Rationale for antifungal prophylaxis with fluconazole in necrotizing pancreatitis

Rationale for antifungal prophylaxis with fluconazole in necrotizing pancreatitis


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911 OCTREOTIDE ACETATE PRETREATMENT IN THE PREVEN· TION OF POST·ERCP ABDOMINAL PAIN. Marko Duvnjak, Vladimir Supanc, Velimir N. Simicevic, Davor Hrabar, Branko Troskot, Tatjana Supanc, Univ Hosp Sestre Milosrdnice, Zagreb, Croatia. Background & Aim. Complications related to endoscopic retrograde cholangiopancreatography (ERCP) represent a serious medical problem for both patient and physician. One such complication is the development of post-ERCP abdominal pain. The aim of this study was, therefore, to determine if prophylactic administration of octreotide acetate (OA) could decrease the incidence of abdominal pain in patients undergoing therapeutic ERCP. Patients & Methods. A double-blind study was conducted in a total of 209 subjects who were randomly allocated to two groups (A and B). Group A (104 patient)received 0.5 mg of OA subcutaneously one hour prior to ERCP; group B (105 patients)was given isotonic sodium chloride in the same manner. Following ERCP, patients were assessed at various times for the following parameters: presence and character of abdominal pain, and requirements for analgetics. Pain was graded using a simple scoring system (0 - none, I - mild, 2 - moderate, 3-severe). Patients who complained of pain were asked about its location and character, whether it was similar to pre-existing pain and whether there was radiation to the back. For those patients who required pain medication, the type of medication and route of administration were recorded.Patients who developed acute pancreatitis were included in the highest score group.Comparison of data between the two groups was performed using Cochran-Mantel-Haenszel analysis. A p value ";0.05 was considered to indicate statistical significance. Results.A total of 39 patients (18%)complained of post-ERCP pain- 10 in group A and 29 in group B, all of which were treated with analgetics.More detailed information is shown in Table 1. Conclusion. The results of our study indicate that OA pretreatment significantly reduced the development of post-ERCP pain.

Table 1.Abdominal pain score


Group A

Group B






2 3


2' 10'



'Distribution ofpain scores was significantly different between both groups.

912 USEFULNESS OF ENDOSCOPIC ULTRASONOGRAPHY OF THE COMMON BILE DUCT IN ACUTE BILIARY PANCREATITIS. Prat Frederic, Edery Joel, Meduri Bruno, Ayoun Charles, Bodart Michel, Grange Didier, Loison Francoise, Nedelec Pierre, Sbai-Idrissi Mohamed, Vergeau Bertrand, Valverde Alain, Hepato-Biliary Ctr Bachaumont, Paris, France; Bachaumont Hepato-Biliary Ctr, Paris, France; Hosp, Mantes-LaJolie, France; Surg Ctr, Melun, France; Hosp, Evry, France; Hosp, Nemours, France; Surg Ctr, ChampignylMame, France; Hosp, Eaubonne, France; Veterans Affairs Hosp, Saint-Mande, France; Hosp, Saint-Denis, France. The management of common bile duct lithiasis (CL) during biliary pancreatitis (BP) remains controversial. Endoscopic sphincterotomy (ES) is beneficial in some subgroups of patients, but also induce complications . Endoscopic Ultrasonography (EUS) is accurate for the diagnosis of CL and can select candidates for ES. Characteristics of patients referred for EUS have been prospectively recorded on a database. Of 2434 bilio-pancreatic EUS performed between january 1993 and june 1999, 355 had acute pancreatitis; 220 had criteria for BP. 123 patients from 22 centers were followed. All had an EUS followed by ES during the same anesthesia in case of CL. We studied patients' outcomes depending on initial severity of BP (Ranson + Balthazar scores), presence of CL and timespan between onset of BP and EUS+ES. The study group included 57 men and 66 women (median age 55 years, range 17-87). 35 patients (28%) had a Ranson score >3 on admission and 38 (31%) were classified Balthazar D or E. 14 patients (11%) were cholecystectomized. 75 (60%) were cholestatic and 39 (30%) had clinical biliary obstruction. The median timespan between admission and EUS was 3 days. EUS exploration of the bile duct was complete in all but 3 patients (1 external drainage, 2 Billroth II gastrectomies). 33 patients (27%) had CL on EUS, 8 of which were impacted in the papilla. CL was more frequent in case of jaundice (p<0.005) and when EUS was performed < 3 days after admission (p<0.05). The incidence of CL on EUS was not different if BP was mild or severe. The 33 patients with CL underwent ES with extraction of 58 stones. 12 other patients underwent ERCP (3 incomplete EUS, 5 inoperable patients, 2 suspected ampullomas and 2 cholecystectomized patients with

