Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
  • A61N1/403—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
  • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
  • A61B18/14—Probes or electrodes therefor
  • A61B18/1492—Probes or electrodes therefor having a flexible, catheter-like structure, e.g. for heart ablation
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
  • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
  • A61B18/14—Probes or electrodes therefor
  • A61B18/16—Indifferent or passive electrodes for grounding

Definitions

• the present invention relates to a radiofrequency hyperthermia device using electric field capacitive coupled energy transfer for the treatment of intraluminar or intracavitary lesions consisting of a catheter with an electrode and at least one means for fixing the position of the catheter in a body cavity, at least one counter- electrode and a radiofrequency source connected to the electrode and counter- electrode.
• the catheter is adjustable to different body lumina or body cavities such as urethra, rectum, esophagus, vagina, stomach, bladder, etc.
• This radiofrequency hyperthermia device is useful for the treatment of inflammation or malignancies located within or close to these body lumina or body cavities by the use of radiofrequency (RF) fields in the range of 250 kHz to 45 MHz.
• RF radiofrequency
• Hyperthermia is widely used in medicine for the treatment of various diseases, especially of solid tumors.
• a major problem of the hyperthermia treatment is the regioselectivity of the radiofrequency (RF) field, especially for the treatment areas located within or in the close neighborhood of body cavities or body lumina.
• RF radiofrequency
• an ultrasound device with an elongate ultrasound transducer which shall be used for ultrasound imaging, radiofrequency hyperthermia, cryotherapy and temperature sensing in a tissue or a lesion.
• the principal idea of this device is the direct thermal contact with the surrounding tissue.
• Ultrasound frequencies normally used for such applications are well below 50 KHz.
• frequencies used in the device of the present invention are in the Megahertz range, for example 13.56 MHz.
• the wiring of the device of US 2001 7940 consequently isn't suitable for a use in the Megahertz range.
• This device does not use an indifferent electrode (counter-electrode) outside the body, the indifferent electrode is part of the applicator.
• the mechanism of action of this device is direct heat application on the wall of a body lumen, but no deep-heating of target tissue.
• ablation of the intraluminar superficial tissue is effected while with the inventive device no ablation takes place.
• Radiofrequency flow is through internal parts of the catheter (cf. fig. 5 parts 45 A and B), but not through the tissue.
• the system is working with piezo sources which are not needed for the present invention.
• US 2003 4506 A is directed to a catheter with a metallic tip electrode and a temperature sensor element.
• the catheter electrode is covered with an electrically isolating biocompatible outer layer. Only the inner layer is thermally conductive. Thus there is no galvanic conductivity with the surrounding tissue, as in the present invention.
• This catheter is used for heat ablation of unwanted tissue.
• a second electrode is co-introduced (bipolar electrode).
• the main field of application is the treatment of arrhythmias.
• the thermistor is electrically insulated towards the inner layer of the catheter and thus can measure the temperature only indirectly, consequently less accurately. This device is suitable for RF surgery (thermoablation) only.
• US 2008 249595 A describes a RF ablation catheter that is working similar like the two previous devices of the state-of-the-art. It is designed for use in vascular surgery. By its dimensions, the applied overall energy and its mechanisms it is not suitable for the treatment of tumors.
• the device disclosed in US 4,522,205 shall be used for the induction of thrombosis. By inflating the catheter balloon blood flow is blocked through the vessel lumen.
• This device uses direct current, but not radiofrequencies. Therefore it is not able to induce any heating in the surrounding tissue and cannot be used for hyperthermia purposes.
• US 5,257,635 is directed to a catheter wherein the polar electrode is partially covered by a heat-conducting layer and partially by a heat-insulating heat-sink layer.
• the problem of overheating is addressed by an intricate cooling system.
• Such a cooling system is not needed in the present invention as it does not heat the surface of the luminal wall.
• This device does not allow for a controlled heat application as energy dissipation will change over time.
• this device uses a different mechanism of action and is not suitable for hour-long hyperthermia treatment of tumors.
• the temperature measurement in the prostate is also a great challenge. Usually, the temperature measured inside the catheter balloon is far away from that of the actually treated tissue and the catheter material (mostly silicon rubber) is thermally well isolating.
• the objective of the present invention is to provide a radiofrequency hyperthermia device which can be used for hyperthermia treatment of various body cavities and body lumina.
• the present invention solves the challenges described above: 1.
• the present invention applies direct metallic or direct electrolyte contact with the lumen/cavity wall, without any thermal isolation (e.g. catheter rubber material). This makes the temperature distribution quite homogeneous and controllable.
• the present invention applies direct galvanic contact with the tissue, thus increasing electric conductivity in the treated surface in comparison to the path of the RF-cable by several orders of magnitude. This renders the RF- heating along the cable negligible, as it can be compensated well by the blood perfusion in the area.
• the temperature is measured directly on a good thermal (and electrical) conductor, which allows a preferably precise temperature measurement of the lumen/cavity wall. This is a safety issue (in order to avoid overheating of the lumen/cavity wall).
• the RF-current can be controlled better. Therefore the temperature distribution caused by the FR current is more homogeneous in the treated deep-situated tissue and the cancer treating electric field is also more effective.
• the catheter fixation is independent from the treatment electrode, i.e. from the RF electrode, so that a possible relocation caused by the treatment itself would not shift the catheter.
• the conventional locoregional hyperthermia modes by outside heating, are not sufficiently selective near air-containing body cavities / lumina.
• the basic selection factors tissue density, tissue impedance, tissue heat diffusion, blood perfusion, etc.
• tissue density, tissue impedance, tissue heat diffusion, blood perfusion, etc. are considerably modified by the cavities / lumina, the simple artificial or natural focusing mechanisms could be inadvertedly affected.
• the inventive catheter/applicator shall meet the following demands:
• Efficacy is measured by the temperature reached in situ [ 0 C] and the safety limit is determined by hot-spots (temperature in situ). The last item is a very important factor because the only adverse effects hyperthermia may cause are burns (hot spots). Temperature measurement in depth is necessary to avoid such internal burns which often may become quite dangerous. This is a major obstacle for quality guidelines in hyperthermia. Temperature is measured either invasively or by approximating it by complex methods like MRI. Temperature measurement is above all a safety issue but not essential for treatment.
• the heating in a patient is not as high as expected (large blood-flow as in the liver or the brain, or air cooling (breathing) as in the lung, or liquid-cooling (like in the kidney or the urinary track), it shows that hyperthermia was not applied, or not as it should be, and that no "temperature optimization occurred.
• the temperature could be reached, but the patient's tolerance limits the power to be applied, the temperature will be down regulated and again the prescribed temperature won't be reached. The same limit is effective when hot-spots arise outside the tumor. The energy uptake must be limited to avoid burns. In this case it is also problematic to comply with the temperature guideline. 3. Being able to measure the average temperature over a large area. The inhomogenities have to be counterbalanced and temperature adjustments (control) have to be oriented towards this average. Hot spots are not tolerated on the antenna surface.
• the applicator being identifiable and continuously controllable for documentation and traceability reasons.
• Fixing the applicator in the desired position during the treatment is mandatory. (Notably, the preferred treatment time is 2-3 hours.)
• the applicator shouldn't be used for several reasons: The hygienic problem, resterilization could damage/change the material of the applicator, the catheter can't be identified if necessary for any after-treatment investigations. (Notably, this is a treatment applicator, not for diagnostic purposes, therefore higher safety standards apply than for a normal catheter endoscope.)
