JP2008514271A - Mechanisms for treatment of tumors - Google Patents

Abstract

  A mechanism for treating a tumor localized within the body, comprising a needle intended to be inserted into the tumor, a ground electrode intended to be applied to the outer surface of the body, and a needle A mechanism having a high-frequency generator intended to apply high-frequency energy between the needle and the ground electrode so that heat is generated in the surrounding tissue. In addition, this mechanism has new temperature measurement means and means that provide better needle penetration into the tumor compared to prior art RFA mechanisms.

Description

TECHNICAL FIELD The present invention relates to a mechanism for the treatment of tumors that can be applied to Radio Frequency Ablation (RFA) techniques. Compared to the prior art RFA mechanism, the mechanism according to the present invention has a means to provide better needle penetration into the tumor. In a preferred embodiment of the invention, the mechanism has temperature control means that provide more accurate temperature control. Furthermore, the mechanism of the present invention provides a more effective tumor treatment. The present invention also relates to a method for treating tumors that provides the aforementioned advantages.

Background Art Many women in Western countries face the potential for breast cancer. Recent trends in breast cancer treatment are moving towards less invasive local treatment of tumors, and minimizing breast shape changes due to treatment has also become important in modern treatment . Thus, breast conservation has become more favored than radical mastectomy in many cases. The purpose of radical surgery is to remove all of the malignant breast tissue, often combined with lymph node resection, which can lead to significant hospital stays and later require breast reconstruction. In addition, tumor free areas are excised to prevent local recurrence. According to recent diagnostic methods, such as routine mammography, many small tumors are detected. If the tumor has not yet spread, ie, the majority of small tumors are 10 mm or less, conventional breast surgery can be viewed as an “overdoing” procedure. Therefore, besides conventional surgery, the possibility of being able to perform treatment even with minimal invasiveness, reduced morbidity, shortened duration of treatment, and patients in poor medical conditions, And other potential benefits such as the possibility of continuing treatment on an outpatient basis are often sought.

  One such technique is the radio frequency ablation (RFA) technique, which causes thermal destruction of the tumor by coagulation necrosis. Liver tumors are the most common type of tumor treated with RFA, but this treatment is now also being performed in other areas of the body, such as lung, bone, prostate, and adrenal glands. Although the use of RFA in breast cancer treatment is relatively new, studies conducted by the inventors of the present invention show that this technique is well suited for the treatment of breast tumors, especially breast duct tumors. Is shown.

  Monopolar RFA techniques require inserting a needle directly into the tumor to be treated and applying a larger, flat ground electrode to the outer surface of the body. When radio frequency (RF) energy generated by a power source is applied between the ground electrode and the needle, the former functions as a counter electrode and a current path is established between the electrodes. The current density at the needle is much higher than the current density at the ground electrode, so the latter is often referred to as the indifferent electrode and is not accompanied by an increase in temperature. The increase in temperature within the tissue occurs due to the agitation of ions being converted to heat by friction, and thus RF energy heats the tissue through the electrical resistance of the tissue. The heat generated in the tissue surrounding the needle destroys the tumor cells without nerve stimulation and pain. Denatured cells are left in the body and later reabsorbed by the body. To prevent tumor regrowth, the surrounding tissue layer, which is a safe area, often must be destroyed as well. The total volume affected by excess temperature is known as the lesion volume, and thus the shape and size of the affected area is known as the lesion shape and lesion size, respectively.

  It is well known that tissue that has been exposed to excessive temperatures for a sufficiently long time is completely killed. In a technique generally referred to as hyperthermia, the temperature produced is approximately 42-43 ° C. At excessive temperatures in this range, the exposure time required to effectively treat the tumor is usually a few minutes, sometimes as long as one hour, depending on the size of the lesion, for example. Thus, hyperthermia temperatures in the field of RFA inevitably prolong the time of patient treatment, causing unnecessary pain and often non-uniform tumor destruction.

  Tissue heating is constantly cooled during treatment, both passively by heat conduction and active by blood circulation. The latter therefore contributes to a great extent to the removal of heat. However, blood circulation depends on heat. A gradual increase in temperature increases blood circulation, but at higher overtemperatures, blood circulation is weakened. The latter therefore leads to a significant increase in temperature diffusion.

  Furthermore, the temperature of the tissue being treated is a very important parameter. For example, at a sufficiently high temperature, the tissue adjacent to the electrode surface will char and attenuate further heating of the tissue due to a dramatic decrease in conductivity. Furthermore, in certain applications, it may be important to avoid the generation of bubbles at the needle surface that tend to insulate the electrode from the tissue. The size of the lesion volume is limited due to the effects described above.

