World Journal of Gastroenterology最新文献

{"title":"Factors influencing diagnostic delays in celiac disease.","authors":"Ting Li, Yan Feng, Man Wang, Chun Wang, Feng Gao","doi":"10.3748/wjg.v31.i30.109585","DOIUrl":"10.3748/wjg.v31.i30.109585","url":null,"abstract":"<p><strong>Background: </strong>Celiac disease (CeD), an autoimmune disorder triggered by gluten ingestion, is characterized by non-specific clinical manifestations such as fatigue, abdominal pain, and nutritional deficiencies, often leading to substantial diagnostic delays. Prolonged delays (≥ 2 years from symptom onset) are associated with increased risks of complications like osteoporosis, small intestinal lymphoma, and reduced quality of life.</p><p><strong>Aim: </strong>To estimate diagnostic delay prevalence and identify risk factors in Chinese CeD patients.</p><p><strong>Methods: </strong>We reviewed clinical records of 166 patients diagnosed with CeD from 2017 onward. Patient-attributed delays were measured from symptom onset to first consultation, while physician-related delays were measured from initial visit to diagnosis/treatment. Data on demographics, symptoms, time from onset to diagnosis, and laboratory results were analyzed. Logistic regression models were used to identify associations, while restricted cubic splines explored nonlinearities. Mediation analysis assessed the roles of intermediate factors in delayed diagnosis.</p><p><strong>Results: </strong>Delayed diagnosis (over 2 years from symptom onset) was observed in 42.2% of patients. Patients with diagnostic delay exceeding 5 years accounted for 18.7%. The mean interval from symptom onset to the first medical visit was 12.32 months, with an average of 20.57 months from the first visit to diagnosis. The time from first consultation to diagnosis significantly increased with prolonged delay (<i>P <</i> 0.001). Multivariate analysis showed that blood urea nitrogen (BUN) was an independent risk factor (OR = 1.29, 95%CI: 1.01-1.65, <i>P =</i> 0.038). A nonlinear association was observed between BUN and delayed diagnosis, with a threshold of 4.3 mmol/L; the risk significantly increased above this threshold (OR = 1.39, <i>P =</i> 0.04). Subgroup analyses indicated that the risk effect of BUN was stronger in females, non-classical CeD patients, Kazak ethnic group members, individuals without vitamin D deficiency/anemia, and those with Marsh III pathology (all <i>P <</i> 0.05). Mediation analysis revealed that folic acid deficiency and anemia mediated 11.9% (<i>P</i> = 0.028) and 13.0% (<i>P =</i> 0.044) of the effect of BUN on diagnostic delay, respectively.</p><p><strong>Conclusion: </strong>Elevated BUN levels are independent predictors of diagnostic delay in CeD, with heterogeneity observed across gender, disease subtype, ethnicity, and pathological type. Clinicians should prioritize high-risk populations with BUN ≥ 4.3 mmol/L, particularly female patients with non-classical CeD and Kazak individuals, to reduce diagnostic delay.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"109585"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression <i>in vitro</i>\".","authors":"Xiao-Dong Wang, Feng Qi","doi":"10.3748/wjg.v31.i30.109418","DOIUrl":"10.3748/wjg.v31.i30.109418","url":null,"abstract":"<p><p>[This corrects the article on p. 1697 in vol. 25, PMID: 31011255.].</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"109418"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Xuanshen decoction: A novel approach to combat slow transit constipation.","authors":"Xing-Lin Zeng, Lian-Jun Zhu, Yu Zhang, Xiang-Dong Yang, Yu-Jun Zhu","doi":"10.3748/wjg.v31.i30.109187","DOIUrl":"10.3748/wjg.v31.i30.109187","url":null,"abstract":"<p><strong>Background: </strong>Xuanshen decoction (XSD) is a traditional Chinese medicine formulation that is often applied in treating slow transit constipation (STC). However, its specific therapeutic mechanism remains to be characterized.</p><p><strong>Aim: </strong>To investigate the mechanism of XSD for STC, we combined network pharmacology prediction, molecular docking analysis, and <i>in vivo</i> studies.