• the present invention relates to a radiofrequency hyperthermia device using electric field capacitive coupled energy transfer for the treatment of intraluminar or intracavitary lesions, preferably tumorous (malignant or benign) lesions or other indications sensitive for heat/electric-current.
• the inventive device comprises a catheter with an electrode and at least one means for fixing the position of the catheter in the body cavity, at least one counter-electrode and a radiofrequency source connected to the electrode and the at least one counter-electrode, wherein the electrode fixed to the catheter is a good heat-conductor metallic electrode and wherein the material of the catheter preferably has a relative dielectric constant ⁇ r larger than 2 ( ⁇ r > 2) and preferably its dielectric loss tg ⁇ is below 3 • 10 '4 (tg ⁇ ⁇ 3 • 10 "4 ) and wherein the at least one counter-electrode is positioned extracorporeal ⁇ , preferably opposite the area to be treated so that the area to be treated is preferably located between the electrode and the counter-electrode.
• the target tissue such as a malignant tumor tissue has a higher complex or overall conductivity (admittance) than healthy tissue and consequently has a higher absorption rate of the current going through it in comparison to healthy or normal tissue so that the Joule heat is mostly generated when the current passes the target tissue.
• RADIATIVE HYPERTHERMIA operates by simple energy absorption; the patient is independent from the electronic device.
• CONDUCTIVE HYPERTHERMIA system like the inventive device the patient is part of the electric circuit (condenser) like a dielectric material. This allows a tight and strict control. [Note: remember: that the patient control is crucial, so RADIATIVE HYPERTHERMIA needs MRI during treatment, CONDUCTIVE HYPERTHERMIA does not request such sophistication.]
• Common RADIATIVE HYPERTHERMIA uses short wavelength, high frequency [70 MHz - 2400 MHz]. CONDUCTIVE HYPERTHERMIA uses 13.56 MHz, at least five times lower. [Note: the penetration depth of the electromagnetic waves into the body is inversely and sharply depends on the frequency. CONDUCTIVE HYPERTHERMIA penetration is around 20 cm, RADIATIVE HYPERTHERMIA (depending in its actual frequency) does not reach one quarter of it on the same patient conditions.]
• CONDUCTIVE HYPERTHERMIA uses artificial focusing, for what very sophisticated software and hardware is necessary.
• CONDUCTIVE HYPERTHERMIA has a self-selective (self-focusing) facility by the RF- conduction selection. [Note: the cancer tissue has higher conductivity than the healthy one, so the RF-current which is used by CONDUCTIVE HYPERTHERMIA automatically chooses that way.]
• RADIATIVE HYPERTHERMIA has no correction of its focus, so the danger of the misfocusing or the larger one than necessary is exists. CONDUCTIVE HYPERTHERMIA corrects it automatically by the above self-selection.
• the inventive radiofrequency hyperthermia device uses target feedback signal modulation based on Chelomey's pendulum theory as disclosed in PCT / EP 2009 / 007342. This method ensures that the focus of hyperthermia induction selectively and constantly remains in the targeted tissue, not depending anymore on shifts in the arrangement of the treatment devices or body movements of the patient.
• the deeply situated diseased tissue is heated by hyperthermia in a directed manner while the surface temperature of the wall of the body lumen or body cavity remains substantially unchanged. Consequently, all the known adverse effects from catheters of the state-of-the-art as e.g. burns and sticky glue when removing the catheter cannot occur with the inventive device. As there is no temperature gradient from the lumen wall to the diseased tissue as in the devices of the state-of-the-art a substantially homogeneous heating of the overall target tissue can be achieved, something impossible with conventional catheters.
• the present invention relates to a radiofrequency hyperthermia device which is useful for the treatment of intraluminar or intracavitary lesions
• a catheter with an RF-electrode and not a radiative antenna or antenna electrode wherein the RF-electrode has no thermal isolation and has a metallic part which is galvanically connected to the tissue and wherein said metallic part allows temperature measurement and a homogeneous temperature distribution, an RF- independent temperature sensor which is isolated from the ground by at least 4kV, at least one counter-electrode and a radiofrequency source connected to the RF- electrode and counter-electrode(s), wherein the RF-electrode fixed to the catheter is a heat-conductor metallic electrode and wherein the counter-electrode is positioned extracorporeally opposite the area to be treated so that the area to be treated is located between the electrode and the counter-electrode(s).
• the RF-electrode of the catheter which is a heat-conductor metallic electrode has a heat-conductivity above 180 W/mK and preferably above 200 W/m/K.
• the inventive radiofrequency hyperthermia device has a microchip-controlled individual calibration and a data-collector. Also preferable is an embodiment of the radiofrequency hyperthermia device wherein a personalized treatment-procedure is programmed as well as single-use guard and documentation.
• the catheter material is most preferably a biocompatible flexible high-temperature tubing, preferably silicon or silicolatex.
• radiofrequency source there is no limitation but preferred ranges. Any common radiofrequency source can be used as long as the radiofrequency source is able to provide radiofrequency fields in the range of preferably 100 kHz to 50 MHz, and could be safely controlled according to the treatment demands.
• the range of frequencies supplied can actually be from below the detection limit (effectively measured as 0 MHz) to 500 MHz, preferably from 100 kHz to 100 MHz, more preferably from 250 kHz to 45 MHz, still more preferably over 1 MHz and most preferably 13.56 MHz or any value obtained by multiplication or division by an integer, preferably division by 40.
• the following frequencies are most preferred: 13.56 MHz, or 1/100, 1/40, 1/20, 1/10, V 2 times, 2 times or 3 times, etc.
• this value (i.e. 6.78 MHz, 27.12 MHz or 40.68 MHz).
• the lower frequencies are preferred for creating definite conduction conditions instead of radiation in the cavity/lumen.
• Frequencies below 200 kHz or even below 100 kHz are not preferred since such frequencies and especially frequencies between 5 kHz and 50 kHz are used for direct contact heating which is not applied in the present invention.
• the frequency also called carrier frequency
• the frequency is amplitude- modulated in the audio range.
• the power supply to the electrodes can be symmetrical (coaxial) and continuous, or symmetrical (coaxial) and pulse supplied.
• the power supply to the electrodes can be asymmetric (non-coaxial or partly coaxial) and continuous, or asymmetrical (non-coaxial or partly coaxial) and pulse supplied.
• the solution of the present invention constrains an RF-current through the complete cross section of the body or a selected part of the cross section, and selects the tumour or the diseased area automatically by its conductivity (impedance).
• the tumour could be far away from the lumen, the only requirement is that the arrangement has to be such that the current must flow through the area which should be treated, i.e. which should be heated. Tumors or diseased regions which are far away from the intracorporeal electrode cannot be treated by the embodiments of the state of the art.
• far away refers to a maximum of 1 cm (like the embodiment of US 2003 4506 A) or to a maximum of about 4 cm (like the embodiment of US 2001 7940 A) while the present invention can still effectively treat regions which are 20 cm away from the intracorporeal electrode.
• Fig. 12A refers to an embodiment of the present invention showing a cross section of a human body.
• the dot in the middle from where the conductive current lines start indicates the location of the intracorporeal electrode which is located in the catheter which is inserted into a body lumen such as urethral tract, anus and vagina.
• the bold line which partly surrounds the lower part of the body cross section stands for the at least one extracorporeal counter electrode.
• the lines between the intracorporeal electrode and the counter electrode are the conductive current lines which cover the area which should be treated.
• the RF-current flows through the full cross section (in Fig. 12A the almost half-coaxial arrangement is shown) and the treatment is made by the impedance selection of the organs (tissues).
