’s diverticulum (ZD) occurs mostly in older patients who have comorbid conditions. Surgical treatment of ZD is still the gold standard. Endoscopic diverticulectomy has been proposed for elderly patients with high surgical risk. The aim of this study was to evaluate safety and efficacy of cap-assisted endoscopic treatment of ZD in symptomatic patients unsuitable for surgery. Methods. From January 2000, 11 patients (mean age 81.5 years) with severe dysphagia and associated symptoms (pulmonary aspiration in two, weight loss in six, chronic cough in four) due to ZD were treated by endoscopy. All procedures were performed under conscious sedation (propofol and/or midazolam) controlled by an anaesthesiologist. With the aid of an oblique cap attached to the tip of the scope, the septum between the diverticulum and the oesophagus was exposed and thereafter incised with a standard needle knife and pure coagulation current. A nasobiliary tube was placed before endoscopic diverticulectomy and left in situ for 48 h after the procedure. Thereafter, oral intake was progressively resumed. Clinical and X-ray control were scheduled. Results. The septum was completely incised in a single session in all cases. Bleeding (requiring APC treatment) occurred in one patient. Perforation occurred in one patient and was treated conservatively. Severe post-procedural pain requiring i.v. analgesics was recorded in eight patients. During F-U (mean 11.8 months) dysphagia and other symptoms caused by ZD disappeared completely and permanently in nine patients. In two patients dysphagia persisted, but of a lower grade (grade 1 instead of grade 3).

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Conclusions. Endoscopic diverticulectomy is a safe and effective alternative treatment in ZD patients at high risk for surgical procedures. VT08 DIAGNOSTIC YIELD OF THE CAPSULE ENDOSCOPY IN GI ANGIODYSPLASIA: THREE INTERESTING CASES A. Sena, R. Monterubbianesi, M. Pellegrini, M. Grazia Mancino, M. Marini, G. Frosini GI Unit, Post-Graduate School of Gastroenterology, University of Siena, Italy Background and aim. Wireless capsule endoscopy is a new method enabling non-invasive diagnostic endoscopy of the entire small intestine. To determine the utility of capsule endoscopy in patients referred for investigation of gastrointestinal occult bleeding and in whom upper and/or lower endoscopy had demonstrated angiodysplasia. Materials and methods. Three patients, with iron deficiency anaemia secondary to obscure and occult GI bleeding (FOBT positive), underwent upper and lower endoscopy. The first one was a 63-year-old female patient. Colonoscopy demonstrated multiple (22 lesions diameter 1–8 mm) angiodysplastic colonic lesions, EGDS was negative. In second patient, an 80-year-old man: colonoscopy did not find vascular lesions, EGDS demonstrated duodenal angiodysplasia (1 lesion 3 mm) treated with bipolar coagulation but anaemia was still present. In the case of the third patient, 74-year-old man: EGDS demonstrated duodenal angiodysplasias (6 lesions 1.2 mm) Colonoscopy demonstrated multiple lesions (n = 5, diameter 2–5 mm). All patients were examinated using the capsule endoscopy (GIVENM2A) to investigate the presence of concomitant bleeding sources in small bowel. In all patients radiological study of small bowel was negative. Results. Examination of the entire small bowel was achieved in all cases. In our three patients, capsule endoscopy was able to demonstrate angiodysplastic lesions. In the first patient, an angiodysplasia was found in proximal jejunum and an other in the ileum. In the second one, two lesions were found in the ileum: one with active bleeding. In the last one, videocapsule demonstrated multiple vascular lesions diffuse in all small bowel and some of them with active bleeding. Conclusions. Capsule endoscopy is a novel, non-invasive diagnostic yield for the investigation of the small intestine. These reported cases could suggest the indication to use the wireless capsule in all patients with vascular lesions for the probability to find angiodysplasia in small bowel. Therefore, according to our initial experience, we believe capsule endoscopy is useful in investigating and guiding further management of patients with GI angiodysplasia. VT09 REMOVAL OF A “BILIO-OESOPHAGEAL” STENT BY PROLONGED BALLOON DILATION AND ARGON PLASMA COAGULATION A. Tringali, M. Mutignani, V. Perri, G. Spera, C. Spada, P. Familiari, M.E. Riccioni, G. Costamagna Digestive Endoscopy Unit, Catholic University, Rome, Italy A 62-year-old gentleman had caustic ingestion in 1999. He developed a stricture of the middle oesophageal third that was treated by endoscopic

dilation. Over a 3-year period, he underwent about 50 sessions of mechanical and pneumatic dilation of the stricture because of continuous recurrence. In June 2002, an oesophageal metallic stent was placed in another hospital. The patient subsequently had worsening of the dysphagia and was referred to the endoscopy unit. X-ray showed the oesophageal stent being of a small diameter like a biliary one. Endoscopy confirmed that a biliary Diamond stent (Boston Scientific, Microvasive, Watertown, MA, USA) had been placed in the oesophagus and the lumen was completely closed from ingrowth of hyperplastic tissue. Due to the diameter of the biliary stent (10 mm) mechanical dilation of the oesophageal stricture was performed using a 9 mm Savary–Gilliard dilator. Three weeks later the patient had dysphagia recurrence and was readmitted for an attempt at endoscopic removal of the “bilio-oesophageal” stent. An Eclipse (Wilson-Cook Inc., Winston-Salem, NC) balloon dilator (length 8 cm, diameter 10 mm) was inflated with contrast into the metallic stent with a pressure of 60 psi; the lumen of the balloon catheter was sealed with cyanoacrylate to keep inflation and passed through the nose. The day after X-ray showed the balloon fully inflated in place. Two days after the procedure, the balloon was deflated and endoscopy showed that the stent was well visible because of ingrowth reduction. Stent removal was obtained by cutting the nitinol stent with Argon Plasma Coagulation and removing the fragments with a foreign body forceps. The patient had a marked dysphagia improvement and over the last year only two episodes of dysphagia recurrence treated by mechanical and balloon dilation. Placement of a removable oesophageal stent to achieve persistent dilation of the stricture have been planned. VT10 ENDOSCOPIC RECANALISATION OF A PANCREA- TICO-JEJUNAL ANASTOMOSIS AFTER DUODENOPANCREATECTOMY A. Tringali, M. Mutignani, C. Spada, P. Familiari, G. Spera, M.E. Riccioni, V. Perri, G. Costamagna Digestive Endoscopy Unit, Catholic University, Rome, Italy A 49-year-old gentleman underwent Whipple duodenopancreatectomy because of chronic pancreatitis in 1997. In June 2001, he developed epigastric pain radiating to the back related to meals. US and MRCP showed a marked dilation of the pancreatic stump without evidence of pancreatic mass. Endoscopy was performed under general anaesthesia with a sideviewing endoscope (Pentax, ED 3440T). The bilio-digestive anastomosis was easily identified, whilst the pancreatico-digestive anastomosis was replaced by a whitish plain scar. After secretin i.v. injection (Secrelux, Germany, 1 IU/kg) and manipulation of the scar with a needle-like ERCP catheter (ERCP-1-Cramer, Wilson-Cook Inc., Winston-Salem, NC) a gush of pancreatic juice and plugs were seen coming out. The pancreatic duct was then deeply cannulated with a hydrophilic guidewire. Balloon dilation of the anastomotic stricture was performed with an 8 mm Max Force (Boston Scientific, Microvasive, Watertown, MA, USA) and four 10 Fr pancreatic stents (three CRPSO, one CHBSO, Wilson-Cook) were placed to obtain persistent stricture dilation. Nine months later, being the patient asymptomatic, the stents were removed and a complete recanalisation of the pancreatico-jejunostomy was observed. The patient did not experience further episodes of pain 15 months after stent removal.

Abstracts POSTERS PO001 ETIOLOGIC SPECTRUM AND CLINICAL OUTCOME OF PATIENTS WITH NON-NATURAL EXCRETION (NNE) OF THE GIVEN M2A® VIDEOCAPSULE (VCE): REPORT OF THREE CASES C. Abbiatia,b , E. Rondonottia,b , C. Signorellia,b , G. Beccaria,b , R. de Franchisa,b a Università

degli Studi di Milano, IRCCS Ospedale Maggiore Policlinico Milano, Italy b Dipartimento di Medicina Interna, Servizio di Gastroenterologia ed Endoscopia Digestiva, Italy VCE is a new minimally invasive tool for the study of the small intestine; the passage of the capsule through the GI tract and excretion with the faeces is usually asymptomatic. However, the capsule may be retained in the GI tract and surgery may be necessary to retrieve it. Out of a total of 142 procedures (114 for obscure GI bleeding), NNE of the capsule occurred in three patients (2.1%), a 57-year-old man and two women aged 32 and 67, all with a history of obscure GI bleeding of 1–12 years duration. Medical history. The man had been operated in 1970 for a post-traumatic diaphragm hernia followed by misplacement of the caecum in the upper left abdominal quadrant. The 32-year-old woman had undergone salpingectomy for tuberculosis in 1987, followed by segmental ileal resection for intestinal obstruction (adhesions). The 67-year-old woman had no history of previous abdominal surgery. All patients had had negative bi-directional endoscopies prior to CE. The man and the younger woman also had previous negative enteroclysis. Results. In the first two patients, CE identified ileal ulcers in dilated prestenotic loops. In the third one, the capsule remained in the stomach throughout the recording time. The man and the younger woman had no symptoms, but retained the capsule in dilated prestenotic loops. The site corresponded to the ileo-ileal anastomosis in the woman and to a misplaced sub-diaphragmatic ileal loop in the man. The older woman developed abdominal pain, vomit and signs of acute abdominal obstruction the day after the exam. X-ray showed the capsule retained at the ileo-caecal valve. Follow-up. The patients underwent surgery. Resections of the stenotic and ulcerated tracts were done in the man and the younger woman. Pathology reports showed mucosal ulcers and strictures, consequence of the previous surgery. In the case of the younger woman, intestinal TB was ruled out by tissue and faecal PCR and culture. In the older woman, a stenosing tumour of the ileo-caecal valve was found and a hemicolectomy was performed. The pathology diagnosis was adenocarcinoma. Conclusions. VCE is a safe and well-tolerated procedure. NNE is a rare complication. In our experience, it was always due to pathologic stenoses responsible for the bleeding history and thus surgery, besides retrieving the capsule, had always a therapeutic value. Previous surgery on the GI tract has to be considered as a relative contraindication to the examination. PO002 A CASE OF ALCOHOL DELIUM TREMENS RAPIDLY SUPPRESSED BY BACLOFEN ADMINISTRATION L. Abenavolia , L. Leggioa , G. DeLorenzia , A. Parentea , A. Ferrullia , M.E. D’Angelo Di Paolaa , S. Farnettia , L. Ghaenia , F. Caputob , E. Capristoa , G.L. Rapaccinia , G. Gasbarrinia , G. Addoloratoa

a Institute b Institute

of Internal Medicine, Catholic University, Rome, Italy of Internal Medicine, University of Bologna, Italy

Background. Delirium tremens (DT) is a clinical condition that appears in some patients affected by severe alcohol withdrawal syndrome (AWS). DT represents a serious complication, being characterised by

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elevated morbidity and mortality. Recent studies have shown that baclofen (␣-aminobutyric acid receptor agonist) is able to suppress AWS. At present, there are no data on the effects of baclofen administration in DT. Here we report a case of DT successfully treated with baclofen. Case report. A 49-year-old man affected by DT, was admitted to our hospital, with nausea, vomiting, clouding of the sensorium, flapping tremor, severe paroximal sweat, agitation, anxiety, headache, visual and auditory hallucination and tactile disturbances. History reported by relatives proved positive for chronic alcohol addiction, interrupted in the last 2 days before hospital admission. The CIWA-Ar score was 25 points, showing the presence of severe AWS with DT. After relatives’ consent, a dose of baclofen 25 mg was administered orally, no other pharmacological agents were given. The CIWA-Ar was administered every hour for 4–8 h. A rescue protocol was available. A rapid decrease of the CIWA-Ar score was observed starting from the first hour after baclofen administration, due to resolution of DT symptoms. The patient was then treated with 25 mg baclofen every 8 h for 3 days, followed by 10 mg every 8 h. The patient remained in our Department of Internal Medicine for 14 days and AWS and DT symptoms did not recur. After hospital discharge, drug administration was entrusted to a family member and the patient was included in a treatment programme consisting of psychological support counselling, a self-help group, baclofen 10 mg three times per day for 30 days. At present, the patient is abstinent from alcohol and drug-free for about 7 months. Discussion. This result indicates the possible utility of baclofen in the treatment of DT. Further clinical trials are necessary to clarify these findings. PO003 RAPID REGRESSION OF SEVERE PSORIASIS IN A COELIAC PATIENT AFTER GLUTEN-FREE DIET L. Abenavolia , L. Leggioa , G. DeLorenzia , A. Parentea , A. Ferrullia , M.E. D’Angelo Di Paolaa , S. Farnettia , E. Capristoa , L. Ghaenia , M. Rotolib , G.L. Rapaccinia , G. Addoloratoa , G. Gasbarrinia a Institute b Institute

of Internal Medicine, Catholic University, Rome, Italy of Dermatology, Catholic University, Rome, Italy

Background. Several skin disorders can be observed in patients affected by coeliac disease (CD). The relationship between CD and psoriasis remains controversial since there are only few and contrasting data on this topic. Here, we describe a case of psoriasis in a CD patient, non-responder to specific psoriasis therapy in whom the regression of skin lesion was evident after a short period of gluten free diet (GFD). Case report. A 53-year-old man affected by CD with low compliance to GFD and suffering from severe psoriasis since 1980 was admitted to our hospital. In the past, he had been treated with corticosteroids, followed by cyclosporin and PUVA therapy, without significant improvement. On admission to our hospital in August 2002, the patient showed severe psoriasis skin lesion, mild peripheral oedema, iron deficiency anaemia with microcytosis, low serum levels of folate, Vitamin B12 , Vitamin D and leukocytosis with neutrophilia. Anti-endomysial antibodies (EmA) were absent, IgA and IgG antibodies to gliadin (AGA) serum levels were not raised, whereas total serum immunoglobulins IgA were increased. The patient underwent endoscopy with duodenal biopsy which showed total atrophy of intestinal villi and intraepithelial inflammatory infiltrate. A GFD was started and after a few days the patient was discharged. This time, the patient was strictly adherent to GFD with rapid improvement of gastrointestinal symptoms and nutritional status, including normalisation of serum levels of Vitamin D. After 1 month of GFD the psoriasis skin lesions disappeared. Biopsy-proven return to normal duodenal mucosa was found after 6 months of GFD. Presently, the patient is still adherent to GFD and free from psoriasis skin lesions. Conclusions. The present case supports the association between CD and psoriasis, taking into account that both diseases are T-cell-mediated disorders. The effect of the GFD on psoriasis skin lesion might be

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partly related to the improvement of the correct intestinal absorption with recovery of the normal levels of vitamin. PO004 SUSPECTED INFLAMMATORY CHANGES OF THE BOWEL WALL: THE ROLE OF BASIC AND PEG 4000 CONTRAST ENHANCED ULTRASONOGRAPHY L. Allegretta, S. Giaccari, S. Tronci, S. Chiri, G. Grasso Department of Gastroenterology, “S. Caterina Novella” Hospital, Galatina (LE), A.S.L. LE/01, Italy Background. Multiples studies more often demonstrate the role of the bowel ultrasound performed by an expert operator, via the basic and PEG 4000 contrast enhanced method as a sensible, useful and cost-effective technique in making a diagnosis and especially in the follow-up of inflammatory bowel diseases (IBD). This claim is well recognised mainly when prior imaging demonstration (Small Bowel RX and/or TC-RMN scan) of such diseases are there. Although we decided to investigate patients with only clinical and not definite suspected inflammatory changes of the bowel wall (not only CD or UC) to stress out a role in imaging steps for basic and PEG 4000 contrast enhanced ultrasonography. Materials and methods. We studied a selected group of 91 consecutive patients (37 males and 54 females; age 16–67 years), with chronic abdominal pain lasting more than 3 months up to 6 months, prevalent in lower quadrants and fluctuating faeces changes (prevalent diarrhoea) to obtain first diagnosis. During the recovery we strong-willed to carry out as a first step, the US study by basic bowel ultrasound (Philips Med. Div. ATL 3500 model, Linear 5–7.5 MHz, and Micro-convex 5 MHz probes) followed by contrast enhanced US performed with PEG 4000 (Macrogol) at the standard doses (37 g in water 500 ml) and scan method. Then, all of them underwent other “gold standard” defined imaging technique (Small Bowel RX, TC or RMN scan) to compare the echo graphic results. A wall thickening (>3 mm), hypo echoic/multiple striped or not banded bowel loop and bloated bowel wall were the principal items to report confirming the suspected inflammatory related changes diagnosis. We demonstrated all this characters in 41 patients (45%). The images were indeed mighty concord with those obtained by the other imaging techniques. The final diagnosis were Crohn’s disease in 15 patients, ulcerative colitis in 10 patients, diverticula’s mild inflammation in 14 patients, follicular lymphoid hyperplasia of the Ileum wall in two cases. Only five US negative patients showed NMR signs of minor jejunum and/or ileum IBD involvement. The remaining cases were all diagnosed as irritable bowel syndrome. Conclusions. This little clinical experience confirms the real efficacy of the bowel ultrasound as sensible, useful and cost effective technique, performed by an expert operator, via both basic and PEG 4000 contrast enhanced method, in those patient suffering from chronic abdominal pain and/or inconstant stool modification evocating inflammatory changes of the bowel wall. In our case reports, we found a high (95% compared to NMR findings) positive predictive value of the contrast enhanced bowel ultrasonography in revealing various inflammatory related bowel diseases, but also the same high negative predictive value for IBS patients. References [1] Hollerbach S, Geissler A, Shiegl H, et al. The accuracy of abdominal ultrasound in the assessment of bowel disorders. Scand J Gastroenterol 1988;33:1201–8. [2] Lim JH, Ko YT, Lee DH, et al. Sonography of inflammatory bowel disease: findings and value in differential diagnosis. Am J Roentgenol 1994;163:343–75. [3] Maconi G, Parente F, Bollani S, et al. Abdominal ultrasound in the assessment of extent and activity of Crohn’s disease: clinical significance and implications of bowel wall thickening. Am J Gastroenterol 1996:91:1604–8.

PO005 M2A CAPSULE ENDOSCOPY IN THE DIAGNOSIS OF GASTROINTESTINAL METASTASIS OF MELANOMA. A CASE REPORT A. Allegretti, E. Vallarino, M. Oppezzi, P. Romagnoli, G. Coccia, R. Tricerri, S. Mesiti, P. Massa, P. Michetti Unit of Gastroenterology, Galliera Hospital, Genoa, Italy Metastasis of malignant melanoma are very common in the small intestine and can show specific symptoms, such as anorexia, abdominal pain and/or anaemia. We discuss the case of a 78-year-old man with diffuse colicky abdominal pain, constipation, weight loss and sideropenic anaemia. He had a history of cutaneous melanoma, operated 1 year before. A CT enteroclysis, a CT enema and total-body CT scan showed multiple nodular lesions of the distal ileum and involvement of regional lymph node. The first diagnostic hypothesis was non-Hodgkin lymphoma or intestinal chronic infectious disease. A total colonoscopy without pathological findings was performed. Retrograde ileoscopy was not possible. The diagnostic work-up was completed by M2A Capsule Endoscopy that showed multiple pigmented polypoid lesions not only in the distal ileum but in the entire small bowel, compatible with metastasis of melanoma to the small intestine. The examination also showed an active bleeding due to an ulcerative metastatic lesion. We conclude that M2A Capsule Endoscopy is a valuable tool, better than conventional radiology and CT scan, in melanoma patients with suspected gastrointestinal involvement and also for gastrointestinal obscure bleeding. PO006 RARE COMPLICATION OF GALLSTONES DISEASE: SUCCESSFUL ERCP DIAGNOSIS OF MIRIZZI SYNDROME TYPE IV C. Alvisia , S. Arcellonia , F. Torello Vieraa , M. Abellib , F.P. Tinozzib , F. Brogliaa , E. Stradaa , P. Colombob , M. Peregoa a Endoscopy

Unit, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy b Surgical Department, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy Background. Mirizzi syndrome is a rare (0.7–1.1%) complication of gallstones disease that has been classified into IV types. Type I consist of compression of common hepatic duct by stone impacted into cystic duct while types II, III and IV are cholecystocholedochal fistula of increasing grade. An accurate diagnosis is very important for therapy choice. ERCP is the best diagnostic procedure that allows to treat concomitant cholangitis or biliary obstruction. Differential diagnosis include gallbladder carcinoma, cholangio-carcinoma and linphadenopathy. Therapy has been traditionally surgical. Case report. A 78-year-old woman with abdominal pain, nausea, fever was observed. Physical examination and laboratory tests were negative. US and TC examination showed hepatic duct dilation and multiple choledocal stone. ERCP was performed with diagnosis of Mirizzi syndrome type IV. Diagnosis was confirmed by surgery that revealed a large biliobiliary communication and destruction of the entire choledocal wall. The gallbladder was similar to giant diverticula of the biliary duct with a lot of impacted stones and no identifiable cystic duct. Surgical therapy consisted of cholecistectomy and direct reparation of the communication over a stent tube of Kehrs. Cholangiography by Kehrs’ tube demonstrated regular bile duct and absence of residual stones. Conclusion. Mirizzi Syndrome is a rare complication of gallstones disease which traditional treatment has been surgical. Recently, endoscopic procedure has been proposed for poor operative candidates and for Type I cases. Stone manipulation back to the gallbladder, endoscopic electrohydraulic or extracorporeal shock wave lithotripsy and chemical dissolution were described. We described a rare type IV case successfully diagnosed by ERCP that, as type III, required surgical therapy.

Abstracts PO007 TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) FOR VARICEAL BLEEDING IN CIRRHOTIC PATIENTS: COMPARISON OF EMERGENCY AND ELECTIVE INTERVENTIONS S. Angelonia , G. Nicolinia , F. Salvatorib , F. Fanellib , D. Pepinob , F.A. Attilia , P. Rossib , M. Merlia , O. Riggioa a II

Gastroenterologia, Dipartimento di Medicina Clinica, Italy di Radiologia, Università di Roma “La Sapienza”, Italy

b Istituto

Background and aims. Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly employed for the treatment of recurrent variceal bleeding in cirrhotic patients. Little information is available about the role of emergency TIPS for acute variceal bleeding unresponsive to endoscopic and drug therapy. Therefore, the aim of the present study was to compare the efficacy of emergency and elective TIPS in cirrhotic patients. Patients and methods. We included 71 cirrhotics consecutively referred to our Gastroenterolgy Unit for TIPS procedure for variceal bleeding from July 1992 to February 2003. A follow-up of all the patients was carried out by the same medical team according to a prospective protocol for a diagnostic work-up and a surveillance strategy. TIPS was performed in emergency in 21 patients with acute variceal bleeding unresponsive to medical (terlipressin 12 mg e.v.) and endoscopic treatment (at least two sessions of sclerotherapy). Elective TIPS was performed in 50 patients with recurrent variceal bleeding despite medical therapy and endoscopic treatment. Results. TIPS was successfully implanted in all the patients. Mean follow-up was 28 ± 27.3 months (range: 0.03–104.3 months). The two groups were similar with regard to age, sex and aetiology of liver disease, while the patients with emergent TIPS had more severe liver disease (Child–Pugh class B or C: 62% versus 90%, P < 0.01; MELD score >12: 26% versus 44%, P < 0.01). Basal portocaval venous gradient was similar and decreased similarly in both groups. The cumulative rate of rebleeding (21% at 1 year and 24% at 3 years versus 10.6% at 1 year and 25.5% at 3 years; P = 0.65) as well as the cumulative survival (15.6% at 1 year and 32.8% at 3 years versus 19.6% at 1 year and 33% at 3 years; P = 0.70) were not different after emergency and elective TIPS. Early mortality (30 days) was 9.5% in the emergency TIPS group (one patient died of uncontrolled bleeding), while no patient died in the elective TIPS group within 30 days after TIPS. The probability of remaining free of hepatic encephalopathy and shunt dysfunction was similar in both groups. Conclusions. TIPS is effective for control of acute variceal bleeding refractory to conventional therapy. Early mortality occurred more often after emergency TIPS. Long-term survival as well as complications (shunt dysfunction, encephalopathy and rebleeding) did not differ from elective TIPS. PO008 HEPATIC ENCEPHALOPATHY AFTER TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS): PTFE-COVERED STENT-GRAFTS VERSUS BARE STENTS S. Angelonia , F. Nicolaoa , F. Salvatoria , F. Fanellib , D. Pepinob , F.A. Attilia , P. Rossib , M. Merlia , O. Riggioa a II

Gastroenterologia, Dipartimento di Medicina Clinica, Italy di Radiologia, Università di Roma “La Sapienza”, Italy

b Istituto

Background and aims. PTFE-covered stent-grafts appear to have the potential to improve TIPS patency. However, to a greater efficacy in the control of variceal rebleeding and ascites/hydrothorax, a long-term patency of the shunt might also increase the risk of hepatic encephalopathy. The aim of this study was to prospectively assess TIPS patency and the incidence of hepatic encephalopathy (HE) with the new PTFE-covered stent-grafts in comparison with a group of controls treated with bare stents. Patients and methods. Eighty-seven cirrhotics were treated with bare

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stents and 50 with PTFE-covered stent-grafts. A follow-up of all the patients was made by the same medical team according to a prospective protocol for a diagnostic work-up and a surveillance strategy. Results. The two groups were comparable for age, sex, aetiology, and severity of cirrhosis. The 1-year probability of remaining free of shunt dysfunction was significantly higher in the covered stent group: 76.8% (95%CI = 58.7–93.9%) versus 56.2% (95%CI = 46.6–68.4%); Log rank test: P = 0.04. At least one episode of HE occurred in 22 of the 50 patients in the study group and in 52 of the 87 patients in the control group. The 1-year probability of remaining free of HE was similar in both groups: 51% (95%CI = 28.9–65.3%) in the stent-graft group and 42.3% (95%CI = 31.9–53.1%) in the control group; Log rank test, P = 0.53. The number of HE episodes in the first 12 months after TIPS was similar in the two groups; however, 6 of the 50 patients treated with a covered stent and none in the bare stent group suffered of recurrent HE which did not respond to the medical therapy and required shunt reduction. Conclusions. PTFE-covered stent-grafts are more likely to remain patent over time, but severe recurrent HE requiring the shunt reduction is a new emerging complication of these covered stents. PO009 ACCURACY OF RETROGRADE ILEOSCOPY VERSUS SMALL BARIUM FOLLOW-THROUGH IN THE EVALUATION OF CROHN’S DISEASE TERMINAL ILEITIS. A PERSPECTIVE STUDY E. Angelucci, A. Cocco, E. Tomei, M. Teresa Pimpo, A. Viscido, R. Caprilli Cattedra di Gastroenterologia, Dipartimento di Scienze Cliniche, Università degli Studi di Roma “La Sapienza”, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy Background. In Crohn’s disease (CD), the small barium follow-through (BaFT) is traditionally considered to be the best method for the study of small intestinal lesions. In the last decades, the diffusion of ileocolonoscopy with retrograde ileoscopy has provided a new tool for the study of terminal ileum, the most frequently site involved in CD. However, the accuracy of ileoscopy has never been carefully evaluated. Aim. To evaluate the accuracy of retrograde ileoscopy versus small barium follow-through in the evaluation of CD ileitis. Methods. The study was perspective and both the radiologists and the endoscopists worked in blind. One hundred and five patients (52 female, 53 male, median age = 42.6 years, range = 18–82 years) admitted to the GI Unit of University of Rome “La Sapienza” for known CD were included. Clinical course was fistulising in 41 patients, stenosing in 38, inflammatory in 26. Forty-three patients were submitted to intestinal resection with ileocolonic anastomosis. CDAI mean value was 227 (range = 40–432). Patients underwent ileocolonoscopy and BaFT in 2 weeks frame time. Data from both examinations were collected using a standard data-base card. The BaFT was considered as “gold standard” for the detection of CD lesions of the terminal ileum. Sensitivity and specificity of retrograde ileoscopy respect “gold standard” were calculated. Results. Retrograde ileoscopy was not performed in 16 patients (15.2%, seven for stenosis and nine for uncompliance). In the whole cohort of patients, ileoscopy had a sensitivity of 98.6% and a specificity of 73.7%. BaFT added additional informations compared to ileoscopy in terms of lesions’ extension, upper disease (10 of 105 patients, 9.5%) and fistulas (7 of 105 patients, 6.6%). In 3 of 43 patients (7%), previously submitted to intestinal resection with ileocolonic anastomosis, ileoscopy showed mucosal lesions that BaFT did not detect. Conclusions. The results of this study showed that ileoscopy had a high sensitivity for the detection of CD lesions of terminal ileum in the whole cohort of patients. In post-surgical settings ileoscopy was able to detect lesions of neoileum which the “gold standard” BaFT did not detect.

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Abstracts

PO010 ROLE OF PRIOR APPENDECTOMY ON ONSET AND CLINICAL COURSE OF CROHN’S DISEASE (CD) E. Angelucci, M. Zippi, A. Cocco, G. Milite, A. Viscido, R. Caprilli GI Unit, Department of Clinical Science, University of Rome “La Sapienza”, Italy Background. Several studies investigated the relationship between appendectomy and onset of Crohn’s disease (CD), showing a positive association which was statistically significant only in a few studies. These studies generally have not addressed the effect of appendectomy on disease characteristics. Aim. To evaluate the rate of appendectomy before diagnosis in CD patients and the effect of prior appendectomy on disease characteristics. Methods. Records of 383 consecutive patients with known CD diagnosis attending the GI Unit, University of Rome “La Sapienza” in the last decade were reviewed retrospectively. For each patient, factors such as age at diagnosis, localisation, clinical course, extraintestinal manifestations, requirement for immunosuppressive therapy and surgery were analysed. A population of 331 CD patients (86.5%) who did not undergo appendectomy prior to the diagnosis served as control. Chi-square test was used for the statistical analysis. Results. Fifty-two (13.5%) of 383 CD patients underwent appendectomy prior to the diagnosis of CD. Median age at diagnosis in these patients was greater (42.5 years, 13–72) compared with the controls (29.5 years, 15–44). Ileocolonic disease localisation seems to be more frequent (46.1% versus 36%) whereas colonic less frequent (9.7% versus 13.6%). Disease behaviour seems to be influenced by prior appendectomy, with a greater frequency of stricturing clinical course (44.2% versus 28.4%) OR: 2 (95% CI: 1.1–3.634) (P < 0.0322), extraintestinal manifestations (46.1% versus 26.3%) OR: 2.4 (95% CI: 1.322–4.371) (P < 0.0056) and need for surgery (59.6% versus 47.1%) respect to the controls. Eighteen of the 52 patients (34.6%) needed more than four recoveries. Thirty-one of 52 patients (59.6%) needed steroids and 13 (25%) needed immunosuppressive therapy. Conclusion. Age at diagnosis tended to be later in those CD patients with prior appendectomy. In addition, appendectomy before diagnosis seems to be associated with a significant prevalence of stricturing clinical course and extraintestinal manifestations. PO011 LATE ONSET OF CROHN’S DISEASE: DIFFERENT CLINICAL PATTERN? E. Angelucci, A. Cocco, M. Zippi, A. Viscido, R. Caprilli Cattedra di Gastroenterologia, Dipartimento di Scienze Cliniche, Università degli Studi di Roma “La Sapienza”, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy Background. Crohn’s disease (CD) affects preferentially young adults. The clinical features and outcome of elderly patients with CD have not been investigated properly. A more frequent colonic localisation and a more aggressive disease in elderly have been reported. Aim. To describe the rate of CD diagnosis after the age of 60 years as well as the clinical pattern in comparison with a CD population younger than 60 years. Methods. The records of 331 consecutive patients with known CD attending the GI Unit of University of Rome “La Sapienza” in the last decade, were reviewed retrospectively. For each patient, factors such as age at diagnosis, symptoms at onset, localisation, clinical course, smoking habit, extraintestinal manifestations, family history, need for surgery and immunosuppressive therapy were analysed. Three hundred and fourteen (94.9%) of 331 patients with diagnosis before the age of 60 served as control. Results. Seventeen (5.1%) of 331 CD patients had diagnosis after 60 years of age (10 females, 6 males, median age 72.5 years, range 62–86

years). The diagnosis was established by small barium follow-through (BafT) in six patients, endoscopy in seven and surgery in four. At the onset of disease, abdominal pain was present in 13 patients, diarrhoea in 11, bleeding in 3, weight loss in 3, fever in 1, anaemia in 1, constipation in 1. Four patients needed for azathioprine, three for infliximab. Only four patients needed for surgery (three at diagnosis). There was no significant difference in the clinical features in patients with diagnosis before and after age of 60 years. Conclusions. Clinical features of the disease are the same in the young adult and in the elderly; even in the elderly immunosuppressive therapy is needed quite often. PO012 ROLE OF NON-INVASIVE DIAGNOSTIC METHODS FOR Helicobacter pylori (HP) INFECTION IN PATIENTS WITH ATROPHIC BODY GASTRITIS (ABG) B. Annibalea , E. Lahnera , D. Vairab , N. Figurac , F. Pernab , G. D’Ambraa , A. Pasqualia , G. Delle Favea , B. Annibalea a Digestive

and Liver Disease Unit, II Medical School, University “La Sapienza”, Rome, Italy b Department of Internal Medicine and Gastroenterology, University of Bologna, Italy c Department of Gastroenterology, University of Siena, Italy

Background. Helicobacter pylori (HP) is involved in atrophic body gastritis (ABG). The detection of HP infection in ABG may be not accurate because during the progression of body atrophy the disappearance of HP has been documented. Moreover, serology may indicate a previous infection only. 13C-Urea Breath test (13C-UBT) and the detection of HP in stool antigen (HpSA) are the non-invasive methods for the diagnosis of HP recommended by Maastricht criteria in non-atrophic patients, but their usefulness in ABG patients is still unknown. Aim. To assess the accuracy of 13C-UBT and HpSA in diagnosing HP infection in ABG patients. Patients. Twenty-seven consecutive patients with newly diagnosed ABG (19 females, 7 males, median age 51.5 years, range 27–53 years). Methods. All patients underwent endoscopy with biopsies (antrum n = 3, body n = 3) and histological evaluation, according to updated Sydney system (Giemsa for H. pylori), 13C-UBT (positive DOB > 4.5‰), blood samples for HP IgG serology, and faecal samples for HpSA (Premier Platinum HpSA test, positive >0.160). HP status was defined according to Maastricht criteria. Results. Ten of the 27 (37%) patients were HP positive at histology, 8 of the 27 (29.6%) were 13C-UBT positive (median DOB 9.4‰, range 4.8– 30.5‰) and 4 of the 27 (14.8%) were HpSA positive (median titre 0.684, range 0.592–0.925). Five of eight patients with positive with 13C-UBT and all four patients with positive HpSA were HP positive at histology. All four patients with positive HpSA had positive 13C-UBT, and only one of the five patients 13C-UBT+ had negative HpSA. In 5 of the 10 patients (H. pylori positive at histology), the infection was not detected by any of the non-invasive tests. Among the 17 patients with negative H. pylori histology, none had positive HpSA+, but 13C-UBT gave three (17.6%) false positives. The specificity and a sensitivity of HpSA and 13C-UBT were of 100 and 40%, and 82 and 50%, respectively. Body atrophy score was not different between histological HP positive ABG compared to positive and negative patients, by non-invasive tests (1.25 ± 0.23 versus 1.67 ± 0.33, P = 0.39). Conclusions. In ABG patients, non-invasive diagnostic methods for HP infection may not be reliable for the detection of active HP infection.

Abstracts PO013 THE YELD OF ENDOSCOPIC AND HISTOLOGICAL STUDY OF TERMINAL ILEUM IN PATIENTS AFFECTED BY CHRONIC DIARRHOEA (CD) G. Aprilea , S. Incarbonea , G. Magrob , A. Gurrerab , G. Bonannoa , A. Calzonaa , A. Russoa a Cattedra b Cattedra

di Gastroenterologia, Università di Catania, Italy di Anatomia Patologica, Università di Catania, Italy

Background and aims. Patients with chronic diarrhoea (CD) (loose and frequent bowel movements of unknown origin lasting longer than 4 weeks) frequently undergo endoscopic examination. To date there are few data when histologic study of the ileum adds anything to colonoscopy alone in these patients. The aim of this study was to assess the yield of ileal biopsy in patients with CD. Materials and methods. A total of 79 patients (45 men, mean age 36.4 years, age range 16–77 years; 34 women, mean age 39.7 years, age range 15–70 years) affected by CD were studied prospectively. The final diagnosis, based on endoscopic and histological findings of colon and ileum is reported. A control group, consisting of 79 consecutive patients submitted to lower endoscopy without CD was considered. Results. In 24 (30.3%) of the 79 patients with CD, the endoscopic examination with biopsy of the colon was abnormal and showed 18 (22.7%) cases of a specific colitis versus 9/79 of the control group (P < 0.05), 4 (5.0%) cases of Crohn’s disease, and 1 (1.2%) case of RCU. Furthermore, the following were also found: two patients with polyps and one with diverticulosis of the left colon. Endoscopic appearance of terminal ileum was normal in 60 (75.9%) cases and consisted with a specific inflammation in 12 (15.2%) cases and with Crohn’s disease in 7 (8.8%) cases. No lesions were observed in the control group. Ileal histology was normal in 58 (73.4%) cases while in 13 (16.4%) cases a diagnosis of non-specific inflammation was made versus 2/79 in the control group (P < 0.05). Significant histopathology was present in eight (10.1%) patients diagnosed as Crohn’s disease, lesions were limited to the ileum (Crohn’s ileitis) in four out of them. Conclusions. Histological study of terminal ileum identified pathology in 26.5% (21/79) of patients with CD versus 2.5% (2/79) in the control group. In eight (8/21) patients with CD a Crohn’s ileitis (extended to colon in 4/8) was identified. In our experience, endoscopic and histological study of the ileum has been strongly useful in the examination of patients referred for unexplained CD, and could be recommended as routine practice in this setting. PO014 EFFICACY OF MESALAZINE IN THE TREATMENT OF SYMPTOMATIC DIVERTICULAR DISEASE A. Giovannia,b,c,d,e , G. Leandroa,b,c,d,e , L. Fanigliuloa,b,c,d,e , G.M. Cavestroa,b,c,d,e , G. Comparatoa,b,c,d,e , L. Caval- laroa,b,c,d,e , P. Muzzettoa,b,c,d,e , A. Franzèa,b,c,d,e , F. Di Marioa,b,c,d,e a University

of Parma, Italy Hospital “S. De Bellis” IRCCS, Castellana Grotte,

b Gastroenterological

Bari, Italy c Gastroenterology Unit, University of Treviso, Italy d Gastroenterology and Endoscopy Unit, Az. Ospedaliera, Parma, Italy e Geriatric Unit “Casa Sollievo della Sofferenza”, IRCCS San Giovanni Rotondo, Foggia, Italy Background and aim. In uncomplicated diverticular disease, treatment is aimed to relieve the symptoms in symptomatic patients. Our aim was to evaluate efficacy of mesalamine in relief symptoms in patients with symptomatic and uncomplicated diverticular disease of the colon. Materials and methods. Two hundred and forty-eight consecutive eligible outpatients (102 male, 146 female; age 66.1 years, range 31–81 years) were enrolled in four different schedules according to a randomisation list: Group R1 (57 patients) rifaximin 200 mg bid; Group R2 (69 patients)

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rifaximin 400 mg bid; Group M1 (60 patients) mesalamine 400 mg bid; Group M2 (62 patients) mesalamine 800 mg bid. Each treatment was administered for 10 days every month. Clinical evaluation was performed at admission and at 3-month intervals for 12 months considering 11 clinical variables (upper and lower abdominal pain/discomfort, tenesmus, diarrhoea, abdominal tenderness, fever, general illness, nausea, emesis, dysuria) scored as 0 = no symptom, 1 = mild, 2 = moderate, 3 = severe. The global symptomatic score (GSS) was calculated by the sum of each symptom score. Results. After 12 months follow-up, Group M2 showed fewer frequency rate of bloating (P < 0.006), tenesmus (P < 0.001), diarrhoea (P < 0.02) and fever (P < 0.02). Mean GSS was lower in Group M2 after 3 (P < 0.0001), 6 (P < 0.0001) and 12 (P < 0.02) months, respectively. Patients treated with mesalazine (Groups M1 and M2 together considered) showed a lower GSS as compared to subjects treated with rifaximin (Groups R1 and R2 together considered) after 3 (P < 0.0001), 6 (P < 0.0001) and 12 (P < 0.005) months follow-up, respectively. Conclusion. Cyclic administration of mesalazine is effective in obtaining symptom relief in uncomplicated diverticular disease of the colon. Some symptoms improved better with mesalazine 800 mg bid than with the other schedules. PO015 SEASONAL VARIATIONS IN THE ONSET OF SYMPTOMS OF INFLAMMATORY BOWEL DISEASES: AN INTERIM ANALYSIS A. Arataria , C. Papib , E. Angeluccia , V. D’Ovidioa , A. Cossua , A. Ciacob , R. Caprillia a Dipartimento

di Scienze Cliniche, Università di Roma “La Sapienza”, Rome, Italy b Dipartimento di Malattie Digestive e Nutrizionali, Ospedale S. Filippo Neri, Rome, Italy Background. Environmental factors seems to play a role in the development of inflammatory bowel disease (IBD). Seasonal variations in the onset of symptoms has been reported in ulcerative colitis but not in Crohn’s disease (CD) [Moum et al., Gut (1996)]. Aim. To investigate whether there are seasonal variations in the onset of symptoms in our population of IBD patients. Methods. Perspective of ongoing study. The protocol includes all consecutive patients observed in our IBD Units from June 2003 to May 2004, with certain diagnosis of IBD (established between January 1995 and October 2003). Data concerning symptoms onset are collected using the patient cards as support to a standard interview. Symptoms leading to diagnosis (diarrhoea, rectal bleeding, abdominal pain, fever, weight loss, perianal fistulae/abscess, and extra-intestinal manifestations) are considered specific symptoms of IBD. The expected onset with a uniform distribution during the year was calculated and compared to the observed onsets. Statistical analysis: chi-square test, OR (95% CI). Results. We report the interim analysis on 296 patients enrolled up to October 2003 (137 Crohn’s disease; 159 ulcerative colitis, UC; females 137; males 159; mean age at diagnosis: 37.2 years, range 11–81 years). Data concerning seasonal onset of symptoms could be collected in 249 of 296 patients. The seasonal onset of symptoms is reported in the table below: Observed

Expected

Chi-square

OR (95% CI)

IBD 249 patients Spring–summer Autumn–winter

155 94

125 124

P = 0.008

1.6 (1.1–2.3)

CD 110 patients Spring–summer Autumn–winter

71 35

55 55

P = 0.04

1.8 (1.0–3.1)

UC 139 patients Spring–summer Autumn–winter

84 55

70 69

P = 0.11

1.5 (0.9–2.4)

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Abstracts

Conclusions. Our preliminary data indicate a seasonality (spring–summer) in symptomatic onset of IBD. In a subgroup analysis, a peak in spring and summer onset is observed in CD, but not in UC. PO016 REFRACTORY AUTOIMMUNE HAEMOLYTIC ANAEMIA AND ULCERATIVE COLITIS S. Ardizzonea , U. Russob , E. Colomboa , G. Maconia , M. Moltenia , E. Rossib , G. Bianchi Porroa a Gastroenterology b Haematology

Unit, “L. SACCO” University Hospital, Milan, Italy Unit, “L. SACCO” University Hospital, Milan, Italy

Background and aims. Autoimmune haemolytic anaemia (AIHA) is a haematological complication observed in patients with ulcerative colitis (UC), which generally becomes evident during active disease or due to pharmacological therapy. We describe two patients suffering from UC with AIHA refractory to immunosuppressive treatment. Methods. First case: a 54-year-old man was admitted to our department for AIHA during a relapse of UC, refractory to therapy with corticosteroids and vincristine. Laboratory tests revealed severe haemolysis with a positive direct antiglobulin test (DAT) IgG and C3d and haemoglobin (Hb) levels of 5.5 g/dl. The patient underwent second line therapy with intravenous gamma-globulin, 400 mg/kg per day for 5 days, and prednisone, 1.5 mg/kg per day, without transfusion. Haemolysis signs were reduced after 2 weeks and Hb levels increased to 10.5 g/dl within 2 months; the steroid was tapered to a maintenance level of 0.7 mg/kg per day for 1 year. Second case: a 32-year-old woman with AIHA during a relapse of UC showed severe haemolysis, positive DAT or IgG and C3d, and Hb levels of 6.5 g/dl. She underwent the same therapy with intravenous gamma-globulin and prednisone; steroid was tapered to maintenance levels when Hb was higher than 10 g/dl. After 6 months, during maintenance therapy and when the UC was in remission, AIHA relapsed, showing Hb levels of 3.5 g/dl. She was treated with intravenous gamma-globulin and prednisone, 1.5 mg/kg per day, without transfusion. After 2 months Hb increased to 8 g/dl and prednisone was reduced. After 1 year both patients showed positive DAT and decreasing Hb levels at every reduction of steroid dosage, together with iatrogenic hypertension and diabetes requiring insulin treatment. Colectomy was therefore performed. Results. After surgery Hb increased, and steroid was reduced and withdrawn within 2 months. After 6 months both patients showed Hb levels higher than 12 g/dl, with negative DAT. Three years after surgery, both the patients did not show symptoms and signs of AIHA. Conclusions. The fact that colectomy allowed AIHA to resolve in these patients suggests that refractory AIHA in UC might be sustained by lymphocyte clones located in the colon. Therefore, colectomy should be always considered in this group of patients. PO017 INFLIXIMAB IN THE TREATMENT OF MODERATE TO SEVERE STEROID DEPENDENT ULCERATIVE COLITIS: A RANDOMISED METHYLPREDNISOLONE CONTROLLED TRIAL A. Armuzzi, P. Fedeli, A. Lupascu, B. De Pascalis, G. Gasbarrini, A. Gasbarrini Department of Internal Medicine, Catholic University, Rome, Italy Background and aim. Infliximab has proven efficacious in the treatment of Crohn’s disease. Limited and contrasting data are available on effectiveness of anti-TNF␣ therapy in ulcerative colitis (UC). We evaluated the efficacy of infliximab in the management of steroid-dependent UC. Methods. We conducted a randomised, open-label, methylprednisolonecontrolled trial of infliximab in the induction and maintenance of remission of patients with moderate to severe steroid dependent UC. Patients were eligible if (1) they had moderate to severe disease according to a

disease activity index (DAI) score >6; (2) they were not in need of urgent colectomy. Patients received either three infusion of infliximab (5 mg/kg) at 0, 2 and 6 weeks and thereafter every 8 weeks (group A) or methylprednisolone (0.7–1 mg/kg) daily for 1 week followed by a tapering regimen up to the minimal dose to maintain a symptom-free condition (group B). Disease activity was assessed at recruitment, 1 week after the first infusion and every 8 weeks thereafter. Clinical remission was defined as a DAI score permanently <3. Results. Twenty patients were studied (10 patients in each group). All patients in group A (DAI: 8.9 ± 1.4) achieved remission after the first infusion (DAI: 1.6 ± 0.7; P = 0.005) and steroids were progressively discontinued. At present (mean follow-up: 9.8 ± 1.1 months), 9 out of 10 patients maintain clinical remission. One patient relapsed (DAI = 5) at 3 months and needed shorter intervals between infusions to achieve and maintain remission. Infusions with infliximab produced no significant adverse events. All patients in group B (DAI: 8.7 ± 1.4) reached clinical remission at 1 week (DAI: 1.9 ± 0.3; P = 0.005). Eight out of 10 patients were maintained at a minimal steroid dosage without any relapse at 9.7 ± 1.0 months follow-up. Two patients relapsed at 6 and 8 months, respectively. They were then treated with infliximab, achieving clinical remission. Conclusions. Infliximab seems to be as effective as steroids in the management of moderate to severe steroid dependent UC. These preliminary data suggest the potential efficacy of repeated infliximab treatment for short-term maintenance of remission and steroid withdrawal in glucocorticoid dependent UC. PO018 CORRELATION BETWEEN C-MYB, SERUM P-53M, GENETIC INSTABILITY, LABELLING INDEX AND ENDOSCOPIC FINDINGS, 5-YEAR FOLLOW-UP IN PATIENTS WITH ADENOMA OR COLORECTAL CANCER D. Assisia , A. Grassia , R. Lapentaa , V. Stiglianoa , C. Grecob , A. Cianciullib , D. Giannarellic , A. Ricciottic , V. Casalec , a Gastroenterology

and Digestive Endoscopy Unit, Regina Elena Cancer Institute, Rome, Italy b Clinical Pathology Service, Regina Elena Cancer Institute, Rome, Italy c Biostatistic Service, Regina Elena Cancer Institute, Rome, Italy Objectives. Structural alterations of c-myb proto-oncogenes and serum p53 mutant level, mitomycin C-induced chromosomal aberrations and sister chromatid exchanges and proliferative activity of mucosa (H3-thymidine-labelling index LI) are often determined to obtain more information about the diagnosis and prognosis of neoplastic and preneoplastic lesions of the colon. The aim of this study was to evaluate the endoscopic findings of a 5-year follow-up in three groups of subjects (normal, adenoma or cancer patients) and to correlate these findings with the biological alterations in the same subjects between 1990 and 1993. Materials and methods. We analysed 200 subjects (118 males and 82 females), 78 normal subjects (group A), 60 patients with adenoma (group B) and 62 with carcinoma (group C). Data regarding endoscopic lesions was collected from June 1998 to December 2000 after a 5-year follow-up and correlated with the biological alterations in the same subjects between 1990 and 1993. Results. We obtained endoscopic findings from 23/137 subject (16.8%), 6/137 (4.4%) died from other causes and 108/137 (78.8%) were negative for lesion. The percentage of disease after 5 years is not statistically different among the three groups (groups A, B and C). There was no statistically significant association between values of the labelling index, structural alterations of c-myb, p-53-M serum levels and chromosomal aberrations and endoscopic findings in the 5-year follow-up. Conclusions. We conclude that the considered biological markers are not able to stratify patients, with a high predictive value, in terms of risk of progression to malignant disease.

Abstracts PO019 EVALUATION OF URINARY AND SEXUAL FUNCTION IN MALE PATIENTS AFTER SURGERY FOR RECTAL CANCER F. Attene, F. Fabio, S. Fabrizio, R. Francesca, T. Mario Università Degli Studi di Sassari, Istituto di Patologia chirurgica, Italy Purpose. Sexual and urinary dysfunctions after surgery of the rectum are an important complication to male patients. Total mesorectal excision with autonomic nerve-preserving operation has been performed within the last 4 years to keep urinary and male sexual functions without damage of therapeutic radicality. The aim of this study was to assess the safety of this kind of operation in terms of sexual, urinary and voiding function. Methods. We compare the post-operative period of two groups of patients. The first group, a series of 19 male patients who were undergoing traditional anterior resection for rectal cancer, the second group, 11 male patients who were operated by autonomic nerve-sparing technique. A detailed history of post-operative sexual, urinary and voiding dysfunction, was obtained by interviews. Results. Twelve patients (66.6%) of the first group developed an impotence; only three patients (30%) in the second group (nerve-sparing technique). We observed that there is a direct relationship between sacrifice of the inferior hypogastric plexus and impotence. Twelve patients (66.6%) of the first group developed ejaculatory dysfunction, three in the second group (30%). Ejaculatory dysfunction is related to sacrifice of the superior hypogastric plexus. Four patients of the first group reported urinary incontinence (22%), only one in the nerve-sparing group. At last seven patients of the first group had a persistently elevated frequency of voiding (36.8%), six patients in the second group. Conclusions. Our data show a direct relationship between sacrifice of specific nerve structures and accompanying dysfunction. Pelvic plexus preservation is necessary to maintain erectile potency, and both hypogastric nerve and pelvic plexus preservation are necessary to maintain ejaculate function and orgasm. The preservation of the total autonomic nerve system is essential for normal sexual function in male patients. Nerve preservation does not compromise radicality in mesorectal excision. The nerve-sparing technique gives good results in terms of morbidity and functional outcome, and could be considered like a standard safety surgical procedure for rectal cancer. PO020 IN PRIMARY HYPERPARATHYROIDISM CONSTIPATION IS RELATED TO THE STAGE OF DISEASE D. Badialia , A. Ragnob , M. Celib , C. Letiziab , E. Romagnolib , S. Minisolab , E. D’Erasmob , E. Corazziaria a Cattedra

di Gastroenterologia e di Medicina Interna, Italy di Scienze Cliniche, Università “La Sapienza”, Rome, Italy

b Dipartimento

Chronic constipation (CC) is reported to be a symptom of primary hyperparathyroidism (PHP), but its prevalence in previous studies varies from 16 to 100%. However, they did not use a standardised definition of CC nor reported the severity of PHP. The aim of this study was to evaluate the prevalence CC in PHP and its relationship with the severity of PHP. Fifty-five patients with the diagnosis of PHP [1,2] (females: 50; age: 62±4 years) and 55 comparable controls (females: 50; age 62±7.5 years) referred for screening of osteoporosis were interviewed using a standardised and validated questionnaire concerning bowel habits. Serum level of total (Ca) and ionised calcium (Ca2+ ), phosphorus (P) and parathyroid hormone (PTH) were measured. Constipation was defined, according to Rome II criteria (2). The degree of PHP was defined severe in patients with Ca >11.5 mg/dl (1 mg/dl more than upper normal limit, which is considered the threshold to indicate surgery treatment). Results. Twelve PHP patients and seven controls met the Rome II criteria for CC (n.s.). The constipated PHP patients differed statistically from non-constipated PHP patients and controls for serum levels of Ca (12.3 ±

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1.0 mg/dl versus 10.8±0.6 mg/dl versus 9.6±0.3 mg/dl; P < 0.001), Ca2+ (1.63 ± 0.14 mmol/l versus 1.42 ± 0.08 mmol/l versus 1.23 ± 0.03 mmol/l; P < 0.001), P (2.29 ± 0.41 mg/dl versus 2.74 ± 0.44 mg/dl versus 3.6 ± 0.52 mg/dl; P < 0.02) and PTH (114 ± 67 pg/ml versus 78 ± 38 pg/ml versus 32 ± 10 pg/ml; P < 0.02). Chronic constipation was referred by 8/13 of the patients with Ca >11.5 mg/dl and by 4/38 of the patients with Ca <11.5 mg/dl (P < 0.001). Conclusion. The results of this study suggest that CC can be a symptom of PHP, but it seems more closely associated with serum levels of total calcium greater than 11.5 mg/dl, rather than with the diagnosis of PHP per se. References [1] Bilezikian JP, et al. J Bone Miner Res 2002;17:N2–11. [2] Thompson WG, et al. Gut 1999;45:43.

PO021 PRELIMINARY EXPERIENCE IN D-PEJ PLACEMENT IN CASES OF FAILURE OF PEG INSERTION M. Ballarè, M. Orsello, E. Garello, F. Montino, P. Occhipinti, M. Del Piano U.O.A Gastroenterologia, Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy Background. PEG placement is routinely used for enteral feeding. In some cases, PEG is not feasible or indicated due to technical difficulties, such as gastric herniation, organ interposition, or presence of gastroparesis. In these cases, surgical gastrostomy or jejunostomy are possible alternatives. More recently, direct percutaneous jejunostomy (D-PEJ) has been proposed to avoid surgical intervention. Aim of the study. To evaluate the need, technical feasibility and outcome of D-PEJ in a group of patients consecutively proposed for PEG placement. Methods. In each patient proposed for PEG placement, an upper gastrointestinal endoscopy was performed, and then a pull traction removal gastrostomy tube (18–20 females) was inserted. When PEG was not feasible or contraindicated, a variable stiffness paediatric videocolonscope was used to reach the jejunum, then D-PEJ was performed with the same technique and materials as PEG. In both groups enteral feeding was started 24 h after the Endoscopic procedure, using an enteral feeding pump and the same schedules. Results. In a 6 months period, 45 patients were proposed for PEG placement. In four of them, PEG could not be inserted for technical reasons in three (gastric herniation in one; organ interposition in two) and gastroparesis in one. The time of the endoscopic procedure was slightly longer in D-PEJ (mean 20 min versus 15 min). No complication related to the endoscopy procedure was observed in both D-PEJ and PEG patients. Besides, no nutritional complication was observed in the D-PEJ group. Conclusions. In our preliminary experience, PEG was not feasible or contraindicated in about 10% of patients proposed for. In these patients, D-PEJ was placed, the procedure resulted to be feasible and safe with the use of o paediatric videocolonscope to easily reach the jejunum. The insertion of D-PEJ did not change the nutritional management of enteral feeding. However, long-term effects or complications remain to be evaluated in larger studies. PO022 FIRST CLINICAL EXPERIENCE ON SUPPLEMENTATION OF BIFIDOBACTERIA IN THE ELDERLY M. Ballarè, M. Orsello, E. Garello, F. Montino, P. Occhipinti, M. Del Piano U.O.A Gastroenterologia, Azienda Ospedaliera “Maggiore della Carità”, Novara, Italy

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Abstracts

Background. Recent data support that after the age of 2 years, intestinal microflora remains relatively constant over time except in elderly people, who harbour fewer bifidobacteria and higher population of fungi and enterobacteria than young adults. Diet supplementation with probiotics may improve the nutritional status and reduce the impaired immunity associated with ageing. Goals. To establish the effect of bifidobacteria supplementation to elderly patients on bifidobacteria faecal counts and some clinical parameters. Materials and methods. Since faecal flora and the bifidobacteria number may be influenced by diet, we studied only patients affected by permanent vegetative status (PVS) in total enteral nutrition (TEN) to establish the effect of bifidobacteria supplementation on bifidobacteria faecal counts, diarrhoea, fever episodes, use of antibiotics and nutritional status (BMI). Thirteen consecutive patients (six men and seven women; mean age 69 years, range 65–76 years) were enrolled. Bifidobacteria and clostridia were searched by microbiological and molecular biology methods in stool specimens collected twice at basal time (T−2 and T0 ) and after 12 and 15 days (T12 and T15 , respectively). Seven patients with basal bifidobacteria counts <10−7 were supplemented with Bifidobacterium longum W 11 for 12 days. The remaining six patients were used as controls. For 1 month diarrhoea, fever episodes, use of antibiotics and nutritional status (BMI) were assessed. Results. In the seven patients with bifidobacteria counts <10−7 , the administration of B. longum W 11 resulted in a 1 log increase in 6/7 patients at T12 and in 3/7 patients at T15 . No statistically significant difference in episodes of fever or diarrhoea, use of antibiotics, BMI was observed between the treatment and control group. Conclusions. The administration of B. longum W 11 in PVS patients fed by TEN is effective in increasing the population of bifidobacteria. Larger studies with longer follow-up could demonstrate the influence of these microbiological changes on clinical settings. PO023 FINDINGS AND CLINICAL IMPACT OF VIDEO CAPSULE ENDOSCOPY IN PATIENTS WITH HISTORY OF OBSCURE GASTROINTESTINAL BLEEDING OR CHRONIC ANAEMIA A. Balzano, R. Bennato, S. Picascia, C. de Nucci Unit of Gastroenterology, A.O.R.N “A. Cardarelli”, Naples, Italy Background and aims. Capsule endoscopy is a new tool which is able to explore the small bowel and to detect bleeding or potential bleeding lesions, as reported from previous studies. Our aims were to evaluate endoscopic findings identified by M2A plus capsule endoscopy (Goven Imaging, Yoqneam, Israel) in patients with history of gastrointestinal bleeding and/or chronic anaemia, and to determinate their clinical impact. Materials and methods. Between February 2003 and October 2003, in 21 consecutive patients (male:female 12:21; mean age 49 years, range 18–77 years) with gastrointestinal bleeding from unknown source or with iron deficiency chronic anaemia, capsule endoscopy was performed using the M2A plus capsule system, after an oral purge (PEG solution). All patients previously had a negative gastroduodenoscopy and colonoscopy. After the examination, the course of illness was registered. Results. All patients were able to swallowed the capsule. The visualisation of the small bowel was complete in 100% of examinations. In two cases, the capsule did not reach the caecum. In 7/21 (33%) patients no potentially bleeding lesion was found. In the remainders, the endoscopic findings led to the following diagnosis: vascular malformations (n = 4), small bowel diverticula (n = 3), jejunal ulcers due to NSAIDs intake (n = 2), ulceration in distal duodenum not seen in previous gastroscopies (n = 2), Crohn’s disease (n = 1), Rendu–Osler disease (n = 1), Whipple disease (n = 1). In 8/21 (38%) patients, the diagnosis led to a significant impact in the therapeutical management with positive clinical outcome. Conclusions. Capsule endoscopy provides an important diagnostic contribute in patients with obscure intestinal bleeding or iron deficiency

chronic anaemia. Moreover, in a proportion of patients, it is useful to determinate a positive change in the therapeutical management. PO024 ENDOSCOPIC THERAPY FOR BILE DUCT STONES IN PATIENTS 90 YEARS OF AGE AND OLDER C. Barbera, G. Aprile, P. Naso, G. Bonanno, A. Calzona, G. Trama, A. Russo Cattedra di Gastroenterologia, Università di Catania, Dir. A. Russo Background. Morbidity and mortality following surgical treatment of common bile duct stones (CBDS) increases with age and with the presence of significant comorbidity. Few studies have assessed the safety of ERCP in the very elderly (90 years of age and older). We reviewed our experience of endoscopic treatment of CBDS in an very elderly group of patients. Patients and methods. Endoscopic therapy for choledocholitiasis was performed in 61 consecutive patients (23 men and 58 women; mean age 93.4 years, range 90–97 years) observed in Gastroenterology and Digestive Endoscopy Unit, University of Catania, between 1989 and 2002. Procedures performed, complications and early outcome were evaluated. Results. ERCP followed by ES was performed in 93.4% of patients (57/61), successful common duct clearance was achieved in 82.6% (47/57), endoprostheses were inserted as permanent therapy in the remaining 10 patients (17.5%) with endoscopically irretrievable CBDS. The rate of early complications (1 bleeding, 1 pancreatitis and 1 retroperitoneal perforation) was 6.5% (4/61), one patient (1.6%) died of cardiac failure 24 h after a failed ERCP. After the ES gallbladders with stones (34/61) were not removed, none of these patients had biliary complications. Five out of the 10 patients with biliary stent did not develop biliary complications until their deaths, the five remaining patients developed acute cholangitis requiring a mean of 1.6 stent exchanges. Mean survival time was 10 months (range 8–25 months). Conclusions. Endoscopic therapeutic approach is safe and effective for treatment of CBDS in patients 90 years of age and older. Morbidity and mortality rate are similar to those observed in younger patients. Regarding the insertion of biliary stent in patients with irretrievable CBDS it is a reasonable and cost-effective alternative for patients with short life expectancy. PO025 TRENDS IN PREVALENCE OF COELIAC DISEASE AND DERMATITIS HERPETIFORMIS: WHY DO THEY NOT CORRESPOND ONE WITH THE OTHER? C. Barberaa , P.L. Callvoa , P. Lerroa , M. Baldia , E. Croveria , T. Palmasa , M. Cuozzoa , M.G. Bechisa , S. Bundinob a Dipartimento b Dipartimento

Scienze Pediatriche, Università di Torino, Turin, Italy Dermatologia, Università di Torino, Turin, Italy

Background and aim. The spectrum of coeliac disease (CD) also includes that of dermatitis herpetiformis (DE), which is considered a variant of CD, with the typical skin rash but less severe jejunal lesions. Both share common immunogenetic background. The aim of this study is to compare the trend of prevalence and age at the onset of the two diseases in a paediatric cohort of patients overtime. Materials and methods. In the period 1973–2003, a cohort of 1250 consecutive childhood CD (diagnosed at the University Department of Paediatric Gastroenterology Turin) and 65 children with a biopsy diagnosis of (DE) with the presence of IgA granular deposits in the papillary dermis of the perilesional skin (from the University Department of Paediatric Dermatology of Turin) were studied. The serological indicator of CD and DE were, at different periods of time—circulating antireticulin (ARA), antigliadin (AGA), anti endomisial (EMA) and anti transglutaminase (tTG)

Abstracts IgA antibodies. All the CD patients and most of the DE had jejunal biopsy. Results. In the first two decades (1973–1983) and (1984–1993) an average of 27 cases per year of coeliac disease and an average of 3.5 (range 1–7) per year of DE cases, for a total of 58, were selected. There has been up to 90 new cases diagnosed coeliac patients per year (average 65) over the last decade, for a total of 634, while a total of only seven children have had evidence of DE. The average age at diagnosis of CD was 24 months in 1970s and has risen progressively to 7.5 years in the 2000s. The average age of DE at diagnosis, that of 6.5, has remained unchanged. Conclusions. Our study confirms the rising trend of prevalence, associated with an upward shift in the mean age at diagnosis of childhood CD, with a significant difference in clinical presentation. The most intriguing observation that emerged from this study is the fact that DE prevalence does not move at the same pace as the increasing prevalence of CD. Since CD and DE share the same genetic background this puzzling result may be due to some environmental factors which seem to have a positive influence on the occurrence of DE. The changes in infant feeding practices, such as prolonged breast feeding, and a later introduction of gluten into diet, may have a pivotal role not only in the late, different clinical presentation of CD, but also in the non-occurrence of DE. Skin rash, was the warning light which consented the diagnosis of the whole DE iceberg as early as the 1970s. PO026 PROSPECTIVE STUDY ON THE USE OF TRANSABDOMINAL ULTRASOUND IN THE DIAGNOSIS OF SLIDING GASTRIC HIATAL HERNIA (SGHH) M. Baronea , P. Di Lerniaa , M. Carbonarab , A. Donnoa , D. Rennaa , D. Franciosoa , A. Di Leoa , A. Francavillaa a Section b Section

of Gastroenterology, D.E.T.O., University of Bari, Italy of Occupational Medicine, D.I.M.I.M.P, University of Bari, Italy

Background and aim. SGHH diagnosis is actually performed by radiology, that involves the use of radiations, and/or endoscopy, that is an invasive procedure. The goal of the present study was to confirm the data of the literature, based on a limited number of patients and lacking of an accurate description of endoscopic findings, suggesting the use of ultrasonography for the diagnosis of SGHH. We evaluated the accuracy of ultrasonography using upper gastrointestinal endoscopy as reference test. The last procedure allowed us to evaluate oesophagitis and/or varices, pathological conditions affecting oesophageal wall that could influence per se ultrasonographic evaluation, based on the assessment of oesophageal diameter (ED) at the level of diaphragmatic hiatus. Patients and methods. One hundred and eighty consecutive patients, admitted to our hospital for various complaints, were examined, in supine or left lateral position, in deep inspiration, after fasting, by the same examiner who was not aware of the subject’s symptoms and/or medical history. Twelve patients were not included in the study since they either refused to complete diagnostic examinations (1.1%) or were not valuable by ultrasonography because of obesity, diffuse meteorism and lack of collaboration (5.5%). Oesophageal diameter, was measured positioning electronic callipers in correspondence of the outer limits of oesophageal wall. Statistical analysis was performed using χ2 -test and the Fisher exact probability test. Results. Using as threshold of sensitivity an ED of 18 mm to identify potential patients with SGHH we found total ED ≤18 mm, ED >18 mm; number of patients, 168, 139, 29; number of SGHH by EGDS, 4 and 24. The analysis of these data demonstrated a positive and negative predictive value of 82.7 and 97.1%, respectively. The distribution of oesophagitis and especially of varices, in the two groups (≤18 mm and >18 mm) excluded the possibility that these pathological conditions could influence oesophageal diameter. Discussion and conclusions. Ultrasonography represents a simple, well-tolerated diagnostic approach with an elevated diagnostic accuracy that makes it ideal for the diagnosis of SGHH in elderly patients or

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those who refuse endoscopy. To our opinion, this diagnostic approach could also be useful to identify the subjects with wider SGHH (with high risk of Barrett’s oesophagus) and therefore select these patients for an accurate endoscopic evaluation/follow-up. PO027 QUALITY OF LIFE AND PSYCO-SOCIAL PROBLEMS IN ADULT COELIAC PATIENTS B. Battistaa , P. Saltarellia , G. Frieria , E. Di Giovambattistab , M. Casacchiab , M. Chiaramonte a Gastroenterology,

Hepatology and Nutrition Unit, ASL 04, University Department of Internal Medicine and Public Health, L’Aquila, Italy b Psychiatric Unit, University L’Aquila, Italy Aim. To study the quality of life and the psychosocial problems in adult patients with different diet length. Studied subjects: 52 consecutive patients (16 males and 36 females, mean age 32.75 years (range 17– 46 years), all with CD diagnosis, histology and serology proved. The patients were subdivided into two groups: (A) 40 patients (mean age 33.7 years) with diet treatment for less than 10 years (mean 3.2 years); (B) 12 patients (mean age 29.3 years) with diet treatment for more than 10 years (18 years). Psychological tests: SF-36 (Short form-health survey questionnaire) (Apollone and Mosconi, 1996); DISS (Disability Scale Scheean) (Scheean, 1986); SCL-90 (Hopkins Symptom Check List 90) [Derogatis, 1976]. Results. CD patients had Quality of Life tests (Social Activities) scores lower than normal population, but not statistically different in the two CD groups. CD patients did not show changes in the family, social and working areas (DISS test). Group A had less scores in the Physical Role, Physical Pain and General Health (SF-36 test) with respect to group B and normal subjects. Group B had higher scores in depression area with respect to Group A (SCL-90 test). Conclusions. In our study all CD patients showed an impaired Quality of Life in the Social Activity area, likely due to the diet restrictions, affecting the self social image and relationships. However, these patients seem to successfully cope with the overall working and social life. Group A patients (more recent diagnosis) had more anxiety trait changes while group B (long-term diagnosis, frequently in childhood) showed more depression trait changes. PO028 EVALUATION OF SEROTONIN TRANSPORTER IN PATIENTS WITH IRRITABLE BOWEL SYNDROME BOTH BEFORE AND AFTER TREATMENT WITH ALOSETRON M. Bellinia , C. Stasia , C. Blandizzib , F. Costaa , L. Rappellia , M. Gloria Mumoloa , S. Biagia , G. Giannaccinic , M. del Taccaa , S. Marchia a Section

of Gastroenterology, Department of Internal Medicine; University of Pisa, Italy b Department of Oncology, Division of Pharmacology and Chemotherapy, University of Pisa, Italy c Laboratory of Biochemistry, Department of Psychiatry; University of Pisa, Italy Irritable bowel syndrome (IBS) is a functional digestive disorder thought to involve alterations in intestinal serotonin activity. Cellular serotonin reuptake is mediated by a transporter protein (SERT), and its dysfunctions can interfere with serotonergic transmission. The present study was aimed to examine the binding profile of platelet SERT in healthy volunteers as well as in patients with diarrhoea-predominant IBS (D-IBS) both before and after treatment with the 5-HT3 receptor antagonist alosetron. Twelve female healthy volunteers (24–68 years) and 12 female D-IBS patients (21–73 years) were included in the study. Admitted patients met the Rome II criteria for IBS. Platelet membranes were prepared from whole

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Abstracts

blood samples and used to assay the binding properties of SERT in the presence of [3 H]paroxetine at concentrations ranging from 0.01 to 1 nM. Fluoxetine (10 mM) was used as the unlabelled competitor. Both maximum binding capacity (Bmax ) and dissociation constant (Kd ) were estimated. In D-IBS patients, binding parameters and symptom severity scores were evaluated at baseline and after treatment with alosetron (1 mg twice daily for 8 weeks). At baseline mean Bmax values estimated for binding of [3 H]paroxetine to platelet SERT were lower in D-IBS patients than in healthy volunteers (518.2 ± 155.9 fmol/mg versus 1160 ± 186 fmol/mg; P < 0.001), whereas opposite results were obtained with regard to mean Kd values (0.19 ± 0.05 nM versus 0.06 ± 0.01 nM, P < 0.001). Symptom severity scores in D-IBS patients (50.9 ± 18.8) were negatively correlated with Bmax (r = −0.964; P < 0.001), but not with Kd values (r = −0.164; P = 0.897). At the end of the treatment with alosetron, symptom severity scores decreased significantly (14.4 ± 3.7; P < 0.001 versus baseline value), whereas Bmax (522.3 ± 39.7 fmol/mg) and Kd values (0.17 ± 0.07 nM) did not vary. In conclusion, the present results indicate that SERT expressed on platelets of D-IBS patients is characterised by both low density and binding affinity and suggest a possible correlation between the reduced capacity of serotonin reuptake and the severity of D-IBS symptoms. It is also suggested that the altered binding properties of SERT do not seem to interfere with the therapeutic responses of D-IBS patients to alosetron. PO029 AMANTADINE PLUS PEGIFNalpha2a OR IFNalpha2a IN IFN-UNRESPONSIVE CHRONIC HEPATITIS C AND TRIPLE COMBINATION (WITH RIBAVIRIN ADDITION) IN STILL VIREMIC PATIENTS AFTER 3 MONTHS A. Bellobuonoa , C. Jamolettia , P. Del Poggiob , P. Cantaluppic , G. Covinid , G. Idéoa a Department

of Hepatology, S. Giuseppe Hospital, Milan, Italy of Hepatology, Treviglio c Infectious Diseases, S. Angelo Lodigiano (Lodi) d Humanitas Institute, Rozzano, Milan, Italy b Center

The retreatment of IFN-unresponsive patients with chronic hepatitis C (CHC) is still controversial. Triple combination therapy with IFNalpha tiw, Ribavirin (RBV) and Amantadine (AMA) was found to be very promising in these patients. The aim of this randomised controlled multicentric study was to compare PEGIFNalpha2a (PEGASYS)+ AMA and IFNalpha2a + AMA combination in IFN-unresponsive patients affected by CHC, and to evaluate the efficacy of RBV addition in still viremic patients after 3 months. Patients and treatment. Sixty patients, affected by biopsy-proven CHC, non-responder to a previous course of IFN, were enrolled in six liver centres and randomised to receive PEGASYS 180 ␮g weekly + AMA 200 mg daily (31 patients, group A) or IFNalpha2a 6 MU/every other day + AMA 200 mg daily (29 patients, group B). Still viremic patients after 3 months received RBV (1000 mg daily) addition. Virological response (negative HCVRNA by PCR, with a detection limit of 50 UI/ml) was evaluated after 3 months (EVR), at the end of treatment (ETR) and after 6-month follow-up (SR). Fisher’s test was used for statistical evaluation. Results. The results are preliminary since 46 (76.6%) of patients reached 6-month follow-up after the end of therapy. EVR was 41.9% in group A, 17.2% in group B, respectively. RBV addition induced a sustained virological response in 46.4% of viremic patients in group A, in 12.5% in group B (P < 0.05). Overall ETR and SR were observed in 23/31 patients (74.2%) and in 11/25 patients (44%) of group A, in 12/29 (41.4%) and in 4/21 (19%) patients in group B, respectively. In patients with genotype 1 overall SR was 29.4% in group A, 8.3% in group B (P < 0.05). Conclusions. PEGASYS and AMA combination therapy was significantly more effective than IFN and AMA combination in IFN-non-responders; triple therapy, with RBV addition, significantly increased the response rate in still viremic patients after 3 months of therapy with PEGIFN + AMA.

