Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A case–control study

Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A case–control study

+ MODEL Asian Journal of Surgery (2016) xx, 1e8 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.e-asianjournalsurger...

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Asian Journal of Surgery (2016) xx, 1e8

Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.e-asianjournalsurgery.com

ORIGINAL ARTICLE

Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study Ayman El Nakeeb*, Ali Salem, Yousef Mahdy, Mohamed El Dosoky, Rami Said, Mohamed Abd Ellatif, Helmy Ezzat, Ahmed M. Elsabbagh, Hosam Hamed, Talaat Abd Alah, Gamal El Ebidy Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt Received 18 August 2016; received in revised form 12 October 2016; accepted 24 October 2016

KEYWORDS endoscopic retrograde cholangiopancreatography; obstructive jaundice; periampullary; pancreaticoduodenectomy; postoperative pancreatic fistula

Summary Background/Objective: The potential benefit of preoperative biliary drainage (PBD) on postoperative outcomes remains controversial. The aim of this study was to elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with PBD and to show the impact of bilirubin level. Methods: We retrospectively studied all patients who underwent PD in our center between January 2003 and June 2015. Patients were divided into: Group A (PBD) and Group B (no PBD). The primary outcome was the rate of postoperative complication. Results: A total of 588 cases underwent PD. Group A included 314 (53.4%) patients while Group B included 274 (46.6%) patients. The overall incidence of complications and its severity were higher in Group A (p Z 0.03 and p Z 0.02). There was significant difference in the incidence of postoperative pancreatic fistula (p Z 0.002), delayed gastric emptying (p Z 0.005), biliary leakage (p Z 0.04), abdominal collection (p Z 0.04), and wound infection (p Z 0.04) in Group A. The mean length of hospital stay was significantly longer in Group A than in Group B (12.86  7.65 days vs. 11.05  7.98 days, p Z 0.01). No significant impact of preoperative bilirubin level on surgical outcome was detected. Conclusion: PBD before PD was associated with major postoperative complications and stentrelated complications. Copyright ª 2016, Asian Surgical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).

* Corresponding author. Gastroenterology Surgical Center, Mansoura University, Mansoura 35516, Egypt. E-mail address: [email protected] (A. El Nakeeb). http://dx.doi.org/10.1016/j.asjsur.2016.10.004 1015-9584/Copyright ª 2016, Asian Surgical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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1. Introduction Periampullary tumor is a widely-used term to define a heterogeneous group of tumors arising from the head of the pancreas (40e60%), ampulla of vater (10e20%), the distal common bile duct (10%), the duodenum wall (5e10%), or uncinate process (2%).1,2 Pancreaticoduodenectomy (PD) is considered the only curative treatment for obstructive jaundice due to periampullary tumor. The resectability rates of periampullary tumor vary from 14% to 30%.3e5 The surgical outcome of PD has improved dramatically over recent years due to improvement in surgical techniques, anesthesia, and perioperative care.3 Although high volume centers have reported decline in the hospital mortality to < 5%, the postoperative morbidity rate is still high, ranging from 25% to 60%.3e9 The hazardous sequence of prolonged and progressive obstructive jaundice affects different organs and can result in hepatic dysfunction due to stasis of bile and superadded infection, renal failure, cardiac dysfunction, hemostatic defects, and altered body immunity.7e11 Preoperative restoration of biliary flow (preoperative biliary drainage; PBD) can be performed by percutaneous transhepatic biliary drainage (PTD) under radiological guidance or by endoscopic retrograde cholangiopancreatography (ERCP) and stent placement.12,13 Some authors performed PBD for selected cases in patients presenting with cholangitis or high serum bilirubin with high liver enzymes to improve their condition sufficiently preoperatively.14,15 However, others perform PBD routinely in all patients with obstructive jaundice to relieve biliary obstruction and treat the pathophysiological changes caused by obstructive jaundice.12e15 Despite effective PBD to reduce serum bilirubin level, the majority of prospective, retrospective, or metaanalysis studies have not shown improvement in postoperative outcomes but increase in infectious complications.11e15 Several experimental studies have demonstrated beneficial effects of PBD: better immune and liver functions and reduction of endotoxemia a few weeks after biliary drainage.13,16 However, the potential benefit of PBD on postoperative outcomes remains controversial and many clinical studies have failed to show this benefit and some studies even showed a harmful effect.14,15,17 The aim of this study was to elucidate the role of PBD on surgical outcomes of PD and to show the impact of serum bilirubin level on the surgical outcomes.