• the diseased or tumorous tissue has not to be in close vicinity to the intracorporeal electrode which means to the catheter.
• the area which should be treated which means which should be heated up can be located anywhere in the area covered by the conductive current lines and is preferably located between the electrode and the counter electrode.
• the area to be treated is preferably located within the shortest distance of electrode and counter electrode. In contrast to the present invention, the area which requires treatment has to be located close to the catheter in the embodiments of the state of the art.
• Fig. 12B refers to a state of the art embodiment according to US 2001 7940 A. Shown is the cross section of a human body.
• the round spot (dot) in the middle indicates the location of an intracorporeal electrode which is incorporated in a catheter.
• the dotted area around the middle dot, i.e. around the catheter indicates the area which can be heated by the catheter and this area has a maximum radius of about 4 cm.
• the diseased area has to be within a radius of about 4 cm around the catheter otherwise said area cannot be treated by the embodiment according to US 2001 7940 A.
• this area is heated by a heat gradient which means that the area close to the catheter is heated more than the area farer away, i.e. 3 cm or 4 cm away from the catheter.
• the present invention does not transport heat, the present invention does transport energy which is converted to heat in the diseased area using the difference in impedance which means the different in the electric conduction properties. This leads to a higher or almost selective conversion of energy into heat in the diseased area or the diseased tissue such as the tumor and selectively or preferably heats up the diseased or tumorous tissue.
• Fig. 12C refers to a state of the art embodiment according to US 2003 4506 A. Shown is the cross section of a human body.
• the round spot (dot) in the middle indicates the location of an intracorporeal electrode which is located in the catheter.
• the circle close around the middle dot indicates the area close around the catheter which is intensively heated in order to cause necrosis.
• the heat is concentrated on the near area of the catheter which is the near area around the lumen into which the catheter is inserted, making ablation (over 60 0 C temperature) at this area (burning-out solution). Only the area about 1 cm around the catheter can be treated by this embodiment so that the catheter must be in close vicinity to the area which requires treatment.
• the treated body cavities or body lumina are all regions which can be reached by catheters such as urethra, rectum, oesophagus, vagina, stomach, bladder, oral cavity, ear canal etc. and the catheter is adjusted in size to the body lumen or body cavity which should be treated.
• catheters such as urethra, rectum, oesophagus, vagina, stomach, bladder, oral cavity, ear canal etc. and the catheter is adjusted in size to the body lumen or body cavity which should be treated.
• lntraluminar or intracavitary lesions which can be treated by means of the inventive radiofrequency hyperthermia device are, for instance, cancer in prostate central/periphery area, benign prostate hyperplasia, prostatitis, oesophagus cancer, bladder cancer, bladder cyst, stomach cancer, cervical carcinoma, vagina cancer, vagina cysts, cancer or papilloma-virus infected cervix-uteri, colon/rectal carcinomas, anus-carcinoma, etc.
• oncothermia refers to the treatment of intraluminar or intracavitary lesions in living bodies (humans and animals) by heat and electric field combination, induced by the radiofrequency current flow through the treated volume.
• hypothermia refers to heating up a target higher than the environment equilibrium (homeostatic) temperature.
• the catheter used as component of the radiofrequency hyperthermia device is resistant against aggressive body fluids and electrolytes, so that such fluids or electrolytes do not affect the catheter (and its built-in electronics) during the treatment and do not alter the properties of the catheter during the treatment.
• Modified common catheters such as Foley-catheters can be used as long as an electrode can be positioned on the end of such a catheter and as long as direct metallic or direct electrolyte contact is possible with the lumen/cavity wall and as long as now thermal isolation is present.
• the electrode and the temperature sensors as well as the RF-filters are built in the Foley catheter/applicator, for example, and conductively connected to the radiofrequency source and to the controlling device.
• the catheters are by their size and shape the same as normal Foley or other prostate catheters.
• the size could be any (e.g. which are in standard use in the urology) but for prostate the 16 Ch size is optimal for most of the cases.
• the basic balloon catheter is produced by various catheter-makers and the special applications and outfit set is made additionally in order to provide the inventive hyperthermia device as disclosed herein.
• the material could be any, but it has to tolerate temperature at lest 8OC. (Preferable silicon or silco-latex. Presently we use the 16Ch Foley silco-latex Foley catheter from Company Ruesh.)
• the catheter or the radiofrequency device preferably further comprise at least one means for fixing the position of the catheter in the body cavity or body lumen, wherein this at least one means is not part of the RF electrode itself.
• the catheter and especially the treatment electrode are fixed in its position even if shifting of the treated tissue occurs during treatment.
• the full catheter is microchip-controlled (built-in processor in its plug) for controlling the single use, for individual calibration and for registration and documentation for later statistical and/or legal use.
• the catheter is able to provide the RF signal, preferably the modulated RF signal, without heating the catheter itself. This is very important for avoiding tissue burns which is in direct contact to the catheter surface along the path to the treatable area.
• the catheter material (of course except the electrode) is similar to an isolator and consists of a material which could also be used for isolators.
• the term "high relative dielectric constant” refers to a relative dielectric constant ( ⁇ r ) larger than 1.0 ( ⁇ r > 1.0), more preferably larger than 1.5 ( ⁇ r > 1.5) and most preferably larger than 2.0 ( ⁇ r > 2.0).
• the term “low dielectric loss” refers to a dielectric loss (tg ⁇ ) lower than 11 -10 "4 (tg ⁇ ⁇ 11 • 10 "4 ), more preferably lower than 6-10 "4 (tg ⁇ ⁇ 6 • 10 "4 ) and most preferably below than 3-10 "4 (tg ⁇ ⁇ 3 • 10 "4 ).
• the electrode or RF electrode or treatment electrode at the end of the catheter is in the form of a metal cylinder, preferably having the same or identical diameter as the catheter tube.
• the RF electrode is located at the end of the catheter tube between the guiding head of the catheter tube and the balloon or below the guiding head and below the balloon or within the balloon.
• the RF electrode is made of a good heat-conductor metallic cylinder. Its material is preferably selected from the group comprising copper, silver, gold, aluminium or iron, or their alloyed, coated, powder-manufactured or cermet forms. Most preferred is pure copper as material for the RF electrode.
• the good heat conduction is essential for the temperature control, and a good electric conduction is essential for the equipotential surface of the inserted electrode.
• Cupper has both the properties, as well as easy to install and cheap (compare to the platinum, used by D2.)
• the surface of the electrode is coated by gold (better gold-silver alloy) for corrosion resistance and silver for antibacterial effect
• the RF electrode is coated with gold or silver or a gold-silver alloy so that such coated aluminium or copper electrodes are more preferred.
• the at least one counter electrode is preferably self adhesively fixed, and it should be well in contact with the skin all the time.
• the coating layer shall cover entirely (no leakages, no porosity) the base material (for being biocompatible), except if the cylinder is made from a biocompatible material as for example silver or gold. (Naturally, in the last cases no coating is necessary.)
• the RF-source has to be well tuneable for different (wide range) body impedances (10 ⁇ ⁇ 500 ⁇ range), and having real-time control of tuning (retuning if it is necessary due to the change of the tumour by distortion process).
• the RF-current has modulation (for example as disclosed in PCT / EP 2009 / 007342), which has to be a speciality of the RF-source.
• the output RF-power is regulated by the temperature, (sent by the sensors built in the catheter).
• the catheter contains or comprises means for temperature measurement.
• Said means for temperature measurement could be thermometers which are able to measure the temperature accurately, preferably measure the average temperature over a large area which is at least the treated area.
