Low-level direct electrical current therapy for hepatic metastases. I. Preclinical studies on normal liver

Abstract

It has been known since the end of the nineteenth century that low-level direct electrical current can be used to destroy tumours. Over the last decade there has been a considerable reawakening of interest in the use of this relatively noninvasive, low-cost modality to treat malignant disease, but much of this work has been empirical and has added little to our knowledge of the mechanisms whereby direct current induces necrosis. Groups in Sweden (Nordenstr6m, 1989) and China (Xin, 1994) are currently treating a wide range of clinical tumours by this technique. Greater understanding of the mechanisms may reveal that the therapy is inappropriate for some sites, while for others modification of treatment conditions could maximise tumour destruction. Our previous work (Griffin et al., 1994) established a direct relationship between charge and volume regression in a mammary carcinoma. A clinical application of interest is the treatment of (multifocal) hepatic metastases from colorectal carcinomas. That treatment of lesions in the liver is feasible is suggested by the encouraging results of an uncontrolled trial for DCI of primary hepatoma in China (Lao et al., 1994). In the approach towards clinical trial, we report here on the patterns of necrosis induced preclinically in liver itself, which will be the primary normal tissue at risk in this proposed new therapy for the condition. Materals and methodsAll procedures to be described complied with the Animals (Scientific Procedures) Act 1986 (UK). Male adult outbred white (OBW) rats bred in the Paterson Institute were used throughout, at a weight of 230-250 g. Up to four rats were treated simultaneously while under general anaesthetic. Anaesthesia was induced by inhalation of enflurane in an ether chamber and then maintained by inhalation of halothane and oxygen via a facial mask system with scavenging of waste gases for the duration of the procedure. After induction of anaesthesia, the peritoneal cavity was opened by a small transverse subcostal incision through the skin and rectus muscle and the left lobe of liver exteriorised. Twin gold electrodes, 0.3 mm in diameter, were then inserted at 90g to the surface of the liver and a constant 10 mm apart within the central region of the exposed lobe. A dry gauze swab placed between the exteriorised liver and the underlying anterior abdominal wall of the animal acted as an insulator, preventing current return via any route other than through the substance of the liver between the two electrodes. The electrodes were held firmly in position by a supporting gantry above the animal. New gold electrodes were used after every 2-3 treatments, thus minimising the effects of gradual roughening of the electrode surface due to dissolution of gold at the anode. Before use, electrodes were sterilised with 70% alcohol. Direct current was then passed between the electrodes by means of a computer-controlled, constant-current power supply, which continually monitored voltage, which was normally in the range 1-16 V. In all procedures the el...

3D Stationary electric current density in a spherical tumor treated with low direct current: An analytical solution

“…The experimental results report different bioeffects around the anode and cathode areas after DC treatment. Also, the cathode has a chemotactic effect during DC treatment [Dodd et al, 1993;Griffin et al, 1994Griffin et al, , 1995von Euler et al, 2003;Yuling, 2004;Veiga et al, 2005;Jarque et al, 2007;Haltiwanger, 2008]. This indicates that the electrode polarity is also an important variable in the design of electrode arrays.…”

“…The induction of necrosis and other bioeffects (e.g., swelling of cells due to ischemia, apoptosis, activation of the humoral and cellular components of the immune system, among others) in the tumor [Dodd et al, 1993;Griffin et al, 1994Griffin et al, , 1995Cabrales et al, 2001;von Euler et al, 2003;Ciria et al, 2004;Veiga et al, 2005;Jarque et al, 2007;Wartenberg et al, 2008] explain that s 1 decreases during and after therapy because the fluid distribution in a tumor changes due to a breakdown of cell membranes. It is expected that s 1 increases after longer periods of DC treatment because of the replacement of dead tissue with fibrotic tissue, in agreement with Foster and Schwan [1996].…”

Combining Electrolysis and Electroporation for Tissue Ablation

“…3,4 Over the last two decades, substantial research has been done on tissue ablation by electrolysis, including cell and animal experiments, mathematical modeling, and clinical work. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] In the contemporary literature, electrolytic ablation is sometimes referred to as Electro-Chemical Therapy, and in this work, these two terms are used interchangeably. Electrolytic ablation has been shown to exhibit several unique attributes.…”

Tumor Treatment by Direct Electric Current: Computation of Electric Current and Power Density Distribution

“…However, no change of bioelectric potential was observed due to electrotherapy (16). Changes in local pH and temperature were measured and calculated (4,6,9,15); the role of different materials for electrodes was investigated (15,22); and metal dissolution from the electrodes was determined (13). Extreme local changes of pH were predicted and observed around the electrodes (4,6,9).…”