Journal of gastrointestinal oncology最新文献

{"title":"The association between coffee consumption and esophageal cancer risk: a systematic review and meta-analysis of current observational evidence.","authors":"Yiwei Zhao, Zixin Cai, Jingjing Zhang","doi":"10.21037/jgo-2026-0327","DOIUrl":"10.21037/jgo-2026-0327","url":null,"abstract":"<p><strong>Background: </strong>Esophageal cancer remains a leading cause of cancer-related mortality worldwide, yet the association between coffee consumption-a ubiquitous dietary exposure-and its risk remains inconclusive. This meta-analysis systematically evaluates the association between coffee consumption and esophageal cancer risk, aiming to quantify the overall effect and explore potential heterogeneity.</p><p><strong>Methods: </strong>A systematic search of PubMed, Cochrane Library, Embase, and Web of Science was conducted up to January 2026 for studies comparing coffee intake between esophageal cancer patients and healthy controls. Two reviewers independently extracted data. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Heterogeneity was assessed using the I2 statistic. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.</p><p><strong>Results: </strong>Across 22 included studies encompassing 1,775,988 participants (7,124 cases), neither cohort nor case-control studies demonstrated a significant association between coffee consumption and esophageal cancer risk. The pooled HR from cohort studies was 0.87 (95% CI: 0.74-1.03; I2=24.2%), while the pooled OR from case-control studies was 1.02 (95% CI: 0.77-1.35; I2=66.7%).</p><p><strong>Conclusions: </strong>This meta-analysis found no statistically significant association between coffee consumption and esophageal cancer risk. The available evidence, of low certainty, does not support coffee as a major risk factor. Exploratory analyses on beverage temperature are inconclusive and require confirmation in prospective studies with standardized exposure assessment. This review was registered in PROSPERO (CRD42024562527).</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"205"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of mucinous adenocarcinoma after curative surgery for stage I-III colorectal cancer: a large population-based cohort study.","authors":"Jiyang Li, Tengyu Zeng, Xianqiang Xie, Dongsheng Li, Kejin Yan, Hongliang Zhu","doi":"10.21037/jgo-2026-0334","DOIUrl":"10.21037/jgo-2026-0334","url":null,"abstract":"<p><strong>Background: </strong>The prognostic significance of mucinous adenocarcinoma (MA) compared to conventional adenocarcinoma (AC) in colorectal cancer (CRC) remains controversial, particularly in the context of modern treatment. This study aims to clarify the independent prognostic value of MA in the contemporary treatment model through large-sample analysis, in order to provide more evidence for risk stratification and treatment decision-making for MA patients.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed patients with stage I-III CRC who underwent curative resection between 2010 and 2022 from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were compared between MA and AC groups. Multivariable Cox regression and subgroup analyses stratified by pathological stage, tumor site, and chemotherapy modality were performed. Propensity score matching (PSM) was applied to stage III cohorts to control for confounding.</p><p><strong>Results: </strong>Among 69,335 patients with CRC, MA was associated with significantly worse OS and CSS before subgroup analysis (P<0.001). However, multivariable analysis revealed that MA was an independent adverse prognostic factor exclusively in stage III both colon and rectal cancer (all P<0.05), but not in stages I or II. Treatment-stratified analysis in stage III patients revealed that the prognostic impact of MA was highly chemotherapy modality-dependent. In stage III colon and rectal cancer patients who did not receive chemotherapy, MA and AC showed comparable OS and CSS. Conversely, among those who received preoperative or postoperative chemotherapy, MA remained an independent poor prognostic factor (all P<0.05), indicating reduced benefit from chemotherapy compared to AC. Notably, in stage III rectal cancer patients who received combined preoperative and postoperative chemotherapy, the survival disadvantage of MA disappeared. PSM analysis confirmed the robustness of these findings.