  It is therefore important to effectively monitor and control the temperature and cool the needle in an effective manner in order to achieve an effective treatment of the tumor.

  The output of the RF source regulates the temperature generated in the tissue. In the RFA technique, during the procedure, for example, the impedance of the circuit including the needle and the indifferent ground electrode is measured, the temperature of the needle tip is measured, and the voltage between the electrodes is adjusted according to the measured impedance and temperature. It is known. It is also known to continually supply impedance and temperature values to the control unit during the procedure and send feedback signals to the RF source by the control unit to increase or decrease the output of the RF source.

  An increase in impedance indicates that, for example, bubbles have occurred or tissue charring has occurred. It is known to use needles that utilize a cooling medium inside the needle to cool the needle to prevent tissue charring and bubble formation. One result of having such a cooling medium inside the needle is that the true maximum temperature of the tissue temperature is not located on the surface of the needle due to temperature deviation, but from this needle inside the tissue. Located at a point located at a distance. This makes it difficult to measure the true maximum temperature of the tissue, and it has been found that known means for temperature control of the temperature of the tissue are not fully satisfactory.

  In recent years, it has become possible to detect smaller and smaller tumors, for example through technical developments in screening mammography and ultrasound diagnostic scanning. It is not uncommon for tumors as small as a few millimeters to be detected. In particular, such small tumors, but tumors as large as 10-20 mm in diameter are often not palpable and are subject to anatomical distortion or at least dislocation when touched by a needle. The reason is that the mammary tissue is surrounded by loose adipose and connective tissue, which makes it difficult to properly position and move the needle into the tumor, if the tumor is hard or fibrous (such as In most cases, this problem is exacerbated. Thus, the insertion of a needle into a tumor is often difficult and even impossible.

  At present, when applied to the treatment of cancer, the RFA technique is most often seen as transient rather than therapeutic, and this technique often avoids surgery. It is used to make the tumor smaller so that it can. Thus, there is a need for improved RFA techniques, particularly means that are small and hard fibromas, but which provide a more effective penetration of the tumor to be treated. There is also a need for shortening the actual treatment time and more effective killing of tumor cells. Furthermore, a need exists for more accurate temperature control of tissue temperature.

DISCLOSURE OF THE INVENTION Accordingly, it is an object of the present invention to provide a mechanism for treating tumors by RFA techniques that provides a means for more effectively penetrating the tumor to be treated compared to prior art RFA mechanisms. Is to provide.

  This object is achieved by a mechanism according to the preceding part of the independent claim, which is provided by the features according to the features of the independent claim.

  In a preferred embodiment, the mechanism according to the present invention provides a means for more precise temperature control of the tissue during the procedure compared to prior art RFA mechanisms. Furthermore, this mechanism treats the tumor in a more effective manner than the prior art RFA mechanism.

  The invention further relates to a method of using the mechanism of the invention. Preferred embodiments are set forth in the dependent claims.

  The mechanism of the present invention has a needle 2 (FIG. 3) and a flat ground electrode 4 that is applied to the outer surface of the patient's body and preferably applied to the patient's back. The dimensions of the needle 2 depend, for example, on the size and shape of the tumor 1 to be treated. Preferably, the needle 2 has an effective portion with a length of about 5-100 mm and a diameter in the range of 1-4 mm. This mechanism is a low impedance RF generator 10 that is configured to apply RF energy between the ground electrode 4 and the active portion of the needle 2 when the needle 2 is correctly positioned inside the tumor 1 to be treated. It has further. When RF energy is applied, the needle 2 functions as the active electrode so that a current path is established between the electrodes 2, 4 and heat is generated in the spherical lesion 12 of the tissue surrounding the needle 2 as described above. .

  According to the present invention, for example, when treating a tumor of the breast, the temperature of the tissue can be made significantly higher than the normally used hyperthermia temperature. This tissue temperature may be, for example, in the range of 50-99 ° C., ie the so-called thermotherapy temperature. Because the physical parameters of the tumor and adipose (lipid) tissue are different, heat is “drawn” to the tumor. The tumor has a higher electrical conductivity than the surrounding adipose tissue. As a result, the tumor attracts electrical energy from the lipid. Thus, tumors have a relatively high specific absorption rate (SAR) compared to adipose tissue. In fact, the inventors of the present invention have confirmed that the thin tumor zone extending from the core tumor is killed, but the surrounding adipose tissue is not affected. The time that an elevated temperature must be maintained to achieve effective treatment depends on the size and shape of the lesion. Usually this time is in the range of 5-15 minutes and is therefore shorter than the treatment time required at temperatures in the hyperthermia temperature range in the same tumor treatment. However, it should be understood that when other types of tumors are treated, for example liver tumors, the treatment temperature may be even higher, for example up to about 130 ° C.

