WO2016165634A1

WO2016165634A1 - Cold and hot treatment device for melanoma

Info

Publication number: WO2016165634A1
Application number: PCT/CN2016/079334
Authority: WO
Inventors: 徐学敏; 张爱丽; 刘苹; 白景峰; 孙建奇; 邹金成
Original assignee: 上海交通大学
Priority date: 2015-04-14
Filing date: 2016-04-14
Publication date: 2016-10-20
Also published as: CN104783890A; CN104783890B

Abstract

A cold and hot treatment device for melanoma comprises a treatment control system (A) and a tumor treatment unit (B). The treatment control system (A) comprises a small industrial personal computer (1) and a display and monitoring module (2), and is used for controlling cooperative work of tumor treatment devices, so that the automatic program control treatment of melanoma is achieved, and the treatment process is displayed and monitored in real time. The tumor treatment unit (B) comprises a cold source (4), a hot source (5), a conformal probe (7), a device control circuit (3) and the like, and is mainly used for treating a melanoma tissue. Further, the tumor treatment unit (B) can feed back the temperature of a tumor tissue by means of a temperature sensor (6), so as to better adjust the treatment temperature. The cold and hot treatment device for melanoma is easy to operate, can completely melt a tumor-in-situ tissue and improve the immune response of a living body, and has a remarkable application effect.

Description

Melanoma cold and heat treatment device

Technical field

The invention relates to a cold and hot alternating treatment device for melanoma, belonging to the field of biomedical engineering.

Background technique

Melanoma is a highly malignant tumor transformed by malignant melanocytes. It is highly invasive and prone to distant metastasis. The common metastatic sites are lung, bone and liver. The average survival time of advanced melanoma patients is only 6-9 months, which brings great harm to human life.

The treatment of melanoma has long been a difficult problem in the medical field. The conventional method for clinical treatment of melanoma is local excision. Other treatments include immunotherapy (vaccine), gene therapy, chemotherapy, and radiotherapy. Local resection is a routine treatment, and the prognosis is extremely poor. The scope and depth of satellite resection are not Accurate and easy to increase the chance of tumor residual; melanoma is not sensitive to chemotherapy and radiotherapy and has very low efficiency (only 20%-30%), chemotherapy has a short duration and poor prognosis; current gene therapy has better gene transfer efficiency Low difficulty, and the carrier is difficult to target tumor cells. In view of the current treatment status of melanoma, it is urgent to seek a new type of tumor treatment.

Like most malignant tumors, melanoma causes varying degrees of immunosuppression, evading immune surveillance and attack to promote tumor development. At present, conventional cancer treatment methods can not effectively alleviate the body's immunosuppressive microenvironment, thereby effectively stimulating the body to produce a systemic anti-tumor immune response, inhibiting the development of cancer metastasis, and the therapeutic effect is very limited. In recent years, thermophysical therapy has received extensive attention due to its minimally invasive, low cost, and immune response. It mainly includes cryotherapy, hyperthermia, and a combination of cold and heat therapy.

Summary of the invention

The object of the present invention is to provide a high-efficiency melanoma treatment device, a melanoma cold and heat treatment device, which can effectively inhibit the distal metastasis of a tumor, the treatment device comprising a tumor treatment unit and a treatment control system, the tumor treatment unit comprising a control circuit a cold source, a heat source, and a conformal probe; the control circuit includes a cold therapy control circuit, a thermotherapy control circuit, and a PCI data bus interface, wherein the control circuit communicates with the treatment control system in the form of a PCI bus, and receives the treatment control The control signal of the system, and the operation of the cold source or the heat source is controlled by the cold therapy control circuit or the thermotherapy control circuit according to the corresponding control signal, and the cold source or the heat source is correspondingly applied to the therapeutic conformal probe, and the conformal probe is passed through The needle acts on the tumor tissue to achieve treatment of the tumor tissue.

