title: Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal Model.
abstract: Purpose To compare both periablational and systemic effects of two mechanistically different types of ablation: thermal radiofrequency (RF) ablation and electroporative ablation with irreversible electroporation (IRE) in appropriately selected animal models. Materials and Methods Animal experiments were performed according to a protocol approved by the Animal Care Committee of Hebrew University. Female C57BL/6 mice (n = 165) were randomized to undergo either RF or IRE ablation of noncancerous normal liver. The inflammatory response, cell proliferation, interleukin 6 (IL-6) levels, and intactness of vessels in the liver were assessed at 6, 12, and 24 hours and at 3, 7, and 14 days after ablation (n = 122 for mechanistic experiments). Systemic effects were then assessed by comparing tumor formation in an Mdr2-knockout (KO) mouse model (n = 15) and tumor growth in a remote BNL 1ME hepatoma xenograft tumor (n = 28). Results were averaged and evaluated by using two-tailed t tests. Results Although RF ablation was associated with a well-defined periablational inflammatory rim, for IRE, the infiltrate penetrated the ablation zone, largely along persistently patent vessels. Peak IL-6 levels (6 hours after ablation) were 10 and three times higher than at baseline for IRE and RF, respectively (P < .03). Mdr2-KO mice that were treated with IRE ablation had more tumors that were 3 mm or larger than mice treated with RF ablation or sham operation (mean, 3.6 ± 1.3 [standard deviation] vs 2.4 ± 1.1 and 2.2 ± 0.8, respectively; P < .05 for IRE vs both RF ablation and sham operation). For BNL 1ME tumors, both RF and IRE liver ablation reduced tumor growth, with a greater effect noted for IRE (1329 mm(3) ± 586 and 819 mm(3) ± 327 vs 2241 mm(3) ± 548 for sham operation; P < .05) that was accompanied by more infiltrating lymphocytes compared with sham operation (7.6 cells per frame ± 1.9 vs 11.2 ± 2.1 vs 0.3 ± 0.1; P < .05). Conclusion Persistent patency of vasculature within the coagulated zone from IRE increases the area and accumulation of infiltrative cells that is associated with a higher serum IL-6 level than RF ablation. These local changes of IRE induce more robust systemic effects, including both tumorigenic and immunogenic effects. (©) RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Baruch E
authors.initials: BE
authors.lastname: Bulvik
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Nir
authors.initials: N
authors.lastname: Rozenblum
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gourevich
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Muneeb
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Andriyanov
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.affiliation: From the Goldyne Savad Institute of Gene Therapy (B.E.B., N.R., S.G., E.G., S.N.G.), Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada (A.V.A.), and Department of Radiology (S.N.G.), Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (M.A., S.N.G.).
authors.forename: S Nahum
authors.initials: SN
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D017115:Catheter Ablation / Q000379:methods*; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D008099:Liver / Q000473:pathology / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL