Radiofrequency Ablation of Hepatocellular Carcinomas Adjacent to the Gallbladder Without Isolation Under Contrast-Enhanced Ultrasound Monitoring: A Comparative Study with Long Term Follow-Up

Figures & data

Table 1 The Baseline Characteristics of the Two Groups

Characteristics	Group A	Group B	P -value
Patients	38	31
Age (Year)^a	58.63±8.81 (range 30–72)	54.35±11.71 (range 25–72)	0.088
Gender (Male/Female)	32/6	26/5	1.000
Tumors (Single/Multiple)	19/19	18/13	0.504
Cirrhosis (Yes/No)	35/3	26/5	0.452
Initial treatment/ Recurrence	18/20	20/11	0.154
Cholecystolithiasis (Yes/No)	9/29	12/19	0.177
The thickness of GB wall (mm)	Median: 4, range 2–8	Median: 4, range 2–7	0.080
Follow-up period (months)^a	41.29 ± 15.35 (range 2–64)	37.74 ± 17.45 (range 2–68)	0.372
Auxiliary measures (artificial ascites/monitor during laparoscopy or open surgery/LC)	-	21/2/8	-
Lesions	39	35
Maximum diameter (mm)	Median: 15, range 8–49	Median: 18; range 6–41	0.119
Tumor location (S4/S5/S8)	12/20/7	7/24/4	0.319
Distance to GB^b (mm)	Median: 0, range 0–9	Median: 2, range 0–9	0.804
Distance to GB^b (0/1–5mm/ 6–9mm)	21/8/10	15/16/4

Notes: Data are numbers of cases in parentheses unless specified otherwise; ^aData are means ± standard deviations (ranges); ^bThe shortest distance between the lesion and GB.

Abbreviations: GB, gallbladder; LC, laparoscopic cholecystectomy.

Figure 1 RFA of a 68-year-old female with HCC abutting the gallbladder under intra-operative contrast-enhanced ultrasound (CEUS) monitoring. (A–C). Conventional ultrasound, CEUS and contrast-enhanced CT image showed HCC nodule in segment V abutting to the gallbladder with a maximum diameter of 22 mm (white arrow). Before ablation, the thickness of the gallbladder wall was 4 mm. (D) The electrode was inserted parallel to the gallbladder wall with a minimum distance of 6 mm (white triangle). (E) CEUS showed that the perfusion of the gallbladder wall was intact (red arrow) and the index tumor had been completely ablated (white arrow). (F) The thickness of the gallbladder wall increased to 10 mm one day after ablation (white triangle). (G) One month later, the contrast-enhanced MR confirmed the result of complete ablation (white arrow). (H) The thickness of the gallbladder wall was restored to 4 mm after 4 months on conventional ultrasound image (white triangle).

Figure 2 A 52-year-old male with HCC abutting the gallbladder underwent RFA with auxiliary artificial ascites. (A and C) Conventional ultrasound and contrast-enhanced MR image indicated a HCC lesion located in segment V abutting the gallbladder with a maximum diameter of 15 mm (white arrow). (A and B) Gallbladder stones were found on ultrasound images and the thickness of gallbladder wall was 4 mm. (D) Artificial ascites (white triangle) were employed to isolate the lesion and gallbladder before radiofrequency ablation. (E) The electrode (white arrow) was inserted parallel to the gallbladder wall. (F) After 4 ablation cycles, contrast-enhanced ultrasound showed that the index tumor had been completely ablated (white arrow). (G) One day after ablation, the thickness of the gallbladder wall increased to 7 mm (white triangle). (H) Contrast-enhanced MR one month after the ablation procedure confirmed the complete ablation of the index tumor (white arrow). (I) The thickness of gallbladder wall was restored to 4 mm after 5 months on conventional ultrasound image (white triangle).

