Developing an Adult Living Donor Liver Transplant Program in Western Europe: The Rotterdam Experience.

Liver transplantation (LT) is curative for end stage liver disease. Expanding LT indications with limited deceased donor grafts has created organ shortages. Living donor liver transplant (LDLT) increases available organs.

Non-invasive identification of steatohepatitis in patients with MASLD using a sterol and lipidomic signature.

The accumulation of cholesterol and other lipids leading to hepatic lipotoxicity drives the progression of metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), the advanced progressive stage of metabolic dysfunction-associated steatotic liver disease (MASLD). For MASH diagnosis, liver biopsy remains the reference standard, despite its invasiveness and limitations. Thus, this study aimed to find blood-derived lipid markers for MASH.

Refinement of histologic subtypes and identification of biomarkers linked to unfavorable prognosis in cholangiocarcinoma: The ENSCCA registries' framework for digital twin advancement.

Background And Aims: Cholangiocarcinoma (CCA) displays remarkable anatomical and histological heterogeneity. Besides diagnosis confirmation, histology currently does not have a major role in the management of CCA. We aimed to study the clinical relevance of histological heterogeneity of CCA and putative tissue biomarkers by creating a multicentric digitalized European CCA Histology Registry.

Endoscopic ultrasound with tissue acquisition of lymph nodes in patients with resectable distal cholangiocarcinoma.

Background: Lymph node (LN) involvement is a negative prognostic factor for patients with distal cholangiocarcinoma (dCCA). Therefore, preoperative assessment of the LN status could potentially aid therapy decision making. Endoscopic ultrasound (EUS) is often used to obtain a tissue diagnosis of the primary tumor, but can also be used to sample suspicious LN.

Global research initiative for patient screening on MASH (GRIPonMASH) protocol: rationale and design of a prospective multicentre study.

Introduction: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) may be as high as 38% in the adult population with potential serious complications, multiple comorbidities and a high socioeconomic burden. However, there is a general lack of awareness and knowledge about MASLD and its progressive stages (metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis). Therefore, MASLD is still far underdiagnosed.

Genome-Wide Methylation Sequencing to Identify DNA Methylation Markers for Early-stage Hepatocellular Carcinoma in Liver and Blood.

Background: Hepatocellular carcinoma (HCC) is associated with a poor 5-year survival mainly due to detection at late stages. Better non-invasive surveillance methods are needed to improve early detection and maximize survival. We performed a strict assessment of DNA methylation markers (DMMs) for HCC detection.

Combined Clinical and Histopathological Risk Stratification for Prediction of (severe) Endoscopic Postoperative Recurrence in Patients with Crohn's Disease after Ileocolic Resection: Results from A Prospective Multicenter Cohort Study.

Objective: This study assessed the association of histopathological features in the resection specimen of CD patients with (severe) endoscopic postoperative recurrence (ePOR) in a large prospective, multicenter cohort study.

Summary Background Data: The predictive value of histopathologic features of the intestinal resection specimen for the risk of Crohn's disease (CD) recurrence after ileocolic (re-)resection (ICR) remains a matter of debate.

Methods: CD patients (≥16 y) scheduled for ICR (n=293) were included.

Neoadjuvant chemoradiotherapy followed by active surveillance versus standard surgery for oesophageal cancer (SANO trial): a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial.

Background: A substantial proportion of individuals with oesophageal cancer have a pathological complete response after neoadjuvant chemoradiotherapy and oesophagectomy. We aimed to investigate whether active surveillance could be an alternative for individuals with a clinical complete response after neoadjuvant chemoradiotherapy.

Methods: We performed a multicentre, stepped-wedge, cluster-randomised, non-inferiority, phase 3 trial in 12 Dutch hospitals.

Stroma and lymphocytes identified by deep learning are independent predictors for survival in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers known to humans. However, not all patients fare equally poor survival, and a minority of patients even survives advanced disease for months or years. Thus, there is a clinical need to search corresponding prognostic biomarkers which forecast survival on an individual basis.

Preoperative stereotactic radiotherapy to prevent pancreatic fistula in high-risk patients undergoing pancreatoduodenectomy (FIBROPANC): prospective multicentre phase II single-arm trial.

Background: Postoperative pancreatic fistula is the main driver of morbidity and mortality after pancreatoduodenectomy. In high-risk patients, the rate of postoperative pancreatic fistula approaches 50%, whereas it is below 5% in patients with pancreatic cancer who receive neoadjuvant chemoradiotherapy. The aim of this study was to evaluate the safety, feasibility, and efficacy of preoperative stereotactic body radiotherapy on the pancreatic neck transection margin in high-risk patients undergoing pancreatoduodenectomy to prevent postoperative pancreatic fistula.

Human Enteric Glia Diversity in Health and Disease: New Avenues for the Treatment of Hirschsprung Disease.

Background & Aims: The enteric nervous system (ENS), which is composed of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation; however, although neuronal aspects have been studied extensively, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.

Classifying histopathological growth patterns for resected colorectal liver metastasis with a deep learning analysis.

Background: Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides.

Tumor organoids improve mutation detection of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) presents challenges in detecting somatic mutations due to its complex cellular composition. This study investigated the utility of patient-derived organoids (PDOs) to overcome these obstacles and enhance somatic mutation identification. Surgically resected PDAC tumors and their paired PDOs from 21 patients were examined.

Combined plasma protein and memory T cell profiling discern IBD-patient-immunotypes related to intestinal disease and treatment outcomes.

Inflammatory bowel disease (IBD) chronicity results from memory T helper cell (Tmem) reactivation. Identifying patient-specific immunotypes is crucial for tailored treatment. We conducted a comprehensive study integrating circulating immune proteins and circulating Tmem, with intestinal tissue histology and mRNA analysis, in therapy-naïve pediatric IBD (Crohn's disease, CD: n = 62; ulcerative colitis, UC: n = 20; age-matched controls n = 43), and after 10-12 weeks' induction therapy.

Feasibility, safety and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the risk of pancreatic fistula after high-risk pancreatoduodenectomy (FIBROPANC): protocol for a multicentre, single-arm trial.

Introduction: Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis.

Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer.

Purpose: Immunotherapies have shown limited responses in patients with advanced pancreatic cancer. Recently, we reported that dendritic cell (DC)-based immunotherapy induced T-cell responses against pancreatic cancer antigens. The primary objective of this study was to determine the efficacy of DC-based immunotherapy to prevent recurrence of disease.

Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation.

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice.

GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery.

This study underscores GATA6's role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype.