Biliary Complications in 108 Consecutive Recipients With Duct-to-Duct Biliary Reconstruction in Living-Donor Liver Transplantation S. Mizuno, H. Inoue, A. Tanemura, Y. Murata, N. Kuriyama, Y. Azumi, M. Kishiwada, M. Usui, H. Sakurai, M. Tabata, R. Yamada, N. Yamamoto, K. Sugimoto, K. Shiraki, Y. Takei, and S. Isaji ABSTRACT Background. Biliary complications remain the leading cause of postoperative complications after living-donor liver transplantation (LDLT) in patients undergoing duct-to-duct choledochocholedochostomy. The aim of this study was to analyze the causes of these complications. Methods. One hundred eight patients who underwent LDLT with duct-to-duct biliary reconstruction at Mie University Hospital were enrolled in this study. The mean follow-up time was 58.4 months (range, 3e132). The most recent 18 donors underwent indocyanine green (ICG) ﬂuorescence cholangiography for donor hepatectomy. The development of biliary complications was retrospectively analyzed. Biliary complications were deﬁned as needing endoscopic or radiologic treatment. Results. Biliary leakages and strictures occurred in 6 (5.6%) and 15 (13.9%) of the recipients, respectively, and 3 donors (2.7%) experienced biliary leakage. However, since the introduction of ICG ﬂuorescence cholangiography, we have not encountered any biliary complications in either donors or recipients. Biliary leakage was an independent risk factor for the development of biliary stricture (P ¼ .013). Twelve (80%) of the 15 recipients with biliary stricture had successful nonoperative endoscopic or radiologic management, and 3 patients underwent surgical repair with hepaticojejunosotomy. Conclusions. Biliary leakage was an independent factor for biliary stricture. ICG ﬂuorescence cholangiography might be helpful to reduce biliary complications after LDLT in both donors and recipients.
INCE Wachs et al ﬁrst reported duct-to-duct direct biliary reconstruction for living-donor liver transplantation (LDLT) in 1998 , duct-to-duct reconstruction has been performed in many institutions. The advantages of duct-to-duct biliary reconstruction compared with hepaticojejunostomy have been pointed out in several reports: It preserves the physiologic bilioenteric circulation, permits easy endoscopic access to the biliary tree for diagnostic and therapeutic instrumentation, and assists the prevention and management of ascending cholangitis [2e5]. As the number of patients who have undergone LDLT with duct-to-duct biliary reconstruction has increased, however, a variety of biliary complications have emerged [6e8], especially for biliary strictures [5,9]. The causes of biliary stricture after LDLT were reported to be cytomegalovirus infection , donor age , biliary leakage , bile duct 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.035 850
size , cold ischemia time , and hepatitis C virus infection . Some of them are inevitable, but others have room for improvement. In other words, biliary complications directly associated with surgical procedures should be avoided or overcome through innovative surgical techniques and understanding of liver anatomy . From the Department of Hepatobiliary-Pancreatic and Transplant Surgery (S.M., A.T., Y.M., N.K., Y.A., M.K., M.U., H.S., M.T., S.I.) and Department of Gastroenterology and Hepatology (H.I., R.Y., N.Y., K. Sugimoto, K. Shiraki, Y.T.), Mie University School of Medicine, Tsu, Mie, Japan. Address reprint requests to Shugo Mizuno, MD, Department of Hepatobiliary-Pancreatic and Transplant Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-0001, Japan. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 850e855 (2014)
COMPLICATIONS AFTER DUCT-TO-DUCT BILIARY RECONSTRUCTION
Recently, a novel ﬂuorescent intraoperative cholangiography technique for cholecystectomy using indocyanine green (ICG) has been used, and in 2009 we started using ICG ﬂuorescence cholangiography in LDLT donors who underwent right or left hepatectomy , because appropriate cutting line of the bile duct in the donor operation is one of the key issues to prevent biliary complications in both donors and recipients after LDLT. In the present study, we retrospectively analyzed biliary complications including biliary leakage and stricture and also evaluated usefulness of ICG ﬂuorescence cholangiography to cut the bile duct during donor hepatectomy in LDLT. PATIENTS AND METHODS Patients From March 2002 to May 2013, 139 patients underwent LDLT at Mie University. Among these patients, the 108 patients who underwent duct-to-duct biliary reconstruction along with LDLT were enrolled in this study. Patient, graft, and operative characteristics are summarized in Table 1. The series comprised 65 men and 43 women (average age, 53 years). The most common indications for LDLT were hepatocellular carcinoma with or without viral hepatitis (n ¼ 47), followed by liver cirrhosis (n ¼ 33), primary biliary cirrhosis (n ¼ 15), acute liver failure (n ¼ 10), and others (n ¼ 3). The most commonly used graft type was right lobe (n ¼ 48), followed by left lobe (n ¼ 41), right lobe with middle hepatic vein (n ¼ Table 1. Patients Backgrounds Characteristics
