eGastroenterology最新文献

{"title":"Preoperative 3D morphological phenotyping of hepatocellular carcinoma via a foundation model: a non-invasive biomarker for recurrence risk stratification.","authors":"Hongbin Wang, Xiaogen Zhou, Kun Zhang, Kan He, Wenao Ma, Mingyang Li, Han Xue, Ye Sun, Yingzhu Cui, Xiaopeng Wang, Alfred Wei Chieh Kow, Wen Shen, Huimao Zhang, Qi Dou, Lei Zhang, Zhongqi Fan, Guoyue Lv","doi":"10.1136/egastro-2026-100533","DOIUrl":"10.1136/egastro-2026-100533","url":null,"abstract":"<p><strong>Background: </strong>Imaging features play a central role in hepatocellular carcinoma (HCC) staging, but current systems remain limited in prognostic precision and treatment guidance. Pathological gross classification, which categorises HCC into four subtypes based on tumour margin morphology, represents a morphological surrogate of aggressive tumour behaviour encompassing histological and molecular features and has demonstrated value in predicting prognosis and guiding adjuvant locoregional therapy selection. Importantly, gross classification is assessable through imaging, but its evaluation utterly depends on postoperative pathology and remains subjective, time-consuming and poorly reproducible. We aimed to develop a three-dimensional (3D) Foundation Model-driven system to automatically perform non-invasive morphological phenotyping and to evaluate its prognostic utility.</p><p><strong>Methods: </strong>A cohort of 551 patients who underwent hepatectomy after gadoxetic acid-enhanced MRI from two medical centres was retrospectively analysed. Pathological gross classification served as the reference standard. The 3D MorphStratify Model was built to automatically phenotype 3D gross classification with a dedicated 3D Foundation Model encoder and a channel-aware fusion module. A combined model integrating 3D MorphStratify and Conventional Imaging Predictors (Morph-CIP) was constructed and validated for recurrence risk stratification. The biological rationale linking imaging morphological phenotyping to underlying biology was preliminarily explored.</p><p><strong>Results: </strong>Eligible patients were divided into a development dataset (n=291), a validation dataset (n=192) and an external test set (n=68). The 3D MorphStratify Model achieved a micro-averaged area under the receiver operating characteristic curve (AUC) of 0.932, significantly outperforming senior radiologists (AUC 0.825) with about 40-fold improved efficiency. The imaging-based 3D morphological phenotyping (3D MorphStratify) independently predicted poor recurrence-free survival (RFS, HR 2.16, 95% CI 1.20 to 3.87, p=0.010). The Morph-CIP Model enables risk stratification through training set (AUC 0.836, 0.768, 0.765 for 1-year, 2-year, 3-year RFS), internal test set (AUC 0.816, 0.690, 0.711) and external test set (AUC 0.737, 0.709, 0.702). The high-risk group is characterised by the enrichment of glycolysis and hypoxia signalling pathways.</p><p><strong>Conclusion: </strong>3D MorphStratify is the first automated 3D morphological phenotyping system for HCC, transforming subjective pathological gross classification into an objective, non-invasive imaging biomarker. The integration of 3D MorphStratify with conventional imaging predictors enables recurrence risk stratification, potentially providing complementary information for prognostic evaluation.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100533"},"PeriodicalIF":10.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanosensitive ion channels in intestinal homeostasis and disease.","authors":"Yubin Cao, Qi Rao, Xiaoyin Bai, Wenzhong Li, Hanqiao Dai, Xiaowei Xue, Lingjuan Jiang, Hong Yang, Nan Ma","doi":"10.1136/egastro-2026-100443","DOIUrl":"https://doi.org/10.1136/egastro-2026-100443","url":null,"abstract":"<p><p>Mechanical deformation is integral to intestinal physiology, linking luminal transit to epithelial adaptation and motor control. These physical cues engage multiple mechanotransduction pathways that coordinate cellular adaptation and help preserve intestinal homeostasis. Inflammation, obstruction and matrix remodelling alter both the physical input and the state of the responding cell, allowing normally transient signals to persist or acquire pathological consequences. Ion channels act at several levels of this process. PIEZO1 and PIEZO2 provide a direct route for force-gated cation entry; mechanically gated two-pore-domain potassium channels can oppose depolarisation, and other conductances shape the conversion of mechanical signals into tissue responses. This review synthesises the current understanding of ion-channel mechanotransduction in intestinal physiology and disease. Studies have established the physiological importance of these pathways and are increasingly defining their contribution to disease, although their regulation in diseased tissue remains poorly understood.