What is the difference in ablation zone of multi-bipolar radiofrequency ablation between liver cirrhosis and normal liver background? – a prospective clinical study

Figures & data

Figure 1. The flow chart for patient enrollment. RFA: radiofrequency ablation; HCC: hepatocellular carcinoma; MLC: metastatic liver cancer; Tx: treatment. Drop off: (a) The electrodes were moved during the RFA treatment. (b) The patients missed follow up of CT/MRI in one month.

Table 1. Comparison of baseline profiles of patients with liver malignancies between liver cirrhosis and normal liver groups.

	Liver cirrhosis	Normal liver	p Value
No. of patients	90	113
Gender			0.034
Male	69	71
Female	21	42
Age (years old)	60.5 ± 11.1 (36–88)	57.7 ± 10.6 (32–82)	0.063
Viral etiology
HBV	86	0
HCV	4	0
Tumor number	109	174
Maximum diameter (cm)	2.3 ± 0.8	2.2 ± 0.8	0.527
Tumor location			0.857
Right lobe	80	126
Left lobe	29	48
Liver function			0.016
Child Pugh-A	85	113
Child Pugh-B	5	0
ALT evaluated (IU/L)			0.659
<50	85	105
≥50	5	8
AFP evaluated(ng/mL)			0.167
<25	43	65
≥25	47	48
CEA evaluated (ng/mL)			0.009
<5	64	55
≥5	32	58
FIB-4 degree			<0.001
<1.3	3	113
1.3 ∼ 3.25	26	0
>3.25	61	0
3 cm tip electrode			0.861
Two electrodes	48	75
Three electrodes	33	49
Distance (cm)	1.3 ± 0.4	1.3 ± 0.3	0.212
Largest	1.8	2.0
4 cm tip electrode			0.664
Two electrodes	5	11
Three	23	39
Distance (cm)	1.6 ± 0.3	1.5 ± 0.3	0.347
Largest	2.1	2.3
RF time (minutes)	19.4 ± 7.3	18.7 ± 6.1	0.436
RF impendence (Ω)	97.4 ± 12.1	96.0 ± 14.7	0.396

HBV: hepatitis B virus; HCV: hepatitis C virus; ALT: alanine aminotransferase; AFP: alpha-fetoprotein; CEA: carcinoembryonic antigen; RF: radiofrequency ablation. Liver cirrhosis background was diagnosed by at least two imaging modalities with specific findings included (1) coarsening of the liver parenchyma secondary to fibrosis and nodularity, (2) increased attenuation with decreased vascular markings, (3) nodularity of edge, accentuation of hepatic fissures and regenerating nodules. Hepatosplenomegaly, ascites and portal hypertension may be seen.

Figure 2. A 54-year-old male had hepatocellular carcinoma with liver cirrhosis. α-AFP was 1848 ng/ml, CEA was 0.97 ng/ml, and CA-199 was 15.02 U/ml. (a) Contrast-enhanced ultrasound (CEUS) before radiofrequency ablation (RFA) showed the tumor size was 2.4 × 1.8 cm. (b) RFA was performed under ultrasound guidance with three 3 cm tip RF electrodes and the distance of electrodes was 1.3 cm. One month follow up contrast enhanced computed tomography on axial section (c) and sagittal section (d) showed the ablation zone (△) had no enhancement and the ablation zone was approximately sphere. The length, width and thickness of ablation zone was 4.0 cm, 3.5 cm, 3.2 cm, respectively.

Figure 3. A 63-year-old female had rectal carcinoma with liver metastasis. CEA was 5.27 ng/ml, CA-199 was 143.8 U/ml and α-AFP was 2.10 ng/ml. (a) Contrast-enhanced ultrasound (CEUS) before RFA showed the tumor size was 2.4 × 1.6 cm. (b) RFA was performed with three 3 cm tip RF electrodes and the distance of electrodes was 1.3 cm. Contrast enhanced computed tomography in one month on axial section (c) and sagittal section (d) showed the ablation zone (△) had no enhancement and the ablation zone was approximately ellipsoid. The length, width and thickness of ablation zone was 2.8 cm, 2.0 cm, 1.9 cm, respectively.

Table 2. Comparison of ablation zone with 3 cm and 4 cm tip RF electrodes between liver cirrhosis and normal liver groups.

