John W K Chia, Eva Segelov, Yanhong Deng, Gwo Fuang Ho, Wei Wang, Shuting Han, Atul Sharma, Kefeng Ding, Gong Chen, Mark G Jeffery, Chee Kian Tham, Joong Bae Ahn, Louise Nott, Robert Zielinski, Tsu-Yi Chao, Tom van Hagen, Po-Li Wei, Fiona Day, Shaesta Mehta, Thomas Yau, Han Chong Toh
{"title":"Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial","authors":"John W K Chia, Eva Segelov, Yanhong Deng, Gwo Fuang Ho, Wei Wang, Shuting Han, Atul Sharma, Kefeng Ding, Gong Chen, Mark G Jeffery, Chee Kian Tham, Joong Bae Ahn, Louise Nott, Robert Zielinski, Tsu-Yi Chao, Tom van Hagen, Po-Li Wei, Fiona Day, Shaesta Mehta, Thomas Yau, Han Chong Toh","doi":"10.1016/s2468-1253(24)00387-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00387-x","url":null,"abstract":"<h3>Background</h3>Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.<h3>Methods</h3>This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East). The trial included patients aged 18 years and older with Dukes' C or high-risk Dukes' B colon cancer or Dukes' B or C rectal cancer who had undergone resection and had completed standard adjuvant therapy (at least 3 months of chemotherapy). Patients with contraindications to aspirin, familial syndromes of colorectal cancer, recent other cancers, and clinically significant history of cardiovascular disease or stroke were excluded. Patients were randomly assigned (1:1) to aspirin 200 mg daily or placebo for 3 years, and were followed up for 5 years. Randomisation was stratified by study centre, tumour site and stage, and inclusion of oxaliplatin in adjuvant chemotherapy. The patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was disease-free survival. The primary analysis used a stratified Cox model in those commencing study treatment (modified intention-to-treat population), analysing all events to March 31, 2023. Safety was analysed in the same population. This trial is registered at <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT00565708</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>). The primary analysis has been completed, but translational studies of putative aspirin sensitivity biomarkers are ongoing.<h3>Findings</h3>Between Feb 25, 2009, and June 30, 2021, 1587 patients underwent randomisation, of whom 1550 were included in the modified intention-to-treat analysis: 791 (51%) in the aspirin group and 759 (49%) in the placebo group. Of these patients, the median age was 57 years (IQR 48–65); 897 (58%) were male and 653 (42%) female; 271 (17%) had Dukes' B colon cancer, 770 (50%) Dukes' C colon cancer, and 509 (33%) rectal cancer. Median follow-up at data cutoff was 59·2 months (IQR 36·7–60·0). 5-year disease-free survival was 77·0% (95% CI 73·6–80·0) in the aspirin group and 74·8% (71·3–77·9) in the placebo group (hazard ratio of 0·91 [95% CI 0·73–1·13]; p=0·38). Any-grade adverse events were reported in 390 (49%) of 791 patients in the aspirin group versus 386 (51%) of 759 in the placebo group. Serious adverse events were reported in 95 (12%) patients in the aspirin group versus 107 (14%) in the placebo gr","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"22 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981468","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":"Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis","authors":"Ziwei Gao, Wei Ye, Jingru Song","doi":"10.1016/s2468-1253(24)00404-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00404-7","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"26 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961887","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":"Research in Brief","authors":"Holly Baker","doi":"10.1016/s2468-1253(24)00440-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00440-0","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Guselkumab for moderately to severely active ulcerative colitis</h2>Guselkumab is a safe and efficacious treatment option for patients with moderately to severely active ulcerative colitis, according to the <span><span>phase 3 QUASAR induction and maintenance studies</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. David T Rubin and colleagues randomly assigned patients with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy to receive guselkumab 200 mg intravenously (n=421) or placebo (n=280) at weeks 0, 4, and 8 (induction study). At 12 weeks, 95 (23%) of 421 patients in the</section></section><section><section><h2>Nivolumab plus ipilimumab for MSI-H colorectal cancer</h2>Nivolumab plus ipilimumab increases survival in patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer, according to the phase 3 <span><span>CheckMate 8HW trial</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. Thierry Andre and colleagues randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive either nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. In this</section></section><section><section><h2><span><span>Impact of coeliac disease on gut function and microbiome</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span></h2>Coeliac disease has an impact on gut function and microbiome composition that is not reversed by a gluten-free diet, according to new research. Carolyn Costigan and colleagues used MRI and stool sample analysis to examine gut function and microbiome composition of 36 patients with newly diagnosed coeliac disease and an equal number of healthy volunteers. At baseline, patients with coeliac disease had significantly higher small bowel water content and delayed gut transit times compared with</section></section><section><section><h2>Combination therapy for acute severe ulcerative colitis</h2>Combination therapy with infliximab plus azathioprine shows promise in patients with acute severe ulcerative colitis responsive to intravenous steroids, according to the <span><span>phase 4 ACTIVE trial</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. Aurelien Am","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"6 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961901","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":"The rise in early-onset colorectal cancer: now a global issue","authors":"","doi":"10.1016/s2468-1253(24)00441-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00441-2","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"21 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961897","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}
Muhammad Usman, Nasir Javed, Aida Jawhari, Nazim Ghouri, Salman Waqar, Fathima Shah, Saqib Ahmad, Ailsa Hart, Bilal Hameed, Mohammad Qasim Khan, Mohammad Farhad Peerally
{"title":"Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals","authors":"Muhammad Usman, Nasir Javed, Aida Jawhari, Nazim Ghouri, Salman Waqar, Fathima Shah, Saqib Ahmad, Ailsa Hart, Bilal Hameed, Mohammad Qasim Khan, Mohammad Farhad Peerally","doi":"10.1016/s2468-1253(24)00283-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00283-8","url":null,"abstract":"Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients’ risk as low or moderate, high, or very high. We advise all patients at very high risk and most patients at high risk to not observe fasting due to potential harm. For others, we offer nuanced recommendations on medication rescheduling, lifestyle changes, and tailored fasting advice to minimise adverse effects. Shared decision making that respects patients’ religious motivations is essential, with risks and benefits carefully weighed on an individual basis.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"84 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961902","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":"The case for reducing the use of diagnostic upper and lower gastrointestinal endoscopy","authors":"Christopher J Black, Alexander C Ford","doi":"10.1016/s2468-1253(24)00428-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00428-x","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"35 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936879","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}