• the temperature measurement has to be "RF-tolerable” in a wide frequency range (up to 45 MHz), so its measured value should not be biased by the active field or its fluctuations (derivatives).
• the means for temperature measurement could be a thermo-pair, a thermistor, a platinum-resistor or any other temperature sensing structure / element. Prefered are micro-thermistors.
• the measured temperature is preferably filtered with high level filters built in the catheter. Their role is to avoid incorrect thermo-signals caused by the RF-field or by its induced currents, which could bias the measured signal.
• This filter is preferably a serial resonance circuit (or simply a condenser with low admittance for the given frequency) tuned to the applied frequency. Its resonance/conduction short circuits the actual RF, but does not modify the measuring signal of the thermo-element. This solution keeps the thermo-signal correct and unaffected from RF-effects.
• the filter is preferably built in directly at every sensor (preferably, the smallest SMD parts are of 0.2 mm size) and preferably in the end-plug of the catheter to block further modification by induction.
• the inventive radiofrequency hyperthermia device comprises a temperature sensing electric system.
• the temperature sensing electric system is preferably highly isolated (at least 4kV) for safety reasons.
• the thermistor resistivity is not measured by DC, which could be sensitive for RF- noises.
• the thermo-signal is measured with low frequency RF, far from the treatment frequency, (preferably 80 kHz at 339 kHz carrier frequency and in the audio modulation range) but emitting a sufficiently strong signal for the preferred isolation transformer or the opto-connection transmission for isolation with the 4 kV standard value.
• the wires or cables as well as all the electronic parts which connect the intracorporeal electrode with the RF source, including the non-inert part of the thermo-sensors, are completely isolated from the body or body fluids by the use of a non-conductive material such as plastics or silicon and preferably flexible biocompatible elastosil N2010 (commercially available from manufacturer: Wacker, Germany, www.wacker.com).
• the temperature is measured in the far ends of the good heat- conductor cylinder (the RF electrode), measuring the average temperature of the treated surface.
• the applied thermo-sensor has to be as tight or as close as possible to the surface and to the treated tissue.
• the sensors are in direct tight contact with the RF-antenna cylinder, preferably run through the catheter tube to the outside of the tube contacting the inner surface of the cylinder.
• the cables are arranged in a spring-like loop within the catheter tube so that the length of the cables is not fixed and can be variable within a certain range provided by the diameter of the loop and the number of loops.
• thermo-wiring is a twisted pair and is electronically protected (shielding, filtering, time-sharing, etc.).
• the full cable branch can be removed in case of emergency with a definite direct pull.
• said definite direct pull is connected with the immediate deflation of the catheter balloon in order to remove the complete catheter immediately.
• the inventive radiofrequency device contains or comprises at least one device for treatment control with preprogrammed protocols, web-browser facility for remote control of the treatment by any web-access (laptop, PDA, MDA, phone, PC, Mac, etc.).
• the counter- electrode is positioned extracorporeal ⁇ directly on the patient's skin and can be any commonly used electrode for hyperthermia applications using radiofrequency fields in the range of 250 kHz to 45 MHz.
• the inventive catheter is fixed in its position in a body lumen or body cavity by inflating a balloon wherein the balloon is inflated in the body cavity distally adjacent to the insertion path of the catheter. Therefore the distance between the non-isolated electrode portion of the catheter and the balloon at the catheter tip may vary, according to the intended therapeutic use.
• the balloon is not inflated in the body lumen to be treated but in the cavity thereafter, for example, in the case of a prostate or urethra treatment in the bladder.
• This method has shown to provide an improved means to fix the catheter in the desired position and secures that the catheter electrode, the tissue to be treated and the at least one counter-electrode are located on a coaxial line.
• the catheter when fixed in a body lumen in such a way does not block the flux of physiological liquids, for example of urine in prostate treatment.
• This is a great advantage over other state-of-the-art catheters.
• the flux of body fluids cools the walls of the body lumens, thus preventing unnecessary heating (and in the extreme case burns) of non-target tissue.
• it provides comfort to the patient during a 2 - 3 hours' treatment session that no urine is held back in the bladder.
• Figure 6 shows the arrangement of the inventive radiofrequency hyperthermia device with the RF source, the catheter inserted through the penis into the prostate and the counter-electrode(s) positioned extracorporeal ⁇ like a half-belt around the patient's back.
• This arrangement is useful for the treatment of prostate cancer.
• a similar arrangement is shown in Figure 7.
• the electrode is positioned in the prostate while the counter-electrode in Figure 6 is positioned directly on the patient's skin dorsal around patient's back from one lateral side to the other lateral side like a half-belt. Further positions of the at least one counter electrode can be on the buttock or both buttocks or on the limb (more precise on the thigh) as disclosed in the legend to Fig.
• the position of the counter electrode or counter electrodes is selected in accordance with the position of the area to be treated and is selected in the way that the area to be treated is well located between the electrode and at least one counter electrode so that the conductive current lines run well through this area.
• the area to be treated is located on the way of the arrow shown in Fig. 10A and Fig. 10B and the counter electrode or counter electrodes have the optimal position when the highest density of conductive current lines which is indicated by the arrow in Fig. 1OA and Fig. 1OB run through the area which should be treated such as the diseased or tumorous area.
• the extracorporeal counter electrode surrounds to intracorporeal electrode at least 120° and preferably 180°.
• the extracorporeal counter electrode surrounds the intracorporeal electrode more than 180 degree, i.e. more than half around the intracorporeal electrode and preferably more than 240°, preferably more than 300° and most preferred almost 360° which means that the extracorporeal counter electrode surrounds completely the intracorporeal electrode.
• 11A refers to a coaxial arrangement where the intracorporeal electrode is as usual inserted into the urethral tract or any other body lumen such as vagina or anus (anal orifice) and the extracorporeal counter electrode or counter electrodes are positioned outside the body directly on the patient's skin.
• a coaxial arrangement means that the counter electrode(s) goes completely around the electrode. The electrode is indicated in the middle of the body cross section and the counter electrode is the outer circle. Within this circle and from the inner circle the RF current lines are shown. Such an arrangement will provide an almost equal distribution of the conductive current lines. In the half-coaxial arrangement the electrode is still positioned in the inner circle while the counter electrode(s) goes only half around the electrode as indicated by the lower half circle in Fig. 11 B.
• Fig 11 C refer to a non-coaxial arrangement where the counter electrode surrounds the electrode only partly as indicated by the upper bold line which is the counter electrode.
• the conductive current lines between the counter electrode and the electrode are also indicated.
• the area treated by radiofrequency hyperthermia is the area between the electrode (also referred to as intracorporeal electrode) and counter-electrode (also referred to as extracorporeal counter electrode or extracorporeal electrode)
• the diseased area can regioselectively be treated by selecting a suitable position and size of the counter-electrode in relation to the intracorporeal electrode.
• the left picture in Fig. 6 shows the treated area as a triangle between the intracorporeal electrode and the half-belt counter-electrode.
• the left picture of Figure 7 shows that the treated area is the whole area between the intracorporeal electrode and the outer counter-electrode in form of a full belt electrode which goes completely around the intracorporeal electrode.
• the counter-electrode is positioned opposite the area to be treated in order to let the RF current flow through the desired region.
• the counter-electrode is preferably in the form and shape of the belt or part of a belt (half-belt, etc.) or the at least one counter-electrode is incorporated into a belt or bandage which can easily be fixed, preferably tightly fixed to the patient's body at a similar height to where the intracorporeal electrode is located.
• the counter- electrode or the counter-electrodes incorporated into a bandage or medical belt, is also called belt electrode or bandage electrode herein.