</p><p><strong>Conclusions: </strong>Our study found that MA was an independent adverse prognostic factor in stage III CRC when patients were receiving standard single-modality chemotherapy. However, among stage III rectal cancer patients treated with combined preoperative and postoperative chemotherapy, the prognostic disadvantage of MA was eliminated.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"238"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction-model development and temporal validation for six-month cancer-specific mortality in <i>de novo</i> metastatic gastroesophageal junction adenocarcinoma: a SEER-based study.","authors":"Lunjian Xia, Ziao Wang, Xiaoqian Guo, Xueting Men, Weikun Fan, Qifeng Lu","doi":"10.21037/jgo-2026-0513","DOIUrl":"10.21037/jgo-2026-0513","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;i&gt;De novo&lt;/i&gt; metastatic gastroesophageal junction adenocarcinoma (GEJA) is associated with heterogeneous short-term outcomes. A six-month cancer-specific mortality (CSM) horizon is clinically relevant because it reflects early disease lethality, limited physiological reserve, and the period in which first-line treatment tolerance and timely palliative discussions are often determined. Existing prediction tools have largely addressed long-term survival, postoperative disease, or metastatic gastric cancer as a broad entity. This study developed and temporally validated an interpretable prediction model for six-month CSM in de novo metastatic GEJA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Patients diagnosed in 2010-2021 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Eligible cases had C16.0 cardia primary site, adenocarcinoma-related histology, malignant behavior, positive histology, single or first primary malignancy, &lt;i&gt;de novo&lt;/i&gt; metastatic disease, and evaluable survival and cause-of-death information. Candidate predictors included demographic characteristics, histology, grade, tumor size, organ-specific metastases, diagnosis year, and first-course treatment-status fields. Patients diagnosed in 2010-2017 formed the development cohort; those diagnosed in 2018-2021 formed the temporal validation cohort. The endpoint was SEER-defined cancer-specific death within six months after diagnosis. Candidate models included logistic regression, elastic net, random forest, extreme gradient boosting (XGBoost), gradient boosting machine, and multilayer perceptron. Discrimination, calibration, Brier score, decision curves, threshold-specific sensitivity and specificity, and SHapley Additive exPlanations (SHAP) were evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The analytic cohort included 6,564 patients, with 4,315 in development and 2,249 in temporal validation. Median age was 64 years, 5,189 patients (79.1%) were male, and liver metastasis was present in 3,249 patients (49.5%). Six-month CSM occurred in 1,941 patients (45.0%) in development and 902 patients (40.1%) in temporal validation. The selected XGBoost model achieved an area under the curve (AUC) of 0.808 [95% confidence interval (CI), 0.795-0.821] in development and 0.786 (95% CI, 0.767-0.806) in temporal validation. In temporal validation, the Brier score was 0.173 versus a null Brier score of 0.240, the calibration slope was 1.130, and the integrated calibration index was 0.026. At the high-risk threshold, sensitivity was 56.7%, specificity was 90.2%, positive predictive value was 79.5%, and negative predictive value was 75.7%. Observed six-month CSM was 20.2%, 32.1%, and 79.5% in low-, intermediate-, and high-risk groups, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A SEER-based prediction model was developed and temporally validated for six-month CSM in de novo metastatic GEJA. The model provided moderate discrimination, acceptable","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"209"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic biopsy-to-treatment interval and risk of recurrence in localized pancreatic ductal adenocarcinoma: every week counts.","authors":"Marisa Siebel, Meredith Akerman, Austin Siebel, Neha Puttagunta, Naveena Chittineedi, Anthony Coelho, Bhupesh Parashar","doi":"10.21037/jgo-2026-0444","DOIUrl":"10.21037/jgo-2026-0444","url":null,"abstract":"<p><p>The