Chen et al.
* 2014 Lippincott Williams & Wilkins
53.
Seo JK, Ryu JK, Lee SH, et al. Endoscopic treatment for biliary stricture after adult living donor liver transplantation. Liver Transpl 2009; 15: 369.
SECTION 11. RADIOLOGICAL INTERVENTION APPROACHES TO BILIARY COMPLICATIONS AFTER LIVING DONOR LIVER TRANSPLANTATION
Gi-Young Ko,1,2 and Kyu-Bo Sung1 Abstract. Although endoscopic treatment has become the first choice to treat biliary complications, percutaneous transhepatic treatment still has important roles to treat biliary stricture or leak after living donor liver transplantation. This study reviewed a total of 527 recipients who had undergone percutaneous transhepatic treatment to treat biliary stricture (n=498) and leaks (n=29). Percutaneous transhepatic treatment included percutaneous transhepatic biliary drainage, perihepatic biloma drainage, balloon dilation of biliary stricture, and drainage catheter interposition or retrievable covered stent placement across a stricture or leak segment. Clinical success was achieved in 440 (88.4%) recipients with biliary stricture and 19 (65.5%) recipients with bile leaks. Percutaneous transhepatic treatment seems to be an effective alternative for treating biliary complications resistant to or inaccessible by endoscopic treatment. Keywords: Liver transplantation, Biliary complications, PTBD, Stent.
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Korea. The initial diagnosis of biliary complications was based on a combination of clinical symptoms, biochemical data, and the results of imaging studies using ultrasonography, computed tomography, and diisopropyl iminodiacetic acid scanning.
Stricture Four hundred ninety-eight of the 527 recipients underwent percutaneous transhepatic treatment to treat biliary stricture. The routine protocol of percutaneous transhepatic treatment included percutaneous transhepatic biliary drainage (PTBD), repeated balloon dilation of biliary stricture, and serial exchanges of biliary drainage catheters (Cook, Bloomington, IN) up to 14 Fr (Group 1). Stone removal using a stone basket was also performed if there were filling defects in the intrahepatic or common bile ducts. Since 2006, dual catheter placement technique, in which insertion of two drainage catheters (14 and 8.5 Fr) via a single percutaneous tract, was also adopted to achieve sufficient dilation of the stricture (Group 2). After at least 3 months of 14 Fr or dual catheter interposition across the stricture, the catheter was repositioned above the stricture, with the tip clamped for 4 weeks to assess the presence of elastic restenosis of the treated stricture. Drainage catheters were removed when the 4-week follow-up cholangiogram revealed fluent internal drainage with stable biochemical data. Retrievable covered stent placement after initial PTBD and balloon dilation was also tried to achieve sufficient dilation of the anastomotic stricture with reduced treatment duration (Group 3). Covered stent (TaeWoong Medical, Seoul, Korea) with 8 to 10 mm in diameter was deployed across the stricture, and it was removed using a 9-Fr braded sheath and a retrieval hook wire (TaeWoong) at least 8 weeks after placement. Detailed procedural technique of each percutaneous transhepatic treatment was described elsewhere (3Y5). Three hundred twenty-two of the 498 recipients had DD anastomotic stricture, 165 had HJ anastomotic stricture, and the remaining 11 had both DD and HJ anastomotic strictures. The initial endoscopic cannulation of the intrahepatic or common bile ducts failed in 199 recipients who had DD anastomosis.
iliary complications, including biliary stricture, leaks, stone or biliary cast syndrome, still remain as common causes of morbidity following living donor liver transplantation (LDLT). Endoscopic treatment is generally accepted as the best initial method for treating biliary complications with low morbidity and mortality (1, 2). However, endoscopic treatment is not easy in patients who have complete duct-to-duct (DD) anastomotic occlusion. In addition, endoscopic treatment is nearly impossible in patients who have hepaticojejunostomy (HJ). In such situations, percutaneous trans-hepatic treatment may be a good alternative. The aim of this current study is to retrospectively review the efficacy of various percutaneous trans-hepatic treatments for treating biliary complications following LDLT at a single institution.
Twenty-nine recipients underwent percutaneous transhepatic treatment to treat bile leaks. Sixteen of them had DD anastomosis, six had HJ anastomosis, and seven had both DD and HJ anastomoses. The indications for PTBD in patients who had DD anastomosis were bile leaks refractory to endoscopic management for 1 week, failed endoscopic cannulation of the intrahepatic bile duct across anastomosis, and a poor general condition for endoscopy. Percutaneous transhepatic treatment included percutaneous drainage of perihepatic biloma under ultrasonographic or fluoroscopic guidance, PTBD, and interposition of a drainage catheter across the leakage site. In patients who had bile leaks with anastomotic biliary stricture, balloon dilation of the biliary stricture was also performed. Serial exchanges of the bile drainage catheter up to 14 Fr were routinely performed at 4-week intervals to avoid postinflammatory stricture or restenosis. Detailed procedural technique was described elsewhere (6).
MATERIALS AND METHODS
The primary patency of clinical success was analyzed with the KaplanMeier method. The analysis was performed with SPSS software, version 19.0 (SPSS, Chicago, IL).
B
During the last 15 years, 527 (18.8%) of 2798 LDLT recipients including 10 pediatric patients (G15 years) underwent percutaneous transhepatic treatment to manage biliary complications at the Asan Medical Center, Seoul, The authors declare no funding or conflicts of interest. 1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Korea. 2 Address correspondence to: Gi-Young Ko, M.D., Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. E-mail: [email protected] G.-Y.K. participated in research design, manuscript writing, performance of the research, and data analysis. K.-B.S. participated in research design, performance of the research, and data analysis.
