Anastomotic leaks (AL) are a devastating complication of simultaneous resection of primary colon cancer and liver metastases. We aimed to determine the risk factors of AL using a 10-year cohort from a nationwide database. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from 2014 to 2023 was used. Patients who underwent simultaneous colectomy and liver resection were included. Multivariate analysis was performed with AL as the outcome variable. The 2:1 propensity score matching (PSM) was performed on preoperative and operative covariates. A total of 1517 patients were included. Median age was 60 years and 824 (54

BACKGROUND:Previously, colorectal liver metastases (CLMs) were a highly morbid condition, for which standard palliative chemoradiation conferred dismal survival. Liver transplantation has emerged as a promising treatment for CLM; however, access has been limited to patients without a history of hepatic artery infusion pump (HAIP) therapy and those with access to living donors. STUDY DESIGN:Six centers participated in a retrospective cohort study evaluating patients undergoing deceased donor liver transplantation (DDLT) for CLM. Our primary endpoints were overall (OS) and disease-free survival (DFS). A subanalysis was performed based on HAIP therapy. RESULTS:Thirty-five patients with CLM were transplanted using DDLT, of whom 15 experienced recurrence (42.9%). Patients underwent primary resection a median of 146 days from diagnosis. Nineteen patients underwent HAIP therapy (54.3%). KRAS mutation was statistically significantly associated with recurrence (p = 0.01). Transplant was performed a median of 1,079 days (35.5 months) from diagnosis, at a median model for end-stage liver disease score of 7. Of those who recurred, median time to recurrence was 218 days and most metastasized to the lung (11) followed by the liver (5). Overall DFS was 62.7% at 1 year and 53.2% at 2 years. Most patients who recurred remain alive: overall, OS was 96.9% at 1 year and 84.8% at 2 years. HAIP therapy was not associated with differences in DFS or OS. CONCLUSIONS:DDLT confers favorable long-term OS to patients with CLM. Although HAIP did not confer improved survival in this cohort, larger studies assessing its impact are necessary.

Hepatocellular carcinoma is a leading cause of cancer-related mortality, with surgical treatments such as liver resection and liver transplantation offering curative potential but a high risk of recurrence. Recent advances in immunotherapy have shown promise in the treatment of advanced-stage hepatocellular carcinoma, and their potential role in earlier stages, particularly in resectable and locally advanced disease, is gaining increased attention. Neoadjuvant immunotherapy, including immune checkpoint inhibitors used alone or in combination, has demonstrated encouraging response rates and favorable pathological outcomes in clinical trials. These therapies may downstage tumors, enhance surgical resectability, and improve survival outcomes. However, challenges persist, particularly in standardizing criteria for treatment response and managing immune-related adverse events. Evidence also supports the combination of immunotherapy with locoregional therapies, such as transarterial chemoembolization and radiation, which may further improve therapeutic efficacy by inducing tumor regression and enhancing immune activation. Ongoing clinical trials and the exploration of emerging biomarkers, such as circulating tumor DNA, are crucial for optimizing patient selection and predicting treatment success. While neoadjuvant immunotherapy holds potential for improving outcomes in hepatocellular carcinoma, further research is needed to determine its precise role and long-term benefits in both resectable and unresectable disease.

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.

Tumor-infiltrating T cells have been the primary focus of cancer immunotherapy; however, accumulating evidence points to a critical role for B cells and plasma cells in shaping responses to immune checkpoint blockade. In this study, we investigated the humoral immune response in 38 patients with hepatocellular carcinoma treated with neoadjuvant anti-programmed cell death protein 1 (PD-1) therapy. In responders, defined by more than 50% tumor necrosis, we observed on-treatment enrichment of clonally expanded IgG1+ plasma cells within the tumor. Clonal tracking revealed that anti-PD-1 treatment expanded preexisting B cell clones associated with favorable clinical outcomes. Moreover, serum from responders contained IgG1 antibodies specific to cancer/testis antigens, including NY-ESO-1, and these humoral responses were linked to tumor-reactive T cell activity. We independently validated these findings across seven additional cohorts, encompassing single-cell and bulk sequencing data from 500 patients, spatial transcriptomics from seven patients and survival analyses from 1,582 patients. Our findings apply to recently approved treatments, such as PD-1 and vascular endothelial growth factor A (VEGF-A) blockade, but not to chemotherapy alone, suggesting broad relevance to individuals treated with immunotherapy. Collectively, our results demonstrate that PD-1 blockade induces tumor-specific IgG1+ plasma cell responses that complement cellular immunity and contribute to clinical benefit, underscoring a coordinated humoral-cellular axis in effective antitumor immunity.

