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Journal of Digestive Diseases 2015; 16; 610–615
doi: 10.1111/1751-2980.12263
Case Report
Bile duct kinking after adult living donor liver transplantation: Case reports and literature review Ping WAN, Qiang XIA, Jian Jun ZHANG, Qi Gen LI, Ning XU, Ming ZHANG, Xiao Song CHEN & Long Zhi HAN Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric living donor liver transplantation (LDLT), but bile duct kinking after adult LDLT is rarely reported. We herein presented two patients who suffered from anastomotic strictures caused by severe bile duct kinking after LDLT. The first patient was a 57‐year‐old woman with hepatitis B virus (HBV)‐ related liver cirrhosis, who developed biliary stricture 5 months after receiving right‐lobe LDLT. Subsequently, endoscopic and percutaneous treatments were attempted, but both failed to solve the problem. The second was a 44‐year‐old woman also having HBV‐related liver cirrhosis. Biliary stricture occurred 14 months after LDLT. Likewise, the guide wire failed to pass through the stricture when endoscopic KEY WORDS:
bile ducts, complication, kinking, liver transplantation, tissue donors.
INTRODUCTION Due to the ultimate need for organs, living donor liver transplantation (LDLT) has been widely performed and currently emerged as an effective alternative to deceased donor liver transplantation (DDLT) for Correspondence to: Qiang XIA, Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China. Email: [email protected] Conflicts of interest: None.
© 2015 Chinese Medical Association Shanghai Branch, Chinese
Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
610
interventions were conducted. Afterwards, both of the two cases underwent reexploration, showing that compensatory hypertrophy of the allografts resulted in kinking and sharp angulation of the bile ducts, and the anastomotic sites were found to be severely stenotic. Finally, re‐anastomosis by Roux‐en‐Y procedure was successfully performed, and long‐term stenosis‐ free survival was achieved in both of them. Our experience suggests that bile duct kinking after LDLT may play a role in the high incidence of anastomotic strictures in adult LDLT recipients, which may also result in the treatment failure of the non‐surgical techniques for anastomotic strictures. Re‐anastomosis in the form of Roux‐en‐Y hepaticojejunostomy is an effective surgical option for the treatment of such a condition.
patients with end‐stage liver diseases.1,2 However, biliary complications are considered as the technical ‘Achilles heel’ of LDLT. The reported incidence of biliary complications after LDLT varies from 15% to 73%.3 Various factors may contribute to the occurrence of biliary complications, including ischemia or fibrosis following suboptimal surgical technique, hepatic artery thrombosis, chronic ductopenic rejection, ABO incompatibility, and so on.4 Specifically, LDLT presents additional problems that are unique to the living donor allograft. Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric LDLT,5,6 which incur an increased risk of biliary complications. However, bile duct kinking or displacement after adult LDLT is rarely
Journal of Digestive Diseases 2015; 16; 610–615 reported. Moreover, although endoscopic techniques have been accepted as the preferred diagnostic and therapeutic modalities for biliary strictures,7,8 surgery still serves as the final back‐up alternative for treatment failure of non‐operative managements. How to utilize surgical interventions for treatments in such conditions remains controversial. In this study, we presented our experience in treating two patients who developed severe anastomotic strictures caused by bile duct kinking after LDLT. Transplantation in this study was strictly implemented in accordance with the declaration of Helsinki, and ethical approval was obtained from the Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China). CASE REPORTS Case 1 In August 2007, a 57‐year‐old woman with hepatitis B virus (HBV)‐related liver cirrhosis was admitted to the Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China) for acute hepatic decompensation. She underwent hysterectomy for hysteromyoma 8 years prior to the admission. The patient was transferred to the Department of Liver Surgery for liver transplantation (LT). After written informed consents
Bile duct kinking after LDLT
611
were obtained from both the donor and the recipient, right‐lobe LDLT without the middle hepatic vein was performed in September 2007. During the surgery, a single opening of the right hepatic duct was observed in the donor graft. A duct‐to‐duct anastomosis with 7‐0 Prolene was performed for the bile duct reconstruction, which included a continuous suture for the posterior wall and an interrupted suture for the anterior wall. The cold ischemia time lasted for 75 min. After LT, a double-drug regimen of tacrolimus and steroid (methylprednisolone/prednisone) was adopted for immunosuppression. Five months after LT, the patient developed liver dysfunction, and magnetic resonance cholangiopancreatography (MRCP) suggested biliary stricture and kinking of the bile duct (Fig.1a–c). Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) was attempted twice for stent placement (Fig.1d), but the guide wire failed to pass through the stricture. The patient was treated with percutaneous transhepatic cholangial drainage (PTCD) in April 2008 (Fig.1e), and soon afterwards her liver function returned to normal level (Fig.2). In August 2008, the patient underwent re-exploration due to partial detachment of the PTCD tube, showing that the compensatory hypertrophy of the allograft resulted in kinking and sharp angulation of the bile duct, and the anastomotic site of the bile duct was found to be severely stenotic. Thus, we performed a bile duct reconstruction with
Figure 1. Magnetic resonance cholangiopancreatography (MRCP) and X‐ray images of case 1. (a,b) MRCP showing severe anastomotic stenosis (arrow) and dilation of intrahepatic bile ducts. (c) Three‐dimensional MRCP images showing bile duct kinking around the anastomotic site (circle). (d) Endoscopic retrograde cholangiopancreatography (ERCP) image shows the stenosis in the upper common hepatic duct. (e) Percutaneous transhepatic cholangial drainage (PTCD) shows biliary obstruction and dilation of upper bile ducts. (f) The T‐tube cholangiography shows an excellent biliary drainage after surgical revision.
