REVIEW URRENT C OPINION

Bile duct strictures after liver transplantation Andreas Pascher, Undine Gerlach, and Peter Neuhaus

Purpose of review Biliary complications account for relevant morbidity and mortality after liver transplantation. Advances have taken place in understanding their aetiology, in preventive operative techniques, imaging procedures, as well as interventional and endoscopic management. However, progress in living donation, donation after cardiac death as well as paediatric transplant procedures have changed the incidence and causes of biliary complications. This review summarizes recent progress in the field, particularly related to biliary strictures after liver transplantation. Recent findings Significant findings in the period of interest for this review focussed on improvements of endoscopic treatment of postliver transplant biliary complications, including novel stenting devices, the routine analysis of bacterial and fungal flora, and the use of steroids to prevent postendoscopic retrograde cholangiopancreaticography pancreatitis. The importance of cytomegalovirus and hepatitis C in the aetiology of biliary complications was highlighted. Under certain circumstances, biliary complications after liver transplantation of organs secondary to donation after cardiac death may be reduced to a level known from liver transplantation after brain death. Further evidence was added to support the risk-adapted use of biliary drainage during liver transplantation. Summary The ongoing research in the aetiology, prevention, and treatment of biliary strictures after liver transplantation highlights the significance of biliary complications for patient and graft outcome. Keywords biliary complications, biliary strictures, liver transplantation

INTRODUCTION Complications involving the biliary tract have been a common problem after liver transplantation since the early beginnings owing to a vulnerable blood supply of the bile ducts. They account for relevant morbidity and mortality. Known risk factors are donor age, extended criteria grafts, and prolonged cold ischemia time. Biliary strictures, which constitute a major portion of biliary complications, may occur at the site of the anastomosis or may be nonanastomotic (NAS) at multiple locations of the donor biliary system [1]. Owing to the limited number of deceased donors after brain death (DBD), alternative donor sources such as partial liver transplantation and living donor liver transplantation (LDLT) have been developed, each of them being associated with new challenges and a higher risk for biliary complications. Additionally, the evolution of allocation rules towards urgency-based algorithms and the growing number of organs from donors after cardiac death (DCD) also have influenced the characteristics and frequency of biliary complications. Notably, the www.co-gastroenterology.com

use of DCD has been reported to result in a significantly higher incidence of ischemic-type biliary lesions (ITBL). Biliary complications often require long-term and repeated multidisciplinary therapies, which include the whole spectrum of percutaneous, endoscopic, and surgical procedures, and, eventually, retransplantation. These treatment modalities have changed towards a primarily nonoperative, endoscopy-based strategy, leaving the surgical intervention for lesions which otherwise are not curable. Applying adequate treatment algorithms, high success rates can be achieved in treating biliary

Department of General, Visceral and Transplant Surgery, Charite´ Universitaetsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany Correspondence to Andreas Pascher, MD, PhD, MBA, FEBS, Department of General, Visceral and Transplant Surgery, Charite´ Universitaetsmedizin Berlin, Campus Virchow Klinikum, Augustenburgerplatz 1, 13353 Berlin, Germany. Tel: +49 30 450 652253; e-mail: andreas. [email protected] Curr Opin Gastroenterol 2014, 30:320–325 DOI:10.1097/MOG.0000000000000061 Volume 30  Number 3  May 2014

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Bile duct strictures after liver transplantation Pascher et al.

KEY POINTS  Main issues in postliver transplantation endoscopic treatment of BCs were novel stenting devices, routine analysis of bacterial and fungal flora in the biliary system, and the use of steroids to prevent post-ERCP pancreatitis.  Biliary complications in DCD liver transplants may be reduced to a level known from liver transplantation after brain death.  Evidence was added to support the risk-adapted use of T-tubes or modified biliary drainage during liver transplantation as well as regular use of microsurgical operative techniques.  Biliary complications have to be considered as one of the strongest predictors of outcome in technically sophisticated and demanding transplant procedures.

strictures; however, nonanastomotic strictures will eventually end in a relevant rate of chronic allograft failure [2 ]. This review is dedicated to summarize the most recent manuscripts published during late 2012 and the year 2013, which covered the aetiology, prevention, treatment, and other innovations in the field of biliary strictures after liver transplantation. &