Further, the treatment control system includes an industrial computer, a display monitoring module, and a high-speed data acquisition card integrated in the industrial computer. The high-speed data acquisition board is connected to the industrial computer by using a PCI bus data interface, and the other end of the bus is connected to The tumor treatment unit; the control circuit further comprises a treatment parameter feedback circuit, and the treatment parameter is fed back to the high-speed data acquisition board for processing; the treatment control system is based on feedback parameters (such as tumor tissue impedance, hyperthermia power, etc.) Adjusting the work of the tumor treatment unit.

Further, the tumor treatment unit further includes a temperature sensor, the control circuit further includes a temperature acquisition processing circuit; the temperature sensor collects a real-time temperature of the tumor tissue during the treatment, and transmits the temperature acquisition processing circuit to the control circuit It is processed and transmitted to the treatment control system via the PCI bus after processing. The treatment control system adjusts the temperature of the cold or heat source based on the collected temperature information.

Optionally, the cold source in the tumor treatment unit is a liquid refrigerant, preferably liquid nitrogen, liquid oxygen or liquid argon; or the cold source is a semiconductor refrigeration sheet. When the cold source is liquid refrigerant, the control circuit adopts PWM control mode to control the speed control pump operation during the cold treatment process, thereby controlling the flow rate of the liquid cold source to achieve rapid cooling of the tumor tissue and low temperature maintenance during the treatment process. When the cold source is a semiconductor refrigeration chip, the control circuit also samples the PWM control mode to directly control the output of the digital power supply of the semiconductor refrigeration chip, thereby controlling the semiconductor refrigeration power to achieve the purpose of cold therapy.

Optionally, the heat source in the tumor treatment unit is preferably one of radio frequency, microwave or infrared. During the hyperthermia process, the control circuit controls the power of the hyperthermia through the thermotherapy control circuit to achieve the function of controlling the heating process and the thermotherapy maintenance of the hyperthermia.

Further, the thermotherapy automatic protection circuit is provided in the thermotherapy control circuit to avoid excessive temperature during the treatment, or accidental injury to the user's body tissue due to malfunction and malfunction.

Preferably, the end of the conformable probe for contacting the tumor tissue has a conformal treatment surface that is capable of conforming to the tumor tissue.

The tumor tissue described herein includes: abnormal proliferation of melanocytes, forming some cell nests in the epidermis or epidermal-dermal boundaries.

In a preferred embodiment of the present invention, the conformal probe has a medium flow channel inside, the channel is provided with a medium inlet and a medium outlet, and the liquid refrigerant flows through the medium inlet and the medium outlet in the probe to the tumor tissue. For cooling and cooling, if a semiconductor cooling sheet is used as a cold source, the cold source joint is connected.

In another preferred embodiment of the present invention, the heat source heats the tumor tissue by being connected to a heat source connection port.

Preferably, the temperature sensor is a thermocouple with a pin-type metal sleeve, which improves the sensitivity of temperature monitoring, anti-interference ability and minimizes the range of trauma.

The melanoma cold and heat treatment device provided by the invention can achieve the ablation of the in situ tumor and the inhibition of the distal metastasis by using the alternating hot and cold treatment method, and the specific operation method comprises the following steps:

1) Firstly, the volume of melanoma to be treated is measured, and the melanoma and its surrounding tissues are anesthetized, disinfected, etc., and the treatment parameters are set to prepare for treatment.

2) heating the melanoma to be treated to a set temperature T1 required for the treatment, and after heating to a set temperature T1, maintaining the temperature T1 for a period of time t1.

3) After the t1 time for the melanoma hyperthermia, the treatment control system will automatically enter the cold therapy according to the setting procedure. During the cold therapy, the melanoma is rapidly cooled by the cold source to the low temperature T2 required for the treatment. Then, the low temperature T2 is maintained to the hold time t2 set by the treatment control system.

4) After the end of the melanoma cold treatment, the treatment control system will automatically turn off the cold treatment, the melanoma tissue enters a rewarming state, and the rewarming is to make the melanoma rewarmed in a natural state.