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
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P Wan etal.
Journal of Digestive Diseases 2015; 16; 610–615
Figure 2. The change in liver function of case 1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBIL, direct bilirubin; LDLT, living donor liver transplantation; PTCD, percutaneous transhepatic cholangial drainage; R‐Y, Roux‐en‐Y hepaticojejunostomy; TBIL, total bilirubin.
Roux‐en‐Y hepaticojejunostomy. The operation was successfully performed, and the T‐tube cholangiography 2 weeks after the surgery showed an excellent biliary drainage (Fig.1f). Biliary complications did not occur afterwards by the last follow‐up (8 March 2014). Case 2 In September 2007, a 44‐year‐old woman who had suffered from HBV‐related liver cirrhosis for more than 10 years was admitted to the Department of Liver Surgery of our hospital. She was diagnosed with acute hepatic decompensation on admission. The gynecological ultrasound detected a right adnexal mass of 4cm in size before surgery, and thus a consultant gynecologist was invited to participate in preoperative assessments and surgical treatments of the patient. After written informed consents were obtained, the patient underwent right‐lobe LDLT (without the middle hepatic vein) plus right adnexectomy in October 2007. During the LT procedure, there was a single opening of the right hepatic duct in the donor graft, and the bile tract reconstruction was performed as described above. The cold ischemia time lasted for 110 min. The immunosuppressive therapy after LT consisted of a double‐drug regimen of tacrolimus and steroid (methylprednisolone/prednisone). Post‐ surgical pathological examination identified the
adnexal mass as a benign ovarian cyst. In December 2008, the patient was re-admitted because of pruritus for one week and was diagnosed as a post-transplant biliary stricture. Just like the first patient, she was treated with ERCP afterwards, which showed that the anastomotic site was seriously stenotic, and two attempts both failed to complete the stent placement. Figures3 shows the latest MRCP images prior to the second operation. In February 2009, re-exploration was performed. Likewise, the stenotic bile duct angularly kinked around the anastomotic site, and re‐anastomosis by Roux‐en‐Y procedure was successfully performed. The changes in the liver function results are shown in Figure4. Long‐term stenosis‐free survival has been achieved after surgical revision, and the last follow‐up was 8 March 2014. DISCUSSION Although the shortage of deceased donation is a universal problem, the situation is particularly serious in Asia because of various social, cultural and historic reasons. Thus, a majority of LDLT procedures are currently performed in Asian countries. LDLT offers the potential advantages of a shortened waiting period, optimal donor graft, and the ability to optimize the recipient's health to those with end‐stage liver diseases. However, biliary complications are the most
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School
of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 610–615
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613
Figure 3. Magnetic resonance cholangiopancreatography (MRCP) images of case 2. (a,b) MRCP shows severe anastomotic stenosis (arrow) and dilation of intrahepatic bile ducts. (c) Three‐dimensional MRCP images showing kinking and angulation of the bile duct around the anastomotic site (circle).
