肝门部胆管癌术后患者预后影响因素：单中心160例分析

doi:10.3877/cma.j.issn.2095-3232.2022.06.017

目的

探讨肝门部胆管癌（PHC）患者术后预后的影响因素。

方法

回顾性分析2002年1月至2019年12月在宁波大学附属李惠利医院行手术切除的160例PHC患者临床资料。患者均签署知情同意书，符合医学伦理学规定。生存分析采用Kaplan-Meier法和Log-rank检验。采用Cox比例风险回归模型分析患者预后影响因素。

结果

160例患者中男86例，女74例；年龄30~83岁，中位年龄63岁。Bismuth-Corlette分型Ⅰ、Ⅱ型42例，Ⅲ、Ⅳ型118例。单纯肝外胆管切除16例，肝中区域切除56例，大范围肝切除88例，其中合并血管切除重建68例，R0切除138例。PHC患者术后1、3、5年总体生存率分别为70.3%、33.5%、24.2%，1、3、5年无复发生存率分别为56.7%、36.6%、33.5%。Cox多因素分析显示，肿瘤低分化、淋巴结转移、R1切除是PHC患者术后总体生存和无复发生存的独立危险因素（HR=1.510，2.346，1.963和1.665，2.862，3.443；P<0.05）。

结论

肿瘤分化程度、淋巴结转移情况及根治切除程度与PHC患者的生存预后密切相关。

关键词: 肝门部胆管癌, 胆管肿瘤, 外科手术, 预后, 危险因素

Objective

To investigate the prognostic factors of patients with perihilar cholangiocarcinoma (PHC) after surgery.

Methods

Clinical data of 160 patients with PHC who underwent surgical resection in Lihuili Hospital Affiliated to Ningbo University from January 2002 to December 2019 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Survival analysis was conducted by Kaplan-Meier method and Log-rank test. The prognostic factors were analyzed by Cox proportional hazards regression model.

Results

Among 160 patients,86 patients were male and 74 female, aged from 30 to 83 years, with a median age of 63 years. 42 patients were classified as Bismuth-Corlette type Ⅰ and Ⅱ, and 118 cases were type Ⅲ and Ⅳ. 16 patients underwent simple extrahepatic bile duct resection, 56 cases of middle hepatic resection, 88 cases of extensive liver resection.68 cases underwent combined vascular resection and reconstruction and 138 cases of R0 resection, respectively. The 1-, 3- and 5-year overall survival rates of PHC patients were 70.3%, 33.5% and 24.2%, and the 1-, 3- and 5-year recurrence-free survival rates were 56.7%, 36.6% and 33.5%, respectively. Multivariate Cox analysis showed that low-grade differentiation, lymph node metastasis and R1 resection were the independent risk factors for the overall survival and recurrence-free survival of PHC patients after surgery (HR=1.510, 2.346, 1.963 and 1.665, 2.862, 3.443; P<0.05).

Conclusions

Tumor differentiation, lymph node metastasis and degree of radical resection are closely correlated with the postoperative prognosis of PHC patients.

Key words: Perihilar cholangiocarcinoma, Bile duct neoplasms, Surgical procedures, operative, Prognosis, Risk factors

图1 肝门部胆管癌患者术后总体生存和无复发生存Kaplan-Meier曲线

表1 肝门部胆管癌患者术后总体生存影响因素的Cox单因素分析

参数		例数	1年生存率（%）	3年生存率（%）	5年生存率（%）	χ²值	P值
肿瘤分化程度						12.453	<0.001
	高中分化	96	78.1	44.5	31.4
	低分化	64	58.5	15.9	12.7
淋巴结转移						20.469	<0.001
	是	65	56.8	18.4	4.6
	否	95	79.1	43.1	35.7
切除类型						4.071	0.044
	R0切除	138	69.4	42.8	27.9
	R1切除	22	75.4	5.0	5.0

表1 肝门部胆管癌患者术后总体生存影响因素的Cox单因素分析

参数		例数	1年生存率（%）	3年生存率（%）	5年生存率（%）	χ²值	P值
肿瘤分化程度						12.453	<0.001
	高中分化	96	78.1	44.5	31.4
	低分化	64	58.5	15.9	12.7
淋巴结转移						20.469	<0.001
	是	65	56.8	18.4	4.6
	否	95	79.1	43.1	35.7
切除类型						4.071	0.044
	R0切除	138	69.4	42.8	27.9
	R1切除	22	75.4	5.0	5.0

