Duct-to-duct biliary reconstruction in adult-to-adult living donor liver transplantation

In living donor liver transplantation (LDLT), Roux-en-Y hepaticojejunostomy has been a standard technique for biliary reconstruction because the majority had been pediatric patients with biliary atresia. Adult-to-adult LDLT using the right lobe graft has recently been developed and we introduced duct-to-duct biliary reconstruction (hepaticohepaticostomy) in such cases. The aim of this study is to evaluate the feasibility of this procedure in adult-to-adult LDLT. From August 2000 to October 2001, five patients underwent adult-to-adult LDLT using the right hepatic lobe and were followed for more than 6 months at our institution. All patients underwent duct-to-duct biliary reconstruction (single hepaticohepaticostomy in one, multiple in four). For the grafts with multiple bile ducts, various techniques were used for reconstruction. In all patients, oral intake could be started early after the operation, and biliary leakage was not encountered. One patient developed two episodes of acute cholangitis who later developed biliary anastomosis stricture which required percutaneous dilatation at 11 months postop. However, otherwise, there were no infectious complications postoperatively. We conclude duct-to-duct biliary reconstruction is feasible and effective in adult-to-adult LDLT.     

Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation

From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end-to-end microanastomosis of the donor right hepatic duct with the recipient's bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux-en-Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end-to-end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T-tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end-to-end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.     

Long-term outcome of living donor liver transplantation for primary biliary cirrhosis

In living donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), the majority of donors are genetically related to their recipients, leading to concerns of an earlier recurrence of PBC and a poorer prognosis due to genetic susceptibility. Totally 81 patients who underwent LDLT for PBC were the subjects of the present study. Immunosuppressive agents consisted of tacrolimus and methylprednisolone. In the outpatient clinic, when the aspartate and alanine aminotransferase level exceeded the upper limit of the normal range, the dose of methylprednisolone was increased from 4 to 6 mg/day for several months. Blood was examined every 2 weeks for 3 months and a liver biopsy was performed when aminotransferase levels did not decrease to the upper limit of the normal range after more than 3 months. Five-year survival and recurrence rates were estimated and the prognostic factors were analyzed. The mean observation period was 6.2 years. Five years after LDLT for PBC, the biopsy-proven PBC recurrence rate was 1%. The 5-year patient survival rate was 80%. The nonrelated or blood-related donor factor and number of human leukocyte antigen matches did not correlate with prognosis. PBC recurrence rate after LDLT in our series was lower than that in previous studies.     

Two-step biliary external stent removal after living donor liver transplantation.

Biliary stenting plays an important role in living donor liver transplantation (LDLT) as the rate of biliary complication is higher in LDLT than in diseased donor whole LT. We use a 2-mm tube for stenting at the biliary anastomosis, externalize it through the lower common bile duct, and fistulize it using duodenal serosa. After 3 months without biliary complications ensured by a cholangiogram, the stent tube is removed in a two-step manner, allowing bile to drain under a fluoroscope. The incidence of local peritonitis was lower, and the hospital stay was shorter with the two-step procedure. We herein report on the method of the two-step removal and its efficacy.     

活体肝移植术后胆道并发症的研究及相关因素的分析

目的 分析活体肝移植（LDLT）术后的胆道并发症（BC）及相关因素。方法 回顾性分析瑞金医院肝移植中心2006年6月至2009年9月实施的42例LDLT的临床资料,对LDLT术后BC的发生进行总结和分析。统计LDLT术后BC发生的可能因素,进行单因素对照分析。结果 42例LDLT其中出现BC 16例（A组）,未出现BC 26例（B组）,BC的发生率为38.1%。A组与B组LDLT患者在右半肝和左半肝所占比例（50% vs 9.1%）（P=0.044）、有无动脉并发症所占比例（70% vs 28.1%）（P=0.045）、冷缺血时间（cold ischemic time,CIT）（P=0.048）、无肝期时间（P=0.037）、移植物受者体重比（graft weight/recipient weight,GWRW）（P=0.04）及GRWR≥1（P=0.029）等6个因素上比较差异有统计学意义。结论 LDLT术后BC的发生率高低与手术医生的熟练程度,手术方法的改进,缩短冷缺血时间、无肝期时间有关,还与左右半肝比例和GWRW有关。     

Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation

Kyoden Y, Tamura S, Sugawara Y, Matsui Y, Togashi J, Kaneko J, Kokudo N, Makuuchi M. Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation.
Clin Transplant 2010: 24: 535–542.
© 2009 John Wiley & Sons A/S. Abstract: Background: There are few detailed reports of biliary complications in a large adult living donor liver transplantation (LDLT) series. Patient and methods: Biliary complications, treatment modalities, and outcomes in these patients were retrospectively analyzed in 310 adult LDLT. Results: One patient underwent retransplantation. Duct‐to‐duct anastomosis was primarily performed in 223 patients (72%). During the observation period (median 43 months), biliary complications were observed in 111 patients (36%); 53 patients (17%) had bile leakage, 70 patients (23%) had bile duct stenosis, and 12 patients (4%) had bile leakage followed by stenosis. A biliary anastomotic stent tube was placed in 266 patients (86%) at the time of transplantation. Univariate analysis of various clinical factors revealed duct‐to‐duct anastomosis as the single significant risk factor (p = 0.009) for biliary complications. The three‐yr and five‐yr overall patient survival rates were 88% and 85% in those with biliary complications, and 85% and 83%, respectively, in those without biliary complications (p = 0.59). Conclusion: Biliary complications are a major cause of morbidity following LDLT. Duct‐to‐duct anastomosis carried a higher risk for bile duct stenosis. With appropriate management, however, there was little influence on overall survival.     

In adult-to-adult living donor liver transplantation hepaticojejunostomy shows a better long-term outcome than duct-to-duct anastomosis.

Roux-en-Y hepaticojejunostomy (RYHJ) has been the standard biliary reconstruction in adult-to-adult living donor liver transplantation (ALDLT). Recently, duct-to-duct anastomosis (DD) has been introduced. This study compared the outcomes of RYHJ and DD. For 4 years, 74 recipients underwent ALDLT and were followed up for at least 2 years. The patients were divided into three groups, RYHJ group (n = 18), DD with a stent (DD + S) group (n = 35), and DD without a stent (DD - S) group (n = 21). Overall, biliary complications were developed in 32.4% patients. The biliary complication rate was 11.1%, 48.5% and 33.3% in RYHJ, DD + S and DD - S groups, respectively (P = 0.047). Bile leaks occurred in 28.5% of DD + S group. The incidence of biliary stricture was 5.3%, 20.2% and 28.6% in RYHJ, DD + S and DD - S group, respectively. Most complications (83.3%) were resolved nonsurgically. RYHJ has a better long-term outcome than DD in ALDLT. Subgroup analysis of DD group showed that DD - S group had no bile leaks, but still had a higher incidence of bile duct strictures. However, because this study was a retrospective review there are limitations in analyzing the data and confirming the conclusion. A randomized-prospective study will be needed to confirm these findings.     

Biliary complications after living donor adult liver transplantation.

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22-64%. We performed 23 ALDLT grafting segments V-VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8-1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication.     

Nonsurgical policy for treatment of bilioenteric anastomotic stricture after living donor liver transplantation.

Biliary complications remain a significant cause of morbidity following living donor liver transplantation. The purpose of this retrospective study was to assess the outcome of nonsurgical management for hepatojejunostomy stricture in our institution. We reviewed 22 patients with hepatojejunostomy stricture among the 231 patients who underwent living donor liver transplantation between June 1990 and December 2005. Hepatojejunostomy stricture was confirmed by percutaneous transhepatic or endoscopic retrograde cholangiography. Anastomotic strictures were treated by balloon dilatation. Percutaneous transhepatic cholangiography was performed on 15 of the 22 patients. Two of 15 patients, with complete obstruction of the anastomosis, were treated successfully by Yamanouchi magnet compression anastomosis. Although another two patients died of infectious disease that was unlikely to have been related to biliary complications, anastomotic patency was maintained in the other 13 patients. Endoscopic retrograde cholangiography was performed on seven of the 22 patients. None of the 22 patients required re-operation or died of biliary complications. The 5-year graft survival rate of 85.6% in the 22 patients with stricture was equivalent to that of the patients without stricture (82.9%, P = 0.98). Advances in intervention techniques have enabled wider application of nonsurgical approaches for this complication, and fair results have been obtained.     

The impact of meticulous management for hepatic artery thrombosis on long‐term outcome after pediatric living donor liver transplantation*

Abstract: To analyze the risk factors in the development of hepatic artery thrombosis (HAT) and assess the impact of our perioperative management for HAT on the long‐term outcome after pediatric living donor liver transplantation (LDLT), we reviewed 382 patients under 12 yr of age who underwent 403 LDLT from January 1996 to December 2005. One‐ and 10‐yr patient survival rates were 78% and 78% in the patients with HAT (27 patients; 6.7%), and 84% and 76% in the patients without HAT, respectively (p = n.s.). Univariate analysis showed gender (female), body weight (lower), and graft‐to‐recipient weight ratio (higher) were significant risk factors in the patients with HAT (p < 0.05). Patients with Doppler ultrasound signal loss of the hepatic artery (HA) accompanied by an increase of liver enzymes underwent thrombectomy and reanastomosis (S‐group, n = 13), and patients with a weak HA signal underwent anticoagulant therapy (M‐group, n = 13). One patient underwent re‐LDLT. One‐ and five‐yr patient survival rates were 83% and 83% in the S‐group, and 77% and 77% in the M‐group (p = n.s.). The incidence of biliary complications in the S‐group (58%) was significantly higher than that of the M‐group (15%). For a successful long‐term outcome, the early detection of HAT and prompt medical and surgical intervention are crucial to minimize the insult of HAT.     

Preoperative evaluation of biliary anatomy of donor in living donor liver transplantation by conventional nonenhanced magnetic resonance cholangiography

Detailed preoperative evaluation of the biliary anatomy of the donor in living donor liver transplantation (LDLT) can minimize postoperative morbidity in the recipient and maximize safety for the donor. We prospectively evaluated the diagnostic accuracy and clinical usefulness of nonenhanced conventional magnetic resonance cholangiography (MRC) for depicting the biliary anatomy of LDLT donors. MRC and intraoperative cholangiography (IOC) examinations of 111 donors were performed between August 2005 and February 2006. We observed the classical branching pattern of the biliary system in 67 subjects (60.4%), with the remaining 44 subjects (39.6%) showing anatomical variations. MRC showed accurate anatomy of the biliary system, using IOC as the reference standard, in 98 (88.3%) subjects. MRC had a sensitivity in differentiating normal from variant anatomy of 95.5%, specificity of 95.2%, a positive predictive value of 96.8% and a negative predictive value of 93.3%. The agreement between MRC and IOC findings, as evaluated by kappa-value (0.865) was statistically significant (P<0.001). In conclusion, the diagnostic accuracy of conventional nonenhanced MRC is sufficient for this method to be used for the preoperative evaluation of biliary anatomy in LDLT donor candidates.     

超声检查在活体肝移植受体术后胆道并发症诊断中的应用

目的 探讨超声检查在活体肝移植术后胆道并发症诊断中的临床应用。方法 对21例成人右半肝活体移植受体术后进行超声检查,观察移植肝及其胆道声像图表现,与经皮经肝穿刺胆道造影引流(PTCD)等影像学结果相对比。结果 21例病例经PTCD及临床随访证实为胆管吻合口狭窄5例,胆泥1例,胆漏1例。超声检查能够诊断并与之相符5例,为4例吻合口狭窄及1例胆泥,胆漏病例可见肝周积液。其中4例胆管吻合口狭窄病例超声诊断时间均明显早于临床出现黄疸或血清胆红素升高的时间。结论 在活体肝移植术后胆道并发症的诊断中,超声检查操作简便、无创、可重复性强、准确性较高,可早期诊断胆管并发症,具有重要的临床应用价值。     

Maternal grafts protect daughter recipients from acute cellular rejection after pediatric living donor liver transplantation for biliary atresia

Some studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor–recipient classifications included mother donor to daughter recipient (MD; n = 43), mother to son (n = 18), father to daughter (FD; n = 33), and father to son (n = 20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P = 0.012). The FD group had a higher incidence of ACR than the MD group (P = 0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.     

Impact of biliary complications in right lobe living donor liver transplantation

Biliary reconstruction is one of the most challenging parts of right lobe living donor liver transplantation (RL LDLT), and biliary complications have been reported as the first source of surgical complications of this procedure. We reviewed biliary reconstruction and complications in 27 consecutive RL LDLTs. We compared the first 14 procedures (group 1) to the last 13 (group 2). Seven patients (25.9%) experienced a biliary complication (five leaks and two strictures). The incidence of biliary complications was 11.1% in RL grafts with a single duct and 55.5% in graft presenting multiple bile ducts (P = 0.03). Four of the 18 patients with a duct-to-duct reconstruction (22.2%) and three of the 11 patients with a Roux-en-Y reconstruction (27.3%) developed a biliary complication (P = ns). The incidence of biliary complications significantly decreased from 42.9% (n = 6) in the first group to 7.6% (n = 1) in the second group (P = 0.05). The overall 1-year graft and patient survival were 57.1% and 64.3% in group 1 versus 100.0% and 100% in group 2 (P = 0.01; P = 0.006). Biliary complications remain one of the most important technical complications affecting RL LDLT. Nevertheless, attention and surgical refinement can lead to a significant reduction of the biliary complication rate, improving graft and patient survival.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Biliary reconstruction in pediatric live donor liver transplantation: duct-to-duct or Roux-en-Y hepaticojejunostomy

Background

Duct-to-duct biliary reconstruction (DD) is currently a standard procedure in adult live donor liver transplantation (LDLT). Its pediatric feasibility, however, has rarely been reported. The goal of this study is to assess the incidence and treatment of biliary complication after pediatric LDLT with DD or Roux-en-Y hepaticojejunostomy (RY).

Method

Sixty children received LDLT between November 2005 and June 2008, and their database was reviewed.

Results

Biliary reconstruction was achieved with DD in 14 patients and with RY in 46 patients with mean follow-up period of 26.0 and 22.3 months, respectively. The incidence of biliary leakage in the DD and RY groups was 7.1% and 8.7%, respectively, and that of stricture was 28.6% and 10.9%, respectively; but the differences were not statistically significant. Biliary stricture in the DD group tended to require revision surgery with RY and longer treatment with percutaneous transhepatic cholangiodrainage compared with that in the RY group.

Conclusion

Theoretical advantages of DD over RY were not confirmed in this study. Duct-to-duct biliary reconstruction tended to encounter more biliary complications, especially stricture, with more difficulty in treating it than RY. Roux-en-Y hepaticojejunostomy seems preferable to DD in the setting of pediatric LDLT, but DD must be considered when making new Roux-en-Y limb seems impossible or troublesome owing to abdominal dense adhesion or short bowel syndrome.     

Removable intraductal stenting in duct-to-duct biliary reconstruction in liver transplantation

Biliary reconstruction during liver transplantation (LT) is most oftenly performed by duct-to-duct biliary anastomosis. We hypothesized that the internal stenting might diminish the incidence and severity of biliary complications in patients receiving small duct size donor grafts. The purpose of this study was to report a technique of biliary reconstruction, including intraductal stent tube (IST) placement followed by postoperative endoscopic removal. A custom-made segment of a T-tube was placed into the bile in 20 patients in whom the diameter of the graft bile duct was smaller than 5 mm. The tube was removed endoscopically 4-8 months after LT, or in case of IST-related adverse events. After a median follow-up of 15.2 (range 2.5-27.5) months, endoscopic removal of the IST was performed in 17 patients. No technical failure and no procedure-related complications were recorded during drain removal. Biliary complications occurred in four patients, including one cholangitis, one hemobilia, one asymptomatic biliary leakage, and one anastomotic stricture. No biliary complication occurred in the group of patients who underwent deceased donor whole graft LT. IST is technically feasible and safe, and may help to prevent severe biliary complication when duct-to-duct biliary anastomosis is performed on small size bile ducts.     

Donor morbidity in right and left hemiliver living donor liver transplantation: the impact of graft selection and surgical innovation on donor safety

This study investigated adequate liver graft selection for donor safety by comparing postoperative donor liver function and morbidity between the right and left hemilivers (RL and LL, respectively) of living donors. Between April 2006 and March 2012, RL (n = 168) and LL (n = 140) donor operations were performed for liver transplantation at Kyoto University Hospital. Postoperative hyperbilirubinemia and coagulopathy persisted in RL donors, whereas the liver function of LL donors normalized more rapidly. The overall complication rate of the RL donors was significantly higher than that of the LL donors (59.5% vs. 30.7%; P < 0.001). There were no significant differences in severe complications worse than Clavien grade IIIa or in biliary complication rates between the two donor groups. In April 2006, we introduced an innovative surgical procedure: hilar dissection preserving the blood supply to the bile duct during donor hepatectomy. Compared with our previous outcomes (1990–2006), the biliary complication rate of the RL donors decreased from 12.2% to 7.2%, and the severity of these complications was significantly lower. In conclusion, LL donors demonstrated good recovery in postoperative liver function and lower morbidity, and our surgical innovations reduced the severity of biliary complications in living donors.     

Endovascular management of early hepatic artery thrombosis after living donor liver transplantation

To study the feasibility of endovascular management of early hepatic artery thrombosis (HAT) after living‐donor liver transplantation (LDLT) and to clarify its role as a less invasive alternative to open surgery. A retrospective review of 360 recipients who underwent LDLT. Early HAT developed in 13 cases (3.6%). Diagnosis was performed using Doppler, CT angiography, and digital subtraction angiography. Intra‐arterial thrombolysis (IAT) was performed using streptokinase or tPA. In case of underlying stricture, PTA was attempted. If the artery did not recanalize, continuous infusion was performed and monitored using Doppler US. Initial surgical revascularization was successful in 2/13 cases. IAT was performed in 11/13 cases. The initial success rate was 81.8% (9/11), the failure rate was 18.2% (2/11). Rebound thrombosis developed in 33.3% (3/9). Hemorrhage developed after IAT in 2/11 cases (18.2%). Definite endovascular treatment of HAT was achieved in 6/11 cases (54.5%) and definite treatment (surgical, endovascular or combined) in 9/13 cases (69%). (Follow‐up 4 months–4 years). Endovascular management of early HAT after LDLT is a feasible and reliable alternative to open surgery. It plays a role as a less invasive approach with definite endovascular treatment rate of 54.5%.