Figure 4. The change in liver function of case 2. ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBIL, direct bilirubin; LDLT, living donor liver transplantation; PTCD, percutaneous transhepatic cholangial drainage; R‐Y, Roux‐en‐Y hepaticojejunostomy; TBIL, total bilirubin.
intractable problems and remain to be the main obstacle in the implementation of adult LDLT.3 For pediatric LDLT, many researches have focused on the technical improvement to prevent adverse events related to regeneration of the partial graft and the growth of children.5,6,9,10 However, biliary complications caused by these reasons do not commonly occur because Roux‐en‐Y hepaticojejunostomy remains the standard treatment of choice for pediatric LDLT, which may be less susceptible to bile duct deformity. A recent study by Yamamoto etal.5 reported two children who developed deformity of the extrahepatic duct 4 and 9 years after LDLT, respectively, but no clinical signs associated with the deformity were observed.
Besides, similar cases were also reported in other researches investigating LDLT recipients.6 However, as for adult LDLT, most surgeons do not pay much attention to the influence of regeneration of the partial liver allograft on the biliary tract. The alignment of the end of bile ducts is straight at the time of transplant, but the graft regeneration may cause marked rotation or kinking of the hepatic hilum. Tension or kinking of the anastomotic site after a duct‐to‐duct anastomosis may impair the blood supply of the bile duct and gradually results in biliary complications. Based on our experience, bile duct kinking after LDLT is comprised of axial kinking and transverse kinking based on the direction of the rotational axis. Axial bile
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
614 Table 1.
Journal of Digestive Diseases 2015; 16; 610–615
P Wan etal.
Management outcomes of biliary strictures in living donor liver transplantation recipients
Patients Authors (publication year) (n) Wadhawan etal.14 (2013) Yaprak etal.15 (2012) Yazumi etal.16 (2006) Tashiro etal.17 (2007) Chang etal.18 (2010) Lladó etal.19 (2012) Shah etal.20 (2007) Kim etal.21 (2009) Lee etal.22 (2011) Kato etal.23 (2009) Seo etal.24 (2009)
338 200 273 80 339 1000 130 NA NA 96 239
Patients with biliary stricture, n (%)
Technical success rate of ERCD, % (n/N)
45 (13.3) 17 (8.5) 80 (29.3) 20 (25) 121 (35.7) 152 (15.2) 22 (16.9) 60 137 41 (42.7) 68 (28.4)
75 54 64 50 64
63 47 76 58
(33/44) (7/13) (48/75) (10/20) (72/113) NA NA (38/60) (64/137) (31/41) (15/26)
Technical success rate of ERCD+PTCD#, % (n/N) 91 (40/44) NA 76 (57/75) 70 (14/20) 75 (90/120) NA NA 85 (51/60) NA 90 (37/41) NA
Patients undergoing surgical revision†, n (%) 2 5 12 6
(4.4) (29.4) (15) (30) NA 47 (31) 4 (18) NA NA NA NA
#
Patients treated by endoscopic retrograde cholangiogram‐guided drainage (ERCD), percutaneous transhepatic cholangial drainage (PTCD) or both are included. † Retransplantation is not included. NA, not available.
duct kinking is due to clockwise regeneration of the right liver graft around the inferior vena cava, which drives the bile duct to rotate around its own axis. Transverse bile duct kinking may arise either from inappropriate surgical technique or regeneration of the partial liver graft. Inappropriate surgical techniques are usually characterized by overlong preservation or incorrect anastomosis of the bile duct, which may result in kinking or fracture of the anastomotic site during the LT procedure or shortly after the surgery. The allograft regeneration after LDLT may cause the bile duct that with originally appropriate tension to become relatively too long, leading to sharp angulation of the bile duct. Graft regeneration rapidly occurs during the first month, and recipient grafts could achieve more than 90% of an expected standard liver volume three months after transplantation.11 The formation of bile duct kinking probably starts during this period. The persistent tension at the anastomotic site could gradually cause anastomotic stricture. Bile duct kinking or angulation has been indicated to be often detected at more than 6 months after LDLT the related clinical manifestations are not commonly presented at the early stage.5,6 Similarly, our cases manifested obstructive jaundice 5 and 14 months after transplantation, respectively. Such conditions turned out to be resistant to tendoscopic treatments, and PTCD could only temporarily relieve the biliary obstruction rather than fundamentally solve the problem. However, both patients achieved favorable outcomes with re‐anastomosis by Roux‐en‐Y procedure. Currently, most biliary complications are amenable to non‐operative managements. Endoscopic intervention
