Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.

Gemcitabine/cisplatin (GemCis) was the long-standing first-line treatment for advanced biliary tract cancers (BTCs). Following positive results from the TOPAZ-01 and KEYNOTE-966 trials, immune checkpoint inhibitors (ICIs) combined with chemotherapy are now the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTCs. Our systematic review included studies from five databases focusing on English-language articles published between January 2010 and June 2024. We included randomized clinical trials (RCTs) that featured GemCis in a treatment arm for treatment-naive adults with advanced BTCs. The primary endpoints were overall survival (OS) and progression-free survival. We conducted a one-stage meta-analysis using reconstructed survival data, Cox-based models, and restricted mean survival time (RMST). After screening 8,797 studies, 17 RCTs were selected, involving a total of 4,584 patients. Of these, 2,140 (46.7%) received GemCis. The majority (68.9%) were diagnosed with intrahepatic or extrahepatic cholangiocarcinoma, and 80% had metastatic disease at the time of treatment. The pooled median OS in the GemCis group was 11.6 months (95% CI 11.3–12.2 months). GemCis plus pembrolizumab (hazard ratio [HR] 0.99, 95% CI 0.98–0.99; p <0.001), GemCis plus durvalumab (HR 0.98, 95% CI 0.97–0.99; p = 0.015), GemCis plus S-1 (HR 0.97 95% CI 0.95–0.99; p <0.001), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.98–0.99; p <0.001) demonstrated superior OS compared with GemCis alone. These combinations also showed increases in RMST by +1.1, +2.5, +2.8, and +2.1 months, respectively. In terms of progression-free survival, GemCis with ICIs (HR 0.91, 95% CI 0.78–0.94; p <0.001), GemCis plus S-1 (HR 0.98, 95% CI 0.96–0.99; p = 0.003), and GemCis plus nab-paclitaxel (HR 0.98, 95% CI 0.97–0.99; p <0.001) also demonstrated superiority, with corresponding RMST increases of +0.7, +1.9, and +2.5 months, respectively. Despite incremental advancements, a breakthrough in advanced BTC treatment remains elusive. Further improvements in treatment efficacy may require biomarker identification to optimize combinational therapies for better patient selection. This study analyzed recent RCTs, including KEYNOTE-966, TOPAZ-1, NIFE, and SWOG 1815, involving 4,584 patients with advanced biliary tract cancer. A meta-analysis of 17 treatment arms, using reconstructed survival data, confirmed the modest survival benefit of GemCis plus ICIs, supporting its guideline adoption. The findings, however, highlight the need for biomarker identification and better patient selection.

Purpose: Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. Methods: We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. Results: Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. Conclusion: It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.

Background: Although living donor liver transplantation (LDLT) is increasingly adopted for pediatric LT, there is limited data whether live donation extends benefits to patients from the time of listing. This study investigated the benefits of pediatric LDLT through an intention-to-treat analysis. Methods: Pediatric candidates listed between 2001-2023 at a single Canadian center were categorized as pLDLT (with a potential live donor) or pDDLT (without a live donor). The primary endpoint was overall survival from the time of listing. The secondary endpoint involved the waitlist outcomes described by the probabilities of receiving LT or waitlist dropout. Results: Among 474 candidates, 219 (46.2%) had potential live donors. The pLDLT group had a higher likelihood of receiving a LT (aHR 1.38, 95%CI:1.16-1.64) and lower risk of dying without a transplant (aHR 0.11, 95%CI:0.01-0.82) compared to the pDDLT group. Survival rates from the time of listing were significantly better in the pLDLT group at 1-(98.6% vs. 87.6%), 5-(96.6% vs. 84.4%), and 10-(96.6% vs. 83.1%) years. Having a potential live donor was linked to a 72% reduction in mortality risk (aHR 0.28, 95%CI:0.12-0.64). Although the number of patients listed annually increased over the study period, the waiting time for deceased donation shortened. This correlated with increased LDLT utilization, suggesting LDLT not only improved outcomes but shortened wait times even for pDDLT patients. Conclusion: Having a potential live donor is associated with substantial survival benefit. Pediatric programs offering LDLT can expand the donor pool and decrease the waiting time for DDLT, supporting the argument for making LDLT a standard for pediatric candidates. Export

Introduction: Solid organ transplantation (SOT) is a lifesaving treatment for end‐stage organ failure. Although many factors affect the success of organ transplantation, recipient and donor sex are important biological factors influencing transplant outcome. However, the impact of the four possible recipient and donor sex combinations (RDSC) on transplant outcome remains largely unclear.Methods: A scoping review was carried out focusing on studies examining the association between RDSC and outcomes (mortality, graft rejection, and infection) after heart, lung, liver, and kidney transplantation. All studies up to February 2023 were included.Results: Multiple studies published between 1998 and 2022 show that RDSC is an important factor affecting the outcome after organ transplantation. Male recipients of SOT have a higher risk of mortality and graft failure than female recipients. Differences regarding the causes of death are observed. Female recipients on the other hand are more susceptible to infections after SOT.Conclusion: Differences in underlying illnesses as well as age, immunosuppressive therapy and underlying biological mechanisms among male and female SOT recipients affect the post‐transplant outcome. However, the precise mechanisms influencing the interaction between RDSC and post‐transplant outcome remain largely unclear. A better understanding of how to identify and modulate these factors may improve outcome, which is particularly important in light of the worldwide organ shortage. An analysis for differences of etiology and causes of graft loss or mortality, respectively, is warranted across the RDSC groups.Practitioner points: Recipient and donor sex combinations affect outcome after solid organ transplantation. While female recipients are more susceptible to infections after solid organ transplantation, they have higher overall survival following SOT, with causes of death differing from male recipients. Sex‐differences should be taken into account in the post‐transplant management.