Gonzalo Sapisochin

Biliary tract cancer (BTC) comprises a family of rare malignancies subclassified by anatomy and pathology. However, this classification scheme may obscure shared biology and limit patient stratification. Here, we tested whether BTC heterogeneity can be explained by coherent latent axes and evaluated the potential to unify diverse clinical and genomic factors under a tractable biological framework. Whole-genome and transcriptome sequencing was performed on 180 tumors enriched for tumor cells by laser capture microdissection to identify shared programs in BTC. Network integration across transcriptomic classes identified two consensus cancer subtypes (CCS). The CCS segregated with anatomical location of primary tumor, and gene expression marker analyses suggested that subtypes reflect tumor cell of origin differences. The CCS displayed strikingly divergent molecular landscapes, explaining more variance than anatomical location of the primary tumor. CCS-B tumors were mutationally loaded with clock-like and APOBEC signatures and extrachromosomal DNA, whereas CCS-A tumors were characterized by chromosome-arm deletions. This approach showed that harnessing the genomic and transcriptomic diversity of BTC provides insights into shared biology and improves stratification.

Background: Hepatic artery complications are a major cause of early graft loss after liver transplantation (LT), especially in pediatric patients. Traditionally, these complications have been managed with surgical reintervention. This study presents the outcomes of early radiological intervention in pediatric LT patients with early hepatic artery thrombosis (HAT). Methods: A retrospective analysis was conducted by reviewing the prospectively collected database in our center. Patients between 0 to 18 years of age who had received an LT between 2003 and 2024 and had presented HAT in the first month after LT were included. Results: Out of 340 LTs, 13 patients (3.8%) presented early HAT and underwent an interventional radiology procedure (IRP) with balloon dilation and local infusion of vasodilators and/or fibrinolytic drugs. Five patients also required stent placement. The median time from LT to IRP was 1 day (0–6.5). IRP primary technical success was achieved in 11 of 13 patients (84.6%). Hepatic artery patency at three months was achieved in 10/13 (76.9%) of our patients, whilst long‐term hepatic artery patency was achieved in 8/13 (61.5%) patients. Two patients ultimately required retransplantation. Conclusions: An early and proactive interventional radiology approach may represent a feasible option for managing early HAT after pediatric LT. When performed promptly after diagnosis, it can help preserve hepatic artery patency and potentially reduce the need for surgical intervention and retransplantation.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Optimal treatment decisions are challenging, and existing treatment allocation frameworks may not fully reflect the evolving therapeutic landscape or contemporary clinical practices in North America. Using a modified Delphi process, a multidisciplinary panel of 20 North American experts in hepatology, medical oncology, surgery, radiology, and radiation oncology developed a consensus-based treatment framework for HCC, termed the BEACON-HCC system. The framework was informed by current evidence and expert opinion through iterative discussion and voting. In a pilot study using 29 real-world patient cases, we assessed concordance between external expert recommendations and BEACON-HCC recommendations and Barcelona Clinic Liver Cancer (BCLC) 2025 treatment recommendations. The BEACON-HCC treatment allocation framework diverges from prior frameworks by incorporating nuanced clinical features such as the degree of intrahepatic tumor burden and vascular invasion, and adverse tumor prognostic markers, to align treatment allocation with tumor biology and therapeutic potential. Key innovations include the incorporation of emerging modalities such as external beam radiation therapy (EBRT), transarterial radioembolization (TARE), and systemic–locoregional combination therapies. In the pilot exercise, expert treatment decisions showed 96.6% concordance with BEACON-HCC recommendations and 72.4% concordance with BCLC recommendations. In conclusion, BEACON-HCC is a consensus-based framework for treatment allocation that incorporates the expanding range of therapeutic options available to patients in the North American HCC population. Expert treatment decisions showed a high concordance with the BEACON-HCC system; further validation using empiric clinical data is planned through the HCC-Live Consortium.

Liver transplantation (LT) provides the best long-term survival outcomes for patients with liver cancer. As a result, the field of transplant oncology has grown greatly over the past few decades, and many centers have expanded their criteria to allow increased access to LT for liver malignancies. Center-level guidelines and practices in transplant oncology significantly vary across the world, leading to debate regarding the best course of treatment for this patient population. An international consensus conference was convened by the International Liver Transplantation Society and the International Liver Cancer Association on February 1–2, 2024, in Valencia, Spain, to establish a more universal consensus regarding LT for oncologic indications. The conference followed the Delphi process, followed by external expert review. Consensus statements were accepted regarding patient assessment and waitlisting criteria, pretransplant treatment (including immunotherapy) and downstaging, living donor LT, post-LT patient management, and patient- and caregiver-related outcomes. The multidisciplinary participants in the consensus conference provided up-to-date recommendations regarding the selection and management of patients with liver cancer being considered for LT. Although participants deferred to center protocols in many cases, there was great interest in safely expanding access to LT for patients with larger tumor burden and biologically amenable lesions.

Background & 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 intra-hepatic and perihilar cholangiocarcinoma. Emphasis is placed on strategies to broaden eligibility, optimize donor organ use, and improve oncologic outcomes. Approach & 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. Additionally, 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. Export

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

The success of living donor liver transplantation (LDLT) has bridged the growing gap between organ demand and availability in patients with liver failure or liver cancer. Safety of the living liver donor (LLD) is paramount, and astute intraoperative management plays a critical role in ensuring optimal outcomes for them. Given that intraoperative surgical and anesthesia practices vary widely across centers, the International Liver Transplantation Society (ILTS) and the International Living Donor Liver Transplantation Group (iLDLT Group) convened a global consensus conference in Toronto in March 2025 to develop guidelines for intraoperative management of the LLD. This manuscript details the recommendations on intraoperative considerations for the safety of LLD developed by Working Group II of the Consensus Scientific Committee, using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for assessment of recommendations, and the Danish model of consensus. Working Group II focused on intraoperative monitoring, fluid and ventilation strategies, surgical techniques for vascular and biliary division, surgeon and center-specific experience, and intraoperative crises planning. These guidelines aim to support both established and emerging LDLT teams to ensure high-quality and safe intraoperative care for the LLD.