Figure 3 A 65-year-old male with cholelithiasis who was planned to undergo LC after RFA. (A–C) Conventional ultrasound and contrast-enhanced ultrasound (CEUS), and contrast-enhanced MR image showed a HCC (15×10 mm) in segment V abutting to the gallbladder (white arrow). Before ablation, the thickness of the gallbladder wall was 4 mm. (D) Sediment-like gallstones (white cross) were found on ultrasound images. (E) The electrode was inserted parallel to the gallbladder wall with a distance less than 5 mm (white cross). (F) CEUS showed that the index tumor had been completely ablated (white arrow) while the perfusion defect of the gallbladder wall was found by accident (red arrow). Patient underwent LC soon after RFA procedure, thermal damage of the gallbladder wall was found in postoperative specimens. (G) Postoperative pathology confirmed the thermal damage of the serosa and mucosa of the GB wall. (H) CEMR one month after the RFA procedure confirmed the technical efficacy (white arrow).

Table 2 Therapeutic Effect and Re-Treatment

Variable	Group A	Group B	P-value
Residual	0% (0/39)	0% (0/35)	1.000
LTP	5.1% (2/39)	5.7% (2/35)	1.000
IDR	39.5% (15/38)	58.1% (18/31)	0.124
ER	21.1% (8/38)	22.6% (7/31)	0.878
Major complications	7.9% (3/38)	6.5% (2/31)	1.000
	Hemothorax (n=1)	Peritonitis (n=1)
	Massive pleural effusion (n=2)	Massive pleural effusion (n=1)
Minor complications	28.9% (11/38)	29.0% (9/31)	0.994
	Fever (n=4)	Fever (n=4)
	Abdominal pain (n=5)	Abdominal pain (n=4)
	Nausea and vomit (n=2)	Vomit (n=1)
Treatment of recurrences	17	20
RFA/MWA/PEI	8/2/1	5/7/0
Resection	0	1
TACE	3	3
Radiotherapy	0	1
Liver transplantation	1	1
Palliative care	2	2

Notes: Data are numbers of cases or with percentages in parentheses unless specified otherwise.

Abbreviations: LTP, local tumor progression; IDR, intrahepatic distant recurrence; ER, extrahepatic recurrence; RFA, radiofrequency ablation; MWA, microwave ablation; PEI, percutaneous ethanol injection. TACE, trans-arterial chemoembolization.

Table 3 Cumulative LTP, IDR, OS and TFS Rates of Group A and Group B

Cumulative Rates	Group A			Group B			P-value^a
	1-Year	3-Year	5-Year	1-Year	3-Year	5-Year
LTP	2.6%	5.7%	5.7%	5.9%	5.9%	5.9%	0.851
IDR	27.2%	30.6%	53.5%	33.8%	56.5%	73.9%	0.030
OS	97.3%	88.8%	88.8%	96.8%	85.8%	85.8%	0.700
TFS	73.1%	55.8%	42.9%	64.2%	39.5%	23.7%	0.081

Note: ^aData were compared using the Log rank test.

Abbreviations: LTP, local tumor progression; IDR, intrahepatic distant recurrence; OS, overall survival; TFS, tumor free survival;

Figure 4 Comparison of the cumulative local tumor progression (A), intrahepatic distant recurrence (B), overall survival (C) and tumor free survival (D) curves between group A and group B.

Table 4 Thickness of Gallbladder Wall

Gallbladder Wall	Group A	Group B	P-value
Thickness before RFA (mm)	Median: 4, range 2–8	Median: 4, range 2–7	0.079^a
Thickness after RFA (mm)	Median: 7, range 2–12	Median: 4, range 2–7	0.001^a
P-value (Thickness before vs after RFA)^a	<0.001	0.004	-
Patients with thickening of the GB wall	14 (14/38, 36.8%)	4 (4/23, 17.4%)	0.106^b
Thickness recovery	50.0% (7/14)	100% (4/4)	0.119^b

Notes: ^aNon-parametric data were analyzed using the Mann Whitney U-test; ^bCategorical variable were analyzed using the χ² test.

Abbreviations: RFA, radiofrequency ablation; GB, gallbladder.