title: 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.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Erik
authors.initials: E
authors.lastname: Velez
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: S Nahum
authors.initials: SN
authors.lastname: Goldberg
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kumar
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Yuanguo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gourevitch
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Jacob
authors.initials: J
authors.lastname: Sosna
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Tyler
authors.initials: T
authors.lastname: Moon
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brace
authors.affiliation: From the Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 1 Deaconess Rd, Boston, MA 02215 (E.V., S.N.G., G.K., Y.W., J.S., M.A.); Division of Image-guided Therapy and Interventional Oncology, Department of Radiology (S.N.G., J.S.), and Goldyne Savad Institute of Gene Therapy (S.G.), Hadassah Hebrew University Hospital, Jerusalem, Israel; and Departments of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, Wis (T.M., C.B.).
authors.forename: Muneeb
authors.initials: M
authors.lastname: Ahmed
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D017115:Catheter Ablation / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006979:Hyperthermia, Induced / Q000009:adverse effects; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000601:surgery*; D008264:Macrophages / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D008872:Microwaves / Q000009:adverse effects*; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D009368:Neoplasm Transplantation; D009372:Neoplasms, Connective Tissue / Q000473:pathology; D011897:Random Allocation; D011916:Rats, Inbred F344; D047368:Tumor Burden / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor