多种免疫炎症指标对肝内胆管癌患者根治性切除术后预后的预测价值
DOI: 10.3969/j.issn.1001-5256.2022.09.021
Prognostic value of several immune and inflammatory indices after curative-intent resection for intrahepatic cholangiocarcinoma
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摘要:
目的 探讨不同的免疫炎症指标对肝内胆管癌(ICC)患者行根治切除术后生存结局预测价值的差异。 方法 回顾性收集2012年1月—2017年12月于潍坊医学院附属医院和天津医科大学肿瘤医院接受根治性切除术的122例ICC患者的病例资料,分析免疫炎症指标中性粒细胞/淋巴细胞比率(NLR)、淋巴细胞/单核细胞比值(LMR)、系统免疫炎症指数(SII)、炎症预后指标(PII)、炎症评分(IS)和系统炎症评分(SIS)与ICC患者术后无瘤生存期(DFS)和总生存期(OS)的相关性,评估上述指标的预后预测价值。计数资料组间比较采用χ2检验或Fisher精确概率法。Kaplan-Meier法绘制生存曲线,组间差异比较采用Log-rank检验;采用Cox回归模型进行单因素和多因素分析,并计算风险比(HR)及95% CI。 结果 单因素生存分析结果显示,NLR、LMR、PII、PNI、IS、SII和SIS是ICC患者术后DFS的预测因素(HR值分别为2.212、0.403、3.013、0.530、1.809、2.107和2.225,P值分别为0.004、0.012、<0.001、0.019、0.001、0.002和<0.001);NLR、LMR、PII、PNI、IS、SII和SIS是患者术后OS的预测因素(HR值分别为2.416、0.297、3.288、0.292、2.048、1.839和2.335,P值分别为0.009、0.008、<0.001、0.003、0.002、0.049和<0.001)。多因素生存分析结果显示,高水平PII、SIS是ICC患者术后DFS的独立影响因素(HR值分别为2.146、2.511,P值分别为0.035、<0.001);高水平PII、PNI、SIS是患者术后OS的独立影响因素(HR值分别为2.981、0.261、2.294,P值分别为0.009、0.002、0.010);高水平PII组ICC患者肿瘤学T分期(χ2=8.777,P=0.003)和M分期(P=0.029)更晚;高级别的SIS组患者肿瘤学N分期(χ2=9.985,P=0.030)和M分期(χ2=8.574,P=0.012)更晚。 结论 在现行的多种炎症指标中,PII和SIS更适用于术前对ICC患者行根治性切除术疗效分层的预测评估。 Abstract:Objective To investigate the value of different immune and inflammatory indices in predicting the survival outcome of patients with intrahepatic cholangiocarcinoma (ICC) after curative-intent resection. Methods A retrospective analysis was performed for the case data of 122 patients with ICC who underwent curative-intent resection in Affiliated Hospital of Weifang Medical University and Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2017 to analyze the correlation of neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), systemic immune-inflammation index (SII), prognostic inflammation index (PII), inflammation score (IS), and systemic inflammation score (SIS) with the disease-free survival (DFS) and overall survival of ICC patients after surgery, and the value of the above indices in predicting prognosis was evaluated. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups; the Cox regression model was used for univariate and multivariate analyses, and hazard ratio (HR) and 95% confidence interval [CI] were calculated. Results The univariate survival analysis showed that NLR (HR=2.212, P=0.004), LMR (HR=0.403, P=0.012), PII (HR=3.013, P < 0.001), prognostic nutritional index (PNI) (HR=0.530, P=0.019), IS (HR=1.809, P=0.001), SII (HR=2.107, P=0.002), and SIS (HR=2.225, P < 