5) After the melanoma is naturally rewarmed to the set temperature T3, the treatment control system automatically performs the hyperthermia treatment on the melanoma to raise the temperature to the set target temperature T4, and maintain the temperature for a period of time. Time t3.

6) Repeat steps 2) to 5) one or more times.

In the above steps, T1 to T4 refer to the temperature of melanoma tissue.

Both the cold treatment step and the heat treatment step in the above method are operated using a non-invasive or minimally invasive method. In steps (2) to (6), the temperature of the tumor tissue is monitored in real time, and in step (2) and step (5), the impedance of the tumor tissue and the course of hyperthermia are monitored in real time. The real-time thermal therapy power, and the collected power and temperature as the feedback input signal of the hyperthermia, so that the thermal therapy is stably performed according to the setting procedure.

The invention has the beneficial effects that the invention provides a thermal and thermal alternating treatment device for melanoma, which can be applied to the complete ablation of melanoma orthotopic tumors, and can improve the immune response of the treated organism to the tumor, and inhibit The distal metastasis of the tumor greatly increases the survival rate of the treatment.

DRAWINGS

Figure 1 is a connection structure diagram of the cold and heat treatment device of the present invention;

2 is a schematic structural view of a conformal probe according to a preferred embodiment of the present invention;

Figure 3 is a photograph of the state of the mice after alternating hot and cold treatment;

Figure 4 is a comparison of overall survival and survival time in different groups of mice;

Figure 5 is a photograph of the results of secondary attacks of different groups of mice against tumor again.

detailed description

Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings and embodiments.

It is to be understood that the examples are not intended to limit the scope of the invention. The following implementation Experimental methods in which no specific conditions are specified, usually in accordance with conventional conditions, such as Sambrook et al., Molecules Cloning: Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989) The conditions stated, or in accordance with the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are Weight percent and parts by weight.

Example 1

For the connection relationship of the thermal therapy device for melanoma in this embodiment, please refer to FIG. 1. The device mainly utilizes the therapeutic control system to control the alternate use of the cold source and the heat source, thereby achieving tumor ablation and distal metastasis inhibition. The device comprises a treatment control system A and a tumor treatment unit B, wherein the treatment control system A is composed of a small chemical control machine 1 and a display monitoring module 2, wherein a small industrial computer integrates a high-speed data acquisition board for Real-time collection of tissue temperature data during treatment, related treatment parameter data, and control by the industrial computer program, the occurrence of numerical control signals, control of the operation of the tumor treatment device; the tumor treatment unit B includes control circuit 3, cold source 4, heat source 5 Temperature sensor 6, conformal probe 7.

The treatment control system A and the tumor treatment unit B in the thermal therapy device communicate in the form of a PCI data bus, and are connected through a PCI data line interface 31. During the system working process, the industrial computer 1 sends corresponding CNC information through the PCI bus control high-speed data acquisition board according to the treatment system software program. Then, after receiving the treatment information, the tumor treatment unit B passes the cold therapy control circuit according to the corresponding information. 32 or the thermotherapy control circuit 33 controls the operation of the cold source 4 or the heat source 5, after which the cold source or the heat source is transferred to the conformal probe 7 through the medium flow channel or the heat source connection port and acts on the tumor tissue to reach the tumor tissue. At the same time, during the treatment, the temperature sensor 6 collects the temperature of the treated tissue in real time, and through the temperature acquisition processing circuit 35 on the control circuit 3, the collected temperature data is processed, and then transmitted to the high-speed data acquisition card, through the collection. The card is transmitted to the industrial computer 1, and during the treatment, the control circuit 3 collects and processes the relevant treatment parameters in the treatment process through the treatment parameter feedback circuit 34, and transmits the treatment parameters to the industrial computer 1 through the high-speed data acquisition board; Finally, the industrial computer 1 according to the treatment process, the temperature data collected, the treatment parameter data, swollen The tumor volume and other related quantities, using the relevant control algorithm, output the corresponding control signals, control the work of the whole system, thus achieving the purpose of automatic tumor control and treatment. At the same time, the display monitoring module 2 of the treatment control system displays and monitors the treatment process of the tumor in real time. After the treatment is finished, the treatment control system automatically stores the relevant treatment parameters in the treatment process in an Excel table or an SQL database for data analysis.

