Implantable device and method for the electrical treatment...

Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Electrical therapeutic systems

Reexamination Certificate

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Reexamination Certificate

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06738663

ABSTRACT:

BACKGROUND OF THE INVENTION
Cancer is one of the major causes of hospitalization and death worldwide. Many of the therapies applied to cancer treatment are either ineffective or not well-tolerated by the patient. A promising approach that is little known but which has been successfully applied in Sweden, China, Germany, and Japan involves the electrical stimulation of a malignant tumor using direct current electricity. This has become known as electrochemical treatment (ECT). The clinical results have been obtained by applying electrical current via electrodes inserted percutaneously into the tumor. The treatment lasts for several hours during one or more sessions and can be used either alone or in conjunction with other therapy such as chemotherapy or radiation therapy. The therapy is well-tolerated in almost all patients.
This method is not to be confused with the electroporation technique which uses high voltages (~1 kV) with very short pulses.
The present invention overcomes some of the disadvantages of the ECT method mentioned above. It involves an implantable device consisting of a generator and one or more wires containing one or more electrodes. The electrodes are implanted in or near the tumor and the generator is implanted subcutaneously as close to the tumor as practical. The generator is powered either by an internal battery or via energy coupled to it from a source external to the body. The implantation is typically performed under local anesthesia and the device is left implanted for a period of months. Implantation permits electric current to be applied at lower levels for longer time periods, thus overcoming some of the drawbacks of the method above.
The nature of the implant results in some key differences from cardiac pacemaker design allowing for less stringent requirements on package and wire longevity. Other differences are manifested in the anchoring of the electrodes and in functions of the generator. The device complexity can range from very basic to sophisticated, including programmability of multiple parameters, patient alert mechanisms, sensors, and telemetry of information. The system may also include an external instrument for programming, telemetry reception, and data analysis. In one embodiment, chemotherapy drugs are infused from the generator in addition to the electrical stimulation.
Disease Prevalence
Cancer malignancies result in approximately 6,000,000 deaths worldwide each year. Of these, 538,000 were in the United States in 1995, representing over 23% of the total deaths in the United States. This number is up from 1970, when 331,000 deaths occurred. The estimated number of new cases in the United States in 1997 was 1,382,000. 40% of Americans will eventually be stricken with the disease and more than 1 in 5 will die from it. The percentage is increasing at about 1% per year and cancer deaths will soon outstrip deaths from heart disease. Much of the medical care cost from cancer results from hospitalization. In 1994 there were 1,226,000 hospital discharges in the United States related to cancer treatment.
The cost of cancer in terms of both human suffering and expenditures is staggering. Effective treatment methods which also result in fewer days of hospital care are desperately needed.
Cancer Treatment Methods
Primary treatment methods used in cancer therapy include surgery, radiation therapy, chemotherapy, hormone therapy and many others including bone marrow replacement, biological response modifiers, gene therapy, and diet. Therapy often consists of combinations of treatment methods. It is well known that these methods may result in sickness, pain, disfigurement, depression, spread of the cancer, and ineffectiveness. Despite recent announcements of potential pharmaceutical “cures,” these may work well in animals and in humans in certain cases, but researchers are cautious in overstating their effectiveness.
The therapy made possible by the novel devices described in this report is seen to have many benefits, including:
They may be used for either the primary treatment of neoplasms or during regression.
They require a single implant procedure, not repeated applications of invasive therapy, an important consideration in seriously ill individuals.
This and the lack of leads passing through the skin reduce the chance of infection.
Slow application of lower levels of current is preferable to larger quantities of charge over a short period of time. Extended use may prevent future metastases.
They have no disabling side effects as are found with chemotherapy or radiation therapy.
Their use is suitable in conjunction with other therapies.
Minimal hospital stays are required.
The device cost and complexity are low relative to pacemakers.
Since the therapy delivered by these implantable devices is based on the theory and clinical experience of B. E. Nordenstrom and others, their work and conclusions are first summarized below.
Early and Related Studies of Electrical Current in Tumors
Reis and Henninger caused regression of Jensen sarcomas in rats in 1951 using direct current and applied the technique to one patient with vulvar cancer. Lung tumors were first treated with direct current by Nordenstrom as reported in a 1978 publication. Experiments using small amounts of direct current to inhibit tumor growth were performed by Schanble et al. as well as others. Srinivasan et al. mention the possibility of controlling malignant tumor growth by direct current. Direct current has been used to coagulate blood in vessels leading to tumors and others (circa 1980) experimented with electrolytic destruction of tissue in animals using direct current (See Nordenstrom 1983). Mir et al. successfully treated tumors with Bleomycin and eight pulses of 100 microsecond width at 1 Hz with a field intensity of 1500 V/cm. They concluded that the minimum intensity required was 1100-1200 V/cm.
The Work of B. E. Nordenstrom
Bjorn Nordenstrom of Sweden, a pioneer and inventor in percutaneous needle biopsy and former Chairman of the Nobel Assembly, performed extensive research in electromedicine, developed a theory on the nature of bioelectricity and the healing process, and treated cancer in his patients as clinical proof of his theories. He called his model of biological control systems “biologically closed electric circuits” (BCEC) and sought to explain structural development in tissue injury and particularly around cancers. He found that treatment of cancer with DC electrodes changes the microenvironment of the cancer cells by electrophoresis of water and fat and electro-osmosis of water. The therapy that is based upon this principle is called “electrochemical treatment” (ECT). Direct current ionizes tissue (as does ionizing radiation). Ionization of tissue via direct electrodes affects normal and malignant tissues differently. Low energy levels build up the therapeutic dose of energy from the inside of the tumor.
Tumor cells are more sensitive to changes in their microenvironment than are normal cells. The effect of the application of direct current to cells with platinum electrodes has been summarized succinctly by Li et al.:
Water migrates from the anode to the cathode while fat moves in the opposite direction (this migration causes local hydration around the cathode and dehydration around the anode).
The tissue becomes strongly acidic at the anode and strongly alkaline at the cathode.
The distributions of macro- and microelements in the tumor tissue are changed.
Protein is denatured in the electrochemical process (hemoglobin is transformed into acid hemming around the anode and alkaline hemming around the cathode).
Chlorine, which is a strong oxidant, is liberated at the anode, whereas hydrogen, which produced local cavitation in the tissue, is liberated at the cathode.
By means of DC delivering adequate electric charge, a series of biological and electrochemical reactions take place in tissue. The cell metabolism and its existing environment are severely disturbed. Both normal and tumor cells are destroyed rapidly and completely in this altered environment.
Bere

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