Lancet Gastroenterology & Hepatology最新文献

{"title":"Germline multigene panel testing for colorectal cancer: a systematic review and meta-analysis.","authors":"Alessandro Mannucci, Marta Puzzono, Giuseppe Marzocca, Ajay Goel, Shuji Ogino, Sapna Syngal, Matthew B Yurgelun, Samir Gupta, Giulia Martina Cavestro","doi":"10.1016/S2468-1253(26)00187-1","DOIUrl":"10.1016/S2468-1253(26)00187-1","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer can arise from an inherited genetic background, but the diagnostic yield of multigene germline panel testing in patients diagnosed with colorectal cancer remains uncertain. The aim of this study was to quantify such yield.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we searched PubMed (MEDLINE), Embase, Scopus, and the Cochrane Central Register of Controlled Trials from database inception to Aug 2, 2025, for studies published in English reporting the results of germline multigene panel testing of at least five genes using next-generation sequencing in unselected patients with colorectal cancer. Eligible study designs included cross-sectional and cohort studies, and clinic-based series in which all consecutive patients with colorectal cancer were offered multigene panel testing. Two independent reviewers, masked from each other's decisions, screened records and extracted summary data and individual participant data, with conflicts resolved by a third reviewer. Risk of bias was assessed using the Newcastle-Ottawa Scale. The primary outcome was the person-level prevalence (diagnostic rate) of at least one pathogenic or likely pathogenic variant in cancer predisposition genes. Analyses were stratified by age at colorectal cancer diagnosis and gene penetrance. Random-effects meta-analyses estimated pooled prevalence. Heterogeneity was quantified using the I<sup>2</sup> statistic. Meta-regression evaluated the effect of age at colorectal cancer diagnosis, panel size, family history, and publication year on diagnostic rates. This study was registered in PROSPERO, CRD42025649177.</p><p><strong>Findings: </strong>Of 2707 records identified, 1682 duplicates were removed and screening excluded a further 985 records. 40 articles underwent full-text review, of which 21 met eligibility criteria and were included (ten [48%] at low, nine [43%] at moderate, and two [10%] at high risk of bias). Across 6925 individuals with colorectal cancer, the pooled rate of any pathogenic or likely pathogenic variant was 15·2% (95% CI 12·8-18·1; 1061/6925; I<sup>2</sup>=84·1%; k=12), with high-penetrance variants identified in 7·9% (5·9-10·5; 551/6909; I<sup>2</sup>=88·4%; k=11) and high-penetrance colorectal cancer predisposition variants in 5·4% (3·5-8·6; 408/6909; I<sup>2</sup>=93·4%; k=11). In early-onset colorectal cancer (age at diagnosis <50 years), yields were 17·7% (15·0-20·7; 1113/7444; I<sup>2</sup>=85·7%; k=16) for any pathogenic or likely pathogenic variant, 14·2% (11·7-17·3; 917/7409; I<sup>2</sup>=85·7%; k=15) for high-penetrance variants, and 12·2% (9·5-15·5; 788/7409; I<sup>2</sup>=89·5%; k=15) for high-penetrance colorectal cancer predisposition variants. In late-onset colorectal cancer (age at diagnosis ≥50 years), yields were 13·0% (10·8-15·7; 711/5243; I<sup>2</sup>=73·3%; k=11) for all variants, 6·5% (4·4-9·5; 349/5227; I<sup>2</sup>=86·4%; k=10) for high-penetrance variants","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":"997-1008"},"PeriodicalIF":39.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889452","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":"On-demand transarterial chemoembolisation combined with atezolizumab and bevacizumab in patients with untreated hepatocellular carcinoma (TALENTACE): a multicentre, randomised, open-label, phase 3 trial.","authors":"Masatoshi Kudo, Sadahisa Ogasawara, Ruibao Liu, Shanzhi Gu, Kunyuan Wang, Ming Zhao, Hongtao Hu, Zhaoyu Liu, Kecan Lin, Jingfeng Liu, Zhengyu Lin, Yonghong Zhang, Tao Peng, Jinhua Song, Makoto Ueno, Jiye Zhu, Lidan Bai, Lin Tong, Yanjun Shi, Guohong Han, Jiahong Dong","doi":"10.1016/S2468-1253(26)00212-8","DOIUrl":"10.1016/S2468-1253(26)00212-8","url":null,"abstract":"<p><strong>Background: </strong>TACE is the standard treatment for intermediate-stage hepatocellular carcinoma but has limited survival benefits. TALENTACE evaluated adding atezolizumab and bevacizumab to on-demand TACE versus on-demand TACE alone in patients with systemically untreated, intermediate-to-high tumour burden unresectable hepatocellular carcinoma.