Hernandez‐Alejandro, Roberto

Living donor liver transplantation for oncologic indications is a complex topic that involves transplantation, oncology, and ethical considerations. The incidence of primary and secondary malignancy of the liver is growing. As transplant oncology continues to provide promising outcomes, the patient population that may benefit from transplantation will grow. In this review, we provide evidence that justify attempting transplantation for oncologic indications through the exploration of outcomes in both deceased donor and living donor liver transplants. This will focus on outcomes for patients with hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine liver metastasis, and colorectal liver metastases. This review aims to summarize the current status of transplant oncology and to develop the considerations of living donor liver transplantation for these indications.

Purpose of review Liver transplantation for metastatic colorectal cancer has been shown to be efficacious in the well selected patient. In the United States, there remains controversy on the appropriate selection criteria and optimal graft type to be utilized in these patients. Our group advocates for strict recipient selection and early access to quality grafts for these recipients. Recent findings In the past two years, there has been an explosion of centers reporting outcomes after liver transplantation for colorectal liver metastases. In North America, the publications have focused on single center experiences. The group in Oslo has reported their long-term outcomes of all transplanted patients. The TransMet randomized controlled trial has demonstrated efficacy of liver transplantation with chemotherapy over chemotherapy alone. Summary Liver transplantation for metastatic colorectal cancer is an efficacious procedure for the well selected patient. Regardless of graft type, potential liver transplant recipients with liver limited unresectable colorectal liver metastases should be evaluated with a strict criterion to determine eligibility. Once eligible, patients should receive early access to high quality grafts.

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016–2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

AbstractBackgroundDuration of functional warm ischemia (f‐WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT).MethodsA retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F‐WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non‐function (PNF), and early graft failure.Results35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f‐WIT variations analyzed, only f‐WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications.ConclusionThis study demonstrates that, of the f‐WITs, f‐WIT with SpO2 ≤ 60% is most predictive of post‐DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role.

The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that “very early” iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with “very early” iCCA and those with “advanced” disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the “very early” iCCA group and 33/48 (69%) the “advanced” group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the “advanced” group (3.1 [2.5‐4.4] versus 1.6 [1.5‐1.8]). After a median follow‐up of 35 (13.5‐76.4) months, the 1‐year, 3‐year, and 5‐year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1‐year, 3‐year, and 5‐year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. Conclusion: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (H epatology 2016;64:1178‐1188)