In either case, the output of the RF generator adjusts the elevated tissue temperature.
In general, the RF generator is 5-100 W, preferably 20-20, depending on changes in the shape of the breast, the diameter of the needle used, and the properties of the tissue during the treatment, for example when treating a tumor of the breast. Operates in the 60W range. The applied RF frequency may be in the range of 0.2-20 MHz, but is preferably about 0.5-1.5 MHz. In accordance with the present invention, the output of the RF generator is automatically adjusted during the procedure as described below.

  Referring to FIG. 3, the needle 2 of the mechanism of the present invention is provided with an insulating portion 3 and a non-insulating portion 5 by covering the outside of the needle with an insulating material 7 such as Teflon (registered trademark). The insulation of the needle may be slidable on the needle so that the effective electrode length can be adjusted.

  According to a preferred embodiment of the mechanism of the invention, the needle 2 to be inserted into the tumor 1 is provided with means that allow the cooling liquid to circulate within the needle 2. The cooling liquid is guided to the needle through the liquid inlet 9, and is guided along the liquid inflow channel 13 a provided in the center of the needle 2 along the horizontal axis of the needle 2. At the tip of the needle, the cooling liquid redirects and is guided through the liquid outflow channel 13b, ie, the empty space between the liquid inflow channel 13a and the outer surface of the needle, and exits the liquid outlet 11. . The liquid inlet 9 and the liquid outlet 11 are preferably provided with luer-lock type connection parts (not shown). Means that allow the cooling liquid to circulate within the needle 2 are, for example, a pump, such as a pump, that directs the liquid through the liquid inlet 9 to the needle 2, through the inlet and outlet channels 13 a, b, and through the liquid outlet 11. There is further provided a liquid flow generator 14 configured to be led out through, preferably at a constant and predetermined flow rate. Thus, the diameter of the channels 13a, b is preferably sufficient to allow equal flow to the liquid inflow channel and the liquid outflow channel. A preferred flow rate is in the range of 5-30 ml / min.

  The cooling liquid is preferably a sterile isotonic liquid to protect the patient against possible leaks.

  The needle 2 is preferably supplied as a disposable article. Alternatively, the needle 2 is preferably configured to be sterilized by use of an autoclave. However, other conventionally used sterilization methods can be used as well.

  According to a preferred embodiment, the mechanism is further provided with temperature control means. This means comprises means (not shown) configured to measure the flow rate value Q of the liquid circulating inside the needle 2, preferably provided in the liquid flow generator 14. This means is, for example, a generally known flow measurement sensor.

The temperature control means further has a temperature measurement means, and in the first embodiment, the temperature measurement means is connected to a generally known temperature sensor or optical fiber (not shown) for the needle 2. Incorporated in the insulating portion, and preferably has a temperature sensor provided at the liquid inlet 9 and configured to measure the temperature T ₁ of the liquid introduced (first set of temperature measuring means, FIG. 1). In this case, the temperature T _meas and T _{1 of the} needle measured by the first set of temperature measuring means and the value Q = dV / dt (ml / s) of the liquid flow rate are preferably a computer or the like. Continuously supplied 23, 20, 24 to the unit 26. The control unit 26 is provided with means for calculating the true _tissue temperature T _tissue according to the values of T _meas , T _{1 and} the value of the flow rate Q, as will be described in more detail below.

Alternatively, the temperature measuring means has means (not shown) for measuring the temperature value T ₁ of the introduced liquid and the temperature value T ₂ of the discharged liquid in the _second embodiment. It is also possible (second set of temperature measuring means, FIG. 2). The means is preferably a generally known temperature sensor provided at each of the liquid inlet 9 and the liquid outlet 11, for example. In the second embodiment (FIG. 2), T ₁ , T ₂ , and the liquid flow rate value Q = dV / dt (ml / s) are continuously supplied 20, 22, 24 to the control unit 26. The In this case, the control unit 26 calculates the true temperature T _tissue of the _tissue according to the value of the temperature difference between T ₁ and T ₂ , ie T _diff = T ₂ −T ₁ and the value of the flow rate Q. Means are provided.

According to a preferred embodiment of the mechanism of the present invention, the control unit 26 further includes an RF generator 10 for adjusting the impedance value Z of the circuit comprising the needle 2 and the indifferent ground electrode 4 and the high tissue temperature produced. The output P = U * I is continuously supplied 28. That is, the mechanism of the present invention comprises a commonly known means 16 configured to measure impedance and a generally known means 18 configured to measure output. Accordingly, the control unit 26 sends a feedback signal 30 to the RF generator 10 in response to the values of Z, P and the true _tissue temperature T _tissue , depending on whether T _tissue should be increased or decreased, respectively. Means for increasing or decreasing the output of the RF generator is further provided.

  The power required to maintain a specific tissue temperature, also called thermal resistance, is a good indicator of tissue perfusion status, i.e. the degree of tissue destruction, and the reduction in perfusion is related to the quality of the treatment session. Can be a good indicator. Furthermore, the impedance measured between the treatment electrode and the indifferent electrode is a good indicator of the condition around the electrode, ie whether carbonization and / or bubbles are present. Accordingly, the control unit 26 is preferably provided with means for calculating thermal resistance as a tool for monitoring tissue perfusion.

Using the value of Q when determining the true tissue temperature value T _tissue , and using the above value to send a feedback signal to the RF generator, the tissue's temperature value is compared to the prior art RFA mechanism. More accurate temperature control is provided for temperature.

The mechanism of the present invention functions in combination with any of the above-mentioned means for temperature measurement. The use of the first set of temperature measuring means, i.e. the use of a temperature sensor incorporated into the needle, for example, is a straightforward temperature measurement method. On the other hand, each measurement of T ₁ and T ₂ can provide a cheaper temperature measurement than when a temperature sensor is used for the needle. This is because, when the size of the needle is small, it is considered that the introduction of the temperature sensor into the needle becomes a problem, and it is considered that the procedure is quite expensive.

  The low level signal obtained from the temperature sensor can be subject to interference from the applied RF output field. In this case, the mechanism is preferably provided with low-pass filter means (not shown) in order to filter out the RF signal to obtain high quality measurements in extreme RF field environments. Furthermore, the mechanism is preferably designed as a Cardiac Floating (CF) to ensure patient leakage current (PLC) and ground leakage current (ELC) according to EN 60-601-1 international standards and EC. The

According to the invention, the mechanism is provided with longitudinal motion means 8 configured to apply a longitudinal vibration motion 6 to the needle 2. The longitudinal vibration 6 of the needle 2 with the appropriate frequency and amplitude effectively penetrates even a small and hard tumor, such as a tumor of only a few millimeters, due to its acceleration component, and indeed the invention of the present invention. They have confirmed that when a frequency of 250 Hz is applied, the resistance during penetration can be reduced by up to 10 times. For example, depending on the dimensions of the needle 2 and the size, condition, and position of the tumor 1, the operator of the mechanism, for example the physician in charge of the procedure, may enter this needle when the needle 2 is about to enter the tumor. You are free to choose the appropriate frequency, amplitude, and waveform to add. Preferably, the applied sine wave frequency is in the range of 30-300 Hz and the amplitude is in the range of 0-4 mm. The penetrating force decreases with increasing frequency and amplitude, and the accelerating force increases with these parameters.

  The oscillating movement 6 of the needle 2 is added to provide a better entry of the needle into the tumor 1.

Calculation of true tissue temperature using a first set of temperature measuring means The true tissue temperature T _tissue is determined, for example, by using the value of T _{meas and} the value of flow Q according to equation (1).
dT = T _tissue −T _meas = k ₁ (T _tissue ) * Q + k ₂ (T _tissue ) * Q ² (1)
Where dT is the temperature gradient across the needle and k ₁ and k ₂ are constants.

k ₁ and k ₂ are found using calibration. For example, FIG. 4 shows flow-dependent measurements at different calibration temperatures (functioning as fictitious tissue temperatures) using a bath unit maintained at temperatures of 70 ° C. (lower curve) and 95 ° C. (upper curve). The temperature T _meas is indicated. In the calibration measurement, the tank units were kept at the calibration temperature, and T _meas was measured at 20 different flow rates. The cooling liquid circulating inside the needle was maintained at 15 ° C. Using a least squares algorithm, k ₁ and k ₂ were calculated for tissue temperatures of 70 ° C. and 95 ° C. At a constant flow rate, there is a linear relationship between T _meas and T _tissue . Thus, T _tissue is calculated by linear interpolation between the 70 ° C. and 95 ° C. curves at all flow rates. When the temperature of the introduced stream changes, the constants k ₁ and k ₂ also change according to a known relationship.