impact of the interval between diagnostic biopsy and treatment initiation on oncologic outcomes in localized pancreatic ductal adenocarcinoma (PDAC) remains poorly characterized. We conducted an institutional review board (IRB)-approved retrospective cohort study of 91 consecutive patients diagnosed with localized PDAC between 2016 and 2024 at a tertiary care academic medical center. The primary exposure was the interval (days) from diagnostic biopsy to initiation of any curative-intent treatment. The primary outcome was time from treatment initiation to develop recurrence or distant metastasis. Kaplan-Meier analysis and Cox proportional hazards (PH) regression were used to assess associations. Models were adjusted for age, sex, radiation therapy, and surgery, and the PH assumption was verified using scaled Schoenfeld residual tests. Of 91 patients (39 male, 52 female), 61 (67%) developed recurrence or distant metastasis during follow-up. The median time to recurrence or metastasis was 21.7 months [95% confidence interval (CI): 17.9-24.9]. The median biopsy-to-treatment interval was 27 days [interquartile range (IQR): 21-38] among patients without recurrence or distant metastasis and 29 days (IQR: 24-44) among those with the event. Each additional 7-day delay from biopsy to treatment initiation was associated with a 9% increase in the hazard of recurrence or metastasis on multivariable analysis [adjusted hazard ratio (aHR), 1.09; 95% CI: 1.02-1.16; P=0.01]. Absence of surgery was also independently associated with worse outcomes (aHR, 2.54; 95% CI: 1.12-5.76; P=0.03). In this single-institution retrospective cohort, a longer biopsy-to-treatment interval was associated with an increased hazard of recurrence and distant metastasis. These findings should be interpreted cautiously given the retrospective single-center design, limited sample size, and absence of key prognostic covariates including resectability status; validation in larger prospective multi-institutional cohorts is warranted.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"269"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Barcelona Clinic Liver Cancer strategy adherence in hepatocellular carcinoma and its influence on long-term outcomes.","authors":"","doi":"10.21037/jgo-20262-05","DOIUrl":"10.21037/jgo-20262-05","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.21037/jgo-2025-639.].</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"283"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships among slow diffusion coefficient and diffusion-derived 'vessel density' signal features, Gadoxetate delayed enhancement, tumor size, tumor grading, and patient survival: an exploratory study of mass-forming intrahepatic cholangiocarcinoma.","authors":"Cun-Jing Zheng, Fan-Yi Xu, Xiao-Hui Duan, Wen-Ting Zeng, Ming-Hua Sun, Jun Shen, Yì Xiáng J Wáng","doi":"10.21037/jgo-2026-0225","DOIUrl":"10.21037/jgo-2026-0225","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Intrahepatic cholangiocarcinoma (ICC) literature suggests that hypervascularity on arterial contrast agent enhancement (CE) is associated with better prognosis, while rich stroma is associated with poorer prognosis. This exploratory study evaluates the relationships among slow diffusion coefficient (SDC) and diffusion-derived 'vessel density' (DDVD) signal features, Gadoxetate delayed enhancement, and survival in patients with mass-forming ICC. An ICC with higher SDC may be associated with potentially better patient survival due to less stromal fibrosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were prospectively acquired in two centers [Center 1 (Sun Yat-Sen Memorial Hospital): ICC 21 cases; Center 2 (Fifth Affiliated Hospital of Anhui Medical University): ICC 3 cases]. SDC maps were derived with &lt;i&gt;b&lt;/i&gt;=500 and 800 s/mm&lt;sup&gt;2&lt;/sup&gt; images for Center 1 data, and with &lt;i&gt;b&lt;/i&gt;=400 and 600 s/mm&lt;sup&gt;2&lt;/sup&gt; images for Center 2 data. DDVD maps were calculated from &lt;i&gt;b&lt;/i&gt;=0 and 10 s/mm&lt;sup&gt;2&lt;/sup&gt; images, ADC was calculated from &lt;i&gt;b&lt;/i&gt;=0 and 800 s/mm&lt;sup&gt;2&lt;/sup&gt; images (Center 1) or &lt;i&gt;b&lt;/i&gt;=0 and 600 s/mm&lt;sup&gt;2&lt;/sup&gt; images (Center 2). Relative to the liver signal, tumor SDC and DDVD signals were assigned