2. Methods 2.1. Patients This retrospective study investigated all consecutive patients who underwent PD in the period between January 2003 and June 2015 in the Gastrointestinal Surgical Center, Mansoura University, Egypt. The indications for PD were periampullary tumors (malignant or benign), solid pseudopapillary tumors, pancreatitis, and neuroendocrinal tumors. The patients were divided into two groups based on PBD: Group A (PBD) and Group B (no PBD). Patient data were recorded in a prospectively maintained database for all patients undergoing pancreatic surgery since

A. El Nakeeb et al. 2000. Collected data included patient demographics, preoperative, operative, postoperative details, including postoperative morbidity, and mortality. Informed consent for the surgical procedures was obtained from each patient. This study was approved by the Institutional Research Board Mansoura Faculty of Medicine (MFM), Mansoura university.

2.2. Preoperative assessment Preoperative assessment included clinical assessment, routine laboratory investigations, radiological investigations (ultrasound, magnetic resonance cholangiopancreatography, and abdominal computerized tomography). PBD was done by ERCP. It was not done routinely preoperative but was performed in selected patients, when biliary obstruction was associated with high bilirubin  10 mg/dL, cholangitis or hepatic dysfunction (transaminase: more than threefold normal i.e., > 120 IU/mL).

2.3. Operative details All patients were operated on by an experienced surgeon in our gastroenterology surgical center. Classic PD was performed. The pancreas was divided anterior and to the left of superior mesenteric vein and portal vein with excision of mesopancreas. All patients underwent regional lymphadenectomy, which included resection of nodes within the outline of celiac, superior mesenteric artery, and all tissues in hepatoduodenal ligaments. Pancreatic reconstruction was performed by pancreaticogastrostomy or pancreaticojejunostomy (simple loop or isolated loop) according to the surgeon’s preference. Biliary drainage was performed retrocolic (end to side hepaticojejunostomy). Gastric drainage was done by antecolic or retrocolic gastrojejunostomy, which was performed manually or by a stapler.

2.4. Postoperative management All patients were managed in the intensive care unit for at least 1 day. All patients received prophylactic antibiotics intraoperatively and for 4 days postoperatively.

2.5. Assessments The primary outcome was the rate of postoperative complication proposed by Dindo and colleagues.18 According to this system, Grade I (no need for specific intervention), Grade II (need for drug therapy such as antibiotics, blood transfusion, total parenteral nutrition), Grade IIIa-b (need for invasive therapy whether radiological, endoscopic, or surgical), Grade IVa-b (organ dysfunction requiring intensive care unit stay and management), Grade V (death). Grades IeIIIa complications were considered minor, while Grades IIIbeV were considered major complications. In patients who experienced more than one complication, we chose the highest-grade complication for the purpose of comparison between the groups. Postoperative complications including postoperative pancreatic fistula (POPF) was defined by International Study Group of Pancreatic Fistula as any measurable volume of fluid on or

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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Biliary drainage before pancreaticoduodenectomy after postoperative day (POD) 3 with amylase content more than three times the serum amylase activity. Nineteen POPF was graded according to the International Study Group of Pancreatic Fistula criteria into Grades A, B, and C according to the clinical course19 and delayed gastric emptying, biliary leakage, bleeding pancreaticogastrostomy, bleeding gastrojejunostomy, internal hemorrhage, and pulmonary complications. Delayed gastric emptying was defined as output from a nasogastric tube of > 500 mL/d that persisted beyond the 10th POD, the failure to maintain oral intake by the 14th POD, or reinsertion of a nasogastric tube. Biliary leak was defined as the presence of bile in the drainage fluid that persists to the 4th POD.19,20 Secondary outcomes were total operative time, operative time needed for reconstruction, length of postoperative stay, reexploration, and survival rate. Statistical analysis of the data in this study was performed using SPSS software, version 17 (SPSS Inc., Chicago, IL, USA). Descriptive data were expressed as median (range). Categorical variables were described using Table 1

3 frequency distributions. Independent sample t test was used to detect differences in the means of continuous variables and Chi-square test was used in cases with categorical variables. A p value < 0.05 was considered significant. Variables with p < 0.05 were entered into a linear regression model to determine independent factors for development of severe postoperative complications.

