Journal of Gastroenterology最新文献

{"title":"Clinical course, prognostic markers, and transplant implications in COVID-19-associated secondary sclerosing cholangitis.","authors":"Johannes Roman Wiessner, Matthias Kis, Daniela Lenggenhager, Caecilia Sophie Reiner, Pedro David Wendel-Garcia, Katharina Endhardt, Daniel Stocker, Nadine Stanek, Georg Leinenkugel, Anna Svarin, Simon Bütikofer, Bernhard Morell, Philipp Karl Bühler, Soleen Ghafoor, Christoph Gubler, Rahel Häuptle, David Semela, Andreas Emanuel Kremer, Beat Müllhaupt, Christoph Jüngst","doi":"10.1007/s00535-026-02491-5","DOIUrl":"https://doi.org/10.1007/s00535-026-02491-5","url":null,"abstract":"<p><strong>Background: </strong>Secondary sclerosing cholangitis (SSC) has emerged as a severe complication in critically ill COVID-19 patients. This study outlines the clinical course, prognostic markers, and liver transplantation (LT) outcomes of COVID-19-associated SSC.</p><p><strong>Methods: </strong>This retrospective multicenter study included 36 COVID-19-associated SSC patients from three Swiss tertiary centers. Clinical, laboratory, imaging, and histopathological data were analyzed with respect to outcomes defined as survival without LT versus LT or death. Post-transplant outcomes were assessed.</p><p><strong>Results: </strong>All 36 critically ill patients developed acute respiratory distress syndrome. SSC was diagnosed post-ICU in 80.6% of cases. After a median follow-up of 537 days, 12 patients died, six progressed to decompensation, 14 had compensated liver disease, and four underwent LT. Among 17 LT-evaluated patients, eight died during evaluation or on the waiting list. All four transplanted patients survived. Univariable analysis identified male sex and extent of elevated alkaline phosphatase (AP), bilirubin, aspartate aminotransferase, and alanine aminotransferase at SSC diagnosis, and at peak as predictors of poor outcomes. Histopathological features associated with adverse outcomes included portal edema and bile infarcts, whereas septal fibrosis, florid inflammation, and MRI-detected parenchymal signal changes correlated with transplant-free survival. In multivariable analysis, parenchymal signal changes (OR 0.03, 95%CI 0.00-0.83) and peak AP (OR 7.23, 95%CI 1.14-45.73) remained independently associated with outcome.</p><p><strong>Conclusions: </strong>COVID-19-associated SSC carries high morbidity and mortality. Clinical, biochemical, imaging, and histopathological parameters enable early risk stratification and predict outcome. Timely LT evaluation is recommended in severe cases, given favorable post-transplant outcomes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin blocks Fusobacterium nucleatum-driven tumor progression and carcinogenesis in ESCC via inhibiting the TLR4/MYD88/TRIF/STAT3 axis.","authors":"Mila Jin, Qiwei Yang, Jiaqi Qin, Defeng Zhao, Senyuan Zhang, Ziyi Wang, Liang Chen, Hui Zhao, Tangnuer Nuerbieke, Huizhong Tian, Danni Li, Wenya Li","doi":"10.1007/s00535-026-02499-x","DOIUrl":"https://doi.org/10.1007/s00535-026-02499-x","url":null,"abstract":"<p><strong>Background: </strong>The molecular mechanisms by which the epidemiologically linked bacterium Fusobacterium nucleatum (Fn) promotes Esophageal Squamous Cell Carcinoma (ESCC) malignancy are poorly defined. Here, we identify the key signaling pathways involved.</p><p><strong>Methods: </strong>We first established the intratumoral microbiota profile to focus on Fn's role in ESCC. Using integrated models, we then confirmed that Fn promotes tumor growth, which a cisplatin (CDDP)-induced senescence model also showed contributes to chemoresistance. Finally, by analyzing key signaling molecules, we elucidated the mechanisms by which Fn drives proliferation and treatment resistance.</p><p><strong>Results: </strong>We began by observing a positive correlation between Fn enrichment and elevated TLR4/STAT3 signaling in ESCC patients. Subsequent experiments in cells and animals confirmed that this correlation functionally contributes to increased tumor aggressiveness. At the mechanistic level, Fn-derived lipopolysaccharide (LPS) acts as the key trigger, activating the TLR4/MYD88/TRIF/STAT3 axis to drive pro-inflammatory signaling and SASP, thereby leading to chemoresistance. Therapeutically, curcumin counters this by directly inhibiting Fn and blocking the pathway, thereby suppressing tumor growth, attenuating SASP, and restoring drug sensitivity.