• the belt electrode or bandage electrode is flexible, expandable, elastic and/or stretchable, can be provided in any desired size and shape and can be easily used and fixed to the patient's body.
• the complete belt electrode or bandage electrode can form the conductive part of the counter-electrode or only parts of the belt electrode or bandage electrode can form the conductive area of the counter- electrode.
• These conductive parts or conductive areas can be made in any desired arrangement, shape, number and size.
• the conductive parts or conductive areas of the belt electrode or bandage electrode are flexible, expandable, elastic and/or stretchable so that they can adhere tightly to the area of the body which should be treated.
• Figure 8 shows a belt electrode or belt-like shape electrode.
• the areas within the dotted lines and the areas with wavy lines indicate the conductive part of the electrode while the left belt electrode has two and the right belt electrode has four conductive parts or electrodes.
• the belt electrode or bandage electrode has the conductive part only dorsal (back-belt) or only lateral (side-belt) or only ventral (front-belt) or dorsal and lateral (e.g. half belt) or dorsal and ventral or ventral and lateral (e.g. half belt) or dorsal and ventral and lateral or completely around the patent's body (full belt).
• the at least one counter- electrode comprises a flexible preferably porous material, carrier or support coated with conductive metal.
• the carrier or support or material and especially the solid carrier or solid support or solid material used for manufacturing the counter-electrode is made of plastic, polymers or natural substances such as biopolymers and is coated with a conductive material such as a conductive metal or metal alloy.
• said coated carrier or coated support or coated material is porous and allows a liquid to pass through said carrier or support or material.
• the coated carrier or coated support or coated material is flexible, i.e. does not have a definite or predefined shape and is able to follow the uneven curvatures of the human or animal body.
• a conductive metallic net or a conductive metallic network can be used manufactured of at least one conductive metal electrode material.
• Such metallic nets or metallic networks do preferably not comprise any backbone such as a polymeric network structure.
• the metallic net or network is preferably a woven structure of metallic fibres having very similar properties as the coated flexible material such as a coated textile.
• the conductive metallic net or network is flexible, elastic or stretchable, allows water and other fluids as well as gases to move through it, can be folded without negative effect concerning conductivity and is able to cover uneven, fractal and/or percolative surfaces. Consequently, all kind of metallic nets and networks having the afore-mentioned properties of the conductively coated materials such as the conductively coated textiles are useful for manufacturing the counter- electrode.
• porous refers to the ability that the coated carrier or coated support or coated material allows water and any gas to move through said coated carrier or coated support or coated material.
• the pore size can be up to 0.1 mm or even larger.
• a porous textile is suitable as the flexible material or flexible, elastic or stretchable carrier or flexible, elastic or stretchable support.
• any porous material having flexibility similar to the flexibility of a woven or non-woven textile could also be used in the present invention.
• any kind of textile, woven textile, non- woven textile and even non-textile material is suitable as flexible porous material.
• Such a flexible porous material can also be described as a flexible porous solid support or flexible porous solid carrier.
• Such materials, carrier or supports are not limited by a specific shape and have the consistency and/or texture of piece of textile or a piece of fabric or drapery. Consequently, all known natural and artificial materials such as polyamide (Nylon ® ), poly- ⁇ -caprolactone, poly-para- dioxanones, polyanhydrides, polyhydroxymethacrylates, fibrin, polyetherester, PEG, poly(butylene terephthalates), polycarbonates, poly(N-vinyl)-pyrrolidone, polyvinylalcohols, polyesteramides, polyethyleneoxide, polypropyleneoxide, polyurethanes, fibrinogen, starch, collagen, zein, casein, ⁇ -cyclodextrins, polyacrylates, polyacrylamide, polyimides, polyethylene, polypropylene, polytetrafluoroethylene, fluorosilicones, rayon, polysulphones, silicones, polysiloxanes, polyvinyl halogens and copoly
• materials, carrier or supports such as these mentioned before which provide a good adhesion for the metallic coating.
• materials, carrier or supports which are manufactured of or which consist of a plurality of single fibers like a woven textile wherein one set of the single fibers extends along more or less the complete length of the textile in a substantially parallel manner while the other set of fibers is arranged in a substantially parallel manner diagonal to the first set of fibers.
• fibers having a length which is similar to the length of the textile comprising said fibers are preferred.
• the single fibers of the material, carrier or support are coated like a tube, meaning that not only a part of the surface of the fiber is coated but the coating is applied all around the fiber.
• such material, carrier or support is percolative and/or fractal or has a percolative and/or fractal structure without any discontinuity between the in and out cables of the RF source means.
• the metallic nets or the coated carriers are so flexible that they are able to cover uneven, fractal or percolative surfaces or that they are able to follow the structure of uneven, fractal or percolative surfaces.
• the conductive metal coating is preferably a multilayer coating.
• one of the layers is silver which has a good antibacterial effect and provides for good radiofrequency (RF) conduction.
• RF radiofrequency
• silver has an anti-odor effect together with moderate anti-perspiration activity. This makes silver preferred for cosmetic, medical and well-being applications.
• the textile can be coated by an extra plastic layer for galvanic isolation. This should preferably not be a continuous layer, but a layer on the fibers only in order to keep the porous structure free and open. If the device is double isolated, direct metallic contact could be used.
• the multilayer structure coats the fibers co-axially and perfectly continuous. If the metal layer-making technology is a dipping electroless process then the crossing of individual fibers could be also perfectly coated individually fiber by fiber, if it is galvanic, and then the crossings could be coated only as a cross, not keeping the individual fiber co-axial structure.
• the plastic coating has to be a dipping process with such a surface tension of the bath which prevents the isolation of the metallic coated fibers at their crossing but only coats their outer surface, wherein the coating, however, does not fill the pores so that the material remains porous.
• the counter-electrodes are suitable for application to all parts of the human or animal body. For this reason there is a need for a flexible counter-electrode that can conform to the contours of the body.
• the coated flexible carrier or the flexible metallic net acts as a counter-electrode for the treatment of a large and/or uneven, fractal and/or percolative surface while these carriers or metallic nets can easily be fixed on said surface via a belt or bandage, or the like.
• the preferred inventive flexible counter-electrode of the present invention is able to fulfill this requirement, i.e. to be conductive, flexible, foldable, porous and able to cover uneven, fractal and/or percolative surfaces smoothly like a cloth following the contour of the surface.
• the flexible counter-electrode is formed from a conductive metal coated flexible material or a metallic network that can be folded or formed freely even into a cylinder-like shape and can be placed around the patient's body.
• the inventive electrode can conform to gradual and sharp curvatures. For example, in the case of sharp curvatures it can easily conform to the shape of an abdomen by being wrapped around the abdomen. Alternatively, in the case of gradual curvatures it can conform to the shape of the torso.
• the inventive flexible electromagnetically coupled counter-electrode is lightweight and therefore can be shaped as to cover a large area, such as the torso, without causing discomfort to the patient due to excessive weight of the counter-electrode. This allows for the treatment of large areas in a single treatment session. Also the flexibility of the energy transfer means allows for a good contact between the counter-electrode and a large application area, for example, the torso.
• the inventive flexible electromagnetically coupled counter-electrode is also porous. This allows for natural cooling of the treatment area due to exchange of heat through the energy transfer means via convection. Also a simple external air cooling system, for example a directed air flow from a fan or a jet, can be used to cool the application area to prevent burning and maintain the patient's comfort.
