经肝动脉化疗栓塞术联合微波消融与重复肝切除术治疗复发性肝细胞癌的效果比较

凌俊; 万文武; 曾政; 姚辉华; 蒋鸥; 丁兵

doi:10.3969/j.issn.1001-5256.2022.09.020

经肝动脉化疗栓塞术联合微波消融与重复肝切除术治疗复发性肝细胞癌的效果比较

DOI: 10.3969/j.issn.1001-5256.2022.09.020

凌俊¹,
万文武^{1, 2},
曾政^{1, 2},
姚辉华³,
蒋鸥¹,
丁兵^1, , ,

1.
内江市第二人民医院，四川内江 641000
2.
西南医科大学临床医学院，四川泸州 646000
3.
成都市第一人民医院肝胆外科，成都 610000

基金项目:

国家科技重大专项 (2018ZX09303-014);

四川省医学会科研课题计划 (S20062)

伦理学声明: 本研究方案于2021年3月5日经由内江市第二人民医院伦理委员会审批，批号2021-0010。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：凌俊、万文武负责文章撰写及数据收集；曾政负责数据收集和整理；姚辉华、蒋鸥负责伦理审批及辅助撰稿；丁兵负责文章修改。

详细信息

通信作者:
丁兵，scdingbing@sina.com

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出版历程
- 收稿日期: 2022-01-12
- 录用日期: 2022-02-15
- 出版日期: 2022-09-20

Clinical effect of transcatheter arterial chemoembolization combined with microwave ablation versus repeat resection in treatment of recurrent hepatocellular carcinoma

Jun LING¹,
Wenwu WAN^{1, 2},
Zheng ZENG^{1, 2},
Huihua YAO³,
Ou JIANG¹,
Bing DING^{1
, ,
,}

1.
The Second People's Hospital of Neijiang, Neijiang, Sichuan 641000, China
2.
School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
3.
Department of Hepatobiliary Surgery, Chengdu First People's Hospital, Chengdu 610000, China

Research funding:

Major National Science and Technology Projects (2018ZX09303-014);

Scientific Research Project Plan of Sichuan Medical Association (S20062)

More Information

Corresponding author: DING Bing, scdingbing@sina.com(ORCID: 0000-0003-4432-9599)

摘要

摘要: 目的比较经肝动脉化疗栓塞(TACE)联合微波消融(MWA)(TACE-MWA)与重复肝切除术(RR)治疗复发性肝细胞癌(RHCC)的效果。方法选取2015年6月1日—2020年9月30日内江市第二人民医院收治的178例RHCC患者，按治疗方式不同分为RR组(n=64例)和TACE-MWA组(n=114)。记录治疗前基线人口学资料、肝功能及肿瘤相关情况等。随访至2021年10月，比较两组患者术后总生存期(OS)和无复发生存期(RFS)。进行基于复发模式(复发时间和肿瘤大小)的亚组分析，并研究预后的影响因素。计量资料两组间比较采用独立样本t检验，计数资料两组间比较采用χ²检验；术后生存率用Kaplan-Meier法，两组间生存差异用Log-rank检验；使用Cox多因素分析方法探寻影响生存的独立危险因素。结果多因素分析显示，肿瘤直径、AFP水平、ALT、Alb和复发时间是OS的独立预后因素(P值均＜0.05)，AFP水平和复发时间是RFS的独立预后因素(P值均＜0.05)。对于晚期复发(＞2年)的RHCC，RR组与TACE-MWA组之间的中位OS有显著差异(54.0个月vs 36.0个月，χ²=6.171，P=0.013)，中位RFS也有显著差异(28.0个月vs 21.0个月，χ²=5.211，P=0.022)。对于肿瘤直径≤5 cm的RHCC，两组的中位OS有显著差异(33.0个月vs 27.0个月，χ²=6.447，P=0.011)。结论对于早期复发或肿瘤直径＞5 cm的RHCC，RR与TACE-MWA有相似的疗效，但对于晚期复发或肿瘤直径≤5 cm的RHCC，RR应为首选。
- 癌, 肝细胞 /
- 化学栓塞, 治疗性 /
- 消融技术 /
- 肝切除术
Abstract: Objective To investigate the clinical effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) (TACE-MWA) versus repeat resection (RR) in the treatment of recurrent hepatocellular carcinoma (RHCC). Methods A total of 178 patients with RHCC who were admitted to The Second People's Hospital of Neijiang from June 2015 to September 2020 were enrolled, and according to the treatment modality, they were divided into RR group with 64 patients and TACE-MWA group with 114 patients. Baseline demographic data, liver function, and tumor conditions before treatment were recorded, and the patients were followed up to October 2021 to compare postoperative overall survival (OS) time and recurrence-free survival (RFS) time between the two groups. Subgroup analysis based on recurrence pattern (recurrence time and tumor size) was performed, and the influencing factors for prognosis were analyzed. The independent samples t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data; the Kaplan-Meier method was used for postoperative survival rate, the Log-rank test was used for survival difference analysis, and a multivariate Cox regression analysis was used to investigate independent risk factors for survival. Results The multivariate analysis showed that tumor diameter, alpha-fetoprotein (AFP) level, alanine aminotransferase, albumin, and time to recurrence were independent prognostic factors for OS (all P < 0.05), and AFP level and time to recurrence were independent prognostic factors for RFS (both P < 0.05). For RHCC with late recurrence (> 2 years), there were significant differences between the two groups in median OS (54.0 months vs 36.0 months, χ²=6.171, P=0.013) and median RFS (28.0 months vs 21.0 months, χ²= 5.211, P=0.022). For RHCC with a tumor diameter of ≤5 cm, there was a significant difference in median OS between the two groups (33.0 months vs 27.0 months, χ²=6.447, P=0.011). Conclusion RR has a similar clinical effect to TACE-MWA in RHCC with early recurrence or a tumor diameter of > 5 cm, but RR should be the first choice for RHCC with late recurrence or a tumor diameter of ≤5 cm.
- Carcinoma, Hepatocellular /
- Chemoembolization, Therapeutic /
- Ablation Techniques /
- Hepatectomy