</p><p><strong>Methods: </strong>In this randomised, open-label, phase 3 study at 40 centres in China and Japan, patients aged 18 years or older with confirmed, unresectable hepatocellular carcinoma and an anticipated life expectancy of 12 months or more were eligible for inclusion. Eligible patients were required to have an Eastern Cooperative Oncology Group performance status of 0-1, Child-Pugh class A liver function, no previous systemic therapy, and a sum of tumour maximum diameter (cm) and lesion number of six or more based on the six-and-twelve score. Patients were randomly assigned (1:1), using a permuted-block method implemented via an interactive voice and web response system, to on-demand TACE plus atezolizumab 1200 mg intravenously and bevacizumab 15 mg/kg intravenously once every 3 weeks (initiated 14 days to 8 weeks after TACE), or on-demand TACE alone, with TACE administered at the investigators' discretion. The randomisation sequence was generated by an independent biostatistician at the system vendor and was concealed from the sponsor study team and investigators until randomisation; allocation was stratified by baseline α-fetoprotein, prior locoregional therapy, and baseline Vp1/2 (and geographic region in earlier protocol versions). Primary endpoints were investigator-assessed TACE progression-free survival (TACE-PFS; time from randomisation to untreatable [unTACEable] progression, TACE failure or refractoriness, or death), and overall survival, both analysed in the intention-to-treat population. Overall survival was assessed under a prespecified adaptive (group sequential) design comprising two interim analyses and one final analysis. Safety was evaluated in the as-treated population, defined as all randomised patients who received any study treatment, analysed according to the treatment received. This study is registered with ClinicalTrials.gov (NCT04712643) and is ongoing.</p><p><strong>Findings: </strong>Between Feb 23, 2021, and August 11, 2023, 342 patients were randomly assigned to TACE plus atezolizumab and bevacizumab (n=171) or on-demand TACE alone (n=171). Median age was 61·0 years (range 21·0-90·0), 66 (19%) of 342 participants were female, 276 (81%) were male, 308 (90%) were Chinese, and 34 (10%) were Japanese. The mean size of the largest target lesion per RECIST 1.1 was 7·7 cm (SD 4·3) in both arms. In the TACE plus atezolizumab and bevacizumab group, 36 (21%) of 171 patients were Barcelona Clinic Liver Cancer stage A, 100 (58%) were stage B, and 35 (20%) were stage C; in the TACE alone group, 42 (25%) of 171 patients were Barcelona Clinic Liver Cancer stage ","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":"971-983"},"PeriodicalIF":39.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820366","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":"Incidence of inflammatory bowel disease in Jakarta, Indonesia, 2021-24.","authors":"Jeffri Gunawan, Charles N Bernstein, Gilaad G Kaplan, Manuel Barreiro-de Acosta, Jessica Jordanes, Jean-Francois Rey, Gerard Pals","doi":"10.1016/S2468-1253(26)00239-6","DOIUrl":"10.1016/S2468-1253(26)00239-6","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":"957-958"},"PeriodicalIF":39.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876603","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":"ALG-055009 in non-cirrhotic adults with metabolic dysfunction-associated steatohepatitis (HERALD): a randomised, double-blind, placebo-controlled, phase 2a trial.","authors":"Rohit Loomba, Stanley Wang, Dimple Desai, Daniel Santillano, Kathryn Jean Lucas, Guy Neff, Antonio C Bianco, Eveline Bruinstroop, Yan Su, Hardean E Achneck, Kha Le, Megan Fitzgerald, Min Wu, Tse-I Lin, Sushmita M Chanda, Lawrence M Blatt, Christos S Mantzoros","doi":"10.1016/S2468-1253(26)00154-8","DOIUrl":"10.1016/S2468-1253(26)00154-8","url":null,"abstract":"<p><strong>Background: </strong>Thyroid hormone receptor β (THR-β) agonists reduce atherogenic lipids, hepatic fat, and improve histology in metabolic dysfunction-associated steatohepatitis (MASH). The phase 2a HERALD study evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of the selective and potent THR-β agonist ALG-055009 in non-cirrhotic adult patients with presumed MASH.