THE CHANGING AND DIVERSIFYING DONOR AND TRANSPLANT TYPE Various studies have analysed the incidence of biliary strictures and reported an incidence between 5 and 25% for NAS and 10–15% for anastomosis, respectively. The risk of NAS seems to be higher in DCD. Additionally, a more liberal acceptance of older and extended criteria donors in recent years has contributed to an increased incidence of NAS [1]. Although the risk of NAS was believed to be as high as 40% using DCD, and concerns have persisted that outcomes associated with DCD liver allografts are not equivalent to those after DBD, a recent article by Vanatta et al. [3 ], which presented data from a matched case–control study, raised the hope that liver transplantation after DCD may be performed with comparable outcome as after DBD by controlling for careful donor and recipient selection. The authors could show that overall patient and graft survival rates as well as the rate of ITBL did not differ between the DBD and DCD group. One of the keys to reduce the risk of NAS after DBD was possibly identified by Taner et al. [4], who performed a multivariate analysis of over 200 DCD liver transplantations and analysed variables at &

different time points during the DCD procurement process. Only the time period between asystole and aortic cross clamping was a significant predictor for development of NAS and overall biliary complications. The issue of higher incidences of biliary complications after LDLT was addressed by the ‘Adult-toadult LDLT cohort study consortium’ [5]. They collected data on the management of biliary complications, the intensity of the interventions and the time to resolution after the diagnosis of biliary complications after liver transplantation. One of the outcome parameters was the comparative effectiveness of interventions in LDLT and DDLT recipients. In a retrospective cohort of 189 DDLT and 356 LDLT recipients, the overall incidence of biliary complications after DDLT amounted to 25 and 40% after LDLT, retrospectively. Biliary strictures constituted 62% of biliary complications after DDLT and 35% after LDLT. It was shown that the median number of months to the resolution of a biliary complication did not significantly differ between the DDLT and LDLT groups or strictures (4.9 vs. 2.3 months, P ¼ 0.61). There was also no difference with regard to reoperations and retransplantations. Another high-risk group for inferior outcome, that is, patients after retransplantation, was analysed recently with regard to biliary complications and their association with outcome. Included was an analysis of the impact of biliary reconstruction on the incidence of biliary complications and to identify risk factors for biliary complications after reliver transplantation [6]. Graft survival rates after 1 year differed by 45% according to the presence or absence of biliary complications (88.5 vs. 43.5%) and by almost 50% after 3 years. These data confirmed that biliary complications have to be considered as one of the strongest predictors of outcome in technically sophisticated and demanding transplant procedures.

AETIOLOGY AND RISK FACTORS It is commonly accepted that early hepatic artery thrombosis (HAT) leads to the most severe forms of NAS and results in partial or complete biliary necrosis with the formation of typical biliary casts and multiple filling defects on endoscopic retrograde cholangiopancreaticography (ERCP) [1,2 ]. Biliary complications after HAT are referred to as the macroangiopathic form of NAS and their severity and clinical course relates to the time of onset and the amount of collateral perfusion via the intrahepatic route, the biliary route, or the capsular route. The microangiopathic form of NAS is characterized by injury to the peribiliary vascular plexus

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owing to immunological and ischemia/reperfusion injury. Several other risk factors, such as ABO-incompatibility, chronic rejection, recurrent PSC, the choice of preservation solution, Roux-en-Y reconstruction, postoperative cytomegalovirus (CMV) infection, donor age, organ quality, repeated rejection episodes, positive lymphocyte cross-match, poor HLA-match, severe macrovascular steatosis (>25%), and some genetic predetermination, for example the CCR5-D32 mutation in recipients, were recently summarized [1]. Review of causes for nonanastomotic strictures after liver transplantation according to latest publications is listed below [1,2 ,7–11]. &

(1) Macroangiopathic form: (a) Hepatic artery thrombosis and stenosis (2) Microangiopathic form: (a) Injury to the peribiliary vascular plexus as a result of ischemia/reperfusion injury or immunological injury (3) Recurrent primary sclerosing cholangitis (4) Use of UW-solution (vs. low-viscosity HTK solution) (5) Intraoperative cryoprecipitate transfusion (6) Roux-en-Y reconstruction (7) Infectious causes: (a) Postoperative CMV infection (b) Hepatitis C (8) Organ quality: (a) Donor age (b) High peak of liver enzymes as indicator of preservation injury and/or organ quality) (c) Severe macrovascular steatosis (>25%) (9) Immunological causes: (a) Chronic rejection (b) Repeated rejection episodes (c) Positive lymphocyte cross-match (d) Poor HLA-match (e) ABO-incompatibility (10) Genetic predetermination: (a) For example, CCR5-delta 32 mutation in recipients Although early HAT constitutes a severe clinical condition, a recent retrospective analysis revealed encouraging data despite HAT in the first 2 weeks after paediatric transplantation. Of 590 liver transplantations performed in 516 children over a 20-year period, 45 experienced early HAT and underwent an immediate attempt of surgical revascularization. The 20-year graft survival rate in those patients with successful revascularization amounted to 77%, with the majority of long-term survivors presenting with normal liver tests, no biliary dilation on ultrasonography, and minimal or moderate fibrosis on liver histology [7]. 322