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
Leak
Statistical Analyses
RESULTS Stricture Percutaneous transhepatic biliary drainage was successfully performed in all 498 recipients. Fifteen recipients had anastomotic as well as nonanastomotic biliary strictures. One hundred twenty-eight recipients required 2 or more PTBD sessions to treat complex anastomotic strictures. Cannulation of the biliary strictures or occlusion and subsequent balloon dilation were technically successful in 488 (98.0%) of 498recipients. In the remaining 10 recipients, cannulation of the biliary stricture failed despite
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Transplantation
several cannulation attempts, and four of them underwent subsequent surgical revision. Thirty-four recipients died, and 24 were lost to follow-up during the course of treatment. Therefore, clinical success was achieved in 440 (88.4%) recipients after percutaneous transhepatic treatments. Two hundred eight-one of the 440 recipients received interposition of a 14-Fr catheter (Group 1), 46 received interposition of dual catheters (Group 2), and 20 received retrievable covered stent placement (Group 3). The other 93 recipients underwent dual-catheter interposition after repeated interposition of a 14-Fr catheter due to elastic restenosis after reposition of the catheter above the initial stricture. All stents, except in one case with complete migration, could be removed successfully at a median of 14 weeks after placement. Drain catheters were finally removed in 426 (96.8%) of 440 recipients. The mean treatment duration and primary patency rate of each group were listed in Table 1 and Figure 1. Bleeding complications necessitating transarterial embolization during percutaneous transhepatic treatment occurred in 17 (3.4%) recipients, and one died of bleeding-related complication. Stent migration occurred in 7 (24.1%) of 29 stents. Leak Cholangiogram during PTBD revealed bile leak at anastomosis (n=27) and at the liver cut surface (n=2). Anastomotic or nonanastomotic biliary strictures were combined with bile leaks in 16 and 2 recipients, respectively. Percutaneous transhepatic biliary drainage was technically successful in all except in one recipient. In one patient who had bile leak at both DD and HJ anastomoses after dual graft LDLT, the PTBD of the left-sided graft failed. The patient finally underwent retransplantation because of persistent bile leak and PTBD-related multiple intrahepatic pseudoaneurysms in the left-sided graft. There were no major procedural complications except the pseudoaneurysms. Cannulation and subsequent balloon dilation of the biliary strictures were technically successful in all 18 patients. Clinical success was achieved in 19 (65.5%) of 29 recipients after percutaneous transhepatic treatments. Biliary drainage catheters were removed in 18 of 19 recipients with clinical success at a median of 9.1 (range, 3Y44) months after PTBD. During a median follow-up period
& Volume 97, Number 8S, April 27, 2014
FIGURE 1. Primary patency of each percutaneous transhepatic treatment of biliary stricture.
of 82.4 (range, 21.7Y153.6) months, 9 of the 18 recipients had to undergo repeat PTBD or endoscopic balloon dilation because of anastomotic restenosis. Primary patency rates at 1, 2, and 3 years were 88.2T7.8%, 69.7T11.4%, and 57.0T12.3%, respectively.
DISCUSSION Despite innovative surgical techniques for LDLT, biliary complication remains the most common cause of postoperative morbidity. Endoscopic treatment has largely replaced percutaneous transhepatic treatment or surgical revision as the initial treatment of biliary complications with low morbidity. However, the success rates of endoscopic treatment for biliary stricture in LDLT recipients appear to be lower than those for deceased donor liver transplant recipients and have ranged from 47% to 75% for anastomotic stricture (7). Therefore, percutaneous transhepatic treatment still remains an important tool to treat biliary complications. Cannulation of a biliary stricture or occlusion is essential during percutaneous transhepatic or endoscopic treatment. Various cannulation techniques, including conventional 0.035-inch guide wire technique, microcatheter technique, and rendezvous or magnetic compression anastomosis technique under both endoscopy and percutaneous transhepatic routes
TABLE 1. Outcomes of percutaneous transhepatic treatments of biliary stricture according to interposed drainage catheters and stents Groups
Group 1 (n=281)
Group 2 (n=46)
Group 3 (n=20)
Treatment duration
10.4T8.2 months
13.0T3.9 months
9.1T5.7 months
Follow-up (in yr) 1 3 5 7 Mean follow-up Recurrence
1- Patency rate (%)
Remaining cases
94.1T1.4 84.8T2.3 83.8T2.3 79.2T2.9 5.6T2.8 years 48/281 (17.1%)
247 187 147 72 3.1T2.8 years 5/84 (10.9%)
1- Patency rate (%) 95.7T3.0 84.8T6.6 84.8T6.6
Remaining Cases 36 21 12
1- Patency rate (%)
Remaining cases
100 94.7T5.1
20 13
3.1T1.2 years 1/20 (5.0%)
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Chen et al.