Age (years, range) Male MELD score ABO incompatibility Indication Hepatocellular carcinoma Liver cirrhosis PBC Acute liver failure Others Donor Age (years, range) Male Graft Left lobe Right lobe Right lobe with MHV Posterior segment GRWR (%) Operation Operation time (min) Blood loss (mL) Warm ischemic time (min) Cold ischemic time (min)
Number ¼ 108
53 65 18 4
(20e70) (61%) (6e44) (3.7%)
47 (HCV 26, HBV 10, NBNC 11) 33 (HCV 15, cryptogenic 8, HBV4, Alcohol 5, BA 1) 15 10 (HBV 4) 3 38 (18e63) 59 (55%) 41 48 17 2 0.952 (0.47e1.57) 819 7810 53 105
(609e1124) (3760e45200) (21e102) (22e323)
Abbreviations: MELD, The Model for End-Stage Liver Disease; HCV, hepatitis C; HBV, hepatitis B; NBNC, non B non C hepatitis; BA, biliary atresia; PBC, primary biliary cirrhosis; MHV, middle hepatic vein; RWR, graft/recipient weight ratio.
17), and posterior segment (n ¼ 2). The donors included 59 men and 49 women (average age, 38 years). Mean score of the Model for End-Stage Liver Disease (MELD) at the time of LDLT was 18.6 (range, 6e44). The mean graft-to-recipient weight ratio was 0.952 (range, 0.47e1.57). The mean operative time was 819 minutes (range, 609e1124). The warm ischemia time was 52 minutes (range, 21e102) and the mean cold ischemia time 105 minutes (range, 22e323). The immunosuppression protocol consisted of tacrolimus and low-dose steroids as described elsewhere .
Donor Assessment and Surgery The donors underwent several preoperative examinations, including computerized tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), to assess the biliary and vascular system. The surgical techniques for donor hepatectomy have been described elsewhere . Since September 2009, we have used ICG ﬂuorescence cholangiography as follows . We performed a standard cholecystectomy and a conventional intraoperative cholangiography. After isolating the left hepatic artery and left portal vein, the hepatic parenchymal resection was performed along the transaction plane, and the anterior surface of the hilar plate was exposed. Then the hilar plate was isolated and taped. At this moment, ICG (0.025 mg/mL; Diagnogreen; Daiichi Sankyo Co) was administered into the bile duct through a transcystic tube. The hepatic duct was clearly visualized with the use of ﬂuorescent imaging (Photodynamic Eye; Hamamatsu Photonics). We decided the cutting line of the bile duct that was appropriate for both donor and recipient under guidance of this imaging.
Recipient Surgery (Duct-to-Duct Biliary Reconstruction) In total hepatectomy, the hilar plate was dissected sharply at or distal to the branch of the bile duct. During dissection, careful attention was paid to keep the tissues surrounding the hilar plate intact as much as possible in an attempt to preserve an adequate blood supply to the bile duct. Bile duct anastomosis was performed after completion of all vascular anastomoses and reperfusion of the liver graft. An end-to-end anastomosis between the graft and recipient bile ducts with the use of 6-0 polydioxanone sutures was completed with a running posterior line and an interrupted anterior row of stitches for 77 patients and with interrupted sutures in both the posterior and the anterior walls for 31 patients with the use of Pair-Watch suturing technique . In the case of more than 1 ductal opening in the graft, if the openings were adjacent to each other, ductoplasty was performed to suture them to form a single oriﬁce. If 2 ductal openings in the graft were far apart, separate duct-to-duct anastomoses were performed without ductoplasty. A stent tube was routinely placed through the anastomosis as a splint and was pulled out through the common bile duct above the duodenum. A cholangiogram was obtained via the inserted stent tube 1 month after LDLT, and then the stent tube was clamped. The tubes for bile duct stenting were removed 3 months after LDLT.