PO030 DIFFICULT COMMON BILE DUCT STONES: THE USE OF EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AFTER FAILURE OF CONVENTIONAL OPERATIVE ENDOSCOPIC PROCEDURES P. Benedicenti, Y. Hadad, F. Maurichi, R. Cavalera, T. Verrienti Division of General Surgery and Digestive Endoscopy, “Cardinale Giovanni Panico” Hospital, Tricase (Le), Italy Background and study aims. Endoscopic extraction of bile duct stones may be difficult and complicated after sfinterotomy even when we include mechanical lithotripsy in our procedures. Through this method about 80– 90% of all stones can be extracted. Failure is related to the diameter of the stones, those that are bigger than 20 mm, or situated in the intrahepatic biliary tree and also for stones that are located in proximity to a bile duct stenosis. Extracorporeal shock wave lithotripsy (ESWL) is a helpful adjunct in these situations. With this communication we want to confirm the validation of this method and its safety when endoscopic procedures fails even after the use of mechanical lithotripsy. Methods. One hundred and twelve patients, with common bile duct stones, underwent endoscopic extraction with mechanical lithotripsy, 18 of them (about 16%) needed ESWL for extraction. These patients (60% men with mean age of 68 years) underwent ESWL. We used fluoroscopy targeting in 16 patients, in whom we had previously inserted a naso-biliary catheter, in the other two patients we used ultrasound for targeting. A mean of 3500 shock-wave discharges per treatment, in two sessions in 10 patients and in one session in the other 6, were delivered with an electromagnetic shock wave lithotriptor. The treatment sessions, usually, were not performed in the same day as endoscopic procedure. Results. We achieved complete clearance of the common bile duct in 16 out of 18 patients (88.8%). In two patients (12.5%), we had spontaneous passage of the fragments, in the other patients (87.5%) a subsequent endoscopic extraction, using Dormia basket, was needed. The treatment failed in two patients who were referred to surgery. No early or late important adverse events were observed except in one patient who presented a self-limiting haemobilia. Conclusions. The ESWL is indicated after failure of conventional operative endoscopic procedures including mechanical lithotripsy. We consider that it is very important to make a large sfinterotomy and to leave a naso-biliary drainage when endoscopic extraction has failed. ESWL is safe, and effective non-invasive therapeutic option with minimal morbidity and no mortality. Probably it should be used more frequently especially in patients that must undergo high-risk bile duct surgery. PO031 ENDOSCOPIC TREATMENT OF HEPATIC ECHINO- COCCOSIS COMPLICATIONS: RETROSPECTIVE ANALYSIS OF 61 PATIENS S. Bergamini, A. Atzei, F. Vadilonga, R. Murgia, P. Spanu, P. Loriga Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale SS. Trinità, Azienda ASL 8, Calgary, Italy ERCP plays a basic role in diagnosis and therapy of pre- and postoperative biliary complications of liver hydatidosis. Intrabiliary rupture of cyst (5–25%) led to fistula’s formation, passage of daughter cysts and CBD obstruction. After surgery the fistula between biliary tract and residual cavity (3.8–27%) usually persists if non-treated. Over a period of 14 years (1989–2003) 61 patients (M/F = 36/25; mean age 54 years, range 17–86 years) underwent ERCP for liver hydatidosis’ complications. Preoperative indications (27 patients): jaundice (15 patients, with cholangitis in 6); only cholangitis (5 patients); abdominal pain (3 patients); acute pancreatitis (2 patients). Two asymptomatic patients with hilar cyst underwent preoperation ERCP for a suspected cysto-biliary communication. Postoperative indications (34 patients): biliary leakage (21 patients); cholangitis

Abstracts (5 patients); jaundice (5 patients, 1 with cholangitis); abdominal pain (1 patients). Two asymptomatic patients underwent ERCP for a suspected fistula between biliary tract and residual cavity showed at i.o. cholangiography (1) and through T tube (1). Results. Preoperative ERCPs (27): cysto-biliary fistula with CBD obstruction due to echinococcal material (15 cases); compression of intrahepatic ducts (10); papillary stenosis (1); cysto-gastric communication (1). The endoscopic treatment was ES with placement of naso-biliary drain (NBD) in 12 patients; ES (without NBD) in 3 patients; NBD without ES in 2 patients. The cysto-gastric fistula was treated with a naso-cystic drainage. ERCP was exclusively diagnostic in 9 patients. NBD with continuous suction led to complete healing of the cyst in three cases. Postoperative ERCPs (34): persistent biliary leakage output (21 patients, in 5 cases with residual cavity); cysto-biliary fistula with CBD obstruction due to membranes (five cases); compression of intrahepatic bile duct due to recurrent cyst (two cases); secondary sclerosing cholangitis (three cases); p.o. biliary stricture (1). No pathologic findings in two cases. Endoscopic treatment was: ES with NBD in 17 patients; ES only in 5 patients; only NBD in 4 patients. Therapy was not necessary or not possible in 8 patients. Endoscopic treatment was risolutive in all patients, save in two cases; one died for sepsis, the other underwent surgical resection of residual cavity with recurrent infections. Our experience shows the great effectiveness of endoscopy in solving complications of liver hydatidosis, always very hard or impossible for surgery. The great variability of clinical and anatomic situations sometimes needs “atypical strategies”. PO032 APPROPRIATE USE OF COLONOSCOPY AND RISK OF MISSING COLORECTAL NEOPLASIA G. Bersania , R. Angeloa , R. Giorgioa , S. Alessandraa , R. Enricob , C. Claudiob , B. Daniloc , C. Paoloc , A. Vittorioa a Postgraduate

School of Gastroenterology, University of Ferrara and Digestive Endoscopy Service, Malatesta Novello Hospital, Cesena, Italy b Gastroenterology and Digestive Endoscopy Service of Morgagni Hospital, Forl`ı, Italy c Gastroenterology and Digestive Endoscopy Service, S. Salvatore Hospital, Pesa, Italy Background. The evaluation systems for the appropriate use of colonoscopy may be very helpful to increase the quality of the open access services for digestive endoscopy. However, the risk of missing some relevant pathologies, such as colorectal cancer and polyps, may occur. The aim of this study was to evaluate if the application of the ASGE criteria could avoid such risk. Methods. Four thousand three hundred and twenty-two colonoscopies (age 14–99 years, 57% females) have been performed in three open-access Endoscopy Services in a county of North-eastern Italy, from January to October 2003. Whenever each patient underwent colonoscopy he was assigned to one class of appropriateness according to ASGE criteria (edition 2000). The overall evaluation of appropriateness was calculated for all the colonoscopies. The percentage of cases with colorectal neoplasms without an indication related to ASGE criteria was recorded. We have analysed those non-ASGE indications, where the colonoscopy demonstrated the presence of neoplasms. Results. In 4322 colonoscopies, we have evidenced 166 colorectal cancer and 777 cases of colorectal polyps. In 122 cases of the neoplasms (74%), the colonoscopies were performed with indications included in ASGE appropriateness criteria. In 43 cases (26%), the indications for colonoscopy like alteration of bowel habit (15), abdominal pain (11), search for neoplasia in case of metastasis of unknown origin (5), bowel occlusion (4), other (8) were not included. In 503 cases of the polyps (65%), the colonoscopies were performed with indications included in ASGE appropriateness criteria. In 274 cases (36%), the indications for colonoscopy were not included.

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Conclusions. According to previous studies [Rossi et al., Gastrointest. Endosc. (2002)], the use of ASGE criteria for digestive endoscopy appropriateness allowed us to find a high percentage of neoplasms in the digestive tract. However, an important percentage of colorectal cancers (26%) and polyps (36%) were evidenced in cases without ASGE indications. PO033 LONG-TERM RESULTS OF SURGERY RECURRENCE IN CROHN’S DISEASE: RESECTION VERSUS STRICTUREPLASTY A. Bertania , A. Scarcellia , A. Merighia , A. Antoniolia , V. Boarinoa , P. Busseib , G.P. Rigoa , E. Villaa a Gastroenterologia,

Università degli Studi di Modena e Reggio Emilia Az. Osp. Policlinico, Modena, Italy b Istituto Nazionale di Fisica della Materia, Parma, Italy

Background and aim. Crohn’s disease (CD) is determined by a recurrent nature particularly after surgery. We investigated the surgical recurrence in relation with the technique (strictureplasty (SPLX), resection, SPLX + resection) and the predictive factors of recurrence. Materials and methods. One hundred and sixty-seven patients with CD were admitted our institution between January 1971 and August 2003. Seventy-three no-surgery-patients (median age 33.3 years, male/female 37/36), 94 surgery-patients (37.3 years, 52/42). Two groups were recorded for familiarity of IBD, smoke, extra-intestinal manifestations, therapy, general state. For surgery-patients we studied the number of surgery procedures, CD start (acute or classic), diagnosis site, surgery procedure used in each treatment and indication of surgery (fistulas, strictures). Type of surgery and free-time reoperation were also considered. The recurrence and the predictive factors were studied by Kaplan–Meier curves and by Cox regression. Results. Extra-intestinal manifestations are 32% in surgery-patients, particularly in patients with more than a surgery treatment and 24.6% in no-surgery-patients. This is the sole difference between the two groups. Thirty-six percent of surgery-patients has an ileum localisation at the diagnosis: a predictive factor of recurrence. The percentage of SPLX, resection, SPLX + resection is 22.3, 28.5, 30.7%, and the free-times reoperation are, respectively, 8.1, 6.0, 7.2 years. Kaplan–Meier curves do not evidence any recurrent difference. Conclusions. The ileum site at the diagnosis is a predictive factor of surgical recurrence, while anastomosis is the most frequent one. Recurrence is not related to the surgery, but to a more aggressive pattern of CD. Patients with more recurrence are indeed characterised by extra-intestinal manifestations. Age at the time of diagnosis, sex, therapy, general state are not predictive factors of recurrence. PO034 COELIAC DISEASE IN THE ITALIAN POPULATION L. Bertolusso, N. Sapone, B. Demarchi, F. Bresso, M. Astegiano, V. Ponti, A. Morgando, M. Bruno, R. Bonardi, S. Rossetti, M. Rizzetto U.O.A.D.U. Gastroepatologia Ospedale Molinette di Torino, Italy Background. Coeliac disease (CD) is a gluten sensitive disorder characterised by a complex clinical picture that varies from severe malabsorption to only minor symptoms. Many individuals suffer from the so called silent form of the disease characterised by vague subjective symptoms. Recent studies suggest that the true prevalence is 1:150. Autoimmune extraintestinal disorders have been reported during the course of CD and are thought to be related to the duration of the intestinal gluten exposure. The development of malignancy, particularly lymphoma, is the most serious complication to affect patients with CD. An increase in gastrointestinal carcinoma and other tumours was also found to occur. The aim of this study is to describe the extremely variable clinical presentation of CD, the association with other disorders and the development of lymphoma and carcinoma.

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Abstracts

Methods. We retrospectively examined clinical data of our patients with CD. All patients had a diagnosis of CD with serological tests and duodenal biopsies with a positive clinical and histological response to a gluten free diet. Results. The clinical data of 249 adults patients with CD were reviewed. Female (175) to male (74) ratio is 2.3:1. Mean age at diagnosis was 37.4 years and mean follow-up after the diagnosis was 4.2 ± 5.8 years. Sideropenic anaemia was found in 23% of the patients, hypertransaminasaemia in 16%, thyroid disease in 6%, dermatitis herpetiformis in 5%, osteoporosis in 5%, neurological and psychiatric disorders (epilepsy, multiple sclerosis, peripheral neuropathy, headache, depression, schizophrenia) in 11%, aphthous stomatitis in 3%, ulcerative colitis in 1% and 2% had other autoimmune diseases (IDDM, rheumatoid arthritis, LES). Delayed menarche, premature menopause, amenorrhoea, recurrent miscarriages were present in 6% of female population. The most frequent associations of symptoms were anaemia/hypertransaminasaemia (6%) and anaemia/osteoporosis (3%). Eight tumours were diagnosed (1.5%): three lymphomas (two diagnosed at the same time of CD—age 53 years), one gastrointestinal carcinoma, two carcinoma of the thyroid and two breast carcinoma. Conclusions. In our study, female to male ratio is according to literature. Subclinical (atypical and minor) CD is the prevalent behaviour in the adult population and is characterised by the absence of symptoms of frank malabsorption and are present minor, transient intestinal or extraintestinal symptoms. Prevalence of lymphomas is 0.6%. PO035 EPIDEMIOLOGY OF IBD: A NATIONAL SURVEY L. Bertolusso, F. Bagagli, C. Nebia Colombo, N. Sapone, S. Rossetti, B. Demarchi, V. Ponti, R. Bonardi, R. Pellicano, M. Astegiano, M. Rizzetto

Table 2 Drug

CD

UC

Total

Number Percentage Number Percentage Number Percentage 5-ASA 359 Steroids 215 Azathioprine 42 Cyclosporine 8

87.3 52.3 10.2 2

894 439 47 9

92.3 45.3 4.9 0.9

1253 654 89 17

90.7 47.4 6.4 1.2

Table 3 Tumour

ICD-9 codes

Number

Percentage

Gastrointestinal tract and peritoneum Respiratory tract and intrathoracic organs Bone, connective tissue, skin, mammary gland and uterus Genitourinary tract Other locations Lymphatic and haematopoietic tissue

150–159

11

0.8

160–169

4

0.3

170–179

23

1.7

180–189 190–199 200–209

20 6 11

1.4 0.4 0.8

Conclusion. The estimated prevalence of IBD in the Italian population is 255/105 . The CD/UC ratio is 1:2.4. Osteoporosis is the most frequent extraintestinal complication followed by cholelithiasis in both IBD; spondylitis is significantly more frequent amongst CD patients. 5-ASA and steroids are the two main drugs used. Five percent of IBD patients developed malignancies, with a higher frequency in ulcerative colitis.

U.O.A.D.U. Gastroepatologia Ospedale Molinette di Torino, Italy PO036 Background. Despite their importance, epidemiological studies on inflammatory bowel disease (IBD) in Italy are very few in literature. The aim of this study is to describe the demography of IBD patients (Crohn’s Disease, CD and Ulcerative Colitis, UC) in a population of individuals afferent to General Practitioners (GP) in Italy. Methods. The disease-related database adopted is the National Health Search database that registers more than 570 GP with a total population of more than 800,000 individuals. Three hundred and twenty GP (142 from the north of Italy, 60 from the centre and 118 from the south) with a population of 491,950 individuals participated in the study and were asked to provide the following data about their patients: number of patients affected by CD or UC and relate demography; prevalence of extraintestinal complications and malignancies and pharmacological treatment in the population of IBD patients. Results. One thousand three hundred and eighty IBD cases (747 M, 54.1%) were found (prevalence: 255/105 individuals): 411 (29.8%) CD patients (mean age 47.8 years) and 969 (70.2%) UC patients (mean age 51 years) (CD/UC ratio 1:2.4). Extraintestinal complications and pharmacological treatment are summarised in Tables 1 and 2. Fifteen CD patients (3.6%) and 55 UC patients (5.7%) developed malignancies. Table 3 shows distribution of tumours according to ICD-9 codes in IBD patients.

Table 1 Complication CD

UC

Total

Number Percentage Number Percentage Number Percentage Spondylitis Poliarthritis Cholelithiasis Cholangitis Osteoporosis

14 11 20 1 43

3.4 2.7 4.8 0.2 10.4

5 19 36 1 68

0.5 2 3.7 0.1 7

19 30 56 2 11

1.4 2.2 4.1 0.1 8

COELIAC DISEASE: A NATION WIDE SURVEY L. Bertolusso, E. Ubaldi, F. Samani, N. Sapone, B. Demarchi, R. Bonardi, M. Bruno, S. Rossetti, F. Bresso, M. Astegiano, M. Rizzetto U.O.A.D.U. Gastroepatologia Ospedale Molinette di Torino, Italy Background. Coeliac disease (CD) is a gluten sensitive disorder characterised by a complex clinical picture that varies from severe malabsorption to only minor symptoms. Many individuals suffer from the so called silent form of disease characterised by vague subjective symptoms. Such individuals would not contact a physician spontaneously but they can be detected by screening high-risk individuals, including family members and patients with other autoimmune diseases. Population based screening studies indicate that the prevalence of CD may exceed 0.5% in many populations and, in particular, the silent form can be surprisingly frequent. The aim of this study is to describe the demography of CD in a population of individuals afferent to General Practitioners (GP) in Italy. Methods. The disease-related database adopted is the National Health Search database that registers more than 570 GP with a total population of more than 800,000 individuals. Three hundred and twenty GP (142 from the north of Italy, 60 from the centre and 118 from the south) with a population of 491,950 individuals participated in the study and were asked to provide the following data about their patients: number of patients affected by CD and relate demography; prevalence of associated disorders. Results. In our database, 558 cases of CD were recorded. The prevalence of disease is 0.11% (558/491,950). The mean age at diagnosis was 19.4 years and the female to male ratio was 2.2:1. Several diseases have been found to be associated to CD: diabetes mellitus in 12 patients (2.1%), thyroid disease in 6 patients (1.1%), and LES in 2 patients (0.3%). Fifteen malignancies (2.6%) occurred: five

Abstracts lymphomas (0.9%), three gastrointestinal carcinoma (0.5%) and seven breast carcinoma (1.2%). Conclusions. CD prevalence in the Italian population is 0.11% but probably is underestimated. In fact, recent studies suggest that the true prevalence is 1:150. Female to male ratio is according to literature data (2.2:1). Several diseases are associated to coeliac disease and in our study in the Italian population, the most frequent associated diseases are diabetes mellitus and thyroid disease. Prevalence of lymphoma is 0.9%. PO037 THE PREVALENCE OF COELIAC DISEASE IN PATIENTS WITH ADDISON’S DISEASE F. Biagia , J. Campanellaa , A. Sorianib , A. Vailatib , G.R. Corazzaa a Gastroenterology

Unit, IRCCS Policlinico San Matteo, University of Pavia, Italy b Endocrinology Unit, IRCCS Policlinico San Matteo, University of Pavia, Italy

Background. Coeliac disease (CD) is well known to be associated with autoimmune endocrine diseases, such as autoimmune thyroid disease and insulin-dependent diabetes mellitus. Recently, it has been shown to be present in ∼10% of patients with autoimmune Addison’s disease (AD), the most common cause of primary adrenocortical insufficiency [1,2]. AD is a major components of autoimmune polyendocrine syndromes (APS) and shares several clinical features with CD. Although hyperpigmentation is the most specific sign, weakness, weight loss, anorexia, nausea, vomiting, hypotension, abdominal pain, and diarrhoea are very frequent and very often are the first complaints of the patients. On the other hand, its treatment, i.e. chronic steroid administration, can mask CD. Aims. We studied the prevalence of CD in Italian AD patients. Methods. Thirteen AD patients (11 females, mean age 52.8 years ± 16.6) were studied. Eight of them were affected by APS2 (i.e. Addison’s disease associated with autoimmune thyroid disease and/or insulin-dependent diabetes mellitus) and five by isolated Addison’s disease. Diagnosis had been performed at the age of 40.4 ± 9.8 years. Steroid treatment had already been started in 12 of them. Endomysial antibodies (EMA) were tested in all of them and a duodenal biopsy was taken in those found to be EMA positive. Results. One out of 13 patients was found to be EMA positive. Duodenal biopsy allowed the diagnosis of CD by showing subtotal villous atrophy. Conclusions. Although we studied a small sample, our preliminary results confirmed that AD is associated to CD, being present in 7.7% of AD patients. Since symptoms can be very similar and treatment of AD can mask CD, this association should always be actively investigated in both CD and AD patients. References [1] O’Leary C, et al. Q J Med 2002;95:79–82. [2] Myhre AG, et al. Scand J Gastroenterol 2003;38:511–5.

PO038 THE MTHFR POLYMORPHISM IN PATIENTS AFFECTED BY PRIMARY BILIARY CIRRHOSIS M.R. Biaginia , M.C. Beninia , N. Lazzerinia , S. Milania , E. Cenia , A. Tozzia , R. Mantaa , R. Abbateb , S. Fedib , A. Casinia , A. Gallia , C. Surrentia a Gastroenterology b Thrombosis

Unit, University of Florence, Florence, Italy Center, University of Florence, Florence, Italy

Background and aim. The factors that modulate the progression of Primary Biliary Cirrhosis (PBC) are still unknown. It has been shown that Homocysteine (Hcy) may modulate liver damage and fibrosis. Methylene-tetrahydro- folate-reductase (MTHFR) is a key enzyme in methionine metabolism and it may influence intrahepatic levels of Hcy.

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Since TT677 genotype of MTHFR is associated with a lower activity of the enzyme, the aim of this study was to verify the prevalence of MTHFR polymorphisms in patients with PBC. Materials and methods. We analysed MTHFR polymorphism by genomic DNA PCR amplification and fasting/post-Methionine Hcy plasma levels in 51 patients (8 males and 43 females, mean age 63 years, range 20–76 years, follow-up mean time 10 years, range 1–26 years) with PBC and 51 healthy volunteers matched for sex and age as controls. Polymorphism distribution was correlated with histological staging and biochemical parameters of liver disease. Results. Allele frequency of CT677 polymorphism was 0.52 in PBC patients and 0.45 in controls. Genotypes distribution (TT = 31.4%, CT = 41.2, CC = 27.4% in patients versus TT 17.5%, CT 55.3%, CC 27.2% in controls) was in Hardy–Weinberg equilibrium (χ2 = 0.08 versus 0.04). The prevalence of homozygous TT677 genotype was significantly higher in PBC patients versus controls (31.4% versus 17.5%; P < 0.05). Hyper Hcy (fasting and/or post-methionine HCY above the 95th percentile of controls was diagnosed in 23/51 patients = 45.1%). Homozygous TT677 genotype-positive patients had higher, but not statistically significant, Hcy plasma levels versus those with CT677 and CC677 genotypes (P = NS). In our population TT genotype was associated with the presence of a higher histological stage (P < 0.003) and higher ALT levels (P < 0.022). Conclusions. The high prevalence of TT677 genotype in patients with PBC might contribute to a worsening of the liver disease by increasing Hcy levels. PO039 FOLIC ACID DEFICIENCY IN PRIMARY BILIARY CIRRHOSIS M.R. Biagini, A.Tozzi, M.C. Benini, N. Lazzerini, M. Capanni, S. Nanni, R. Manta, A. Galli, S. Milani, C. Surrenti, A. Casini Gastroenterology Unit and Nutrition Center, Department of Clinical Pathophysiology, University of Florence, Florence, Italy Background and aim. We previously demonstrated that patients with Primary Biliary Cirrhosis (PBC) display serum levels of homocysteine higher than healthy controls. Since hyperhomocysteinaemia is generally associated with low serum levels of folate, the aim of this study was to evaluate the prevalence of folic acid deficiency in PBC patients and its possible pathogenetic mechanisms. Materials and methods. Erythrocyte and plasma levels of folic acid, serum Vitamin B12 and B6 were investigated in 57 patients (7 males and 50 females, mean age 58.8 years, range 20–77 years) with PBC. All patients were asked to fill in a questionnaire on their alimentary intake during the 12 months preceding blood sampling, in order to evaluate their daily intake of folic acid. In addition, a daily oral supplement of foline (5 mg) was administered for 3 months in 10 patients with folate deficiency (folic acid <6.4 ng/ml). Results. Folate deficiency was found in 40/57 (70.2%) patients. The daily intake of folic acid was normal in all patients. In 10 patients with folate deficiency, daily supplementation with 5 mg of folate for 3 months increased folic acid plasma levels from 4.5 ± 2.3 to 15.6 ± 4.6 ng/ml. Conclusions. Reduced blood levels of folic acid are present in a large number of PBC patients, and are not consistently associated with an absolute deficiency of dietary intake. Intestinal absorption of folic acid is not impaired in these patients. Other mechanisms are likely to be responsible for folate deficiency in PBC.

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Abstracts

PO040 SEROPREVALENCE OF ANTI-CHLAMYDIA PNEUMONIAE ANTIBODIES IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS: A BACTERIAL ROLE IN THE PATHOGENESIS OF THE DISEASE? M.R. Biagini, B. Orsini, M. Capanni, A. Tozzi, M.C. Benini, R. Manta, N. Lazzerini, A. Galli, S. Milani, C. Surrenti Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy Background. The role of environmental agents in the pathogenesis of Primary Biliary Cirrhosis (PBC) is still debated. Several studies suggest that molecular mimicry between pathogens and self antigens results in tolerance break-down and in the development of T and B cell autoreactivity. In a previous study, immunohistochemistry investigation on liver explant specimens detected expression of Chlamydia pneumoniae (Cp) antigens in a whole group (25/25) of PBC. On the contrary, those antigens were present only in 8% of 15 livers explanted for other chronic liver diseases. Recently, we found Cp DNA genomes by PCR in 2/2 cases of PBC undergone liver biopsy. Aim. To analyse the seroprevalence of anti-Cp antibodies (Cp Ab) as a sign of either active or previous Cp infection in patients with PBC, in comparison with patients affected by chronic hepatitis C (CHC). Materials and methods. We prospectively enrolled 54 patients with PBC (6 males, 48 females; mean age 59 years; range 24–77 years), and 54 patients with CHC (51 patients with chronic active hepatitis and 3 cirrhosis) as pathologic controls (3 males, 51 females; mean age 56 years; range 27–78 years). Cp Ab were assessed on sera either freshly collected or stored at −20 ◦ C for not more than 1 month. IgG and IgM Cp Ab were measured by microimmunofluorence assay (MIF, Thermo Labsystems, Helsinki, Finland): titres >1:16 for IgM and >1:32 for IgG were considered positive. IgA Cp Ab were measured by enzyme-linked immunosorbent assay (ELISA, Savyon Diagnostic, Ashdod, Israel): titres >1:105 were considered positive. Data were analysed by chi-square test. Results. Cp Ab positivity was found in 39/54 (72%) patients with PBC versus 36/54 (67%) patients with CHC (P = NS). In PBC, IgG Cp Ab were found in 33/54 (61%) patients, IgM in 8/54 (15%) patients, and IgA in 31/54 (57%) patients. In CHC, IgG Cp Ab were positive in 35/54 (65%) patients, IgM in 6/54 (11%) patients, and IgA in 24/54 (44%) patients. Biopsy was available in 48 patients with PBC: 19/36 (53%) patients at stages I–II versus 9/12 (75%) patients at stages III–IV were positive for Cp Ab (P = NS). Conclusions. Cp Ab are present in most patients with PBC, in accordance with a possible pathogenic role of the infection. However, the prevalence of antibodies is not significantly different from that found in CHC. More studies are required to verify if persistent intrahepatic infection is present in PBC, even in the cases with negative serology, and if it may elicit a local immune reaction. PO041 EFFICACY OF PROTON PUMP INHIBITORS IN THE MANAGEMENT OF NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING: A META-ANALYSIS M. Bianchi, A. Moretti, C. Papi, A. Dezi, M. Koch, L. Capurso U.O.C. di Gastroenterologia A.C.O. San Filippo Neri, Rome, Italy Background and aim. Non-variceal upper gastrointestinal bleeding (NVUGIB) is an emergency condition still associated with high rates of mortality, morbidity and health care costs, despite progresses brought by appropriate endoscopic therapy. The aim of our study was to assess the efficacy of Proton Pumps Inhibitors (PPI), combined with endoscopic therapy, in the management of NVUGIB: a meta-analysis of randomised controlled trials (RCTs).

Materials and method. Pertinent studies were selected from the Medline Database, references from published studies and reviews. Prospective RCTs published as full papers comparing PPI versus placebo after appropriate endoscopic therapy were considered suitable for meta-analysis. Seven RCTs including 1885 patients were identified. In three RCTs, PPI were administered orally and in four, intravenously. Two independent observers on the basis of intention-to-treat principle extracted data. Conventional meta-analysis according to Der Simonian and Laird method was used for the pooling of the results. The Absolute Risk Reduction (ARR) and the Number Needed to Treat (NNT) for three main outcomes (re-bleeding or continuous bleeding, need for surgery and mortality) were used as a measure of the therapeutic effect. Results. Compared to placebo, PPI treatment had an ARR (95% CI) of 9.3% (−14.2 to −5.9%) (P < 0.001) for preventing re-bleeding or continuous bleeding by 72–120 h. The NNT was 10. No heterogeneity was found. For surgery and mortality by day 30 ARR (95% CI) was 3.7% (−7.2 to −0.3%; P = 0.03; NNT = 25) and 0.4% (−6.1 to 5.2; P = 0.8), respectively. No different efficacy was observed for oral or intravenous PPI administration for preventing re-bleeding: ARR = 19.6% (−26 to −13%; P < 0.0001; NNT = 5) and 8.7% (−13.4 to −3.9%; P < 0.0003; NNT = 11), respectively. No efficacy of oral PPI administration was observed for reducing surgery and mortality. Intravenous PPI administration significantly reduced surgery, ARR = 6.7% (−11–8 to −1.6%; P = 0.009; NNT = 15) but not mortality. Conclusions. In NVUGIB PPI treatment, after appropriate endoscopic treatment, reduces re-bleeding and need for surgical intervention but has no effect on mortality. Oral PPI administration is as effective as intravenous administration for preventing re-bleeding or continuous bleeding. PO042 “INVASIVE PATTERN” DISCLOSED WITH MAGNIFYING CHROMO-ENDOSCOPY IS AN INDICATION FOR SURGICAL TREATMENT OF SESSILE COLORECTAL POLYPOID AND NON-POLYPOID LESIONS M.A. Biancoa , G. Rotondanoa , M.L. Garofanoa , R. Marmoa , R. Piscopoa , L. Baronb , L. Cipollettaa a UO

Gastroenterologia, ASL NA5, Ospedale Maresca, Torre Del Greco (NA), Italy b UO Anatomia Patologica, ASL NA5, Ospedale San Eonardo, Castellammare di Stabia (NA), Italy Background. By using magnifying colonoscopy it is possible to diagnose a typical pit pattern called “invasive pattern” (type V) which consists of irregular, distorted colonic gland crypts in a demarcated area. Such pattern is strongly associated with submucosal invasive cancer. Aims. To evaluate the effectiveness of magnifying chromo-endoscopy in differentiating the “invasive pattern” from the rest (“non-invasive patterns”) and assess the correlation with histopathological findings. Methods. A total of 53 sessile or flat colorectal lesions were evaluated in our hospital from December 2002 to October 2003 using chromoendoscopy with 0.4% indigo carmine and magnifying colonoscopy (Olympus CF-Q160Z). Pit pattern was classified as “invasive pattern” or “non-invasive pattern” during colonoscopy procedures. All lesions, endoscopically or surgically resected, were histologically evaluated and compared with the pit pattern diagnosis performed previously. Results. Of the 19 lesions endoscopically diagnosed as having an “invasive pattern”, 94.7% were submucosal invasive cancers (sm slight: 8.7%, sm deep: 86.0%), while in the remaining 87 lesions, endoscopically diagnosed as having a “non-invasive pattern,” 97.7% were intramucosal lesions (adenoma: 84.0%, m cancer: 13.7%). Conclusions. Among the lesions which were endoscopically diagnosed as having an “invasive pattern” a high percentage was invasive cancer, especially sm deep invasive cancer, where surgical resection is undoubtedly the adequate treatment. On the other hand, the lesions, which were

Abstracts endoscopically diagnosed as having a “non-invasive pattern” were mostly intramucosal lesions, where endoscopic resection is feasible. PO043 INFLAMMATORY CHANGES OF THE ILEUM AFTER ILEO-RECTAL ANASTOMOSIS FOR ULCERATIVE COLITIS: A RELATIONSHIP WITH COLONIC METAPLASIA L. Biancone, G.P. Palmieri, R.M. Bozzi, A. Colantoni, M. Cretella, L.G. Spagnoli, F. Pallone Cattedra di Gastroenterologia, Dipartimento di Medicina Interna e Cattedra di Anatomia Patologica, Università di Roma “Tor Vergata”, Rome, Italy Background. Inflammatory changes of the ileum in ulcerative colitis (UC) have been described in the ileal pouch (“pouchitis”) and in backwash ileitis. Pouchitis has recently been associated to morphologic changes of the ileum including flattening, reduced number of disappearance of the villi (“colonic metaplasia”). Aims. To assess whether inflammatory changes are observed in the pre-anastomotic (PA) ileum of UC patients with ileo-rectal anastomosis (IRA). We also investigated whether the development of these lesions in UC are related to morphological changes of the PA-ileum towards colon (“colonic metaplasia”). Methods. Study population: 10 patients with IRA (seven UC; two Crohn’s disease, CD; one familial polyposis, FAP) and four patients with ileal pouch for UC were enrolled. Endoscopy: endoscopic assessment was performed in all patients, with biopsies taken from the pouch or from the pre-anastomotic (PA) ileum and from the rectum in patients with IRA. Histology: biopsies were stained by H&E for routine histology and morphological changes of the ileum assessed according to the Pouchitis Disease Activity Index (PDAI). Possible relations between colonic metaplasia and inflammatory changes in the pre-anastomotic ileum or in the pouch were searched. Results. IRA group: in UC, endoscopic lesions of the PA-ileum with deep ulcers were observed in 5/7 patients (one anastomotic stricture). Histological analysis of the pre-anastomotic ileum was performed in 6/7 UC patients (due to anastomotic stricture in one), showing endoscopic ulcers in 4/6. In all these four patients, histology showed colonic metaplasia of the ileum, while in both patients with no ileal lesions (2/6) histology showed no colonic metaplasia. Ileal lesions in UC were associated to morphological changes of the ileum towards colonic epithelium (flattening, reduced number, disappearance of the villi). In CD, ileal lesions were observed in 2/2 patients (both Rutgeerts score 2), being not associated to colonic metaplasia. Pouch group: pouchitis was detected in 2/4 UC, both showing colonic metaplasia. Conclusions. In UC, ileal lesions may be observed not only in pouchitis but also in the PA ileum of patients with IRA. The development of these lesions appears associated to morphological changes of the ileum towards colonic epithelium (“colonic metaplasia”). These preliminary observations suggest that in UC patients, changes of the ileal content after colectomy contribute to the development of ileal lesions not only in the ileal pouch but also in the PA-ileum after IRA. PO044 INTERLEUKINS OF GASTRIC MUCOSA IN YOUNG AND OLD DYSPEPTIC HP POSITIVE AND NEGATIVE PATIENTS L. Biertia , G. Ferrarioa , N. Caronnia , C. Vergania , C. Calabresia , S. Scuratia , L. Fazzinib , R. de Franchisb a Operating b Internal

Unity of Geriatrics, Gastroenterology Service, Italy Medicine Department, Policlinic of Milan I.R.C.C.S., Italy

Background. Helicobacter pylori (Hp) is a major aetiopathological factor of peptic disease. Studies prove that the damage to the mucosa is medi-

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ated by the host’s immunological system versus Hp. The immunological response is regulated by a pattern of interleukins such as INF␥, IL12 and IL10. Aim. To evaluate if the major prevalence of peptic disease and the different symptoms observed in elderly respected young patients is related to a change of gastric interleukin’s pattern in response to Hp infection. Patients and methods. Sixty-two dyspeptic patients divided into two groups A (<65 years: 27 patients; mean age: 52.6 years, S.D. 9.2 years) and B (>65 years: 35 patients; mean age: 75.6 years, S.D. 7.3 years), undergoing upper GI endoscopy with multiple biopsies for histological examination and interleukin’s assay. Hp status and gastrites were determined by Sidney System score. The levels of interleukins (INF␥, IL10, IL12) were evaluated in supernatants by enzyme linked immunosorbant assay (ELISA). Statistical analysis was performed by non-parametric test of Mann–Whitney. Results. In group A, 9 out of the 27 patients and in group B 10 out of the 25 patients were Hp positive. In Hp negative patients the INF␥ value was not different into the two groups (A = 82.04, S.D. 53.68 pg/ml; B = 76.27, S.D. 58.25 pg/ml), while in Hp positive subjects INF␥ levels were higher in group B (>65 years) but not statistically significant (A = 39.36, S.D. 34.79 pg/ml; B = 58.36, S.D. 34.84 pg/ml). IL10 and IL12 concentrations were not statistically different in the two groups of age, both in Hp positive (IL10: A = 2.81, S.D. 1.57 pg/ml, B = 2.97, S.D. 0.69 pg/ml. IL12: A = 43.41, S.D. 26.84 pg/ml, B = 45.41, S.D. 17.55 pg/ml) and both Hp negative patients (IL10: A = 2.90, S.D. 0.91 pg/ml, B = 2.6, S.D. 1.02 pg/ml. IL12: A = 36.40, S.D. 31.99 pg/ml, B = 30.28, S.D. 12.09 pg/ml). Conclusions. Our data do not support any differences between young and old dyspeptic patients in the gastric production of interleukins in response to the H. pylori infection. PO045 CORRELATION BETWEEN ANTI-ENDOMISIUM IgA ANTIBODIES AND VILLOUS ATROPHY IN COELIAC DISEASE PATIENTS C. Bilardia , A. Parodia , P. Dulbeccoa , E. Iiritanoa , S. Reglionia , P. Zentilina , L. Accorneroa , C. Mansia , L. Mastraccib , V. Savarinoa a Dipartimento

di Medicina Interna, Università di Genova, Italy di Discipline Chirurgiche, Morfologiche e Metodologiche Integrate, Università di Genova, Italy b Dipartimento

Introduction. Circulating autoantibodies are used as non-invasive markers for detection of coeliac disease (CD). However, false-negative results are more frequent than expected in several recent studies. Aim. The aim of our study was to assess the relationship between anti-endomisium antibodies IgA (EMA) and the grade of mucosal damage according to Oberhuber classification in order to verify whether EMA-negative patients have different histological patterns from EMA-positive ones. Methods. During the period from June 2002 to June 2003, 49 consecutive patients (M/F = 16/33; mean age = 35 years) with clinically suspected coeliac disease (abdominal pain, anaemia, diarrhoea, weight loss) were enrolled in this study. All patients underwent EGDS, EMA IgA and total serum IgA assay. In three patients, the diagnosis of CD was excluded because of normal histological findings and in the remaining 46 cases it was based on altered duodenal histology and was confirmed by the improvement of clinical symptoms after gluten-free diet. Statistical analysis was done by means of Fischer’s exact test. Results. The results are shown in the as follows: EMA Number of patients Infiltrative Hyperplastic Type I Type II Type III pattern pattern Atrophy Atrophy Atrophy positive 33 patients 3–13, 11, 6 negative 13 patients 13 . . . Almost all EMA-positive patients had an atrophic histological pattern, while all EMA-negative patients had only infiltrative histological pattern (P < 0.001). Conclusions. The negativity of EMA IgA antibodies in histologically positive patients with normal total IgA assay may be due to the low

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sensitivity of this serological test in patients with initial infiltrative instead of more severe atrophic patterns. PO046 PAEDIATRIC OPERATIVE ENDOSCOPY: INDICATIONS AND USE OF ADULT INSTRUMENTS AND DEVICES P. Billi, F. Rossi, G. Sciarretta, V. Cennamo, C. Fabbri, A. Grilli, C. Mwangemi, L. De Luca, L. Frisari, A. Pasquini, C. Fidone, N. D’Imperio U.O. di Chirurgia Pediatrica, Pediatria e Gastroenterologia ed Endoscopia Digestiva, P.O. Bellaria-Maggiore, Bologna, Italy

Conclusions. We think our data could demonstrate the safety of this type of surgical treatment that allows performance of aggressive liver resection (in 9/14 cases it was possible to perform a right hepatectomy) because the liver has not been treated by chemotherapy. This procedure avoids the cumulative risk due to reintervention that is necessary in the case of hepatic resection performed after resection of the primary tumour and adjuvant chemotherapy, too. Percutaneous radiofrequency ablation should be reserved only in the cases of inoperable liver metastases and not in patients awaiting for surgery. PO048 IS THERE A RISK OF RUPTURE IN LIVER ADENOMATOSIS?

Paediatric patients may suffer from diseases and complications usually managed endoscopically in adults. This may be difficult to achieve in the paediatric patient due to limited experience in paediatric endoscopy, differences in age and weight related protocols and scant availability of paediatric instruments and devices. We report our preliminary experience using adult endoscopes and devices, and adapting our endoscopic experience in the adult to paediatric patients with indications for endoscopy. All patients were treated in an operating theatre under general anaesthesia. Four patients were referred for oesophago-gastric varices due to portal vein thrombosis (three males, one female, mean age 10.7, range 2–17); three of them had at least one previous episode of GI bleeding, treated conservatively. In three patients, it was possible to introduce a standard diagnostic endoscope with a multiple band ligator: the mean number of bands per session were 4 (range 3–6) with an average of 2.6 sessions(range 2–3) to achieve eradication. One patient re-bled 4 days after the first session, and was managed with octreotide and blood transfusion and another presented melena without severe blood loss. The fourth patient, 2 years of age, weighing 8 kg, referred for acute re-bleeding, was treated using a paediatric endoscope and sclerotherapy with atoxysclerol 1% with a mean amount of 6.2 ml (range 3–8) and four treatment sessions to obtain complete eradication. Two patients were treated for anastomotic strictures following surgery for oesophageal atresia (two males, 8 months and 4 years old); in these patients we used a standard diagnostic scope and proceeded perform progressive pneumatic dilations TTS to achieve 10 and 12 mm dilation, respectively. Our experience demonstrates the possibility of using of therapeutic endoscopy in a selected paediatric population. PO047 SYNCHRONOUS COLORECTAL LIVER METASTASES: SURGERY OR PERCUTANEOUS RADIOFREQUENCY ABLATION? F. Biolchini, M. Federica Lerro, N. Candeloro, L. Mastrangelo, A. Grilli, N. D’Imperio, E. Jovine UU.OO. di Chirurgia Generale “A”, di Gastroenterologia ed Endoscopia Digestiva, Ospedale Maggiore, Bologna, Italy Brief background and aim. The 15–25% of patients affected by colorectal neoplasm, present liver metastases at diagnosis and treatment is still controversial, even though surgery has now become the treatment of choice. Two different types of surgical interventions can be performed: the first is represented by combined resection of the colorectal tumour and liver metastases; in the second approach, the metastases are resected after the resection of colorectal cancer and 2 months of adjuvant chemotherapy. Materials and methods. From October 2002, we adopted the practice of combined resection for patients with synchronous colorectal liver metastases. To date 14 patients has been treated, 8 with colonic primary and 6 with rectal primary; metastases were confined to one lobe of the liver in 9 cases and were bilobar in the others. The types of surgical intervention are listed in Table 1. In one patient, a two-stage procedure was performed: a right hepatectomy, followed after 2 months, by a left liver lobectomy. Results. The operative mortality was 0% while the morbidity was 7% (a patient had an anastomotic leakage treated surgically) and only five patients necessitated blood transfusion in theatre.

F. Biolchini, S. Selleri, G. Landolfo, C. Fabbri, V. Cennamo, N. D’Imperio, E. Jovine UU.OO. di Chirurgia Generale “A”, di Gastroenterologia ed Endoscopia Digestiva, Ospedale Maggiore, Bologna, Italy Brief background and aim. With the terms “Hepatic Adenomatosis” (HA), we refer to a rare benign pathology of the liver that is characterised by the presence of multiple adenomas in a liver parenchyma otherwise normal. In literature only 62 cases were described: the disease affected more frequently the female (80%), median age of 32 years old and the clinical presentation is, in the 37% of cases, the intralesional rupture of greater adenomas. In patient with HA, malignant transformation is rare and the risk for haemorrhagic complication is difficult to estimate. Materials and methods. The authors described the case of a 17-year-old young woman, admitted for a sudden acute abdominal pain, localised to her left side and subsequently irradiated to the left hypochondrium, accompanied by fever (38.5 = B0C), hepatomegaly and anaemia (Hb 8 mg/dl). The imaging, abdominal ultrasound (US), CT scan, MRI, arteriography, showed the presence of several nodular liver neoformation, compatible with adenomas, the bigger, about 15 cm in diameter, localised in the left lobe of the liver, with the presence of necrotic and haemorrhagic areas inside. The patient underwent a laparotomy. Intra-op US confirmed the presence of the greater lesion, that originated from the caudate lobe, and, in addition, showed the presence of several other adenomas scattered along the entire liver; two of these, about 5 cm in diameter, were localised in the left lobe. The surgical intervention consisted of a left lobectomy plus resection of the segment I in order to resect the main lesion and other two lesions, located in the segments II and III, that were at great risk of bleeding for its dimensions. The dissection was carried out intraparenchymally, avoiding manipulation of the hepatic hilum, foreseeing future orthotopic liver transplantation (OLT) possibility. Results. The post-operatory was uneventful and the patients was discharged 8 days after surgery. A 3-month follow-up showed no signs of recurrence. Conclusions. Surgery represents the treatment of choice in the acute emergencies following bleeding and, as a preventive measure, in the patients with adenomas of greater dimension, that is considered at high risk of haemorrhage. Usually, conservative surgery is indicated; liver transplantation could also be an option, but it should be performed only in case of highly symptomatic forms with a severe impairment of day-to-day life in young patients or in case of evidences or suspecting malignant transformation. PO049 ALBUMIN IN THE MANAGEMENT OF LIVER DISEASES: AN AIGO SURVEY IN GASTROENTEROLOGY CENTRES S. Bocciaa , L. Simonea , C. Rizzoa , G.F. Spinzib , G. Minolib , S. Gullinia a U.O.

Gastroenterologia ed Endoscopia Digestiva Azienda Ospedaliera, Universitaria di Ferrara, Italy b U.O. Medicina Interna Ospedale Valduce Como, Italy

Abstracts Background. There are strong evidences in literature showing that albumin is useful for its therapeutic properties in liver diseases. Nevertheless, its use is often discouraged because of its high cost. Therefore, we performed a survey of albumin use in cirrhotic patients in both Gastroenterology and Internal Medicine Units in Italy. The aim of our study is to verify the main indications of albumin in clinical settings and to check its appropriate use. Methods. We sent a questionnaire by e-mail to Associazione Italiana Gastroenterologi Ospedalieri (AIGO) members. The main questions deal with the type and dimension of the Units (Gastroenterology or Internal Medicine), indications of albumin use in cirrhosis, definitions of refractory ascites and hepatorenal syndrome (HRS), elaborations of local guidelines for the use of albumin. Results. We obtained 39 answers (85% from Gastroenterology Units and 15% from Internal Medicine Units). The main indications were: 41% after paracentesis of any entity, 61% after paracentesis greater than 5 l, 46% during spontaneous bacterial peritonitis (PBS), 79% in diuretic resistant ascites, 76% in HRS, 46% in case of hyponatremia. We asked if the International Ascites Club Criteria for refractory ascites and HRS had been used: 74% of centres used this criteria. We asked if the plasma level of albumin was taken into consideration in the decision to use i.v. infusion. Only 18% of participants thought that the concentration of albumin needed to be lower than 2.5 mg/dl before the infusion of albumin. We analysed if there were any differences in the use of albumin between Gastroenterologists and Internists: gastroenterologists used albumin more frequently in paracentesis of any entity, in PBS and in HRS (45% versus 20%; 51% versus 20%; 85% versus 40%). Finally, only 53% of these Centres had produced formal local criteria for the appropriate use of albumin in liver disease. Conclusions. This preliminary survey has shown that there is a large variability in the use of albumin in the management of cirrhotic patients in Italy. There is general agreement that the main indication of the use of albumin in cirrhotic patients is not hypoalbuminaemia. These data underline the need of guidelines endorsed by Italian Gastroenterological Associations. PO050 OBSTRUCTIVE SLEEP APNEA (OSA) IS IMPROVED BY A PROLONGED TREATMENT OF GASTRO-OESOPHAGEAL REFLUX (GER) WITH OMEPRAZOLE M. Bortolotti, M. Giovannini, M. Miglioli Department of Internal Medicine, University of Bologna, Bologna, Italy Background/aim. Obstructive sleep apnea (OSA) has been demonstrated to induce gastro-oesophageal reflux (GER) through the highly negative intrathoracic pressure during the attacks. However, we believe that GER on its part may favour or aggravate the apnea attacks. So we investigated whether the treatment of GER with omeprazole is able to decrease the apnea attacks. Methods. Twenty patients (mean age 55.4 years, range 49–73; 17 males) with confirmed OSA at overnight polysomniography and pathologic GER at ambulatory 24 h oesophageal pH-metry were asked to note in a diary the occurrence of apnea attacks for a basal period of 4 weeks. Subsequently the patients were randomly treated with omeprazole 20 mg (10 patients, group A) or placebo (10 patients, group B) by giving 1 cp 30 before breakfast and 1 cp 30 before dinner for another 6 weeks with a diary documentation. The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between groups and in each group before and after treatment. Results. The mean weekly frequency of apnea attacks significantly decreased in group A from 3.50 + 1.67 (mean + S.D.) of the basal period to 1.97 + 0.95 of the omeprazole treatment, while group B did not show a significant difference from 3.74 + 1.58 (basal) to 3.38 + 1.23 (placebo). The value observed during omeprazole treatment was also significantly lower than that of group B during placebo. The weekly frequency of

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apnea attacks in group A started from the third week was significantly lower than both the corresponding values of group B and the basal period, reaching a decrease of about 73% in the sixth week. Conclusion. The occurrence of apnea attacks progressively decreased during the treatment of GER with omeprazole. This fact suggests that GER may play a role in triggering and/or worsening OSA. The mechanism through which the treatment of GER with omeprazole improves OSA is unknown. It may be related to the stoppage of chemoreceptor stimulation of the pharyngo-palatal mucosa, but, because the maximal effect is obtained after 6 weeks of treatment, it is more likely that the decrease of OSA attacks is due to a regression of the acid-dependent inflammation and oedema of the oro-pharyngeal tissues that collapse during the attacks closing the air passage. PO051 RADIATION THERAPY AND CONCURRENT TW- ICE-WEEKLY GEMCITABINE IN PATIENTS WITH ADVANCED PANCREATIC CANCER G. Boza , A. De Paolia , R. Innocentea , C. Rossib , R. Cannizzaroc , G. Carlo Tosolinid , C. Bassie , M. Falconie , P. Pederzolie , R. Talaminif , M. Gaetano Trovòa a Radiotherapy

Department, Centro Riferimento Oncologico Aviano, Italy Department, Centro Riferimento Oncologico Aviano, Italy c Gastroenterology Department, Centro Riferimento Oncologico Aviano, Italy d 2nd Surgery Department, General Hospital, Pordenone, Italy e Endrocrinosurgery, University of Verona, Italy f Epidemiology Department, Centro Riferimento Oncologico Aviano, Italy b Surgery

Purpose. Gemcitabine (GEM) has been shown to be a potent radiosensitiser both in lab studies and in the clinic. Phase I clinical data indicate that both the acute toxicity and the efficacy of the combination of GEM and radiotherapy (RT) is strongly related to the dose and schedule of GEM administration. Our previous experiences (AISP, EPC, ASTRO 2001) with twice-weekly GEM, 5FU and concurrent RT was quite satisfactory in terms of local control and survival. However, 5FU and GEM administered concurrently with RT have a synergistic effect which increase toxicity in comparison with more conventional treatments. On the basis of these data, we started a study to determine the toxicity and efficacy of twice-weekly GEM delivered concurrently with RT in advanced pancreatic cancer. Materials and methods. Twenty-five patients with cytologic and/or histologic proof of unresectable pancreatic adenocarcinoma, were entered in this study between May 2000 and October 2002. Median age was 61 (41–74), median Karnofsky score 90 (70–100). RT was delivered using a 4-field technique to a total dose of 45 Gy followed by a boost of 9– 14.4 Gy. GEM was given weekly on Tuesday and Friday at a daily dose of 40 mg/meq. throughout the entire course of RT. WBC and platelets counts were obtained twice per week; in case of toxicity greater than grade I GEM administration was stopped and then resumed at haematologic recovery. Results. All patients completed the RT program whereas the GEM scheduled treatment was completed by five patients only. Median GEM cycles were 8 (2–13). Median follow-up time was 10 months, median survival time 13 months; disease-free-survival was 12 months. Radiological confirmed response was: RP in 9 patients and no change in 16; subjective response was RP in 12 and no change in 13. Haematological toxicity of grade III was observed in 1 patient, grade II in 8 and grade I in 10. Gastrointestinal toxicity was grade II in five patients and grade I in eight. Conclusions. Twice-weekly GEM administered concurrently with RT is well tolerated when compared with our previous study with GEM, 5FU and RT. In addition, this combination achieves a good local control. The survival is satisfactory when compared with the data from the literature.

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PO052 GASTRO-OESOPHAGEAL REFLUX, OESOPHAGEAL DYSPHAGIA AND ANAL INCONTINENCE ARE HIGHLY PREVALENT SYMPTOMS IN PARKINSON’S DISEASE F. Braccia , L. d’Albab , D. Badialia , G. Iacopinib , E. Corazziaria , Anemgi and Italian Patient Associations on Parkinson’s Disease a Dipartimento

di Scienze Cliniche, Università “La Sapienza”, Italy di Gastroenterologia e endoscopia Digestiva “Azienda Ospedaliera S. Giovanni-Addolorata”, Rome, Italy b UOC

Dysphagia and constipation are the more frequently reported gastrointestinal (GI) symptoms in Parkinson’s Disease (PD). However, the prevalence of the entire spectrum of GI symptoms in PD is not well known. The aim of this study was to assess the prevalence of GI complaints in Italian PD subjects. A standardised and validated questionnaire, enquiring about GI symptoms, was hand out to PD patients through PD associations located in 11 Italian towns. The questionnaire was filled in by 138 subjects (males: 86, females: 52; mean age = 69 ± 10 years); duration of disease was 8.6 ± 6.9 years. The following symptoms were reported: dysphagia by 54 subjects (39.13%), chest pain by 13 (9.42%), heartburn by 28 (20%), acid oesophageal regurgitation by 13 (9.42%), abdominal pain by 46 (33.3%), constipation (defined according to Rome II Criteria or less than 3 e.v. per week) by 68 (49%). At least one bowel dysfunction was present in 115 (83%), strain at evacuation in 40 (28.9%), incomplete evacuation in 9 (6.52%), use of laxatives in 70 (50.7%), bowel movement <3 per week by 42 (30%), faecal incontinence in 40 (28.9%). Dysphagia was associated with heartburn in 23 (16.7%) and with chest pain in 7 (5%). Conclusions. In addition to oro-pharyngeal dysphagia and constipation several other GI symptoms may be present in PD patients. Anal incontinence was reported by about one-third of the subjects; the high prevalence of heartburn, pain and dysphagia associated with heartburn and chest pain indicate the frequent occurrence of gastro-oesophageal reflux disease and oesophageal dysphagia. PO053 AUTONOMIC BALANCE IN INFLAMMATORY BOWEL DISEASES, IRRITABLE BOWEL SYNDROME AND GASTROOESOPHAGEAL REFLUX DISEASE V. Brambillaa , B. Pratib , G. Aragonab , L. Cavallarob , G.M. Cavestrob , L. Brambillaa , M. Gualerzia , S. Bosib , G. Nervic , A. Frazèc , F. Di Mariob , P. Coruzzia a UORPC

Fondazione Don Gnocchi Onlus, Parma, Italy of Gastroenterology, University of Parma, Italy c Gastroenterology and Endoscopy Unit, Az. Ospedaliera, Parma, Italy b Chair

Background and aim. Few studies exist about autonomic function in inflammatory bowel disease (IBD), gastro-oesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). Analysis of heart rate variability (HRV), and baroreflex sensitivity (BRS) can increase the knowledge of this field. Our aim was to evaluate the autonomic imbalance in IBD, GERD and IBS patients by means of a non-invasive test based on the analysis of heart rate variability and baroreflex sensitivity. Patients and methods. Study population comprised of 48 IBD patients (17 Crohn’s disease; 31 ulcerative colitis), 15 IBS patients, 28 GERD patients and 21 healthy, sex and age-matched controls. All patients included in the study have been investigated by means of heart rate variability and baroreflex sensitivity. Different parameters were analysed in the time domain (RR interval; HRV; pNN50; rMSSD) and in the frequency domain (VLF = very low frequency (0.04 H2); LF = low frequency (0.04– 0.15 H2); HF = high frequency (0.15–0.50 H2), baroreflex sensitivity (sequences and alpha index techniques). Results. In IBD and IBS patients, respectively, RR interval (P = 0.004; 0.001), HRV (P < 0.0001; P = 0.002), pNN50 (P < 0.0001; P = 0.002), rRMSSD (P = 0.004; 0.007), VLF (P = 0.002; 0.003), LF (P = 0.001;

0.004) and HF (P = 0.002; P < 0.0001) were significantly different respect to the healthy controls. The BRS decreased significantly in IBS patients only (P < 0.05). No difference was found in GERD patients compared to the healthy controls. Conclusion. Our data demonstrate a shift in the autonomic balance in IBD and IBS patients. All studied parameters suggest the existence of an impaired autonomic balance in such diseases. PO054 RIFAXIMIN/MESALAZINE FOLLOWED BY MESA- LAZINE ALONE IS HIGHLY EFFECTIVE IN OBTAINING REMISSION OF UNCOMPLICATED DIVERTICULITIS OF THE COLON G. Brandimartea , A. Tursib , W. Eliseia , V. Annunziataa , S. Villaa a Department

of Internal Medicine, Division of Gastroenterology, “Cristo Re”, Hospital, Rome, Italy b Digestive Endoscopy Unit, “L. Bonomo” Hospital, Andria (BA), Italy

Background. Rifaximin has been effectively used for the treatment of uncomplicated diverticular disease, but rifaximin plus mesalazine have been showed to be more effective than rifaximin alone in the treatment of recurrent diverticulitis of the colon. Aims. To investigate the effectiveness of the association rifaximin/mesalazine, followed by mesalazine alone, in order to evaluate its effectiveness in obtaining remission of uncomplicated diverticulitis of the colon and its tolerability. Methodology. A prospective study was conducted on 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32–91 years), affected by diverticulitis of the colon. Diagnosis was performed by colonoscopy. We assessed the following symptoms, scoring them with a quantitative scale (0–10 according to worsening of symptoms): (1) constipation, (2) diarrhoea, (3) abdominal pain, (4) rectal bleeding, (5) mucus passage with the stools. All patients were treated with rifaximin 800 mg per day plus mesalazine (Pentacol® 800, Sofar S.p.A., Trezzano Rosa [MI]) 2.4 g per day for 10 days, followed by mesalazine 1.6 g per day for 8 weeks. The patients were re-evaluated at the end of the eighth week of treatment with mesalazine alone. Results. All patients were fully compliant. Eighty-six patients completed the study (95.56%): all of them were completely asymptomatic after the eighth week of treatment with mesalazine alone (overall symptomatic score: 0). Two patients (2.22%) showed recurrence of symptoms after 4 and 6 weeks of treatment with mesalazine alone. Two other patients (2.22%) were withdrawn from the study due to severe diarrhoea after mesalazine treatment started (one after 4 days of mesalazine alone and other after 8 days of rifaximin/mesalazine treatment). Finally, two other patients (2.22%) showed transitory pruritus (one) and epigastric pain (one). Conclusions. The results obtained clearly show that rifaximin/mesalazine followed by mesalazine alone are extremely effective in obtaining the resolution of symptoms in patients with uncomplicated diverticulitis. Moreover, this study reinforced the hypothesis that anti-inflammatory drugs may play a key role in the treatment of uncomplicated diverticulitis instead of antibiotics. PO055 VIDEO CAPSULE ENDOSCOPY FOR EVALUATING OBSCURE GASTROINTESTINAL BLEEDING AND SUSPECTED SMALL BOWEL PATHOLOGY G. Bresci, P. Giuseppe, B. Michele, E. Tumino, C. Alfonso U.O. di Gastroenterologia, Azienda Ospedaliera Pisana, Pisa, Italy Aim. To report our preliminary experience on the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB). Materials and methods. Of 408 patients with gastrointestinal haemorrhage referred to our institution between June and December 2002, 30 had an OGIB and they were offered to be submitted to VCE (Given

Abstracts M2A). To be eligible for VCE, patients had to have undergone upper endoscopy, small bowel series and colonscopy without discovering any source of bleeding. Exclusion criteria were bowel obstruction, pacemaker implantation, small intestine diverticula and pregnancy. Three investigators independently reviewed the capsule images. Patients were asked to complete a questionnaire concerning their impressions during VCE and to retrieve the capsule after passage per rectum. Results. The cases included in the trial were 30 (16 women, average age 54 years, range 30–73). Two patients were excluded after the barium study owing to some big diverticula of the small intestine. One patient had been submitted to total colectomy some years before for familial adenomatous polyposis (FAP). All cases completed the study and there were no complications. No patients had difficulty in swallowing the capsule. The capsule reached the stomach on an average of 40 s (range 9–55 s), it remained there on an average of 50 min (range 1–86 min) and showed the entire small bowel within 270 min (range 180–362 min). Two capsules failed to reach the colon during the acquisition time. The batteries resisted on an average of 376 min (range 350–414 min). Capsules were retrieved within 30 h (range 8–70). The mean time required to review the capsule images was 150 min (range 120–180). Lesions were found by VCE in ten cases. Three of these patients showed some angioectasia-like lesions of the small bowel but without signs of bleeding. Two polyps in the jejunum were revealed in the patient with a history of FAP. Aspecific linear erosions of ileum were showed in two cases. A short segmental tubular stenosis of terminal ileum with oedema and erosions was found in one case. The bleeding site was identified in one patient and the surgery showed a tumour of terminal ileum. Conclusions. VCE was well tolerated, was able to acquire good images, showed lesions in 10 of the 30 patients (33%) and identified the source of bleeding in one case. New cunnings however are necessary to reduce physician review time, to determine the real location of the capsule and to perform biopsies or cauterisation as well as at conventional endoscopies. PO056 TRANSCRIPTOMES OF THE RIGHT AND LEFT COLON: DIFFERENCES IN GENE EXPRESSION? F. Bressoa , P von Steinb , N. Kouznetsovb , V. Arulampalama , M. D’Amatoa , R. Löfbergc , S. Petterssona a Microbiology

and Tumour Biology Center, Karolinska Institute, Stockholm, Sweden b InDex Pharmaceuticals, Stockholm, Sweden c Karolinska Institutet, IBD-Unit at HMQ Sophia Hospital, Stockholm, Sweden Introduction. Distinct pathological characteristics of colorectal carcinomas (CRCs) and inflammatory bowel disease (IBD) based on their anatomical location suggest different risk factors and pathogenetic mechanisms ongoing in proximal and distal colon. Distinct biological characteristics between the left and right colon may reflect: (I) different embryonic or postnatal development, (II) different physiological functions or (III) different concentrations of epigenetic factors in the lumen (for example nutrients, microbes). Taken together, these differences in combination with the variation of epigenetic load may set different thresholds for the development of disease, in the different anatomical regions in genetically predisposed individuals. Aim. To determine gene expression patterns in ascendens colon compared to descendens colon in healthy humans. Materials and methods. Biopsy samples were taken from the left and the right colon in five patients (IBD-Unit Sophiahemmet, Stockholm) who underwent colonoscopy in suspect of organic disease. The pathologist excluded microscopic inflammation. The samples were directly stored in RNA later to avoid RNA degradation and then kept at −70 ◦ C. The biopsies were analysed at Microbiology and Tumour Biology Center, MTC, Karolinska Institute, Stockholm, with the suppressive subtractive hybridisation (SSH) in close collaboration with InDex Pharmaceuticals

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AB. With this technique the different genes expressed in the left versus the right colon were studied. Results. One hundred and eighty-four differentially expressed cDNA clones were sequenced. Bioinformatic analysis showed 10% of these genes to be of unknown function. Known genes are likely to be involved in areas of metabolism, signal transduction, cytoskeleton/extracellular matrix composition, mitochondrial and general cellular function. We are currently validating our results by means of real time PCR. Conclusions. A difference in gene expression pattern between the right and left colon does exist. The biological implications of these findings will be discussed in the light of the clinical observation-malignant. PO057 DUODENAL BILIARY ILEUS: AN UNUSUAL CASE ENDOSCOPICALLY RESOLVED P. Brosolo, A. Ederle, N. Carone, E. Dall’O, A. Fantin, P. Inturri, F. Sforza U.O.A. di Gastroenterologia, Ospedale di San Bonifacio, ULSS 20, Verona, Italy Biliary ileus is a rare, but serious condition, generally requiring emergency surgery to resolve the intestinal occlusion. We describe the case of a 70-year-old woman, admitted for acute epigastric pain and vomiting. Mild signs of inflammation and cholestasis were present. An abdominal radiography resulted negative and the abdominal ultrasonography pointed out the presence of a contracted gallbladder with wall thickening. An oesophago-gastro-duodenoscopy demonstrated the presence of a large gallstone at the level of proximal second part of duodenum, with complete lumen occlusion, preventing the endoscopic transit. Other small stones were present at the level of duodenal bulb where, on the anterior wall, fistulous orifice was highlighted. A radiogram with contrast confirmed the presence, distally to the duodenal bulb, of a stone of size of about 4 cm, and partially visualised gallbladder through the fistulous orifice. Under radiologic control, mechanical lithotripsy of the stone with Soehendra lithotriptor was performed following with easy endoscopic transit. A cholangiography through fistula and cystic duct highlighted a normal common bile duct, without biliary stones. The following clinical course was regular, with parenteral nutrition, naso-gastric aspiration for 5 days and antibiotic and antisecretive therapy. Then, the patient again started taking oral feeding gradually and, during a follow-up of 90 days, she did not show any symptom, refusing the endoscopic control. A radiogram of the digestive tract point out a regular morphology of the duodenum and the disappearance of the fistulous tract. Conclusions. This case point out the capability of the resolution of duodenal biliary ileus (also called Bouveret’s syndrome) by endoscopic therapy, with spontaneous repair of the entero-cholecystic fistula. PO058 DIAGNOSTIC COLONOSCOPY AS A PRESURGERY EXAM IN INGUINOCRURAL HERNIA. FINAL RESULTS R. Bucchianeria , L. Maria Tomarellib , M. Silvestrellib , G. Mazzocconia , E. Fiorea , S.A. Rita Curtoc a U.O.

Chirurgia Generale DIP. Gastroenterologia ED Endoscopia Digestiva c U.O. di Pronto Soccorso Azienda USL No. 7, Ancona, Presidio Ospedaliero di Osimo, Ospedale SS Benvenuto E. Rocco, Italy b Mod.

Introduction. Colonoscopy deserves to be recognised as the “gold standard” exam for colorectal cancer prevention. In our opinion inguinocrural hernia should be added to the other well known risk factors (familiality and age over 50) since it is regarded as a consequence of collagen degeneration (associated with loss of elasticity in elderly) and in literature there is evidence of a relationship between some abnormalities in collagen or in extracellular collagen matrix (ECM) and polyposis or colorectal cancer. We show the final results of our study.

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Method. In collaboration with general surgery department colleagues, a colonoscopy to all patients over 40 yaers of age admitted for inguinocrural hernioplastic surgery was performed. Results. From September 2002 to November 2003, 63 patients have been screened with colonoscopy (before surgical treatment): adenomatous polyposis has been detected in 24 patients (38%). Conclusions. Real colorectal cancer prevention is obtained by removal of adenomatous polyps (i.e. potentially degenerating ones). Our study suggests that if supported by larger studies, an additional strategy for the prevention of colorectal cancer can be obtained. PO059 WIRE-GUIDED MINIPROBES FOR INTRADUCTAL ENDOSCOPIC ULTRASONOGRAPHY (IDUS): PRELIMINARY DATA ON DIAGNOSTIC EFFECTIVENESS IN BILIARY OBSTRUCTION E. Buscarini, G. Lupinacci, L. La Mantia, F. De Grazia, G. Brambilla, F. Menozzi, A. Zambelli U.O. Gastroenterologia ed Endoscopia Digestiva, ASL Ospedale Maggiore, Crema, Italy Background/aims. IDUS can improve diagnostic accuracy of retrograde cholangiography (ERC) in patients with biliary obstruction. This study aimed to compare lesion detection of IDUS with ERC/EST results. Materials and methods. Patients with biliary obstruction of undetermined cause were first studied with ERC; thereafter intraductal probe (2.4 mm diameter, 20 MHz mechanical radial scanning, UM-G60 Olympus) was advanced over a guidewire up to the liver hilum. Data concerning bile duct wall, presence of lesion/s and/or stones were recorded. Results were controlled by EST. Results. Three patients (males, mean age 58.2) were studied. ERC showed a suspected stenosis of proximal bile duct in two cases, stones in one. IDUS confirmed a proximal cholangiocarcinoma in one case, excluded stenosing lesions in the other case in which multiple small stones were found, confirmed stones and microlithiasis in the third case. EST allowed to confirm stones in two cases. Conclusions. These initial data confirm potential utility of IDUS in selected patients with biliary obstruction. High-frequency guide-wired miniprobes are particularly handy and effective for this purpose. PO060 TISSUE HARMONIC IMAGING (THI) FOR THE STUDY OF THE GALLBLADDER: IS IT LIKELY TO CHANGE EPIDEMIOLOGICAL DATA ON GALLSTONES? E. Buscarini, R. Byanima, G. Lupinacci, L. La Mantia, F. De Grazia, G. Brambilla, F. Menozzi, A. Zambelli U.O. Gastroenterologia ed Endoscopia Digestiva, ASL Ospedale Maggiore, Crema, Italy Background/aims. THI provides a marked improvement in image quality and clarity. Purpose of this study was to compare conventional sonography (US) and THI for the detection of gallbladder abnormalities. Materials and methods. A consecutive series of 44 patients (27 males, 17 females, mean age 44.6) referred for abdominal sonography were studied for gallbladder abnormalities, both of the wall and of the content, by conventional US and THI. Patients with previous diagnosis of gallstones and severely ill patients were excluded from the study. Every patient was first examined by a physician using only conventional US and then by a different physician unaware of previous results with THI. Every examination of the gallbladder was done both in supine and in left lateral decubitus. Findings of each examination were independently recorded; final diagnosis was given on the basis of THI results. Results of both techniques were compared for lesion detection, lesion conspicuity and overall image quality.

