CN214632313U - Solid tumor therapeutic instrument - Google Patents

Abstract

A therapeutic apparatus for solid tumor. The tumor is heated by a heating device, the temperature change of normal tissues around the tumor is monitored by a temperature measuring needle, the heating temperature is controlled by a controller, the temperature value of the normal tissues is monitored, the tumor is inactivated, and the normal tissues are not damaged to carry out tumor treatment.

Description

Solid tumor therapeutic instrument

Technical Field

The utility model relates to a therapeutic instrument for solid tumors. The apparatus is suitable for the treatment of benign and malignant solid tumors.

Background

Among the factors that affect the thermotherapy effect of tumor, the most important is the heating technology, and the ideal heating requires that 100% of tumor tissue is heated to a temperature above its killing value and maintained for a certain time to destroy the focal tissue, but at the same time avoid the damage of normal tissue or organ around the tumor due to overheating.

In order to obtain a desired tumor hyperthermia effect, the following conditions must be satisfied when heating: firstly, heating the tumor tissue to be over 42.5 ℃ within a limited time and maintaining for a certain time; ② no cold spot below 41 ℃ can exist in the tumor tissue; ③ the temperature of the tissue surrounding the tumor must be kept below 45 ℃.

Disclosure of Invention

An object of the utility model is to provide a therapeutic equipment of solid tumour. In order to overcome the radiation that present various tumour thermotherapeutics produced because of improper heating methods, lead to the current situation of the bad treatment result that the thermotherapy apparatus temperature measurement is inaccurate, the estimation heating caused, the utility model provides a solid tumour's thermotherapy apparatus, this kind of brand-new thermotherapy apparatus can provide accurate, real-time, controllable needs temperature to the tumour.

In the following description, reference is made to the accompanying drawings that are not necessarily drawn to scale, but that are shown without departing from the spirit and scope of the invention. The description is not intended to limit the contents of the following examples.

A solid tumor therapeutic apparatus is provided with a heating needle with a temperature sensor, the front end of the heating needle is completely sealed, the shell is made of heat conduction materials such as metal or ceramics, and the like, and an internal heater and the temperature sensor are respectively led out of the heating needle by leads, fixed on the other end head of the heating needle and connected with a host computer for controlling temperature through lead plug connectors; the method is characterized in that:

in the utility model, the front end of the heating needle is a part of the shell, and the shape is one of a sharp shape, a hemispherical shape, a plane and arc combined shape, a plane and inclined plane combined shape and a plane and curved surface combined shape;

in the utility model, the heating needle shell is a metal or ceramic heat conduction material;

in the utility model, the heater is directly connected with the shell without a gap;

in the utility model, the heater and the temperature sensor are directly connected with the shell without gaps; the internal lead is directly connected to a host control module for controlling the heating temperature of the heating needle.

The utility model discloses, temperature sensor arranges the inside of heating needle and temperature measuring needle in respectively, and the end is directly to the temperature control module of host computer.

The utility model discloses, host computer temperature control module is a controller that provides direct current for the temperature of control heating needle monitors the temperature measuring needle temperature simultaneously.

The utility model comprises a heating needle, a temperature measuring needle and a host controller for measuring and controlling temperature, wherein the controller sets the optimal temperature value of the temperature measuring needle to be 44 ℃; the heating needle and the temperature measuring needle are respectively arranged at the center and the edge of the tumor by an ultrasonic image clinical medical means, the controller sends an instruction to the heating needle to heat the tumor, and when the temperature rises to a certain value, the temperature value detected by the temperature measuring needle is higher than the body temperature of a human body; when the temperature value monitored by the temperature measuring needle reaches the optimal temperature value of the temperature measuring needle set by the controller, such as 44 ℃, the controller records the temperature value of the heating needle at the moment, the controller controls the heating needle to keep the temperature constant for a specific time, the specific time carries out heating inactivation on the tumor according to the individual difference of tumor patients and the constant-temperature heating treatment time determined by a clinician, and the constant-temperature treatment time is generally within the range of 20 minutes to 90 minutes; the heating temperature of the heated solid tumor is determined according to the size of the tumor, the central temperature of the heated tumor is any one temperature value between 42.5 ℃ and 70 ℃, and the tumor edge is at an optimal temperature value such as 44 ℃.

The utility model has the advantages that:

1. the instrument can inactivate tumors and simultaneously does not damage normal tissues.

2. The instrument can realize conformal heating treatment of tumors with any shapes and sizes.

3. The inactivation temperature of the instrument to the whole tumor is below 70 ℃, the tumor tissue is not carbonized, and the generation of complications of postoperative heat absorption is avoided.