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An important addition to the knowledge on the delicate blood supply was provided by a study assessing the contribution of the hepatic artery, gastroduodenal artery, and portal vein to the microvascular blood flow in the common bile duct (CBD). It was shown that after transection of the CBD, similar to the situation after liver transplantation, the contribution of the portal vein to the microvascular blood flow through the CBD was 40%, thus emphasizing a potential important role of disturbances in portal venous blood flow for the induction of biliary damage [8]. In addition to the above-mentioned potential role of CMV infection in the development of NAS, a recent study evaluated occult CMV-cholangitis. Biliary CMV DNA levels were measured in patients undergoing ERC after liver transplantation for NAS or other indications. In summary, biliary CMV was more often found in NAS patients vs. patients with anastomosis. The authors concluded that biliary CMV was detected in a substantial number of patients after liver transplantation and was significantly associated with NASs or microscopic biliary lesions [9]. Further potential damage to the biliary system potentially resulting in NAS was associated with intraoperative cryoprecipitate transfusion during liver transplantation. The authors speculated about microthrombus formation as potential mechanism of action [10]. Another group showed that HCV positivity and a high-HCV RNA serum load were risk factors for anastomotic strictures and had an additive effect on graft loss [11]. A potential way to anticipate the later extent of biliary damage was suggested by Brunner et al. [12] who performed histological analysis of bile duct epithelium during and after cold storage. The authors stated that there was considerable damage after cold ischemia with further damage occurring after reperfusion. They suggested quantification by a bile duct damage score, which was shown to have some prognostic value for biliary complications and graft loss in a small group of patients. The question whether postischemic cholangiopathy may be treated therapeutically was addressed in a mouse-model of HAT after liver transplantation with prolonged cold ischemia. It was shown that integrin avb6 strongly induced de-novo cholangiocyte proliferation during ischemia-related biliary fibrogenesis after liver transplantation and its inhibition retarded the progression of biliary fibrosis of liver allograft significantly, suggesting that avb6 is a potential target for the treatment of ischemic biliary complications [13 ]. &

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Bile duct strictures after liver transplantation Pascher et al.

PREVENTIVE STRATEGIES Prevention of biliary complication includes all types of medical and surgical interventions in the recipient, selection of donors, donor procurement, immunosuppressive strategies, prevention, and treatment of infections. One field of action, the reperfusion strategy, was assessed by two groups independently. One group performed an online survey among all transplant centres (n ¼ 37) within Eurotransplant to collect information on their reperfusion strategy together with a literature review. Eleven of 28 evaluated centres (39%) reported simultaneous reperfusion (SIMR), 13 (46%) initial portal vein reperfusion (IPR), one (4%) initial hepatic artery reperfusion (IAR), and three (11%) performed retrograde reperfusion (RETR). Meta-analysis resulted in no difference between the various techniques [14]. In contrast, another prospective pilot trial, which compared SIMR and IPR, found significantly less NAS after SIMR than after IPR (0 vs. 23%; P ¼ 0.0008) [15]. The use of internal stenting or T-tubes has been a matter of debate for more than 2 decades. Lo´pezAndu´jar et al. [16 ] contributed another prospective, randomized trial to compare the incidence and severity of biliary complications after liver transplantation by using a choledochocholedochostomy with or without a T-tube. They summarized that fewer anastomotic strictures were found in the T-tube group (2.1%) than in the non-T-tube group (14.1%; P ¼ 0.002). Particularly in the situation of a risky anastomosis and when the bile duct diameter is less than 7 mm, the authors recommended a T-tube unequivocally. This is in line with an earlier prospective randomized trial published in 2009 [17]. A further innovation may be achieved by using a less invasive rubber transcystic biliary drainage compared with a standard silicone T-tube as proposed by Panaro et al. [18]. Two recent articles emphasized the importance of the use of elaborated microsurgical techniques in paediatric deceased-donor and living-donor liver transplantation, respectively. Both works revealed a decrease in the number of early and long-term anastomotic biliary complications by more than two-fold [19,20]. As tissue trauma caused by suturing the bilioenteric anastomosis certainly contributes to anastomotic complications, it appears worthwhile challenging the current surgical standards. In this context, Seal et al. [21 ] described a catheter-based, suture-free approach to bilioenteric anastomosis in a pig model by successfully using a percutaneously inserted device based on a novel ‘umbrella’ anchoring mechanism to approximate the bowel to the transected bile duct, thus reducing or even &

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eliminating tissue trauma and ischemia to the anastomotic tissue.