Results. Conventional US diagnosed gallbladder as normal in 32 cases, abnormal in 8, doubtful in 4, depicting content abnormalities (stones) in 6, wall polyps in 2, doubt of microlithiasis in 1 of wall polyps in 3. THI diagnosed gallbladder as normal in 26 cases, abnormal in 18, depicting 10 content abnormalities (stones or microlithiasis), 6 wall polyps (multiple in 2 cases), microlithiasis and wall abnormality in 2 cases (polyps, vegetative lesion of gallbladder fundus). Statistical analysis showed that THI was significantly superior to conventional US for lesion detection (P < 0.001), lesion conspicuity (P < 0.001) and overall image quality (P < 0.05). Conclusions. THI provides significantly more information on gallbladder than conventional US, it is particularly effective for microlithiasis detection and thus it has the potential to change epidemiological data on gallstones. PO061 DGER: EFFECT OF OMEPRAZOLE ON SYMPTOMS AND ULTRASTRUCTURAL DAMAGE OF THE OESOPHAGEAL MUCOSA C. Calabrese, A. Fabbri, M. Bortolotti, G. Cenacchi, C. Scialpi, A. Areni, M. Miglioli, G. Di Febo Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Italy Background. The effect of PPI on DGER, even if it is a field of interest, is reported in few studies which are not focalised on the clinical outcome but on the pharmacological effects induced by PPI. Recently, it has been demonstrated that dilation of intercellular spaces (DIS) is a very sensitive and responsible for early damage in gastro-oesophageal reflux disease. Its reversibility after PPI treatment have been verified. Aim. To evaluate whether omeprazole can induce the healing of DIS and regression of symptoms in patients with DGER. Materials and methods. We enrolled 12 patients (four male; mean age 42.5 ± 9.1 years, range 26–59) with typical symptoms of oesophageal reflux disease and with a pathological 24 h pH-metry and bile-monitoring. Patients underwent endoscopy and biopsies were taken from the distal oesophagus. Specimens were analysed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg once daily for 3 months. After this period endoscopy with biopsies was repeated. Subjects with persistent heartburn and/or with an incomplete recovery of DIS, were treated for 3 more months and a new endoscopy was performed. Results. Eight patients had a normal oesophageal mucosa at endoscopy (two men; mean age 41.1 ± 9.3 years) while four had erosive oesophagitis (two men; mean age 45.2 ± 9.1 years). At histology, among four patients affected by erosive oesophagitis, three had mild oesophagitis and one moderate oesophagitis. No patients with NERD showed histological signs of oesophagitis. After 3 months of therapy 11 patients (91.67%) showed a complete ultrastructural recovery of the mucosa and resolution of heartburn. One patient with erosive oesophagitis required three more months of therapy because of an incomplete recovery of the epithelium at TEM correlated with sporadic heartburn. The healing of the mucosa was achieved with complete resolution of symptoms. Conclusions. Three or six months of omeprazole therapy led to a complete regression of the ultrastructural oesophageal damage in all patients with DGER. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

Abstracts PO062 GERD AND ASTHMA. A STRICT CORRELATION BETWEEN SYMPTOMS AND PANTOPRAZOLE THERAPY. A PRELIMINARY REPORT C. Calabrese, A. Fabbri, C. Scialpi, A. Areni, G. Cenacchi, M. Miglioli, G. Di Febo Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Italy Background. Gastro-oesophageal reflux is regarded as an asthma trigger. Its prevalence and the effects of PPIs treatment on its decors is still uncertain. In fact, bias in selection of asthmatic patients, or during PPIs treatment and the absence of a morphological high sensitive parameter to define oesophageal mucosa damage, may affect the results of studies. Aim. To value the prevalence of GERD in patients with mild/moderate persistent asthma and to estimate the answer to pantoprazole therapy in relation with asthmatic symptoms and respiratory function. Materials and methods. Fourteen (five men, mean age 29.36 ± 8.58 years, range 18–45 years) consecutive asthmatic patients were enrolled. Among them eight (four men, mean age 26.37 ± 7.87 years, range 18–42 years) presented GERD symptoms (heartburn and/or acid regurgitation) and six (one man, mean age 33.3 ± 8.45 years, range 27– 45 years) were asymptomatic for reflux disease. Patients underwent an endoscopy and five biopsies, from the lower oesophagus 5 cm above gastro-oesophageal junction, were taken for ultrastructural evaluation. Patients with ultrastructural signs of mucosal damage, dilation of intercellular spaces (DIS) >0.74 ␮m (mean value of 100 intercellular space diameters), were treated with pantoprazole 80 mg once daily for 6 months. At the end of this period a new endoscopy with biopsies was performed and DIS valuated. Monthly FEV1 and symptoms were recorded for each patient. Results. Among six asymptomatic patients, three presented DIS while all symptomatic patients showed ultrastructural oesophageal damage. Patients with DIS (11/14) were treated for 6 months with pantoprazole. Seven patients (two asymptomatic and five symptomatic for GERD) completed the study to date. Asymptomatic patients improved their asthmatic symptoms and pulmonary parameters, while among symptomatic subjects, four had a complete recovery of DIS with disappearance of asthmatic symptoms, and one had a complete resolution of DIS but a partial regression of respiratory symptoms. Conclusions. GERD is a high prevalent condition in asthma. Treatment with pantoprazole 80 mg once daily for 6 months led to an improvement till a complete regression of asthmatic symptoms and respiratory functional alterations. PO063 VISCERAL SENSITIVITY IN PATIENTS WITH COELIAC DISEASE (CD) AND IRRITABLE BOWEL SYNDROME (IBS) M.P. Caldarella, S. Flora, L. Francesco, M. Angelo, B. Crisanthy, M. Neri Section of Internal Medicine and Gastroenterology, Department of Medicine and Aging Sciences, Università Gabriele D’Annunzio, Chieti, Italy Visceral sensitivity in patients with Coeliac Disease (CD) and Irritable Bowel Syndrome (IBS) Caldarella Maria Pia, Sacco Flora, Laterza Francesco, Milano Angelo, Balatsinou Crisanthy, Matteo Neri Department of Medicine and Aging Sciences, Section of Internal Medicine and Gastroenterology, Università Gabriele D’Annunzio, Chieti, Italy. Recent studies suggest that a significant mutual overlap exists between IBS and CD, whether the two ailments also share some pathophysiological features is still unknown. Aim. To evaluate visceral sensitivity in patients with IBS and untreated CD (with and without gastrointestinal symptoms) in comparison to healthy subjects.

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Materials and methods. We evaluated 16 IBS patients (eight males, eight females; 34 + 4 years, Rome II criteria) with negative biochemistry, colonscopy and histology. Thirteen patients with CD (six males, seven females; 32 + 4 years), newly diagnosed by serology, endoscopy and histology, were grouped according to the predominant clinical features: six patients (three males, three females; 28 + 3 years) showed GI symptoms while seven (four females, three males; 36 + 2 years) presented with anaemia but without GI symptoms. Six healthy subjects (four females, two males; 38 + 2 years) were used as controls. Visceral sensitivity was assessed with a computerised tensostat with the bag located into the rectum; rectal distensions were performed in 4 g increments of tension up to 64 g or to discomfort with a 1 min interval between distensions. At each distension, an abdominal Symptoms Score (SS) was achieved by a validated questionnaire with a rating scale from 0 (no sensation) up to 6 (painful sensation). Results. The threshold of perception in IBS was similar to CD (respectively, 8 + 3 g, SS 2.4 + 0.3; 8 + 4 g, SS 1.5 + 0.4) and in both was lower than healthy subjects (32 + 9 g, SS 1.5 + 0.3 P < 0.001). The threshold of discomfort in IBS (36 + 4 g) was significantly lower than healthy volunteers, who tolerated all distensions without discomfort. The threshold of discomfort of CD patients with GI symptoms was higher than IBS and lower than controls (48 + 4 g, SS 5.2 + 0.3) while CD patients without GI symptoms exhibited results similar to controls (SS 3.2 + 0.2; P < 0.05 versus CD–GI). The predominant symptom elicited by rectal distension in IBS patients was cramp/colicky sensation, while it was urgency in CD patients and healthy subjects. Conclusions. Visceral hypersensitivity is a feature of some CD patients and IBS, and this may partly justify the clinical overlap between the two conditions. PO064 AN UNUSUAL CASE OF MULTIPLE OESOPHAGEAL RINGS S. Caliari, C. Manfrini, A. Fuini, A. Battocchia Divisione di Gastroenterologia ed Endoscopia Digestiva, Ospedale Civile Maggiore, Azienda Ospedaliera di Verona, Verona, Italy Usually, oesophageal rings are single, placed in the lower oesophagus and related to gastro-oesophageal acid reflux. We reported the case of a 22-year-old male student with multiple rings placed both in the middle and in the lower oesophagus who had been complaining of intermittent dysphagia with solid foods since he was a young boy. Dysphagia became more frequent and more severe so that the patient needed hospital care for repeated retrosternal blockage of a food bolus. X-rays showed a normal oropharyngeal phase of swallowing. X-ray of the oesophageal body was limited because the patient was not able to swallow enough barium to fill the oesophagus; however, the presence of a short stenotic tract of the middle oesophagus was reported by the radiologist. The gastro-oesophageal junction was also normal. A series of six complete circumferential rings was seen in the middle and distal oesophagus using an endoscope. The oesophageal lumen was too narrow for a normal size gastroscope (diameter: 11 mm), but not for a slim one (diameter: 5.5 mm). Reduced mean amplitude of peristaltic pressure waves was only seen at the oesophageal body with an oesophageal manometric study. Blood tests, X-rays and CT study of the chest were normal. The oesophageal rings were treated by bougienage using Savary’s dilators up to a diameter of 12.8 mm. The patient stopped complaining of dysphagia. A month later, an X-ray study with barium showed a normal oesophageal transit. Two endoscopic studies were performed 6 and 18 months later. The oesophageal rings were still present, but the normal size gastroscope passed through the oesophageal lumen without much difficulty. The patient no longer complained of dysphagia.

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PO065 STEATOSIS IS A COFACTOR FOR FIBROSIS AND RESPONSE TO THERAPY IN GENOTYPE 1b CHRONIC HEPATITIS C (CHC) C. Cammà, V. Di Marco, D. Di Bona, A. Licata, M. Camozzi, S. Bruno, M. Grazia Rumi, M. Vinci, M.U. Mondelli, M. Colombo, G. Pinzello, A. Crax`ı Gastroenterologia, Palermo. IBIM, CNR Palermo. Azienda Ospedaliera Niguarda, Milan ISB S. Paolo, Milan Gastroenterologia, Ospedale Maggiore, Milan Malattie Infettive, IRCCS S. Matteo, Pavia, Italy Background. The role of steatosis, a frequent feature of CHC, in conditioning the development of fibrosis and IFN responsiveness is unclear. Aims. To assess in genotype 1b CHC the prevalence and degree of steatosis and its correlation to stage of fibrosis and sustained virological response (SVR) to antivirals. Database. Clinical and virological data and pre-treatment biopsies of 311 naive genotype 1b patients from a RCT of ribavirin combination comparing PEG to standard IFN. Methods. One pathologist (M.C.) graded (inflammation) and staged (fibrosis) all biopsies according to Ishak and quantified steatosis as absent, mild (1%–20% hepatocytes), moderate (21%–40%), severe (>40%). Results. Steatosis was absent in 113 (42.8%), mild in 114 (36.7%), moderate in 53 (17%) and severe in 11 (3.5%) patients. The degree of steatosis was associated with age (P < 0.0001), BMI (P = 0.03) and g-GT (P < 0.001). Multivariate analysis showed that young age (odds ratio [OR] 0.96; 95% CI, 0.94–0.99), high platelets (OR 1.017; 95% CI, 1.011–1.023), low necro-inflammation (OR 0.82; 95% CI 0.70–0.95) and absent or mild steatosis (OR 0.72; 95% CI 0.52–0.98) were related to mild fibrosis. By logistic regression, treatment with PEG IFN (OR 1.93; 95% CI 1.13–3.28), young age (OR 0.38; 95%CI 0.22–0.66), normal g-GT (OR 0.53; 95% CI 0.30–0.93), mild fibrosis (OR 0.59; 95% CI 0.41–0.85) and absence of steatosis (OR 0.50; 95% CI 0.29–0.87) at liver biopsy were independent predictors of SVR. Conclusions. Subjects with genotype 1b and moderate or severe steatosis (∼20% of all with CHC) are more prone to develop significant fibrosis and to be less responsive to antiviral treatment. PO066 PREOPERATIVE CHEMORADIOTHERAPY FOR OESOPHAGEAL CANCER: A META-ANALYSIS C. Cammàa,b,c , D. Di Bonaa,b,c , A. Licataa,b,c , F. Fioricaa,b,c , F. Schepisa,b,c , A. Venturia,b,c , A.M. Falchia,b,c , A. Crax`ıa,b,c a Cattedra

di Gastroenterologia, Università di Palermo, Italy CNR, Palermo, Italy c Cattedra di Radioterapia Oncologica e Dipartimento di Medicina Interna, Università di Modena e Reggio Emilia, Italy b IBIM,

Background. The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied, but data on survival are still equivocal. Objective. To assess the effectiveness of chemoradiotherapy followed by surgery in reducing mortality of patients with resectable oesophageal cancer. Methods. Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2002) were supplemented with hand searches of reference lists. Study selection. Studies were included if they were randomised controlled trials (RCTs) comparing preoperative chemoradiotherapy plus surgery with surgery alone, and if they included patients with resectable, histologically proven oesophageal cancer without metastatic disease. Six eligible RCTs were identified and included in the meta-analysis. Data extraction. Data on study populations, interventions and outcomes were extracted from each RCT according to the intention-to-treat method

by three independent observers and combined using the DerSimonian and Laird method. Results. Chemoradiotherapy plus surgery compared with surgery alone significantly reduced the 3-year mortality rate (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.31–0.93, P = 0.03) (number needed to treat = 10). Pathological examination showed that preoperative chemoradiotherapy downstaged the tumour (i.e. less advanced stage at pathological examination at the time of surgery) compared with surgery alone (OR 0.43; 95% CI 0.26–0.72, P = 0.001). The risk for postoperative mortality was higher in the chemoradiotherapy plus surgery group (OR 2.10; 95% CI 1.18–3.73, P = 0.01). Conclusions. In patients with resectable oesophageal cancer, chemoradiotherapy plus surgery significantly reduces the 3-year mortality rate compared with surgery alone. However, postoperative mortality is significantly increased by neoadjuvant chemoradiotherapy. PO067 PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION (RFTA) OF SMALL HEPATOCELLULAR CARCINOMA: A PROSPECTIVE STUDY C. Cammà, V. Di Marco, A. Orlando, L. Sandonato, P. Parisi, E. Sciarrino, R. Virdone, A. Casaril, D. Cabibi, S. Pardo, D. Di Bona, S. Alizzi, G. Montalto, M.A. Latteri, N. Nicoli, A. Crax`ı Cattedra di Gastroenterologia, Università di Palermo, IBIM CNR Palermo, AO V. Cervello, Palermo, Dipartimento di Oncologia, Università di Palermo, Università di Verona, Anatomia Patologica Università di Palermo, Radiologia, Università di Palermo, Medicina Interna Università di Palermo, Italy RFTA may prolong the survival of patients with small hepatocellular carcinoma (HCC) associated with cirrhosis. The aims of this study were to evaluate efficacy and safety of RFTA and to identify prognostic factors of survival in a cohort of patients with compensated cirrhosis. Methods. We performed Cox regression analysis in 202 consecutive patients with HCC (mean age 66.9 ± 7.8; 131/71 male/female; 165 Child– Pugh class A and 37 Child–Pugh class B) treated by RFTA. A single lesion was observed in 160/202 (79.2%), two lesions in 29/202 (14.3%), and three lesions in 13/202 (6.4%) of patients. The tumour size was <3 cm in 165/202 (81.6%). Results. A total of 67 deaths occurred. Overall survival rates were 80, 67, and 49% at 1-, 2-, and 3-year, respectively. The 1-, 2-, and 3-year survival rates were 83, 69, and 49%, respectively, for Child–Pugh class A patients and 65, 54 and 48%, respectively, for Child–Pugh class B. Serum albumin (P < 0.03), platelet levels (P < 0.01), and tumour size (P < 0.001) were the only independent variables significantly associated with survival. The 3-year rate of appearance of separate new lesions and local recurrence were 34 and 19%, respectively. Five major complications and 25 minor complications were observed. In three patients portal vein thrombosis occurred after treatment. Conclusions. Survival of patients with HCC treated by RFTA is related to baseline albumin and platelet levels and to tumour size. The high rate of recurrence (both local and distant) points out the palliative role of this therapy. PO068 VISUALISATION OF DUODENAL VILLI BY HIGH-RESOLUTION, HIGH-MAGNIFICATION UPPER GI ENDOSCOPY. A VALIDATION STUDY G. Cammarotaa , A. Martinoa , G.A. Pirozzia , R. Ciancia , G. Zuccalàa , L. Cuocoa , V. Ojettia , P. Cesaroa , F. Arancioa , G.L. Leccaa , L. Mielea , A. Griecoa , F.M. Vecchiob , F. Pandolfia , G. Gasbarrinia , A. Gasbarrinia a Departments

of Internal Medicine and Gastroenterology, Catholic University of Medicine and Surgery, Rome, Italy

Abstracts b Institute of Pathology, Catholic University of Medicine and Surgery, Rome, Italy

Background. Conventional endoscopy is unable to visualise intestinal villi and directly detect overt villous atrophy. Methods. The reliability of a new generation video-endo- scope to visualise duodenal villi were investigated, and results were compared with the histological evaluation of villi. One hundred and ninety-one patients underwent upper GI endoscopy, with the clinical indication to perform duodenal biopsies. Patients were examined by three independent experienced observers using a clinically available, high-resolution and high-magnification (2×) video-endoscope. The duodenal villous profile was determined by endoscopic magnification (EM) and by endoscopic magnification after water application into the duodenum (EMW). By both EM and EMW, the villous patterns were scored as: definitely present (DP), partially present (PP) or definitely absent (DA). Villous patterns were also histologically scored as: normal, partial villous pattern (PVP) or total villous atrophy (TVA). Results. Inter-observer variability was excellent (k = 0.93). The concordance between either EM or EMW and histology was 100% for presence/absence of villi. The sensitivity, specificity, positive- and negative predictive values of EM to detect any villous abnormalities were 95, 99, 95 and 99%, respectively; the values of EMW were 95, 98, 92 and 99%. Conclusions. High-resolution, high-magnification upper endoscopy can reliably predict the presence or absence of duodenal villi. PO069 RELIABILITY OF THE DIRECT VISUALISATION OF DUODENAL VILLI BY THE “IMMERSION TECHNIQUE” DURING ROUTINE UPPER GI ENDOSCOPY IN A POPULATION OF DYSPEPTIC SUBJECTS G. Cammarotaa , A. Martinoa , G.A. Pirozzia , R. Ciancia , G. Zuccalàa , L. Cuocoa , V. Ojettia , P. Cesaroa , G.L. Leccaa , F. Arancioa , L. Mielea , A. Griecoa , F.M. Vecchiob , F. Pandolfia , G. Gasbarrinia , A. Gasbarrinia a Departments

of Internal Medicine and Gastroenterology, Catholic University of Medicine and Surgery, Rome, Italy b Institute of Pathology, Catholic University of Medicine and Surgery, Rome, Italy Background. Upper gastrointestinal endoscopy is not routinely performed to directly detect duodenal villous abnormalities. We investigated the reliability of the immersion technique to evaluate duodenal villi in a series of dyspeptic patients. Methods. Three hundred and ninety-six subjects, who underwent standard upper gastrointestinal endoscopy for dyspeptic symptoms, were included. Patients with suspected malabsorption were excluded. By performing a “modified immersion technique”, duodenal villous profiles were scored as definitely present, partially present or definitely absent. Villous patterns were also histologically scored as normal, partial villous pattern or total villous atrophy. Results. Sensitivity, specificity, positive- and negative-predictive values of the MIT procedure to detect total villous atrophy were 100, 99.7, 85.7 and 100%, respectively. Sensitivity, specificity, positive- and negativepredictive values of the MIT procedure to detect partial villous patterns were 75, 99.5, 60 and 99.7%, respectively. Sensitivity, specificity, positiveand negative-predictive values of the MIT procedure to detect any villous abnormalities (partial or total villous patterns) were 90.9, 99.5, 83.3 and 99.7%, respectively. Conclusions. During standard upper gastrointestinal endoscopy, duodenal evaluation by MIT can reliably predict abnormalities of duodenal villi. We suggest that this simple diagnostic procedure may be routinely performed during the endoscopic exploration of duodenum.

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PO070 COLOUR-DOPPLER AND CONTRAST-ENHANCED ULTRASONOGRAPHY IN THE EVALUATION OF CROHN’S DISEASE ACTIVITY T. Cammarotaa , D. Robottia , A. Sarnoa , N. Saponeb , B. Demarchib , S. Rossettib , P. Debania , M. Astegianob , M. Rizzettob a Dipartimento

di Radiologia, Ospedale San Giovanni Battista di Torino, Italy b Dipartimento Gastroepatologia, Ospedale San Giovanni Battista di Torino, Italy Background. Diagnosis and follow-up of Crohn’s disease need often invasive instrumental examinations with high risk of iatrogenic damage. Ultrasound examination of bowel walls could be the first choice in managing patients with Crohn’s disease. The role of tissue colour Doppler and B-mode ultrasound contrast medium intravenous injection, in detection of disease activity has to be evaluated. Methods. Fifty-two patients affected by Crohn’s disease underwent ultrasound examination. Each study was completed with tissue colour Doppler and intravenous injection of ultrasound contrast medium (SonoVue, Bracco), to evaluate intestinal wall vascularisation as an index of disease activity. Then, we compared our results with clinical and laboratory tests. Results. Ultrasound examination with intravenous injection of SonoVue data partly agree with clinical and laboratory tests and colour-powerDoppler in disease activity evaluation, but they have been more useful in the follow-up than these tests. Conclusions. Bowel ultrasound examinations, associated with colour Doppler and particularly ultrasound contrast medium injection, allows to detect Crohn’s disease activity and to modulate the therapy. PO071 PANCREATIC INVOLVEMENT IN SJOGREN’S SYNDROME M. Candellia , C. Manganellib , E.C. Nistaa , S. Turcob , G. Pignataroa , M.A. Zoccoa , A. Armuzzia , L. Scullicab , G. Gasbarrinia , A. Gasbarrinia

a Internal

Medicine, Catholic University of Sacred Heart, Gemelli Hospital, Rome, Italy b Ophthalmology, Catholic University of Sacred Heart, Gemelli Hospital, Rome, Italy

Background. Primitive Sjogren’s syndrome (pSS) has been related to exocrine pancreatic involvement. Several diagnostic tests are available to investigate pancreatic function but most of them show low sensitivity. The aims of our study was to assess the prevalence of pancreatic involvement in pSS using non-invasive test: faecal chymotrypsin (FC), faecal elastase-1 (E1) and 13C Mixed Triglyceride Breath Test (MBT) and to investigate a relation between exocrine function and Schirmer’s Test (ST). Methods. We enrolled 24 patients (18 females, 6 males; mean age 43 ± 7 years) affected by pSS and 24 healthy sex and age matched controls. Each subject underwent MBT. Four milligrams per kilogram of 13C Mixed Triglyceride were administered. Breath samples were collected every 30 min for 6 h just before and after labelled meal ingestion. 13C enrichment was evaluated by isotope ratio mass spectrometer. Results were expressed as cumulative percentage dose of 13C recovered at 6 h (CPDR 6). Serum amylase, lipase, FC and E1, were also evaluated. Lacrimal function was studied by ST expressed as mm. Results. Four patients and one control showed low levels of FC (<6.8 UL/g), five patients and no controls showed low levels of E1 (<200 UI/g) and CPDR6 low values were found in four patients and in no controls (<27.8%). Patients showed lower levels of E1 (285 ± 124 versus 391 ± 103; P < 0.01) and FLC (34.8 ± 21.1 versus 57.6 ± 22.3 P < 0.01) than controls. No difference on serum amylase an lipase were found between the groups. Patients with at least two pancreatic function tests positive were considered affected by pancreatic impairment. Pancreatic impairment was more prevalent in pSS than in controls (6/24, 25%

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versus 0/24; P < 0.001). Interestingly, patients with pancreatic impairment showed a lower values of ST than other pSS patients (1.6 ± 0.58 versus 5.0 ± 1.2; P < 0.01). Conclusion. Exocrine pancreatic involvement is frequent in pSS and should be suspected in case of severe lacrimal dysfunction (ST < 2 mm). Not invasive pancreatic function tests could be useful to investigate pancreatic function in pSS. PO072 EXOCRINE PANCREATIC FUNCTION IN YOUNG TYPE I DIABETIC PATIENTS M. Candelli, E.C. Nista, D. Rigante, G. Marietti, I.A. Cazzato, G. Pignataro, R. Nista, G. Gasbarrini, A. Gasbarrini Departments of Internal Medicine and Pediatrics, Catholic University of Rome, Italy Introduction. Recent reports suggested a high prevalence of exocrine pancreatic involvement in both type 1 and type 2 diabetes mellitus. Few and limited by small samples, studies are present on this issue in literature on children and adolescents affected by Type I diabetes mellitus. Faecal elastase, a non-invasive pancreatic function test, allowed the evaluation of pancreatic function in children. Methods. Sixty-three type 1 young diabetic patients (mean age 12.5 ± 5.5 years; 38 males, 25 females; diabetes duration: 64.8 ± 55.3 months) were consecutively enrolled from our day hospital of paediatrics in Rome, Italy. Sixty-three sex and age matched healthy children were recruited as controls. Faecal elastase-1 concentrations was performed by ELISA (Meridian diagnostic, Milan, Italy for ScheboTech, Germany). Glycosilated haemoglobin a (Hba1c), daily insulin requirement and the duration of illness were established. A screening questionnaire concerning the presence and intensity of gastrointestinal symptoms was administered. Results. No differences in faecal elastase-1 concentration was found between young type 1 diabetic patients and controls. Elastase 1 < 200 ␮g/g stool was found in 5 of 63 (8%) diabetics patient and 2 out of 63 controls (3.2%). Among patients affected by diabetes, faecal levels of elastase lesser than 200 were associated to disease duration (99.4 months versus 59 months; P < 0.05). Hba1c, gastrointestinal symptoms and diabetes were not associated to lower levels of elastase 1. Conclusions. Our result showed that exocrine pancreatic involvement in type 1 diabetes mellitus was not more prevalent than in healthy control. Likely, as the low elastase 1 is associated to longer disease, pancreatic exocrine insufficiency may be a late complication of type 1 diabetes. PO073 GASTRODUODENAL AND INTESTINAL PERMEABILITY IN PATIENTS UNDERGOING HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PERIPHERAL BLOOD STEM-CELL TRANSPLANTATION (PBSCT) R. Cannizzaroa , M. Michielib , M. Rupolob , A. Franceschinc , E. Bidolid , M. Mazzuccatoe , M. Berrettab , U. Tirellib a Gastroenterology,

Centro Riferimento Oncologico-Aviano, Italy Oncology, Centro Riferimento Oncologico-Aviano, Italy c Clinical Pathology, General Hospital, Pordenone, Italy d Epidemiology, Centro Riferimento Oncologico-Aviano, Italy e Transfusion Medicine, Centro Riferimento Oncologico-Aviano, Italy b Medical

Administration of high-dose chemotherapy in patients undergoing autologous peripheral blood stem-cell transplantation (PBSCT) may damage gastrointestinal epithelium. The aim of our study was to evaluate gastroduodenal and intestinal permeability in patients undergoing high-dose chemotherapy and autologous peripheral blood stem-cell transplantation. Patients and methods. Thirty-two consecutive patients (24 male, 9 female; median age 47.3 years, range 18–69 years) were admitted

in our study between September 2001 and August 2003. Twenty patients had lymphoma, 11 multiple myeloma, 3 soft tissue sarcoma. Gastroduodenal and intestinal permeability was determined using sucrose/lactulose/mannitol absorption (SLM) test. Sucrose, lactulose and mannitol levels in the urine samples were determined by HPLC. Gastroduodenal permeability was expressed as the percentage recovery of the ingested dose of sucrose (%S) in the 6 h urine. Intestinal permeability was expressed as the ratio of the percentage recovery of the ingested dose of lactulose (%L) relative to that of mannitol (%M) in the 6 h urine (%L/%M). The SLM test was performed before administration of high-dose chemotherapy and after 15 days of autologous peripheral blood stem-cell transplantation. All patients were treated by omeprazole 40 mg during the period of treatment with PBSCT. Statistics: Wilcoxon test and χ2 -test were used. Results. Median levels of %L before PBSCT were: 0.98, after 15 days: 1.33; %M before: 14.9, after: 14.0; L/M before: 0.53; after: 0.57; %S before: 0.45, after: 0.87. No significant statistical difference was noted between levels of %L, %M and L/M before and after PBSCT. A significant statistical difference was noted in levels of %S before and after PBSCT (P = 0.01). Conclusions. In our study PBSCT does not affect intestinal permeability. A different approach rather than a reduction of gastric secretion to reduce gastroduodenal damage need to be evaluated. PO074 CLINICAL CHARACTERISTICS OF 98 CONSECUTIVE PATIENTS WITH GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOURS: A MONOINSTITUTIONAL EXPERIENCE IN AN ONCOLOGICAL INSTITUTION R. Cannizzaro, A. Buonadonna, L. De Appollonia, E. Borsatti, M. Cimitan, L. Balestreri, A. Gloghini, A. Carbone S.O. Gastroenterologia Oncologica, Centro di Riferimento Oncologico, Aviano, Italy Gastroenteropancreatic Neuroendocrine Tumours (G-NET) are rare neoplasias derived from cellular populations of the diffuse neuroendocrine system. The aim of our report was to describe clinical and histological characteristics of a consecutive series of patients with G-NET. From 1992 up to now, 98 patients with histological diagnosis of G-NET were admitted to our Institute. Results. Out of 98, 55% of patients were male and 45% female; median age at diagnosis was 54.5 years (range 15–78). Fifty-eight patients had well differentiated neuroendocrine tumour, 10 well differentiated neuroendocrine carcinoma, 22 poorly differentiated neuroendocrine carcinoma, 2 glucagonomas, 1 VIPoma, 2 gastrinomas and 3 insulinomas. The most frequent sites of disease were: pancreas (25.5%), colorectal (20.2%), small bowel (18.3%) and stomach (12.2%). At diagnosis, 50% of patients showed metastatic disease: liver (67%), lymphnodes (10%). In 28 asymptomatic patients, the diagnosis was casual; in symptomatic patients the most frequent symptoms were: abdominal pain (16%), diarrhoea (11%), dyspepsia (7%), acute abdomen (6%), flushing (5%), jaundice (4%) and rectal bleeding (3%). The diagnostic delay was less than 6 months in 43% of patients with no difference related to gender; it was more than 1 year in 11.2% (more frequent in male patients and in small bowel localisation of primitive tumour). No difference about diagnostic delay was reported according to histological diagnosis. Conclusions. In our experience a diagnosis of G-NET is asymptomatic in a quarter of patients while most of the diagnosis occurs in patients with metastatic, symptomatic disease. Therefore, we need man improved biochemical and instrumental tools to detect an early diagnosis.

Abstracts PO075 DIAGNOSTIC ROLE OF CAPSULE ENDOSCOPY WITH GIVEN VIDEO CAPSULE SYSTEM (VEC): OUR EXPERIENCE A. Cantone, A. Fuini, C. Manfrini, S. Benedetti, A. Battochhia Divisione di Gastroenterologia ed Endoscopia Digestiva, Ospedale Civile Maggiore, Verona, Italy Background. Enteroscopy with a Given capsule (VEC) is a recently introduced method which provides endoscopic images of the entire small bowel. The most important indication for this method is chronic occult gastro-intestinal bleeding, frequently located in the small intestine and therefore more difficult to detect with conventional radiology, enteroscopy and scintigraphy. Aim. To report our experience and assess, in retrospect, VEC indications and results. Patients and methods. From April 2002 to November 2003 we performed VEC on 37 patients (17 males and 20 females, average age 60, range 22– 87). Thirty patients (81%) suffered from chronic gastro-intestinal bleeding (obscure/occult), five (13.5%) were screened for a family history of polyposis and two (5.5%) for pseudopolypoid intestinal mass, the origin and nature of which had not been ascertained with CT scan. The average duration of the examination was 7 h and 6 min (range 4 h and 24 min to 8 h and 38 min) with an average gastric transit time between 5 and 15 min. All patients had had gastroscopy and colonoscopy. Results. The examination could not be completed in 2 of the 30 patients with gastro-intestinal bleeding: in one case because it proved impossible to go beyond the pylorus and in the other because the patient could not swallow the capsule. Out of the 28 remaining cases: 16 were negative. A diagnosis was made in 12 cases: 10 angiodysplasia/teleangiectasia of the small intestine, 2 of which were treated endoscopically with argon plasma (APC); 1 acute erosions due to FANS ingestion and one case of actual bleeding without any detectable lesion, which was treated with injection therapy. In patients with digestive bleeding, VEC had a diagnostic role in 42.8%. Only one of the five patients with familial polyposis had ileal polyps. Submucosal tumours (sessile pseudopolyp, covered by smooth mucosa) were found in both patients with an X-ray diagnosis of mass. Conclusions. Our experience confirms that the most important indication for VEC is digestive bleeding of unknown origin (81% of cases). A diagnosis was possible in 42.8% of our patients. This figure is in line with the extreme variability (30–67%) of the results described in literature. Further indications for this examination are still been evaluated because of the very small number of cases assessed so far. PO076 LOW PREVALENCE AND SEVERITY OF OESOPHAGITIS IN ENDOSCOPIC OUTPATIENTS M. Capanni, F. Calella, M.R. Biagini, A. Galli, G. Macr`ı, S. Milani, C. Surrenti, E. Surrenti Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy Background and aim. The prevalence of oesophagitis and its symptomatic manifestations are still a matter of controversy. In this study, we analysed the occurrence of oesophagitis and symptoms related to gastro-oesophageal reflux in outpatients undergoing upper gastrointestinal endoscopy (UGE) for unselected indications. Materials and methods. One hundred and sixty-nine outpatients (78 male, 91 females), mean age 55 years (range 21–87 years) consecutively referred to our Endoscopic Unit for UGE were enrolled from April to June 2003. Symptoms were recorded immediately before endoscopy. The presence of oesophagitis was diagnosed and scored according to both Savary–Miller and Los Angeles scoring systems. Data were analysed by chi-square test.

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Results. Erosive oesophagitis was found in 21/169 (12%) patients (11 males, 10 females), mean age 53 years (range 24–74 years). According to Savary–Miller score, 19 patients displayed grade I, 1 patient grade II, and 1 patient grade IV oesophagitis with Barrett disease. According to Los Angeles score, 16 patients showed grade A, 3 patients grade B, 1 patient grade C, and 1 patient grade D oesophagitis with Barrett disease. Twelve patients showed grade 0 oesophagitis according to Savary–Miller, represented by hyperemic or oedematous pattern of Z line. Completely normal oesophageal mucosa was seen in 148/169 (88%) patients (67 males, 81 females), mean age 57 years (range 21–87 years). Typical gastro-oesophageal reflux disease (GERD) symptoms were reported in 13/21 (62%) patients with oesophagitis (12 with grade I, and 1 grade II) versus 20/148 (14%) normal subjects (P < 0.001); atypical GERD symptoms occurred in 2/21 (9%) patients with oesophagitis (both with grade I) versus 3/148 (2%) patients with normal findings (P = NS). Six out of 21 (29%) patients with oesophagitis had no GERD symptoms, but 5 of them complained of either dysmotility-like (three patients) or ulcer-like dyspepsia two patients). Sliding hiatus hernia was seen in 14/21 (67%) patients with oesophagitis (13 grades I, and 1 grade IV) versus 52/148 (35%) patients with normal findings (P < 0.01). Conclusions. Prevalence of oesophagitis in outpatients undergoing UGE for unselected indications is relatively low. Most cases show initial erosive lesions, with a high prevalence of typical GERD symptoms and hiatus hernia. Atypical GERD symptoms occur in a small number of patients, with no significant differences in comparison to normal subjects. A significant number of patients displays oesophagitis even in the absence of GERD symptoms. PO077 HOMOCYSTEINE ALTERATIONS IN CHRONIC ALCOHOLIC LIVER DISEASE: COMPARISON BETWEEN ABUSER AND ABSTINENT PATIENTS M. Capannia , M.R. Biaginia , D. Nigroa , S. Nannia , N. Lazzerinia , R. Abbateb , S. Fedib , A. Gallia , S. Milania , V. Patussia , C. Surrentia a Gastroenterology

Unit and Alcohol Research Center, Department of Clinical Pathophysiology, University of Florence, Florence, Italy b Thrombosis Center, University of Florence, Florence, Italy

Background. Hyperhomocysteinaemia has been reported in chronic alcoholic liver disease (CALD) as a consequence of both dietary deficiency of folate, Vitamin B6 , Vitamin B12 and impaired function of liver enzymes involved in methionine metabolism. Moreover, hyperhomocysteinaemia has been indicated as a factor that may favour the development of liver fibrosis in these patients. Aim. To assess the prevalence of hyperhomocysteinaemia in patients with CALD, comparing patients on active alcohol abuse with patients having a history of previous abuse and at least 6 months of alcohol abstention. Materials and methods. Homocysteine blood levels were measured both in basal conditions and after methionine oral load in 42 patients (36 males, 6 females; mean age 51 years; range 19–66 years) with CALD and a history of heavy alcohol abuse (100–150 g daily of alcohol) for 5 or more years. Daily alcohol intake was evaluated by a validated questionnaire and abstinence for more than 6 months was recorded. Clinical, laboratory and instrumental data were collected and analysed by t-test and chi-square test. Results. Nineteen patients were abstinent for at least 6 months (16 males, 3 females; mean age 53 years; range 37–66 years), while 23 patients were active drinkers (20 males, 3 females; mean age 50 years; range 19–66 years). Basal levels of homocysteine were increased in 8/42 (19%) patients. In particular, high levels were found in 4/19 (21%) abstinents versus 4/23 (17%) active drinkers (P = NS). After methionine oral load, homocysteine levels were increased in 10/42 (24%) patients, specifically in 5/19 (26%) abstinents versus 5/23 (22%) abusers (P = NS). Folic acid blood level were not significantly different in abstinents versus active drinkers, with values of 6.6 ± 7.4 and 4.3 ± 2.6 ng/ml (P = NS), respectively. In contrast, alcohol abstention, compared with

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unbroken abuse, obtained significant decreases of AST (24±9.7 U/l versus 51.4 ± 50.6 U/l, P < 0.04), ALT (28.5 ± 16.8 U/l versus 42.3 ± 23.4 U/l, P < 0.05), GGT (53.8 ± 61.9 U/l versus 252.5 ± 272.3 U/l, P < 0.01), and mean corpuscular volume (93.9±7.3 fl versus 99.5±7.8 fl, P < 0.04). No significant changes were found in prothrombin time, triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol. Conclusions. Increased homocysteine level is present in high rates of patients with CALD. Patients in abstention for at least 6 months maintain a similar prevalence of hyperhomocysteinaemia than continuous alcohol abusers, whereas abstinence significantly improves liver enzymes and function. PO078 PREVALENCE OF TROMBOPHILIC FACTORS AND CORRELATION WITH LIVER FIBROSIS IN HCV-RELATED CHRONIC HEPATITIS M. Capannia , M.R. Biaginia , M. Pacia , N. Lazzerinia , R. Abbateb , S. Fedib , A. Gallia , C. Surrentia , S. Milania a Gastroenterology

Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy b Thrombosis Center, University of Florence, Florence, Italy

Background and aim. It has been suggested that the presence of thrombotic risk factors may influence the development of liver fibrosis in patients with chronic hepatitis C (CHC). We aimed to analyse the prevalence of thrombotic risk factors in patients with CHC and its correlation with the histological staging of the disease. Materials and methods. Thirty-eight patients (22 males, 16 females; mean age 51 years; range 28–71 years) affected by CHC were investigated for a large panel of coagulation parameters. Biopsy was performed on 31 patients. Laboratory data were compared to histologic findings. Statistical analysis was performed by t-test and Fisher exact test. Results. Low stage fibrosis (LF: stages F1–F2 Metavir) was found in 19/31 (61%) patients, while high stage fibrosis (HF: stage F3 Metavir) in 12/31 (39%) patients. No patients had cirrhosis. Among the various coagulation findings it resulted in the platelet count of 164,818.2 ± 51,646.5 ␮l−1 in patients with HF versus 224,222.2 ± 139,934 ␮l−1 in patients with LF; prothrombin time: 90.5 ± 8.8% versus 97.3 ± 6.2%; fibrinogen: 280.4 ± 39.4 mg/dl versus 289.2 ± 47.5 mg/dl; factor VIII: 107.5 ± 46.6% versus 109.1 ± 39.2%; protein C: 88.3 ± 16.2% versus 104 ± 21.2%; protein S: 78.5 ± 14.7% versus 74.3 ± 12.5%; lipoprotein a: 153 ± 78.2 mg/l versus 150.8 ± 80.4 mg/l; PAI-1 (plasminogen activator inhibitor-1): 29.8 ± 12.1 ng/ml versus 46.4 ± 29.7 ng/ml; IgM anti-cardiolipin antibodies: 1.6 ± 1 U/ml versus 2.1 ± 1.5 U/ml; IgG anti-cardiolipin antibodies: 3.9 ± 1.6 U/ml versus 4.4 ± 3.8 U/ml; tissue factor: 280 ± 84.9 pg/ml versus 326.7 ± 91.7 pg/ml; homocysteine: 12.9 ± 3.9 ␮mol/l versus 12.6 ± 6.1 ␮mol/l; folic acid: 4.1 ± 0.8 ng/ml versus 3.9 ± 1.5 ng/ml. We did not find statistical differences of any trombophilic factors in patients with HF compared with patients with LF (t-test: P = NS). Moreover, we analysed, by Fisher test, the presence of one or more ematochemical thrombotic risk factors (TRF). In the group with HF there were 4/12 (33%) patients with no TRF, 3/12 (25%) patients with 1 TRF, and 5/12 (42%) patients with >1 TRF; in the group with LF there were 8/19 (42%) patients with no TRF, 4/19 (21%) patients with 1 TRF, and 7/19 (37%) patients with >1 TRF. Differences of TRF in liver disease with HF versus liver disease with LF were not statistically significant. Conclusions. Most patients with different stages of CHC do not show multiple coagulative alterations. From our data, a significant correlation of thrombophilic factors with liver fibrosis could not be found. On the other hand, this study does not include cirrhotic patients, where hyperhomocysteinaemia may be involved in a cause–effect mechanism with liver impairment and fibrosis.

PO079 PROLONGED n-3 PUFA DIETARY SUPPLEMENTATION IMPROVES FATTY LIVER IN PATIENTS WITH NAFLD: PRELIMINARY RESULTS FROM A PILOT STUDY M. Capannia , F. Calellaa , G.R. Centenaroa , M.R. Biaginia , S. Milania , L. Raimondib , A. Mugellib , C. Surrentia , A. Casinia a Nutrition

Center and Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy b Department of Clinical Pharmacology, University of Florence, Florence, Italy

Background. Non-alcoholic fatty liver disease (NAFLD) is a common, multifactorial disease. Several studies have shown that omega (n-3) polyunsaturated fatty acids (PUFA) are effective to prevent cardiovascular diseases, but scarce information is available regarding the liver. Aim. To analyse the effects of prolonged PUFA dietary supplementation in patients with NAFLD. Materials and methods. Patients with preliminary ultrasound findings of fatty liver were consecutively enrolled into the study. Subjects with liver steatosis due to viral hepatitis, alcohol abuse and drugs were excluded. All patients were planned for oral administration of PUFA (eicosapentaenoic acid/docosahexaenoic acid) 1000 mg daily for 12 months. They underwent ematochemical and ultrasound investigation at baseline and after 6 and 12 months of treatment. Data were analysed by t-test, chi-square test and Fisher exact test. Results. We enrolled 31 patients: 16 males, 15 females; mean age 56.9 years (range 28–77); body mass index 28.6 ± 4.5 (range 23–38.6). The t-test analysis after 6 months of PUFA intake did not find significant differences, compared with baseline, in blood level of AST (23.3 ± 6.9 U/l versus 28.6 ± 4.5 U/l), ALT (32.2 ± 18.2 U/l versus 31.9 ± 16.7 U/l), GGT (50.4 ± 37.9 U/l versus 50.1 ± 51.9 U/l), total cholesterol (214.6 ± 38 mg/dl versus 222.6 ± 39.8 mg/dl), lipoprotein a (255.4 ± 258.4 mg/l versus 215.5 ± 223.5 mg/l), glucose (1.01 ± 0.2 g/l versus 1.01 ± 0.26 g/l), C-reactive protein (0.65 ± 0.5 mg/dl versus 1.32 ± 1.42 mg/dl), homocysteine (15.7 ± 10.9 ␮mol/l versus 11.3 ± 3.7 ␮mol/l), and folic acid (6.3 ± 3.2 ng/ml versus 5.4 ± 2.2 ng/ml). Significant increases were found for LDL cholesterol (135.7 ± 34.9 mg/dl versus 116.5 ± 31.2 mg/dl; P < 0.001), and HDL cholesterol (65.5 ± 13 mg/dl versus 51.3 ± 16.8 mg/dl; P < 0.04). A significant reduction of triglycerides (141.9 ± 61 mg/dl versus 182.2 ± 42.4 mg/dl; P < 0.01) was also found. The ultrasound control after 6 months of treatment was performed on 26 patients. Improvement in liver echotexture with regression of steatosis was seen in 12/26 patients (46%), although data were not significant by chi-square test and Fisher exact test. Conversely, the Doppler perfusion index (hepatic artery blood flow/liver total blood flow) was significantly increased (0.19 ± 0.03 versus 0.13 ± 0.05; t-test: P < 0.001), next to the normal range (0.20–0.30), thus suggesting a reduction in the extension of liver fat deposition. Conclusions. Prolonged dietary supplementation with PUFA ameliorates fatty liver in patients with NAFLD and opens new therapeutical approaches for this disease. PO080 PEG-INTERFERON ALPHA-2b PLUS RIBAVIRIN COMBINATION THERAPY REMOVES HCV INFECTION ALMOST IN ALL PATIENTS WITH 2–3 GENOTYPE HCV-RELATED CHRONIC HEPATITIS M. Capannia , G.R. Centenaroa , E. Loreficea , E. Gaia , S. Nannia , P. Pignalosab , C. Surrentia , S. Milania a Gastroenterology

Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy b Gastroenterolgy Unit, Santa Verdiana Hospital, Castelfio- rentino, Empoli, Italy Background and aim. Phase III studies have shown that combination therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) is more

Abstracts effective than standard interferon and RBV in naive patients with chronic hepatitis C (CHC). Data on treatment of non-responders and relapsers to combined therapy are however still controversial. We evaluated the efficacy of PEG-IFN alpha-2b and RBV, both in naive and retreated patients. Materials and methods. Consecutive patients with CHC eligible for therapy were scheduled to receive PEG-IFN alpha-2b 1 ␮g/kg weekly s.c. plus RBV 800–1200 mg daily per os, for 24 (genotypes 2–3) or 48 weeks (genotypes 1–4). All patients underwent liver biopsy before treatment. Sustained virological response (SVR) was defined as undetectable circulating HCV-RNA by a qualitative PCR assay (sensitivity 100 IU/ml) after 24 weeks of follow-up. Data were analysed by chi-square test. Results. We studied 74 patients: 48 naives (33 males, 15 females; mean age 48 years, range 19–69 years), and 26 previously either non-responder or relapser patients (22 males, 4 females; mean age 54 years, range 39–69 years). SVR was as follows: naive patients: overall, SVR was found in 34/48 (71%) patients. Precisely, SVR was achieved in 11/23 (48%) 1–4 genotypes versus 23/25 (92%) 2–3 genotypes (P < 0.001); 14/19 (74%) patients with baseline HCV-RNA <500,000 IU/ml versus 20/29 (69%) patients with baseline HCV-RNA >500,000 IU/ml (P = NS); 29/39 (74%) patients with chronic hepatitis versus 5/9 (56%) patients with cirrhosis (P < 0.01); 12/15 (80%) F versus 21/33 (67%) M (P < 0.05); 15/19 (79%) <40-year-old patients versus 19/29 (66%) >40-year-old patients (P < 0.05); 22/27 (81%) patients with body mass index (BMI) <25 versus 12/21 (57%) patients with BMI >25 (P < 0.001) retreated patients: overall, SVR was found in 12/26 (46%) patients. 4/18 (22%) 1–4 genotypes versus 8/8 (100%) 2–3 genotypes (P < 0.001); 6/10 (60%) patients with baseline HCV-RNA <500,000 IU/ml versus 6/16 (38%) patients with baseline HCV-RNA >500,000 IU/ml (P < 0.003); 11/23 (48%) patients with chronic hepatitis versus 1/3 (33%) patients with cirrhosis (P < 0.04); 2/4 (50%) F versus 10/22 (45%) M (P = NS); 3/5 (60%) <40-year-old patients versus 9/21 (43%) >0-year-old patients (P < 0.02); 8/16 (50%) patients with BMI <25 versus 4/10 (40%) patients with BMI >25 (P = NS). Conclusions. Combination therapy with PEG-IFN alpha-2b and RBV achieves SVR in most cases of 2–3 HCV genotypes (over 90% of patients), whereas in 1–4 genotypes SVR is limited to less than 50% of naives and about 20% of retreated patients. HCV genotype is the most important predictor of therapy effectiveness, both in naive and retreated patients. The table shows the comparison between favourable and unfavourable predictive factors (chi-square test): number and percentage of sustained virological response with PEG-IFN alpha-2b plus RBV.

Favourable predictive factors Naive patients HCV 1–4 genotypes: 11/23 (48%) Basal viral load <500,000 IU/ml: 14/19 (74%) Chronic hepatitis: 29/39 (74%) Females: 12/15 (80%) Age <40 years: 15/19 (79%) BMI <25: 22/27 (81%) Patients on retreatment HCV 1–4 genotypes: 4/18 (22%) Basal viral load <500,000 IU/ml: 6/10 (60%) Chronic hepatitis: 11/23 (48%) Females: 2/4 (50%) Age <40 years: 3/5 (60%) BMI <25: 8/16 (50%)

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PO081 INCREASED APOPTOSIS AND FAVOURABLE PROGNOSIS IN T LYMPHOCYTE-RICH GASTRIC CARCINOMAS C. Capella, A.M. Chiaravalli, M. Feltri, D. Furlan, R. Cerutti Department of Human Morphology, University of Insubria, Ospedale di Circolo Varese, Italy Background and aim. Gastric carcinomas (GCs) with abundant tumour infiltrating lymphocytes (TILs) are usually characterised by the presence of high level DNA microsatellite instability (MSI+) or Epstein Barr virus infection (EBV+). Both these types of tumours are associated with a better prognosis. The aim of this study was to determine if TILs are associated with a better clinical outcome in GCs patients and if the nature and the activation status of TILs of MSI+ GCs could be involved in tumour cell apoptosis. Materials and methods. A series of 86 GCs was analysed for the presence of CD3 + TILs. In addition, the tumour cell apoptosis and the phenotype of TILs were evaluated with immunohistochemistry in 66 cases, including 35 MSI+ GCs, and 31 MSI− GCs with abundant TILs, 7 of which were EBV+. Kaplan–Meier curves were used to estimate overall survival and were compared with the use of the log-rank test. Results. The mean number of CD3+ TILs, evaluated in 10 high power fields for case, varied from 0 to 77 (mean: 18.07; median 12.3). The overall survival of patients with a number of CD3 + TILs higher than the median value was significantly better than that of the other patients (P = 0.0154). MSI+ and MSI-/EBV+ GCs displayed a significantly higher mean number of cytotoxic TILs than MSI-/EBV- tumours (CD3: 30.7 and 29.8 versus 9.9; CD8: 21.7 and 22.1 versus 6.4; TIA-1: 16.7 and 15.6 versus 5.2; P < 0.01). In addition, the activated TILs were more frequent in MSI+ than in MSI−/EBV− GCs (mean granzyme B immunoreactive TILs: 7.5 versus 0.8; perforin 5.9 versus 0.9; P < 0.01). The percentage of apoptotic tumour cells, evaluated with the M30 CytoDeath antibody, was higher in both MSI+ and MSI−/EBV+ GCs than in MSI−/EBV− GCs (5.99% and 4.31% versus 2.5%; P < 0.01). Conclusions. The presence of TILs in GCs correlated with a better overall survival of the patients. In addition, the lymphoid infiltration in MSI+ GCs was significantly higher than that of MSI- GCs (except for EBV+ GCs). This could be consistent with a tumour-specific immune response and might explain the increased apoptotic index and the relatively better prognosis of these tumours.

Unfavourable predictive factors

P-value

PO082

HCV 2–3 genotypes: 23/25 (92%)

<0.001

IN VITRO ACTIVITY OF FLUOROQUINOLONES AGAINST HUMAN H. pylori

Basal viral load >500,000 IU/ml: 20/29 (69%)

NS

S. Capodicasa, L. Cellini, S. Di Bartolomeo, D. Coraggio, L. Marzio

Cirrhosis: 5/9 (56%) Males: 21/33 (67%) Age >40 years: 19/29 (66%) BMI >25: 12/21 (57%)

<0.01 <0.05 <0.05 <0.001

HCV 2–3 genotypes: 8/8 (100%)

<0.001

Basal viral load >500,000 IU/ml: 6/16 (38%) Cirrhosis: 1/3 (33%) Males: 10/22 (45%) Age >40 years: 9/21 (43%) BMI >25: 4/10 (40%)

<0.003 <0.04 NS <0.02 NS

G. D’Annunzio University, Chieti-Pescara, Italy Background and aim. Primary and secondary resistance of H. pylori to metronidazole, tinidazole and clarithromycin, represents the main cause of treatment failure. Therefore, the search for new and more effective agents with low or absent resistance (primary or secondary) is mandatory. In vitro antibiotic susceptibility test is the main step when such search is undertaken. The aim of this study has been to evaluate in vitro the sensitivity of human H. pylori to the new fluoroquinolones moxifloxacin and levofloxacin in comparison with other antibiotics commonly used for triple therapy. Materials and methods. H. pylori strains were obtained from antral biopsies during upper endoscopy in patients with chronic dyspepsia. The specimens were spread on selective agar plates (Columbia Agar base supplemented with 0.4% DENT and 7% horse sterile blood) and on no-selective agar plates (Columbia agar base supplemented with 1% isovitalex and 10% horse sterile blood). Plates were incubated in micro aerobic atmosphere (85% N2 , 10% CO2 , 5% O2 ) at 37 ◦ C for 3–5 days. Positive samples were submitted to susceptibility test to the following antibiotics:

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amoxicillin, tinidazole, clarithromycin, rifabutin, moxifloxacin and levofloxacin. The susceptibility test was performed using agar plates containing 7% sterile horse blood plus the antimicrobial agents moxifloxacin and levofloxacin were tested at the concentration of 5 ␮g/ml. After 3–5 days incubation at 37 ◦ C in microaerobic atmosphere bacterial growth at various antibiotics concentration (from 0.05 to 5 ␮g/ml) was observed. Results. Twenty H. pylori strains were totally tested. Ten from patients with no history of specific treatment for H. pylori in their past, and ten from patients who had already undergone to triple therapy. Resistance to antibiotics is shown in the table.

Resistance primary Resistance secondary

No.

Amoxicillin

Rifabutin

Tinidazole

Claritromycin

Moxifloxacin

Levofloxacin

10

0

0

0

5

0

0

10

1

2

5

5

2

2

multi-resistant strains showed a sensitivity pattern similar to the one expressed by the sensitive strains. The strains resistant to antibiotics were inhibited by the ethanol extracts from C. cyminum and Propolis with a MIC of 0.3 mg/ml. Ethanol extracts from C. scolymus and Z. officinalis were effective in inhibiting all the tested strains with a MIC of 0.3–0.6 mg/ml. Conclusions. Our results show an antagonising effect of some plant extracts against in vitro growth of human H. pylori. This effect is not associated with antibiotic resistance. Whether plant extracts may be used alone or as adjuvants in the treatment of H. pylori infection remains to be investigated. PO084 INFLIXIMAB IN THE TREATMENT OF STEROID-REFRACTORY SEVERE ULCERATIVE COLITIS: OUR EXPERIENCE M. Cappello, S. Peralta, V. Calvaruso, M. Pia Savarino, A. Crax`ı Department of Gastroenterology, Policlinico di Palermo, Italy

Conclusions. Primary resistance to fluoroquinolones is absent in our series, while secondary resistance is present at various degree for all antibiotic tested with higher values for clarithromycin and tinidazole. Although these data await further validation with greater number of strains, it may be suggested that fluoroquinolones may be proposed for empirical first line therapy for H. pylori infection. In case of patients already treated for H. pylori infection, the various antibiotics must be chosen on the basis of susceptibility test. PO083 PLANT EXTRACTS SHOW INHIBITORY ACTIVITY AGAINST HUMAN H. pylori “IN VITRO” S. Capodicasa, L. Cellini, S. Di Bartolomeo, R. Grande, M. Di Campli, L. Marzio G. D’Annunzio University, Chieti-Pescara, Italy Background and aim. H. pylori therapeutic failure due to resistant strains was increased in the last years. New therapies are under investigation and among these the potential antibacterial effect of plant extracts has been an attractive alternative. The aim of this study has been to investigate the effect of water and ethanol extracts obtained from 17 plant materials on human H. pylori. Materials and methods. Seventeen dried plants (Cichorium intybus, Cinnamomum zeylanicum, Coriandrum sativum, Cuminum cyminum, Cynara scolymus, Electaria cardamomum, Foeniculum vulgare, Juniperus communis, Menta piperita, Origanum vulgare, Propolis, Prunus avium, Rosmarinus officinalis, Salvia officinalis, Thymus serpyllum, Tilia platyphyllos, Zingiber officinalis) have tested using water and ethanol extracts for a total of 34 preparation. The antibacterial effect of these plants were preliminarily tested on H. pylori ATCC43629. The extracts giving an inhibition zone >9 mm in diameter were chosen to assay the Minimum Inhibitory Concentration (MIC) on H. pylori strains obtained from patients who had undergone upper endoscopy for chronic dyspepsia. H. pylori was cultured with agar dilution method according to the NCCLS guidelines. The MIC was determined using a concentration of substance from 10 to 0.15 mg/ml on solid media. All strains were also tested for sensitivity to clarithromycin, amoxicillin, rifabutin and tinidazole. Results. Eleven strains of human H. pylori were tested. Eight water extracts from (Coriandrum sativum, Cynara scolymus, Origanum vulgare, Propolis, Prunus avium, Salvia officinalis, Thymus serpyllum, Zingiber officinalis) and 13 ethanol extracts (Cichorium intybus, Cinnamomum zeylanicum, Coriandrum sativum, Cuminum cyminum, Cynara scolymus, Electaria cardamomum, Juniperus communis, Propolis, Prunus avium, Rosmarinus officinalis, Salvia officinalis, Thymus serpyllum, Zingiber officinalis) were effective in inhibiting H. pylori. Maximal MIC reached was 1.25 mg/ml. The bacterial strains showed in some case resistance to one or multiple antibiotics. However, when tested with plant extracts, the

Background and aim. The role of Infliximab in acute severe attacks of ulcerative colitis is still controversial. Response rates between 50 and 70% have been reported in patients with severe steroid-refractory disease in at least six studies (four open label and one RCT), while a recent RCT on patients with moderate active steroid resistant disease shows no difference between infliximab and placebo. We carried out a small pilot study in patients with severe ulcerative colitis resistant to high doses of steroids. Materials and methods. Five patients with a severe episode of ulcerative colitis admitted to our Unit have been studied. The diagnosis of UC was proven by histology in all patients. Disease severity was defined according to Truelove and Witts criteria. In all cases the Truelove score was ≥10. All patients were treated with high doses of steroids (methylprednisolone 60 mg per day) and total parenteral nutrition for at least 7 days. One of them had also received a course of i.v. cyclosporine. All patients were treated with a single intravenous infusion of Infliximab 5 mg/kg. Results. Infusions of infliximab produced no adverse events. Four patients (80%) had a favourable clinical response to therapy as defined by a clinical activity index (Truelove score ≤2) and avoided surgery. One patient who did not respond to infliximab received a subsequent course of i.v. cyclosporine and went into clinical remission. The mean time of follow-up was 13.6 months (range 3–24). All patients (100%) maintain up to now a stable clinical remission and have been able to discontinue steroid therapy. Two of them are on long-term immunosuppression with azathioprine. None of the patients has been operated. Conclusions. Infliximab appears to be effective in inducing long-standing remission in patients with steroid-refractory severe ulcerative colitis. It could be used as a rescue therapy for avoiding urgent colectomy and a safer alternative to cyclosporine in terms of side-effects. The results need to be verified in large randomised studies. PO085 REDUCED PLASMA GHRELIN CONCENTRATION IN COELIAC DISEASE AFTER GLUTEN-FREE DIET TREATMENT E. Capristo, S. Farnetti, M. Certo, G. Addolorato, L. Leggio, G. De Lorenzi, L. Abenavoli, A. Ferrulli, G. Mingrone, A.V. Greco, G. Gasbarrini Istituto di Medicina Interna, Università Cattolica, Rome, Italy Background and aim. Coeliac disease (CD) is characterised by weight loss, malabsorption and increased energy expenditure. The gastro-intestinal tract represents a site of production of leptin and ghrelin, which are involved in energy balance regulation in humans. The aim of the present study was to evaluate changes in body composition, energy metabolism, plasma leptin and ghrelin concentration in patients with CD before and after a gluten-free diet (GFD) treatment. Materials and methods. Body composition (by dual-energy X-ray absorptiometry), resting metabolic rate (RMR), and substrate oxidation rates

Abstracts (by indirect calorimetry) were assessed in 18 adult women with the classic form of CD (age 31.4 + 17.8 years, body mass index (BMI) 20.8 ± 12.1 kg/m2 ) before and 1 year after GFD treatment and in 20 age-matched healthy women (age 32.8±17.0 years, BMI 23.2 = B12.3 kg/m2 ). Plasma leptin and ghrelin concentrations were assessed by an ELISA procedure and a RIA kit, respectively. Results. CD patients had a lower body weight both before (P < 0.01) and after GFD (P < 0.05) than healthy subjects. Fat-free mass (kg) was reduced before and after GFD compared to controlled subjects (P < 0.01), while fat mass increased after treatment (P < 0.01). A higher carbohydrate oxidation rate was found in untreated patients compared to treated and control subjects (P < 0.001). Plasma leptin concentration (ng/ml) was significantly lower in CD patients compared to healthy subjects (untreated CD: 12.1 ± 14.0; treated CD: 13.1 ± 13.9; controls: 16.0 ± 12.8, respectively; P < 0.05) and positively correlated only with BMI (P < 0.0001) and percentage body fat (P < 0.0001) in both patients and controls. Circulating ghrelin level (pg/ml) was similar between untreated patients and control subjects, but decreased after GFD treatment (untreated CD: 282.6 ± 155.5 versus treated 109.2 ± 149.9, P < 0.0001 and versus control subjects 281.8 ± 148.0, P < 0.0001). Conclusions. This is the first longitudinal study that evaluates circulating leptin and ghrelin concentration in CD. Plasma leptin concentration did not correlate with the changes in body composition and substrate oxidation found in CD patients. The low plasma ghrelin concentration shown by patients after GFD treatment could be almost partially explained by the slight increase in body weight. Further studies are needed to better ascertain the role played by an incomplete functional or quantitative recovery of ghrelin-producing cells in CD. PO086 RELATIONSHIP BETWEEN CIRCULATING LEPTIN, INFLAMMATORY ACTIVITY AND INSULIN SENSITIVITY IN PATIENTS WITH CROHN’S DISEASE E. Capristo, S. Farnetti, G. Addolorato, L. Leggio, G. De Lorenzi, L. Abenavoli, M. Eugenia Di Paola, G. Mingrone, A.V. Greco, G. Gasbarrini Istituto di Medicina Interna, Università Cattolica, Rome, Italy Background and aim. Patients with chronic inflammatory diseases, such as Crohn’s disease (CD), may be at risk of developing an insulin-resistant state, due to increased inflammatory mediator concentration and long-term steroid treatment. The aim of this study was to evaluate whole body glucose uptake and oxidation in CD patients with different degrees of disease activity, and the potential relationship between insulin sensitivity and serum leptin, a hormone involved in energy balance regulation. Materials and methods. Eighteen male patients with inactive (CDAI < 120; n = 6), mild (CDAI = 150–250; n = 6) or active (CDAI > 250; n = 6) disease were enrolled in the study. All patients had clinical, radiologic, histologic and biochemical assessment. Twenty healthy subjects matched for age and height were used as controls. Body composition was determined by dual-energy X-ray absorptiometry; substrate oxidation was measured by indirect calorimetry; a 7-day food diary was collected to evaluate energy intake. Insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp. Serum tumour necrosis factor (TNF)-␣ receptors (RR) and leptin were determined by an ELISA procedure. Results. Regardless of the disease activity, CD patients showed lower body weight (P < 0.001) due to reduced fat mass (P < 0.01), compared to controls. Peripheral glucose uptake (±5 mol/kg min) did not differ between CD patients and controls (42.1±16.2 in inactive CD, 42.8±17.2 in mild CD, 39.8 ± 19.1 in severe CD and 41.8 ± 18.4 in controls, respectively). Glucose storage and oxidation did not differ between groups. Insulin concentration tended to be higher in patients with mild (P = 0.055) and severe (P = 0.052) disease than in controls. Serum TNF-␣ RR concentration was higher in patients with mild (P < 0.05) and severe disease (P < 0.001) compared to inactive patients and controls, and negatively correlated with energy intake (R2 = 0.63; P < 0.0001).

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Serum leptin concentration showed a positive correlation with fat mass in all groups (P < 0.001), while no correlation was found with the other variables examined. Conclusions. Whole body glucose disposal was similar between CD patients and control subjects, probably as a consequence of fat-free mass preservation. Serum leptin did not influence insulin sensitivity in CD patients, while increased blood cytokine level could be responsible for the higher insulinaemia and decrease energy intake found in patients with active disease. PO087 GENE EXPRESSION PROFILES OF NON-FUNC- TIONING PANCREATIC ENDOCRINE TUMOURS G. Capursoa , T. Crnogorac-Jurcevicb , S. Lattimoreb , F. Panzutoa , V. Bhaktab , S. Nasonia , M. Milionec , C. Bordic , N. Lemoineb , G. Delle Favea a Department

of Digestive and Liver Disease, II School of Medicine, University “La Sapienza”, Rome, Italy b Molecular Oncology Unit, Cancer Research UK, Imperial College School of Medicine, London, UK c Department of Pathology, University of Parma, Italy

Background. Pancreatic neuroendocrine tumours (PNETs) are a rare group of neoplasms arising from pancreatic islet cells, with an incidence of around 0.4/100.000. From a clinical viewpoint, they are classified as either “functioning” or “non-functioning” depending on the presence or absence of a clinical syndrome due to excessive hormone secretion from the neoplastic cells. Non-functioning (NF) tumours account for about one third of all PNETs. The molecular events culminating in a PNET are not understood properly, due to the low prevalence and the significant heterogeneity of these tumours, and for NF PNETs few markers are available. A large-scale approach, such as that offered by microarrays, could potentially identify biomarkers associated with NF PNET growth and metastasis, and possibly also novel targets for therapy. Aim and methods. We, therefore, aimed to define the genetic profiles involved in developmental pathways in NF PNETs by microarrays. Methods. We obtained gene expression profiles by microarray using Affymetrix Human Genome U133 (HG-U133) Set (chips A and B) from 14 NF PNET samples (8 primary and 6 liver metastases) from 10 individual patients, 3 human PNET cell lines (QGP-1, BON and CM), normal pancreas and isolated normal pancreatic islets. Results. Preliminary analysis of the emerging array data has identified a subset of ∼1000 highly differentially expressed genes, segregating into 674 over-expressed genes in the samples when compared to normal, and 330 under-expressed. Validation of some of these targets is already underway for those identified as differentially expressed and of potential clinical interest. Conclusion. These preliminary data represent the first study of its kind aimed at elucidating the molecular events contributing to the establishment and progression of PNETs. PO088 THE SYRE (SYMPTOMS IN RE-OESOPHAGITIS) PROJECT: AN EVIDENCE BASED APPROACH TO UNINVESTIGATED DYSPEPSIA. PRELIMINARY DATA L. Capurso, A. Dezi, T. Casetti, S. Balzani, M. Del Piano, P. Cognein, A. Franzé, A. Bertelé, G. DePretis, S. Giaccari, L. Allegretta, S. Gullini, A. Marangoni, G. Iaquinto, R. Grasso, C. Virgilio, F. Chilovi, K. Mauer, M. Koch, L. Capurso Prof. L. Capurso, Unità Operativa Gastroenterologia, Azienda Osperaliera S. Filippo Neri v Martinotti 20, 00135 Rome, Italy Aim. To measure in a 2◦ referral subset (a) the prevalence of functional dyspepsia subgroups, (b) the “natural history” of symptoms during a

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12-month follow-up (FU), (c) the symptom and gastritis evolution in the functional dyspepsia (FD) patients during a 12-month follow-up. Recommendations. The observational study utilised a digital record based on the actual evidences. The system provided recommendations on diagnostic tests and therapies for FD and GERD patients based on four algorithms: (1) the presence of alarm symptoms; (2) NSAIDs use; (3) the dominant symptom; (4) HP infection. Materials and methods. Fourteen GI Units participated accepting consecutive patients with uninvestigated dyspepsia. Each patient underwent endoscopy and therapy, and was followed according to the clinical algorithms evaluated using visual analogue scores (VAS) and a functional dyspepsia index (FDI: symptom frequency + intensity/100 of maximum scores) at base line and at 1, 6, 12 months PRELIMINARY DATA. The table show the preliminary data on symptoms variations after the first 1-month period of therapy. PPI in FD&GERD and eradication in HP+ seems to be efficacious in this preliminary evaluation. The evolution of symptoms and of gastritis according to a preestablished algorithm will come from further analysis. Number

Pyrosis

Nausea

Acidity

Epig. pain

Retrost. pain

FD

149

125 R

7 R

34 R

112 R

34 R

1-month FU drug

138

117 PPI

76

71 R 68

GERD 1-month FU HP+ eradicated 1-month FU

52

U 8

2 PK

U

5 R

U 3

30 PPI

U

75 R

U 2

53 PK

U

44 R

U 48

20 PPI

U 11

US, GEC, baseline, 1 and 2 h Cleps after standard meal (1200 kcal, 50% carbohydrates, 30% lipids, 20% proteins). Results. LFTs were normal in all subjects. US showed bright (hyperechoic) liver only in obese patients. FLM values were similar in the two groups (507 ± 102 versus 540 ± 140, ns). Baseline FLPF was lower in obese than in controls (569 ± 150 ml/min versus 700 ± 156 ml/min, P < 0.05). However, meal significantly increased FLPF (P < 0.01) and 1 h FLPF was similar in both groups (888 ± 295 versus 997 ± 205, ns). Conclusions. The lower values of FLPF in obese possibly depend on fatty infiltration of the liver. Normal response of FLPF to post-prandial hyperaemia and normal FLM values suggest intact flow reserve and preserved liver function in simple steatosis. Follow-up with non-invasive dynamic tests in NAFLD is proposed to investigate progression to fibrosis. PO090 EMERGENCY HIGH-FREQUENCY US MINIPROBES: A QUICK AND SAFE PROCEDURE IN THE DIAGNOSIS AND MANAGEMENT OF A DUODENAL BLEEDING GANGLIOCYTIC PARAGANGLIOMA P. Caruccia , F. Curria , A. Repicia , S. Konstantinidoua , P. De Paolib , N. Leonea , D. Garabelloc , D. Gallianod , M. Rizzettoa , C. De Angelisa a Department

U

621 R

U

3

2

3

72

3

32

4

58

4

48 R

U

12 R

U

48 R

U

41 R

U

22 R

U

41

7

5

7

44

4

35

6

10

12

R, responder (FDI <0–1); U, non-responder (FDI >1); PPI, proton pump inhibitor; PK, prokinetic.

Acknowledgement. Sponsored by Malesci, Florence. PO089 DYNAMIC EVALUATION OF FUNCTIONAL LIVER PLASMA FLOW (FLPF) IN OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) V. Caramello, M. Tinivella, P. Peretti, R. Gabriella Masera, A. Dovio, A. Angeli, P. Avagnina Department of Clinical and Biological Sciences, University of Turin, A.S.O. San Luigi di Orbassano, Turin, Italy Background and aims. Non-alcoholic fatty liver disease (NAFLD) is an emerging clinical problem in obese and is the most common diagnosis in patient with persistent abnormalities of liver function tests (LFTs). NAFLD is an increasing histological finding in liver biopsy (47% of criptogenic cirrhosis). Although traditionally described as an asymptomatic liver disease with a benign prognosis, NAFDL includes a spectrum of hepatic pathology that ranges from fatty liver (steatosis) and non-alcoholic steatohepatitis (NASH) to cirrhosis and liver failure. Furthermore NAFLD may exacerbate postnecrotic, iron-, toxic- and drug-induced liver damage. The diagnosis, grade and stage can only be made by liver biopsy while traditional LFTs and ultrasound (US) have low sensitivity and fail to give reliable information about liver function and progressive disease. The present case-control study is aimed to evaluate changes of liver function in obesity using non-invasive dynamic liver function tests [sorbitol hepatic clearance (Cleps) measuring functional liver plasma flow (FLPF) and galactose elimination capacity (GEC) assessing functional liver mass (FLM)]. Materials and methods. Seventeen obese patients aged 23–72 years [M/F: 5/12, BMI = 38.5 kg/m2 ± 7 (mean ± S.D.)] and 12 healthy non-obese controls (BMI ≤25 kg/m2 ) were enrolled. All subjects underwent: LFTs,

of Gastroenterology and Hepatology, ASO S. Giovanni Battista, Turin, Italy b Department of Surgery, ASO S. Giovanni Battista, Turin, Italy c Department of Radiology, ASO S. Giovanni Battista, Turin, Italy d Department of Human Pathology, ASO S. Giovanni Battista, Turin, Italy Background and aim. Gangliocytic paraganglioma (GP) is an uncommon non-epithelial tumour, generally benign, occurring almost exclusively in the II portion of the duodenum, sometimes involving the ampulla of Vater. Just a few reports in the literature have presented its endoscopic ultrasonographic (EUS) features. This is the first case discussing the use of high-frequency ultrasound probe sonography (HFUPS) in emergency to diagnose and help decision making in a patient bleeding from an ulcerated GP, close to the major papilla. Case report. A 41-year-old man presented with precordial chest pain, weakness and melena in the last few days. On examination he was normal except for paleness. Laboratory demonstrated mainly anaemia (haemoglobin 5.7 g/dl). Emergency endoscopy showed a smooth-surfaced polyp, with a central ulcer, whose base was haemorrhagic. It appeared to arise from the distal part of the papilla. During EGD we performed a HFUPS with a miniprobe (Aloka, 8 Fr, 10–30 MHz) inserted through one of the accessory channels of a double-channel therapeutic videoendoscope. Results. HFUPS revealed a 12 mm × 20 mm hypoechoic lesion on a very brief and squat stalk, originating from the submucosa, slightly inhomogeneous, with a few anechoic areas, due to vascular structures, one of which communicating with the base of the ulcer. HFUPS clearly demonstrated the integrity of the major papilla and the termination of the main pancreatic and biliary ducts. Three metallic endoclips were positioned on the ulcer because of the rebleeding risk from the vascular structures demonstrated by the miniprobe beneath the ulcer. After a contrast-enhanced CT showing no metastatic disease, the patient underwent a laparotomy and a simple tumour resection via a duodenotomy, based on HFUPS findings. Conclusions. This is the first case evaluating the usefulness of the HFUPS not only in the emergency diagnosis and management of a bleeding duodenal GP but also in indicating the best subsequent therapeutic strategy.

