微血管侵犯对肝癌肝移植患者生存预后的影响

doi:10.3877/cma.j.issn.2095-3232.2023.06.007

目的

探讨微血管侵犯（MVI）对肝癌肝移植患者术后预后的影响。

方法

回顾性分析2011年1月至2021年12月在佛山市第一人民医院行肝移植治疗的78例肝癌患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男71例，女7例；平均年龄（53±9）岁。HBsAg阳性72例；肝功能Child-Pugh评分（8±2）分，终末期肝病模型（MELD）评分（14±7）分。根据术后病理结果将患者分为MVI阳性组（19例）和MVI阴性组（59例）。比较两组患者术后生存情况。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影响患者术后生存的因素。

结果

MVI阳性组术后1、3、5年总体生存（OS）分别为89.5%、68.6%、58.8%，MVI阴性组相应为94.5%、89.8%、86.0%，MVI阳性组术后OS明显较差（χ²=5.495，P<0.05）。MVI阳性组术后1、3、5年无进展生存（PFS）分别为79.0%、60.3%、51.7%，MVI阴性组相应为92.6%、85.5%、76.0%，MVI阳性组术后PFS明显较差（χ²=3.960，P<0.05）。Cox多因素分析结果显示，患者年龄、Child-Pugh评分、肿瘤数目及MVI阳性是术后OS的独立影响因素（OR=0.068，14.861，50.102，3.201；P<0.05）。患者肿瘤直径及MVI阳性是术后PFS的独立影响因素（OR=2.150, 2.333；P<0.05）。对于符合米兰标准患者，MVI阳性组术后OS、PFS也明显差于MVI阴性组（χ²=6.013，6.595；P<0.05）。

结论

MVI阳性是肝癌肝移植患者术后生存的独立影响因素，MVI阳性患者复发率更高，生存更差。

关键词: 癌，肝细胞, 微血管侵犯, 肝移植

Objective

To evaluate the effect of microvascular invasion (MVI) on the postoperative prognosis of liver transplantation recipients with liver cancer.

Methods

Clinical data of 78 patients with liver cancer who underwent liver transplantation in the First People's Hospital of Foshan from January 2011 to December 2021 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 71 patients were male and 7 female, aged (53±9) years on average. 72 cases were positive for HBsAg. Child-Pugh score was 8±2 and the model for end-stage liver disease (MELD) score was 14±7. All patients were divided into the positive (n=19) and negative MVI groups (n=59) according to postoperative pathological results. Postoperative survival of patients was compared between two groups. Survival analysis was assessed by Kaplan-Meier method and Log-rank test. The factors affecting postoperative survival were analyzed by Cox proportional hazard regression model.

Results

The postoperative 1-, 3- and 5-year overall survival (OS) in the positive MVI group was 89.5%, 68.6% and 58.8%, significantly lower than 94.5%, 89.8% and 86.0% in the negative MVI group (χ²=5.495, P<0.05). In the positive MVI group, the postoperative 1-, 3- and 5-year progression-free survival (PFS) was 79.0%, 60.3% and 51.7%, significantly lower than 92.6%, 85.5% and 76.0% in the negative MVI group (χ²=3.960, P<0.05). Cox multivariate analysis showed that patients' age, Child-Pugh score, number of tumors and positive MVI were the independent influencing factors of postoperative OS (OR=0.068, 14.861, 50.102, 3.201; P<0.05). The tumor diameter and positive MVI were the independent influencing factors of postoperative PFS (OR=2.150, 2.333; P<0.05). For patients who met Milan criteria, postoperative OS and PFS in the MVI positive group were also significantly worse than those in the negative MVI group (χ²=6.013, 6.595; P<0.05).

Conclusions

Positive MVI is an independent influencing factor of postoperative survival of liver cancer patients after liver transplantation. Patients positive for MVI have higher recurrence rate and worse survival compared with their negative counterparts.

