肝癌术后复发补救性肝移植疗效及预后影响因素

doi:10.3877/cma.j.issn.2095-3232.2021.04.006

中华肝脏外科手术学电子杂志 ›› 2021, Vol. 10 ›› Issue (04) : 365 -370. doi: 10.3877/cma.j.issn.2095-3232.2021.04.006

临床研究

肝癌术后复发补救性肝移植疗效及预后影响因素

陈拓¹, 张全保¹, 陶一峰¹, 沈丛欢¹, 李瑞东¹, 马震宇¹, 李建华¹, 陆录¹, 陈进宏¹, 钦伦秀¹, 王正昕¹^,^†(

)

^1. 200040　上海，复旦大学附属华山医院普通外科　复旦大学器官移植研究所

收稿日期:2021-04-27 出版日期:2021-08-18
通信作者: 王正昕
基金资助:
国家科技重大专项(2017ZX10203205); 国家自然科学基金面上项目(81773089，81873874); 上海申康医院发展中心临床三年行动计划(SHDC2020CR2021B)

Clinical efficacy and prognostic factors of salvage liver transplantation for postoperative recurrence of primary liver cancer

Tuo Chen¹, Quanbao Zhang¹, Yifeng Tao¹, Conghuan Shen¹, Ruidong Li¹, Zhenyu Ma¹, Jianhua Li¹, Lu Lu¹, Jinhong Chen¹, Lunxiu Qin¹, Zhengxin Wang¹^,^†()

^1. Department of General Surgery, Huashan Hospital Affiliated to Fudan University, Institute of Organ Transplantation, Fudan University, Shanghai 200040, China

Received:2021-04-27 Published:2021-08-18
Corresponding author: Zhengxin Wang

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引用本文：

陈拓, 张全保, 陶一峰, 沈丛欢, 李瑞东, 马震宇, 李建华, 陆录, 陈进宏, 钦伦秀, 王正昕. 肝癌术后复发补救性肝移植疗效及预后影响因素[J/OL]. 中华肝脏外科手术学电子杂志, 2021, 10(04): 365-370.

Tuo Chen, Quanbao Zhang, Yifeng Tao, Conghuan Shen, Ruidong Li, Zhenyu Ma, Jianhua Li, Lu Lu, Jinhong Chen, Lunxiu Qin, Zhengxin Wang. Clinical efficacy and prognostic factors of salvage liver transplantation for postoperative recurrence of primary liver cancer[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(04): 365-370.

目的

探讨原发性肝癌（肝癌）术后复发补救性肝移植（SLT）疗效及预后影响因素。

方法

回顾性分析2014年5月至2019年10月在复旦大学附属华山医院行肝移植的273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252例，女21例；平均年龄（51±9）岁。根据术式不同分组，行初始肝移植（PLT）196例（PLT组），肝癌根治性切除后复发行SLT 77例（SLT组）。比较两组围手术期和并发症发生情况。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SLT患者术后预后的独立影响因素。

结果

患者一般资料按1∶1倾向性评分匹配后，两组各70例。SLT组手术时间（479±106）min，明显长于PLT组的（438±79） min（t=2.587，P<0.05）；SLT组和PLT组围手术期死亡率分别为11%（8/70）、6%（4/70），差异无统计学意义（χ²=1.458，P>0.05）。SLT组术后1、3、5年总体生存率分别为85.7%、75.0%、63.3%，PLT组相应为88.3%、79.0%、70.3%；SLT组术后1、3、5年无瘤生存率分别为98.4%、72.2%、57.1%，PLT组相应为92.5%、74.3%、54.7%；两组总体生存和无瘤生存差异无统计学意义（χ²=1.627，0.265；P>0.05）。多因素分析显示，AFP>200 μg/L和肿瘤最大径>3 cm是SLT患者术后总体生存的独立危险因素（HR=2.630，3.082；P<0.05），亦是术后无瘤生存的独立危险因素（HR=5.965，3.166；P<0.05）。

结论

SLT是肝癌术后复发的一种安全可靠治疗手段，可获得与PLT相似的治疗效果。AFP和肿瘤直径为SLT患者术后预后的独立影响因素。

关键词: 肝肿瘤, 肝移植, 治疗结果, 危险因素

Objective

To evaluate the clinical efficacy and to explore the prognostic factors of salvage liver transplantation (SLT) for postoperative recurrence of primary liver cancer.

