I. Tumor thermal therapy 1. Mechanism of tumor thermal therapy 1) Biological basis of thermal resection therapy: Heating can cause significant changes in cellular biomolecules and biochemical metabolism, which can induce cell degeneration and even irreversible damage. Studies have shown that when the temperature is slightly increased to 400C, the cells can still maintain their stability; when the temperature is increased to 420C~450C, the cell stability decreases and the sensitivity of tumor cells to radiation and chemotherapy drugs etc. increases, but this temperature does not lead to cell necrosis; if the temperature is increased to 450C and lasts for 60 minutes, irreversible damage will occur to the cells; by further increasing the temperature to 500C to 520C, the time required for cell necrosis is significantly shortened; if the temperature reaches 600C to 1000C, protein denaturation occurs immediately and coagulative necrosis occurs, which constitutes the biological basis for treating tumors. Thermal resection for tumor treatment is to use energy sources such as radiofrequency, microwave, ultrasound and laser to produce high temperature of 600C~1000C in the target area of tumor treatment through energy conversion to induce coagulative necrosis of tumor cells. (2) Biological basis of traditional thermotherapy: Traditional thermotherapy is a heating treatment method that takes advantage of the difference in heat sensitivity between tumor tissues and normal tissues. Studies have shown that the microenvironment such as hypoxia, lactic acid accumulation (acidic, low PH value) and poor nutrition in tumor tissues, and the characteristics of tumor peripheral environment are one of the factors that make tumor sensitive to temperature and heat. Tumor thermotherapy is precisely the use of physical heating technology to heat tumor cells up to a certain temperature and act for a certain time, so as to achieve the purpose of killing tumor cells. Modern thermal biology reveals that a temperature of 41oC~45oC and maintained for more than 30 minutes can kill some cancer cells. The abnormal morphology and structure of tumor blood vessels cause poor heat dissipation, which makes a temperature difference of 5OC~10OC between normal tissues and tumor tissues, and this temperature difference can effectively protect the normal tissues around the tumor from damage. (3) Studies have shown that the anti-tumor mechanism of thermo-therapy is due to the induction of apoptosis of cancer cells and the inhibition of proliferation of mainly S-phase cells. High temperature has the greatest damage to S-phase cancer cells and the high sensitivity of oxygen-depleted cells to heat, which has a complementary synergistic effect with radiotherapy or chemotherapy. Heating can inhibit the repair of sublethal damage and potentially lethal damage of cancer cells caused by radiotherapy or chemotherapy, inhibit the vascular growth of primary tumors and metastases, and achieve the effect of inhibiting tumor proliferation, thus enhancing the effect of radiotherapy and chemotherapy, which is often used as a sensitizing measure of radiotherapy or chemotherapy. 2.The heat source of local thermotherapy Tumor local thermotherapy is also called thermal coagulation (ablation) therapy, including: high-intensity focused ultrasound (HIFU), image-guided radiofrequency, microwave, laser percutaneous percutaneous thermal coagulation therapy technology, etc. It is through image guidance and accurate positioning, or through electrodes inserted into the tumor tissue, around the tumor tissue for dose control and temperature field regulation, to achieve the effect of one-time in situ inactivation of tumor. It can become one of the important means of tumor treatment after surgery, radiotherapy and chemotherapy. At present, the heat therapy to denature, coagulate and necrotize tumor mainly adopts the heat effect generated by local microwave, radio frequency, ultrasonic radiation, laser, etc. as heat source in clinical practice. Microwave thermotherapy Microwave coagulation therapy (PMC). Microwave is a kind of electromagnetic wave, which is inserted into tumor tissue through coaxial needle antenna, generating a high frequency electromagnetic field locally, using the molecular vibration of water-based components in the tissue as the heat source, transforming microwave electrical energy into heat energy, causing the tissue temperature to rise and producing thermal effects. As in the case of liver cancer treatment by microwave coagulation necrosis, the microwave emitted from the needle electrode inserted into the lesion generates heat, causing the temperature of the central part of the electrode to rise to 650C ~ 1200C, and the adjacent parts can also reach 450C ~ 500C, using microwave heat to rapidly denature, coagulate and necrosis of cancer cells. In April 1996, it was applied to the treatment of liver cancer. Japanese scholars reported that <2 cm liver cancer microwave therapy alone is similar to liver resection. After 1995, the coagulation range was extended to <3 cm. Its efficacy is related to tumor developmental pattern, vascular content, size and location. Treatment requirements for obtaining complete tumor necrosis: treatment reaches cancer and peri-cancerous tissue, satellite focal cancer and cancer foci not revealed by ultrasound should be thought of to ensure treatment margins of 5 mm or more. Indications: lesions <3 cm, small hepatocellular carcinoma mainly; liver function grade II, caution should be taken for carcinoma foci in the hilar area with the possibility of damaging the bile duct. Radiofrequency thermotherapy Radiofrequency thermotherapy is also called radiofrequency thermal ablation. Radiofrequency refers to the generation of high frequency (460~500KHZ) by a special device to make the non-insulated part of the electrode in working state flow out the alternating current into the tissue, which activates the ions in the tissue and makes the ions oscillate rapidly, transforming into heat energy and generating high temperature of 80OC~100OC, using the high temperature to make the protein coagulate and necrosis and destroy the tumor tissue, while the electrode itself does not heat up. Some domestic hospitals have introduced the world's most advanced electronic computerized automatic navigation system multi-bullet radiofrequency therapy instrument, so that the inactivation of liver cancer tissues of 5-7cm can be completed at one time. The treatment is automatically navigated and commanded by the computer system, and 10 small electrodes of "multiple warheads" are sent out from the catheter to "lock" the liver cancer tissue, and the "cluster multiple warheads" send out high-energy radiofrequency waves to cause coagulation and necrosis of the cancerous tissue proteins. The "warhead" will automatically stop when it reaches the boundary between liver cancer tissue and normal tissue, thus protecting normal tissue and adjacent organs from damage. This therapy is effective for certain liver and lung cancers. In Japan, laparoscopic radiofrequency ablation therapy under general anesthesia has been carried out since February 1999 and has become the preferred treatment method. Its indications: tumor <4 cm; <3 cancer foci, liver function Child-pugh A or B, no vascular involvement. A non-randomized controlled study showed that for small hepatocellular carcinoma ≤2 cm in diameter, radiofrequency ablation therapy was similar to percutaneous anhydrous alcohol injection therapy with no significant difference. The study concluded that for patients with small hepatocellular carcinoma with tumor diameter up to 3 cm, percutaneous radiofrequency ablation treatment was chosen to be more effective. And for patients with liver cancer with tumor diameter between 3.1 and 5 cm, surgical radiofrequency ablation treatment may improve their survival rate. High-energy focused ultrasound (HIFU) therapy High-energy focused ultrasound (HIFU) therapy is a method to focus high-energy ultrasound on the deep target tissues of the body, so that the temperature of the target area can rise 80℃～120℃ in a very short time to directly kill the tumor in the target area. It is a kind of local physiotherapy, using high temperature to cause tissue coagulation and necrosis, which is called "thermal resection". In the field of tumor therapeutics, there is a breakthrough in high-intensity focused ultrasound, i.e. "ultrasound focused knife". Ultrasound has the characteristics of good directionality, intra-tissue penetration and focus. The high-intensity focused ultrasound knife emits hundreds of beams of high power rate ultrasound directed to the internal tumor area of human body through the concave surface of the machine, which penetrates into the tumor entity through the coupling effect of water medium, and generates thousands of times of energy superposition at the focal point. The high temperature effect makes the temperature of tumor tissue reach 800C~1000C, and through transient high temperature, it causes protein denaturation of cancer mass in the target area (tumor), resulting in coagulative necrosis and irreversible damage to tumor cells for treatment purpose. In addition to high temperature effect, "ultrasound focused knife" also has cavitation effect, mechanical effect and acoustic-chemical effect. The cavitation effect is to damage tumor tissues by generating free radicals in biological tissues until collapse; the mechanical effect refers to the large amplitude mechanical wave generated by ultrasonic waves, which can pull through tumor cells and cause them to lose their vitality; the acoustic chemical effect can make the chemical components in the cell membrane structure to produce chemical reaction under the action of high-energy ultrasonic waves and kill tumor cells. The biological effect of "ultrasound focused knife" is based on high temperature coagulation plus the comprehensive effect of cavitation and mechanical effect, which is a new technology for minimally invasive treatment of tumor. The disadvantage of high energy focused ultrasound (HIFU) treatment is that its focusing area is small, and it often needs to be repeatedly performed several times when treating tumors, and it is limited by the existing imaging technology. The treatment access is also limited by the absorption and reflection of high-intensity ultrasound by cavity organs such as ribs and stomach and intestines. V. Laser-induced mesenchymal thermotherapy A laser head is placed into the cancer (such as liver cancer) under local or general anesthesia with ultrasound, CT or MRI-guided percutaneous puncture or open abdominal direct vision. The low-energy laser (3W-15W) is transmitted to the laser head through optical fiber, and the light energy is converted into heat energy to continuously heat the cancerous tissue (3-30 minutes) to a certain temperature range (450C-950C) to cause its coagulation and necrosis, while the normal tissue is not damaged. Ablation is the direct destruction or melting of cancerous tissues by physical or chemical methods. Ablation is further divided into physical ablation and chemical ablation. Physical ablation is to put microwave antenna or radiofrequency electrode into the tumor after puncture, using the principle of electromagnetic wave heating in the tissue to make the cancer tissue coagulate and necrosis, so it is also called microwave knife, radiofrequency knife or thermal coagulation knife; chemical ablation is to inject protein coagulant directly into the tumor center through puncture needle, using the protein coagulation effect of chemical drugs to make the cancer tissue coagulate and necrosis, so it is also called chemical knife. The superiority of thermal resection therapy and traditional thermal therapy The superiority of the above local tumor thermal therapy, also called thermal resection therapy, compared with traditional warm therapy are: ① High temperature and short treatment time. It raises the temperature of tumor cells to more than 600C in a short period of time, causing irreversible damage to them. ②High precision. Heat resection treatment is highly concentrated and the tissues inside the target area (tumor) are completely destroyed, while the tissues outside the target area are relatively safe. ③The effect of heat dissipation from large blood vessel blood flow is significantly weakened. Due to the high energy intensity and short radiation time, even the tumor tissues located around the large blood vessels can reach the temperature required for treatment in a short time. As a class of minimally invasive or non-invasive tumor treatment technology, thermal resection therapy of thermotherapy is a new rewarding trial in the history of local tumor treatment. However, as an emerging tumor treatment method, it is not mature enough, such as the formulation of protocols, intraoperative monitoring, postoperative follow-up, etc. There are still many shortcomings, and a lot of multicenter studies are needed for its continuous development and improvement. VII. Whole-body thermotherapy for cancer Whole-body thermotherapy is a method to kill cancer cells by raising the whole-body temperature to 39.50C~41.50C for 2~4 hours with the heat effect. Heat treatment works by destroying cancer cells to denature proteins. The vascular and microcirculatory structural characteristics of tumor tissues, as well as the physiological environmental factors of tumors, constitute the biological basis of high temperature treatment of cancer. Solid tumor tissues lack smooth muscle and innervation, and lack the function of regulating heat, so that the diffusion rate of tumor tissues to heat is reduced, the temperature is easy to rise, the heat storage time is long, and it is in the state of lack of oxygen. In clinical thermal therapy, it is often found that the central area of large tumor is easy to die after heat