Gastric Cancer最新文献

This review provides a comprehensive analysis of phase-specific management strategies for type 2 diabetes (T2D) in patients undergoing gastric cancer (GC) surgery, encompassing the preoperative, intraoperative and postoperative phases within the context of oncodiabetology. In the preoperative phase, predicting T2D remission and evaluating antidiabetic medications while considering their adverse event profiles are important. These medications include metformin and sodium-glucose cotransporter 2 inhibitors, which may help prevent both T2D progression and GC advancement. Regarding surgical approaches, Roux-en-Y reconstructions are associated with better T2D remission rates than Billroth I/II reconstructions, likely because of enhanced glucose metabolism. The considerable effects of gastrectomy and reconstruction on glucose levels have led to the development of a new surgical approach, known as oncometabolic surgery. This approach integrates oncologic treatment with metabolic benefits and has gained attention as a promising strategy for managing T2D in patients undergoing GC surgery. In the postoperative phase, glucose monitoring, individualized medication adjustments, weight management, and patient education are essential for maintaining remission and preventing relapse. A comprehensive, stage-specific approach to glycemic care is crucial for improving both metabolic and oncologic outcomes in patients with GC.

Background: Despite significant advancements in cancer treatment, gastric cancer (GC) continues to have a high incidence and mortality rate. Antibody-drug conjugates (ADCs) are emerging as a viable treatment option for GC. Glypican-1 (GPC1), a cell surface proteoglycan, has garnered interest for its role in tumor growth and its potential as a biomarker. This study evaluated the efficacy of an ADC comprising a humanized anti-GPC1 monoclonal antibody conjugated with monomethyl auristatin E (GPC1-ADC) to target GPC1 in GC.

Methods: GPC1 expression was assessed in GC cell lines and tissues. The cytotoxic efficacy and mechanism of action of GPC1-ADC were evaluated through comprehensive in vitro assays. In vivo efficacy was further assessed in xenograft mouse models, focusing on tumor growth inhibition and its performance against peritoneal dissemination.

Results: In vitro, GPC1-ADC exhibited significant cytotoxicity against GPC1-positive cell lines by inducing cell cycle arrest and apoptosis. Additionally, GPC1-ADC demonstrated promising bystander-killing activity via cancer-associated fibroblasts, highlighting its potential to target the heterogeneous tumor microenvironment characteristic of GC. In vivo, GPC1-ADC significantly inhibited tumor growth and demonstrated substantial therapeutic effects in a peritoneal dissemination model. Immunohistochemical analysis of tumor specimens from GC patients revealed that 90.2% of differentiated types and 66.7% of poorly differentiated types exhibited high GPC1 expression. High GPC1 expression in tumor samples was significantly associated with poorer progression-free and overall survival.

Conclusions: Our findings suggest that GPC1-targeting ADCs represent a promising therapeutic option for GPC1-positive GC.

Background: The purpose of this study was to examine the eligibility criteria in phase 3 randomized controlled trials (RCTs) in gastric cancer.

Methods: The analysis included 207 RCTs of systemic treatments, started between 2009 and 2024, and registered at the WHO International Clinical Trials Registry Platform (ICTRP).

Results: 93 (44.9%) trials had an upper age limit of 85 years of age or lower (coprimary outcome). In multivariable analysis, these limits were less likely in RCTs with the sites located in North America (adjusted odds ratio [aOR], 0.06; 95% confidence interval [CI] 0.01-0.26; p < 0.001). Only 3 (1.4%) trials were specifically dedicated to older patients. 138 (66.7%) trials excluded patients with Eastern Cooperative Oncology Group (ECOG) score > 1 (coprimary outcome); these criteria were more likely in more recent trials (aOR, 4.49; 95% CI 2.11-9.94; p < 0.001). However, the odds of excluding individuals with ECOG score > 1 were not significantly associated with any type of the investigational treatment including chemotherapy (p > 0.05). Moreover, many trials excluded patients with brain metastases (n = 91; 44%) and those with comorbidities, most frequently liver disorders (n = 170; 82.1%). None of the RCTs excluded patients based on frailty.

Conclusions: The eligibility criteria in phase 3 RCTs in gastric cancer are fairly strict. Recommendations presented in this article will allow the investigators to improve the enrollment of some clinically relevant populations of patients, especially older persons, individuals with inadequate performance status, and those with comorbidities, without substantially compromising the safety of trials participants.

Background: Composite metrics including Textbook Outcome (TO) and Textbook Oncological Outcome (TOO) are increasingly utilised to assess quality in gastric cancer surgical research. However, inconsistent and variable reporting limits their clinical application.

Objective: This scoping review aimed to catalogue definitions and criteria of TO and TOO in gastrectomy, report achievement rates and determinants, associations with survival outcomes, and identify methodological gaps.