	No. of tumors	Length (cm)	Width (cm)	Thickness (cm)	Volume (cm^3)
Two 3 cm electrodes	123
Liver cirrhosis	48	3.5 ± 0.5	2.6 ± 0.3	2.5 ± 0.3	11.2 ± 3.6
Normal liver	75	3.1 ± 0.4	2.2 ± 0.3	2.0 ± 0.2	7.3 ± 2.2
p Value		0.001	<0.001	<0.001	<0.001
Three 3 cm electrodes	82
Liver cirrhosis	33	4.0 ± 0.4	3.0 ± 0.4	2.7 ± 0.4	15.8 ± 4.8
Normal liver	49	3.5 ± 0.5	2.5 ± 0.4	2.3 ± 0.3	10.6 ± 3.9
p Value		0.001	0.006	0.004	0.001
Two 4 cm electrodes	16
Liver cirrhosis	5	4.4 ± 0.4	2.7 ± 0.2	2.4 ± 0.1	14.6 ± 3.2
Normal liver	11	4.3 ± 0.7	2.4 ± 0.2	2.3 ± 0.1	12.5 ± 2.9
p Value		0.876	0.262	0.374	0.447
Three 4 cm electrodes	62
Liver cirrhosis	23	4.8 ± 0.8	3.6 ± 0.5	3.3 ± 0.5	30.8 ± 10.5
Normal liver	39	4.2 ± 0.7	3.1 ± 0.5	2.7 ± 0.5	19.8 ± 8.9
p Value		0.060	0.019	0.002	0.004

RF: radiofrequency ablation.

Figure 4. A 65-year-old male had hepatocellular carcinoma with liver cirrhosis. CEA was 1.61 ng/ml, α-AFP was 2.14 ng/ml and CA-199 was 10.20 U/ml. (a) Enhanced magnetic resonance imaging (MRI) before radiofrequency ablation (RFA) showed the tumor size was 2.6 × 2.3 cm (↑). (b) RFA was performed under ultrasound guidance with three 4 cm tip RF electrodes and the distance of electrodes was 1.6 cm. One month follow up contrast enhanced computed tomography on axial section (c) and coronary section (d) showed the ablation zone (△) had no enhancement. The length, width and thickness of ablation zone was 5.5 cm, 4.0 cm, 3.7 cm, respectively.

Figure 5. A 39-year-old male had rectal carcinoma with liver metastasis. CEA was 30.06 ng/ml, α-AFP was 10.36 ng/ml, CA-125 was 14.70 U/ml and CA-199 was 23.01 U/ml. (a) The tumor was hypodense at the portal venous phase of contrast enhanced computed tomography before radiofrequency ablation (RFA). And the tumor size was 2.5 × 2.0 cm (↑). (b) RFA was initiated under ultrasound guidance with three 4 cm tip RF electrodes and the distance of electrodes was 1.5 cm. One month follow up enhanced magnetic resonance imaging (MRI) on axial section (c) and coronary section (d) showed the ablation zone (△) had no enhancement and the length, width and thickness of ablation zone was 4.2 cm, 2.8 cm, 2.5 cm, respectively.

Table 3. Comparison of the maximum flow velocity and arrival time of hepatic vessels between liver cirrhosis and normal liver background with color Doppler flow imaging and contrast-enhanced ultrasound.

	Maximum flow velocity (cm/s)			Arrival time (s)
	HA	PV	HV	HA	PV	HV
Liver cirrhosis	66.1 ± 24.8	18.6 ± 2.9	20.2 ± 14.5	15.6 ± 4.6	21.5 ± 5.6	28.6 ± 6.7
Normal liver	49.6 ± 15.1	19.3 ± 3.9	24.9 ± 8.9	14.4 ± 3.2	18.9 ± 4.0	24.4 ± 4.5
P value	0.105	0.463	0.207	0.029	<0.001	<0.001

HA: hepatic artery; PV: portal vein; HV: hepatic vein.

Figure 6. The simple linear regression analysis between ablation zone of two 3 cm electrodes and the arrival time (AT) of hepatic vein. The width (a), thickness (b) and volume (c) were statistically associated with the AT of hepatic vein (Adjusted R² = 0.271, adjusted R² = 0.289, adjusted R² = 0.294; p < 0.001, p < 0.001, p < 0.001).

Table 4. Multiple linear regression analysis between ablation zone and the hepatic flow parameters.

	No. of tumors	Linear regression equation	Adjusted R^2	p Value
Two 3 cm electrodes	123
Length (Y1)		Y1 = 0.036 × X3+0.341 × X4+1.716	0.196	<0.001
Width (Y2)		Y2 = 0.038 × X3+1.353	0.271	<0.001
Thickness (Y3)		Y3 = 0.034 × X3+1.223	0.289	<0.001
Volume (Y4)		Y4 = 0.383 × X3−1.294	0.294	<0.001
Three 3 cm electrodes	82
Length (Y5)		Y5 = 0.051 × X2+2.599	0.212	0.001
Width		No linear correlation
Thickness		No linear correlation
Volume		No linear correlation
Two 4 cm electrodes	16
Length		No linear correlation
Width		No linear correlation
Thickness		No linear correlation
Volume		No linear correlation
Three 4 cm electrodes	62
Length		No linear correlation
Width (Y6)		Y6 = 0.469 × X4+1.869	0.359	<0.001
Thickness		No linear correlation
Volume (Y7)		Y7 = 7.035 × X4+2.429	0.210	0.004

X1 = arrival time of hepatic artery; X2 = arrival time of portal vein; X3 = arrival time of hepatic vein; X4 = maximum diameter of tumor; X5 = distance of electrodes.