* 2014 Lippincott Williams & Wilkins
can be used (8, 9). In our experience, cannulation of a stricture was successfully achieved in 98%, and final clinical success was achieved in 88.4% after percutaneous transhepatic treatment. These results were superior to reported immediate success rates of 55.8% to 78.5% and final success rates of 33.3% to 57% of endoscopic treatment alone (2, 7, 10Y12). There is no consensus regarding the standard protocol of percutaneous transhepatic treatment of biliary stricture after LDLT. Therefore, we adopted the interposition of a 14-Fr drainage catheter as the basic treatment protocol. Using this protocol, however, we found frequent occurrence of elastic restenosis or occlusion in cholangiograms performed 4 weeks after drainage catheter positioning above the stricture. After modifying our protocol using dual catheter placement, we could reduce the occurrence of elastic restenosis or occlusion. Gwon et al. (3) reported that clinical success rate was achieved in 78 (98.7%) of 79 recipients using dual catheter placement. These results indicate that interposition of larger diameter drainage catheter is better to minimize the incidence of early recurrence. Retrievable covered stent placement seems to be a good alternative to shorten treatment duration. Successful treatment of biliary stricture or leak after deceased donor liver transplantation using retrievable covered stent placement under endoscopy has been reported (13, 14). In comparison, application of retrievable covered stents in LDLT recipients is limited owing to high frequency of complex biliary anastomotic strictures and a risk of branching bile duct occlusion by a covered stent. In our experiences, however, retrievable covered stent placement was feasible to treat biliary stricture in selected LDLT recipients with shorter treatment duration (mean, 197 days) compared with interposition of a 14 Fr catheter (mean, 278 days) (4). Further investigation is still needed to overcome various limitations of retrievable covered stent placement in LDLT recipients. The preferred treatment modality to treat posttransplant bile leaks is endoscopy (38%), followed by surgical revision (28%) and percutaneous transhepatic treatment (10%) (2). Percutaneous transhepatic treatment of bile leaks is generally the same as that for stricture, although initial PTBD of decompressed intrahepatic bile ducts is difficult. Interestingly, bile leaks associated with biliary stricture is not uncommon in LDLT recipients, and the reported incidence ranges from 33% to 69% (15Y17). In our cases, we found the coexistence of bile leaks and stricture in 18 (66.7%) of 27 recipients. Several investigators demonstrated bile leaks as a significant risk factor for subsequent biliary stricture (17Y20). Primary patency rate after percutaneous transhepatic treatment of bile leaks was not excellent in our experience, and it might be attributed to delayed occurrence after postinflammatory stricture. Further investigation is needed to minimize recurrence after completion of percutaneous transhepatic or endoscopic treatment. Although percutaneous transhepatic treatment is effective to treat biliary complications after LDLT, the patients’ discomfort related to prolonged maintenance of a drainage catheter is a main limitation. Replacement of a biliary drainage catheter with endoscopic drainage catheters after cannulation of a stricture via percutaneous transhepatic approach may solve this limitation (21, 22). Another limitation of percutaneous transhepatic treatment is its invasiveness. In our
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experiences, bleeding that required transarterial embolization or pseudoaneurysm requiring retransplantation occurred in 18 (3.4%) of 527 recipients. Careful percutaneous transhepatic treatment with experienced skill is mandatory. In summary, percutaneous transhepatic treatment is an effective alternative for treating biliary stricture or leaks resistant to or inaccessible by endoscopic treatment. However, further investigation is needed to overcome various limitations of percutaneous transhepatic treatment. REFERENCES 1. 2.
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Yazumi S, Chiba T. Biliary complications after a right-lobe living donor liver transplantation. J Gastroenterol 2005; 40: 861. Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction, its complications and management of biliary complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome. Transpl Int 2011; 24: 379. Gwon DI, Sung KB, Ko GY, et al. Dual catheter placement technique for treatment of biliary anastomotic strictures after liver transplantation. Liver Transpl 2011; 17: 159. Kim J, Ko GY, Sung KB, et al. Percutaneously placed covered retrievable stents for the treatment of biliary anastomotic strictures following living donor liver transplantation. Liver Transpl 2010; 16: 1410. Ko GY, Sung KB, Yoon HK, et al. Percutaneous transhepatic treatment of hepaticojejunal anastomotic biliary strictures after living donor liver transplantation. Liver Transpl 2008; 14: 1323. Kim JH, Ko GY, Sung KB, et al. Bile leak following living donor liver transplantation: clinical efficacy of percutaneous transhepatic treatment. Liver Transpl 2008; 14: 1142. Lee YY, Gwak GY, Lee KH, et al. Predictors of the feasibility of primary endoscopic management of biliary strictures after adult living donor liver transplantation. Liver Transpl 2011; 17: 1467. Yoon HM, Kim JH, Ko GY, et al. Alternative techniques for cannulation of biliary strictures resistant to the 0.035’’ system following living donor liver transplantation. Korean J Radiol 2012; 13: 189. Jang SI, Kim JH, Won JY, et al. Magnetic compression anastomosis is useful in biliary anastomotic strictures after living donor liver transplantation. Gastrointest Endosc 2011; 74: 1040. Chang JH, Lee IS, Choi JY, et al. Biliary stricture after adult right-lobe living-donor liver transplantation with duct-to-duct anastomosis: long-term outcome and its related factors after endoscopic treatment. Gut Liver 2010; 4: 226. Kim TH, Lee SK, Han JH, et al. The role of endoscopic retrograde cholangiography for biliary stricture after adult living donor liver transplantation: technical aspect and outcome. Scand J Gastroenterol 2011; 46: 188. Yazumi S, Yoshimoto T, Hisatsune H, et al. Endoscopic treatment of biliary complications after right-lobe living-donor liver transplantation with duct-to-duct biliary anastomosis. J Hepatobiliary Pancreat Surg 2006; 13: 502. Marin-Gomez LM, Sobrino-Rodriguez S, Alamo-Martinez JM, et al. Use of fully covered self-expandable stent in biliary complications after liver transplantation: a case series. Transplant Proc 2010; 42: 2975. Tee HP, James MW, Kaffes AJ. Placement of removable metal biliary stent in post-orthotopic liver transplantation anastomotic stricture. World J Gastroenterol 2010; 16: 3597. Chang JM, Lee JM, Suh KS, et al. Biliary complications in living donor liver transplantation: imaging findings and the roles of interventional procedures. Cardiovasc Intervent Radiol 2005; 28: 756. Lee CS, Liu NJ, Lee CF, et al. Endoscopic management of biliary complications after adult right-lobe living donor liver transplantation without initial biliary decompression. Transplant Proc 2008; 40: 2542. Shah SA, Grant DR, McGilvray ID, et al. Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center. Am J Transplant 2007; 7: 161. Seo JK, Ryu JK, Lee SH, et al. Endoscopic treatment for biliary stricture after adult living donor liver transplantation. Liver Transpl 2009; 15: 369.
