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围手术期炎症反应指标对肝内胆管癌患者肝切除术后的预测价值

The Predictive Value of Perioperative Inflammatory Indicatorsin Prognosis of the Intrahepatic Cholangiocarcinoma Patients after Hepatectomy

  • 摘要:
      目的  评估肝内胆管细胞癌(intrahepatic cholangiocarcinoma, ICC)患者围手术期炎症指标与预后的关系。
      方法  回顾分析2006年12月−2016年12月期间四川大学华西医院收治的231例 ICC 患者临床资料,对围手术期(术前及术后第3、5天)中性粒细胞与淋巴细胞比率(neutrophil-to-lymphocyte ratio, NLR)、衍生中性粒细胞与淋巴细胞比率(derived neutrophil-to-lymphocyte ratio, d-NLR)、血小板与淋巴细胞比率(platelet-to-lymphocyte ratio, PLR)进行检测和比较。X-tile软件确定术前及术后第3、5天的NLR、d-NLR、PLR的最佳截断值,将所有患者分为高水平组和低水平组,并用Kaplan-Meier曲线分析NLR、d-NLR、PLR水平高低与患者的无病生存(disease free survival,DFS)、总生存(overall survival,OS)的相关性,单因素和多因素Cox回归分析评估它们的预后价值。最后建立预测列线图预测ICC患者预后,并通过一致性指数(C指数)评估列线图的预测准确性。
      结果  本研究共纳入231例ICC患者,男性115例,女性116例,年龄<60岁的占多数(57.1%)。有161例患者(69.7%)复发,156例(67.5%)死亡。中位DFS、OS分别为8.9个月和12.5个月。Kaplan-Meier生存曲线示:与患者DFS有关(P<0.05)的有d-NLR和NLR水平(术前,术后第3、第5天),PLR水平(术前);与患者OS有关(P<0.05)的有d-NLR和 PLR水平(术前,术后第3、第5天),NLR水平(术前,术后第3天)。单因素和多因素Cox回归分析示,术前高水平的NLR和d-NLR以及术后第3天高水平NLR是不良DFS的独立影响因素;术前高水平的NLR和d-NLR以及术后第3天高水平NLR是不良OS的独立影响因素;PLR水平则与DFS和OS无关。建立Cox回归模型以及列线图预测ICC患者的DFS和OS,其C指数分别为0.738(95%置信区间:0.699~0.777)、0.778(95%置信区间:0.758~0.818)。
      结论  ICC患者术前高水平的NLR、d-NLR及术后第3天高水平NLR预示术后生存差,PLR对ICC预后无指导意义。

     

    Abstract:
      Objective  To evaluate the effect of perioperative inflammatory indicators on the prognosis of the patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy.
      Methods  The clinical data of 231 ICC patients in the West China Hospital of Sichuan University from December 2006 to December 2016 were retrospectively collected. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR) and platelet-to-lymphocyte ratio (PLR) of patients during the perioperative period (pre-operation, postoperative day 3 and day 5) were analyzed. The X-tile software was used to determine the optimal cut-off values of NLR, d-NLR and PLR in pre-operation, postoperative day 3 and day 5. Based on the cut-off values, all patients were divided into high level group and low level group, and Kaplan-Meier methods were used to analyze the correlations of NLR, d-NLR and PLR with the disease-free survival (DFS) and overall survival (OS) of patients. Univariate and multivariate Cox regression models were applied to assess the prognostic values of NLR, d-NLR and PLR. Nomogram was established to predict the prognosis for ICC patients, and the predicting accuracy was evaluated by the Consistency index (C-index).
      Results  A total of 231 ICC patients including 115 males and 116 females were enrolled into this study, and the proportion of patients aged <60 years was 57.1%. Among the patients enrolled, 161 patients (69.7%) recurred and 156 patients (67.5%) died after hepatectomy. The median time of DFS and OS were 8.9 and 12.5 months respectively. The Kaplan-Meier curves showed that d-NLR and NLR levels in pre-operation, postoperative day 3 and day 5, together with the preoperative PLR level were correlated with the time of DFS (P<0.05). Meanwhile, d-NLR and PLR levels in pre-operation, postoperative day 3 and day 5, together with the NLR level in pre-operation and postoperative day 3 were correlated with the time of OS (P<0.05). Univariate and multivariate Cox regression model analysis suggested that high level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of poor DFS. High level of the preoperative NLR and d-NLR, together with the high level of NLR on postoperative day 3 were the independent influencing factors of OS. The level of PLR level was not correlated with DFS and OS. The C-index values of nomogram for predicting DFS and OS were 0.738 (95% confidence interval: 0.699-0.777) and 0.778 (95% confidence interval: 0.758-0.818), respectively.
      Conclusion  High level of the preoperative NLR, preoperative d-NLR and NLR on postoperative day 3 in ICC patients indicate poor prognosis, and PLR has no prognostic value for ICC patients after hepatectomy.

     

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