3. Results A total number of 588 cases underwent classic PD for resection of periampullary neoplasm in the Gastroenterology Surgical Center. Group A (PBD) included 314 (53.4%) patients while Group B (no PBD) included 274 (46.6%) patients. The groups were comparable with no significant difference between them as regard the patient demographics (age, sex, body mass index, diabetes mellitus), preoperative laboratory investigation (Table 1). Sixty-five patients (17.8%) with PBD had post endoscopic PBD

Demographic data and intraoperative data.

Variables Age (y) < 60 > 60 Sex Male Female Body mass index (kg/m2)  25 >25 Diabetes mellitus No Yes Median prestent bilirubin (mg/dL) Median preoperative bilirubin (mg/dL) Median preoperative albumin (g/dL) Median preoperative SGPT (IU/L) Median preoperative serum amylase (U/L) Complication of PBD Pancreatitis and hyperamylasemia Acute cholecystitis Duodenal perforation Cirrhotic liver Pancreatic consistency Firm Soft Common bile duct diameter (mm) Common bile duct pus Empyema gall bladder Type of pancreatic reconstruction Pancreaticogastrostomy Simple loop pancreaticojejunostomy Isolated loop pancreaticojejunostomy Operative time (h) Blood loss (mL) Blood transfusion (units)

PBD

No PBD

p

358 (60.9) 230 (39.1)

182 (58) 132 (42)

176 (64.2) 98 (35.8)

0.12

352 (59.9) 236 (40.1)

183 (58.3) 131 (41.7)

169 (61.7) 105 (38.3)

0.4

429 (73) 159 (27)

222 (70.7) 92 (29.3)

207 (75.5) 67 (24.5)

0.19

454 (77.2) 134 (22.8) 12.3 (0.4e40) 4.45 (0.4e20) 4 (3e5.1) 56 (25e495) 121 (15e1331)

241 (76.8) 73 (23.2) 14 (5e40) 3.2 (0.4e20) 4 (3e5) 52 (38e392) 123 (19e1331)

213 (77.7) 61 (22.3) 8.1 (0.4e15) 8.1 (0.4e15) 4.1 (3.2e5.1) 62 (25e495) 113 (15e971)

0.77

42 12 2 89 (15.1)

42 (13.4) 12 (3.9) 2 (0.64) 55 (17.5)

0 0 34 (12.4)

0.09

228 (38.8) 360 (61.2) 15 (5e30) 51 (8.7) 51 (8.7)

124 (39.5) 190 (60.5) 15 (5e30) 34 (10.8) 34 (10.8)

104 (38) 170 (62) 15 (5e30) 17 (6.2) 17 (6.2)

0.7

474 (80.6) 68 (11.6) 46 (7.8) 5 (3e9) 500 (50e3000) 0 (0e4)

253 (80.6) 32 (11.7) 21 (7.7) 5 (3e9) 500 (100e3000) 0 (0e4)

221 (80.7) 36 (11.5) 25 (8) 5 (3e9) 400 (50e3000) 0 (0e4)

0.0001 0.0001 0.49 0.03 0.92

0.42 0.05 0.05 0.98

0.9 0.71 0.05

Data are presented as n (%) or median (range). PBD Z preoperative biliary drainage; SGPT Z serum glutamicepyruvic transaminase.

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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A. El Nakeeb et al.

complications in the form of pancreatitis, acute cholecystitis, or duodenal perforation that delayed PD. In the current study, 314 patients (53.4%) underwent PBD. The indications for PBD were 210 patients (66.9%) with bilirubin > 10 mg%, 80 patients (25.8%) with high liver enzymes (above 120 mg %), 17 patients (5.4%) considered for neoadjuvant therapy, and only seven patients (2.2%) with cholangitis. Post-ERCP complications developed only in 56 cases (17.8%): pancreatitis and hyperamylasemia in 42 cases (13.4%), acute cholecystitis in 12 cases (3.9%), and duodenal perforation in two cases.

3.1. Operative data There was no difference in pancreatic texture, liver status, common bile duct (CBD) diameter, blood loss, type of pancreatic reconstruction, or operative time between groups. Blood transfusion is significantly more in Group A. There was a statistically higher incidence of CBD pus and empyema of the gall bladder in Group A (p Z 0.05; Table 1).

