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Biliary Complications Following Liver Transplantation: Single-Center Experience
Biliary Complications Following Liver Transplantation: Single-Center Experience M. Pacholczyk, B. Ła˛giewska, G.W. Gontarczyk, L. Adadyn´ski, A. Chmura, D. Wasiak, R. Samsel, P. Malanowski, A. Perkowska-Ptasin´ska, and W. Rowin´ski ABSTRACT Biliary complications (BC) following orthotopic liver transplantation (OLT) remain one of the major causes of postoperative complications and treatment failures. The list of common BC consists of biliary stricture, fistula, ischemic type biliary lesions (ITBL), cholangitis, and bile leakage following T-drain removal. Between July 2000 and December 2004, 101 consecutive cadaveric OLTs were performed in our institution. All but three were first full-size grafts. Seventeen patients were transplanted from the urgent list, the remaining 84 (83.16%) from the elective list. All but three patients had a choledochocholedochostomy over a straight drain. Bile cultures were taken routinely. The bile drain was removed following cholangiography 6 weeks after OLT. All patients received antibiotic prophylaxis. Ursodeoxycholic acid was used in selected cases. During the first 6 weeks positive bile cultures in absence of clinical and biochemical symptoms of cholangitis were found in 61 (60.4%) cases. Symptomatic cholangitis requiring antibiotic treatment was observed in 19 (18.8%) patients during the first 6 weeks. Two patients required endoscopic sphincterotomy and temporary stenting due to anastomotic stricture (1) or papilla of Vater fibrosis (1). Bile leakage following drain removal was observed in 8 (7.9%) patients. Five of them were treated conservatively, the remaining 3 (2.9%) required surgery (lavage) and stenting. In one case extrahepatic bile duct necrosis was diagnosed requiring reconstruction of the biliary anastomosis. No case of ITBL, bile leak at the anastomostic site, or stricture requiring surgical repair was noted. Despite the high incidence of positive bile cultures most likely related to use of a drain, the overall number of BC was low.
B
ILIARY TRACT COMPLICATIONS have been reported as common after orthotopic liver transplantation occurring in 13% to 35% of patients.1–3 These complications are a continuing source of morbidity in liver transplant recipients. Nonanastomotic and anastomotic biliary strictures are the most common of these complications. The strictures distributed in the intra- and extra-hepatic donor ducts (nonanastomotic) were frequently related to hepatic artery thrombosis or ischemic biliary lesions (ITBL). Biliary duct strictures at the level of the end-to-end anastomosis of the donor and recipient bile ducts occur most frequently within the first 4 months after surgery.1,4 Anastomotic posttransplant strictures are commonly managed by endoscopic procedures, which can define the morphology of the bile duct enabling balloon dilatation with or without stent insertion. The other common biliary complication is bile leaks, which are frequently related to the use and removal of the biliary drain. The use of bile © 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 38, 247–249 (2006)
drains (T-tube) and internal stent insertion as well as biliary strictures may lead to another problem— cholangitis. Hemobilia, a rare complication, is commonly intermittent related to invasive liver investigations, such as liver biopsy or percutaneous transhepatic cholangiography. The records of 101 patients who underwent orthotopic liver transplantation (OLT) were reviewed to determine type and frequency of biliary complication and outcome of the treatment.