表2 肝门部胆管癌患者术后无复发生存影响因素的Cox单因素分析

参数		例数	1年生存率（%）	3年生存率（%）	5年生存率（%）	χ²值	P值
肿瘤分化程度						9.194	0.002
	高中分化	96	66.5	45.1	45.1
	低分化	64	42.7	25.0	16.7
淋巴结转移						16.698	<0.001
	是	65	36.4	16.9	0
	否	95	69.8	49.0	49.0
切除类型						10.279	0.001
	R0切除	138	58.9	4.08	40.8
	R1切除	22	40.0	13.3	13.3

表2 肝门部胆管癌患者术后无复发生存影响因素的Cox单因素分析

参数		例数	1年生存率（%）	3年生存率（%）	5年生存率（%）	χ²值	P值
肿瘤分化程度						9.194	0.002
	高中分化	96	66.5	45.1	45.1
	低分化	64	42.7	25.0	16.7
淋巴结转移						16.698	<0.001
	是	65	36.4	16.9	0
	否	95	69.8	49.0	49.0
切除类型						10.279	0.001
	R0切除	138	58.9	4.08	40.8
	R1切除	22	40.0	13.3	13.3

表3 肝门部胆管癌患者术后总体生存影响因素的Cox多因素分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P值
肿瘤低分化	0.412	0.142	8.464	1.510	1.144~1.994	0.004
淋巴结转移	0.853	0.209	16.618	2.346	1.557~3.536	<0.001
R1切除	0.675	0.264	6.553	1.963	1.171~3.290	0.010

表3 肝门部胆管癌患者术后总体生存影响因素的Cox多因素分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P值
肿瘤低分化	0.412	0.142	8.464	1.510	1.144~1.994	0.004
淋巴结转移	0.853	0.209	16.618	2.346	1.557~3.536	<0.001
R1切除	0.675	0.264	6.553	1.963	1.171~3.290	0.010

表4 肝门部胆管癌患者术后无复发生存影响因素的Cox多因素分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P值
肿瘤低分化	0.510	0.196	6.786	1.665	1.135~2.444	0.009
淋巴结转移	1.052	0.265	15.692	2.862	1.701~4.815	<0.001
R1切除	1.236	0.325	14.495	3.443	1.822~6.507	<0.001

表4 肝门部胆管癌患者术后无复发生存影响因素的Cox多因素分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P值
肿瘤低分化	0.510	0.196	6.786	1.665	1.135~2.444	0.009
淋巴结转移	1.052	0.265	15.692	2.862	1.701~4.815	<0.001
R1切除	1.236	0.325	14.495	3.443	1.822~6.507	<0.001