ENDOSCOPIC MANAGEMENT The management of biliary complications after liver transplantation requires a multidisciplinary approach involving transplant surgeons, endoscopists, and interventional radiologists [1,2 ]. Endoscopic therapy of biliary disease including biliary complications after liver transplantation has developed greatly over the past years. Progressive stenting for anastomoses after liver transplantation was reported to be demanding and burdensome, necessitating a median of five ERCP procedures with complications occurring in one out of five procedures. However, its success rate was shown to be as high as 81%, avoiding surgery in the large majority of patients [22]. There seems to be no difference in the response to ERCP treatment after LDLT and DDLT, respectively [23]. Further studies confirmed almost 100% resolution rates of aggressive endoscopy-based treatment with a maximal stent placement strategy of all duct-to-duct anastomotic biliary complications after LDLT without the need for surgical intervention or retransplantation [24]. Despite the very high success rates, certain factors were identified, predicting failure of ERCP treatment, such as recipient age, operation time, and morphology of stricture [25]. Although only plastic stents were available in earlier times, there is a selection of different stents including plastic, bare metal, self-expandable uncovered and covered metal stents (SEMS), drug diluting and resorbable stents nowadays. Dumonceau et al. [26 ] recently published the European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline on biliary stenting including indications, choice of stents, and results. In patients with benign CBD strictures, including patients after liver transplantation, they recommended temporary placement of multiple plastic stents provided that the patient is believed to be compliant with repeat interventions. The insertion of uncovered biliary SEMSs was strongly discouraged with highest grade of evidence. Instead, covered SEMSs [26 ,27–29] are currently preferred for selected benign CBD strictures. Even in those patients in whom traditional endoscopic treatment including multiple stenting failed, fully covered SEMSs (FCSEMSs) resulted in an overall long-term clinical success rate of 94% after a mean follow-up of 13 months [30]. Further on, the highest clinical success rates were observed with temporary simultaneous placement of multiple plastic stents (94%), followed by placement of uncovered SEMSs (80%), and by

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placement of a single plastic stent (60%) [26 ]. On the contrary, uncovered SEMSs were associated with the highest complication rates (40%) compared with single plastic stents (36%) and multiple plastic stents (20%). They reported that the patency of uncovered biliary SEMSs sharply decreased over time from 1 year after SEMS insertion and the occurrence of late occlusion of uncovered SEMS frequently necessitated surgery, percutaneous drainage, or unconventional endoscopic procedures (e.g. brachytherapy) [31,32]. The use of drug-diluting stents may further contribute to improve endoscopic therapy in selected cases. In a prospective case series the safety and efficacy of paclitaxel-eluting balloons was evaluated in 13 patients requiring treatment for symptomatic anastomosis following liver transplantation. Sustained clinical success was achieved in 92% [33]. There are important new data on the relevance of bacteriobilia and fungibilia in patients with endoscopic treatment of biliary complications after liver transplantation. It was shown in a retrospective analysis that bacteriobilia and fungibilia can frequently be detected by routine microbiological sampling in patients after liver transplantation and was a predictor of outcome, thus suggesting regular bile sampling [34 ]. Another group clearly depicted that prednisone use was found to have a protective effect for post-ERCP pancreatitis in a retrospective cohort of over 700 patients in both univariate [odds ratio (OR) ¼ 0.34, 95% confidence interval (CI) 0.14–0.84] and multivariate analyses (OR ¼ 0.22, 95% CI 0.09–0.57) after adjustments for difficult biliary cannulation and postliver transplantation index ERCP [35]. Two recent studies analysed innovative imaging procedures for the evaluation of the biliary system. One assessed the technical feasibility and operating characteristics of probe-based confocal laser endomicroscopy (pCLE) in a cohort of PSC patients with dominant biliary strictures in order to aid in riskstratifying of dominant strictures in primary sclerosing cholangitis . Although being small and retrospective in nature, the study showed sufficient visualization of DS by pCLE in 95%. pCLE sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100% (95% CI 19.3–100), 61.1% (95% CI 35.8–82.6), 22.2% (95% CI 3.5–59.9), and 100% (95% CI 71.3–100), respectively, in detecting neoplasia and such achieved a high technical success rate [36]. In a descriptive study, single-operator peroral cholangioscopy (SOC) was evaluated in liver transplantation patients. Although this approach certainly needs further assessment, SOC in liver transplantation recipients was demonstrated to be &

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feasible and allow adequate visualization and tissue sampling of anastomosis and bile ducts [37].

