Identifying occult high-risk features and stratified management strategies following curative resection for ampullary adenocarcinoma

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Objective: The aim of the current study was to identify independent prognostic factors, evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups, and define adjuvant chemotherapy-sensitive populations. Methods: A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy (2011–2020) was performed. Cases were classified into intestinal (28.0%), pancreatobiliary (30.4%), and mixed subtypes (18.5%) per NCCN (v2.2025) criteria. Independent prognostic factors for AAC patients were identified through uni- and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range, gender, differentiation, T stage, N stage, BVI, TDs, and PNI. Results: The pancreatobiliary signature (HR = 2.884, P < 0.001) and BVI (HR = 2.330, P = 0.001) were independent poor prognostic factors. Adjuvant chemotherapy improved overall survival (OS) in the following AAC patients: T3–T4 stage (HR = 0.485, P = 0.050); N1–N2 stage (HR = 0.365, P = 0.008); and TD-positive (HR = 0.401, P = 0.026). The median OS increased from 22.3–51.3 months with adjuvant chemotherapy in TD-positive patients (P = 0.019). TD positivity conferred a worse prognosis in BVI-negative subgroups (OS: HR = 3.840, 95% CI: 2.058–7.166, P < 0.001; and progression-free survival (PFS): HR = 2.950, 95% CI: 1.550–5.617, P = 0.002). Conclusions: The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC. TD status identified high-risk cohorts, thus enabling postoperative risk-stratified treatment strategies. In patients negative for pancreatobiliary signature or BVI, TD positivity predicted significantly worse survival.

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