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

Abstract

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. 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. 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). 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.