Journal of gastrointestinal oncology最新文献

{"title":"Establishment of a chemoradio-resistance colorectal cancer cell model and its changes in biological behavior.","authors":"Shan Liu, Zeng Zhang, Qian An, Yue Jia, Qin Su, Dezhi Zhu, Likun Luan, Hongying Yang, Zhirui Chuan, Xinyuan Liu, Siyu Wang, Yanyan Liu, Fenglian Fu, Qiong Sun, Luyao Ma, Juanrong Yang, Yiming Zhang, Mingzhi Duan, Peijun Yao, Changqing Yang, Yiming Xing, Hongmei Shen, Yongxin Jiang","doi":"10.21037/jgo-2025-812","DOIUrl":"10.21037/jgo-2025-812","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the most prevalent and malignant gastrointestinal tract tumor. The incidence remains high, and the issue of resistance to radiotherapy and chemotherapy is prominent. The aims were therefore to establish a model for radio- and chemoresistance in CRC, elucidating the underlying mechanism that could help identify measures to reverse its resistance and improve the clinical efficacy of radiotherapy and chemotherapy.</p><p><strong>Methods: </strong>A HCT116 and HT29 cell model of radiotherapy and chemotherapy resistance in CRC was established by simulating clinical high-dose shock therapy as a key in vitro method. For the in vivo animal studies, healthy 6-week-old BALB/c nude mice (both genders) were used. The changes in its biological behavior were studied to provide a theoretical basis for improving the efficacy of radiotherapy and chemotherapy in clinical practice.</p><p><strong>Results: </strong>We successfully established a CRC cell line with radio- and chemoresistance, and it exhibited stronger potential for cell proliferation, colony formation, invasion, and migration than its parental cell line. Furthermore, in nude mouse models, the resistant cells showed stronger tumorigenicity and stronger liver and lung metastasis ability than the parental cells.</p><p><strong>Conclusions: </strong>This research helps elucidate the molecular mechanism of chemo- and radiotherapy resistance in CRC and can potentially improve the molecular diagnosis and gene therapy of CRC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"241"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900535","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":"Evolving burden of pancreatic cancer in the Middle East and North Africa Region, 1990-2023: an analysis based on the Global Burden of Disease Study 2023.","authors":"Emad Aljohani, Abdullah Albarrak, Badr F Al-Khateeb, Noof Alwatban, Khadijah Angawi, Maryam Alhabas, Raed Aldahash, Amani Alharthy, Abdullah T Alanazi, Ashraf El-Metwally","doi":"10.21037/jgo-2026-0539","DOIUrl":"10.21037/jgo-2026-0539","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a highly lethal malignancy characterized by an aggressive biological behavior and a narrow therapeutic window, making it a significant public health challenge. In the Middle East and North Africa (MENA) region, monitoring the evolving disease burden is essential for identifying high-risk populations and guiding the allocation of resources for early detection and palliative care. This study provides a longitudinal examination of pancreatic cancer prevalence, mortality, and disability-adjusted life years (DALYs) across the region from 1990 to 2023.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease (GBD) 2023 study, we analyzed the burden of pancreatic cancer across 21 MENA countries. The primary outcomes were age-standardized prevalence, mortality, and DALY rates per 100,000 population. All estimates were age-standardized using the GBD world standard population to ensure comparability. Trends were assessed regionally, sub-regionally, and by sex from 1990 to 2023, with 95% uncertainty intervals (UIs) reported.</p><p><strong>Results: </strong>The overall regional age-standardized prevalence of pancreatic cancer increased by 55.9% from 1990 to 2023, rising from 2.38/100,000 to 3.71/100,000. In terms of sex-specific prevalence rates, men had an overall age-standardized prevalence of 4.45/100,000, whereas women had an overall age-standardized prevalence rate of 2.97 per 100,000 in 2023. The same 55.3% increase trend is evidenced by the regional DALY rates (81.82 to 127.07/100,000). When considering rates of prevalence and DALYs by country, there was considerable variability. Egypt and Iraq had the most rapid increases in prevalence of pancreatic cancer (with Egypt's prevalence being a staggering 238%), while Turkey and Lebanon had the highest overall burdens of pancreatic cancer, and the UAE and Qatar had the largest decreases of prevalence (i.e., UAE dropping by 48%). Afghanistan and Yemen had steady increases in pancreatic cancer since beginning with low rates from 1990.