Diagnosis and Treatment of Biliary Complications Biliary leakage was diagnosed clinically and radiologically on the basis of a bile leak through abdominal drains, evacuation of extrahepatic biloma through a newly inserted drain under CT guidance, or identiﬁcation of a leak by endoscopic retrograde cholangiography (ERC) or cholangiography via an inserted stent tube. For biliary leakage, endoscopic retrograde nasobiliary drainage
MIZUNO, INOUE, TANEMURA ET AL
(ENBD) or percutaneous drainage under CT guidance were most commonly performed. Biliary stricture was primarily suspected when cholestatic enzymes were increased, and cholangiography was performed via the biliary stent tube during the early postoperative period. After the stent tube was taken out, MRCP was performed. For all patients who were strongly suspected for the presence of strictures, we performed ERC and/or percutaneous transhepatic cholangiography. Biliary stenosis was deﬁned as the need for endoscopic or radiologic treatment. Primary transpapillary intervention was attempted in all patients who underwent duct-to-duct biliary reconstruction. Endoscopic retrograde balloon cholangioplasty was performed; this was followed by the placement of a plastic internal stent tube. When endoscopic treatment failed, percutaneous management of the biliary stricture was undertaken. Surgical revision was indicated when both these modalities failed.
were no hepatic arterial complications in patients who experienced biliary complications. Risk Factors for Biliary Stricture After LDLT
With the use of univariate analysis, we found 4 variables to be associated with an increased risk of biliary stricture: right lobe graft, prolonged cold ischemia time (>120 min), multiple anastomoses, and a postoperative biliary leakage (Table 3). After multivariate analysis, only a postoperative biliary leakage was the signiﬁcant factor (P ¼ .013; risk ratio, 2.463; 95% conﬁdence interval, 2.022e19.246). There were no signiﬁcant differences in the incidence of biliary stricture regarding donor age, MELD score, graft type, ICG cholangiography, or anastomotic sutures. Biliary StrictureeFree Survival Rate After LDLT
Statistical Analyses Categoric variables were compared with the use of the chi-square test. Continuous data were compared with the use of the MannWhitney test. Patient survival after liver transplantation was analyzed with the use of the Kaplan-Meier survival method. Variables with a P value of 5 years after LDLT. Management of Biliary Complications
For biliary leakage, ENBD was possible in 4 patients. Two patients with biliary leakage underwent percutaneous drainage under CT guidance. All patients were successfully treated by these modalities, and no patient needed surgical revision. Figure 2 shows the summary of the various modalities used for the treatment of biliary strictures. Initially, the patients with biliary strictures were referred for ERC. Twelve of the 15 patients successfully underwent ERC, a guidewire could pass through the stricture, and these patients were treated with the use of endoscopic internal Table 3. Uni-and Multivariate Analysis of Risk Factors for Biliary Strictures Univariable Variable
Preoperative factor Donor age >50-year MELD score >25 Malignancy HCV positive Emergency operation Operative factor Right lobe graft Cold ischemic time >120 Multiple anastomoses Graft-recipient bile duct discrepancy ICG-cholangiography using Continuous suture Postoperative factor Biliary leakage Hepatic artery thrombosis CMV infection
Multivariable HR (95% CI)
.138 .163 .771 .960 .893 .035 .024 .020 .781
1.187 (0.649e39.334) .258 1.131 (0.551e7.911) .235 1.897 (0.650e4.296) .549
.301 .648 .002 .982 .268
2.463 (2.022e19.246) .013
Abbreviations: MELD, The Model for End-Stage Liver Disease; HCV, hepatitis C; CMV, cytomegalovirus.
COMPLICATIONS AFTER DUCT-TO-DUCT BILIARY RECONSTRUCTION
Fig 1. Biliary strictureefree survival rate after living-donor liver transplantation (LDLT). Proportion of patients not requiring interventional treatment for biliary stricture. The 1-year and 3-year biliary strictureefree survival rates were 88.4% and 83.0%, respectively. Biliary stricture occurred in 2 patients >5 years after LDLT.
balloon dilatation or stent placement. In 9 patients (75%), no symptoms of biliary stricture had been observed since ballooning or stenting. Three patients required percutaneous transhepatic biliary drainage (PTBD), and all patients underwent balloon dilataion. Consequently, 3 patients underwent Roux-en-Y reconstruction to repair the stricture. DISCUSSION
In our retrospective analysis, biliary leakages and strictures after LDLT occurred in 14% and 6%, respectively, of the recipients who underwent duct-to-duct biliary
reconstruction. In earlier reports, biliary strictures after LDLT with duct-to-duct biliary reconstruction range from 20% to 60% [20,21], whereas in patients who have undergone cadaveric-donor liver transplantation with duct-to-duct biliary reconstruction, biliary stricture occurred in