BACKGROUND: Ampullary carcinoma (AC) has a poor prognosis in patients with pancreatic and perineural invasion beyond the duodenal muscularis propria. However, no studies were focused on evaluating Auerbach's plexus (AP) invasion in AC, and its clinical pathological significance remains unclear. In this study, we examined the clinical significance of AP invasion in patients with AC. METHODS: Clinicopathological examinations for AP invasion were performed in 80 patients with AC (median age: 70 years, male-to-female ratio: 43:37) who underwent endoscopic and surgical resection at Kurume University Hospital between 2005 and 2022. Statistical analysis was performed using the Kaplan-Meier method (log-rank test) and Cox proportional hazards models. RESULTS: The median AC tumor size was 20 mm, and the most common histological type was well-differentiated adenocarcinoma (59/80, 74%). Tumor invasion beyond the duodenal muscularis propria occurred in 38 patients (48%), of whom 21 (55%) had AP invasion. Univariate analysis identified several prognostic factors, including histological type, tumor depth, stage, AP invasion, and lymph node metastasis. Multivariate analysis confirmed AP invasion (hazard ratio=2.716, 95% confidence: 1.130-6.529, p=0.026) as an independent prognostic factor. Additionally, patients with AP invasion had a significantly worse prognosis than those without AP invasion (p<
0.001). CONCLUSIONS: AP invasion is a critical prognostic factor in patients with AC. Closer monitoring and more aggressive treatment strategies may be warranted for patients with AP invasion to improve their prognosis.