is considered as a well‐established treatment for anastomotic strictures after DDLT (only for patients undergoing a duct‐to‐duct anastomosis), and the overall success rate ranges from 70% to 100%.4,7 However, for LDLT, anastomotic strictures could only be successfully treated by endoscopic retrograde cholangiogram‐ guided drainage (ERCD) in a smaller group of patients.13 A literature review for the management outcomes of biliary strictures after LDLT is shown in Table1. The technical success rate of ERCD ranged from 47% to 76%,14–18,21–24 and the main reason of endoscopic failure was the failure of the guidewire to pass through the stricture. PTCD is considered as the second‐line option for the treatment of biliary complications in most studies due to the invasive nature of the procedure, and surgical revision is currently regarded as the final back‐up treatment option. A systematic review involving 61 studies revealed that PTCD or surgical revision was chosen as the first choice for biliary strictures in 42% of the LDLT populations compared with 3% of the DDLT populations, and surgical revision was performed in 24.9% of biliary strictures cases after LDLT.8 Due to the unique problem originated from the living donor allograft, bile duct kinking may not only involve in the formation of the biliary strictures after LDLT, but also in the high incidence of treatment failure with non‐surgical interventions. Based on these data, a considerable proportion of patients undergo repeated ERCD or PTCD unsuccessfully before receiving surgical revision. However, Davidson etal.25 sought to investigate the influence of nonsurgical managements on the outcome of post‐LT patients requiring surgical revision,
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School
of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 610–615 and found that the complication rate after surgical revisions was less in those who failed non-surgical approach than those proceeding directly to surgery. Nonetheless, the current study showed that re‐anastomosis in the form of Roux‐en‐Y hepaticojejunostomy served as an effective surgical option for anastomotic strictures caused by bile duct kinking. In conclusion, bile duct kinking in adult LDLT recipients, although rare, may play a role in the high incidence of anastomotic strictures after LDLT, and also result in the treatment failure of non‐ surgical techniques. Surgical revision with Roux‐en‐Y hepaticojejunostomy is an appropriate option for the treatment of such condition. ACKNOWLEDGMENTS The study was supported by the Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning, and the Key Joint Research Program of Shanghai Health Bureau (2013ZYJB0001).
REFERENCES 1 Thuluvath PJ, Yoo HY. Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation. Liver Transpl 2004; 10: 1263–8. 2 Abt PL, Mange KC, Olthoff KM, Markmann JF, Reddy KR, Shaked A. Allograft survival following adult‐to‐adult living donor liver transplantation. Am J Transplant 2004; 4: 1302–7. 3 Wan P, Yu X, Xia Q. Operative outcomes of adult living donor liver transplantation and deceased donor liver transplantation: a systematic review and meta‐analysis. Liver Transpl 2014; 20: 425–36. 4 Sharma S, Gurakar A, Jabbour N. Biliary strictures following liver transplantation: past, present and preventive strategies. Liver Transpl 2008; 14: 759–69. 5 Yamamoto H, Hayashida S, Asonuma K etal. Single‐center experience and long‐term outcomes of duct‐to‐duct biliary reconstruction in infantile living donor liver transplantation. Liver Transpl 2014; 20: 347–54. 6 Tanaka H, Fukuda A, Shigeta T etal. Biliary reconstruction in pediatric live donor liver transplantation: duct‐to‐duct or Roux‐en‐Y hepaticojejunostomy. J Pediatr Surg 2010; 45: 1668–75. 7 Thuluvath PJ, Pfau PR, Kimmey MB, Ginsberg GG. Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 2005; 37: 857–63. 8 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: 379–92. 9 Kimura T, Hasegawa T, Ihara Y etal. Feasibility of duct‐to‐duct biliary reconstruction in pediatric living related liver transplantation: report of three cases. Pediatr Transplant 2006; 10: 248–51.