</p><p><strong>Methods: </strong>In this double-blind, placebo-controlled, phase 2a trial, participants aged 18-75 years with a BMI of at least 25 kg/m<sup>2</sup> and a diagnosis of presumed non-alcoholic steatohepatitis (NASH) or MASH with F1-F3 liver fibrosis were randomly assigned to receive oral ALG-055009 (0·3 mg, 0·5 mg, 0·7 mg, or 0·9 mg) or placebo once daily for 12 weeks. Enrolment in the 0·9 mg group was limited to participants with bodyweight of more than 85 kg. The primary endpoint was percentage relative change from baseline in liver fat by MRI-proton density fat fraction (MRI-PDFF) at week 12 in the MRI-PDFF analysis population. The trial is registered at ClinicalTrials.gov, NCT06342947, and is now completed.</p><p><strong>Findings: </strong>102 participants (39 [38%] males and 63 [62%] females) were randomly assigned to receive ALG-055009 0·3 mg (n=20), ALG-055009 0·5 mg (n=22), ALG-055009 0·7 mg (n=20), ALG-055009 0·9 mg (n=18), or placebo (n=22); five participants (two in the 0·3 mg group, one in the 0·5 mg group, one in the 0·9 mg group, and one in the placebo group) did not have baseline and week 12 MRI-PDFF data and were thus not included in the analysis of the primary endpoint. Least-squares mean relative change in liver fat at week 12 was -6·9% (95% CI -19·2 to 5·3) with 0·3 mg ALG-055009, -11·2% (-22·9 to 0·4) with 0·5 mg ALG-055009, -25·9% (-37·7 to -14·1) with 0·7 mg ALG-055009, -24·3% (-37·9 to -10·6) with 0·9 mg ALG-055009, and 7·3% (-4·0 to 18·6) with placebo. Placebo-adjusted least-squares mean relative changes in liver fat at week 12 were therefore -14·3% (95% CI -29·6 to 1·0; p=0·067) for 0·3 mg ALG-055009, -18·5% (-33·3 to -3·8; p=0·014) for 0·5 mg ALG-055009, -33·2% (-48·1 to -18·3; p<0·0001) for 0·7 mg ALG-055009, and -31·6% (-47·4 to -15·8; p=0·0001) for 0·9 mg ALG-055009. Treatment-emergent adverse events occurred in 13 (65%) participants receiving 0·3 mg ALG-055009, ten (45%) receiving 0·5 mg ALG-055009, 13 (65%) receiving 0·7 mg ALG-055009, 11 (61%) receiving 0·9 mg ALG-055009, and in 16 (73%) receiving placebo. Most treatment-emergent adverse events were mild or moderate, with the most common being diarrhoea (ten [10%]), fatigue (six [6%]), and constipation (five [5%]). One serious adverse event occurred in the placebo group, and no deaths occurred. Gastrointestinal treatment-emergent adverse event rates for ALG-055009 were similar to placebo, and no clinically meaningful changes in laboratory tests, electrocardiogram, vital signs, physical exams, or thyroid function were observed.</p><p><strong>Interpretation: </st","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":"984-996"},"PeriodicalIF":39.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148834940","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":"Guinea-Bissau HepB birth-dose vaccine trial: still unethical","authors":"","doi":"10.1016/s2468-1253(26)00306-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(26)00306-7","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"2 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231831","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":"Updated treatment targets in inflammatory bowel disease (STRIDE-III): an initiative of the International Organization for the Study of IBD.","authors":"Dan Turner, Amanda Ricciuto, Shira Yuval Bar-Asher, Sudheer K Vuyyuru, Virginia Solitano, Nadine Bock, Maria Manuela Estevinho, Yuhong Yuan, Marietta Iacucci, Florian Rieder, Rupert W Leong, Walter Reinisch, Edward V Loftus, Laurent Peyrin-Biroulet, Silvio Danese, Remo Panaccione, Takayuki Yamamoto, Stefan Schreiber, Marla Dubinsky, Vineet Ahuja, Charles N Bernstein, David T Rubin, Gerassimos J Mantzaris, Fernando Magro, Iris Dotan, Vipul Jairath, Axel Dignass","doi":"10.1016/S2468-1253(26)00292-X","DOIUrl":"https://doi.org/10.1016/S2468-1253(26)00292-X","url":null,"abstract":"<p><p>Since Selecting Therapeutic Targets in Inflammatory Bowel Disease-II (STRIDE-II), new evidence has become available across inflammatory and patient-centred outcomes. We aimed to update the STRIDE recommendations for Crohn's disease and ulcerative colitis. We searched MEDLINE, Embase, and Cochrane CENTRAL for studies published after the STRIDE-II search period. Findings were integrated with surveys of International Organization for the Study of IBD (IOIBD) members and paediatric gastroenterologists from the Porto group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Statements were subsequently voted on using a modified Delphi approach; consensus was defined as ≥75% of participants rating a statement 7-10 on a 10-point scale. Of 13 071 records identified in the systematic review, 1018 were included. Surveys were completed by 60 of 79 IOIBD gastroenterologists and 23 of 30 paediatric gastroenterologists in the Porto group. STRIDE-III defines three conceptually distinct categories of treatment targets. Actionable targets include clinical response and remission, which reflect patient priorities, and objective inflammatory targets (C-reactive protein normalisation, faecal calprotectin within target range, and endoscopic remission), supported by interventional evidence demonstrating benefits of target-guided treatment modification. Adjunctive targets (ie, urgency, histological remission in ulcerative colitis, transmural remission in Crohn's disease, and growth) are supported by studies showing association with favourable outcomes and guide treatment optimisation and tighter monitoring but do not necessarily require a change in therapeutic class. Patient-centred targets (ie, disability, fatigue, and quality of life) directly reflect patients' well-being and are impaired in a substantial proportion of patients with inflammatory bowel disease; impairment should prompt assessment of inflammation and alternative causes and management through shared decision-making. Targets are further classified as immediate, short-term, intermediate, and long-term. STRIDE-III also defines treatment-specific times to target achievement, new faecal calprotectin thresholds, and adaptations for resource-limited settings. STRIDE-III distinguishes targets that should prompt treatment change from those that primarily guide optimisation and monitoring, while establishing a separate patient-centred pathway based on shared decision-making. This framework supports consistent, evidence-based treat-to-target care.</p>","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":39.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225329","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":"Thyroid hormone receptor-β agonist simedeutirom (HSK31679) for Chinese patients with metabolic dysfunction-associated steatohepatitis: a 52-week, multicentre, randomised, double-blind, placebo-controlled, phase 2b trial.","authors":"Feng Xue, Jianfeng Liu, Jinjun Chen, Xing Li, Sikui Wang, Yawen Luo, Bangjie Zhang, Jiawei Geng, Weihong Wang, Rui Zhao, Chuanwu Zhu, Junjun Bi, Xiqing Guo, Lungen Lu, Guangming Li, Hong Peng, Li Dong, Weifang Zeng, Tingting Wu, Fangqiong Li, Lai Wei","doi":"10.1016/S2468-1253(26)00243-8","DOIUrl":"https://doi.org/10.1016/S2468-1253(26)00243-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Simedeutirom is a selective thyroid hormone receptor-β agonist that has previously been shown to reduce hepatic fat content in metabolic dysfunction-associated steatotic liver disease. We assessed the efficacy and safety of simedeutirom in patients of Asian descent with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and F2 or F3 fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicentre, randomised, double-blind, placebo-controlled, phase 2b trial was conducted at 42 clinical sites in China. Adults (aged 18-74 years) with biopsy-confirmed MASH, a non-alcoholic fatty liver disease activity score (NAS) of at least 4, F2 or F3 fibrosis, and MRI-proton density fat fraction liver fat content of at least 8% were randomly assigned (1:1:1) by block randomisation (block size of six; no stratification) via a centralised web-based system to receive once-daily simedeutirom 80 mg, simedeutirom 160 mg, or placebo for 52 weeks. Participants and study personnel were masked to treatment assignment. The primary endpoint was MASH improvement (ie, two-point or more reduction in NAS, one-point or more improvement in hepatocellular ballooning, and no increase in steatosis score) without worsening of fibrosis (ie, no increase in fibrosis stage) at week 52. Efficacy was analysed in the full analysis set, which included all randomly assigned participants who received at least one dose and had at least one efficacy assessment after baseline; participants without liver biopsy data after treatment or who used prohibited medications affecting efficacy were considered non-responders. The trial is registered with ClinicalTrials.gov (NCT06168383) and is complete.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Jan 5, 2024, and Jan 16, 2026, 186 participants were randomly assigned (62 per group). In the full analysis set (n=179), the median age was 42·0 years (IQR 35·0-54·0), 116 (65%) participants were men, and 63 (35%) were women. 