Abstracts PO091 AUTOIMMUNE GASTRITIS AND HCV CHRONIC HEPATITIS: AN ASSOCIATION TO BE CONSIDERED IN PRESENCE OF MILD IRON DEFICIENCY ANAEMIA (IDA) G. Casellaa , V. Villanaccib , D. Peregoa , A. Sommaa , G. Ginia , E. Bareggia , C. Montic , V. Baldinia

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Conclusion. First-degree relative screening should be performed in every patient with coeliac disease and its prevalence is more than reported by Bevan et al. [1]. Reference [1] Bevan S, Popat S, Braegger CP, et al. Contribution of the MHC region to the familial risk of coeliac disease. J Med Genet 1999;36:687l–90.

a Medical

Department, Desio Hospital, Desio, Milan, Italy Pathological Department, “Spedali Civili”, Brescia, Italy c Claudio Monti, Medical Department, Policlinico di Monza, Monza, Italy b II

PO093 CLINICAL HYPOTHYROIDISM IN COELIAC PATIENTS

The association between hepatitis C virus (HCV) and extrahepatic manifestations is well noted [1]. We describe an association between autoimmune gastritis (AG) and HCV infection revealed by mild iron deficiency anaemia (IDA). Case report. We observed a female 54-year-old affected by HCV hepatic infection genotype 1b with mild elevation of liver enzymes (AST 58 U/l n.v. <38; ALT 62 U/l n.v. <34). She has an autoimmune thyroiditis well compensated with hormonal therapy. During routine blood examination, an IDA was evident (Hb 12 g/dl, RBC 4.01 million/mmc, HCT 35%) with hypoferritinaemia (12 ng/ml). Blood folic acid was normal and Vitamin B12 was normal, but near lower limits (294 pg/ml n.v. 378–1526). Anti parietal cell autoantibodies (APCA) were positive, while anti endomysium IgA was negative; no IgA deficit was noted. No bleeding sources were evident at upper and lower gastrointestinal endoscopy. Coeliac disease was ruled out by histology, while fundic and body gastric biopsies revealed a picture suggestive per AG with hyperplasia of fundic endocrine cells. Helicobacter pylori infection was absent. Liver biopsy was not performed, considering the patient’s autoimmune disorders and previous literature report [1]. Conclusions. Autoimmune gastritis should be considered before starting Interferon and Ribavirin therapy in patients affected by HCV infection with IDA, after ruling out sources of bleeding in gastro-intestinal tract and coeliac disease. Borgia et al. [1] report an appearance of important anaemia, paresthesia and ataxia in a patient with AG and Chronic hepatitis C treated with interferon therapy. Reference

G. Casellaa , C. Montib , G. Casellaa , M. De Novaa , G. Ginia , E. Bareggia , A. Sommaa , C. Crespic , V. Baldinia

[1] Borgia G, Reynaud L, Gentile I, et al. Pernicious anaemia during IFN-alpha treatment for chronic hepatitis C. J Interferon Cytokine Res 2003;23:11–2.

[1] Counsell CE, Taha A, Ruddell WS. Coeliac disease and autoimmune thyroid disease. Gut 1994;35:844–6.

a Medical

Department, Desio Hospital, Desio, Milan, Italy Department, Policlinico di Monza, Monza, Milan, Italy c Department of Laboratory Medicine, Desio Hospital, Desio, Milan, Italy b Medical

Introduction. Hypothyroidism may be present in 2.7–14% of all patients with coeliac disease [1]. Materials and methods. We studied a population of 106 coeliac patients (85 females and 21 males). The diagnosis was performed serologically (serum anti-endomysium IgA positive) and histologically. Histological duodenal sample was considered diagnostic in patients with blood IgA deficiency. Assessment of thyroid function (FT4, TSH) was performed in every patient. If a condition of clinical hypothyroidism was present, thyroid auto-antibodies (anti thyroglobulin and anti microsomal) were researched associated to an ultrasound study. Results. Nine females (8.5%) had a clinical hypothyroidism (FT4 mean value 8 ng/ml range 4–9, TSH mean value 20 range 6–44.4 U/l) and six showed the presence of thyroid auto-antibodies. In all patients, a heterogeneous ultrasound pattern was evident and in four patients thyroid nodules with size of 1–1.5 cm were noted; a cytological examination excluded malignant cells. Conclusion. Our data confirms, according to previous reports, that the percentage of clinical hypothyroidism and the research of hypothyroidism in coeliac patient should be considered a good clinical practice. Reference

PO094 PO092 FAMILIAL INHERITANCE OF COELIAC DISEASE

IRON DEFICIENCY ANAEMIA (IDA): A FREQUENT CLINICAL SIGN IN COELIAC PATIENTS

G. Casellaa , C. Montib , M. Denovaa , G. Ginia , E. Bareggia , A. Sommaa , S. Signorinic , V. Baldinia

G. Casellaa , C. Montib , G. Ginia , M. Denovaa , A. Sommaa , D. Peregoa , B. Mariac , V. Baldinia

a Medical

a Medical

b Medical

b Medical

Introduction. Familial inheritance is described in coeliac disease (CD). We have studied the prevalence in our population of coeliac patients. Materials and methods. We studied a population of 106 CD patients (85 females and 21 males), mean age 39 years (18–80 years). The diagnosis was possible in presence of anti-endomysium IgA and typical mucosal alterations. An interview and a serological screening was performed in first-degree relatives. Results. Sixteen patients (13 females and 3 males) (15%) are first-degree relatives. The patients are sisters in two cases (all females), mother and daughter in other two cases (all females), uncle and nephews in two cases (five patients: a male uncle and two female nephews; a female uncle and a female nephew) and father and sons in the last case (male father, son and daughter).

Introduction. Iron deficiency anaemia (IDA) is one of the most important extra-intestinal symptoms of coeliac disease; in some cases, it is the only clinical sign. Materials and methods. We studied, from May 1998 to June 2003, a population of 106 coeliac patients (85 females and 21 males). The diagnosis was performed according to the presence of serum anti-endomysium IgA and histological alterations of duodenal mucosa suggestive of coeliac disease. In every patient, an IgA deficiency was researched. Serum ferritin level was evaluated as an important marker to confirm this condition. Results. Twenty-seven patients (26 females and 1 male) (25.5%) showed IDA as clinical sign of coeliac disease. In eight females (6.9%), anaemia was the only clinical sign of the disease. Mean value of haemoglobin (Hb) was 10.2 g/dl (range 6.3–11.6) associated, in all cases, to low serum ferritin level (<10 ng/ml). Intestinal symptoms were evident only in 10

Department, Desio Hospital, Desio, Milan, Italy Department, Policlinico di Monza, Monza, Milan, Italy c Department of Laboratory Medicine, Desio Hospital, Desio, Milan, Italy

Department, Desio Hospital, Desio, Milan, Italy Department, Policlinico di Monza, Monza, Milan, Italy c Department of Laboratory Medicine, Desio Hospital, Desio, Milan, Italy

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of all 27 females (37%). In five females (5.8%), an IgA deficiency was present. Conclusion. In our experience, the percentage of IDA is higher (27.9%) than those reported (5%) by Halsted [1]. We suggest that coeliac disease be considered in every patient, particularly in young and females, with iron deficiency anaemia. Reference [1] Halsted CH. The many faces of celiac disease. N Engl J Med 1996;334:1190–1.

PO095 DEMONSTRATION OF ESTROGEN AND ANDROGEN RECEPTORS ON DENDRITIC CELLS A. Castellaneta, A. Di Leo, M. Rendina, A. Francavilla Department of Emergency and Organ Transplantation Section of Gastroenterology, University of Bari, Bari, Italy Background and aim. Dendritic cells (DC), which are very rare (<1% of total leukocytes) but efficient antigen-presenting cells, are believed to play a pivotal role in regulating immune responses in normal conditions, in neoplastic and autoimmune diseases. Recently, Liu et al. showed that DC are involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) in mouse. It’s interesting to know that oestrogen treatment suppress EAE onset by impairing the ability of DC to present Ag and shifting cytokine production towards a prevalent Th2 profile (IL-4 and IL-10). The same author showed that spleen DC express specific receptors for oestrogen. These data suggest that oestrogen, through DC, could affect immune responses. Considering the role of androgen and oestrogen in the development of hepatocellular carcinoma and autoimmune disease, this study was performed to demonstrate whether Liver, Spleen and Peyer’s patch DC express oestrogen (ER) and androgen receptor (AR). Methods. Liver (L), spleen (SP) and Peyer’s patch (PP) bulk DC were immunobead-isolated from 10- to 12-week-old female and male C57BL/6JICO mice with a purity consistently >96%. Costimulatory molecules, MHC class II and androgen/estrogen (alpha/beta) receptors expression in DC were examined using flow cytometry analysis. Results. Freshly-isolated immunobead-purified liver, spleen and Peyer’s patch CD11c+ DC showed an immature phenotype, characterised by a low-moderate level of costimulatory molecules (CD40, CD80 and CD86) and a moderate (LDC and SPDC)—high (PPDC) levels of surface MHC class II (IAb). Immature CD11c+ DC isolated from female animals showed a significant lower AR expressions compared to male mice: 30% versus 78% in LDC; 35% versus 61% in PPDC and 40% versus 69% in SPDC. No significant difference in ER expression was detected on DC isolated from female and male animals. ER expression was 74, 85 and 87%, respectively, in SPDC, PPDC and LDC. Conclusions. On the basis of these data it may be assumed that all diseases characterised by an imbalance of sex steroid hormones (cirrhosis), may affect the behaviour of tissue DC thus promoting carcinogenesis and autoimmune disease. PO096 TRANSABDOMINAL ULTRASONOGRAPHY IN THE EVALUATION OF COLORECTAL CANCER: A STUDY IN 322 PATIENTS REFERRED FOR COLONOSCOPY L. Castellanoa , L. Tibullob , D. Tarantoc , L. Coppolab , F. Mangusod , C. Del Vecchio Blancob , I. de Siob a Casa

di Cura Nostra Signora di Lourdes Massa di Somma, Naples, Italy di Medicina Interna e Gastroenterologia II, Università di Napoli, Naples, Italy c Clinica Mediterranea, Naples, Italy d Cattedra di Gastroenterologia, Università Federico II Napoli, Italy b Dipartimento

Background and aims. Ultrasonography has been recently used in the diagnosis of gastrointestinal tract diseases. In neoplastic diseases of the large bowel, however, the diagnostic value of transabdominal ultrasonography (T-US), is considered still limited. The aim of this study was to assess the value of T-US as a diagnostic procedure in patients with colon carcinoma. Study population. Three hundred and twenty-two patients, referred for colonoscopy because of different indications, were examined with T-US in a prospective study and the diagnosis was verified by endoscopy. In all cases T-US was performed (real time ultrasound scanners Toshiba Ecocee and Toshiba 140-SHG with 3.75 MHz convex and 8 MHz linear array transducers) before colonoscopy. The ultrasound operator was blinded to the results of previous laboratory, clinical or instrumental data. The ultrasonographic diagnosis of colonic tumour was based on the presence of the following features: localised, irregular thickening of colonic wall and absence of wall stratification. T-US results were compared to endoscopy considered as gold standard. Results. Twenty-three patients had cancer on colonoscopy. T-US detected 13/23 colonic cancers; there were no false positive findings. Compared with colonoscopy, T-US showed a sensitivity of 56.5% and a specificity of 99.3%. T-US positive predictive and negative predictive values were, respectively, 86.7 and 96.7%. T-US diagnosis showed good concordance with endoscopy at k Cohen test (k 0.665; P < 0.001). T-US sensitivity in the diagnosis was higher for colonic carcinoma proximal to rectosigmoidal transition (100%) than to those distal (33%). T-US sensitivity was higher in colonic carcinoma with stenosing pattern (66.7%) than in polypoid or sexile ones. Conclusions. Screening for colon cancer is being intensively investigated. Up to 70% of colonic carcinomas cannot be diagnosed by faecal occult blood test [1]. Total colonoscopy is the most sensitive diagnostic technique but is unsuitable for screening because it is time consuming, requires considerable technical expertise and is not widely accepted by patients. Sigmoidoscopy is accepted as a screening diagnostic tool but about 40% of colonic tumours occur outside the sigmoid. Our results suggest that T-US may be a useful imaging technique in the diagnosis and screening of colonic cancer. Reference [1] Lieberman DA. N Engl J Med 2001;345:555.

PO097 INFLIXIMAB IN THE TREATMENT OF EXTRA-INTESTINAL MANIFESTATIONS OF CROHN’S DISEASE F. Castiglionea , A. Rispoa , E. Di Girolamoa , A. Cozzolinoa , R. Scarpab , M. Attenob , A. Compagnaa , R. Grassiaa , G. Mazzaccaa a University

“Federico II” of Naples, Italy and Rheumatology, Italy

b Gastroenterology

Background. Crohn’s disease (CD) is frequently associated with extra-intestinal manifestations (EIM), particularly involving joints, skin and eyes. Infliximab has been recently proposed for the therapy of CD with EIM. Aim. To verify the efficacy of infliximab in the treatment of CD with EIM. Patients and methods. From January 2000 to September 2003, 30 patients affected by CD were treated with infliximab (5 mg/kg; 0, 2, 6 weeks). Fifteen patients (50%) showed EIM before starting therapy. Ten patients presented an axial arthritis according to ESSG criteria; six of them also referred peripheral arthralgias. Four patients presented cutaneous manifestations of the disease (one refractory pyoderma gangrenosum; one refractory metastatic disease; two erytema nodosum). Two patients showed an ocular EIM in the form of episcleritis. Eight patients had active intestinal disease, while in seven cases no intestinal symptoms were present and EIM (five arthritis; one pyoderma gangrenosum; one metastatic disease) was the main indication for treatment. All the patients were unresponsive

Abstracts to aminosalicylates. Six patients were intolerant to azathioprine, whereas the other nine patients were refractory to a long course of therapy with the immunosuppressor. Treatment response was evaluated as subjective clinical benefit (no response, partial response, complete response) for the arthropathy and as an objective improvement of the lesions for the cutaneous and ocular manifestations. Results. At week 10, all patients reported an improvement of EIM. Eight out of 10 patients (80%) with the axial arthritis presented a complete remission of spinal symptoms while in the other two patients (20%) only a partial response was recorded. The six patients with peripheral arthralgias completely responded to the treatment. In the four patients with cutaneous EIM and in the two with episcleritis complete healing of the lesions was recorded. In the eight patients with active intestinal disease the resolution of symptoms was reported. No adverse effect to infliximab was recorded. We observed disease recurrence (eight articular; two cutaneous) in 10 out of 15 patients (66%) within 8 weeks from the third infusion and the re-treatment was required. In all these cases re-treatment with infliximab was effective. Conclusions. Infliximab is an effective and well tolerated drug for patients with Crohn’s disease and EIM. Although relapse of EIM frequently occurs, in all these cases re-treatment assures an effective control of extra-intestinal symptoms. PO098 THE BEST CUT-OFF VALUES FOR SERUM PEPSINOGEN II TO DISCRIMINATE A SUCCESS OF ERADICATION THERAPY OF H. pylori L.G. Cavallaroa,b,c,d,e , A.M. Moussaa,b,c,d,e , P. Caruanaa,b,c,d,e , R. Merlia,b,c,d,e , V. Ioria,b,c,d,e , N. Stefania,b,c,d,e , A. Nouvennea,b,c,d,e , G.M. Cavestroa,b,c,d,e , N. Dal Bòa,b,c,d,e , A. Pilottoa,b,c,d,e , V. Correntea,b,c,d,e , G. Leandroa,b,c,d,e , A. Franzéa,b,c,d,e , F. Di Marioa,b,c,d,e a Department

of Clinical Sciences, University of Parma, Italy Unit, Treviso, Italy c Geriatrics Unit, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy d Gastroenterology Unit Parma, Italy e Gastroenterology Unit, Castellana Grotte, Italy b Gastroenterology

Objective. Current guidelines recommend also UBT or HpSA to assess Hp eradication. Serum pepsinogen II (sPGII) levels increase during Hp infection. Aim. To determine the best threshold for sPGII to discriminate H. pylori infection after eradication therapy. Subjects and methods. Three hundred and thirteen consecutive patients (177 females, mean age 51, range 18–88 years) referred to our outpatient service for dyspeptic symptoms were studied; 156 patients were Hp+ve and 157 were Hp−ve. Hp status was assessed by means of endoscopy with multiple biopsies. At baseline, in all patients a blood sample was taken to determine sPGII levels. Additionally, sPGII determination was performed in 70/156 Hp +ve patients 4 weeks after completion of the Hp eradication therapy; in 29/70 subjects gastroscopy with biopsies were performed to evaluate histologically the effect of Hp therapy on both gastric activity and inflammation. Results. At baseline Hp+ve subjects showed mean sPGII levels significantly higher than Hp−ve (16.81 ± 7.4 ␮g/l versus 8.6 ± 3.7 ␮g/l; P < 0.001). The sensitivity and the specificity of the PGII test to detect Hp infection were, respectively, 74 and 83%. After successful eradication therapy, sPGII levels significantly decreased from 17.56 ± 7.5 to 8 ± 2.08 ␮g/l, P < 0.001 along with the improvement of activity of gastritis; mean sPGII levels slightly decreased from 18.66 ± 11.3 to 15.6 ± 5.9 ␮g/l (P = 0.03) in subjects who still remained Hp+ve after treatment. Table 1 summarised the cut-off values and test performance characteristics for sPGII, variation sPGII before and after therapy, and delta values of sPGII to discriminate between eradicated and not eradicated patients.

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Conclusions. sPGII levels could be proposed as non-invasive test to evaluate both Hp eradication and the consequent changes in gastric inflammation. PO099 NEW OPTIONS FOR Helicobacter pylori MOXIFLOXACIN-BASED STRATEGIES

ERADICATION:

I.A. Cazzato, E.C. Nista, M. Candelli, L. Fini, F. Franceschi, G. Cammarota, G. Gasbarrini, A. Gasbarrini Department of Internal Medicine, Catholic University, Rome, Italy Introduction. Recently, standard 7 days anti-Helicobacter pylori (Hp) triple therapies did not allow a satisfactory eradication rate in clinical practice. For this reason several alternative schemes have been proposed for Hp eradication. Fluoroquinolones, in particular moxifloxacin, are promising agents for Hp eradication which present the advantage of single daily administration. Aims and methods. The aim of this study was to compare the efficacy of 1-week moxifloxacin-based Hp eradication regimens with standard treatments. Two hundred and fifty-one Hp-positive subjects were randomised into four groups to receive: moxifloxacin (400 mg per day), tinidazole (500 mg bid) and esomeprazole (20 mg bid) (Group MTE: 60 patients); moxifloxacin (400 mg per day), amoxicillin (1 g bid), esomeprazole (20 mg bid) (Group MAE: 64 patients), standard triple therapies with esomeprazole (20 mg bid), clarithromycin (500 mg bid) and amoxicillin (1 g bid) (Group CAE: 65 patients) or tinidazole (500 mg bid) (Group CTE: 62 patients) for 7 days. Hp status was re-assessed 6 weeks after the end of the therapy by 13C urea breath test. Results. All the patients completed the study. H. pylori eradication rate in Group MTE was 98.3% (59/60 patients), in Group MAE was 82.8% (53/64 patients), in Group CAE was 67.7% (44/65 patients) and in Group CTE was 72.6% (45/62 patients). Eradication rates of both 1-week moxifloxacin-based triple therapies were significantly higher than those observed using standard triple schemes (98.3% versus 67.7% P < 0.0005; 98.3% versus 72.6%; P < 0.005; 82.8% versus 67.7%; P < 0.05; 82.8% versus 72.6; P = ns). Moreover, moxifloxacin showed a significantly higher eradication rate when associated with tinidazole rather than with amoxicillin (98.3% versus 82.8%; P < 0.01). Minor side-effects (disgeusia, nausea) were reported in all groups with similar incidence. Conclusion. Seven days moxifloxacin-based triple therapies are simple and provide optimal eradication rates with a good compliance when compared with the actual standard triple schemes. Taking into account the efficacy of moxifloxacin in antibiotic resistant Hp strains, further studies are strongly needed. PO100 GUIDEWIRE PLACEMENT OF NASOGASTRIC FEEDING TUBES USING A TRANSNASAL VIDEO ENDOSCOPE V. Cennamoa , G.M. Idèob , L. De Lucaa , C. Fabbria , D. Baroncinia , P. Billia , A. Grillia , M. Giogolia , N. D’Imperioa a Gastroenterology

and Digestive Endoscopy Unit, Bellaria-Maggiore Hospital, Bologna, Italy b Gastroenterology and Digestive Endoscopy Unit, S. Giuseppe Hospital, Milan, Italy

Background. The traditional nasogastric/nasoenteric feeding tube is the preferred access device for short-term feeding (<30 days). In some patients, this method of feeding is impossible because of repeated failures of nasogastric tube placement, requiring either general anaesthesia for enteral access or total parenteral nutrition. Other patients have characteristics considered potentially risky for traditional placement (recent pharyngoesophageal surgery or oesophageal diverticula).

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Abstracts

Methods. We describe our experience of guidewire nasogastric tube placement after guidewire insertion through the video transnasal ultrathin endoscope in patients either with failure or high risk of traditional enteral tube placement. Results. Three patients in whom enteral tube placement had failed and four patients considered to be at high risk for traditional placement (two having recently undergone surgery and two having pharyngoesophageal diverticula) were submitted to guidewire (through transnasal video endoscope) placement of nasogastric feeding tubes, all with success. Conclusions. The use of the transnasal video ultrathin scope for enteral tube placement seems to be a specific field of employment of this kind of scope but should be reserved for selected cases. PO101 BENEFITS AND RISKS OF EARLY PRE-CUT. A PROSPECTIVE RANDOMISED COMPARISON WITH THE COMMON OF DELAYED PRECUTTING: A SHORT-TERM FOLLOW-UP V. Cennamoa , D. Baroncinia , P. Billia , L. De Lucaa , C. Fabbria , A. Piemontesea , A. Grillia , A. Repicib , D. Bonoraa , N. D’Imperioa a Gastroenterology

and Digestive Endoscopy Unit, Bellaria-Maggiore Hospital, Bologna, Italy b Endoscopy Unit, Department of Gastroenterology, Molinette Hospital, Turin, Italy Background and aims. Achieving bile duct access with standard cannulation attempts fails in about 10–15% of the cases. Failed access necessitates trying a different technique: the pre-cut. The aim of this study was to compare the benefits and the effective risk between early pre-cut (EPC) procedures and pre-cut performed after intensive standard cannulation attempts, the late pre-cut (LPC). Materials and methods. Between January 1999 and December 2001, 78 consecutive patients from the Endoscopy Unit of Bellaria Hospital, Bologna, considered to have problematic papilla according to established criteria, were randomised into two groups to undergo EPC procedures (group 1) or LPC (group 2), respectively, after several attempts, without any limitation regarding the number of attempts (Table 1). Table 1 Patients

EPC LPC

M/F

Mean age

16/20 15/17

68 69

Indications Lithiasis

Pancreatitis

Pancreatic Neoplasia

Biliary tract Neoplasia

Other diseases

12 (33%) 9 (28%)

5 (14%) 6 (19%)

7 (20%) 5 (15%)

5 (14%) 4 (13%)

7 (19%) 8 (25%)

Results. Cannulation and the overall complications between the two groups is shown in Table 2. Table 2 (P = ns) Cannu- Overall lation complications

Pancreatitis Mild

EPC 33/36 (92%) LPC 26/32 (81%)

Haemorrhage

Severe Without transfusion

CORRELATION BETWEEN ALIMENTARY HABITS AND HEALTH STATE IN A SAMPLE OF ITALIAN POPULATION G.R. Centenaroa , F. Calellaa , M. Capannia , M.R. Biaginia , D. Nigroa , O. Bazzania , C. Dinib , C. Surrentia , A. Casinia a Nutrition

Center and Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy b Dietetic Unit, Careggi Hospital, Florence, Italy

Background. Emerging evidence is accumulating on the key role of alimentary habits in the definition of health state and the development of different diseases. Aim. To analyse dietary habits and lifestyle in a representative sample of Italian population and to correlate these findings to the health state. Materials and methods. Eight hundred and sixty-two subjects (49% males and 51% females; age: 18–65 years) of Florence population were randomly enrolled. They underwent medical visits with ematochemical investigation, measurement of antropometric parameters, and a validated alimentary questionnaire combined by a specific software. Results. On the alimentary questionnaire an excessive lipidic intake resulted: 32% in males and 34% in females of total daily calories (2276 ± 385 kcal per day) came from lipids, while 48 and 16% from carbohydrates and proteins, respectively. In dietary lipid composition, saturated fatty acids accounted for 10% of total kcal per day (<7% is recommended), while monounsaturated and polyunsaturated fatty acids gave 13 and 3% of total kcal per day (>16 and 7–8% is recommended). These dietary habits and the poor physical activity are, at least in part, responsible for the high levels of blood cholesterol (>200 mg/dl) found in 67.1% of subjects (32.3% of them had also HDL-cholesterol <45 mg/dl). Impaired glucose tolerance (fasting glycemia >1.10 g/l) was observed in 9.1% of subjects. A low consumption of fibres (19.1 g per day versus 25 g per day recommended) and calcium (777 mg per day versus RDA of 1000 mg per day) was observed in the male population; calcium intake was higher (957 mg per day) in female because of a wider use of milk and cheese. Both in male and female, a poor daily consumption of folic acid and Vitamin B occurred. Conversely, we found an excessive intake of Vitamin C (117 mg per day in males and 151 mg per day in females versus RDA of 60 mg per day), Vitamin A (852 mg per day in males and 1046 ␮g per day in females versus RDA of 600 and 758 ␮g per day, respectively), and zinc (10.5 mg per day in males and 13 mg per day in females versus RDA of 10 and 7 mg per day). Antropometry showed that 39.6% of subjects were overweight, and 9.7% were obese. Waist circumference was >100 cm in 29% of males, and >88 cm in 20% of females. WHR (waist/hip ratio) was >0.95 in 28% of males, and >0.88 in 16% of females. Conclusions. This study underlines the role of wrong dietary habits and poor physical activity in inducing altered blood lipid and glucose composition, and obesity. Furthermore, the excessive use of micro-nutrients such as Vitamin A, Vitamin C and zinc may be explained by their anti-oxidant properties highlighted by media.

Perforation With transfusion

With sclerosis

PO103

7 (21%)

1 (3%) 0

4 (12%)

1 (3%)

0

1 (3%)

3 (9%)

0

2 (6%)

0

1 (3%)

0

0

PO102

Conclusions. EPC and LPC seem to be similar in terms of complications and bile duct cannulation. Intensive attempts allow bile duct access in several patients with problematic papilla and do not increase the risk of the pre-cut technique.

QUALITY INDICATORS FOR COLORECTAL CANCER (CRC) SCREENING: POPULATION ADHERENCE TO LEVEL I (FOBT) AND TO LEVEL II (COLONOSCOPY) E. Cervellina,b , S. Milania , C. Ferrarab , R. Marinb , G. Marinb a Dipartimento b U.O.

di Prevenzione Ospedale di Dolo (VE), ULSS 13, Italy Medicina, Italy

During the course of colorectal cancer (CRC) screening, the organisational model should bring the adherence to level I testing and, especially, colonoscopy to an optimal level. In the territory of our Local Health Service (LHS), a CRC screening campaign began over a year ago, directed at the population between 50 and 70 years of age based on checking for

Abstracts faecal occult blood (FOBT) every 2 years and colonoscopy when FOBT results positive. Materials and methods. The organisation involved: community administrators, parish priests, pharmacy owners, general medicine doctors, district heads, hospital services heads (laboratory, prevention, endoscopy, anaesthesia, data processing). The priority choices were: (1) successive involvement of the individual communities of the LHS; (2) information and advertising in community and parish bulletins, posters, leaflets, street banners; (3) mailing of invitation and instructions; (4) distribution of FOBT in pharmacies and collection of samples in boxes at health districts, district sample collection sites and hospitals reception; (5) colonoscopy scheduling by the screening service; (6) sedation for colonoscopy using anaesthesiologist assisted analgesia sedation. Each step was programmed with the objective to reduce, as much as possible, any discomfort for the general public. Results. From May 2002 to September 2003, eight communities (target population 22,330) were successively involved. Adherence to level I test was 57% (12,361 samples). Inadequate samples were 333 (2.5%) and 579 (4.7%) resulted positive. Of the 570 eligible cases, 550 subjects underwent colonoscopy, equal to 96.5%. Colonoscopy was carried out to the caecum in 95.5%. Colonoscopy showed: CRC in 36 cases (6.5%, stage T1-2-3 N0 in 66% of cases), high-risk polyps in 172 cases (31.3%), low-risk polyps in 49 cases, hyperplasia in 29 cases and negative results in 266 cases (48.5%). Conclusion. Population adherence both to level I (FOBT) and level II (Colonoscopy) testing was high and greater than that in other national and international experiences. We believe that this success is due to: (1) an adequate advertising and information campaign; (2) designing of easy steps for the general public; (3) the use of analgesia sedation for colonoscopy, which leads to two more fundamental objectives of quality: (a) wide acceptance of endoscopic exam (principle objective of the screening), (b) completeness of endoscopic investigation and ease of endoscopic procedure (polypectomy). PO104 BIOFEEDBACK THERAPY IS EFFECTIVE LONG-TERM IN SLOW TRANSIT CONSTIPATION WITH OUTLET DYSFUNCTION G. Chiarionia , L. Salandinia , W.E. Whiteheadb a Divisione

di Riabilitazione, Gastroenterologica dell’Univ- ersità di Verona, C.O.C. Valeggio sul Mincio, Azienda Ospedaliera di Verona, Italy b Division of Digestive Diseases, UNC Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, USA Biofeedback is designed to correct outlet dysfunction constipation, but it has also been reported to be effective in slow transit constipation [Gut 42 (1998) 517]. Aims of the study. (A) To determine whether successful biofeedback treatment is limited to patients with outlet dysfunction (paradoxical contraction of the anal sphincter when straining or inability to defaecate a rectal balloon). (B) To evaluate the long-term treatment effectiveness. Seventy-five consecutive patients with refractory constipation were screened for 30 days on a rich fibre diet and restricted laxatives’ regimen, ending with a Sitzmark study of transit time. Excluded were five patients for poor compliance and 18 patients who had normal transit times. Fifty-two patients (49 women, average age 35 years) received 5 weekly biofeedback sessions to improve the use of abdominal muscles to strain, to relax the anal sphincter while straining and to practice defaecating a rectal balloon. Patients were re-evaluated 6 months later by manometry, balloon defaecation, Sitzmark study and questionnaire. Subjective success was defined as a self-report of major improvement or complete recovery. Responders underwent again clinical evaluation, balloon defaecation test and Sitzmark study 12 and 24 months later. Results. At the 6 months check (1) 54% (28/52) of patients were subjective successes and 50% (26/52) achieved normal transit times; (2) 89% who

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reported subjective success were initially dyssynergic, compared to 54% of unsuccessful patients; (3) no successful patient was dyssynergic at the end of treatment and all successes gain the capability to evacuate a rectal balloon. All the 28 responders came back for the 12 months’ check. Subjective rating of treatment benefit was unchanged as well as transit times and rectal balloon tests. At the 24 months’ control, all the responders came back, but for two people. Physiology variables and clinical outcome were still favourable. The two drop-outs moved too far away to come, but they stated that the treatment was still effective. In conclusion, biofeedback therapy benefits long term only for patients with refractory constipation and outlet dysfunction, not patients with isolated slow transit constipation. PO105 COELIAC CHILDREN GROW UP C. Ciacci, P. Iovino, D. Amoruso, M. Siniscalchi, R. Tortora, A. Di Gilio, G. Mazzacca Gastroenterologia, Università Federico II Napoli, Italy In the past, diagnosis of coeliac disease (CD) was made mainly on clinical and histological basis. After a variable period of gluten free diet (GFD) most children were re-exposed to gluten. In the case of absence of clinical signs they were often left on free diet (FD). In most recent years many of these children, now adult, were re-examined for CD. Aim. To evaluate health status of adults with childhood diagnosis of CD. Patients. Two hundred and fifteen adults with a biopsy suggestive for CD in childhood and who were on GFD for at least 1 year after diagnosis. Methods. A complete medical work-up was offered to all of them. Results. Eleven patients were EMA-negative and CD was not confirmed. Nine of EMA positive patients refused endoscopy for fear of such procedure. Then, the study cohort is made of 195 adults with complete data. Patients were divided in to two groups depending on their diet, GFD or FD (data in Table 1). Dietetic interview revealed that 29/85 on GFD assumed gluten on regular basis. Histology revealed villous atrophy in 87 patients on GFD and normal mucosa in 1/171 on free diet. Psychological features were not significantly different in the two groups. Thyroid disease was found in four women (two on GFD), IDDM in two (on GFD). Herpetiform dermatitis was found in six patients (three on GFD). Dental enamel defects were found in 15 patients on free diet and in 0 on GFD. One of the patient, 19 years, with bad compliance to GFD died during follow-up by intestinal lymphoma. Conclusion. Most of the patients on GFD examined were badly compliant to GFD (80%). Nevertheless, even a bad GFD during childhood seems to have a protective effect on most nutritional indexes examined when compared to those of coeliac patients on FD. Table 1. Main findings of the study GFD (n = 110) Age at visit BMI BMD (femur) HGB Total serum proteins Cholesterol a-tTG

20.9 21.7 0.73 13.4 7.2 15.2 12.2

± ± ± ± ± ± ±

3.7 2.7 1.5 1.4 0.67 29.4 13.4

FD (n = 85) 23.7 20.3 0.67 12.2 6.9 140.9 20.4

± ± ± ± ± ± ±

5.3 3.0 2.0 2.0 0.8 27.0 9.9

P, Student’s t-test 0.001 0.001 0.09 0.0001 0.0036 0.029 0.09

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Abstracts

PO106 AGRESSIVE ACID SUPPRESSION DECREASES NOT ONLY ACID BUT ALSO BILE REFLUX IN GASTRO-OESOPHAGEAL REFLUX DISEASE P. Ciamarra, G. Sarnelli, M. Flavia Savarese, L. Russo, G. Budillon, R. Cuomo Gastroenterologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Naples, Italy Background. Duodenogastro-oesophageal reflux (DGER) is involved, together with acid reflux, in the pathogenesis of GERD, with and without oesophagitis. Although it has been shown that proton pump inhibitors (PPI) reduce acid reflux and heal oesophagitis, there are still scanty data on their effect on bile reflux and its related symptoms. Aims. To study the effect of PPI on bile reflux upon GERD-related symptoms. Patients and methods. Sixteen patients (eight males, mean age 48.5 years) complaining of gastro-oesophageal reflux symptoms were enrolled. All patients underwent upper endoscopy and stationary oesophageal manometry. A standardised symptoms questionnaire and combined 24 h bilirubin and acid measurement were recorded in all patients, before and after a 4-week course therapy with esomeprazole 40 mg twice daily. Data are expressed as mean ± S.E.M. Results. Eleven patients had hiatal hernia, 12 patients had oesophagitis; none of the patients had significant abnormalities of the primary peristalsis. Before treatment, average symptoms score for heartburn and regurgitation was 1.9 ± 0.9 and 1.5 ± 0.9, respectively. Acid exposure (% time pH < 4) was 7.3 ± 2.1, number of acid refluxes (NAR) 99.3 ± 21.9. Bile exposure was (% time absorbance >0.14) 23.7±6.4, number of bile refluxes (NBR) 32.3 ± 12. After treatment symptoms score was significantly reduced for both heartburn (0.4 ± 0.8; P < 0.05 versus before) and regurgitation (0.6 ± 0.8; P < 0.05). Furthermore, aside from acid reflux (% pH < 4: 0.34 ± 0.2, NAR: 14.6 ± 6.5), bile reflux (% ads >0.14: 5.0 ± 3.6, NBR: 11.2 ± 4.9) was also significantly reduced. Conclusions. A strong acid suppression decreases both acid and DGER in gastro-oesophageal reflux disease and improves heartburn and regurgitation. The effect on DGER could be explained by the decrease in the volume of gastric contents available to reflux into the oesophagus. PO107 ENDOSCOPIC TREATMENT OF MALIGNANT COLORECTAL OBSTRUCTION. OUR EXPERIENCE G. Ciancioa , M. Campaiolia , G. Di Fiorea , M. Nutib , A. Soldia , A. Candidi Tommasia a Sezione b Unità

di Gastroenterologia ed Endoscopia Digestiva, Italy di Medicina Interna III, Azienda Ospedaliera USL 4 Prato, Italy

Background. Management of malignant colorectal obstruction presents a challenge that frequently calls for emergency surgical treatment with a significant morbidity and mortality. Metal stents have been reported as an effective alternative to surgery in the treatment of colorectal neoplastic obstruction. We report our experience in endoscopic treatment of large bowel malignant obstruction by self-expanding metal stents insertion. Methods. From January 2002 to September 2003, we treated eight patients (four males, four females) with a mean age of 79.25 years (range 72–86 years). Under endoscopic and fluoroscopic guidance, a Placehit Wallstent 60–90 mm 10 Fr was attempted in three patients, whereas a Wallstent Unistep plus 60–80 mm 8 Fr (Microvasive, Boston Scientific) in five patients. Endoprothesis was used in five patients to palliate unresectable intestinal obstruction whereas in three patients as a preoperative procedure (bridge to surgery). Results. Stenting was technically successful with resolution of large bowel obstruction in 7/8 patients (87.5%). After 24 h relief of bowel obstruction was documented in all successfully treated patients (100%).

No perforation and no stent migration occurred in all successfully treated patients. A mild bleeding in one patient (12.5%) was observed without the need of blood transfusion. The mean follow-up in patients treated to unresectable intestinal cancer was 20.8 weeks (range 4–44). During the follow-up, a recurrence of obstruction due to stool impact was observed in 2/4 patients (50%) with laxatives successfully treated. Conclusion. In our experience, emergency endoscopic treatment of malignant colon–rectal obstruction by metal stenting is a safe and effective technique that provides time for a complete preoperative evaluation and restore patient’s general conditions. If surgery is not recommendable, stenting also represent a simple and safe palliation technique. PO108 GASTROINTESTINAL STROMAL TUMOURS: UNUSUAL PRESENTATION V. Ciardo, M. Melato, N. Orzes, E. Benedetti Servizio di Gastroenterologia ed Endoscopia Digestiva, Ospedale Civile di Gorizia Via Vittorio, Veneto 171, Gorizia, Italy Backgrounds and aims. Gastrointestinal stromal tumour (GIST) is a mesenchymal neoplasm of the abdomen and gastrointestinal tract that can be identified on a histological basis by the activation of the kit protein (CD 117), detected by immunohistochemistry and retained an important event in the GIST pathogenesis. They are the most common in the stomach followed by the small intestine, the colon and rectum and the oesophagus. Other tumours can be variably kit-positive and sometimes enter in the differential diagnosis of GISTs. Small GISTs are usually clinically harmless or often give vague symptoms, GISTs of the oesophagus typically give dysphagia. The current therapy involves surgery and administration of Imatinib mesylate, a competitive inhibitor the tyrosine kinase associated with the kit protein, recently approved for patients with advanced GIST. The aims of this study are: (1) to point out two cases of gastric GIST presented with GI bleeding, a rare modality of presentation due to mucosal ulceration of the lesion, (2) to review the criteria of malignant lesions and the indications of surgical and/or medical therapy. Methods and results. From January to July 2003, we observed three cases of gastric GISTs, two of which admitted to our hospital for anaemia and melena and the third for a gastro-oesophageal reflux. The medical history reported no NSAIDs consumption and the physical examinations were in the norm. Endoscopical examination revealed a submucosal nodular lesion, ulcerated in two cases, without other lesions in the upper GI tract (see pictures). No metastasis were found in the CAT scan for the three patients. Regarding the size of the neoplasms one patient underwent total gastrectomy, omentectomy and lymphadenectomy and two patients underwent partial gastrectomy with the resection of the lesions. Histological examination showed two GIST with kit and NSE-positivity, negativity for smooth muscular actin, desmin and S-100, and a mitotic rate of 4 and 7 per 50 hpf, respectively. The third patient, presented for gastro-oesophageal reflux, had a neoplasm with fusal cells without any evident mitotic activity and with a central necrotic area, positive for CD117, vimentin, CD34, QBEND10 and negative for desmin, S100, CD31, EMA, CD68. Conclusions. We observed two rare cases of gastrointestinal bleeding due to GIST. Surgery is the only effective radical treatment even after considering the recently demonstrated efficacious use of Imatinib mesylate in the management of advanced GISTs that could offer a glimpse of hope and a better prognosis for patients in which radical surgery is not possible. PO109 SENSIBILITY OF DUAL PHARYNGOESOPHAGEAL 24-HOURS pH MONITORING IS RELATED TO THE PRESENCE OF ORGANIC OR NOT ORGANIC EXTRAOESOPHAGEAL PATHOLOGY A. Ciarleglio, F. Ievoli, G. Piai, P. Rocco, M. Pacelli, G. Forte UOC Gastroenterologia, AORN San Sebastiano, Caserta, Italy

Abstracts Background and aim. Sensibility of dual pharyngoesophageal pH monitoring (DPphM) in defining pathologic proximal reflux is still controversial, due to heterogeneity of studied pathologic conditions and because there is no consensus on the value of cut-off of percentage of reflux total time with pH < 4 (RTT < 4) classifying pathologic and not pathologic reflux. The aim of this study is to evaluate if sensibility of test is related to presence of organic extra oesophageal pathology. Materials and methods. Thirty patients, with suspected proximal reflux (PR) without oesophagitis at endoscopy, were studied using a dual channel probe, placed after manometric determination of sphincters. A PR was defined as pathologic when fraction of acid reflux total time was = 1% (RTT). Patients were divided in two groups according to the presence or absence of organic disease. An organic disease (OD) had been diagnosed in nine patients (six laryngeal carcinoma, three corditis), while in 21 patients no organic disease (NOD) had been found after several persisting symptoms (nine cough, three hoarseness, two asthma, four suffocating symptom, two globus, one hiccup). Results. The mean age was 63 ± 9 years in the first group (seven males and two females) and 49 ± 14 years in the second (17 males and 4 females) (P < 0.05). Overall

Organic lesion

No organic lesion

P

RTT < 4 > 1%

10 (33%)

7 (80%)

3 (15%)

<0.002

RTT < 4 < 1%

20 (67%) 30

2 (20%) 9 (30%)

18 (85%) 21 (70%)

<0.002

Four patients with RTT < 4 < 1% (1 OD and 3 NOD) showed a positive response to therapy with PPI: they all had a value of RTT < 4 < 0.4%. Data recalculated according to this last cut-off value improved test sensitivity from 78 to 89%.

RTT < 4 ≥ 0.4% RTT < 4 < 0.4%

Overall

Organic lesion

No organic lesion

P

15 (50%) 15 (50%)

8 (88%) 1 (12%)

7 (30%) 14 (70%)

<0.05 <0.05

In patients with OD, clinostatic reflux episodes were more frequent than orthostatic reflux episodes; a contrary pattern was observed in patients with NOD. Conclusions. (1) The sensibility of DPphM is influenced by organic character of disease; (2) the clinostatic reflux can play a pathophysiologic role in OD; (3) the cut-off value should be re-evaluated for not organic lesions. PO110 PERIPHERAL BLOOD DENDRITIC CELLS IN COELIAC DISEASE (CD) R. Ciccocioppoa,b , I. Pescea,b , D. Millimaggia,b , G. Riccia,b , F. Cupellia,b , A. Di Sabatinoa,b , A. Agnifilia,b , M. Grazia Cifonea,b , G. Roberto Corazzaa,b a Departments

of Internal and Experimental Medicine and of Surgical Sciences, University of L’Aquila, Italy b Gastroenterology Unit, IRCCS Policlinico San Matteo, University of Pavia, Italy Background and aim. Dendritic cells (DCs) are professional antigen-presenting cells having an extraordinary capacity to orchestrate both primary immune response by acting on naive T cells, and innate immune response by regulating natural killer cell and macrophage functions. In peripheral blood DCs are present in a so-called immature state, unable to stimulate T cells, but equipped to capture either self or foreign antigens which in turn induce full maturation of DCs. Recently,

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at least two distinct human DC subsets, i.e. myeloid DC (MDC) were able to generate a Th1 response, and plasmacytoid (PCD) responsible for Th2 response, have been characterised by using novel antibodies (anti-BDCA). In CD pathogenesis, the strong association with the class II MHC molecules emphasises the importance of antigen presentation to CD4+ T cells but, up to now, no informations about DCs are available. Therefore, the aim of our study was to analyse peripheral blood DCs in this pathological condition. Patients and methods. We used the new Blood Dendritic Cell Enumeration Kit (Miltenyi Biotec, Bergisch Gladbach, Germany) for the enumeration and identification of DCs by three-colour staining FACS analysis. Peripheral blood samples from 7 untreated and 9 treated CD adult patients, and from 12 healthy controls were used. BDCA-1 positivity corresponded to MDC and BDCA-2 to PDC. The simultaneous use of anti-CD19 and anti-CD14 antibodies permitted to discriminate DC population. Results. DCs represent less than 1% of total cells in peripheral blood in healthy controls, with a mean percentage of 0.47% (range: 0.29–0.65%) as concern MDC and 0.35% (range: 0.25–0.52%) as concern PDC. In both untreated and treated CD patients the total number of DCs was more than 1% and the characterisation shows the presence of an increase of MDC (mean: 1.03%, range: 1.87–0.67% and mean: 0.65%, range: 0.41– 1.13%, respectively), together with a slight increase of PDC population in comparison to control group. Conclusions. It is known that the immature DC phenotype is characteristic of the “regulatory” DCs that might act as guardians for the induction and maintenance of peripheral T cell tolerance and the prevention of autoimmune reactions. Then, the presence of mature, myeloid polarised DCs in both active and treated CD support the hypothesis that the loss of tolerance is a primitive defect in this condition and fit with the well documented Th1 polarisation. PO111 MATRIX METALLOPROTEINASE EXPRESSION IN LAMINA PROPRIA MONONUCLEAR CELLS OF COELIAC DUODENAL MUCOSA R. Ciccocioppoa,b,c , A. Di Sabatinoa,b,c , M. Bauera,b,c , M. Rossia,b,c , M. Antonietta Pistoiaa,b,c , M. Grazia Cifonea,b,c , D. Schuppana,b,c , G. Roberto Corazzaa,b,c a Departments

of Internal and Experimental Medicine and of Surgical Sciences, University of L’Aquila, Italy b Gastroenterology Unit, IRCCS Policlinico San Matteo, University of Pavia, Italy c Department of Medicine I, Friedrich-Alexander University of ErlangenNuremberg, Germany Background and aim. Matrix metalloproteinases (MMPs) are a family of endopeptidases produced by cytokine-stim- ulated lamina propria mononuclear cells (LPMCs) and myofibroblasts, playing a key role in tissue remodelling in both physiological and pathological conditions. Till now, a quantitative assessment of MMP expression in coeliac disease (CD) has never been performed. Therefore, the aim of the present study was to characterise the MMP pattern in LPMCs isolated from coeliac duodenal mucosa in comparison to normal condition, and to investigate the putative influence of the two main Th1 cytokines, IFN-g and TNF-␣, on their expression. Patients and methods. Duodenal biopsies of 11 untreated, 12 treated adult coeliac patients, and 10 controls were used to isolate LPMCs that were incubated for 48 h in the presence or in the absence of IFN-␥ (R&D System, Minneapolis, MN) at a concentration of 1000 U/ml, or TNF-␣ (R&D System) at 50 ng/ml. At the end of the incubation, LPMC suspensions were centrifuged and the pellets were used to quantify MMP-1, -2, -3, -9, -12, -14, TIMP-1 and B2-microglobulin expression by using real-time reverse-transcription polymerase chain reaction. Results. In normal mucosa, unstimulated LPMCs produced very low levels of MMPs, whereas they were highly sensitive to IFN-␥ as to MMP-12

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production and to TNF-␣ as to the production of the other MMPs is concerned. When LPMCs were isolated from active CD mucosa, the basal pattern was strongly dominated by MMP-9 and MMP-12. This pattern was not further modified by the addition of IFN-␥ and TNF-␣. LPMCs isolated from treated CD mucosa expressed very low levels of all MMPs either in basal conditions, or after cytokine treatments. Finally, regarding TIMP-1 mRNA, while in normal and treated CD cells both cytokines resulted able to increase its expression, in active CD an unmodifiable high basal level was found. Conclusions. Our findings demonstrated that the MMP pattern produced by unstimulated and stimulated LPMCs differed markedly in the studied three groups, confirming that in pathological condition, Th1 cytokine are able to induce MMP production involved in tissue damage. The observed unresponsiveness in active CD suggest that a pre-existing cytokine hyperstimulation disables LPMCs to respond to a further stimulation. In this context, it is likely that the observed increase of TIMP-1 transcript levels is not sufficient to completely block MMP activity. PO112 ENDOSCOPIC MUCOSAL RESECTION FOR ADVANCED NONPOLYPOID COLORECTAL ADENOMA AND EARLY STAGE CARCINOMA L. Cipolletta, M.A. Bianco, G. Rotondano, R. Marmo, A. Prisco, T. De Simone, R. Piscopo UO Gastroenterologia, ASL NA5, Ospedale Maresca, Torre Del Greco, NA, Italy Purpose. Endoscopic mucosal resection (EMR) techniques were evaluated in the treatment of non-polypoid colorectal lesions. Methods. One hundred and fifty-four patients with non-polypoid colorectal lesions (n = 170) were included in the study. Tumour location, shape, size, and depth (in malignant lesions) were determined by endoscopy and endoscopic ultrasound (in left-sided lesions with a non-lifting sign). EMR was performed using either the lift and cut or the suck and cut technique with a cap-fitted endoscope for type IIc (depressed) lesions. Results. Lesion size ranged from 0.8 to 30 mm. Complete resection was achieved in all 162 adenomas and 6 of 8 carcinomas. En-bloc resection was accomplished in 124 lesions, whereas 46 lesions were removed with “piecemeal” technique. Histopathological examination of neoplasm treated by EMR showed adenoma in 162 and early-stage carcinoma (pT1) in eight cases. Because of the non-lifting sign, 2 of 170 tumours were not treated endoscopically and referred to surgical resection revealing a pT2 adenocarcinoma in both cases. Only two patients experienced a procedure-related bleeding, successfully treated by haemoclip application in both cases. No local recurrence was observed for both and early-stage carcinomas during a mean follow-up of 21 months (range 6–36 months). Conclusions. Advanced non-polypoid colorectal adenomas and early-stage carcinomas can be safely and effectively resected by endoscopic mucosal resection. PO113 ADULT COELIAC DISEASE AND OVERWEIGHT/ OBESITY: A PROBLEM IN THE PROBLEM? P.

Cogneina ,

M.

Brugnanib ,

F.

D’Andreab ,

M. Del

Pianoa

a S.C.

Gastroenterologia, Italy Dietologia e Nutrizione Clinica, ASO “Maggiore della Carità”, Novara, Italy b S.C.

Background/aim. Coeliac disease is a genetic, immunologically mediated small bowel enteropathy that causes malabsorption. The immune inflammatory response to gluten frequently causes damage to many other tissues of the body. The condition is frequently underdiagnosed because of its protein presentations. New prevalence data indicate that symptomatic

and latent coeliac disease is present in one of 300 people of European descent. Age of onset ranges from infancy to old age. Symptomatic presentations include general ill-health, as well as dermatologic, haematologic, musculoskeletal, psychologic and neurologic diseases. Since untreated patients have an increased incidence of malabsorption-related pathologies and/or malignancies (i.e. osteoporosis; intestinal lymphoma), it therefore arises the importance of a correct and early diagnosis. Patients and methods. We accurately reviewed 154 coeliac patients (127 females, mean age 39.6 years, range 18–74) that we have diagnosed from 1994 to September 2003, as regards the presence of overweight/obesity at the moment of diagnosis and during the follow-up while on gluten-free diet. Results. We evidenced an incidence of 11.7% of overweight/obese patients at the moment of diagnosis: 14 overweight patients (12 females, mean age 39.4 years), with a mean body mass index (BMI) of 27.7, range 26.1–29.7. 4 obese patients (three females, mean age 38.9 years), with a mean BMI of 36.1, range 32.2–44.1. Clinical onset were: iron deficiency/anaemia with/without gastrointestinal symptoms (bloating, dyspepsia) in 11 cases (61.1%), only aspecific gastrointestinal symptoms in four cases (22.2%), one case of dermatitis herpetiformis (5.5%), one case of diarrhoea and weight loss (5.5%), one case discovered incidentally while performing upper endoscopy for bleeding (5.5%). Twenty-three (17 females, mean age 38.6 years, range 18–64) out of 132 patients (with a mean follow-up period of 18.2 months) were within normal BMI ranges (mean BMI 22.1, range 18.7–24) at the moment of CD diagnosis but developed a 15.5% of weight increase while on gluten free diet for a mean time of 18.2 months (range 6–30). Clinical onset were: malabsorption and weight loss in 10 cases (43.5%), iron deficiency/anaemia with or without gastrointestinal symptoms (bloating, dyspepsia, diarrhoea) in 9 cases (39.1%), 2 cases of dermatitis herpetiformis (8.7%), 2 cases of transaminases increase (8.7%). Conclusions. Our results evidenced that in a cohort of 154 CD patients almost 12% of cases were overweight or obese at the time of diagnosis, while almost 15% developed weight increase related problems while on gluten free diet. Therefore, coeliac disease is no longer only characterised by weight loss and an overweight/obese patient may be suspected as being affected by coeliac disease. Furthermore, our data underlined the importance of an accurate nutritional follow-up of CD patients, in order to avoid the onset of a new pathological condition, namely the overweight/morbid obesity. PO114 EFFECT OF CHRONIC ADMINISTRATION OF URSODEOXYCHOLIC ACID ON GALLBLADDER AND GASTRO-INTESTINAL MOTILITY IN GALLSTONE PATIENTS AND HEALTHY CONTROLS A. Colecchiaa , L. Sandria , P. Simonia , F. Azzarolia , A. Vestitoa , G. Mazzellaa , A. Rodab , E. Rodaa , D. Festia a Department

of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy b Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy

Background. Gastrointestinal motility defects play a role in gallstone pathogenesis. The effect of ursodeoxycholic acid (UDCA) on gastrointestinal motility is poorly understood. Aim. To evaluate the effect of chronic UDCA administration on gallbladder motility, oro-ileal transit time (OITT) and gastric emptying (GE) in gallstone patients (GS) and controls (CTR). Materials and methods. Gallbladder motility and gastric emptying (by ultrasound), and OITT (by an immunoenzymatic technique) were evaluated before and after 3 months of UDCA (12 mg/kg b.w. per day) administration in 10 symptomatic GS (two men, eight women; age: 51.8 ± 10.3 years; BMI: 26.6 ± 3.8 kg/m2 ) and 10 matched healthy CTR (two men, eight women; age: 52.8 ± 9.5 years; BMI: 26.0 ± 3.4 kg/m2 ).

Abstracts Results. OITT was longer in GS than in CTR (312.0 ± 22.2 min versus 213.0 ± 25.0 min, P < 0.001); UDCA significantly reduced OITT in GS (240.0 ± 16.4 min, P < 0.05 before versus after) but not in CTR (186.0 ± 32.0 min, P = n.s. before versus after). Fasting gallbladder volume (FV), residual volume (RV) and percent emptying (%E) were significantly different (P < 0.05) in GS (22.5 ± 0.7; 5.2 ± 0.1 ml, 63.0 ± 8.0%) in comparison with CTR (18.4 ± 3.9; 4.5 ± 3.1 ml; 77.0 ± 10.6%). After UDCA treatment, FV significantly increased (27.3 ± 3.2 ml versus 22.5±0.7 ml, P < 0.005) such as residual volume RV (9.1±3.0 ml versus 5.2 ± 0.2 ml) and %E increased but not significantly in GS compared to baseline, while in CTR only FV increased (23.1 ± 2.3 ml versus 18.4 ± 3.9 ml, P < 0.03). As regard gastric emptying before UDCA, GS had longer gastric half-emptying time (T1/2 ) than CTR (33.9 ± 7.3 min versus 23.4 ± 4.9 min, P < 0.02) at baseline; after UDCA, T1/2 significantly decreased (33.9 ± 7.2 min versus 24.0 ± 5.1 min, P < 0.05) in GS but not in CTR (28.2 ± 8.6 min versus 23.4 ± 4.9 min, P = ns). Conclusions. GS has delayed gastric emptying and OITT and reduced % gallbladder emptying. UDCA administration restores these motility defects in GS, but it has no effect in CTR. These results suggest a new and additional UDCA mechanism of action. PO115 ECONOMIC EVALUATION OF RABEPRAZOLE VERSUS OMEPRAZOLE IN THE CURATIVE TREATMENT OF REFLUX OESOPHAGITIS G. Lorenzo Colomboa , A. Muzioa , M. Pantaleonia , M. Caragliab , S. Casalinib , P. Nardinib a S.A.V.E.

Studi Analisi Valutazioni Economiche, Milan, Italy SpA, Cologno Monzese, Milan S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy b Janssen-Cilag

Background and aim. GERD is a chronic condition that may affect patients’ quality of life. It is one of the most common complaints in primary care settings with relevant consequences on health economics in terms of increasing health costs and limited resources. At present proton pump inhibitors are considered the best choice for GERD management. An objective of this multicentre trial was to evaluate the time of action of rabeprazole 20 mg daily (RAB) and omeprazole 20 mg daily (OME) in inducing symptom relief in patients with reflux oesophagitis in the curative phase. A prospective health economic analysis was performed to compare the costs of the two treatments in obtaining symptoms improvement. Methods. Five hundred and sixty patients, with mild to severe reflux oesophagitis (Savary–Miller grades I–III), were randomised in a double-blind, parallel group fashion, to receive RAB or OME for a period of 4–8 weeks (depending on endoscopic and symptom response) with control visits every 2 weeks. The patients had to fill in a daily diary regarding the number of tablets/capsules taken and the daytime and night-time heartburn intensity using the following score: 0 (absent), 1 (mild), 2 (moderate), 3 (severe) and 4 (terrible). The economic analysis was designed and carried out from a societal and National Health Service perspective. Results. In the curative phase of reflux oesophagitis (from 4 to 8 weeks) treatment with RAB resulted less expensive than OME. The estimated mean total costs (direct medical cost and loss of productivity) were found to be lower in RAB group ( 58,04) than in OME one ( 64,34; P < 0.001). With regard to numbers of symptom-free days, RAB (5111 days) was found to be more effective than OME (4839 days). Conclusions. Rabeprazole 20 mg once daily is cost effective compared with omeprazole 20 mg once daily in the curative phase of reflux oesophagitis. Rabeprazole represents good value for money and efficient use of health care resources in the treatment of reflux oesophagitis. Acknowledgement. Research supported by Janssen-Cilag SpA, Italy

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PO116 INTRAGASTRIC BALLOON IN OBESE PATIENTS. CAN ACCURATE SELECTION OF PATIENTS AND ADHERENCE TO A FOLLOW-UP PROTOCOL REDUCE COMPLICATIONS AND IMPROVE WEIGHT LOSS? R. Conigliaro, L. Camellini, C. Guatti Zuliani, R. Sassatelli, E. Della Valle, G. Bedogni Digestive Endoscopy Unit, Department of Surgery, Azienda Ospedaliera Santa Maria Nuova, Reggio E, Italy Background and aim. The BioEnterics Intragastric Balloon (BIB) is a device intended to induce weight loss by limiting food consumption. Results of this technique are controversial and complications average 8%. Proposed indications for BIB are: (1) as “a bridge to bariatric surgery” in patients with BMI >50; (2) to reduce the risk of elective surgery in patients with BMI 40–50; (3) in patients with BMI 30–35, but with important co-morbidity; as a “BIB-test” in candidates with restrictive surgical procedures. The aim of this study is to validate prospectively a protocol dealing with the criteria of selection of patients candidates for BIB placement and with the modalities of their further follow-up. Considered outcomes were weight loss and complications. Methods. Patients were evaluated by a team including an endocrinologist, a digestive endoscopist, a dietician and a psychiatrist, in order to assess not only the general health-status, but also the social, relational and economic impact of the obesity. All patients underwent physical examination, medical history (including in particular previous surgery, co-morbidities, dietary habits and quality of life), laboratory work-up, upper endoscopy. BIB placement was carried out on inpatient basis, under conscious sedation. Inflation was standardised at 500 ml 2% methylene blue saline solution. Intravenous therapy (spasmolitics, antiemetics, PPI) was administrated to control post-insertion symptoms and switched to oral therapy before discharge. A dietician prescribed a personalised 800–1000 calories menu and re-evaluated each patient monthly. The balloon diameter was checked by US at 1, 3 and 5 months. The balloon was left in place for 3 to a maximum of 6 months, on the basis of the evaluation of the weight reduction. Results. We evaluated 12 patients and 3 were excluded, because of not enough motivation. All patients were female (mean age 41.6 years; 24– 67). Mean time with BIB in situ was 5 months (1–7). Mean BMI was 43.2 (33.4–60.9) at inclusion, 37.9 (27.2–54) at 3 months and 37.7 at the time of BIB removal. We did not observed any complication requiring surgery, or admission. In one patient the BIB was removed before 3 months, for intolerance. Conclusion. BIB placement may be effective for selected and highly motivated obese patients, but a supervised nutritional and behavioural regimen is mandatory. A close clinical follow-up may be useful to avoid complications and to improve compliance. PO117 BOWEL GAS EXPLOSION WITH COLON PERFORATION DURING ARGON PLASMA ENDOSCOPIC COAGULATION IN PATIENTS OPERATED FOR ADENOCARCINOMA OF THE SIGMA. A CASE REPORT C. Continia , F. Zinib , G. Bacchib a Sezione

di Gastroenterologia ed Endoscopia Digestiva, Italy di Chirurgia Generale Casa di Cura Accreditata “Città di Parma”, 43100 Parma, Italy b Sezione

Argon Plasma treatment of sessile polyps in the gastrointestinal tract is now a well-established procedure liable to rare complications such as submucous emphysema or perforation. A case of bowel gas explosion is being reported which occurred in the ascending colon during the removal of a sessile polyp from the transverse colon of a patient who had undergone sigma resection due to adenocarcinoma. A 63-year-old

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Abstracts

man underwent follow-up colonscopy prepared by oral administration of 4 l isoelectrolytic solution (SELG-S), 6 months after laparoscopic resection of the sigma for adenocarcinoma and colo-rectal anastomosis. On colonscopy, bowel cleaning was found to be very poor on the upstream side of the anastomosis, and a sessile polyp measuring 1.5 cm in diameter was detected in the transverse colon. As a result, removal by means of a polypectomy loop was arranged. Owing to the presence of residual adenomatous tissue, Argon Plasma treatment was performed and, as soon as the ionised gas was released, the colon exploded causing sharp pain and a state of shock in the patient. The man was resuscitated by means of Plasma expander, painkiller and dopamine infusions and was sent to the operating room, where the ascending colon was found to have been broken. Resection of the ascending colon was performed with permanent ileo-transverse anastomosis. The patient was discharged after 11 days’ treatment and appeared to have recovered his regular living functions by the next follow-up examination. The case appears to be a significant one, as only two other instances of colon explosion with the same procedure have been reported so far, both following preparation with simple phosphosoda cleaning enemas. With the case under study, bowel cleaning was performed by way of regular oral administration of 4 l iso-electrolytic solution, which proved to be inadequate as it apparently brought about an explosive gas mixture within the bowel resulting in colon perforation. PO118 ENDOSCOPIC CHROMO-ENDOSCOPY IN PATIENTS WITH HEAD AND NECK CANCER F. Coppolaa , A. Carlinoa , M. Bono-Galvaniob , R. Roccaa , A. Peraa a Divisione b Divisione

di Gastroenterologia, Ospedale Mauriziano, Turin, Italy di Otorinolaringoiatria, Ospedale Mauriziano, Turin, Italy

Background. Patients with head and neck cancers are at increased risk of developing oesophageal cancers. A cancerisation “field effect” may help explain the occurrence of multiple cancers in the upper aero-digestive tract. Aim. To assess the presence of pre-neoplastic lesions in the oesophagus of patients who had been treated by surgery or chemo-radiotherapy for head and neck cancers. Methods. After performing standard upper digestive endoscopy (EGDS), a 2% iodine solution (Lugol) was sprayed over the entire oesophageal mucosa. Biopsies were performed in all the unstained areas (voiding areas) in order to assess epithelial dysplasia. In each patient, the grade of dysplasia, number, localisation, endoscopic characteristics of voiding areas, the presence of oesophagitis and TNM classification of the primary cancer were recorded. Results. Forty-four patients (40 males and 4 females), age range 39–81 years, have been studied so far; the diagnosis of head and neck cancer was made within the last 3 years before endoscopy in 15 cases and 3 or more years before in 29 cases. There were four voiding lesions per patient, localised in the oesophageal middle third in 22 patients (48%). In 65% of the voiding areas there were only inflammatory changes, in 30% parakeratosis or acanthosis and in 5% normal mucosa. No dysplasia was found in any biopsy sample. In three patient we diagnosed an oesophageal cancer, and in one patient an adenocarcinoma of the gastric fundus; three of these patients were asymptomatic, whereas mild dysphagic symptoms were elicited in one patient. All cancer lesions were clearly visible before staining and were histologically advanced. No significant differences were present for alcohol consumption and smoking habits between patients with and without oesophago-gastric cancers. Conclusions. Four of the 44 patients (9%) with head and neck cancer submitted to EGDS were found to have a gastro-oesophageal carcinoma, but if we consider the subgroup of seven patients with hypofarynx carcinoma, three of seven developed oesophageal cancer (43%). In our cases endoscopic iodine staining has demonstrated to be inefficacious. These preliminary data recommend to focus on an early screening of patients

with hypofarynx carcinoma, in which iodine staining will probably be useful in discovering precancerous oesophageal lesions. PO119 INFLIXIMAB: POSSIBLE MAINTENANCE THERAPY IN PATIENTS WITH CROHN’S DISEASE ASSOCIATED WITH GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY C. Cosco, R. Marasco, S. Tammaro, P. Cosimo, V. Cosco, P. Doldo Department of Gastroenterology, Policlinico Mater Domini, Università degli Studi Magna Graecia di Catanzaro, Italy Introduction. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common defect of the hexose monophosphate shunt. The enzymatic deficit may cause a reduced capacity of haemoglobin to resist oxidant stress or drugs. Antimalarials, nitrofurantoin, sulphonamides and acetylsalicylic acid must be avoided in these subjects in order to prevent acute haemolytic crisis (1). Systemic administration of mesalamine is commonly used in the maintenance therapy of patients with inflammatory bowel disease (IBD). As derivative of acetylsalicylic acid, mesalamine is toxic in patients affected by G6PD deficiency. Anti-TNF alpha is a chimeric monoclonal antibody (IgG) commercially available, effective in treatment and maintenance of remission of Crohn’s disease (CD) (2). Aims and methods. To evaluate the efficacy of infliximab as maintenance therapy in patients with Crohn’s disease associated with G6PD deficiency. A 23-year-old male, affected by CD with ileo-colonic involvement associated with recurrent aphthous stomatitis and G6PD deficiency, was treated with infliximab. Induction of remission was obtained, 2 years before, with metronidazole (2 g per day) and prednisone (1 mg/kg body weight); treatment was continued with budesonide (9 mg per day) as maintenance regimen (3). These drugs partially improved abdominal symptoms, but had poor effects on laboratory data (iron-deficiency anaemia, thrombocytosis and increased reactive C protein) and on aphthous stomatitis. Crohn’s disease activity index (CDAI), used to assess response, was always > 280. The patient received single infusion of infliximab (5 mg/kg body weight). Results. Dramatic response was observed within 24 h for abdominal symptoms while aphthous stomatitis disappeared and laboratory data returned in the normal ranges 72 h after the infusion. The CDAI decreased to 150 and so was maintained after 4 weeks. No acute or delayed adverse events have been noted. Conclusion. Our results suggest that infliximab can be safely used in patients affected by CD associated with G6PD deficiency. PO120 STHENOSIS OF THE UPPER OESOPHAGUS WITH DYSPHAGIA BY HETEROTOPIC GASTRIC MUCOSA. CASE REPORT L. Costaa , D. Bernardinib , G. Bollac a U.O.

Chirurgia Pediatrica, U.L.S.S. N. 6 Vicenza, Italy Endoscopia Digestiva U.L.S.S. N. 6 Vicenza, Italy c U.O. Chirurgia Generale, Serv. Chirurgia Pediatrica U.L.S.S. Dolo (VE), Italy b Serv.

We describe a 10-year-old boy, dysphagic, diagnosed as having upper oesophageal stenosis. Biopsies of the stricture showed heterotopic gastric mucosa; endoscopic treatment with Savary’s dilatators was safe and effective in a follow-up of 18 months. This case is instructive because of rarity, location of the lesion, treatment and patient’s age.

Abstracts PO121 ENDOSCOPIC ARGON-PLASMA TREATMENT OF BLEEDING ANGIODYSPLASIA OF THE GASTRIC FUNDUS. CASE REPORT L. Costaa , D. Bernardinib , L. Milanb a U.O. b Serv.

Chirurgia Pediatrica, U.L.S.S. N. 6 Vicenza, Italy Endoscopia Digestiva U.L.S.S. N. 6 Vicenza, Italy

The gastric fundus angiodysplasias are rare artero-venous malformation, that can cause chronic iron-deficiency anaemia or sometimes serious acute blood loss. We describe a 9-year-old boy with a diffuse angiodysplasia interesting completely and only the gastric fundus. This lesion had endoscopic characters of linear bright red streaking, flat or slightly protruded, with frond-like margin. He come to our observation because of vomiting with ematemesis. Treated with endoscopic argon-plasma, the boy became symptoms free and without lesion’s relapse in a 13-month follow-up. This case is instructive because of rarity, patient’s age, location of the lesions, and effectiveness of the treatment. PO122 RESPONSE TO PROTON PUMP INHIBITORS IN NON-CARDIAC CHEST PAIN: META-ANALYSIS F. Cremonini, J. Wise, N.J. Talley Clinical Enteric Neuroscience, Translational and Epidemiological Research (C.E.N.T.E.R.) Group, Mayo Clinic and Foundation, Rochester, MN, USA Background and aims. Non-cardiac chest pain (NCCP) is a common disorder in the general population that might have a negative impact on quality of life and health care cost [Aliment. Pharmacol. Ther. 17 (2003) 115]. There are currently no therapeutic approaches of established value for NCCP. We performed a meta-analysis to test the hypothesis that proton pump inhibitors (PPIs) are superior to placebo for inducing symptomatic relief in NCCP. Methods. Search of the electronic databases Medline and EMBASE (1966–2003) and a hand-search from retrieved papers’ cross-references and from the abstract books from the major gastroenterology meetings (1998–2003). The data were extracted independently by two authors. Therapeutic response was defined as improvement of remission of pain. A random-effects model was used to pool the results and the number needed to treat (NNT) for patient-rated symptom improvement, assessed with symptom diaries or scores. Results. Five studies using omeprazole (3) or lansoprazole (2) were retrieved. All the studies investigated short-term administration of PPIs. The pooled odds ratio for therapeutic response to PPIs was 3.51 (95% CI 2.11–5.95) and the NNT was 3.7 (95% CI 2.7–6.1). One study was the source of heterogeneity (P = 0.04). After removal of the study, the pooled odds ratio remained significant (3.4, 95% CI 1.97–5.96). Conclusions. Short-term PPIs were superior to placebo in NCCP. PO123 META-ANALYSIS OF THE STUDIES ON THE ASSOCIATION BETWEEN H. pylori INFECTION AND ISCHAEMIC STROKE F. Cremoninia , M. Gabriellib , L. Santarellib , G. Gasbarrinib , P. Polab , A. Gasbarrinib a Clinical

Enteric Neuroscience, Translational and Epidemiological Research Program (C.E.N.T.E.R.) Mayo Clinic and Mayo Foundation, Rochester, USA b Internal Medicine, Catholic University of Sacred Heart, Gemelli Hospital, Rome, Italy Background and aim. There is a contrasting evidence on the relevance of chronic infection by Helicobacter pylori as a risk factor for stroke.

