微血管侵犯对小肝细胞癌和大肝细胞癌术后远期预后的影响

doi:10.3877/cma.j.issn.2095-3232.2017.03.013

目的

探讨微血管侵犯（MVI）对小肝细胞癌（肝癌）和大肝癌患者术后远期预后的影响。

方法

回顾性分析2008年1月至2008年7月在第二军医大学附属东方肝胆外科医院行根治性肝切除术的549例肝癌患者临床资料。其中男467例，女82例；年龄≤60岁426例，>60岁123例。根据肿瘤直径将患者分为小肝癌组（直径≤5 cm，319例）和大肝癌组（直径>5 cm，230例）。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生存曲线，肝癌术后远期生存的影响因素分析采用Cox比例风险回归模型。

结果

小肝癌组MVI（-）患者术后1、3、5年无瘤生存率和总体生存率分别为76%、55%、44%和95%、77%、62%，明显高于MVI（+）患者的53%、30%、27%和82%、50%、37%（χ²=12.767，18.937；P<0.05）。大肝癌组MVI（-）患者术后1、3、5年无瘤生存率和总体生存率分别为59%、40%、36%和82%、55%、41%，明显高于MVI（+）患者的35%、14%、14%和67%、42%、26%（χ²=20.378，9.733；P<0.05）。多因素分析结果显示，小肝癌组肿瘤数量、MVI和Edmondson-Steiner分级是患者术后无瘤生存的独立影响因素（HR=1.86，1.46，1.49；P<0.05）；CA19-9、MVI、Edmondson-Steiner分级是患者术后总体生存的独立影响因素（HR=2.07，1.85，1.52；P<0.05）。大肝癌组MVI和肿瘤直径是患者术后无瘤生存的独立影响因素（HR=2.01，1.05；P<0.05）；AFP、MVI和肿瘤直径是患者术后总体生存的独立影响因素（HR=1.75，1.46，1.06；P<0.05）。

结论

MVI是影响小肝癌和大肝癌患者术后无瘤生存和总体生存的独立危险因素。

关键词: 癌，肝细胞, 微血管侵犯, 存活率, 危险因素, 预后

Objective

To investigate the effect of microvascular invasion (MVI) on postoperative long-term prognosis of the patients with small and large hepatocellular carcinoma (HCC).

Methods

Clinical data of 549 patients who underwent radical hepatectomy in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between January 2008 and July 2008 were retrospectively analyzed. Among the patients, 467 cases were males and 82 females, 426 cases aged ≤60 years old and 123 aged >60 years old. According to the tumor diameter, the patients were divided into the small HCC group (tumor diameter ≤5 cm, n=319) and large HCC group (tumor diameter> 5 cm, n=230). The informed consents of all patients were obtained and the local ethical committee approval was received. Survival analysis was performed using Kaplan-Meier survival curve. Risk factors of postoperative long-term survival were analyzed using Cox proportional hazard regression model.

Results

In the small HCC group, the postoperative 1-, 3-, 5-year tumor-free survival rate and overall survival rate of the patients with MVI (-) was respectively 76%, 55%, 44% and 95%, 77%, 62%, significantly higher than 53%, 30%, 27% and 82%, 50%, 37% of the patients with MVI (+) (χ²=12.767, 18.937; P<0.05). In the large HCC group, the postoperative 1-, 3-, 5-year tumor-free survival rate and overall survival rate of the patients with MVI (-) was respectively 59%, 40%, 36% and 82%, 55%, 41%, significantly higher than 35%, 14%, 14% and 67%, 42%, 26% of the patients with MVI (+) (χ²=20.378, 9.733; P<0.05). Multivariate analysis indicated that, in the small HCC group, the tumor number, MVI and Edmondson-Steiner grade were the independent influence factors for postoperative tumor-free survival (HR=1.86, 1.46, 1.49; P<0.05), and CA19-9, MVI and Edmondson-Steiner grade were the independent influence factors for postoperative overall survival (HR=2.07, 1.85, 1.52; P<0.05). In the large HCC group, MVI and tumor diameter were the independent influence factors for postoperative tumor-free survival (HR=2.01, 1.05; P<0.05), and AFP, MVI and tumor diameter were the independent influence factors for postoperative overall survival (HR=1.75, 1.46, 1.06; P<0.05).

Conclusion

MVI is an independent risk factor for postoperative tumor-free survival and overall survival of patients with small and large HCC.

