Digestive Endoscopy 2015; 27: 505–511

doi: 10.1111/den.12420

Original Article

Endoscopic treatment of pediatric post-transplant biliary complications is safe and effective Alexander Dechêne,1 Cathrin Kodde,1 Simone Kathemann,2 Jürgen Treckmann,3 Elke Lainka,2 Andreas Paul,3 Guido Gerken,1 Ariel E. Feldstein,4 Peter F. Hoyer2 and Ali Canbay1 Departments of 1Gastroenterology and Hepatology, 2Pediatrics II, 3General Surgery and Transplantation, University Hospital, University Duisburg-Essen, Essen, Germany; and 4Department of Pediatrics, University of California San Diego (UCSD), San Diego, USA Background and Aim: Biliary complications (BC) after liver transplantation (LT) are associated with significant morbidity and mortality. Incidence of BC after pediatric LT is more than 10%. In adults, treatment by endoscopic retrograde cholangiopancreaticography (ERCP) is successful. As data in pediatric patients are limited, endoscopic treatment of BC in a pediatric cohort in a German transplant center was analyzed. Methods: LT recipients 8% with 20% of all patients requiring additional surgery.10 For percutaneous transhepatic cholangiography, Feier et al. described successful treatment of AST in 77% of 45 pediatric transplant recipients with complications in 12% and a median duration of drainage indwelling of 8 months.16 In the 11 patients with AST in our series, endoscopic treatment was successful in 100% with a major complication rate of 9%. This was a duodenal hematoma treated surgically, which was probably because of pressure of the therapeutic

duodenoscope to the duodenal wall opposite the major papilla. Zoepf et al. reported endoscopic balloon dilation and stent placement to be successful in adult transplant recipients (whole organ grafts and living-related grafts) with a median of four treatment sessions and treatment duration of 4 months. In the presented pediatric cohort, a median of four treatment sessions was required over a median of 3 months until resolution of AST.17 This implies similar effectiveness of endoscopic procedures in adult and pediatric LT recipients. ITBL were found in only two patients, which is in line with the relatively low incidence of 5–15% reported by Buis et al.18 Both patients were in the mid-third age-group (aged 9 and 13 years, respectively) with unremarkable early posttransplant period. The younger patient received three treatment sessions until resolution of biliary stenoses. The older patient was treated six times over a period of 21 months with refractory disease and ultimately developed biliary cirrhosis necessitating re-transplantation. This patient has to be regarded as treatment failure for endoscopic measures, although this was the only one in the presented cohort. Although the number of patients with ITBL was too small for a relevant statistic, these findings are in accordance with the reported lower success rate of endoscopic therapy in ITBL strictures as compared to anastomotic strictures.19 Biliary casts were found in five patients, and in three cases simultaneously with other BC (ITBL, AST, leak). Reasons for this relatively high proportion of patients in comparison to reported incidence figures of between 2% and 18% could not be identified.20,21 Four of five patients were recipients of a cadaveric liver graft with a choledocho-choledochostomy. Each of those four patients became symptomatic between 30 to 60 days after transplantation and was endoscopically treated for biliary casts in one to three sessions, resulting in complete removal of casts. The remaining patient was much younger (5 months at transplantation) and showed symptoms of cholestasis only 6 months after LDLT with hepaticojejunostomy. This represents an unusual history for the development of BCS. The following clinical course was unremarkable after removal of all casts in three endoscopic sessions. In a larger series by Shah et al., adult transplant recipients with biliary casts underwent one to 10 procedures with a median of 3.5 sessions, again demonstrating comparable results in pediatric patients.4 The type of liver graft plays a major role in the probability of leakage with incidences of between 4% in whole liver grafts up to 16% in split livers.3 The most frequent leakage sites reported in the literature are T-tube tracts and the biliary anastomosis. The cystic duct and intrahepatic ducts are much rarer sources of bile leakage.22 Of the two patients with leaks reported here, one had an anastomotic leak in combination

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with AST, the latter presumably developed following the leak. The other patient showed leakage from an accessory bile duct to the (removed) gall bladder. Endoscopic techniques frequently used in adult patients, where endoscopic sphincterotomy and stent implantation are part of the treatment of postoperative bile leaks, were successfully used in both patients.23 Endoscopic approaches to PTBC can be characterized as minimally invasive compared to percutaneous and/or surgical interventions. However, they are not without specific complications. In this case series, post-sphincterotomy bleeding without spontaneous resolution occurred in three patients receiving endoscopic sphincterotomy. However, in all cases, endoscopic hemostatic treatment was successful. In adults, the incidence of significant post-sphincterotomy bleeding has been reported to be 2–10%, a much lower proportion than in our series.24

CONCLUSIONS

E

NDOSCOPIC TREATMENT OF PTBC in pediatric patients is safe and effective. The main prerequisite for accessibility of the biliary tract after LT is a duct-to-duct anastomosis. If possible, this method should be used in a higher proportion of patients, given the high incidence of PTBC. In selected cases, bilioenteric anastomoses allow for endoscopic access, thus enabling endoscopic treatment of bile duct disorders. The most common complication was AST, followed by BCS, leaks, and ITBL. When applying endoscopic techniques to pediatric patients that are widely accepted in the treatment of adult transplant recipients, we found success rates similar to larger non-pediatric patient series. Compared to management of PTBC by percutaneous or surgical approaches, purely endoscopic therapies may limit invasiveness and morbidity. When looking at complication rates after ERCP in this collective, postsphincterotomy bleeding was found more often than in adult series but were mild in the majority of affected patients. Post-ERCP pancreatitis was infrequent.