Methods

Clinical data of 273 patients with primary liver cancer who underwent liver transplantation in Huashan Hospital Affiliated to Fudan University from May 2014 to October 2019 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 252 patients were male and 21 female, aged (51±9) years on average. According to different surgical methods, 196 patients undergoing primary liver transplantation were assigned into the PLT group and 77 patients receiving SLT due to postoperative recurrence after radical resection were allocated into the SLT group. The perioperative conditions and incidence of complications were statistically compared between two groups. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The independent influencing factors of postoperative prognosis of SLT patients were analyzed by Cox proportional hazards regression model.

Results

After propensity score matching of baseline data at a ratio of 1:1, 70 patients were assigned into each group. In the SLT group, the operation time was (479±106) min, significantly longer than (438±79) min in the PLT group (t=2.587, P<0.05). The perioperative mortality rate in the SLT group was 11%(8/70), which did not significantly differ from 6%(4/70) in the PLT group (χ²=1.458, P>0.05). The 1-, 3-, 5-year overall survival rates were 85.7%, 75.0%, 63.3% in the SLT group and were 88.3%, 79.0%, 70.3% in the PLT group, respectively. The 1-, 3-, 5-year tumor-free survival rates were 98.4%, 72.2%, 57.1% in the SLT group, and were 92.5%, 74.3%, 54.7% in the PLT group, respectively. The overall survival and tumor-free survival rates did not significantly differ between two groups (χ²=1.627, 0.265; P>0.05). Multivariate analysis demonstrated that AFP >200 μg/L and the maximal tumor diameter >3 cm were the independent risk factors for postoperative overall survival of SLT patients (HR=2.630, 3.082; P<0.05), which were also the independent risk factors for postoperative tumor-free survival (HR=5.965, 3.166; P<0.05).

Conclusions

SLT is a safe and reliable treatment for postoperative recurrence of primary liver cancer, which can yield equivalent clinical efficacy to PLT. AFP and tumor diameter are the independent risk factors for the postoperative prognosis of SLT patients.

Key words: Liver neoplasms, Liver transplantation, Treatment outcome, Risk factors

表1 PSM前后PLT组和SLT组肝癌患者一般资料比较

参数		PSM前				PSM后
参数		PLT组	SLT组	统计值	P值	PLT组	SLT组	统计值	P值
性别（例，男/女）		183/13	69/8	χ²=1.099	0.295	63/7	64/6	χ²=0.085	0.771
年龄（岁，±s）		51±9	50±9	t=0.924	0.357	52±9	51±9	t=0.181	0.857
BMI（kg/m²，±s）		24±4	24±5	t=-0.155	0.877	24±5	25±5	t=-0.424	0.672
MELD评分（分，±s）		32±12	29±11	t=2.259	0.025	29±10	29±11	t=-0.109	0.913
术前辅助治疗（例）		37	34	χ²=18.357	<0.001	28	27	χ²=0.030	0.863
AFP >200 μg/L（例）		70	19	χ²=3.066	0.080	17	19	χ²=0.150	0.699
乙型病毒性肝炎（例）		175	73	χ²=2.024	0.155	66	66	χ²=0	1.000
Child-Pugh分级（例）				χ²=4.405	0.111			χ²=1.234	0.540
	A级	15	11			6	7
	B级	43	21			15	10
	C级	138	45			49	53
腹腔积液（例）		96	31	χ²=1.690	0.194	31	30	χ²=0.029	0.865
米兰标准（例）		81	25	χ²=1.827	0.177	24	23	χ²=0.032	0.858
UCSF标准（例）		95	33	χ²=0.699	0.403	33	30	χ²=0.260	0.610
杭州标准（例）		145	63	χ²=1.872	0.171	59	56	χ²=0.438	0.508
肿瘤数目（例）				χ²=6.511	0.039			χ²=4.500	0.105
	1个	108	32			40	31
	1～3个	53	21			20	19
	>3个	35	24			10	20
微血管侵犯（例）		151	59	χ²=0.005	0.941	51	54	χ²=0.343	0.558
肿瘤最大径>3 cm（例）		113	37	χ²=2.059	0.151	43	35	χ²=1.853	0.173
肿瘤中低分化（例）		81	37	χ²=1.019	0.313	26	35	χ²=2.353	0.125