0.001) were predictive factors for postoperative DFS of patients with ICC, and NLR (HR=2.416, P=0.009), LMR (HR=0.297, P=0.008), PII (HR=3.288, P < 0.001), PNI (HR=0.292, P=0.003), IS (HR=2.048, P=0.002), SII (HR=1.839, P=0.049), and SIS (HR=2.335, P < 0.001) were predictive factors for postoperative OS of patients with ICC. The multivariate survival analysis showed that high levels of PII (HR=2.146, P=0.035) and SIS (HR=2.511, P < 0.001) were independent influencing factors for postoperative DFS of ICC patients, and high levels of PII (HR=2.981, P=0.009), PNI (HR=0.261, P=0.002), and SIS (HR=2.294, P=0.010) were independent influencing factors for postoperative OS. The patients with a high level of PII tended to have advanced tumor T stage (χ2=8.777, P=0.003) and M stage (P=0.029), and the patients with high-grade SIS tended to have advanced N stage (χ2=9.985, P=0.030) and M stage (χ2=8.574, P=0.012). Conclusion Among the various inflammation indices, PII and SIS are recommended for preoperative stratification and prediction of the outcome of ICC patients after curative-intent resection. -
Key words:
- Bile Duct Neoplasms /
- Bile Ducts, Intrahepatic /
- Prognosis /
- Forecasting
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表 1 ICC患者的一般资料比较
Table 1. Demographic and baseline clinicopathological data of patients with intrahepatic cholangiocarcinoma
指标 A组(n=41) B组(n=81) P值 指标 A组(n=41) B组(n=81) P值 年龄[例(%)] 0.209 TBil[例(%)] 0.464 <65岁 27(65.9) 62(76.5) <21.0 μmol/L 36(87.8) 67(82.7) ≥65岁 14(34.1) 19(23.5) ≥21.0 μmol/L 5(12.2) 14(17.3) 性别[例(%)] 0.839 INR[例(%)] 0.564 男 23(56.1) 47(58.0) <1.0 27(65.9) 49(60.5) 女 18(43.9) 34(42.0) ≥1.0 14(34.1) 32(39.5) 中性粒细胞计数[例(%)] 0.338 CA19-9[例(%)] 0.566 <3.95×109/L 18(43.9) 43(53.1) <39.0 U/mL 26(63.4) 47(58.0) ≥3.95×109/L 23(56.1) 38(46.9) ≥39.0 U/mL 15(36.6) 34(42.0) 淋巴细胞计数[例(%)] 0.296 CEA[例(%)] 0.069 <1.52×109/L 16(39.0) 24(29.6) <5.00 μg/L 35(85.4) 57(70.4) ≥1.52×109/L 25(61.0) 57(70.4) ≥5.00 μg/L 6(14.6) 24(29.6) 血小板计数[例(%)] 0.849 组织学分级[例(%)] 0.337 <165×109/L 8(19.5) 17(21.0) G1~2 26(63.4) 44(54.3) ≥165×109/L 33(80.5) 64(79.0) G3 15(36.6) 37(45.7) 单核细胞计数[例(%)] 0.750 T分期[例(%)] 0.397 <0.51×109/L 29(70.7) 55(67.9) T1 20(48.8) 33(40.7) ≥0.51×109/L 12(29.3) 26(32.1) T2~4 21(51.2) 48(59.3) ALT[例(%)] 0.445 N分期[例(%)] 0.783 <40 U/L 32(78.0) 58(71.6) N0 17(41.5) 29(35.8) ≥40 U/L 9(22.0) 23(28.4) N1 6(14.6) 15(18.5) Alb[例(%)] 0.373 Nx 18(43.9) 37(45.7) M分期[例(%)] 0.884 <40 g/L 5(12.2) 15(18.5) M0 39(95.1) 75(92.6) ≥40 g/L 36(87.8) 66(81.5) M1 2(4.9) 6(7.4) 注:INR,国际标准化比值;CEA,癌胚抗原;CA19-9,糖类抗原19-9。 表 2 ICC患者预后指标的单因素分析