Methods: A search was conducted in MEDLINE, Embase, Web of Science, and Scopus from inception to April 2025. Eligible studies reported TO or TOO for adults undergoing curative-intent gastrectomy for cancer. Reviewers screened studies and extracted data on characteristics, definitions, achievement rates, and survival outcomes. Owing to heterogeneity, findings were summarised narratively.

Results: Forty-five studies (published 2017-2025; n = 139,972 patients) were included. Definitions varied, with 26 unique components identified. Common components were adequate lymphadenectomy (≥ 15 nodes), absence of postoperative complications (Clavien-Dindo grade ≥ II), and no 30-day readmission. Median TO and TOO achievement rates were 58.6% (IQR: 37.6-75.8) and 30.3% (IQR: 23.6-40.2). The primary barriers were inadequate lymphadenectomy and CD ≥ II complications. Twelve studies reported a significant association between TO/TOO and improved overall and disease-free survival. Influencing factors included age, comorbidity, tumour characteristics, surgeon volume, and surgical approach. Limitations included non-standardised definitions, limited patient-reported outcomes, and a lack of prospective validation.

Conclusion: TO and TOO are associated with improved survival in gastrectomy but are hampered by inconsistent definitions and limited prospective evidence. Standardisation, patient-reported outcomes, and prospective validation are needed to realise their potential as clinically useful quality metrics.

Background: Gastric cancer is an aggressive malignancy with high metastatic potential, limiting effective treatments. Resveratrol, a natural polyphenol, exhibits anti-cancer properties by modulating mitochondrial function and inducing programmed cell death (PCD) pathways. However, its role in mitochondrial disruption and the regulation of deubiquitination remains unclear.

Methods: Clinical samples and gastric cancer cell lines were analyzed to assess USP36 and SOD2 expression. Cells were treated with resveratrol, followed by functional assays (WB, qPCR, colony formation, Transwell migration, fluorescence staining) to evaluate its effects on USP36-mediated SOD2 stabilization, mitochondrial function, autophagy, and ferroptosis. A xenograft model was used to examine in vivo tumor growth.

Results: USP36 deubiquitinates and stabilizes SOD2, thereby preserving mitochondrial integrity and facilitating tumor progression. Resveratrol disrupts this axis, reducing SOD2 stability, inducing mitochondrial dysfunction, and triggering autophagy and ferroptosis. In vitro, resveratrol significantly inhibited gastric cancer cell proliferation and migration; in vivo, it suppressed tumor growth.

Conclusion: This study identifies the USP36-SOD2 axis as a critical driver of gastric cancer progression and reveals the therapeutic potential of resveratrol in targeting this pathway. By destabilizing mitochondrial function, resveratrol induces both autophagy and ferroptosis, thereby suppressing tumor progression and offering a promising strategy to improve clinical outcomes. Resveratrol inhibits USP36-mediated stabilization of SOD2, which further induces autophagy and ferroptosis by inducing mitochondrial damage and ROS accumulation, and suppressing tumor progression in a xenograft model. These findings underscore the USP36-SOD2 axis as a potential therapeutic target and highlight the adjunctive chemotherapeutic potential of resveratrol.

Background: Tumor regression grade (TRG) and ypTNM are primarily employed to evaluate the efficacy of Neoadjuvant chemotherapy (NAC) in gastric cancer (GC) patients, however, have limited prognostic value. In this study, we established a clinical-radiomic fusion model, without TRG information, for better prognosis assessment of patients following NAC.

Methods: A retrospective multicenter study comprising 875 GC patients from three centers was conducted. Cox hazard regression model was used for variable screening and risk weight assignment. Lasso regression was applied for dimensionality reduction and screening of radiomic features. Models were constructed for better prognosis assessment, and were verified in external cohorts.

Results: Survival analysis showed that dynamic T/N staging changes after NAC could effectively distinguish patients based on prognosis. Moreover, the Clinical SCORE model based on the dynamic T/N staging changes and other clinicopathological data had also been found in internal and external validations to be capable of effectively stratifying patients' risks. For CT images, the identified radiomics features were employed to establish the CT SCORE model, which was subsequently integrated with the Clinical SCORE model to construct the Final SCORE model for prognostic evaluation. In the training and validation cohorts, the prognostic discrimination performance of the Final SCORE model exceeded that of TRG and ypTNM. Furthermore, the final model might also be helpful for the screening of the population benefiting from postoperative adjuvant therapy.

Conclusion: The developed clinical-radiomic Final SCORE model showed superior prognostic assessment performance than TRG and ypTNM for prognostic assessment of GC patients following NAC.

Background: Gastric cancer is divided into differentiated and undifferentiated types and sometimes exhibits mixed histology. However, the risk of gastric cancer-related death after curative endoscopic resection for mixed histology remains unknown. This study evaluated the long-term prognosis of mixed histological type gastric cancers treated with endoscopic resection.

Methods: Data from a Japanese multicenter prospective cohort study were analyzed. Patients with single gastric cancer lesions who underwent curative endoscopic resection were included and divided into those with pure or mixed histological types. Patients with both types of gastric cancer were compared in terms of 5-year overall survival and 5-year disease-specific survival related to primary gastric cancers.