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Previous studies have emphasised the potential role of more virulent H. pylori strains, bearing the CagA antigen, and have shown higher H. pylori seroprevalence in patients with stroke due to large vessel disease compared to other types of stroke. Materials and methods. Meta-analysis of cross-sectional studies. Outcome measure was the seropositivity for H. pylori and for CagA in patients with stroke versus controls, and the seroprevalence for H. pylori in patients with stroke due to large-vessel stroke versus patients with other types of stroke and controls. Seven cross-sectional, case-control studies were included. Results. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 [95% CI 1.24–1.81], for the association between stroke and anti-CagA positivity was 2.23 [95% CI 1.49–3.36]. Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65 [95% CI 1.12–2.45]), and than controls (odds ratio 1.61 [95% CI 1.13–2.32]). However, only 4/7 studies gave information on other risk factors for cerebrovascular disease or performed multivariate adjustment of risk estimates. Conclusions. There is a modest association between H. pylori positivity, anti-CagA positivity and stroke. Association seems higher with stroke due to large-vessel disease. However, the clinical relevance of such an association is questionable. PO124 SEVERE ACUTE COLITIS ASSOCIATED WITH CYTOMEGALOVIRUS: A PREVALENCE STUDY V. Criscuolia , A. Orlandoa , G. Pecorarob , L. Olivaa , A. Casèa , M. Trainaa , A. Rizzoc , M. Cottonea a Clinica

Medica “R”, Divisione di Medicina, Istituto di Medicina Generale e Pneumologia, Università degli Studi di Palermo, Italy b Laboratorio di Microbiologia, Istituto di Medicina Generale e Pneumologia, Italy c Istituto di Anatomia Patologica, Ospedale “V. Cervello” Palermo, Italy

Objectives. The aim of this study was to determine the overall prevalence and the role of cytomegalovirus (CMV) infection in a consecutive series of patients with acute severe colitis admitted to our department from 2000 to 2003. Methods. The 39 patients (35 with Ulcerative colitis and 4 with Crohn’s disease) admitted to our hospital for acute severe colitis, proctoscopy and biopsy were performed together with blood sample cytomegalovirus determination at the time of admission regardless of their steroid resistance. Results. In the 39 patients, we discovered an overall CMV infection prevalence of 23% in our geographical area. In seven patients (18%) cytomegalovirus was detected through biopsy. The presence of cytomegalovirus in biopsies was not always predictive of steroid resistance. Three patients with cytomegalovirus in biopsies responded to conventional treatment without needing any antiviral treatment, which suggests that the virus plays only an incidental role. Conclusions. Cytomegalovirus is frequently associated with colitis but it is not always pathogenic. Studies on the genotyping of the virus might explain the diversity of its biological behaviour. PO125 SAFETY OF AZATIOPRINE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: RESULTS OF A LONG-TERM FOLLOW-UP STUDY P. Crispino, F. Iacopini, O.A. Paoluzi, R. Pica, A. Consolazio, A. Marcheggiano, M. Rivera, D. Palladini, P. Paoluzi Gastroenterology, Department of Clinical Sciences, University “La Sapienza”, Rome, Italy

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Abstracts

Background. Azathioprine (AZA) in patients with inflammatory bowel disease has been demonstrated to be effective but its safety in long-term regimens is not well known. Aim. To evaluate the efficacy and the safety of a long-term treatment with AZA in a series of corticosteroids-dependent patients with ulcerative colitis (UC) or Crohn’s diseases (CD). Methods. A total of 34 corticosteroids-dependent patients (mean age ± S.D.: 50.8±14.9 years) with UC (n = 26) or CD (n = 8) received AZA at a dosage of 2 mg/kg per day, in addition to a standard treatment with oral salicylates. After 3 months of AZA intake, steroids were gradually tapered to discontinuation. Efficacy of treatment was evaluated by periodical clinical, endoscopic and histological controls and a successful response was defined as persistent remission following discontinuation of steroids. Safety was evaluated on the basis of occurrence of laboratory (full blood count and parameters of renal, hepatic and pancreatic function) and/or clinical adverse events. Results. All patients were under AZA treatment for a median period of 4 years and remained in clinical, endoscopic and histological remission. Steroids were discontinued in 22 patients (65%) and only reduced in 12 (35%). Adverse events occurred in 18 patients (56%), the most frequent being macrocitosis (35%), leukopaenia (29%), iperamilasaemia and iperlipasaemia and cholestasis (6%). The incidence of side-effects was significantly higher in patients without a complete response to AZA (P = 0.02). The timing of occurrence of adverse events was superior of 1 month from the beginning of treatment with AZA. Conclusions. Long-term treatment with AZA was tolerated in majority of patients. Occurrence of adverse events, generally mild, did not interfere with the assumption or the dosage of AZA. The predominance of adverse events in patients without a complete response to AZA indicate the tolerability of the drug and is related with the individual metabolic pathways. PO126 DIAGNOSIS OF Helicobacter pylori INFECTION: COMPARISON BETWEEN INVASIVE AND NON-INVASIVE TESTS P. Crispinoa , F. Iacopinia , A. Consolazioa , O.A. Paoluzia , R. Picaa , M. Riveraa , D. Palladinia , F. Nardib , P. Paoluzia a Gastroenterology b Department

Unit, Department of Clinical Sciences, Rome, Italy of Pathology, University “La Sapienza”, Rome, Italy

Background. Invasive tests are considered as the gold standard for the diagnosis of Helicobacter pylori (Hp) infection, but non-invasive tests are better tolerated. Aim. To compare the accuracy of different tests as histology, rapid-urease test (RUT), urea-breath test (UBT), Hp-stool antigen (HpSA), anti-Hp antibodies (anti-Hp Ab) in the diagnosis of Hp status. Methods. One hundred and fifteen consecutive dyspeptic patients, never treated for Hp infection, underwent histological evaluation of two biopsies both in antrum and corpus (H&E), RUT in antrum, serum Ab anti-Hp, 13C-UBT and HpSA. Hp status was established by concordance of at least four out of five tests. Results. In 13 (11%) patients Hp status remained undetermined due to the presence of more than one non-concordant to the others while 102 patients were Hp-negative (52%) and Hp-positive (37%). Performances of each test are shown in the table.

HpSA Anti-Hp Ab UBT Histology (H&E) RUT

Sensitivity

Specificity

Accuracy

PPV

NPV

84 100 90 100

95 95 100 80

93 97 95 89

87 94 100 80

97 100 92 100

77

97

88

95

84

PPV: positive predictive value; NPV: negative predictive value numbers are percentages.

Conclusions. None of the test used should be considered as a gold standard for the determination of Hp status. In dyspeptic patients the combination of histology and UBT ameliorate the global accuracy respect to the use of one test only. The combination of UBT and anti-Hp Ab could be used as a screening tests in populations with low risk of Hp-related complications. PO127 VARIABLES RELATED TO ANXIETY INDUCED BY GASTROINTESTINAL ENDOSCOPIC EXAMINATIONS S. Crotta, S. Paganin, P. Servi, B. Dagnes, M. Jasmine Gastroenterology and Endoscopy Unit, Ospedale Beauregard, Aosta, Italy Background and aims. Gastrointestinal endoscopy procedures can induce anxiety in patients. The aim of this study is to provide a quantitative measure of anxiety and some hypothesis about its causes. We measured anxiety level before endoscopic exams and its relation to: sex, education, kind of endoscopic exam (gastro/colonoscopy), previous written information about the procedures. We evaluated also the declared causes in the patient’s judgement of anxiety and the best ways to reduce it. Patients and methods. We considered 245 outpatients waiting for endoscopic exam (120 males/125 females) and 58 age/sex matched controls. Out of the 245 examined patients 56.7% of them received informative brochure; 70.2% had a low education grade. Gastric endoscopy was performed on 161 patients (63%), colon endoscopy on 84 patients. Endoscopic exam was performed for the first time in life in 39.1% of them. Anxiety was evaluated by visual analogic scale (0–10). Statistical analysis was performed by Association Measures (η). Results. Average anxiety was 5.14 ± 3.1 (S.D.) (female 6.03 ± 3.02 S.D., males 4.21 ± 3.08 S.D.); controls showed 3.33 ± 2.78 S.D. (Eta 0.226; P < 0.05). Anxiety was not significantly different in patients waiting for colonoscopy (5.55 ± 3.21) versus patients waiting for gastroscopy (4.96 ± 3.14 S.D.) and in patients in which endoscopy was performed for the first time versus persons with history of endoscopic examinations. Written information brochure did not modify anxiety (received versus not received brochure = 5.29 ± 3.3 S.D. versus 4.90 ± 3.02 S.D.). Patients without education had a higher anxiety level compared with others (η = 0.375). Anxiety causes in waiting room were: fear about endoscopy results (25%), about pain (20%) and long waiting time (19%). One half of patients (49%) would prefer oral information instead of written informations (39.2%). Conclusions. Despite the wide S.D. of results in our study, endoscopic examinations are likely to induce anxiety in patients, independently from sex, kind of examination and previous endoscopic examinations performed. Fear of endoscopy results and of pain and trouble deriving from waiting time are the most important causes of anxiety. Written information brochures are not able to reduce this state. Oral information is better than written one according to the patient’s judgement. It can be argued that adding a personal contact between the endoscopist and the patient can decrease patient’s anxiety and improve performance. PO128 LIFE THREATNING ADVERSE EVENT AFTER INJECTION OF MICROBUBBLE CONTRAST AGENT FOR TRANSABDOMINAL ULTRASONOGRAPHY (US): THE FIRST REPORT N. Crucinioa , M.C. Nacchierob , E. Celaa , N. Della Valleb , C. Ricciardellib , V. Stoppinoa , E. Ierardib , C. Panellab a Section

of Gastroenterology, Department of Medical Sciences, University of Foggia, Italy b Gastroenterology Unit, Ospedali Riuniti, Foggia, Italy

Background. A growing interest has been raised by microbubble contrast agents for US for the possibility of both detecting and characterising hepatic focal lesions without biopsy performance as well as controlling

Abstracts short-term effect of loco-regional therapies. Contraindications are few and rare and, therefore, the method is considered to be safe even when used in patients with severe liver, kidney, hearth and lung diseases [1,2]. For these reasons, to report the case of a life threatening adverse event observed during the performance of US with counter agent is considered necessary. Case report. Our case regards a 77-year-old female patient, admitted to our Unit for the onset of ascites and oedemas at lower limbs. Physical examination revealed hepatomegaly and laboratory tests showed mild anaemia (9.8 g/dl) and marked increase (7.2 times normal value) of g-glutamil-transpeptidase. Conventional US demonstrated a picture of chronic liver disease with a dishomogeneous ultrasonographic pattern associated to a focal lesion (14 cm × 10 cm) whose nature was decided to be better defined with the use of a counter agent (SonoVue, Bracco, Italy). Additionally, the patient was affected by chronic disorders such as obstructive pulmonary disease, hypertension, atrial fibrillation and diabetes. All these diseases did not represent active clinical problems, at the moment of hospitalisation, since an appropriate medical treatment was assumed. Adverse event. About 5 min after the injection of 4.8 ml of SonoVue, acute severe dyspnea and a fall of blood pressure until undetectable values occurred. Basic life support manoeuvres associated to steroid and plasma expander intravenous administration allowed reaching a normalisation of cardiac and respiratory functions within 20 min. Conclusions. This case report suggests that SonoVue administration and acute cardio-respiratory failure could be directly related, despite the safety of this counter agent has been assessed in a large series of patients with lung and heart chronic disorders. References [1] Senior R, et al. Echocardiography 2000;17:705. [2] Bikor D, et al. Invest Radiol 2001;36:104.

PO129 RELATIONSHIP BETWEEN ENVIRONMENTAL FACTORS AND INFLAMMATORY BOWEL DISEASE C. Cucino, M. Fasani, S. Gallus, G. Maconi, S. Ardizzone, G. Bianchi Porro Luigi Sacco University Hospital, Milan, Italy Background and aim. The aetiology of inflammatory bowel disease (IBD) is unknown. The rise in incidence of IBD during the 20th century suggests strong environmental influences. The role of diet, social class and the level of physical activity were shown to be associated with IBD, but only few authors considered incident cases. The aim of this study was to evaluate the relationship between those factors and the risk of IBD in incident cases. Patients and methods. Between June and September 2003 we interviewed, a telephonic interview was done about the dietary habits, the occupation and the level of education, 48 new cases of IBD (24 with UC and 24 with CD) and 96 frequency-matched controls (by quinquennia of age and sex) discharged from the University Hospital Luigi Sacco in Milan. The odds ratios (OR) and their 95% confidence intervals (CI) were estimated by multiple logistic regression, conditioned by age and sex, and after allowance for education and, for dietary factors, number of portions per week. Results. An increased risk for IBD was associated with a high consumption of pasta (OR for the highest versus the lowest approximate percentile of portions per week was 3.05; 95% CI 1.20–7.75), red meat and pork (OR 3.00; 95% CI 1.11–8.07), and poultry and rabbit (OR 2.33; 95% CI 0.99–5.46), whereas a decreased risk was associated with a high intake of fruit and vegetables (OR 0.56; 95% CI 0.25–1.26 and 0.25; 95% CI 0.09–0.66, respectively). Although not statistically significant, an increased risk with a high level of education and a decreased risk related to a high level of physical activity at work were found. Discussion. Although based on a small number of cases, this is one of the few studies providing information on the role of several environmental fac-

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tors and the risk of IBD using incident cases. This allows, at least in part, to reduce the so called “recall bias” when considering the dietary aspects. PO130 SKELETAL MUSCLE MYOPATHY IN PATIENTS WITH CROHN’S DISEASE: THE ROLE OF INFLAMMATION, INTESTINAL PERMEABILITY AND MUSCULAR APOPTOSIS L. Cuocoa , R. Castamana , L. Dalla Liberab , B. Ravarab , G. Vescovoa , M. Salvagninia a Gastroenterology

and Internal Medicine Unit, S. Bortolo Hospital, Vicenza, Italy b CNR Unit for Muscle Disease, Padua, Italy

Background and aim. Growth retardation, weight loss and changes in body composition are common features of active Crohn’s disease (CD) because of malnutrition, protein loss, anorexia, increased requests. In active CD lean body (muscles) mass (LBM) impairment is not strictly related to malnutrition, suggesting that other factors may play a role in this process. In our study, we have evaluated the body composition and the pathological changes of skeletal muscle in patients with CD and their relationships with proinflammatory cytokines, intestinal permeability (PI). Materials and methods. Seven consecutive steroid-free patients with active CD (three males, four females, mean age 37 years CDAI >200) underwent evaluation of BMI and body composition (DEXA), sugar test for PI, measure of serum levels of TNF-␣, sphingosine (SPH), bacterial lipopolisaccaride (LPS) and biopsy of gastrocnemius. In bioptic samples we determined cross sectional area (CSA) as an index of muscle atrophy, distribution of myosin heavy chains (MHC) and apoptosis (TUNEL). The results were compared with 20 healthy subjects (t-test for unpaired data). Despite the small sample size a multivariate analysis (ANOVA) was performed. Results. BMI and LBM were reduced in ACD versus controls (20.1 + 0.7 versus 23.2 + 0.9; 60.1% versus 68.4%; P < 0.01); PI was increased in ACD (ratio lactulose/mannitole 1.358 versus 0.018, P < 0.01) as well as TNF-␣, SPH (13.6 pg/ml versus 3 pg/ml; 3528 pmol/ml versus 1975 pmol/ml, P < 0.01) and LPS (0.93 EU/ml versus 0.52 EU/ml, P < 0.01). In bioptic samples, CSA was reduced in ACD (3759 mm2 versus 4415 mm2 , P < 0.01) with shift of MHC from type I to type IIb fibres (fast, anaerobic). Apoptosis was demonstrated in four samples (P < 0.01). Discussion. In CD, a myopathy, characterised by myocyte apoptosis, modifications of MHC distribution and muscle atrophy has been found. This process seems to be related to inflammation (increased levels of TNF-␣ and SPH that have also proapoptotic effects). Increased PI with seric translocation of bacterial breakdown products may be a further source on increased TNF-␣ and SPH. PO131 PREVALENCE OF UNINVESTIGATED DYSPEPSIA AND IDENTIFICATION OF DYSPEPTIC SYMPTOMS GROUPINGS IN A GENERAL POPULATION R. Cuomo, D. Bruzzese, G. Giolitto, G. Sarnelli, G. Budillon Gastroenterologia, Dipartimento di Medicina Clinica e Sperimentale and Dipartimento di Matematica e Statistica, Università degli Studi di Napoli “Federico II”; Unità Operativa di Medicina Interna, Presidio Ospedaliero, Polla, Salerno, Italy Background. Dyspepsia prevalence varies considerably, with the average reported value being approximately 25%. Despite the epidemiological studies performed in Italy in primary care, tertiary referral centres or endoscopy centres, observations in the general population are lacking. Dyspeptic patients have been subdivided based on the predominant symptoms, but in most cases the pathophysiological mechanism does not explain the different dyspepsia subtypes.

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Abstracts

Aim. To explore, in a general population, prevalence and symptom association of uninvestigated dyspepsia. Method. Presence and severity of eight dyspeptic symptoms were explored in age and sex-stratified random sample of 1300 Southern Italians aged 18–82 years living in a restricted area. A standardised questionnaire was used to score the severity (absent, mild, moderate and disabling; 0–3) of epigastric pain, postprandial fullness, bloating, early satiety, nausea, vomiting, belching, epigastric burning. We first analysed the overall prevalence of dyspepsia and then used exploratory factor analysis (Principal Component extraction method and Varimax rotation) to evaluate the significant relationship between dyspeptic symptoms and latent factors (the components) to search for the possible new subtypes of dyspepsia. Results. Considering the presence of (at least one symptom scored as mild, the prevalence of dyspepsia was 23.8% (310 subjects, males 139 mean age 48 years); if the symptom was scored as moderate or more, the prevalence decreased to 6.2% (80 subjects, males 24, mean age 46). With exploratory factor analysis performed on all people referring at least one dyspeptic symptom scored as mild or more, we found three valid components (eigen values greater than 1, cumulative percentage of explained variability equal to 63%), each of which having some of the following related symptoms (r value): component 1, characterised by satiety (0.71), fullness (0.69), belching (0.67) and bloating (0.61); component 2, characterised by nausea (0.87), vomiting (0.83), satiety (0.36) and fullness (0.26); component 3, characterised by epigastric burning (0.83), epigastric pain (0.73), bloating (0.41), fullness (0.26). Conclusion. The prevalence of dyspepsia in our sample population is similar to the one reported in other studies but the marked symptoms are present in only 6.2%. In a general population, uninvestigated dyspepsia is characterised by three components that could express three new subtypes. PO132 COELIAC DISEASE AND HCV-RELATED CHRONIC HEPATITIS: IS THERE ANY CORRELATION? A. Cuomoa , A. Roccob , M. Romanoa , V. La Murac , R. Salernoa , C. Loguercioa , G. Nardoneb , C. Del Vecchio Blancoa , M. Persicoc a Gastroenterologia,

Seconda Università di Napoli, Italy Università “Federico II” Napoli, Italy c Medicina Interna, Seconda Università di Napoli, Italy b Gastroenterologia,

Background. A higher prevalence of coeliac disease was recently reported among patients with HCV-related chronic hepatitis. Moreover, alpha-Interferon therapy seems to trigger the occurrence of coeliac disease in patients treated for HCV infection. Aim. To evaluate the prevalence of coeliac disease in a population of HCV-related chronic hepatitis treated with alpha-Interferon plus Ribavirin and, on the other hand, to study the prevalence of HCV infection among coeliac patients in an area of Southern Italy. Materials and methods. Two hundred-ten consecutively enrolled patients (male:female = 140:70, median age 46.5 years, ranged between 35 and 58 years) with biopsy proven chronic hepatitis C infection underwent serologic screening for antiendomysial IgA antibodies (EMA) analysed by indirect immunofluorescence and IgA-IgG antibodies against tissue transglutaminase (tTg-Ab) detected by ELISA. One hundred ninety-four coeliac patients (male:female = 52:142, median age 34 years, ranged between 18 and 74 years) were screened for HCV antibodies by ELISA. Positivity for HCV antibodies in coeliac patients were confirmed by detection of serum HCV-RNA by RT-PCR. Results. (1) None of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening nor did coeliac disease develop following alpha-Interferon plus ribavirin therapy. (2) Prevalence of HCV infection in coeliac patients was 1.54% (3/194) which is not significantly different from that reported in the general population. Conclusion. Coeliac disease does not seem to be associated with HCV-related chronic hepatitis in an area of Southern Italy.

PO133 CYCLOOXYGENASE-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR ARE OVER-EXPRESSED IN ILEAL POUCH-ANAL ANASTOMOSIS A. Cuomoa,b , A. Roccoa,b , C. Tuccilloa,b , C. Di Stazioa,b , G. Sciaudonea,b , A. Giuliania,b , C. Mucherinoa,b , G. Piccoloa,b , S. Staibanoa,b , G. Nardonea,b , G. Rieglera,b , M. Romanoa,b , F. Selvaggia,b a Dipartimento

di Internistica Clinica e Sperimentale, Cattedra di Gastroenterologia e C.I.R.A.N.A.D., I Chirurgia Generale e Servizio di Endoscopia Digestiva, Seconda Università di Napoli, Italy b Dipartimento di Medicina Clinica e Sperimentale-Gastro- enterologia e Dipartimento di Patologia, Università Federico II, Naples, Italy Background. The pathophysiology of pouchitis occurring after ileal pouch-anal anastomosis is controversial as well as potential for development of carcinoma in pouchitis patients. Prostaglandins synthesised in excess by cyclooxygenase-2 (COX-2) are thought to be involved in the inflammatory process and have been demonstrated to play a role in the pathogenesis of cancer in the gastrointestinal tract. Moreover, vascular endothelial growth factor (VEGF) plays a major role in the maintenance of mucosal integrity and is over-expressed in a number of gastrointestinal malignancies. Aim. To evaluate the expression and the localisation of COX-2 and VEGF in patients with ileal pouch-anal anastomosis. Methods. (1) Endoscopic biopsies were obtained from 15 patients with ileal pouch-anal anastomosis. Eight biopsies were taken from the ileal pouch and eight more biopsies were obtained from ileal nonpouch mucosa, snap-frozen in liquid nitrogen and stored at −80 ◦ C until assayed; (2) COX-1, COX-2, and VEGF mRNA expression was determined by RT-PCR; (3) COX-2 and VEGF protein expression was evaluated by western blot analysis; (4) COX-2 and VEGF mucosal localisation was evaluated by immunohistochemistry; (5) Pouchitis disease activity index (PDAI) was calculated for each patient. Results. (1) No difference in COX-1 mRNA expression was found between ileal pouch and ileal nonpouch mucosa; (2) COX-2 and VEGF mRNA and protein expression was increased in ileal pouch mucosa compared with ileal nonpouch mucosa; (3) COX-2 and VEGF immunostaining in ileal pouch mucosa was more intense in the crypt area than in the surface epithelium, whereas, in ileal nonpouch mucosa, COX-2 and VEGF immunostaining was mostly superficial. Conclusions. (1) COX-2 and VEGF (mRNA and protein) are over-expressed in the ileal pouch mucosa in ileal pouch-anal anastomosis patients, COX-2 and VEGF immunoreactivity being lower in the surface epithelium and increased in the crypt compared with ileal nonpouch mucosa; (2) we postulate that COX-2 and VEGF over-expression may play a role in the pathogenesis of pouchitis and partially explain the increased risk for adenocarcinoma in ileal pouch-anastomosis patients. PO134 FAECAL MARKERS, CALPROTECTIN AND LACTOFERRIN, FOR SIMPLE AND OBJECTIVE ASSESSMENT OF INTESTINAL INFLAMMATION: CORRELATION WITH COLONOSCOPY E. Dal Pont, R. D’Incà, C. Venturi, V. Di Leo, K. Padovan, G.C. Sturniolo Gastroenterology Section, Department of Surgical and Gastroenterological Sciences, University of Padua, Italy Detecting intestinal inflammation in a simple and objective way is important in the identification of organic diseases in patients presenting with gastrointestinal symptoms. Calprotectin (Cp) and lactoferrin (Lf) are specific neutrophil-derived proteins, stable in faeces which can be easily measured by enzyme-linked immunosorbent assay kits in spot stool samples. Cut off level for Cp is 50 mg/g faeces whereas Lf is measured by qualitative assay, Lf being positive for OD > 0.200 (corresponding to a concentration of 12.8 mg/g faeces). Sensitivity (S), specificity (Sp),

Abstracts positive predictive value (PPV) and negative predictive value (NPV) for detecting intestinal inflammation are calculated for both tests. Proportion of correctly diagnosed patients with each test and the relationship with endoscopic and histologic findings was measured by χ2 -test. Diagnostic accuracy of Cp and Lf were evaluated by receiver-operating-characteristic (ROC) curves and the areas under the curve (AUC) were calculated. We measured Cp and Lf concentration in 67 patients (37 females, mean age 47 ± 15 years) in stool samples taken the day prior to colonoscopy performed for diagnosis or follow-up purposes. Thirty healthy subjects served as controls. Final diagnoses were: inflammatory bowel disease (IBD) in 42, colorectal cancer in 1, diverticular disease in 4, colonic polyps in 3 and irritable bowel syndrome (IBS) in 17 patients. A highly significant correlation was found between the two tests (P < 0.001). Sensitivity (S), specificity (Sp), positive predictive value and negative predictive value are given for each test. Cp: S 82%, Sp 73%, PPV 75%, NPV 81%; Lf: S 64%, Sp 94%, PPV 91%, NPV 73%. Faecal excretion of Cp and Lf are significantly correlated with both histological activity (P < 0.005 and 0.0001, respectively) and endoscopic features (P < 0.003 and 0.0001, respectively). Lf false negatives were found in one patient with colonic carcinoma, one with colonic polyp and 10 with mildly active IBD. Cp false negatives were seen exclusively in six IBD patients with mild activity. No false positive results were seen for both tests in healthy controls. Lf did not give false positives in patients, while Cp was positive in nine patients; six of them had quiescent IBD, one had diverticular disease without inflammation and two had IBS. AUCs for Lf and Cp were 0.878 and 0.836, respectively. Both the tests are quite inexpensive, easy to perform and rapid: Cp is slightly more expensive but has the advantage of being quantitative. Conclusions. Faecal markers are non-invasive and rather inexpensive tests for screening patients with gastrointestinal symptoms in order to identify those who need further investigation. The two tests have high diagnostic accuracy with similar performance. PO135 EARLY EXTENSION AND PORTAL THROMBOSIS AFTER RADIOFREQUENCY ABLATION-TREATED PATIENTS WITH HEPATOCELLULAR CARCINOMA: REPORT OF FOUR CASES A. D’Alessandroa , L. Cuocoa , M. Manzib , A. Marangonb , G. Mansib , R. Castamana , T. Bertina , M. Salvagninia a Gastroenterology, b Radiology

S. Bortolo Hospital, Vicenza, Italy Unit, S. Bortolo Hospital, Vicenza, Italy

Background and aim. Radiofrequency ablation (RFA) is reported as a safe and effective treatment for HCC; however rapid and aggressive recurrences with portal neoplastic thrombosis after this application has been described. We reviewed a series of 35 patients (patients) with HCC treated with RFA to evaluate the incidence and the main factors related to this evolution. Materials and methods. From 2000 to July 2003, 92 consecutive patients were admitted for management of HCC in liver cirrhosis (Child A–B). Selection criteria for RFA were: presence of 1–3 nodules non-surgically resectable, with maximum 6 cm diameter. In 35 selected patients, RFA by a percutaneous, US guided approach (expandable needle with four or nine hooks) was performed. Contrast-enhanced triphasic CT scan was performed before and 30 days after procedure. Results. Early extension of liver tumour was found in four patients (11.4%). In two cases, incomplete necrosis with appearance of portal neoplastic thrombus not detected in CT before RFA. The first was a 70-year-old man with a cryptogenetic liver cirrhosis and multiple HCCs, the greater treated with RFA (segment VIII, size 5 cm); the other a 74-year-old woman with HCV-positive cirrhosis and a single 5 cm diameter HCC in segment IV. In other two cases, both with alcoholic liver cirrhosis, CT-scan revealed partial persistence of cancer at the ablation site with peripheral extension of the lesion (“satellitosis”): they were a 75-year-old man with a 6 cm diameter HCC in segment VIII and a

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73-year-old man with a 4 cm diameter solitary HCC in segment V. The patients with early extension of tumour were older (73.7 years versus 67, P < 0.01), with shorter history of liver disease (1.5 years versus 4.2 years, P < 0.01), and larger nodules (4.7 diameter versus 3.3, P = ns) when compared with the other patients of the series. No other differences were found in the clinical and biochemical variables. Conclusions. In our series early extension of HCC nodules after RFA appears in four patients, while portal neoplastic thrombosis appeared in two of them. These complications seem related to a more advanced age and probably to a larger size of tumour. PO136 ENDOSCOPIC REMOVAL OF A SWALLOWED LONG SPOON: A CASE REPORT T. D’amico, N. Saccá, S. Rodinó, A. Giglio U.O. di Gastroenterologia ED Endoscopia Digestiva, Azienda Ospedaliera Pugliese, Ciaccio, Catanzaro Foreign objects ingestion is a common event in emergency department; 80% of foreign bodies occur in the paediatric age group, followed by edentulous adults, prisoners and psychiatric patients. Eighty to ninety percent of swallowed objects pass spontaneously. Ten to twenty percent have to be removed endoscopically and about 1% require surgery. The ingestion of a long spoon is uncommon. We report the a case of a woman, 25 years old, with anorexia nervosa, who had voluntarily ingested a long (19 cm), metallic spoon. The spoon handle occupied the body and antrum of the stomach, with the voluminous portion fixed on the lower oesophageal sphincter (LES). This patient experienced epigastric pain and dysphagia and the spoon handle was visible in sit down position through abdominal wall. This patient was given general anaesthesia. We remove the presenting blunt to prevent perforation or impaction during extraction, orienting long axis in the line of extraction and applying traction with dormia snare, without overtube. The passage through the superior oesophageal sphincter (SES) was difficult but possible with ulterior anaesthetic relax of the spincter. The procedure was successful and the patient left hospital the day after without complaints. We think that endoscopic approach is the first treatment to remove voluminous foreign body, reserving gastrostomy to endoscopic failure. PO137 THE MUCOSAL MICROENVIRONMENT OF INFLAMMATORY BOWEL DISEASE PROMOTES A NEOANGIOGENIC RESPONSE IN HUMAN INTESTINAL MICROVASCULAR ENDOTHELIAL CELLS S. Danesea,b,c , M. Sansa,b , B. Rivera-Reyesa,b , A. Gasbarrinib,c , C. Fiocchia,b a Division

of Gastroenterology, University Hospitals of Cleveland Case Western Reserve University School of Medicine, USA b Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA c Università Cattolica del S. Cuore, Rome, Italy Background and aims. Neoangiogenesis has been recently demonstrated to occur in actively involved mucosa of inflammatory bowel disease (IBD) patients, but the mediators that promote local neoangiogenesis have not been investigated. The aim of this study was to investigate whether the IBD mucosal microenvironment is pro-angiogenic by assessing the concentration of the angiogenic molecules IL-8, bFGF and VEGF, define their cellular source(s), and test whether these mediators induce an angiogenic response from human intestinal microvascular endothelial cells (HIMEC) in vitro. Methods. ELISA or immunoblotting measured IL-8, bFGF and VEGF in mucosal extracts from actively inflamed Crohn’s disease (CD) and ulcerative colitis (UC) tissues, and cultures of human intestinal fibroblasts

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(HIF) after TNF-␣ stimulation and lamina propria mononuclear cells (LPMC) after LPS exposure or CD3 engagement. A chemotaxis assay tested the capacity of mucosal extracts to induce HIMEC migration, and blocking antibodies assessed the relative contribution of individual angiogenic factors. Results. Compared to normal mucosa both CD and UC extracts contained a significantly (P < 0.05) higher levels of IL-8 (25-fold), bFGF (2-fold) and VEGF (2-fold). HIF dramatically increased the production of IL-8 and VEGF, but not bFGF, after TNF-␣ stimulation. LPMC doubled their production of IL-8 after LPS or CD3 engagement, while bFGF and VEGF increased solely after LPS stimulation, suggesting a monocytic source. Compared to controls IBD-derived extracts induced a four-folds increase of migrated HIMEC, migration being primarily dependent on IL-8, moderately on bFGF, and less on VEGF. Conclusions. The production of critical pro-angiogenic mediators is significantly increased in the intestinal mucosa involved by active IBD. PO138 T-CELLS TRIGGERED CD40-DEPENDENT PLATELET ACTIVATION: A NOVEL PATHWAY FOR AMPLIFICATION OF INTESTINAL MICROVASCULAR INFLAMMATION S. Danesea,c , C. de la Motteb , B. Mariola Rivera-Reyesa , M. Sansa , A. Gasbarrinic , C. Fiocchia a Division

of Gastroenterology, University Hospitals of Cleveland Case Western Reserve University School of Medicine, USA b Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA c Università Cattolica del S. Cuore, Rome, Italy

Background. Platelets contribute to immunity and inflammation in the intestinal mucosa of inflammatory bowel disease (IBD) patients. The recent report that platelets express CD40 lead us to hypothesise that CD40L-positive T-cells, which are present in IBD mucosa, could bind to platelets, cause their activation, trigger granular RANTES release, and create a T-cell recruitment feedback loop in the inflamed intestine. Methods. Platelets were co-cultured with resting or activated autologous T-cells, CD40L-negative Jurkat or CD40L positive D1.1 cells as controls, and their activation state assessed by cytofluorometric measurement of P-selectin and phosphorylation of MAP kinases by immunoblotting. Binding of platelet-derived RANTES to human intestinal microvascular endothelial cells (HIMEC) was assessed by confocal microscopy, and its chemotactic activity demonstrated by a T-cell adhesion assay. Results. CD40L-positive T-cells directly induced platelet activation through a contact-mediated, CD40-dependent pathway, as shown by P-selectin up-regulation. Platelet activation was critically dependent on p38, but not ERK, phosphorylation, as demonstrated by the specific blockade of p38 with the inhibitor SB203510. CD40-mediated platelet activation resulted in RANTES release which bound to HIMEC and induced T-cell adhesion to HIMEC in a RANTES-dependent manner, as shown by the almost complete blockade observed with Met-RANTES, a specific RANTES receptor antagonist. Conclusions. Our data support a novel contribution of platelets close to the level of pathogenic relevance traditionally attributed to classical immune cells. PO139 A CASE REPORT: SYNCHRONOUS LEIOMYOSARCOMA AND ADENOCARCINOCA OF THE COLON V. D’Angeloa , G. Amalfia , C. Farinatoa , M. Schettinoa , E. D’Ambrosiob , M. Saccoc , G. Iannacid , L. Maiorinoe , S. Monastraa , L. Simolob , R. Pepec , R. Rossiellod a UOC

Gastroenterologia ed Endoscopia Digestiva, PO San Gennaro ASL NA 1, Italy

b Ch.

Urgenza, Via S. Gennaro dei Poveri, 25 80100 Naples, Italy Via S. Gennaro dei Poveri, 25 80100 Naples, Italy d Anat. Patologica, Via S. Gennaro dei Poveri, 25 80100 Naples, Italy e Oncologia, Via S. Gennaro dei Poveri, 25 80100 Naples, Italy c Radiologia,

Background. Gastrointestinal stromal tumours (GISTs), mesenchymal tumours largely specific for the GI tract, have been well defined in the stomach and small intestine, but have not been extensively documented or differentiated from true, extremely rare, smooth muscle tumours in the colon. Leiomyomas (LMs) and leiomyosarcomas (LMSs), comparable to retroperitoneal or vascular tumours, have clinicopathologic differences that warrant their separation from GISTs. Case report. We report the case of a 74-year-old man with synchronous focal adenoca and large LMS arising in the hepatic flexure. The patient was admitted in Emergency Surgery because of abdominal pain and weight loss. Endoscopy revealed a predominant intraluminal growth mass. Endoscopic deep biopsies was negative for malignancy, only necrosis was recorded. CT-scan revealed multifocal liver metastases, coeliac and mesenteric lymphadenopathy and level in hypodense lesion corresponding to gallbladder. Right colectomy was performed. Pathology revealed an extensive ulcerated neoplastic transmural lesion and peritoneal seeding. Focal irregularity of 0.5 cm mucosal area. Eleven lymph nodes. I lesion: spindle cell tumour that resembled smooth muscle with oval to mildly elongated nuclei and large eosinophilic cytoplasm, high mitotic index. The tumour was negative for CD 117 (KIT) and positive for actin. II lesion: moderately differentiated adenoca infiltrating muscularis lamina. One lymph node with both malignancy was detected. The patient died of severe bleeding, 4 days after discharge from the hospital. Conclusion. Endoscopic biopsies are often negative, the typical endoscopic pattern allow to suspect a stromal tumour. LMSs are predominant intraluminal growth tumours, they appear as polypoid intraluminal masses. GISTs are externally bulging tumours, they present as intraluminal polypoid masses. LMSs appear to be much less common than GISTs. Synchronous LMS and adenoca have not been previously reported in our review of the literature. CD117 (KIT) is currently the most specific marker to define GIST and to differentiate it from true smooth muscle tumours. PO140 ECONOMIC PHARMACEUTICAL COSTS AND DRUG PRESCRIPTIONS FOR INFLAMMATORY BOWEL DISEASE: A POPULATION STUDY IN NORTHERN ITALY M. Dapernoa , E. Caglierob , R. Sostegnia , A. Lavagnaa , R. Roccaa , A. Peraa , M. Paireb a Gastroenterology b Servizio

Unit, Ospedale Mauriziano Umberto I, Turin, Italy Farmaceutico Territoriale ASL 17, Saluzzo, Italy

Background. The use of drugs in inflammatory bowel disease (IBD) has been mainly analysed in the setting of clinical trials and referral centres. Drug consumption and relative costs in the general population are useful for evaluation of exposure to drugs and for accurate modelling of costs of illness; moreover costs are probably country-specific and could vary considerably. Aims and methods. The aims were to evaluate the economic costs of IBD drug treatment and the drug prescription profile in a population-based study. The National Health System database for drug sales of a northern Italian district (ASL 17 in Piedmont, with 160,838 inhabitants, mainly rural, no referral hospitals) was searched for IBD patients. All drug prescriptions in the year 2002 referring to the identified patients were screened for 25 drug types (salicylates, steroids, antibiotics, immunosuppressives, and other drugs not strictly related to the treatment of IBD). Results. One hundred and fifty-eight patients with IBD were found, mean age 48.7 years, 41% females. The total costs for the drug prescriptions in the year 2002 was 59,680, giving a mean cost of 377.7 per patient per year (95% CI 326.7–428.7). In 2002, the mean cost per patient per year for the total population was 157.7 (95% CI 154.8–160.5, P-value

Abstracts for difference <0.0001, total costs presented in table as shown below. Total costs ( ) (%)

25,359,259). Detailed results are

Patients treated (% of total IBD patients)

Mean daily dose among treated patients

305.6 42.6 7.8 15.3

139 55 10 31

0.89 g [MSZ] 4.12 mg [PRED] 34.98 mg [AZA] 23.8 g [CIPRO]

377.7

158 (100%)

Mean cost per patient per year (

Salicylates Steroids Immunosuppressives Antibiotics

46,448 6,733 1,236 2,418

(78%) (11%) (2%) (4%)

Total

59,680 (100%)

)

(88%) (35%) (6%) (20%)

Conclusions. The observed prevalence of IBD in the specified area (98.2/100,000) matches well with the expected IBD prevalence in southern Europe. In this population-based study of IBD patients, salicylates were the main source of pharmacological costs for IBD therapy. As expected, costs in IBD patients are significantly higher than in the reference (general) population. This population based study also outlines a prescription profile notably different from that observed in referral centres (too low doses of salicylates, fewer patients on immunosuppressive drugs). PO141 EVIDENCE FOR SOMATOSTATIN RECEPTORS IN COLON OF RATS WITH TNBS-INDUCED COLITIS G. D’Argenioa , F. Mangusoa , L. Celentanob , F.P. D’Armientoc , N. Della Vallea , V. Cosenzaa , P. Sommac , G. Mansuetoc , L. Terraccianod , A. D’Arienzoa a Section

of Gastroenterology, Department of Clinical and Experimental Medicine, School of Medicine, Federico II University, Naples, Italy b Section of Radiology, Department of Biomorphologic and Functional Science, School of Medicine, Federico II University, Naples, Italy c Section of Pathology, School of Medicine, Federico II University, Naples, Italy d Department of Pathology, University Hospital, Basel, Switzerland Background/aim. Somatostatin receptors (SSTR) have been identified on immune cells including mononuclear leucocytes and peripheral blood lymphocytes, and 111 In-[DTPA-d-Phe1]-octreotide (Octreoscan) scintigraphy was found useful to reveal the site of inflammation. The neuropeptide somatostatin exert multiple function in the gastrointestinal tract and may also play a regulatory role in inflammatory bowel disease (IBD). In the present study, we evaluated the expression of SSTR-1 and somatostatin in colonic mucosa of rats with experimental colitis. Methods. A dose of 0.5 ml of Octreoscan (activity 55.5 MBq/ml) was administered in 10 rats via the femoral vein at baseline. Four hours later they underwent a total body scintigraphic examination with a 4 min static image to reveal a colonic activity. The intensity of colonic radioactivity was evaluated in vivo by an arbitrary score scale referred to the heart uptake. Four out of the 10 rats were killed after the scintigraphic procedure, and colitis was induced by trinitrobenzensulphonic acid (TNBS) on the remaining six rats. Two weeks later, the Octreoscan scintigraphy was repeated in the six TNBS treated rats that were killed after the procedure. Ten rats, five of which with TNBS induced colitis, did not undergo scintigraphy and were used as controls. In all the rats, the last 8 cm of colon were excised, damage was assessed by macroscopic and microscopic evaluations according to the appropriate score criteria. The presence and distribution of SSTR-1 and somatostatin was evaluated by immunohistochemistry in colonic mucosa of all rats. Results. Octreoscan scintigraphy showed colonic activity only in rats with TNBS induced colitis, in which the damage was confirmed by macroscopic and microscopic examination. Anti-somatostatin antibody did not stain colonic mucosa both in normal and colitic rats. Interestingly, SSTR-1 was upregulated in TNBS rats, showing a strong positive pattern in the surviving epithelial cells bordering the damaged areas. Conclusions. Osctreoscan scintigraphy is a useful tool to evaluate the extent and the degree of colonic inflammation. Moreover, this is the first

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report showing the expression of SSTR-1 and not somatostatin in the colonic epithelial cells of rats with experimental colitis. The presence of SSTR-1 in mucosa epithelial cells may suggest a role for somatostatin in the treatment of IBD. PO142 DOES SERUM PANCREATIC POLYPEPTIDE FIT IN CLINICAL PRACTICE AS GENERAL MARKER OF NEUROENDOCRINE DIFFERENTIATION? C. De Angelisa , E. Brignardellob , F. Curria , R. Mantib , L. Tesioc , A. Repicia , A. Isabellod , M. Rizzettoa a SCDU

Gastroenterologia ed Epatologia, ASO S. Giovanni Battista di Torino, Università di Torino, Italy b SCDU Endocrinologia Oncologica, ASO S. Giovanni Battista di Torino, Università di Torino, Italy c SC Dea Medicina Generale 9, ASO S. Giovanni Battista di Torino, Università di Torino, Italy d UOA Cardiologia, Ospedale degli Infermi di Rivoli, Turin, Italy Background and aim. Pancreatic polypeptide (PP) is a GI hormone produced mainly by specific cells (F cells) within pancreatic islets. The biological action of PP depends on activation of a specific receptor (Y4) and affects body weight regulation. Due to the cellular heterogeneity of neuroendocrine tumours, which often include F cells, PP has been proposed as “general marker” of neuroendocrine differentiation, but its diagnostic reliability remains controversial. The aim of this study was to evaluate the diagnostic role of PP serum assay in an heterogeneous group of gastroenteropancreatic (GEP) endocrine tumours. Materials and methods. Serum PP concentration was measured by a competitive radioimmunoassay in 56 patients (25 males, 31 females). The most frequent diagnoses were: foregut (17) and midgut (6) carcinoids, with or without liver metastasis, and endocrine pancreatic tumours, both sporadic (4 gastrinomas, 3 insulinomas, 2 glucagonomas, 1 LH secreting tumour, 6 non-functioning tumours) or MEN1-related (2 gastrinomas, 2 glucagonomas). In MEN1 patients, serum PP was also measured after a standard meal test. Results. Fasting PP levels up to 100 pmol/l were considered to be normal. All patients with carcinoids (foregut or midgut, metastatic or not) had fasting PP levels within the normal range. Among patients with sporadic endocrine pancreatic tumours, 19% (one insulinoma, one LH secreting tumour and one non-functioning tumour) displayed raised levels of serum PP. By contrast, all patients with MEN1-related endocrine pancreatic tumours showed high levels of PP both in the basal and after standard meal test. Conclusions. Our data suggest a diagnostic role of serum PP levels in the diagnosis of endocrine pancreatic tumours, mainly MEN1; in other GEP endocrine tumours (foregut and midgut carcinoids) the serum PP assay does not appear useful as a diagnostic discriminant. PP cannot be considered a “general marker” of neuroendocrine differentiation and the value of the standard meal test in MEN1 patients can be questioned. PO143 EOSINOPHILIC OESOPHAGITIS: A PAEDIATRIC EXPERIENCE P. De Angelisa , F. Torronia , A. Paneb , T. Caldarob , G. Federici di Abriolaa , R. Boldrinic , L. Dall’Oglioa a UO

Chirurgia Endoscopia Digestiva, IRCCS Ospedale Pediatrico “Bambino Gesù”, Rom, Italy b Scuola di Specializzazione in Chirurgia Pediatrica, Università di Roma “Tor Vergata”, Italy c Anatomia Patologica, IRCCS Ospedale Pediatrico “Bambino Gesù”, Rome, Italy Eosinophilic oesophagitis (EE) is diagnosed by histology (>15 eosinophils/HPF in the oesophagus), ruling out GERD, eosinophilic gas-

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troenteritis, collagen diseases and infections. Therapy aims: to eliminate offending allergens, treat acute symptoms, induce remission. M&M. We followed seven patients (four males) with EE; dysphagia/slow growth in four, epigastric pain/vomiting in two, heartburn/chest pain in one. They underwent EGDS before/after therapy, endoscopic ultrasonography (EUS), barium oesophagogram, 24 h pHmetry. Acute therapy: Savary dilations, oral prednisone (1.5 mg/kg for 2 weeks), diet restriction (cow milk/eggs proteins). Maintenance therapy: fluticasone (two swallowed puffs for 6 months), diet. R. Familiarity of allergy in 6 patients; four allergic patients Mean age at beginning of symptoms: 6 years and 7 months (range 4–17 years). Endoscopy before diagnosis: three patients strictures (in two, endoscopic disimpaction) treated by dilation (mean 3) but dysphagia persisted; in two, patients aspecific oesophagitis, partially sensitive to PPI. Mean age at diagnosis: 12 years and 4 months (7–18 years and 10 months). Diagnosis time: 13 years and 5 months. In all patients, 24 h pHmetry disclosed GERD; oesophageal manometry: normal motility; oesophagogram: normal in three patients, GER in two, oesophageal stricture in three. Endoscopy: granularity in one patient, vertical linear furrow in four, concentric rings in two patients. Biopsy proximal/distal oesophagus: 6–45 eosinophils/HPF (median 32) within squamous epithelium; no eosinophilia in stomach and duodenum of six patients, mild in one. EUS (miniprobe 20 MHz): asymmetric thickening of mucosa, submucosa and muscularis propria. Allergologic test for common allergens: positive in three patients. Peripheral eosinophilia in one patient. Six patients successfully treated with prednisone; in three of them: elimination diet. One patient had immediately a good response to diet and did not undergo corticotherapy. In all patients symptom relief was complete, endoscopy and histology improved. In all patients fluticasone; four patients followed diet. In mean follow-up of 9 males (range 2–19), 5 patients were asymptomatic; in 2, mild dysphagia persisted. In one (none antigen identified) a relapse occurred after 1 year from diagnosis, successfully treated with prednisone. The oesophagus is an active participant in immune responses. The antigen involved in inflammatory cascade is unique to the individual patients. Diet and steroids may lead to symptoms resolution but a specific therapy could be necessary. A better knowledge of EE with a precocious treatment avoid the delay in diagnosis and severe complications such as stricture. PO144 SEQUENTIAL TREATMENT FOR Helicobacter pylori DOES NOT SHARE THE RISK FACTORS OF TRIPLE THERAPY FAILURE V. De Francescoa , E. Ierardie , A. Zullob , M. Margiottac , S. Marangic , O. Burattinic , P. Berlocod , F. Russod , A. Di Leoc , M.F. Minennaa , V. Stoppinoa , S. Morinib , C. Panellae , A. Francavillac a Gastroenterology

Unit, Ospedali Riuniti, Foggia, Italy and Digestive Endoscopy Unit, Ospedale Nuovo Regina Margherita, Rome, Italy c Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy d Biochemistry Laboratory, IRCSS De Bellis, Castellana Grotte, Italy e Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Italy b Gastroenterology

Background. Predicting factors for the outcome of Helicobacter pylori conventional triple therapy have been identified. Among them, CagA gene is a strong predictor of successful treatment, while smoking habit and non-ulcer dyspepsia seem to predict a failure. A novel therapeutic scheme (sequential) has shown, in this last period, a significantly higher eradication rate when compared to the triple therapy. Aim. To evaluate the predicting factors for the outcome of H. pylori eradication using two therapeutic schemes (triple and sequential) of an equal duration (10 days). Patients. Ninety-six patients with H. pylori infection were randomly assigned to receive one of the following therapeutic schemes: group A, Rabeprazole (20 mg b.i.d.) plus Amoxycillin (1 g b.i.d.) for 5 days

followed by Rabeprazole (20 mg b.i.d.) plus Tinidazole (500 mg b.i.d.) and Clarithromycin (500 mg b.i.d.) for further 5 days; group B, Rabeprazole (20 mg b.i.d.) plus Amoxycillin (1 g b.i.d.) and Clarithromycin (500 mg b.i.d.) for 10 days. Methods. H. pylori was detected by histology, rapid urease and urea breath tests before the therapy, whose outcome was evaluated only by the last investigation after 8 weeks. Age, sex, smoking, endoscopic and histological picture, CagA status of H. pylori were considered as candidates for a model of multivariate analysis which used therapeutic outcome as dependent variable. CagA status as assessed by polymerase chain reaction on DNA isolated from gastric antral specimens (primers by Tummuru et al.). Results. Sequential scheme was significantly more effective than prolonged triple therapy (97.7% versus 82.3%; P < 0.05). Moreover, smoking habit (P < 0.001) and absence of CagA gene (P < 0.05) were significantly associated to the failure of triple therapy. Nevertheless, the effectiveness of sequential treatment was not predicted by these factors. Conclusions. Our data suggest that sequential therapy is not affected by bacterial and host factors which have, until now, predicted the failure of conventional eradicating treatments and this could encourage a review of the criteria used for the choice of a first line therapy for H. pylori infection. PO145 RADIOFREQUENCY TERMAL ABLATION OF HEPATOCELLULAR CARCINOMA (HCC): LIGHTS AND SHADOWS M. De Giorgio, C. Angonese, A. Baldan, U. Cillo, M. De Antoni, F. Farinati, S. Gianni, A. Masotto, M. Massani, M. Mazzucco, D. Neri, E. Miola, D. Pacagnella, G. Pivetta, L. Tommasi, A. Tufano GENE, Hepatocellular Carcinoma Group, Italy Radiofrequency termal ablation (RFTA) is becoming the first option for percutaneous treatment of HCC, with percutaneous ethanol injection (PEI) being abandoned. However, data about RFTA efficacy and safety are not sound and are derived from series treated in very few highly experienced units. The aim of this study was to carry out an audit on the experience on RFTA in north-east Italy, involving a collaborative group on HCC (GENE). Patients. Data were collected with a purposely prepared form from 293 patients with HCC (223 males, mean age 66 years (range 34–86 years); 70 females, mean age 68 years (range 54–75 years). They were treated with RFTA in seven centres with cooled-tip needles (Radionics, Kerna). Results. Indication to treatment was: single nodule, not eligible for surgical treatment, in 76.2% of the patients, two to three nodules in 18.9% and multiple in 4.9%. Mean size of nodules was 3 cm (range 0.8–8 cm). Treatment response was assessed at 1 month by sCT while subsequent follow-up was with US examination and new sCT every 6 months (sCT were randomly reviewed by a referring radiologist). Complete response was seen in 61% of the patients; in 27% of the patients, response was from 75 to 99%; in 12% of the patients, response was less than 74%. Complete response increased to 75% in lesions smaller than 3 cm. The morbidity rate was 33%; the mortality rate 0.4%, seeding was observed in two patients. Ten patients (3%) presented an “explosion” of disease. Despite the pre-RFTA staging by sCT showing no lesions beyond that they were treated for, after a mean time of 3.6 months (range 1–18 months) they developed an intrahepatic dissemination with more than three new nodules, also far from the primitive, that was completely treated in four cases. In one case, multiple lung metastases appeared after RFTA, with the hepatic lesion completely treated. Conclusions. The above data show that by treating HCC with RFTA, complete response can be achieved only in about 60% of the cases, much less than expected, and that, beyond described cases of seeding, an explosive disease can be observed in some cases, thus suggesting an intratumoural explosion leading to intra- and extra-hepatic dissemination with accelerated tumour growth, probably due to cytokine release.

Abstracts PO146 CONTRAST-ENHANCED TRANSABDOMINAL ULTRASONOGRAPHY (US) WITH SECOND GENERATION CONTRAST MEDIUM IN CROHN’S DISEASE: A PRELIMINARY REPORT V. De Girolamoa , F. Moracea , S. De Martinoa , S. Scotto di Santoloa , G. Lapiccirellab , A. Maronea , M. Alabisoc , G.P. Maronea a U.O.C.

di Gastroenterologia, Ospedale C. Ascalesi, Naples, Italy di Radiologia, Ospedale S. Paolo, Naples, Italy c U.O. di Radiologia Ospedale C. Ascalesi, Naples, Italy b U.O.

Introduction. US has been shown to be useful in the diagnosis and follow-up of inflammatory bowel disease. In B-mode US, inflamed intestinal wall shows increased thickness and “pseudo-kidney” appearance, in which a venous pattern of vascularisation can be shown with colour Doppler. SonoVue® (sulphur exafluoride) is a second generation contrast medium for US that has been used to enhance the visualisation of blood flow in inflammatory or tumoural tissue. The aim of the present study was to evaluate the diagnostic efficacy of SonoVue® in differentiating active wall inflammation from fibrotic wall thickening in comparison to helical multiplanal CT scan with oral and i.v. contrast medium (CT). Methods. We enrolled 36 patients (20 males, 16 females; mean age 34.7 years), with Crohn’s disease (CD) having a CDAI ranging between 80 and 470 (22 patients CDAI >150). Localisation of Crohn’s disease was colonic in 20 patients, ileocolonic in 13, jejunal and ileal in 2, and jejunal and colonic in 1. All patients underwent colonoscopy and CT scan to evaluate extension and endoscopic score of the disease. These data were compared to the US appearance of intestinal wall obtained after injection of SonoVue® and studied using an Esotune® with a convex multifrequency probe. A dose of 25 mg of SonoVue® was diluted in 5 ml of 0.9% NaCl and injected as an i.v. bolus. Results. In all the patients, US showed an increased wall thickness (6.3 ± 2.8 mm; mean ± S.D.). After the injection of SonoVue® , we observed in all the patients with CDAI >150 and in two patients with CDAI <150, a marked enhancement involving all wall layers, probably due to inflammatory hypervascularisation. The imaging of wall thickness obtained by US was similar to that of CT. However, the latter gave a better visualisation of perivisceral inflammation. Furthermore, in three patients, CT scan correctly detected a jejunal involvement which was undiagnosed by US. In the 14 patients with CDAI <150, we found a mild increase of wall thickness (4.2 ± 2.2 mm;) but in 12 we did not record any enhancement after SonoVue® . Conclusion. The present study suggests that contrast enhanced US with SonoVue® can improve the sonographic study of intestinal wall and help in detecting active wall inflammation in CD. This method is easy and minimally invasive. Larger studies are needed to evaluate the usefulness of this method in diagnosis and follow-up of CD. PO147 LONG-TERM OUTCOME OF APC TREATMENT FOR WATERMELON STOMACH IN PATIENTS WITH PORTAL HYPERTENSION A. De Lioa , A. Truscellia , R. Nicitaa , A. Repicib a Unità

di Gastroenterologia, Presidio Ospedaliero Praia a Mare (CS), Italy b Dipartimento di Gastroenterologia, Ospedale Molinette, Turin, Italy

Background. Watermelon stomach is a well-recognised cause of chronic gastrointestinal blood loss in patients with portal hypertension. The aim of this study was to evaluate the safety and efficacy of APC in the treatment of severe anaemia secondary to watermelon stomach. Method. We retrospectively reviewed the case records of 16 patients (7 male and 9 female, mean age 59.7 years) with severe iron-deficiency anaemia due to watermelon stomach who were treated by APC and for whom an F-U of more than 12 months was available. Six patients were

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transfusion dependent. Other potential cause of gastrointestinal bleeding have been excluded before APC by extensive endoscopic, radiologic and clinical evaluation. Results. A mean number of 3.6 sessions per patient were required. APC was delivered at 60 W power with a stripe-like technique. A mean interval of 12.3 days was recorded between each APC session. High doses of PPI were delivered to all patients along the treatment period. One patient developed severe post-procedural bleeding controlled by APC plus somatostatin infusion. All patients except one had an endoscopically observed response and a sustained rise in haemoglobin level (mean Hb level before APC: 6.7 g/dl versus 10.8 g/dl after APC, P > 0.01). Transfusion dependence ceased in all the patients. After a mean F-U of 17.3 months watermelon stomach recurred in three patients (18.6%) who were successfully retreated by APC. Recurrence of watermelon stomach was associated with recurrence of iron-deficiency anaemia in all three patients. Conclusions. APC can be considered as the first-line treatment for iron-deficiency anaemia secondary to watermelon stomach in cirrhotic patients. PO148 CO-EXPRESSION OF TWO Helicobacter pylori’S PROTEINS CagA AND HspB INDUCES CELL PROLIFERATION IN GASTRIC EPITHELIAL CELLS, INDEPENDENTLY FROM THE BACTERIAL INFECTION A. De Lucaa , A. Todiscob , N. Giardulloc , V. D’Onofrioc , S. Iaquintoc , M.C. Parodid , G. Iaquintoc a Department

of Medicine and Public Health, Second University of Naples, Naples, Italy b Pathology and Clinical Laboratory, San G. Moscati Hospital, Avellino, Italy c Division of Gastroenterology, San G. Moscati Hospital, Avellino, Italy d Digestive Endoscopy and Gastroenterology Division, San Martino Hospital, Genoa, Italy

Gastric cancer is currently the second most prevalent cancer in the world. Epidemiological studies have demonstrated an up to six-fold increased risk of developing adenocarcinoma in the patients infected with Helicobacter pylori, suggesting a link between persistent gastric H. pylori infection in human patients and the development of gastric carcinoma. The first observation suggesting that primary bacterial infection can lead to carcinogenesis has come from two independent groups, using Mongolian gerbils. In this animal model, long-term infection with H. pylori induced gastric cancer. The purpose of this study was to evaluate the potential role in carcinogenesis of two secreted H. pylori’s proteins, CagA and HspB, both shown to increase the risk of gastric carcinoma in patients infected with H. pylori positive strain. The effects of these two proteins on cell kinetics and the ability to selectively affect the expression of cell cycle-related proteins by transfection of a human gastric epithelial cell line (AGS), were analysed. Using a genomic library of H. pylori, we isolated and cloned CagA and HspB. The effects of the over-expression of these proteins on cell growth were analysed in AGS cells by immunoblots, proliferation assay and flow cytometry. Co-expression of CagA and HspB in AGS cells in the first 48 h, caused an increase of the level of E2F transcription factor, cyclin D3 and phosphorylated retinoblastoma protein, all involved in the G1/S checkpoint of the cell cycle. Consistently, an increase of cell proliferation, corresponding to an augment of the fraction of the cells in the S/G2-M phase of the cell cycle, was also demonstrated. Moreover, an increase of c-jun protein levels, but not of c-fos, was also found after co-expression of CagA and HspB. All these data suggest that CagA and HspB, independent of the bacterial infection, have a direct effect on the cell growth of the gastric cells acting on the G1/S checkpoint of the cell cycle. Reference [1] De Luca, et al. Cancer Res 2003;63:6350–6.

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Abstracts

PO149 PRELIMINARY ANALYSIS OF THE NEW 24-HOUR EMERGENCY ENDOSCOPY SERVICE IN BOLOGNA L. De Luca, C. Fabbri, V. Cennamo, P. Billi, P. Landi, D. Lo Cuoco, C. Mwangemi, D. Baroncini, N. D’Imperio Gastroenterology and Digestive Endoscopy Unit, Bellaria–Maggiore Hospital, Bologna, Italy Background. In July 2003, resulting from a merger between Gastroenterology and Endoscopy Units of Bellaria and Maggiore Hospital, a new 24 h digestive endoscopy emergency service, including only highly skilled personnel, was instituted in the “Azienda citta di Bologna” which caters for a population of about 350,000 inhabitants. Aim. The primary objective of the service is prompt, correct diagnosis, appropriate and timely treatment. Methods. The aim of the project was to create a highly specialised team able to effectively deal with emergency cases. The surgery team included two nurses and one doctor. To standardise care and implement protocol, advanced training sessions were held for all staff involved. The project has a 6-month experimental phase and access to the therapeutic endoscopy service is for both in- and outpatients affected by gastrointestinal bleeding (GI), ingestion of caustic substances or foreign bodies and all other emergency condition. Results. In the first 5 months, there were 82 night-time and week-end admissions: 86% were due to GI bleeding, 6% due to extraction of foreign bodies, 6% due to PEG substitution and 2% due to ingestion of caustic substances. GI bleeding site remained unidentified in 8% of the cases. When GI bleeding was identified, in 83% upper GI tract was involved and in 17% the lower GI tract. Haemostasis was performed in 58% of the cases: monotherapy was utilised (injection or thermal coagulation or endoclips) in 40% and combined treatment (injection plus thermal coagulation) in 60%. Conclusions. On the basis of our preliminary data, we suggest that qualified/skilled staff and adequate resources in a 24 h therapeutic endoscopy unit are able to accurately diagnose and appropriately treat most emergency admissions. PO150 LOCOREGIONAL STAGING OF RECTAL CANCER USING RADIAL SCANNING ECHO-ENDOSCOPE L. De Lucaa , C. Fabbria , S. Macchiaa , V. Cennamoa , P. Fusarolib , D. Baroncinia , P. Billia , A. Fornellib , A. Maestric , T. Fiorinie , A. Grillia , A. Rampazzoa , N. D’Imperioa a Gastroenterology

and Digestive Endoscopy Unit, Bellaria–Maggiore Hospital, Bologna, Italy b Gastroenterology and Digestive Endoscopy Unit, University of Bologna, Castel S. Pietro Terme Hospital, Italy c Department of Anatomic Pathology, Maggiore Hospital, Bologna, Italy d Department of Oncology, Bellaria Hospital, Bologna, Italy e Department of Statistical Science, University of Bologna, Bologna, Italy Background. Endoscopic ultrasonography (EUS) is one of the tools that has been commonly used in the clinical staging of the rectal tumours. Preoperative evaluation of the depth of tumour infiltration and of the presence of iliac and pararectal adenopathy is essential in planning the correct treatment. Aim. To evaluate the diagnostic accuracy of EUS in the locoregional staging of rectal cancer. Setting. Gastroenterology and Digestive Endoscopy Unit of Bellaria Hospital. Methods. Eighty-one subjects with rectal cancer were evaluated during the period from February 2000 to June 2003 (56 males, 25 females, age range 46–86 years, mean age 64.4). In all the patients, we performed a flexible sigmoidoscopy first to assess the luminal extent of the tumour and to gauge

the proximal distal margins relative to the anal verge. EUS examination was performed using an Olympus GF UM 20 echo-endoscope with radial scanner (7.5–12 MHz). The EUS staging was compared with the pathology findings based on the surgical specimens of the 35 patients who had surgery without adjuvant preoperative chemoradiation. Non-traversable stenotic tumours were excluded. Results. Overall, accuracy in assessing the level of rectal wall invasion was 82.9%, with 11.4% of the tumours overstaged and 5.7% understaged. In assessing nodal staging, the overall accuracy was 71.4%, sensitivity was 72%, specificity was 70%, positive predictive value was 85.7% and the negative predictive value was 50%. Conclusions. According to our experience, EUS may be an accurate diagnostic method for the locoregional staging of rectal cancer. EUS is a useful technique for determining the preoperative surgical therapy strategies of patients with rectal cancer and potentially, compared with other diagnostic tools, could have economic advantages. PO151 USEFULNESS OF EUS FOR DIAGNOSIS OF A RARE TUMOUR OF THE GALL BLADDER: CARCINO-SARCOMA L. De Lucaa , S. Espositob , L.C. Cirillob , R. D’Erricoc , P. Angelinic , F.M. Maiellod , D. Bifanod , B. De Lucaa a U.O.C.

di Gastroenterologia, Presidio Ospedaliero dei Pellegrini, ASLNA1, Naples, Italy b U.O.C. di Diagnostica per Immagini, Presidio Ospedaliero dei Pellegrini, ASLNA1, Naples, Italy c U.O. di Chirurgia Laparoscopica, Presidio Ospedaliero dei Pellegrini, ASLNA1, Naples, Italy d U.O. di Anatomia Patologica, Presidio Ospedaliero dei Pellegrini, ASLNA1, Naples, Italy Background and aim. Carcinosarcoma, a rare kind of gall bladder (GB) carcinoma, is composed of malignant epithelial and mesenchymal elements that grow intermingled with each other. The aim of this report is to describe a case of carcinosarcoma seen through EUS at an early stage. Methods. A 70-year-old woman was admitted to hospital for epigastralgia. Examination revealed a palpable mass in the right hypochondrium. An abdominal ultrasound (US), carried out about 1 year before, had revealed an enlarged GB containing two stones. Recent lab tests were normal and another US visualised a diffuse thickening of the wall as well as the stones. The gastroscopy showed an extrinsic compression of the anterior wall of the gastric antrum. EUS showed a 9 cm × 4 cm anechoic structure (GB) containing a 4 cm × 2.5 cm heterogeneous, hypoechoic, broad-based intraluminal mass and thickening of the wall, with an irregular surface and some small stones inside. No lymph nodes were seen. A CT scan confirmed the stones and the thickening of the wall but did not pick up the mass. The patient underwent laparotomic cholecystectomy, removal of adjacent liver tissue and lymphadenectomy. Result. Histopathological evaluation diagnosed a carcinosarcoma of the GB at stage pT2 N0. Since the operation, 7 months ago, her clinical condition has improved considerably. Conclusion. EUS, which diagnosed a GB cancer not seen by other techniques, suggested a laparotomy which enabled the surgeon to remove the cancer and the bed of the GB with a single operation. PO152 CAPSULE ENDOSCOPY IN THE FOLLOW-UP OF PATIENTS WITH SMALL BOWEL RESECTION G.D. De Palma, M. Rega, F. Patrone, P. Ciamarra, I. Simeoli, L. Noceroni, L. Mastantuono, G. Persico Section of Diagnostic and Therapeutic Endoscopy, Department of Surgery and Advanced Technologies, School of Medicine, University of Naples Federico II, Naples, Italy

Abstracts Background and aims. Wireless capsule endoscopy is a new, painless method of imaging the entire small bowel. However, because capsule endoscopy is relatively new, indication, contraindications and complications have not been fully delineated. The present study was undertaken to determine the utility and safety of capsule endoscopy in the patients following small bowel resection. Methods. Ten patients, mean ages 48.5 years (S.D. 8.4 years) were included in the study. Eight underwent surgical resection for Crohn disease and two for malignancy. The symptoms of the patients were consistent with suspected recurrent disease. Capsule endoscopy was performed with the Given M2A video capsule system. Results. All the patients ingested the capsule smoothly and there were no side-effects. Natural excretion of the capsule was reported from all the patients within 72 h, on average. Recurrent disease of the small bowel was diagnosed in seven (70%) patients (recurrent malignancy in one; recurrent Crohn disease in six). Conclusions. Wireless capsule endoscopy is safe and effective in the follow-up of patients who underwent surgical resection of the small bowel for benign or malignant disease. Although impact of a capsule requiring endoscopic or surgical removal was not evident in this series, patients should be informed about this risk. PO153

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Patients and methods. Ninety-five patients with suspected malabsorption syndrome or with coeliac disease on GFD were randomly chosen among all the patients of our DH. A push-type Fujinon EVE EN7-MR2 with ASE 1174B clips was used. The endoscopist always evaluated the aspect of the duodenum and of the jejunum to search for possible predictive signs of malabsorption. At least three bioptical specimens were taken in the second portion of the duodenum and in the first loop of the jejunum and anywhere else the mucosa showed signs that rendered this necessary. The histological examination was carried out by expert histopathologist and Marsh score was used for villar atrophy, if present. Results. The enteroscopy was completely carried out in all the patients, but the biopsy specimens were sufficient for the diagnosis only in 87 (91.5%). The endoscopical examination showed morphological alterations of the mucosa in 57 patients: 21 (36.8%) had these signs only in the second duodenal portion, while 36 (63.2%) also in first jejunal loop. Twenty-three patients had final diagnosis of coeliac disease: four of these (17.4%) had villar atrophy only in jejunum. Conclusion. Enteroscopy can be used as a further diagnostic step in detecting coeliac disease. We emphasise the diagnosis of coeliac disease was made possible in about 17%, only thanks to the histological examination of biopsies from the jejunum. We think that the routine use of enteroscopy and of the biopsies taken near the Treitz in suspected coeliac patients can improve the diagnosis, showing patchy form of coeliac disease.

METASTATIC TUMOURS TO THE STOMACH. CLINICAL AND ENDOSCOPIC FEATURES OF 74 PATIENTS

PO155

G.D. De Palma, P. Ciamarra, M. Rega, F. Patrone, M. Persico, L. Mastantuono, I. Simeoli, G. Persico

ENTEROULTRASONOGRAPHIC (EUS) FINDINGS IN COELIAC DISEASE OF ADULTS: A NEW DIAGNOSTIC PATHWAY?

Section of Diagnostic and Therapeutic Endoscopy, Department of Surgery and Advanced Technologies, School of Medicine, University of Naples Federico II, Naples, Italy

P. Dell’Aquilaa , E.M. Celab , L. Pietrinic , A. Amorusod , M.F. Minennab , D. Iannuzzielloa , A. Pennae , V. De Francescob , C. Panellac , E. Ierardic

Background and study aims. Clinical and endoscopic findings in gastric metastases have not been previously examined in large numbers due to the low frequency of the conditions. The present study reports the clinicopathological features of metastatic tumours in the stomach in a large series of cases. Patients and methods. A total of 74 patients with gastric metastases from solid malignant tumours were retrospectively examined between 1985 and 2003. The clinicopathological findings were reviewed along with tumour characteristics such as endoscopic pattern, locations, size and origin of the primary sites. Results. Common indications for endoscopy were anaemia, bleeding and epigastric pain. Metastases presented as solitary (68%) or multiple (32%) and were mainly located in the middle or upper third of stomach. Lung and breast cancer and malignant melanoma were the main primary sites. Conclusions. As the prognosis for cancer patients has been improving gradually, GI metastases will be encountered more often. Endoscopic examinations should be conducted carefully in patients with malignancies, and endoscopic biopsies and information on the patient’s clinical history are useful for correct diagnosis of gastric metastases. PO154 ENTEROSCOPY USEFULNESS IN DETECTING “PATCHY” FORM OF COELIAC DISEASE I. De Vitis, S. Ennas, G. Pirozzi, F. Faustini, L. Guidi, A. Papa, R. Urgesi, G. Fedeli, G. Gasbarrini Gastroenterology Unit, Department of Internal Medicine, Catholic University of Sacred Heart, Rome, Italy The exploration of the intestinal tract, between the third duodenal portion and the jejunal loops—unknown to the endoscopist till now—have allowed us to expand our diagnosis and therapeutic capacities. The aim of this study is to verify if the use of routine enteroscopy in suspected coeliac patients improves diagnosis.

a Servizi

Ecotomografia, Endoscopia Digestiva S. Rita C.B.H., Bari, Italy di Gastroenterologia “OO.RR.”, Foggia, Italy c Sezione Gastroenterologia, Dip. Scienze Mediche, Università Foggia, Italy d Sezione Gastroenterologia, Dip. dell’Emergenza e dei Trapianti d’Organo, Università Bari, Italy e Servizio Endoscopia Digestiva IRCCS Castellana Grotte, Italy b Unità

Background. EUS with anechoic contrast agents represents a new technique which allows obtaining useful information about the morphology of the small bowel. Preliminary data show that its diagnostic accuracy is similar to X-ray examination after barium administration. Aim. To evaluate the possibility of identifying some parameters whose alteration could be strongly predictive of a common disorder (coeliac disease) confined to the small bowel. Patients and methods. EUS was performed in blind by two operators using PEG 4000 at the dose of 37 mg/500 ml of water as counter agent. Thirteen patients with coeliac disease were enrolled at the time of the first diagnosis and a group of 26 healthy volunteers, homogeneous for sex and age, was used as control. Coeliac disease was diagnosed on the basis of the positivity for anti-gluten, anti-endomysium and anti-transglutaminase antibodies as well as of histological examination of endoscopic jejunal biopsies. A series of echographic parameters was evaluated in each subject: the diameter of loops, the number of folds and peristaltic propulsive waves were calculated in the jejunum at the level of the left hypocondrium, while Doppler resistance index (R.I.) of mesenteric superior artery pulsed at arterial beginning from aorta. Statistical analysis was performed by Mann–Whitney U-test. Results. Our results are summarised as follows (coeliac disease versus control (P)): diameter of small bowel loops (cm) 2.49 ± 0.3 versus 1.78 ± 0.2 (<0.001); Kerckring folds (number/2.5 cm) 3.15 ± 1.7 versus 6.24 ± 1.09 (<0.001); peristaltic waves (number/min) 17.1 ± 2.04 versus 11.3 ± 1.7 (<0.001); Doppler R.I. (Vmax − Vmin /Vmin ): 0.69 ± 0.03 versus 0.85 ± 0.01 (<0.001). Additionally, coeliacs showed liquid content in the small bowel before counter administration in the 53.8% and mesenterial

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Abstracts

lymphoadenomegaly in the 93%, while these aspects were never observed in controls. Conclusions. EUS could be a reliable and non-invasive technique in coeliac disease, since peculiar diagnostic aspects may be identified and expressed by a numerical value which differs from that found in normal subjects. Moreover, the possibility of investigating the whole small bowel could be useful to detect patchy localisations of the disorder. Finally, the safety of repeating the investigation suggests that it can be employed for the follow-up of the disorder. PO156 HVPG AND CLINICAL/ENDOSCOPIC FEATURES IN LIVER CIRRHOSIS: CORRELATIONS AND THRESHOLD VALUES FOR COMPLICATIONS OF PORTAL HYPERTENSION A. Dell’Era, F.M. Fabris, R. de Franchis, F. Salerno, A. Sangiovanni, G. Borroni, S. Visentin, A. Nicolini, G. Meregaglia, L. Fazzini, M. Primignani Department of Internal Medicine and Radiology Service, IRCCS Ospedale Maggiore of Milan, Milan, Italy Background and aims. The relationship between HVPG and Child–Pugh class has been demonstrated in several studies, whereas the relationship with variceal size remains controversial. Moreover, the relationship between HVPG and other portal hypertension-related complications has been poorly investigated. In this study, we correlated clinical/endoscopic features and HVPG in cirrhotic patients without recent bleeding. In addition, we looked for threshold HVPG values for the development of complications of portal hypertension such as ascites, oesophageal varices and portal hypertensive gastropathy. Patients and methods. Eighty-eight cirrhotic patients (55 males, mean age 58 ± 10 years) underwent HVPG measurement. Results. The results are illustrated in the table. HVPG was: ≥10 mmHg in 76 of the 80 patients with oesophageal varices (95%), ≥13 mmHg in 41 of the 42 ascitic patients (98%) and ≥15 mmHg in 35 of the 36 patients with portal hypertensive gastropathy (97%) Conclusions. The severity of cirrhosis, the presence and severity of ascites, the occurrence of portal hypertensive gastropathy, but not the presence or size of oesophageal varices, correlate with HVPG. Threshold HVPG values for the development of oesophageal varices, ascites and portal hypertensive gastropathy are 10, 13 and 15 mmHg, respectively. HVPG value mmHg (mean ± S.D.) Child–Pugh class (A–C) Ascites (absent, responsive, refractory) Portal gastropathy (absent, present) Oesophageal varices (absent, F1, F2, F3)

14.7 ± 4.3 16.6 ± 6.6

20.7 ± 6.6 18.4 ± 4.2

16.9 ± 5.6

20.6 ± 6.7

19 ± 9.4

18.6 ± 6.4, 17.7 ± 4.9

P 22.6 ± 5.1 22.5 ± 6

0.0001 0.001 0.013

19.8 ± 8.4

0.708

PO157 INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS: OUR EXPERIENCE B. Demarchi, N. Sapone, F. Bresso, G.C. Actis, R. Bonardi, S. Rossetti, V. Ponti, M. Astegiano, M. Rizzetto Background. Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD) and most commonly with ulcerative colitis (UC) in 55–75% of the patients. Although extent, duration or severity of IBD poorly correlates with the natural course of PSC, patients with PSC usually have mild or asymptomatic but extensive colitis. Orthotopic liver transplantation (OLT) is the only potential curable therapy for PSC. Aim. The purpose of this study was to evaluate the outcome of patients with IBD and PSC with or without transplantation.