22 (37%) of 59 participants in the 80 mg group, 18 (30%) of 60 in the 160 mg group, and six (10%) of 60 in the placebo group had MASH improvement without worsening of fibrosis at week 52. ORs versus placebo were 4·87 (95% CI 1·76-13·48; p=0·0023) in the 80 mg group and 5·24 (1·74-15·72; p=0·0032) in the 160 mg group, with absolute differences of 27·3 percentage points (95% CI 12·2-41·1) and 20·0 percentage points (5·7-33·6), respectively. Grade 3 treatment-emergent adverse events occurred in three (5%) of 61 participants in the simedeutirom 80 mg group, five (8%) of 62 in the simedeutirom 160 mg group, and three (5%) of 62 in the placebo group; no individual grade 3 event affected more than one participant, and no grade 4-5 treatment-emergent adverse events occurred. Serious adverse events occurred in three (5%) participants in the simedeutirom 80 mg group, four (6%) in the simedeutirom 160 mg group, and three (5%) in the placebo group; none were treatment related. No deaths or adverse events leading","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":39.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208175","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":"THR-β agonism in MASH: expanding the evidence to Asia.","authors":"Wenhao Li, William Alazawi","doi":"10.1016/S2468-1253(26)00264-5","DOIUrl":"https://doi.org/10.1016/S2468-1253(26)00264-5","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":39.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208246","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":"Strategies to develop therapeutic cancer vaccines for pancreatic cancer.","authors":"Matilde M Coppi, Michele Graciotti, Antonia Digklia, Lana E Kandalaft","doi":"10.1016/S2468-1253(26)00149-4","DOIUrl":"https://doi.org/10.1016/S2468-1253(26)00149-4","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. Conventional immunotherapies have shown little clinical benefit, largely due to the low neoantigenicity and profoundly immunosuppressive microenvironment of this cancer. Therapeutic cancer vaccines have emerged as a rational strategy to prime or amplify antitumour immunity, supported by advances in antigen discovery, genomic profiling, and vaccine engineering. Here, we report a review of clinical trials evaluating therapeutic cancer vaccines in PDAC. Eligible studies were identified through searches of ClinicalTrials.gov from database inception to Aug 31, 2025, with manual screening of trial-linked publications up to Jan 31, 2026. 135 records were identified, of which 120 met the eligibility criteria and were included in the qualitative synthesis. Across vaccine platforms-cell-based, nucleic acid-based, protein and peptide-based, microorganism-based, and multiplatform strategies-early-phase clinical studies consistently show feasibility, favourable safety profiles, and the induction of tumour-specific immune responses. However, immune activation has rarely translated into durable clinical benefit. To date, the most compelling biological signals derive from personalised neoantigen vaccines, particularly mRNA-based approaches, which can elicit high-magnitude CD8⁺ T-cell responses and long-lived clonal persistence in postoperative PDAC. Emerging evidence also supports the potential of shared neoantigens, such as KRAS^mut, as biologically relevant and scalable targets. Collectively, our findings highlight a shift towards rational vaccine combination strategies aimed at overcoming stromal and myeloid-mediated immunosuppression. Future progress will depend on integrating therapeutic vaccination into multimodal regimens and evaluating these approaches in adequately powered, biomarker-selected clinical trials.</p>","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":""},"PeriodicalIF":39.1,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186430","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":"WHO global hepatitis report 2026: guiding global action for elimination.","authors":"Olufunmilayo Lesi, Diana Faini, Irwin Law, Mathieu Bastard, Daniel Low-Beer, Tereza Kasaeva, Katherine Floyd","doi":"10.1016/S2468-1253(26)00220-7","DOIUrl":"10.1016/S2468-1253(26)00220-7","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":" ","pages":"865-867"},"PeriodicalIF":39.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610170","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}