to six semi-quantitative score (SQS) categories: low signal (scored as '0'), iso-signal (scored as '1'), slightly high signal (scored as '1.5'), high signal (scored as '2'), higher signal (scored as '2.5'), and markedly high signal (scored as '3'). SDC and ADC were also quantitatively measured. Delayed phase magnetic resonance imaging (MRI) scan was obtained at a median of 3 min 51 sec after the contrast agent injection. Percentage area of CE during delayed phase ('% delay CE') was estimated visually and also quantified with the spleen CE signal intensity as the reference. Follow-up data were available in 20 cases from Center 1 (n=9 alive till the last follow-up, n=11 died during the follow-up), and we conducted additional histopathological grading for 14 cases from Center 1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Tumor aggressiveness was negatively correlated with quantitative '% delay CE' (Spearman &lt;i&gt;r&lt;sub&gt;s&lt;/sub&gt;&lt;/i&gt; =0.703, P=0.008). Based on visual assessment, both SDC SQS and DDVD SQS were moderately and positively correlated with '% delay CE', with a Spearman &lt;i&gt;r&lt;sub&gt;s&lt;/sub&gt;&lt;/i&gt; of 0.504 (P=0.02) and 0.549 (P=0.03), respectively&lt;i&gt;.&lt;/i&gt; Correlation of quantitative '% delay CE' with relative threshold of spleen CE signal intensity and ln(SDC&lt;sub&gt;ICC&lt;/sub&gt;/SDC&lt;sub&gt;liver&lt;/sub&gt;) derived a Pearson &lt;i&gt;r&lt;/i&gt; of 0.481 (P=0.03). The alive group (n=9) had a SDC SQS higher than the dead group (n=11, mean: 2.89 &lt;i&gt;vs.&lt;/i&gt; 2.23, P=0.007). The dead group had 4 cases with SDC SQS ≥2.5, three of them had tumor sizes &gt;4,000 mm&lt;sup&gt;2&lt;/sup&gt;, and an additional patient had an advanced age of 76 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;ICCs with higher SDC score (≥2.5) and small/intermediate presenting tumor size (&lt;4,000 cm&lt;sup&gt;2&lt;/su","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"253"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between preoperative statin use and survival after pylorus-preserving pancreaticoduodenectomy for pancreatic or periampullary cancer: a propensity score-matched cohort study.","authors":"Chan-Sik Kim, Yeon-Ju Kim, Namho Kim, Hyeong-Seok Yoon, Young-Ki Kim, Eun-Kyung Ryu, Ji-Hoon Sim, Sung-Moon Jeong","doi":"10.21037/jgo-2026-0469","DOIUrl":"10.21037/jgo-2026-0469","url":null,"abstract":"<p><strong>Background: </strong>Beyond their primary lipid-lowering role, statins exert pleiotropic properties such as anti-inflammatory and endothelial-stabilizing effects. In this study, we investigated whether preoperative statin exposure was associated with postoperative survival outcomes and disease-free survival (DFS) in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD) for pancreatic or periampullary malignancies.</p><p><strong>Methods: </strong>We retrospectively analyzed patients who underwent PPPD at a tertiary center between 2012 and 2016. Short-term (1-year) and long-term outcomes, including 5-year mortality, overall mortality, and DFS, were compared between statin users and nonusers. To minimize baseline imbalance, 1:2 propensity score (PS) matching was performed using a model that incorporated demographic, clinical, and major pathologic prognostic factors, including age, sex, comorbidities, tumor location, tumor-node-metastasis (TNM) stage, resection margin status, lymph-node ratio, tumor grade, and carbohydrate antigen 19-9 (CA19-9). Cox proportional hazards regression was used to assess associations between statin use and outcomes.</p><p><strong>Results: </strong>Among 718 patients, 130 (18.1%) received preoperative statins. After 1:2 matching, 116 statin users and 193 nonusers were analyzed. One-year, 5-year, and overall mortality did not differ significantly between groups before or after matching, and preoperative statin use was not independently associated with 5-year or overall mortality [5-year mortality: adjusted hazard ratio (HR), 0.96, 95% confidence interval (CI), 0.72-1.27; PS-matched HR, 1.09, 95% CI, 0.80-1.49]. Although a lower 1-year mortality was observed after multivariable adjustment, this association was not significant in the crude or PS-matched analyses. DFS likewise showed no significant difference at any outcome in either unadjusted or adjusted analyses.