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10 Liu C, Loong CC, Hsia CY etal. Duct‐to‐duct biliary reconstruction in selected cases in pediatric living‐donor left‐lobe liver transplantation. Pediatr Transplant 2009; 13: 693–6. 11 Olthoff KM, Emond JC, Shearon TH etal. Liver regeneration after living donor transplantation: adult‐to‐adult living donor liver transplantation cohort study. Liver Transpl 2015; 21: 79–88. 12 Macfarlane B, Davidson B, Dooley JS etal. Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation. Eur J Gastroenterol Hepatol 1996; 8: 1003–6. 13 Gómez CM, Dumonceau JM, Marcolongo M etal. Endoscopic management of biliary complications after adult living‐donor versus deceased‐donor liver transplantation. Transplantation 2009; 88: 1280–5. 14 Wadhawan M, Kumar A, Gupta S etal. Post‐transplant biliary complications: an analysis from a predominantly living donor liver transplant center. J Gastroenterol Hepatol 2013; 28: 1056–60. 15 Yaprak O, Dayangac M, Akyildiz M etal. Biliary complications after right lobe living donor liver transplantation: a single‐centre experience. HPB (Oxford) 2012; 14: 49–53. 16 Yazumi S, Yoshimoto T, Hisatsune H etal. Endoscopic treatment of biliary complications after right‐lobe living‐ donor liver transplantation with duct‐to‐duct biliary anastomosis. J Hepatobiliary Pancreat Surg 2006; 13: 502–10. 17 Tashiro H, Itamoto T, Sasaki T etal. Biliary complications after duct‐to‐duct biliary reconstruction in living‐donor liver transplantation: causes and treatment. World J Surg 2007; 31: 2222–9. 18 Chang JH, Lee IS, Choi JY etal. 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: 226–33. 19 Lladó L, Fabregat J, Baliellas C etal. Surgical treatment of biliary tract complications after liver transplantation. Transplant Proc 2012; 44: 1557–9. 20 Shah SA, Grant DR, McGilvray ID etal. Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center. Am J Transplant 2007; 7: 161–7. 21 Kim ES, Lee BJ, Won JY, Choi JY, Lee DK. Percutaneous transhepatic biliary drainage may serve as a successful rescue procedure in failed cases of endoscopic therapy for a post‐living donor liver transplantation biliary stricture. Gastrointest Endosc 2009; 69: 38–46. 22 Lee YY, Gwak GY, Lee KH etal. Predictors of the feasibility of primary endoscopic management of biliary strictures after adult living donor liver transplantation. Liver Transpl 2011; 17: 1467–73. 23 Kato H, Kawamoto H, Tsutsumi K etal. Long‐term outcomes of endoscopic management for biliary strictures after living donor liver transplantation with duct‐to‐duct reconstruction. Transpl Int 2009; 22: 914–21. 24 Seo JK, Ryu JK, Lee SH etal. Endoscopic treatment for biliary stricture after adult living donor liver transplantation. Liver Transpl 2009; 15: 369–80. 25 Davidson BR, Rai R, Nandy A, Doctor N, Burroughs A, Rolles K. Results of choledochojejunostomy in the treatment of biliary complications after liver transplantation in the era of nonsurgical therapies. Liver Transpl 2000; 6: 201–6.
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 610–615
doi: 10.1111/1751-2980.12263
Case Report
Bile duct kinking after adult living donor liver transplantation: Case reports and literature review Ping WAN, Qiang XIA, Jian Jun ZHANG, Qi Gen LI, Ning XU, Ming ZHANG, Xiao Song CHEN & Long Zhi HAN Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric living donor liver transplantation (LDLT), but bile duct kinking after adult LDLT is rarely reported. We herein presented two patients who suffered from anastomotic strictures caused by severe bile duct kinking after LDLT. The first patient was a 57‐year‐old woman with hepatitis B virus (HBV)‐ related liver cirrhosis, who developed biliary stricture 5 months after receiving right‐lobe LDLT. Subsequently, endoscopic and percutaneous treatments were attempted, but both failed to solve the problem. The second was a 44‐year‐old woman also having HBV‐related liver cirrhosis. Biliary stricture occurred 14 months after LDLT. Likewise, the guide wire failed to pass through the stricture when endoscopic KEY WORDS:
bile ducts, complication, kinking, liver transplantation, tissue donors.
INTRODUCTION Due to the ultimate need for organs, living donor liver transplantation (LDLT) has been widely performed and currently emerged as an effective alternative to deceased donor liver transplantation (DDLT) for Correspondence to: Qiang XIA, Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China. Email: [email protected] Conflicts of interest: None.
© 2015 Chinese Medical Association Shanghai Branch, Chinese
Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
610
interventions were conducted. Afterwards, both of the two cases underwent reexploration, showing that compensatory hypertrophy of the allografts resulted in kinking and sharp angulation of the bile ducts, and the anastomotic sites were found to be severely stenotic. Finally, re‐anastomosis by Roux‐en‐Y procedure was successfully performed, and long‐term stenosis‐ free survival was achieved in both of them. Our experience suggests that bile duct kinking after LDLT may play a role in the high incidence of anastomotic strictures in adult LDLT recipients, which may also result in the treatment failure of the non‐surgical techniques for anastomotic strictures. Re‐anastomosis in the form of Roux‐en‐Y hepaticojejunostomy is an effective surgical option for the treatment of such a condition.