</p><p><strong>Methods: </strong>The therapeutic effects of XSD on loperamide-induced STC in rats were assessed through 24-hour fecal number, fecal moisture content, and intestinal propelling rate. Hematoxylin-eosin and Alcian blue/periodic acid-Schiff staining were applied to analyze colonic mucosa for histopathological presentation and mucin production. Next, the mechanism of action of XSD for STC was elucidated through network pharmacology and molecular docking analyses, and the findings were validated by the animal experiments.</p><p><strong>Results: </strong>XSD significantly alleviated the symptoms of STC in rats. Relative to the STC rats, in the medium-dose XSD and high-dose XSD rats, stem cell factor, C-kit, phospho-phosphoinositide 3-kinase/phosphoinositide 3-kinase, phospho-protein kinase B/protein kinase B, catalase, and superoxide dismutase were substantially upregulated (<i>P</i> < 0.01); nuclear factor erythroid 2-related factor 2 (nuclear/cytoplasmic) and B-cell lymphoma 2 (Bcl-2) were increased (<i>P</i> < 0.05), while cleaved caspase-3, Bcl-2-associated X protein (Bax)/Bcl-2, and malondialdehyde were significantly reduced (<i>P</i> < 0.01). Heme oxygenase-1 and glutathione peroxidase in the high-dose XSD group were significantly increased (<i>P</i> < 0.01), and Bax was statistically lowered (<i>P</i> < 0.01); glutathione peroxidase in the medium-dose XSD group was increased (<i>P</i> < 0.05), while Bax was reduced (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>XSD may inhibit oxidative-stress-induced apoptosis in interstitial cells of Cajal by stimulating the phosphoinositide 3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 pathway, thereby effectively treating STC.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"109187"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of triglyceride-glucose index with long-term prognosis in advanced hepatocellular carcinoma patients receiving immunotherapy and targeted therapy.","authors":"Geng-Chen Li, Zhi-Yuan Yao, Hong-Sen Mao, Zheng-Xiang Han","doi":"10.3748/wjg.v31.i30.109863","DOIUrl":"10.3748/wjg.v31.i30.109863","url":null,"abstract":"<p><strong>Background: </strong>Primary liver cancer, particularly hepatocellular carcinoma (HCC), ranks as the sixth most prevalent cancer globally and the third major cause of cancer-associated mortality. Despite the available immunotherapies and combined immunotherapy and targeted therapy, the prognosis for many patients remains dismal. Accurately identifying the appropriate patient cohorts is crucial for improving treatment outcomes.</p><p><strong>Aim: </strong>To investigate the prognostic value of the triglyceride-glucose (TyG) index - a novel, accessible marker of insulin resistance - in predicting therapeutic outcomes among patients with hepatitis B virus (HBV)-related HCC treated with camrelizumab and lenvatinib.</p><p><strong>Methods: </strong>In this study, we conducted a retrospective review of 278 patients diagnosed with stage B/C HBV-related HCC who underwent combination therapy. Based on their TyG index, patients were categorized into high and low TyG index groups. A nomogram prediction model was developed based on independent prognostic factors for overall survival (OS) and validated using the C-index and calibration curves.</p><p><strong>Results: </strong>Of the 278 patients enrolled in the study, 144 were assigned to the high TyG index group, while the remaining 134 were classified into the low index group. Importantly, patients with a low TyG index demonstrated a significantly prolonged median progression-free survival and OS relative to those with a high index. Additionally, the objective response rate and disease control rate were 22.39% and 64.18% in the low TyG index group, whereas they were 12.50% and 51.39% in the high TyG index group, respectively. Moreover, the incidence of hypertension was higher in the high TyG index group than in the low TyG index group. The incidence of other adverse effects did not differ significantly between the groups. Multivariate regression analysis identified independent prognostic factors for OS, including the Barcelona Clinic Liver Cancer stage, alpha-fetoprotein level, Eastern Cooperative Oncology Group score, distant metastasis, and the TyG index. The risk ratio of the TyG index was 0.48 (95% confidence interval: 0.31-0.72, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>The TyG index is a reliable long-term predictor of response to combined immunotherapy and targeted therapy in patients with HBV-related HCC. Patients with a low TyG index tend to experience better clinical outcomes.