Influence of Perineural (Pn), Lymphangio (L) and Vascular (V) Invasion on Survival after Resection of Perihilar Cholangiocarcinoma

Cancers (Basel). 2024 Oct 12;16(20):3463. doi: 10.3390/cancers16203463.

Abstract

Introduction: Perihilar cholangiocarcinoma is a rare malignancy of the biliary tract, for which surgery remains the treatment of choice. However, even after radical resection, the prognosis is poor. In addition to tumor size, depth of invasion and nodal/metastatic status, the TNM classification includes additional parameters such as perineural (Pn), lymphangio (L) and vascular (V) invasion. The prognostic impact of these factors is not yet fully understood. The aim of this study was to investigate the influence of these parameters on overall survival after resection of perihilar cholangiocarcinoma.

Material and methods: Data from all patients who underwent surgical exploration for perihilar cholangiocarcinoma between January 2013 and December 2023 were included into an institutional database. The impact of perineural, lymphangio and vascular invasion on overall survival was analyzed.

Results: Over the 11-year period, a total of 214 patients underwent surgical exploration for perihilar cholangiocarcinoma. Curative intended resection was possible in 168 patients (78.5%). Perineural invasion, lymphangio invasion and vascular invasion were present in 79.2%, in 17.3% and in 14.3% of patients, respectively. Cross tabulation revealed a significant association between the presence of L1 and V1 (p = 0.006). There was also a significant association of Pn1, L1, and V1 with R-status (p = 0.010; p = 0.006 and p ≤ 0.001). While V1 was associated with significantly worse overall survival across the entire cohort, Pn1 alone showed only a tendency towards worse overall survival without reaching statistical significance. In Bismuth type IV, both L1 and V1, but not Pn1, were significantly associated with worse overall survival (p = 0.001; p = 0.017 and p = 0.065).

Conclusions: Perineural invasion is very common in perihilar cholangiocarcinoma. Although Pn1 was associated with a tendency toward worse survival, it did not reach statistical significance. In contrast, vascular invasion significantly worsened overall survival in the entire cohort, and lymphangio invasion was linked to worse overall survival in Bismuth type IV tumors. The combination of perineural invasion with positivity of more than one additional factor (either L or V) was also associated with worse overall survival. In patients with Bismuth type IV, these pathological markers appeared to have even greater prognostic relevance.

Keywords: liver surgery; lymphangio invasion; overall survival; perihilar cholangiocarcinoma; perineural invasion; vascular invasion.

Grants and funding

This research received no external funding.