术前/术后中性粒细胞-淋巴细胞比值与格拉斯哥预后评分对胆囊癌预后的预测价值
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罗昆仑, Email: lkl197041@163.com

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南京军区医药卫生科研基金资助项目(14D05)。


Predictive value of preoperative plus postoperative neutrophil-lymphocyte ratio and Glasgow prognostic score for prognosis of gallbladder carcinoma
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    摘要:

    背景与目的:胆囊癌(GBC)是高病死率的恶性肿瘤,快速有效术前诊断及预后评估手段的缺乏为胆囊癌的手术及随访治疗增加了难度。近年来围绕着外周血炎症相关指标与肿瘤预后的研究较为广泛,但由于外周血参数的不稳定性,预测价值往往有限。本研究旨在探讨新型外周血参数模型术前/术后中性粒细胞-淋巴细胞数比值(PP-NLR)及格拉斯哥预后评分(GPS)在GBC预后评估中的作用。
    方法:回顾2005年1月—2015年12月收治的140例GBC患者临床资料,根据ROC曲线界值决定手术前后NLR界值,升高则分别赋值为1,反之则为0,PP-NLR定义为两者赋值之和,分别为0、1、2;将术前血清白蛋白<35 g/L和术前CRP>10 g/L分别赋值为1,否则为0,GPS定义为两者赋值之和,分别为0、1、2。采用Kaplan-Meier法与Log-rank检验及单因素分析方法分析PP-NLR和GPS与患者生存及临床病理因素的关系,用Spearman相关性分析方法分析PP-NLR和GPS与临床病理因素的相关性,用多因素Cox风险模型确定预后的独立危险因素。
    结果:ROC曲线确定术前及术后NLR的界值分别为2.51(敏感度0.961,特异度0.788)和2.38(敏感度0.745,特异度0.712)。生存分析显示,不同PP-NLR或GPS水平患者间生存率均有统计学差异(均P<0.05),生存率在PP-NLR=1、PP-NLR=2、PP-NLR=3组呈依次降低(均P<0.05);GPS=0组的生存率明显高于GPS=1组或GPS=2组(均P<0.05),但GPS=1和GPS=2组间生存率无统计学差异(P>0.05)。单因素分析显示,PP-NLR和GPS水平均与根治率、肿瘤侵润、淋巴结转移、远处转移、分化程度及炎症指标及肿瘤标志物水平等明显有关(均P<0.05);相关性分析提示,PP-NLR与GPS与根治率、肿瘤侵润、淋巴结及远处转移、TNM分期及分化程度明显相关(均P<0.05)。单因素分析提示,PP-NLR及GPS的升高均与低生存率有关(均P<0.05),多因素分析显示,PP-NLR为影响患者预后的独立危险因素(PP-NLR=1:HR=0.357,95% CI=0.221~0.575,P<0.05;PP-NLR=2:HR=0.357,95% CI=0.221~0.575,P<0.05)。
    结论:PP-NLR和GPS均与GBC患者预后相关,且PP-NLR为独立预后危险因素,提示外周血参数PP-NLR及GPS可以简便、快速、有效的评估患者预后。此外,PP-NLR整体考虑了术前及术后的系统炎症及免疫状态,相对于GPS及单纯的手术前后NLR预测更为全面、价值更高,可为临床随访治疗提供理论依据。

    Abstract:

    Background and Aims: Gallbladder carcinoma (GBC) is a malignant tumor with a high mortality rate. The lack in quick and effective methods of preoperative diagnosis and prognostic assessment has increased the difficulty of operation and follow-up treatment for GBC. In recent years, the relations of the peripheral blood inflammation-related indicators with tumor prognosis have been extensively studied, but the predictive values are often limited due to the instability of the peripheral blood parameters. The purpose of this study was to investigate the role of the new peripheral blood parameter models preoperative plus postoperative neutrophil-lymphocyte ratio (PP-NLR) and Glasgow prognosis score (GPS) in prognostic assessment of GBC. 
    Methods: The clinical data of 140 patients with GBC treated from January 2005 to December 2015 were retrospectively analyzed. The cut-off values of NLR before and after operation were determined by ROC curve, based which, the NLR value was assigned as 1 if it was increased, or as 0 if not, and the PP-NLR value was defined as the sum of the two assigned values and was 0, 1 and 2, respectively; the preoperative serum albumin <35 g/L and preoperative CRP >10 g/L were assigned as 1 respectively and were assigned as 0 if not, and GPS value was defined as the sum of the two assigned values and was 0, 1 and 2, respectively. The relations of PP-NLR and GPS with the prognosis and clinicopathologic factors of the patients were analyzed by Kaplan-Meier method, Log-rank test and univariate analysis, respectively. The correlations of PP-NLR and GPS with the clinicopathologic factors were determined by Spearman correlation analysis. The independent prognostic factors were determined by multivariate Cox hazard model. 
    Results: The cut-off values of NLR before and after operation determined by ROC curve were 2.51 (sensitivity: 0.961, specificity: 0.788) and 2.38 (sensitivity: 0.745, specificity: 0.712). Survival analysis showed that the survival rates were significantly different among patients with different PP-NLR and GPS levels (all P<0.05), which presented a successive decrease in PP-NLR=1, PP-NLR=2 and PP-NLR=3 group, and was significantly higher in GPS=0 group than those in GPS=1 group or GPS=2 group (both P<0.05), but had no significant difference between GPS=1 group and GPS=2 group (P>0.05). Univariate analysis suggested that both PP-NLR and GPS were related to the radical resection rate, tumor invasion, lymph node or distal metastases, TNM classification and degree of differentiation as well as the inflammatory indexes and tumor markers (all P<0.05). The correlation analysis indicated that PP-NLR and GPS were significantly correlated to the radical resection rate, tumor invasion, lymph node or distal metastases, TNM classification and degree of differentiation (all P<0.05). Univariate analysis demonstrated that both the increased PP-NLR and GPS were significantly associated with low survival rate (both P<0.05), and multivariate analysis revealed that PP-NLR was an independent risk factor affecting the prognosis of the patients (PP-NLR=1: HR=0.357, 95% CI=0.221–0.575, P<0.05; PP-NLR=2: HR=0.357, 95% CI=0.221–0.575, P<0.05). 
    Conclusion: Both PP-NLR and GPS are related to the prognosis of GBC patients, and PP-NLR is an independent prognostic factor, suggesting that peripheral blood parameters PP-NLR and GPS can easily, quickly and effectively assess the prognosis of the patient. In addition, PP-NLR integrates the pre- and postoperative systemic inflammation and immune status, so it is more comprehensive and reliable that that GPS and preoperative or postoperative NLR alone for prediction, and can provide a theoretical basis for follow-up treatment. 

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朱振成, 罗昆仑, 谢伟选, 祝梦娇, 朱庆洲, 柏杨, 李福利, 刘伟伟.术前/术后中性粒细胞-淋巴细胞比值与格拉斯哥预后评分对胆囊癌预后的预测价值[J].中国普通外科杂志,2020,29(8):947-957.
DOI:10.7659/j. issn.1005-6947.2020.08.005

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  • 收稿日期:2019-11-01
  • 最后修改日期:2020-02-13
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  • 在线发布日期: 2020-08-25