Gastroenterology最新文献

{"title":"Hypoxic and acidic tumor microenvironment-driven AVL9 promotes chemoresistance of pancreatic ductal adenocarcinoma via the AVL9-IκBα-SKP1 complex","authors":"Jinsheng Ding, Yongjie Xie, Ziyun Liu, Zhaoyu Zhang, Bo Ni, Jingrui Yan, Tianxing Zhou, Jihui Hao","doi":"10.1053/j.gastro.2024.10.042","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.042","url":null,"abstract":"<h3>Background &amp; Aims</h3>Gemcitabine combined with albumin-paclitaxel (AG) is a crucial therapeutic option for pancreatic ductal adenocarcinoma (PDAC). However, the response to chemotherapy is relatively poor, with rapid development of resistance. The aim of this study was to explore the mechanism of resistance to AG and to develop strategies that can sensitize the AG regimen.<h3>Methods</h3>We utilized organoid models, patient-derived xenografts (PDX), and genetically engineered mouse models (GEMM) in our study. Chromatin-Immunoprecipitation (Ch-IP), double luciferase assay, Co-immunoprecipitation (Co-IP), and far-western blotting analysis were performed to investigate the mechanism. The AVL9 inhibitors were identified through protein structure analysis and molecular docking analysis, and their efficacy was verified in PDX, PDOX, and KPC models.<h3>Results</h3>Through multi-strategy screening, we identified AVL9 as a key target for AG resistance in PDAC. Its tumor-promoting effects were confirmed in our clinical cohorts. Mechanistically, HIF-1α, a hypoxia-related transcription factor, drives the expression of AVL9. AVL9 acts as a scaffold that facilitates the binding of IκBα to SKP1, leading to enhanced ubiquitination and degradation of IκBα, which further activates the NF-κB pathway. The potential AVL9-targeting inhibitor, Edotecarin, was shown to reverse AG chemo-resistance in PDAC.<h3>Conclusion</h3>AVL9 expression is driven by HIF1α in PDAC. The physical interaction of AVL9, IκBα, and SKP1 provides a novel molecular mechanism for the abnormal activation of the NF-κB pathway. Therefore, the AVL9-targeting drug Edotecarin could be a promising therapeutic strategy for sensitizing PDAC to AG.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"99 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDO-Based Drug Screening in Advanced Pancreatic Cancer: Addressing Predictive Value and Broader Clinical Implications","authors":"Chaojie Liang, Dan Shan, Zhigang Wei","doi":"10.1053/j.gastro.2024.10.045","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.045","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"8 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Differential Diagnosis: Severe, Swollen Hepatocytes in a Patient with an ALT above 1000 U/L","authors":"Michael Eller, Lindsey Westbrook, Avash Kalra","doi":"10.1053/j.gastro.2024.10.044","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.044","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"247 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AGA Clinical Practice Update on Nonampullary Duodenal Lesions: Expert Review.","authors":"Michael J Bourke, Simon K Lo, Ross C D Buerlein, Koushik K Das","doi":"10.1053/j.gastro.2024.10.008","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.008","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Description: &lt;/strong&gt;Nonampullary duodenal polyps are found in up to 5% of all upper endoscopies; the vast majority are identified incidentally in asymptomatic patients. Although most are benign, adenomas are estimated to account for 10%-20% of these lesions. Most international guidelines recommend that all duodenal adenomas should be considered for endoscopic resection; this may be associated with a near 15% adverse event rate (predominantly bleeding and perforation) in prospective studies, with substantial local recurrence on surveillance. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to describe how individuals should be evaluated and risk-stratified for duodenal polyps, the best approaches to endoscopic resection and surveillance, and management of complications, highlighting opportunities for future research to fill gaps in the existing literature.