Abstract
BACKGROUND AND OBJECTIVES: Esophagojejunal (EJ) leakage is a serious complication following total gastrectomy for gastric cancer. While several nutritional and treatment-related risk factors have been described, the role of Candida esophagitis (CE) in anastomotic failure has not been previously investigated. METHODS: This retrospective cohort study included 268 patients with gastric adenocarcinoma who underwent total gastrectomy with EJ anastomosis. The study was conducted between March 2021 and March 2025 at a tertiary referral center. CE was diagnosed by histopathologic examination of proximal esophageal margins submitted during surgery. Univariable and multivariable logistic regression analyses were performed to determine predictors of EJ leakage. Best subsets variable selection using Akaike's Information Criterion (AIC) and the Bayesian Information Criterion (BIC) guided final model development. RESULTS: Among the 268 patients, 48 (17.9%) developed EJ leakage. Multivariable analysis identified CE (OR: 2.19, p = 0.043), hypoalbuminemia (< 3.5 g/dL) (OR: 3.08, p = 0.007), BMI ≥ 25 kg/m(2) (OR: 3.68, p = 0.004), and administration of neoadjuvant therapy (OR: 2.34, p = 0.024) as independent predictors of EJ leakage. Additional analyses of diagnostic timing indicated that CE detected only on permanent histology (delayed treatment) was associated with higher odds of leak (adj OR 3.62; 95%CI: 1.42-9.23; p = 0.007), whereas CE detected on intraoperative frozen section was not. CONCLUSION: CE was associated with increased odds of EJ leakage after adjustment, but causality cannot be inferred from this retrospective study. The finding that delayed CE diagnosis was linked to higher leak risk suggests diagnostic timing may matter. Prospective validation of targeted esophageal assessment and timed antifungal strategies is warranted. Elevated BMI, hypoalbuminemia, and neoadjuvant therapy also contributed to higher odds of EJ leakage.