</p><p><strong>Conclusions: </strong>The rapidly increasing burden of pancreatic cancer in the MENA region, largely driven by metabolic risk factors and an aging population, necessitates targeted public health strategies. Regional policy should prioritize aggressive primary prevention, specifically tobacco control and metabolic health, alongside the expansion of palliative care services. Furthermore, establishing robust, unified regional cancer registries is critical to improving surveillance and informing health planning.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"260"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900538","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":"Metabolic-cell-death gene trio predicts survival and cuproptosis sensitivity in colorectal cancer.","authors":"Wei Zhuang, Ya Zhang, Zhengyong Liu, Wenxue Yan, Tao Wei, Qiuping Deng, Qi Liu","doi":"10.21037/jgo-2026-0419","DOIUrl":"10.21037/jgo-2026-0419","url":null,"abstract":"<p><strong>Background: </strong>Metabolic cell death (MCD) modulates colorectal cancer (CRC) progression, yet its prognostic value remains unexplored. We aimed to build an MCD-centred gene signature for outcome prediction and precision therapy.</p><p><strong>Methods: </strong>Transcriptomes of 1,174 CRC patients were integrated. Weighted gene co-expression network analysis, differential expressions and least absolute shrinkage and selection operator (LASSO) + random survival forest were successively applied to derive a three-gene (<i>CDKN2A/MPC1/AHCY</i>) risk model. Functional, immune-infiltration, drug-sensitivity and genomic analyses were performed, followed by validation in fresh clinical specimens and cell lines.</p><p><strong>Results: </strong>Integrative metabolic-death transcriptomics identified CDKN2A, MPC1 and AHCY as the hub drivers of CRC. Their three-gene signature robustly stratified patients into high- and low-risk subsets [3-year area under the curve (AUC) 0.83-0.85, P<0.001]. High-risk tumors were enriched for extracellular matrix (ECM)-receptor-interaction pathways, displayed abundant myeloid-derived suppressor cell (MDSC) infiltration and were more vulnerable to AZD8186, AZ960 and JAK inhibitors. Guided by these in-silico findings, we functionally confirmed that CDKN2A silencing markedly repressed proliferation, invasion and migration of SW480/HCT116 cells and potentiated cuproptosis via up-regulation of lipoylated DLAT/DLST and CTR1.</p><p><strong>Conclusions: </strong>We report the first MCD-derived prognostic platform for CRC that simultaneously predicts survival and therapeutic response. Targeting CDKN2A-enhanced cuproptosis represents a promising metabolic-precision strategy for high-risk patients.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"229"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900723","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 metabolic dysfunction-associated steatotic liver disease and risk of early-onset advanced colorectal neoplasia: a systematic review and meta-analysis.","authors":"Yan Zhong, Xianhang Li, Siqi Chen, Min Deng","doi":"10.21037/jgo-2026-0401","DOIUrl":"10.21037/jgo-2026-0401","url":null,"abstract":"<p><strong>Background: </strong>With the rising global incidence of early-onset colorectal cancer (EOCRC) and its aggressive clinical behavior, we conducted a systematic review and meta-analysis to synthesize evidence from cohort studies and quantify the association between metabolic dysfunction-associated steatotic liver disease (MASLD), including its prior definitions (non-alcoholic fatty liver disease/metabolic associated fatty liver disease), and early-onset advanced colorectal neoplasia (eoACRN), providing evidence for risk stratification and early intervention.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) was conducted up to March 20, 2026, including English and Chinese studies. Observational cohort and cross-sectional studies evaluating MASLD-related hepatic steatosis and eoACRN were included. Adjusted odds ratios (ORs) were pooled using random-effects models. Subgroup and sensitivity analyses assessed heterogeneity and robustness. Publication bias was evaluated using Egger's test and funnel plots.</p><p><strong>Results: </strong>Ten observational studies (n=76,688) showed that MASLD-related hepatic steatosis was associated with increased risk of early-onset advanced colorectal adenoma (OR =2.03) and EOCRC (OR =1.29). In sensitivity analyses excluding cross-sectional studies, the association with EOCRC remained significant [OR =1.28, 95% confidence interval (CI): 1.20-1.37]. Subgroup analyses suggested a higher effect in males (OR =3.93), based on three studies. In the diabetes subgroup, the association was not significant (OR =2.16), but became significant after excluding one study (OR =2.93, 95% CI: 1.34-6.43). BMI-stratified analyses did not identify overweight/obesity-defined MASLD as a distinct high-risk phenotype; however, sensitivity analyses combining studies using different BMI cut-offs showed a significant association (OR =2.67).