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Non-neoplastic duodenal lesions (eg, metaplastic foveolar epithelium and gastric heterotopia) may mimic neoplastic adenomatous pathology. Careful optical evaluation and pathologic correlation may be necessary to exclude dysplasia. Nondysplastic lesions do not require endoscopic resection unless they are symptomatic or bleeding. BEST PRACTICE ADVICE 2: Ideal duodenal endoscopic inspection includes identification of the major and minor papilla with photodocumentation to ensure no involvement by the lesion. Adding a clear distal attachment device to a forward-viewing gastroscope improves visualization of the papilla and the medial wall. A side-viewing duodenoscope should be used when the major and minor papilla are not visible with the gastroscope and for most lesions on the medial wall of the duodenum within 5 cm of the ampulla. BEST PRACTICE ADVICE 3: All duodenal polyps should be described according to their size, Paris morphology, suspected histologic layer of origin (mucosal lesion or subepithelial lesion), duodenal location (D1-4) and orientation (anterior, posterior, medial, or lateral wall), and proximity/relationship to the major papilla to facilitate therapeutic planning and subsequent surveillance. BEST PRACTICE ADVICE 4: Given the high frequency of concomitant c","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High serum pesticide levels are associated with increased odds of inflammatory bowel disease in a nested case-control study","authors":"Manasi Agrawal, Ryan C. Ungaro, Palak Rajauria, Jared Magee, Lauren Petrick, Vishal Midya","doi":"10.1053/j.gastro.2024.10.041","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.041","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"16 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AGA Clinical Practice Update on Endoscopic Enteral Access: Commentary","authors":"Dejan Micic, John A. Martin, John Fang","doi":"10.1053/j.gastro.2024.09.043","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.09.043","url":null,"abstract":"<h3>Description</h3>The purpose of this American Gastroenterological Association (AGA) Clinical Practice Update is to facilitate understanding and improve the clinical practice of endoscopic enteral access.<h3>Methods</h3>This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of <em>Gastroenterology</em>.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"6 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential of Real-Time Audio-Visual Interactions of ChatGPT-4o in Endoscopy Training and Practice","authors":"Qiqi Wu","doi":"10.1053/j.gastro.2024.06.042","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.06.042","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"25 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sucrase isomaltase dysfunction reduces sucrose intake in mice and humans","authors":"Peter Aldiss, Leire Torices, Stina Ramne, Marit Eika Jørgensen, Mauro D’Amato, Mette K. Andersen","doi":"10.1053/j.gastro.2024.10.040","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.040","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"6 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unexpected Cause of Fistulizing Small Intestinal Disease","authors":"Saam Dilmaghani, Rondell P. Graham, Seth Sweetser","doi":"10.1053/j.gastro.2024.10.039","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.039","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"1 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 3 validation of PAaM for hepatocellular carcinoma risk stratification in cirrhosis","authors":"Naoto Fujiwara, Camden Lopez, Tracey L. Marsh, Indu Raman, Cesia A. Marquez, Subhojit Paul, Sumit K. Mishra, Naoto Kubota, Courtney Katz, Hiroaki Kanzaki, Michael Gonzalez, Lisa Quirk, Sneha Deodhar, Pratibha Selvakumar, Prithvi Raj, Neehar D. Parikh, Lewis R. Roberts, Myron E. Schwartz, Mindie H. Nguyen, Alex S. Befeler, Yujin Hoshida","doi":"10.1053/j.gastro.2024.10.035","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.10.035","url":null,"abstract":"<h3>Background and aims</h3>Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.<h3>Methods</h3>Molecular (Prognostic Liver Secretome signature with alpha-fetoprotein) and clinical (aMAP score) variable-based scores were integrated to develop PAaM, which was subsequently validated in two phase 3 biomarker validation studies: the statewide Texas HCC Consortium (THCCC) and nationwide HCC Early Detection Strategy (HEDS) prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation (PRoBE) design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.<h3>Results</h3>Of 2,156 cirrhosis patients in THCCC, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared to low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios (sHRs) for incident HCC of 7.51 (95% confidence interval [CI], 4.42-12.8) and 4.20 (95%CI, 2.52-7.01), respectively. Of 1,328 cirrhosis patients in HEDS, PAaM identified 201 (15%) high-risk, 540 (41%) intermediate-risk, and 587 (44%) low-risk patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate risk groups were associated with sHRs for incident HCC of 6.54 (95%CI, 3.85-11.1) and 1.77 (95%CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD) and cured hepatitis C infection.<h3>Conclusion</h3>PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"36 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}