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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Melcher ML, Pomposelli JJ, Verbesey JE, et al. Comparison of biliary complications in adult living-donor liver transplants performed at two busy transplant centers. Clin Transplant 2010; 24: E137. Tashiro H, Itamoto T, Sasaki T, et al. Biliary complications after ductto-duct biliary reconstruction in living-donor liver transplantation: causes and treatment. World J Surg 2007; 31: 2222. Hsieh TH, Mekeel KL, Crowell MD, et al. Endoscopic treatment of anastomotic biliary strictures after living donor liver transplantation: outcomes after maximal stent therapy. Gastrointest Endosc 2013; 77: 47. Chang JH, Lee IS, Chun HJ, et al. Usefulness of the rendezvous technique for biliary stricture after adult right-lobe living-donor liver transplantation with duct-to-duct anastomosis. Gut Liver 2010; 4: 68.
SECTION 12. LIVING DONOR LIVER TRANSPLANTATION FOR PATIENTS WITH HIGH MODEL FOR END-STAGE LIVER DISEASE SCORES AND ACUTE LIVER FAILURE
Toshimi Kaido,1,2 Koji Tomiyama,1 Kohei Ogawa,1 Yasuhiro Fujimoto,1 Takashi Ito,1 Akira Mori,1 and Shinji Uemoto1 Abstract. Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease score and acute liver failure patients have little or not gained any substantial following among Western centers because of the ‘‘donor high risk-low recipient benefit scenario’’ that puts the donor at a significant risk against the survival odds for a recipient who is receiving a partial graft and considered marginal by Western standards. In most Asian countries, there is sometimes no other source of live graft but a willing live liver donor. There are individual Asian center reports that conclude that LDLT has comparable outcome to deceased donor liver transplant. However, the outcomes of a large number of patients after undergoing adult LDLT for high model for end-stage liver disease scores and acute liver failure at a single center have not been investigated. Here in, we present our experience with such subgroup of patients undergoing LDLT. Keywords: Liver transplantation, Model for end-stage liver disease score, Acute liver failure.
iving donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores remains debatable. Some reports describe decreased
L
The authors declare no funding or conflicts of interest. 1 Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2 Address correspondence to: Toshimi Kaido, M.D., Ph.D., Division of HepatoBiliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected] T.K. participated in research design, writing of the paper, performance of the research, and data analysis. K.T. participated in research design, performance of the research, and data analysis. K.O. participated in the performance of the research. Y.F. participated in the performance of the research. T.I. participated in the performance of the research. A.M. participated in the performance of the research. S.U. participated in research design and the performance of the research.
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
Transplantation
& Volume 97, Number 8S, April 27, 2014
overall patient and graft survival rates for patients with high MELD scores after LDLT (1, 2). Others report that LDLT could provide excellent graft function and survival rates in such patients (3, 4). Liver transplantation is also an effective modality for treating acute liver failure (ALF) when patients are refractory to medical treatment. Acute liver failure has been predominantly treated using LDLT in Asian countries such as Japan and Korea (5Y7). However, the outcomes of a large number of patients after undergoing adult LDLT for ALF at a single center have not been investigated. We therefore assessed the impact of MELD scores on the outcomes of 223 patients who underwent adult-to-adult LDLT between January 2006 and April 2011 at Kyoto University. We also reviewed 72 adult patients who underwent LT for ALF at a single center over a period of 15 years.
LDLT FOR PATIENTS WITH HIGH MELD SCORES This study enrolled 223 patients who underwent adult-to-adult LDLT between January 2006 and April 2011 at Kyoto University. Patients who underwent a repeated LT or LT for ALF were excluded. The ethics committee at Kyoto University approved the study, which proceeded in accordance with the Declaration of Helsinki of 1996. The median MELD score was 17 (range, 6Y47; Fig. 1). The graft-to-recipient weight ratio and incidence of ABOincompatible LT did not differ among patients with MELD scores of G10, Q10Y15, Q15Y20, Q20Y25, Q25Y30, Q30Y35, and 935. Overall patient survival rates did not differ among the patients assigned to these groups. Overall patient survival rates also did not significantly differ between patients with low (G25) and high (Q25) MELD scores (Fig. 2). In conclusion, LDLT can facilitate acceptable outcomes for patients with high MELD scores.
LDLT FOR ACUTE LIVER FAILURE We reviewed data from 72 adult ALF patients (male, n=33; median age, 42 years, range 19Y68 years) with a median MELD score of 19 (range, 7Y41) who underwent LDLT at a single center over a period of 15 years. Six patients were ABO incompatible, and 66 were identical or compatible. Total scores for predictive variables affecting the mortality of each patient with ALF were calculated based on the proposal of the Study Group of Intractable Hepatobiliary Diseases in Japan (8). Among the 72 patients, 17 and 55 had acute and subacute ALF, respectively. The etiologies of ALF were hepatitis B virus (n=29), drug exposure (n=11), autoimmune hepatitis (n=2), and unknown (n=30). The total scores for predictive variables varied from 2 to 10 with a median of 7. The average score was significantly higher in patients with subacute than acute ALF (7.2 vs. 4.4; PG0.001). Patient survival rates were 65%, 65%, and 61% at 1, 3, and 5 years, respectively. The overall survival rates did not differ among patients according to the etiology of ALF (P=0.693), type of ALF (P=0.745), ABO compatibility (P=0.912), total scores for predictive variables (P=0.975), or having a graft-to-recipient weight ratio above or below 0.8% (P=0.063). Among the 72 patients, 27 died at a median of 1 (range, 0Y60) month after LT. The most frequent cause of death after LT was infection (n=14) followed by multiple
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
* 2014 Lippincott Williams & Wilkins
53.