</p><p><strong>Conclusion: </strong>The inhibition of the Fn-activated TLR4/MYD88/TRIF/STAT3 cascade represents a key mechanism through which curcumin blocks ESCC progression, identifying it as a promising candidate for therapeutic development.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic immune activity reflects a coordinated immune microenvironment and is associated with response to total neoadjuvant therapy in rectal cancer.","authors":"Erina Haraguchi, Norio Tanaka, Kentaro Sato, Tatsuki Noguchi, Takashi Sakamoto, Shimpei Matsui, Toshiki Mukai, Tomohiro Yamaguchi, Eiji Shinozaki, Senzo Taguchi, Akiko Chino, Manabu Takamatsu, Ippei Fukada, Takayuki Ueno, Tetsuo Noda, Seiichi Mori, Takashi Akiyoshi","doi":"10.1007/s00535-026-02502-5","DOIUrl":"https://doi.org/10.1007/s00535-026-02502-5","url":null,"abstract":"<p><strong>Background: </strong>Total neoadjuvant therapy (TNT) has emerged as a promising treatment strategy for locally advanced rectal cancer; however, robust biomarkers predicting treatment response remain lacking. We aimed to identify pretreatment transcriptomic determinants of TNT response, focusing on cytotoxic immune activity and its broader immune context.</p><p><strong>Methods: </strong>We analyzed two independent cohorts of patients with rectal cancer treated with TNT: a laser-capture microdissection (LCM) cohort (n = 154) and a bulk tumor cohort (n = 80). Differential gene expression, gene set enrichment, and immune deconvolution analyses were performed using pretreatment RNA sequencing data. Associations between cytotoxic activity and treatment response were evaluated using multivariable models.</p><p><strong>Results: </strong>Only a limited number of genes were reproducibly associated with response across cohorts. Pathway-level analyses revealed enrichment of immune-related signatures in complete responders in the bulk cohort, whereas no significant enrichment was observed in the LCM cohort. Cytotoxic scores showed a consistent directional association with complete response in both cohorts, although modestly, and did not reach statistical significance in the LCM cohort. Cytotoxic activity was strongly correlated with multiple immune cell populations and signaling pathways, including effector and regulatory components, indicating a coordinated immune microenvironment. Multivariable analyses demonstrated that cytotoxic activity was independently associated with treatment response in the bulk cohort and recurrence-free survival in the LCM cohort.</p><p><strong>Conclusions: </strong>Cytotoxic immune activity represents a biologically relevant but modest determinant of response to TNT in rectal cancer. These findings suggest that treatment sensitivity is shaped by a coordinated immune microenvironment rather than cytotoxic activity alone.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal MRI reveals glymphatic system activity associated with systemic inflammation and neuropsychiatric symptoms in Crohn's disease.","authors":"Yu Yin, Xuehong Wang, Dalian Ou, Zihan Zhou, Min Luo, Jun Liu","doi":"10.1007/s00535-026-02505-2","DOIUrl":"https://doi.org/10.1007/s00535-026-02505-2","url":null,"abstract":"<p><strong>Background: </strong>While animal studies suggest that intestinal inflammation can remodel glymphatic function, glymphatic alterations in Crohn's disease (CD) remain poorly understood. This study aims to characterize glymphatic activity in CD patients and explore its associations with systemic inflammation and neuropsychiatric symptoms.</p><p><strong>Methods: </strong>In this prospective study, we enrolled 89 patients with CD and 48 age- and sex-matched healthy controls (HCs). Glymphatic function was assessed using advanced MRI metrics including free water in white matter (FW-WM), diffusion tensor image analysis along the perivascular space (DTI-ALPS), and global coupling of blood-oxygen-level-dependent with cerebrospinal fluid signals (gBOLD-CSF coupling). General linear models were applied to compare group differences, and partial correlation analyses were conducted to examine the associations of these metrics with inflammatory levels and neuropsychological scores.</p><p><strong>Results: </strong> Compared with HCs, patients with CD showed significantly higher FW-WM, lower DTI-ALPS index, and weaker gBOLD-CSF coupling. Within the CD group, elevated FW-WM was associated with higher CRP levels (r = 0.308, p = 0.021), SAS scores (r = 0.355, p = 0.018), and SDS scores (r = 0.290, p = 0.029), whereas a lower DTI-ALPS index correlated with higher ESR levels (r = - 0.271, p = 0.042) and MFI scores (r = - 0.312, p = 0.021). Furthermore, weaker gBOLD-CSF coupling was significantly associated with higher PSQI scores (r = 0.329, p = 0.021).