The cold source 4 in the cold treatment process may use a liquid refrigerant such as liquid nitrogen, liquid oxygen, or liquid argon, or may be cooled by means of semiconductor refrigeration. In the process of cold source cooling, the cold therapy control circuit 32 in the control circuit 3 controls the cold therapy by the PWM control mode according to the corresponding treatment signal generated by the treatment control system to achieve the adjustment of the refrigeration process; The method can directly control the operation of the low temperature speed regulating pump by using the PWM control mode when the system uses the liquid refrigerant, so as to control the flow rate of the refrigerant, thereby achieving the effect of program-controlled cooling, so as to realize cold treatment and cold treatment of the tumor tissue. The purpose of low temperature maintenance; if the system uses semiconductor to perform cooling, the same PWM control can be used to control the power of the digitally controlled power supply connected to the semiconductor refrigeration chip, thereby controlling the cooling power of the semiconductor refrigeration chip to achieve the purpose of cold therapy.

The heat source 5 in the hyperthermia project can use the radio frequency, microwave, infrared or hot water to heat the tissue, and the control process is that the upper computer issues control information to control the hyperthermia control circuit 33, thereby controlling the hyperthermia process of the system. Since the heat source used in the control process may be radio frequency, microwave, etc., in the design of the system, the temperature sensor 6 uses a thermocouple with electromagnetic field shielding function, and a pin plug is used in the tip design of the thermocouple. Easy to insert tissue and reduce trauma during treatment.

Example 2

2 is a schematic structural view of a preferred embodiment of the conformal probe 7 of the present invention. The preferred embodiment uses a liquid refrigerant for cold therapy, and uses radio frequency or microwave for hyperthermia; the conformal probe has a refrigerant flow channel, and There is a refrigerant inlet 71 and a refrigerant outlet 72, and further has a heat source connection port 73. The inner wall of the conformal probe is made of a metal material, and the heat source can be conducted to the conformal treatment surface 74 (the shape of the conformal treatment surface is not unique) Any shape suitable for closely adhering to the surface of the tumor can be used), and the outer wall of the probe is protected by a heat insulating layer 75 made of an insulating material. During cryotherapy, the refrigerant enters the inside of the probe through the refrigerant inlet 71, and carries heat away after heat exchange on the conformal treatment surface 74. The vaporized cold source flows out from the refrigerant outlet 72. When the treatment is heated, the heat source is connected to the heat source. The mouth 73 is such that the heat source is transferred to the conformal treatment surface 74 through the metal tube to heat treat the treated tissue.

Example 3

The cold and heat treatment device of the invention can effectively treat melanoma, and the present embodiment obtains a good therapeutic effect by treating the mouse melanoma with the invention. The specific experimental process is as follows:

1. Materials and methods

1.1 Animals, cell lines and main reagents

6-8 weeks old SPF C57BL/6 female mice (Shanghai Slack Animal Center) were housed in independent ventilation cages and manually controlled for 12 hours to change light. Mice are free to ingest 60Co radiation-sterilized feed And high temperature sterilized water. Mouse B16F10 melanoma cells (ATCC) were cultured with 10% newborn fetal bovine serum (Hangzhou Sijiqing Co., Ltd.) and double antibody (100 U/mL penicillin, 100 g/mL streptomycin) (Shanghai Bioengineering Bioengineering) Technical Services Ltd.) in RPMI1640 medium (Hyclone, USA).