</p><p><strong>Conclusions: </strong>In Asian populations, MASLD-related hepatic steatosis is associated with increased eoACRN risk. However, substantial heterogeneity, limited subgroup evidence, and low certainty warrant cautious interpretation. Further prospective studies are needed to clarify mechanisms, and to improve personalized screening strategies for high-risk young populations.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"231"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900732","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":"Modifiable risk factors contributing to the rising incidence of early-onset colorectal cancer in the United States over three decades: a Global Burden of Disease analysis.","authors":"Mohammed Y Youssef, Mohamed H Eldesouki, EzzElDien A Ibrahim, Mohamed Elgozair, Mona A Ali, Ahmed Salem, Mohammed Bakry, Asim Usman, Aasma Shaukat, Sherif E Elhanafi","doi":"10.21037/jgo-2026-0314","DOIUrl":"10.21037/jgo-2026-0314","url":null,"abstract":"<p><strong>Background: </strong>Early-onset colorectal cancer (EOCRC), diagnosed in adults under the age of 50 years, is a significant public health challenge in the United States (US). While traditional colorectal cancer (CRC) incidence in older populations has declined due to screening, rates among younger adults are rising, likely driven by shifting birth cohort exposures to modifiable risk factors. This study aims to quantify the longitudinal burden of EOCRC and evaluates the contribution of dietary and metabolic risks from 1990 to 2023.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease (GBD) 2023 study, we analyzed age-specific incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for EOCRC. Trends were evaluated using joinpoint regression to calculate annual percent changes (APCs). Risk factor attribution was performed for dietary, metabolic, and behavioral exposures. Future burdens were projected to 2050 using mixed-effects and autoregressive integrated moving average (ARIMA) models.</p><p><strong>Results: </strong>Between 1990 and 2023, the age-specific incidence rate (ASIR) of EOCRC increased by 47.1%, rising from 8.01 to 11.79 per 100,000. Age-specific mortality rose from 2.48 to 3.00, and DALYs increased from 125.41 to 150.82. Males consistently carried a higher burden, with widening sex disparities in incidence by 2023 (13.10 in males versus 10.44 in females). By 2023, diet high in processed meat (18.4%) surpassed diet low in whole grains (17.6%) as the leading modifiable contributor to EOCRC mortality, followed by high body-mass index and smoking. Under a risk-reduction scenario, projected mortality could decline by more than 50% by 2050 (1.14 per 100,000) compared to the reference trend (2.42 per 100,000).</p><p><strong>Conclusions: </strong>The EOCRC burden in the US has intensified over three decades. The shifting dominance toward processed meat and metabolic dysfunction highlights a critical need for targeted primary prevention. Achieving significant mortality reductions by 2050 will require population-level interventions addressing dietary quality and metabolic health early in life.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"240"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900738","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":"Metabolic burden but not metabolic dysfunction-associated steatotic liver disease affects the prognosis of patients with hepatocellular carcinoma after hepatectomy: a retrospective cohort study.","authors":"Ming Zhang, Zhan-Cheng Qiu, Jun-Long Dai, Tian-Fu Wen, Chuan Li","doi":"10.21037/jgo-2026-0552","DOIUrl":"10.21037/jgo-2026-0552","url":null,"abstract":"<p><strong>Background: </strong>The impact of concurrent metabolic dysfunction associated steatotic liver disease (MASLD) on the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy is controversial. Moreover, there is little information regarding the effect of metabolic burden on HCC patients. This study aimed to identify the influence of concurrent MASLD and metabolic burden on the prognosis of HCC patients after hepatectomy.</p><p><strong>Methods: </strong>Data of HCC patients who received hepatectomy between 2013 and 2018 at West China Hospital were retrospectively reviewed. Metabolic burden was defined as the cumulative number of metabolic abnormalities including overweight/obesity, blood hypertension, prediabetes/diabetes and dyslipidemia [including hypertriglyceridemia and/or low high-density lipoprotein cholesterol (HDL-C)]. Logistic regression and Cox regression analyses were carried out to identify the independent risk factors associated with severe postoperative complications and oncological outcomes respectively.