Objective: To explore the value of preoperative peripheral blood inflammatory biomarkers for predicting the prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection. Methods: A total of 124 patients who underwent radical resection for ICC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Receiver operating characteristic (ROC) curve was conducted to determine the best cut-off values of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), systemic immune inflammatory index (SII), and systemic inflammatory response index (SIRI). Univariate and multivariate analyses of prognostic factors were performed using Cox proportional hazards regression model. Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC patients after radical resection was established. Results: Among the 124 patients, 87 patients died and 37 patients survived during the follow-up period. The median overall survival time of the whole patients was 21 months. ROC curve analysis showed that the areas under the curve (AUC) of NLR, PLR, LMR, SII and SIRI for predicting the overall survival of ICC patients after radical resection were 57.86%, 64.21%, 60.61%, 67.57% and 66.03%, respectively. Univariate Cox regression analysis showed that the inflammatory biomarkers of NLR, PLR, SII, and SIRI were associated with overall survival of ICC after radical resection (HR=1.787, 95%CI: 1.165-2.741; HR=1.181, 95% CI: 1.224-2.892; HR=2.412, 95% CI: 1.565-3.717; HR=1.648, 95% CI: 1.081-2.513). Multivariate Cox regression analysis showed that the inflammatory biomarker of SII was an independent prognostic factor of ICC after radical resection (HR=1.863, 95% CI: 1.161-2.989). According to the best cut-off value of SII to predict the overall survival of ICC patients after radical resection (709.86×10(9)/L), the patients were divided into low SII group (SII≤709.86×10(9)/L) and high SII group (SII>709.86×10(9)/L). In the high SII group, the proportions of NLR>3.31, PLR>3.31, SIRI>1.30×10(9)/L, carbohydrate antigen 19-9>39.0 U/ml, Child-Pugh liver function (grade B), hemi-hepatic/extended hepatectomy, combined perineural invasion, N1 stage and TNM stage (ⅢB) were higher than those in the low SII group (P<0.05). Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC after radical resection was established, the C-index values of the training set and testing set were 0.774 and 0.737, respectively. Conclusions: Preoperative peripheral blood inflammatory marker SII is an independent risk factor for the prognosis of intrahepatic cholangiocarcinoma patients after radical resection. The nomogram model of overall survival prediction established that included SII has a good predictive ability and can be used to evaluate the prognosis of intrahepatic cholangiocarcinoma patients after radical resection.
目的： 探讨术前外周血炎性标志物在肝内胆管癌(ICC)根治性切除术后的预后预测价值。 方法： 回顾性分析2010年1月至2018年12月于西安交通大学第一附属医院因ICC行根治性切除术的124例患者的临床病理资料，采用受试者工作特性(ROC)曲线确定中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)、淋巴细胞/单核细胞比值(LMR)、系统免疫炎症指数(SII)、全系统性炎症反应指数(SIRI)的最佳界值。预后影响因素的单因素和多因素分析采用Cox比例风险回归模型。基于多因素Cox回归分析筛选的预后独立影响因素，建立ICC根治性切除术后的总生存列线图预测模型。 结果： 124例患者中，随访期间死亡87例，存活37例。全组患者中位总生存时间为21个月。ROC曲线分析显示，NLR、PLR、LMR、SII和SIRI预测ICC患者根治术后总生存的曲线下面积分别为57.86%、64.21%、60.61%、67.57%和66.03%。单因素Cox回归分析显示，炎性标志物中NLR、PLR、SII、SIRI与ICC根治性切除术后的总生存有关(HR＝1.787，95% CI：1.165~2.741；HR＝1.181，95% CI：1.224~2.892；HR＝2.412，95% CI：1.565~3.717；HR＝1.648，95% CI：1.081~2.513)。多因素Cox回归分析显示，炎性标志物中SII为ICC根治性切除术后预后的独立影响因素(HR＝1.863，95%CI：1.161~2.989)。根据SII预测ICC患者根治术后总生存的最佳界值(709.86×10(9)/L)，将患者分为低SII组(SII≤709.86×10(9)/L)和高SII组(SII>709.86×10(9)/L)。高SII组中NLR>3.31、PLR>3.31、SIRI>1.30×10(9)/L、糖类抗原19-9>39.0 U/ml、Child-Pugh肝功能分级呈B级、半肝或扩大肝切除范围、合并神经浸润、N1期及ⅢB期患者的比例高于低SII组(均P<0.05)。基于多因素Cox回归分析筛选的预后独立影响因素建立ICC根治性切除术后的总生存列线图预测模型，建模组和验证组C指数分别为0.774和0.737。 结论： 术前外周血炎性标志物SII是ICC根治性切除术后患者预后的独立影响因素，所建立的总生存列线图预测模型具有良好的预测能力，可用于ICC患者根治性切除术后预后的评估。.
Keywords: Cholangiocarcinoma; Inflammatory biomarkers; Nomogram; Prognosis; Radical resection; Systemic immune-inflammation index.