Results. Fourteen patients were identified (11 males; 78%). IBD were predominantly UC (10 patients, 71%), 3 patients had Crohn’s disease and 1 had indeterminate colitis. A majority of UC patients showed pancolitis (80%), quiescent course in five (50%), active in three and steroid dependent in two. The mean age at diagnosis was 28.4 years (range 17–46 years). Two patients suffered from Crohn’s colitis and one from ileitis, and the mean age at diagnosis was 23 years (range 10–28 years). The clinical behaviour was inflammatory in all the patients. PSC were diagnosed after IBD onset in nine patients (64%), with a mean interval of 6.7 years (range 1–25 years). In the remaining cases, PSC was diagnosed at the same time in three patients or before in two patients with a mean interval of 7 years (range 5–9 years). The mean time from diagnosis of PSC to liver transplantation was 8 years (range 3–11 years). Eight patients were transplanted. Median follow-up pre- and post-OLT was 5 and 3 years, respectively. Retransplantation was required in three patients. Biliary strictures both anastomotic and non-anastomotic occurred in two patients. The incidence of recurrent PSC was 25%. Two patients (14%) died in the follow-up for cholangiocarcinoma and hepatocellular carcinoma. Conclusions. A gender difference was noted such that two-thirds (78%) of the patients with PSC were male. PSC was associated most commonly with UC (71%) and 64% of the patients were diagnosed having IBD before PSC. Eight patients (56%) underwent transplantation and two (25%) presented recurrence of PSC. Two patients died of cholangiocarcinoma and hepatocellular carcinoma. PO158 THE CLINICAL COURSE OF ULCERATIVE COLITIS AFTER ORTHOTOPIC LIVER TRANSPLANTATION FOR PRIMARY SCLEROSING CHOLANGITIS B. Demarchi, S. Rossetti, N. Sapone, F. Bresso, D. Reggio, M. Bruno, G.C. Actis, M. Astegiano, M. Rizzetto Background. Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel diseases (IBD) particularly with ulcerative colitis (UC). The effect of orthotopic liver transplantation (OLT) on the course of IBD in these patients remains unclear and published studies have given conflicting results. Predictive factors for post-transplant IBD course were not identified. In many centres, steroids are often withdrawn soon after transplantation and this may affect IBD activity. Aim and methods. To evaluate the course of UC pre- and post-OLT in patients with PSC and UC, who underwent OLT in Molinette Hospital in Turin between 1996 and 2003. In this period, 25 patients underwent transplantation; 8/25 (32%) had a diagnosis of IBD before transplantation (6 UC, 1 Crohn’s disease, 1 IBD). All the patients underwent colonoscopy before and after OLT and all received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression. Results. Only the patients with UC were studied. There were four males and two females, mean age at OLT was 33.6 years (range 22–42 years) and five patients had total and one had distal UC. Median follow-up preand post-OLT was 5 and 3 years, respectively. In the period up to 5 years before OLT, UC was quiescent in three (50%), active in two and steroid dependent in one. The clinical course after OLT was stable in two and deteriorated in four patients. It remained quiescent in one and worsened in two of the three patients with pre-transplant quiescent course whereas it worsened in two patients with pretransplant active course. No colorectal cancer or dysplasia has been diagnosed till date. Conclusion. Despite immunosuppression (often with early steroid withdrawal), UC in patients after OLT for PSC has a more aggressive course than before transplant and steroids are very often needed to treat the UC. Whether steroid should be maintained long term remains a moot point; perhaps the azathioprine dose could be increased but the potential side-effects, including possible oncogenesis, may be more likely and/or more severe in immunosuppressed patients.

Abstracts PO159 MESALAMINE ALONE VERSUS MESALAMINE PLUS GIFLOREXÒ IN PREVENTION OF POST-OPERATIVE CLINICAL RECURRENCE OF ILEAL CROHN’S DISEASE: A PILOT STUDY B. Demarchia , S. Rossettia , N. Saponea , F. Bressoa , L. Bertolussoa , M. Astegianoa , A. Mussoa , A. Resegottib , G.R. Frondab , R. Sostegnic , A. Perac , M. Rizzettoa a Gastroepatologia,

Ospedale Molinette, Turin, Italy Generale B, Ospedale Molinette, Turin, Italy c Gastroenterologia, Ospedale Mauriziano, Turin, Italy b Chirurgia

Background. Ileal recurrence of Crohn’s disease after ileocaecal resection is a common event in the natural history of the disease. The microbial flora seems to play a role in the pathogenetic mechanism; there can be a positive effect of modulation of the bacteria in the post-operative outcome and perhaps in the development of a post-operative recurrence. Aim. To evaluate the efficacy of the mesalamine plus high concentration of probiotics (Giflorex, Errekappa Euroterapiciò) in the prevention of Crohn’s disease clinical recurrence after ileocaecal resection. Methods. A prospective, randomised, double blinded study in 20 Crohn’s disease patients with ileocaecal resection. Mesalamine 2.4 g daily plus Giflorex three bags daily or placebo three bags daily were given to the patients. At 3, 6 and 12 months, the disease activity was evaluated with the following parameters: CDAI, inflammatory markers, total proteins and blood cell count. In the statistical analysis, the data were analysed with Fisher exact test and t-test and expressed as mean ± S.D. Results. Sixty-nine percent of the population was male and the mean age was 43.4 ± 15.9 years. Ileal location of the disease was present in 77% of the patients as a lone lesion, the inflammatory-like behaviour was evident in 38% of the cases. Some of the parameters evaluated during the follow-up at the third month showed a slight improvement even if not statistically significant (CDAI: 83.6 ± 35.6 versus 59.8 ± 50.4, P = 0.27 NS; VES: 22.5 ± 16.1 versus 9.0 ± 7.8, P = 0.20 NS; Hb: 12.2 ± 1.6 versus 13.5 ± 0.9, P = 0.22 NS) in patients treated with mesalamine plus Giflorex. At month 12, 33% of the patients treated with Giflorex developed the clinical recurrence versus 14.3% in the placebo group (P = 0.58). Location, disease behaviour, gender and age at onset did not differ in the two patients group whether they developed clinical recurrence or not. Conclusions. The mesalamine plus probiotics did not show efficacy in the prevention of the clinical recurrence of Crohn’s disease in patients with ileocaecal resection even if a positive trend is visible. This result is possibly due to the small number of involved patients and further studies will be needed for a better understanding. PO160 HFE GENE MUTATIONS WILSON’S DISEASE

AND

IRON

METABOLISM

IN

L. Demeliaa,b , M.S.O. Sorbelloa,b a Department b SS

of Internal Medicine, University of Calgary, Italy 554 Sestu, Policlinico Universitario Monserrato, Italy

Background and aim. There is increasing evidence for an interaction between iron and copper metabolism in Wilson’s disease (WD). The ceruloplasmin, a copper protein with ferroxidase activity, plays a role in the hepatocellular transfer and transport of iron. Hypoceruloplasminaemia can lead to tissue iron storage in WD. The HFE gene encodes a protein HFE intimately involved in intestinal iron absorption. The aim of this study was to determine iron indices, the prevalence of HFE gene mutations and to evaluate the significance of the various HFE genotypes for iron metabolism in WD patients. Methods. Nineteen patients with WD were investigated for iron indices (ferritin, serum iron, transferrin), copper indices (ceruloplasmin, serum copper, urinary copper) and hepatic copper and iron concentration. HFE

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genotyping for the C282Y and H63D mutations was performed on all patients. Results. All the 19 patients (12 women and 7 men) fulfilled the clinical and histological criteria of WD. Of the 19 WD patients, 3 were H63D heterozygotes, while the other 16 were negative for both mutations. One patient (woman, 39 years), with H63D heterozygosis, had at the same time heterozygosity for beta-thalassaemia. She did not develop iron overload, showing persistently normal serum and liver iron parameters, although the histopathological study highlighted a pattern of haemocromathosis. A second patient (woman, 18 years) showed high liver iron content (3388 ␮g/g d.w.) and constantly normal ferritin level. In the third patient (woman, 25 years), ferritin level was increased (266 ng/ml). Sixteen HFE wildtype patients did not present significant alterations of iron metabolism. Significant increasing of hepatic iron content was noticed in HFE heterozygotes compared to wildtype WD patients (P < 0.01). Conclusions. Iron overload related to hypoceruloplasminaemia and HFE mutations may be clinically and histologically important in patients with WD. Our results suggest that assessment of iron indices should be recommended in WD patients. The view that the altered hepatic iron deposition in actively menstruating female strongly supports the hypothesis that the impact of HFE mutations in WD may be considerable. PO161 STUDY OF NEUROENDOCRINE NEOPLASMS OF THE SMALL BOWEL WITH CAPSULE ENTEROSCOPY: REPORT OF TWO CASES M. Devani, C. Abbiati, E. Rondonotti, C. Signorelli, G. Beccari, M. Vecchi, R. de Franchis Servizio di Gastroenterologia ed Endoscopia Digestiva, Dipartimento di Medicina Interna, Università degli Studi di Milano, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Background. Carcinoids are the second most frequent neoplasms of the small bowel after adenocarcinomas; early diagnosis and staging is difficult because primary nodules are usually subclinical, submucosal, small and multicentric. Traditional investigations of the small bowel are unsatisfactory and/or invasive. Capsule Enteroscopy (CE) is emerging as a new tool for small bowel investigation. We report two cases of carcinoid in which CE played a key role in the diagnosis and clinical management of the patients. Patients. Patient 1, 53-year-old male, with GERD, underwent upper GI endoscopy showing a duodenal nodule (diameter: 1 cm; biopsy: carcinoid). A subsequent endoscopic US scan confirmed the finding and excluded local lymph-node involvement. Total body CT, colonoscopy: all negative. Octreoscan: equivocal results. GI hormones: normal values of VIP, somatostatin, GIP, gastrin, chromogranin A; increased levels of PP, motilin, neurotensin. CE showed at least two submucosal polypoid lesions in the duodenum. The patient underwent surgical resection and gastro-duodenoplasty. Pathology confirmed the presence of two major nodules (1 and 0.4 cm) and identified one as a carcinoid limited to the submucosa and the other as gastric heterotopy. Patient 2, 33-year-old female with iron-deficiency anaemia and dyspepsia. Upper GI endoscopy, ileo-colonoscopy and bronchoscopy: all negative. Abdominal US scan showed multiple focal lesions in the liver, confirmed by CT and NMR. Tentative diagnosis: metastatic neuroendocrine tumour. Fine needle liver biopsy: normal. Laparoscopic biopsy confirmed liver metastases from a neuroendocrine tumour. Enteroclysis: no small bowel lesion found. CE findings: several nodules in distal jejunum/proximal ileum. Surgical exploration found five ileal mucosal lesions and tumour of the appendix. Small bowel resection and appendectomy were performed. Pathology report: (a) appendix, infiltrating carcinoid; (b) ileum, multifocal malignant neuroendocrine tumour (carcinoid); one lymph-node metastasis. The patient was treated with subcutaneous octreotide. Follow-up abdominal US scan (5 months postoperatively) showed three small residual nodules in

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the liver. Repeat CE (6 months postoperatively): no lesion found; visible T-T anastomosis in the ileum. Conclusions. CE may help in identifying the primary site of metastatic carcinoids, and probably also in the staging and follow-up of these tumours. PO162 HAEMATOPOIETIC STEM CELL MOBILISATION DOES NOT OCCUR IN PATIENTS SUBMITTED TO HEPATECTOMY OR IN CIRRHOTIC PATIENTS C. Di Camplia , A.C. Piscagliaa , M. Nestolaa , M. Zoccoa , S. Rutellab , G. Bonannob , A. Mariottib , F. Maria Vecchioc , F. Giulianted , F. Arditod , P. Polae , G. Leoneb , G. Gasbarrinia , A. Gasbarrinie a Medicina

Interna, Gemelli Hospital, Catholic University of Rome, Italy Gemelli Hospital, Catholic University of Rome, Italy c Anatomia Patologica, Gemelli Hospital, Catholic University of Rome, Italy d Chirurgia, Gemelli Hospital, Catholic University of Rome, Italy e Patologia Medica, Gemelli Hospital, Catholic University of Rome, Italy b Ematologia,

Background. After partial hepatectomy, mature hepatocytes can divide, replacing the hepatic mass within a few weeks. However, when liver damage is extensive or chronic stem cells should be involved in liver regeneration. We aimed to assess if bone marrow stem cells could migrate to the liver in patients submitted to partial hepatectomy on a healthy or cirrhotic liver. Methods. Four patients (mean age 47 years, two male, two female) submitted to partial hepatectomy were enrolled. Two patients presented with hepatic angioma; two with hepatocarcinoma on a cirrhotic liver (group 1). Four patients (mean age 46 years, male) affected by liver cirrhosis (potus or HCV related, Child B–C) with an acute decompensation were also enrolled (group 2). Mobilisation of haematopoietic stem cells (HSC) was evaluated by cytofluorimetry on the peripheral blood samples at 1, 3, 7, 15 and 30 days after surgical procedures in the first group or at admission and discharge in the second group. Results. No HSC were detected either in the blood of patients submitted to hepatectomy or in the cirrhotic patients at point of time. Conclusions. As expected, HSC are not recruited after surgical procedure in patients with a previously healthy liver; but also in patients with cirrhotic liver submitted to partial hepatectomy or undergoing an acute decompensation is not possible to demonstrate a HSC mobilisation. In all cases, liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. PO163 EFFECT OF LACTOBACILLUS GG ON GENES EXPRESSION PATTERN IN SMALL BOWEL MUCOSA USING DNA MICROARRAY ANALYSIS S. Di Caroa,b , H. Taob , A. Grilloa , C. Eliaa , P. Fedelia , G. Cammarotaa , G. Gasbarrinia , A.R. Sepulvedab , A. Gasbarrinia a Department

of Internal Medicine, UCSC Microarray-Corelab, Catholic University, Rome, Italy b Department of Pathology, UPMC, University of Pittsburgh, PA, USA

Background. Probiotics have been used for cure or prevention of several clinical conditions. However, the rationale of their usage needs to be substantiated by understanding how they affect the intestinal mucosa. Aims. To identify the genes expression pattern induced by LGG supplementation in small bowel mucosa in healthy subjects. Methods. Six patients affected by mild oesophagitis were treated for 1 month with esomeprazole (PPI) and randomised to receive or not receive two sachets per day, each containing 6 × 109 of viable LGG (groups I and II, respectively). Total RNA was extracted from biopsies of the duodenal

mucosa taken pre- and post-treatment. Genes with more than two-fold changes in expression levels had been selected as target candidate of LGG effect using GeneChip Human U133A array (Affymetrix Inc., USA). To confirm the results, real-time RT-PCR of five amongst the selected genes was conducted (Applied Biosystem, USA). Results. PPI therapy by itself did not determine significant changes in genes expression pattern. Conversely, after LGG administration 334 and 92 genes resulted in up- and down-regulation, respectively. Quantitative PCR confirmed the reliability of this analysis. LGG mainly affected the expression of a large number of genes involved in immune response and inflammation (TGF-beta and TNF family members, cytokines, chemokines, nitric oxide synthase 1, defensin alpha1), apoptosis, cell growth and cell differentiation (cyclins and caspases family members, oncogenes), cell– cell signalling (ICAMs and integrins family members), cell adhesion (cadherins family members), signal transcription, transduction and genes of unknown function. Conclusions. Our results demonstrate a wide modification of gene expression pattern in the duodenal mucosa induced by LGG administration in subjects with a healthy duodenum. These data represent a basic step to understand the complex interplay between the bacterium and the host. PO164 BACILLUS CLAUSII EFFECT ON GENES EXPRESSION PATTERN IN SMALL BOWEL MUCOSA USING DNA MICROARRAY ANALYSIS S. Di Caroa,b , H. Taob , A. Grilloa , C. Eliaa , P. Fedelia , G. Cammarotaa , G. Gasbarrinia , A.R. Sepulvedab , A. Gasbarrinia a Department

of Internal Medicine, UCSC Microarray-Corelab, Catholic University, Rome, Italy b Department of Pathology, UPMC, University of Pittsburgh, PA, USA

Background. The functional properties of probiotics, which positively affect the bowel microecology and improve health, have to be supported by scientific evidences. Aims. To identify the patterns of genes expression induced by Bacillus clausii in duodenal mucosa in healthy subjects. Methods. Six patients affected by mild oesophagitis were treated for 1 month with esomeprazole (PPI) and randomised to receive or not three vials per day, each containing 2 × 109 of spores of Bacillus clausii (groups I and II, respectively). Total RNA was extracted from biopsies of the duodenal mucosa taken pre- and post-treatment. Genes with greater changes in expression levels have been selected as candidate targets of B. clausii effect using GeneChip Human U133 array (Affymetrix Inc., USA). To validate the reliability of microarray analysis, real-time RT-PCR (Applied Biosystem, USA) of five amongst the selected genes was conducted. Results. One hundred and fifty-eight and 265 genes showed a greater than two-fold up- or down-regulation, respectively, after B. clausii administration. The PPI did not determine a significant alteration of genes expression. The quantitative PCR confirmed the results. B. clausii mainly affected the expression of a large number of genes involved in immune response and inflammation (IL1beta, IL13, IL6R, IL15RA, Jag2, Defensin beta 126, NFkB-binding protein), apoptosis and cell growth (jun, caspase 5, growth differentiation factor 3, IGF1, IGF2, HGF), cell differentiation (cyclin E1, cyclin D1, IGF2, HGF), cell–cell signalling (nitric oxide synthase 1, mitogen-activated protein kinase kinase kinase 3), cell adhesion (cadherin 6, villin 2, protocadherin 12), signal transcription, transduction and genes of unknown function. Conclusions. The identification of B. clausii-induced genes expression profile in healthy duodenum provides the basis for clarification of the molecular mechanisms by which these agents interact with the host and exert their beneficial effects.

Abstracts PO165 HIGH LEVELS OF SOLUBLE CD14 AND TNF- ALPHA IN CROHN’S DISEASE PATIENTS WITH INCREASED INTESTINAL PERMEABILITY

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one patient, diagnosed with ileal CD, underwent surgery as the capsule remained trapped in a stricture. Conclusions. Wireless endoscopy effectively visualised small bowel abnormalities also for indications other than bleeding. However, a more accurate selection of the patients is desired to optimise its performance.

V. Di Leo, R. D’Incà, F. Lamboglia, M.G. Vettorato, G.C. Sturniolo Gastroenterology Section, Department of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy Disruption of intestinal barrier function plays an important role in triggering clinical relapse in Crohn’s disease (CD). Antibiotics are an effective treatment for CD, suggesting that resident bacteria are involved in the pathogenesis of intestinal inflammation. CD14 is the receptor for LPS, a component of Gram-negative bacteria, which generates the production of proinflammatory cytokines. After binding LPS, the extracellular segment of CD14 splits: serum levels of soluble CD14 (sCD14) are a sign of the interaction between CD14+ cells and LPS. Aim and methods. We hypothesised that the inflammatory response which follows increased intestinal permeability may be in part induced by LPS. We assessed intestinal permeability by lactulose/mannitol (L/M) test and serum levels of sCD14 and TNF-alpha by ELISA in 39 CD patients and 10 healthy controls. Data are expressed as mean ± S.E.M. Results. Average L/M test value was significantly increased in CD patients compared to controls (0.038 ± 0.001 versus 0.015 ± 0.001; P < 0.001). Serum levels of sCD14 were significantly higher in the CD group than in controls (4313.34 ± 30.91 ml versus 2955.25 ± 70.80 ng/ml; P < 0.001) as well as TNF-alpha (18.7 ± 3.2 pg/ml versus 11.6 ± .2.0, respectively; P < 0.05). L/M test and sCD14 significantly correlated with each other (P < 0.05, r = 0.65) and with clinical activity (P < 0.01, P = 0.57). Conclusions. Altered epithelial permeability may allow passage of bacterial products into the intestinal wall which, in turn, may lead to mucosal and systemic inflammation. Maintaining or correcting the integrity of barrier function can represent a valid therapeutic option for the CD patients. PO166 CAPSULE ENDOSCOPY FOR THE EVALUATION OF SMALL BOWEL: GREAT EXPECTATIONS STILL WAITING TO BE MET V. Di Leo, R. D’Incà, M.G. Vettorato, G.C. Sturniolo Gastroenterology Section, Department of Surgical and Gastroenterological Sciences, University of Padua, Italy Capsule endoscopy is becoming a valid tool for investigating small bowel. Its ability in identifying sources of obscure bleeding is constantly substantiated. Fewer data are available about its diagnostic yield and clinical value for indications other than GI bleeding. Subjects and methods. From November 2002 to September 2003, 90 wireless endoscopies were performed at our clinic. Sixty patients, 31 females, mean age 47 years (range 14–80 years) with no signs of overt GI bleeding were investigated by Given M2A video capsule for suspected small bowel disease, for a total of 62 procedures. Main clinical features were: iron-deficient anaemia (20), abdominal pain (12), chronic diarrhoea (9), malabsorption and weight loss (7), Crohn’s disease (CD) (5), familial adenomatous polyposis (3). Three patients underwent wireless endoscopy for suspect GI neoplasm and one for portal thrombosis. Two patients repeated the procedure during the follow-up. Results. Complete vision of the small bowel was achieved in 55 patients. No small bowel lesions were found in 17 patients, but 5 of them had gastric abnormalities. Small bowel was abnormal in 38 patients. Lesions compatible with CD were found in 14 patients, diffuse or patchy enteropathy in 7 patients and polyps in 6 patients. Actively bleeding lesions were detected in six patients and potential bleeding sources in five. Capsule endoscopy had an overall diagnostic yield of 62%. In particular, three small bowel malignancies were detected and nine patients had a better definition of their already known pathology. However, further endoscopies were needed in 10 patients to reach a diagnosis. In addition,

PO167 THE ETIOLOGAL PATTERN OF HEPATOCELLULAR CARCINOMA (HCC) IN ITALY IS CHANGING V. Di Marco, P. Parisi, S. Alizzi, G. Alaimo, L. Sandonato, S. Pardo, D. Cabibbi, P.L. Almasio, A. Licata, C. Cammà, M.A. Latteri, A. Crax`ı Unità Interdipartimentale per le Neoplasie Epatiche (UINE), University of Palermo, Palermo, Italy Background and aims. The prevalence of HCV infections have been stable over the last years, while the rate of HBV carriers is steadily declining. We reviewed the aetiology and main features of HCC over the last 5 years. Methods. Three hundred and ten consecutive patients with a new diagnosis of HCC were seen between January 1999 and June 2003. Cryptogenic disease was defined by the absence of HBsAg, anti-HCV, markers of autoimmunity and of metabolic disease and of significant use of alcohol. Results. The mean age of patients was 66 years, younger for those with alcoholic (56.2 years) and HBV (58.6 years) disease, as compared to HCV (67.3 years) and cryptogenic (69.9 years) (P < 0.001 by rank sum). Majority of the subjects (98%) had underlying cirrhosis. Patients with HCV and cryptogenic diseases were more frequently well compensated (Child–Pugh A) than those with HBV or alcoholic disease (P < 0.05). Overall, 81.2% of the patients were anti-HCV positive, 9.1% were HBsAg positive; 3.6% had alcoholic liver disease and 5.9% patients had cryptogenic disease. Over the last 5 years, the rate of cryptogenic (from 3.2% during 1999 to 13.1% during 2003) and to a lesser degree of alcoholic disease, have increased particularly in parallel with a decrease in HBV cases (from 14.5% during 1999 to 5.2% during 2003). Conclusions. The shift in aetiology of HCC may reflect either a true decrease in the number of HBV-related HCC, or rather a masking effect due to progressive loss of HBsAg seropositivity with advancing age with retained HBV-DNA in the liver (occult HBV infection). The role of non-alcoholic fatty liver disease in determining HCC must also be evaluated prospectively. PO168 NATURAL HISTORY OF PATIENTS WITH CHILD–PUGH A CIRRHOSIS AND UNTREATABLE HEPATOCELLULAR CARCINOMA: A PROSPECTIVE STUDY V. Di Marco, P. Parisi, S. Alizzi, D. Di Bona, G. Alaimo, N. Alessi, A. Licata, A. Crax`ı, C. Cammà Cattedra e Unità Operativa di Gastroenterologia, Università of Palermo, Palermo, Italy Objective. The natural course of patients with compensated cirrhosis and hepatocellular carcinoma (HCC) is very heterogeneous. This variability is related to both characteristics of the tumour and the severity of the underlying liver disease. The aim of this study was to identify prognostic factors of survival in a cohort of patients with Child–Pugh class A cirrhosis and untreatable HCC. Methods. We performed Cox regression analysis in 49 consecutive patients with Child–Pugh class A cirrhosis and untreatable HCC (mean age 67.4 ± 9.2 years; 38 male and 11 female) with a median follow-up of 12 months. As HCC in these patients was untreatable since presentation (tumour size >5 cm in 13/49 (26.5%); multinodular in 20/49 (40.8%); vascular invasion in 8/49 (16.3%) or refused treatment 8/49 (16.3%)), patients received only standard supportive therapy for cirrhosis.

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Results. A total of 34 deaths occurred. The causes of death were liver related in 29, non-liver related in 2 and unknown in 3 patients. Overall survival rates were 54 and 24% at 1 and 2 years, respectively. By Cox multivariate model, number of lesions (risk ratio (RR) 1.40; 95% CI 1.05– 1.86) and vascular invasion (RR 2.90; 95% CI 1.25–6.70) were the only variables significantly associated with poor survival. In contrast, tumour size, baseline albumin, bilirubin and alpha-fetoprotein levels were not significantly associated with survival. Conclusions. The natural course of patients with Child–Pugh A cirrhosis and untreatable HCC was very poor. Among the variables included in the current clinical staging systems, vascular invasion and number of lesions are the best predictors of poor survival in these patients. PO169 LAMIVUDINE VERSUS ADEFOVIR-DIPIVOXIL IN THE TREATMENT OF PRE-CORE MUTANT HBV INFECTION: WHICH SHOULD BE USED FIRST? D. Di Paolo, I. Lenci, R. Lionetti, A. Petrolati, G. Tisone, M. Angelico Gastroenterology and Liver Transplant Units, Tor Vergata University, Rome, Italy Background. Lamivudine (LAM) and Adefovir-Dipivoxil (ADV) are both highly effective and well-tolerated nucleosidic analogues for the treatment of HBV infection. Yet, as the two drugs have very different profiles, which one should be used first is undecided. Methods. We studied eight patients with pre-core mutant HBV infection (7 male, 1 female, 56.2 ± 4 years, four end-stage cirrhotics listed for OLT and four OLT recipients with recurrent HBV infection) who were first treated on LAM (100 mg per day) and then shifted, as LAM resistance developed, to ADV (10 mg per day). ALT and HBV-DNA levels (Cobas, Roche) (detection limit <1000 copies/ml) were determined monthly. Results. Improvement of liver function was observed with both treatments. No adverse events occurred. All the patients obtained HBV-DNA negativisation and ALT normalisation during both LAM and ADV. HBV-DNA negativisation was obtained after 59 ± 27 days for LAM and 197 ± 165 days for ADV, respectively (P = 0.03). A >2 log drop of HBV-DNA levels required 42 ± 21 days for LAM and 48 ± 27 days for ADV (n.s.). ALT values became normal after 145 ± 77 and 181 ± 173 days, respectively (n.s.). YMDD-‘resistant mutant during LAM treatment developed after 20 ± 21 months (range 12–75 months). Conclusions. Although LAM and ADV do not differ in the time needed to obtain significant HBV-DNA reduction and ALT normalisation, LAM is significantly faster than ADV in reaching HBV-DNA negativisation. This suggests that LAM could be preferable to ADV in patients in urgent need of optimal control of HBV infection, such as those listed for liver transplantation with high priority scores and those with fulminant hepatitis B. PO170 SURVEY ON MANAGEMENT OF GASTROENTEROLOGIC AND ENDOSCOPIC EMERGENCIES: A PRELIMINARY REPORT. AIGO-GISEG GROUP (INTERDISCIPLINARY GROUP FOR THE STUDY OF GASTROENTEROLOGICAL EMERGENCIES) M.C. Di Paoloa , Battagliab , G. de Pretisc , P. Leod , S. Moscae , L. Tammaroa (AIGO-GISEG Group) a Gastroenterologia

Oncologica, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy b Clinica Chirurgica 4, Università di Padova, Padua, Italy c UO Multizonale di Gastroenterologia, Ospedale Santa Chiara, Trento, Italy d Servizio di Gastroenterologia ed Endoscopia Digestiva, Policlinico Sant’Orsola-Malpighi, Bologna, Italy e Divisione di Gastroenterologia, Azienda Ospedaliera A. Cardarelli, Naples, Italy

A survey on the management of emergency in gastroenterology is going on. A preliminary analysis of the data available was performed. The aim of the survey is to have a picture of the Italian situation. Methods. A questionnaire of 56 multiple choice questions was sent via e-mail to 119 gastroenterologists endoscopists. Forty-three of them, belonging to 37 centres, replied on line. In the questionnaire different items were addressed: characteristics of colleagues, organisation of emergency gastroenterology and specifically of urgent digestive endoscopy, human and technical resources, therapeutic procedures used. Results. There is a great variability in every item addressed. In 70% of the centres, emergency endoscopy out of hours is managed on call, while in 16% on duty and in 14% of centres, both on duty and on call. In 92% of centres, where emergency endoscopy is managed on call, both the endoscopist and the endoscopy nurse are on the call. In three centres, two endoscopy nurses are on call at the same time, while in three other centres no nurse is on call and a non-dedicated nurse on duty helps. Gastrointestinal bleeding patients when managed by gastroenterologists recover earlier and cost less, from the analysis of the questionnaire, only in 22% of the centres are these patients managed directly by the gastroenterologist. In 61% of the centres, there is no predefined path for these kind of patients. This ongoing survey could show how emergency in gastroenterology works at the moment and possibly how it could be improved. PO171 OROPHARYNGEAL RECONSTRUCTION BY FREE JEJUNUM TRANSFER AFTER TUMOUR RESECTION IN THE ORAL CAVITY: A MODEL OF SMALL BOWEL ISCHAEMIA/REPERFUSION (I/R) INJURY AND TRANSPLANTATION A. Di Sabatinoa,b , C. Casellaa,b , R. Ciccocioppoa,b , S. Martuccia,b , M. Brunia,b , P. Cazzolaa,b , R. Moreraa,b , L. Ricevutia,b , M. Benazzoa,b , G.R. Corazzaa,b a Gastroenterology

Unit, Department of Otorhinolaryngology, IRCCS Policlinico S. Matteo, University of Pavia, Italyb Department of Internal Medicine, University of L’Aquila, Italy

Background and aims. Oropharyngeal reconstruction following resection for locally advanced carcinoma by free jejunum transfer allows an evaluation of I/R injury without the additional immunological factors complicating an allogeneic intestinal transplantation. By using an exteriorised jejunal segment for flap monitoring, changes in morphology (mucosal flattening, abnormal enterocyte apoptosis and Paneth cell (PC)/goblet cell behaviour) of a transplanted bowel segment can be monitored. Methods. Two patients affected by an infiltrative squamous cell carcinoma of piriform sinus were treated with circular pharyngolaryngectomy and free jejunal interposition reconstruction. Postoperative monitoring of perfusion was achieved by a minor jejunal segment (monitor) supplied by the same segmental mesenteric vessels and brought out through the wound at the lateral neck. Biopsies were collected from the jejunal segment during the surgical procedures (T0 = normally perfused tissue, T1 = end of cold ischaemia, T2 = end of warm ischaemia, T3 = post-reperfusion); from the monitor, daily, until its removal on the seventh postoperative day; and from the transplanted jejunal segment by upper endoscopy performed 45 days after surgery. Sections were processed for TUNEL assay and phloxine–tartrazine staining. To quantify the degree of mucosal damage, surface area to volume ratio (S/V) was measured. Results. Mean S/V decreased during ischaemia from 48.9 (T0) to 36.3 (T2), but returned to basal level after reperfusion (T3 = 48.1). Mean S/V decreased from 45.2 to 18.7 during the seven postoperative days, and after 45 days in the transplanted jejunum was 10.1. Mean percentage of TUNEL+ enterocytes increased during ischaemia from 1.3 (T0) to 9.2% (T2), and decreased to 2.3% after reperfusion. During the seven postoperative days, it increased from 5.2 to 16.4%, and after 45 days in the transplanted jejunum was 19.1%. Evaluation of PC and goblet cells/100 enterocytes did not reveal any significant difference during I/R phases,

Abstracts but they showed opposite behaviour during the seven postoperative days: PC decreased from mean 7.7 to 1.2%, while goblet cells increased from mean 15.1 to 24.6%. Conclusions. These results suggest that I/R injured small bowel mucosa is capable of rapid and significant recovery after reperfusion and that jejunal transplantation is associated with villous flattening, crypt hyperplasia and PC loss. Goblet cell hyperplasia might contribute to mucosal protection and repair after transplantation. PO172 FASTING AND POSTPRANDIAL RECTAL TONE IN PATIENTS WITH CONSTIPATION-PREDOMINANT IRRITABLE BOWEL SYNDROME AND THE EFFECT OF TEGASEROD M. Di Stefano, E. Miceli A. Missanelli S. Mazzocchi G.R. Corazza Gastroenterology Unit, IRCCS “S. Matteo” Hospital, University of Pavia, Italy Background and aims. Tegaserod is a 5HT4 partial agonist demonstrated to be effective in the treatment of female patients with irritable bowel syndrome and constipation (C-IBS). In clinical studies, a significant reduction of severity of symptoms and an improvement of bowel movements were shown. However, no data are available on rectal tone in patients with C-IBS both during fasting and postprandial periods. Similarly, it is not known whether tegaserod modifies rectal tone. Methods. At entry and after a 4-week period of tegaserod therapy 6 mg b.i.d., six female patients with C-IBS (mean age 31±10 years) underwent rectal barostat testing to evaluate rectal tone in fasting condition and after a caloric meal. After determining minimal distending pressure (MDP), fasting rectal tone was measured for a 30 min period at MDP +2, then a liquid caloric meal (200 ml, 200 kcal, 19% fat, 41% carbohydrate, 40% protein) was given. Rectal tone measurement continued for a further 60 min. Fasting rectal tone was calculated as the mean of the 30 min fasting period; postprandial rectal tone was subdivided in two consecutive 30 min postprandial periods. A group of five healthy volunteers underwent only the basal test for statistical comparison of the results and rectal tone in fasting condition and postprandially were evaluated. Results. In C-IBS, mean fasting rectal tone (156 ± 66 ml) was not significantly different from that in healthy volunteers (147 ± 75 ml). On the contrary, postprandial rectal tone was significantly higher in healthy volunteers than in C-IBS patients: mean volume of the second 30 min period showed a 50% reduction in HV and no modification in IBS-C patients (73 ± 43 ml versus 155 ± 65 ml, P < 0.05). Moreover, in C-IBS patients, tegaserod induced a significant increase (P < 0.05) of postprandial rectal tone (105±89 ml, 37% reduction) which now showed no significant difference in comparison with healthy volunteers. In IBS-C patients, tegaserod had no effect on fasting rectal tone (166 ± 192 ml). Conclusions. In patients with IBS-C, postprandial rectal tone but not fasting tone is significantly lower than in healthy volunteers. Tegaserod therapy normalises rectal tone response to a caloric meal. PO173 A PILOT STUDY ON THE EFFECT OF BUSPIRONE, A 5HT1A RECEPTOR AGONIST, IN PATIENTS WITH NON-SPECIFIC OESOPHAGEAL MOTOR DISORDER M. Di Stefano, S. Mazzocchi, E. Miceli, A. Missanelli, G.R. Corazza Gastroenterology Unit, IRCCS “S. Matteo” Hospital, University of Pavia, Italy Background. Recently, we observed that the 5HT1A receptor agonist buspirone enhanced oesophageal peristalsis in man, suggesting potential therapeutic application in ineffective oesophageal motility. The aim of the present study was to investigate whether buspirone improves oesophageal body motility and lower oesophageal sphincter (LES) function

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in patients with non-specific oesophageal motor disorder characterised by low-amplitude waves. Methods. Five heartburn/dysphagia patients without systemic disorders and with a manometric diagnosis of non-specific oesophageal motor disorder characterised by low amplitude oesophageal waves took part in the study. None of them had oesophagitis at endoscopy. All underwent oesophageal manometry using a water-perfused manometric catheter with axial channels at 5 cm intervals proximal to a 6 cm sleeve sensor. After an overnight fast, the manometric catheter was inserted through the nostril and positioned with the sleeve straddling the LES. Oesophageal wave amplitude and duration, residual pressure and percentage pressure decrease during LES relaxation were calculated. The same test was repeated after a 15-day treatment with buspirone 10 mg b.i.d. Severity of symptoms was evaluated at entry and after therapy by VAS. Results. The protocol and treatment were well tolerated. Compared to baseline, buspirone significantly increased mean oesophageal wave amplitude 13 (29.6 ± 8 mmHg versus 17.3 ± 7 mmHg; P < 0.03), 8 (37.7 ± 7 mmHg versus 20.8 ± 5 mmHg; P < 0.01) and 3 cm (44.2 ± 8 mmHg versus 27.1 ± 9 mmHg; P < 0.01) above LES. Mean wave duration was significantly enhanced by buspirone only 3 cm above LES (10.0 ± 4 s versus 6.1 ± 2 s; P < 0.01). LES resting pressure (15 ± 4 mmHg versus 14 ± 5 mmHg; NS) was not modified but mean residual pressure (2.2 ± 0.4 mmHg versus 6.5 ± 0.9 mmHg; P < 0.0001) and mean percentage pressure decrease during relaxation (84.0 ± 1.8% versus 71.8 ± 3.2%; P < 0.0001) were significantly increased by buspirone. Heartburn (3.5 ± 0.5 to 3.0 ± 0.6) and dysphagia (4.5 ± 0.7 to 4.0 ± 0.8) were not significantly improved in this small group of patients. Conclusions. In patients with non-specific oesophageal motor disorder, the 5HT1A receptor agonist buspirone enhances oesophageal peristalsis and reduces LES relaxation. If confirmed in a larger cohort, buspirone could be considered for the treatment of non-specific oesophageal motor disorder. PO174 TEGASEROD IMPROVES ABDOMINAL BLOATING WITHOUT MODIFYING INTESTINAL GAS PRODUCTION CAPACITY M. Di Stefano, A. Missanelli, E. Miceli, S. Mazzocchi, G.R. Corazza Gastroenterology Unit, IRCCS “S. Matteo” Hospital, University of Pavia, Italy Introduction and aims. Tegaserod improves abdominal bloating in irritable bowel syndrome (IBS). It has been suggested that this effect is due to an increased elimination of intestinal gas as a result of the increased intestinal motility induced by the drug. However, since no data are available as yet on the effect of tegaserod on intestinal gas production, the aim of this study was to investigate intestinal gas production in patients on tegaserod therapy. Patients and methods. Five female patients (mean age 37 ± 15 years) suffering from IBS with constipation were enrolled. At the start and after 4 weeks of tegaserod therapy, patients underwent intestinal gas production capacity evaluation by hydrogen (H2 ) breath test after lactulose, symptom evaluation by VAS and rectal sensitivity evaluation by barostat test. H2 and methane (CH4 ) breath excretion were measured at fasting and for a 7 h period after the administration of 10 g of lactulose. Intestinal gas excretion was evaluated by calculation of area under time–concentration curve (AUC). Symptom evaluation was performed by a 100 mm VAS, including flatulence, bloating, and abdominal pain. After minimal distension pressure (MDP) determination. Rectal distensions (2 mmHg steps for 2 min) were performed and perception and discomfort threshold were estimated. Results. Mean AUC for H2 breath excretion before tegaserod (8109 ± 6225) was not significantly different than those measured after therapy (10,122 ± 7535). Only one subject proved to be a CH4 producer and this production was not modified by tegaserod. Mean scores for flatulence and discomfort before therapy (8.6 ± 2.7 and 5.5 ± 3.2) were not significantly different from after therapy (7.6 ± 3.2 and 5.4 ± 4.3, P = NS). The mean

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Abstracts

score for bloating was significantly lower after therapy (4.2 ± 1.4) than before therapy (8.8±1.5, P < 0.05). With respect to basal values (6.7±3.9 and 18.3 ± 6.4 mmHg), mean perception and discomfort thresholds after tegaserod were not significantly different (4.6 ± 4.1 and 14.3 ± 6 mmHg). Conclusions. As expected, tegaserod improves bloating in functional patients. This effect is not due to a reduction of intestinal gas production, nor to a modification of rectal sensitivity thresholds. The main pathophysiological mechanism could be related to the prokinetic effect on intestinal motility which in turn increases gas elimination. PO175 HOW DIFFERENT CYTOSKELETON PATTERNS CAN PREDICT THE THREE-DIMENSIONAL GROWTH IN FOUR COLON ADENOCARCINOMA CELL LINES E. Dolfinia , R. Colomboc , L. Roncoronia,b , C. Fumagallia , C. Mariania , L. Ellib , G. Alfierid , M.T. Bardellab a Department

of Biology and Genetics for Health Sciences, University of Milan, Milan, Italy b Department of Gastroenterology, University of Milan, Milan, Italy c Department of Biology, University of Milan, Milan, Italy d Milan Research Centre Bracco SpA, Milan, Italy

Background and aim. In vitro culture of cancer cells as three dimensional multicellular spheroids (MCS) has led to significant insight in cancer and micrometastases biology. This is due to MCS capacity of maintaining specific biochemical and morphological features, similar to those of the corresponding tissues. This study aims to evaluate different cytoskeleton patterns in four colon adenocarcinoma cell lines grown in two dimensional monolayer as a parameter predictive of their aggregations in MCS. Materials and methods. We cultured HT-29, LoVo, Caco-2 and LoVo DX (obtained by exposure to doxorubicin increasing concentrations and maintained under the same culture conditions; RI = 26). We investigated: (1) two- and three-dimensional cell line organisation of cytoskeleton actin (phalloidin fluorescence detection method); (2) cell monolayer and MCS morphology (light microscopy, SEM and confocal laser scanning microscopy). Results. The complex actin cytoskeleton network of LoVo and HT-29, growing in monolayer conditions, showed a completely different distribution in comparison with Caco-2 and LoVo DX. The results indicated that HT-29 and LoVo cells assembled a specialised cytoskeleton structure under the plasmatic membrane, containing filamentous actin, whereas Caco-2 had actin microfilaments arranged in evident stress fibres and LoVo DX exhibited patchy spots. LoVo and HT-29 formed rounded spheroids with smooth surface, while Caco-2 and LoVo DX created irregular clusters made of few cells only. Conclusions. The above results suggest that cytoskeleton conformation and, more specifically, F-actin under-membrane distribution are crucial factors contributing to spheroids-forming capability. They also show that actin microfilaments organisation of LoVo cell line can be modified by exposure to doxorubicin, thus preventing spheroids aggregation. PO176 IN VITRO INHIBITION OF TYROSINE KINASE ACTIVITY REDUCES SURVIVAL, GROWTH AND INVASIVE POTENTIAL OF COLORECTAL CARCINOMA CELL LINES L. Dugheraa , G. Bellonea , A. Carbonea , F. Gasparia , E. Tonela , D. Tibaudia , C. Smirnea , D. Ferrerob , P.R. Miolic , G. Emanuellia a Department

of Clinical Physiopathology, University of Turin, Turin, Italy of Hematology, University of Turin, Turin, Italy c Department Surgical Emergency, San Giovanni Battista Hospital, Turin, Italy b Department

The inhibition of tyrosine kinase activity has been pointed out as a therapeutic modality in several forms of neoplasia in which the tyrosine

kinase activity is critical to the malignant phenotype. The specific tyrosine kinase inhibitor imatinib mesylate (STI571, Gleevec) was shown to be effective in the treatment of malignancies expressing the BCR/ABL fusion protein and other cell surface receptors, including c-Kit. Some alterations of the c-Kit system have been demonstrated in the development of gastrointestinal stromal tumours and colorectal carcinoma. In previous works, our group demonstrated that colorectal carcinoma cell lines over-express c-Kit: the paracrine activation of the receptor induces the growth of metastases, while its autocrine activation protects the tumour against apoptosis. The aim of this study was to verify whether Gleevec exerts antitumoural effects on colon carcinoma cell expressing c-Kit, in order to sustain a possible role in the treatment of colorectal cancer. Materials. The effect of Gleevec on anchorage-independent growth, invasion and survival of DLD-1 cell line and on survival of two early passage primary colorectal cancer cells was assessed by clonogenic survival assay, Matrigel invasion assay, cell cycle analysis and apoptosis detection, RNAse protection assay and immunoblotting. Results. Gleevec has shown to affect several aspects of the malignant phenotype of DLD-1 cells, reducing anchorage-independent colony formation, inhibiting SCF-mediated tissue invasion and enhancing susceptibility to apoptosis; this latter effect is due to inhibition of the expression of anti-apoptotic factors such as Bcl-2 and to induction of pro-apoptotic factors such as Bad, Bax and Bclx. The pro-apoptotic effects of Gleevec on DLD-1 cells was partially reverted by foetal calf serum, suggesting that the c-Kit activation may represent a rate-limiting event in colorectal carcinoma when the supply of growth factor is limited. The incubation of primary cultures with Gleevec blocked colony formation and reduced survival by the induction of apoptosis. Conclusions. These in vitro effects suggest that Gleevec could play a role in the treatment of colorectal carcinoma, which is known to depend upon c-Kit activation for growth and survival; the induction of a pro-apoptotic state might increase the tumour sensitivity to cytotoxic drugs, as it has been demonstrated in chronic myeloid leukaemia and gastrointestinal stromal tumours. PO177 FIFTEEN-YEAR FOLLOW-UP OF A CASE OF IDIOPATHIC ADULTHOOD DUCTOPAENIA V. Durante, S. Loffreda, A. Pirazzoli U.O. Medicina Interna, AUSL 40 Rimini, Italy We describe the case of a 36-year-old male with biochemical evidence of a cholesctatic liver disease from 1989, who received a definitive diagnosis in 1995, on the basis of a laparoscopic wedge biopsy. The patient had been admitted in 1989 for polydypsia and polyurea resulting in a diagnosis of diabetes type I; during the mentioned hospital stay raised levels of ALT 9× ULN, AST 4× ULN, ALP 6× ULN, GGT 12× ULN and normal bilirubin were also noted. At that time, no certain diagnosis had been made, notwithstanding two needle biopsies of the liver. In 1995, he was admitted for the first time to our ward for de-compensated IDDM and a liver panel showed similar abnormalities as had previously been noted. HbsAG, HCV-RNA, anti-HIV, autoantibodies, iron status were negative; alpha1-antitrypsin, ceruloplasmin, amylase, lipase, IgM, protein electrophoresis, INR were within normal limits. Abdominal ultrasound showed normal hepatic pattern, splenomegaly indicative of mild portal hypertension, bile ducts appeared normal. Cholangiogram and upper endoscopy was normal. We chose to perform a laparoscopic approach for the biopsy in order to increase tissue yield. The procedure was diagnostic as the pathologist reported bile duct paucity in the absence of signs of inflammation or other lesions. It was thus concluded that the diagnosis was that of Idiopathic Adulthood Ductopaenia. In 2003, the patient remains asymptomatic, abdominal ultrasound, EGDS and labs remain unvaried. Since 1995, he has been on UDCA and is being followed up for an eventual indication for OLT.

Abstracts PO178 A CASE OF PARADOXICAL INTOLERANCE TO MESALAZINE AND BALSALAZIDE A. Ederle, P. Brosolo, E. Soldinger, N. Carone, P. Inturri, E. Dall’O’, A. Fantin, F. Sforza U.O.A. di Gastroenterologia, Ospedale di San Bonifacio, ULSS 200, Verona, Italy A 58-year-old man presented to our Gastroenterology Unit in October 2002, complaining of abdominal pain and emission of mucous stools or bloody diarrhoea. There was no history of allergy and the only drug intolerance reported was to tenoxicam (skin rash) many years before. In May 2000, he was admitted to a hospital (not in our unit), because of the presence of bloody diarrhoea and mild fever: a course of antibiotics and 5-ASA was empirically started, before endoscopy in the suspicion of IBD. The number of bowel movements increased to 50 per day, chest pain appeared and fever increased. Both antibiotics and 5-ASA were withdrawn. A colonscopy and histology demonstrated active ulcerative colitis and the patient was discharged on steroids. In August 2002, the patient reported mucous stools mixed with blood and rectal tenesmus. Then, a course of 5-ASA was started: the patient immediately presented increase in bowel movements, fever and chest pain. The therapy was discontinued and steroid therapy was started. Then, the patient was referred to our unit. We tried, as rechallenge, a very low dosage therapy with the new prodrug balsalazide, but, as could be expected, the patient again presented fever, chest pain and diarrhoea. A therapy with local systemic steroid was started. The patient is now only on azathioprine with good clinical response. Discussion. The report of intolerance to mesalazine is rare but already described (episodic reports <10). It could be underestimated because of the contemporary administration of steroids. Almost all cases characteristically reported chest pain. Rarely, it appears without allergy or intolerance to salicylate which were not present in our patient. In this clinical case also, balsalazide was proved to cause the same paradoxical reaction (no previous report). PO179 POLYFLEX STENTS IN COLON OCCLUSION NOT DUE TO COLON RECTAL CANCER (CRC) A. Ederle, P. Brosolo, E. Dall‘O’, A. Fantin, N. Carone, P. Inturri, F. Sforza U.O.A. di Gastroenterologia, Ospedale di San Bonifacio, ULSS 20, Verona, Italy The management of benign colonic stenosis with metal stents which are generally contraindicated because of the high rate of complications yields poor results. The same problems can arise with stenosis secondary to extrinsic non-colon rectal cancer (CRC). Aim. We have thought to evaluate the possibility of treating colonic stenoses with oesophageal polyflex prosthesis. Materials and methods. We have placed nine polyflex removable prostheses (Rush International) in seven patients without therapeutic alternatives (four peritoneal carcinosis from ovarian and prostatic cancer, two anastomotic stenosis, one with fistula, one diverticulitis in aplastic anaemia). Results. In six of the seven patients, symptoms due to bowel obstruction immediately improved. Four of the seven patients are still alive. The stents were removed from the patients with anastomotic stenosis after 3 and 4 months, but because of recurrent occlusion, they underwent a second stent placement. The devices have been in place for 7 and 2 months, respectively, till now. In the diverticulitis the stent resolved the occlusion but the patient died quickly. In two carcinosis cases, the stents dislocated after 1 and 5 months because the lumen remained fairly wider. Both quickly died because of the progression of their diseases. In the third patient with carcinosis who was undergoing chemotherapy after 10

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weeks it was possible to remove the stent with occlusion resolution. In the last carcinosis case, the stenosis was too long and angulated and the stent dislocated after a few hours. In three patients, the stents were dislocated few times but it was easily possible to put again them in place. Severe complications were not present in our series and we could resolve occlusion symptoms in six of the seven patients. These stents seemed to be really less traumatic, because they do not become embedded in the mucosa and are easily removable, reducing the risks of major complications. On the other hand, the risk of stent displacement is higher, especially at the sigma, where the stent does not fit to the bends of the viscus. Conclusions. Our series is small to provide definitive conclusions. However, modification of polyflex stent (more soft and less rigid and with wider diameters) may provide new therapeutic options in colonic obstruction not due to CRC. PO180 COLON OBSTRUCTION: THE ROLE OF GASTROENTEROLOGIST A. Ederle, P. Brosolo, P. Inturri, E. Dall‘O’, N. Carone, A. Fantin, F. Sforza U.O.A. di Gastroenterologia, Ospedale di San Bonifacio, ULSS 20, Verona, Italy No complicated colonic obstruction can be managed with conservative treatment in up to 80% of the cases. However, surgical treatment becomes necessary for acute colonic obstruction which either does not improve or worsens within 24 h. The gastroenterologist can help in the resolution of colonic obstruction with medical treatment or with new endoscopic techniques. In elderly or in very sick patients, it is possible to avoid surgery definitively or to bring the patient to elective surgery (bridge to surgery). Our Gastroenterology Division became part of a Department including surgery service and we have common clinical pathways and common management of colonic obstruction. No complicated colonic obstructions belong to gastroenterology unit, complicated colonic obstructions belong to surgery unit. However, the patient is monitored by a surgeon and gastroenterologist in relation to evolution of his clinical picture. Materials and methods. From January to June 2003, 53 patients were evaluated. Results. Twenty (38%) patients were treated with medical therapy: 19 (36%) endoscopically (total 74% resolved by gastroenterologist), 14 (26%) with surgical treatment. The causes were: 22 cancer, 12 faecal impaction, 6 diverticulitis, 4 volvulus, 3 hernias, 3 adhesion bridles, 2 anastomotic strictures and 1 invagination. The endoscopic procedures consisted of: 10 stents (2 bridges to surgery), 1 dilatation, 6 decompression tubes, 3 derotation of volvulus and 1 rupture of faecaloma. Fifteen of the 22 neoplastic colonic obstruction have been resolved in gastroenterology service (6 with medical treatment and 10 with endoscopy), 7 in surgery service. Ten of the 12 faecal impactions have been treated with medical therapy and 2 with endoscopy; 4/6 diverticulitis have been resolved medically, 1 with endoscopy and 1 with surgery. Three of the four volvulus have been resolved with endoscopic derotation and one with surgery. All three hernias and adhesions bridles have been treated with surgery. Two of the two anastomotic strictures and one invagination have been resolved endoscopically in gastroenterology. The length of stay averaged 6.5 days in gastroenterology and 13.5 days in surgery. Complications: there were one (5%) small perforation after endoscopic dilatation treated medically and three major surgery complications (21%) with one death. Conclusions. The gastroenterologist may play a major role in the management of colonic obstruction. Therefore, the surgeon may perform elective surgery and, working side by side with the gastroenterologist, may avoid inappropriate admissions.

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PO181 DETECTION OF PROXIMAL OESOPHAGEAL ACID EXPOSURE ENHANCES SENSITIVITY OF THE pH TEST IN NON-EROSIVE GASTRO-OESOPHAGEAL REFLUX DISEASE PATIENTS S. Emerenziani, M. Ribolsi, M.P.L. Guarino, R. Caviglia, T. Petitti, M. Cicala Dipartimento di Malattie Apparato Digerente, Università Campus Bio Medico, Rome, Italy Background. The relationship between typical gastro-oeso- phageal reflux disease (GERD) symptoms and oesophageal acid exposure is poorly understood, particularly in non-erosive reflux disease (NERD) patients, whose 24 h pH test is in the normal range in 50% of the cases. NERD patients have been shown to be characterised by a high proportion of proximal refluxes and are highly sensitive to these short-lived reflux events [1]. Aim. To investigate whether assessment of acid exposure at different oesophageal sites enhances the sensitivity of pH test, multisensor 24 h pH monitoring was performed in 65 consecutive NERD patients (42 females, mean age 51 years) and in 15 asymptomatic volunteers (controls) with no history of GERD (9 females, mean age 39 years). According to manometric findings, the four pH sensors were placed at gastric level, 5 cm above LES, 10 and 3 cm below UES. Acid exposure time at 5 cm above LES was considered abnormal if >4.5% of total recording time. Symptom association probability (SAP) values were evaluated at each oesophageal level, according to standardised criteria. Results. AET in asymptomatic controls was (mean (95% confidence intervals)): 1.8% (0.3–4.3) at distal oesophagus, 0.37% (0.1–0.9) for 10 cm below UES and 0.22% (0–0.8) for 3 cm below UES. AET values (mean and 95% CI) in patients and proportion of patients with a positive pH test are shown in the table. AET of proximal oesophagus was considered abnormal if it exceeded 95th percentile values derived from control group (0.9% at 10 cm and 0.8% at 3 cm below UES). SAP detected at distal sensor was positive in 32/65 patients; the proportion of positive patients was higher (41/65) when SAP was determined both at distal and middle oesophagus. Conclusions. In NERD patients, assessment of acid exposure of proximal oesophageal body (10 cm below UES) from 50% increases sensitivity of pH test to 69%. Accordingly, the proportion of positive patients improves when SAP is determined both at distal and proximal oesophageal levels. Two sensors pH monitoring could improve accuracy of this test in NERD patients AET 5 cm above LES Mean (95% confidence intervals, %) Positive patients (sensitivity, %)

11 (7–15)

33/65 (50.7)

AET 10 cm below UES 3.9 (2.5–5.2)

45/65 (69.2)

Introduction. Transabdominal ultrasound examination of the bowel (bowel US) is an inexpensive and widespread tool. A relevance for diagnosis and follow-up of Crohn’s disease and of its complications has been proposed for bowel US, however the reproducibility of echographic findings was not clearly demonstrated to date. Aims and methods. The aim of this study was to prospectively evaluate interobserver agreement between two observers for the most frequently used echographic signs for bowel US. Thirty-three consecutive Crohn’s disease patients scheduled for bowel US underwent two subsequent examinations on the same day, each carried out by a different investigator. The investigators recorded independently 15 echographic variables. Results. Since March 2003, 33 Crohn’s disease patients were enrolled, all were studied by two different observers. Inter-observer agreement was moderate to excellent for many of the variables. The table gives the kappa and weighted kappa statistics values for the interobserver agreement. Variable

Characteristic

Kappa value

P-value

Abnormal examination

Yes

1.000

<0.001

No Wall thickness

<3 mm 3–4 mm 4–5 mm >5 mm

0.775

<0.001

Wall echo-pattern

Types 1–5

0.834

<0.001

Location

None Small bowel only Small and large bowel Large bowel only

0.947

<0.001

Stenosis

None Single, no dilatation Single, with dilatation Multiple

0.836

<0.001

Abscesses

Yes No

1.000

<0.001

Fistulae

Yes No

0.720

<0.001

AET 3 cm below UES 2.2 (1.2–3.2)

34/65 (52.3)

Conclusion. This preliminar results show an excellent interobserver agreement for the major echographic characteristics considered for Crohn’s disease (wall thickness and echopattern, disease location) and for its complications. Based on the results of this ongoing study, reproducibility of this diagnostic tool is adequate for clinical practice. PO183

Reference [1] Cicala M, et al. Aliment Pharmacol Ther 2003.

INTESTINAL PERMEABILITY AND HCV RELATED CHRONIC LIVER DISEASE

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P. Espositoa , R. Fiandraa , L. deMagistrisa , L. Mattorellia , M. Bellettaa , M. Generosob , M. Cartenib , M. Russoa , M. Bassia , R. Carratùa , C. Del Vecchio Blancoa , C. Loguercioa

PROSPECTIVE STUDY OF INTEROBSERVER AGREEMENT FOR BOWEL ULTRASOUND EXAMINATION IN CROHN’S DISEASE E. Ercole, C. Laudi, C. Rigazio, A. Lavagna, L. Crocellà, M. Daperno, R. Sostegni, R. Rocca, A. Pera UOA Gastroenterologia, Ospedale Mauriziano Umberto I, Turin, Italy

a Dip.

Medico-Chirurgico di Internistica, Clinica E. Sperimentale “F. Magrassi E.A. Lanzara”, Italy b Dip. di Medicina Sperimentale, Seconda Università Degli Studi di Napoli, Naples, Italy Intestinal permeability (IP) alterations were reported in liver cirrhosis (LC) patients and a possible—primary or secondary—role of detective intestinal

Abstracts barrier in liver damage evolution as well as in the decompensated stages of disease was suggested. The aim of the present preliminary report was to investigate IP in patients with HCV-related chronic liver disease. Patients. Forty-seven consecutive outpatients entered the study; they were HCV-RNA positive, genotype 1, non-responder to a previous treatment with IFN, stopped at least 2 years earlier, with no other associated diseases. Thirty-three of these patients had chronic hepatitis (22 male, 11 female; median age 52 years, range 28–72 years) and 14 (8 male, 6 female; median age 58 years, range 37–73 years) had cirrhosis (9 in good functional compensation, 8 Child A and 1 Child B, and 5 in decompensation). We also studied 23 healthy subjects (12 male, 11 female; mean age ± S.D. 27.9 ± 8.1 years) negative for hepatitis virus infection. Methods. IP was studied by the oral administration of a lactulose/mannitol test; the oral isosmolar load was made up with 2 g mannitol and 5 g lactulose. By means of HPLC-Dionex, the percentage of absorbed sugars in 5 h urine were determined and the LA/MA ratio calculated, which is an index of IP; normal values <0.028. Results. Mean IP values were within normal range both in chronic hepatitis and in well-compensated liver cirrhosis patients, while they were altered in decompensated LC. In 5 out of 33 chronic hepatitis patients, however, IP individual values were altered and no correlation to other investigated parameters was found. Valori di LA/MA ± S.D.: healthy subjects (n = 23), 0.014±0.006; chronic hepatitis (n = 33), 0.024±0.017; compensated cirrhosis (n = 9), 0.018 ± 0.005; decompensated cirrhosis (n = 5), 0.093 ± 0.074. Conclusions. The data suggest that, in HCV patients, IP alterations could be related to the severity of liver impairment. PO184 MISINTERPRETATION OF ENDOSCOPIC ULTRASONOGRAPHY RE-STAGING AFTER PREOPERATIVE RADIOCHEMOTHERAPY IN RECTAL CANCER: PRELIMINARY RESULTS C. Fabbria , L. De Lucaa , S. Macchiaa , F. Salvib , V. Cennamoa , A. Piemontesea , D. Baroncinia , P. Billia , M.P. Foschinid , A. Maestric , G. Frezzab , A. Grillia , A. Repicie , N. D’Imperioa a Gastroenterology

and Digestive Endoscopy Unit, Bellaria–Maggiore Hospital, Bologna, Italy b Department of Oncology, Bellaria Hospital, Bologna, Italy c Radiotherapy Unit, Bellaria Hospital, Bologna, Italy d Department of Anatomical Pathology, Bellaria Hospital, Bologna, Italy e Department of Gastroenterology, Endoscopy Unit, Molinette Hospital, Turin, Italy Background and aims. Endoscopic ultrasonography (EUS) is usually the imaging technique of choice used for the locoregional staging of rectal cancer. Radiochemotherapy (RCT) in locally advanced rectal cancer requires an evaluation of the depth of tumour infiltration (T-status) and of the presence of ilial and pararectal lymph node metastasis (N-status). The purpose of this ongoing study is to present preliminary data regarding re-staging using EUS in patients who underwent preoperative RCT. This was part of a research project dealing with molecular markers as predictive factors of the neoadjuvant treatment response. Methods. From January 2003 to October 2003, 13 subjects with rectal cancer (8 male, 5 female, mean age 63 years, range 49–75 years) were investigated using flexible sigmoidoscopy and multiple biopsies for histological and molecular analysis. EUS was performed before RCT. Four weeks after the preoperative treatment (which combined radiotherapy at a dosage of 46 Gy in 23 fractions of 2 Gy per day for 5 days per week and chemotherapy at a dosage of 5-FU in continuous infusion, 200– 225 mg/meq. per day), all patients underwent re-staging by EUS. At 6 weeks, tumour resection was performed. The patients underwent EUS examination using an Olympus GF UM 20 echo-endoscope with radial scanner (7.5–12 MHz). The EUS staging was compared to the pathology findings based on the surgical specimens.

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Results. Overall, the EUS pre-RCT staging was: 1 uT2N0, 2 uT2N1, 2 uT3N0, 7 uT3N1, 1uT4N0; the EUS re-staging after preoperative RCT shown: 1 uT1N0, 6 uT2N0, 5 uT3N0, 1 uT3N1. At 4 weeks after preoperative RCT, the histology was negative in 7/13 subjects (53.8%). Presently, tumour resection has been performed in 76.9% (10/13 subjects) and 3 complete sterilisations of the lesion have been observed in surgical specimens. Conclusions. Our preliminary data show that, after neoadjuvant therapy, EUS is not a very accurate tool for the rectal cancer T-staging because of its tendency to overstage. However, the N-status assessment could be a predictive factor of the preoperative RCT treatment response. Moreover, EUS can provide useful information for the surgeon in planning the surgical approach. PO185 MRCP VERSUS ERCP: A COMPARATIVE STUDY IN THE DIAGNOSIS OF COMMON BILE DUCT STONES L. Familiaria , M. Scaffidia , M. Bonicaa , P. Consoloa , P. Familiaria , A. Blandinob , M. Gaetab a Unità

di Endoscopia Digestiva, Dipartimento di Medicina e Farmacologia, Università di Messina, Messina, Italy b Dipartimento di Scienze Radiologiche, Università di Messina, Messina, Italy

Background. The magnetic resonance cholangiography (MRCP) will soon replace ERCP in the diagnosis of pancreato-biliary diseases because it is a non-invasive method, without complications. Although many studies documented a high sensitivity and specificity of MRCP, its ability in detecting microlithiasis (<5 mm in diameter) of common bile duct stones (CBD), responsible for acute biliary pancreatitis, is still controversial. Aim. To evaluate sensitivity, specificity, diagnostic accuracy, positive predictive value (PPV) and negative predictive value (NPV) of MRCP in the diagnosis of choledocolithiasis using ERCP+ endoscopic sphincterotomy (ES) as the gold standard. Patients and methods. One hundred and twenty-three individuals, suspected for lithiasis of CBD were prospectively enrolled in the study. Clinical findings were: jaundice, fever, abdominal and/or biliary pain, weight loss with altered cholestatic enzymes (ALP >270; GGT >50 UI/l). Patients underwent upper abdominal ultrasonography (US), then MRCP and, within 72 h, diagnostic and/or operative ERCP. All patients signed an informed consent. The statistical analysis was based on the report of true positives and negatives, false positives and negatives. Results. One hundred and six out the 123 patients completed the study. MRCP diagnosed lithiasis of CBD in 73; did not document stones in 33. ERCP confirmed the presence of lithiasis in 66/73 patients who were submitted to ES. Seven were not found to have stones after ES. Among 33 negative patients, ERCP documented stones in 9: in 4 only after ES (it was performed according to clinico-biochemical data and to CBD dilation, though ERCP did not identify stones). The stones were 2–3 mm in size. In 24/33 patients negative at MRCP, ERCP confirmed this response: 10/24 were submitted to ES. ES was not performed in 14/24 subjects, without CBD dilation and/or cholestasis. After a 27.8 months follow-up (range: 4–54 months), 8/14 remained asymptomatic, 6 underwent laparoscopic cholecystectomy without finding of CBD stones at the intra-operative cholangiography. The sensitivity, specificity, diagnostic accuracy, PPV, NPV of MRCP were: 88, 77, 85, 90 and 73%. Conclusions. As MRCP still has a limitation in the diagnosis of small stones, missed at US, the question of which patient is candidate to ERCP/ES is left unresolved. The recognition of microlithiasis should refer to other imaging techniques preliminary to ERCP (e.g. EUS), though their limited availability makes MRCP a method of choice in the diagnosis of biliary disease till date.

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PO186 UNUSUAL BLEEDING AFTER ENDOSCOPIC SPHINCTEROTOMY: A CASE REPORT L. Familiaria , G. Di Giuseppeb , C. Famularib , A. Macrib , M. Longoc , G. Ricciardic , B. Gallettid a Unità

di Endoscopia Digestiva, Dipartimento di Medicina e Farmacologia, Università di Messina, Messina, Italy b Dipartimento di Scienze Chirurgiche, Università di Messina, Messina, Italy c Dipartimento di Scienze Radiologiche, Università di Messina, Messina, Italy d Dipartimento di Otorinolaringoiatria, Università di Messina, Messina, Italy One hour after both laparoscopic cholecystectomy and endoscopic sphincterotomy were performed in a 39-year-old woman, due to stones observed at the intraoperative cholangiography, she presented a massive haematemesis. The upper endoscopy performed in emergency showed both the presence of blood in the stomach and a moderate oozing at the site of sphincterotomy; the latter was treated by endoscopic injecting therapy (adrenalin + saline = 1:10,000). Despite these procedures, the laboratory tests showed a persistent reduction in haemoglobin value, as the bleeding continued and 5 h after the first EGDS, the patient underwent a second endoscopic look, which showed blood in stomach but not the oozing of the papilla, previously documented. Then, an arteriography of the superior mesenteric artery and of the coeliac tripod was performed, without the recognition of any source of bleeding. Indeed, during the next 10 h the bleeding did not stop and seven blood units were necessary to be transfused. Before performing an exploratory laparotomy which had been not yet decided, a third endoscopic look stressed the presence of blood both in the oesophagus and the stomach; this time, anyway, the EGDS identified that the bleeding came from rhynopharynx and the endoscope was taken off. Bilateral nasal packs were inserted to obtain immediate haemostasis. The angiography revealed an arteriovenous fistula treated at the same time by the embolisation of the internal mascellary artery. The patient was discharged on the 15th day. In such a case, the endoscopic sphincterotomy, because of its possible haemorrhagic complications, had misled the operators with possible relevant medico-legal consequences, avoided only after the third endoscopic look. PO187 EMR OF LARGE SESSILE COLORECTAL POLYPS: ARE COMPLICATIONS AND RECURRENCES RELATED TO THE TECHNIQUE? P. Familiaria , L. Petruzzielloa , M. Pandolfib , A. Gabbriellib , G. Speraa , A. Tringalia , C. Spadaa , G. Costamagnaa

a Digestive

Endoscopy Unit, Catholic University, Rome, Italy Campus Bio Medico, Rome, Italy

b Gastroenterology,

Background. Several techniques have been proposed for endoscopic mucosal resection (EMR) of large flat adenomas of the colon. Aims. To evaluate bleeding and recurrence rates after EMR of large sessile colonic adenomas as a function of different techniques. Methods. Sixty-five sessile colonic adenomas larger than 2 cm were treated by EMR in 57 patients. Mean larger diameter of the polyps was 28 mm (20–80 mm). Lesions were lifted with saline solution alone (n = 26) or saline solution plus epinephrine 1:10,000 (n = 39). En bloc EMR (n = 29) or piecemeal EMR (n = 36) were performed. APC was used when residual adenomatous tissue was recognised after EMR (n = 36). Endoscopic follow-up was performed at 3, 6 and 12 months.