</p><p><strong>Results: </strong>After propensity score matching (PSM), severe postoperative complication rates were 5.4% and 6.9% in MASLD and non-MASLD patients, respectively (P=0.54). Moreover, both the 5-year recurrence-free survival (RFS) and overall survival (OS) rates of MASLD and non-MASLD patients were similar (RFS: 44.7% <i>vs</i>. 40.2%, P=0.33; OS: 61.2% <i>vs</i>. 60.7%; P=0.69). Multivariate analyses revealed that metabolic burden was independently associated with severe postoperative complications, RFS and OS, whereas MASLD was not. Severe postoperative complication rates in patients with metabolic burden 0, 1-2 and 3-4 were 2.8%, 5.7%, and 9.4%, respectively (P_{for trend}=0.007). The 5-year RFS rates were 50.5%, 38.4%, and 29.6%, respectively (P_{for trend}=0.04), while the 5-year OS rates were 65.2%, 56.2%, and 43.7%, respectively (P_{for trend}=0.001), in patients with metabolic burden 0, 1-2 and 3-4.</p><p><strong>Conclusions: </strong>The metabolic burden, but not MASLD, adversely affects the prognosis of HCC patients after hepatectomy. The more metabolic burden patients have, the more likely they are to have a poor prognosis after hepatectomy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"249"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900741","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":"Organ-specific response to atezolizumab + bevacizumab combination therapy for unresectable hepatocellular carcinoma with extrahepatic metastases: a retrospective cohort study.","authors":"Akihiro Dejima, Kuniaki Arai, Tomoyoshi Chiba, Hidenori Kido, Noboru Takata, Takeshi Terashima, Tatsuya Yamashita, Taro Yamashita","doi":"10.21037/jgo-2026-0282","DOIUrl":"10.21037/jgo-2026-0282","url":null,"abstract":"<p><strong>Background: </strong>The combination of atezolizumab plus bevacizumab is a standard first-line therapy for advanced hepatocellular carcinoma (HCC). However, the liver possesses a uniquely immunosuppressive microenvironment that often leads to discordant therapeutic responses between intrahepatic lesions and extrahepatic metastases. Conventional assessments relying on binary Response Evaluation Criteria in Solid Tumors (RECIST) criteria have failed to capture the organ-specific longitudinal dynamics. This exploratory study evaluated the organ-specific antitumor dynamics of atezolizumab plus bevacizumab in patients with advanced HCC presenting with extrahepatic metastases.</p><p><strong>Methods: </strong>We retrospectively analyzed 42 consecutive patients with extrahepatic metastases who received atezolizumab plus bevacizumab for HCC at Kanazawa University Hospital between October 2020 and November 2024. Best overall response (BOR), objective response rate (ORR), and disease control rate (DCR) were evaluated per RECIST version 1.1. Organ-specific response rates (OSRR), depth of response (DpR), duration of response (DoR), and time to progression (TTP) were also evaluated.</p><p><strong>Results: </strong>The BORs (complete response/partial response/stable disease/progressive disease) were 0/13/15/14 patients, respectively, yielding an ORR of 31% and a DCR of 67%. OSRRs were 30% in the liver, 11% in the lung, 50% in lymph nodes, and 57% in peritoneal dissemination, and 0% in bone and adrenal glands. The median DpR was 1% in the liver, 7% in the lung, -28% in lymph nodes, -32% in peritoneal dissemination, 9% in bone (n=2), and 8% in adrenal glands (n=3), with no significant differences among organs (P=0.31). Median DOR and TTP were 16.5 and 9.7 months for the liver, not reached and 5.5 months for the lung, not reached and 21.3 months for lymph nodes, and 15.9 and 19.8 months for peritoneal dissemination, respectively, without significant differences. Although no statistically significant differences were observed across organs in median DpR (P=0.31), DoR (P=0.37), or TTP (P=0.09), these exploratory comparisons were severely underpowered due to the restricted sample size and subgroup fragmentation.