Table 2. Univariate analysis of prognostic indicators in intrahepatic cholangiocarcinoma
指标 DFS OS HR 95%CI P值 HR 95%CI P值 中性粒细胞计数(×109/L) 1.762 1.117~2.779 0.015 1.941 1.080~3.487 0.027 淋巴细胞计数(×109/L) 0.662 0.419~1.046 0.077 0.590 0.331~1.050 0.073 单核细胞计数(×109/L) 1.737 1.083~2.785 0.022 1.831 1.015~3.302 0.045 血小板计数(×109/L) 1.489 0.804~2.759 0.205 0.802 0.397~1.620 0.539 CA19-9(U/mL) 1.951 1.242~3.066 0.004 2.076 1.162~3.710 0.014 T分期 1.847 1.153~2.961 0.011 1.940 1.022~3.686 0.043 M分期 5.273 2.506~11.094 <0.001 3.666 1.623~8.284 0.002 NLR 2.212 1.290~3.793 0.004 2.416 1.242~4.700 0.009 LMR 0.403 0.199~0.817 0.012 0.297 0.121~0.727 0.008 PLR 1.688 0.984~2.896 0.057 0.822 0.449~1.505 0.526 PII 3.013 1.753~5.179 <0.001 3.288 1.768~6.115 <0.001 PNI 0.530 0.312~0.900 0.019 0.292 0.130~0.655 0.003 IS 1.809 1.266~2.585 0.001 2.048 1.306~3.211 0.002 SII 2.107 1.310~3.388 0.002 1.839 1.003~3.371 0.049 SIS 2.225 1.606~3.083 <0.001 2.335 1.481~3.679 <0.001 表 3 ICC患者预后炎症指标的多因素分析
Table 3. Multivariate analysis of prognostic indicators in intrahepatic cholangiocarcinoma
指标 DFS OS HR 95%CI P值 HR 95%CI P值 NLR 0.743 0.368~1.501 0.408 0.794 0.345~1.824 0.586 LMR 2.336 0.838~6.509 0.105 1.747 0.510~5.982 0.374 PII 2.146 1.053~4.372 0.035 2.981 1.315~6.756 0.009 PNI 0.646 0.369~1.133 0.128 0.261 0.109~0.622 0.002 IS 1.558 0.898~2.702 0.115 0.916 0.436~1.923 0.816 SIS 2.511 1.528~4.125 <0.001 2.294 1.218~4.320 0.010 表 4 ICC患者PII水平和SIS分级与临床病理指标的相关性分析
Table 4. Association of PII and SIS with clinicopathological characteristics in intrahepatic cholangiocarcinoma
指标 例数 PII SIS 低水平 高水平 χ2值 P值 Ⅰ级 Ⅱ级 Ⅲ级 χ2值 P值 年龄[例(%)] 0.135 0.713 0.812 0.702 <65岁 89 73(82.0) 16(18.0) 61(68.5) 23(25.8) 5(5.6) ≥65岁 33 28(84.8) 5(15.2) 23(69.7) 7(21.2) 3(9.1) 性别[例(%)] 0.895 0.344 0.145 >0.05 男 70 56(80.0) 14(20.0) 48(68.6) 17(24.3) 5(7.1) 女 52 45(86.5) 7(13.5) 36(69.2) 13(25.0) 3(5.8) 组织学分级[例(%)] 2.408 0.152 1.897 0.372 G1~2 70 55(78.6) 15(21.4) 51(72.9) 14(20.0) 5(7.1) G3 52 46(88.5) 6(11.5) 33(63.5) 16(30.8) 3(5.8) T分期[例(%)] 8.777 0.003 3.250 0.238 T1 53 50(94.3) 3(5.7) 38(71.7) 14(26.4) 1(1.9) T2~4 69 51(73.9) 18(26.1) 46(66.7) 16(23.2) 7(10.1) N分期[例(%)] 7.409 0.022 9.985 0.030 N0 46 34(73.9) 12(26.1) 31(67.4) 12(26.1) 3(6.5) N1 21 16(76.2) 5(23.8) 9(42.9) 9(42.9) 3(14.3) Nx 55 51(92.7) 4(7.3) 44(80.0) 9(16.4) 2(3.6) M分期[例(%)] 0.029 8.574 0.012 M0 114 97(85.1) 17(14.9) 82(71.9) 26(22.8) 6(5.3) M1 8 4(50.0) 4(50.0) 2(25.0) 4(50.0) 2(25.0) -
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