</p><p><strong>Conclusion: </strong>This study provides noninvasive MRI evidence of glymphatic alterations in patients with CD that are associated with systemic inflammation and neuropsychiatric symptoms.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of subcutaneous adiposity with survival outcomes in advanced biliary tract cancer treated with gemcitabine, cisplatin, and immune checkpoint inhibitor.","authors":"Tsuyoshi Takeda, Takashi Sasaki, Tatsuki Hirai, Yoichiro Sato, Jun Hamada, Yuri Maegawa, Takafumi Mie, Takaaki Furukawa, Yukari Suzuki, Takeshi Okamoto, Masato Ozaka, Naoki Sasahira","doi":"10.1007/s00535-026-02498-y","DOIUrl":"https://doi.org/10.1007/s00535-026-02498-y","url":null,"abstract":"<p><strong>Background: </strong>The obesity paradox, in which obese patients experience improved outcomes following immune checkpoint inhibitor (ICI) therapy, has been reported in several malignancies. However, its clinical relevance in advanced biliary tract cancer (BTC) remains unclear.</p><p><strong>Methods: </strong>We retrospectively analyzed patients with advanced BTC who received first-line gemcitabine and cisplatin with ICI (ICI cohort; n = 68) or without ICI (non-ICI cohort; n = 179). Obesity was evaluated using body mass index (BMI) and computed tomography (CT)-based adipose tissue parameters, including total adipose tissue index (TATI), visceral adipose tissue index, and subcutaneous adipose tissue index (SATI). Skeletal muscle mass was quantified on CT images. Progression-free survival (PFS) and overall survival (OS) were assessed using Cox proportional hazards models.</p><p><strong>Results: </strong>High TATI was associated with a lower prevalence of sarcopenia in both cohorts. In the ICI cohort, high SATI was independently associated with prolonged PFS (hazard ratio [HR], 0.45; P = 0.004) and OS (HR, 0.27; P = 0.001), whereas BMI and sarcopenia were not. High SATI showed a trend toward improved survival in both sarcopenic (P = 0.16) and non-sarcopenic subgroups (P < 0.001). In contrast, no significant associations between adipose tissue parameters and survival outcomes were observed in the non-ICI cohort.</p><p><strong>Conclusions: </strong>Higher subcutaneous adiposity was independently associated with improved survival outcomes in patients with advanced BTC receiving ICI therapy, but not in those treated without ICI, suggesting that it may serve as a clinically relevant prognostic factor in this setting.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor.","authors":"Hassan Iqbal, Zulfiqar Ahmad, Abdur Rehman, Muhammad Sudais Hassan, Manal Sharif","doi":"10.1007/s00535-026-02501-6","DOIUrl":"10.1007/s00535-026-02501-6","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rs57494551 increases CXCR5 expression and IgM⁺ CXCR5⁺ B-cell infiltration in the portal area of primary biliary cholangitis.","authors":"Yuki Hitomi, Yoshihiro Aiba, Kazuko Ueno, Haruka Takahashi, Michihiro Kono, Kazuhiro Sugi, Yuji Teraoka, Shintaro Takaki, Atsushi Naganuma, Motoyuki Kojima, Nao Nishida, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Michio Yasunami, Atsumasa Komori, Shinji Shimoda, Kazuyoshi Ishigaki, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura","doi":"10.1007/s00535-026-02493-3","DOIUrl":"https://doi.org/10.1007/s00535-026-02493-3","url":null,"abstract":"<p><strong>Background: </strong>Primary biliary cholangitis (PBC) is a chronic, progressive, cholestatic liver disease caused by autoimmune reactions. A previous international meta-analysis of a genome-wide association study (GWAS) reported a robust association of the human chr.11q23.3 locus including C-X-C motif chemokine receptor 5 (CXCR5) with susceptibility to PBC. However, the molecular mechanism by which CXCR5 confers disease susceptibility in PBC remains unclear.</p><p><strong>Methods: </strong>Cutting-edge post-GWAS analyses were conducted using in silico and in vitro functional approaches, including multi-omics analysis, machine-learning-based transcription factor prediction, and prime editor as a genome-editing technology. Expression data for CXCR5 and correlated genes were obtained by RNA-seq and immunohistochemistry analyses.