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Ablative therapies in oncology surgery Fernando Burdío

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Irreversible electroporation

Hepatopancreaticobiliary tumours are often diagnosed at an advanced stage of the disease, when local bile or vascular structures have already been invaded, or there are distant metastases. Irreversible electroporation (IRE) is an emerging, image-guided tumour ablation technology that induces cell death by exposing the tumour to high-voltage electrical pulses between electrodes.

As it preserves the integrity of the surrounding tissues, IRE is an attractive treatment option for tumours located near vital structures. This technique has been used in our group's animal experimentation laboratory, as well as in the clinic, to treat liver (https://www.youtube.com/watch?v=dZEn0bAUggk) and pancreatic tumours that are in close proximity to vital structures.

Figura 1. IRE application model with plate electrodes, in tumoral liver either without (A) or with (B) hypersaline infusion through the portal vein and its corresponding numerical simulation (C and D) obtained from the electrical field received in healthy and tumour tissues. (C) With no hypersaline infusion through the portal vein, there is no selective effect on the scattered tumour nodules. However, in (D) with hypersaline infusion through the portal vein, the electric field is increased in scattered tumours (meaning the IRE has a preferential ablative effect on these nodules) due to the increased conductivity of healthy tissue (σ).

Unfortunately, the electrical conductivity difference between tumour and liver tissue hinders the selective IRE of tumour nodules. It is usually assumed that the conductivity of a liver tumour is higher than that of healthy tissue, therefore limiting the effect of this technique on the tumour. This conductivity differential between tumour tissue and healthy tissue can be reversed by injecting saline solution into the hepatic artery or portal vein, as the hepatic artery is the only blood supply for liver tumours.

Our group has demonstrated that by applying IRE, the electric field is significantly higher in scattered tumour nodules allowing them to be selectively removed while preserving healthy tissue. We have promising evidence that this change in conductivity could enhance the IRE's targeting of the tumour by protecting the healthy tissue. This is why it is being studied in a clinical trial

Important publications:

• López-Alonso B, Hernáez A, Sarnago H, Naval A, Güemes A, Junquera C, Burdío JM, Castiella T, Monleón E, Gracia-Llanes J, Burdio F, Mejía E, Lucía O. Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator. Sci Rep. 2019 Feb 25;9(1):2647. doi: 10.1038/s41598-019-39433-6.
• Pañella C, Moll X, Quesada R, Villanueva A, Iglesias M, Andaluz A, Lucía O, Sánchez-Velázquez P, Grande L, Burdío F. Hypersaline Infusion Protocol through the Portal Vein may Focus Electroporation on Tumor Tissue, but is it really Safe? Preliminary Results Clin Surg. 2019 Feb; 4(1): 2335.
• Castellví Q, Sánchez-Velázquez P, Moll X, Berjano E, Andaluz A, Burdío F, Bijnens B, Ivorra A. Modeling liver electrical conductivity during hypertonic injection. Int J Numer Method Biomed Eng. 2018 Jan;34(1). doi: 10.1002/cnm.2904.
• P. Sánchez-Velázquez, Q. Castellví, A.Villanueva, M. Iglesias, R.Quesada, C. Pañella, M. Cáceres, D. Dorcaratto, A.Andaluz, X. Moll, J. M. Burdío, L.Grande, A. Ivorra & F. Burdío. Long-term effectiveness of irreversible electroporation in a murine model of colorectal liver metástasis. Sci Rep. 2017 March; 7:44821. doi: 10.1038/srep44821
• Pañella C, Castellví Q, Moll X, Quesada R, Villanueva A, Iglesias M, Naranjo D, Sánchez-Velázquez P, Andaluz A, Grande L, Ivorra A, Burdío F. Focused Transhepatic Electroporation Mediated by Hypersaline Infusion through the Portal Vein in Rat Model. Preliminary Results on Differential Conductivity. Radiol Oncol. 2017 Nov 29; 51(4):415-421. doi: 10.1515/raon-2017-0051.
• Qasrawi R, Silve L, Burdío F, Abdeen Z, Ivorra A. Anatomically Realistic Simulations of Liver Ablation by Irreversible Electroporation: Impact of Blood Vessels on Ablation Volumes and Undertreatment. Technol Cancer Res Treat. 2017 Dec;16(6):783-792. doi: 10.1177/1533034616687477.
• Sánchez-Velázquez P, Castellví Q, Villanueva A, Quesada R, Pañella C, Cáceres M, Dorcaratto D, Andaluz A, Moll X, Trujillo M, Burdío JM, Berjano E, Grande L1, Ivorra A, Burdío F. Irreversible electroporation of the liver: is there a safe limit to the ablation volume? Sci Rep. 2016 Apr 1;6:23781. doi: 10.1038/srep23781.