Lena Sibulesky

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole‐to‐cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021‐1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368‐21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole‐to‐cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts. Liver Transpl 18:101–112, 2012.

Asystole to cross‐clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole‐cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole‐cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole‐cross‐clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts.

Update on Biliary Strictures in Liver Transplants

Biliary complications continue to be the Achilles heel of orthotopic liver transplantation. These include ischemic-type biliary lesions that mostly affect liver allografts donated after cardiac and lead to increased morbidity and retransplantation in patients undergoing liver transplantation. Although this entity has been recognized for >20 years, the true mechanism of injury remains unknown. Identification of the pathogenesis will likely lead to the increased use of grafts donated after cardiac death and thus increase the organ pool. This update reviews the risk factors that have been implicated in ischemic-type biliary lesion formation, potential therapies, and mechanisms that might lead to their formation.

Intraoperative intracardiac thrombosis in a liver transplant patient

A 66-year-old female with cryptogenic cirrhosis complicated by ascites, hepatic encephalopathy, variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique. Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow. The liver graft was recirculated without any hemodynamic instability. Subsequently, the patient became hypotensive progressing to asystole. She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle. The patient was noted to be coagulopathic at the time. She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.

Preneoplastic conditions underlying bile duct cancer

BackgroundMalignancies arising from the biliary tract can arise from the epithelial lining of the biliary tract and surrounding tissues. Conditions that predispose to malignancy as well as preneoplastic changes in biliary tract epithelia have been identified. In this overview, we discuss preneoplastic conditions of the biliary tract and emphasize their clinical relevance.ResultsChronic biliary tract inflammation predisposes to cancer in the biliary tract. Biliary tract carcinogenesis involves a multistep process as a consequence of chronic biliary epithelial injury or inflammation. Reminiscent of other gastrointestinal epithelial malignancies such as gastric, colon, and pancreatic cancer, biliary tract cancers may evolve via multistep progression from epithelial hyperplasia and dysplasia to malignant transformation. The potential role of initiating cells is also becoming recognized.ConclusionsIn spite of improved risk factor recognition, and advances in diagnostic tools, the early diagnosis of pre-malignant or malignant biliary tract conditions is extremely challenging, and there is a paucity of evidence on which to base their management. As a result, the role of pre-emptive surgery remains largely undefined.

Outcomes following liver transplantation in intensive care unit patients.

AIM To determine feasibility of liver transplantation in patients from the intensive care unit (ICU) by estimating graft and patient survival. METHODS This single center retrospective study included 39 patients who had their first liver transplant directly from the intensive care unit and 927 non-ICU patients who were transplanted from hospital ward or home between January 2005 and December 2010. RESULTS In comparison to non-ICU patients, ICU patients had a higher model for end-stage liver disease (MELD) at transplant (median: 37 vs 20, P < 0.001). Fourteen out of 39 patients (36%) required vasopressor support immediately prior to liver transplantation (LT) with 6 patients (15%) requiring both vasopressin and norepinephrine. Sixteen ICU patients (41%) were ventilator dependent immediately prior to LT with 9 patients undergoing percutaneous tracheostomy prior to transplantation. Twenty-five ICU patients (64%) required dialysis preoperatively. At 1, 3 and 5 years after LT, graft survival was 76%, 68% and 62% in ICU patients vs 90%, 81% and 75% in non-ICU patients. Patient survival at 1, 3 and 5 years after LT was 78%, 70% and 65% in ICU patients vs 94%, 85% and 79% in non-ICU patients. When formally comparing graft survival and patient survival between ICU and non-ICU patients using Cox proportional hazards regression models, both graft survival [relative risk (RR): 1.94, 95%CI: 1.09-3.48, P = 0.026] and patient survival (RR: 2.32, 95%CI: 1.26-4.27, P = 0.007) were lower in ICU patients vs non-ICU patients in single variable analysis. These findings were consistent in multivariable analysis. Although not statistically significant, graft survival was worse in both patients with cryptogenic cirrhosis (RR: 3.29, P = 0.056) and patients who received donor after cardiac death (DCD) grafts (RR: 3.38, P = 0.060). These findings reached statistical significance when considering patient survival, which was worse for patients with cryptogenic cirrhosis (RR: 3.97, P = 0.031) and patients who were transplanted with DCD livers (RR: 4.19, P = 0.033). Graft survival and patient survival were not significantly worse for patients on mechanical ventilation (RR: 0.91, P = 0.88 in graft loss; RR: 0.69, P = 0.56 in death) or patients on vasopressors (RR: 1.06, P = 0.93 in graft loss; RR: 1.24, P = 0.74 in death) immediately prior to LT. Trends toward lower graft survival and patient survival were observed for patients on dialysis immediately before LT, however these findings did not approach statistical significance (RR: 1.70, P = 0.43 in graft loss; RR: 1.46, P = 0.58 in death). CONCLUSION Although ICU patients when compared to non-ICU patients have lower survivals, outcomes are still acceptable. Pre-transplant ventilation, hemodialysis, and vasopressors were not associated with adverse outcomes.

