Korean J Radiol.  2018 Dec;19(6):1099-1109. 10.3348/kjr.2018.19.6.1099.

No-Touch Radiofrequency Ablation of VX2 Hepatic Tumors In Vivo in Rabbits: A Proof of Concept Study

• Kim TH
• Choi HI
• Kim BR
• Kang JH
• Nam JG
• Park SJ
• Lee S
• Yoon JH
• Lee DH
• Joo I
• Lee JM

• KMID: 2424849
• DOI: http://doi.org/10.3348/kjr.2018.19.6.1099

Abstract

OBJECTIVE
In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model.
MATERIALS AND METHODS
Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation.
RESULTS
Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group.
CONCLUSION
No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.

Keyword

Dissemination; Serum hepatocyte growth factor (HGF); Vascular endothelial growth factor (VEGF); Interleukin-6 (IL-6)

MeSH Terms

Autopsy
Biotechnology
Catheter Ablation*
Enzyme-Linked Immunosorbent Assay
Follow-Up Studies
Hepatocyte Growth Factor
Interleukin-6
Necrosis
Punctures
Rabbits*
Vascular Endothelial Growth Factor A
Hepatocyte Growth Factor
Interleukin-6
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Study protocol.In total, 62 New Zealand white rabbits with VX2 tumors confirmed by CT on day 9 (range, 7–12) were randomized into three groups (DTP-RFA group, NtRFA group, and control group). Each group was further divided into two subgroups for pathologic analysis (A-1, B-1, C-1) and for 6 weeks of CT follow-up (A-2, B-2, C-2). CT = computed tomography, DTP-RFA = direct tumor puncture radiofrequency ablation, NtRFA = no-touch RFA

• 

  Fig. 2 Illustration of DTP-RFA and NtRFA.A. DTP-RFA technique. One of dual electrodes is inserted directly into tumor, penetrating tumor capsule. This technique initiates ablation within tumor. B. NtRFA technique. Dual bipolar needles are inserted into periphery of tumor, not penetrating tumor capsule. This technique induces ablation starting from healthy tissues surrounding tumor, then extending centripetally into tumor.

• 

  Fig. 3 Histopathology in DTP-RFA, NtRFA, and control.A–C. DTP-RFA technique. A. Gross anatomic picture showing one of bipolar needles (arrow) penetrating tumor. B. H&E staining of ablation zone reveals needle insertion site (asterisks) in main mass within ablation zone. Note that incomplete ablation was performed for satellite tumor nodule (arrowhead). Satellite nodule is located 6 mm from main tumor. C. Another H&E stain of ablation zone reveals needle insertion site (asterisks) within tumor. Note that lateral border of main tumor abutted ablation margin. D–G. NtRFA. D. Gross anatomic picture showing dual bipolar needles (dotted arrows) penetrating periphery of tumor. E, F. H&E staining of ablation zone in two different rabbits reveals needle insertion site (asterisks) with both main tumor and satellite nodules (arrowhead) completely ablated. G. NADH staining of ablation zone. Contrary to normal viable cells with NADH staining outside of ablation zone, there is no viability within ablation zone. H, I. Control group. H. H&E staining reveals main tumor with multinodular satellite tumors. Note that all satellite nodules are located within 2 mm from main tumor (I) NADH staining shows both viable hepatocytes and main tumor. H&E = hematoxylin & eosin, NADH = nicotinamide adenine dinucleotide

• 

  Fig. 4 DTP-RFA.A. Pre-RFA CT showing 0.8 cm peripheral enhancing tumor in left medial lobe subcapsular area. B. US-guided RFA was performed, and one of two dual bipolar needles (arrows) accurately penetrated tumor (dotted circle). C. 6-week post-RFA CT reveals multiple peritoneal seeding nodules (dotted arrows) and local recurrence (double lined arrow) at inferior aspect of previous tumor. D. Gross anatomic picture showing peritoneal seeding nodules (arrowheads) and local recurrence. Lung metastasis (asterisk) also appears. E. H&E staining of peritoneal seeding nodules confirmed VX2 carcinoma. US = ultrasonography

• 

  Fig. 5 NtRFA.A. Pre-RFA CT showing 0.7 cm peripheral enhancing tumor in left medial lobe subcapsular area. B. US-guided RFA was performed, and dual bipolar needles (arrows) accurately penetrated periphery of tumor (dotted circle). C. 6-week post-RFA CT reveals complete ablation of tumor (double line arrow) with small amount of localized fluid collection within soft tissue anterior to left lobe of liver (dotted arrows). D. Gross anatomic picture showing complete necrosis of tumor (asterisk) and localized peritoneal fluid collection (arrowheads). E. H&E staining of peritoneal fluid collection confirmed reactive fibrosis with few lymphocytes and no tumor.

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