</p><p><strong>Results: </strong>Among the variants around CXCR5, rs57494551 was identified as a disease-causal variant for PBC. rs57494551 regulates endogenous CXCR5 expression in B-cells through binding to the transcription repressor TEA domain transcription factor 3 (TEAD3). CXCR5 expression was correlated with disease activity, as identified by hierarchical clustering of mRNA expression patterns, and portal inflammation markers, such as serum IgM, Aspartate Transferase (AST), and Mac-2 binding protein glycosylation isomer (M2BPGi). The number of IgM⁺ CXCR5⁺ B-cells was increased in the portal area of PBC with high-disease activity.</p><p><strong>Conclusions: </strong>Immune dysregulation and portal inflammation are affected by increased expression of CXCR5 on IgM⁺ B-cells in PBC patients who have the risk allele of rs57494551, indicating that CXCR5 is a potential therapeutic target for PBC.</p><p><strong>Highlights: </strong>Among hundreds of genetic variants in CXCR5, rs57494551 was identified as a disease-causal variant using cutting-edge post-GWAS in silico and in vitro analyses, including multi-omics analysis, machine learning-based prediction, and the genome-editing technology \"Prime Editor.\" The disease risk allele of rs57494551 increases endogenous CXCR5 expression in B-cells by releasing the binding of the transcriptional repressor TEAD3. RNA-seq and immunohistochemistry analyses revealed that CXCR5 expression is correlated with disease activity and portal inflammation markers. Furthermore, the number of IgM+ CXCR5+ B-cells was increased in the portal area of PBC with high disease activity. As well as PBC, the signifi cant associations between CXCR5 and susceptibility to various autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, systemic sclerosis, celiac disease, and Sjögren's syndrome, could be explained by the effect of rs57494551.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell analysis reveals crosstalk between TREM1-positive myeloid cells and cancer-associated fibroblasts in colorectal cancer progression.","authors":"Shang-Yin Wu, Po-Chuan Chen, Ren-Hao Chan, Chung-Hsing Chen, Yi-Hsuan Huang, Yi-Jing Huang, Bing-Syuan Chung, Che-Hung Shen, Hsin-Yu Kuo, Jui-Wen Kang, Chung-Ta Lee, Hui-Ju Tsai, Yu-Chen Fang, Peng-Chan Lin, Yu-Min Yeh, Shang-Hung Chen","doi":"10.1007/s00535-026-02430-4","DOIUrl":"10.1007/s00535-026-02430-4","url":null,"abstract":"<p><strong>Background: </strong>The limited efficacy of immunotherapy in colorectal cancer (CRC) underscores the need to better define immunosuppressive mechanisms within the tumor microenvironment (TME). We applied single-cell RNA sequencing (scRNA-seq) to characterize stromal-immune interactions shaping the CRC TME.</p><p><strong>Methods: </strong>Paired tumor and adjacent normal mucosa samples from eight patients with CRC were analyzed by scRNA-seq. Integrated bioinformatic approaches, including trajectory inference, transcriptional regulon analysis, and cell-cell communication modeling, were used to define cellular differentiation and intercellular signaling. Key findings were validated using The Cancer Genome Atlas datasets, multiplex immunofluorescence staining, and in vitro functional assays.</p><p><strong>Results: </strong>Trajectory analysis demonstrated a progressive increase in triggering receptor expressed on myeloid cells 1 (TREM1) expression during tumor-associated myeloid differentiation. TREM1-positive myeloid cells exhibited enriched M2-like signatures and were preferentially associated with consensus molecular subtype 4 tumors, characterized by stromal activation and poor clinical outcomes. Stromal profiling identified an α-smooth muscle actin (ACTA2)-positive population associated with CRC progression. Spatial analyses revealed close localization of TREM1-positive myeloid cells and ACTA2-positive cancer-associated fibroblasts (CAFs) in tumor tissues. Mechanistically, integrated bioinformatic analyses indicated that TREM1-positive myeloid cells engage CAFs primarily through secreted phosphoprotein 1 (SPP1) signaling, while CAFs reinforce immunosuppressive myeloid phenotypes via TGF-β-associated extracellular matrix pathways. Functional assays showed that TREM1 inhibition reduced SPP1 expression and attenuated M2 macrophage polarization.</p><p><strong>Conclusions: </strong>These findings identify a bidirectional interaction between TREM1-positive myeloid cells and CAFs that contributes to a profibrotic and immunosuppressive CRC microenvironment, highlighting the TREM1-SPP1 axis as a pathway of potential translational relevance.