“effect of the irreversible electroporation in a murine model of colorectal liver metastases”
- Autores: Patricia Sánchez Velázquez
- Directores de la Tesis: Fernando Burdio (dir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Manuel Pera Román (presid.), Oscar Lucia Gil (secret.), Filip Lukas Grochola (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
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- Resumen
Irreversible electroporation is a fast-growing liver ablation technique. Although safety has been well documented in small ablations, little is known about it safety when a large portion of liver is ablated neither its oncological long-term outcomes.
In this study a tumoral animal model (athymic-nude implanted with a tumor from the KM12C cell line) and a non-tumoral model C57-Bl6 mice were subjected to high voltage pulses directly delivered across parallel plate electrodes comprising 40% of mouse liver in order to create a massive ablation.
It was delivered two different field strengths (1000 V/cm, 2000 V/cm) and a subset of the animals received anti-hyperkalemia therapy. To determine the long-time survival of animals treated with a high dose of IRE tumors were allowed to continue to grow until the animals reached the end-point criteria.
Early mortality (less than 24 hours post-IRE) in the 2000 V/cm group was observed and revealed considerably higher mean potassium levels. In contrast, the animals subjected to a 2000 V/cm field treated with the anti-hyperkalemia therapy had higher survival rates (OR= 0.1, 95%CI=0.02-0.32, p<0.001). Early mortality also depended on the electric field magnitude of the IRE protocol, as mice given 1000 V/cm survived longer than those given 2000 V/cm (OR= 4.7, 95% CI=1.8-11.8, p=0.001). However, IRE treatment with the 2000V/cm protocol significantly prolonged median mouse survival from 74.3 ± 6.9 days in the sham group to 112.5 ± 15.2 days in 2000V/cm group. No differences were observed between the mean survival of the 1000V/cm and the sham group (83.2 ± 16.4 days, p = 0.62).
Histology revealed 63.05% ± 23.12 of tumor necrosis in animals of the 2000 V/cm group as compared to 17.50% ± 2.50 in the 1000 V/cm group and 25.6% ± 22.1 in the Sham group (p = 0.001). The highest IRE protocol is needed to achieve a prolonged survival und more grade of tumoral necrosis but it also arise concerns about safety.