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"109863"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum metabolomic characteristics and their predictive value for ninety-day prognosis in patients with acute-on-chronic liver failure.","authors":"Yan Liu, Ying Xiao, Lian-Feng Ai, Jing-Jing Zhang, Jian-Dong Zhang, Ze-Qiang Qi, Lei Dong, Ya-Dong Wang","doi":"10.3748/wjg.v31.i30.110401","DOIUrl":"10.3748/wjg.v31.i30.110401","url":null,"abstract":"<p><strong>Background: </strong>Acute-on-chronic liver failure (ACLF) is characterized by severe metabolic disturbances; however, the specific metabolomic features and their predictive value on 90-day prognosis remain unclear.</p><p><strong>Aim: </strong>To identify serum metabolomic changes in patients with ACLF with different prognoses to support clinical prediction of outcomes and treatment decisions.</p><p><strong>Methods: </strong>This non-interventional, observational case-control study enrolled 58 patients with ACLF. Fasting venous blood samples were analyzed using targeted metabolomics. Univariate and multivariate statistical analyses identified differential metabolites among 18 amino acids, 11 fatty acids, 5 gut microbiota-related metabolites, and 4 bile acid metabolites. Binary logistic regression identified independent mortality risk factors, visualized <i>via</i> forest plots and receiver operating characteristic curves.</p><p><strong>Results: </strong>Significant differences (<i>P</i> < 0.05) were observed between the death and survival groups in baseline age, model for end-stage liver disease score, model for end-stage liver disease with sodium, neutrophil-to-lymphocyte ratio (NLR), total bilirubin, serum creatinine, blood urea nitrogen, and platelet count. Metabolites, including L-carnitine, creatinine, alanine, arginine (Arg), proline, choline, and oleic acid, also showed statistically significant differences between the groups. Multivariate analysis identified age, NLR, and Arg as independent risk factors for 90-day mortality in patients with ACLF. The predictive model, age-NLR-Arg = -15.481 + 0.135 × age + 0.156 × NLR + 0.203 × Arg, with a cutoff of 0.759, achieved an area under the receiver operating characteristic curve of 0.945 with sensitivity of 84.0% and specificity of 87.9%.</p><p><strong>Conclusion: </strong>The age-NLR-Arg model demonstrates a strong predictive value for 90-day mortality risk in patients with ACLF.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"110401"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.","authors":"Jing Lv, He-Ping Zhao, Yan Yu, Ji-Han Wang, Xiao-Jun Zhang, Zhi-Qi Guo, Wen-Yan Jiang, Kai Wang, Lei Guo","doi":"10.3748/wjg.v31.i30.108680","DOIUrl":"10.3748/wjg.v31.i30.108680","url":null,"abstract":"<p><p>Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis <i>via</i> lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"108680"},"PeriodicalIF":5.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flotillin-1 promotes the progression of hepatocellular carcinoma by activating TFE3-mediated Golgi stress response <i>via</i> inhibition of mTORC1/2.","authors":"Liang Zhang, Cheng-Zhi Bai, Jia-Yan Shan, Hong-Li Xue, Shu-Mei Zheng, Ya-Lun Chen, Shan-Hong Tang","doi":"10.3748/wjg.v31.i29.106895","DOIUrl":"10.3748/wjg.v31.i29.106895","url":null,"abstract":"<p><strong>Background: </strong>It is critical to explore effective therapeutic targets for improving the survival rate of patients with hepatocellular carcinoma (HCC). Although many studies have focused on flotillin-1 (FLOT1) as a lipid raft-associated protein that regulates the activation of some proteins or kinases to promote tumor cell survival and proliferation, few studies have explored the regulation of Golgi apparatus function.