Key words: Carcinoma Hepatocellular, Microvascular invasion, Survival rate, Risk factor, Prognosis

表1 小肝癌组患者临床病理学特征（例）

组别	例数	性别		年龄		Plt		ALT		ALB		TB
组别	例数	男	女	≤60岁	>60岁	≤100×10⁹/L	>100×10⁹/L	≤44 U/L	>44U/L	≤35 g/L	>35 g/L	<17 μmol/L	≥17 μmol/L
MVI(-)	247	206	41	183	64	60	187	163	84	14	233	172	75
MVI(+)	72	62	10	57	15	18	54	48	24	7	65	51	21
χ²	?	0.035		0.771		0.015		0.011		1.490		0.038
P	?	>0.05		>0.05		>0.05		>0.05		>0.05		>0.05
组别	例数	PT		HBsAg		HBV-DNA		AFP		CA19-9		CEA
组别	例数	≤13 s	>13 s	（-）	（+）	<10⁴ IU/ml	≥10⁴ IU/ml	≤20 μg/L	>20 μg/L	≤39 μg/L	>39 μg/L	≤5 μg/L	>5 μg/L
MVI(-)	247	205	42	37	210	154	93	124	123	208	39	225	22
MVI(+)	72	60	12	5	37	35	37	19	53	51	21	65	7
χ²	?	0.005		3.148		4.357		12.783		6.533		0.045
P	?	>0.05		>0.05		<0.05		<0.05		<0.05		>0.05
组别	例数	术中输血		肿瘤数量		肿瘤包膜		肝硬化		Edmonson-Steiner分级
组别	例数	无	有	单发	多发	不完整	完整	无	有	无	有
MVI(-)	247	60	187	222	25	173	74	91	156	104	143
MVI(+)	72	18	54	60	12	38	34	14	58	10	62
χ²	?	0.023		2.329		7.419		7.642		19.327
P	?	>0.05		>0.05		<0.05		<0.05		<0.05

表1 小肝癌组患者临床病理学特征（例）

组别	例数	性别		年龄		Plt		ALT		ALB		TB
组别	例数	男	女	≤60岁	>60岁	≤100×10⁹/L	>100×10⁹/L	≤44 U/L	>44U/L	≤35 g/L	>35 g/L	<17 μmol/L	≥17 μmol/L
MVI(-)	247	206	41	183	64	60	187	163	84	14	233	172	75
MVI(+)	72	62	10	57	15	18	54	48	24	7	65	51	21
χ²	?	0.035		0.771		0.015		0.011		1.490		0.038
P	?	>0.05		>0.05		>0.05		>0.05		>0.05		>0.05
组别	例数	PT		HBsAg		HBV-DNA		AFP		CA19-9		CEA
组别	例数	≤13 s	>13 s	（-）	（+）	<10⁴ IU/ml	≥10⁴ IU/ml	≤20 μg/L	>20 μg/L	≤39 μg/L	>39 μg/L	≤5 μg/L	>5 μg/L
MVI(-)	247	205	42	37	210	154	93	124	123	208	39	225	22
MVI(+)	72	60	12	5	37	35	37	19	53	51	21	65	7
χ²	?	0.005		3.148		4.357		12.783		6.533		0.045
P	?	>0.05		>0.05		<0.05		<0.05		<0.05		>0.05
组别	例数	术中输血		肿瘤数量		肿瘤包膜		肝硬化		Edmonson-Steiner分级
组别	例数	无	有	单发	多发	不完整	完整	无	有	无	有
MVI(-)	247	60	187	222	25	173	74	91	156	104	143
MVI(+)	72	18	54	60	12	38	34	14	58	10	62
χ²	?	0.023		2.329		7.419		7.642		19.327
P	?	>0.05		>0.05		<0.05		<0.05		<0.05

图1 小肝癌组和大肝癌组MVI（-）和MVI（+）患者Kaplan-Meier无瘤生存曲线

表2 大肝癌组患者术后生存预后的Cox比例风险回归模型多因素分析

变量	无瘤生存						总体生存
变量	b	SE(b)	waldχ²	HR	95%CI	P	b	SE(b)	waldχ²	HR	95%CI	P
AFP	0.255	0.185	1.904	1.29	0.89～1.85	0.168	0.560	0.220	6.509	1.75	1.13～2.69	0.011
MVI	0.702	0.169	17.151	2.01	1.44～2.81	<0.001	0.379	0.183	4.298	1.46	1.02～2.09	0.038
Edmondson Steiner分级	-	-	-	-	-	-	0.293	0.267	1.207	1.34	0.79～2.26	0.272
肿瘤直径	0.057	0.021	7.626	1.05	1.01～1.10	0.006	0.067	0.022	9.462	1.06	1.02～1.11	0.002

表2 大肝癌组患者术后生存预后的Cox比例风险回归模型多因素分析

变量	无瘤生存						总体生存
变量	b	SE(b)	waldχ²	HR	95%CI	P	b	SE(b)	waldχ²	HR	95%CI	P
AFP	0.255	0.185	1.904	1.29	0.89～1.85	0.168	0.560	0.220	6.509	1.75	1.13～2.69	0.011
MVI	0.702	0.169	17.151	2.01	1.44～2.81	<0.001	0.379	0.183	4.298	1.46	1.02～2.09	0.038
Edmondson Steiner分级	-	-	-	-	-	-	0.293	0.267	1.207	1.34	0.79～2.26	0.272
肿瘤直径	0.057	0.021	7.626	1.05	1.01～1.10	0.006	0.067	0.022	9.462	1.06	1.02～1.11	0.002

