Gut最新文献

{"title":"Correction: Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma","authors":"BMJ Publishing Group Ltd and British Society of Gastroenterology","doi":"10.1136/gutjnl-2021-325564corr1","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-325564corr1","url":null,"abstract":"Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al . Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut 2023;72:345-59. The …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"9 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158817","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":"p53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett’s oesophagus","authors":"Guodong Lian, Ermanno Malagola, Chengguo Wei, Qiongyu Shi, Junfei Zhao, Masahiro Hata, Hiroki Kobayashi, Yosuke Ochiai, Biyun Zheng, Xiaofei Zhi, Feijing Wu, Ruhong Tu, Osmel Companioni Nápoles, Wenjing Su, Leping Li, Changqing Jing, Man Chen, Leah Zamechek, Richard Friedman, Karol Nowicki-Osuch, Michael Quante, Jianwen Que, Timothy C Wang","doi":"10.1136/gutjnl-2024-332095","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332095","url":null,"abstract":"Background While p53 mutations occur early in Barrett’s oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear. Objective This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury. Design We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r+ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo. Results The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation towards metaplasia, but only amidst chronic injury. In L2-IL1β mice, p53 mutation increased progenitors expansion and lineage-tracing with a shift from metaplasia to dysplasia. scRNA-seq revealed dysplastic cells arise directly from mutant progenitors rather than progressing through metaplasia. In vitro, p53 mutation enhanced BE progenitors’ organoid-forming efficiency, growth, DNA damage resistance and progression to aneuploidy. Sorted metaplastic cells grew poorly with no progression to dysplasia, while mutant progenitors gave rise to dysplasia in orthotopic transplantation. Computational analyses indicated that p53 mutation inhibited stem cell differentiation through Notch activation. Conclusions p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"17 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363095","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":"Impact of margin thermal ablation after endoscopic mucosal resection of large (≥20 mm) non-pedunculated colonic polyps on long-term recurrence.","authors":"Timothy O'Sullivan, Francesco Vito Mandarino, Julia L Gauci, Anthony M Whitfield, Clarence Kerrison, James Elhindi, Catarina Neto do Nascimento, Sunil Gupta, Oliver Cronin, Anthony Sakiris, Juan Francisco Prieto Aparicio, Sophie Arndtz, Gregor Brown, Spiro Raftopoulos, David Tate, Eric Y Lee, Stephen J Williams, Nicholas Burgess, Michael J Bourke","doi":"10.1136/gutjnl-2024-332907","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332907","url":null,"abstract":"<p><strong>Background and aims: </strong>The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown. We evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA.</p><p><strong>Methods: </strong>LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. EMR scars were evaluated at SC1 and in the absence of recurrence, SC2 colonoscopy was conducted in a further 12 months. A historical control arm was generated from LNPCPs that underwent EMR without MTA. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1.</p><p><strong>Results: </strong>1152 LNPCPs underwent EMR with complete MTA over 90 months until October 2022. 854 LNPCPs underwent SC1 with 29/854 (3.4%) LNPCPs demonstrating recurrence. 472 LNPCPs free of recurrence at SC1 underwent SC2. 260 LNPCPs with complete SC2 follow-up formed the control arm from January 2012 to May 2016. Recurrence at SC2 was significantly less in the MTA arm versus controls (1/472 (0.2%) vs 9/260 (3.5%); p<0.001)).</p><p><strong>Conclusion: </strong>LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are unlikely to develop recurrence in subsequent surveillance out to 2 years. Provided the colon is cleared of synchronous neoplasia, the next surveillance can be potentially extended to 3-5 years. Such an approach would reduce costs and enhance patient compliance.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345114","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":"Variceal band ligation and carvedilol: together forever, or not?","authors":"Philip D J Dunne, Ewan H Forrest, Adrian J Stanley","doi":"10.1136/gutjnl-2024-333643","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333643","url":null,"abstract":"We extend our congratulations to Tevethia et al for their recently published ‘CAVARLY trial’, which suggests the combination of variceal band ligation (VBL) and carvedilol is superior to VBL or carvedilol alone in the reduction of the first episode of oesophageal variceal bleeding (OVB) in patients with high-risk varices.1 This is the first primary prophylaxis randomised control trial to examine combination therapy