肝内胆管癌根治术后生存的列线图预测模型

doi:10.3877/cma.j.issn.1674-0793.2020.02.016

目的

探讨肝内胆管癌（ICC）患者预后生存的影响因素，并构建列线图个体化预测患者总生存期（OS）。

方法

回顾性分析中山大学第一附属医院2008年1月至2017年12月收治的263例行ICC根治性切除术患者资料。单因素和多因素Cox比例风险回归分析筛选患者OS的独立影响因素，并以此构建列线图，个体化预测ICC根治术后患者生存情况。绘制前白蛋白密度图，研究ICC患者中前白蛋白与临床特征之间的潜在相关性。

结果

263例患者中位随访30（1~118）个月，OS为11（0.5~118）个月，1、2、3年累积生存率分别为55.0%、40.2%及27.5%。单因素及多因素回归分析显示，前白蛋白（P=0.002）、CA19-9（P<0.001）、肿瘤个数（P=0.006）、血管侵犯（P=0.042）、肿瘤细胞分化程度（P=0.004）是影响ICC患者OS的独立危险因素，建立的列线图模型可以较好、较准确地预测ICC患者的总体生存情况，一致性指数为0.730。前白蛋白与肿瘤的T、N、M分期存在一定相关性。

结论

包含前白蛋白指标的列线图可以较准确地预测ICC患者肝部分切除术后生存。

关键词: 胆管肿瘤, 肝切除术, 预后, 列线图

Objective

To investigate the factors influencing the prognosis and survival of patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram to predict the patient’s overall survival (OS) individually.

Methods

A retrospective analysis was performed in two hundred and sixty-three ICC patients who underwent radical hepatectomy from January 2008 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate Cox proportional hazard regression methods were used to screen the independent influencing factors of the OS of patients, and then to construct the nomogram to individually predict the survival of patients after ICC radical surgery. The potential correlation between pre-albumin and clinical characteristics of ICC patients were also investigated with density mapping.

Results

The median follow-up period of the 263 patients was 30 (1-118) months, and the OS was 11 (0.5-118) months. The 1, 2, and 3-year cumulative survival rates were 55.0%, 40.2%, and 27.5%, respectively. Univariate and multivariate Cox proportional hazard regression methods demonstrated that prealbumin (P=0.002), CA19-9 (P<0.001), the number of tumors (P=0.006), vascular invasion (P=0.042) and differentiation of tumors (P=0.004) were the independent risk factors for OS, and the nomogram constructed by the above factors can predict the OS of ICC patients well and accurately, with the C-index of 0.730. There was a certain correlation between the prealbumin and T, N and M stages of the tumor.

Conclusion

A nomogram containing the prealbumin can accurately predict the prognosis of ICC patients after radical hepatectomy.

Key words: Bile duct neoplasms, Hepatectomy, Prognosis, Nomogram

表1 263例肝内胆管癌根治术患者基线资料

项目		数值	项目		数值
性别［例(%)］		?	前白蛋白(g/L)^a		182(15~395)
?	男	137(52.1)	AST(U/L)^a		26(5~421)
?	女	126(47.9)	ALT(U/L)^a		29(11~415)
年龄(岁) ^a		57(21~79)	γ-GGT (U/L)^a		90(14~2 026)
乙型肝炎病毒感染［例(%)］		?	乳酸脱氢酶(U/L) ^a		199(119~811)
?	有	74(28.1)	肿瘤大小(cm) ^a		5(1~8)
?	无	189(71.9)	肿瘤个数［例(%)］		?
结石病史［例(%)］		?	?	1	188(71.5)
?	有	62(23.6)	?	>1	75(28.5)
?	无	201(76.4)	血管侵犯［例(%)］		?
AFP(μg/L)^a		3.36(1.03~10 714.32)	?	有	55(20.9)
CEA(μg/L)^a		3.14(0.50~3 203.5)	?	无	208(79.1)
CA19-9(U/ml)^a		110.51(0.4~12 000)	分化程度［例(%)］		?
CA125(U/ml)^a		22.4(2.6~10 000)	?	G1+G2	172(65.4)
总胆红素(μmol/L)^a		11.9(2.2~412.7)	?	G3+G4	91(34.6)
白细胞(×10⁹/L)^a		7.12(2.61~16.45)	淋巴结转移［例(%)］		?
中性粒细胞(×10⁹/L)^a		4.43(0.64~11.59)	?	有	85(32.3)
淋巴细胞(×10⁹/L)^a		1.7(0.10~4.41)	?	无	178(67.7)
血小板(×10⁹/L)^a		241(4.83~590)	?	?	?

