Biomedical Engineering Reference
In-Depth Information
TABLE 7.8
Typical Parameters Used in Electrochemotherapy (Electroporation) Instruments
Clinical
Method of
Typical
Typical Current
Application
Current Delivery
Waveform
or Voltage
Deliver high doses of
Genetronics: six needle electrodes
Genetronics: voltage pulses, 100
µ
s
Maximum pulse amplitude
chemotherapeutic
in a circle in contact with tumor
in duration, delivered at a frequency
of 3 kV to yield
fi
field
drugs to cancerous
driven in opposing pairs at any
of 1 to 100 Hz
intensity of 600 to
tumors
one time
1200 V/cm
Daskalov et al. [1999]: pair of
Daskalov et al. [1999]: burst of eight
Maximum pulse amplitude
stainless-steel wires 0.8 mm in
biphasic voltage pulses of 50
µ
s
of 1.25 kV to yield
fi
field
diameter and 14 mm in length
duration per phase at a frequency
intensity of 330 to
spaced 5 to 30 mm
of 1 kHz
1250 V/cm
Electroporation therapy can be delivered to external tumors by placing electrodes on
opposite 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 properly
and measure the distance between them. For this type of tumors, needles are the preferred
type of electrodes. Since the use of only two needles creates an inhomogeneous
fi
field,
Genetronics uses an array of six needles to optimize the uniformity of the pore formation
around the cell [Hofmann, 2001]. Genetronics drives the needle electrodes in opposing
pairs because the resulting
fi
field is more homogeneous than that between opposing single
needles. After each electroporation pulse the polarity of the needles is reversed immedi-
ately and the needle pair is pulsed again. After each of these paired pulsings, the sequence
for the next electric
fi
field is rotated 60 degrees. A fairly uniform distribution, which maxi-
mizes pore formation in the cells over a circular section of the tissue, is generated by rotat-
ing the
fi
fi
field three times.
Electrochemical Therapy
Electrochemical therapy (EChT), also known as electrochemical tumor therapy or cancer
galvanotherapy consists of placing a platinum wire anode electrode into a tumor and a
number of similar cathode electrodes in the tumor's periphery.
100 mA dc is passed
between 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 processes
at the electrodes. Positively charged ions (e.g., H ,Na ) migrate to the cathode, resulting
in the formation of an extremely alkaline environment (pH
fl
12.9). At the same time, neg-
atively charged ions (e.g., Cl ) migrate to the anode, creating an extremely acidic envi-
ronment (pH
2.1). These local pH levels are well outside the physiologic range and have
a destructive e
ect on tissue.
The hypothesis is that the cancerous tissue is more sensitive to than normal tissue
extreme pH levels and is thus selectively killed. It is also thought that the change in ion
concentrations permanently depolarizes cancer cell membranes, causing their further
destruction. Last, proponents of the technique suggest that the EChT process may also
generate heat shock proteins around the cancer cells, inducing the body's own killer cells
to better target the tumor.
The technique has reportedly been applied with success, mostly in China and Japan, for
the treatment of lung, breast, and bladder cancers. The technique has been used primarily
in conjunction with systemic or topical chemotherapy agents (e.g., adriamycin), which
because of their polar nature may be attracted by the electrodes and concentrate at the
tumor site. Yuling [2000] reviewed the experience at 108 hospitals of treating 7642 patients
of malignant tumors with EChT between 1978 and 1998. Yuling reported complete remis-
sion in 33.2% of the cases and partial remission in 42.8% of the cases, concluding that the
ff
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