patients with end‐stage liver diseases.1,2 However, biliary complications are considered as the technical ‘Achilles heel’ of LDLT. The reported incidence of biliary complications after LDLT varies from 15% to 73%.3 Various factors may contribute to the occurrence of biliary complications, including ischemia or fibrosis following suboptimal surgical technique, hepatic artery thrombosis, chronic ductopenic rejection, ABO incompatibility, and so on.4 Specifically, LDLT presents additional problems that are unique to the living donor allograft. Regeneration of the partial allograft and the growth of children may cause kinking of the biliary tract after pediatric LDLT,5,6 which incur an increased risk of biliary complications. However, bile duct kinking or displacement after adult LDLT is rarely
Journal of Digestive Diseases 2015; 16; 610–615 reported. Moreover, although endoscopic techniques have been accepted as the preferred diagnostic and therapeutic modalities for biliary strictures,7,8 surgery still serves as the final back‐up alternative for treatment failure of non‐operative managements. How to utilize surgical interventions for treatments in such conditions remains controversial. In this study, we presented our experience in treating two patients who developed severe anastomotic strictures caused by bile duct kinking after LDLT. Transplantation in this study was strictly implemented in accordance with the declaration of Helsinki, and ethical approval was obtained from the Ethics Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China). CASE REPORTS Case 1 In August 2007, a 57‐year‐old woman with hepatitis B virus (HBV)‐related liver cirrhosis was admitted to the Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (Shanghai, China) for acute hepatic decompensation. She underwent hysterectomy for hysteromyoma 8 years prior to the admission. The patient was transferred to the Department of Liver Surgery for liver transplantation (LT). After written informed consents
Bile duct kinking after LDLT
611
were obtained from both the donor and the recipient, right‐lobe LDLT without the middle hepatic vein was performed in September 2007. During the surgery, a single opening of the right hepatic duct was observed in the donor graft. A duct‐to‐duct anastomosis with 7‐0 Prolene was performed for the bile duct reconstruction, which included a continuous suture for the posterior wall and an interrupted suture for the anterior wall. The cold ischemia time lasted for 75 min. After LT, a double-drug regimen of tacrolimus and steroid (methylprednisolone/prednisone) was adopted for immunosuppression. Five months after LT, the patient developed liver dysfunction, and magnetic resonance cholangiopancreatography (MRCP) suggested biliary stricture and kinking of the bile duct (Fig.1a–c). Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) was attempted twice for stent placement (Fig.1d), but the guide wire failed to pass through the stricture. The patient was treated with percutaneous transhepatic cholangial drainage (PTCD) in April 2008 (Fig.1e), and soon afterwards her liver function returned to normal level (Fig.2). In August 2008, the patient underwent re-exploration due to partial detachment of the PTCD tube, showing that the compensatory hypertrophy of the allograft resulted in kinking and sharp angulation of the bile duct, and the anastomotic site of the bile duct was found to be severely stenotic. Thus, we performed a bile duct reconstruction with
Figure 1. Magnetic resonance cholangiopancreatography (MRCP) and X‐ray images of case 1. (a,b) MRCP showing severe anastomotic stenosis (arrow) and dilation of intrahepatic bile ducts. (c) Three‐dimensional MRCP images showing bile duct kinking around the anastomotic site (circle). (d) Endoscopic retrograde cholangiopancreatography (ERCP) image shows the stenosis in the upper common hepatic duct. (e) Percutaneous transhepatic cholangial drainage (PTCD) shows biliary obstruction and dilation of upper bile ducts. (f) The T‐tube cholangiography shows an excellent biliary drainage after surgical revision.
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
612
P Wan etal.
Journal of Digestive Diseases 2015; 16; 610–615
Figure 2. The change in liver function of case 1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBIL, direct bilirubin; LDLT, living donor liver transplantation; PTCD, percutaneous transhepatic cholangial drainage; R‐Y, Roux‐en‐Y hepaticojejunostomy; TBIL, total bilirubin.