From the Department of General and Transplant Surgery; Warsaw Medical University, Warsaw, Poland. Address reprint request to Marek Pacholczyk, MD, PhD, Department of General and Transplant Surgery, Warsaw Medical University, ul. Nowogrodzka 59, 02-006 Warsaw, Poland. E-mail: [email protected] 0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2005.12.076 247
248
PATIENTS AND METHODS Patients were identified retrospectively from a group of 101 OLT recipients from July 2000 to December 2004. Medical records of all of these patients were reviewed, including available records of the corresponding donors. The data were screened for any biliary complications within a 1-year period from OLT. We used a standard donor procurement technique with simultaneous University of Wisconsin infusion via the portal vein and the hepatic artery. Separate retrieval of all intra-abdominal organs was performed. We used University of Wisconsin solution for back table flushing. Thorough bile duct flushing with perfusion solution prior to cold storage was performed in all cases. The cold ischemic time was kept shorter than 10 hours. Orthotopic full-size liver transplantation was performed in all but one case (reduced graft, right lobe). The piggyback technique was used in 98 cases (97%); 3 (2.97%) patients underwent a classical orthotopic transplant. Seventeen patients were transplanted from the urgent list, the remaining 84 (83.16%) from the elective list. Bile duct continuity was reestablished by end-to-end choledochocholedochostomy in 98 patients (97%) using a 4-F to 8-F silicone Levin tube. In 3 (2.97%) patients biliary reconstruction was performed by using choledochojejunostomy (Roux-en-Y loop) over an 6-F silicone Levin tube. The Levin drain was removed at 6 to 10 weeks after the operation. All patients received maintenance immunosuppression consisting of Prograf and methylprednisolone. In selected cases the maintenance immunosuppression therapy was modified (ie, PSC, PBC, AIH) to add Cell-Cept if there was a normal blood count (WBC, PLT). Routine antibiotic prophylaxis used in all elective transplantation was Tazobactam/Piperacslin and Fluconazol. For urgent cases Imipenem was used instead of Tazocin. Ninety-six patients underwent cholangiography between days 10 and 18 followed by bile drain clamping in 91 cases. In the remaining five patients, bile tube clamping lead to temporary subcostal discomfort or pain and/or elevation of liver function tests. For these patients the bile tube was reopened until it was removal. Regular bile cultures were taken at days 1, 3, 7, and 10 and if required. All patients suspected biliary problem with cholestasis or bile leak were referred for ERCP.
RESULTS
Immediate graft function was observed in 94 of 101 patients (93.6%). In seven cases poor initial function was noted, but there was no case of primary nonfunction. One-year graft and patient survival rates in elective recipients was 70% and 96% it was after urgent transplantation. Choledochocholedochal anastomotic stricture was diagnosed in one case. We performed ERCP therapy with placement of an 10-F internal prosthesis. The endoprosthesis was exchanged every 3 months for a period of 9 months. Extrahepatic bile duct necrosis was also diagnosed 1 month after transplantation in one case. The patient commenced surgical reconstruction of biliary tract by conversion to choledochojejunostomy. Another case of cholestatic problem was diagnosed immediately after bile drain clamping. Cholangiography showed tight narrowing of the distal part of remnant recipient bile duct. Endoscopic sphincterotomy solved the problem. The most common complication was bile leak following tube removal. Overall eight patients (7.9%) were treated for this complication. Among these three patients required
PACHOLCZYK, ŁA˛GIEWSKA, GONTARCZYK ET AL
endoscopic placement of 10-F endoprosthesis and laparotomy for biloma (lavage). Conservative treatment in five patients lead to spontaneous recovery. There was one case of biliary leakage from the liver resection surface in an partial graft recipient who underwent transplantation from the urgent list. The early finding of bile collection lead to ERCP, which showed contrast extravasation at the liver resection surface. Sphincterotomy associated with stent placement and surgical biloma drainage cured the patient. In the whole cohort of patients we did not observed nonanastomotic biliary tract strictures and anastomotic leakage in the first year of observation. Widespread (intra- and extrahepatic) biliary changes with sludge formation related to hepatic artery thrombosis was observed in one patient. Subsequently the patient was placed on the list for re-OLT, which was performed 6 weeks after the first transplant. Currently the patient is well. During the first 6 weeks of follow-up 61 (60.4%) patients had positive bile cultures. Among these 19 patients were treated for mild episodes of cholangitis while the bile tube was in place. All episodes of cholangitis were successfully treated with bile tube declamping and administration of antibiotic. DISCUSSION
