Marino, Rebecca

Background and Aims: Liver transplantation has evolved from a treatment restricted to patients with end-stage liver disease to a therapeutic option for selected patients with primary and metastatic liver malignancies. This review explores the rapidly expanding field of transplant oncology, highlighting its role in hepatocellular carcinoma, colorectal liver metastasis, neuroendocrine liver metastasis, and intrahepatic and perihilar cholangiocarcinoma. Emphasis is placed on strategies to broaden eligibility, optimize donor organ use, and improve oncologic outcomes. Approach and Results: We synthesized current evidence from clinical series, registries, and experimental protocols to evaluate patient selection criteria, outcomes, and peri-transplant management. Key topics include downstaging approaches to meet transplant criteria, such as locoregional therapies and systemic regimens, and their prognostic implications. Advances in donor utilization have been analyzed for their capacity to expand the graft pool. In addition, the review addresses the integration of oncologic principles into immunosuppression regimens, balancing graft protection with cancer control. Collectively, the reported studies demonstrate improved survival and reduced recurrence when stringent selection and multimodal therapy were applied. Conclusions: Transplant oncology reshapes the therapeutic landscape of liver malignancies, with growing evidence supporting liver transplantation in carefully selected patients beyond traditional indications. Optimized downstaging, innovative donor strategies, and tailored immunosuppression are pivotal for safe expansion. Continued collaboration between the transplant and oncology disciplines, along with prospective trials, is essential to further define standardized protocols and solidify transplantation as a cornerstone of multidisciplinary cancer care.

Objective: To establish benchmark cutoffs for robotic liver resection (R-LR), encompassing both major and minor resections, and to determine the impact of patient selection on outcomes. Background: R-LR is a key advancement in minimally invasive liver surgery but lacks standardized benchmarks, especially for minor resections. While guidelines endorse R-LR, its role in optimizing outcomes remains unclear. This study establishes the first benchmarks for R-LR, enabling comparisons across surgical modalities and refining patient selection. Methods: This retrospective, multicenter study analyzed consecutive adult patients undergoing R-LR at 30 international centers (2020–2023). Benchmark centers had an annual case volume of ≥15 R-LR. Benchmark criteria included ASA ≤2, no major comorbidities, no prior liver resections, and Child-Pugh A status. Benchmark cutoffs for 14 key outcomes were set at the 50th and 75th percentiles of median values across benchmark centers. Multivariable logistic regression identified predictors of textbook outcomes. Results: Eighteen high-volume centers contributed 4028 cases with 2632 (65.3%) meeting benchmark criteria. Malignancy was the indication in 29.6%, most commonly hepatocellular carcinoma followed by colorectal liver metastases. Major liver resection was performed in 42.6%. The distribution of Iwate difficulty scores was low (25.4%), intermediate (53.9%), advanced (15.9%), and expert (4.9%). Benchmark cutoffs were established for minor and major resection, and stratified by Iwate low (0-3), intermediate (4-6) and high (7-12): Open conversion (≤6.5% minor, ≤10.5% major), major complications within 90 days (≤5.2% minor, ≤16.7% major), R1 resection (≤9.2% minor, ≤6.7% major). Benchmark cases performed at low-volume centers were able to achieve outcomes within the corresponding benchmark cutoffs. In fact, patient selection reflected by the proportion of benchmark patients, rather than case volume, was associated with textbook outcomes. Conclusions: This study defines R-LR benchmarks, emphasizing patient selection over center volume for optimal outcomes. Benchmark cutoffs guide training and support the expansion of R-LR.

614 Background: Liver transplantation (LT) offers a 5-year survival exceeding 70% for selected patients with hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs) may be used to downstage or bridge to transplantation. This study aims to evaluate the safety of ICIs prior to LT. Methods: Multicenter retrospective study, involving 9 centers, included adults who received ICIs and, subsequent LT, between 2019 and 2023. The ICI cohort was matched by age, sex, liver diseases and transplant date (1:3) with a similar cohort of HCC transplanted patients that did not receive ICIs. Results: The ICI cohort included 45 patients (Table part 1). The most common underlying liver diseases were viral. 15.5% of patients had macrovascular invasion and, 62.2% multifocal disease. The most commonly used ICI was nivolumab (75.6%), followed by atezolizumab-bevacizumab (17.8%). The median follow up was 32.5 months (17.4 - 47.6). The median ICI duration was 147 days (129.5-276.5), with a median interval of 58 days (22–193) between the last ICI dose and LT. There were 8 (17.8%) cases of graft rejection, 2 steroid-resistant leading to 1 graft failure. There were 4 (8%) HCC recurrences. During follow-up there were 6 deaths, 2 related to HCC recurrence and 4 non liver related. When compared with 135 non-ICI cohort patients, there were no differences within the groups (Table part 2). Importantly, we found no significant differences in crude rejection rates (p=0.5). Conclusions: Our study suggest that ICI treatment prior to LT is safe. ICI rejection primarily occurs in the acute post-transplant period (within 3 months), with a low risk of death due to graft failure. Further clinical trials are needed. Part 1: ICI cohort descriptive analysis. N (%); Median (IQR); Part 2: Comparison between cohorts. N (%); Mean (SD). (part 1) ICI-cohort n=45 General data Male 38 (84.4) Age 61.2 (7.6) Etiology of liver diseases Hepatitis C 17 (37.8)Hepatitis B 6 (13.3)MASLD 6 (13.3)Viral +Alcohol 5 (11.1)Alcohol 3 (6.7)Autoimmune 3 (6.7)Other 3 (6.7)Combined viral 2 (4.4) Largest tumor (mm) 39 (22) Macrovascular invasion 7 (15.5) Multifocal 28 (62.2) Locoregional therapy 36 (80.0) Number of locoregional therapies 2 (2) Immunotherapy Nivolumab 34 (75.6) Atezolizumab/bevacizumab 8 (17.8) Pembrolizumab 1 (2.2) Nivolumab+pembrolizumab 1 (2.2) PD1 inhibitor clinical trial 1 (2.2) Days of ICI treatment 147 (203) Radiological tumor response ICI No 17 (37.8) Transplant Deceased donor 43 (95.6) Washout period (days) 58 (171) Induction therapy (anti-thymoglobulin) 8 (17.8) Outcomes Rejection Biopsy proven 8 (17.8) 8 (100) Time to rejection (days) 43 (102) Graft failure Rejection 2 (4.4)1 (2.2) HCC recurrence 4 (8) Deaths 6 (13.3) Follow up Since transplant (months) 32.5 (30.2) (part 2) ICI-cohort (n=45) Non-ICI cohort (n= 135) P Post transplant rejection rate 8 (17.8) 32 (23.7) 0.53 Time to rejection (days) 180.1 (SD 218) 62.2 (SD 62.8) 0.25 Overall deaths 6 (13.3) 10 (7.4) 0.36