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100443"},"PeriodicalIF":10.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic prediction of the development of extrahepatic organ failures in ICU patients with decompensated cirrhosis.","authors":"Yee Hui Yeo, Linjie Que, Mengyi Zhang, Jian Zu, Yuankai Wu, Dian-Jung Chiang, Tao Chen, Yu Shi, Yingli He, Fengping Wu, Feng Han, Qing-Lei Zeng, Yu-Chen Fan, Hirsh D Trivedi, Xiaogang Xiang, Yadong Wang, Yu Chen, Ju Dong Yang, Jun Li, Rajiv Jalan, Fanpu Ji","doi":"10.1136/egastro-2026-100463","DOIUrl":"https://doi.org/10.1136/egastro-2026-100463","url":null,"abstract":"<p><strong>Background: </strong>Extrahepatic organ failure (EOF) is a critical determinant of short-term mortality in patients with decompensated cirrhosis within the intensive care unit (ICU). However, traditional prognostic tools are largely static and fail to capture the rapidly fluctuating physiological characteristic of critical illness. This study aimed to develop and validate a dynamic artificial intelligence (AI) framework to provide real-time predictions of the presence of ≥2 EOF 12 hours later.</p><p><strong>Methods: </strong>We analysed adult patients with decompensated cirrhosis from the Medical Information Mart for Intensive Care IV (MIMIC-IV; derivation) and eICU Collaborative Research Database (eICU-CRD; external validation). Using a late-fusion architecture, we combined risk estimates from a machine-learning model and a deep-learning model. Both models incorporated longitudinal vital signs and non-time-series clinical variables, using summary features and sequential vital signs, respectively. The model processed 45 variables subsequently refined to 14 key predictors. The sliding-window framework combined hourly vital signs (6-hour dynamic window), recent laboratory parameters (24-hour window) and current organ failure status. The model continuously incorporated newly available data to predict the presence of ≥2 EOF 12 hours later. Performance was evaluated via area under the receiver operating characteristic curve (AUROC), calibration and decision curve analysis (DCA).</p><p><strong>Results: </strong>The derivation cohort included 1486 patients, with 1666 patients in the external validation cohort. The optimal late-fusion configuration paired a CatBoost model trained after synthetic minority over-sampling technique (SMOTE) resampling with a deep-learning model combining fully convolutional networks and gated recurrent units (FCN-GRU). The combined model achieved an AUROC of 0.830 (95% CI 0.783 to 0.876) at the 12-hour prediction horizon. The model demonstrated strong calibration (intercept -0.027) and consistent net clinical benefit across relevant probability thresholds in DCA. Sensitivity analyses showed stable performance across 6-hour (AUROC 0.821) and 24-hour (AUROC 0.834) prediction horizons as well as within the sepsis subgroup (AUROC 0.820). Robust discriminative capability was maintained in external validation (AUROC 0.774, 95% CI 0.743 to 0.805).</p><p><strong>Conclusion: </strong>By tracking continuously evolving physiological trajectories, this AI-driven approach accurately predicts EOF in patients with decompensated cirrhosis. It provides reliable risk estimates 12 hours ahead, serving as a dynamic alternative to conventional static risk scores.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100463"},"PeriodicalIF":10.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide for MASH cirrhosis: a new therapeutic frontier or a false dawn?","authors":"Xiao-Dong Zhou, Naim Alkhouri, Jörn M Schattenberg, Mark D Muthiah, Frank Tacke, Ming-Hua Zheng","doi":"10.1136/egastro-2026-100619","DOIUrl":"https://doi.org/10.1136/egastro-2026-100619","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100619"},"PeriodicalIF":10.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysosmobacter: from a serendipitous discovery to a next-generation beneficial gut commensal linked to health.","authors":"Patrice D Cani, Camille Petitfils, Matthias Van Hul","doi":"10.1136/egastro-2026-100574","DOIUrl":"10.1136/egastro-2026-100574","url":null,"abstract":"<p><p><i>Dysosmobacter</i> is a genus of strictly anaerobic, butyrate-producing bacteria of the family <i>Oscillospiraceae</i> that was first described in 2020 with the human faecal type species <i>Dysosmobacter welbionis</i> J115^T. The organism was recovered by chance during a targeted attempt to isolate new <i>Subdoligranulum</i> species, a project that failed in its original aim but yielded a bacterium that fulfilled the criteria for an entirely new