Calculation of true tissue temperature using a second set of temperature measuring means In this scheme, the true tissue temperature T _tissue is replaced by T _meas instead of the difference between the inlet temperature and the outlet temperature T _diff = Determined by T ₁ -T ₂ . Otherwise, this procedure preferably follows the same mechanism as the measurement calculation method described above.

  Although the mechanism of the present invention has been described by a procedure for the treatment of human breast tumors, this mechanism should not be considered limited to such a procedure alone. This mechanism is fully functional in other types of tumors such as prostate tumors, liver tumors, and animal tumors.

  It should be understood that the present invention is not limited to the above-described exemplary embodiments of the present invention, and that several variations of the present invention are possible within the scope of the following claims. I will.

1 schematically shows a mechanism of the invention comprising a first set of temperature measuring means. Fig. 4 schematically shows the mechanism of the present invention comprising a second set of temperature measuring means. 1 schematically illustrates a cross-section of a needle of the mechanism of the present invention. The temperature measured depending on the flow is shown for various calibration temperatures.

Claims (10)

To treat tumors that are localized inside the body,
A needle (2) intended to be inserted into the tumor,
A ground electrode (4) intended to be applied to the outer surface of the body and intended to apply high frequency energy between the needle and the ground electrode so that heat is generated in the tissue surrounding the needle High frequency generator (10)
A mechanism having
Longitudinal movement means (8) adapted to apply a longitudinal vibration movement to the needle, preferably when inserting the needle into the tumor
A mechanism characterized by comprising: The needle (2) is provided with a liquid inlet (9) that communicates with the liquid inflow channel (13a) and a liquid outlet (11) that communicates with the liquid outflow channel (13b). Along the inside of the needle (2),
The mechanism according to claim 1, characterized in that the mechanism is provided with a liquid flow generating device (14) configured to cause a flow of liquid in the channels (13a, 13b). A mechanism according to claim 2, characterized in that means are provided which are arranged to measure the flow value of the liquid. Having means configured to measure the temperature of the tissue;
The means is a temperature sensor incorporated into the needle (2), means configured to measure the temperature of the liquid at the liquid inlet (9), and said means configured to measure the flow value of the liquid The mechanism according to any one of claims 1 to 3, wherein the mechanism is included. Having means configured to measure the temperature of the tissue;
Means for measuring the temperature of the liquid at the liquid inlet (9); means for measuring the temperature of the liquid at the liquid outlet (11); and a flow rate value of the liquid. 4. A mechanism according to any one of the preceding claims, including the means configured to measure.   Means (16) for measuring the impedance of the circuit including the needle (2) and the ground electrode (4), and means (18) configured to measure the output of the high frequency generator (10) The mechanism according to any one of claims 1 to 5, wherein: A control unit (26),
The control unit is
a) the flow rate of the liquid in the channels (13a, 13b) of the needle (2),
b) the temperature measured by the temperature sensor incorporated in the needle (2) and the temperature of the liquid at the liquid inlet (9),
c) configured to receive the impedance of the circuit including the needle (2) and the ground electrode (4), and d) the value of the output of the high frequency generator (10),
comprising means configured to calculate the temperature of the tissue depending on the values of a) and b);
Depending on whether the tissue temperature should be lowered or raised, a signal (30) having instructions for decreasing or increasing the output of the high frequency generator is transmitted to the high frequency generator (10). 7. The mechanism according to claim 1, wherein the mechanism is configured as follows. A control unit (26),
The control unit is
a) Liquid flow rate in the channels (13a, 13b) of the needle (2),
b) the temperature of the liquid at the liquid inlet (9) and the temperature of the liquid at the liquid outlet (11),
c) configured to receive the impedance of the circuit including the needle (2) and the ground electrode (4), and d) the value of the output of the high frequency generator (10),
comprising means configured to calculate the temperature of the tissue depending on the values of a) and b);
Depending on whether the tissue temperature should be lowered or raised, a signal (30) having instructions for decreasing or increasing the output of the high frequency generator is transmitted to the high frequency generator (10). 7. The mechanism according to claims 1 to 3, and 5 and 6, wherein the mechanism is configured as follows.   9. A means according to claim 7 or 8, characterized in that the control unit (26) is provided with means for calculating the output required for the high-frequency generator (10) to maintain a predetermined tissue temperature. The mechanism described.   The use method of the mechanism of any one of Claims 1-9.

Images