Gastric Cancer最新文献

Background: There is substantial global variation in demographics, disease burden, and treatment for gastric cancer patients. Benchmarking is an instrument to assess such variation and enables to investigate to which extent case-mix and treatments explain differences in outcomes. We aimed to evaluate hospital-level variation in surgical outcomes following gastrectomy for gastric cancer before and after adjusting for case-mix and treatment-related factors.

Methods: Data were retrieved from the GastroBenchmark and GASTRODATA databases, including consecutive gastric cancer resections performed between 2017 and 2021 from 43 centers. Patients who underwent a (sub)total gastrectomy for adenocarcinoma were identified. Outcomes included 30-day mortality, severe complications (Clavien-Dindo grade ≥ 3a), > 15 lymph nodes retrieved, negative resection margin (R0), prolonged hospitalization (> 14 days), readmissions (< 30 days), reoperations, and escalation of care. We assessed absolute inter-hospital variation for outcomes, and estimated outcomes using mixed-effect logistic regression models with a random intercept. We estimated crude, case-mix adjusted, and case-mix and treatment adjusted hospital effects. The conditional and marginal pseudo-R² were used to quantify the variance in outcome explained by case-mix and treatment-related factors.

Results: A total of 7818 patients from 41 hospitals were included, with contributions ranging from 12 to 2554 patients per hospital (IQR: 49-146). Observed 30-day mortality and severe complications ranged from 0 to 9.7% (IQR: 3.2%) and 5.3 to 31% (IQR: 7.7%), respectively. Larger variation between hospitals was observed for retrieval of > 15 lymph nodes (IQR: 12.3%), prolonged hospitalization (IQR: 14.4%) and readmissions (IQR 11.3%). This variation was reduced in the crude model, while adjusting for case-mix and treatment-related factors did not significantly reduce variation for any outcome. Case-mix factors had a limited contribution to the explained variance, except for 30-day mortality (33.9%) and negative resection margins (31.7%). Adding treatment-related factors increased the explained variance for 30-day mortality by 40.8%, but had low impact (< 10%) on the variance in most surgical outcomes.

Conclusions: Case-mix and treatment factors are not the primary drivers of variation in surgical outcomes following gastrectomy. Case-mix adjustment can improve the validity of global comparisons for 30-day mortality, but does not seem essential for comparing other investigated outcomes.

Background: Steatotic liver disease (SLD) has emerged as a heterogeneous condition with distinct subtypes defined by metabolic dysfunction and alcohol exposure. We aimed to investigate the associations of SLD subtypes-metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with elevated alcohol intake (MetALD), and alcohol-related liver disease (ALD)-with the risk of gastric cancer (GC) and esophageal cancer (EC) in a nationwide cohort.

Methods: We analyzed a cohort of 362,285 individuals aged ≥ 40 years using the Korean National Health Insurance Service claims data. Participants underwent screening in 2009-2010 with follow-up through 2019. They were categorized into no SLD, MASLD, MetALD, or ALD. Cox proportional hazards models adjusted for demographic, clinical, and lifestyle factors estimated hazard ratios (HRs) for GC and EC. Subgroup analyses were conducted by alcohol intake levels and cardiometabolic burden.

Results: Over 10 years, 4,842 participants (1.98%) developed GC or EC. The risk of GC increased progressively across SLD subtypes, with HRs of 1.09 (95% CI: 1.02-1.16) for MASLD, 1.31 (1.16-1.48) for MetALD, and 1.40 (1.16-1.68) for ALD. For EC, MASLD was not significant associated (HR 0.81, 95% CI: 0.63-1.05), whereas risks were significantly elevated in MetALD (1.68, 1.17-2.42) and ALD (2.18, 1.36-3.49).

Conclusions: GC risk is modestly increased in MASLD and more pronounced in alcohol-related SLD subtypes, whereas EC risk is primarily driven by alcohol exposure. These findings indicate that GC is influenced by both metabolic dysfunction and alcohol, while alcohol plays the predominant role in EC.

Background: Positive peritoneal cytology (CY1) is classified as stage IV gastric cancer and typically treated with systemic chemotherapy. However, upfront surgery is sometimes performed when CY1 is identified intraoperatively or postoperatively and may improve long-term survival when followed by adjuvant chemotherapy. It remains unclear which patients benefit most from this approach. This study aimed to identify patient subgroups likely to achieve long-term survival with upfront surgery followed by adjuvant chemotherapy.

Methods: We retrospectively analyzed patients diagnosed with P0CY1 who underwent upfront surgery between 2008 and 2020. Prognostic factors for overall survival (OS) and progression-free survival were evaluated using univariate and multivariate analyses.

Results: A total of 147 patients were included; 65% were male, with a median age of 72 years. Macroscopic types 3 and 4 were present in 80% of patients, 91% had pathological T4 tumors, and 63% had lymph node metastasis. Total gastrectomy was performed in 54%, and 81% received adjuvant chemotherapy. Median OS was 27.0 months. Univariate analysis showed age, macroscopic type, tumor size, and adjuvant chemotherapy were significantly associated with OS. Multivariate analysis identified adjuvant chemotherapy tumor size  ≥  80 mm, and macroscopic types 1 and 2 as independent favorable prognostic factors. Among patients receiving adjuvant chemotherapy, those with macroscopic types 1 and 2 had significantly better OS (5-year OS rate: 46%) compared to types 3 and 4.