Key words: Carcinoma, hepatocellular, Microvascular invasion, Liver transplantation

表1 MVI阳性和阴性肝癌肝移植患者临床病理特征比较

组别	例数	年龄(岁，±s)	性别(例)		AFP>400 μg/L(例)	HBsAg阳性(例)	Child-Pugh评分(分，±s)	MELD评分(分，±s)	肿瘤直径[cm，±s]	单发病灶(例)	AJCC分期Ⅲ~Ⅳ期(例)
组别	例数	年龄(岁，±s)	男	女	AFP>400 μg/L(例)	HBsAg阳性(例)	Child-Pugh评分(分，±s)	MELD评分(分，±s)	肿瘤直径[cm，±s]	单发病灶(例)	AJCC分期Ⅲ~Ⅳ期(例)
MVI阳性	19	51±8	19	0	7	18	8.4±2.5	14±8	5.9±4.2	8	8
MVI阴性	59	54±9	52	7	8	54	7.9±2.3	14±7	3.7±2.8	34	6
统计值		t=-1.171	-		χ²=5.016	χ²=0.209	t=0.796	t=0.374	t=2.607	χ²=1.393	χ²=9.953
P值		0.245	0.185		0.025	0.648	0.428	0.710	0.011	0.238	0.002

表1 MVI阳性和阴性肝癌肝移植患者临床病理特征比较

组别	例数	年龄(岁，±s)	性别(例)		AFP>400 μg/L(例)	HBsAg阳性(例)	Child-Pugh评分(分，±s)	MELD评分(分，±s)	肿瘤直径[cm，±s]	单发病灶(例)	AJCC分期Ⅲ~Ⅳ期(例)
组别	例数	年龄(岁，±s)	男	女	AFP>400 μg/L(例)	HBsAg阳性(例)	Child-Pugh评分(分，±s)	MELD评分(分，±s)	肿瘤直径[cm，±s]	单发病灶(例)	AJCC分期Ⅲ~Ⅳ期(例)
MVI阳性	19	51±8	19	0	7	18	8.4±2.5	14±8	5.9±4.2	8	8
MVI阴性	59	54±9	52	7	8	54	7.9±2.3	14±7	3.7±2.8	34	6
统计值		t=-1.171	-		χ²=5.016	χ²=0.209	t=0.796	t=0.374	t=2.607	χ²=1.393	χ²=9.953
P值		0.245	0.185		0.025	0.648	0.428	0.710	0.011	0.238	0.002

图1 MVI阳性和阴性肝癌肝移植患者术后Kaplan-Meier生存曲线注：MVI为微血管侵犯

表2 肝癌肝移植患者术后OS单因素及多因素Cox分析

指标	单因素分析			多因素分析
指标	OR	95%CI	P值	OR	95%CI	P值
年龄	0.561	0.187~1.681	0.302	0.068	0.009~0.532	0.010
男性	0.846	0.109~6.600	0.874	11.504	0.926~142.956	0.057
AFP>400 μg/L	4.753	1.531~14.756	0.007	1.518	0.397~5.801	0.542
HBsAg阳性	27.756	0.010~39.068	0.409	16.036	0.001~47.417	0.989
Child-Pugh评分	2.542	1.153~5.606	0.021	14.861	2.404~91.882	0.004
MELD评分	3.536	1.046~11.960	0.042	0.470	0.047~4.733	0.522
移植前治疗	1.133	0.379~3.390	0.823	1.281	0.273~6.017	0.754
肿瘤直径	3.621	1.179~11.124	0.025	1.860	0.417~8.293	0.416
肿瘤多发	7.261	1.608~32.792	0.010	50.102	3.639~689.731	0.003
AJCC Ⅲ~Ⅳ期	6.310	2.107~18.897	0.001	0.541	0.068~4.301	0.561
MVI阳性	3.433	1.148~10.271	0.027	3.201	1.652~15.717	0.015

