Gastric Cancer最新文献

Helicobacter pylori (H. pylori) infection is a recognized risk factor for gastric cancer (GC), which is the leading cause of cancer-related deaths worldwide. As a Class I carcinogen, H. pylori plays a central role in the occurrence and development of GC. Recent studies have highlighted the critical role of metabolic reprogramming inthe gastric cancer, and H. pylori infection has been shown to significantly alter metabolic pathways in gastric cancer. This review explores the mechanisms by which H. pylori infection drives metabolic changes in GC, particularly in glycolysis, lipid metabolism, and amino acid metabolism. By altering these metabolisms, H. pylori enhances the survival, proliferation, and metastasis of tumor cells, and also promotes immune evasion. Therefore, understanding the ways in which H. pylori-induced metabolic reprogramming of GC cells is essential for identifying new therapeutic targets. By summarizing the latest research progress of these metabolic pathways, new strategies and directions can be provided for gastric cancer treatment.

Background: Peritoneal dissemination is a major cause of poor prognosis in gastric cancer (GC). Although conventional peritoneal lavage cytology (CY) is used to detect micrometastatic peritoneal spread, its sensitivity is limited. This study aimed to evaluate the clinical utility of droplet digital methylation-specific PCR (ddMSP) targeting cancer-specific methylation for DNA-based detection of peritoneal dissemination.

Methods: Peritoneal lavage fluid was prospectively collected from 400 samples in 357 GC patients, including 360 samples from 339 patients with chemotherapy-naïve tumors. DNA was extracted, bisulfite-converted, and analyzed by ddMSP targeting CDO1 and HOPX methylation. Diagnostic performance was assessed by ROC analysis, and associations with clinicopathological features and prognosis were evaluated using logistic and Cox regression models.

Results: CDO1 and HOPX methylation levels were significantly elevated in CY1 cases compared with CY0 (p < 0.0001). CDO1 methylation demonstrated excellent diagnostic accuracy for CY1 (AUC: 0.93; sensitivity: 83.9%; specificity: 90.9%), while HOPX methylation showed slightly lower performance (AUC: 0.86). Multivariate analysis revealed that ddMSP CDO1-hi was independently associated with serosal invasion (pT4), and HOPX-hi with both pT4 and nodal metastasis. Furthermore, CDO1-hi status was an independent adverse prognostic factor for peritoneal dissemination-free survival (HR: 2.73, p = 0.018).

Conclusions: ddMSP-based detection of CDO1 methylation provides a sensitive and specific method for identifying micrometastatic peritoneal spread in GC. This DNA-based approach may serve as a valuable prognostic biomarker and contribute to improved perioperative management in gastric cancer.

Background: Prognostic factors for conversion surgery in patients with metastatic gastric cancer remain unclear. This study aimed to identify the prognostic factors associated with conversion surgery, and evaluate the safety and survival outcomes of conversion surgery using data from Japanese patients enrolled in the CONVO-GC-1 study.

Methods: Clinical background, chemotherapy before and after surgery, surgical outcomes, postoperative complications, and survival were analyzed. Prognostic factors were assessed using univariate and multivariate regression analyses.

Results: A total of 773 Japanese patients were included. Categories 1, 2, 3, and 4 included 345, 156, 225, and 47 patients, respectively. R0 resection was achieved in 571 (73.9%) patients. Incidence rate of Clavien-Dindo grade ≥ III complications was 12.0%. Surgery-related mortality rate was 0.1%. Median overall survival (OS) among patients with R0 resection was 47.8 months. The OS of patients with R0 resection by category was 47.6, 116.6, 40.1, and 54.4 months for categories 1, 2, 3, and 4, respectively. In the multivariate analysis, male sex (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.30-2.22), undifferentiated histological type (HR, 1.35; 95% CI 1.04-1.75), Eastern Cooperative Oncology Group Performance Status ≥ 1 (HR, 1.57; 95% CI 1.18-2.08), ypT4 (HR,1.79; 95% CI 1.38-2.33), ypN + (HR, 1.92; 95% CI 1.42-2.58), and preoperative chemotherapy duration < 6 months (HR, 1.43; 95% CI 1.10-1.87) were poor prognostic factors.

Conclusion: Conversion surgery was safely performed, yielding favorable survival outcomes in patients with R0 resection. Therefore, careful patient selection is warranted, particularly in those with poor prognostic indicators.

Background: In late-line treatment for advanced gastric cancer (AGC), evidence supporting the use of irinotecan in older patients remains limited. We conducted a post-hoc age-subgroup analysis of the phase III RINDBeRG study, which randomized AGC patients previously treated with ramucirumab-based chemotherapy to receive ramucirumab plus irinotecan (RAM + IRI) or irinotecan alone (IRI).

Methods: Patients were classified as elderly (≥ 70 years; n = 83 [RAM + IRI], 80 [IRI]) or non-elderly (< 70 years; n = 117, 113). Efficacy outcomes-including overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)-and safety were compared. Prognostic factors for OS were explored via multivariable Cox regression.