Seo JK, Ryu JK, Lee SH, et al. Endoscopic treatment for biliary stricture after adult living donor liver transplantation. Liver Transpl 2009; 15: 369.
SECTION 11. RADIOLOGICAL INTERVENTION APPROACHES TO BILIARY COMPLICATIONS AFTER LIVING DONOR LIVER TRANSPLANTATION
Gi-Young Ko,1,2 and Kyu-Bo Sung1 Abstract. Although endoscopic treatment has become the first choice to treat biliary complications, percutaneous transhepatic treatment still has important roles to treat biliary stricture or leak after living donor liver transplantation. This study reviewed a total of 527 recipients who had undergone percutaneous transhepatic treatment to treat biliary stricture (n=498) and leaks (n=29). Percutaneous transhepatic treatment included percutaneous transhepatic biliary drainage, perihepatic biloma drainage, balloon dilation of biliary stricture, and drainage catheter interposition or retrievable covered stent placement across a stricture or leak segment. Clinical success was achieved in 440 (88.4%) recipients with biliary stricture and 19 (65.5%) recipients with bile leaks. Percutaneous transhepatic treatment seems to be an effective alternative for treating biliary complications resistant to or inaccessible by endoscopic treatment. Keywords: Liver transplantation, Biliary complications, PTBD, Stent.
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Korea. The initial diagnosis of biliary complications was based on a combination of clinical symptoms, biochemical data, and the results of imaging studies using ultrasonography, computed tomography, and diisopropyl iminodiacetic acid scanning.
Stricture Four hundred ninety-eight of the 527 recipients underwent percutaneous transhepatic treatment to treat biliary stricture. The routine protocol of percutaneous transhepatic treatment included percutaneous transhepatic biliary drainage (PTBD), repeated balloon dilation of biliary stricture, and serial exchanges of biliary drainage catheters (Cook, Bloomington, IN) up to 14 Fr (Group 1). Stone removal using a stone basket was also performed if there were filling defects in the intrahepatic or common bile ducts. Since 2006, dual catheter placement technique, in which insertion of two drainage catheters (14 and 8.5 Fr) via a single percutaneous tract, was also adopted to achieve sufficient dilation of the stricture (Group 2). After at least 3 months of 14 Fr or dual catheter interposition across the stricture, the catheter was repositioned above the stricture, with the tip clamped for 4 weeks to assess the presence of elastic restenosis of the treated stricture. Drainage catheters were removed when the 4-week follow-up cholangiogram revealed fluent internal drainage with stable biochemical data. Retrievable covered stent placement after initial PTBD and balloon dilation was also tried to achieve sufficient dilation of the anastomotic stricture with reduced treatment duration (Group 3). Covered stent (TaeWoong Medical, Seoul, Korea) with 8 to 10 mm in diameter was deployed across the stricture, and it was removed using a 9-Fr braded sheath and a retrieval hook wire (TaeWoong) at least 8 weeks after placement. Detailed procedural technique of each percutaneous transhepatic treatment was described elsewhere (3Y5). Three hundred twenty-two of the 498 recipients had DD anastomotic stricture, 165 had HJ anastomotic stricture, and the remaining 11 had both DD and HJ anastomotic strictures. The initial endoscopic cannulation of the intrahepatic or common bile ducts failed in 199 recipients who had DD anastomosis.
iliary complications, including biliary stricture, leaks, stone or biliary cast syndrome, still remain as common causes of morbidity following living donor liver transplantation (LDLT). Endoscopic treatment is generally accepted as the best initial method for treating biliary complications with low morbidity and mortality (1, 2). However, endoscopic treatment is not easy in patients who have complete duct-to-duct (DD) anastomotic occlusion. In addition, endoscopic treatment is nearly impossible in patients who have hepaticojejunostomy (HJ). In such situations, percutaneous trans-hepatic treatment may be a good alternative. The aim of this current study is to retrospectively review the efficacy of various percutaneous trans-hepatic treatments for treating biliary complications following LDLT at a single institution.
Twenty-nine recipients underwent percutaneous transhepatic treatment to treat bile leaks. Sixteen of them had DD anastomosis, six had HJ anastomosis, and seven had both DD and HJ anastomoses. The indications for PTBD in patients who had DD anastomosis were bile leaks refractory to endoscopic management for 1 week, failed endoscopic cannulation of the intrahepatic bile duct across anastomosis, and a poor general condition for endoscopy. Percutaneous transhepatic treatment included percutaneous drainage of perihepatic biloma under ultrasonographic or fluoroscopic guidance, PTBD, and interposition of a drainage catheter across the leakage site. In patients who had bile leaks with anastomotic biliary stricture, balloon dilation of the biliary stricture was also performed. Serial exchanges of the bile drainage catheter up to 14 Fr were routinely performed at 4-week intervals to avoid postinflammatory stricture or restenosis. Detailed procedural technique was described elsewhere (6).
MATERIALS AND METHODS
The primary patency of clinical success was analyzed with the KaplanMeier method. The analysis was performed with SPSS software, version 19.0 (SPSS, Chicago, IL).
