Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma

Abstract

Objective: To better understand the impact of a microscopically positive margin (R1) on patterns of disease recurrence and survival after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma.

Summary background data: A positive resection margin after PD is considered to be a poor prognostic factor, and some have proposed that an R1 margin may be a biologic predictor of more aggressive disease. The natural history of patients treated with contemporary multimodality therapy who underwent a positive margin PD has not been described.

Methods: We analyzed our experience from 1990 to 2004, which included the prospective use of a standardized system for pathologic analysis of all PD specimens. All patients who underwent PD met objective computed tomographic criteria for resection. Standard pathologic evaluation of the PD specimen included permanent section analysis of the final bile duct, pancreatic, and superior mesenteric artery (SMA) margins. First recurrences (all sites) were defined as local, regional, or distant. Survival and follow-up were calculated from the date of initial histologic diagnosis to the dates of first recurrence or death and last contact, respectively.

Results: PD was performed on 360 consecutive patients with pancreatic adenocarcinoma. Minimum follow-up was 12 months (median, 51.9 months). The resection margins were negative (R0) in 300 patients (83.3%) and positive (R1) in 60 (16.7%); no patients had macroscopically positive (R2) margins. By multivariate analysis (MVA), high mean operative blood loss and large tumor size were independent predictors of an R1 resection. Patients who underwent an R1 resection had a median overall survival of 21.5 months compared with 27.8 months in patients who underwent an R0 resection. After controlling for other variables on MVA, resection status did not independently affect survival. By MVA, only lymph node metastases, major perioperative complications, and blood loss adversely affected survival.

Conclusions: There was no statistically significant difference in patient survival or recurrence based on R status. However, this series is unique in the incorporation of a standardized surgical technique for the SMA dissection, the prospective use of a reproducible system for pathologic evaluation of resection margins, the absence of R2 resections, and the frequent use of multimodality therapy.

FIGURE 1. Illustration of a pancreaticoduodenectomy specimen demonstrating how the superior mesenteric artery margin should be inked at the time of permanent section pathologic examination. This margin cannot be retrospectively evaluated if the margin was not inked for identification at the time of gross inspection. SMPV, superior mesenteric-portal vein.

FIGURE 2. Kaplan-Meier survival curves for patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy resulting in an R0 or an R1 resection. Median survival for 300 patients undergoing R0 resection was 27.8 months. Median survival for 60 patients undergoing R1 resection was 21.5 months (P = 0.027 on univariate analysis). On multivariate analysis, an R1 resection did not independently affect survival.