4. Clinical experiments show that the function and the function of an organism immune system to kill residual cancer cells in a patient body can be stimulated by low-heat stimulation at the temperature of less than 70 ℃ through heat treatment.

5. According to clinical pathological observation, necrosis is thorough in a region far away from a blood vessel, the outline of a glandular cavity is visible, nuclei disappear, eosinophilia is obtained, and cell ghosts are distinguishable.

6. According to clinical pathological observation, the necrotic area is degenerated in plasma vessels, the wall of the vessel is thickened, and the vessel cavity is blocked.

7. According to clinical pathological observation, lymph and plasma cell infiltration can be seen around the residual tumor, the degenerative and necrotic areas.

Drawings

FIG. 1: schematic representation of tumor treatment

FIG. 2: structure of heating needle

FIG. 3: temperature measuring needle structure diagram

FIG. 4: thermal field schematic representation of a single heater pin

Detailed Description

The heating needle leads 25 and 26 are connected with a controller, the temperature measuringneedle lead 34 is connected with the controller, the controller is powered on, and the next step can be carried out after the controller displays that the temperature value of the heating needle is stable.

The heating needle (figure 2) acts on the central position of the tumor of the patient.

Further, the heating needle body is a metalheat conducting casing 21, and the operator can directly insert thesharp front end 211 into the tumor of the patient. Theheater 22 is arranged at the front end inside the heating needle, and the heating needle is led out through alead 25 and is connected to the controller. Thetemperature sensor 23 is arranged in the heating needle, the heating needle is led out through alead 26 and is connected to the controller, and the temperature value monitored by thetemperature sensor 23 in real time can be transmitted to the controller. The tail of the heating needle is provided with ahandle 24, so that the operation is convenient for an operator.

Further, a temperature probe (fig. 3) is applied to the good tissue near the tumor. The temperature probe body is a metalheat conducting shell 31, and an operator can directly insert thesharp front end 311 of the temperature probe into the tumor edge of a patient. Atemperature sensor 32 is arranged in the temperature measuring needle, the temperature measuring needle is led out through alead 34 and is connected to the controller, and the temperature value monitored by thetemperature sensor 32 in real time can be transmitted to the controller.

Further, the operation of the heating pin and the temperature measuring pin has been completed as shown in fig. 1.

The controller can set the optimal temperature value of the temperature measuring needle to be 44 ℃; the operation controller can send an instruction to the heating needle to heat the tumor, and when the temperature of the tumor rises to a certain temperature value, the temperature value sensed by the temperature measuring needle is higher than the body temperature of a human body; when the temperature value of the temperature measuring needle reaches the optimal temperature value 44 ℃ of the temperature measuring needle set by the controller, the controller records the temperature value of the heating needle at the moment, and the temperature value of the heating needle can be ensured to be constant through the control of the controller.

Each heating device, namely the heating needle and the temperature measuring needle, works independently and supplies power independently; the stabilized direct current output by the controller is within a safety range of 36V.

Fig. 4 shows the principle of the thermal field of a single heating pin. After thefront end part 2 of the heating needle intervenes in a human body, a thermal field is formed around and gradually expands due to the heating action of a heat source, the temperature at the heat source is highest, the temperature is lower towards the periphery, and the temperature reaches the 'slope type' temperature balance of high inside and low outside within a certain time, for example, the temperature of the tumor edge is set to be a warning temperature value of 44 ℃ by a host controller, when the temperature of the heat source of the heating needle at the tumor center is continuously increased to 67 ℃, the temperature of the tumor edge is increased to 44 ℃ due to the biological heat conduction principle, the host controller immediately indicates that the temperature increasing action of the heating needle is stopped at 67 ℃ and is in a constant temperature state, and at the time, a constant temperature tumor state of 44 ℃ or less than 67 ℃ is formed from the tumor edge to the tumor center and is continuously kept at a constant temperature for 40 minutes (within the constant temperature treatment time range of 20 minutes to 90 minutes, determined according to the clinical needs of doctors). Here, the heating temperature determines theheating radius 41 range.

The first embodiment is as follows:

establishing a transplantation tumor model:

mouse colon carcinoma cell line CT26, purchased from American Type Culture Collection (ATCC) in the United states. The culture conditions are as follows: cultured in 1640 medium (Hyelene) containing 10% inactivated fetal bovine serum (Hyelene), and the cells were incubated in a CO2 incubator at 37 ℃ under 95% air and 5% CO₂Cultured under the conditions that the O2 concentration is 21%, and the cultured cells are digested with 0.25% pancreatin for passage.