</p><p><strong>Conclusions: </strong>Preoperative statin use was not associated with short-term or long-term survival or oncologic outcomes after PPPD.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"261"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape of acquired resistance alterations in gastrointestinal malignancies after genomically targeted therapy.","authors":"Priyadarshini Pathak, Bennett Caughey, Haley Barnes, Matthew Strickland, Elizabeth Walsh, Jeffrey Clark, Lawrence Blazkowsky, Aparna Parikh, Colin Weekes, Samuel Klempner, Ryan Corcoran","doi":"10.21037/jgo-2025-1-1025","DOIUrl":"10.21037/jgo-2025-1-1025","url":null,"abstract":"<p><strong>Background: </strong>Targeted therapies directed at specific genomic alterations have transformed the management of gastrointestinal (GI) cancers; however, acquired resistance remains inevitable. Circulating tumor DNA (ctDNA) analysis via liquid biopsy provides a non-invasive approach to characterize genomic mechanisms of resistance. We therefore evaluated patterns of acquired genomic resistance in patients with GI cancers treated with targeted therapies.</p><p><strong>Methods: </strong>Patients with GI cancers treated with standard of care or investigational therapies targeting EGFR, HER2, FGFR, MET, KRAS, BRAF for at least 60 days who underwent both baseline comprehensive genomic profiling and post-progression ctDNA sequencing were retrospectively evaluated.</p><p><strong>Results: </strong>Of 106 patients meeting inclusion criteria, 45 had biliary tract cancer (BTC), 42 colorectal cancer (CRC), and 19 other GI malignancies. At least one putative resistance-associated alteration was detected in ctDNA in 53% of cases. Resistance patterns were heterogeneous with 47% showing no detectable alterations and 33% harboring ≥2 resistance alterations. Among 164 total alterations, the majority were single nucleotide variants (82%), followed by amplifications (17%). Overall, 48% were classified as 'bypass' alterations-activating alternative oncogenic pathways, most commonly MAPK signaling-while 52% were 'on-target' alterations involving secondary changes within the drug target. RAS alterations represented a key mechanism of bypass resistance, accounting for 28% of all resistance alterations. Interestingly, in CRC, bypass alterations predominated (69%), whereas in BTCs, on-target alterations were more frequent (61%).</p><p><strong>Conclusions: </strong>Liquid biopsies frequently identify acquired resistance following targeted therapy across GI cancers, often revealing multiple concurrent alterations. Patterns of resistance varied by tumor type, with both on-target and bypass mechanisms observed. These findings highlight common themes of resistance and support the growing clinical role of ctDNA analysis in defining resistance and guiding management in GI malignancies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"243"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of molecular signatures based on the co-expression network of NECSO-related gene <i>TRPM4</i> and its prognostic value in hepatocellular carcinoma.","authors":"Junze Chen, Jiamei Li, Zhiyong Lin, Cheng Zhang, Yongyuan Jian, Kaiyong Huang, Ruiling Su, Xuelin Tan, Xianxiang Chen, Mei Yao","doi":"10.21037/jgo-2026-0363","DOIUrl":"10.21037/jgo-2026-0363","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) demonstrates significant prognostic variability that is not entirely accounted for by traditional staging systems. Necrosis by sodium overload (NECSO) is an emerging programmed cell death pathway, but its clinical relevance in HCC remains undefined. Therefore, this study aimed to identify TRPM4-associated core genes, develop and validate a prognostic signature, and investigate its relationship with the tumor immune microenvironment, tumor mutational burden, and single-cell expression patterns in HCC.</p><p><strong>Methods: </strong>We integrated transcriptomic, clinical, and mutational datasets from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (n=421) and Gene Expression Omnibus (GEO) cohorts (n=115) to identify genes co-expressed with <i>TRPM4</i>-a key NECSO mediator-and those differentially expressed in HCC. A prognostic signature was developed using least absolute shrinkage and selection operator (LASSO)-Cox regression and validated through survival analysis, time-dependent receiver operating characteristic (ROC) curves, and multivariate Cox regression analysis. The immune landscape was characterized using CIBERSORT, somatic mutation data were used to calculate tumor mutational burden (TMB) and assess its correlation with the risk score, and single-cell RNA sequencing (scRNA-seq) resolved cell-type-specific expression patterns.