Gastric Cancer最新文献

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: This study assessed the impact of an institutional certification system that was newly introduced by the Japanese Gastric Cancer Association on short-term surgical outcomes in patients with gastric cancer using data from the National Clinical Database.

Methods: A retrospective cohort study of distal gastrectomy and total gastrectomy procedures performed between January 2020 and December 2022 was conducted. The institutions were classified into three categories: type A, type B, and non-certified institutions, in decreasing order of certification stringency. The primary outcome was the incidence of grade ≥ IIIa postoperative complications based on the Clavien-Dindo classification system. The secondary outcome was surgery-related mortality. Logistic regression with risk adjustment, estimated using generalized estimating equations, was used to account for intra-cluster correlation.

Results: There was no significant difference in the risks of distal gastrectomy-related complications across the three institution types. However, type A- (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.31-0.49) and type B-certified institutions (OR 0.59, 95% CI 0.49-0.71) had a significantly lower mortality risk than non-certified ones. On the other hand, Type A- (OR 1.25, 95% CI 1.09-1.44) and type B-certified institutions (OR 1.17, 95% CI 1.03-1.33) had higher risks of postoperative total gastrectomy-related complications than non-certified ones. Nevertheless, type A- (OR 0.41, 95% CI 0.29-0.58) and type B-certified institutions (OR 0.67, 95% CI 0.51-0.88) had significantly lower surgery-related mortality risks than non-certified ones.

Conclusions: Certified institutions demonstrated lower surgical mortality risks, highlighting the benefits of the certification system and the importance of institutional quality.

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.

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.