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图 1 接受TACE-MWA和RR的RHCC患者OS和RFS的Kaplan-Meier曲线

注：a, OS; b，RFS。

Figure 1. Kaplan-Meier curves of OS and RFS in RHCC patients receiving TACE-MWA and RR

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图 2 早期复发的RHCC患者OS和RFS的Kaplan-Meier曲线

注：a, OS; b, RFS。

Figure 2. Kaplan-Meier curves of OS and RFS in patients with early recurrent RHCC

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图 3 晚期复发的RHCC患者OS和RFS的Kaplan-Meier曲线

注：a, OS; b, RFS。

Figure 3. Kaplan-Meier curves of OS and RFS in patients with late recurrent RHCC

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图 4 肿瘤直径＞5 cm的RHCC患者OS和RFS的Kaplan-Meier曲线

注：a, OS; b, RFS。

Figure 4. Kaplan-Meier curves of OS and RFS in RHCC patients with tumor diameter > 5 cm

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图 5 肿瘤直径≤5 cm的RHCC患者OS和RFS的Kaplan-Meier曲线

注：a, OS; b, RFS。

Figure 5. Kaplan-Meier curves of OS and RFS in RHCC patients with tumor diameter≤5 cm

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表 1 两组基线资料比较

Table 1. Comparison of baseline data between the two groups

项目	RR组(n=64)	TACE-MWA组(n=114)	统计值	P值
年龄(岁)	54.26±8.99	53.27±10.39	t=0.635	0.526
男性[例(%)]	55(85.9)	106(93.0)	χ²=2.355	0.104
HBV感染[例(%)]	59(92.2)	103(90.4)	χ²=0.169	0.681
TBil(μmol/L)	39.055±13.384	36.738±12.230	t=1.143	0.243
AST(U/L)	66.930±25.791	69.720±29.467	t=-0.633	0.527
ALT(U/L)	70.183±26.244	71.210±31.624	t=-0.221	0.817
Alb(g/L)	38.853±3.910	38.752±5.175	t=0.137	0.891
PLT(×10⁹/L)	177.912±71.565	194.029±66.438	t=-1.510	0.133
INR	1.334±0.189	1.384±0.170	t=-1.723	0.088
肿瘤直径(cm)	5.121±2.709	4.582±2.089	t=1.480	0.171
肿瘤个数[例(%)]			χ²=3.383	0.066
单发	49(76.6)	72(68.0)
多发	15(23.4)	42(42.0)
AFP[例(%)]			χ²=0.387	0.534
＞400 ng/mL	25(39.1)	50(43.9)
≤400 ng/mL	39(60.9)	64(56.1)
Child-Pugh分级[例(%)]			χ²=1.369	0.242
A	47(73.4)	74(64.9)
B	17(26.6)	40(35.1)
BCLC分期[例(%)]			χ²=0.472	0.492
A	48(75.0)	80(70.2)
B	16(25.0)	34(29.8)
距离初次切除后的复发时间(年)			χ²=0.090	0.764
≤2	35(54.7)	65(57.0)
＞2	29(45.3)	49(43.0)