</p><p><strong>Results: </strong>From 294 <i>TRPM4</i>-associated core genes, we identified an 11-gene signature (<i>BRSK1</i>, <i>MMP1</i>, <i>GRIN2D</i>, <i>GP6</i>, <i>MYOM2</i>, <i>N4BP3</i>, <i>CCDC112</i>, <i>TSEN54</i>, <i>MAP3K9</i>, <i>SPP1</i>, <i>B3GNT4</i>) that independently predicted overall survival (OS) (hazard ratio =5.419, P<0.001) with areas under the curve (AUCs) of 0.779, 0.693, and 0.701 at 1, 3, and 5 years. These values were superior or comparable to conventional clinicopathologic variables after direct comparison. High-risk patients exhibited an immunosuppressive microenvironment, characterized by enrichment of M0 macrophage, a higher M2/M1 ratio (P<0.001) and distinct immune checkpoint profiles. When integrated with TMB, the prognostic stratification was further refined: high-TMB/high-risk patients had poorest outcomes (median OS, 15.3 months), while low-TMB/low-risk patients had the most favorable survival (median OS, 68.7 months). Single-cell analysis revealed that <i>MMP1</i> was induced in cancer-associated fibroblasts (CAFs) and <i>SPP1</i> was downregulated in macrophages, single-cell risk scores confirmed TAFs and macrophages as the main contributors to the prognostic model.</p><p><strong>Conclusions: </strong>The TRPM4-centered 11-gene signature provides robust and independent prognostic stratification in HCC by integrating immune, mutational, and single-cell features. This signature serves as a potential tool for prognostic evaluation and may help inform immunotherapeutic strategies for HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"254"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, regional, and national burden of colorectal cancer attributable to modifiable risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.","authors":"Miao Yu, Yi-Ping Lu","doi":"10.21037/jgo-2026-0335","DOIUrl":"10.21037/jgo-2026-0335","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) represents a major global health burden, with modifiable risk factors including high body-mass index, insufficient physical activity, tobacco use, and dietary risks contributing substantially to its incidence and mortality. However, comprehensive spatiotemporal analyses of this burden, particularly within Brazil, Russia, India, China, and South Africa (BRICS) countries, remain limited. This study aimed to assess the global, regional, and national burden of CRC attributable to these four modifiable risk factors from 1990 to 2021 using Global Burden of Disease Study 2021 data.</p><p><strong>Methods: </strong>Data from 204 countries and territories were analyzed to estimate attributable CRC burden, stratified by sex, age, region, and country. Temporal trends were assessed, projections to 2050 were generated using autoregressive integrated moving average and exponential smoothing models, and health inequalities across Socio-demographic index (SDI) levels were evaluated using the Slope Index of Inequality and Concentration Index.</p><p><strong>Results: </strong>In 2021, males in BRICS countries exhibited higher attributable CRC burden. Age-standardized rates decreased in high-SDI regions but increased in low-SDI regions. Between 1990 and 2021, absolute attributable CRC cases increased across all BRICS countries, although age-standardized trends varied. Projections indicated continued increases in absolute case numbers in BRICS countries by 2050. Global burden remained concentrated in low-SDI regions, with modest reductions in absolute inequalities but persistent relative inequalities.</p><p><strong>Conclusions: </strong>Substantial disparities in CRC burden attributable to modifiable risk factors exist across sociodemographic contexts. Targeted, equity-oriented public health strategies are essential to mitigate the projected burden increase, particularly within BRICS countries, by 2050.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"237"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}