Results of Choledochojejunostomy in the Treatment of Biliary Complications After Liver Transplantation in the Era of Nonsurgical Therapies

Transcription

1 Results of Choledochojejunostomy in the Treatment of Biliary Complications After Liver Transplantation in the Era of Nonsurgical Therapies Brian R. Davidson, Rakesh Rai, Ashim Nandy, Nilesh Doctor, Andrew Burroughs, and Keith Rolles Advances in radiological and endoscopic techniques have allowed many biliary complications after orthotopic liver transplantation (OLT) to be managed without surgery. The influence of nonsurgical management on the outcome of patients requiring surgical revision has not been addressed. We reviewed our 10-year experience (October 1988 to January 1998) of Roux-en-Y choledochojejunostomy (CDJ) to treat biliary complications after OLT. Forty-six patients underwent CDJ for biliary complications (32 men, 14 women; age, 22 to 65 years; median, 60 years). Biliary reconstruction at the time of OLT was duct to duct in 41 patients, primary CDJ in 3 patients, and gall bladder conduit in 2 patients. T-tubes were used only in patients with gallbladder conduit. The indication for CDJ was biliary leak (23 patients), stricture (20 patients), biliary stones (2 patients), and biliary sludge (1 patient). Two patients (4.3%) had associated hepatic artery thrombosis. The bile leaks were diagnosed at a median of 29 days post-olt (range, 2 to 65 days) and strictures at a median of 2 years (range, 33 days to 6.5 years) post-olt. Before surgery, 25 patients (54%) underwent an attempt at radiological or endoscopic therapeutic intervention that failed. Median follow-up was 5 years (range, 9 months to 10 years). Early complications occurred in 12 patients (26%); the most common was chest infection (4 patients). There were 3 perioperative deaths (6%); 1 death was directly related to surgery. Late complications, mainly anastomotic strictures, occurred in 10 patients (22%), half of which were successfully treated by biliary balloon dilatation. The complication rate post-cdj was less in those who underwent a failed nonsurgical approach than those proceeding straight to surgery (9 of 25 patients; 36% v 13 of 21 patients; 62%; P.21, not significant). The procedure-related mortality for surgical revision of biliary complications after OLT is low, but early and late complications are common. A failed attempt at nonsurgical management does not increase the complications of reconstructive surgery. Strictures after CDJ should be considered for biliary balloon dilatation. Copyright 2000 by the American Association for the Study of Liver Diseases D espite an overall improvement in survival after orthotopic liver transplantation (OLT), biliary complications still remain a significant source of morbidity and have been associated with mortality rates of 8% to 15%. 1-7 Early diagnosis and treatment of these complications may reduce the mortality rate. 2 Recent advances in endoscopic and interventional radiological techniques have led to the nonsurgical management of biliary complications. Patients are usually selected for nonsurgical treatment, and no controlled trials comparing it with surgery have been published. Nonsurgical results need to be viewed both against and with the results from surgical intervention. A review of biliary complications in our unit over a period of 5 years found that only 50% of the strictures and none of the bile leaks were successfully treated by nonsurgical methods. 8 We performed a 10-year review of Roux-en-Y choledochojejunostomy (CDJ) in the management of biliary complications after OLT to analyze early and late complications after CDJ, the success of their management, and the effect of nonsurgical treatment before biliary reconstruction. Patients and Methods Over a 10-year period (October 1988 to January 1998), 477 liver transplantations were performed at our institute. Clinical information was obtained from a computerized liver transplantation database. The medical records of all patients who underwent CDJ over this period for the management of biliary complications were reviewed. Data included patient age, primary indication for transplantation, number of liver transplants, date of presentation of biliary complication, type of intervention for management of the complication, date of CDJ, postoperative course after CDJ, duration of hospital stay, and details of readmissions. During this time, 80 biliary complications (leaks or strictures) required intervention (17%), of which 20 patients (25%) were successfully treated nonsurgically. Of the 60 patients undergoing surgery, 46 patients underwent CDJ, and the others underwent further suture of bile leaks, T-tube insertion, or retransplantation. In 25 of the 46 patients (54%) who underwent CDJ, prior attempts at nonsurgical treatment had failed (Fig. 1). At the time of liver transplantation, biliary continuity had From the Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital and Royal Free and University College Medical School, London, UK. Address reprint requests to Brian R. Davidson, MBChB, MD (Glasg), FRCPS (Glasg), FRCS (Eng), University Department of Surgery, Royal Free Hospital and Medical School, Pond St, London NW3 2QG, UK. Copyright 2000 by the American Association for the Study of Liver Diseases /00/ $3.00/0 Liver Transplantation, Vol 6, No 2 (March), 2000: pp

2 202 Davidson et al Figure 1. Management overview of biliary complications after OLT: a 10-year experience. *Other procedures included T-tube insertion, further duct suturing, and retransplantation. been established after graft revascularization in the vast majority of patients by duct-to-duct anastomosis without T-tube splintage (n 41) and, in a few, by Roux-en-Y CDJ (n 3) or a gallbladder conduit with T-tube (n 2). The 2 patients with gallbladder conduits had undergone transplantation in the 1980s. Of the 3 patients undergoing primary Roux-loop reconstruction, 2 patients had primary sclerosing cholangitis (PSC; 1 patient was complicated by cholangiocarcinoma) and 1 patient had a short donor duct. Biliary complications were diagnosed by clinical symptoms and signs, abnormal liver function test results, and radiological investigation. Postoperative cholangiography by endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography has been part of the routine transplantation protocol, even for asymptomatic patients, since mid Patients in whom endoscopic retrograde cholangiopancreatography fails to show the biliary tract undergo biliary scintigraphy. If this raises the suspicion of a biliary leak, the patients proceed to percutaneous transhepatic cholangiography. Ultrasound examination, computed tomographic scanning, and biliary scintigraphy were also performed if clinically indicated. Hepatic artery thrombosis was diagnosed by duplex ultrasound scan and hepatic artery angiography. Complications after CDJ were defined as early if they occurred within 30 days of surgery. Complications occurring beyond 30 days were considered delayed. Median follow-up after biliary reconstruction was 5 years (range, 9 months to 10 years). Results Forty-six adult patients underwent CDJ for biliary complications (32 men, 14 women; age, 22 to 65 years; median, 60 years). The indications for liver transplantation are listed in Table 1. There was no association between the type or number of biliary complications and the disease process necessitating transplantation. Twenty-three patients underwent CDJ for biliary leak; 20 patients for biliary stricture; 2 patients for bile duct stones associated with a stricture; and 1 patient for sludge in the biliary tree. Two patients with biliary leak had associated hepatic artery thrombosis (4.3%). Of the 20 biliary strictures, 13 were anastomotic and 7 were nonanastomotic. None was associated with hepatic artery thrombosis. Of the 7 patients with nonanastomotic strictures, 2 had evidence of cytomegalovirus infection and 1 had chronic rejection. The time between OLT and presentation of the biliary complica- Table 1. Indications for OLT in Patients Requiring CDJ for Biliary Complications End-Stage Liver Disease No. of Patients Biliary Reconstruction Hepatitis C 12 D-D (11), CDJ (1) Alcoholic cirrhosis 8 D-D (8) Primary sclerosing cholangitis 5 D-D (3), CDJ (1), GB (1) Cryptogenic cirrhosis 3 D-D (3) Fulminant hepatic failure 4 D-D (4) Hepatitis B 3 D-D (3) Primary biliary cirrhosis 3 D-D (2), GB (1) Others* 8 D-D (7), CDJ (1) NOTE. Numbers in parentheses indicate number of patients. Abbreviations: D-D, duct-to-duct anastomosis; CDJ, Roux-en-Y choledochojejunostomy; GB, gallbladder conduit. *Acute Budd-Chiari syndrome, 1 patient; autoimmune cirrhosis, 1 patient; Wilson s disease, 1 patient; type IV glycogen storage, 1 patient; alcoholic liver disease and hepatitis C virus, 1 patient; primary sclerosing cholangitis and cholangiocarcinoma, 1 patient; alcoholic liver disease and hepatitis C virus, 1 patient; and hepatitis C virus and hepatitis B virus, 1 patient.

