Journal Article

Reduction of intrapancreatic neural density in cancer tissue predicts poorer outcome in pancreatic ductal carcinoma

Esaki, Minoru, Ino, Yoshinori, Nakajima, Kosei, Nara, Satoshi, Kishi, Yoji, Hiraoka, Nobuyoshi, Iwasaki, Toshimitsu, Katai, Hitoshi, Shimada, Kazuaki

2019

Overview

Neural invasion is one of the malignant features contributing to locally advanced and/or metastatic disease progression in patients with pancreatic ductal adenocarcinoma (PDAC). Few studies exist on the distribution and state of nerve fibers in PDAC tissue and their clinicopathological impacts. The aim of the present study was to investigate the clinicopathological characteristics and prognostic value of intrapancreatic neural alterations in patients with PDAC. We retrospectively analyzed 256 patients with PDAC who underwent macroscopic curative surgery. Nerve fibers, immunolabeled with a specific neural marker GAP‐43, were digitally counted and compared among PDAC, chronic pancreatitis (CP) and normal pancreatic tissues. Interlobular nerve fibers were apparently hypertrophic in both CP and PDAC, although intrapancreatic neural density and nerve number decreased characteristically in PDAC. They tended to decrease toward the center of the tumor. Kaplan‐Meier survival analyses revealed a statistically significant correlation between low neural density and shorter overall survival (OS) (P = 0.014), and between high neural invasion and shorter OS (P = 0.017). Neural density (P = 0.04; HR = 1.496; 95% CI 1.018‐2.199) and neural invasion ratio (P = 0.064; HR = 1.439; 95% CI .980‐2.114) were prognostic factors of shorter OS in the multivariate analysis. These findings suggest low intrapancreatic neural density in patients with PDAC as an independent prognosticator, which may represent aggressive tumor behavior. Furthermore, we propose a simple, practical and reproducible method (to measure neural density and the neural invasion ratio during conventional histopathological diagnosis of PDAC), which has been validated using another cohort (n = 81). Neural invasion is one of the malignant features in patients with pancreatic ductal adenocarcinoma (PDAC), but few studies exist on the distribution and state of nerve fibers in PDAC tissue. Here we investigated the clinicopathological characteristics of intrapancreatic neural alterations in patients with PDAC and we concluded that low intrapancreatic neural density was an independent prognosticator. We also propose a simple, practical and reproducible method to measure neural density and the neural invasion ratio during conventional histopathological diagnosis of PDAC.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adenocarcinoma / Aged / Aged, 80 and over / Carcinoma, Pancreatic Ductal - mortality / Carcinoma, Pancreatic Ductal - pathology / Carcinoma, Pancreatic Ductal - therapy / Chemotherapy / ductal carcinoma / Female / Fibers / Humans / Immunohistochemistry / intrapancreatic neural density / intrapancreatic neural invasion / Kaplan-Meier Estimate / Lymphatic system / Male / Medical prognosis / Metastases / Metastasis / Middle Aged / Multivariate analysis / Neoplasm Metastasis / Neoplasm Staging / Nerve Fibers - pathology / Original / Pancreas / Pancreas - innervation / Pancreas - pathology / Pancreatic cancer / Pancreatic carcinoma / Pancreatic Neoplasms / Pancreatic Neoplasms - mortality / Pancreatic Neoplasms - pathology / Pancreatic Neoplasms - therapy / Pancreatitis / Pancreatitis, Chronic - pathology / Patients / Prognosis / Statistical analysis / Studies / Surgery / Survival / Tumors