1.2 Establishment of B16F10 melanoma model and determination of tumor size

A 5 x 10 ⁵ U/0.1 mL B16F10 cell suspension was prepared and placed on ice for use. The animals were anesthetized by intraperitoneal injection of 0.016 g/mL sodium pentobarbital at 0.5 mL/100 g mouse body, and 0.1 mL of cell suspension was subcutaneously injected into the back of the mice. After 12 days of tumor inoculation, the vernier caliper measures the tumor volume, and then the volume of the tumor is calculated based on the most recently calculated tumor volume calculation formula based on multiple experimental measurements. Tumor-bearing mice were randomly divided into control group and cold-heat combined treatment group.

1.3 alternating hot and cold treatment

1.3.1 Experimental plan

Control group (Control), Alternate cooling and heating treatment. The study contents were as follows: After 12 days of inoculation, the mice were randomly divided into 2 groups and treated differently: control group and cold-heat combined treatment group. After treatment, 10 mice in each group were observed for long-term treatment; in addition, 4 mice in each group were given a secondary tumor challenge 45 days after treatment to detect tumor growth and survival rate. Tumor mice were used as controls.

1.3.2 hot and cold alternating treatment system

The treatment device for melanoma in the present embodiment, such as the cold and heat treatment device described in

Embodiments

1 and 2 of the present invention, mainly includes cold treatment for cooling the tumor tissue; heat treatment is used for the given Tumor tissue warming; and real-time monitoring and control of the tumor treatment system for real-time control of the operation of the tumor treatment device and monitoring of the working state of the system. During the treatment of the tumor tissue, a conformal probe of the device is used to adhere to the tumor tissue, and a cold source is used to cool the tumor tissue by a conformal probe, and the heat source is contacted with the conformal probe to the tumor. The organization warms up.

1.3.3 Experimental process

Tumors were treated 12 days after tumor inoculation and tumor volume was measured before treatment. Before treatment, tumor-bearing mice were randomly divided into two groups: control group and cold-heat combined treatment group. The mice in need of treatment were first anesthetized, and then the tumor site was disinfected with alcohol and iodine. The following treatment process is then performed.

Step S1: Firstly, the volume of the tumor is measured and measured before the treatment, and after the anesthesia, disinfection, and the like are treated for the tumor to be treated, the treatment parameters are set and the treatment is prepared.

Step S2: after the end of the therapeutic preparation work, heating the tumor to a set temperature T1 required for the tumor treatment, and after heating the tumor to the set temperature T1, the system will automatically maintain a period of time t1, The maintenance time is the optimal time determined by the laboratory after the study and treatment of the tumor.

Step S3: After the system heat maintenance time, the system will automatically enter the cold therapy according to the setting procedure. During the cold therapy process, the system cold source is used to rapidly cool the tumor to the low temperature T2 required for the treatment, and then, the cold treatment is maintained. To the set system hold time chart t2.

Step S4: After the end of the cold treatment of the tumor, the system will automatically turn off the cold treatment, and the tumor tissue enters a rewarming process, and the tumor is rewarmed in a natural state during the rewarming process.

Step S5: After the set temperature T3 of the tumor tissue is naturally rewarmed, the system automatically performs hyperthermia treatment on the tumor to raise the temperature to a set target temperature T4, and maintain the temperature for a period of time t3.

Step S6: Repeat steps S2 to S5 one or more times.

The treatment temperatures T1, T2, T3, T4 mentioned in the above steps S2 to S5, and the time parameters t1, t2, and t3 are the treatment parameters determined by experimental experiments, and the above parameters are used for the treatment of the tumor. Higher survival rate.

1.3.4 Evaluation of the efficacy of cold and heat therapy

After treatment, the survival status of the mice was comprehensively observed. This section mainly includes: observation of the growth of orthotopic tumors in the control group, ablation and recurrence of orthotopic tumors in the treatment group, and metastasis of each group of mice (daily), and recording changes in body weight before and after treatment (twice a week) ), statistics on long-term survival and survival time of mice, etc. These indicators can effectively reflect the survival of mice, and the statistics of survival rate and survival time are the most important indicators for evaluating the therapeutic effect.