Results. Procedural bleedings occurred in nine EMR (13.8%): 5/26 in the saline group and 4/39 in the epinephrine group (P = NS). They were all successfully treated by APC and/or clips application. All the resected specimens were retrieved for histological examination: 22 were adenomas with LGD, 26 with HGD/in-situ carcinoma, 14 were carcinomas infiltrating the upper third of the submucosa, 3 were infiltrating deep submucosa. Thirteen patients (15 polyps) eventually underwent surgery: none of these patients had lymph node metastases or residual adenoma at the site of polypectomy; five patients (five polyps) were lost to follow-up. Residual adenomatous tissue or recurrences were observed at the site of 13 EMR: 8/21 in the APC group and 5/24 in the non-APC group (P = NS), 5/20 in the en bloc and 8/25 in the piecemeal group (P = NS), respectively. All recurrences were endoscopically retreated (by APC or EMR) with complete eradication in 10 cases, while in 3 patients treatment is still going on. Conclusion. EMR for large colonic polyps is feasible and safe. Adrenaline injection did not significantly prevent bleeding; use of APC on residual adenoma and type of resection did not significantly influence the recurrence rate. The incidence of recurrence usually being high for these polyps, a close follow-up is required. Endoscopic retreatment of recurrences can to obtain the complete eradication of the lesion. PO188 SOCIAL AND PSYCHOLOGICAL FEATURES OF A COMPLIANT POPULATION TO A COLONOSCOPIC SCREENING PROGRAM R. Fasolia , S. Baronia , A. Piconea , C. Cuccob , S. Brunatia a Servizio

di Gastroenterologia ed Endoscopia Digestiva, Unità Operativa di Medicina, Ospedale Costantino Cantù. Abbiategrasso, Milan, Italy b General Practitioner, Comune di Arconate, Milan, Italy

Introduction. We have recently started a screening program in colo-rectal cancer prevention in a small (4500 inhabitants approximately) municipality in greater Milan western area. Patients and methods. All citizens born between 1928 and 1956 have been sent an invitation for a screening colonoscopy, with the exclusion of subjects with a relevant reduction of life expectancy and subjects who had undergone a total colonoscopy or a double contrast barium enema in the previous 5 years. Results. After 3 months, we have screened 118 subjects (mean age 60 years; 64 female; 54 male). Education level has been the following: primary graduation 58 subjects (49.2%); secondary graduation 34 (28.8%); high school graduation 23 (19.5%); university graduation 3 (2.5%). The main reason for adhesion to screening colonoscopy has been: fear of tumour in 24 cases (20.3%); relatives affected by colo-rectal adenomas or carcinomas 16 cases (13.6%); friends or acquaintances affected by the same conditions 3 cases (2.5%); sub-clinical symptoms 12 cases (10.2%); trust towards preventive programs 63 cases (53.4%). Fifty-six subjects (47.5%) declared to take part regularly in other screening programs (mainly breast cancer and/or cardiovascular disease). Thirty-eight out of 56 (67.9%) patients taking part in other screening programs admitted trust in prevention as the main reason to induce acceptance of screening colonoscopy. Conclusions. Although data are indeed preliminary, a dominant attitude in the compliant population in the studied community seems to be identifiable: subjects with low educational level (78% primary and secondary school) induced to be screened by a trust towards preventive medicine rather than by a worrisome personality or by stress due to relatives or acquaintances affected by malignant disease, enthusiastic as regards multiple screening programs (mainly breast cancer and cardiovascular disease).

Abstracts

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PO191

DISSOLUTION OF GASTRIC PHITOBEZOAR WITH COCA COLA

ENDOSCOPY ACTIVITY AND FINDINGS IN COLON–RECTAL CANCER SCREENING: RESULTS OF ONE YEAR USING BIANNUAL FOBT AND COLONOS- COPY

I. Febbraro, I. De Felici, M. Di Giovan Paolo, E. Mattei, G. Traversa, G. Occhigrossi

C. Ferraraa , E. Cervellina , R. Marina , L. Chinelloa , S. Milanib , G. Marina

U.O.C. Gastroenterologia ed Endoscopia Digestiva, Ospedale Sandro Pertini V. Dei Monti Tiburtini, 389 00158 Rome, Italy

a U.O.

The treatment of gastric phytobezoars includes dissolution with enzymes, endoscopy fragmentation and surgery. We report a case of gastric phytobezoar (5 cm) of diameter, in a man who was admitted to our observation with lower abdominal pain and vomiting. The patient was treated with a low diet and 1.5 l of coca cola once for 5 days. Finally, after 5 days, we have observed the complete dissolution of phytobezoar with endoscopy and radiologic examination. Conclusion. This non-invasive procedure is well tolerated, it has no related complication and the patient may be treated at home.

Colorectal cancer (CRC) screening campaigns represent an important undertaking for Digestive Endoscopy Unit. Colonoscopy is, in fact, the prime test for tumour prevention (diagnosis and removal of colon polyps). Material and methods. In our Local Health System, a CRC screening campaign began over a year ago using faecal occult blood test (FOBT) every 2 years and colonoscopy, when FOBT resulted positive, under anaesthesiologist assisted analgesia sedation. Results. In 1 year of activity (target population 22,330), adherence was 57%, with positive FOBT in 4.7% (579 subjects); 570 were considered eligible for colonoscopy and 550 subjects (96.5%) underwent the procedure. Exploration to the caecum was completed in 95.5%. In 266 (48.5%), colonoscopy was negative. In the remaining subjects, lesions detected were: polyps in 254 (46%) and neoplasia in 30 (5.5%). A total of 266 polypectomies were carried out immediately after identification. Histology showed: hyperplastic polyps in 29 cases (5%); adenomatous polyps in 227 (41%) of which 67 were of a low-risk histologic and morphologic nature (18 cases with more than two polyps); high-risk polyps in 154 (25 with severe dysplasia and 3 with carcinoma in situ); invasive adenocarcinoma in 6. Therefore, the total number of subjects with high-risk polyps was 172 (31%). In 36 cases, invasive neoplasia was diagnosed and surgical resection was performed. The pathologic TNM stage of the 33 noted cases was T1–3 N0 in 22 (66%), T4 N0 in 2, and T2–4 N1–2 in 9 cases (27%). The location of adenomatous polyps and malignant neoplasia was in 61% in the rectosigmoid segment and in 39% in the more proximal segments (descending 15%, transverse 12%, caecum ascending 12%). Secondary complications to colonoscopy (haemorrhage) were registered after polypectomy in three cases (0.5%), only one needed transfusion. Conclusions. The percentage of neoplastic lesions in the course of colonoscopy after FOBT for CRC screening was high and greater than that in routine endoscopic activity. The introduction of analgesia sedation was advantageous for the colonoscopic activity: (1) high adherence to colonoscopy (96.5%), higher than that reported in other national and international experiences; (2) greater effectiveness: 95% of the colonoscopies were carried out to the caecum and easier execution of polypectomy. Finally, the pathologic stage of the carcinomas diagnosed were less advanced than that expected in common endoscopic practice.

PO190 ARE HEPATOCELLULAR CARCINOMAS (HCC) NEUROENDOCRINE TUMOURS? L.M. Fenoglioa , C. Gaunab , E. Scalabrinoa , V. Benedettia , M. Bellòc , A. Ponzettod , P. Cavallo Perina , E. Ghigob , S. Grottolib a Division

of Internal Medicine, University of Turin, Italy of Endocrinology and Metabolism, University of Turin, Italy c Department of Nuclear Medicine, University of Turin, Italy d Department of Gastroenterology, University of Turin, Italy b Division

It is well known that HCC is one of the most common malignancies and that its prognosis is extremely poor. HCC are drug-resistant tumours. Clinical trials with chemotherapy did not demonstrate an increased survival in patients with advanced disease. Some authors reported that treatment with long-acting somatostatin analogues (SA), octreotide or lanreotide, improved overall survival in patients with advanced HCC. Moreover, evidences that SA suppress DNA synthesis, tumoural cells growth, inhibit angiogenesis, paracrine and systemic growth factors (IGF-I) secretion are reported. Scintigraphy with radiolabelled octreotide allowed evidence of in vivo presence of SS receptors in normal and in tumoural tissue. In HCC, in vitro and in vivo studies show somatostatin receptors expression. The aim of our study was to evaluate the endocrine features of HCC patients and define a possible, if any, role of SA in treatment of these neoplasms. In 30 HCC (19 male, 11 female, age 67.49 ± 1.37 years; HCV- and/or HBV-related cirrhosis (n = 27), alcohol-dependent cirrhosis (n = 2) and cryptogenic cirrohosis (n = 1); Child A (n = 15), B (n = 8) and C (n = 7)), we studied cromogranine A (CGA), neuron-specific enolase (NSE), IGF-I, IGFBP-3, DHEAS levels. In 23 subjects, scanning by means of 111 In-octreotide (OCT) was performed. Mean (±S.E.M.) alpha-fetoprotein (AFP) levels were 19,155.5±15,203.0 ng/ml, range 5.0– 435,284.0 ng/ml. CGA was increased in 17 (57%) while NSE in 3 (10%) patients. IGF-I levels (70.7 ± 5.3 ␮g/l, range 27–154 ␮g/l) and IGFBP-3 (1.56 ± 0.15 ␮g/l, 0.4–3.1 ␮g/l) were lower than in age-matched normal subjects. A negative correlation was demonstrated between IGF-I or IGFBP-3 and Child–Pugh score (r = −0.45 and −0.52, respectively, P < 0.05). DHEAS levels (44.0 ± 8.6 ␮g/dl, range 9.9–220 ␮g/dl) were reduced in comparison to age-matched controls. After 111 In-OCT administration, 23 patients (56%) displayed positive uptake at the site of hepatic or metastatic lesions. Our data demonstrate that HCC could show neuroendocrine differentiation and somatostatin receptors could be demonstrated in most of them. Somatostatin analogues could be suggested as adjuvant therapy in HCC that shows neuroendocrine features.

Medicina, Ospedale di Dolo (VE), ULSS 13, Italy Prevenzione, Ospedale di Dolo (VE), ULSS 13, Italy

b Dipartimento

PO192 INTESTINAL PERMEABILITY AND LIVER CIRRHOSIS R. Fiandraa , P. Espositoa , L. deMagistrisa , M. Bellettaa , M. Generosob , M. Cartenèb , R. Carratùa , C. Del Vecchio Blancoa , C. Loguercioa a Dip.

Medico-Chirurgico di Internistica Clinica E. Sperimentale “F. Magrassi E.A. Lanzara”, Italy b Dip. di Medicina Sperimentale, Seconda Università Degli Studi di Napoli, Naples, Italy

Intestinal permeability alterations (IP) were reported in liver cirrhosis (LC) patients, mainly in decompensated stage and in alcohol-related chronic liver disease. Previous studies were conducted, however, on few patients and the results were conflicting. Aim. The aim of this study was to investigate IP in liver cirrhosis and to correlate any IP alterations to the stage and the aetiology of the disease. Subjects. Twenty-nine consecutive outpatients with liver cirrhosis (males <22, females <11; median age <52 years, range 28–72 years), of whom 19 were HCV positive and 10 were alcoholics; 19 of these had a well-compensated liver disease and 10 had a decompensated liver disease.

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Among the 10 alcoholics, all in good compensation, 7 were abstainers and 3 alcohol users. Methods. IP was studied by the oral administration of a lactulose/mannitol test; the oral isosmolar load was made up with 2 g mannitol and 5 g lactulose. By means of HPLC-Dionex, the percentage of absorbed sugars in 5 h urine were determined and the LA/MA ratio calculated, which is an index of IP; normal values <0.028. Results. The number of patients with altered IP is reported in the two liver cirrhosis groups as well as in the subgroups of alcoholics with compensated LC. Compensated LC <2/19 (10.5%); alcoholics: abstainers 0/7, users 2/3; decompensated LC <10/10 (100%).

Results. Nineteen spots or spot series (encircled in the left-side figure) were significantly differently represented in 328 and 328Km (central figure) maps: 13 spots corresponding to full-length CagA and to truncated species of CagA were completely lacking in the cagA negative mutant, while 4 spots identified by mass spectrometry as isoforms of FlaA and 2 spots corresponding to isoforms of FlaB were significantly reduced. In addition, the cagA-negative mutant was not motile (right-side figure). Conclusions. The cagA gene may influence flagellar genes expression and bacterial motility. Although cagA-negative strains are motile, their milder virulence may be attributed to a different bacterial flagellin protein expression, which may cause a differential motility.

Conclusions. These data could indicate that both impaired liver function and persistent alcohol use are factors capable of affecting intestinal permeability.

PO194

PO193 DELETION OF H. pylori cagA GENE ALSO AFFECTS THE EXPRESSION OF FLAGELLAR PROTEINS FLA A AND FLA B AND BACTERIAL MOTILITY IN VITRO N. Figuraa , R. Minib , G. Bernardinib , P. Lusinib , A. Scalonic , F. Talamoc , L. Trabalzinizb , P. Martellib , A. Santuccib a Department

of Internal Medicine, University of Siena, Italy b Department of Molecular Biology, University of Siena, Italy c I.A.B.B.A.M. National Research Council, Naples, Italy

Background and aims. cagA-positive Helicobacter pylori strains are endowed with increased virulence. Our purpose was to determine whether the deletion of the cagA gene could have an effect on the expression of bacterial proteins other than CagA. Materials and methods. Strain 328 was cagA(+), B/D cagA subtype, vacA(+), s1/m1 subtype. Disruption of the cagA gene was obtained with kanamycin resistance cassette and electroporation-mediated allelic-exchange mutagenesis. The mutant strain was named 328Km. The protein repertoires of the two strains were examined by 2D-PAGE. Gels were stained with silver nitrate. The digitalised images, obtained by laser densitometer, were analysed qualitatively and quantitatively by the Melanie II 2D-PAGE software (Bio-Rad, Hercules, CA). The spot intensities were obtained in pixel and calculated as the ratio of spot intensity (percentage relative volumes) between the 328 and 328Km gel maps. CagA was identified on nitrocellulose replica of 2D gel by immunoblotting using an anti-CagA rabbit polyclonal serum. Immunodetection was revealed by enhanced chemiluminescence. Spots from 2D-PAGE were excised from the gel and proteins were in-gel reduced, S-alkylated and digested with trypsin. Protein digests were analysed with a Voyager DE-PRO MALDI-TOF spectrometer. ProteinProspector and PROWL software packages were used to identify spots. To assess motility, we used 0.3% agar motility test.

PREVALENCE OF CagA+ H. pylori INFECTION AND LEVELS OF ANTI-Hsp60 ANTIBODIES IN PATIENTS WITH ISCHAEMIC HEART DISEASE AND CONTROLS N. Figura, C. Lenzi, A. Palazzuoli, S. Kristodhullu, S. Campagna, F. De Regis, F. Borrello, B. Lucani, B. Franci, P. Nardi Dipartimento di Medicina Interna, Sci. End.-Metabol. e Biochimica, University of Siena, Italy Background and aims. Recent studies have suggested that individuals infected by Helicobacter pylori may run an increased risk of developing ischaemic heart disease (IHD). The presence of systemic antibodies to heat shock protein 60 (Hsp60) can be considered as a marker of enhanced cardiovascular risk, as well. We aimed to determine the prevalence of infection by overall H. pylori and CagA-positive (CagA+) H. pylori strains, and C. pneumoniae, E-B virus, herpes simplex virus and cytomegalovirus, and the levels of immunoglobulin G (IgG) to Hsp60, in 80 consecutive patients with IHD and 80 age-, gender and smoking habit-matched controls coming from the same socio-economic background. Methods. The infectious and CagA status were determined by ELISA. IgG to Hsp60 were measured by a sandwich ELISA developed in our lab; results were expressed in optical density. Statistics were performed by the χ2 -test and t-test for independent samples. Results. Almost all patients and controls were seropositive for pathogens other than H. pylori. The overall prevalence of H. pylori infection was 78.7% in patients and 76.2% in controls; 71.4% of infected patients were seropositive for CagA, versus 52.4% of infected controls (P = 0.030, OR 2.27; 95% CL 1.0–5.1). Levels of antibodies to Hsp60 in HP− patients were significantly higher than in HP− controls (341.5 (S.D. 159.6) versus 197.6 (S.D. 44.4); P < 0.001, 95% CL 66.4–221.3); those in CagA+ patients were higher than in CagA+ controls (P = 0.007, 95% CL 28.8–174.3), but were not significantly higher than in HP+/CagA− patients (P = 0.110) and in HP− patients (P = 0.072). Levels of antibodies to Hsp60 in CagA+ controls (317.2, S.D. 175.6) and HP+/CagA− controls (297.1, S.D. 80.82) were higher than in HP− controls (197.6, S.D. 44.42) (P = 0.006, and <0.001, respectively).

Abstracts Conclusions. CagA+ H. pylori infection increases the risk of IHD development. High levels of antibodies to Hsp60 were found to be associated with IHD, independently of H. pylori infection, which, however, was associated with increased levels of anti-Hsp60 IgG in controls. The latter observation suggests that a relation between chronic infections and development of antibodies to Hsp60 cannot be excluded. PO195 CagA+ H. pylori INFECTION INCREASES THE RISK OF OSTEOPOROSIS IN MEN AND IS ASSOCIATED WITH REDUCED SYSTEMIC LEVELS OF OESTROGEN IN PATIENTS N. Figura, L. Gennari, M. Campagna, C. Lenzi, B. Franci, B. Lucani, D. Merlotti, S. Kristodhullu, P. Nardi, De Regis, R. Nuti Dipartimento di Medicina Interna, Sci. End.-Metabol. e Biochimica, Università di Siena, Italy Background and aims. Helicobacter pylori infection, especially by CagA+ strains, may increase the systemic levels of inflammatory cytokines, such as TNFa, IL-6, etc. The same cytokines regulate the bone turnover and may influence the pathogenesis of skeleton disorders, such as osteoporosis. We aimed to investigate the possibility that this infection could increase the risk of osteoporosis in men and affect the bone metabolism in osteoporotic male patients. Patients and methods. We examined 80 patients and 160 age- and socio-economic class-matched male controls, for serum IgG to H. pylori and the CagA protein by an ELISA and determined, in patients alone, the most important biochemical and instrumental parameters of osteoporosis. Data were evaluated by chi-square test or the t-test for independent samples; results were presented as mean ± S.D.; P-values <0.05 were considered significant. Results. Fifty-one patients (63.7%) and 107 controls (66.8%) were seropositive for H. pylori infection (difference non-significant); 30 infected patients (58.8%) and 43 infected controls (40.1%) were positive for anti-CagA antibodies (P = 0.028; OR 2.13). Levels of estradiol in infected CagA-positive patients were significantly lower than in infected CagA-negative patients (28.5 pg/ml (S.D. 10.18 pg/ml) versus 39.5 pg/ml (S.D. 14.50 pg/ml), P = 0.002) and uninfected patients (35.2 pg/ml (S.D. 12.7 pg/ml)), P = 0.028). Levels of urinary cross-laps (a marker of bone resorption) were increased in patients infected by CagA positive strains, with respect to patients infected by CagA negative strains (282.9 mg/mmol (S.D. 103.8 mg/mmol) versus 210.5 mg/mmol (S.D. 150.1 mg/mmol), P = 0.048) and uninfected patients (204.3 mg/mmol (S.D. 130.1 mg/mmol), P = 0.016). Differences among uninfected and infected patients, independent of the CagA status, were observed for other markers of bone turnover, but they did not reach a statistical significance. Conclusions. The infection by CagA-positive H. pylori strains increases the risk of osteoporosis in men. The pathogenesis of osteoporosis, in males infected by CagA-positive H. pylori strains, may include reduced systemic levels of oestrogens, which may concur to determine an increased bone turnover. PO196 FIRST-LINE TREATMENT FOR Helicobacter pylori ERADICATION: LEVOFLOXACIN/AZITHROMY- CIN-BASED STRATEGIES L. Fini, E.C. Nista, M. Candelli, I.A. Cazzato, R. Finizio, A. Martino, F. Franceschi, L. Santarelli, M.A. Zocco, M. Gabrielli, G. Cammarota, G. Gasbarrini, A. Gasbarrini Departments of Internal Medicine, Catholic University, Rome, Italy Background and aim. In clinical practice, antibiotics resistance and patient compliance can affect the eradication rate of a 7 days standard anti-Helicobacter pylori treatment. Levofloxacin and azithromycin, broad

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spectrum antibiotics administrable in single daily dose, could increase patients compliance. The aim of this study is to compare the efficacy of a levofloxacin/azithromycin based H. pylori eradication regimen against standard 7-day triple therapy. Material and methods. Sixty H. pylori-positive patients (infection was assessed by histology and 13 C UBT) were randomised to receive for 7 days: group A (30 patients), levofloxacin (500 mg od), azithromycin (500 mg od) and esomeprazole (20 mg bid); group B (30 patients), clarythromycin (500 mg bid), amoxicillin (1 g bid) and esomeprazole (20 mg bid). H. pylori status was re-checked by 13 C UBT 6 weeks after the end of therapies. Results. H. pylori eradication rate in group A was 93.3% (28/30 patients), in group B was 70% (21/30) in either ITT or PP analysis. Eradication rate of 1 week levofloxacin/azithromycin-based triple therapy was significantly higher than that observed using standard triple therapy (93.3% versus 70%, P < 0.05). Minor side-effects were present in all groups. Conclusions. According to the present data, a 7-day levofloxacin/azithromycin-based triple therapy may be considered a new and highly effective therapy for H. pylori eradication. PO197 10 DAYS LEVOFLOXACIN-BASED TRIPLE THERAPY IN SECOND-LINE TREATMENT FOR Helico- bacter pylori ERADICATION L. Fini, E.C. Nista, M. Candelli, I.A. Cazzato, R. Finizio, G. Pignataro, L. Santarelli, A. Martino, M. Gabrielli, G. Cammarota, G. Gasbarrini, A. Gasbarrini Department of Internal Medicine, Catholic University, Rome, Italy Background and aim. Complexity and compliance are the limits of second-line treatment for Helicobacter pylori infection. The aim of this study was to compare efficacy and tolerability of a 10-day levofloxacin/azithromycin with a levofloxacin/amoxicillin-based therapy and a 7-day quadruple therapy in second-line treatment. Material and methods. Ninety-five consecutive patients (42 males, 18– 65 years) who had failed standard triple therapy (clarithromycin 500 mg bid, amoxycillin 1 g bid, esomeprazole 20 mg bid) were randomised to receive: levofloxacin 500 mg od, esomeprazole 40 mg od and amoxycillin 1 g bid (group A: 30 patients) for 10 days (4 pills per day); levofloxacin 500 mg od, esomeprazole 40 mg and azitromycin 500 mg od (group B: 30 patients, 3 pills per day); tetracycline 500 mg qid, metronidazole 500 mg tid, rabeprazole 20 mg bid and bismuth salt 120 mg qid (group C: 35 patients) for 7 days (13 pills per day). H. pylori status was re-checked by 13C-UBT 6 weeks after the end of the treatment. A questionnaire on side-effects and overall assessment of treatment tolerability was administered to patients. Results. Ninety-one patients completed the efficacy analysis per protocol; four drop outs occurred in group C due to side-effects. Eradication rate in group A was 86.6% (26/30 patients) and in group B was 80% (24/30 patients) in either ITT and PP analysis. In group C, H. pylori eradication was achieved in 71.4% (25/35) and 80.6% (25/31) patients in ITT and PP analyses. Eradication rate of levofloxacin-based therapy was higher, even if not statistically significant, than that observed using quadruple therapy in either ITT (86.6% versus 71.4%, and 80% versus 71.4%; P = NS) or PP (86.6% versus 80.6%, and 80% versus 80.6%; P = NS) analysis. The commonest side-effect (diarrhoea, dysgeusia, nausea) were significantly lower in group A (8/30; 26.6%) and B (7/30; 23.3%) than in group C (21/30; 60%) (A versus C P < 0.01; B versus C P < 0.005). Conclusions. Two levofloxacin-based triple therapy showed similar eradication rates than quadruple second-line treatment. However, levofloxacin-based treatment appears to be simpler and provides a better patient compliance.

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PO198 SINGLE NUCLEOTIDE POLYMORPHISMS IN THE HUMAN OESTROGEN RECEPTOR GENES AND OSTEOPOROSIS SUSCEPTIBILITY IN PRIMARY BILIARY CIRRHOSIS (PBC) A. Floreania , F. Ferraraa , A.M. Tommasia , G. Luisettob , V. Camozzib , M.L. Brandic a Department

of Surgical and Gastroenterological Sciences, University of Padua, Padua, Italy b Department of Medical and Surgical Sciences, University of Padua, Padua, Italy c Department of Internal Medicine, University of Florence, Italy

Background. Osteoporosis is a common complication of PBC. As mediators of oestrogen hormone action, the genes encoding estrogens (ERs) have been considered as candidates for the determination of osteoporotic risk. Moreover, an altered metabolism of ERs has been observed in PBC. Aims. To evaluate whether ER alpha and ER beta polymorphisms are correlated with the reduced bone mass in either PBC and in osteoporotic female subjects. Methods. Seventy-three female PBC patients (mean age 60 ± 12 years) were evaluated; 80 sex- and age-matched controls from the same geographical area, and 41 female with osteoporosis (t-score <2.5 S.D.) were chosen as controls. Restriction fragment polymorphisms of ER alpha (PvuII, XbaI) and ER beta (AluI) were determined in each subject by standard PCR, and detection with agarose gel electrophoresis. Clinical information, bone mineral density assessment, disease severity, and osteoporosis risk factors were documented, and multivariate regression analysis was performed. Results. No different distribution of ER alpha and ER beta polymorphisms was found in the three groups of subjects, except ER beta AluI wild-type homozygosity which was significantly higher in PBC compared with healthy controls (P < 0.026). The multivariate regression analysis failed to find any correlation between ERs polymorphisms and osteoporosis. However, the reduced bone mass in PBC was significantly correlated with the histological stage (P < 0.05). Conclusions. Osteoporosis is a multifactorial condition, significantly correlated with disease progression in PBC. The contribution of the ERs genetic polymorphism to the osteoporosis has not been confirmed. PO199 PROTON-PUMP INHIBITOR (PPI) AND ACUTE PEPTIC ULCER BLEEDING: EFFECTIVENESS OF ORAL ESOMEPRAZOLE VS. INTRAVENOUS OMEPRAZOLE IN REDUCING THE RISK OF RECURRENT BLEEDING R. Focareta, A. Ciarleglio, G. Piai, F. Ievoli, G. Forte UOC Gastroenterologia, AORN San Sebastiano, Caserta, Italy Background and aim. Endoscopic therapy is a safe and effective method of treating acute ulcer bleeding. However, failure of therapy, in terms of rebleeding, is seen in 15–20% of patients. The use of intravenous high dose of a PPI has been shown to reduce frequency of rebleeding after endoscopic treatment. We have compared this therapy with a cheaper and easier oral administration of a new powerful PPI. Material and methods. A prospective randomised controlled trial has been conducted in patients referring to our unit for non-variceal upper gastrointestinal bleeding between January and September 2003, and showing high risk of rebleeding endoscopic stigmata (HRS) (Forrest Ia, Ib, IIa, IIb). All patients were treated with 1/10,000 adrenaline injection, haemoclips or combined methods. After endoscopic therapy they were randomly assigned to receive either intravenous omeprazole as a 80 mg bolus, followed by 40 mg three times daily for 72 h, or esomeprazole 40 mg orally two times daily for 72 h. After this period, all patients were given, respectively, 20 mg of omeprazole or 40 mg of esomeprazole orally per day for 4 weeks. Outcome measures were recurrent bleeding and need of surgery.

Results. We enrolled consecutively 87 patients, 42 in the omeprazole intravenous group and 45 in the esomeprazole oral group. The two groups were homogeneous in regard to age, sex and HRS distribution (overall: 13 Forrest Ia, 17 Forrest Ib, 24 Forrest IIa, and 33 Forrest IIb). Seven second endoscopic treatments were necessary during the hospitalisation (three in the omeprazole group and four in the esomeprazole group). No patient underwent surgery. Conclusions. Our study confirms that after endoscopic treatment of bleeding peptic ulcer, a high dose of PPI reduces risk of recurrent bleeding, need for surgery and mortality. The oral administration of esomeprazole is as effective and safe as the intravenous omeprazole with a more simple way of administration and a lower drug cost. PO200 CIRCULATING CRYOGLOBULINS CHRONIC HEPATITIS C

AND

OUTCOME

OF

C. Folli, M. Viganò, L. Maggioni, E. Del Ninno, M. Colombo, M. Cicardi Department of Internal Medicine, IRCCS Ospedale Maggiore di Milano, Milan, Italy Background and aim. The association between chronic hepatitis C and the presence of serum cryoglobulins (CG) is well established, but their clinical importance in the course of the disease is poorly known. We tested a cohort of chronic hepatitis C patients for the presence of CG and studied the long-term outcome of the disease comparing CG-positive and -negative patients. Patients and methods. Three hundred and forty-five patients (175 men, median age 56 years) consecutively seen at our Liver Unit with diagnosis of chronic hepatitis C were enrolled in the study. Two hundred and thirty-six (76%) had chronic hepatitis, 76 had cirrhosis, 33 did not have an available liver biopsy. Follow-up was of 83 months (range 17–101 months). End-points of this study were the development of hepatocellular carcinoma (HCC), lymphoma, extrahepatic tumour, death or liver transplantation (OLT), liver decompensation, IFN treatment and response. The presence of CG was determined after cryoprecipitation and the amount of the cryoprecipitate was measured spectrophotometrically. Results. In 165 patients (48%), CG were present (mean level 181 + 182 mg/l), predominantly of type III (85%). CG were more common in women than in men (58% versus 37% P = 0.0001), in cirrhotic than in chronic hepatitis patients (59% versus 34%, P = 0.00001) and in patients with genotype non-1 than in patients with genotype 1 (61% versus 50%, P < 0.05). The presence of CG did not correlate with liver function tests. During the follow-up period, 57 patients underwent treatment with IFN or IFN + RIBA, with 13/30 responders in CG negative patients and 16/27 responders in CG positives (P = N.S.). HCC developed in 14 CG negative and in 17 CG positive patients (8% versus 10%, P = N.S.); liver decompensation occurred in six CG-positive and in seven CG-negative patients. Prevalence of HCC and liver decompensation was not different in type III and II CG positive patients. The number of patients who died for hepatic or extrahepatic causes or who underwent OLT was not significantly different between CG positive and negative patients (17 versus 11; 4 versus 4; 3 versus 1, respectively). Conclusions. In HCV+ patients, presence of CG is more frequent in women, in cirrhotic patients and in patients with genotype non-1. The presence of CG has no effect on the long-term outcome of HCV related liver disease. PO201 GASTRIC CARCINOID: ENDOSCOPIC TREATMENT WITH ARGON PLASMA C. Fonderico, G. Capece, P. Cocchia ASL NA1, “S.G. Bosco” Hospital Service of Gastroenterology, Italy

Abstracts Background. Carcinoid is the most common neuroendocrin gastro-intestinal tumour. It manifests sporadic use, rarely associated at MEN syndrome. This neuroendocrine tumour exhibits various symtomatologies. Gastric carcinoid is very rare in our region and is localised frequently at gastric mucous of body and foundues. Methods. We report a clinical case of a young women (43 years old) admitted in the hospital for a serious anaemia (Hb 4 g/dl) in November 2001 without any other symtomatologies. An upper endoscopy demonstrated very little multiple red polypoid masses at gastric mucous of body and foundues of stomach. Biopsy revealed carcinoid tumour in a background of atrophic gastritis and area of intestinal metaplasia in fondues of stomach. The diagnosis was confirmed at immune-istochimical with chromogranin-a and NSE. Urinary 5-hydroxyindolacetic acid was more than normal (1250 mg/24 h). Results. A coagulation of the polypoids lesion with electrobistury argon plasma was done during the other three EGDS. After this treatment, the patient is in good condition with normal value of haemoglobin and urinary 5-hydroxyndolacetic acid. Now, she is in follow-up. Conclusions. It is possible, in patients with very little carcinoid lesions of gastric mucous, a complete devitalisation of these lesions with argon plasma electrocoagulation. PO202 BODY COMPOSITION AND INSULIN RESISTANCE IN NORMAL AND OVERWEIGHT PATIENTS WITH NON-ALCOHOLIC STEATO-HEPATITIS A. Forgione, E. Capristo, L. Miele, M.L. Gabrieli, V. Vero, D. Iemma, G. Mingrone, G. Gasbarrini, A. Grieco Institute of Internal Medicine, Catholic University, Rome, Italy Background and aim. Metabolic alterations are common in patients with non-alcoholic steato-hepatitis (NASH). Dietary treatment represents a key point in the therapeutical approach to these patients. Leptin, a hormone secreted by the adipocytes, is involved in body weight haemostasis and in regulation of matrix deposition during wound healing. Increased circulating leptin was reported in NASH, although the relationship with the progression of liver damage and hyperinsulinaemia is still controversial. The aim of the present study was to evaluate serum leptin, body composition and insulin resistance in NASH patients with different body weight. Materials and methods. Twenty-five male outpatients with proven histological NASH (age: 43 ± 12 years; BMI: 27.2 ± 3.5 kg/m2 ) and 28 healthy overweight male subjects (age: 39 ± 10 years; BMI: 26.8 ± 2.8) were enrolled in this study. All the patients, of the two groups, were divided in two subgroups according to body mass index (BMI, kg/m2 ) (BMI ≤26; BMI >26). Body composition was assessed by dual-energy X-ray absorptiometry; nutrient oxidation by indirect calorimetry. Serum leptin and fasting insulin concentration were assessed by ELISA. Insulin resistance was measured using the haemostasis model assessment of insulin resistance index. (HOMA-IR). Results. According to our BMI classification, NASH patients showed increased total body fat and waist circumference when compared to control group (P < 0.05 and P < 0.01). NASH patients had higher insulin (17.6 ± 8.4 ␮UI/ml versus 8.2 ± 2.3 ␮UI/ml; P < 0.01) and leptin level (10.4 ± 5.3 ng/ml versus 7.1 ± 2.2 ng/ml; P < 0.01) than controls. HOMA-IR index (units) was significantly higher in overweight than in normal weight NASH patients (4.23 ± 0.72 versus 2.95 ± 1.34; P < 0.01), and higher in NASH patients compared to BMI-matched controls. In NASH patients, a positive relation was found between body fat, leptin and HOMA-IR (R2 = 0.76, P < 0.001 and R2 = 0.62, P < 0.001, respectively). Conclusions. Our results evidenced an increased total body fat, higher leptin and insulin level, and insulin resistance in NASH patients when compared to BMI-matched controls. Insulin resistance in NASH was strictly correlated to BMI. These results seems to indicate that maintenance

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of a normal body weight could prevent the risk of developing metabolic alterations in NASH. PO203 ELIGIBILITY FOR THERAPY AMONG CHRONIC HCV-INFECTED PATIENTS IN A PRIMARY REFERRAL CENTRE L. Framarin, G. Tappero, M. Ayoubi, E. Solerio, F. Rosina Division of Gastroenterology and Hepatology, Presidio Sanitario Gradenigo, Turin, Italy Background. Combination therapy with alpha-interferon (alpha-IFN) and ribavirin (RBV) and now with pegylated IFN + RBV has substantially improved the response rates for patients with chronic hepatitis C. Unfortunately, current treatment strategies still carry significant constitutional and psychiatric side-effects. Due to these and other issues, many patients are currently not eligible for treatment. Aim. To assess the eligibility rate for therapy and reasons for non-treatment in a cohort of anti-HCV positive patients consecutively referred to our primary Gastroenterology and Hepatology Unit. Methods. From January 1998 to September 2003, 343 consecutive anti-HCV patients referred to our Unit. At referral, complete history was taken, as well as physical examination, biochemical and qualitative HCV-RNA assessment. Patients without indication to treatment (absence of circulating HCV-RNA, persistently normal ALT levels (PNAL)) decompensated cirrhosis and HCC were not included in the study. The remaining patients with chronic hepatitis C were considered ineligible for therapy if were >65 years old, had medical contraindications (severe untreated depression, concomitant autoimmune diseases, decompensated diabetes and severe cardiac or pulmonary insufficiency), ongoing history of alcohol and/or substance abuse, non-adherence of office appointments, and personal preference. Results. Eighty-nine out of the 343 patients had no indications for therapy (25.9%) (undetectable HCV/RNA 16/89 (18%), PNAL 31/89 (35%), decompensated cirrhosis 28/89 (31%) and HCC 14/89 (15%)). Of the remaining 254 patients with chronic hepatitis, 167 (65.7%) were not treated for the following reasons: age >65 years 94/167 (56%), medical contraindications 13/167 (8%), patient preference 15/167 (9%), non-adherence of office appointment 40/167 (24%) and substance abuse 5/167 (3%). Only 87 patients (34.2%) with chronic hepatitis were treated. Conclusions. At the primary level of referral, only a minority of chronic hepatitis C patients are actually eligible for therapy. PO204 GENE-EXPRESSION PROFILE OF COLORECTAL ADENOCARCINOMA TISSUE IDENTIFIED BY GENE MICROARRAY ANALYSIS F. Franceschi, L. Fini, A. Manno, E. Carloni, M.A. Zocco, S. Di Caro, D. Leo, E.C. Nista, I.A. Cazzato, N. Gentiloni Silveri, A. Picciocchi, C. Coco, G. Gasbarrini, A. Gasbarrini Department of Surgical Sciences, UCSC Microarray Core-Lab, Catholic University of Rome, Italy Background. Several genes have been found to be differentially expressed during the multistep process of colorectal carcinogenesis. Aim. To identify the genes expression pattern of colorectal adenocarcinoma tissue samples were compared to the normal mucosa of the same patients. Methods. Total RNA was extracted from three samples of moderately differentiated sporadic rectal adenocarcinoma and three samples of normal rectal mucosa obtained from the same patients and hybridised against the human U133A array set (Affymetrix Inc., USA). Genes expression of tumoural tissues and normal samples has been compared. To validate the results, real-time PCR (Roche, Mannheim) using the same RNA

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has also been performed on a pool of either up- or down-regulated randomly-selected genes. Results. Five hundred and thirty-seven and 13 genes were up- and downregulated (more than 3-fold), respectively, in neoplastic tissues in respect with the normal tissue samples. Among the up-regulated genes: several angiogenic factors (VEGF, PD-ECGF, EGF), markers of proliferation (PCNA), tumoural markers (CEA, ACE), genes involved in chemotherapy activity (farnesyl-transferase, topoisomerase-1) and several other genes of unclear function. The down-regulated genes included: transcription factors (SPIB), adhesion molecules (Desmin), anti-oxidant (GPX3) and other genes of unclear activity. RT-PCR confirmed the results of the microarray analysis. Conclusions. Colorectal cancer tissues show a different gene expression compared to the normal mucosa. The modified genes are several known genes involved in cell growth, angiogenesis, transcription and proliferation as well as other genes of unclear activity, which have never previously been associated with cancer. The identification of a panel of genes specifically expressed in neoplastic tissues may provide a new tool for the molecular diagnosis of colorectal cancer and provide new molecular targets for innovative therapeutical strategies. PO205 WHAT DOES “INDEFINITE FOR GASTRIC DYSP- LASIA” MEAN? M. Franco, C. Tieppo, M. Rugge, F. Greco, E. Georgopoulou, F. Farinati Department of Surgical and Gastroenterological Sciences, Section of Gastroenterology, Padua University, Padua, Italy According to standardised histologic criteria, the lesions in which a clear-cut diagnosis of dysplasia cannot be drawn but that are suspicious for dysplastic changes are identified as “indefinite for dysplasia”. However, the lesion is not clinically and pathologically well-defined. The aim of this study was to evaluate the association of these lesions with clinical, endoscopic and histological parameters also in relation with the possible evolution from “indefinite” to dysplasia. Materials and methods. We have considered all patients who underwent an upper GI endoscopy in our centre from 1999 to 2003 and with a histological finding of indefinite for dysplasia as the first diagnosis. Thirty-eight patients with “indefinite for dysplasia” were identified and compared with 4 patients with indefinite for dysplasia that evolved into clear-cut dysplasia and 74 in whom dysplasia was the first histologic finding. We considered patients’ age (<40, 40–65 or >65 years), gender, Helicobacter pylori positivity and density, gastritis, disease activity (PMN cells infiltrate), atrophic or metaplastic changes score (o to +++) and distribution (antrum, body). Results. We found no significant difference in the patients’ gender, positivity and density of H. pylori and histological gastritis and activity score among the three subgroups. Statistically significant differences were observed in age (P = 0.003), with an older age in patients with dysplasia. Patients with dysplasia presented more frequently high grade multifocal intestinal metaplasia (P = 0.03) and a trend towards more frequent high grade atrophic changes. Conclusions. Patients with “indefinite for dysplasia”, in comparison with those affected by clear-cut dysplastic changes are relatively younger and present less frequently high grade multifocal metaplastic (and atrophic) gastric mucosal changes. This indicates a strong association of dysplasia with other precancerous lesions, that constitute the scenario in which dysplasia develops. Although only a low percentage of patients with “indefinite for dysplasia” evolve into dysplasia during the follow-up, this risk is by no means negligible and the patients with this finding are to be followed until a definition of the situation is reached and eradicated in the case of H. pylori positivity.

PO206 PREVALENCE OF H. pylori cagA+ IN SUBURBAN AREA WITH HIGH INCIDENCE OF GASTRIC CANCER A. Franzéa , G. Comparatob , A.M. Moussab , G. Nervib , V. De Lisic , C. Carlonib , S. Liatopouloub , G. Di Colad , F. Fontanad , G. Aragonab , L.G. Cavallarob , G.M. Cavestrob , V. Iorib , M. Mainob , F. Marcuccib , F. Di Mariob a Gastroenterology

Unit, University of Parma, Parma, Italy of Clinical Sciences, University of Parma, Parma, Italy c Oncology Unit, University of Parma, Parma, Italy d Bio-Tech Laboratory, Parma, Italy b Department

Background. Epidemiological studies have shown that Helicobacter pylori infection is associated closely with the development of gastric cancer. Several studies have suggested a higher risk of gastric carcinoma associated with H. pylori strains possessing the cytotoxin-associated gene (cagA). Yet, only a minority of subjects infected will develop cancer. Other environmental factors such as diet, host immune response, genetics must be important in determining cancer occurrence. Aim. To evaluate the prevalence of H. pylori cagA+ infection in suburban area with high prevalence of gastric cancer (Langhirano, Parma, Italy). Materials and methods. A total of 3116 inhabitants of Langhirano have been invited to evaluate the status of H. pylori cagA+ infection, from 1998 to 2000; 2011 subjects (914 male, 1097 female; mean age 51 years, range 20–77 years) accepted to submit for the test. In all subjects, stool specimen were collected and tested for cagA gene by means of polymerase chain reaction (PCR). The cagA+ subjects have been subdivided for age bands and confront with the incidence data of gastric cancer reported on the Cancer Registries in such zone. All subjects were divided into two groups according to age, with a cut off of 50 years. Results. Four hundred and sixty-nine out of the 2117 (215 male, 254 female) subjects were resulted positive for cagA: (232 (49.5%) <50, range 20–49; 237 (50.5%) >50, range 51–77) without statistically significant difference. Idem for the prevalence of H. pylori cagA+ according to age band. Conclusion. In our population, the prevalence of H. pylori cagA+ is not associated with the increase of age and there is no relationship between the prevalence of H. pylori cagA+ and the incidence of gastric cancer. PO207 PREVALENCE OF COLORECTALCARCINOMA IN A HIGH-RISK AREA OF NORTH ITALY A. Franzèa,b,c,d , V. De Lisia,b,c,d , V. Ioria,b,c,d , G. Di Colaa,b,c,d , A. Gnocchia,b,c,d , G. Aragonaa,b,c,d , L.G. Cavallaroa,b,c,d , M. Ali Moussaa,b,c,d , C. Missorinia,b,c,d , G. Collaa,b,c,d , F. Di Marioa,b,c,d a Gastroenterology

Unit, University of Parma, Parma, Italy Unit, University of Parma, Parma, Italy c Department of Clinical Sciences, University of Parma, Parma, Italy c Bio-Tech Laboratory, Parma, Italy d General Practitioner, Italy b Oncology

Background. Colorectal carcinoma (CRC) is a leading cause of cancer mortality. By screening asymptomatic, average-risk individuals, curable carcinomas and removable polyps can be detected to interrupt the natural history of the disease or the increased chance of curing it. Aim of the study. To evaluate incidence of CRC in a suburban area (Langhirano, Parma, Italy), and to evaluate reduction of incidence and mortality after 10 years. Material and methods. We screened 2582 (male/female 1:1, age range 45–75 years) for CRC by means of faecal occult blood test (FOBT). Colonoscopy was offered if the test was positive. Results. Fifty-eight (2.2%) subjects resulted positive for FOBT, and 10 of them presented CRC at colonoscopy, and 12 adenomatous lesions. CRC was classified according to Duke classification (Dukes A: five

Abstracts patients, Dukes B: four patients, Dukes C: one patient). We observed a significant reduction of mortality for CRC after 10 years from the screening, compared to mortality rates for CRC reported on the cancer registry (1989–1999) in urban area (Parma) as shown in Fig. 1. Conclusion. Death from CRC could be preventable. An effective and safe method for screening people older than 45 years led to a detectable reduction of mortality for CRC in a suburban area of north Italy. PO208 LONG-TERM FOLLOW-UP OF ACUTE RECURRENT PANCREATITIS L. Frulloni, B. Ferri, A. Katsotourchi, L. Bernardoni, E. Coato, K. Faitini, S. Biasin, F. Patrizi, P. Bovo, B. Vaona, G. Cavallini Department of Surgical and Gastroenterological Sciences, University of Verona, Italy Background. There are many evidences that acute pancreatitis (AP) may recur and evolve in chronic pancreatitis, particularly in patients with CFTR gene mutations. Few data are reported about the natural history of patients suffering from recurrent pancreatitis. The aim of this study was to evaluate the potential evolution to chronic pancreatitis of patients suffering from recurrent pancreatitis. Patients and methods. Patients who had suffered from at least two documented episodes of AP before the admission to our hospital between the period from January 1997 to December 2002 entered in the study. We enrolled 106 patients (52 males, 54 females, mean age 39 ± 14.8 years at the onset of AP) and 89 out of 106 patients were still in the follow-up in 2003 (mean follow-up time from the onset of AP: 8.3 ± 5.5 years). Seven patients (7%) drank more than 80 g of alcohol per day, 41 (42%) were smokers. The aetiological factors were: biliary lithiasis in 72/106 patients, SOD (stenosis) in 52/106, CFTR gene mutations in 9/73, pancreatic cancer in 10/106, autoimmunity in 7/106, other in 3/106, whereas 9 patients (10%) were idiopathic. Pancreas divisum was documented in 24 patients (23%). Results. We observed 568 episodes of AP (0.86 ± 0.64 episodes per year). Necrosis of the pancreatic gland was documented in 14 patients (at the first episode in 13). During the follow-up, the diagnosis of CP was made on the basis of instrumental finding in 23 patients (22%): we found calcifications in 3 patients (3%), diabetes in 8 (8%), steatorrhoea in 3 (3%), whereas 8 patients (8%) underwent pancreatic surgery for CP. In these 23 patients, the mean time to the second episode of AP was 1.6 years, to the diagnosis of CP 5 more years, and to the onset of calcifications 2 more years. Alcohol and smoking habits did not favour the evolution of pancreatitis, whereas a previous episode of necrotising pancreatitis and the presence of CFTR gene mutations were risk factors for CP. The mean follow-up time was longer in patients with a final diagnosis of CP that in those with ARP (10.2 ± 4.8 versus 7.8 ± 5.2 years; P = 0.044). Conclusions. AP may evolve in ARP and CP. Pancreatic necrosis and CFTR gene mutations are risk factors for this possible evolution. PO209 EFFICACY OF MAIN PANCREATIC DUCT (MPD) ENDOSCOPIC DRAINAGE IN PATIENTS WITH CHRONIC PANCREATITIS (CP), CONTINUOUS PAIN (CoP) AND DILATED MPD DUCT A. Gabbriellib , M. Pandolfib , M. Mutignania , G. Costamagnaa a Unità

di Endoscopia Operativa Chirurgica, Università Cattolica del Sacro Cuore, Rome, Italy b Dipartimento delle Malattie dell’Apparato Digerente, Università Campus Bio Medico, Rome, Italy Background. MPD obstruction is a cause of pain in patients with CP. Detension and clearance of MPD from pancreatic stones are the mainstay of endotherapy. Most of the patients with CP suffer from relapsing pain making it difficult to evaluate the efficacy of endotherapy.

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Aim. To evaluate the efficacy of pancreatic duct drainage on pain relief in patients with CP, dilated MPD duct and CoP. Patients and methods. Twenty-six patients out of 343 (7.5%) with CP treated endoscopically in a 15 years period presented with CoP (at least 5 days a week for more than 1 month). Four patients with biliary strictures and/or pseudocysts were excluded from the study. Twenty-two patients (6.4%) (19 males, mean age 48 years, range 20–74 years, 14 alcoholics) presented with CoP and dilated MPD. All patients had morphologically severe forms of CP. Twenty-one patients (95.4%) were receiving continuous analgesics (NSAID: nine patients; narcotics: five patients; NSAID+ narcotics: seven patients). Twenty-two pancreatic and 19 biliary sphincterotomies were performed along with 14 ESWL and 10 pancreatic stent placements. Results. There was no mortality; one bleeding from pancreatic sphincterotomy and one from the pancreatic duct after ESWL were recorded. Both were successfully treated by conservative therapy. Adequate drainage and clearance of MPD was obtained in all patients. Mean diameter of MPD decreased from 10.8 mm (7–23 mm) to 6.5 mm (3–9 mm) after endoscopic treatment. Pain disappeared and analgesics could be discontinued in all patients immediately after endotherapy. Follow-up. One patient died of myocardial infarction after 41 months without pain relapse; six patients are lost; four patients eventually underwent surgery. Mean follow-up of the remaining 11 patients is 6 years (1– 15 years). Six patients are pain free since the first treatment after a mean follow-up of 5.5 years (1–13.5 years). Ten pain relapses were recorded in five patients (MPD “de novo” stricture: three, pancreatic stent obstruction: three, dislodgement: four). Endoscopic retreatment was successful in all cases. Conclusions. Drainage of MPD is a very effective treatment in patients with CP, MPD dilation and CoP. Ductal hypertension should be regarded as the principal cause of symptoms in these patients. PO210 GATEKEEPER (tm) REFLUX REPAIR SYSTEM. RESULTS OF TWO YEARS FOLLOW-UP A. Gabbriellia , L. Cipollonia , M. Pandolfia , S. Emerenziania , M. Cicalaa , G. Costamagnab a Dipartimento

Malattie Apparato Digerente, Università Campus Bio Medico, Rome, Italy b Unità di Endoscopia Operativa Chirurgica, Università Cattolica del Sacro Cuore, Rome, Italy

Background. Endoscopic treatment is an alternative option to medical treatment in the management of patients with gastro-oesophageal reflux disease (GERD). Gatekeeper (tm) system (Medtronic Inc., MN, USA) consists of a new endoscopic device that allows the insertion of expandable polyacrylonitrile-based hydrogel prostheses in the oesophageal submucosa in the region of the lower oesophageal sphincter, utilising a 16 mm overtube. Short-term follow-up showed good results with 70% of patients off PPIs after 6 months. Aim. To report clinical results in patients with a mean follow-up of 2 years. Inclusion criteria: patients >18 years, documented symptoms of GERD (heartburn, regurgitation) (pH metry; total pH <4: >4%), no endoscopic oesophagitis or Savary oesophagitis grade I or II, hiatal hernia <2 cm, symptomatic improvement on proton pump inhibitors (PPI) and relapsing symptoms after discontinuation. Methods. Thirteen patients (six males, mean age 46 years, range 19–67 years) (Savary grade I: one patient; grade II: five patients) were treated with submucosal insertion of four prostheses in the same session. Results. There were no morbidity and mortality related to the procedure. Two patients were retreated because of symptoms relapse and prostheses migration after 1 and 2 months, respectively. After 6 months, 10/13 patients were off PPIs and 65% of prostheses were still in place. There were no statistical differences in mean LES pressure and %pH <4 before and 6 months after the treatment. However, a reduced proximal spread of

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acid reflux was demonstrated. GERD-HRQL symptom scores improved after 6 months from 38.9 (13–67) to 10.9 (0–35) (P < 0.002). One patient had a Nissen fundoplication for symptoms relapse after 19 months. Mean follow-up of the remaining 12 patients is 24 months (range 13–32 months). Medication use: no therapy 6/13 (46.1%), on demand antacid therapy (less than 5 days a month) 4/13 (30.7%), full dose PPIs 2/13 (15.4%). Conclusions. Gatekeeper system is a safe procedure in patients with GERD. In a medium-term follow-up, it is associated with reduced symptoms and medication use. PO211 PRIMARY AUTOIMMUNE HAEMOLYTIC ANAEMIA AND COELIAC DISEASE M. Gabriellia , M. Candellib , F. Franceschib , L. Santarellib , A. Villitaa , G. Gasbarrinib , P. Polaa , A. Gasbarrinia

(mono-prophylaxis with HBIG or HBIG–LAM in combined) were used. HBV-DNA viral load (COBAS, Roche) at the time of LT was available in 177 patients. Results. Overall HBV recurrence: cumulative rate 7%; 5 and 8 years actuarial rate: 8 and 21%. HBV recurred in 10 and 70%, respectively, of patients transplanted with HBV-DNA higher or lower then 100,000 copies/ml (log-rank calculation, P = 0.0002). Risk of hepatitis B recurrence and HBV-DNA viral load at the time of LT in 177 patients: • low risk: 79 patients with HBV-DNA negative by PCR (spontaneous or antiviral induced pre-LT) had no HBV recurrence with mono or combined prophylaxis after LT. • intermediate risk: 80 patients with HBV-DNA between 200 and 100,000 copies/ml had the HBV recurrence in 0 and 20%, with combined or mono-prophylaxis. • high risk: 18 patients with a viral load >100,000 copies/ml had the HBV recurrence in up to 70%, with mono-prophylaxis.

a Department

of Internal Medicine and Angiology, Catholic University the Sacred Heart, Rome, Italy b Department of Internal Medicine and Gastroenterology, Catholic University the Sacred Heart, Rome, Italy

Background and aim. A close association between coeliac disease (CD) and autoimmune disorders has been recently showed. Cases were described of patients developing autoimmune haemolytic anaemia (AIHA) in association to their CD. The aim of the present study was to assess the prevalence of CD in patients with primary AIHA and in a population of healthy controls. Materials and methods. Eighty-eight patients (28 men and 60 women, age 39 ± 8 years) affected by primary AIHA were consecutively enrolled. Two hundred and seventy-four blood donors (93 men and 171 women, age 36 ± 9 years) also took part in the study as control population. The diagnosis of AIHA was based on the following criteria: clinical or laboratory evidence of haemolysis; serologic evidence of an autoantibody against RBC; absence of a secondary cause of the disease. Concentrations of both serum tTG-IgA and AEA-IgA antibodies (Eurospital, Trieste, Italy) were evaluated in all subjects. In subjects positive to serological screening, diagnosis was confirmed by the presence of villous atrophy on jejunal biopsy samples at endoscopy. The difference between groups was assessed by the χ2 -test or Fischer’s exact test as appropriate. Results. Among patients’ population, all the 88 patients with primary AIHA were negative for both AEA and tTG antibodies. Among the blood donors, 1 subject out of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between groups. Conclusions. Although the plausibility of the association between coeliac disease and primary autoimmune haemolytic anaemia could base on common autoimmune phenomena, the present study does not confirm the tested hypothesis. PO212 ROLE OF HBV-DNA LOAD IN DETERMINIG HBV RECURRENCE AFTER LIVER TRANSPLANTATION AND THE CHOICE FOR MONO OR COMBINED PROPHYLACTIC THERAPY S. Gaia, A. Marzano, S. Carenzi, A. Premoli, V. Ghisetti, M. Fadda, M. Salizzoni, M. Rizzetto Department of Gastroenterology, Liver Transplantation Center, Molinette Hospital, Turin, Italy Background and aims. Hepatitis B immunoglobulins (HBIG) and/or lamivudine (LAM) are effective in HBV recurrence after liver transplantation (LT). Selection criteria able to identify low and high-risk patients candidates to mono or combined prophylaxis are needed. Patients and methods. Two hundred and forty-five HBsAg-carriers from 1000 patients, transplanted in our centre (1990–2002) are described. Different antiviral pre-emptive therapies pre-LT and post-LT

Conclusions. HBV-DNA higher or lower then 100,000 copies/ml by PCR can be used to select patients needing a pre-emptive therapy pre-LT and a combined prophylaxis (HBIG and lamivudine or other effective antivirals) after surgery. Patients spontaneously negative by PCR before LT are the optimal candidates to mono-therapy after LT. PO213 ANTIDIABETIC THIAZOLIDINEDIONES PROMOTE REGRESSION OF COLLAGEN DEPOSITS IN RAT MODELS OF LIVER FIBROSIS A. Galli, E. Ceni, T. Mello, M. Tarocchi, M.R. Biagini, M. Capanni, N. Lazzerini, B. Casanova, A. Casini, C. Surrenti, S. Milani Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy Recent evidences indicate that the fibrosis is a dynamic process and suggests that a capacity for recovery from advanced cirrhosis and fibrosis is possible. Thiazolidinedione drugs (TZD) such as pioglitazone (PGZ) and rosiglitazone (RGZ) are a new class of antidiabetic, which attenuate the insulin resistance associated with obesity, hypertension and impaired glucose tolerance. We have recently demonstrated that TZD prevents collagen deposition and hepatic stellate cells activation, via transcriptional induction of PPAR␥. Aim. Our study was to evaluate the effect of TZD treatment on the recovery of hepatic collagen deposits in CCl4 model of liver fibrosis. Methods. Reversible fibrosis and cirrhosis were established by injecting rats with CCl4 intraperitoneally for 6 or 12 weeks, respectively. Afterwards, rats were treated with 3 mg/kg per day of TZD for 28 days. Fibrosis was evaluated by Sirius red and immunoistochemistry for collagens. Gene expression of MMPs and fibrinolitic system was performed by RT-PCR. Results. Sirius red staining showed that both PGZ and RGZ treatments accelerated spontaneous recovery in the 6-week model of CCl4 intoxication and induced a significant regression of collagen deposits in the 12-week cirrhotic model. Immunoistochemistry for collagen types I and III confirmed the effect of TZD on the fibrosis recovery. Analysis of the expression and the activity of MMPs demonstrated that a significant induction of the interstitial collagenase (MMP-13) in TZD-treated rats occurred. In conclusion, TZD do not only retard collagen deposition but also reverse advance liver fibrosis and they show the promise of becoming a future therapy of liver fibrosis. PO214 PAEDIATRIC ENDOSCOPY IN ITALY: A NATIONAL SURVEY P. Gandullia, A Barabino, F. Torrente, C. Romano, L. Dall’Oglio, D. Falchetti, S. Cucchiara, G. de Angelis and Italian Pediatric Panel Endoscopy (IPPE)

Abstracts Introduction. Paediatric endoscopy is a growing field involving several professional figures, i.e. gastroenterologists, surgeons, anaesthetists and specialist nurses. This study consisted in a survey of the paediatric endoscopic centres in Italy, with the aim of assessing credential practices by each centre. Methods. A form was mailed to every member of the Italian society of paediatric gastroenterology (SIGEP) and paediatric surgery (SICP) in order to establish the number of centres performing procedures and areas dedicated in each centre, professionals (medics and paramedics) and equipments involved, number of procedures and overall time dedicated to endoscopy, as well as to review the type of sedation/anaesthesia techniques used. Results. Forms were returned completed by 21 members belonging to 20 different centres, out of which 7 (35%) were from northern Italy, 8 (40%) from the centre of Italy and 5 (25%) from the south. Only in six centres, a fully dedicated endoscopy service was identified; in 10/20 (50%) centres, all procedures were performed by paediatric gastroenterologists, whereas in 7/10 (35%), surgeons were the main medical personnel involved. In most cases (70%), time dedicated to endoscopic procedures was less than half of the total working hours, and only six centres could rely on a fully trained endoscopy specialist nurse. Means of total procedures per centre per year were 262 for upper endoscopy and 95 for lower endoscopy; whereas each centre carried out a mean of 32 operative procedures per year. Ileoscopy was performed in 65% of the centres only. In all centres but one, procedures were carried out under deep or conscious sedation, but in six centres only a dedicated room for recovery was available. Conclusions. This survey suggests that endoscopy practise is widely spread among Italian paediatric and surgical centres. However, in order to increase safety, it is of vital importance to improve quality of endoscopic standards for both diagnostic and therapeutic procedures. PO215 A FIVE MINUTES IMMUNOCHROMATOGRAPHIC ASSAY FOR Helicobacter pylori IN PRE- AND POST-TREATMENT

PO216 A NOVEL 25 mg UREA 13C UBT FOR DIAGNOSIS AND MONITORING H. pylori INFECTION L. Gatta, C. Ricci, A. Tampieri, F. Perna, E. Casalicchio, G. Liuzzi, M. Miglioli, D. Vaira Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy Background. By reducing the cost of the 13C UBT it would increase its acceptance, in cost-benefit areas being the main cost related to the expensive substrate (13C urea). Aim. To assess the diagnostic accuracy of newly developed rapid UBT containing low-dose (25 mg) of 13C urea for diagnosing and monitoring Helicobacter pylori eradication, compared with an endoscopic/biopsy gold standard (EGD). Methods. Two hundred and twenty-five consecutive patients (101 male, 124 female; mean age ± S.D. 51.7 ± 14.8 years) with upper GI symptoms, underwent endoscopy and biopsies were taken for culture, urease test (RUT) and histology. Patients with two out of three positive endoscopic tests were considered infected. All patients also underwent breath tests carried out after an overnight fast. Citric acid was used as test meal and 25 mg of 13C-urea as water solution (Breathquality UBT; 13C urea, AB Analitica Srl, Italy) was given to the patients after collection of a baseline sample. A further sample was collected 10 min later. Patients were considered positive if DOB was ≥4.5. Results. Ninety patients were found to be H. pylori positive according to the gold standard used. Till to date, 71 patients were also followed up after eradication treatment. Sensitivity, specificity, likelihood ratio for a positive and negative test before and after treatment are shown in the table. Conclusions. The 25 mg 13C are highly accurate for the detection and monitoring H. pylori infection.

L. Gatta, F. Perna, C. Ricci, A. Tampieri, E. Casalicchio, G. Liuzzi, M. Miglioli, D. Vaira Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy Background. A new rapid one-step lateral flow immunoassay stool test (ImmunoCard STAT), which requires only 5 min to be performed, has recently been released. Aim. To evaluate the accuracy of the ImmunoCard STAT compared to endoscopic gold standard. Methods. Two hundred and eight-two consecutive endoscoped patients (histology, urease test, and culture performed) (age range 24–74 years) complaining of dyspepsia were enrolled. To be enrolled, patients had not been on proton pump inhibitors, antibiotics, bismuth compound in the previous 4 weeks. Patients with two out of three positive tests have been considered as Helicobacter pylori positive. All patients provided stool samples als. The ImmunoCard STAT required: dilution of a specimen, transfer of four drops into the sample port of the device and reading the result after 5 min. The appearance of a coloured line indicates a positive test. Up to date, 93 patients were followed up after treatment. Results. The performance of ImmunoCard before and after treatment is shown in the table. Conclusion. The ImmunoCard STAT proved to be fast, easy to perform and accurate compared to the gold standard. It could be useful as near patients test for physician in their daily practice. No. of Sensitivity patients (95% CI, %) Before treatment 282

91.5 (85.7–95.1)

After treatment

92 (75–97.8)

93

Specificity (95% CI, %)

LR+ (95% CI) LR− (95% CI)

93.6 (88.3–96.6) 14.333 0.091 (7.602–27.024) (0.053–0.156) 100 (94.7–100) ∞ (17.191–∞) 0.123 (0.123–∞)

CI: confidence interval; LR+: likelihood ratio for a positive test; LR−: likelihood ratio for a negative test.

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Before treatment After treatment

No. of patients

Sensitivity (95% CI, %)

Specificity (95% CI, %)

LR+ (95% CI)

LR− (95% CI)

225 71

98.9 (94–99.8) 100 (81.6–100)

100 (97.2–100) 100 (93.4–100)

∞ (35.740–∞) –

0.011 (0.028–∞) –

CI: confidence interval; LR+: likelihood ratio for a positive test; LR−: likelihood ratio for a negative test.

PO217 COX1 PLUS PPI OR COX2 IN ACUTE OSTEOARTHRITIS FOR PREVENTION OF GASTRODUODENAL DAMAGE? A PROSPECTIVE FOUR-WEEK STUDY B. Germanàa , E.A. Galliania , P. Lecisa , F. Costan Biedoa , F. Di Mariob a Gastroenterology b Gastroenterology

Unit, S. Martin Hospital, Belluno, Italy Unit, Parma University, Italy

Introduction. Current evidence indicates that therapy with non-steroidal anti-inflammatory drugs (NSAIDs) associated with a proton-pump inhibitor (PPI) or with NSAIDs selective for cyclooxigenase-2, reduce the risk for ulcer complication in patients with arthritis and at risk (peptic ulcer history and/or age >65 years) for ulcer disease. Aims and methods. The aim of this study was to compare the efficacy and safety of two therapeutic strategy: Piroxicam 20 mg plus Omeprazole 20 mg per day (treatment A) versus Celecoxib 200 mg per day (treatment B) in a short-term therapy (30 days). Forty general physician after approval of the protocol performed a prospective randomised study involving 540 consecutive patients with history of ulcer disease and/or age >65 years affected by osteoarthritis; 261 (97 male, 167 female; age 69.2 ± 13.4 years) received treatment A and 279 (95 male, 184 female; age 68.5±14.2 years) received treatment B. Efficacy for arthritis was evaluated by two scores ranged from 1 (non-limitation of normal activity and no pain) to 5 (inability to carry out all normal activity and severe pain) at the baseline

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and after 30 days; side-effects were evaluated after 30 days on the bases of physical examination and adverse events were recorded, as well as gastrointestinal symptoms, based on a standardised questionnaire. Results. The patients global assessment of arthritis activity and pain did not differ between the two groups: treatment A was efficient in 205 patients (78.2%) and treatment B in 221 (79.3%) (P = NS). Thirty-nine patients discontinued medication 11 in group A (4.3%) and 28 in group B (10.1%) (P < 0.05). The main cause of discontinued treatment was a lack of efficacy for both groups: 5 patients in group A and 14 patients in group B. Other causes of discontinued therapy for both groups were gastric pain, constipation, skin rash; all symptoms disappeared at the end of therapy. Gastrointestinal symptoms of mild severity (epigastric pain, heartburn acid regurgitation, dyspepsia, bloating, gastric swelling, dysphagia, nausea, vomiting, diarrhoea) occurred in 61 patients of group A (23.6%) and in 45 patients of group B (16.2%) but without discontinuing treatment (P = NS). Conclusion. Among 540 patients with arthritis and at risk for side-effects (previous ulcer and/or age >65 years), nobody had symptoms for ulcer, gastrointestinal bleeding or serious adverse events with both strategies. Treatment with Piroxicam and Omeprazole was as effective as treatment with Celecoxib even if the rate of patients who discontinued treatment for inefficacy was significantly lower in the first group. Gastrointestinal mild symptoms were similar in the two groups. PO218 GASTROPANEL AS SCREENING OF GASTRIC ATROPHY IN PRIMARY CARE B. Germanàa , S. Liatopouloub , G. Comparatob , M. Ali Moussab , C. Carlonib , P. Lecisa , B. Bertiatoc , C. Doglionid , G. Aragonab , L.G. Cavallarob , G.M. Cavestrob , V. Iorib , R. Merlib , S. Bertolinib , P. Caruanae , F.C. Biedoa , F. Di Mariob a Gastroenterology

Unit, Belluno, Italy of Clinical Sciences, Belluno, Italy c Laboratory Unit, Belluno, Italy d Pathology Unit, Belluno, Italy e Department of Pathology, Parma, Italy b Department

Background. Histological examination is essential to give information about the topography of gastric damage. Serum pepsinogens and gastrin-17 were found useful biomarkers in detecting morphologic alterations of gastric mucosa. Aim. To assess by means of a non-invasive test (gastropanel parameters: serum pepsinogen (sPGI) and II (sPGII), PGI/PGII ratio, gastrin-17 levels (G-17) and IgG-anti Helicobacter pylori) both morphology and function of gastric mucosa in primary care. Patients and methods. Three hundred and sixty-three consecutive out-patients (208 female, mean age 50.6 years, range 18–88 years) were studied for dyspeptic symptoms. In each subject, blood samples were taken to evaluate IgG anti-H. pylori, sPGI, sPGII and gastrin-17 levels (EIA, Biohit, Helsinki, Finland) and upper gastrointestinal endoscopy with biopsy (two antrum, two corpus) was performed. We designed the topography of gastric atrophy as antral predominant (APA, antrum > corpus), diffused (PAN, antrum = corpus) and corpus predominant atrophy (CPA, corpus > antrum). Results. Seventy-six subjects were excluded after antisecretory therapy was carried out. One hundred and thirty-two subjects resulted positive for H. pylori infection (mean age 52 years, range 19–83 years) and 155 H. pylori-negative (mean age 48 years, range 18–88 years) with respective values (sPGI: 120.69 ␮g/l versus 88.8 ␮g/l, P < 0.001; sPGII: 15.95 ␮g/l versus 8.96.92 ␮g/l, P < 0.001; PGI/PGII: 9.63 ␮g/l versus 11.88 ␮g/l, P = 0.003; gastrin-17: 8.46 pmol/l versus 12.91 pmol/l, P = 0.354; IgG anti-H. pylori: 79.95 versus 21.12, P < 0.001). The statistically significant differences were found: APA versus CPA: P < 0.001 for mean sPGI; P = 0.002 for mean sPGII; P < 0.001 for mean PGI/PGII; P < 0.001 for mean gastrin-17; P < 0.001 for mean IgG anti-H. pylori PAN versus CPA: P = 0.43 for mean sPGI.