• the porosity of the counter-electrode also allows for the exchange of fluids through the counter-electrode. Thus perspiration can evaporate naturally through the porous counter-electrode and therefore increase the patient's comfort.
• inventive flexible counter-electrode Due to the simple construction of the preferred inventive flexible counter-electrode it can be provided as a single-use disposable electrode or could be produced to specification for an individual patient. A further advantage of the inventive flexible counter-electrode is that there is no requirement for a bulky, rigid-frame and difficult to operate bolus electrode applicator.
• the radiofrequency hyperthermia device of the present invention can be used to treat intraluminar or intracavitary lesions, cancer, tumors and malignancies.
• the intraluminar or intracavitary area in need of treatment could be an area within the urethra, prostate, penis, rectum, esophagus, vagina, uterus-cervix, anus, rectum, colon, sigma, stomach, bladder, oral cavity or ear canal.
• the inventive radiofrequency hyperthermia device is useful for the prophylaxis, especially after-treatment or prophylaxis after a successful cancer treatment in order to prevent the development of a new cancer or new tumors and the treatment of cancer, benign and malignant tumors, especially urethral lesions, malignant or benign prostate cancer, benign prostate hyperplasia, rectum lesions and rectum cyst, rectum cancer, colon cyst, colon cancer, anus cancer, anus cyst, oesophagus lesions and oesophagus cancer, cervical carcinoma, vagina cyst, vagina tumors, penis cancer, stomach cyst, stomach cancer or bladder cyst and bladder cancer, adenoma of the prostate, myoma and fibromyoma, gastric ulcer, duodenal ulcer.
• inflammatory diseases and/or states can be treated with the inventive hyperthermia device, or a prophylactic use can be made.
• Inflammatory urogenital conditions that may be treated with the inventive device include, but are not limited to acute and chronic cystitis, urethritis, reflux-uropathy, urinary tract infection without definite localization, acute and chronic prostatitis, prostatocystitis, epididymitis, vaginitis, salpingitis, oophoritis, vulvovaginitis, ovarial cysts, endometriosis.
• symptomatic treatment of urogenital infections can be carried out with the inventive device, for example in infections with Chlamydia spec.
• Candida spec Trichomonas vaginalis, Herpes simplex virus, Neisseria gonorhoeae, Treponema pallidum, Gardnerella vaginalis, human papilloma virus, hepatitis B virus, Hemophilus ducreyi, Mycoplasma hominis, HIV.
• Inflammatory gastrointestinal conditions that may be treated with the inventive device include, but are not limited to oral cavity diseases, pyrosis, oesophagitis, acute and chronic gastritis and duodenitis of various origin, Crohn's disease, ulcerative colitis, acute and chronic gastroenteritis and colitis, irritated intestine syndrome with and without diarrhea, anal and rectal fissurae and fistulae, hemorrhoids, acute and chronic pancreatitis, appendicitis, acute and chronic diverticulitis.
• intraluminar or intracavitary lesions also refers to cancer, tumors and malignancies or malignant diseases of gastroenterological, gynecological, andrological and otolaryngological cavities and lumina.
• the present invention is directed to a catheter for a radiofrequency hyperthermia device which is useful for the treatment of intraluminar or intracavitary lesions as defined herein consisting of an RF-electrode, wherein the RF-electrode has no thermal isolation against the contacted tissue and has a metallic part which is galvanically connected directly or by conductive electrolyte indirectly to the tissue and wherein said metallic part allows preferably precise temperature measurement and a homogeneous temperature distribution, and has an RF-independent temperature sensor which is isolated from the ground by at least 4kV, wherein the RF-electrode fixed to the catheter is a heat-conductor metallic electrode.
• precise refer to a temperature measurement in 0.1 0 C steps.
• the metallic electrode is coated with an antibacterial and anti- stickiness coating for avoiding infections and/or a sticky burn-fixed electrode after the treatment which could block its pulling out from the lumen.
• the size of the metallic electrode fits to the lumen diameter and fits in its length to the area of treatment. Especially for prostate treatment it is Ch16 in lumen-size (5.3 mm diameter) and 1.8 cm length (the prostate interior, for not risking incontinence by overheating the closing muscle.
• the RF-electrode has no thermal isolation against the contacted tissue meaning that the RF-electrode has a metallic contact (or direct metallic contact) or electrolyte contact with the surrounding lumen wall or cavity wall without any thermal isolation, for instance, through a rubber material on the catheter or the electrode surface.
• This guarantees a homogeneous and controlled temperature distribution.
• the direct galvanic contact with the tissue, i.e. the missing thermal isolation is essential to the present invention, because that generates higher electric conductivity in the treated tissue by few orders of magnitudes in comparison with the path of the RF-cable so that substantially the diseased tissue is heated and not the tissue along the way on which the catheter was inserted into the body.
• the direct galvanic contact allows better control of the RF- current so that the temperature distribution caused by the FR current is more homogeneous in the treated deep-situated diseased tissue, thus increasing treatment efficiency.
• the afore-mentioned catheter can be used for the manufacture of a radiofrequency hyperthermia device for the treatment of intraluminar or intracavitary lesions consisting of said catheter with an RF-independent temperature sensor which is isolated from the ground by at least 4kV, wherein the RF-electrode fixed to the catheter is a heat-conductor metallic electrode, and a counter-electrode and a radiofrequency source connected to the RF-electrode and counter-electrode, wherein the RF-electrode fixed to the catheter is a heat- conductor metallic electrode and wherein the counter-electrode is positioned extracorporeal ⁇ opposite the treated area so that the area to be treated is located between the electrode and the counter-electrode.
• the counter electrode is positioned around the patients body and around the intracorporeally electrode and opposite to the treated area and surrounds the intracorporeal electrode in such a manner and degree that the area to be treated is covered by the area, i.e. by the plane spanned between the electrode and counter electrode between the electrode and the counter electrode.
• Said arrangement of electrode and counter-electrode makes the deep heating of the tissue which is preferably the diseased or tumorous tissue possible. That means that not the intracorporeal catheter itself is heated and thereby the surrounding tissue but rather the tissue in between the electrode and counter- electrode which has not to be in direct vicinity to the catheter. Moreover the catheter itself is not or only slightly warmed up which avoids necrosis of the tissue around the catheter. Only the inventive arrangement of the electrode and counter-electrode and the use of RF waves and capacitive coupling allows the treatment of a diseased or tumorous area between the electrode and counter- electrode since only this inventive arrangement is able to deliver energy deep into the tissue which is converted into heat exactly within the diseased or tumorous area where the heat is needed for treatment purposes.
• the present application relates also to a method for treating a patient including a human in need thereof with radiofrequency hyperthermia comprising inserting a catheter with an electrode connected to an RF source into a body lumen or body cavity and positioning the counter-electrode connected to said RF source on the patient's skin in such a way that the area which should be treated is located between the electrode and the counter-electrode, and applying a radiofrequency field in the range of 250 kHz to 45 MHz in order to heat up the diseased area between the electrode and counter-electrode.
• This method is useful for the treatment of lesions of gastroenterological or gynecological, andrological or otolaryngological cavities or lumina. Each treatment session is preferably between 1 and 4 hours.
• the hyperthermia or oncothermia treatment can perfectly be used in combination with common chemotherapy treatment.
• the inventive radiofrequency hyperthermia device can perfectly be used in combination with chemotherapy treatment with cytostatic, anti-proliferative and/or cytotoxic drugs.
