Use of electrolysis for the treatment of non‐resectable hepatocellular carcinoma

Technol Cancer Res Treat

Guenther

Mikus

et al. 2016

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.

Section: Introductionmentioning

confidence: 99%

Electrolytic Effects During Tissue Ablation by Electroporation

Technol Cancer Res Treat

Guenther

Mikus

et al. 2016

“…The length is related to the slow diffusion of electrochemically produced species in tissue and the need for high concentrations of electrolytic products to cause cell death. A clinical study on tissue ablation with electrolysis states that— “Currently, a limitation of the technique is that it is time consuming” (Fosh et al, 2002; Fosh et al, 2003). …”

Section: Introductionmentioning

confidence: 99%

Cryoelectrolysis—electrolytic processes in a frozen physiological saline medium

Lugnani¹,

Macchioro²,

2017

PeerJ

BackgroundCryoelectrolysis is a new minimally invasive tissue ablation surgical technique that combines the ablation techniques of electrolytic ablation with cryosurgery. The goal of this study is to examine the hypothesis that electrolysis can take place in a frozen aqueous saline solution.MethodTo examine the hypothesis we performed a cryoelectrolytic ablation protocol in which electrolysis and cryosurgery are delivered simultaneously in a tissue simulant made of physiological saline gel with a pH dye. We measured current flow, voltage and extents of freezing and pH dye staining.ResultsUsing optical measurements and measurements of currents, we have shown that electrolysis can occur in frozen physiological saline, at high subzero freezing temperatures, above the eutectic temperature of the frozen salt solution. It was observed that electrolysis occurs when the tissue resides at high subzero temperatures during the freezing stage and essentially throughout the entire thawing stage. We also found that during thawing, the frozen lesion temperature raises rapidly to high subfreezing values and remains at those values throughout the thawing stage. Substantial electrolysis occurs during the thawing stage. Another interesting finding is that electro-osmotic flows affect the process of cryoelectrolysis at the anode and cathode, in different ways.DiscussionThe results showing that electrical current flow and electrolysis occur in frozen saline solutions imply a mechanism involving ionic movement in the fluid concentrated saline solution channels between ice crystals, at high subfreezing temperatures. Temperatures higher than the eutectic are required for the brine to be fluid. The particular pattern of temperature and electrical currents during the thawing stage of frozen tissue, can be explained by the large amounts of energy that must be removed at the outer edge of the frozen lesion because of the solid/liquid phase transformation on that interface.ConclusionElectrolysis can occur in a frozen domain at high subfreezing temperature, probably above the eutectic. It appears that the most effective period for delivering electrolytic currents in cryoelectrolysis is during the high subzero temperatures stage while freezing and immediately after cooling has stopped, throughout the thawing stage.

“…INIMALLY invasive tissue ablation is an important alternative to surgical resection, often allowing for reduced duration of the surgery and of the subsequent hospitalization, improved access to the surgical site, and optimized treatment of the target tissue [1,2]. For example, processes such as non-thermal irreversible electroporation [3,4] and electrolytic ablation [5][6][7] can be used to ablate cells in a volume of tissue while maintaining important structures in that volume, such as blood vessels, intact. These and many other physical and chemical principles are used as the basis for various minimally invasive tissue ablation techniques, each with their advantages and disadvantages.…”

Section: Introductionmentioning

confidence: 99%

An Electrochemistry Study of Cryoelectrolysis in Frozen Physiological Saline

Manuel

Munnangi

IEEE Trans. Biomed. Eng.

2017

Cryoelectrolysis is a new minimally invasive tissue ablation surgical technique that combines the processes of electrolysis and solid/liquid phase transformation (freezing). This study investigated this new technique by measuring the pH front propagation and the changes in resistance in a tissue simulant made of physiological saline gel with a pH dye as a function of the sample temperature in the high subzero range above the eutectic. Results demonstrated that effective electrolysis can occur in a high subzero freezing milieu and that the propagation of the pH front is only weakly dependent on temperature. These observations are consistent with a mechanism involving ionic movement through the concentrated saline solution channels between ice crystals at subfreezing temperatures above the eutectic. Moreover, results suggest that Joule heating in these microchannels may cause local microscopic melting, the observed weak dependence of pH front propagation on temperature, and the large changes in resistance with time. A final insight provided by the results is that the pH front propagation from the anode is more rapid than from the cathode, a feature indicative of the electro-osmotic flow from the cathode to the anode. The findings in this paper may be critical for designing future cryoelectrolytic ablation surgery protocols.