</p><p><strong>Aim: </strong>To investigate the molecular mechanism through which FLOT1 activates the Golgi stress response downstream of transcription factor E3 (TFE3), thereby promoting the progression of HCC.</p><p><strong>Methods: </strong>FLOT1 expression in HCC tissue, HCC cell lines, and nude mouse tumor models was assessed. The impact of FLOT1 silencing or its overexpression on the proliferation of HCC cells was studied. CCK-8, flow cytometry, and transwell assays were used to assess the proliferation, cell cycle, migration, and invasion abilities of HCC cells. A dual-luciferase reporter assay was used to study the effect of FLOT1 on the transcriptional activity of the downstream Golgi apparatus stress element promoter of TFE3. Western blotting, co-immunoprecipitation, and immunofluorescence staining were employed to detect relevant proteins.</p><p><strong>Results: </strong>High FLOT1 expression was correlated with a poor prognosis in patients with HCC. The knockdown of FLOT1 suppressed the proliferation, migration, and invasion of HCC cells and promoted their apoptosis. Xenograft assays revealed that FLOT1 knockdown inhibited HCC tumorigenesis <i>in vivo</i>. Mechanistically, FLOT1 inhibited the expression of mechanistic target of rapamycin complex 1/2 proteins through ubiquitination and downstream effector p-S6 kinase-T389, leading to the dephosphorylation and nuclear translocation of TFE3 and promotion of Golgi stress-mediated responses, ultimately resulting in HCC progression.</p><p><strong>Conclusion: </strong>FLOT1 recruits and inhibits mechanistic target of rapamycin complex 1/2, causing dephosphorylation and TFE3 nuclear translocation, thereby activating the Golgi stress response and further promoting the proliferation, migration, and invasion capabilities of HCC cells. These results underscore the potential of FLOT1 as a promising therapeutic target for HCC.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 29","pages":"106895"},"PeriodicalIF":5.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the pathogenesis in Crohn's disease and ulcerative colitis.","authors":"Himanshu Agrawal, Nikhil Gupta","doi":"10.3748/wjg.v31.i29.109892","DOIUrl":"10.3748/wjg.v31.i29.109892","url":null,"abstract":"<p><p>This article discusses Yang and Zhang's review on Crohn's disease and ulcerative colitis pathogenesis, emphasizing immune dysregulation, genetics, microbiota, and environmental factors. It highlights the need for personalized approaches, longitudinal studies, and better diagnostic tools to improve treatment strategies and patient outcomes in inflammatory bowel disease.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 29","pages":"109892"},"PeriodicalIF":5.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positioning and sequencing of advanced therapies in inflammatory bowel disease: A guide for clinical practice.","authors":"Marcello Imbrizi, Matheus F C Azevedo, Julio P Baima, Natália S F Queiroz, Rogério S Parra, Sandro D C Ferreira, Ligia Y Sassaki, Julio Maria F Chebli","doi":"10.3748/wjg.v31.i29.107745","DOIUrl":"10.3748/wjg.v31.i29.107745","url":null,"abstract":"<p><p>Over the past decade, the therapeutic armamentarium for inflammatory bowel disease (IBD) has substantially expanded with the incorporation of multiple classes of advanced therapies. Currently, in addition to tumor necrosis factor-α inhibitors, the therapeutic arsenal for IBD includes anti-integrin agents, interleukin (IL)-12/23p40 and IL-23p19 antibodies, Janus kinase inhibitors, and sphingosine 1-phosphate receptor modulators. Although advances in IBD pharmacotherapy have enabled disease remission and improved control of intestinal inflammation in many individuals previously considered clinically 'intractable', they have also