Predictive value of preoperative circulating tumor cells on recurrence of hepatocellular carcinoma after radiofrequency ablation

doi:10.3877/cma.j.issn.1674-0793.2021.02.012

Abstract

Abstract:

Objective

To study and analyze the application value of preoperative circulating tumor cells (CTC) in predicting recurrence of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

Methods

From June 2016 to September 2019, the data of 168 HCC patients in Zhongshan City People’s Hospital were collected, and the peripheral blood CTC was analyzed by Cyttel test before RFA. Kaplan-Meier module of X-tile software was used to determine the cut-off value of CTC, so as to analyze the relationship between CTC and clinical parameters. Cox proportional hazards model was used to analyze the independent risk factors of recurrence after RFA. Kaplan-Meier method was used to clarify the relationship between CTC and recurrence after RFA.

Results

The optimal cut-off value of CTC for predicting recurrence of HCC after RFA was 2 cells per 3.2 ml. Preoperative CTC was correlated with the number of tumor nodules, the maximum tumor diameter, preoperative AFP level and clinical stage of liver cancer in China (CNLC) (P<0.05). Preoperative CTC (HR=1.965, 95% CI: 1.314-2.937, P=0.001), AFP level (HR=1.743, 95% CI: 1.158-2.623, P=0.008), PIVKA-Ⅱ (HR=1.559, 95% CI: 1.008-2.411, P=0.046) and maximum tumor diameter (HR=1.994, 95% CI: 1.104-3.602, P=0.022) were independent risk factors for recurrence of HCC after RFA. The postoperative recurrence rate was 62.5% (105/168). The cumulative recurrence rate of patients with CTC≤2/3.2 ml was significantly lower than that of patients with CTC>2/3.2 ml(P<0.001).

Conclusion

Preoperative detection of CTC has certain application value and clinical significance in predicting the recurrence of HCC after RFA.

Key words: Hepatocellular carcinoma, Radiofrequency ablation, Circulating tumor cells, Cyttel detection

Yongzhu He, Shaowei Ye, Liwen Liu, Junlin Qian, Kun He, Ruiqin Huang, Peng Peng, Qijie Luo, Zemin Hu. Predictive value of preoperative circulating tumor cells on recurrence of hepatocellular carcinoma after radiofrequency ablation[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(02): 137-141.

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References 17

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项目		阴性组	阳性组	χ²值	P值
例数		93	75
性别				0.092	0.762
	男	83(89.2)	68(90.7)
	女	10(10.8)	7(9.3)
年龄(岁)				0.168	0.682
	≤60	55(59.1)	42(56.0)
	>60	38(40.9)	33(44.0)
乙型肝炎病毒感染				0.005	0.944
	阳性	79(84.9)	64(85.3)
	阴性	14(15.1)	11(14.7)
合并肝硬化				0.308	0.579
	阳性	62(66.7)	53(70.7)
	阴性	31(33.3)	22(29.3)
肝功能Child-Pugh分级				0.086	0.769
	A	82(88.2)	65(86.7)
	B	11(11.8)	10(13.3)
术前行TACE				0.924	0.336
	是	27(29.0)	27(36.0)
	否	66(71.0)	48(64.0)
肿瘤结节数目(个)				6.934	0.008
	1	61(65.6)	34(45.3)
	≥2	32(34.4)	41(54.7)
最大肿瘤直径(mm)				4.615	0.032
	≤30	68(73.1)	43(57.3)
	>30	25(26.9)	32(42.7)
甲胎蛋白(μg/L)				4.690	0.030
	≤20	67(72.0)	42(56.0)
	>20	26(28.0)	33(44.0)
PIVKA-Ⅱ(mAU/ml)				0.048	0.827
	≤40	40(43.0)	31(41.3)
	>40	53(57.0)	44(58.7)
丙氨酸转氨酶(U/L)				0.325	0.569
	≤50	81(87.1)	63(84.0)
	>50	12(12.9)	12(16.0)
天冬氨酸转氨酶(U/L)				0.173	0.677
	≤40	72(77.4)	56(74.7)
	>40	21(22.6)	19(25.3)
总胆红素(μmol/L)				1.041	0.308
	≤20.4	71(76.3)	52(69.3)
	>20.4	22(23.7)	23(30.7)
白蛋白(g/L)				1.116	0.291
	≤35	14(15.1)	16(21.3)
	>35	79(84.9)	59(78.7)
谷氨酰转移酶(U/L)				0.026	0.872
	≤60	52(55.9)	41(54.7)
	>60	41(44.1)	34(45.3)
碱性磷酸酶(U/L)				0.234	0.628
	≤125	84(90.3)	66(88.0)
	>125	9(9.7)	9(12.0)
肌酐(μmol/L)				0.610	0.435
	≤104	87(93.5)	73(97.3)
	>104	6(6.5)	2(2.7)
国际标准化比值				2.639	0.104
	≤1.2	90(96.8)	67(89.3)
	>1.2	3(3.2)	8(10.7)
CNLC分期				-2.570	0.010
	Ⅰa	61(65.6)	35(46.7)
	Ⅰb	22(23.7)	24(32.0)
	Ⅱa	10(14.4)	16(21.3)

项目		阴性组	阳性组	χ²值	P值
例数		93	75
性别				0.092	0.762
	男	83(89.2)	68(90.7)
	女	10(10.8)	7(9.3)
年龄(岁)				0.168	0.682
	≤60	55(59.1)	42(56.0)
	>60	38(40.9)	33(44.0)
乙型肝炎病毒感染				0.005	0.944
	阳性	79(84.9)	64(85.3)
	阴性	14(15.1)	11(14.7)
合并肝硬化				0.308	0.579
	阳性	62(66.7)	53(70.7)
	阴性	31(33.3)	22(29.3)
肝功能Child-Pugh分级				0.086	0.769
	A	82(88.2)	65(86.7)
	B	11(11.8)	10(13.3)
术前行TACE				0.924	0.336
	是	27(29.0)	27(36.0)
	否	66(71.0)	48(64.0)
肿瘤结节数目(个)				6.934	0.008
	1	61(65.6)	34(45.3)
	≥2	32(34.4)	41(54.7)
最大肿瘤直径(mm)				4.615	0.032
	≤30	68(73.1)	43(57.3)
	>30	25(26.9)	32(42.7)
甲胎蛋白(μg/L)				4.690	0.030
	≤20	67(72.0)	42(56.0)
	>20	26(28.0)	33(44.0)
PIVKA-Ⅱ(mAU/ml)				0.048	0.827
	≤40	40(43.0)	31(41.3)
	>40	53(57.0)	44(58.7)
丙氨酸转氨酶(U/L)				0.325	0.569
	≤50	81(87.1)	63(84.0)
	>50	12(12.9)	12(16.0)
天冬氨酸转氨酶(U/L)				0.173	0.677
	≤40	72(77.4)	56(74.7)
	>40	21(22.6)	19(25.3)
总胆红素(μmol/L)				1.041	0.308
	≤20.4	71(76.3)	52(69.3)
	>20.4	22(23.7)	23(30.7)
白蛋白(g/L)				1.116	0.291
	≤35	14(15.1)	16(21.3)
	>35	79(84.9)	59(78.7)
谷氨酰转移酶(U/L)				0.026	0.872
	≤60	52(55.9)	41(54.7)
	>60	41(44.1)	34(45.3)
碱性磷酸酶(U/L)				0.234	0.628
	≤125	84(90.3)	66(88.0)
	>125	9(9.7)	9(12.0)
肌酐(μmol/L)				0.610	0.435
	≤104	87(93.5)	73(97.3)
	>104	6(6.5)	2(2.7)
国际标准化比值				2.639	0.104
	≤1.2	90(96.8)	67(89.3)
	>1.2	3(3.2)	8(10.7)
CNLC分期				-2.570	0.010
	Ⅰa	61(65.6)	35(46.7)
	Ⅰb	22(23.7)	24(32.0)
	Ⅱa	10(14.4)	16(21.3)