Roux‐en‐Y hepaticojejunostomy. The operation was successfully performed, and the T‐tube cholangiography 2 weeks after the surgery showed an excellent biliary drainage (Fig.1f). Biliary complications did not occur afterwards by the last follow‐up (8 March 2014). Case 2 In September 2007, a 44‐year‐old woman who had suffered from HBV‐related liver cirrhosis for more than 10 years was admitted to the Department of Liver Surgery of our hospital. She was diagnosed with acute hepatic decompensation on admission. The gynecological ultrasound detected a right adnexal mass of 4cm in size before surgery, and thus a consultant gynecologist was invited to participate in preoperative assessments and surgical treatments of the patient. After written informed consents were obtained, the patient underwent right‐lobe LDLT (without the middle hepatic vein) plus right adnexectomy in October 2007. During the LT procedure, there was a single opening of the right hepatic duct in the donor graft, and the bile tract reconstruction was performed as described above. The cold ischemia time lasted for 110 min. The immunosuppressive therapy after LT consisted of a double‐drug regimen of tacrolimus and steroid (methylprednisolone/prednisone). Post‐ surgical pathological examination identified the
adnexal mass as a benign ovarian cyst. In December 2008, the patient was re-admitted because of pruritus for one week and was diagnosed as a post-transplant biliary stricture. Just like the first patient, she was treated with ERCP afterwards, which showed that the anastomotic site was seriously stenotic, and two attempts both failed to complete the stent placement. Figures3 shows the latest MRCP images prior to the second operation. In February 2009, re-exploration was performed. Likewise, the stenotic bile duct angularly kinked around the anastomotic site, and re‐anastomosis by Roux‐en‐Y procedure was successfully performed. The changes in the liver function results are shown in Figure4. Long‐term stenosis‐free survival has been achieved after surgical revision, and the last follow‐up was 8 March 2014. DISCUSSION Although the shortage of deceased donation is a universal problem, the situation is particularly serious in Asia because of various social, cultural and historic reasons. Thus, a majority of LDLT procedures are currently performed in Asian countries. LDLT offers the potential advantages of a shortened waiting period, optimal donor graft, and the ability to optimize the recipient's health to those with end‐stage liver diseases. However, biliary complications are the most
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School
of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 610–615
Bile duct kinking after LDLT
613
Figure 3. Magnetic resonance cholangiopancreatography (MRCP) images of case 2. (a,b) MRCP shows severe anastomotic stenosis (arrow) and dilation of intrahepatic bile ducts. (c) Three‐dimensional MRCP images showing kinking and angulation of the bile duct around the anastomotic site (circle).
Figure 4. The change in liver function of case 2. ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBIL, direct bilirubin; LDLT, living donor liver transplantation; PTCD, percutaneous transhepatic cholangial drainage; R‐Y, Roux‐en‐Y hepaticojejunostomy; TBIL, total bilirubin.
intractable problems and remain to be the main obstacle in the implementation of adult LDLT.3 For pediatric LDLT, many researches have focused on the technical improvement to prevent adverse events related to regeneration of the partial graft and the growth of children.5,6,9,10 However, biliary complications caused by these reasons do not commonly occur because Roux‐en‐Y hepaticojejunostomy remains the standard treatment of choice for pediatric LDLT, which may be less susceptible to bile duct deformity. A recent study by Yamamoto etal.5 reported two children who developed deformity of the extrahepatic duct 4 and 9 years after LDLT, respectively, but no clinical signs associated with the deformity were observed.
Besides, similar cases were also reported in other researches investigating LDLT recipients.6 However, as for adult LDLT, most surgeons do not pay much attention to the influence of regeneration of the partial liver allograft on the biliary tract. The alignment of the end of bile ducts is straight at the time of transplant, but the graft regeneration may cause marked rotation or kinking of the hepatic hilum. Tension or kinking of the anastomotic site after a duct‐to‐duct anastomosis may impair the blood supply of the bile duct and gradually results in biliary complications. Based on our experience, bile duct kinking after LDLT is comprised of axial kinking and transverse kinking based on the direction of the rotational axis. Axial bile
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd
614 Table 1.
Journal of Digestive Diseases 2015; 16; 610–615
P Wan etal.
Management outcomes of biliary strictures in living donor liver transplantation recipients
Patients Authors (publication year) (n) Wadhawan etal.14 (2013) Yaprak etal.15 (2012) Yazumi etal.16 (2006) Tashiro etal.17 (2007) Chang etal.18 (2010) Lladó etal.19 (2012) Shah etal.20 (2007) Kim etal.21 (2009) Lee etal.22 (2011) Kato etal.23 (2009) Seo etal.24 (2009)
338 200 273 80 339 1000 130 NA NA 96 239
Patients with biliary stricture, n (%)
Technical success rate of ERCD, % (n/N)
45 (13.3) 17 (8.5) 80 (29.3) 20 (25) 121 (35.7) 152 (15.2) 22 (16.9) 60 137 41 (42.7) 68 (28.4)
75 54 64 50 64
63 47 76 58
(33/44) (7/13) (48/75) (10/20) (72/113) NA NA (38/60) (64/137) (31/41) (15/26)
Technical success rate of ERCD+PTCD#, % (n/N) 91 (40/44) NA 76 (57/75) 70 (14/20) 75 (90/120) NA NA 85 (51/60) NA 90 (37/41) NA
Patients undergoing surgical revision†, n (%) 2 5 12 6
(4.4) (29.4) (15) (30) NA 47 (31) 4 (18) NA NA NA NA
#
Patients treated by endoscopic retrograde cholangiogram‐guided drainage (ERCD), percutaneous transhepatic cholangial drainage (PTCD) or both are included. † Retransplantation is not included. NA, not available.
duct kinking is due to clockwise regeneration of the right liver graft around the inferior vena cava, which drives the bile duct to rotate around its own axis. Transverse bile duct kinking may arise either from inappropriate surgical technique or regeneration of the partial liver graft. Inappropriate surgical techniques are usually characterized by overlong preservation or incorrect anastomosis of the bile duct, which may result in kinking or fracture of the anastomotic site during the LT procedure or shortly after the surgery. The allograft regeneration after LDLT may cause the bile duct that with originally appropriate tension to become relatively too long, leading to sharp angulation of the bile duct. Graft regeneration rapidly occurs during the first month, and recipient grafts could achieve more than 90% of an expected standard liver volume three months after transplantation.11 The formation of bile duct kinking probably starts during this period. The persistent tension at the anastomotic site could gradually cause anastomotic stricture. Bile duct kinking or angulation has been indicated to be often detected at more than 6 months after LDLT the related clinical manifestations are not commonly presented at the early stage.5,6 Similarly, our cases manifested obstructive jaundice 5 and 14 months after transplantation, respectively. Such conditions turned out to be resistant to tendoscopic treatments, and PTCD could only temporarily relieve the biliary obstruction rather than fundamentally solve the problem. However, both patients achieved favorable outcomes with re‐anastomosis by Roux‐en‐Y procedure. Currently, most biliary complications are amenable to non‐operative managements. Endoscopic intervention
is considered as a well‐established treatment for anastomotic strictures after DDLT (only for patients undergoing a duct‐to‐duct anastomosis), and the overall success rate ranges from 70% to 100%.4,7 However, for LDLT, anastomotic strictures could only be successfully treated by endoscopic retrograde cholangiogram‐ guided drainage (ERCD) in a smaller group of patients.13 A literature review for the management outcomes of biliary strictures after LDLT is shown in Table1. The technical success rate of ERCD ranged from 47% to 76%,14–18,21–24 and the main reason of endoscopic failure was the failure of the guidewire to pass through the stricture. PTCD is considered as the second‐line option for the treatment of biliary complications in most studies due to the invasive nature of the procedure, and surgical revision is currently regarded as the final back‐up treatment option. A systematic review involving 61 studies revealed that PTCD or surgical revision was chosen as the first choice for biliary strictures in 42% of the LDLT populations compared with 3% of the DDLT populations, and surgical revision was performed in 24.9% of biliary strictures cases after LDLT.8 Due to the unique problem originated from the living donor allograft, bile duct kinking may not only involve in the formation of the biliary strictures after LDLT, but also in the high incidence of treatment failure with non‐surgical interventions. Based on these data, a considerable proportion of patients undergo repeated ERCD or PTCD unsuccessfully before receiving surgical revision. However, Davidson etal.25 sought to investigate the influence of nonsurgical managements on the outcome of post‐LT patients requiring surgical revision,
© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School
of Medicine and Wiley Publishing Asia Pty Ltd
Journal of Digestive Diseases 2015; 16; 610–615 and found that the complication rate after surgical revisions was less in those who failed non-surgical approach than those proceeding directly to surgery. Nonetheless, the current study showed that re‐anastomosis in the form of Roux‐en‐Y hepaticojejunostomy served as an effective surgical option for anastomotic strictures caused by bile duct kinking. In conclusion, bile duct kinking in adult LDLT recipients, although rare, may play a role in the high incidence of anastomotic strictures after LDLT, and also result in the treatment failure of non‐ surgical techniques. Surgical revision with Roux‐en‐Y hepaticojejunostomy is an appropriate option for the treatment of such condition. ACKNOWLEDGMENTS The study was supported by the Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning, and the Key Joint Research Program of Shanghai Health Bureau (2013ZYJB0001).
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