[1]	Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
[2]	Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update[J]. Hepatology, 2011, 53(3):1020-1022.
[3]	European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma[J]. J Hepatol, 2012, 56(4):908-943.
[4]	Zhou YM, Yang JM, Li B, et al. Risk factors for early recurrence of small hepatocellular carcinoma after curative resection[J]. Hepatobiliary Pancreat Dis Int, 2010, 9(1):33-37.
[5]	Bertuzzo VR, Cescon M, Ravaioli M, et al. Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers[J]. Transplantation, 2011, 91(11):1279-1285.
[6]	Neumann U. Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria (Br J Surg 2011; 98: 1292-1300) [J]. Br J Surg, 2011, 98(9):1300-1301.
[7]	Huang ZY, Liang BY, Xiong M, et al. Long-term outcomes of repeat hepatic resection in patients with recurrent hepatocellular carcinoma and analysis of recurrent types and their prognosis: a single-center experience in China[J]. Ann Surg Oncol, 2012, 19(8):2515-2525.
[8]	Ruzzenente A, Guglielmi A, Sandri M, et al. Surgical resection versus local ablation for HCC on cirrhosis: results from a propensity case-matched study[J]. J Gastrointest Surg, 2012, 16(2):301-311.
[9]	Yuan SX, Yang F, Yang Y, et al. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy[J]. Hepatology, 2012, 56(6):2231-2241.
[10]	Rodríguez-Perálvarez M, Luong TV, Andreana L, et al. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability[J]. Ann Surg Oncol, 2013, 20(1):325-339.
[11]	Andreou A, Vauthey JN, Cherqui D, et al. Improved long-term survival after major resection for hepatocellular carcinoma: a multicenter analysis based on a new definition of major hepatectomy[J]. J Gastrointest Surg, 2013, 17(1):66-77.
[12]	Cheng Z, Yang P, Qu S, et al. Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection[J]. HPB, 2015, 17(5):422-427.
[13]	Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma[J]. Oncogene, 2010, 29(36):4989-5005.
[14]	Fan ST, Poon RT, Yeung C, et al. Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria[J]. Br J Surg, 2011, 98(9):1292-1300.
[15]	Chan SC, Fan ST, Chok KS, et al. Survival advantage of primary liver transplantation for hepatocellular carcinoma within the up-to-7 criteria with microvascular invasion[J]. Hepatol Int, 2011, 6(3):646-656.
[16]	Lim KC, Chow PK, Allen JC, et al. Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria[J]. Ann Surg, 2011, 254(1):108-113.
[17]	Lei Z, Li J, Wu D, et al. Nomogram for preoperative estimation of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma within the Milan criteria[J]. JAMA Surg, 2016, 151(4):356-363.
[18]	McHugh PP, Gilbert J, Vera S, et al. Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma[J]. HPB, 2010, 12(1):56-61.
[19]	Chou CT, Chen RC, Lee CW, et al. Prediction of microvascular invasion of hepatocellular carcinoma by pre-operative CT imaging[J]. Br J Radiol, 2012, 85(1014):778-783.

[1]	张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[2]	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.
[3]	李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[4]	常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[5]	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.
[6]	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.
[7]	公宇, 廖媛, 尚梅. 肝细胞癌TACE术后复发影响因素及预测模型建立[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 818-824.
[8]	李一帆, 朱帝文, 任伟新, 鲍应军, 顾俊鹏, 张海潇, 曹耿飞, 阿斯哈尔·哈斯木, 纪卫政. 血GP73水平在原发性肝癌TACE疗效评价中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 825-830.
[9]	刘敏思, 李荣, 李媚. 基于GGT与Plt比值的模型在HBV相关肝细胞癌诊断中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 831-835.
[10]	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.
[11]	焦振东, 惠鹏, 金上博. 三维可视化结合ICG显像技术在腹腔镜肝切除术治疗复发性肝癌中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 859-864.
[12]	董佳, 王坤, 张莉. 预后营养指数结合免疫球蛋白、血糖及甲胎蛋白对HBV 相关慢加急性肝衰竭患者治疗后预后不良的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 555-559.
[13]	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.
[14]	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.
[15]	郭曌蓉, 王歆光, 刘毅强, 何英剑, 王立泽, 杨飏, 汪星, 曹威, 谷重山, 范铁, 李金锋, 范照青. 不同亚型乳腺叶状肿瘤的临床病理特征及预后危险因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(06): 524-532.

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

Effect of microvascular invasion on postoperative long-term prognosis of small and large hepatocellular carcinoma

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

Effect of microvascular invasion on postoperative long-term prognosis of small and large hepatocellular carcinoma