[1]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[2]	Hu HJ, Jin YW, Zhou RX, et al. Hepatic artery resection for bismuth typeⅢ andⅣhilar cholangiocarcinoma: is reconstruction always required?[J]. J Gastrointest Surg, 2018, 22(7):1204-1212.
[3]	Vanwien A, Colard M, Godart J, et al. "Extended" right hepatectomy for primary cholangiocarcinoma of the liver[J]. Acta Chir Belg, 1964, 63:725-728.
[4]	郑树国, 项灿宏, 冯晓彬, 等. 肝门部胆管癌诊断和治疗指南(2013版)[J]. 中华外科杂志, 2013, 51(10):865-871.
[5]	Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience[J]. Ann Surg, 2009, 250(2):187-196.
[6]	Koch M, Garden OJ, Padbury R, et al. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery[J]. Surgery, 2011, 149(5):680-688.
[7]	Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6 336 patients and results of a survey[J]. Ann Surg, 2004, 240(2):205-213.
[8]	Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver[J]. Surg Gynecol Obstet, 1975, 140(2):170-178.
[9]	Jarnagin WR, Fong Y, Dematteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma[J]. Ann Surg, 2001, 234(4):507-517.
[10]	Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC cancer staging manual: pancreas and hepatobiliary cancers[J]. Ann Surg Oncol, 2018, 25(4):845-847.
[11]	Deoliveira ML, Schulick RD, Nimura Y, et al. New staging system and a registry for perihilar cholangiocarcinoma[J]. Hepatology, 2011, 53(4):1363-1371.
[12]	Shinohara K, Ebata T, Shimoyama Y, et al. Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth[J]. Br J Surg, 2019, 106(4):427-435.
[13]	Takahashi T, Iizuka M, Sato H, et al. Doppler echocardiographic-determined changes in left ventricular diastolic filling flow velocity during the lower body positive and negative pressure method[J]. Am J Cardiol, 1990, 65(3):237-241.
[14]	Kikuchi Y, Matuyama R, Hiroshima Y, et al. Surgical and histological boundary of the hepatic hilar plate system: basic study relevant to surgery for hilar cholangiocarcinoma regarding the "true" proximal ductal margin[J]. J Hepatobiliary Pancreat Sci, 2019, 26(5):159-168.
[15]	Wakai T, Shirai Y, Moroda T, et al. Impact of ductal resection margin status on long-term survival in patients undergoing resection for extrahepatic cholangiocarcinoma[J]. Cancer, 2005, 103(6):1210-1216.
[16]	Cheng QB, Yi B, Wang JH, et al. Resection with total caudate lobectomy confers survival benefit in hilar cholangiocarcinoma of Bismuth type Ⅲ and Ⅳ[J]. Eur J Surg Oncol, 2012, 38(12):1197-1203.
[17]	Kow AW, Wook CD, Song SC, et al. Role of caudate lobectomy in type ⅢA and ⅢB hilar cholangiocarcinoma: a 15-year experience in a tertiary institution[J]. World J Surg, 2012, 36(5):1112-1121.
[18]	Birgin E, Rasbach E, Reissfelder C, et al. A systematic review and meta-analysis of caudate lobectomy for treatment of hilar cholangiocarcinoma[J]. Eur J Surg Oncol, 2020, 46(5):747-753.
[19]	Neuhaus P, Thelen A, Jonas S, et al. Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma[J]. Ann Surg Oncol, 2012, 19(5):1602-1608.
[20]	Tamoto E, Hirano S, Tsuchikawa T, et al. Portal vein resection using the no-touch technique with a hepatectomy for hilar cholangiocarcinoma[J]. HPB, 2014, 16(1):56-61.
[21]	De Lu C, Huang J, Wu SD, et al. Total hilar en bloc resection with left hemihepatectomy and caudate lobectomy: a novel approach for treatment of left-sided perihilar cholangiocarcinoma (with video)[J]. J Gastrointest Surg, 2017, 21(11):1906-1914.
[22]	Nagino M, Ebata T, Yokoyama Y, et al. Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections[J]. Ann Surg, 2013, 258(1):129-140.
[23]	朱菁莪, 冯铭彬, 王捷, 等. 单中心不同时期肝门部胆管癌外科治疗患者预后及术式变化[J/OL]. 中华肝脏外科手术学电子杂志, 2020, 9(1):36-40.
[24]	Hadjis NS, Blenkharn JI, Alexander N, et al. Outcome of radical surgery in hilar cholangiocarcinoma[J]. Surgery, 1990, 107(6):597-604.
[25]	胡海洁, 靳艳文, 林圯昕, 等. 肝门部胆管癌肿瘤直径及相关预后指标对患者预后的影响因素分析[J]. 中华消化外科杂志, 2018, 17(3):266-272.
[26]	Marrelli D, Caruso S, Pedrazzani C, et al. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions[J]. Am J Surg, 2009, 198(3):333-339.

[1]	许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[2]	高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[3]	李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[4]	孙莲, 马红萍, 吴文英. 局部进展期甲状腺癌患者外科处理[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 112-114.
[5]	梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[6]	张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[7]	李伟, 宋子健, 赖衍成, 周睿, 吴涵, 邓龙昕, 陈锐. 人工智能应用于前列腺癌患者预后预测的研究现状及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 541-546.
[8]	郭兵, 王万里, 何凯, 黄汉生. 腹腔镜下肝门部胆管癌根治术[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(01): 143-143.
[9]	魏丽霞, 张安澜, 周宝勇, 李明. 腹腔镜下Ⅲb型肝门部胆管癌根治术[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(01): 145-145.
[10]	陈宗杰, 胡添松. 肝外伤破裂患者治疗后胆漏发生影响因素分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 836-840.
[11]	关小玲, 周文营, 陈洪平. PTAAR在乙肝相关慢加急性肝衰竭患者短期预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 841-845.
[12]	张润锦, 阳盼, 林燕斯, 刘尊龙, 刘建平, 金小岩. EB病毒相关胆管癌伴多发转移一例及国内文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 865-869.
[13]	陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[14]	王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
[15]	颜世锐, 熊辉. 感染性心内膜炎合并急性肾损伤患者的危险因素探索及死亡风险预测[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 618-624.

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

Prognostic factors of patients with perihilar cholangiocarcinoma after surgery: a single-center analysis of 160 cases

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

Prognostic factors of patients with perihilar cholangiocarcinoma after surgery: a single-center analysis of 160 cases