Conclusion. Gastropanel provides more information about the morpho-functional status of gastric mucosa and the presence of H. pylori-related gastritis and could be used as a first approach strategy (“test and treat”) in primary care to select subject for upper gastrointestinal endoscopy and biopsy identifying gastric precancerous conditions or lesions. PO219 GASTROINTESTINAL STROMAL TUMOURS: OUR CASES REPORTS S. Giaccaria , C. Mancab , A. Mazzottab , L. Allegrettaa , S. Chiria , G. Grassoa , S. Troncia , I. Sicilianoa , A. Montefuscoa a Department

of Gastroenterology, “S. Caterina Novella” Hospital, A.S.L. LE/01, Galatina (LE), Italy b Department of Surgery, “SV. Fazzi” Hospital, A.S.L. LE/01, Lecce (LE), Italy Introduction. Gastrointestinal stromal tumours (GISTs) have been an argument for the clinical and pathological anatomy. Only recently the discovery of c-Kit gene and the expression of c-Kit protein on tumoural cells have been helpful to point on these tumours. Majority of the cases are often symptomatic and their discovery is found incidentally at the time of upper endoscopy. They tend to be slow growing, indolent tumours that are symptomatic until they become quite large and in this case symptoms may be abdominal pain, sub-obstruction or gastrointestinal bleeding. Of all GISTs in the GI tract occur in the stomach (50–60%), followed by small bowel (20–30%). Very rarely occur in the colon (10%) and in the oesophagus (5%). Materials and methods. We have carried out the procedure on our patients from January 1998 to September 2003 that had required a surgical treatment for GISTs. We have reported malignant score following actual criteria in Table 1. With regard to gastric tumours all are discovered incidentally during endoscopy done for dyspeptic symptoms (four cases) or gastric pain (eight cases). Tumours occurring in the duodenum in two cases were ulcerated and the symptoms consisted in ulcer-like symptoms. Tumours occur in jejuno-ileal tract induced in one patient a mechanic obstruction, in two cases relapsing crisis of abdominal pain with sub-obstruction, in another case with an occult bleeding. Tumours occurring in rectum appeared with tenesmus and in caecum with occult bleeding (discovered with a colonscopy performed for occult blood in faeces) (Table 2). Conclusions. GISTs therapy remain surgical, even if in tumours of large size or metastatic can be used for the tyrosine-kinase inhibitor imaf`ınib mesylate (GLIVEC). Table 1

Risk Very low Low Medium High

0 cm <2 cm 2–5 cm <5 cm a 5–10 >10 cm ogni 0

Mitosis × 50 CFI∗ <5 × 50 <5 × 50 6–10 × 50 and <5 × 50 Whatever no. of mitosis >10 × 50

Table 2 No. (site)

Ring diameter (cm)

No. of mitosis

Risk of mtx

Anatomic–pathologic GIST

5 1 3 1 2 2 2 2 1 1

2.5–12 2 5 6 4–16 6–9 3.5–23 10–13 8 8

0–2 × 50 6 × 50 <5 × 50 <5 × 50 >30–40 × 50 <5 × 50 5–50 × 50 >5 × 50 >10 × 50 >50 × 50

No Very low Low Medium High Medium High High High High

Leiomyoma Very low malignity Very low malignity Medium malignity High malignity (leiomyosarcoma) Medium malignity High malignity (leiomyosarcoma) High malignity (leiomyosarcoma) High malignity (leiomyosarcoma) High malignity (leiomyosarcoma)

(Stomach) (Stomach) (Stomach) (Stomach) (Stomach) (Duodenum) (Jejunum) (Ileum) (Caecum) (Rectum)

Abstracts PO220 GENOTYPE–PHENOTYPE CORRELATIONS IN CROHN DISEASE: THE ROLE OF CARD15 AND CD14 VARIANTS D. Giachinoa , M. Dapernob , P. Salaconec , N. Saponed , M.M. van Duista , S. Regazzonia , R. Sostegnib , A. Sambataroc , E. Gaiac , A. Perab , M. Astegianod , M. De Marchia , D. Gregorie a Department

of Clinical and Biological Sciences, University of Turin, ASO San Luigi, Orbassano, Italy b Gastroenterology Unit, Ospedale Mauriziano, Turin, Italy c Gastroenterology Unit, ASO S. Luigi, Orbassano, Italy d Gastroenterology Unit, ASO S. Giovanni Battista, Turin, Italy e Department of Public Health and Microbiology, University of Turin, Italy

Within the “Gruppo di Studio Piemontese sulle Malattie Infiammatorie Croniche Intestinali” [van Duist et al., this congress], which up to now includes 233 retrospectively enrolled Crohn patients, here we analyse CARD15 and CD14 genotype correlations with the clinical phenotype. For each patient, known risk factors as familiarity and smoke, and detailed clinical features according to Vienna criteria were encoded, together with information on steroid-resistance and perianal disease. Statistical analysis was performed with Splus package. We first considered the frequency of positivity for CARD15 variants in patients with different clinical features. The estimated chance of finding at least one genetic variant was significantly increased among patients with a stricturing behaviour (OR 2.2, CI 1.2–4.2), and in those with ileal location (OR 3.6, CI 1.5–8.5). The CARD15-positive patients also showed a significant risk of resistance to steroid therapy (57% versus 32%, OR 2.9, CI 1.2–7.2). The same contingency tables were then used to consider each clinical feature (age at onset, behaviour, location, extra-intestinal manifestations, steroid resistance, perianal disease, type of onset) as an outcome, with sex, familiarity, positivity for a CARD15 variant, CD14 TT genotype and smoking as explanatory variables. After adjusting CARD15 positivity for smoking, familiarity and sex, multivariate analysis resulted in higher and more significant risk estimates for stricturing behaviour and ileal location, with OR 3.02 and 5.44, respectively; and there became significant even the risks of fistulising behaviour (OR 2.79) and surgical onset (OR 2.04). The analysis of CD14 SNP resulted in a significant risk of a penetrating behaviour for T homozygotes (OR 3.3, CI 1.4–7.9), which was also validated by multivariate analysis and by the absence of additive interaction with the CARD15 genotype. Interestingly, preliminary results suggest an increase of perianal fistulae in CD14 T homozygotes (31% versus 8%, OR 5.2) in agreement with Brant et al. (2003). This OR increased to 22.3 after multivariate analysis with weighting for other risk factors. The interaction of genetic background (CARD15 positivity and CD14 TT) with smoke history significantly increased the risk of early onset (P < 0.01), worse behaviour (P < 0.01), resistance to steroid therapy (P < 0.03) and perianal disease (P < 0.01), compared with the risk independently conferred by each factor. PO221 COMPARISON AMONG US, CONTRAST-ENHAN- CED US, SPIRAL CT IN THE EVALUATION OF HEPATIC METASTASES IN A CONSECUTIVE SERIES OF NEOPLASTIC PATIENTS F. Giangregorio, M. Di Stasi, M.G. Marinone, G. Sbolli, P. Tansini, F. Fornari Divisione di Gastroenterologia, Ospedale “G. da Saliceto”, Piacenza, Italy Aim. To compare conventional US, contrast-enhanced harmonic ultrasonography (CEUS), spiral CT in the evaluation of hepatic metastases in a consecutive series of patients with extrahepatic cancer. Material and methods. One hundred and nine consecutive patients (51 male, 58 female; mean age 67.7 years, range 33–87 years) were enrolled. The primary site of cancer was: GI tract in 63 patients, pancreas in 27,

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breast in 6, lung in 6, uterus in 3; lung in 1 and malignant endocrine cancer in 1. All patients performed a contrast-enhanced spiral CT. CEUS was performed using a suspension of sulphur hexafluoride in sterile saline (SonoVue, Bracco), as contrast agent, and two machines (Esatune and Technos MPX, Esaote) with a new harmonic sonography (called CnTI). Results. Final diagnoses revealed hepatic metastases in 57 patients. Conventional US revealed: 41 true positive patients, 46 true negative ones, 6 false positive and 16 false negative patients (sensitivity 71.9%; specificity 88.5%). Spiral CT revealed: 44 true positive patients, 51 true negative ones, 1 false positive and 13 false negative patients (sensitivity 77.2%; specificity 98.1%). CEUS detected: 55 true positive patients, 51 true negative cases, 1 false positive and 2 false negative patients (sensitivity 96.5%; specificity 98.1%). Conclusions. CEUS with second generation contrast agents has had a better sensitivity and equal specificity in detection and characterisation of hepatic metastases in comparison with spiral CT. PO222 PANCREATIC LESIONS EVALUATED WITH A NEW CONTRAST US: COMPARISON WITH CONVENTIONAL US, EUS AND CT F. Giangregorio, M. Di Stasi, M.G. Marinone, G. Sbolli, P. Tansini, F. Fornari Divisione di Gastroenterologia, Ospedale “G. da Saliceto”, Piacenza, Italy Aim. To assess the diagnostic accuracy of a new contrast harmonic US (CEUS) for the characterisation and the staging of pancreatic lesions, comparing these data with conventional US, helical CT and EUS. Material and methods. Forty-six consecutive patients (25 male, 21 female; mean age 68.8 years) with pancreatic mass lesions were enrolled in this study. The final diagnoses were: 18 benign lesions, 9 single cysts (mean diameter 1 cm), 1 patient with several small cystic lesions, 3 solid pseudocyst (10 cm), 5 peripancreatic abscess (4 cm); and 28 malignant tumours, 26 adenocarcinomas, 1 mucinous neoplasm and 1 endocrine tumour (mean diameter 3.6 cm). Hepatic metastasis were present in 16/28; vascular invasion in 18/28, lymph nodes metastases were present in 6/28 patients. Endoscopic ultrasound (EUS) (OLYMPUS EUM 20) was performed in nine patients with malignant neoplasm. The CEUS was performed using a suspension of sulphur hexafluoride in sterile saline (SonoVue, Bracco), as contrast agent. We evaluated the modality of the uptake of the contrast agent, size of the lesions, local infiltration and N/M staging. Results. CEUS was superior to conventional US in all the 16 benign lesions. In the 26 ADK, we observed an early arterial contrast enhancement, that outlined a larger diameter than that showed by US. In 23/28 malignant lesions, CEUS was superior to US for staging (23 local infiltration; and 11 hepatic metastasis). CEUS and CT were concordant in 35/46 cases; CT was superior in 3/46 patients (two local infiltration and one lymph nodes metastasis); CT was inferior to CEUS in 8/46 cases (three local infiltration and five hepatic metastasis). EUS was better than CEUS in evaluating local infiltration in three patients, two of them with a pancreatic mass <3 cm and one with a bigger mass but with a high meteorism. CEUS was better than EUS in local infiltration in three patients with a pancreatic mass bigger than 4 cm. CEUS was superior to EUS in evaluating hepatic metastases in eight patients. CEUS and EUS were equal in lymph nodes evaluation in 7/9 patients. Conclusions. CEUS was superior to conventional US and demonstrated a diagnostic accuracy similar to CT in the characterisation and staging of pancreatic mass lesions. Furthermore, CEUS may be complementary with EUS in TNM evaluation of malignant pancreatic masses.

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PO223 HEPATIC CIRRHOSIS AND DIABETES MELLITUS: CHARATERISTICAL FEATURES OF DIABETES ASSOCIATED TO LIVER CIRRHOSIS G. Gianquinto, P. Guerzoni, I. Arena, L. Marelli, P. Porta, M. Curzio U.O. di Gastroenterologia Ospedale di Circolo, Varese, Italy Objective. The association between hepatic cirrhosis and diabetes mellitus is well known. The objective of our research was to show the characteristical features of diabetes associated to hepatic cirrhosis. Methods. We evaluated three groups of patients: 20 cirrhotic and diabetic patients (group I), 20 cirrhotic patients (group II) and 20 diabetic patients (group III) and we investigated: (a) the presence of family history of diabetes; (b) therapeutic behaviour for diabetes; (c) short and long time metabolic control of diabetes (glycemia and HbA1c); (d) residual endocrine pancreatic function (C-peptide); and (e) clinical and laboratory features of hepatic cirrhosis (aetiology, Child–Pugh score, presence of portal hypertension and platelets count). Our aim was also to calculate: (a) the prevalence of macroangiopatic complications of diabetes (ictus cerebri, coronary heart disease and peripheral arteriopathy); (b) the prevalence of diabetic retinopathy; and (c) the prevalence of microalbuminuria, as index not only of diabetic nephropathy but also of diffuse vascular damage. Results. In our retrospective study, the prevalence of diabetes in liver cirrhosis was 30.1%, a value which is similar to the results found by previous investigations. Family history of diabetes was more frequent in group III than in group I (60% versus 25%, P < 0.05); oral antidiabetic drugs were rarely used in diabetes of cirrhotic patient (5% versus 55%, P < 0.05); values of glycemia and HbA1c were similar in groups I and III, while basal C-peptide levels were increased in cirrhotic-associated diabetic patients as compared to non-cirrhotic-associated diabetic patients (2.9±2.1 versus 1.6 ± 0.9, P < 0.05); aetiology, severity of cirrhosis (valued with Child–Pugh score), portal hypertension and platelets count were not different in cirrhosis of groups I and II. The prevalence of macroangiopatic complications of diabetes was higher in non-cirrhotic-related diabetes than in diabetes secondary to hepatic cirrhosis (40% versus 10%, P < 0.05); the prevalence of diabetic retinopathy was not significantly different between groups I and III; the prevalence of microalbuminuria was lower in group I than in group III (10% versus 40%, P < 0.05). Conclusions. Our results suggest that diabetes secondary to cirrhosis has some different features from classical type 2 diabetes mellitus: the absence of family history, which lays stress on the importance of cirrhosis as a diabetogenic factor; kind of therapy; initial hyperinsulinaemia and insulin resistance that shows a different pathogenesis. On the contrary, features of cirrhosis seems not to be modified by the development of diabetes. Moreover, our study might show that cirrhotic patients are at a low risk of developing micro and macrovascular complications of diabetes mellitus, as if cirrhosis was able to protect from vascular damage. PO224 PREHARVEST DONOR ARTERIAL HYPEROXIA AMELIORATES GRAFT SURVIVAL IN LIVER TRANSPLANTATION BY REDUCING NITRIC OXIDE SYNTHASE LIVER EXPRESSION BEFORE GRAFT ISCHAEMIA S. Ginanni Corradinia , M. Sicilianoa , I. Blottac , R. De Marcoa , A. Eramoa , M. Iappellib , F. Rubertob , F. Puglieseb , D. Stabileb , L. Polib , G. Novellib , F. Liguoria , M. Merlia , A.F. Attilia , P. Berlocob , M. Rossib , A. Cantaforac a Div.

Gastro Dip. Med Clinica, Univ. “La Sapienza”, Rome, Italy Chir. Generale “P. Stefanini”, Univ. “La Sapienza”, Rome, Italy c Lab. Metab. Lipidico Ist Superiore di Sanitá, Rome, Italy b Dip.

Background and aims. Preharvest donor hyperoxia protects from adverse events shortly after liver transplantation [Dig. Liver Dis. 35 (2003) S4]. We investigated the effect of donor hyperoxia on graft survival and hepatic

gene expression of proteins involved in the ischaemia–reperfusion injury. Methods. Sixty-nine cadaveric orthotopic non-status 1 full-size adult liver transplantations were studied during February 2001 to August 2003 at a single centre. Donor arterial partial pressure of oxygen (PaO2 ) was measured no longer than 4 h before organ harvest. Liver tissue was obtained before harvesting from the donor and immediately stored in liquid nitrogen. Hepatic expression of the heath shock protein 72 (HSP72), of the endothelial nitric oxide synthase (eNOS) and of the inducible nitric oxide synthase (iNOS) were measured by RT-PCR based on competimer technology with microchip electrophoresis. Results. Graft survival (median follow-up 13 months; range 0.1–33 months), was significantly (P = 0.04) longer in recipients who received the graft from donors with a PaO2 value greater than 150 mmHg (n = 22) than in those who received the graft from donors with a PaO2 value lower than 150 mmHg (n = 47). eNOS and iNOS expression in the liver were significantly lower in the graft obtained from donors with PaO2 values greater than 150 mmHg (n = 7) than in those with a PaO2 value lower than 150 mmHg (n = 14).

HSP72 (arbitrary units)

eNOS (arbitrary units)

iNOS (arbitrary units)

Donor PaO2 >150 mmHg 0.70 ± 0.30 0.24 ± 0.27∗∗ 0.03 ± 0.03∗ Donor PaO2 <150 mmHg 1.27 ± 0.21 1.00 ± 0.19 0.07 ± 0.02 Mean ± S.E. ∗ P < 0.05;

∗∗ P

< 0.005 (Student’s t-test).

Conclusions. A donor preharvest PaO2 greater than 150 mmHg helps to define the optimal liver donor. Donor hyperoxia down-regulates NO synthase gene expression. A reduced synthesis of NO could protect from subsequent liver injury by minimising superoxide and peroxynitrite production during graft ischaemia. PO225 PREHARVEST DONOR ARTERIAL HYPEROXIA PROTECTS FROM INITIAL POOR GRAFT FUNCTION AFTER LIVER TRANSPLANTATION BY INCREASING TOTAL PROTEIN LIVER CONCENTRATION S. Ginanni Corradinia , R. De Marcoa , M. Sicilianoa , F. Liguoria , M. Iappellib , F. Puglieseb , F. Rubertob , A. Eramo, R. Pretagostinib , F. Nudob , A. Bussottib , M. Merlia , P. Berlocob , M. Rossib , A.F. Attilia a Div. b Dip.

Gastro Dip. Med Clinica, Univ. “La Sapienza”, Rome, Italy Chir. Gen. “P. Stefanini”, Univ. “La Sapienza”, Rome, Italy

Background and aims. It has been shown previously that preharvest donor hyperoxia protects from the occurrence of adverse events shortly after cadaveric liver transplantation [Dig. Liver Dis. 35 (2003) S4). We investigated the relation of donor arterial partial pressure of oxygen (PaO2 ) with initial graft function and total protein liver content in human liver transplantation. Methods. Thirty-nine cadaveric orthotopic non-status 1 full-size liver adult transplantations were divided into two groups according to a score obtained from the serum ALT concentration, bile output and prothrombin activity during the first 72 h after transplantation [Hepatology 20 (1994) 565]: initial poor graft function (IPGF; score 7–9) and initial good graft function (IGGF; score 3–6). Donor PaO2 was measured no longer than 4 h before organ harvest. Total protein concentration (Bio-Rad protein assay) was assayed on donor hepatic biopsy obtained before harvesting. Results. Donor PaO2 and total protein liver concentration were significantly higher in the IGGF than in the IPGF group (see table). Total protein liver concentration correlated positively with donor PaO2 (r = 0.399; P < 0.05) and negatively with recipient serum AST on the first postoperative day (r = −0.421; P < 0.01).

Abstracts

Donor PaO2 (mmHg) Liver total proteins (␮g/mg) Mean ± S.E. ∗ P < 0.05;

∗∗ P

IPGF (n = 14)

IGGF (n = 25)

99.6 ± 8.1 91.4 ± 4.4

154.3 ± 13.7∗∗ 110.1 ± 6.0∗

< 0.01 (Kruskal–Wallis test).

Conclusions. Preharvest donor hyperoxia is beneficial for early graft function and increases the total protein liver concentration. A relatively high protein preharvest liver content ensures a high protein reserve before the proteolysis occurring during ischaemia and protects from post-ischaemic protein depletion which has deleterious effects on hepatic cells. PO226 EXPERIENCE OF TWO YEARS ACTIVITY IN THE ENDOSCOPIC DIAGNOSIS OF COLONIC POLYPS A. Gioieni, C. Ciarletti, G. Di Trapani, C.A. Gervasi, F. Goffredo, L. Tessieri, G. Zirizzotti, C. Giannelli

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Material and method. Twelve patients (10 males) with persistent bleeding induced by radiation proctitis from January to October 2003 underwent endoscopic APC treatment. Their average age was 69.2 years (range 56– 78 years). Nine patients had prostate cancer, two uterine and only one had proximal rectal cancer. APC treatment was administered a couple of times per month. The argon flow was seat at 1.5 l/m with electrical power of 40 W. A mean of 2.5 sessions needs to relieve symptoms. Results. At a mean follow-up of 6 months, 11 patients (92%) had a significant reduction in severity and frequency of bleeding. In six patients, bleeding ceased after two treatments. In three patients (25%), the bleeding was significantly reduced to occasional spotting. In two patients (17%) (uterine Ca), the presence of radiation sigmoiditis was associated with reduced but persistent bleeding. Only one patient with severe proctitis ad hepatic metastases did not respond to the treatment. Eleven patients had an improvement in haemoglobin levels (11.5–12.6 g/dl). The tolerance was good without short-term related complications. Follow-up is in progress to evaluate the risk of rectal stenosis. Conclusions. APC treatment of radiation induced proctitis is more effective than pharmaceutical topical therapy with high tolerance and few short-term complications.

Unit of Digestive Diseases and Gastrointestinal Rehabilitation, Italy Background and aim. Adenomas are the most frequent precancerous lesions of colon and colonoscopy is the best tool for the localisation and identification of its histological features. Then, the number of colonoscopy performed yearly is increasing and screening programme are reasons of further development. The aim of our experience is to evaluate the frequency of colic adenomas in the activity of an endoscopic unit in a city population of 450,000 residents. Material and method. Our study concerns the experience, during 2 years, of 2846 colonoscopy (Olympus video-endoscope 145), from May 2001 to April 2003; 2390 of them (84%) were pancolonoscopy. Results. Adenomas were identified 502 polyps in 392 patients (16.4%), mean age 64 years (18–86 years). Two hundred and one (64%) were males. In 292 patients (74.%) we observed one polyp, in 54 (14%) 2 polyps, in 16 (4%) 3 polyps, in 19 (5%) 4 and in 13(3%) 5 or more polyps. Four hundred and eighteen of them (83%) were left sided (splenic flexure) and 84 (17%) right sided. At histology, 11.5% were iperplastic, 1.2% inflammatory, 72.5% adenomas (60% tubular, 29% villous and 11% mixed), 4% mixed iperplastic and adenomas “serrated”. In 36 patients (11%), we have found severe dysplasia. After 385 polypectomy (77%), the size identification reveals 73 (19%) polyps smaller than 5 mm, 120 (31.5%) between 5 and 10 mm, 165 (42.5%) between 11 and 20 mm, and 27 (7%) larger than 20 mm. Severe dysplasia was observed in 12 polyps (33%) between 11 and 20 mm, 22 (61%) larger than 20 mm and only in 2 (6%) between 5 and 10 mm. Argon laser coagulation was needed for 11 (3%) early minor haemorrhagic complication. Delayed bleeding and major complication not occurred. Conclusions. Our experience confirms the role of colono- scopy in the polyps identification and represent a pilot study to evaluate the impact and the cost of screening programme in Lazio County. PO227 ARGON LASER THERAPY IS EFFECTIVE IN THE TREATMENT OF BLEEDING RADIATION PROCTITIS A. Gioieni, C. Ciarletti, G. Ditrapani, C.A. Gervasi, F. Goffredo, L. Tessieri, G. Zirizzotti, C. Giannelli Unit of Digestive Diseases and Gastrointestinal Rehabilitation, S. Camillo Hospital, Rome, Italy Background and aim. Chronic radiation proctitis is a common complication of pelvic radiotherapy with persistent rectal bleeding frequently severe and has either poor or no response to steroid and 5ASA topical therapy. The aim of this study was to assess the efficacy of argon plasma coagulation (APC) treatment in the management of bleeding radiation induced proctitis.

PO228 PREVALENCE OF GERD SYMPTOMS IN THE GENERAL POPULATION FROM A RURAL AREA IN THE SOUTH ITALY G. Giolittoa,b,c , D. Bruzzesea,b,c , G. Sarnellia,b,c , G. Russoa,b,c , G. Budillona,b,c , R. Cuomoa,b,c a Dipartimento

di Medicina Clinica e Sperimentale, Università degli Studi di Napoli “Federico II”, Naples, Italy b Dipartimento di Matematica e Statistica, Università degli Studi di Napoli “Federico II”, Naples, Italy c Unità Operativa di Medicina Interna, Presidio Ospedaliero, Polla, Salerno, Italy

Background. Data on the prevalence of gastro-oesophageal reflux disease (GERD) in Italy have been derived from epidemiological studies performed in primary care, tertiary referral centres or endoscopy centres. However, the data on the prevalence of GERD symptoms in the general population are lacking. Aim. To analyse the prevalence of GERD symptoms in a sample population from a rural area in southern Italy. Methods. Data were collected using a standardised questionnaire administered directly to 1300 subjects by the investigators. This sample population was extracted from an age- and sex-stratified randomisation of 64,370 subjects (aged 18–82 years) living in a rural area of southern Italy. The first question was about the presence of discomfort perception in the stomach or chest; this perception was better specified with the following descriptions: burning sensation rising from the stomach and/or base of the chest up to the throat, chest pain during swallowing and feeling of sickness and nausea. Acid regurgitation was also investigated. Frequency of symptoms was calculated as occurrence in the previous year (absent; mild: ≤1 per month; moderate: ≥1 per week; severe: ≥1 per day). Information on the use of antacids and their effects on burning was also collected. The data were assembled in an Access© database (Microsoft) and analysed with SSPS 11.0. Results. Two hundred and fifty-five individuals (19%, 114 males) reported feelings of discomfort. Frequency of symptoms was absent, mild, moderate and severe in 12, 52, 33 and 4%, respectively. Burning sensation was reported by 188 subjects (14.5%), chest pain by 26 (2%) and nausea by 40 (3.1%). Acid regurgitation was observed in 172 subject (13.2%; 70 males) and its frequency of occurrence was absent, mild, moderate and severe in 10, 58, 31 and 2%, respectively. Combination of burning and acid regurgitation were present in 95 subjects (7.3%), so that the whole fraction of sample complaining of typical GERD symptoms comprised 257 subjects (19.8%). Antacids were used by 137 subjects (73% of the patients complaining of burning) but only 26 (14%) resolved the symptom.

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Conclusions. Typical symptoms of GERD are frequent in a sample of general population in southern Italy and the prevalence appears similar to that of other studies reported in the international literature. Analysis of the frequency of occurrence reveals that a marked degree of severity is present only in one-third of GERD patients. Antacids have a weak effect on burning.

EIGHT-WEEK OPEN TRIAL OF ORAL BUDESONIDE FOR THE TREATMENT OF REFRACTORY POUCHITIS P. Gionchettia,b , F. Rizzelloa,b , C. Morsellia,b , G. Poggiolia,b , F. Pierangelia,b , R. Romagnolia,b , F. Ugolinia,b , S. Lauretia,b , M. Campieria,b b Department

PO231 EFFECTIVENESS OF THERAPY FOR CHRONIC HEPATITIS C IN CLINICAL PRACTICE: A RETROSPECTIVE STUDY

PO229

a Department

multivariate analysis was early CMV infection (r = 0.3211; 95% CI = 0.061–0.54; P = 0.0168). Conclusions. Our study demonstrates that in HCV-related recurrence after OLT, particularly early CMV infection is associated with worse prognosis.

of Internal Medicine and Gastroenterology, Italy of Anesthesiology, Surgery and Transplantation, Italy

Background. Ten to fifteen percent of patients with pouchitis experience refractory or recurrent disease. This study aimed to evaluate the effectiveness of oral budesonide in inducing remission and improving quality-of-life in such patients. Methods. Patients with active pouchitis not responding after 1 month of antibiotic treatment (metronidazole 1 g per day or ciprofloxacina 1 g per day), were treated with budesonide 9 mg per day for 2 months. Symptomatic, endoscopic and histological evaluations were made before and after treatment using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a clinical PDAI score <2 and endoscopic PDAI <1. QOL was assessed with Inflammatory Bowel Disease Questionnaire (IBDQ). Results. Sixteen patients (11 male, 5 female, median age 35.4 years) entered the trial and completed treatment. Twelve (72.2%) went into remission. The median PDAI scores before and after therapy were 13 (range 8–16) and 3 (range 2–9), respectively (P < 0.001). The median IBDQ score also significantly improved from 102 (range 77–176) to 182 (range 84–225) (P < 0.001). Conclusion. Eight-week treatment with oral budesonide at 9 mg per day is effective in inducing remission patients with active pouchitis, refractory to antibiotic treatment, objectively improving the inflammation and quality of life. PO230 CMV INFECTION AND BILIARY TRACT COMPLICATIONS ARE RELATED WITH A POOR OUTCOME OF LIVER TRANSPLANTATION FOR HCV-RELATED CIRRHOSIS S. Giovanelli, A. D’Errico, F. Lodato, A. Colecchia, M.R. Tamé, F. Azzaroli, G. Vetrone, M. Del Gaudio, G.L. Grazi, E. Roda, G. Mazzella Department of Internal Medicine and Gastroenterology, University of Bologna, Italy Introduction. After liver transplantation for HCV-related cirrhosis, recurrence of infection is universal, with development of histological hepatitis in the majority of patients. Several variables are implicated in the outcome of hepatitis C post-transplantation. Aim. The aim of this study was to evaluate factors related to HCV relapse after liver transplantation. Materials and methods. Seventy-two patients (53 male and 19 female) were transplanted for HCV cirrhosis between January 2000 and December 2002 in Liver Transplantation Unit of Ospedale S. Orsola-Malpighi of Bologna. Results. Mean age of female patients (59.7±0.86 years) was significantly higher than male age (52.4 ± 1.09 years) (P = 0.0002). At univariate analysis biliary tract stenosis (P = 0.0012), early CMV infection (P = 0.014), MELD score >25 at the time of transplantation (P = 0.004) and the age of donor (P = 0.043) were associated with poorer prognosis and graft failure. Independent factor associated with worse outcome at

S. Gozzi, A. Agnolucci, D. Angioli, F. Caneschi, P. Ceccatelli, F. Magnolfi, F. Pompili U.O. Gastroenterologia, Ospedale S. Donato, Arezzo, Italy Background and aim. Treatment with peginterferon alpha-2a or alpha-2b plus ribavirin for chronic hepatitis C produces significantly higher sustained virological responses (54–63%) than treatment with interferon alone (SVR: 13–19%) or with interferon plus ribavirin (SVR: 38–43%). It is not know whether these results can be achieved outside clinical trials. We determined effectiveness of treatment for hepatitis C in a hospital clinic setting and we tested the hypothesis that effectiveness and tolerability of therapy would be inferior to that reported from published trials. Methods. A total of 193 patients, who had not taken interferon previously, received therapy for chronic hepatitis C between 1994 and 2003; 118 patients received 3 or 6 million units of interferon three times per week for 24–48 weeks, 37 patients received 3 million units of interferon three times per week plus ribavirin (1000–1200 mg per day, depending on body weight) for 24–48 weeks and 38 patients received peginterferon alpha-2a (180 ␮g per week) or alpha-2b (1.5 ␮g/kg each week) plus daily ribavirin (800 or 1000–1200 mg, depending on genotype and body weight) for 24–48 weeks. All the patients were assessed for a sustained virological response, defined as undetectable HCV-RNA in serum 6 months after completion of treatment. During therapy, all patients had a careful professional support, including education and counselling by a nurse consultant. Results. The SVR rates were higher in the peginterferon plus ribavirin group (63%) than in interferon (20%) or interferon plus ribavirin (51%) groups. In the interferon and interferon plus ribavirin groups, there was a duration effect (12 months versus 6 months) upon the sustained response rate (25 and 17% in interferon group, 57 and 48% in interferon plus ribavirin group). Among patients with HCV genotype 1, the SVR rates were 23% in interferon plus ribavirin group and 50% in peginterferon plus ribavirin group. The rate for patients with genotype 2 and 3 infections was 77 and 73%, respectively. Twenty of 193 (10%) patients discontinued treatment because of adverse events or missed the examination at the end of treatment or follow-up. Conclusions. Our analysis indicates that the effectiveness of therapy for patients with chronic hepatitis C delivered in a hospital clinic setting is similar to that reported from published trials. Certainly, a close monitoring of the patients during therapy can produce effective outcomes. PO232 WHIPPLE DISEASE: A CASE REPORT G. Grasso, S. Giaccari, L. Allegretta, S. Tronci, S. Chiri Department of Gastroenterology, “S. Caterina Novella” Hospital, Galatina (LE), A.S.L. LE/01, Italy Background. Whipple’s disease (WD) is an uncommon chronic systemic disorder, by Tropheryma whippelii, involving a variety of organs, particularly the short bowel. The intestinal involvement can also arise some years after the clinical onset, often causing important diagnostic problems or serious interpretation mistakes. Case report. A 73-year-old male was admitted to hospital for evaluation of diarrhoea and weight loss. About 8 years earlier, he received diagnosis of polydistrict chronic artropathy by uric acid, treated with allopurinole and NSAIDs. After 6 years, the patient presented with left hemi-

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paresis by right silvian ischaemia. One year before our observation, he experienced progressive weight loss; thus, a barium enema, that demonstrated a dolichocolon, was performed. Then, the patient underwent a total body TC, that showed bilateral pleural effusion, suprarenal glands enlargement and intestinal loops dilatation. Laboratory findings showed anaemia, low serum iron and low serum albumin. At the admission, the patient’s general status was very serious, the whole body fat and muscle mass were hypotrophic (body weight 50 kg). Abdominal physical examination revealed intestinal meteorism. Laboratory findings demonstrated haemoglobin 9.8 g/dl, haematocrit 30.2%, MCV 68 fl, K 3.4 meq./l, Ca 8.1 meq./l. Chest X-ray, abdominal ultrasonography and colonoscopy were negative. An abdomen TC revealed mesenteric lymph nodes enlargement. At the EGDS, the duodenal folds were flat, with granulous mucosa. The duodenal biopsies showed massive infiltration of large, PAS-positive, diastase-resistant, Ziehl–Nielsen negative foamy cells, with lipidic vacuoles and lymphatic vessels dilatation, findings indicative for the diagnosis of WD. The patient underwent therapy based initially on streptomycin and amoxicilline, then on minocycline for 1 year, with clear improvement at the 12 months follow-up: in particular, the diarrhoea cleared up and the body weight increased to 80 kg. Conclusions. This case report puts in evidence the quick response to antibiotic therapy with rapid regress of diarrhoeic symptomatology and sharp improvement of general status.

Results. In the year 2002, 178,175 subjects aged 50–70 years were invited by mail to undergo screening test. Regional extension of the screening programmes was 36.8%. A total of 82,541 subjects (47.8%) performed the screening test. Positivity rate of the test was 5.0% and assessment compliance was 79.4%. Malignancies were found in 219 patients and at least a high-risk adenomatous polyp in 725 patients. Detection rate for histologically confirmed lesions per 1000 compliers was 2.6 for cancer and 8.8 for high-risk adenomas. In about one-fourth of the positive subjects who underwent assessment, cancer or high-risk adenoma was detected. Conclusions. Data from this experience supported the feasibility of biennial colorectal screening programme by FOBT, particularly regarding invitation compliance and positivity rate. Further efforts are necessary for implementing screening extension and for improving data collection.

PO233

According to standardised histologic criteria, the presence of lymphoepithelial lesions (LEL) in the gastric mucosa is diagnostic of or heralds gastric MALT lymphoma. However, the meaning of LEL is not clinically and pathologically well-defined. The aim of this study was to evaluate the association of these lesions with clinical, endoscopic and histological parameters also in relation with the possible evolution to gastric MALT lymphoma. Materials and methods. We have considered all patients who underwent an upper GI endoscopy in our centre from 1999 to 2003 and with a histological finding of LEL as the first diagnosis. Given the similar meaning in the context of two different pathways to cancer (adenocarcinoma and MALT lymphoma) they were compared with 42 patients with detection of “indefinite for dysplasia” (IfD) epithelial changes. Results. One hundred and forty-four cases of LEL were diagnosed in the time period considered (76 male, 70 female; mean age 52 years). LEL were an isolated finding in 133/146 and multifocal in 13. In 98 cases, there was an associated follicular infiltrate of mononuclear cells. Gastritis was moderate to severe in 139/146 cases and disease activity in 128. Atrophic changes were absent in 80/146 and intestinal metaplasia was similarly absent in 106. Helicobacter pylori was detected in 141/146 cases. In comparison with patients with IfD, patients with LEL had more severe gastritis, more severe disease activity and much less atrophic and metaplastic changes (P < 0.0001 for all parameters). Three patients developed MALT lymphoma in the follow-up and the only difference in this albeit small subgroup was a more frequent finding of multifocal LEL (P = 0.02). In conclusion, patients with LEL constitute a subgroup of patients in whom H. pylori infection causes a distinct type of gastritis, with more disease activity and much less “traditional” precancerous changes. The extent of which this is linked to host or bacterial factors is open to discussion and is under investigation. The risk of evolution to or association with MALT lymphoma is small but not negligible.

COLORECTAL CANCER SCREENING PROGRA- MME BY FAECAL OCCULT BLOOD TEST IN TUSCANY G. Grazzinia , C.B. Visiolia , M. Biaginib , G. Castiglionea , M. Confortinia , U. Ferroc , G. Finuccid , F. Franceschinie , S. Gozzif , P. Lopaneg , M. Percoh , T. Rubecaa , M. Zappaa a Centre

for Study and Prevention of Cancer (CSPO), Scientific Institute of Tuscany, Florence, Italy b Endoscopic Unit Civil Hospital Castelfiorentino, Local Health Unit 11, Italy c Endoscopic Unit, Versilia Hospital Lido di Camaiore, Local Health Unit 12, Italy d Endoscopic Unit, Civil Hospital Lucca, Local Health Unit 2, Italy e Department of Surgery, S.M. Annunziata Hospital Florence, Local Health Unit 10, Italy f Department of Gastroenterology, San Donato Hospital Arezzo, Local Health Unit 8, Italy g CORAT Civil Hospital Livorno, Local Health Unit 6, Italy h Department of Epidemiology, Local Health Unit 5 Pisa, Italy Introduction and aims. Screening with faecal occult blood test (FOBT) has been shown to be effective in reducing mortality from colorectal cancer. Tuscany was the first region in Italy where a screening programme for colorectal cancer by FOBT was activated region-wide. In the period 2000–2002, 7 out of 12 Local Health Units implemented a colorectal cancer screening programme by FOBT. The aim of this paper was to describe organisational aspects, a quality control model and the results of this experience. Material and methods. Colorectal cancer screening protocol was addressed to all subjects aged 50–70 years, living in the regional area who were invited via mail to perform a 1-day immunochemical FOBT, without any dietary restriction. Kits for FOBT were usually distributed by health operators of Sanitary Districts, General Practitioners, and volunteers. Subjects with negative FOBT were informed about their result by mail and advised to repeat screening after 2 years. Non-responders to the first invitation received a reminder, usually within 6 months, by mail. Subjects with a positive screening test were invited to undergo full colonoscopy. Colonoscopies were carried out at an endoscopic referral centre. Double contrast barium enema was performed when complete colonoscopy was not possible. Patients who had neoplasms were referred to surgical or endoscopic therapy, and subsequently they were enrolled in a follow-up programme.

PO234 LYMPHOEPITHELIAL GASTRIC LESIONS: WHAT IS THEIR MEANING AND WHEN ARE THEY TO BE DETECTED? F. Greco, M. Cassaro, F. Farinati, M. Franco, E. Georgopoulou, M. Rugge, C. Tieppo Department of Gastroenterology and Pathology, Padua University, Padua, Italy

PO235 USEFULNESS OF ENDOSCOPIC-APPLIED PLATE- LET-RICH PLASMA FOR HEALING OF ISCHAEMIC SURGICAL INTESTINAL ANASTOMOSES E. Grimaldi, G. Piai, M. Pacelli, R. Focareta, S. Misso, A. Minerva, G. Forte UOC Gastroenterologia, UOC Medicina Trasfusionale ed Immunoematologia, AORN San Sebastiano, Caserta, Italy

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Background and aim. Anastomosis ischaemia in patients surgically resected for various diseases is not a rare event, above all in patients with predisposing systemic diseases. Gastrointestinal bleeding is its most important prognostic feature and diagnosis is based mainly on endoscopic examination, in addition to radiologic imaging. Treatment is problematic due to ischaemia itself and to frequent co-morbidity. Platelet-rich plasma (PRP), a modification of fibrin glue made from autologous blood, is being widely used to deliver growth factors in high concentration to diseased sites, in most experiences those requiring osseous grafting. We evaluated the usefulness of application of PRP directly on the lesion at the moment of endoscopy in order to obtain a double result on haemostasis and on promoting ischaemic tissue regeneration. Material and methods. Autologous PRP has been prepared in our laboratory immediately after the endoscopic diagnosis and, always in less than 1 h, applied onto the lesion, under endoscopic guidance, by injection through standard endoscopic needles and by apposition through standard CPRE catheters. Seven patients (55–77 years old) with ischaemic anastomoses (five colonic and three gastro-jejunal) have been treated in the period June–October 2003. Healing of ischaemic areas was endoscopically verified at 7, 14 and 30 days. Results. Three patients at day 3 after the first PRP application and one patient at day 7 required a second PRP haemostatic treatment. Six patients had at least 70% of their lesion repaired at day 7. In all patients, at least 90% at day 14. One hundred percent of ischaemic areas were repaired at day 30. Conclusions. Our pilot experience shows that endoscopic-applied, autologous, safe and cheap, PRP may have a role in the treatment of ischaemic intestinal anastomoses, both for haemostasis and for promoting the tissue repair by its growth factors. This novel and potentially promising technique deserves a well-designed randomised controlled study to provide ultimate evidence of its efficacy. PO236 BILIARY STRICTURE BY CHOLEDOCHAL VAR- ICES: AN EXTREMELY RARE CAUSE OF OBSTRUCTIVE JAUNDICE C. Grossi, G. Coscarella, R. Travaglini, L. Risa, A. Scozzarro U.O.C Gastroenterologia ed Endoscopia Digestiva, Ospedale S. Giuseppe, Marino, Rome, Italy The case of 43-year-old patient with protein S deficiency and severe painless obstructive jaundice is reported. At clinical history, the patient had a small bowel resection due to superior mesenteric vein thrombosis 4 years before. Abdominal US with a high-resolution real-time sector scanner and Doppler detected a portal vein thrombosis, dilatation of intrahepatic ducts and proximal common hepatic duct (CHD) stricture. A spiral-CT confirmed the extra hepatic portal vein obstruction (EHPVO) and demonstrated the presence of choledochal varices. An endoscopic retrograde cholangiography (ERC), performed subsequently, evidenced a marked obstruction of the CHD, suggestive of extraluminal compression, with regular intrahepatic biliary ducts and alythiasic gallbladder. A 10F plastic stent 10 cm long was successfully placed and maintained for 6 months. The anti-thrombotic treatment, began soon after diagnosis of EHPVO, resulted in complete regression of the thrombus with a mild decrease in the size of the choledochal varices at CT scan. The vasculature of the bile ducts has separate capillary and venous plexuses in its wall and dual venous drainage through paracholedochal and epicholedochal venous plexuses. Multiple bridging collateral veins bypass the obstructed portal vein and, anastomosing with cystic and pyloric veins, provide an anatomic basis for the development of choledochal and gallbladder varices. EHPVO rarely results in obstructive jaundice due to decompression of the common bile duct by choledochal varices, and symptomatic biliary obstructions are even more rare. In this case, CT scan diagnosis of choledochal varices prior to ERC prevented to have brushing of the stenosis that may have caused massive bleeding, and internal drainage with a biliary stent successfully resolving the jaundice.

PO237 COLORECTAL CANCER (CCR) PREVENTION: A CASE-FINDING STUDY IN SYMPTOMATIC PATIENTS (PTS) S. Grossoa , D. Mazzuccoa , M. Vajoa , N. Segnanb , C. Senoreb , M. Sartorib , R. Suriania a Unità b Unità

di Gastroenterologia, Ospedale di Rivoli, Turin, Italy di Epidemiologia, CPO Piemonte, ASO S.G. Battista, Turin, Italy

Introduction and aim. CCR is the second most common cause of cancer-related death in Italy and prevention programmes can reduce the rate of death by detecting early cancer or premalignant lesions. Screening for CCR requires high costs and a complex planning. The association between CCR and macroscopical rectal bleeding is well established in adults more than 60 years of age; so it would be useful to select high-risk population to underwent colonoscopy for early diagnosis. Nevertheless, the exact rate of CCR and polyps as well as their colonic localisation are not known in people with rectal bleeding. Aim. (1) To estimate the incidence of CCR and polyps in subject presenting with “macroscopical rectal bleeding” in a setting of 55–75 years. (2) To evaluate the preferential colonic localisation of these lesions. Patients and methods. From May to October 2003, 40 patients were included in a preferential reservation list. All patients satisfied the following requisites: presence of macroscopical rectal bleeding; age from 55 to 75 years; no colonoscopy performed within the previous 2 years; no previous diagnosis of polyps, CCR, inflammatory bowel disease (IBD), any other cancer with a prognosis less than 5 years. Results. Thirty-nine out of the 40 eligible patients (19 selected by generalist and 20 by gastronterologist) underwent colonoscopy. Eighteen patients (46%) had a relevant diagnosis: seven (18%) CCR, eight (20.5%) major (size >10 mm) adenomatous polyps, two (5%) IBD, one (2.5%) ischaemic colitis. Three out of the seven CCR presented a polyp with carcinoma foci and four had advanced cancer. Ten out of the 11 major polyps and 3 out of the 4 advanced tumours (altogether 87%) were found distally to splenic flexure. Conclusions. Our results support the conception that the macroscopical rectal bleeding in over 55 years old patients is associated to remarkable bowel disease, particularly CCR and premalignant lesions with left colonic localisation. The total colonoscopy in this setting is useful in early diagnosis of CCR at low cost and should be encouraged in the prevention programme of CCR. PO238 ACUTE INTESTINAL OBSTRUCTION IS ASSOCIATED TO CARD15 MUTATIONS IN ITALIAN CROHN’S DISEASE (CD) PATIENTS D. Guagnozzia , A. Cossua , A. Viscidoa , V. Corletoa , V. Anneseb , A. Latianoa , G. Delle Favea , R. Caprillia a GI

Unit, Department of Clinical Sciences, University “La Sapienza”, Rome, Italy b GI Unit, S. Giovanni Rotondo (FG), Italy

CD results from a dysregulated intestinal immune response to intestinal microbial antigens, in genetically susceptible individuals. Three independent mutations (SNP8, SNP12, SNP13) in CARD15 gene was significantly associated with CD. However, the contribution of CARD15 mutations to disease susceptibility also varies in the different ethnic populations and genotype–phenotype relationships are still to be defined. Aims. To evaluate the prevalence of three CARD15 mutations in 91 in– out consecutive CD, 109 ulcerative colitis (UC) and 101 healthy controls, and to examine the genotype–phenotype relationships in CD group. Material and methods. The three CARD15 mutations were determined by using PCR with genomic DNA and direct sequencing analysis. All CD were classified on the basis of phenotype characteristics: age, disease location, behaviour and symptoms at diagnosis; smoking habits, disease

Abstracts location and behaviour during the follow-up, number of stenosis and fistulas, perianal disease, extraintestinal manifestations, pharmacological and surgical therapeutic management. Data analysis was performed by using χ2 or Fisher test applying Bonferroni’s correction and a two-tailed P < 0.05 was considered as significant. Results. In our population, the allelic and genotype frequencies of CARD15 mutations were significantly associated to CD. None of the controls or UC were homozygotes (OM) or compound heterozygotes (CET) for one of these mutations. In CD, the carriers of at least one mutation were 26/91 (28.6%). The frequencies of simple heterozygotes (ET), CET and OM were: 19/91, 4/91 and 3/91, respectively. A significant positive association was found between small bowel location and an acute intestinal obstruction at diagnosis and the carriers of at least one mutation (P = 0.036, OR: 0.33 (0.12–0.9) and P = 0.0025, OR: 0.125 (0.03–0.5), respectively), particularly with OM and CET genotype (P = 0.005, OR: 0.07 (0.01–0.6)). A positive trend between the number of surgery and the carriers of at least one mutation was found, but it did not reach statistical significance (P = 0.0469, OR: 0.3 (0.1–0.96)). No relationship between CARD15 mutations and the other phenotype characteristics was found. Conclusions. Our data confirm that CARD15 mutations were significantly associated with CD also in Italian population. The previous reported positive association of OM and CET genotype with small bowel location has been confirmed. A new positive association between the carriers of at least one mutation and the acute intestinal obstruction at diagnosis was also found. PO239 COMPUTER FLUID DYNAMICS ANALYSIS OF POST-PRANDIAL GALLBLADDER BILE FLOW IN GALLSTONE PATIENTS: EFFECT OF SHORT-TERM THERAPY WITH URSODEOSSICOLIC ACID M.P.L. Guarinoa , M. Sarzanob , S. Carottia , S. Emerenziania , M. Vannib , R. Cavigliaa , M. Grossoc , R. Allonia , P.L. Maffettoneb , M. Cicalaa a Dipartimento

Malattie Apparato Digerente, Università Campus Bio Medico, Rome, Italy b Dipartimento di Scienza dei Materiali e Ingegneria Chimica, Politecnico, Turin, Italy c Dipartimento di Ingegneria, Chimica Università Federico II, Naples, Italy

Background. Oral treatment with ursodeoxycholic acid (UDCA) prevents in vitro gallbladder (GB) muscle damage caused by acute cholecystitis and seems to reduce the risk of biliary pain and complications in gallstone (GS) patients. The effect of UDCA on in vivo GB motility is still controversial. Aim and methods. To assess the effect of short-term therapy with UDCA on GB motility, computer fluid dynamics (CFD) analysis of GB bile flow was performed before and after 30 days of UDCA therapy (10 mg/kg per day) in seven GS patients. Each patient underwent ultrasonographic (US) assessment of the GB in fasting condition and after a 500 ml, 500 kcal liquid meal. GB volumes were measured in the post-prandial phase for 90 min with a time sampling of 1 min. US study was also performed at the same times in two untreated patients. To simulate GB bile flow (two-dimensional description), the CFD software FluentTM was performed using the US volumes in all patients and in two healthy controls. US data were successively analysed with statistical tools. Results. Results of CFD analysis showed that bile mixing was significantly reduced in patients with respect to controls, thus supporting the important role of GB motility in GS formation. Ejection fraction, assessed by US, was unchanged after treatment (z = 0.5). After UDCA, CFD analysis showed an improved bile flow of the geometrical model that simulates the GB as shown by the increased number of wall fluctuations. The post-prandial phase was also characterised by a greater volume of bile in entrance into the GB and by a greater expulsion of the tracing spots which were present into the model at the beginning of the simulation. The results were also supported by the statistical–mathematical analysis of

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the US motility data: prior and after treatment the volumes were scarcely correlated (0.02 < K < 0.35) (k patients untreated from differently 0.6). The average GB volume of the 90 min study was increased upon UDCA treatment (range 7–67%). The increase was statistically significant in all patients. Conclusions. Despite the results of the traditional US parameters of GB motility, the fluido-dynamic analysis shows that short-time treatment with UDCA improves post-prandial GB bile turnover in GS patients. A controlled trial with long-term follow-up could better evaluate the relation, if any, between GB motility and GS disease complications. PO240 OXIDATIVE STRESS IN IBD: “d-Roms TEST” EVALUATION IN PATIENTS WITH CLINICAL REMISSION F.W. Guglielmia , S. Mazzuolib , D. Capognaa , R. Messanellia , N. Reganoa , S. Pispisaa , A. Guglielmic , C Panellad , A Francavillaa a DETO,

U.O. Gastroenterologia, Università degli Studi di Bari, Italy Gastrenterologia ed Endoscopia Digestiva, Centro di Riferimento Oncologico di Basilicata, Italy c DETO, U.O. Chirurgia e Trapianti di Fegato, Università degli Studi di Bari, Italy d Cattedra di Gastroenterologia, Università di Foggia, Italy b UO

Background. Oxidative stress (OS) is now considered an important pathogenetic factor in inflammatory bowel disease (IBD). In fact, few studies show that a significant increase of reactive oxygen metabolites (ROMs), sometime associated with a sensible reduction of antioxidant mechanisms, could be detected in IBD patients. The complete evaluation of OS requires multiple plasmatic and tissue determinations; for this reason, it is usually considered inadequate for a routine use in clinical practice. A new, simple, quick and inexpensive method is now available to assess ROMs (d-Roms test) plasma levels [1]. Aim of the study. In this study, we used d-Roms test to evaluate OS in Crohn disease (CD) and ulcerative colitis (UC) patients and to compare disease activity index with antioxidants plasma levels. Material and methods. Twenty-five IBD patients (13 male, 12 female) in stable clinical remission (15 CD and 10 UC) and 10 controls (CONT) were enrolled. The disease activity index was assessed, respectively, in CD and in UC, with CDAI and UCAI. Nutritional state was evaluated using body mass index (BMI) and plasma levels of antioxidants: zinc (Zn), copper (Cu) and magnesium (Mg). OS was measured with d-Roms test (Diacron, Grosseto, Italy). Results. CDAI (126 ± 85) and UCAI (2 ± 4) values confirm clinical remission in enrolled patients. In the table, we report results of our study.

CONT IBD

Age

BMI

d-Roms

Zn

Cu

Mg

40 ± 12 39 ± 15

22 ± 2 23 ± 3

293 ± 021 473 ± 119∗

120 ± 33 74 ± 16∗

121 ± 12 130 ± 34

1.9 ± 0.5 2.0 ± 0.1

Conclusion. The results of this study point out that oxidative abnormalities could be detected also in patients with clinical remission and without malnutrition. In fact, our data confirm the presence OS in IBD as demonstrated by a significant (P < 0.0001) increase of d-Roms test and by a significant (P < 0.0001) decrease of plasma Zn. Furthermore, we observed that CD patients with short bowel disease treated with home parenteral nutrition have normal SO levels. Reference [1] Cornelli U, Terranova R, Luca S, Cornelli M, Alberti A. Bioavailability and antioxidant activity of some food supplements in men and women using the d-Roms test as a marker of oxidative stress. J Nutr 2001;131:3208–11.

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PO241 CT ENTEROCLYSIS AND CONTRAST RADIOLOGY FINDINGS IN CROHN’S DISEASE: CLINICAL CORRELATIONS L. Guidia , L.M. Minordib , S. Semeraroa , I. De Vitisa , A. Papaa , C. Giangregoriob , M. Politib , I. Robertoa , S. Ennasa , R. Urgesia , A. Grilloa , A. Parrellab , M.G. Brizib , A. Vecchiolib , G. Fedelia a UO

di Gastroenterologia, Istituto di Medicina Interna e Geriatria, Università Cattolica del Sacro Cuore, Rome, Italy b UO di Radiodiagnostica, Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy

Aim. The aim of this study was to evaluate the clinical correlates of CT enteroclysis patterns in patients with Crohn’s disease, as compared to contrast radiology and endoscopic findings. Patients and methods. Twenty-seven patients with pathologically proven Crohn’s disease were studied by means of helical single detector CT (13) or multidetector CT (14), after administration of low density contrast by mouth (9) or by nasojeunal tube (18). The following parameters have been evaluated: bowel wall thickening, bowel wall enhancement with contrast, presence of target sign and of complications. Approximately 8 h after performing CT, all patients were studied by means of small bowel follow-through (9) or by small bowel enteroclysis by nasojeunal tube (18). Clinical activity was assessed by CDAI score, and ESR, CRP, alpha1 glycoprotein and fibrinogen values were also recorded. In 21 patients, colonoscopy with retrograde ileoscopy and histology was also performed. Results. CT findings were rated as pathological in 85% of our patients, while barium studies detected abnormal findings in 70% of the patients. Concordance with endoscopy was recorded in 62% of the patients for CT and in 52% of the patients for barium studies. All patients with CDAI >150 had one or both exams scored as pathologic. Moreover, 80% of the patients with CDAI <150 showed abnormalities in one or both exams, including previously unknown internal fistulas in six patients (40%). Conclusions. The present study underscores the clinical usefulness of performing CT enteroclysis in combination with conventional diagnostic studies in Crohn’s disease patients. We detected a relatively high number of fistulising disease among low CDAI patients: possible modifications of patient management in this subgroup could be driven by this combined imaging modality. PO242 SHORT-TERM OUTCOME OF THE LONGO PROCEDURE FOR RECTOCELE: A CLINICAL AND DEFECOGRAPHIC STUDY F.I. Habiba , M. Zippia , A. Coccoa , D. Badialia , A. Cavigliab a Dipartimento b Ospedale

di Scienze Cliniche, Università ‘La Sapienza’, Italy Forlanini, Rome, Italy

The aim of the present study was to evaluate the short-term clinical and anorectal function outcome in a consecutive series of patients who underwent surgery according to the Longo procedure [1] for rectocele in patients with anorectal dysfunctions. Material and method. From January 2002 to November 2003, 14 consecutive female patients with a mean age of 50 ± 9 years, range 37–70 years, were included in the study. No one was previously submitted to any other kind of surgery. All pre-menopausal women were checked for pregnancy. Before and 36 months after surgery, all patients were studied with a validated questionnaire for evaluation of symptoms and defecography, according to a previously published method [2]. Results. Before surgery, 11/14 patients experienced straining in >25% defaecation and lumpy or hard stools. These symptoms persisted after surgery in only one patient. After surgery, 7/14 patients reported more than three small amount of stool frequency per day (piecemeal evacuation). Furthermore, while no patient complained of faecal urgency/incontinence before surgery, five patients experienced faecal incontinence 3–6 months postoperatively. Other subjective symptoms reported before and/or after

the surgical procedure included: sensation of incomplete evacuation (six patients before and six after), manual manoeuvres to facilitate defaecations (four patients before and one after), less than three defaecations per week (seven patients before and four after). Of the eight patients using laxatives before the procedure, three discontinued their use after the procedure and four continued to use bulking agents. At defecography, rectal diameter and size of rectocele were significantly reduced after surgery (7.5 cm versus 5.4 cm, P = 0.0006; 3.8–1.9 cm, P = 0.0002, respectively). No significant change was observed after surgery in pelvic floor location at rest or pelvic floor descent during evacuation and in anorectal angle during functional manoeuvres. Conclusions. The Longo procedure besides reducing the size of the rectocele and the rectal diameter appears to affect anorectal function. Straining in >25% evacuations is relieved in the majority of patients, however, urgency incontinence and piecemeal evacuation is a frequent finding after surgery. Data suggest that the reduced volume of the rectum plays a major role in determining the outcome of anorectal function in patients submitted to the Longo procedure. References [1] Longo A. Dis Colon Rectum 2002;571–2. [2] Habib FI, et al. Dig Dis Sci 1992;37:500–5.

PO243 ENDOSCOPIC MANAGEMENT OF A GIANT GASTRIC PHYTOBEZOAR Y. Hadad, P. Benedicenti, F. Letizia, F. Maurichi, T. Verrienti Division of General Surgery and Digestive Endoscopy, “Cardinale Giovanni Panico” Hospital, Tricase (LE), Italy Case report. Bezoars are tightly packed foreign masses of solidified organic or non-organic materials that are formed in the gastrointestinal tract and are commonly found in the stomach and small bowel. Large gastric bezoars may occur in patients with gastric dysmotility disorders like gastroparesis or in patients with partial gastric resection or vagotomy. Treatment options include a variety of methods: dissolution with gastric saline or coca cola lavage, enzymatic therapy, promotility agents, endoscopic methods and surgery. We report the case of a 57-year-old man who presented a 2-day history of nausea vomiting abdominal pain and symptoms of upper partial small bowel obstruction. In the history, the patient had peptic ulcer disease and was operated for a vagotomy. Material and methods. The upper endoscopic examination showed a giant phytobezoar, about 10 cm of diameter, located in the gastric antrum. Motility of the gastric body was rare, the pylorus was opened. We decided to use a polypectomy snare and grasping forceps for the fragmentation of the phytobezoar. The procedure required about 50 min and the particles small enough to pass through the pylorus were left to do so. Later on the same day, we began an oral lavage with polyethyleneglycol (PEG) based solution about 6 l in 2 days. Results. The endoscopy control showed the complete success, without any complication, and no residual material of the phytobezoar was found. In the antrum, there were two benign ulcers. Conclusions. Endoscopic therapy is the ideal treatment even for a giant phytobezoar, its outcome is immediately evident. It is minimally invasive with a lower morbidity compared to surgery. It is a rapid and effective method if compared to medical dissolution which may take weeks with an uncertain result. The treatment should also be taken into consideration to prevent the recurrence of phytobezoars and may alter the conditions that contribute to their formation.

Abstracts PO244 Helicobacter pylori ERADICATION RESULTS IN THE REGRESSION OF MILD GLANDULAR ATROPHY BUT NOT OF INTESTINAL METAPLASIA WITHIN 36 MONTHS OF FOLLOW-UP F. Iacopini, A. Consolazio, P. Crispino, M. Rivera, O.A. Paoluzi, R. Pica, D. Palladini, P. Paoluzi Gastroenterology Unit, Department of Clinical Sciences, University “La Sapienza”, Rome, Italy Background. Presence and progression of glandular atrophy (GA) and intestinal metaplasia (IM), considered as preneoplastic conditions, are correlated to Helicobacter pylori infection, however, contradictory data exist about the regression of these lesions after eradication. Aim. To investigate the evolution of atrophic gastritis and intestinal metaplasia after H. pylori eradication during a long-term follow-up. Methods. Eighty-one H. pylori-positive patients in whom the infection was eradicated after standard triple therapy at histology, urea-breath test and rapid-urease test were enrolled. All patients were controlled endoscopically and histologically at 2, 6, 12, 24 and 36 months after eradication. Histopathology was carried out on three biopsies from antrum and two from the corpus at each control. Score of gastritis and H. pylori status was evaluated according to the updated Sydney system. Results. Before H. pylori eradication, active and chronic inflammation were significantly higher in antrum than in corpus (P < 0.001, both), disappearing almost completely in 12 and 36 months, respectively, both in antrum and corpus. Prevalence and severity of atrophy and IM were significantly higher in the antrum (34 and 29%, respectively) than in corpus (7 and 3%, respectively). After eradication, severity of GA decreased significantly at 24 months both in antrum and corpus (P = 0.003 and 0.41), while IM did not change neither in antrum or in corpus. However, the regression of atrophy appeared to be limited to mild lesions (grade 0–1) (P = 0.01). At 36 months after eradication, no significant changes in the patterns of gastritis were found both in antrum and corpus. Conclusions. H. pylori eradication is followed by a progressive reduction, till a complete disappearance, of active and chronic inflammation in the antrum and in the corpus prevents the progression of atrophy and intestinal metaplasia, and induces a regression of mild glandular atrophy. Severity of GA and GIM di grado lieve e severo nell’antro e nel corpo (mean ± S.D.) before and after H. pylori eradication. Antrum 0 Month

Corpus 12 Months

36 Months

0 Month

12 Months

36 Months

GA Mild (0–1) 0.85 ± 0.36 0.88 ± 0.33 0.75 ± 0.44∗ 0.44 ± 0.50 0.40 ± 0.52 0.33 ± 0.47∗ Severe (2–3) 2.21 ± 0.41 2.03 ± 0.43 2.08 ± 0.47 2.22 ± 0.44 2.00 ± 0.50 2.11 ± 0.60 GIM Mild (0–1) 0.87 ± 0.34 0.78 ± 0.52 0.71 ± 0.51 Severe (2–3) 2.19 ± 0.40 2.17 ± 0.45 2.14 ± 0.54 ∗

0.36 ± 0.46 0.31 ± 0.49 0.31 ± 0.46 2.33 ± 0.52 2.00 ± 0.85 2.17 ± 0.41

P < 0.05 when compared with follow-up.

PO245 CENTRAL ADIPOSITY AND TRYGLICERIDAEMIA AS RISK FACTORS OF COLON AND RECTAL ADENOMA F. Ievoli, G. Grimaldi, M. Pacelli, P. Rocco, F. Forte, G. Forte UOC Gastroenterologia, AORN San Sebastiano, Caserta, Italy Background and aim. Insulin and insulin-like growth factor (IGF) axes are major determinants of proliferation and apoptosis, thus influencing colorectal carcinogenesis. Central adiposity is a critical determinant of insulin resistance. Hyperinsulinaemia and triglyceridaemia may be considered reliable markers of this metabolic imbalance. Few data are available about the risk of colon and rectal adenomas in relation to these factors. The aim of this study is to evaluate the association between body fat distribution, triglyceridaemia and colorectal adenomas risk.

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Material and methods. In the period January–December 2002, 180 patients with colon adenoma and 47 with rectal adenoma were observed in our Endoscopy Unit for polypectomy. The colon adenomas were separated in three groups according to: small (<5 mm), medium (>5 mm and <10 mm), and large (>10 mm). Controls were subjects with negative colonoscopy. The waist/hip ratio (WHR), as marker of central adiposity, was calculated in each patient. Results are reported for each group as relative risk (RR), defined as the incidence of adenoma in the highest quartile of WHR divided by the corresponding value among the patients in the lowest quartile. Triglyceridaemia was expressed as mean ± S.D. Results. Controls

Colon adenomas Small

Patients number WHR H/L quartile, RR (95% CI) Triglyceridaemia (mg/dl)

93 1.0

92 1.6 (1.2–2.4)

106 ± 47 135 ± 72

Rectal adenomas Medium 60 2.1 (1.6–3.0)

173 ± 77 (P < 0.01)

Large 28 3.6 (2.8–6.4)

178 ± 41 (P < 0.01)

47 1.2 (1.0–1.7)

98 ± 24

Conclusions. Central adiposity and triglyceridaemia strongly correlate with increased risk of colon, but not of rectal adenomas. This correlation is higher in large than in small colon adenomas and suggests a major role of growth factors of hyperinsulinaemia just in the multistep carcinogenesis process of colon. PO246 ENDOSCOPIC THERAPY FOR MALIGNANT BILIARY STRICTURES IN PATIENTS 90 YEARS OF AGE AND OLDER S. Incarbone, G. Trama, G. Bonanno, A. Calzona, G. Aprile, P. Naso, A. Russo Cattedra di Gastroenterologia, Università di Catania, Italy Background. Palliation for malignant biliary obstruction should be achieved with minimum disturbance to the patient and with as good a quality of life as possible for the remaining weeks or months. Few studies have assessed the safety and the early outcome of stent insertion in the very elderly patients (90 years of age and older). We reviewed our experience of endoscopic palliation for malignant biliary strictures in this type of patients. Patients and methods. Retrospective review of 36 consecutive patients (14 men and 22 women; mean age 92.5 years, range 90–97 years) observed in one institution (Gastroenterology and Digestive Endoscopy Unit, University of Catania) between January 1990 and December 2002. Index neoplasia were located on the biliary tree in 24 cases (12 CBD, 6 gallbladder and 6 ampullary), the remaining 12 cases were pancreatic cancer. The insertion of a plastic stent (10–12 F) was attempted in all cases. Success rate, complications and early outcome were evaluated. Results. ERCP was performed in 97.2% of the patients (35/36), one failure was related to neoplastic infiltration of the duodenal wall. The success rate of stent insertion was 88.6% (31/35). The rate of early complications (three bleedings) was 8.3%. No death was related to endoscopic manoeuvres Twenty of the 35 patients did not develop biliary complications until their deaths (mean survival time 6 months, range 5–11 months). The remaining 15 patients developed obstructive jaundice (9) or cholangitis (6) requiring a mean of 1.4 stent exchanges. Mean survival time was 8 months, range 3–13 months. Conclusions. Endoscopic palliation for malignant biliary obstruction is safe and effective for very old patients. Early morbidity is similar to that reported for younger patients. The insertion of a plastic stent is cost-effective in patients with a short life expectancy.

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Abstracts

PO247 NON-EROSIVE REFLUX DISEASE (NERD) IN PATIENTS WITH NON-CARDIAC CHEST PAIN (NCCP) A. Indriolo, F. Negrini, S. Signorelli, M.G. Lucà M. Strazzabosca Gastroenterology and Endoscopy Unit, Ospedali Riuniti, Bergamo, Italy The identification of non-erosive reflux disease (NERD) as a cause of symptoms in patients presenting with NCCP has not been systematically investigated. Aim. To investigate the occurrence of NERD in patients presenting with NCCP and assess the pathophysiological differences between NERD, patients with erosive disease and patients without reflux. Methods. One hundred and two patients (52 males; mean age 47 years) diagnosed with NCCP after a complete cardiac evaluation underwent upper gastrointestinal endoscopy, ambulatory 24 h oesophageal pH-monitoring and oesophageal manometry. Data obtained from pH-manometry performed on 22 healthy volunteers used as control. Results. In 42% of the patients, both endoscopy and pH-metry were normal (group 1); in 40% of the patients, endoscopy was normal but pH-metry showed pathological reflux (NERD) (group 2); in 18% an erosive disease was present at endoscopy and pathological reflux at pH-metry (GERD) (group 3). No difference was found between NERD and GERD patients in total time of pH below 4 (NERD 7.2% median value, 4.4– 21.0 range; GERD 10.0%, 4.0–21.0) as well as in the pattern of acid reflux (NERD’s percentage of time below 4 in supine position median value 5, range 0–33; GERD’s 6, 0.3–21; in upright position 10, 2.7–18.8 in NERD and 10, 3–29.3 in GERD). Positive symptom index (SI) was present in 20% of cases in group 1, 23% in group 2 and 11.7% in group 3 (P < 0.005 versus group 3). Major motility abnormalities were significantly more common in patients without reflux as compared to NERD and GERD (18.6% group 1, 4.8% group 2 and 5.5 and group 3, respectively) (P < 0.003). The prevalence of reflux-related aspecific motility disorders (AMD) was not significantly different in NERD as compared to GERD (13.9% in group 1, 39% in group 2 and 61.1% in group 3). Conclusions. (1) An oesophageal abnormality was the possible cause of NCCP in 72% of patients (NERD, GERD, positive SI or major motility abnormalities). (2) Reflux disease accounted for 58% of patients with NCCP with an higher prevalence of NERD (40%) as compared to GERD (18%). (3) SI positivity was significantly increased in NERD as compared to GERD, in spite of similar reflux pattern and AMD, suggesting that an increased visceral sensitivity may be responsible for symptoms in NCCP patients and NERD.

Results. PGI values before and after different PPI treatment were (baseline sPGI after therapy, sPGI, P (Wilcoxon test)): omeprazole (20 patients), 83 ± 25, 134 ± 90, 0.019; pantoprazole (27 patients), 72 ± 18, 110 ± 27, 0.000; esomeprazole (29 patients), 74 ± 24, 125 ± 56, 0.000; lansoprazole (21 patients), 67 ± 15, 112 ± 29, 0.000; rabeprazole (26 patients), 72 ± 21, 101 ± 22, 0.000. Conclusions. sPGI levels are significantly influenced by antisecretory therapy, increasing under PPI treatment. PO249 A NEW MARKER FOR MONITORING ALCOHOL ABUSE? A PILOT STUDY ON HEAVY DRINKERS A. Ingegnolia , E. Biasinib , I. Bonib , N. Altavillaa , F. Landinib , R. Merlia , V. Ioria , G.M. Cavestroa , G. Aragonaa , G.L. Cavallaroa , M. Mainoa , A. Franzèc , P. Vescovib , F. Di Marioa a Department

of Clinical Sciences, University of Parma, Italy of Internal Medicine, University of Parma, Italy c Gastroenterology Unit, Parma, Italy b Department

Gastric mucosa actively participate in the absorption of alcohol. Data in literature show an alteration of serum pepsinogens (sPGI and sPGII) in case of drinking habits. The influence of quitting alcohol on gastric secretion in patients with alcohol abuse problems is still be assessed. Aims and methods. To evaluate the effect of quitting alcohol on serum pepsinogens levels in patients with alcohol abuse problems. In a group of 27 patients (20 male, 7 female; mean age 46±11 years; range 31–70 years), all with alcohol intake problems (>60 g per day), first blood samples were taken. Second blood samples were taken after 15 days quitting alcohol. In both cases, sPGI, sPGII and IgG anti-Helicobacter pylori levels were determined by ELISA method (Biohit, Helsinki, Finland). H. pylori status was also assessed with H. pylori stool antigen (HpSA) with a commercial EIA test (Meridian, Bioscence, Ohio, USA). Results. The mean values of sPGI in alcoholic patients were 88 ± 155 relative to the first blood samples and 81 ± 161 relative to the second one (P = 0.033); the mean values of sPGII were 9.7 ± 6.06 for the first blood samples and 8.3 ± 17.8 for the second one (P = 0.002 by Wilcoxon test). Nine out of the 27 patients resulted H. pylori positive. The mean value of PGI and PGII in H. pylori positive were 90.63 ± 42.6 and 9.8 ± 4.9, respectively. Conclusion. sPGI and sPGII levels decreased with statistically significance in patients with alcohol abuse problems after a 2-week period of no alcohol intake. PO250

PO248 INFLUENCE OF ANTISECRETORY TREATMENT WITH PROTON PUMP INHIBITORS (PPIs) ON SERUM PEPSINOGENS LEVELS

DOES Helicobacter pylori INFECTION ERADICATION MODIFY PEPTIC ULCER PREVALENCE? A COMPARATIVE OF TWO AREAS WITH DIFFERENT SENSIBILISATION FOR H. pylori ERADICATION BY GENERAL PRACTITIONERS

A. Ingegnolia , N. Altavillaa , S. Bertolinia , R. Merlia , G.M. Cavestroa , V. Ioria , G.L. Cavallaroa , G. Serenia , N. Stefania , S. Liatopouloua , A. Bertelèb , A. Franzèb , F. Di Marioa

V. Ioria , G. Nervib , N. Dal Bòc , A.M. Moussaa , L.G. Cavallaroa , A. Ingegnolia , G.M. Cavestroa , A. Gnocchib , P. Muzzettob , A. Pilottod , G. Collab , A. Franzéb , F. Di Marioa

a Department

a Department

of Clinical Science, University of Parma, Italy Unit, Parma, Italy

of Clinical Sciences, University of Parma, Italy Unit, Parma, Italy c Gastroenterology Unit, Treviso, Italy d Geriatrics Unit, San Giovanni Rotondo, Italy

b Gastroenterology

b Gastroenterology

Aim of the study. To evaluate the influence of proton pump inhibitors therapy on PGI levels. Methods. It has been evaluated PGI levels (EIA, Biohit, Helsinki, Finland) in 126 consecutive patients (57 male, 69 female; mean age 53 years, range 15–91 years), with upper gastrointestinal symptoms at baseline condition and after 2 months of proton pump inhibitors (PPI) treatment. Patients underwent a therapy with: omeprazole 20 mg bid (20 patients), pantoprazole 40 mg bid (27 patients), esomeprazole 40 mg bid (29 patients), lansoprazole 15 mg bid (21 patients) and rabeprazole 20 mg bid (26 patients).

Helicobacter pylori infection eradication deeply modified the natural history of peptic ulcer disease. The use of eradication therapy by general practitioners could change in peptic ulcer prevalence. Aim. The aim of our study was to compare peptic ulcer prevalence in patients referred to Endoscopy Unit of two zones in era-H. pylori and 10 years after the progressive diffusion of therapy. Methods. We double checked all the endoscopy consecutively performed in Gastroenterology Department of University of Padua area with diffuse

Abstracts sensibilisation of general practitioners (Project Ulcer Free) for peptic ulcer prevention with H. pylori eradication (from 1986 to 1997), and in Gastroenterology Unit of Parma (area with minor sensibilisation (from 1992 to 2002). Statistics. Chi-square test. Results. The table summarises the changes of prevalence of peptic ulcer after 10 years. Conclusion. These findings suggest that H. pylori eradication may lead to consider peptic ulcer as a rare endoscopic finding in area with diffuse sensibilisation of eradication of H. pylori by general practitioners. The prevalence of peptic ulcer after 10 years is given in the table. 1986 (%) Padua Total ulcers Duodenal ulcer Gastric ulcer

Parma Total ulcers Duodenal ulcer Gastric ulcer

11.5 8.2 3.3

1997 (%)

4.2 3.2 1.0

P-value <0.001 <0.001 <0.001

1992 (%)

2002 (%)

P-value

18.22 11.92 6.3

11.93 6.68 5.25

NS NS NS

PO251 EPIDEMIOLOGY OF THE IBD IN A GEOGRAPHICAL MICROAREA OF THE NORTHERN SUBURBS OF NAPLES R. Iorio, G. Bruno, L. Morlando, F. Guardascione Gastroenterology Unit, “St. Giuliano” Hospital, ASL NA2, Italy We have calculated from 1986 to December 2001, the incidence and the prevalence of the IBD on our territory. The considered patients are 208 (94 females, 114 males), none black. Pathologies were defined as Crohn’s disease (CD, 6 cases, 2.8%, mean age 41 years), ulcerative colitis (UC, 152 cases, 73.07%, mean age 43 years) and indefinite colitis (50 cases, 24.03%, mean age 45 years) according to Lennard–Jones; Truelove, Ashley B. Prince criteria. All the cases of CD were of colic location. The 22% of the UC were females; 22.7% were pancolitis, 48.9% were left colitis and 28.4% were proctitis. There is in apparent inverse relationship among social condition and UC. The 16% of Crohn are smokers against 15.5% of RCI; but high percentage (37%) of UC are ex-smokers. The 6.3% of the women included in the study does or did use the oral contraceptives. The 2.7% of patients with familiarity for IBD has CD; 3.1% has CU. Conclusions. The annual incidence of the IBDs in our area is of 5.3/100,000, similar to the rest of Italy but with differences in the greater subgroups. The prevalence is of 13/100,000 inhabitants per year, inferior to the national average. PO252 SMALL BOWEL AUTOTRANSPLANTATION FOR PANCREATIC ADENOCARCINOMA INVOLVING THE SUPERIOR MESENTERIC ARTERY E. Jovine, F. Biolchini, F. Martuzzi, F. Talarico, A. Lazzari, E. Polito, P. Billi, N. D’Imperio UU.OO. di Chirurgia Generale A e di Gastroenterologia ED Endoscopia Digestiva, Ospedale Maggiore, Bologna, Italy Brief background and aim. The presence of vascular involvement due to adenocarcinoma of the head of the pancreas is still considered by some authors as a contraindication for surgery. Nevertheless, several authors recently demonstrated an improved survival after pancreatectomy with

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associated resection of the superior mesenteric vein or the portal vein. The involvement of the superior mesenteric artery, however, still remains an absolute contraindication for surgery. Material and methods. The authors described the sixth case in the literature of small bowel autotransplantation in a 60-year-old woman, affected by an adenocarcinoma of the head of the pancreas with infiltration of the superior mesenteric artery. Intraoperatively, a neoplastic involvement of the common hepatic artery was detected, thus, a revascularisation of the liver by an end-to-end anastomosis of the common hepatic artery with the left gastric artery, had to be performed. Then, the stomach, duodenum, pancreas, spleen, small, bowel, right colon, extrahepatic bile duct, cephalad superior mesenteric vein and proximal superior mesenteric artery were resected, with en-bloc dissection of the paraaortic lymph nodes. The resected organs were flushed through the superior mesenteric artery with chilled Celsior solution, placed in an ice-cold bath and, then, the total pancreatectomy was performed. The free small bowel was autotransplanted by anastomosing the cephalad portal