</p><p><strong>Conclusions: </strong>Atezolizumab plus bevacizumab combination therapy showed no significant differences in organ-specific efficacy and demonstrated consistent antitumor effects regardless of intrahepatic disease or metastatic site. elicited objective tumor responses across diverse intrahepatic and extrahepatic sites. While the small sample size precludes a definitive conclusion of uniform efficacy, the descriptive trends showing preserved intrahepatic efficacy support the clinical rationale of this regimen in advanced HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"255"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900774","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":"Comparison of the efficacy of transarterial chemoembolization combined with different molecular targeted agents and/or immune checkpoint inhibitors for unresectable hepatocellular carcinoma: a systematic review and network meta-analysis.","authors":"Jia-Ye Long, Xin-Hong Wang, Yong-Run Li, Shang-Ren Huang, Zhi-Jian Li, Yan Luo","doi":"10.21037/jgo-2026-0436","DOIUrl":"10.21037/jgo-2026-0436","url":null,"abstract":"<p><strong>Background: </strong>Transarterial chemoembolization (TACE) combined with molecular targeted agents (MTAs) and/or immune checkpoint inhibitors (ICIs) has been increasingly used in patients with unresectable hepatocellular carcinoma (uHCC). However, the efficacy differences among these combination regimens have not been systematically compared. This study aimed to compare the efficacy of these treatment strategies and provide evidence for optimizing combination therapies in clinical practice.</p><p><strong>Methods: </strong>PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched up to February 26, 2026. Randomized controlled trials (RCTs) and cohort studies involving patients with uHCC were included. The interventions were TACE combined with MTAs and/or ICIs. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were objective response rate (ORR) and disease control rate (DCR). A frequentist network meta-analysis (NMA) with a random-effects model was performed, and treatment regimens were ranked using P-scores. This NMA was registered in PROSPERO (CRD420261350164).</p><p><strong>Results: </strong>A total of 108 studies involving 19,761 patients and 26 treatment regimens were included, comprising 84 retrospective cohort studies and 24 RCTs. Compared with TACE alone, most combination regimens significantly improved patient outcomes. For OS, TACE + anlotinib + sintilimab (TACE + Anl + Sin), TACE + donafenib + toripalimab (TACE + Don + Tor), TACE + lenvatinib + tislelizumab (TACE + Len + Tis), TACE + sorafenib + camrelizumab (TACE + Sor + Cam), and TACE + apatinib + camrelizumab (TACE + Apa + Cam) were all significantly superior to TACE alone. P-score ranking showed that TACE + Anl + Sin was most likely to achieve the best OS outcome. For PFS, compared with TACE alone, TACE + Anl + Sin, TACE + Don + Tor, TACE + lenvatinib + pembrolizumab (TACE + Len + Pem), TACE + Len + Tis, and TACE + Apa + Cam significantly prolonged PFS. Among them, TACE + Len + Pem still showed strong benefit when compared with some triple-combination regimens and ranked first by P-score. For ORR, TACE + Len + Cam, TACE + Len + Tis, TACE + Anl + Sin, and TACE + Don + Tor all significantly improved ORR compared with TACE alone. Among these, TACE + Len + Cam had the highest P-score. For DCR, TACE + Len + Tis showed the best performance, while TACE + atezolizumab + bevacizumab (TACE + Ate + Bev), TACE + Anl + Sin, and TACE + Apa + Cam also demonstrated relatively high DCR.</p><p><strong>Conclusions: </strong>Compared with TACE alone, TACE combined with MTAs and ICIs can significantly improve outcomes in patients with uHCC. TACE + Anl + Sin, TACE + Len + Tis, and TACE + Apa + Cam may be promising treatment options, although more prospective studies are needed for further validation.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"252"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900783","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":"Human epidermal growth factor receptor 2 expression loss after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma: a retrospective study.","authors":"Jean-Baptiste Demigné, Marie Heinisch, Julia Gilhodes, Shems Kettani, Domitille Dano, Christelle de la Fouchardière","doi":"10.21037/jgo-2026-0393","DOIUrl":"10.21037/jgo-2026-0393","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2) overexpression/<i>ERBB2</i> amplification represents an established therapeutic target in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, the reliability of HER2 assessment between diagnostic biopsies and surgical specimens (SS), and the potential impact of neoadjuvant therapy on HER2 status, remain incompletely characterized in localized disease. This study aimed to evaluate HER2 concordance between pre-treatment biopsies (PTB) and matched SS, and to describe HER2 changes following neoadjuvant treatment in localized gastric and GEJ adenocarcinoma.</p><p><strong>Methods: </strong>We conducted a retrospective single-center cohort study including patients with localized gastric or GEJ adenocarcinoma who underwent curative-intent surgery between 2017 and 2021. HER2 status was assessed on PTB and matched SS using immunohistochemistry (IHC) with reflex in situ hybridization (ISH) for IHC-2+ cases, according to gastric cancer guidelines. Concordance between PTB and SS, the impact of biopsy sampling adequacy, and dynamic changes in HER2 status following neoadjuvant therapy were analyzed descriptively.