Hepatic Thermal Ablation: Effect of Device and Heating Parameters on Local Tissue Reactions and Distant Tumor Growth.

Abstract

Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Materials and Methods In this institutional Animal Care and Use Committee-approved study, F344 rats (150 gm, n = 96) with subcutaneous R3230 breast adenocarcinoma tumors had normal non-tumor-bearing liver treated with RFA (70°C × 5 minutes), rapid higher-power MWA (20 W × 15 seconds), slower lower-power MWA (5 W × 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). Ablation settings produced 11.4 mm ± 0.8 of coagulation for all groups. Distant tumor growth rates were determined to 7 days after treatment. Liver heat shock protein (HSP) 70 levels (at 72 hours) and macrophages (CD68 at 7 days), tumor proliferative indexes (Ki-67 and CD34 at 7 days), and serum and tissue levels of interleukin 6 (IL-6) at 6 hours, hepatocyte growth factor (HGF) at 72 hours, and vascular endothelial growth factor (VEGF) at 72 hours after ablation were assessed. All data were expressed as means ± standard deviations and were compared by using two-tailed t tests and analysis of variance for selected group comparisons. Linear regression analysis of tumor growth curves was used to determine pre- and posttreatment growth curves on a per-tumor basis. Results At 7 days, hepatic ablations with 5-W MWA and RFA increased distant tumor size compared with 20-W MWA and the sham procedure (5-W MWA: 16.3 mm ± 1.1 and RFA: 16.3 mm ± 0.9 vs sham: 13.6 mm ± 1.3, P < .01, and 20-W MWA: 14.6 mm ± 0.9, P < .05). RFA and 5-W MWA increased postablation tumor growth rates compared with the 20-W MWA and sham arms (preablation growth rates range for all arms: 0.60-0.64 mm/d; postablation: RFA: 0.91 mm/d ± 0.11, 5-W MWA: 0.91 mm/d ± 0.14, P < .01 vs pretreatment; 20-W MWA: 0.69 mm/d ± 0.07, sham: 0.56 mm/d ± 1.15; P = .48 and .65, respectively). Tumor proliferation (Ki-67 percentage) was increased for 5-W MWA (82% ± 5) and RFA (79% ± 5), followed by 20-W MWA (65% ± 2), compared with sham (49% ± 5, P < .01). Likewise, distant tumor microvascular density was greater for 5-W MWA and RFA (P < .01 vs 20-W MWA and sham). Lower-energy MWA and RFA also resulted in increased HSP 70 expression and macrophages in the periablational rim (P < .05). Last, IL-6, HGF, and VEGF elevations were seen in 5-W MWA and RFA compared with 20-W MWA and sham (P < .05). Conclusion Although hepatic MWA can incite periablational inflammation and increased distant tumor growth similar to RFA in an animal tumor model, higher-power, faster heating protocols may potentially mitigate such undesired effects. © RSNA, 2016.

• Authors: Erik Velez, S Nahum Goldberg, Gaurav Kumar, Yuanguo Wang, Svetlana Gourevitch, Jacob Sosna, Tyler Moon, Christopher L Brace, Muneeb Ahmed
• Journal: Radiology (Radiology) Vol. 281 Issue 3 Pg. 782-792 (Dec 2016) ISSN: 1527-1315 [Electronic] United States
• PMID: 27409564 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Interleukin-6
• Ki-67 Antigen
• Vascular Endothelial Growth Factor A
• Hepatocyte Growth Factor

Topics

• Adenocarcinoma (pathology)
• Animals
• Catheter Ablation (adverse effects, methods)
• Disease Models, Animal
• Female
• Hepatocyte Growth Factor (metabolism)
• Hyperthermia, Induced (adverse effects)
• Inflammation (etiology)
• Interleukin-6 (metabolism)
• Ki-67 Antigen (metabolism)
• Liver (surgery)
• Macrophages (pathology)
• Mammary Neoplasms, Experimental (pathology)
• Microwaves (adverse effects)
• Neoplasm Metastasis
• Neoplasm Seeding
• Neoplasm Transplantation
• Neoplasms, Connective Tissue (pathology)
• Random Allocation
• Rats, Inbred F344
• Tumor Burden (physiology)
• Vascular Endothelial Growth Factor A (metabolism)