Background and Aims: Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced HCC patients awaiting liver transplantation (LT). However, concerns about the risk of posttransplant rejection persist. Approach and Results: We conducted an international retrospective cohort study including 119 HCC patients who received ICIs prior to LT. We analyzed the incidence of allograft rejection, graft loss, and posttransplant recurrence with a particular focus on the washout period between the last ICI dose and LT. In this study, 24 of the 119 (20.2%) patients experienced allograft rejection with a median time to rejection of 9 days (IQR 6–10) post-LT. A linear relationship was observed between shorter washout periods and higher rejection risk. Washout periods <30 days (OR: 21.3, 95% CI: 5.93–103, p<0.001) and between 30 and 50 days (OR: 9.48, 95% CI 2.47–46.8, p=0.002) were significantly associated with higher rejection rates in the univariate analysis compared to the washout period above 50 days. Graft loss as a result of rejection occurred in 6 patients (25%) with rejection. No factors related to grafts were associated with rejection. A longer washout period was not associated with a lower recurrence-free survival posttransplantation at 36 months (71% vs. 67%, p=0.71). Conclusions: Our findings suggest that a washout period longer than 50 days for ICIs before LT appears to be safe with respect to rejection risk. While these results may help guide clinical decision-making, future prospective studies are essential to establish definitive guidelines.

The lack of suitable kidney donor organs has led to rising numbers of patients with end stage renal disease waiting for kidney transplantation. Despite decades of clinical experience and research, no evaluation process that can reliably predict the outcome of an organ has yet been established. This review is an overview of current methods and emerging techniques in the field of donor kidney evaluation prior to transplantation. Established techniques like histological evaluation, clinical scores, and machine perfusion systems offer relatively reliable predictions of delayed graft function but are unable to consistently predict graft survival. Emerging techniques including molecular biomarkers, new imaging technologies, and normothermic machine perfusion offer innovative approaches toward a more global evaluation of an organ with better outcome prediction and possibly even identification of targets for therapeutic interventions prior to transplantation. These techniques should be studied in randomized controlled trials to determine whether they can be safely used in routine clinical practice to ultimately reduce the discard rate and improve graft outcomes.

Candida glabrata is an important fungal pathogen in human diseases and is also rapidly acquiring drug resistance. Drug resistance can be mediated by the transcriptional activator PDR1 , and this results in the upregulation of multidrug transporters. Intriguingly, this resistance mechanism is associated in C. glabrata with increased virulence in animal models and also with increased adherence to specific host cell types. The C. glabrata adhesin gene EPA1 is a major contributor of virulence and adherence to host cells. Here, we show that EPA1 expression is controlled by PDR1 independently of subtelomeric silencing, a known EPA1 regulation mechanism. Thus, a relationship exists between PDR1 , EPA1 expression, and adherence to host cells, which is critical for efficient virulence. Our results demonstrate that acquisition of drug resistance is beneficial for C. glabrata in fungus-host relationships. These findings further highlight the challenges of the therapeutic management of C. glabrata infections in human patients.

Objective: The aim of this study was to evaluate the different phases of the learning curve for robotic distal pancreatectomy (RDP) in international expert centers. Background: RDP is an emerging minimally invasive approach; however, only limited, mostly single-center data are available on its safe implementation, including the learning curve. Methods: Consecutive patients undergoing elective RDP from 16 expert centers across 3 continents were included to assess the learning curve. Based on the first 100 RDPs at each center, 3 cutoffs were used to define the learning curve: operative time for competency, major complications (Clavien-Dindo grade ≥III) for proficiency, and textbook outcome for mastery. Clinical outcomes before and after the cutoffs were compared. Results: The learning curve analysis was conducted on 1109 of 2403 RDPs. Competency, proficiency, and mastery, respectively, were reached after 46, 63, and 73 RDP procedures. After competency, operative time decreased from 245 to 235 minutes ( P = 0.002). Attaining proficiency was reflected by a reduction in the rate of major complications from 20% to 15% ( P = 0.012), and mastery was associated with a higher proportion of patients with textbook outcomes (71% vs 63%; P = 0.028). The postoperative pancreatic fistula rate remained stable along the learning curve, ranging between 18.5% and 21.5%. Previous laparoscopic experience accelerated the learning process by virtue of reduced operative time and an earlier decrease in major complications. Conclusions: Competency, proficiency, and mastery for RDP were reached after 46, 63, and 73 procedures, respectively, at international expert centers. The findings highlight that the learning curves for intraoperative parameters are completed earlier; however, extensive experience is needed to master RDP.

The global obesity epidemic particularly affects women of reproductive age. Offspring of obese mothers suffer from an increased risk of liver disease but the molecular mechanisms involved remain unknown. We performed an integrative genomic analysis of datasets that investigated the impact of maternal obesity on the hepatic gene expression profile of the offspring in mice. Furthermore, we developed a murine model of maternal obesity and studied the development of liver disease and the gene expression profile of the top dysregulated genes by quantitative real-time polymerase chain reaction (qPCR). Our data are available for interactive exploration on our companion webpage. We identified five publicly available datasets relevant to our research question. Pathways involved in metabolism, the innate immune system, the clotting cascade, and the cell cycle were consistently dysregulated in the offspring of obese mothers. Concerning genes involved in the development of liver disease, Egfr, Vegfb, Wnt2,Pparg and six other genes were dysregulated in multiple independent datasets. In our own model, we observed a higher tendency towards the development of non-alcoholic liver disease (60 vs. 20%) and higher levels of alanine aminotransferase (41.0 vs. 12.5 IU/l, p = 0.008) in female offspring of obese mothers. Male offspring presented higher levels of liver fibrosis (2.4 vs. 0.6% relative surface area, p = 0.045). In a qPCR gene expression analysis of our own samples, we found Fgf21, Pparg, Ppard, and Casp6 to be dysregulated by maternal obesity. Maternal obesity represents a looming threat to the liver health of future generations. Our comprehensive transcriptomic analysis will help to better understand the mechanisms of the development of liver disease in the offspring of obese mothers and can give rise to further explorations.

Over the past two decades since the introduction of the Milan criteria, the field of transplant oncology has undergone a rapid development with a rising proportion of liver transplantations being performed for oncological indications. For many patients with liver tumours, transplantation represents the only chance for cure. However, many challenges remain, such as the adequate patient selection, management of post‐transplant recurrence and refinement of neoadjuvant treatment protocols. This review provides an overview of the current state of the art of liver transplantation for oncological indications such as hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastasis and metastatic neuroendocrine tumours. We also summarize the ongoing research and explore future trends. Clinical trials are currently studying new diagnostic modalities, innovative pharmacological treatments, novel surgical techniques, downstaging regimens and new indications for liver transplantation. These emerging results will continue to shape the field of transplant oncology and provide us with the necessary tools to better select, treat and follow patients with liver tumours qualifying for liver transplantation.