1.3.5 Secondary inoculation analysis

In order to verify the treatment of immune memory aroused cold binding response, 45 days after the second treatment the mice were Vaccination 1.25 × 10 ⁵ th B16F10 melanoma cells in situ in the contralateral tumor. After inoculation, the state of the mice was observed.

2. Results

2.1 mouse survival status

After the combination of cold and heat treatment, the mice recovered to normal levels. After 5 days of treatment, the tumors in situ began to subside and scab, and by the 10th day, the tumors ablated and the skin gradually returned to normal. As shown in Figure 3, the state of the mice before and after the alternating hot and cold treatment is: before treatment A (there is a larger tumor in the right rear of the body), 5 days after treatment B (most tumors have fallen off, leaving a treatment wound) 10 days after treatment C (wound shrinkage and gradual healing), 4 weeks after treatment D (wound basically healed), 8 weeks after treatment E (complete healing and new hair growth). It can be seen from Fig. 3 that the tumor-bearing mice were completely ablated 4 weeks after the combination of cold and heat, and the tumor in situ was completely ablated, and there was no metastase on the surface, and the living condition was good.

2.2 cold heat treatment improves survival rate in mice

Ten mice in each group were observed for 2 months, and the time of death was recorded (Fig. 4). Cold and heat alternate treatment After treatment, 8 of the mice were in good condition, and only 2 mice died 15 days after treatment (27 days after inoculation) and 25 days (37 days after inoculation), and the remaining 8 were observed in two months. No recurrence of the in situ was found. The control mice died all within 2 months after inoculation. Therefore, alternating hot and cold treatment of tumors can greatly improve the survival rate of mice and achieve a good therapeutic effect.

2.3 hot and cold treatment against secondary tumor attacks

The B16F10 melanoma cells used in this experiment can be transferred to the lungs, liver, bone marrow, and brain, and are often transferred to the lungs on days 7-9 after inoculation, which is a highly metastatic model. Forty-five days after the orthotopic tumor treatment, the mice were given a second inoculation on the opposite side of the tumor in situ to observe the inhibition of the contralateral tumor. In the control group, 4 mice showed visible tumors on the contralateral side 10 days after the inoculation, and the growth was rapid, and all died within 35 days after the inoculation. The contralateral tumors of the mice in the cold-heat combined treatment group were inhibited, and the growth state was good in the one-month survival observation. It shows that the combination of cold and heat treatment has produced strong anti-tumor immune memory and can resist the secondary attack of tumor again. As shown in Figure 5, the contralateral tumors of the control mice are grown, and four mice within 35 days. All died. In situ tumor ablation was performed in mice in the alternating hot and cold group and inhibited the growth of secondary tumors. The arrows represent secondary inoculation of tumors.

The experimental results show that the treatment of in situ melanoma with the cold and heat treatment device of the invention can achieve a higher therapeutic effect and greatly improve the survival rate of the mouse.

The description and application of the present invention are intended to be illustrative, and not intended to limit the scope of the invention. Variations and modifications of the embodiments disclosed herein are possible, and various alternative and equivalent components of the embodiments are well known to those of ordinary skill in the art. It is apparent to those skilled in the art that the present invention may be embodied in other forms, structures, arrangements, ratios, and other components, materials and components without departing from the spirit or essential characteristics of the invention. Other variations and modifications of the embodiments disclosed herein may be made without departing from the scope and spirit of the invention.