Biliary tract complications are a common cause of morbidity and mortality after OLT.1,2,4 In the present series a bile leak following drain tube removal and colonization of the bile were the most common biliary complications. Both of these were related to use of a biliary drain. In our series all patients received a biliary drain, but the T-tube was replaced by a silicone Levine tube with the headlight and multiple side holes. The pro and cons are well known. The presence of a biliary tube in the bile duct enabled monitoring of bile quality and volume, provided access to harvest material for bacteriological culturing, as well as decompressed the biliary tree in the case of cholestasis or cholangitis. The easy and safe access compared to an endoscopic retrograde technique for radiological contrast study was an additional benefit. On the other hand, frequent episodes of bile colonization may lead to bacterial cholangitis as well as to a bile leak following removal of the choledochostomy and may support the policy of not using the drain. In our study 61 recipients had at least one positive bile culture, but 19 of 61 (31.14%) were treated for cholangitis with benign courses. For obvious reasons no comparison can be made with respect to positive bile cultures between groups with and without a drain, though episodes of cholangitis seem to be more commonly diagnosed in the group with biliary drainage.5 Overall the incidence of nonseptic biliary tract complications in our study group was relatively low (11.88%). REFERENCES 1. Moreli J, Mulcahy HE, Willner IR, et al: Long term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement. Gastrointest Endosc 58: 374, 2003
BILIARY COMPLICATIONS 2. Rerknimitr R, Sherman S, Fogel EL, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc Vol. 55:224, 2002 3. Patkowski W, Nyckowski P, Zieniewicz K, et al: Biliary tract complications following liver transplantation. Transplant Proc 35:2316, 2003
249 4. Bourgeois N, Deviere J, Yeaton P, et al: Diagnostic and therapeutic endoscopic retrograde cholangiography after liver transplantation. Gastrointest Endosc 42:527, 1995 5. Scatton O, Meunier B, Cherqui D, et al: Randomized trial of choledochocholedochostomy with or without a T tube in orthotopic liver transplantation. Ann Surg 233:432, 2001
B
ILIARY TRACT COMPLICATIONS have been reported as common after orthotopic liver transplantation occurring in 13% to 35% of patients.1–3 These complications are a continuing source of morbidity in liver transplant recipients. Nonanastomotic and anastomotic biliary strictures are the most common of these complications. The strictures distributed in the intra- and extra-hepatic donor ducts (nonanastomotic) were frequently related to hepatic artery thrombosis or ischemic biliary lesions (ITBL). Biliary duct strictures at the level of the end-to-end anastomosis of the donor and recipient bile ducts occur most frequently within the first 4 months after surgery.1,4 Anastomotic posttransplant strictures are commonly managed by endoscopic procedures, which can define the morphology of the bile duct enabling balloon dilatation with or without stent insertion. The other common biliary complication is bile leaks, which are frequently related to the use and removal of the biliary drain. The use of bile © 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 38, 247–249 (2006)
drains (T-tube) and internal stent insertion as well as biliary strictures may lead to another problem— cholangitis. Hemobilia, a rare complication, is commonly intermittent related to invasive liver investigations, such as liver biopsy or percutaneous transhepatic cholangiography. The records of 101 patients who underwent orthotopic liver transplantation (OLT) were reviewed to determine type and frequency of biliary complication and outcome of the treatment.
From the Department of General and Transplant Surgery; Warsaw Medical University, Warsaw, Poland. Address reprint request to Marek Pacholczyk, MD, PhD, Department of General and Transplant Surgery, Warsaw Medical University, ul. Nowogrodzka 59, 02-006 Warsaw, Poland. E-mail: [email protected] 0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2005.12.076 247
248
PATIENTS AND METHODS Patients were identified retrospectively from a group of 101 OLT recipients from July 2000 to December 2004. Medical records of all of these patients were reviewed, including available records of the corresponding donors. The data were screened for any biliary complications within a 1-year period from OLT. We used a standard donor procurement technique with simultaneous University of Wisconsin infusion via the portal vein and the hepatic artery. Separate retrieval of all intra-abdominal organs was performed. We used University of Wisconsin solution for back table flushing. Thorough bile duct flushing with perfusion solution prior to cold storage was performed in all cases. The cold ischemic time was kept shorter than 10 hours. Orthotopic full-size liver transplantation was performed in all but one case (reduced graft, right lobe). The piggyback technique was used in 98 cases (97%); 3 (2.97%) patients underwent a classical orthotopic transplant. Seventeen patients were transplanted from the urgent list, the remaining 84 (83.16%) from the elective list. Bile duct continuity was reestablished by end-to-end choledochocholedochostomy in 98 patients (97%) using a 4-F to 8-F silicone Levin tube. In 3 (2.97%) patients biliary reconstruction was performed by using choledochojejunostomy (Roux-en-Y loop) over an 6-F silicone Levin tube. The Levin drain was removed at 6 to 10 weeks after the operation. All patients received maintenance immunosuppression consisting of Prograf and methylprednisolone. In selected cases the maintenance immunosuppression therapy was modified (ie, PSC, PBC, AIH) to add Cell-Cept if there was a normal blood count (WBC, PLT). Routine antibiotic prophylaxis used in all elective transplantation was Tazobactam/Piperacslin and Fluconazol. For urgent cases Imipenem was used instead of Tazocin. Ninety-six patients underwent cholangiography between days 10 and 18 followed by bile drain clamping in 91 cases. In the remaining five patients, bile tube clamping lead to temporary subcostal discomfort or pain and/or elevation of liver function tests. For these patients the bile tube was reopened until it was removal. Regular bile cultures were taken at days 1, 3, 7, and 10 and if required. All patients suspected biliary problem with cholestasis or bile leak were referred for ERCP.
