Electrochemical Treatment of Tumours

von Euler, H., 2002. Electrochemical treatment of tumours. Doctor’s dissertation. ISSN 1401-6257, ISBN 91-576-6386-6. By electrochemical treatment (EChT) neoplastic tissue is supplied with a continuous direct current through two or more electrodes placed in or near the tumour. The EChT has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of the therapy is the minimal invasive approach and few serious side effects. EChT has not yet been universally accepted due to the absence of essential preclinical studies and controlled clinical trials. Uncertainties regarding the destruction mechanism of EChT also hinder the development of an optimised and reliable methodology for serving as a complement in the oncologic treatments used in the Western world. This thesis investigates the correlation between the pH profile in the tissue surrounding the electrodes and the macroscopic, histopathological and ultrastructural tissue destruction obtained after EChT. Experiments designed to display both the normal, as well as tumour tissue response, is described. A separation between the polarities of the electrodes has been assured to allow specific examinations of the different reactions. To verify the relation between cell damage and pH an in vitro model was conducted where tumour cells were exposed to a pH gradient. To investigate if the same destructive mechanisms could be observed in tumour tissue in vivo an animal model was performed with the same cell line. The in vivo experiments also served as a control and calibration of a mathematical dose-planning model. To examine the change of pH in tissue extensive in situ pH-measurements were performed with a micro-combination glass electrode. The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose-response). Histopathological examination confirmed the macroscopically detectable lesions. The type of necrosis differed due to electrode polarity. Ultrastructural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the tissue close to the border of the lesions displayed a normal morphology. In the tumour model in vivo, significant changes in proliferation rate were seen both in the cathode and anode reaction. Apoptosis were induced in the anodic treatment suggesting that secondary cell destruction was caused by necrosis with cathodic EChT and apoptosis or necrosis at the anode. The findings agree with the results from the in vitro experiment.