表1 263例肝内胆管癌根治术患者基线资料

项目		数值	项目		数值
性别［例(%)］		?	前白蛋白(g/L)^a		182(15~395)
?	男	137(52.1)	AST(U/L)^a		26(5~421)
?	女	126(47.9)	ALT(U/L)^a		29(11~415)
年龄(岁) ^a		57(21~79)	γ-GGT (U/L)^a		90(14~2 026)
乙型肝炎病毒感染［例(%)］		?	乳酸脱氢酶(U/L) ^a		199(119~811)
?	有	74(28.1)	肿瘤大小(cm) ^a		5(1~8)
?	无	189(71.9)	肿瘤个数［例(%)］		?
结石病史［例(%)］		?	?	1	188(71.5)
?	有	62(23.6)	?	>1	75(28.5)
?	无	201(76.4)	血管侵犯［例(%)］		?
AFP(μg/L)^a		3.36(1.03~10 714.32)	?	有	55(20.9)
CEA(μg/L)^a		3.14(0.50~3 203.5)	?	无	208(79.1)
CA19-9(U/ml)^a		110.51(0.4~12 000)	分化程度［例(%)］		?
CA125(U/ml)^a		22.4(2.6~10 000)	?	G1+G2	172(65.4)
总胆红素(μmol/L)^a		11.9(2.2~412.7)	?	G3+G4	91(34.6)
白细胞(×10⁹/L)^a		7.12(2.61~16.45)	淋巴结转移［例(%)］		?
中性粒细胞(×10⁹/L)^a		4.43(0.64~11.59)	?	有	85(32.3)
淋巴细胞(×10⁹/L)^a		1.7(0.10~4.41)	?	无	178(67.7)
血小板(×10⁹/L)^a		241(4.83~590)	?	?	?

表2 影响肝内胆管癌总体生存期的单因素Cox比例风险分析

变量	P值	HR	95% CI	变量	P值	HR	95% CI
年龄	0.998	1.000	0.985~1.015	总胆红素	0.981	1.000	0.998~1.002
性别(男vs女)	0.326	1.167	0.857~1.588	乳酸脱氢酶	0.012^a	1.002	1.000~1.004
乙型肝炎病毒感染(有vs无)	0.968	1.007	0.717~1.414	AFP	0.800	1.000	1.000
结石(有vs无)	0.173	1.277	0.898~1.815	CEA	0.230	1.000	1.000
白细胞	0.087	1.055	0.992~1.122	CA125	0.008^a	1.000	1.000
中性粒细胞	0.084	1.064	0.992~1.141	CA19-9	<0.001^a	1.000	1.000
淋巴细胞	0.446	0.920	0.743~1.140	肿瘤大小	0.061	1.052	0.998~1.110
血小板	0.120	1.001	1.000~1.003	肿瘤个数(>1 vs 1)	<0.001^a	1.900	1.371~2.633
AST	0.533	1.001	0.999~1.003	血管侵犯(有vs无)	<0.001^a	2.569	1.783~3.702
ALT	0.393	1.001	0.999~1.004	分化程度(G3+G4 vs G1+G2)	0.003^a	1.638	1.187~2.261
γ-GGT	0.301	1.000	1.000~1.001	淋巴结转移(有vs无)	0.007^a	1.553	1.130~2.133
前白蛋白	<0.001^a	0.995	0.993~0.997	?	?	?	?