Curative-intent treatments for hepatocellular carcinoma (HCC), including liver resection and transplantation, are limited by high recurrence rates and strict patient selection criteria. The success of immune checkpoint inhibitors (ICIs) in advanced disease has driven their integration into the perioperative setting, with the aim of improving long-term outcomes and expanding access to curative strategies. Neoadjuvant immunotherapy represents a biologically attractive approach, leveraging the intact tumour microenvironment to enhance systemic antitumour immunity and eradicate micrometastatic disease. Early-phase trials have demonstrated feasibility and promising efficacy outcomes, while recent phase 2/3 data suggest improved event-free survival with perioperative ICI-based combinations (CARES-009 trial), but no survival benefit with adjuvant ICI alone (IMbrave050 trial). In parallel, conversion strategies incorporating ICIs with tyrosine kinase inhibitors and locoregional therapies are increasing resectability rates in selected patients with initially unresectable disease. In the transplant setting, ICIs show potential as a bridging or downstaging strategy, although concerns regarding allograft rejection and optimal washout intervals remain. Emerging biomarkers, including pathological response and circulating tumour DNA, may refine patient selection and guide the design of adaptive clinical trials. Collectively, these advances support a shift toward biomarker-driven, perioperative immunotherapy strategies to optimise curative-intent management of HCC.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of hepatocellular carcinoma (HCC). Landmark trials, including IMbrave150 and HIMALAYA, have established combination ICI therapies as the standard of care for advanced HCC. Beyond these indications, ICIs are now being explored as neoadjuvant therapies for liver transplantation (LT), offering potential benefits in downstaging tumors and serving as bridging therapies for patients outside traditional transplant eligibility criteria. While early evidence from case reports and trials highlights promising oncologic and survival outcomes, the current understanding of ICI use before LT introduces new, unexplored challenges. Allograft rejection, safety concerns regarding immune-related adverse events, and the effective management of the complex interplay between immunosuppression and immune therapy represent ongoing themes of discussion. The tumor microenvironment and immunomolecular profiles, which critically influence ICI efficacy, remain the true cornerstones of patient stratification that are yet to be fully understood. Additionally, the lack of reliable biomarkers and the limitations of current radiologic criteria complicate treatment planning and response evaluation. Overcoming these obstacles requires multidisciplinary collaboration, refined patient selection strategies, and robust clinical trials to establish the safety and efficacy of ICIs in this context. This review aims to provide an up-to-date summary of the ever-evolving role of ICIs in LT strategies, offering a comprehensive overview of proposed therapeutic protocols, their oncologic and safety profiles, and the integration of emerging biological insights into clinical practice.

PURPOSE:To compare histopathologic outcomes of transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) and determine predictors of complete pathologic necrosis (CPN). MATERIALS AND METHODS:Patients with hepatocellular carcinoma treated with segmental (≤2 segments) or subsegmental TACE or TARE and underwent liver transplantation between January 2014 and March 2022 at a single center were retrospectively reviewed. Histopathologic and posttransplant outcomes were assessed within 2 years. Multivariable logistic regression, propensity score matching (PSM), and Kaplan-Meier survival analysis were performed. RESULTS:A total of 208 tumors in 148 patients were treated with segmental or subsegmental TACE (n = 76) or TARE (n = 132). In total, 132 tumors (63.5%) achieved CPN, and 156 (75.0%) had >90% necrosis on explant. The CPN rates by tumor in the TACE and TARE cohorts were 29.0% and 83.3%, respectively (P < .0001). Target tumor complete radiologic response (modified Response Evaluation Criteria in Solid Tumours) after TARE had a higher positive predictive value (89.0%) for CPN than that after TACE (42.9%). PSM analysis of TACE and TARE demonstrated that independent predictors of CPN were time from last treatment to transplant, subsegmental injection, and TARE. Patients who achieved overall CPN had significantly longer recurrence-free survival at 2 years (P = .02). CONCLUSIONS:In a cohort of patients who were bridged or downstaged to LT, there was improved recurrence-free survival in those who achieved CPN. Overall, TARE was superior to TACE in achieving pathologic necrosis.