CONFLICT OF INTERESTS

A

UTHORS DECLARE NO conflict of interests for this article.

REFERENCES 1 Ng VL, Fecteau A, Shepherd R et al. Outcomes of 5-year survivors of pediatric liver transplantation: report on 461 children from a north american multicenter registry. Pediatrics 2008; 122: e1128–35.

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2 Heffron TG, Pillen T, Welch D, Smallwood GA, Redd D, Romero R. Biliary complications after pediatric liver transplantation revisited. Transplant. Proc. 2003; 35: 1461–2. 3 Diamond IR, Fecteau A, Millis JM et al. Impact of graft type on outcome in pediatric liver transplantation: a report From Studies of Pediatric Liver Transplantation (SPLIT). Ann. Surg. 2007; 246: 301–10. 4 Shah JN, Haigh WG, Lee SP et al. Biliary casts after orthotopic liver transplantation: clinical factors, treatment, biochemical analysis. Am. J. Gastroenterol. 2003; 98: 1861–7. 5 Egawa H, Uemoto S, Inomata Y et al. Biliary complications in pediatric living related liver transplantation. Surgery 1998; 124: 901–10. 6 Morelli J, Mulcahy HE, Willner IR, Cunningham JT, Draganov P. Long-term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement. Gastrointest. Endosc. 2003; 58: 374–9. 7 Tsujino T, Isayama H, Sugawara Y et al. Endoscopic management of biliary complications after adult living donor liver transplantation. Am. J. Gastroenterol. 2006; 101: 2230–6. 8 Zoepf T, Maldonado de Dechene EJ, Dechene A et al. Optimized endoscopic treatment of ischemic-type biliary lesions after liver transplantation. Gastrointest. Endosc. 2012; 76: 556– 63. 9 Otte JB, de Ville de Goyet J, Reding R et al. Pediatric liver transplantation: from the full-size liver graft to reduced, split, and living related liver transplantation. Pediatr. Surg. Int. 1998; 13: 308–18. 10 Darius T, Rivera J, Fusaro F et al. Risk factors and surgical management of anastomotic biliary complications after pediatric liver transplantation. Liver Transpl. 2014; 20: 893–903. 11 Moreira AM, Carnevale FC, Tannuri U et al. Long-term results of percutaneous bilioenteric anastomotic stricture treatment in liver-transplanted children. Cardiovasc. Intervent. Radiol. 2010; 33: 90–6. 12 Haberal M, Karakayali H, Atiq A et al. Duct-to-duct biliary reconstruction without a stent in pediatric living-donor liver transplantation. Transplant. Proc. 2011; 43: 595–7. 13 Ghobrial RM, Farmer DG, Amersi F, Busuttil RW. Advances in pediatric liver and intestinal transplantation. Am. J. Surg. 2000; 180: 328–34. 14 Tanaka H, Fukuda A, Shigeta T et al. Biliary reconstruction in pediatric live donor liver transplantation: duct-to-duct or Roux-en-Y hepaticojejunostomy. J. Pediatr. Surg. 2010; 45: 1668–75. 15 Sugawara Y, Makuuchi M, Sano K, Ohkubo T, Kaneko J, Takayama T. Duct-to-duct biliary reconstruction in livingrelated liver transplantation. Transplantation 2002; 73: 1348–50. 16 Feier FH, Chapchap P, Pugliese R et al. Diagnosis and management of biliary complications in pediatric living donor liver transplant recipients. Liver Transpl. 2014; 20: 882–92. 17 Zoepf T, Maldonado-Lopez EJ, Hilgard P et al. Balloon dilatation vs. balloon dilatation plus bile duct endoprostheses for treatment of anastomotic biliary strictures after liver transplantation. Liver Transpl. 2006; 12: 88–94.

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18 Buis CI, Hoekstra H, Verdonk RC, Porte RJ. Causes and consequences of ischemic-type biliary lesions after liver transplantation. J. Hepatobiliary Pancreat. Surg. 2006; 13: 517– 24. 19 Shah JN, Ahmad NA, Shetty K et al. Endoscopic management of biliary complications after adult living donor liver transplantation. Am. J. Gastroenterol. 2004; 99: 1291–5. 20 Voigtlander T, Negm AA, Strassburg CP, Lehner F, Manns MP, Lankisch TO. Biliary cast syndrome post-liver transplantation: risk factors and outcome. Liver Int. 2013; 33: 1287– 92. 21 Gor NV, Levy RM, Ahn J, Kogan D, Dodson SF, Cohen SM. Biliary cast syndrome following liver transplantation: Predictive factors and clinical outcomes. Liver Transpl. 2008; 14: 1466– 72.

22 Thuluvath PJ, Atassi T, Lee J. An endoscopic approach to biliary complications following orthotopic liver transplantation. Liver Int. 2003; 23: 156–62. 23 Dechene A, Jochum C, Fingas C et al. Endoscopic management is the treatment of choice for bile leaks after liver resection. Gastrointest. Endosc. 2014; 80: 626–33.e1. 24 Ferreira LE, Baron TH. Post-sphincterotomy bleeding: who, what, when, and how. Am. J. Gastroenterol. 2007; 102: 2850–8.

SUPPORTING INFORMATION

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DDITIONAL SUPPORTING INFORMATION may be found in the online version of this article at the publisher’s web-site: Appendix S1 Supplementary online methods.

© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society

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Endoscopic treatment of pediatric post-transplant biliary complications is safe and effective.

Biliary complications (BC) after liver transplantation (LT) are associated with significant morbidity and mortality. Incidence of BC after pediatric L...
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