Persistent Systemic Inflammation Mediates the Impact of Postoperative Complications on Survival After Gastric Cancer Surgery

BACKGROUND: Postoperative complications (POCs) are associated with poor long-term outcomes in gastric cancer. However, the underlying biologic mechanisms remain unclear, and systemic inflammation may mediate this association. METHODS: This study retrospectively analyzed 4177 gastric cancer patients who underwent curative gastrectomy between 2013 and 2018. The neutrophil-to-lymphocyte ratio (NLR) was assessed preoperatively (pre-NLR), on postoperative day 2 (early NLR), and 3 months postoperatively (late NLR). Multivariable Cox and logistic regression models assessed the associations of NLR and POCs with survival and complication risk. RESULTS: For 20.3% of the patients, POCs occurred and were associated with significantly higher NLR at all time points. In the multivariable analysis, early and late NLR independently predicted complication risk. In the Kaplan-Meier survival analysis, POCs were significantly associated with worse overall survival (OS) (hazard ratio [HR], 1.80; p < 0.001) and disease-specific survival (DSS) (HR, 1.80; p < 0.001). However, in multivariate COX regression, POCs were not independently associated with OS or DSS, whereas late NLR remained a significant predictor for both OS (HR, 1.02; p = 0.049) and DSS (HR, 1.03; p = 0.008). When stratified by POC status, high late NLR was significantly associated with worse OS (HR, 2.776; p < 0.001) and DSS (HR, 2.677; p < 0.001) in the POC group. In the no-POC group, high late NLR also was associated with worse OS (HR, 1.587; p < 0.001), but not DSS (HR, 1.274; p = 0.150). CONCLUSIONS: Persistent systemic inflammation, reflected by elevated late NLR, is a key mediator of the relationship between POCs and survival. Monitoring persistent inflammation may improve risk stratification and guide management strategies for gastric cancer patients.