genus. Since then, <i>D. welbionis</i> has emerged as one of the best-supported examples of a candidate next-generation beneficial microbe. It is carried by roughly two thirds to more than 90% of adults depending on the cohort and detection method, its faecal abundance correlates inversely with fasting glucose and glycated haemoglobin, and, in contrast to most microbiome markers, live supplementation of the type strain reproducibly improves diet-induced insulin resistance, brown adipose tissue thermogenesis and hepatic steatosis in mice. At the biochemical level <i>D. welbionis</i> is distinguished by a non-canonical route that converts <i>myo</i>-inositol to butyrate, by the production of bioactive lipids that act as peroxisome proliferator-activated receptor gamma agonists and by the capacity to convert cholesterol to poorly absorbed coprostanol. A rapidly growing body of clinical and veterinary literature now places <i>Dysosmobacter</i> at the crossroads of metabolic disease, liver disease, cardiovascular health, oncology, the gut-brain axis and drug-microbiome interactions. This review provides a comprehensive overview of the genus. It brings together its discovery, taxonomy, physiology and genomics, its ecology and prevalence in humans and animals, the mechanistic and preclinical evidence, the expanding catalogue of human disease associations and the prospects and hurdles for its development as a live biotherapeutic.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100574"},"PeriodicalIF":10.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cell remodelling and the peribiliary immune niche in primary biliary cholangitis: from initiation to chronicity.","authors":"Jiaqi Xiong, Zeyi Zhang, Ziying Zhang, Mengqi Yuan, Kaidi Zhu, Fu-Sheng Wang, Lei Shi","doi":"10.1136/egastro-2026-100526","DOIUrl":"10.1136/egastro-2026-100526","url":null,"abstract":"<p><p>Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterised by immune-mediated destruction of small intrahepatic bile ducts. Although ursodeoxycholic acid remains the standard first-line therapy and peroxisome proliferator-activated receptor agonists have expanded treatment options, current therapies do not fully address the immune mechanisms that drive disease initiation and persistence. Recent work suggests that PBC cannot be explained by abnormalities in a single immune-cell population but instead reflects coordinated immune remodelling around injured bile ducts. In this review, we organise current evidence within an overlapping, process-oriented framework encompassing immune initiation, effector amplification and immune-regulatory dysfunction. Stressed biliary epithelial cells provide autoantigens, immune-sensing signals and inflammatory cues while myeloid cells and lymphocyte subsets cooperate to sustain tissue-resident cytotoxic, inflammatory and profibrogenic circuits. Disease chronicity is further promoted by defective regulatory mechanisms, including impaired Treg stability and dysfunction of non-conventional regulatory populations. We also discuss mechanism-guided therapeutic strategies targeting effector T cells, myeloid inflammation, B-cell activation, immune tolerance and the cholestatic microenvironment. Understanding the peribiliary immune niche may facilitate immune phenotype-guided stratification and precision therapy in PBC.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100526"},"PeriodicalIF":10.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global and regional burden of colorectal cancer potentially related to Helicobacter pylori exposure: a risk attribution modelling study.","authors":"Yunhao Li, Can Cui, Dianqin Sun, Kimberly Ho, Cong Qian, Yanyan Guo, Wai Keung Leung, Shailja C Shah","doi":"10.1136/egastro-2026-100436","DOIUrl":"10.1136/egastro-2026-100436","url":null,"abstract":"<p><strong>Background: </strong>Emerging epidemiological and mechanistic studies suggest that <i>Helicobacter pylori</i> (<i>H. pylori</i>) exposure may be associated with colorectal cancer (CRC); however, the findings remain controversial. We aim to quantify the CRC burden potentially related to <i>H. pylori</i> exposure, with the overarching objective to inform prioritisation and future evaluation of <i>H. pylori</i> control as a candidate adjunct to existing CRC prevention efforts in settings with high prevalence and limited resources.