Contrast-enhanced ultrasound-guided feeding artery ablation as add-on to percutaneous radiofrequency ablation for hypervascular hepatocellular carcinoma with a modified ablative technique and tumor perfusion evaluation

Figures & data

Figure 1. Flowchart of the study. HCC: hepatocellular carcinoma; CEUS: contrast-enhanced ultrasound; RFA: radiofrequency ablation; FAA: feeding artery ablation.

Figure 2. The practical technique of FAA as add on to RFA. FAA was performed by ablating the target feeding artery but sparing the non-feeding branches, and after that RFA was performed to ablate the tumor. FAA: feeding artery ablation.

Figure 3. The examples illustrated the selection of target feeding arteries. (A) One subsegmental feeding artery (arrowhead) of the tumor (asterisk) was clearly depicted in the early arterial phase of 2D-CEUS, which is typically suitable for FAA. The principle of both sparing the non-feeding branches (fine arrow) and non-contact to the tumor could be achieved. (B) The tumor (asterisk) was not selected for FAA because of insufficient distance to the bifurcation of feeding (arrowhead) and non-feeding branches (arrow). (C) two subsegmental feeding arteries (arrowhead and thick arrow) of the tumor (asterisk) were selected as the targets of FAA, which were partly visible on 2D-CEUS through back-and-forth breathing movement. (D) Real-time 3D-CEUS depicted the two feeding arteries (arrowhead and thick arrow) in the reconstructed image with good continuity and contributed to feasibility determination. FAA: feeding artery ablation; CEUS: contrast-enhanced ultrasound.

Figure 4. Images in a 41-year-old male with recurrent HCC measured 3.2 cm in diameter. (A) one feeding artery (arrowhead) of the tumor (asterisk) was depicted in the early arterial phase of 2D-CEUS. (B) FAA created a small ablation zone (arrowhead) using 1 cycle and 4 min cauterization mode. The target tumor was generally intact (asterisk). The arrow showed the electrode inserting path. (C) Immediate 2D-CEUS after FAA showed complete non-enhancement within the contour of the tumor in the arterial phase, which was identified as a complete perfusion response to FAA. (D) Hyperechoic area covered the tumor (arrowhead) after RFA, using two electrodes with a switch controller, 16 min in total. (E) 2D-CEUS performed in 30 min after RFA showed a large ablation zone measuring 5.2 cm × 4.2 cm without residue. FAA: feeding artery ablation; CEUS: contrast-enhanced ultrasound.

Figure 5. Images in a 43-year-old male with recurrent HCC measured 2.8 cm in diameter. (A) one feeding artery (arrowhead) of the tumor (cross) was depicted in the early arterial phase of 2D-CEUS. (B) Before FAA, 2D-CEUS showed hyperenhancement of the entire tumor at 23 s. (C) FAA created a small ablation zone (arrowhead) using 2 cycles and 8 min cauterization mode. The target tumor was intact (cross). The arrow showed the electrode inserting path. (D,E) After FAA, dual imaging showed intratumoral enhancement defect of the tumor at 23 s, which identified as a partial perfusion response to FAA. FAA: feeding artery ablation; CEUS: contrast-enhanced ultrasound.

Table 1. Demographic and Baseline Clinical Characteristics of Patients.

Variable	FVA–RFA (n = 25)
Sex
Male	24 (96)
Female	1 (4)
Age (years)*	54.1 ± 10.4 (36-76)
Child-pugh classification
Class A	24 (96)
Class B	1 (4)
Background liver disease
HBV hepatitis	25 (100)
Nonalcoholic steatohepatitis	0 (0)
AFP level
≤ 20 ng/mL	14 (56)
>20 ng mL	11 (44)
Platelet count
≤100 × 10^9/L	4 (16)
>100 × 10^9/L	21 (84)
Tumor type
Primary	9 (36)
Recurrent	16 (64)
No. of nodules^b
1	19 (76)
2	6 (24)
Size of target tumor (cm)^a	3.0 ± 0.7 (2.1-5.0)
Size of non-target tumor (cm)^a	1.8 ± 0.8 (1.1-3.2)

AFP: alpha fetoprotein; HBV: hepatitis B virus.

^a Data are mean ± standard deviation (range), others are number of counts (percentages).

^b When multiple tumors occurred, one was selected as target tumor and the others were non-target tumors.

Table 2. Technical details of FAA as add-on to RFA in 25 tumors with 29 target feeding arteries.

