Risk factors and conservative therapy outcomes of anastomotic leakage after gastrectomy: Experience of 3,926 patients from a single gastric surgical unit

**Background:** Anastomotic leakage (AL) after gastrectomy is a severe postoperative complication associated with increased mortality, prolonged hospitalization, and higher costs. Despite its clinical importance, no consensus guidelines exist for AL treatment. This large single-center cohort study aimed to identify risk factors for AL and evaluate the efficacy of conservative management in gastric cancer patients.

**Methods:** The study retrospectively reviewed prospectively collected clinicopathological data from 3,926 gastric cancer patients who underwent gastrectomy at the First Affiliated Hospital of Nanjing Medical University, China, between January 2014 and December 2021. Potential risk factors analyzed included age, sex, BMI, ASA score, hemoglobin, albumin, cholesterol, neutrophil and lymphocyte counts, diabetes, smoking, drinking, previous laparotomy, neoadjuvant chemotherapy, tumor location, TNM stage, surgical approach, resection type, reconstruction method, and operation duration. AL was diagnosed using clinical presentation, biochemical markers, CT scan, fluoroscopy, or methylene blue test. Most patients initially received conservative treatment (fasting, gastrointestinal decompression, nutritional support, antibiotics, and CT-guided percutaneous drainage as needed). Statistical analyses included univariate and multivariate Cox proportional hazard regression, propensity score matching (PSM), and Kaplan-Meier survival analysis.

**Key Results:** AL occurred in 80 of 3,926 patients (2.03%). The most frequent AL site was esophagojejunostomy (73.8%, 59/80). One patient (1.25%, 1/80) died from septic shock 4 months post-surgery. The median time from surgery to AL diagnosis was 6 days (IQR 5–8 days). Multivariate analysis identified five independent risk factors for AL: low albumin concentration (OR 0.917, 95% CI 0.873–0.964, P=0.001), presence of diabetes (OR 2.009, 95% CI 1.094–3.690, P=0.025), laparoscopic surgery (OR 3.172, 95% CI 1.743–5.771, P<0.001), total gastrectomy (OR 3.593, 95% CI 1.546–8.352, P=0.003), and proximal gastrectomy (OR 5.576, 95% CI 1.856–16.750, P=0.002). Of the 80 AL patients, 77 (96.3%) underwent conservative treatment alone, 1 (1.2%) required emergency surgery for splenic hemorrhage, and 2 (2.5%) received endoscopic intervention. The median time from AL diagnosis to closure was 17 days (IQR 11–26 days), and the closure rate within the first month was 83.5% (66/79). The median time from AL diagnosis to discharge was 23 days (IQR 17–32 days). Low preoperative albumin concentration was significantly associated with delayed leakage closure (P=0.004). After PSM, no significant difference in 5-year overall survival was observed between patients with and without AL (mean survival 75.78 months [95% CI 67.28–84.23] vs. 72.43 months [95% CI 61.00–82.36], P=0.631).

**Clinical Implications:** This large cohort study confirms that AL after gastrectomy is relatively uncommon (2.03%) but carries a mortality risk of 1.25%. Key modifiable risk factors include low albumin and diabetes, suggesting that preoperative nutritional optimization and glycemic control may reduce AL risk. The finding that laparoscopic surgery was associated with higher AL risk (OR 3.172) may reflect a learning curve or patient selection bias, warranting careful patient selection and surgeon experience. Conservative treatment achieved a high closure rate (83.5% within one month), supporting its role as a first-line strategy for AL management, potentially avoiding the morbidity of reoperation. The lack of survival difference between AL and non-AL patients after PSM is reassuring but should be interpreted cautiously given the small number of AL events.