B
During the last 15 years, 527 (18.8%) of 2798 LDLT recipients including 10 pediatric patients (G15 years) underwent percutaneous transhepatic treatment to manage biliary complications at the Asan Medical Center, Seoul, The authors declare no funding or conflicts of interest. 1 Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Korea. 2 Address correspondence to: Gi-Young Ko, M.D., Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. E-mail: [email protected] G.-Y.K. participated in research design, manuscript writing, performance of the research, and data analysis. K.-B.S. participated in research design, performance of the research, and data analysis.
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
Leak
Statistical Analyses
RESULTS Stricture Percutaneous transhepatic biliary drainage was successfully performed in all 498 recipients. Fifteen recipients had anastomotic as well as nonanastomotic biliary strictures. One hundred twenty-eight recipients required 2 or more PTBD sessions to treat complex anastomotic strictures. Cannulation of the biliary strictures or occlusion and subsequent balloon dilation were technically successful in 488 (98.0%) of 498recipients. In the remaining 10 recipients, cannulation of the biliary stricture failed despite
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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www.transplantjournal.com
Transplantation
several cannulation attempts, and four of them underwent subsequent surgical revision. Thirty-four recipients died, and 24 were lost to follow-up during the course of treatment. Therefore, clinical success was achieved in 440 (88.4%) recipients after percutaneous transhepatic treatments. Two hundred eight-one of the 440 recipients received interposition of a 14-Fr catheter (Group 1), 46 received interposition of dual catheters (Group 2), and 20 received retrievable covered stent placement (Group 3). The other 93 recipients underwent dual-catheter interposition after repeated interposition of a 14-Fr catheter due to elastic restenosis after reposition of the catheter above the initial stricture. All stents, except in one case with complete migration, could be removed successfully at a median of 14 weeks after placement. Drain catheters were finally removed in 426 (96.8%) of 440 recipients. The mean treatment duration and primary patency rate of each group were listed in Table 1 and Figure 1. Bleeding complications necessitating transarterial embolization during percutaneous transhepatic treatment occurred in 17 (3.4%) recipients, and one died of bleeding-related complication. Stent migration occurred in 7 (24.1%) of 29 stents. Leak Cholangiogram during PTBD revealed bile leak at anastomosis (n=27) and at the liver cut surface (n=2). Anastomotic or nonanastomotic biliary strictures were combined with bile leaks in 16 and 2 recipients, respectively. Percutaneous transhepatic biliary drainage was technically successful in all except in one recipient. In one patient who had bile leak at both DD and HJ anastomoses after dual graft LDLT, the PTBD of the left-sided graft failed. The patient finally underwent retransplantation because of persistent bile leak and PTBD-related multiple intrahepatic pseudoaneurysms in the left-sided graft. There were no major procedural complications except the pseudoaneurysms. Cannulation and subsequent balloon dilation of the biliary strictures were technically successful in all 18 patients. Clinical success was achieved in 19 (65.5%) of 29 recipients after percutaneous transhepatic treatments. Biliary drainage catheters were removed in 18 of 19 recipients with clinical success at a median of 9.1 (range, 3Y44) months after PTBD. During a median follow-up period
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FIGURE 1. Primary patency of each percutaneous transhepatic treatment of biliary stricture.
of 82.4 (range, 21.7Y153.6) months, 9 of the 18 recipients had to undergo repeat PTBD or endoscopic balloon dilation because of anastomotic restenosis. Primary patency rates at 1, 2, and 3 years were 88.2T7.8%, 69.7T11.4%, and 57.0T12.3%, respectively.
DISCUSSION Despite innovative surgical techniques for LDLT, biliary complication remains the most common cause of postoperative morbidity. Endoscopic treatment has largely replaced percutaneous transhepatic treatment or surgical revision as the initial treatment of biliary complications with low morbidity. However, the success rates of endoscopic treatment for biliary stricture in LDLT recipients appear to be lower than those for deceased donor liver transplant recipients and have ranged from 47% to 75% for anastomotic stricture (7). Therefore, percutaneous transhepatic treatment still remains an important tool to treat biliary complications. Cannulation of a biliary stricture or occlusion is essential during percutaneous transhepatic or endoscopic treatment. Various cannulation techniques, including conventional 0.035-inch guide wire technique, microcatheter technique, and rendezvous or magnetic compression anastomosis technique under both endoscopy and percutaneous transhepatic routes
TABLE 1. Outcomes of percutaneous transhepatic treatments of biliary stricture according to interposed drainage catheters and stents Groups
Group 1 (n=281)
Group 2 (n=46)
Group 3 (n=20)
Treatment duration
10.4T8.2 months
13.0T3.9 months
9.1T5.7 months
Follow-up (in yr) 1 3 5 7 Mean follow-up Recurrence
1- Patency rate (%)
Remaining cases
94.1T1.4 84.8T2.3 83.8T2.3 79.2T2.9 5.6T2.8 years 48/281 (17.1%)
247 187 147 72 3.1T2.8 years 5/84 (10.9%)
1- Patency rate (%) 95.7T3.0 84.8T6.6 84.8T6.6
Remaining Cases 36 21 12
1- Patency rate (%)
Remaining cases
100 94.7T5.1
20 13
3.1T1.2 years 1/20 (5.0%)
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Chen et al.