3 Biliary Complications After Liver Transplantation 203 tion ranged from 2 days to more than 6 years. Patients presented with leak (median, 29 days; range, 2 to 65 days) much earlier than stricture (median, 2 years; range, 33 days to 6.5 years) post-olt. Of the 46 patients, 25 had radiological or endoscopic intervention for management of the biliary complication before undergoing CDJ (Table 2). This involved nasobiliary drainage (12 patients), endoscopic stenting (2 patients), percutaneous drainage (9 patients), balloon dilatation of stricture (1 patient), and ultrasound-guided aspiration of subphrenic collection (1 patient). The other 21 patients were not considered for nonsurgical intervention because of complete disruption of the anastomosis considered to be caused by donor duct necrosis (5 patients), associated peritonitis (3 patients), previous CDJ (associated with a large bile leak in 2 patients and a tight stricture in 1 patient), very tight stricture (6 patients), stricture associated with stones (2 patients), and bile leak associated with hepatic artery thrombosis (2 patients). These patients proceeded to CDJ without an attempt at nonsurgical management. Twenty-two of the 46 patients had an early or late complication after CDJ (48%). The complication rate after CDJ was less in the group of patients in whom endoscopic or percutaneous management had failed (9 of 25 patients; 36%) than in those who proceeded straight to CDJ for management of the biliary complication (13 of 21 patients; 62%), although this was not statistically significant (Chi-squared, P.21). There were no complications during surgery or Table 2. Preoperative Endoscopic or Percutaneous Intervention for Post-OLT Biliary Complications Complication Leak (n 11) Stricture (n 14) Preoperative Intervention (n 25)* US-guided drainage of subphrenic collection (1) Nasobiliary drainage (8) Endoscopic stenting (1) Percutaneous drainage (1) Balloon dilatation and nasobiliary drainage (1) Nasobiliary drainage (4) Percutaneous drainage (8) Endoscopic stent (1) NOTE. Numbers in parentheses indicate number of patients. Abbreviation: US, ultrasound. *Twenty-one patients were not considered for nonsurgical intervention. intraoperative deaths. Twelve patients developed early complications after CDJ (26%; Table 3). Chest infection was the most common; a causative organism was isolated in 3 of 4 cases. One patient bled on the third postoperative day from the recipient bile duct, and the CDJ was revised. There was 1 death related to the surgery; the patient developed peritonitis and septicemia 3 days after CDJ because of anastomotic disruption. Postmortem examination showed a patent hepatic artery. Two patients with biliary complications post-olt required retransplantation after CDJ (original liver disease, PSC, 1 patient; hepatitis C virus, 1 patient). One patient developed an infected subhepatic collection after ultrasound-guided drainage of an early bile leak. At laparotomy, the infected collection involved the hepatic artery, which was therefore ligated. Retransplantation (after 14 days) was required for liver infarction associated with a further bile leak. The second patient developed a chest infection after CDJ for a bile leak. While ventilated in the Intensive Therapy Unit (ITU) hepatic arterial thrombosis occurred 2 weeks postoperatively and produced acute graft failure requiring retransplantation. Both patients who underwent retransplantation survived and are well. Ten patients (22%) developed late complications between 2 and 16 months after CDJ (median, 13 months; Table 4). All presented with obstructive jaundice and/or cholangitis. Three patients had associated hepatic artery thrombosis (30%), 1 of whom had widespread ischemic strictures at 5 months after CDJ. Angiography in the patient with diffuse stricturing showed the main hepatic artery to be thrombosed but with good collaterals. This patient underwent balloon dilatation of a dominant extrahepatic biliary stricture and has had no further problems over the subsequent years. The 2 other patients with late complications after CDJ and hepatic artery thrombosis underwent retransplantation 4 and 5 months after CDJ for poor graft function and biliary stricturing. Balloon dilatation was performed in 5 other patients with strictures at the anastamosis (1 patient) or right (2 patients) or left (2 patients) hepatic duct. Only 1 of the 5 patients has required surgical revision because of recurrent cholangitis at 5 months after CDJ (median follow-up, 1.5 years; range, 2 months to 5 years). Of the remaining 2 patients with late complications, 1 patient developed biliary sludge, which was removed by openduct exploration 8 months post-cdj after failed attempts at endoscopic removal. No biliary stricturing was found at the time of exploration. The last patient with a late complication had a right hepatic duct