表2 肝癌肝移植患者术后OS单因素及多因素Cox分析

指标	单因素分析			多因素分析
指标	OR	95%CI	P值	OR	95%CI	P值
年龄	0.561	0.187~1.681	0.302	0.068	0.009~0.532	0.010
男性	0.846	0.109~6.600	0.874	11.504	0.926~142.956	0.057
AFP>400 μg/L	4.753	1.531~14.756	0.007	1.518	0.397~5.801	0.542
HBsAg阳性	27.756	0.010~39.068	0.409	16.036	0.001~47.417	0.989
Child-Pugh评分	2.542	1.153~5.606	0.021	14.861	2.404~91.882	0.004
MELD评分	3.536	1.046~11.960	0.042	0.470	0.047~4.733	0.522
移植前治疗	1.133	0.379~3.390	0.823	1.281	0.273~6.017	0.754
肿瘤直径	3.621	1.179~11.124	0.025	1.860	0.417~8.293	0.416
肿瘤多发	7.261	1.608~32.792	0.010	50.102	3.639~689.731	0.003
AJCC Ⅲ~Ⅳ期	6.310	2.107~18.897	0.001	0.541	0.068~4.301	0.561
MVI阳性	3.433	1.148~10.271	0.027	3.201	1.652~15.717	0.015

表3 肝癌肝移植患者术后PFS单因素及多因素Cox分析

指标	单因素分析			多因素分析
指标	OR	95%CI	P值	OR	95%CI	P值
年龄	0.985	0.934~1.039	0.580	0.982	0.914~1.055	0.619
男性	1.683	0.383~7.397	0.491	3.040	0.427~21.675	0.267
AFP>400 μg/L	3.768	1.429~9.937	0.007	2.386	0.671~8.480	0.179
HBsAg阳性	23.239	0.014~38.620	0.406	13.632	0.162~25.360	0.563
Child-Pugh评分	1.074	0.880~1.311	0.484	0.744	0.495~1.117	0.154
MELD评分	1.045	0.989~1.105	0.119	1.080	0.915~1.274	0.363
移植前治疗	1.415	0.538~3.722	0.482	1.928	0.583~6.378	0.282
肿瘤直径	1.229	1.099~1.375	<0.001	2.150	1.021~3.294	0.021
肿瘤多发	3.130	1.101~8.895	0.032	1.933	0.384~9.727	0.424
AJCCⅢ~Ⅳ期	5.079	1.949~13.237	0.001	2.648	0.456~15.365	0.278
MVI阳性	2.761	1.065~7.163	0.037	2.333	1.340~5.225	0.036

表3 肝癌肝移植患者术后PFS单因素及多因素Cox分析

指标	单因素分析			多因素分析
指标	OR	95%CI	P值	OR	95%CI	P值
年龄	0.985	0.934~1.039	0.580	0.982	0.914~1.055	0.619
男性	1.683	0.383~7.397	0.491	3.040	0.427~21.675	0.267
AFP>400 μg/L	3.768	1.429~9.937	0.007	2.386	0.671~8.480	0.179
HBsAg阳性	23.239	0.014~38.620	0.406	13.632	0.162~25.360	0.563
Child-Pugh评分	1.074	0.880~1.311	0.484	0.744	0.495~1.117	0.154
MELD评分	1.045	0.989~1.105	0.119	1.080	0.915~1.274	0.363
移植前治疗	1.415	0.538~3.722	0.482	1.928	0.583~6.378	0.282
肿瘤直径	1.229	1.099~1.375	<0.001	2.150	1.021~3.294	0.021
肿瘤多发	3.130	1.101~8.895	0.032	1.933	0.384~9.727	0.424
AJCCⅢ~Ⅳ期	5.079	1.949~13.237	0.001	2.648	0.456~15.365	0.278
MVI阳性	2.761	1.065~7.163	0.037	2.333	1.340~5.225	0.036

图2 符合米兰标准的MVI阳性和阴性肝癌肝移植患者术后Kaplan-Meier生存曲线注：MVI为微血管侵犯

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Effect of microvascular invasion on survival and prognosis of liver transplantation recipients with liver cancer

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Effect of microvascular invasion on survival and prognosis of liver transplantation recipients with liver cancer