RESULTS
Immediate graft function was observed in 94 of 101 patients (93.6%). In seven cases poor initial function was noted, but there was no case of primary nonfunction. One-year graft and patient survival rates in elective recipients was 70% and 96% it was after urgent transplantation. Choledochocholedochal anastomotic stricture was diagnosed in one case. We performed ERCP therapy with placement of an 10-F internal prosthesis. The endoprosthesis was exchanged every 3 months for a period of 9 months. Extrahepatic bile duct necrosis was also diagnosed 1 month after transplantation in one case. The patient commenced surgical reconstruction of biliary tract by conversion to choledochojejunostomy. Another case of cholestatic problem was diagnosed immediately after bile drain clamping. Cholangiography showed tight narrowing of the distal part of remnant recipient bile duct. Endoscopic sphincterotomy solved the problem. The most common complication was bile leak following tube removal. Overall eight patients (7.9%) were treated for this complication. Among these three patients required
PACHOLCZYK, ŁA˛GIEWSKA, GONTARCZYK ET AL
endoscopic placement of 10-F endoprosthesis and laparotomy for biloma (lavage). Conservative treatment in five patients lead to spontaneous recovery. There was one case of biliary leakage from the liver resection surface in an partial graft recipient who underwent transplantation from the urgent list. The early finding of bile collection lead to ERCP, which showed contrast extravasation at the liver resection surface. Sphincterotomy associated with stent placement and surgical biloma drainage cured the patient. In the whole cohort of patients we did not observed nonanastomotic biliary tract strictures and anastomotic leakage in the first year of observation. Widespread (intra- and extrahepatic) biliary changes with sludge formation related to hepatic artery thrombosis was observed in one patient. Subsequently the patient was placed on the list for re-OLT, which was performed 6 weeks after the first transplant. Currently the patient is well. During the first 6 weeks of follow-up 61 (60.4%) patients had positive bile cultures. Among these 19 patients were treated for mild episodes of cholangitis while the bile tube was in place. All episodes of cholangitis were successfully treated with bile tube declamping and administration of antibiotic. DISCUSSION
Biliary tract complications are a common cause of morbidity and mortality after OLT.1,2,4 In the present series a bile leak following drain tube removal and colonization of the bile were the most common biliary complications. Both of these were related to use of a biliary drain. In our series all patients received a biliary drain, but the T-tube was replaced by a silicone Levine tube with the headlight and multiple side holes. The pro and cons are well known. The presence of a biliary tube in the bile duct enabled monitoring of bile quality and volume, provided access to harvest material for bacteriological culturing, as well as decompressed the biliary tree in the case of cholestasis or cholangitis. The easy and safe access compared to an endoscopic retrograde technique for radiological contrast study was an additional benefit. On the other hand, frequent episodes of bile colonization may lead to bacterial cholangitis as well as to a bile leak following removal of the choledochostomy and may support the policy of not using the drain. In our study 61 recipients had at least one positive bile culture, but 19 of 61 (31.14%) were treated for cholangitis with benign courses. For obvious reasons no comparison can be made with respect to positive bile cultures between groups with and without a drain, though episodes of cholangitis seem to be more commonly diagnosed in the group with biliary drainage.5 Overall the incidence of nonseptic biliary tract complications in our study group was relatively low (11.88%). REFERENCES 1. Moreli J, Mulcahy HE, Willner IR, et al: Long term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement. Gastrointest Endosc 58: 374, 2003
BILIARY COMPLICATIONS 2. Rerknimitr R, Sherman S, Fogel EL, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc Vol. 55:224, 2002 3. Patkowski W, Nyckowski P, Zieniewicz K, et al: Biliary tract complications following liver transplantation. Transplant Proc 35:2316, 2003
249 4. Bourgeois N, Deviere J, Yeaton P, et al: Diagnostic and therapeutic endoscopic retrograde cholangiography after liver transplantation. Gastrointest Endosc 42:527, 1995 5. Scatton O, Meunier B, Cherqui D, et al: Randomized trial of choledochocholedochostomy with or without a T tube in orthotopic liver transplantation. Ann Surg 233:432, 2001