4 204 Davidson et al Table 3. Early Complications After CDJ and Their Management Complications No. of Patients Treatment Outcome Chest infection 4 Antibiotics; 1 Streptococcus viridans, 2 staphylococcal, Recovered 1 no isolate Pseudomembranous colitis 1 Metronidazole Recovered Hematemesis (gastric erosions) 1 Conservative No complication Renal impairment (cyclosporine related) 1 Conservative Recovered Biloma 1 US-guided aspiration No complication Intraperitoneal bleed from recipient bile duct 1 Revision of biliary reconstruction No complication Septicemia (anastomotic disruption) 1 Conservative Died Leak associated with HAT 1 Retransplantation Well HAT 14 days after CDJ 1 Retransplantation Well NOTE. N 12. Abbreviations: US, ultrasound; HAT, hepatic artery thrombosis. stricture and jaundice. The patient was known to have chronic graft rejection, and the stricture was not believed to be clinically significant. This patient died after 4 months of graft failure from chronic rejection. Three patients (6.5%) died within 30 days of CDJ. Two patients died at 24 and 72 hours after biliary reconstruction of sepsis that occurred after the initial bile leak. Both had an intact biliary tree at postmortem examination. The third patient, previously mentioned, died of sepsis 10 days after CDJ and was found to have a further bile leak from the anastomosis at postmortem examination. Discussion The main biliary tract complications after OLT are leaks and strictures. Traditionally, both have been Table 4. Late Complications After CDJ and Their Management Complication No. of Patients Management Biliary stricture with hepatic artery thrombosis 3 2, Retransplantation 1, Balloon dilatation Anastomotic, right or left 5 Balloon dilatation hepatic duct strictures Biliary sludge 1 Surgical clearance Right hepatic duct stricture with chronic graft rejection 1 No intervention NOTE. Late complication was defined as greater than 30 days after surgery. corrected surgically, 3,5 but more recently, nonsurgical endoscopic and percutaneous radiological techniques have been advocated. 9,10 The application of nonsurgical treatments varies widely. In 1989, Stratta et al 6 reported that only 13% of biliary complications required surgery, whereas in a report in 1994 by Greif et al, 4 90% of biliary complication were treated by surgery. These differences are likely to be caused by the local availability of endoscopic and radiological expertise, in addition to the initial results of nonsurgical treatment from the center. There have been no prospective randomized trials comparing the results of surgical and nonsurgical management of post-olt biliary complications; thus, the controversy still exists regarding the ideal treatment method. In a recent review of our experience with nonsurgical management of biliary complications post- OLT in 90 consecutive patients with duct-to-duct primary anastomosis, 50% of the biliary strictures required surgical intervention despite balloon dilatation, and no bile leaks were managed successfully by endoscopic stenting or nasobiliary drainage. There are few reports on the outcome of surgery for biliary complications after OLT since the widespread introduction of endoscopic and percutaneous radiological treatment. To compare with our nonsurgical experience of managing biliary complications, we retrospectively studied our surgical experience in 46 consecutive patients undergoing CDJ for management of biliary complications over a 10-year period. More than half the patients who underwent CDJ had undergone a failed attempt at nonsurgical management. Proponents of surgical intervention for biliary complications have suggested that a failed nonsurgical approach may

5 Biliary Complications After Liver Transplantation 205 increase the risks for surgical intervention. Our results would not support this view; patients in whom a nonsurgical approach failed had a lower complication rate after CDJ than those proceeding straight to surgery. This finding may reflect a selection bias for nonsurgical treatment in patients with less severe biliary complications or the efficacy of nonsurgical treatments in controlling biliary or intra-abdominal sepsis. However, nonsurgical approaches with a fatal outcome in this series are not included in the patient group in whom nonsurgical intervention failed because they did not proceed to biliary reconstruction. The incidence and outcome of biliary tract complications is influenced by the initial management of the bile duct at the time of OLT. The majority of patients in this series (90%) had duct-to-duct anastomosis without a T-tube, which we have previously shown to be an effective method of bile duct reconstruction. 