• cytostatic, anti-proliferative and/or cytotoxic drugs examples include actinomycin D, alemtuzumab, aminoglutethimide, amsacrin, anastrozol, antagonists of purine and pyrimidine bases, anthracycline, apolizumab, aromatase inhibitors, asparaginase, antiestrogenes, azathioprine, bevacizumab, bexaroten, bicalutamide, bisantrene, bleomycin, buselerin, busulfan, camptothecin, cantuzumab, capecitabin, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribin, cyclophosphamide, cytarabin, cytosinarabinoside, alkylating cytostatics, dacarbacin, dactinomycin, daunorubicin, docetaxel,
• the radiofrequency hyperthermia device of the present invention can be used in combination with an anti-inflammatory drug treatment such as a non-steroidal anti-inflammatory drug (NSAID), for example, alcofenac, aceclofenac, sulindac, tolmetin, etodolac, fenopren, thiaprofenic acid, meclofenamic acid, meloxicam, tenoxicam, lornoxicam, nabumetone, acetaminophen, phenacetin, ethenzamide, sulpyrine, mefanamic acid, flufenamic acid, diclofenac, loxoprofen, phenylbutazone, indomethacin, ibuprofen, ketoprofen, naproxen, oxaprozin, flurbiprofen, fenbufen, pranoprofen, flocta
• NSAID non-steroidal anti-inflammatory drug
• anti-inflammatory agents are algestone acetonide; alpha amylase; amcinafal; amcinafide; amfenac; amiprilose; anakinra; anirolac; anitrazafen; apazone; balsalazide; bendazac; benoxaprofen; bromelains; broperamole; budesonide; carprofen; cicloprofen; cintazone; cliprofen; clobetasol; clobetasone; clopirac; cloticasone; cormethasone; cortodoxone; deflazacort; diflorasone; diflumidone; diflunisal; difluprednate; diftalone; dimethyl sulfoxide; drocinonide; endrysone; enlimomab; enolicam; etofenamate; felbinac; fenamole; fenclofenac;
• the pharmaceutically acceptable salts of the aforementioned antineoplastic and anti-inflammatory drugs can be used also.
• the advantages of the inventive radiofrequency hyperthermia device are that this device and especially the catheter of said device are easily, safely and hygienically applicable and that the catheter is fixed in its position during the treatment time which is preferably 2 - 3 hours. Moreover, the heat generation can be continuously controlled and adjusted and can be regioselectively applied. Furthermore, the catheter is sufficiently safe to be deflated and removed from the lumen or body- cavity, so that the SFC (single-fault-conditions) and the requirements of CE MDD (CE medical device directive) are fulfilled, such as appropriate mechanical properties till 80 0 C.
• SFC single-fault-conditions
• CE MDD CE medical device directive
• Figure 1 shows an example of a common Foley catheter.
• FIG. 2 shows two embodiments of an oncothermia catheter of the present invention.
• the charriere (Ch) or French gauge (Fg) units in sizes 6-28 Ch16 (5.3mm) Foley catheter is preferable.
• the Foley-balloon fixes the catheter in the urethra.
• the Charriere is the outer circumference of the catheter in millimeters. 8-10
• Ch is generally used for paediatrics and 12-30 Ch for adult catheters.
• the most common sizes of the retention balloon are 5-1OmI and 30ml, respectively.
• the standard length of a male catheter is approximately 45cm and of a female catheter 21cm approximately.
• the diameter of the catheter tube is Ch 16 (5.3 mm outside) and that the balloon in its dilated state has a diameter, depending on prostate size, in the range of 2 cm (preferably 1.8 cm in average).
• the balloon is located at the end of the catheter tube just below the guiding wire or guiding head of the catheter and the electrode is like a metal cylinder positioned below the balloon.
• the electrode has a length of about 2 cm.
• diameter, and length of the catheter tube, the electrode and the balloon as well as the position of the electrode and the balloon can be adjusted to the body lumen or body cavity which should be treated.
• Figure 3 shows the application of the inventive catheter for prostate treatment.
• the extracorporeal part of the catheter is fixed to the thigh and the catheter tube is inserted through the penis to the prostate where the balloon is inflated to fix the catheter tube and the electrode during the treatment procedure.
• Fig. 4 shows the catheter tube positioned in the prostate.
• Figure 4 shows the inventive catheter inserted into the prostate (autopsy picture).
• the left picture shows the inventive catheter which was inserted through the penis into the prostate.
• the balloon is in the inflated state in order to fix or stabilize the position of the catheter tube in the urethra and thereby the position of the electrode within the prostate.
• the electrode is not visible since it is complete positioned within the prostate.
• the right picture shows the identical catheter as in the left picture, while the prostate was cut and pulled apart in order to show the position of the cylindrical electrode which is positioned within the prostate.
• a Ch16 (5.3 mm) Foley-catheter was used for the transurethral prostate treatment as shown in Fig. 4 a Ch16 (5.3 mm) Foley-catheter was used.
• Figure 5 shows a schematic arrangement (superpositioned on a MRI pattern) of the radiofrequency hyperthermia device for prostate treatment.
• No. 1 is the RF source which is conductively connected to the counter-electrode No. 3 which is located extracorporeal ⁇ and directly attached to the patient's skin.
• the RF source has also a conductive connection through the catheter tube to the electrode position at the end of the catheter which is inserted through the penis into the prostate.
• a Foley-Catheter No. 2 having a 5.3 mm diameter was used for the prostate treatment.
• No. 5 is the catheter balloon in the dilated state in order to fix the inserted catheter in its position.
• a radiofrequency of 339 kHz is applied between the electrodes.
• the heated area is the area No. 4 between the electrode and the counter- electrode No.
• FIG. 6 shows the arrangement of the inventive radiofrequency hyperthermia device with the RF source, the catheter inserted through the penis into the prostate and the counter-electrode positioned extracorporeal ⁇ like a half belt around the patient's back.
• Fig. 6A shows the treated or heated area which is like a triangle between the electrode located in the prostate and the counter-electrode around the patient's back. With this arrangement the ventral area of the patient's body is not treated and not heated.
• size and position of the counter-electrode or the relative positions of electrode and counter-electrode are used to regioselectively treat an area of the patient's body.
• the inventive radiofrequency hyperthermia device can be used in different arrangements in order to focus the hyperthermia treatment on the malignant tissue.
• Figure 7 Fig. 7B shows the arrangement of the inventive radiofrequency hyperthermia device with the RF source, the catheter inserted through the penis into the prostate and the counter-electrode positioned extracorporeal ⁇ like a belt (or full belt) around the patient's back and abdomen (dorsal and ventral part).
• Fig. 7A shows the treated or heated area which is approximately oval between the electrode located in the prostate and the counter-electrode positioned completely around the patient and consequently completely around the electrode. With this arrangement the ventral area and the dorsal area of patient's body are equally treated and heated.
• the inventive radiofrequency hyperthermia device can be used in different arrangements in order to focus the hyperthermia treatment on the malignant tissue.
• Figure 8 shows an embodiment of belt-like counter-electrodes.
• the counter- electrode or the counter-electrodes are incorporated in a belt so that the complete belt (full-belt counter-electrode) or the half-belt (half-belt counter-electrode) or only parts of the belt function as counter- electrodes.
• Figure 9 shows the top of the cervix uteri seeing from the vagina. The cancerous center is the target of the treatment.
• Figure 10 Figures 10A and 10B show possible arrangements of the counter electrode when the intracorporeal electrode is positioned in the prostate.
• the electrode is inserted through the urethral tract and its position is fixed by a catheter balloon positions in the bladder. Moreover the cable going through the penis to the catheter electrode is also shown.