</p><p><strong>Methods: </strong>We estimated global and regional <i>H. pylori</i> exposure and its epidemiological association with CRC using data from systematic reviews and meta-analyses, stratified by region, diagnostic method and eradication status, among others. We derived CRC estimates from the Global Cancer Observatory (GLOBOCAN). To evaluate the related CRC burden, we calculated the estimated related proportion (ERP) with 95% uncertainty intervals (UIs) and absolute and rate-based burdens using Monte Carlo simulations. We further examined correlations between country-level ERPs, <i>H. pylori</i> prevalence and CRC incidence. Lasty, we used a pseudo-cohort approach to explore birth cohort-related patterns based on GLOBOCAN 2022.</p><p><strong>Results: </strong>Exposure to <i>H. pylori</i> was associated with a 1.59-fold increased risk of CRC (95% CI 1.36 to 1.87), consistent across most subgroups. In limited observational studies, <i>H. pylori</i> eradication was associated with a reduced risk of CRC, but only after 10 years of follow-up. Globally, under the pooled risk-attribution model based on estimates from 43 studies, an estimated 22.0% (95% UI 14.7% to 29.4%) of CRC cases were potentially related to <i>H. pylori</i> exposure; corresponding estimates were lower when restricted to population-based and cohort studies (n=14). Higher <i>H. pylori</i>-related burdens were observed in settings with lower CRC incidence and increased with rising <i>H. pylori</i> prevalence. Exploratory pseudo-cohort patterns suggested higher ERPs in later birth cohorts, while absolute case counts remained relatively stable.</p><p><strong>Conclusion: </strong><i>H. pylori</i> exposure may meaningfully contribute to global CRC burden, with the extent of preventable burden dependent on the causal nature and other modifying variables related to <i>H. pylori</i> exposure (eg, timing, duration). This underscores the importance of well-designed randomised clinical trials and other prospective investigations evaluating the impact of <i>H. pylori</i> and its eradication on CRC risk, as well as potential modifying factors.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100436"},"PeriodicalIF":10.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver-nervous system axis in MASLD: mechanistic insights and emerging targeted therapies.","authors":"Xin Wang, Jianlei Zhang, Junzhe Guo, Boya Sheng, Jinwei Xu, Yinuo Yuan, Wajahat Mehal, Li Zuo, Hua Wang","doi":"10.1136/egastro-2026-100397","DOIUrl":"10.1136/egastro-2026-100397","url":null,"abstract":"<p><p>The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) extends beyond intrinsic hepatic metabolic defects, involving critical bidirectional communication between the liver and the central nervous system-termed the liver-nervous system axis. This review proposes that dysregulation of this axis, characterised by sympathetic overactivation and parasympathetic hypofunction, is a central driver of MASLD onset and progression. We review the 'brain-to-liver' and 'liver-to-brain' signalling pathways, highlighting how their disruption forms a reciprocally detrimental feedback loop that exacerbates systemic metabolic disturbance. Furthermore, we summarise preclinical and clinical evidence to demonstrate that targeting this axis, through pharmacological, neuromodulatory or behavioural interventions, represents a promising therapeutic frontier. By moving beyond traditional paradigms, this approach offers a novel framework for the mechanism-based management of MASLD across disease stages.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100397"},"PeriodicalIF":10.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma cell-CD8+ T cell co-enrichment distinguishes immunotherapy-responsive hepatocellular carcinoma subtypes.","authors":"Aryan Neupane, Anuradha Budhu, Farid Rashidi Mehrabadi, Aiwu He, Lipika Goyal, Robin Kate Kelley, Tim F Greten, Xin Wei Wang","doi":"10.1136/egastro-2026-100423","DOIUrl":"10.1136/egastro-2026-100423","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is characterised by significant racial disparities in incidence and outcomes, yet whether these reflect distinct tumour biology or differential distribution of molecular subtypes among immunotherapy patients remains unclear.</p><p><strong>Methods: </strong>We characterised molecular heterogeneity among 46 patients with HCC of differing background population from the NCI-CLARITY cohort receiving immune checkpoint inhibitor therapy, using transcriptomic and genomic profiling, with validation across multiple independent cohorts.