Table 2

3.2. Postoperative data The overall incidence of complications and its severity were higher in Group A (p Z 0.03 and p Z 0.02). There was significant difference in the incidence of POPF and its severity (p Z 0.002), delayed gastric emptying and its grads (p Z 0.005), biliary leakage (p Z 0.04), abdominal collection (p Z 0.04), and wound infection (p Z 0.04) in Group A. Hospital mortality was higher in Group A but this was not statistically significant (p Z 0.06; Table 2). The median length of hospital stay was significantly greater after PD in group A (10 days; range, 5e71 days) compared to in Group B (8 days; range, 5e71 days; p Z 0.01). However, there was no significant difference between groups as regards postoperative stay (p Z 0.73), nasogastric tube removal (p Z 0.59), and resuming oral intake (p Z 0.33; Table 2). Direct logistic regression was performed to assess the impact of a number of variables that they had a problem with severity of postoperative complications. The model

Postoperative outcomes.

Variables Postoperative albumin (gm%) Postoperative bilirubin (mg%) Median postoperative SGPT (IU/L) Median postoperative serum amylase (U/L) Complications Complications grade I II III IV V Severe complications ( IIIb) Minor Major Pancreatic leakage Pancreatic leakage Grade A Pancreatic leakage Grade B Pancreatic leakage Grade C Delayed gastric emptying Grade A Grade B Grade C Biliary leakage Abdominal collection Wound infection Bleeding pancreaticogastrostomy Bleeding gastrojejunostomy Pancreatitis Reoperation Nasogastric tube removal (d) Oral intake (d) Hospital mortality Postoperative stay (d) Hospital stay (d)

PBD

No PBD

p

3 (2.1e4) 2.3 (0.4e44) 84 (26e1323) 125 (9e4500) 168 (28.6)

3 (1.8e4) 1.9 (0.5e44) 80 (27e1140) 125 (9e2094) 102 (32.5)

3 (2.3e4) 3.5 (0.4e30) 85 (26e1323) 125 (12e4500) 66 (24.1%)

0.27 0.0001 0.24 0.55 0.03

99 (16.8) 26 (4.4) 21 (3.6) 1 (0.5) 22 (3.8)

53 20 14 0 16

(5.1)

46 (16.8) 6 (2.2) 7 (2.6) 1 (0.36) 6 (2.2)

129 (21.9) 40 (6.8) 86 (14.6) 39 (6.6) 31 (5.3) 16 (2.7) 105 (17.9) 43 (7.3) 53 (9) 9 (1.5) 49 (8.3) 91 (15.5) 43 (7.3) 10 (1.7) 16 (2.7) 12 (2) 46 (7.8) 5 (2e56) 6 (4e56) 22 (3.7) 8 (5e71) 9 (5e71)

75 (23.9) 28 (8.9) 59 (18.8) 27 (8.6) 21 (6.7) 12 (3.8) 69 (22) 24 (7.6) 39 (12.4) 6 (1.9) 33 (10.5) 62 (19.7) 32 (10.2) 3 (1) 8 (2.5) 7 (2.2) 25 (8) 5 (2e50) 6 (5e50) 16 (5.1) 8 (5e70) 10 (5e71)

54 (19.7) 12 (4.4) 27 (9.9) 12 (4.4) 10 (3.6) 4 (1.5) 36 (13.1) 19 (6.9) 14 (5.1) 3 (1.1) 16 (5.8) 29 (5.8) 11 (4) 7 (2.6) 8 (2.9) 5 (1.8) 21 (7.7) 5 (2e56) 6 (4e56) 6 (2.2) 8 (5e71) 8 (5e71)

(16.9) (6.4) (4.5)

0.02

0.03 0.002 0.01 0.005 0.01

0.04 0.04 0.004 0.13 0.78 0.73 0.89 0.59 0.33 0.06 0.73 0.01

Data are presented as n (%) or median (range). PBD Z preoperative biliary drainage; SGPT Z serum glutamicepyruvic transaminase.

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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Biliary drainage before pancreaticoduodenectomy

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contained 10 variables (Table 3). The full model containing all predictor below with p < 0.05. The strongest predictors of reporting severe postoperative complication were pancreatic duct diameter and body mass index > 25 kg/m2 (independent variables; Table 3).

Table 4 outcome. Variables

There was no significant difference between groups of bilirubin level as regards preoperative data, blood loss, blood transfusion, pancreatic texture, pancreatic duct, operative time, postoperative complications, time to remove nasogastric tube, time to resume oral intake, hospital mortality, and hospital stay (Tables 4 and 5). The incidence of pus in CBD was significantly more in the group with bilirubin level < 10 mg% (p Z 0.01). The CBD diameter was 15 mm (range, 5e30 mm) in the group with bilirubin level < 10 mg% compared to 15 mm (range, 8e30 mm) in the other group (p Z 0.0001; Table 4).