Results: OS and PFS did not differ significantly between age groups. In the RAM + IRI group, median OS was 9.7 vs. 8.9 months (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.63-1.15), and PFS was 4.0 vs. 3.6 months (HR 0.84, CI 0.63-1.12). In the IRI group, OS was 8.5 months in both groups (HR 0.99, CI 0.7-1.34), and PFS was 3.1 vs. 2.2 months (HR 0.87, CI 0.65-1.17). ORRs were 20.5% vs. 14.5% (RAM + IRI) and 18.8% vs. 9.7% (IRI) in elderly vs. non-elderly patients. Grade ≥ 3 adverse events were comparable. Multivariable analysis identified ECOG PS 1, peritoneal metastasis, elevated LDH, modified Glasgow Prognostic Score ≥ 1, and low alkaline phosphatase as poor prognostic factors. Age was not prognostic.

Conclusions: Irinotecan-based therapy offers comparable efficacy and tolerability in older and younger patients with refractory AGC.

Peritoneal metastasis (PM) is a major contributor to poor prognosis in advanced gastric cancer (GC), yet its molecular mechanisms remain insufficiently understood. The results of bioinformatic analysis and clinical sample validation reveal that LncRNA MZF1-AS1 is significantly upregulated in GC tissues, particularly in peritoneal metastases, and is associated with worse overall and post-progression survival. MZF1-AS1 enhances malignant phenotypes and PM of GC cells in vitro and in vivo. Mechanistically, RAB13 is demonstrated as a functional effector of MZF1-AS1 via RNA-seq. MZF1-AS1 enhances RAB13 expression by promoting its mRNA stability, thereby facilitating GC cell proliferation, EMT, migration, invasion, and stemness. Further, RNA pulldown and Mass Spectrometry reveal that MZF1-AS1 directly binds to NSUN2. MZF1-AS1 strengthens the interaction between NSUN2 and RAB13 mRNA, promoting NSUN2-mediated m5C modification and stabilizing RAB13 mRNA. Our findings uncover a novel epi-transcriptomic mechanism by which MZF1-AS1 promotes GC progression via NSUN2-dependent m5C methylation of RAB13 mRNA, offering new insights into PM pathogenesis and highlighting potential therapeutic targets for advanced GC.

Background: Telesurgery is gaining traction across surgical specialties. However, its use in radical gastrectomy for gastric cancer remains limited. This study evaluated the safety and feasibility of fifth-generation (5G) robot-assisted remote radical gastrectomy using the Toumai Endoscopic Surgery Robotic System.

Methods: In this prospective single-center single-arm clinical study, eligible patients underwent 5G remote radical gastrectomy over a distance of 15 km. The primary outcome was the incidence of intraoperative and postoperative complications. Secondary outcomes included surgical completion rate, operative duration, estimated blood loss, number of lymph nodes dissected, time to first flatus and diet, and hospital stay.

Results: Twenty-seven patients were enrolled between September and December 2023. All surgeries were completed successfully, with no conversion and a 100% R0 resection rate. No intraoperative complications occurred. Postoperative complications occurred in 18.5% of patients, with no Clavien-Dindo grade ≥ III. The mean operative time was 192.6 ± 34.8 min, and mean blood loss was 35.9 ± 15.9 mL. Lymph nodes were dissected at an average of 38.4 ± 13.2 lymph nodes. Median time to first flatus and oral intake was 2.0 days, to liquid diet was 4.0 days, and hospital stay was 7.0 days. The 5G network was highly stable, with total delay of 226.2 ± 4.4 ms, round-trip delay of 31.6 ± 3.8 ms, and packet loss < 0.1%.

Conclusions: The 5G robot-assisted remote radical gastrectomy using the Toumai system is safe and feasible for selected patients with gastric cancer. The integration of 5G and robotics may offer a promising telemedicine approach to surgical oncology.

Objective: This study aimed to evaluate the impact of drain placement on the incidence of postoperative complications in patients undergoing gastrectomy.

Background: The effectiveness of prophylactic abdominal drain placement in gastrectomy remains unclear. Nevertheless, they are still commonly used following gastrectomy.

Methods: We conducted a retrospective cohort study using a nationwide inpatient database in Japan. Patients who underwent gastrectomy for gastric cancer between January 2014 and March 2022 were included. We applied overlap weighting based on propensity scores to adjust for baseline characteristics. The primary outcome was the incidence of intra-abdominal infections. Secondary outcomes included postoperative percutaneous drainage, in-hospital death, length of hospital stay, and total hospitalization costs.

Results: A total of 217,750 patients met the inclusion criteria, and 196,660 (90.3%) received prophylactic abdominal drains. After overlap weighting, the drain group had a significantly lower incidence of intra-abdominal infections compared to the no-drain group (6.3% vs. 7.6%; 95% confidence interval [CI] - 1.7 to - 1.0). The prophylactic drains were also associated with reduced in-hospital postoperative mortality (0.6% vs. 0.8%; 95% CI - 0.3 to - 0.1). No significant differences were observed between the two groups in postoperative percutaneous drainage or hospital stay duration.

Conclusion: This study suggests that prophylactic abdominal drainage was associated with a reduced incidence of intra-abdominal infections after gastrectomy without increasing hospitalization duration or medical costs.