Claims

A melanoma cryotherapy device, characterized in that the treatment device comprises a tumor treatment unit and a treatment control system; the tumor treatment unit comprises a control circuit, a cold source, a heat source and a conformal probe; the control circuit comprises a cold therapy control circuit, a thermotherapy control circuit and a PCI data bus interface, the control circuit is in communication with the treatment control system in the form of a PCI bus, receives a control signal of the treatment control system, and passes the cold therapy control circuit according to the corresponding control signal Or the thermotherapy control circuit controls the operation of the cold source or the heat source, and the cold source or the heat source acts accordingly on the therapeutic conformal probe, and then acts on the tumor tissue through the conformal probe.
The melanoma cold and heat treatment device according to claim 1, wherein the treatment control system comprises an industrial computer, a display monitoring module, and a high-speed data acquisition card integrated in the industrial computer, wherein the high-speed data acquisition board adopts The PCI bus data interface is connected to the industrial computer, and the other end of the bus is connected to the tumor treatment unit; the control circuit further includes a parameter feedback circuit, and the treatment parameter is fed back to the high-speed data acquisition board for processing; the treatment control system is The feedback parameters adjust the work of the tumor treatment unit.
The melanoma cold and heat treatment apparatus according to claim 2, wherein said tumor treatment unit further comprises a temperature sensor, said control circuit further comprising a temperature acquisition processing circuit; said temperature sensor collecting said tumor during treatment The real-time temperature of the tissue is transmitted to a temperature acquisition processing circuit in the control circuit for processing, and after processing, is transmitted to the treatment control system through the PCI bus, and the treatment control system adjusts the temperature of the cold source or the heat source according to the collected temperature information.
The melanoma cold and heat treatment device according to any one of claims 1 to 3, wherein the cold source in the tumor treatment unit is one of liquid nitrogen, liquid oxygen, liquid argon or a semiconductor refrigeration sheet. Kind of, the control method uses PWM control.
The melanoma cryotherapy apparatus according to claim 4, wherein the PWM control mode is used to control the flow rate of the liquid cold source, and the power of the semiconductor refrigeration chip can also be controlled to achieve rapid growth of the tumor tissue. The role of cooling and cryopreservation during treatment.
The melanoma cold and heat treatment apparatus according to any one of claims 1 to 3, wherein the heat source in the tumor treatment unit is one of radio frequency, microwave, and infrared, and the control circuit is controlled by hyperthermia. The circuit controls the power of the hyperthermia to achieve a program that controls the heating process of the hyperthermia and the maintenance of the hyperthermia.
A melanoma cold and heat treatment apparatus according to any one of claims 1 to 3, wherein the apparatus is provided with a thermotherapy automatic protection circuit to prevent damage to the treatment subject by erroneous operation or malfunction.
A melanoma thermotherapy apparatus according to any one of claims 1 to 3, wherein one end of the conforming probe for contacting the tumor tissue has a conformal treatment surface, the conformal treatment surface Can be attached to tumor tissue.
A method for using a treatment device for melanoma, characterized in that it comprises the following steps Step:

1) First, determine the volume of the melanoma to be treated, and after anesthesia, disinfection, etc., the melanoma to be treated, set the treatment parameters and prepare for treatment.

2) heating the melanoma to be treated to a set temperature T1 required for treatment, and after heating the melanoma to be treated to a set temperature T1, the temperature of the melanoma to be treated is maintained for a period of time T1. T1.

3) After the heat maintenance time of the melanoma to be treated, the treatment control system will automatically enter the cold treatment according to the setting procedure, and during the cold treatment, the cold source is used to rapidly cool the tumor to the treatment requirement. At a low temperature T2, then cold therapy is maintained to a hold time t2 set by the treatment control system.

4) After the end of the cold treatment of the melanoma to be treated, the treatment control system will automatically turn off the cold treatment, the melanoma tissue to be treated enters a rewarming treatment, and the rewarming of the tumor is to make it in a natural state. Rewarming.

5) After the melanoma tissue to be treated is naturally rewarmed to a set temperature T3, the treatment control system automatically performs hyperthermia treatment on the melanoma to be treated, and raises the temperature to a set target temperature T4, maintaining this A temperature for a period of time t3.

6) Repeat steps (2) to (5) one or more times.
The method of claim 9 wherein a non-invasive or minimally invasive method is employed in said cold processing and said heat treating step.