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1104-1122"},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal treatment selection for hepatocellular carcinoma in the era of immunotherapy.","authors":"Chen-Ta Chi, Yi-Hsiang Huang","doi":"10.1007/s00535-026-02411-7","DOIUrl":"10.1007/s00535-026-02411-7","url":null,"abstract":"<p><p>Immunotherapy has revolutionized hepatocellular carcinoma (HCC) management, necessitating personalized strategies in current guidelines. Despite curative intent for early-stage HCC, recurrence rates remain high. While antiviral therapy mitigates risk, no adjuvant therapy is currently established for high-risk patients. Artificial intelligence (AI) models now offer promising tools for predicting post-resection recurrence.For intermediate-stage HCC, the 7-11 criteria and radiological patterns guide treatment selection. Combining transarterial chemoembolization (TACE) with tyrosine kinase inhibitors has already improved objective response rates (ORR) and progression-free survival (PFS) over TACE monotherapy. Furthermore, the Phase III EMERALD-1 and LEAP-012 trials demonstrated that TACE plus immunotherapy significantly extends PFS. The TALENTACE trial further investigates this synergy, evaluating the efficacy and safety of TACE combined with immune checkpoint inhibitors (ICIs) combination therapy to optimize outcomes in this population.Achieving a cancer-free state through curative conversion-utilizing liver-directed, systemic, or combination therapies-remains a primary clinical goal. While ICIs are the standard for advanced HCC, reliable biomarkers are still lacking. Emerging evidence suggests that the tumor microenvironment, genetic signatures, and the gut microbiota-metabolite axis are significantly associated with ICI outcomes. Integrating these complex biological features through machine learning holds the potential to identify robust biomarkers, ultimately refining immunotherapy selection and patient prognosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1041-1058"},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of lymph-node metastasis in early onset T1 colorectal cancer: a systematic review and meta-analysis.","authors":"Hiromu Fukuda, Yoshito Hayashi, Shinji Yoneda, Yujiro Adachi, Ayaka Tajiri, Eiji Kimura, Ryotaro Uema, Takeo Yoshihara, Yoshiki Tsujii, Takahiro Kodama, Tetsuo Takehara","doi":"10.1007/s00535-026-02465-7","DOIUrl":"10.1007/s00535-026-02465-7","url":null,"abstract":"<p><strong>Background: </strong>Despite the increasing incidence of early onset T1 colorectal cancer (T1 CRC), its features remain poorly understood. We examined whether early onset T1 CRC is associated with a higher rate of lymph-node metastasis (LNM).</p><p><strong>Methods: </strong>We included studies reporting age-specific LNM rates for patients aged < 50 and ≥ 50 years. Sensitivity analyses were performed to assess the impact of overlapping and selected subset datasets. Subgroup analyses were conducted to evaluate the association between clinicopathological variables and age. The risk of bias was assessed using the Risk of Bias In Non-randomized Studies of Interventions Version 2.</p><p><strong>Results: </strong>Of the 1214 records identified, 10 studies comprising 11 databases were included. After excluding overlapping and selected subset data, six databases from five studies with 29,132 patients were analyzed. Of these, 2759 (9.4%) were aged < 50 years at diagnosis, and the pooled LNM rates were 19.2% (95% confidence interval [CI], 17.8-20.6) in early onset and 11.1% (95% CI 10.7-11.5) in late-onset T1 CRC, representing an absolute difference of approximately 8%. Early onset T1 CRC was associated with higher odds of LNM than late-onset disease (OR: 1.94; 95% CI 1.75-2.15; I² = 0%). Despite serious confounding in three studies, multivariable analyses adjusting for clinical covariates showed that younger age was associated with higher odds of LNM, and adjusted ORs for older patients ranged between 0.46 and 0.90 compared with those aged < 50 years.</p><p><strong>Conclusions: </strong>This meta-analysis demonstrated that early onset T1 CRC is associated with higher odds of LNM compared with late-onset T1 CRC in surgically treated patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1068-1082"},"PeriodicalIF":5.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13407934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}