Hepatic thermal ablation: Effect of device and heating parameters on local tissue reactions and distant tumor growth

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 3 5 minutes), rapid higherpower MWA (20 W 3 15 seconds), slower lower-power MWA (5 W 3 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at±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 interleukin6(IL-6) at6hours, 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.