because it is in low nutrition and low PH (acidic) state. In turn, low PH and nutrient deficiency are usually caused by chronic hypoxia. Chronic hypoxic cells are sensitive to heat therapy and resistant to radiation therapy, which is the rationale for the combined application of heat and radiation therapy. The advantage of combined application of whole-body thermotherapy and chemotherapy is that heating destabilizes the membrane of cancer cells and increases the permeability of the membrane, which is conducive to the penetration and absorption of chemical drugs, and at the same time, it can reduce or prevent the generation of drug resistance in the organism. There are two types of whole-body thermotherapy that should be used in clinical practice at present. One is the body surface heating method, which is to transfer the heat emitted from external heat sources into the body through the body surface, resulting in whole-body heating, and the application of far-infrared radiation method to induce whole-body thermotherapy, which puts the patient into a closed far-infrared radiation chamber and raises his whole-body temperature through infrared radiation. One is composed of two major parts: the whole-body heat therapy machine extracorporeal circulation system and blood heating, multi-parameter real-time monitoring system. That is, the blood is drawn out from the patient's body and heated through the heating system of the heat therapy machine, and then transfused back into the body. Since the blood is flowing all over the body, it can raise the temperature of any part of the body to about 420C (the limit acceptable to the human body) and maintain it within this temperature range for 2 hours, thus achieving the effect of systemic destruction of cancer cells. Argon-helium superconducting treatment for cancer The new argon-helium superconducting targeted surgery system, also known as "argon-helium knife". Argon-helium knife cryotherapy (ASCS) is a new cryotherapy technique developed from traditional cryotherapy in recent years, which combines ultra-low temperature and warming technology to surpass the effect of freezing or heat therapy alone. Its characteristic is that argon gas can make the lesion tissue in the tumor target area drop to minus 100OC~165OC within ten seconds through the knife head, and then introduce helium gas to the knife head to make the frozen tumor re-temperate and warm up to 40OC degrees rapidly, which makes the temperature rise and fall instantly and the tumor is destroyed into pieces. This treatment process can make the intracellular ice crystals expand and "burst", which is more destructive than the single freezing or heat therapy in the past, and at the same time, while the hot and cold effect kills cancer cells, the destroyed dead cell fragments can also modulate the tumor antigen, which has the effect of significantly increasing the anti-tumor immunity, achieving the double treatment. It has a double therapeutic effect. The clinical application shows that it has achieved good efficacy in liver cancer and lung cancer. Since Ar-He knife can only kill most of the cancer cells in the target area, it is a kind of local treatment, so it is better to use chemotherapy or radiotherapy together with Ar-He knife before or after surgery. Photodynamic therapy for tumors Photodynamic therapy is a new technology to diagnose and treat tumors by using photodynamic reaction. Its principle is to irradiate hematoporphyrin with appropriate wavelength laser to make it fluoresce and produce toxic oxygen radicals to kill tumor cells. Firstly, hematoporphyrin, a photosensitizer, is injected into the patient, and the latter reaches the tumor tissue with blood flow in the body, and its affinity with the tumor tissue is much greater than that of normal tissue, and accumulates in the tumor tissue. The monomorphic oxygen reacts with the adjacent biomolecules to produce cytotoxic effect, which directly inactivates the tumor cells without damaging the normal tissues. The laser source in photodynamic therapy is a cold light source with low laser energy, which does not cause thermal damage to the irradiated tissues and only plays the role of activating photosensitizer, and this method is suitable for the treatment of small (<3 cm) and inoperable malignant tumors of esophagus/airway. All of the above methods of tumor treatment except systemic thermotherapy are local treatment methods, each with certain indications and limitations. Only by complementing the shortcomings of these methods and applying them in a reasonable way can we improve the cure rate and survival rate of tumor patients.