Perineural and Intraneural Invasion in Posttherapy Pancreaticoduodenectomy Specimens Predicts Poor Prognosis in Patients With Pancreatic Ductal Adenocarcinoma

Abstract

Perineural invasion (PNI) is one of the established prognostic factors in pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of PNI in patients with PDAC who received neoadjuvant therapy and pancreaticoduodenectomy (PD) is not clear. In this study, we performed detailed examination of neural invasion in PD specimens from 212 patients with PDAC who received neoadjuvant chemoradiation (treated group) and 60 untreated patients at our institution between January 1999 and December 2007. The frequency of PNI was higher in untreated group (80%, 48/60) than the treated group (58%, 123/212). For the 123 treated cases that were positive for PNI, extra-tumoral PNI, intra-tumoral PNI, intra-pancreatic PNI only, extra-pancreatic PNI, and intra-neural invasion were identified in 86 (69.9%), 37 (30.1%), 11 (8.9%), 112 (91.1%), and 35 (28.5%) respectively. Presence of PNI correlated with tumor size, margin status, lymph node metastasis, pathologic tumor and AJCC stages in the treated group. Tumor involvement of nerves >0.8 mm correlated with higher frequency of positive margin compared to those with PNI involving nerves ≤0.8 mm, but not with other clinicopathologic parameters and survival. In treated group, the presence of PNI or intra-neural invasion correlated significantly with shorter disease-free survival (DFS) and overall survival (OS) compared to those with no PNI or PNI only respectively. PNI was an independent prognostic factor for both DFS and OS in multivariate analysis. Our results showed that PNI plays an important role in the progression of PDAC and in predicting the prognosis in this group of patients.

How Schwann cells facilitate cancer progression in nerves

“…The innermost layer of the nerve is the endoneurium. The invasion of cancer cells in the endoneurium, named intraneural invasion, is associated with a worse prognosis than the invasion around or in the other layer of the nerves [18, 19]. A variety of cells from the nerve can facilitate cancer progression.…”

Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma

“…Most patients are in an advanced or metastatic condition at the time of diagnosis, which results in a poor prognosis (Chatterjee et al, 2012;Li et al, 2004). Recurrence remains the main cause of cancer-related death after curative resection in a substantial proportion of patients with PDAC (Lee et al, 2012).…”

Influence of Perineural Invasion on Survival and Recurrence in Patients with Resected Pancreatic Cancer

“…14 of the remaining 35 studies (Kim et al, 2006;Murakami et al, 2008;Balentine et al, 2010;Chu et al, 2010;Kanda et al, 2010;de Jong et al, 2011;Jamieson et al, 2011;Kneuertz et al, 2011;Maithel et al, 2011;Singal et al, 2011;Chatterjee et al, 2012;Watanabe et al, 2012;Xie et al, 2012;Fisher et al, 2013) were excluded because they were reported by the same institutions as other studies. 21 studies (Ozaki et al, 1999;Mitsunaga et al, 2005;Nakagohri et al, 2006;Pawlik et al, 2007;Kazanjian et al, 2008;Kato et al, 2009;Nagai et al, 2009;Sergeant et al, 2009;Ben et al, 2010;Murakami et al, 2010;Bachellier et al, 2011;Kim et al, 2011;Schiffman et al, 2011;Cheng et al, 2012;Jamieson et al, 2012;Lee et al, 2012;Murata et al, 2012;Sahin et al, 2012;Takahashi et al, 2012;Turrini et al, 2013;Xie et al, 2013) were included in the final meta-analysis, comprising one case matched controlled study and 20 retrospective cohort studies (Table 1).…”