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can be used (8, 9). In our experience, cannulation of a stricture was successfully achieved in 98%, and final clinical success was achieved in 88.4% after percutaneous transhepatic treatment. These results were superior to reported immediate success rates of 55.8% to 78.5% and final success rates of 33.3% to 57% of endoscopic treatment alone (2, 7, 10Y12). There is no consensus regarding the standard protocol of percutaneous transhepatic treatment of biliary stricture after LDLT. Therefore, we adopted the interposition of a 14-Fr drainage catheter as the basic treatment protocol. Using this protocol, however, we found frequent occurrence of elastic restenosis or occlusion in cholangiograms performed 4 weeks after drainage catheter positioning above the stricture. After modifying our protocol using dual catheter placement, we could reduce the occurrence of elastic restenosis or occlusion. Gwon et al. (3) reported that clinical success rate was achieved in 78 (98.7%) of 79 recipients using dual catheter placement. These results indicate that interposition of larger diameter drainage catheter is better to minimize the incidence of early recurrence. Retrievable covered stent placement seems to be a good alternative to shorten treatment duration. Successful treatment of biliary stricture or leak after deceased donor liver transplantation using retrievable covered stent placement under endoscopy has been reported (13, 14). In comparison, application of retrievable covered stents in LDLT recipients is limited owing to high frequency of complex biliary anastomotic strictures and a risk of branching bile duct occlusion by a covered stent. In our experiences, however, retrievable covered stent placement was feasible to treat biliary stricture in selected LDLT recipients with shorter treatment duration (mean, 197 days) compared with interposition of a 14 Fr catheter (mean, 278 days) (4). Further investigation is still needed to overcome various limitations of retrievable covered stent placement in LDLT recipients. The preferred treatment modality to treat posttransplant bile leaks is endoscopy (38%), followed by surgical revision (28%) and percutaneous transhepatic treatment (10%) (2). Percutaneous transhepatic treatment of bile leaks is generally the same as that for stricture, although initial PTBD of decompressed intrahepatic bile ducts is difficult. Interestingly, bile leaks associated with biliary stricture is not uncommon in LDLT recipients, and the reported incidence ranges from 33% to 69% (15Y17). In our cases, we found the coexistence of bile leaks and stricture in 18 (66.7%) of 27 recipients. Several investigators demonstrated bile leaks as a significant risk factor for subsequent biliary stricture (17Y20). Primary patency rate after percutaneous transhepatic treatment of bile leaks was not excellent in our experience, and it might be attributed to delayed occurrence after postinflammatory stricture. Further investigation is needed to minimize recurrence after completion of percutaneous transhepatic or endoscopic treatment. Although percutaneous transhepatic treatment is effective to treat biliary complications after LDLT, the patients’ discomfort related to prolonged maintenance of a drainage catheter is a main limitation. Replacement of a biliary drainage catheter with endoscopic drainage catheters after cannulation of a stricture via percutaneous transhepatic approach may solve this limitation (21, 22). Another limitation of percutaneous transhepatic treatment is its invasiveness. In our
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experiences, bleeding that required transarterial embolization or pseudoaneurysm requiring retransplantation occurred in 18 (3.4%) of 527 recipients. Careful percutaneous transhepatic treatment with experienced skill is mandatory. In summary, percutaneous transhepatic treatment is an effective alternative for treating biliary stricture or leaks resistant to or inaccessible by endoscopic treatment. However, further investigation is needed to overcome various limitations of percutaneous transhepatic treatment. REFERENCES 1. 2.
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Yazumi S, Chiba T. Biliary complications after a right-lobe living donor liver transplantation. J Gastroenterol 2005; 40: 861. Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction, its complications and management of biliary complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome. Transpl Int 2011; 24: 379. Gwon DI, Sung KB, Ko GY, et al. Dual catheter placement technique for treatment of biliary anastomotic strictures after liver transplantation. Liver Transpl 2011; 17: 159. Kim J, Ko GY, Sung KB, et al. Percutaneously placed covered retrievable stents for the treatment of biliary anastomotic strictures following living donor liver transplantation. Liver Transpl 2010; 16: 1410. Ko GY, Sung KB, Yoon HK, et al. Percutaneous transhepatic treatment of hepaticojejunal anastomotic biliary strictures after living donor liver transplantation. Liver Transpl 2008; 14: 1323. Kim JH, Ko GY, Sung KB, et al. Bile leak following living donor liver transplantation: clinical efficacy of percutaneous transhepatic treatment. Liver Transpl 2008; 14: 1142. Lee YY, Gwak GY, Lee KH, et al. Predictors of the feasibility of primary endoscopic management of biliary strictures after adult living donor liver transplantation. Liver Transpl 2011; 17: 1467. Yoon HM, Kim JH, Ko GY, et al. Alternative techniques for cannulation of biliary strictures resistant to the 0.035’’ system following living donor liver transplantation. Korean J Radiol 2012; 13: 189. Jang SI, Kim JH, Won JY, et al. Magnetic compression anastomosis is useful in biliary anastomotic strictures after living donor liver transplantation. Gastrointest Endosc 2011; 74: 1040. Chang JH, Lee IS, Choi JY, et al. Biliary stricture after adult right-lobe living-donor liver transplantation with duct-to-duct anastomosis: long-term outcome and its related factors after endoscopic treatment. Gut Liver 2010; 4: 226. Kim TH, Lee SK, Han JH, et al. The role of endoscopic retrograde cholangiography for biliary stricture after adult living donor liver transplantation: technical aspect and outcome. Scand J Gastroenterol 2011; 46: 188. Yazumi S, Yoshimoto T, Hisatsune H, et al. Endoscopic treatment of biliary complications after right-lobe living-donor liver transplantation with duct-to-duct biliary anastomosis. J Hepatobiliary Pancreat Surg 2006; 13: 502. Marin-Gomez LM, Sobrino-Rodriguez S, Alamo-Martinez JM, et al. Use of fully covered self-expandable stent in biliary complications after liver transplantation: a case series. Transplant Proc 2010; 42: 2975. Tee HP, James MW, Kaffes AJ. Placement of removable metal biliary stent in post-orthotopic liver transplantation anastomotic stricture. World J Gastroenterol 2010; 16: 3597. Chang JM, Lee JM, Suh KS, et al. Biliary complications in living donor liver transplantation: imaging findings and the roles of interventional procedures. Cardiovasc Intervent Radiol 2005; 28: 756. Lee CS, Liu NJ, Lee CF, et al. Endoscopic management of biliary complications after adult right-lobe living donor liver transplantation without initial biliary decompression. Transplant Proc 2008; 40: 2542. Shah SA, Grant DR, McGilvray ID, et al. Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center. Am J Transplant 2007; 7: 161. Seo JK, Ryu JK, Lee SH, et al. Endoscopic treatment for biliary stricture after adult living donor liver transplantation. Liver Transpl 2009; 15: 369.