</p><p><strong>Results: </strong>Fifty-seven patients were included. Median age was 67 years; 77% were male. Neoadjuvant treatment was administered in 89.5% of patients, while 10.5% underwent upfront surgery. HER2 positivity was observed in 21.1% of biopsies and 15.8% of SS. Overall concordance of HER2 status between PTB and SS was 87.7% [95% confidence interval (CI): 76.3-94.9%]. Seven discordant cases were identified, including five cases of HER2 loss (biopsy-positive/resection-negative) and two cases of HER2 gain. Among the 12 tumors initially classified as HER2-positive on biopsy, HER2 positivity was maintained in seven cases (58.3%) but lost in five (41.7%; 95% CI: 15.2-72.3%). When restricted to patients receiving neoadjuvant therapy, HER2 loss occurred in 5 of 10 HER2-positive cases (50.0%; 95% CI: 18.7-81.3%). Increasing the number of biopsy fragments did not significantly reduce discordance between biopsy and SS.</p><p><strong>Conclusions: </strong>HER2 status shows overall good concordance between diagnostic biopsies and SS in localized gastric and GEJ adenocarcinomas. However, a substantial proportion of initially HER2-positive tumors exhibited loss of HER2 expression following neoadjuvant chemotherapy. These findings suggest that HER2 expression/<i>ERBB2</i> amplification may evolve during perioperative treatment and support further evaluation of HER2 reassessment on SS.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"207"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900657","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":"Immunological characteristics of calmodulin-related genes in hepatocellular carcinoma and their potential for prognostic prediction and diagnostic applications.","authors":"Wenjia Wei, Shuangling Ni, Luxiang Liu, Siqin Long, Yuli Ge","doi":"10.21037/jgo-2026-0204","DOIUrl":"10.21037/jgo-2026-0204","url":null,"abstract":"<p><strong>Background: </strong>As a primary liver cancer with high malignancy, hepatocellular carcinoma (HCC) is notoriously difficult to detect early, which often leads to an unfavorable prognosis for patients. Calmodulin-related genes (CRGs) participate in the regulation of cellular calcium signaling, yet their roles in HCC development, immune microenvironment remodeling, and clinical application value remain incompletely understood. This study aims to systematically screen key CRGs and evaluate their clinical value as prognostic biomarkers for HCC.</p><p><strong>Methods: </strong>Intersection analysis identified differentially expressed calmodulin-related genes (DECRGs). Integration of three algorithms-least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest-identified core diagnostic genes, whose efficacy was validated by receiver operating characteristic (ROC) curves and a diagnostic nomogram. Based on DECRGs, we screened prognosis-related genes and constructed prognosis risk models using LASSO regression and multivariate Cox regression. Model performance was validated in the external GSE14520 cohort. We investigated differences in immune infiltration and gene enrichment features across risk groups, analyzed associations between risk scores and clinical characteristics, and assessed predictive value for immune therapy response.</p><p><strong>Results: </strong>Through analysis of 51 DECRGs, we identified a five-gene HCC diagnostic signature demonstrating robust diagnostic performance in both training and validation cohorts. Concurrently, a nine-gene prognostic risk model based on DECRGs was constructed, validated in an external cohort, with its associated nomogram successfully predicting patient survival. High- and low-risk groups exhibited distinct biological characteristics: the low-risk group displayed an active immune phenotype and predicted superior response to immune checkpoint inhibitors, while the high-risk group enriched cell cycle pathways and metabolic processes.</p><p><strong>Conclusions: </strong>The calmodulin-related core genes identified in this study may serve as potential diagnostic biomarkers for HCC. The prognostic risk model constructed based on these CRGs effectively enables risk stratification and prognosis assessment in HCC patients. Furthermore, CRG expression is closely associated with the HCC immune microenvironment and response to immunotherapy, offering new insights for optimizing HCC diagnosis and treatment strategies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"17 4","pages":"251"},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900660","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}