</p><p><strong>Results: </strong>Differential expression analysis comparing African American versus non-African American patients identified 126 genes, of which 55 demonstrated tumour-specific expression across independent validation cohorts with paired tumour-normal samples. Consensus clustering revealed two molecular subtypes with no significant race association, indicating these clusters capture tumour-intrinsic biology rather than ancestry. The genomic landscape showed minimal differences between subtypes. A prognostic signature derived from these expression profiles demonstrated significant risk stratification in the NCI-CLARITY cohort and TCGA-LIHC, but not in Asian cohorts, suggesting population-specific applicability. Immune deconvolution revealed that the two subtypes represent distinct immune microenvironments: one subtype exhibited markedly elevated plasma cell infiltration with strong plasma cell-CD8+T cell correlation suggesting coordinated adaptive immunity, along with elevated tertiary lymphoid structure signatures. The other subtype showed regulatory T cell-macrophage correlation and enrichment for immune-excluded phenotypes. The immune-enriched subtype trended towards higher immunotherapy response rates.</p><p><strong>Conclusions: </strong>Molecular heterogeneity in HCC reveals distinct tumour-immune ecosystems that transcend racial classification. Tumour immune heterogeneity in HCC reflects distinct molecular patterns, with immune hot tumours characterised by elevated tertiary lymphoid structure signatures and enriched plasma cell and CD8+T cells. These patterns may serve as prognostic biomarkers for immunotherapy patient stratification and demonstrate the value of diverse cohort representation in identifying clinically relevant therapeutic targets.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100423"},"PeriodicalIF":10.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-low-pass whole-genome sequencing of bile cfDNA in patients with biliary strictures.","authors":"Carla Rojo, María Rullan, Miguel Sogbe, José Maria Herranz, María Elizalde, Daniel Oyón, Juan J Vila, Ana Purroy, María Azkona, Francesco P Marchese, Marcin Krawczyk, Maite G Fernández-Barrena, Bruno Sangro, Josepmaría Argemi, Jesús Urmán, Matías A Ávila, Carmen Berasain, Maria Arechederra","doi":"10.1136/egastro-2026-100425","DOIUrl":"https://doi.org/10.1136/egastro-2026-100425","url":null,"abstract":"<p><strong>Background: </strong>Accurate discrimination of malignant versus benign biliary strictures remains clinically challenging. We previously showed that targeted bile cell-free DNA (cfDNA) mutation analysis (Bilemut assay) enables sensitive detection of malignancy, but it does not distinguish cholangiocarcinoma (CCA) from pancreatic ductal adenocarcinoma (PDAC), and its prognostic value remains unclear. In this study, we evaluated ultra-low-pass whole-genome sequencing (ULP-WGS) of bile cfDNA as a potentially cost-effective, technically simple and low-DNA input demanding genomic approach for early tumour detection, tumour-origin discrimination and prognostic stratification.</p><p><strong>Methods: </strong>Bile samples from 95 patients with biliary strictures under radiological suspicion of malignancy, classified as malignant (n=26) or indeterminate (n=69) based on the result of cytology or biopsy at the first endoscopic retrograde cholangiopancreatography (ERCP), were analysed by ULP-WGS. Tumour fraction (TF) and copy-number alterations (CNAs) were inferred using ichorCNA. Tumour mutational burden (TMB) was assessed with the Bilemut panel. Overall survival was analysed by Kaplan-Meier analysis and log-rank test. A supervised classifier based on discriminant analysis of principal components was used to distinguish CCA from PDAC.</p><p><strong>Results: </strong>In matched samples, bile LP-WGS showed higher sensitivity than plasma for tumour detection. Among patients with an initial malignant diagnosis, bile ULP-WGS detected circulating tumour DNA (ctDNA) in 73% of cases. In patients initially classified as indeterminate but later confirmed as malignant, tumour DNA was detected in 51%, anticipating final diagnosis by a median of 38 days; notably, in seven patients, ctDNA was detectable more than 100 days before routine diagnosis, highlighting its potential for very early tumour detection. Specificity in strictures with a final benign outcome was 96%. CNA profiling revealed recurrent chromosomal alterations consistent with tissue-based data, and a 50-region CNA classifier discriminated CCA from PDAC with an accuracy of 0.864. Although neither TF nor TMB alone was associated with overall survival, their combination identified a subgroup with poorer prognosis.</p><p><strong>Conclusions: </strong>Our exploratory study shows that bile ULP-WGS performed at the first ERCP could represent a complementary, scalable and potentially cost-effective genomic strategy for early malignancy detection in biliary strictures, with additional value for tumour-origin classification and, combined with TMB analysis, for identifying patients with poorer prognosis.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"4 3","pages":"e100425"},"PeriodicalIF":10.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}