High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma. Partridge, B. R., O'Brien, T. J., Lorenzo, M. F., Coutermarsh-Ott, S. L., Barry, S. L., Stadler, K., Muro, N., Meyerhoeffer, M., Allen, I. C., Davalos, R. V., & Dervisis, N. G. J Vasc Interv Radiol, 31(3):482-491.e4, 2020. 1535-7732 Partridge, Brittanie R O'Brien, Timothy J Lorenzo, Melvin F Coutermarsh-Ott, Sheryl L Barry, Sabrina L Stadler, Krystina Muro, Noelle Meyerhoeffer, Mitchell Allen, Irving C Davalos, Rafael V Dervisis, Nikolaos G R01 CA240476/CA/NCI NIH HHS/United States Journal Article United States 2020/01/21 J Vasc Interv Radiol. 2020 Mar;31(3):482-491.e4. doi: 10.1016/j.jvir.2019.10.015. Epub 2020 Jan 16.
doi  abstract   bibtex   
PURPOSE: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. MATERIALS AND METHODS: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. RESULTS: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3(+)/CD4(-)/CD8(-) lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm(3) ± 0.74 and 1.56 cm(3) ± 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm ± 28.2 and 957 V/cm ± 24.4 V/cm (P = .0004). CONCLUSIONS: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.
@article{RN137,
   author = {Partridge, B. R. and O'Brien, T. J. and Lorenzo, M. F. and Coutermarsh-Ott, S. L. and Barry, S. L. and Stadler, K. and Muro, N. and Meyerhoeffer, M. and Allen, I. C. and Davalos, R. V. and Dervisis, N. G.},
   title = {High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular Carcinoma},
   journal = {J Vasc Interv Radiol},
   volume = {31},
   number = {3},
   pages = {482-491.e4},
   note = {1535-7732
Partridge, Brittanie R
O'Brien, Timothy J
Lorenzo, Melvin F
Coutermarsh-Ott, Sheryl L
Barry, Sabrina L
Stadler, Krystina
Muro, Noelle
Meyerhoeffer, Mitchell
Allen, Irving C
Davalos, Rafael V
Dervisis, Nikolaos G
R01 CA240476/CA/NCI NIH HHS/United States
Journal Article
United States
2020/01/21
J Vasc Interv Radiol. 2020 Mar;31(3):482-491.e4. doi: 10.1016/j.jvir.2019.10.015. Epub 2020 Jan 16.},
   abstract = {PURPOSE: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. MATERIALS AND METHODS: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. RESULTS: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3(+)/CD4(-)/CD8(-) lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm(3) ± 0.74 and 1.56 cm(3) ± 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm ± 28.2 and 957 V/cm ± 24.4 V/cm (P = .0004). CONCLUSIONS: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.},
   keywords = {Ablation Techniques/*veterinary
Animals
CD3 Complex/immunology
Carcinoma, Hepatocellular/immunology/pathology/surgery/*veterinary
Dog Diseases/immunology/pathology/*surgery
Dogs
Electroporation/*veterinary
Feasibility Studies
Female
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Liver Neoplasms/immunology/pathology/surgery/*veterinary
Lymphocytes, Tumor-Infiltrating/immunology
Male
Proof of Concept Study
Sus scrofa},
   ISSN = {1051-0443 (Print)
1051-0443},
   DOI = {10.1016/j.jvir.2019.10.015},
   year = {2020},
   type = {Journal Article}
}

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