4. Discussion

Table 3

Bilirubin < 10 mg (n Z 318)

Age (y) < 60 y 189 (59.4) > 60 y 129 (40.6) Sex Male 204 (64.15) Female 114 (37) Body mass index 234 (73.6)  25 kg/m2 84 (44) > 25 kg/m2 Diabetes mellitus No 245 (77) Yes 73 (23) Cirrhotic liver 55 (17.3) Preoperative 210 (66) biliary drainage Pus in common 36 (11.3) bile duct Common bile duct 15 (5e30) diameter (mm) Pancreatic texture Soft 202 (63.5) Firm 116 (36.5) Pancreatic duct diameter (mm) <3 111 (34.9) >3 207 (65.1) Operative time (h) 5 (3e9) Blood loss (mL) 475 (50e3000) Blood transfusion 0 (0e4) (units)

3.3. Impact of bilirubin level on outcome

Obstructive jaundice is associated with an inflammatory response and increased systemic and portal levels of endotoxins and different cytokines such as tumor necrosis factor and interleukin 6.21,22 The endotoxin increased in portal circulation as a result of decreased bile salts in the intestinal lumen leading to increased bacterial microflora and increased intestinal permeability promoting bacterial translocation.23 The exposure to endotoxemia and bacterial translocation altered the immune system and Kupffer cells and lead to an uncontrolled inflammatory cascade. Thus, obstructive jaundice increased the risk of infectious complications, coagulopathy, myocardial dysfunction, and renal impairment.21e23 There are different methods of PBD either internal (by ERCP) or external (by PTD). Although both procedures draining the biliary system, the pathophysiologic consequence of ERCP is different from PTD in terms of restoration of enterohepatic circulation, inflammatory reaction and colonization of biliary system.23e25 The drawbacks of

Impact of preoperative bilirubin level on Bilirubin >10 mg (n Z 270)

p

169 (62.6) 101 (37.4)

0.43

174 (64.4) 96 (35.6)

0.56

195 (72.2) 75 (27.8)

0.71

209 (77.4) 61 (22.9) 34 (12.6) 104 (38.5)

0.91 0.11 0.001

15 (5.6)

0.01

15 (8e30)

0.0001

158 (58.5) 112 (41.5)

0.21

78 (28.9) 192 (71.1) 5 (3e9) 500 (50e3000) 0 (0e4)

0.12 0.11 0.97 0.97

Data are presented as n (%) or median (range).

ERCP have become clear: biliary stent induce bacterial contamination, cholangitis, liable to obstruction and generate severe inflammation and thickening in the wall of CBD which increase the risk of bile leakage of

Predictors of severity of postoperative surgical complications. Unstandardized coefficients B

(Constant) 1.582 Pre ERCP bilirubin level 0.005 ERCP 0.060 Pancreatic duct diameter 0.043 Pancreatic duct < 3 mm 0.159 Pancreatic duct close to posterior border 0.002 Pancreatic duct close to posterior border < 3 mm 0.094 Diabetes mellitus 0.096 0.108 Body mass index > 25 kg/m2 Pathological type 0.005

Standardized t coefficients

Std. Error b 0.177 0.003 0.049 0.012 0.073 0.013 0.061 0.056 0.053 0.005

0.070 0.050 0.208 0.123 0.007 0.078 0.066 0.079 0.041

p

95.0% confidence interval for B Lower

8.921 1.730 1.232 3.704 2.191 0.133 1.548 1.703 2.031 1.036

< 0.001 1.234 0.084 0.000 0.218 0.036 < 0.001 0.066 0.029 0.301 0.894 0.028 0.122 0.214 0.089 0.015 0.043 0.004 0.301 0.005

Upper 1.930 0.011 0.156 0.020 0.016 0.024 0.025 0.206 0.212 0.015

a

Dependent Variable: severity of complications. ERCP Z endoscopic retrograde cholangiopancreatography.

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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A. El Nakeeb et al. Table 5

Impact of preoperative bilirubin level on outcome (postoperative data).

Variables

Bilirubin < 10 mg (n Z 318)

Bilirubin >10 mg (n Z 270)

p

Postoperative albumin (g%) Postoperative bilirubin (mg%) Complications Complications grade I II III IV V Severe complications ( IIIb) Minor Major Abdominal collection Biliary leakage Pancreatic leakage Pancreatic leakage Grade A Pancreatic leakage Grade B Pancreatic leakage Grade C Delayed gastric emptying Bleeding pancreaticogastrostomy Bleeding gastrojejunostomy Wound infection Pancreatitis Re-exploration Nasogastric tube removal (d) Oral intake (d) Hospital stay (d) Hospital mortality

3 (2.9e4) 1.3 (0.4e18) 95 (29.9)

3 (2e4) 5.7 (0.5e44) 73 (27)

0.82 0.0001 0.45

60 (18.9) 13 (4.1) 13 (4.1) 0 9 (2.8)

39 (14.4) 13 (4.8) 8 (3) 1 (0.38) 11 (4.1)

0.24

75 (23.6) 20 (6.3) 53 (16.7) 53 (7.2) 50 (15.7) 24 (7.5) 15 (4.7) 11 (3.5) 63 (19.8) 5 (1.6) 5 (1.6) 22 (6.9) 7 (2.2) 19 (6) 5 (2e56) 6 (4e56) 8 (5e71) 12 (3.8)

54 (20) 20 (7.4) 38 (14.1) 26 (9.6) 36 (13.3) 15 (5.6) 16 (5.9) 5 (1.9) 42 (15.6) 5 (1.9) 11 (4.1) 21 (7.8) 5 (1.9) 27 (10) 5 (2e35) 6 (4e40) 9 (5e45) 10 (3.7)

0.53 0.39 0.29 0.41 0.43

0.18 0.79 0.06 0.69 0.76 0.07 0.58 0.63 0.86 0.69

Data are presented as n (%) or median (range).

hepaticojejunostomy.13,15,25 Hepatic function, immune system, bile duct epithelium, and Kupffer cells will fully recover only after at least 4e6 weeks after biliary drainage even if the bilirubin level has decreased to normal level.23,26 The reduction of bilirubin level has been found in some experimental studies to correct coagulation abnormalities, improve immune system, and decrease the incidence of bacterial translocation and endotoxemia. Despite these experimental results, PBD remains controversial. Furthermore, some recent studies suggest a harmful effect of PBD on postoperative outcomes due to infectious complications.23,24 Also, biliary drainage carries its own complications including pancreatitis, cholecystitis, cholangitis, and perforation.24 PBD is associated with increased incidence of postoperative complication when performed before PD. Furthermore, the procedures used for PBD carry their own morbidity. Unfortunately, most of the available studies about PBD before PD suffers from heterogeneity and methodological defects (difference in type of study, type of PBD, duration of drainage, sample size).13,15,23e25 Recently, magnetic resonance cholangiopancreatography and spiral computed tomography have replaced diagnostic ERCP for assessment of patients with obstructive jaundice, as routine stenting of CBD after diagnostic ERCP

in patients with obstructive jaundice is mandatory to prevent cholangitis.23,24 Many studies found that PBD was associated with higher incidence of positive intraoperative bile culture and morbidity related to infection with high mortality rate.12,23,27e29 They reported that PBD was performed in selected patients and should be avoided in patients who undergo PD.27e29 Several meta-analysis studies published in the past 10 years concluded that there was no significant increase in major morbidity and mortality rate and reported that PBD should performed for selected patients and not performed routinely.12e14 Lygidakis et al,30 in a prospective randomized study support PBD and reported less postoperative complication in the PBD group (16% vs. 70%) and increased hospital mortality in the non-PBD group (0 vs. 2/19). Smith et al31 concluded that high bilirubin level had adverse effect on early postoperative outcome. Singhirunnusorn et al27 studied 100 consecutive patients who underwent PD and found no significant difference in rates of mild complications (42% in PBD group vs. 35% in non-PBD group) or severe complications (37% in PBD group vs. 32.8% in non PBD). Also, no significant difference as regards hospital mortality and individual complication such as POPF, delayed gastric emptying, bile leaks, reoperation, collection, and wound infection between both groups.32,33

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

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Biliary drainage before pancreaticoduodenectomy In this study, the overall incidence of complications was higher in the PBD group (32.5% in Group A vs. 24.1% in Group B). The rate of serious complications was higher in Group A (8.9% vs. 4.4%) There was significant difference in the incidence of POPF and its severity, delayed gastric emptying and its grads, biliary leakage, abdominal collection and wound infection in Group A. Mezhir et al34 reported that PBD was associated with procedure-related morbidity in 23% and more than double the postoperative infectious complications over the non-PBD group (19% vs. 8%). In the current study, 65 patients (17.8%) with PBD had postendoscopic PBD complications that delayed PD by nearly 4 weeks. Despite effective improvement of hyperbilirubinemia by PBD, the surgical outcomes were not improved.33,34 Sewnath et al33 divided the patients according to preoperative bilirubin level into three subgroups (normal, moderate, and severe jaundice) and found that there was no difference in overall complications (49%, 50%, and 52%, respectively) and hospital stay. The bilirubin level alone should not be the routine indication for PBD as our results showed that no impact of bilirubin level in any postoperative morbidity after PD.35e37 Therefore, PBD before PD should be performed in selected patients who have cholangitis, renal impairment, dehydration, coagulopathy, profound malnutrition, or who receive neoadjuvant therapy.32,34 In our study, PBD is a desirable procedure in patients with cholangitis, severe jaundice, or highly elevated transaminase. In these circumstances, PD cannot be safely performed without PBD. A limitation of this study was the retrospective design, but patient data were recorded in a prospectively maintained database for all patients undergoing PD since 2000 in our center. Therefore, prospective randomized studies are needed to confirm the role of PBD in surgical outcome after PD and to show the optimum duration of drainage if needed.

5. Conclusion PBD before PD was associated with major postoperative complications and stent-related complications. There was no impact of preoperative bilirubin level in any postoperative morbidity after PD. PBD should be performed in selected patients who have cholangitis, renal impairment, dehydration, coagulopathy, or profound malnutrition or who receive neoadjuvant therapy.

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Conflicts of interest All authors have no conflicts of interest to declare.

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References

20.

1. Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985e1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1e7. 2. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Bu ¨chler MW. Curative resection is the single most important factor

21.

determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586e594. Engelken FJ, Bettschart V, Rahman MQ, Parks RW, Garden OJ. Prognostic factors in the palliation of pancreatic cancer. Eur J Surg Oncol. 2003;29:368e373. El Nakeeb A, Salah T, Sultan A, et al. Pancreatic anastomotic leakage after pancreaticoduodenectomy. Risk factors, clinical predictors, and management (single center experience). World J Surg. 2013;37:1405e1418. Yamashita Y, Shirabe K, Tsujita E, et al. Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients. Langenbecks Arch Surg. 2013;398:539e545. El Nakeeb A, El Shobary M, El Dosoky M, et al. Prognostic factors affecting survival after pancreaticoduodenectomy for pancreatic adenocarcinoma (single center experience). Hepatogastroenterology. 2014;133:1426e1438. Smith RA, Bosonnet L, Ghaneh P, et al. The plateletelymphocyte ratio improves the predictive value of serum CA19-9 levels in determining patient selection for staging laparoscopy in suspected periampullary cancer. Surgery. 2008;143:658e666. Robinson JR, Marincola P, Shelton J, Merchant NB, Idrees K, Parikh AA. Peri-operative risk factors for delayed gastric emptying after a pancreaticoduodenectomy. HPB (Oxford). 2015;17:495e501. Pauli-Magnus C, Meier PJ. Hepatocellular transporters and cholestasis. J Clin Gastroenterol. 2005;39(Suppl. 2):S103eS110. Nehe ´z L, Andersson R. Compromise of immune function in obstructive jaundice. Eur J Surg. 2002;168:315e328. Papadopoulos V, Filippou D, Manolis E, Mimidis K. Haemostasis impairment in patients with obstructive jaundice. J Gastrointestin Liver Dis. 2007;16:177e186. Fang Y, Gurusamy KS, Wang Q, et al. Meta-analysis of randomized clinical trials on safety and efficacy of biliary drainage before surgery for obstructive jaundice. Br J Surg. 2013;100: 1589e1596. Sewnath ME, Karsten TM, Prins MH, Rauws EJ, Obertop H, Gouma DJ. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg. 2002;236:17e27. El Nakeeb A, Hamdy E, Sultan AM, et al. Isolated Roux loop pancreaticojejunostomy versus pancreaticogastrostomy after pancreaticoduodenectomy: a prospective randomized study. HPB (Oxford). 2014;16:713e722. Wang Q, Gurusamy KS, Lin H, Xie X, Wang C. Preoperative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2008;3:CD005444. Hunt DR, Allison ME, Prentice CR, Blumgart LH. Endotoxemia, disturbance of coagulation, and obstructive jaundice. Am J Surg. 1982;144:325e329. Saleh MMA, Norregaard P, Jorgensen HL, Andersen PK, Matzen P. Preoperative endoscopic stent placement before pancreaticoduodenectomy: a metaanalysis of the effect on morbidity and mortality. Gastrointest Endosc. 2002;56:529e534. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240: 205e213. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8e13. Pratt WB, Maithel SK, Vanounou T, Huang ZS, Callery MP, Vollmer Jr CM. Clinical and economic validation of the International Study Group of Pancreatic Fistula (ISGPF) classification scheme. Ann Surg. 2007;245:443e451. Parks RW, Clements WD, Smye MG, Pope C, Rowlands BJ, Diamond T. Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal biliary drainage. Br J Surg. 1996;83:1345e1349.