11 However, most centers perform duct-to-duct anastomosis using T-tube drainage, 4,12,13 which has suggested advantages that include decompressing the bile ducts, stenting the anastomosis, monitoring bile output, and maintaining access for cholangiography. 9 Although cholangiography may be facilitated, bile leaks associated with a T-tube account for 45% of all complications in some series, 12 and a prospective randomized trial has shown no advantage to using T-tubes. 14 However, biliary reconstruction without a T-tube requires careful post-olt surveillance for bile leaks. 15 Three patients in this series had Roux-en-Y CDJ and 2 patients had gallbladder conduit as the primary method of bile duct reconstruction. The patients with gallbladder conduit underwent transplantation in 1988, and this technique has since been discontinued because of the incidence of bile stasis, stone formation, and cholangitis. 16 The incidence of primary Roux-en-Y CDJ is low because duct-to-duct anastomosis has been used in this series in patients with PSC if there is no evidence of distal duct stricturing. We have shown this group of patients to have similar outcomes to others undergoing duct-to-duct reconstruction. 17 The incidence of overall surgical intervention of 12% (60 of 477 patients) and Roux-loop biliary reconstruction of 10% (46 of 477 patients) is similar to that reported from other centers. 6 There was significant morbidity in the perioperative period (26%), although many of the early complications may be related to local peritonitis and sepsis rather than the method of managing the biliary complication. Similarly, 2 of 3 perioperative deaths were related to septicemia and cardiac failure. The severity of these complications can only be reduced by the earlier diagnosis and control of biliary leaks. This is complicated by the occult nature of some biliary complications. Protocol cholangiography may be 1 method of achieving an earlier diagnosis, 15 although its efficacy has not been proven in a prospective randomized trial. The most common late complication after CDJ was biliary stricturing, affecting 8 of the 43 patients discharged from the hospital after CDJ (16%). Biliary balloon dilatation was found to be an effective method for treating post-cdj strictures; only 1 of 6 patients required surgical revision. There was no significant morbidity and no mortality related to biliary balloon dilatation, suggesting it should be the first-line treatment for post-cdj biliary strictures. However, benign biliary strictures can be associated with late recurrence, and the follow-up of these patients is limited (median, 1.5 years). Our previous experience of balloon dilatation would also support its use as first-line treatment for post-olt biliary anastomotic strictures. 8 In a comparative study of surgical and nonsurgical treatment of post-olt biliary complications, Kuo et al 18 found that endoscopic and radiological methods had 1-year patency rates of 45% and surgery had a 1-year patency rate of 89%. Although this difference was significant, this was an uncontrolled, nonrandomized, retrospective study in which the patient groups were different and the patients undergoing surgery usually were unsuitable for nonsurgical treatment or it had failed. Biliary sludge without a focal biliary stricture occurred as a late complication after CDJ in 1 patient in this series. Recently, several forms of nonsurgical therapy have been reported for biliary sludge. These include oral chemolysis, percutaneous transhepatic biliary drainage with saline irrigation, and basket extraction. In a series in which all these treatment methods were considered, 43% of the patients finally required surgery. 19 The late complications seen after CDJ were biliary obstruction and/or acute cholangitis. Of interest, many of the biliary strictures were nonanastomotic, even in patients without hepatic artery thrombosis. Factors suggested as possible causes for these stricture include blood group incompatibility, chronic rejection, cytomegalovirus infection, and recurrence of primary ductal disease in those with sclerosing cholangitis. 20 In our series, 2 patients had evidence of cytomegalovirus infection and 1 patient had chronic rejection. No patient had an ABO incompatible graft. The incidence of early complications after CDJ was 26% in this series, with a 30-day mortality rate of 2% (1 patient). The main complication was sepsis. Even