因素	复发的单因素分析		复发的多因素分析
因素	HR(95% CI)	P值	HR(95% CI)	P值
性别(男/女)	0.931(0.482~1.797)	0.831
年龄(≤60/>60,岁)	1.155(0.784~1.701)	0.465
乙型肝炎病毒感染(阳性/阴性)	0.932(0.540~1.611)	0.802
合并肝硬化(阳性/阴性)	1.166(0.764~1.778)	0.477
肝功能Child-Pugh分级(A/B)	0.879(0.481~1.604)	0.674
术前行TACE(是/否)	1.544(1.050~2.272)	0.027	0.913(0.587~1.419)	0.686
肿瘤结节数目(1/≥2,个)	1.665(1.135~2.443)	0.009	3.191(0.954~10.679)	0.060
最大肿瘤直径(≤30/>30, mm)	2.004(1.365~2.944)	<0.001	1.994(1.104~3.602)	0.022
甲胎蛋白(≤20/>20, μg/L)	1.883(1.280~2.772)	0.001	1.743(1.158~2.623)	0.008
PIVKA-Ⅱ(≤40/>40, mAU/ml)	1.859(1.239~2.789)	0.003	1.559(1.008~2.411)	0.046
术前循环肿瘤细胞(阴性/阳性)	2.257(1.527~3.335)	<0.001	1.965(1.314~2.937)	0.001
丙氨酸转氨酶(≤50/>50, U/L)	0.823(0.476~1.423)	0.485
天冬氨酸转氨酶(≤40/>40, U/L)	0.863(0.543~1.371)	0.532
总胆红素(≤20.4/>20.4, μmol/L)	1.336(0.872~2.047)	0.184
白蛋白(≤35/>35, g/L)	0.968(0.582~1.609)	0.900
谷氨酰转移酶(≤60/>60, U/L)	1.466(0.997~2.156)	0.052
碱性磷酸酶(≤125/>125, U/L)	1.649(0.937~2.903)	0.083
肌酐(≤104/>104, μmol/L)	0.819(0.333~2.014)	0.663
国际标准化比值(≤1.2/>1.2)	1.376(0.668~2.834)	0.387
CNLC分期(Ⅰa/Ⅰb/Ⅱa)	1.499(1.169~1.922)	0.001	0.618(0.285~1.340)	0.223

因素	复发的单因素分析		复发的多因素分析
因素	HR(95% CI)	P值	HR(95% CI)	P值
性别(男/女)	0.931(0.482~1.797)	0.831
年龄(≤60/>60,岁)	1.155(0.784~1.701)	0.465
乙型肝炎病毒感染(阳性/阴性)	0.932(0.540~1.611)	0.802
合并肝硬化(阳性/阴性)	1.166(0.764~1.778)	0.477
肝功能Child-Pugh分级(A/B)	0.879(0.481~1.604)	0.674
术前行TACE(是/否)	1.544(1.050~2.272)	0.027	0.913(0.587~1.419)	0.686
肿瘤结节数目(1/≥2,个)	1.665(1.135~2.443)	0.009	3.191(0.954~10.679)	0.060
最大肿瘤直径(≤30/>30, mm)	2.004(1.365~2.944)	<0.001	1.994(1.104~3.602)	0.022
甲胎蛋白(≤20/>20, μg/L)	1.883(1.280~2.772)	0.001	1.743(1.158~2.623)	0.008
PIVKA-Ⅱ(≤40/>40, mAU/ml)	1.859(1.239~2.789)	0.003	1.559(1.008~2.411)	0.046
术前循环肿瘤细胞(阴性/阳性)	2.257(1.527~3.335)	<0.001	1.965(1.314~2.937)	0.001
丙氨酸转氨酶(≤50/>50, U/L)	0.823(0.476~1.423)	0.485
天冬氨酸转氨酶(≤40/>40, U/L)	0.863(0.543~1.371)	0.532
总胆红素(≤20.4/>20.4, μmol/L)	1.336(0.872~2.047)	0.184
白蛋白(≤35/>35, g/L)	0.968(0.582~1.609)	0.900
谷氨酰转移酶(≤60/>60, U/L)	1.466(0.997~2.156)	0.052
碱性磷酸酶(≤125/>125, U/L)	1.649(0.937~2.903)	0.083
肌酐(≤104/>104, μmol/L)	0.819(0.333~2.014)	0.663
国际标准化比值(≤1.2/>1.2)	1.376(0.668~2.834)	0.387
CNLC分期(Ⅰa/Ⅰb/Ⅱa)	1.499(1.169~1.922)	0.001	0.618(0.285~1.340)	0.223

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