a gallbladder remnant containing stones). 99 patients (80%) recovered without complications, 79 were cholecystectomized shortly after recovery. 2 patients (1.6%) died, I developed recurrent BP within 2 months, 6 (5%) had further biliary symptoms and 17 (14%) developed complications of pancreatitis (9 pseudocysts and 3 mild ES-related complications -i.e. 6.6% post-ES complications-). Our management strategy was based on selective ES depending on the presence of ductal stones on early EUS during BP, not on the predicted severity of BP. In this series, mortality and complications of ES were low and not related to the predicted severity of BP or to the presence of CL. Controlled trials are needed to confirm the superiority of this strategy over current recommendations for the management of BP.

913 RATIONALE FOR ANTIFUNGAL PROPHYLAXIS WITH FLUCONAZOLE IN NECROTIZING PANCREATITIS. Helmut Friess, Shailesh Shrikhande, Marcus E. Martignoni, Claudia Issenegger, Huang Yong, Jorg H. Kleeff, Markus W. Buchler, Univ of Bern, Bern, Switzerland. A significant shift in the microbial spectrum of infected pancreatic necrosis towards fungi has been observed in recent years. This seems to be caused by prophylactic antibiotic use to prevent bacterial contamination of pancreatic necrosis. In order to evaluate the potential role of the antifungal drug fluconazole in the prophylaxis andlor treatment of fungal contamination of pancreatic necrosis, in this study we have evaluated the penetration of the antifungal agent fluconazole into human pancreatic tissue and in acute edematous and necrotizing pancreatitis in rats. In 15 patients (9 men and 6 women) undergoing pancreatic surgery, 400 mg fluconazole was given intravenously and serum and pancreatic tissue andlor juice concentrations were measured simultaneously. Furthermore, fluconazole penetration into the pancreas of rats with edematous and necrotizing pancreatitis, was also examined. In man, the mean (:!: SD) serum concentration of fluconazole after 1 h, 2 h, and 4 h was 6.19 :!: 1.30, 10.40 :!: 2.06, and 7.82 :t 1.01 ILg/ml, respectively. The mean pancreatic tissue concentration was 8.19 :t 3.38 ILg/g (96% of corresponding serum concentration) at the time of resection (162 :!: 52 min after the start of fluconazole infusion). In edematous and necrotizing pancreatitis in rats, fluconazole tissue levels were 88% and 91% of the corresponding serum levels, respectively. In conclusion, our study demonstrates, that fluconazole penetrates in sufficient concentrations into the human pancreas and also in pancreatitis tissues. Our results suggest that clinical trials are needed to analyze whether antifungal prophylaxis -in addition to antibiotic prophylaxis- is useful in the treatment of necrotizing pancreatitis.

914 INCREASED EXPRESSION OF PHOSPHOLIPASE A2 ISOFORMS IN ACUTE PANCREATITIS SUGGESTS A ROLE IN ITS PATHO· BIOLOGY. Helmut Friess, Jorg H. Kleeff, Erick Riesle, Mikiya Kashiwagi, Arthur Zimmermann, Waldemar Uhl, Markus W. Buchler, Univ of Bern, Bern, Switzerland; Univ of Ulm, Ulm, Germany. Phospholipase A2 (PLA2) plays an important role in inflammatory conditions by generating arachidonic acid, which is the substrate for prostaglandin, prostacyclin, and leucotrien synthesis. In the present study, we examined phospholipase A2 isoforms (Group I, II and IV) in acute pancreatitis in humans and rats to determine whether the source of these mediators lies in the exocrine pancreas itself. The expression and localization of PLA2 isoforms were analyzed by Northern blot analysis and immunohistochemistry in pancreatic tissues obtained from 21 patients with acute necrotizing pancreatitis. PLA2 isoforms were also analyzed in pancreatic tissues of rats with acute edematous and necrotizing pancreatitis. In human acute pancreatitis PLA2-1 mRNA expression decreased 8.9 fold (p