Nerve Fibers in the Tumor Microenvironment as a Novel Biomarker for Oncological Outcome in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma
Open Access
- 6 May 2021
- journal article
- research article
- Published by S. Karger AG in Liver Cancer
- Vol. 10 (3), 260-274
- https://doi.org/10.1159/000515303
Abstract
Introduction: Perihilar cholangiocarcinoma (pCCA) is a biliary tract cancer with a dismal prognosis, with surgery being the only chance of cure. A characteristic aggressive biological feature of pCCA is perineural growth which is defined by the invasion of cancer cells to nerves and nerve fibers. Recently, nerve fiber density (NFD) was linked to oncological outcomes in various malignancies; however, its prognostic role in pCCA remains to be elucidated. Materials and Methods: Data of 101 pCCA patients who underwent curative-intent surgery between 2010 and 2019 were included in this study. Extensive group comparisons between patients with high and low NFD were carried out, and the association of cancer-specific survival (CSS) and recurrence-free survival with NFD and other clinicopathological characteristics was assessed using univariate and multivariable cox regression models. Results: Patients with high NFD showed a median CSS of 90 months (95% CI: 48–132, 3-year CSS = 77%, 5-year CSS = 72%) compared to 33 months (95% CI: 19–47, 3-year CSS = 46%, 5-year CSS = 32%) in patients with low NFD (p = 0.006 log rank). Further, N1 category (HR = 2.84, p = 0.001) and high NFD (HR = 0.41, p = 0.024) were identified as independent predictors of CSS in multivariable analysis. Patients with high NFD and negative lymph nodes showed a median CSS of 90 months (3-year CSS = 88%, 5-year CSS = 80%), while patients with either positive lymph nodes or low NFD displayed a median CSS of 51 months (3-year CSS = 59%, 5-year CSS = 45%) and patients with both positive lymph nodes and low NFD a median CSS of 24 months (3-year CSS = 26%, 5-year CSS = 16%, p = 0.001 log rank). Conclusion: NFD has been identified as an important novel prognostic biomarker in pCCA patients. NFD alone and in combination with nodal status in particular allows to stratify pCCA patients based on their risk for inferior oncological outcomes after curative-intent surgery.Keywords
This publication has 55 references indexed in Scilit:
- Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysisHPB, 2012
- Interstitial guidance of cancer invasionThe Journal of Pathology, 2011
- Neural stem cell niches: Roles for the hyaluronan-based extracellular matrixFrontiers in Bioscience-Scholar, 2011
- Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract CancerThe New England Journal of Medicine, 2010
- Extended Liver Resection for Intrahepatic CholangiocarcinomaAnnals of Surgery, 2009
- Radical surgery for hilar cholangiocarcinomaEuropean Journal of Surgical Oncology, 2008
- Combined vascular resection in operative resection for hilar cholangiocarcinoma: Does it work or not?Surgery, 2007
- Impact of integrated positron emission tomography and computed tomography on staging and management of gallbladder cancer and cholangiocarcinomaJournal of Hepatology, 2006
- Chirurgische Therapie hilärer Gallengangskarzinome (Klatskin-Tumoren)Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie, 2003
- Increased risk of cancer mortality after vagotomy for peptic ulcerEuropean Journal of Cancer Prevention, 1991