Parameter	Data
FAA
Diameter of feeding artery (mm)^a	2.8 ± 0.4 (2.0–3.6)
Speed of arterial blood flow (cm/s)^b	60.0 ± 30.0 (16.6–128.2)
RFA mode^c
Cauterization only	18 (62.1%)
Standard ablation only	5 (17.2%)
Cauterization + Standard ablation	6 (20.7%)
No. of electrode insertions per vessel	1.1 ± 0.3 (1–2)
No. of ablation cycles per vessel	1.9 ± 0.7 (1–3)
Total ablation time	6.5 ± 1.9 (4–10)
RFA
No. of electrode insertions	2.0 ± 0.7 (1–4)
Total ablation time (min)	16.6 ± 6.5 (8–36)

Data are mean ± standard deviation (range) unless otherwise specified. FAA: feeding artery ablation. RFA: radiofrequency ablation.

^a Diameter was measured as the enhanced thickness of the feeding artery in early arterial phase, allowing error and CEUS artifact.

^b Data are from 22 arteries. Speed measurement with Pulse Wave Doppler was inaccurate in 7 arteries due to interference caused by heart movement (n = 1), a Doppler angle > 60° (n = 2) and inconspicuous vessel display (n = 4).

^c Data are the number of counts (percentages). Two target feeding arteries were selected for each tumor in 4 cases.

Table 3. Comparison of ablation sizes according to perfusion reduction (complete vs. partial response).

Items	Parameter	Total	Complete response	Partial response	p
Immediate evaluation	Long-axis (cm)	5.3 ± 1.0	5.5 ± 1.2	5.1 ± 0.7	0.663
		(3.9–8.3)	(4.3–8.3)	(3.9–6.3)
	Short-axis (cm)	4.4 ± 0.8	4.6 ± 0.8	4.1 ± 0.7	0.339
		(3.0–6.8)	(3.7–6.8)	(3.0–5.0)
1-month evaluation	Long-axis (cm)	5.1 ± 1.0	5.3 ± 1.1	4.9 ± 0.8	0.279
		(3.4–7.2)	(3.7–7.2)	(3.4–6.1)
	Short-axis (cm)	3.9 ± 0.7	3.9 ± 0.7	3.9 ± 0.8	0.937
		(2.9–5.7)	(3.0–5.1)	(2.9–5.7)
	Perpendicular-axis (cm)	4.0 ± 0.6	4.2 ± 0.6	3.8 ± 0.5	0.107
		(3.0–5.1)	(3.2–5.1)	(3.0–4.7)
	Volume (cm^3)	41.9 ± 17.5	47.0 ± 15.9	36.3 ± 18.0	0.128
		(14.9–78.2)	(28.9–74.4)	(14.9–78.2)
	Ablative margin (mm)	8.2 ± 1.9	8.7 ± 2.1	7.6 ± 1.7	0.155
		(4–12)	(5–12)	(4–9)

Data are mean ± standard deviation (range).

Figure 6. Follow-up of FAA-RFA. (A) cumulative rate of LTP, (B) cumulative overall survival and (C) cumulative recurrence-free survival. LTP: local tumor progression; FAA-RFA: feeding artery ablation-radiofrequency ablation.

Table 4. Univariate and multivariate cox analysis of the predictors of overall survival.

Variable	Univariate analysis		multivariate analysis
	p	HR (95% CI)	p	HR (95% CI)
Age	0.502	0.975 (0.906–1.050)
AFP level (>20 ng/mL)	0.024	11.542 (1.376–96.837)	0.015	16.501 (1.724–157.902)
Platelet count (≤100 × 10^9/ L)	0.951	0.935 (0.112–7.837)
Tumor type (recurrent HCC)	0.675	1.422 (0.274–7.375)
Tumor number (more than one)	0.074	4.086 (0.874–19.101)	0.037	7.307 (1.123–47.545)
Target tumor size	0.788	1.160 (0.392–2.433)
Perfusion response (partial response)	0.917	0.923 (0.205–4.162)

Table 5. Univariate and multivariate Cox analysis of the predictors for recurrence-free survival.

Variable	Univariate analysis		multivariate analysis
	p	HR (95% CI)	p	HR (95% CI)
Age	0.212	0.969 (0.922–1.018)
AFP level (>20 ng/mL)	0.796	1.144 (0.414–3.160)
Platelet count (≤100 × 10^9/ L)	0.815	1.196 (0.268–5.343)
Tumor type (Recurrent HCC)	0.027	4.274 (1.178–15.510)	0.069	3.569 (0.908–14.036)
Tumor number (more than one)	0.055	2.977 (0.978–9.067)	0.349	1.751 (0.543–5.651)
Target tumor size	0.683	1.180 (0.533–2.611)
Perfusion response (partial response)	0.495	1.431 (0.511–4.006)