• the counter-electrode or the counter electrodes can be positioned on the buttock (Fig. 10A) especially in these cases where the area to be treated is located on the rear lobe periphery of the prostate and another possibility is to fix the counter-electrode or the counter electrodes on the limb if the area to be treated is located below the prostate.
• the direction of the RF current flow is indicated in Fig. 10A by an arrow and in Fig. 10B by the conductive current lines in addition to an arrow.
• FIG. 11A shows a coaxial arrangement of the electrode (intracorporeal electrode) and the at least one counter electrode (extracorporeal electrode).
• the electrode is placed in a body lumen indicated as inner circle of the body cross section.
• the outer circle refers to the at least one counter electrode and the straight lines from the inner circle to the outer circle are the RF current lines (also referred to as conductive current lines).
• the area which will be treated by this arrangement is the complete body cross section namely the area where the conductive current lines run through.
• Fig. 11 B shows a half-coaxial arrangement of the electrode (intracorporeal electrode) and the at least one counter electrode (extracorporeal electrode).
• the electrode is placed in a body lumen indicated as inner circle of the body cross section.
• the outer half-circle on the lower half of the body cross section refers to the at least one counter electrode and the straight lines from the inner circle to the outer half-circle are the RF current lines (also referred to as conductive current lines).
• the area which will be treated by this arrangement is the lower half of the body cross section namely the area where the conductive current lines run through.
• Fig. 11C shows a non-coaxial arrangement of the electrode (intracorporeal electrode) and the at least one counter electrode (extracorporeal electrode).
• the electrode is placed in a body lumen indicated as inner circle of the body cross section.
• the outer upper line on the body cross section refers to the at least one counter electrode and the straight lines from the inner circle to the upper line are the RF current lines (also referred to as conductive current lines).
• the area which will be treated by this arrangement is the upper triangular area of the body cross section namely the area where the conductive current lines run through.
• Figure 12 Fig. 12A refers to an embodiment of the present invention. Shown is the cross section of a human body. The dot in the middle from where the conductive current lines start indicates the location of the intracorporeal electrode which is incorporated in the catheter which is inserted into a body lumen. The bold line which partly surrounds the lower part of the cross section indicates the at least one extracorporeal counter electrode. The lines between the intracorporeal electrode and the counter electrode are the conductive current lines which cover the area which should be treated.
• Fig. 12B refers to a state of the art embodiment according to US 2001 7940 A. Shown is the cross section of a human body.
• the dot in the middle indicates the location of an intracorporeal electrode which is incorporated in a catheter.
• the dotted area around the middle dot, i.e. around the catheter indicates the area which can be heated by the catheter, i.e. by the heat emitted from the heated catheter. This area is heated by a heat gradient which means that the area close to the catheter is heated more than the area farer away from the catheter.
• Fig. 12C refers to a state of the art embodiment according to US 2003 4506 A. Shown is the cross section of a human body. The dot in the middle indicates the location of an intracorporeal electrode which is incorporated in a catheter. The circle close around the middle dot indicates the area close around the catheter which is intensively heated in order to cause necrosis.
• the catheter is inserted to the prostate through the penis and after blowing up the balloon it is fixed in such a way that the RF antenna is inside the prostate.
• the position could be controlled (preferably) by conventional ultrasound imaging.) Fix the position and connect the urine-container to the catheter. Choose the position which does not heat the closing muscles of the prostate, in order to avoid after- treatment incontinence. Position the counter electrode on the buttock surface if the cancer is located on the rear lobe periphery of the prostate.
• FIG. 10A and 10B possible positions are shown.
• the counter-electrode or the counter electrodes can be positioned on the buttock (Fig. 10A) especially in these cases where the area to be treated is located on the rear lobe periphery of the prostate and another possibility is to fix the counter-electrode or the counter electrodes on the limb if the area to be treated is located below the prostate.
• the direction of the RF current flow is indicated in Fig. 10A by an arrow and in Fig. 10B by the conductive current lines in addition to an arrow.
• the treatment temperature (preferably between 48-52°C) and start the treatment.
• the device controls all parameters automatically.
• the treatment time is preferably 120 minutes for cancer.
• a patient was treated three times a week for about two hours over a treatment period of 6 months. After the treatment period the patient was cured and until now, 24 months after the hyperthermia treatment was stopped, the patient has not developed new prostate cancer.
• Example 1/b Benign prostate hyperplasia (BPH) treatment
• the catheter is inserted to the prostate through the penis and after blowing up the balloon it is fixed in such a way that the RF antenna is inside the prostate.
• the position could be controlled (preferably) by conventional ultrasound imaging.)
• Fix the treatment temperature (preferably between 48-52°C) and start the treatment.
• the device controls all parameters automatically.
• the treatment time is preferably 180 minutes for benign prostatic hyperplasia.
• a patient was treated two times a week for about three hours over a treatment period of 12 months and thereafter once a week for two to three hours. After a treatment period of about 4 months, further enlargement of the prostate was not detected and after a treatment period of 18 months the prostate was brought to its original size. Treatment was continued for about two hours every two weeks for prophylactic reasons.
• the catheter of the inventive radiofrequency hyperthermia device connected to the RF source is inserted into the end of vagina to the cervix head of a patient suffering from cervical carcinoma (Figure 10).
• the electrode ( Figure 11 ) which is cylindrically positioned around the catheter tube has a total length of 2.5 cm and a diameter of Ch12.
• the electrode has an annulus neck-piece (1 cm diameter) to fix the position in the cervix.
• the insertion of the catheter could be followed with the naked eye by conventional professional tools for inspecting the area.
• the counter-electrode is a flexible woven polymeric material which is coated with a conductive metallic copper layer so that a flexible conductive metallic network is obtained. Such a counter-electrode is placed on the ventral part of the patient's lower abdomen (upper pubic area). Between the intracorporeal cylindrical electrode and the extracorporeal flexible counter-electrode a radiofrequency 339 kHz is applied for 60 minutes. Within 20 minutes a temperature of 44°C is reached in the treated area between the electrode and counter-electrode and kept for the remaining treatment time.
• the temperature is continuously measured and controlled during the treatment through a micro-thermistor located in the catheter guiding head.
• the diseased area between the intracorporeal electrode and the counter-electrode was regioselectively heated and the cervical carcinoma was effectively treated by radiofrequency hyperthermia which could be applied in combination with conventional treatments.
• the catheter of the inventive radiofrequency hyperthermia device connected to the RF source is inserted into the urethra (female) and guided to the urinary bladder for a patient suffering from bladder carcinoma.
• the electrode which is cylindrically positioned around the catheter tube has a total length of 2.0 cm and a diameter of Ch12.
• the bladder has to be filled up by urine-infusion solution mixture electrolyte (the composition is irrelevant, only the filling up is important for RF current conduction).
• the electrode by ultrasound, keeping the electrode in the electrolyte in the vicinity of the cancer, turning the patient on the right position for stabilizing her.
• the counter electrode has to be extra-corporeally on the opposite side,.
• the counter-electrode is a flexible woven polymeric material which is coated with a conductive metallic copper layer so that a flexible conductive metallic network is obtained.
• a radiofrequency of 339 kHz is applied for 60 minutes. Do not use ultrasound control together with the RF-treatment. The parallel use could damage both devices. However, check the electrode position every 10-20 minutes when RF-power is switched off. The temperature is continuously measured and controlled during treatment through a micro-thermistor located in the catheter guiding head.
• the diseased area between the intracorporeal electrode and the counter-electrode was regioselectively heated and the bladder carcinoma was effectively treated by radiofrequency hyperthermia which could be applied in combination with conventional treatments.

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