increased the complexity of decision-making related to the initial positioning and sequencing of therapies in the heterogeneous clinical presentations of IBD. Until molecular and genetic markers capable of predicting therapeutic responses become available in practice, the choice of initial and subsequent therapy in individuals with IBD is based on factors including disease severity, phenotype, risk of complications, comorbidities, extraintestinal manifestations, and the balance between efficacy, safety, convenience, and access. This review explores the factors that influence treatment decisions regarding initial therapy selection and sequencing across IBD scenarios, offering practical tips for personalizing therapy based on the safety and efficacy of advanced treatments and the individual's risk of disease- or therapy-related adverse outcomes.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 29","pages":"107745"},"PeriodicalIF":5.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted therapy combined with immunotherapy <i>vs</i> trifluridine/tipiracil with bevacizumab as late-line therapy in metastatic colorectal cancer.","authors":"Zhao Gao, Xiao-Yan Wang, Tao Song, Zhi-Gang Shen, Xiao-Yun Wang, Shi-Kai Wu, Xuan Jin","doi":"10.3748/wjg.v31.i29.109947","DOIUrl":"10.3748/wjg.v31.i29.109947","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Targeted therapy combined with anti-programmed cell death 1 immunotherapy (TP) and trifluridine/tipiracil (TAS-102) combined with bevacizumab (TB) are two common therapies for patients with late-line therapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). However, it is still unclear which therapy can bring better prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To evaluate the effectiveness and safety of TP &lt;i&gt;vs&lt;/i&gt; TB as the late-line regimen for MSS mCRC in the real world.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received at least the second line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Landmark analysis was performed to create segmented survival curves, studying the impact of treatment regimen on prognosis during different follow-up periods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Between July 2019 and March 2025 (data cutoff), 127 eligible patients were enrolled, with 88 and 39 patients assigned to the TP and TB cohorts, respectively, based on treatment allocation. At a global median follow-up of 9.73 months, the crude median PFS was 3.9 months (95%CI: 3.03-5.53) in the TP cohort &lt;i&gt;vs&lt;/i&gt; 4.17 months (95%CI: 2.87-5.6) in the TB cohort, yielding a nonsignificant HR of 1.43 (95%CI: 0.94-2.18, &lt;i&gt;P&lt;/i&gt; = 0.092; TB as reference). Multivariate Cox regression analysis, adjusted for sex, age &gt; 60 years, Eastern Cooperative Oncology Group performance status, &lt;i&gt;RAS&lt;/i&gt; mutation, primary tumor location (left &lt;i&gt;vs&lt;/i&gt; right), number of metastatic organs (liver/lung), and treatment line (≥ 3&lt;sup&gt;rd&lt;/sup&gt; line), demonstrated an adjusted HR of 1.23 (95%CI: 0.80-1.88, &lt;i&gt;P&lt;/i&gt; = 0.348). PS-based analyses using three methodologies: Inverse probability weighting, PS matching (post-matching &lt;i&gt;n&lt;/i&gt; = 55 &lt;i&gt;vs&lt;/i&gt; 30), and PS-adjusted multivariate Cox regression. These analyses revealed consistent nonsignificant trends favoring TB, with HRs for TP of 1.26 (95%CI: 0.76-2.10, &lt;i&gt;P&lt;/i&gt; = 0.077), 1.42 (95%CI: 0.87-2.34, &lt;i&gt;P&lt;/i&gt; = 0.164), and 1.26 (95%CI: 0.76-2.10, &lt;i&gt;P&lt;/i&gt; = 0.367), respectively. Notably, landmark PFS analyses at 90, 120, and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints (&lt;i&gt;P&lt;/i&gt; = 0.048, 0.031, and 0.035, respectively), suggesting sustained clinical benefits in TP responders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses. However, patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advan","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 29","pages":"109947"},"PeriodicalIF":5.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}