Browsing by Author "DeWitt, Matthew R."
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- Bursts of Bipolar Microsecond Pulses Inhibit Tumor GrowthSano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn Rose; DeWitt, Matthew R.; Cho, Hyung J.; Szot, Cchristopher S.; Saur, Dieter; Cissell, James M.; Robertson, John L.; Lee, Yong Woo; Davalos, Rafael V. (Nature Publishing Group, 2015-10-13)Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.
- Treatment of Infiltrative Superficial Tumors in Awake Standing Horses Using Novel High-Frequency Pulsed Electrical FieldsByron, Christopher R.; DeWitt, Matthew R.; Latouche, Eduardo L.; Davalos, Rafael V.; Robertson, John L. (Frontiers, 2019-08-14)Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strongmuscle contractions associated with the electrical impulses (duration, 50–100 μs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable electroporation of tumors without stimulation of nearby skeletal muscle. H-FIRE administers bursts of electrical pulses (duration, 0.5–2 μs) through bipolar electrodes placed in tumor parenchyma. We hypothesized that H-FIRE could be used to safely ablate superficial tumors in standing, awake horses without the need for general anesthesia. Here, we describe the treatment of superficial tumors in five horses using this novel ablation therapy without the need for general anesthesia. In each case, H-FIRE therapy predictably ablated tumor volume. All patients tolerated the procedure, no complications developed, and veterinary personnel safety was maintained. The H-FIRE treatment may be useful for treatment in veterinary and human patients in an outpatient setting without the need for hospitalization, general anesthesia, and advanced monitoring techniques.