A single-center experience with biliary reconstruction in retransplantation: Duct-to-duct or roux-en-Y choledochojejunostomy

Retransplantation is the only therapy for patients who have a failing liver graft, and it can be technically challenging. Although duct‐to‐duct (DD) biliary reconstruction is considered standard in deceased donor orthotopic whole organ liver transplantation, Roux‐en‐Y (RY) choledochojejunostomy is preferred by most for biliary reconstruction in retransplantation. We performed a retrospective review of 128 patients who underwent retransplantation after a first transplant with DD biliary construction. Of these 128 patients, 83 had DD biliary reconstructions, and 45 had RY biliary reconstructions. Log‐rank tests were used to compare the complication rates between the DD and RY groups, whereas multivariate Cox proportional hazards models were used to compare patient and graft survival between the groups. The median Model for End‐Stage Liver Disease score at retransplantation was significantly higher in the DD group (27 versus 21, P = 0.005). The median length of follow‐up was 3.3 years. The biliary complication rates were 7% and 11% in the DD group and 10% and 10% in the RY group 30 days and 1 year after retransplantation, respectively (P = 0.73). The rates of primary graft nonfunction complications, hepatic artery thrombosis complications, and reoperation did not differ significantly between groups (all P ≥ 0.37). In comparison with RY reconstruction, there was no evidence of a difference in patient survival (relative risk = 0.79, P = 0.47) or graft survival (relative risk = 0.94, P = 0.85) for patients with DD reconstruction in multivariate analysis. In conclusion, our results provide evidence that DD biliary reconstruction is feasible in liver retransplantation without increased rates of biliary complications or compromised patient and graft survival. Further studies with larger sample sizes are needed. Liver Transpl 710‐716, 2011.

Left-sided grafts for living-donor liver transplantation and split grafts for deceased-donor liver transplantation: Their impact on long-term survival

BACKGROUND A small-for-size graft is important in living-donor liver transplantation (LDLT) and deceased-donor liver transplantation (DDLT). SUBJECTS AND METHODS First, we confirmed the effect of initial graft volume on survival using a rat model of liver transplantation (LT). We then evaluated the actual long-term survival based on graft type in 1421 LTs (including 1364 LDLTs) at Kyoto University and 2000 DDLTs at the Mayo Clinic, to evaluate donor safety in LDLT and the possibility of shifting to split orthotopic liver transplantation (SOLT) in DDLT. RESULTS In the rat model, SOLTs with 40%- and 20%-grafts had a poor survival. A total of 697 pediatric LTs showed good long-term outcomes (survival rate was 0.764 at 21.2 years). The survival rate of 724 adult LTs was 0.664 at 17.8 years. The survival rates of auxiliary partial orthotopic liver transplantation with a left-sided graft (0.421 at 15.0 years) and SOLT with a left-sided graft (0.000 at 0.8 years) need to be improved. Although the survival rate of 1965 adult DDLTs with a whole-liver graft in the Mayo Clinic was 0.727 at 12.8 years, that of adult SOLT was 0.595 at 11.0 years. CONCLUSION From the viewpoint of greater donor safety and expanded donor candidates in LDLT, the choice of a left-sided graft still remains controversial. A shift to SOLT to achieve excellent results should be established to resolve a donor shortage in DDLT.

Reactive Nodular Hyperplasia Mimicking Malignant Lymphoma in Donor Liver Allograft

The transmission of malignancy from donor to recipient can have devastating outcomes. Therefore, careful examination of the thoracic cavity, abdominal organs, and lymphoid tissue is important. In this report, we have described a case of a healthy 37-year-old donor with no significant past medical history who was found to have a nodule in the liver allograft during the examination at the back table. The frozen section revealed atypical lymphoid hyperplasia. Further workup revealed a rare benign lesion in the liver known as reactive lymphoid hyperplasia. Unfortunately, the liver allograft had to be discarded since low-grade lymphoma could not be excluded at the time of transplantation.

Bile duct stenting in liver transplantation

Dear Sirs, We read with great interest the article by Tranchart et al. [1] regarding their biliary reconstruction technique in liver transplantation in patients whose donor common bile duct was less than 5 mm in diameter. They describe their experience in 20 patients who had placement of an intraductal stent tube across the reconstructed common bile duct with subsequent removal months later using ERCP. They report overall four biliary complications, including cholangitis, hemobilia, bile leak, and anastomotic stricture. The stents were removed successfully using ERCP in 17 patients (85%). Fifteen patients required limited sphincterotomy during ERCP prior to stent removal. No complications were noted following the ERCP procedure. The authors set out to investigate this new technique because various studies have shown that placement of a T-tube during liver transplantation does not prevent biliary stricture formation and does not decrease incidence of bile leaks [2]. In fact, T-tubes are associated with increased morbidity. We agree with the authors’ concern that biliary complications continue to remain the ‘‘Achilles heel’’ in liver transplantation, and we would like to share our experience with the bile duct stenting technique during liver transplantation. Since 1998, we have performed over 2300 liver transplants at our center and have successfully used trancystic biliary tubes in the majority of cases [3]. Once the allograft gallbladder is removed and before the initiation of bile duct anastomosis, we thread a 5-Fr ureteral stent (Bard polyurethane ureteral catheter; C. R. Bard Inc., Covington, GA, USA) through the donor cystic duct. The stent is subsequently secured to the donor cystic duct with a 5–0 Vicryl suture and a hemorrhoidal rubber band [4,5]. The duct-to-duct biliary reconstruction is then completed. The anastomosis is tested intraoperatively by injecting the biliary tube with saline. Before closure of the abdominal incision, the tube is externalized, secured to the anterior abdominal wall, and left to gravity drainage. After post-transplant cholangiogram on day 3, the biliary tube is capped until day 21 cholangiogram (Fig. 1). If this