BALB/c male mice, 6-8 weeks old, weighing 18-20 g, purchased from Beijing Wittiulihua laboratory animal technology GmbH, were also bred at the animal experiment center of the first clinical medical school of Harbin medical university.

Taking tumor cells CT26 in logarithmic growth phase, after trypsinization, washing twice in serum-free 1640 medium, then re-suspending into single cell suspension, adjusting the cell concentration to 106/ml, extracting 0.2ml of tumor cell suspension by using a disposable 1ml syringe, and inoculating the tumor cell suspension to the left flank abdomen of the mouse. The subcutaneous palpable tumor nodules are about 2-3 mm in diameter for about 7-9 days. 40 tumors formed, the tumor formation rate is about 95%.

Experimental grouping and treatment:

step 1: and (3) observing the growth condition of the tumor, observing the hair color, appetite and activity condition of the mouse every day after subcutaneous planting of the tumor cells, and measuring the weight every other day. Tumor size was measured with a vernier caliper every other day from day 7 of tumor loading, and tumor volume was calculated by the following formula V (cm3) 1/2ab2(a is the major diameter of the tumor, and b is the minor diameter perpendicular to the major diameter). When the long diameter of the tumor is more than 1.8-2.0cm and the short diameter is more than 1.2cm, the treatment is started, and the treatment is carried out 32 days after the tumor is loaded. The mice are fasted for 12h before grouping, 40 mice are numbered according to the weight from big to small and are divided into three groups, a forced-warm hyperthermia group (the numbers are 3, 4, 9, 10, 15, 16,. about.39 and 40 and total 14 mice), a microwave ablation group (the numbers are 2, 5, 8, 11, 14, 17.. 35 and 38 and total 13 mice), and a control group (the numbers are 1, 6, 7, 12, 13, 18,. 36 and 37 and total 13 mice), wherein the heated-warm hyperthermia group randomly selects 5 mice, and the other two groups randomly select 4 mice with broken necks to be killed and tumor tissues to be pathologically examined. The remaining 9 of each group were used for life time observation.

Step 2: the treatment system is used for treating thermotherapy groups. In the preliminary experiment, the time required for the heating thermotherapy to reach the specific temperature is longer than the time required for the microwave radio frequency therapy, so that the mice in the heating thermotherapy group are administrated with 10% chloral hydrate (0.03ml/10g) for intraperitoneal injection anesthesia, and the microwave ablation group and the control group are not subjected to anesthesia treatment. Before the experiment, the temperature of the heating needle of the therapeutic apparatus of the therapeutic system is preheated and adjusted to 40 ℃, and the temperature measuring needle is kept consistent with the room temperature of a laboratory, about 23-24 ℃. After the mouse is completely anaesthetized, the heating needle is inserted into the center of the tumor along the long diameter, and the temperature measuring needle is placed at the edge of the tumor (the distance is kept between 0.5 and 0.6cm, and the length and the short diameter are properly adjusted in some cases).

And step 3: and (5) treating the microwave ablation group. In order to facilitate observation of the life state of the mice, the microwave ablation time is short, and no anesthesia treatment is given before treatment. The microwave ablation needle is combined for treatment by adopting 54W microwave power and treatment time of 15-25 seconds (provided by oncology department of Kangyou microwave ablation therapeutic instrument, KY2000, Hayao Hospital, microwave ablation needle subjected to sterilization treatment, wherein the outer diameter of the microwave ablation needle is 1.9mm, the length of the needle head is 11mm, and the total length of the needle is 180 mm). And no temperature measurement link is adopted in the microwave ablation process.

And 4, step 4: the control group is not treated, and the pathology is taken simultaneously with the thermotherapy group and the microwave ablation group of the treatment system.

And 5: and (5) pathological observation. And (3) 24h after treatment, the pathological mice are taken out quickly after neck-broken parts die, fixed by 10% of Jiaxing buffer solution, sliced by paraffin embedding, stained by HE, and observed for tumor histological change under a microscope.

Therapeutic effect of different thermotherapy methods on tumor-bearing mice. Since the mice of each group showed the phenomena of shedding of tumor tissues and ulceration in different degrees in succession from the 2 nd day of treatment, the measurement of tumor volume could not be realized. Meanwhile, compared with the weight of 20-25 g of the mouse, the objectivity of the treatment effect evaluation through the weight of the tumor-bearing mouse is seriously influenced by the shedding of tumor tissues, so that the treatment effect of various methods is evaluated through a method for comparing the area of tumor necrosis areas (the percentage of the necrotic area of a tissue specimen to the total area) and the survival time of the tumor-bearing mouse in an experiment.

