Experimental application of electrolysis in the treatment of liver and pancreatic tumours: Principles, preclinical and clinical observations and future perspectives

Gravante, Gianpiero; Ong, Seok Ling; Metcalfe, Matthew S.; Bhardwaj, Neil; Maddern, Guy J.; Lloyd, David M.; Dennison, Ashley R.

doi:10.1016/j.suronc.2009.12.002

Cited by 21 publications

(20 citation statements)

References 59 publications

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“…Large blood vessels are still patent in the middle of the treated volume, and this observation that large blood vessels are not aff ected by electrolytic ablation was also reported in Ref. 12.…”

Section: Discussionsupporting

confidence: 81%

Modulating electrolytic tissue ablation with reversible electroporation pulses

Phillips

Raju²,

Rubinsky

et al. 2015

Technology

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Electrolytic ablation is a minimally invasive tissue ablation technique that operates by delivering low magnitude direct current to the target region over long periods of time, generating electrolytic products that destroy cells. Our study seeks to examine the hypothesis that permeabilizing the cell membrane with reversible electroporation will reduce the electrolytic dose required for tissue ablation, by exposing the interior of the cell to the electrolytic products. The hypothesis is examined by evaluating the extent of tissue damage when electrolytic and reversible electroporation sequences are delivered separately and in combination, in vivo, to rat liver tissue. The study shows that combining reversible electroporation with electrolysis produces a substantial increase in the extent of tissue ablation compared to that achieved by electrolysis alone. INNOVATIONTh is study shows that when reversible electroporation is used to modulate electrolytic ablation, the combination of electrolytic products generated at the electrodes and the permeabilization of the cell membrane greatly increases the extent of tissue ablation. Th us, the electrical parameters typical to reversible electroporation protocols can be harnessed to facilitate cell death. Th is suggests a new technology for tissue ablation. Th e advantage of this technology is that it uses much lower electric fi elds than conventional irreversible electroporation and requires a much lower dose of electrolytic products than typically seen with electrolytic ablation.

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Section: Discussionsupporting

confidence: 81%

Modulating electrolytic tissue ablation with reversible electroporation pulses

Phillips

Raju²,

Rubinsky

et al. 2015

Technology

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“…The death of 11 mice during and after DC action is an unexpected result. This finding has not been reported in preclinical [Chou et al, 1997;Li et al, 1997;Miklav ci c et al, 1997;Cabrales et al, 2001;Ren et al, 2001;von Euler et al, 2003;Ciria et al, 2004;Wartenberg et al, 2008;Gravante et al, 2011] or clinical [Song et al, 1995;Xin et al, 2004;Jarque et al, 2007;Jing-Hong, 2011] studies. Death of three mice during DC application (TG1-F, TG2-M and TG3-F) may be explained from the quick increase of the voltage because the tumor electric resistance increases due to the increase of dissipated potency in the tumor, maintaining constant DC intensity.…”

Section: Discussionmentioning

confidence: 85%

Dose‐response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current

González

Morales

Cabrales

et al. 2018

Bioelectromagnetics

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Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

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“…These include electrolysis, ionthoporesis, and electro-osmotic flows. The phenomena of electroporation [8][9][10][11][12][13][14][15] and the phenomena of electrolysis [16][17][18][19][20][21][22][23][24][25] were both used in the past for tissue ablation, each separately. However, in 2 recent articles, we show that various optimized combinations of electrolysis with electroporation can increase the extent and control of tissue ablation over protocols designed for each modality separately.…”

Section: Introductionmentioning

confidence: 99%

Electrolytic Effects During Tissue Ablation by Electroporation

Rubinsky

Guenther

Mikus

et al. 2016

Technol Cancer Res Treat

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Nonthermal irreversible electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation ablation protocols.

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Experimental application of electrolysis in the treatment of liver and pancreatic tumours: Principles, preclinical and clinical observations and future perspectives

Cited by 21 publications

References 59 publications

Modulating electrolytic tissue ablation with reversible electroporation pulses

Modulating electrolytic tissue ablation with reversible electroporation pulses

Dose‐response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current

Electrolytic Effects During Tissue Ablation by Electroporation

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