Comparison of procedure-related complications between percutaneous cryoablation and radiofrequency ablation for treating periductal hepatocellular carcinoma

Figures & data

Figure 1. Flow diagram of patient selection for the study. HCC: hepatocellular carcinoma; RFA: radiofrequency ablation.

Table 1. Demographic and clinical characteristics of study patients.

Variables	Radiofrequency ablation (n = 31)	Cryoablation (n = 25)	p Value
Patients and tumor characteristics
Age at enrollment (years)	59.6 ± 10 (43–83)	60.9 ± 9.7 (41–78)	^a0.616
Number of male patients (%)	21 (67.7)	21 (84.0)	^b0.220
Tumor size (cm)	2.0 ± 0.4 (1.3–2.8)	1.5 ± 0.4 (1.0–2.5)	^a<0.001
Tumor location (Couinaud segment)			^c0.438
I / II / III / IV	0 / 1 / 4 / 4	0 / 1 / 3 / 1
V / VI / VII / VII	4 / 7 / 3 / 8	9 / 6 / 2 / 3
Tumors abutting the bile duct			^b0.571
Central duct (equal to or smaller than a second-order branch)	12	7
Peripheral duct (equal to or larger than a third-order branch)	19	18
Underlying liver disease			^c0.866
HBV / HCV	22 / 5	19 / 3
Both HBV and HCV	1	0
Others	3	3
Child–Pugh score			^c0.999
A / B	29 / 2	24 / 1
Albumin–bilirubin grade			^c0.016
1 / 2 / 3	16 / 15 / 0	20 / 4 / 1
a-fetoprotein (ng/mL) (median)	17.1 (1.3–4730.7)	7.7 (1.9–6301.6)	^d0.127
Platelet count (×10 ^9/L)	110.6 ± 80.4 (39.0–395.0)	132.3 ± 46.2 (61.0–273.0)	^d0.009
Total bilirubin (mg/dL)	0.8 ± 0.4 (0.2–1.7)	0.7 ± 0.4 (0.2–1.9)	^d0.119
Albumin (g/dL)	3.9 ± 0.3 (3.4–4.6)	4.0 ± 0.5 (2.7–4.7)	^d0.080
Procedure-related factors
Number of applicator (median)	1 (1–3)	2 (1–3)	^d<0.001
Ablation time (minute) (median)	14 (6–25)	30 (30–47)	^a<0.001
Ablation volume (cm^3) (median)	13.9 (3.2–48.1)	10.5 (1.6–39.4)	^a0.154
Hospital stay (median)	3 (3–12)	3 (3–4)	^d0.177

^aStudent’s t-test, ^bChi-square test, ^cFisher’s exact test, ^dMann–Whitney test.

HBV: Hepatitis B virus; HCV: Hepatitis C virus.

p-value < 0.05 is considered to be statistically significant as bold.

Figure 2. A 76-year-old woman with autoimmune hepatitis. (A) Hepatobiliary phase magnetic resonance image shows a 1-cm HCC (arrow) abutting the right bile duct in segment 7. The bile duct is visualized as a tubular structure with high-signal intensity (arrowheads) because of contrast excretion. The tumor is also close to the right main portal vein (anterior side) and right hepatic vein (posterior side). (B) Portal-phase CT scan obtained immediately after cryoablation show an oval-shaped ablation zone covering the entire tumor; the ablation zone size is small because a single cryoprobe was used. There is no bile duct dilatation, suggesting the absence of severe bile duct damage. In addition, the adjacent portal vein and hepatic vein seem to be patent, and there is no perfusion abnormality in the liver. (C) Hepatobiliary phase magnetic resonance image obtained 4 months after the procedure shows the intact right bile duct. There is no upstream bile duct dilatation (not shown). No local tumor progression was noted during the 29-month follow-up period.

Figure 3. A 48-year-old man with liver cirrhosis due to chronic hepatitis B viral infection. (A) Hepatobiliary phase magnetic resonance image shows a 2.1-cm hepatocellular carcinoma (arrow) abutting the right anterior portal vein and right anterior bile duct (arrowheads) in segment 8. (B) Portal-phase computed tomography scan obtained immediately after radiofrequency ablation shows that the tumor is completely ablated with no immediate procedure-related complications. (C) Additional computed tomography (CT) scan obtained 4 days after the procedure because of high fever and abdominal pain. Portal-phase CT image shows air bubbles (arrowhead) in the radiofrequency ablation (RFA) zone and fat stranding in the perihepatic space near the RFA zone, indicating possible abscess and inflammation. The patient’s condition recovered after administration of empirical antibiotics.

Table 2. Complications after treatment of hepatocellular carcinoma.