The statistical method comprises the following steps: the data from the experiment were processed using SPSS 13.0 statistical software, and the tumor necrosis area was compared between groups using the rank-sum test, and the Mann-WhitneyU test was used to compare between groups. P < 0.05 is statistically significant. And (4) carrying out survival analysis by adopting a Kaplan-Meier survival curve, and testing the survival curve by using Log rank. Test level alpha is 0.050

Treatment of the condition:

the treatment system can be used for heating treatment. According to the difference of the tumor size, the temperature of the heating needle can be preset between 45 ℃ and 51 ℃, timing is started when the temperature of the edge needle reaches 42.5 ℃, and the treatment time is about 1800s 2200s (30-36.7 min). The heating needle can be finely adjusted (+ -2 ℃) according to actual conditions in the process, so as to keep the temperature of the edge needle constant in a range of 42.5-44 ℃. And (4) always participating in the test process, and adjusting the central temperature and the edge temperature according to the real-time temperature display. The heating process is stable, the sensitivity of the heating needle and the temperature measuring needle is high, and the amplitude is +/-0.1 ℃. (Table 5)

The heating condition of the microwave ablation therapeutic apparatus. The experiment adopts 54W microwave power, and the experiment process has no temperature measurement and image guidance process [. sup.3 ]. Two of them died within 24h after surgery.

Histological observation

General observation: therefore, the treatment system has the advantages that the large-area bleeding of the tumor of the thermal treatment group is realized, and the tumor necrotic tissues are thorough. The tumor ablation area formed by the microwave ablation group along the direction of the microwave needle is blackened in color and solidified. Necrotic areas, damaged areas and normal tumor tissue are visible at the same time. In the control group, a small focus-shaped pink necrotic area at the center of a tumor body can be seen, the differentiation with the surrounding normal tumor tissue is clear, the tumor tissue is fish-like, and the edge of the tumor can be seen to be broken spontaneously.

Under-lens (optical microscope) observation:

the heat treatment group of the treatment system comprises: the boundary between the tumor tissue and the necrotic tissue in the lower edge area of the 40-time lens is obvious, the tumor cells at the periphery are hyperplastic and dense, the tumor cells are large and round, the nuclei are large and deep-dyed, and the heteromorphism is obvious. Under the 100 times of microscope, the large bleeding and the red blood cell overflow of the junction area caused by thermal injury can be clearly seen. A large amount of powder-stained necrotic tissues from the central area to the boundary area of the tumor under a 40-time microscope are nuclear fragments and non-structural substances formed by necrosis, falling off and fragmentation of cancer cells. No significant inflammatory cell infiltration was seen.

The microwave ablation group can see the tumor cells and residual tumor cells which are necrotic in the 40-fold and 100-fold mirrors to be mutually staggered, and no obvious boundary area exists. The invasion capacity of the residual tumor cells is strong, the shapes of the tumor cells in the necrotic area disappear, and the tumor cells are stained by powder. Blood vessel congestion, thrombosis and blood supply interruption can be seen in the 100-fold area under the microscope, and obvious inflammatory cell infiltration is not seen.

The contrast group can see the dense, disorderly arranged and low differentiation degree of tumor cells under the condition of 40 times and 100 times of the contrast group. The tumor cells are large and round, and the large deep staining of the cell nucleus has obvious heteromorphism. A large amount of red blood cells overflow from a plurality of areas and blood stasis in blood vessels can be seen, so that peripheral tumor cells are promoted to be necrotic. The necrotic area was seen with a 400-fold under the mirror with a small amount of lymphocyte infiltration.

In the experiment, evaluation calculation statistics is carried out on gross specimen dead zone areas by using a Sony digital camera and Photoshop (Photoshop v7.0 Adobe company) software. In the experiment, tumor necrosis areas of tumor-bearing mice among three groups are different, the P value is 0.012, and the statistical significance exists. The heat treatment group of the treatment system has statistical significance for the microwave ablation group and the control group, and the P values are 0.032 and 0.016 respectively. There was no statistical significance between the microwave ablation group and the control group.

Survival group observations:

tumor growth status: after the thermotherapy treatment, the general state of the mice was observed daily and no significant difference was seen between the groups. With the prolongation of tumor bearing time, the hair color of the mice is gradually withered, the mice have little appetite and poor activity.

