Sex disparity, prediagnosis lifestyle factors, and long-term survival of gastric cancer: a multi-center cohort study from China.

BACKGROUND: This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. METHODS: Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. RESULTS: Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881-0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616-0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035-1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019-1.286, P = 0.023; BMI: 23-27.4, HR = 0.875, 95%CI: 0.824-0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735-0.886, P < 0.001). CONCLUSIONS: Sex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer.

The minimum number of examined lymph nodes was 24 for optimal survival of pathological T2-4 gastric cancer: a multi-center, hospital-based study covering 20 years of data.

INTRODUCTION: The current National Comprehensive Cancer Network (NCCN) guidelines recommend that at least 16 lymph nodes should be examined for gastric cancer patients to reduce staging migration. However, there is still debate regarding the optimal management of examined lymph nodes (ELNs) for gastric cancer patients. In this study, we aimed to develop and test the minimum number of ELNs that should be retrieved during gastrectomy for optimal survival in patients with gastric cancer. METHODS: We used the restricted cubic spline (RCS) to identify the optimal threshold of ELNs that should be retrieved during gastrectomy based on the China National Cancer Center Gastric Cancer (NCCGC) database. Northwest cohort, which sourced from the highest gastric cancer incidence areas in China, was used to verify the optimal cutoff value. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In this study, 12,670 gastrectomy patients were included in the NCCGC cohort and 4941 patients in the Northwest cohort. During 1999-2019, the average number of ELNs increased from 17.88 to 34.45 nodes in the NCCGC cohort, while the number of positive lymph nodes remained stable (5-6 nodes). The RCS model showed a U-curved association between ELNs and the risk of all-cause mortality, and the optimal threshold of ELNs was 24 [Hazard ratio (HR) = 1.00]. The ELN ≥ 24 group had a better overall survival (OS) than the ELN < 24 group clearly (P = 0.003), however, with respect to the threshold of 16 ELNs, there was no significantly difference between the two groups (P = 0.101). In the multivariate analysis, ELN ≥ 24 group was associated with improved survival outcomes in total gastrectomy patients [HR = 0.787, 95% confidence interval (CI): 0.711-0.870, P < 0.001], as well as the subgroup analysis of T2 patients (HR = 0.621, 95%CI: 0.399-0.966, P = 0.035), T3 patients (HR = 0.787, 95%CI: 0.659-0.940, P = 0.008) and T4 patients (HR = 0.775, 95%CI: 0.675-0.888, P < 0.001). CONCLUSION: In conclusion, the minimum number of ELNs for optimal survival of gastric cancer with pathological T2-4 was 24.

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study.

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.

Using nomogram, decision tree, and deep learning models to predict lymph node metastasis in patients with early gastric cancer: a multi-cohort study.

The accurate assessment of lymph node metastasis (LNM) in patients with early gastric cancer is critical to the selection of the most appropriate surgical treatment. This study aims to develop an optimal LNM prediction model using different methods, including nomogram, Decision Tree, Naive Bayes, and deep learning methods. In this study, we included two independent datasets: the gastrectomy set (n=3158) and the endoscopic submucosal dissection (ESD) set (n=323). The nomogram, Decision Tree, Naive Bayes, and fully convolutional neural networks (FCNN) models were established based on logistic regression analysis of the development set. The predictive power of the LNM prediction models was revealed by time-dependent receiver operating characteristic (ROC) curves and calibration plots. We then used the ESD set as an external cohort to evaluate the models' performance. In the gastrectomy set, multivariate analysis showed that gender (P=0.008), year when diagnosed (2006-2010 year, P=0.265; 2011-2015 year, P=0.001; and 2016-2020 year, P<0.001, respectively), tumor size (2-4 cm, P=0.001; and ≥4 cm, P<0.001, respectively), tumor grade (poorly-moderately, P=0.016; moderately, P<0.001; well-moderately, P<0.001; and well, P<0.001, respectively), vascular invasion (P<0.001), and pT stage (P<0.001) were independent risk factors for LNM in early gastric cancer. The area under the curve (AUC) for the validation set using the nomogram, Decision Tree, Naive Bayes, and FCNN models were 0.78, 0.76, 0.77, and 0.79, respectively. In conclusion, our multi-cohort study systematically investigated different LNM prediction methods for patients with early gastric cancer. These models were validated and shown to be reliable with AUC>0.76 for all. Specifically, the FCNN model showed the most accurate prediction of LNM risks in early gastric cancer patients with AUC=0.79. Based on the FCNN model, patients with LNM rates of >4.77% are strong candidates for gastrectomy rather than ESD surgery.