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004

+

MODEL

8 22. Clements WD, McCaigue M, Erwin P, Halliday I, Rowlands BJ. Biliary decompression promotes Kupffer cell recovery in obstructive jaundice. Gut. 1996;38:925e931. 23. van der Gaag NA, Kloek JJ, de Castro SM, Busch OR, van Gulik TM, Gouma DJ. Preoperative biliary drainage in patients with obstructive jaundice: history and current status. J Gastrointest Surg. 2009;13:814e820. 24. Lermite E, Pessaux P, Teyssedou C, Etienne S, Brehant O, Arnaud JP. Effect of preoperative endoscopic biliary drainage on infectious morbidity after pancreatoduodenectomy: a casecontrol study. Am J Surg. 2008;195:442e446. 25. Cahill CJ. Prevention of postoperative renal failure in patients with obstructive jaundice- the role of bile salts. Br J Surg. 1983;70:590e595. 26. Koyama K, Takagi Y, Ito K, et al. Experimental and clinical studies on the effect of biliary drainage in obstructive jaundice. Am J Surg. 1981;142:293e299. 27. Singhirunnusorn J, Roger L, Chopin-Laly X, Lepilliez V, Ponchon T, Adham M. Value of preoperative biliary drainage in a consecutive series of resectable periampullary lesions. From randomized studies to real medical practice. Langenbecks Arch Surg. 2013;398:295e302. 28. Povoski SP, Karpeh MS, Conlon KC, Blumgart LH, Brennan MF. Preoperative biliary drainage: impact on intraoperative bile cultures and infectious morbidity and mortality after pancreaticoduodenectomy. J Gastrointest Surg. 1999;3:496e505. 29. Povoski SP, Karpeh Jr MS, Conlon KC, Blumgart LH, Brennan MF. Association of preoperative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann Surg. 1999; 230:131e142.

A. El Nakeeb et al. 30. Lygidakis NJ, van der Heyde MN, Lubbers MJ. Evaluation of preoperative biliary drainage in the surgical management of pancreatic head carcinoma. Acta Chir Scand. 1987;153: 665e668. 31. Smith RA, Dajani K, Dodd S, et al. Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2008;15:3138e3146. 32. Pisters PW, Hudec WA, Hess KR, Lee JE, Vauthey JN, Lahoti S. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg. 2001;234:47e55. 33. Sewnath ME, Birjmohun RS, Rauws EA, et al. The effect of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy. J Am Coll Surg. 2001;192: 726e734. 34. Mezhir JJ, Brennan MF, Baser RE, et al. A matched case-control study of preoperative biliary drainage in patients with pancreaticadenocarcinoma: routine drainage is not justified. J Gastrointest Surg. 2009;13:2163e2169. 35. Arkadopoulos N, Kyriazi MA, Papanikolaou IS, et al. Preoperative biliary drainage of severely jaundiced patients increases morbidity of pancreaticoduodenectomy: results of a casecontrol study. World J Surg. 2014;38:2967e2972. 36. van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:129e137. 37. Qiu YD, Bai JL, Xu FG, Ding YT. Effect of preoperative biliary drainage on malignant obstructive jaundice: a meta-analysis. World J Gastroenterol. 2011;17:391e396.

Please cite this article in press as: El Nakeeb A, et al., Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A caseecontrol study, Asian Journal of Surgery (2016), http://dx.doi.org/10.1016/j.asjsur.2016.10.004