CONCLUSION Significant findings in the period of interest for this review focussed on innovative stenting methods and risk-reduction in endoscopic treatment of postliver transplantation biliary complications. There are ongoing studies addressing the higher risk for biliary complications when using sophisticated transplant procedures and DCD livers. With regard to the aetiology of biliary strictures, the impact of CMV and hepatitis C was highlighted. Preventive strategies include microsurgical operative techniques, modified reperfusion strategies, and biliary drainage. Acknowledgements None. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Seehofer D, Eurich D, Veltzke-Schlieker W, Neuhaus P. Biliary complications after liver transplantation: old problems and new challenges. Am J Transplant 2013; 13:253–265. 2. Arain MA, Attam R, Freeman ML. Advances in endoscopic management of & biliary tract complications after liver transplantation. Liver Transpl 2013; 19:482–498. Comprehensive and concise review of current endoscopic management after liver transplantation. 3. Vanatta JM, Dean AG, Hathaway DK, et al. Liver transplant using donors after & cardiac death: a single-center approach providing outcomes comparable to donation after brain death. Exp Clin Transplant 2013; 11:154–163. Single-centre experience demonstrating that under certain circumstances, particularly with diligent donor selection, outcome of liver transplantation after DCD may be comparable to DBD. 4. Taner CB, Bulatao IG, Perry DK, et al. Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors. Transpl Int 2012; 25:838–846. 5. Zimmerman MA, Baker T, Goodrich NP, et al. Development, management, and resolution of biliary complications after living and deceased donor liver transplantation: a report from the adult-to-adult living donor liver transplantation cohort study consortium. Liver Transpl 2013; 19:259–267. 6. Enestvedt CK, Malik S, Reese PP, et al. Biliary complications adversely affect patient and graft survival after liver retransplantation. Liver Transpl 2013; 19:965–972. 7. Ackermann O, Branchereau S, Franchi-Abella S, et al. The long-term outcome of hepatic artery thrombosis after liver transplantation in children: role of urgent revascularization. Am J Transplant 2012; 12:1496–1503. 8. Slieker JC, Farid WR, van Eijck CH, et al. Significant contribution of the portal vein to blood flow through the common bile duct. Ann Surg 2012; 255:523– 527. 9. Gotthardt DN, Senft J, Sauer P, et al. Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile. Liver Transpl 2013; 19:1142– 1150. 10. Liu S, Fan J, Wang X, et al. Intraoperative cryoprecipitate transfusion and its association with the incidence of biliary complications after liver transplantation – a retrospective cohort study. PLoS One 2013; 8:e60727. 11. Horster S, Ba¨uerlein FJ, Mandel P, et al. Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation. Transpl Infect Dis 2013; 15:306–313.