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表 2 两组并发症比较

Table 2. Comparison of complications between the two groups

项目	RR组(n=64)	TACE-MWA组(n=114)	χ²值	P值
轻微并发症(等级Ⅰ/Ⅱ)[例(%)]
发热	21(32.8)	45(39.5)	0.780	0.377
疼痛	23(35.9)	32(28.1)	1.188	0.276
呕吐	13(20.3)	35(30.7)	2.246	0.134
胃肠道反应	14(21.9)	13(11.4)	3.493	0.062
严重并发症(等级Ⅲ/Ⅳ/Ⅴ)[例(%)]	12(18.8)	11(9.6)	3.017	0.082
胆瘘	1(1.6)	0
出血	1(1.6)	0
腹水/胸水	6(9.4)	3(2.6)
肝功能衰竭	4(6.3)	5(4.4)
治疗相关死亡	0	3(2.6)

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表 3 影响RHCC患者OS的单因素和多因素分析

Table 3. Univariate and multivariate analysis of OS in patients with RHCC

项目	单因素分析		多因素分析
项目	HR(95%CI)	P值	HR(95%CI)	P值
性别(男vs女)	0.674(0.359~1.264)	0.219
年龄(＞60岁vs ≤60岁)	0.671(0.437~1.031)	0.069
HBV感染(是vs否)	0.712(0.369~1.373)	0.311
肿瘤直径(＞5 cm vs ≤5 cm)	1.832(1.228~2.733)	0.003	2.299(1.504~3.513)	＜0.001
多发肿瘤(是vs否)	0.355(0.234~0.538)	＜0.001	0.611(0.370~1.007)	0.053
Child-Pugh分级(A vs B)	0.470(0.313~0.706)	＜0.001	0.693(0.451~1.065)	0.094
BCLC分期(A vs B)	0.424(0.279~0.642)	＜0.001	1.110(0.662~1.861)	0.691
AFP＞400 ng/mL(是vs否)	0.228(0.143~0.362)	＜0.001	0.368(0.212~0.637)	＜0.001
TBil(＞34.2 μmol/L vs ≤34.2 μmol/L)	1.038(0.694~1.551)	0.856
AST (＞40 U/L vs ≤40 U/L)	0.995(0.602~1.646)	0.985
ALT (＞40 U/L vs ≤40 U/L)	2.891(1.768~4.727)	＜0.001	3.395(1.978~5.827)	＜0.001
Alb (＞35.0 g/L vs ≤35.0 g/L)	2.565(1.587~4.146)	＜0.001	2.824(1.718~4.641)	＜0.001
复发时间(＞2年vs ≤2年)	5.854(3.599~9.522)	＜0.001	3.098(1.777~5.403)	＜0.001
治疗方式(RR vs TACE-MWA)	0.682(0.453~1.029)	0.068

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表 4 影响RHCC患者RFS的单因素和多因素分析

Table 4. Univariate and multivariate analysis of RFS in patients with RHCC

项目	单因素分析		多因素分析
项目	HR(95%CI)	P值	HR(95%CI)	P值
性别(男vs女)	0.822(0.486~1.388)	0.463
年龄(＞60岁vs ≤60岁)	0.914(0.631~1.324)	0.635
HBV感染(是vs否)	0.853(0.492~1.479)	0.571
肿瘤直径(＞5 cm vs ≤5 cm)	1.427(1.037~1.964)	0.029	1.136(0.816~1.581)	0.451
多发肿瘤(是vs否)	0.479(0.339~0.676)	＜0.001	0.907(0.612~1.344)	0.627
Child-Pugh分级(A vs B)	0.637(0.454~0.894)	0.009	0.771(0.547~1.089)	0.140
BCLC分期(A vs B)	0.467(0.330~0.660)	＜0.001	0.699(0.468~1.043)	0.080
AFP＞400 ng/mL(是vs否)	0.321(0.223~0.461)	＜0.001	0.533(0.356~0.796)	0.002
TBil(＞34.2 μmol/L vs ≤34.2 μmol/L)	1.044(0.757~1.440)	0.792
AST(＞40 U/L vs ≤40 U/L)	1.318(0.886~1.961)	0.173
ALT(＞40 U/L vs ≤40 U/L)	1.841(1.225~2.767)	0.003	1.382(0.911~2.097)	0.128
Alb(＞35.0 g/L vs ≤35.0 g/L)	1.498(1.005~2.231)	0.047	1.142(0.760~1.716)	0.523
复发时间(＞2年vs ≤2年)	6.158(4.179~9.076)	＜0.001	4.327(2.800~6.687)	＜0.001
治疗方式(RR vs TACE-MWA)	0.757(0.540~1.060)	0.105

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