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Nerve Fibers in the Tumor Microenvironment as a Novel Biomarker for Oncological Outcome in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma
Liver Cancer ( IF 11.6 ) Pub Date : 2021-05-06 , DOI: 10.1159/000515303
Jan Bednarsch 1 , Jakob Kather 2 , Xiuxiang Tan 1, 3, 4 , Shivan Sivakumar 5, 6 , Claudio Cacchi 7 , Georg Wiltberger 1 , Zoltan Czigany 1 , Florian Ulmer 1 , Ulf Peter Neumann 1, 3 , Lara Rosaline Heij 1, 4, 7
Affiliation  

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.
Liver Cancer


中文翻译:

神经纤维在肿瘤微环境中作为一种新的生物标志物,用于接受胆囊周围胆管癌手术的肿瘤治疗结果。

简介:肝门周围胆管癌(pCCA)是一种胆道癌,预后不良,手术是唯一治愈的机会。pCCA的特征性侵袭性生物学特征是神经周生长,其定义为癌细胞侵袭神经和神经纤维。最近,神经纤维密度(NFD)与各种恶性肿瘤的肿瘤学结局相关。然而,其在pCCA中的预后作用仍有待阐明。材料和方法:该研究纳入了2010年至2019年间接受根治性手术的101例pCCA患者的数据。在高和低NFD患者之间进行了广泛的组比较,并使用单变量和多变量Cox回归模型评估了癌症特异性生存(CSS)和无复发生存与NFD和其他临床病理特征的关系。结果: NFD高的患者显示中位CSS为90个月(95%CI:48-132,3年CSS = 77%,5年CSS = 72%),而33个月(95%CI:19-47) ,NFD低的患者(3年CSS = 46%,5年CSS = 32%)(p = 0.006 log rank)。此外,N1类(HR = 2.84,p = 0.001)和高NFD(HR = 0.41,p= 0.024)在多变量分析中被确定为CSS的独立预测因子。NFD高且淋巴结阴性的患者显示中位数CSS为90个月(3年CSS = 88%,5年CSS = 80%),而淋巴结阳性或NFD低的患者则显示CSS中位数为51个月(3年CSS = 59%,5年CSS = 45%),同时淋巴结阳性和NFD低的患者中位CSS为24个月(3年CSS = 26%,5年CSS = 16%,p = 0.001对数秩)。结论: NFD已被鉴定为pCCA患者的重要新型预后生物标志物。单独使用NFD并结合淋巴结转移状态,尤其可以使pCCA患者根据根治性手术后肿瘤学结果较差的风险进行分层。
肝癌
更新日期:2021-05-06
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