What question did this study set out to answer?

To evaluate the prognostic significance of histopathologic subtype and impact of adjuvant chemotherapy in ampullary adenocarcinoma after surgical resection.

March 14, 2026

Histopathologic Subtype as a Determinant of Prognosis and Chemotherapy Benefit in Resected Ampullary Adenocarcinoma

Key Points

To evaluate the prognostic significance of histopathologic subtype and impact of adjuvant chemotherapy in ampullary adenocarcinoma after surgical resection.
Retrospective review of patients with ampullary adenocarcinoma post-pancreatoduodenectomy at University of Colorado Hospital
Analysis of clinicopathologic variables associated with overall and recurrence-free survival
Use of multivariable Cox regression for outcome prediction
Median overall survival was 93.9 months with significant variability at different time points
Older age, lymph node involvement, and R1 margin associated with poorer overall survival
Pancreatobiliary subtype exhibited worse overall survival compared to intestinal subtype; 5-year OS of 48% vs. 75%
Adjuvant chemotherapy correlated with improved survival in pancreatobiliary subtype but showed no benefit in intestinal subtype

Abstract

ABSTRACT Background Ampullary adenocarcinoma (AAC) is a rare malignancy with heterogeneous biological behavior. Although surgical resection is the only potentially curative option, the prognostic role of histopathologic features and adjuvant chemotherapy (AC) remains unclear. Methods Consecutive patients undergoing curative‐intent pancreatoduodenectomy for AAC at the University of Colorado Hospital between January 2013 and May 2025 were retrospectively reviewed. Clinicopathologic variables associated with overall (OS) and recurrence‐free survival (RFS) were analyzed using multivariable Cox regression. Results Ninety‐seven patients were included. Median OS was 93.9 months with 1‐, 3‐, 5‐, and 10‐year OS rates of 89%, 67%, 59%, and 46%. Older age (HR, 3.79; 95% CI, 1.71–8.41), lymph node (LN) involvement (HR, 4.92; 95% CI, 1.87–12.93), and R1 margin (HR, 4.33; 95% CI, 1.09–17.25) independently predicted poorer OS. The pancreatobiliary subtype (pbAAC) showed worse OS than the intestinal subtype (iAAC) (5‐year OS, 48% vs. 75%; p = 0.012). In pbAAC, LN metastasis (HR, 4.16; 95% CI, 1.31–13.18) and R1 margin (HR, 5.47; 95% CI, 1.10–27.20) predicted worse OS, whereas AC was associated with improved survival (HR, 0.404; 95% CI, 0.18–0.91). No AC benefit was observed in iAAC ( p = 0.323). Conclusions Histopathologic subtype is a key prognostic factor in AAC, with AC associated with better survival in pbAAC.

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