and provides some interesting results which require further thought. Despite significantly lower rates of OVB and mortality in the combination therapy group, other indicators of disease severity such as; progression of ascites, …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"12 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321531","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":"What defines a healthy gut microbiome?","authors":"Matthias Van Hul, Patrice D Cani, Camille Petifils, Willem M De Vos, Herbert Tilg, Emad M El Omar","doi":"10.1136/gutjnl-2024-333378","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333378","url":null,"abstract":"The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term ‘dysbiosis’, which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining ‘healthy individuals’ to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population—whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity. This review advocates for delineating ‘what defines a healthy microbiome?’ by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of ‘gut health’ due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented. The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"36 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321532","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":"Alcohol-associated hepatitis: a neutrophile disease?","authors":"Maximilian Joseph Brol, Ali Canbay, Jonel Trebicka","doi":"10.1136/gutjnl-2024-333222","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333222","url":null,"abstract":"Alcohol-associated hepatitis (AH) is the acute deterioration of alcohol-related liver disease (ArLD) with rapid onset or worsening of jaundice, which, in severe cases, may transition to acute-on-chronic liver failure (ACLF) with extremely high short-term mortality, increasing with the number and severity of hepatic and extra-hepatic organ dysfunction. Systemic inflammation is a hallmark, driving acute decompensation (AD) towards ACLF. Diagnosis and treatment are insufficient and challenging, especially due to the complex, multifactorial and as yet not fully understood pathogenesis. In patients with AH, this inflammation is characterised by increased levels of circulating and hepatic neutrophils, which are essential immune cells responsible for pathogen defence. However, the exact role of neutrophils in AH remains controversial, with ongoing debate over whether their hyperactivation exacerbates liver damage or helps to resolve the disease. Current treatment for AH primarily relies on steroids, but their use is restricted in cases of bacterial infections. Consequently, there is a clinical need to better understand the mechanisms underlying AH and the associated organ dysfunction. Moreover, early detection and treatment of bacterial infections are critical to improve patient outcomes. These challenges, coupled with its rising prevalence in Germany and other Western countries, highlight a significant gap in patient care.1 Chronic alcohol consumption is associated with gut dysbiosis, leading to alterations in the composition of bacteria, viruses and fungi. Several bacterial metabolites were identified to foster liver disease progression. Among them, cytolysin, an endotoxin secreted by Enterococcus faecalis, is associated with higher hepatic inflammation and higher short-term mortality in patients with AH.2 …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"11 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317592","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":"Rethinking routine mapping biopsies in gastric intestinal metaplasia: justification for endoscopic stratification.","authors":"Duc Trong Quach,Toru Hiyama,Gwang Ha Kim,Takuji Gotoda,Kentaro Sugano","doi":"10.1136/gutjnl-2024-333773","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333773","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":"104 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275218","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-risk varices in patients with Child-Pugh-Turcotte B and C: consider band ligation with carvedilol for preventing first variceal bleeding, especially in patients with MASLD-associated cirrhosis","authors":"Alexander Zipprich, Ruben Hernaez","doi":"10.1136/gutjnl-2024-333263","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333263","url":null,"abstract":"International guidelines recommend that primary prophylaxis of varices in patients with cirrhosis be either non-selective beta-blockers (NSBBs) or variceal band ligation (VBL). These recommendations are based on studies that include both compensated and decompensated patients. Notably, the European Association for the Study of the Liver 2018 guidelines recognise a gap in the efficacy of NSBB therapy for patients with decompensated cirrhosis.1 The Baveno guidelines recommend preventing further decompensation in patients with ascites and high-risk varices (large varices >5 mm, or with red spot signs, or Child-Pugh-Turcotte (CPT-C)), with traditional NSBBs or carvedilol preferred over VBL.2 The American Association for the Study of Liver Diseases guidelines support NSBBs or VBL for large high-risk varices.3 However, a recent systematic review with network meta-analysis indicated that VBL is associated with higher risks of complications and mortality compared with NSBBs.4 The supporting evidence for these recommendations is limited, and it remains unclear whether the same treatment options or combination therapies are more effective in decompensated cirrhosis (CPT B or C). In Gut , Tevethia et al report the results of the CAVARLY trial.5 The study compared carvedilol, VBL and a combination of both for preventing the first variceal bleed in patients with CPT- B/C cirrhosis (up to C-13) and high-risk oesophageal varices (>5 mm or <5 mm with red signs). The authors excluded patients with contraindications to carvedilol, hepatocellular carcinoma, portal vein thrombosis, platelet count <30 000 per µL, those on therapeutic anticoagulation, or with previous VBL or transjugular intrahepatic portosystemic shunt (TIPS). They enrolled 330 patients (110 for each arm) …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"333 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245448","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":"Statins for MAFLD/MASH: another brick in the wall while waiting for final answers","authors":"Jaime Bosch","doi":"10.1136/gutjnl-2024-333426","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333426","url":null,"abstract":"I read with pleasure the paper by Zhou et al 1 analysing the long-term clinical outcomes and changes in liver elastography associated with statin usage in patients with metabolic-associated steatotic liver disease (MASLD). This is a population-based study of 7988 patients selected from a total of 17 849 MASLD patients seen in 16 centres in Europe, America and Asia and who had also transient elastography measurements of liver stiffness (LSM). The final cohort included patients >18 years that had at least two LSM, a controlled attenuation parameter denoting steatosis (over ≥248 dB/m), a prolonged follow-up (over 1 year, median 4.6 years), and no other cause of liver disease or excessive alcohol intake. Usage of statins was defined as the consistent use of statins on most days for more than 1 month within a year, which occurred in 3233 patients (40.4%). Patients were considered to have compensated advanced chronic liver disease (cACLD) if the first LSM was >10 kPa, which occurred in 17.2%. The primary outcome was a composite of all-cause death and liver-related events (LREs) (developing cirrhosis decompensation, hepatocellular carcinoma (HCC) or liver-related mortality). In addition, a secondary outcome was the change in LSM, categorised as progression, regression or stable based on observing or not changes in LSM of at least 20% or crossing the threshold of 10 kPa. The authors did Cox regression analysis for examining the association between statin …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"7 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245449","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":"Commentary on: the management of patients with gastric intestinal metaplasia","authors":"David Y Graham, Yi-Chia Lee","doi":"10.1136/gutjnl-2024-333684","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333684","url":null,"abstract":"Recently, Gut published a review of guidelines for the management of gastric intestinal metaplasia (GIM) with the goal of promoting harmonisation of the guidelines regarding indications for endoscopic screening for gastric cancer and GIM detection/staging, metrics for high-quality endoscopy and non-endoscopic interventions for gastric cancer prevention in patients with GIM.1 GIM is not a disease per se but rather is a reparative response to gastric mucosal injury that may be present, at least temporarily, as part of healing such as of an ulcer.2 Clinically, widespread GIM is best considered a manifestation of healing of another disease, typically Helicobacter pylori infection or autoimmune gastritis. When present in autoimmune gastritis, GIM has no malignant potential and is potentially completely reversible.3 In contrast, when associated with chronic H. pylori infection, GIM is typically permanent and, at most, minimally reversible.4 The underlying H. pylori -induced inflammation is carcinogenic. H. pylori -related GIM is a manifestation of the duration, extent and severity of an H. pylori infection which, in turn, is related to the risk of gastric cancer. Because GIM is easily recognised and reflects the extent and severity of the infection, it is a valuable surrogate for the risk of developing gastric cancer. This has given GIM a role in the determination of an individual’s cancer risk. However, because GIM is neither a disease nor a cause of cancer, eradication of gastric cancer should focus on the eradication of the cause, that is, H. pylori infections. The population …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"36 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245450","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}