6 206 Davidson et al with nonsurgical therapy, sepsis is a common cause of morbidity, and mortalities have been reported. 21 We conclude that patients undergoing Roux-en-Y CDJ in the management of biliary complications after OLT have a high incidence of early and late complications but a low mortality. Endoscopic or percutaneous management of patients who subsequently require surgery does not increase and may reduce the complication rate. Strictures are the common late complication of CDJ and can be effectively treated by biliary balloon dilatation. We recommend surgery in the treatment of biliary complications after OLT in patients who have a large bile leak caused by duct necrosis or in whom an endoscopic or percutaneous approach failed. References 1. Lemmer GR, Spearman CW, Krige JE, Millar AJ, Bornman PC, Terblanche J, et al. The management of biliary complications following orthotopic liver transplantation. S Afr J Surg 1997;35: Colonna JO, Shaked A, Gomes AS, Colquhoun SD, Jurim O, McDiarmid SV, et al. Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management and outcome. Ann Surg 1992;216: Lerut J, Gordon RD, Iwatsuki S, Esquivel CO, Todo S, Tzakis A, et al. Biliary tract complications in human orthotopic liver transplantation. Transplantation 1987;43: Greif F, Bronsther OL, Van Thiel DH, Casavilla A, Iwatsuki S, Tzakis A, et al. The incidence, timing and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 1994;219: Lopez RR, Benner KG, Ivancev K, Keeffe EB, Deveney CW, Pinson CW. Management of biliary complications after liver transplantation. Surgery 1992;163: Stratta RJ, Wood RP, Langnas AN, Hollins RR, Bruder KJ, Donovan JP, et al. Diagnosis and treatment of biliary tract complications after orthotopic liver transplantation. Surgery 1989;106: Klein AS, Savader S, Burdick JF, Fair J, Mitchell M, Colombani P, et al. Reduction of morbidity and mortality from biliary complications after liver transplantation. Hepatology 1991;14: Macfarlane B, Davidson B, Dooley JS, Dawson K, Osborne MJ, Rolles K, et al. Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation. Eur J Gastroenterol Hepatol 1996;8: Osorio RW, Freise CE, Stock PG, Lake JR, Laberge JM, Gordon RL, et al. Nonoperative managment of biliary leaks after orthotopic liver transplantation. Transplantation 1993;55: Hintze RE, Adler A, Veltzke W, Abou-Rebyeh H, Felix R, Neuheus P. Endoscopic management of biliary complications after orthotopic liver transplantation. Hepatogastroenterology 1997;44: Rolles K, Dawson K, Novell R, Hayter B, Davidson BR, Burroughs AK. Biliary anastomosis after liver transplantation does not benefit from T tube splintage. Transplantation 1994;57: O Connor TP, Lewis WD, Jenkins RL. Biliary tract complications after orthotopic liver transplantation. Arch Surg 1995;130: Sherman S, Jamidar P, Shaked A, Kendall BJ, Goldstein LI, Busuttil RW. Biliary tract complications after orthotopic liver transplantation. Endoscopic approach to diagnosis and therapy. Transplantation 1995;60: Vougas V, Rela M, Gane E, Muiesan P, Melendez HV, Williams R, et al. A prospective randomised trial of bile duct reconstruction at liver transplantation: T tube or no T-tube? Transpl Int 1996;9: Kurzawinski TR, Selves L, Farouk M, Dooley J, Hilson A, Buscombe JR, et al. A prospective trial of hepatobiliary scintigraphy and endoscopic cholangiography for the detection of early biliary complications after orthotopic liver transplantation. Br J Surg 1997;84: Halff G, Todo S, Hall R, Starzl TE. Late complications with gallbladder conduit biliary reconstruction after liver transplantation. Transplantation 1989;48: Distante V, Farouk M, Kurzawinski TR, Ahmed SW, Burroughs AK, Davidson BR, et al. Duct to duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis. Transpl Int 1996;9: Kuo PC, Lewis WD, Stokes K, Pleskow D, Simpson MA, Jenkins RL. A comparison of operation, endoscopic retrograde cholangiopancreatography, and percutaneous transhepatic cholangiography in biliary complications after hepatic transplantation. J Am Coll Surg 1994;179: Barton P, Steininger R, Maier A, Muhlbacher F, Lechner G. Biliary sludge after liver transplantation: 2. Treatment with interventional techniques versus surgery and/or oral chemolysis. AJR Am J Roentgenol 1995;164: Ward EM, Kiely MJ, Maus TP, Wiesner RH, Krom RA. Hilar biliary strictures after liver transplantation: Cholangiography and percutaneous treatment. Radiology 1990;177: Sherman S, Jamidar P, Shaked A, Kendall BJ, Goldstein LI, Busuttil RW. Biliary tract complications after orthotopic liver transplantation. Endoscopic approach to diagnosis and therapy. Transplantation 1995;60: