Jan Bednarsch1, Jakob Kather2, Xiuxiang Tan1,3,4, Shivan Sivakumar5,6, Claudio Cacchi7, Georg Wiltberger1, Zoltan Czigany1, Florian Ulmer1, Ulf Peter Neumann1,3, Lara Rosaline Heij1,4,7. 1. Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany. 2. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany. 3. Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands. 4. NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands. 5. Department of Oncology, University of Oxford, Oxford, United Kingdom. 6. Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom. 7. Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
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.
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.
Authors: Jesus M Banales; Jose J G Marin; Angela Lamarca; Pedro M Rodrigues; Shahid A Khan; Lewis R Roberts; Vincenzo Cardinale; Guido Carpino; Jesper B Andersen; Chiara Braconi; Diego F Calvisi; Maria J Perugorria; Luca Fabris; Luke Boulter; Rocio I R Macias; Eugenio Gaudio; Domenico Alvaro; Sergio A Gradilone; Mario Strazzabosco; Marco Marzioni; Cédric Coulouarn; Laura Fouassier; Chiara Raggi; Pietro Invernizzi; Joachim C Mertens; Anja Moncsek; Sumera Rizvi; Julie Heimbach; Bas Groot Koerkamp; Jordi Bruix; Alejandro Forner; John Bridgewater; Juan W Valle; Gregory J Gores Journal: Nat Rev Gastroenterol Hepatol Date: 2020-06-30 Impact factor: 46.802
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