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Introduction To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer. Materials and Methods Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival. Results In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P  < .001), distal location (83.51% vs. 64.19%, P  < .001), intestinal type (42.21% vs. 34.46%, P  < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P  = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P  = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P  = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P  = .186 and HR = 0.912, 95% CI, 0.464-1.793, P  = .822, respectively). Conclusion In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The survival outcomes of younger patients with gastric cancer (GC) have remained controversial. This study explores the clinicopathological characteristics, survival outcomes, and genetic alterations of younger and older patients with GC. Methods: Patients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998–2018. Survival analysis was conducted using Kaplan–Meier estimates and Cox proportional hazards models. Sequencing datasets were enrolled from The Cancer Genome Atlas (TCGA) and Memorial Sloan–Kettering Cancer Center (MSKCC) databases. Results: A total of 1146 younger (<40 years of age) and 16,988 older (≥40 years of age) cases were included in the study. Younger patients had more poorly differentiated lesions than older patients (53.7% vs. 33.8%, respectively; p < 0.0001), and were more often pTNM stage IV (19.5% vs. 11.8%, respectively; p < 0.001). The 5‐year overall survival (OS) of patients from the NCCGCDB increased from 1998 to 2018. Younger patients with pTNM stage III had a lower survival rate than older patients (p = 0.014), while no differences by age were observed at other stages. The mutation frequency of the LRP1B, GNAS, APC, and KMT2D genes was higher for older than younger patients (p < 0.05 for all genes). While not significantly different, younger patients from the TCGA and MSKCC databases were more likely to have CDH1, RHOA, and CTNNB1 gene mutations. Conclusions: A stable proportion and improved survival of younger patients were reported using NCCGCDB data. Younger patients with pTNM stage III had lower rates of survival than older patients. Distinct molecular characteristics were identified in younger GC patients which may partly explain the histopathology and prognosis specific to this subpopulation. [ABSTRACT FROM AUTHOR]

It was generally believed that the prognosis of gastric neuroendocrine carcinoma (GNEC) was worse than gastric adenocarcinoma (GAC). However, almost all previous studies compared the prognosis of GNEC and GAC based on East Asians. In this study, we evaluated the clinicopathological features and prognosis of GNEC and GAC in Whites. Patients with GNEC and GAC were identified from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity score matching (PSM) analysis to match the age, sex, TNM stage, and treatments received between GNEC and GAC, then compared the overall survival (OS) and cancer-specific survival (CSS) in the two types. A total of 392 cases of GNEC and 12,835 cases of GAC in Whites were recognized. After PSM, the 5-year OS rates of GNEC and GAC were 50.3% and 43.0%, respectively (p = 0.010). The 5-year CSS rates of GNEC and GAC were 57.4% and 50.1%, respectively (p = 0.012). Besides, multivariable cox regression analyses showed that GNEC was an independent predictor of improved OS (HR 0.719; 95% CI 0.607–0.853) and CSS (HR 0.691; 95% CI 0.571–0.835) in the matched data. The prognosis of GNEC was better than GAC in Whites, showing significant ethnic differences. Appropriate treatments and follow-up strategies for GNEC in Whites are probably different from East Asians. The potential genetic and molecular mechanisms need to be further explored. [ABSTRACT FROM AUTHOR]

Background: Margin positivity after gastric cancer resection is associated with poorer outcomes. However, the prognostic factors and the choice of postoperative adjuvant treatment of patients with positive margin (PM) after gastrectomy are still being debated. Methods: A single-center, retrospective analysis was conducted for patients with PM after gastrectomy from the China National Cancer Center Gastric Cancer Database (NCCGCDB) from 1998 to 2018. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS). Results: A total of 449 patients were included in the study, including 192 (42.8%) in the proximal PM group (PPM), 205 (45.7%) in the distal PM group (DPM), and 52 (11.6%) in the bilateral PM group (BPM). The 3- and 5-year OS rates for the PM patients investigated were 47.5% and 39.3%, respectively, and the 3- and 5-year RFS rates were 60.0% and 53.6%, respectively. Multivariate Cox regression analysis proved total gastrectomy (hazard ratio (HR): 1.783, 95%CI: 1.133–2.805, p = 0.012), pT4 (HR: 5.264, 95%CI: 1.493–18.565, p = 0.01), pN2 (HR: 2.263, 95%CI: 1.164–4.397, p = 0.016), pN3 (HR: 2.327, 95%CI: 1.233–4.393, p = 0.009), and combined resection (HR: 1.952, 95%CI: 1.256–3.034, p = 0.003) to be independent risk factors of OS, and pT3 (HR: 9.257, 95%CI: 1.152–74.386, p = 0.036) and pT4 (HR: 11.361, 95%CI: 1.469–87.847, p = 0.020) to be independent risk factors for RFS. Adjuvant chemotherapy prolonged OS in the PPM group (p = 0.032) and prolonged RFS in the PPM group (p < 0.001) and the DPM group (p = 0.035) compared with surgery alone. Conclusions: Advanced pathologic stage was associated with poor prognosis, and postoperative adjuvant chemotherapy might be recommended in PM patients after gastrectomy. Still, further prospective trials are warranted to verify and support our conclusions. [ABSTRACT FROM AUTHOR]

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan‐Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P =.171). However, the ELNs ≥ 30 group had a better disease‐free survival (DFS) outcome compared with the others (all P <.05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182‐0.866, P =.020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152‐0.860, P =.021) and pT4 patients (HR = 0.484, 95%CI: 0.277‐0.844, P =.011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C‐index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000‐2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients. [ABSTRACT FROM AUTHOR]