Insulin for hyperglycemia prevention and management during postgastrectomy nutrition support in gastric cancer: Reduced complications in a retrospective cohort study in China.

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness of insulin addition to the total nutrition admixture (TNA) for glycemic control among patients with gastric cancer (GC) receiving supplementary parenteral nutrition (SPN) after gastrectomy. METHODS AND STUDY DESIGN: A retrospective cohort study was conducted among 208 noncritical ill patients who underwent gastrectomy for GC from 2017 to 2019 at a tertiary teaching hospital in Lanzhou, China. All the included patients received individualized SPN and enteral nutrition treatment after gastrectomy. The patients were randomly divided into insulin and noninsulin groups based on the TNA composition. Blood glucose (BG) measurements, glycemic fluctuation, and hypoglycemia incidence during SPN were compared between the two groups. The postoperative comprehensive complications index (CI) and infections were compared according to insulin regimen and postoperative glycemic status. RESULTS: The mean BG was significantly lower and fluctuated less in the insulin group than in the noninsulin group (p<0.05). One unit of insulin per 6 g of parenteral nutrition glucose addition to TNA did not increase hypoglycemia incidence (p>0.05). Comparing CI and the infection rate, no significance was observed between the insulin and noninsulin groups, but a higher postoperative CI was observed in patients with hyperglycemia than in euglycemic patients (p<0.05). CONCLUSIONS: Appropriate insulin addition to TNA has an overall positive effect on glycemic management in patients with noncritical GC who received SPN after gastrectomy. Postoperative glycemic status was associated with the incidence of relevant complications. Further research is needed for conclusive recommendations.

The Impact and Clinical Prediction of Hyperglycemia During Parenteral Nutrition for Nondiabetic Patients After Gastrectomy for Gastric Cancer.

BACKGROUND AND PURPOSE: Hyperglycemia (HG) is associated with increased postoperative complications. This study aims to evaluate the effect of HG during supplemental parenteral nutrition (SPN) on short-term prognosis in non-diabetic patients undergoing gastrectomy for cancer and to analyse the risk factors and prevention methods for HG. METHODS: A total of 359 patients were divided into three groups according to blood glucose (BG) during SPN: normoglycemic patients ( ≤ 125 mg/dL), mild HG (125~200 mg/dL), and severe HG (>200 mg/dL). The effect of BG on postoperative short-term outcomes was analyzed. Multivariate regression was performed to investigate influencing factors for severe HG. The safety and efficacy of insulin addition to total nutrient admixture (TNA) for the prevention and management of HG were assessed by propensity score matching (PSM). In addition, regression analysis was performed in the noninsulin group to investigate the predictive factors of severe HG, and a nomogram was plotted. RESULTS: The postoperative complication rate was 18.9%, but it was significantly higher in patients with severe HG than in mild HG and normoglycemic patients (25.2, 15.0, and 10.0%, respectively, p < 0.05). Multivariate logistic regression analysis showed that anemia, myosteatosis, higher postoperative capillary blood glucose (CBG) before TNA infusion, and insulin in the TNA were independent influencing factors for severe HG. Based on the above factors, 75 pairs of patients (insulin group and non-insulin group) with comparable baseline data were successfully matched by PSM. The HG incidence and the glycemic fluctuation were significantly improved through 1 U insulin/6 g glucose (1/6 scheme) to TNA. A nomogram containing hemoglobin, skeletal muscle radiodensity, pre-SPN CBG, and pTNM stage with good predictive efficacy (C-index: 0.750) was constructed based on the noninsulin group. CONCLUSION: Poor postoperative glycemic control was related to worse outcomes in non-diabetic patients undergoing gastrectomy for cancer. Pre-operative anemia, myosteatosis, and high postoperative CBG before TNA infusion are risk factors for severe HG. Insulin in TNA can improve the blood glucose control of patients. Our proposed nomogram rendered an individualized predictive tool for HG during SPN, which helps screen high-risk patients requiring insulin therapy. Future studies with larger samples are needed to develop a complete insulin application protocol for SPN.