Complications	All tumors			Tumors abutting the central bile duct
	Radiofrequency ablation (n = 31)	Cryoablation (n = 25)	p Value	Radiofrequency ablation (n = 12)	Cryoablation (n = 7)	p Value
Biliary complications	21 (67.7%)	7 (28.0%)	^A0.007	9 (75.0%)	2 (28.6%)	^B0.074
Asymptomatic biliary stricture	19 (61.3%)	7 (28.0%)	^A0.017	8 (66.7%)	2 (28.6%)	^B0.170
Abscess or biloma	^a3 (9.7%)	0	^B0.245	1 (8.3%)	0	^B0.999
Portal vein thrombosis	^b2 (6.4 %)	0	^B0.497	1 (8.3%)	0	^B0.999
Tract bleeding	1 (3.2 %)	0	^B0.999	1 (8.3%)	0	^B0.999
Severity of complications			^B0.002			^B0.052
None	8 (25.8%)	18 (72.0%)		2 (16.7%)	5 (71.4%)
Minor	21 (67.7%)	7 (28.0%)		8 (66.7%)	2 (28.6%)
Major	^c2 (6.5%)	0		2 (16.7%)	0

^AChi-square test, ^BFisher’s exact test.

^aOne patient presented both asymptomatic biliary stricture and biloma.

^bIn a patient, both portal vein thrombosis and asymptomatic biliary stricture occurred.

^cTwo cases with abscess or tract bleeding were considered to have major complications because further treatment and delayed hospital discharge were needed.

p-value < 0.05 is considered to be statistically significant as bold.

Table 3. Univariable and multivariable analyses of risk factors for biliary complications (biliary stricture, biloma, or abscess).

	Univariable analysis
	Odds ratio	p Value
Age	1.04 (0.99, 1.10)	0.143
Female[male]	1.47 (0.43, 4.97)	0.538
Tumor size	1.49 (0.47, 4.73)	0.502
Child–Pugh score (6 versus 5)	1.12 (0.11, 11.61)	0.999
Child–Pugh score (7 versus 5)	7.90 (0.15, 416.94)	0.486
Albumin–bilirubin grade (1 versus 2, 3)	1.88 (0.62, 5.70)	0.267
Tumor location (peripheral versus central bile duct)	0.62 (0.20, 1.89)	0.399
Ablation method (radiofrequency ablation versus cryoablation)	5.40 (1.71, 17.10)	0.004
Number of applicators	0.51 (0.23, 1.12)	0.093
Ablation time	0.94 (0.89, 0.99)	0.019
Ablation volume	0.99 (0.94, 1.04)	0.744
	^aMultivariable analysis
	Odds ratio	p-value
Ablation method (radiofrequency ablation versus cryoablation)	4.66 (1.38, 15.73)	0.013
Number of applicators	0.74 (0.32, 1.71)	0.477

Odds ratios and p-values were obtained using univariate and multivariate logistic regression analyses. 95% confidence intervals are shown in parenthesis.

^aThe multicollinearity between ablation time and ablation method was considered to be present and thus ablation time was not included in multivariable analysis.

p-value < 0.05 is considered to be statistically significant as bold.

Figure 4. Cumulative local tumor progression rate of cryoablation and radiofrequency ablation. * Patients in the radiofrequency ablation group were censored to assess local tumor progression at 58 months based on the longest follow-up period for the cryoablation group.

Table 4. Univariable and multivariable analyses of risk factors for local tumor progression.

	Univariable analysis		^aMultivariable analysis
	Hazard ratio	p Value	Hazard ratio	p Value
Age	1.01 (0.95, 1.07)	0.872	1.03 (0.95, 1.10)	0.499
Female gender (male)	0.23 (0.03, 1.79)	0.160	0.42 (0.07, 2.61)	0.348
Tumor size	0.63 (0.18, 2.24)	0.479	0.31 (0.04, 2.69)	0.289
Child–Pugh score (6 versus 5)	0.51 (0.02, 15.67)	0.999	0.26 (0.01, 11.18)	0.851
Child–Pugh score (7 versus 5)	0.51 (0.02, 15.73)	0.999	0.26 (0.00, 16.22)	0.931
Albumin–bilirubin grade (1 versus 2, 3)	0.52 (0.14, 1.93)	0.327	1.43 (0.28, 7.19)	0.665
Tumor location (peripheral versus central bile duct)	0.29 (0.09, 0.91)	0.034	0.30 (0.08, 1.09)	0.067
Ablation method (radiofrequency ablation versus cryoablation)	1.16 (0.37, 3.65)	0.806	4.05 (0.49, 33.63)	0.195
Biliary complications (presence versus absence)	0.91 (0.29, 2.84)	0.875	0.54 (0.11, 2.60)	0.444
Number of applicators	0.87 (0.37, 2.03)	0.740	1.54 (0.42, 5.72)	0.516
Ablation time	1.00 (0.95, 1.06)	0.952
Ablation volume	(0.95, 1.06)	0.970	1.01 (0.94, 1.09)	0.748

A time-dependent Cox proportional hazards model was used for multivariate analysis.

95% confidence intervals are shown in parentheses.

^aThe multicollinearity between ablation time and ablation method was considered to be present and thus ablation time was not included in multivariable analysis.

p-value < 0.05 is considered to be statistically significant as bold.