DESIGN AND DEVELOPMENT OF MEDICAL ELECTRONIC ...

OTHER CLINICAL APPLICATIONS OF ELECTRICAL CURRENT DELIVERY TO TISSUES 363TABLE 7.8 Typical Parameters Used in Electrochemotherapy (Electroporation) InstrumentsClinical Method of Typical Typical CurrentApplication Current Delivery Waveform or VoltageDeliver high doses of Genetronics: six needle electrodes Genetronics: voltage pulses, 100 µs Maximum pulse amplitudechemotherapeutic in a circle in contact with tumor in duration, delivered at a frequency of 3 kV to yield fielddrugs to cancerous driven in opposing pairs at any of 1 to 100 Hz intensity of 600 totumors one time 1200 V/cmDaskalov et al. [1999]: pair of Daskalov et al. [1999]: burst of eight Maximum pulse amplitudestainless-steel wires 0.8 mm in biphasic voltage pulses of 50 µs of 1.25 kV to yield fielddiameter and 14 mm in length duration per phase at a frequency intensity of 330 tospaced 5 to 30 mm of 1 kHz 1250 V/cmElectroporation therapy can be delivered to external tumors by placing electrodes onopposite sides of a tumor so that the electric field is between the electrodes. However,when large or internal tumors are to be treated, it is not easy to locate electrodes properlyand measure the distance between them. For this type of tumors, needles are the preferredtype of electrodes. Since the use of only two needles creates an inhomogeneous field,Genetronics uses an array of six needles to optimize the uniformity of the pore formationaround the cell [Hofmann, 2001]. Genetronics drives the needle electrodes in opposingpairs because the resulting field is more homogeneous than that between opposing singleneedles. After each electroporation pulse the polarity of the needles is reversed immediatelyand the needle pair is pulsed again. After each of these paired pulsings, the sequencefor the next electric field is rotated 60 degrees. A fairly uniform distribution, which maximizespore formation in the cells over a circular section of the tissue, is generated by rotatingthe field three times.Electrochemical TherapyElectrochemical therapy (EChT), also known as electrochemical tumor therapy or cancergalvanotherapy consists of placing a platinum wire anode electrode into a tumor and anumber of similar cathode electrodes in the tumor’s periphery. 100 mA dc is passedbetween the electrodes until the delivered charge reaches some 50 to 100 C/mL of tumor(Table 7.9). The flow of direct current through tumor tissue triggers electrolytic processesat the electrodes. Positively charged ions (e.g., H ,Na ) migrate to the cathode, resultingin the formation of an extremely alkaline environment (pH 12.9). At the same time, negativelycharged ions (e.g., Cl ) migrate to the anode, creating an extremely acidic environment(pH 2.1). These local pH levels are well outside the physiologic range and havea destructive effect on tissue.The hypothesis is that the cancerous tissue is more sensitive to than normal tissueextreme pH levels and is thus selectively killed. It is also thought that the change in ionconcentrations permanently depolarizes cancer cell membranes, causing their furtherdestruction. Last, proponents of the technique suggest that the EChT process may alsogenerate heat shock proteins around the cancer cells, inducing the body’s own killer cellsto better target the tumor.The technique has reportedly been applied with success, mostly in China and Japan, forthe treatment of lung, breast, and bladder cancers. The technique has been used primarilyin conjunction with systemic or topical chemotherapy agents (e.g., adriamycin), whichbecause of their polar nature may be attracted by the electrodes and concentrate at thetumor site. Yuling [2000] reviewed the experience at 108 hospitals of treating 7642 patientsof malignant tumors with EChT between 1978 and 1998. Yuling reported complete remissionin 33.2% of the cases and partial remission in 42.8% of the cases, concluding that the