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Bile duct strictures after liver transplantation Pascher et al. 12. Brunner SM, Junger H, Ruemmele P, et al. Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation. J Hepatol 2013; 58:1133–1139. 13. Chen G, Zhang L, Chen L, et al. Role of integrin avb6 in the pathogenesis of & ischemia-related biliary fibrosis after liver transplantation. Transplantation 2013; 95:1092–1099. Promising new approach for a potential therapeutic approach to postischemic biliary damage. 14. Manzini G, Kremer M, Houben P, et al. Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature. Transpl Int 2013; 26:508–516. 15. Baccarani U, Rossetto A, Lorenzin D, et al. Protection of the intrahepatic biliary tree by contemporaneous portal and arterial reperfusion: results of a prospective randomized pilot study. Updates Surg 2012; 64:173–177. 16. Lo´pez-Andu´jar R, Oro´n EM, Carregnato AF, et al. T-tube or no T-tube in & cadaveric orthotopic liver transplantation: the eternal dilemma: results of a prospective and randomized clinical trial. Ann Surg 2013; 258:21–29. Important contribution to the discussion of whether to use or not to use a biliary drainage during liver transplantation. 17. Weiss S, Schmidt SC, Ulrich F, et al. Biliary reconstruction using a side-toside choledococholedocostomy with or without T-tube in deceased donor liver transplantation A prospective randomized trial. Ann Surg 2009; 250: 766. 18. Panaro F, Glaise A, Miggino M, et al. Rubber transcystic drainage reduces the postremoval biliary complications in liver transplantation: a matched casecontrol study. Langenbecks Arch Surg 2013; 398:169–176. 19. Chen CL, Concejero AM, Lin TS, et al. Outcome of routine use of microsurgical biliary reconstruction in pediatric living donor liver transplantation. J Hepatobiliary Pancreat Sci 2013; 20:492–497. 20. Lin TS, Chen CL, Concejero AM, et al. Early and long-term results of routine microsurgical biliary reconstruction in living donor liver transplantation. Liver Transpl 2013; 19:207–214. 21. Seal JB, Stern JR, Vanha T, et al. A catheter-based suture-free approach to & bilioenteric anastomosis: a pilot study. Surg Innov 2013; 20:142–149. Innovative new technique assessed in a porcine model of bilioenteric anastomosis. 22. Poley JW, Lekkerkerker MN, Metselaar HJ, et al. Clinical outcome of progressive stenting in patients with anastomotic strictures after orthotopic liver transplantation. Endoscopy 2013; 45:567–570. 23. Chan CH, Donnellan F, Byrne MF, et al. Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation. Hepatobiliary Pancreat Dis Int 2013; 12:488–493. 24. 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; 77:47–54.

25. Chok KS, Chan SC, Cheung TT, et al. A retrospective study on risk factors associated with failed endoscopic treatment of biliary anastomotic stricture after right-lobe living donor liver transplantation with duct-to-duct anastomosis. Ann Surg 2013. [Epub ahead of print] 26. Dumonceau JM, Tringali A, Blero D, et al. European Society of Gastrointestinal & Endoscopy. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2012; 44:277–298. Excellent and comprehensive guideline for the use of stents in general and after liver transplantation in particular. 27. Curcio G, Traina M, Miraglia R, et al. Treatment of a refractory biliary stricture after living donor liver transplantation, with a short fully covered metal stent with a long string. Endoscopy 2012; 44 (Suppl 2 UCTN):E74–E75. 28. Sauer P, Chahoud F, Gotthardt D, et al. Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation. Endoscopy 2012; 44:536–538. 29. Tarantino I, Traina M, Mocciaro F, et al. Fully covered metallic stents in biliary stenosis after orthotopic liver transplantation. Endoscopy 2012; 44:246–250. 30. Luigiano C, Bassi M, Ferrara F, et al. Placement of a new fully covered selfexpanding metal stent for postoperative biliary strictures and leaks not responding to plastic stenting. Surg Laparosc Endosc Percutan Tech 2013; 23:159–162. 31. Siriwardana HPP, Siriwardena AK. Systematic appraisal of the role of metallic endobiliary stents in the treatment of benign bile duct stricture. Ann Surg 2005; 242:10–19. 32. van Boeckel PGA, Vleggaar FP, Siersema PD. Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review. BMC Gastroenterol 2009; 9:96. 33. Kabar I, Cicinnati VR, Beckebaum S, et al. Use of paclitaxel-eluting balloons for endotherapy of anastomotic strictures following liver transplantation. Endoscopy 2012; 44:1158–1160. 34. Gotthardt DN, Weiss KH, Rupp C, et al. Bacteriobilia and fungibilia are & associated with outcome in patients with endoscopic treatment of biliary complications after liver transplantation. Endoscopy 2013; 45:890–896. Important publication on the necessity of routine microbiological testing during endoscopic interventions after liver transplantation. 35. Law R, Leal C, Abu Dayyeh B, et al. Role of immunosuppression in postendoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis. Liver Transpl 2013; 19:1354–1360. 36. Heif M, Yen RD, Shah RJ. ERCP with probe-based confocal laser endomicroscopy for the evaluation of dominant biliary stenoses in primary sclerosing cholangitis patients. Dig Dis Sci 2013; 58:2068–2074. 37. Balderramo D, Sendino O, Miquel R, et al. Prospective evaluation of singleoperator peroral cholangioscopy in liver transplant recipients requiring an evaluation of the biliary tract. Liver Transpl 2013; 19:199–206.

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Bile duct strictures after liver transplantation.

Biliary complications account for relevant morbidity and mortality after liver transplantation. Advances have taken place in understanding their aetio...
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