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

[1]	Squadroni M, Tondulli L, Gatta G, et al. Cholangiocarcinoma[J]. Crit Rev Oncol Hematol, 2017, 116: 11-31.
[2]	Nakanuma Y, Kakuda Y. Pathologic classification of cholangiocarcinoma: new concepts[J]. Best Pract Res Clin Gastroenterol, 2015, 29(2): 277-293.
[3]	Liu H, Cen X, Suo T, et al. Trends and hospital variations in surgical outcomes for cholangiocarcinoma in New York State[J]. World J Surg, 2017, 41(2): 525-537.
[4]	Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma[J]. J Hepatol, 2014, 60(6): 1268-1289.
[5]	Zhang H, Yang T, Wu M, et al. Intrahepatic cholangiocarcinoma: epidemiology, risk factors, diagnosis and surgical management[J]. Cancer Lett, 2016, 379(2): 198-205.
[6]	Spolverato G, Vitale A, Cucchetti A, et al. Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma?[J]. Cancer, 2015, 121(22): 3998-4006.
[7]	Yoshida N, Baba Y, Shigaki H, et al. Preoperative nutritional assessment by Controlling Nutritional Status (CONUT) is useful to estimate postoperative morbidity after esophagectomy for esophageal cancer[J]. World J Surg, 2016, 40(8): 1910-1917.
[8]	Sakurai K, Ohira M, Tamura T, et al. Predictive potential of preoperative nutritional status in long-term outcome projections for patients with gastric cancer[J]. Ann Surg Oncol, 2016, 23(2): 525-533.
[9]	Verdonck-de Leeuw IM, Cuijpers P, Leemans CR. Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer[J]. Cancer, 2016, 122(6): 971-972.
[10]	Zhou H, Jiang X, Li Q, et al. A simple and effective prognostic staging system based on clinicopathologic features of intrahepatic cholangiocarcinoma[J]. Am J Cancer Res, 2015, 5(5): 1831-1843.
[11]	Kawai H, Ota H. Low perioperative serum prealbumin predicts early recurrence after curative pulmonary resection for non-small-cell lung cancer[J]. World J Surg, 2012, 36(12): 2853-2857.
[12]	Han WX, Chen ZM, Wei ZJ, et al. Preoperative pre-albumin predicts prognosis of patients after gastrectomy for adenocarcinoma of esophagogastric junction[J]. World J Surg Oncol, 2016, 14(1): 279.
[13]	Bergquist JR, Puig CA, Shubert CR, et al. Carbohydrate antigen 19-9 elevation in anatomically resectable, early stage pancreatic cancer is independently associated with decreased overall survival and an indication for neoadjuvant therapy: A national cancer database study[J]. J Am Coll Surg, 2016, 223(1): 52-65.
[14]	Kondo N, Murakami Y, Uemura K, et al. Elevated perioperative serum CA19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma[J]. J Surg Oncol, 2014, 110(4): 422-429.
[15]	Kannagi R, Izawa M, Koike T, et al. Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis[J]. Cancer Sci, 2004, 95(5): 377-384.
[16]	Kannagi R. Carbohydrate antigen sialyl Lewis a--its pathophy-siological significance and induction mechanism in cancer progression[J]. Chang Gung Med J, 2007, 30(3): 189-209.
[17]	池小斌，罗祥基. 肝内胆管细胞癌外科治疗的疗效相关因素研究[J]. 实用癌症杂志, 2015, 30 (11): 1697-1700.
[18]	徐建，李敬东. 肝内胆管结石合并胆管癌诊治经验[J/CD]. 中华肝脏外科手术学电子杂志, 2018, 7(2): 115-118.
[19]	许远，王兆洪，吴志豪, 等. 肝内胆管细胞癌患者肝切除术预后影响因素[J]. 中华肝胆外科杂志, 2015, 21(1): 52-53.
[20]	Hu LS, Weiss M, Popescu I, et al. Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma[J]. J Surg Oncol, 2019, 119(1): 21-29.
[21]	Spolverato G, Ejaz A, Kim Y, et al. Tumor size predicts vascular invasion and histologic grade among patients undergoing resection of intrahepatic cholangiocarcinoma[J]. J Gastrointest Surg, 2014, 18(7): 1284-1291.
[22]	Okubo S, Mitsunaga S, Kato Y, et al. The prognostic impact of differentiation at the invasive front of biliary tract cancer[J]. J Surg Oncol, 2018, 117(6): 1278-1287.
[23]	Ali SM, Clark CJ, Mounajjed T, et al. Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo clinic experience[J]. HPB (Oxford), 2015, 17(3): 244-250.

[1]	孙帼, 谢迎东, 徐超丽, 杨斌. 超声联合临床特征的列线图模型预测甲状腺乳头状癌淋巴结转移的价值[J]. 中华医学超声杂志（电子版）, 2023, 20(07): 734-742.
[2]	应康, 杨璨莹, 刘凤珍, 陈丽丽, 刘燕娜. 左心室心肌应变对无症状重度主动脉瓣狭窄患者的预后评估价值[J]. 中华医学超声杂志（电子版）, 2023, 20(06): 581-587.
[3]	衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[4]	施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.
[5]	谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[6]	唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[7]	杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[8]	王春荣, 陈姜, 喻晨. 循Glisson蒂鞘外解剖、Laennec膜入路腹腔镜解剖性左半肝切除术临床应用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 37-40.
[9]	栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[10]	甄子铂, 刘金虎. 基于列线图模型探究静脉全身麻醉腹腔镜胆囊切除术患者术后肠道功能紊乱的影响因素[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 61-65.
[11]	马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[12]	江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[13]	李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[14]	王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[15]	索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Nomogram model for the prognosis of intrahepatic cholangiocarcinoma after radical resection

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Nomogram model for the prognosis of intrahepatic cholangiocarcinoma after radical resection