Since FDA approval in 2021, normothermic machine perfusion (NMP) has emerged as a transformative tool to expand transplantation access for patients with end-stage liver disease. This study details the design, implementation, and outcomes of our liver NMP program, highlighting implementation of a stratification algorithm for grafts into low-, medium-, and high-risk categories and evaluation of high-risk grafts from the first 100 cases. A secondary analysis compares NMP outcomes with historical cohorts. The final analysis included 53 grafts from donation after brain death (DBD) and 39 from donation after circulatory death (DCD) donors, excluding eight NMP grafts that were not transplanted. No significant differences were observed in allograft dysfunction, primary non-function, biliary or arterial complications, or patient survival, even among high-risk graft recipients. NMP significantly reduced intraoperative cryoprecipitate (0.41 vs. 1.44 units, p = 0.003) and platelet (0.59 vs. 1.56 units, p = 0.001) use in DCD recipients. While recipients of DBD-NMP grafts experienced longer ICU stays (17.17 vs. 8.96 days, p = 0.03) and higher rates of renal replacement therapy (41.14% vs. 20.75%, p = 0.04) than the historic cohort, inpatient length of stay and long-term dialysis requirements were unaffected. Higherrisk graft use facilitated transplant access for patients with lower MELD scores at our center. These findings highlight NMP's potential to safely expand the donor pool, facilitating transplantation of previously non-utilized livers while maintaining comparable outcomes. The risk stratification developed alongside our program provides a practical algorithm to advance equity in organ allocation through NMP by enabling safe access to high-risk grafts and demonstrates its value in optimizing liver transplantation practices.

BACKGROUND:Laparoscopic liver resection has been associated with less morbidity than, and similar global outcomes to, open liver resection. There is no robust evidence that these outcomes lead to similar clinical outcomes in patients aged over 80 years. The aim of this study was to analyse the short-term outcomes between open and laparoscopic liver resection in patients over 80 years old. METHODS:A retrospective analysis was undertaken. The study population comprised patients aged ≥ 80 years who underwent laparoscopic or open liver resection between January 2014 and December 2019, and who presented with resectable malignant tumours. The primary outcome was postoperative morbidity, according to Dindo-Clavien grading. Cox regression models were used to compute hazard ratios and 95% confidence intervals. Propensity score matching (1 : 1) was performed to balance the two groups according to independent prognostic factors for morbidity. RESULTS:A total of 988 patients were analysed from 34 centres (16 from Asia, 14 from Europe and 4 from America): 487 in the open group and 501 in the laparoscopic group. Independent risk factors associated with severe morbidity were the open approach (hazard ratio 1.59, 95% confidence interval 1.19 to 2.11; P < 0.001), Charlson Co-morbidity Index score > 7 (HR 1.69, 1.26 to 2.27; P < 0.001), more than one resected tumour (hazard ratio 1.55, 1.13 to 2.11; P = 0.006), major hepatectomy (hazard ratio 1.86, 1.22 to 2.83; P = 0.003), and Iwate score ≥ 7 (hazard ratio 1.43, 1.02 to 2.01; P = 0.03). Before propensity score matching, severe morbidity, length of intensive care unit stay, 90-day mortality, length of hospital stay, and readmission were better in the laparoscopic group (P < 0.050). These observations were confirmed after propensity score matching. CONCLUSION:The laparoscopic approach is a safe procedure for elderly patients, with better morbidity and mortality outcomes than the open approach, and should be considered as a default option.

BACKGROUND AND AIMS:The RETREAT(Risk Estimation of Tumor REcurrence After Transplant) score is a simple risk stratification tool for postliver transplantation (LT) HCC recurrence that has been validated in retrospective cohort studies. A prospective, multicenter study is needed to further demonstrate accuracy especially given the evolving clinical demographics and HCC transplant practice. Our aim is to validate and compare the RETREAT score to other post-LT HCC recurrence risk scores in a contemporary, prospective cohort of patients. APPROACH AND RESULTS:We prospectively enrolled patients with HCC who underwent LT from 8 centers between 2018 and 2022. The primary outcome was post-LT recurrence-free survival. Secondary outcomes included post-LT and post-recurrence survival. Model performance, determined using the concordance index, Akaike information criterion, integrated Brier score, and calibration, was compared to that of other established risk scores.We included 1166 patients with HCC who underwent LT, of which 78 (6.7%) had post-LT HCC recurrence after a median follow-up time of 2.2 years (IQR 1.2-3.2). The median RETREAT score was 4 (IQR 3-5) in patients with post-LT HCC recurrence and 1 (IQR 1 - 2) in patients without. Those with a RETREAT score of 0, 3, and 5+ had a 99.4%, 84.1%, and 55.6% recurrence-free survival, respectively, at 3 years post-LT. The RETREAT score was also able to stratify post-LT overall and postrecurrence survival. The RETREAT score's concordance index was 0.81 (95% CI: 0.77-0.85) and outperformed the MORAL and RELAPSE scores across multiple metrics. CONCLUSIONS:The RETREAT score retains high accuracy for predicting post-LT HCC recurrence, further supporting RETREAT-guided post-LT HCC surveillance and care.