Effects of pulse repetition rate in static electrochemotherapy models.

Electroporation alters cell membrane structure and tissue electrical properties by short and intense pulsed electric fields (PEF). Static mathematical models are often used to explain the change in electrical properties of tissues caused by electroporation. Electric pulse repetition rate may play an important role, as tissue dielectric dispersion, electroporation dynamics, and Joule heating may affect the electrical properties. In this work, we investigate the effects on the magnitude of the electric current when the repetition rate of the standard electrochemotherapy protocol is increased. Liver, oral mucosa, and muscle tissues were studied. Ex vivo animal experiments show that the magnitude of the electric current increases when the repetition rate is changed from 1 Hz to 5 kHz (10.8% for liver, 5.8% for oral mucosa, and 4.7% for muscle). Although a correction factor could reduce the error to less than 1%, dynamic models seem to be necessary to analyze different protocol signatures. Authors should be aware that static models and experimental results can only be compared if they use exactly the same PEF signature. The repetition rate is a key information to consider in the pretreatment computer study because the current at 1 Hz PEF differs from a 5 kHz PEF.

Adjuvant electrochemotherapy after debulking in canine bone osteosarcoma infiltration.

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high-intensity electric fields during short periods with anti-cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction.