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Yossi Mandel, Shahar Frenkel, Shlomi Laufer, Boris Rubinsky, Michael Belkin, Jacob Pe'er; Treatment Of Uveal Melanoma By Non-thermal Irreversible Electroporation - Mathematical Model, Animal And Preliminary Ex-vivo Human Experiments. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3284.
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Non Thermal Irreversible Electroporation (NTIRE) is a novel technique which employs electrical pulses for selectively and permanently damaging cell membrane while sparing non- cellular structures. The purpose of this work was to evaluate the possibility to use NTIRE for uveal melanoma treatment by simulation, animal study as well as ablation of human uveal melanoma ex-vivo.
A 3D model of the eye with a moderate size uveal melanoma tumor was created by Comsol Multyphysics 3.5. We simulated NTIRE to the eye while changing various combinations of internal and external electrodes. The electric potential and electric field for each spatial point in the eye were calculated by the Laplace equation. The Joule heating rate per unit volume caused by the electrical field was added to the Pennes bio-heat equation for temperature calculation. Porcine eyes and live rats eyes were used for model validation and for studying the effect of NTIRE on ocular structures. The electric properties of human uveal melanoma tumor were measured immediately after enucleation in 2 patients. Tumors were treated by 90-150 pulses of more then 1000 Volts/cm and were sent for pathological examination.
Highest intratumor electric fields were found for configurations of combined intra and extraocular electrodes. The fraction of tumor within the various target fields was dependent on the pulse potential, electrode configuration and tumor conductivity. Pulse duration of 100 microseconds was associated with significant increase in temperature in some electrode configurations. However, pulse duration of 1 microsecond was not associated with significantly increased scleral temperature in all electrode configurations and pulse frequencies. Animal data supported the results obtained by the mathematical model. Histopathology of treated tumor showed extensive destruction of the tumors on both the architectural and the cellular levels.
This research supports the possibility to consider NTIRE as a treatment option for uveal melanoma. Further animal and human research need be conducted to substantiate the efficacy of NTIRE for the treatment of uveal melanoma.
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