The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial.

Gennaro Nappo,Alessandro Coppola,Paola Spaggiari,Domenico Borzomati,Giuseppe Perrone,Roberto Coppola,Łukasz Liszka,Fabio Vistoli,Michela Amato,Sławomir Mrowiec,Marco Montorsi,Damiano Caputo,Daniela Campani,Ugo Boggi,Tommasangelo Petitti,Alessandro Zerbi

doi:10.3390/cancers13092097

Abstract

Simple SummaryThere is no clear evidence on the most effective method of pathological analysis and clearance definition (0 vs. 1 mm) to define R1 resection after pancreatoduodenectomy (PD). However, several studies showed that the R1 resection is a poor prognostic factor in patients that have undergone PDs for periampullary cancers. In this randomized clinical trial, specimens were randomized with two pathological methods, the Leeds Pathology Protocol (LEEPP) or the conventional method adopted before the study. The 1 mm clearance is the most effective factor in determining R1 rate after PD but only when adopting the LEEP, the R1 resection represents a significant prognostic factor.Background: There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. Methods: PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. Results. One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. Conclusions. The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.

Highlights

The evaluation of margin status after pancreatoduodenectomy (PD) for periampullary tumors has been a widely debated topic over the past decade [1,2,3]
Our aims were to evaluate the effect of the pathological method (LEEPP vs. conventional) and the definition of clearance (0 vs. 1 mm) in terms of R1 resection rate and to assess with which pathological method and clearance R1 resection can be considered a significant prognostic factor
Our aims were to evaluate the effect of the pathological method (LEEPP vs. convenFollow-up was conducted according to a standardized schedule (1 month after surgery, tional) and the definition of clearance (0 vs. 1 mm) in terms of R1 resection rate and to every 4–6 months for the first 5 years)

Summary

Introduction

The evaluation of margin status after pancreatoduodenectomy (PD) for periampullary tumors has been a widely debated topic over the past decade [1,2,3]. Other pathological protocols have been described in the literature [11,12], but no consensus on which one should be adopted has been reached [13] These heterogeneities mean that an interpretation of the available literature is difficult, especially for the evaluation of the prognostic role of. There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. The pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis

Objectives

Methods

Conclusion