Results: Pure histological type was observed in 6434 patients with 6434 lesions, and mixed histological type was observed in 161 patients with 161 lesions. Overall survival was not significantly different between patients with both types (p = 0.415). The 5-year disease-specific survival was lower in patients with mixed histological type than in those with pure histological type (p = 0.003). After stratification by curative endoscopic resection criteria, in cases of pT1a/M, differentiated-type dominance, tumor size ≤ 3 cm with ulcerative findings, no lymphovascular invasion, and R0 resection, the 5-year disease-specific survival was significantly lower in patients with mixed histological type than in those with pure type (p < 0.001).

Conclusions: The long-term prognosis in cured cases, including those with mixed histological type, was favorable. Stratification analysis showed that mixed histological types with ulcers were more likely to cause primary gastric cancer-related death than pure histological type and might need more careful surveillance.

Clinical trial registration: UMIN Clinical Trial Registry, UMIN000005871.

We report a rare case of protein-losing enteropathy (PLE) during zolbetuximab treatment in a 73-year-old woman with Stage IVB gastric cancer. After chemo-immunotherapy and curative surgery, 3rd-line treatment with capecitabine, oxaliplatin, and zolbetuximab was initiated due to recurrence. The patient developed persistent right upper abdominal pain; imaging revealed gallbladder wall edema, followed by mild gastric wall edema, despite unremarkable laboratory findings. Protein-losing scintigraphy demonstrated abnormal gastric protein leakage, leading to a diagnosis of PLE. While gastrointestinal toxicity is known with zolbetuximab, this is, to our knowledge, the first clinically diagnosed case of PLE in which gallbladder edema served as a diagnostic clue. As treatment strategies for advanced gastric cancer grow increasingly complex, achieving maximum therapeutic benefit requires not only optimal drug selection but also timely recognition and management of adverse events. With the broader use of zolbetuximab, clinicians should be mindful of this rare but potentially significant complication.

Gastric cancer with sarcomatous changes is relatively rare and often detected at an advanced stage. We report the case of an 82-year-old man with early stage gastric cancer exhibiting an unusual morphology with a polypoid growth of a sarcomatous component arising from a flat area of a well-differentiated adenocarcinoma. He achieved mid-term remission after endoscopic submucosal dissection (ESD). Upon admission, upper gastrointestinal endoscopy revealed a 60-mm flat elevated lesion with a nodule; no lymph node or distant metastasis was noted. He was diagnosed with early stage gastric cancer and underwent ESD. Pathological examination of the nodule revealed carcinomatous cells transitioning to atypical spindle cells and sarcomatous changes, suggesting that the sarcomatous component originated from a gastric-type adenocarcinoma. There was no local recurrence or metastasis at 21 months post-ESD. This is the first report of a case of early stage gastric cancer with a sarcomatous change that achieved mid-term outcome after ESD.

Background: Oncolytic viruses (OVs) selectively replicate in and lyse tumor cells. Epstein-Barr virus-associated gastric carcinoma (EBVaGC), representing ~ 10% of gastric cancers globally, remains a therapeutic challenge. We developed Ad-TBZ, a novel oncolytic adenovirus engineered to selectively target EBVaGC by inducing EBV lytic reactivation.

Methods: Ad-TBZ was constructed by inserting an hTERT promoter (hTERTp)-driven E1A/IRES-E1B cassette and a CMV promoter (CMVp)-driven BZLF1 gene into the adenoviral genome. We evaluated Ad-TBZ replication, cytotoxicity, and EBV lytic reactivation in EBVaGC cell lines (SNU719, NCC24, YCCEL1, AGS-EBV, MKN1-EBV), EBV-negative cells, and normal fibroblasts (CCD-986sk). In vivo efficacy was assessed using SNU719 and MKN1-EBV xenograft mouse models. Combination effects with platinum-based drugs and ganciclovir were also investigated.

Results: Ad-TBZ selectively replicated in EBVaGC cells and demonstrated cell line-specific cytotoxic effects while sparing normal cells. It significantly upregulated EBV lytic genes (BRLF1, BMRF1, BGLF4, BXLF1, BALF4, BLLF1), increased viral genome copies, and induced cell line-specific late apoptosis. In vivo, Ad-TBZ effectively suppressed tumor growth in both xenograft models without systemic toxicity. Sequential treatment with oxaliplatin showed modest synergistic effects at specific concentrations in limited conditions, while most combination approaches showed no significant synergistic effects. These findings indicate Ad-TBZ functions optimally as a monotherapy.

Conclusions: Ad-TBZ demonstrates potent and selective antitumor activity against EBVaGC through hTERTp-mediated selective replication and BZLF1-induced EBV lytic reactivation. These findings support Ad-TBZ as a promising novel monotherapeutic strategy for EBVaGC.