After the heat treatment group of the treatment system treats, partial tumor bodies begin to have local necrosis and damage in the central region of the tumor in 2-3 d, the surface of the tumor bodies is uneven, and no obvious abnormality is seen in the peripheral region after the initial treatment.

After the microwave ablation group is used for treatment, the tumor surface is eschared, the color is darkened, and the tumor is hardened. Lesions formed after shedding of necrotic tissue in the central region of the tumor can also be seen over time. Mouse tumor size initially changed insignificantly, and tumor margins began to grow after approximately one week.

The control group developed ulceration at the later stage, but significantly later than the two groups. Through observation, the mobility of the mouse is slightly enhanced after the tumor surface is broken, and the flexibility of the mouse is enhanced by considering the weight loss of the mouse possibly caused by the shedding of the tumor body. The tumor size of the control group always showed an increasing trend.

And (3) life cycle comparison:

through observation, the death speed of the heating and heat treatment group of the treatment system is obviously slower than that of the microwave ablation group and the control group. Two deaths occurred within 24h after the microwave ablation group treatment, 1 death occurred within 48 h, with a mortality rate of 33% around the operative period. Compared with a microwave ablation group, the thermotherapy group of the treatment system has high safety in the process of treating tumor-bearing mice, and death cases do not occur in the period of operation. And (3) drawing a Kaplan-Meier survival curve of each group of mice inoculated with the tumor.

Log-rank test is carried out on the survival curves of the mice in each group, the median survival time of the thermotherapy group of the treatment system is 69d, the median survival time of the microwave ablation group is 51d, and the median survival time of the control group is 51 d. The overall survival time distribution of the three groups has difference, the thermotherapy group of the treatment system has statistical difference between the microwave ablation group and the control group, and the P values are 0.035 and 0.033 respectively. There was no significant statistical difference between the microwave ablation group and the control group. The method for thermal therapy based on the treatment system can obviously prolong the survival time of tumor-bearing mice. Microwave ablation is the most common heating mode applied in tumor thermotherapy, but there are still many technical problems, and the microwave thermotherapy is actually lacking in temperature measurement function due to the failure of the temperature sensing system caused by the strong interference of the high-energy microwave field. In the case where the internal temperature cannot be controlled, the duration of heating is difficult to control. Both excessive heating and insufficient heating can directly affect the therapeutic effect. The two mice are respectively treated by adopting 54W microwave power for 15-2 seconds, 5 seconds and 30-35 seconds before formal start of the experiment, and finally die after 30-35 seconds of treatment on the 12 th day. Prolonged microwave ablation has also been difficult to tolerate in mice already loaded for more than 1 month. Therefore, the formal experiment adopts relatively conservative 54W, and the treatment time is 15-25 s, but 1 mouse in the 9 mice in the survival group still dies within 24 hours and 2 mice die within 48 hours. The matching selection of power and time and the temperature measurement technology become main factors for restricting the treatment effect of the microwave ablation group in the experiment.

The embodiment of this specific implementation mode is the preferred embodiment of the present invention, not limit according to this the utility model discloses a protection scope, so: all equivalent changes made according to the structure and shape of the utility model are covered by the protection scope of the utility model.

Claims (3)

1. A solid tumor therapeutic apparatus comprises a heating device with a temperature sensor, the front end of the heating device is completely sealed, the shell is made of heat conducting material, and a heater and the temperature sensor inside the heating device are respectively led out of the heating device by leads and then fixed on one end; the method is characterized in that:

the front end is a part of the shell, and is in one of a sharp shape, a spherical shape, a plane shape, a curved shape, a combined shape of a plane and an arc, a combined shape of a plane and an inclined plane, and a combined shape of a plane and a curved surface;

the shell is made of a metal heat conduction material or a non-metal heat conduction material;

the heating device is connected with the outer shell in a gapless mode, or the heater is connected with the outer shell through a heat conduction material;

the temperature measuring needle is connected with the control module through a lead;

the temperature sensor is connected with the outer shell without a gap, or the temperature sensor is connected with the outer shell through a heat conduction material;

the wire is directly connected to the control module which controls the heating temperature of the heating device.

2. The solid tumor therapy apparatus according to claim 1, wherein: the temperature measuring needle comprises a temperature sensor, and the end head is directly connected to a control module for reading the temperature of the temperature measuring needle.

3. The solid tumor therapy apparatus according to claim 1 or 2, wherein: the control module is a controller for providing direct current and is used for controlling the temperature of the heating device and monitoring the temperature of the temperature measuring needle; the heating device and the temperature measuring needle are connected with the controller through a lead.

Images