表1 PSM前后PLT组和SLT组肝癌患者一般资料比较

参数		PSM前				PSM后
参数		PLT组	SLT组	统计值	P值	PLT组	SLT组	统计值	P值
性别（例，男/女）		183/13	69/8	χ²=1.099	0.295	63/7	64/6	χ²=0.085	0.771
年龄（岁，±s）		51±9	50±9	t=0.924	0.357	52±9	51±9	t=0.181	0.857
BMI（kg/m²，±s）		24±4	24±5	t=-0.155	0.877	24±5	25±5	t=-0.424	0.672
MELD评分（分，±s）		32±12	29±11	t=2.259	0.025	29±10	29±11	t=-0.109	0.913
术前辅助治疗（例）		37	34	χ²=18.357	<0.001	28	27	χ²=0.030	0.863
AFP >200 μg/L（例）		70	19	χ²=3.066	0.080	17	19	χ²=0.150	0.699
乙型病毒性肝炎（例）		175	73	χ²=2.024	0.155	66	66	χ²=0	1.000
Child-Pugh分级（例）				χ²=4.405	0.111			χ²=1.234	0.540
	A级	15	11			6	7
	B级	43	21			15	10
	C级	138	45			49	53
腹腔积液（例）		96	31	χ²=1.690	0.194	31	30	χ²=0.029	0.865
米兰标准（例）		81	25	χ²=1.827	0.177	24	23	χ²=0.032	0.858
UCSF标准（例）		95	33	χ²=0.699	0.403	33	30	χ²=0.260	0.610
杭州标准（例）		145	63	χ²=1.872	0.171	59	56	χ²=0.438	0.508
肿瘤数目（例）				χ²=6.511	0.039			χ²=4.500	0.105
	1个	108	32			40	31
	1～3个	53	21			20	19
	>3个	35	24			10	20
微血管侵犯（例）		151	59	χ²=0.005	0.941	51	54	χ²=0.343	0.558
肿瘤最大径>3 cm（例）		113	37	χ²=2.059	0.151	43	35	χ²=1.853	0.173
肿瘤中低分化（例）		81	37	χ²=1.019	0.313	26	35	χ²=2.353	0.125

表2 PLT组和SLT组肝癌患者围手术期死亡和并发症比较（例）

组别	例数	围手术期死亡	感染	肾衰竭	急性排斥反应	胆道并发症	血管并发症	移植物丢失
SLT组	70	8	6	1	8	3	2	2
PLT组	70	4	4	0	10	9	3	2
χ²值		1.458	0.431	-	0.255	3.281	0	0
P值		0.227	0.512	1.000	0.614	0.070	1.000	1.000

表2 PLT组和SLT组肝癌患者围手术期死亡和并发症比较（例）

组别	例数	围手术期死亡	感染	肾衰竭	急性排斥反应	胆道并发症	血管并发症	移植物丢失
SLT组	70	8	6	1	8	3	2	2
PLT组	70	4	4	0	10	9	3	2
χ²值		1.458	0.431	-	0.255	3.281	0	0
P值		0.227	0.512	1.000	0.614	0.070	1.000	1.000

图1 PSM后PLT组和SLT组肝癌患者术后生存的Kaplan-Meier生存曲线

表3 影响补救性肝移植肝癌患者预后的Cox多因素分析

参数	总体生存			无瘤生存
参数	HR	95%CI	P值	HR	95%CI	P值
AFP>200 μg/L	2.630	1.122～6.166	0.026	5.965	2.397～14.844	<0.001
肿瘤最大径>3 cm	3.082	1.285～8.181	0.013	3.166	1.252～8.005	0.015

表3 影响补救性肝移植肝癌患者预后的Cox多因素分析

参数	总体生存			无瘤生存
参数	HR	95%CI	P值	HR	95%CI	P值
AFP>200 μg/L	2.630	1.122～6.166	0.026	5.965	2.397～14.844	<0.001
肿瘤最大径>3 cm	3.082	1.285～8.181	0.013	3.166	1.252～8.005	0.015

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Clinical efficacy and prognostic factors of salvage liver transplantation for postoperative recurrence of primary liver cancer

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Clinical efficacy and prognostic factors of salvage liver transplantation for postoperative recurrence of primary liver cancer