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SECTION 12. LIVING DONOR LIVER TRANSPLANTATION FOR PATIENTS WITH HIGH MODEL FOR END-STAGE LIVER DISEASE SCORES AND ACUTE LIVER FAILURE
Toshimi Kaido,1,2 Koji Tomiyama,1 Kohei Ogawa,1 Yasuhiro Fujimoto,1 Takashi Ito,1 Akira Mori,1 and Shinji Uemoto1 Abstract. Living donor liver transplantation (LDLT) for patients with high model for end-stage liver disease score and acute liver failure patients have little or not gained any substantial following among Western centers because of the ‘‘donor high risk-low recipient benefit scenario’’ that puts the donor at a significant risk against the survival odds for a recipient who is receiving a partial graft and considered marginal by Western standards. In most Asian countries, there is sometimes no other source of live graft but a willing live liver donor. There are individual Asian center reports that conclude that LDLT has comparable outcome to deceased donor liver transplant. However, the outcomes of a large number of patients after undergoing adult LDLT for high model for end-stage liver disease scores and acute liver failure at a single center have not been investigated. Here in, we present our experience with such subgroup of patients undergoing LDLT. Keywords: Liver transplantation, Model for end-stage liver disease score, Acute liver failure.
iving donor liver transplantation (LDLT) for patients with high model for end-stage liver disease (MELD) scores remains debatable. Some reports describe decreased
L
The authors declare no funding or conflicts of interest. 1 Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2 Address correspondence to: Toshimi Kaido, M.D., Ph.D., Division of HepatoBiliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected] T.K. participated in research design, writing of the paper, performance of the research, and data analysis. K.T. participated in research design, performance of the research, and data analysis. K.O. participated in the performance of the research. Y.F. participated in the performance of the research. T.I. participated in the performance of the research. A.M. participated in the performance of the research. S.U. participated in research design and the performance of the research.
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
Transplantation
& Volume 97, Number 8S, April 27, 2014
overall patient and graft survival rates for patients with high MELD scores after LDLT (1, 2). Others report that LDLT could provide excellent graft function and survival rates in such patients (3, 4). Liver transplantation is also an effective modality for treating acute liver failure (ALF) when patients are refractory to medical treatment. Acute liver failure has been predominantly treated using LDLT in Asian countries such as Japan and Korea (5Y7). However, the outcomes of a large number of patients after undergoing adult LDLT for ALF at a single center have not been investigated. We therefore assessed the impact of MELD scores on the outcomes of 223 patients who underwent adult-to-adult LDLT between January 2006 and April 2011 at Kyoto University. We also reviewed 72 adult patients who underwent LT for ALF at a single center over a period of 15 years.
LDLT FOR PATIENTS WITH HIGH MELD SCORES This study enrolled 223 patients who underwent adult-to-adult LDLT between January 2006 and April 2011 at Kyoto University. Patients who underwent a repeated LT or LT for ALF were excluded. The ethics committee at Kyoto University approved the study, which proceeded in accordance with the Declaration of Helsinki of 1996. The median MELD score was 17 (range, 6Y47; Fig. 1). The graft-to-recipient weight ratio and incidence of ABOincompatible LT did not differ among patients with MELD scores of G10, Q10Y15, Q15Y20, Q20Y25, Q25Y30, Q30Y35, and 935. Overall patient survival rates did not differ among the patients assigned to these groups. Overall patient survival rates also did not significantly differ between patients with low (G25) and high (Q25) MELD scores (Fig. 2). In conclusion, LDLT can facilitate acceptable outcomes for patients with high MELD scores.
LDLT FOR ACUTE LIVER FAILURE We reviewed data from 72 adult ALF patients (male, n=33; median age, 42 years, range 19Y68 years) with a median MELD score of 19 (range, 7Y41) who underwent LDLT at a single center over a period of 15 years. Six patients were ABO incompatible, and 66 were identical or compatible. Total scores for predictive variables affecting the mortality of each patient with ALF were calculated based on the proposal of the Study Group of Intractable Hepatobiliary Diseases in Japan (8). Among the 72 patients, 17 and 55 had acute and subacute ALF, respectively. The etiologies of ALF were hepatitis B virus (n=29), drug exposure (n=11), autoimmune hepatitis (n=2), and unknown (n=30). The total scores for predictive variables varied from 2 to 10 with a median of 7. The average score was significantly higher in patients with subacute than acute ALF (7.2 vs. 4.4; PG0.001). Patient survival rates were 65%, 65%, and 61% at 1, 3, and 5 years, respectively. The overall survival rates did not differ among patients according to the etiology of ALF (P=0.693), type of ALF (P=0.745), ABO compatibility (P=0.912), total scores for predictive variables (P=0.975), or having a graft-to-recipient weight ratio above or below 0.8% (P=0.063). Among the 72 patients, 27 died at a median of 1 (range, 0Y60) month after LT. The most frequent cause of death after LT was infection (n=14) followed by multiple
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