The Association Between Gastro-Esophageal Microbiome and Anastomotic Leakage in Esophageal Cancer Surgery: A Prospective Observational Cohort Study

Abstract Background Anastomotic leakage (AL) following esophagectomy is a severe complication in esophageal cancer surgery due to the increase in morbidity and mortality. The influence of the gastro-esophageal microbiome on anastomotic leakage is not well studied in esophageal cancer surgery. Therefore, the aim of this study was to investigate whether certain peroperatively cultured gastro-esophageal bacteria or yeasts are associated with anastomotic leakage. Methods Patients with resectable (cT1N + M0 or cT2–4aN0-3 M0) esophageal adeno- or squamous cell carcinoma, undergoing elective esophagectomy with gastric conduit (GC) reconstruction between June 2020 and December 2024, were eligible for this prospective observational cohort study. Patients were included if peroperative esophageal- and GC-culture swabs were obtained for microbiological analysis. AL was defined according to the Esophagectomy Complications Consensus Group (ECCG). The primary outcome was the bacterial/yeast spectrum in AL-positive versus negative patients. Secondary outcome measures included AL severity (according to Clavien-Dindo and ECCG), and survival. Statistical analysis included multivariable logistical regression for chance of developing AL per cultured microbiome subgroup. Results 209 patients were included, of which 30 (14.4%) developed AL. Baseline-, tumor- and pathological-characteristics were comparable between AL-positive versus negative subgroups. Bacterial subtypes (including morphology and gram-staining) were comparable between subgroups. Yeast positive cultures from the GC (predominantly Candida Albicans), were more frequently observed in patients with AL (52% vs. 27%, p = 0.02). Multivariable logistical regression showed an increased risk of developing AL in patients with yeast positive GC-cultures, aOR 3.37 (95% CI: 1.34–8.69, p 0.01). The overall complications, severity of AL, and survival were comparable between bacterial- and yeast-subgroups. The quantity of cultured yeast-colonies was not correlated with complication severity. Conclusion Peroperatively obtained positive yeast-cultures from the gastric conduit were associated with anastomotic leakage in patients undergoing elective esophagectomy. Future research should focus on the role of peroperative obtained culture swabs as potential screening tool, and whether the incidence of anastomotic leakage could be reduced by yeast-specific treatment in patients with positive cultures.