The word “hyperthermia” comes from the Greek of which original meaning is “heat” or “overheat”. Hyperthermia is a physical therapy in which heat is transferred to the body to achieve its treatment goal through all kinds of heat sources. Common hyperthermia can be divided into three categories, i.e., diathermy, photo-thermal therapy and conductive heat therapy.
The blood circulation of the cancer cell population is quite special, as its blood capillary is fragile and the population has low heat dissipation. Therefore, when the whole-body temperature reaches 40.5℃, the temperature of local tumor tissue can be up to 45℃ or above. The sustained high temperature for a short period makes the tumor tissue and cancer cell die and encourages apoptosis but normal histocyte survives. In the mean time, high temperatures can damage tumor angiogenesis and inhibit the infiltration and metastasis of tumor cell through inhibiting the vitality of vascular endothelial growth factor in the tumor and matrix metalloproteinases.
Hyperthermia can boost the immune system, strengthen the vitality and immunity of Natural Killer cells (NK cells), T lymphocyte and macrophage. Meta-protein of tumor cell and breakdown products of necrotic tissue produced by hyperthermia can boost specific immunity for anti-tumors and enhance body immunity to fight tumors.
Additionally, hyperthermia can open up the pores and cause people to sweat, which is a way to detoxify your body. If certain drugs are infused to the body during hyperthermia, their efficacy can be significantly improved. Moreover, hyperthermia can increase the sensitivity of chemotherapy and local radiotherapy.
Local and Regional Hyperthermia
Local hyperthermia means a heating method in which the heating range is limited to including pathologic changes in local tissues without the overall rise of temperature in the body. While regional hyperthermia is another form of local hyperthermia, with heat sources such as, microwave, radio frequency and ultrasonic waves. Some researchers include it with whole body hyperthermia because it can cause the rise of temperature of the whole body. The therapeutic range of regional hyperthermia includes early, medium and advanced malignant tumors in various parts of the trunk, except for the head, neck, and limbs.
Whole Body Hyperthermia
Whole body hyperthermia refers to a hyperthermia method whereby various heating methods are used to raise the temperature of the human body to reach the therapeutic temperature which is maintained for a certain period of time.
The heating methods for whole body hyperthermia are divided into three categories: biological method, extracorporeal circulation method and superficial heating method. The biological method aims to heat the body by injection of microbial or biological agent, such as early injection of Coley toxin or short corynebacterium. It is rarely applied at present, because the degree of sensitivity reaction by the human body to the pyrogen is unpredictable and the heating temperature and time can not be easily controlled, resulting in high risk. The extracorporeal circulation method is to take some of the blood out of the body and heat it in vitro to a predetermined temperature with a special device, and then re-circulate it into the body to achieve elevated body temperature. This method is not popular due to high cost equipment and an elaborate procedural requirement.
The superficial heating method refers to thermal energy transferred to the body by radiation or conduction, such as infrared radiation, hot water bath, hot wax bath, and electric blanket wrapping. However, hot water bath, hot wax bath, and electric blanket wrapping have been rarely applied since the 1980s due to their various defects. Infrared radiation has been widely accepted clinically due to its definite heating effect, fewer side effects, easy monitoring, and lower cost.
Endoceliac Chemohyperthermia
Endoceliac chemohyperthermia refers to the method that the wherein liquid with chemotherapeutic drugs is infused into the body cavity and kept for a certain amount of time using the heating equipment, aiming to cure malignant tumors. The current common chemohyperthermias include intraperitoneal chemohyperthermia, intrapleural Hyperthermic infusion chemotherapy, bladder chemohyperthermia, and pericardial cavity chemohyperthermia which are under research. Endoceliac chemohyperthermia is characterized by high concentrations of local drugs, and low systemic toxicity. It is the most recognized, mature and common method of hyperthermia.
1.Intraperitoneal Chemohyperthermia
Intraperitoneal chemohyperthermia, as a relatively mature method applied clinically, it aims to heat the liquid with the chemotherapeutic drug which is filled into the abdominal cavity and kept in constant temperature. Under the condition of high temperature, the liquidity of tumor cell membranes increases, and then the chemotherapeutic drug with synergistic effect enters and congregates there. Since the concentration of the drug in the abdominal cavity tissue is much higher than that in plasma, it can kill any intraperitoneal metastatic carcinoma without great systemic toxicity. For this reason, it is widely used on the intraperitoneal digestive tract, gynecological tumors and ascites.
The indications of intraperitoneal chemohyperthermia mainly include treatment on peritoneal wide metastatic carcinoma (including gastric cancer, carcinoma of the large intestine, ovarian cancer, biliary cancer, pancreatic carcinoma, and peritoneal pseudo mucous gland cancer); prevention of postoperative peritoneal metastasis of gastric cancer, carcinoma of the large intestine, ovarian cancer, biliary cancer, pancreatic carcinoma, peritoneal pseudo mucous gland cancer; and treatment on malignant ascites. Its contraindications include; patients with intraperitoneal wide synechia, abdominal cavity with multiple tumors, complete intestinal obstruction, end-stage cachexia and severe cruor-promoting disorder.
2.Intrapleural Chemohyperthermia
As for the intrapleural chemohyperthermia, researchers adopt various methods and different apparatuses, but certain risks are present due to various physical limitations, such as vacuum sealing of the chest cavity, while the therapeutic result is invigorative and its efficiency on a malignant hydrothorax can be as high as 88% ~ 100%.
Indications of intrapleural chemohyperthermia include: ① cancer hydrothorax accompanied by non-small cell lung cancer; ② diffused cancer focuses in the pleura; ③ breakage of tumor during therapy; ④ less residue of recurrent cancer after resection; ⑤ reoccurrence and metastasis after surgery. Its contraindications include: ① patients with poor constitutional condition (KPS score＜60); ② patients with severe cardio-pulmonary dysfunction; ③ patients with tumor metastasis in the liver, brain, and bone; ④ patients with tuberculosis at tumor position; ⑤ fever, body temperature＞38 ℃, or accompanied by active infection; ⑥leukocytes or blood platelets less than normal and patients with bleeding tendency.
3.Bladder Chemohyperthermia
Through modern hyperthermic technology, bladder chemohyperthermia aims to heat the perfusate continuously and maintain it for a certain period of time. The sensitization and synergistic effects of hyperthermic chemotherapy, which, with its definite anti-cancer properties and pharmacokinetics advantage, can effectively kill the free cancer cells in the bladder, eliminate smaller residual cancer foci, prevent and cure bladder cancer and its postoperative recurrence, and improve the clinical therapeutic effect on bladder cancer. It is a therapeutic method characterized by low cost, effectiveness, simple operation, less toxic and less side- effects, fewer complications, and repeatable treatments.
Indications for bladder chemohyperthermia include the following: postoperative patients with non-muscle invasive bladder cancer, bladder cancer in situ, mastoid tumors which are distributed widely and with ablation difficulty, palliative therapy of invasive bladder cancer which cannot tolerate surgery or multiple superficial bladder tumors which can not receive any surgery or unsuitable for surgery due to poor body condition, preoperative cooperative therapies on invasive bladder cancers, and prevention of high-risk patients from tumor evolution.
Its contraindications include invasive tumors which have penetrated the bladder wall, urinary tract infections, and bladder inflammation.