Conclusions: In P0CY1 gastric cancer, upfront surgery followed by adjuvant chemotherapy may result in long-term survival, particularly in patients with macroscopic types 1 and 2.

Gastric cancer remains a major clinical challenge owing to its insidious onset and marked heterogeneity, which contribute to poor prognosis and limit the effectiveness of chemotherapy‑based systemic therapy. Antibody‑drug conjugates (ADCs) deliver potent cytotoxins to tumor cells with antigen specificity and have emerged as a therapeutic class that can enhance efficacy while reducing off‑target toxicity. Recent trials of ADCs targeting HER2, CLDN18.2, TROP2, CEACAM5/6, and HER3 demonstrate substantial therapeutic activity. Notably, the HER2‑directed agents trastuzumab deruxtecan and disitamab vedotin have improved survival and response in previously treated advanced disease. ADCs targeting CLDN18.2 and TROP2 have also yielded encouraging early results. Accumulating evidence from ongoing programs indicates movement into earlier lines of therapy in advanced gastric cancer, including evaluation in first‑line combination regimens. Broader clinical use has highlighted resistance mechanisms, including antigen loss or heterogeneity, impaired internalization and lysosomal processing, increased drug efflux, and an immunosuppressive tumor microenvironment that limits delivery. This review synthesizes clinical advances in ADC therapy for gastric cancer, delineates resistance biology, and evaluates strategies to overcome therapeutic resistance. Deeper mechanistic insight, biomarker‑guided patient selection, and continued innovation in targets, linkers, payloads, and rational combinations will be critical to overcome resistance and improve outcomes for patients with gastric cancer.

Background: A fibrotic tumor microenvironment (TME) promotes tumor progression by the interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the extracellular matrix (ECM), which enhance tumor cell survival and growth, and by suppressing antitumor immunity. However, how characteristic gene expression and amplification in cancer cells drive the formation of a fibrotic TME in patients with gastric cancer (GC) is unclear.

Methods: We performed genomic and transcriptomic analyses via datasets from The Cancer Genome Atlas and the Asian Cancer Research Group to identify amplified and overexpressed genes associated with the presence of a fibrotic TME in tumors. Syngeneic mouse models of GC and multiplexed immunohistochemistry (IHC) were used to validate the findings of the transcriptomic analysis and investigate the underlying mechanisms.

Results: The Frizzled class receptor 1 (FZD1) gene was frequently amplified and highly expressed in GC patients with fibrotic tumors, and FZD1 expression was related to a poor prognosis. The overexpression of Fzd1 in murine GC tumor cells was significantly associated with enhanced tumor fibrosis and growth and reduced infiltration of CD3⁺ lymphocytes and CD8⁺ T cells into tumors. SLIT2 secretion was increased in Fzd1-overexpressing tumor cells via the canonical WNT-β-catenin pathway, and SLIT2 activated CAFs to produce more ECM through the SLIT2‒ROBO1 axis.

Conclusions: This study highlights the potential of FZD1 as a biomarker for predicting fibrotic status in patients with GC and the SLIT2‒ROBO1 axis as a therapeutic target to reverse a fibrotic and immunosuppressive TME.

Background: Leptomeningeal carcinomatosis (LMC) from gastric cancer is rare but carries a poor prognosis, and its risk factors and clinical presentation remain unclear.

Methods: Among 3850 patients treated with palliative chemotherapy, those with pathologically or cytologically confirmed LMC were included. Responsiveness to intrathecal methotrexate (IT-MTX) was defined as a malignant cell count < 1/μL on ≥ 2 consecutive cerebrospinal fluid analyses. Survival outcomes were compared across subgroups with different clinical presentations.

Results: During a median follow-up of 13.7 months, LMC was diagnosed in 0.8% (32/3850) of patients. At the time of LMC diagnosis, 27 patients were undergoing palliative systemic chemotherapy, 4 were diagnosed with recurrence following curative surgery, and 1 was diagnosed with the initial presentation of metastatic gastric cancer. Multivariate logistic regression analysis revealed that signet ring cell carcinoma (SRC) and/or poorly differentiated adenocarcinoma (PD) was the most relevant risk factor for LMC (adjusted odds ratio 4.78; p = 0.036). Thirty patients received IT-MTX, with responders (n = 23) showing longer overall survival (OS) than non-responders (n = 7) (p = 0.004). Among the 29 patients with available data on extracranial disease control, those with controlled extracranial disease at LMC diagnosis (n = 19) demonstrated significantly better OS following IT-MTX than those with progressive extracranial disease (n = 10) (p = 0.023).

Conclusions: SRC and/or PD is a key risk factor for LMC, which often arises despite controlled extracranial disease, necessitating early evaluation for neurologic symptoms. Survival outcomes depend on IT-MTX response and the status of extracranial disease.