肝细胞癌术前炎症指标的预后价值

Prognostic value of preoperative inflammatory indicators for hepatocellular carcinoma

目的探讨肝细胞癌术前炎症指标的预后价值。方法采用回顾性队列研究方法。收集2014年12月至2019年7月清华大学附属北京清华长庚医院收治的73例行根治性肝部分切除术原发性肝细胞癌病人的临床病理资料;男57例,女16例;中位年龄为58岁,年龄范围为33~81岁。收集病人术前入院第1次血液检测指标。观察指标:(1)最大选择秩统计计算炎症指标最佳截断值。(2)随访情况。(3)肝细胞癌病人预后影响因素分析。(4)肝细胞癌病人临床病理特征比较。(5)总体生存预测效能比较。采用门诊和电话方式进行随访,了解病人术后生存情况。随访时间截至2019年9月。正态分布的计量资料以x±s表示,组间比较采用t检验。偏态分布的计量资料以M(范围)表示。依据随访截至时间病人生存状态,采用最大选择秩统计计算计量资料最佳截断值。计数资料以绝对数表示,组间比较采用χ^(2)检验或Fisher确切概率法。采用Kaplan-Meier法计算生存率,采用Log-rank检验进行生存分析。单因素分析采用Log-rank检验,多因素分析采用COX比例风险模型。采用时间依赖性受试者工作特征曲线(ROC)比较独立预后因素的预测效能。结果(1)最大选择秩统计计算炎症指标最佳截断值:最大选择秩统计计算中性粒细胞与淋巴细胞比率(NLR)、血小板与淋巴细胞比率(PLR)、预后营养指数(PNI)的最佳截断值分别为3.46、131.05、45.65。(2)随访情况:73例病人均获得随访,随访时间为31个月(2~57个月)。随访期间20例病人死亡。(3)肝细胞癌病人预后影响因素分析。单因素分析结果显示:NLR、PNI、肿瘤长径、肿瘤分化程度是影响病人预后的相关因素(χ^(2)=10.213,4.434,5.174,4.306,P<0.05)。多因素分析结果显示:NLR和肿瘤分化程度是病人预后的独立影响因素(风险比=4.429,13.278,95%可信区间为1.662~11.779,1.056~10.169,P<0.05)。(4)肝细胞癌病人临床病理特征比较:73例病人中,64例NLR<3.46,9例NLR≥3.46。64例NLR<3.46病人肿瘤长径(>5 cm和≤5 cm)、中性粒细胞、淋巴细胞分别为23例和41例、(2.9±1.2)×10^(9)/L、(1.7±0.6)×10^(9)/L;9例NLR≥3.46病人上述指标分别为8例和1例、(5.8±2.9)×10^(9)/L、(1.0±0.3)×10^(9)/L,两者上述指标比较,差异均有统计学意义(χ^(2)=7.017,t=2.982、-3.168,P<0.05)。(5)总体生存预测效能比较:NLR和肿瘤分化程度时间依赖性ROC预测病人1、2、3、4年总体生存情况的曲线下面积分别为0.735、0.611、0.596、0.574和0.554、0.583、0.572、0.556。NLR对病人总体生存的预测效能较肿瘤分化程度高。结论术前NLR是病人预后的独立影响因素,其预后预测效能优于肿瘤分化程度。

Objective To investigate the prognostic value of preoperative inflammatory indicators for hepatocellular carcinoma(HCC).Methods The retrospective cohort study was conducted.The clinicopathological data of 73 patients with primary HCC who underwent radical partial hepatectomy in the Beijing Tsinghua Changgung Hospital of Tsinghua University from December 2014 to July 2019 were collected.There were 57 males and 16 females,aged from 33 to 81 years,with a median age of 58 years.Results of blood examination indicators at the first time in hospital were determined for patients.Observation indicators:(1)the best cut-off values ofpreoperative inflammatory indicators calculated by the maximally selected rank statistics;(2)follow-up;(3)influencing factors for prognosis of HCC patients;(4)comparison of clinicopathological parameters of HCC patients;(5)comparison of predictive value for overall survival.Follow-up was conducted using outpatient examination and telephone interview to determine postoperative survival of patients up to September 2019.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M(range).The best cut-off valuesfor continuous variables were obtained using the maximally selected rank statistics based on survival at endpoint of follow-up.Count data were represented as absolute numbers,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Kaplan-Meier method was used to calculate survival rates,and Log-rank test was used for survival analysis.Univariate analysis was performed using the Log-rank test.Multivariate analysis was performed using the COX proportional hazard model.The time-dependent receiver operating characteristic curve(ROC)was used to compare the predictive value of independent prognostic factors.Results(1)The best cut-off values of preoperative inflammatory indicators calculated by the maximally selected rank statistics:the best cut-off values of neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and prognostic nutrition index(PNI)were 3.46,131.05,and 45.65.(2)Follow-up:73 patients were followed up for 31 months(range,2-57 months).Twenty patients died during the follow-up.(3)Influencing factors for prognosis of HCC patients:results of univariate analysis showed that NLR,PNI,tumor diameter,and tumor differentiation degree were related factors affecting prognosis of patients(χ^(2)=10.213,4.434,5.174,4.306,P<0.05).Results of multivariate analysis showed that NLR and tumor differentiation degree were independent factors affecting prognosis of patients(hazzard ratio=4.429,13.278,95%confidence interval as 1.662-11.779,1.056-10.169,P<0.05).(4)Comparison of clinicopathological parameters of HCC patients:of 73 patients,64 cases had NLR<3.46 and 9 cases had NLR≥3.46.Cases with tumor length>5 cm or≤5 cm,neutrophils,lymphocytes were 23,41,(2.9±1.2)×10^(9)/L,(1.7±0.6)×10^(9)/L for 64 patients with NLR<3.46,versus 8,1,(5.8±2.9)×10^(9)/L,(1.0±0.3)×10^(9)/L for 9 patients with NLR≥3.46;there were significant differences in above indicators between the two groups(χ^(2)=7.017,t=2.982,-3.168,P<0.05).(5)Comparison of predictive value for overall survival:time-dependent ROC curves of NLR and tumor differentiation degree for 1-,2-,3-,4-year survival rates had the area under curve of 0.735,0.611,0.596,0.574 and 0.554,0.583,0.572,0.556,respectively.NLR had better predictive value for overall survival of patients than tumor differentiation degree.Conclusion Preoperative NLR is an independent factor affecting prognosis patients,and its predictive efficacy is better than tumor differentiation degree.