表2 影响肝内胆管癌总体生存期的单因素Cox比例风险分析

变量	P值	HR	95% CI	变量	P值	HR	95% CI
年龄	0.998	1.000	0.985~1.015	总胆红素	0.981	1.000	0.998~1.002
性别(男vs女)	0.326	1.167	0.857~1.588	乳酸脱氢酶	0.012^a	1.002	1.000~1.004
乙型肝炎病毒感染(有vs无)	0.968	1.007	0.717~1.414	AFP	0.800	1.000	1.000
结石(有vs无)	0.173	1.277	0.898~1.815	CEA	0.230	1.000	1.000
白细胞	0.087	1.055	0.992~1.122	CA125	0.008^a	1.000	1.000
中性粒细胞	0.084	1.064	0.992~1.141	CA19-9	<0.001^a	1.000	1.000
淋巴细胞	0.446	0.920	0.743~1.140	肿瘤大小	0.061	1.052	0.998~1.110
血小板	0.120	1.001	1.000~1.003	肿瘤个数(>1 vs 1)	<0.001^a	1.900	1.371~2.633
AST	0.533	1.001	0.999~1.003	血管侵犯(有vs无)	<0.001^a	2.569	1.783~3.702
ALT	0.393	1.001	0.999~1.004	分化程度(G3+G4 vs G1+G2)	0.003^a	1.638	1.187~2.261
γ-GGT	0.301	1.000	1.000~1.001	淋巴结转移(有vs无)	0.007^a	1.553	1.130~2.133
前白蛋白	<0.001^a	0.995	0.993~0.997	?	?	?	?

表3 影响肝内胆管癌总体生存期的多因素Cox风险比例分析

变量	Coef.	Std.Err	P值	HR	95% CI
乳酸脱氢酶	<0.001	0.001	0.655	1.000	0.998~1.003
前白蛋白	-0.004	0.001	0.002^a	0.996	0.994~0.999
CA125	<0.001	<0.001	0.131	1.000	1.000
CA19-9	<0.001	<0.001	<0.001^a	1.000	1.000
肿瘤个数(>1 vs 1)	0.475	0.173	0.006^a	1.608	1.146~2.257
血管侵犯(有vs无)	0.424	0.208	0.042^a	1.529	1.016~2.300
分化程度(G3+G4 vs G1+G2)	0.488	0.171	0.004^a	1.629	1.165~2.278
淋巴结转移(有vs无)	0.165	0.169	0.328	1.180	0.847~1.644

表3 影响肝内胆管癌总体生存期的多因素Cox风险比例分析

变量	Coef.	Std.Err	P值	HR	95% CI
乳酸脱氢酶	<0.001	0.001	0.655	1.000	0.998~1.003
前白蛋白	-0.004	0.001	0.002^a	0.996	0.994~0.999
CA125	<0.001	<0.001	0.131	1.000	1.000
CA19-9	<0.001	<0.001	<0.001^a	1.000	1.000
肿瘤个数(>1 vs 1)	0.475	0.173	0.006^a	1.608	1.146~2.257
血管侵犯(有vs无)	0.424	0.208	0.042^a	1.529	1.016~2.300
分化程度(G3+G4 vs G1+G2)	0.488	0.171	0.004^a	1.629	1.165~2.278
淋巴结转移(有vs无)	0.165	0.169	0.328	1.180	0.847~1.644

图1 肝内胆管癌患者总生存期预测　A为列线图，B、C为列线图校准曲线

图2 肝内胆管癌患者前白蛋白与肿瘤T、N、M分期密度图

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Nomogram model for the prognosis of intrahepatic cholangiocarcinoma after radical resection

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Nomogram model for the prognosis of intrahepatic cholangiocarcinoma after radical resection