# Inflammation and fibrosis at pancreatic resection margin and their role in post-operative pancreatic fistula development after pancreaticoduodenectomy: a pilot study from a single institution

## TL;DR

This study shows that lack of fibrosis and inflammation at the pancreatic resection margin increases the risk of post-operative pancreatic fistulas after surgery.

## Contribution

The study introduces a feasible intraoperative method using frozen sections to assess fibrosis and inflammation as predictors of pancreatic fistulas.

## Key findings

- Absence of fibrosis and chronic lymphomononuclear inflammation at the resection margin independently predicts post-operative pancreatic fistulas.
- Combined absence of fibrosis and inflammation significantly elevates the risk of clinically relevant fistulas.
- Intraoperative frozen section evaluation of these factors is feasible and could guide surgical decisions.

## Abstract

Postoperative pancreatic fistula (POPF) is a major complication after pancreaticoduodenectomy (PD), with significant impact on outcomes. While the absence of pancreatic fibrosis is a known risk factor, its intraoperative assessment is often subjective. Moreover, the potential protective role of chronic inflammation at the pancreatic resection margin (PRM) has not been fully explored. This study aimed to evaluate the histological presence of fibrosis and chronic lymphomononuclear inflammatory infiltrate (CLII) at the PRM as predictors of POPF and clinically relevant POPF (CR-POPF), and to assess their intraoperative feasibility via frozen sections.

A retrospective analysis was performed on 141 patients who underwent PD (2014–2022). Intraoperative frozen sections of the PRM were reviewed for fibrosis and CLII using standardized semi-quantitative grading. Univariate and multivariate analyses identified predictors of POPF and CR-POPF.

POPF and CR-POPF occurred in 42.5 % and 22.7 % of patients, respectively. Absence of fibrosis and CLII were independently associated with increased risk of POPF (OR 7.51 and 4.30; p < 0.0001) and CR-POPF (OR 4.43 and 3.40; p = 0.0003 and p = 0.0099). Combined absence of both further elevated risk (OR 5.20 for POPF; OR 4.83 for CR-POPF). In multivariate analysis, absence of fibrosis and CLII and main pancreatic duct <3 mm remained independent predictors.

The absence of fibrosis and CLII at the PRM strongly predicts POPF and CR-POPF. Their intraoperative evaluation via frozen sections is feasible and may support tailored surgical strategies, especially in minimally invasive PD.

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