Seventy-eight patients with an untreated rectal cancer were randomly divided into two groups A and B. To 40 cases of Group A, the radiotherapy was received first, and then, in thirty minutes, the intracavitary hyperthermia using 915 MHz microwave was given in twice a week. The dosage selected for the radiotherapy were severally 30Gy/3 weeks and 40Gy/4 weeks. In Group A (combined treatment) CR and PR were observed in 57.5% and 32.5%. As compared with it, in Group B (radiotherapy alone) CR and PR were seen in only 5.3% and 26.3%. In both groups the radical resection was performed after preoperative procedures, and the combined effect between radiotherapy and hyperthermia was confirmed histologically.

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Hyperthermia has emerged as a promising alternative or adjunct to other forms of brain tumor therapy. Interstitial microwave irradiation is an effective method of inducing localized brain hyperthermia. However, one of the problems of this technique is the overheating of the tissue adjacent to the antenna. In this study, a cooling system for interstitial microwave antenna was developed for the purpose of making more uniform and accurate heating by elimianting this overheating. The ability to generate more uniform hyperthermic field was evaluated in normal monkey brain.
Ten brain hyperthermia trials have been performed in 5 Japanese monkeys. Under general anesthesia and controlled respiration, a perieto-occipital craniectomy of 4 × 4 cm in size was performed. The antenna cooling system was made of silicon tube of 5 mm in outer diameter. The microwave antenna of 1.5 mm in diameter was inserted into the brain with the system at the depth of 2 cm. The antenna was cooled by cold water perfusing in the cooling system. The brain tissue was heated by 2450 MHz microwave irradiation with net forward power of 10 W. Temperature distribution was mapped using nonperturbing thermocouples. This distribution with the cooling system was compared with that of without the cooling system.
Using the same net forward power, the maximum cross-sectional diameter of brain heated to 42°C or above was roughly equal (about 2.6 cm in diameter) regardless the existence of the cooling system. However, this cooling system prevented the rapid radial fall off in temperature by changing the water flow volume in the system.
This study shows that this cooling system enables more uniform and accurate heating with the interstitial microwave antenna and may be applied for clinical use.

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Although it is very important in practice of systemic or local hyperthermia to know the influence of heat on brain function, little is known about it. In this experiment, the changes of electroencephalogram (EEG) during hyperthermia was studied to see the tolerance of the brain to heat.
Unanesthetized and immobilized adult rabbits were used in the experiments under controlled respiration. The whole body or head alone were heated by bathing in hot air. Monopolar records of EEG of the motoriosensory area analyzed by the Berg-Fourier analyzing system.
In the whole body bathing, the animals died of abrupt fall of the arterial blood pressure when the temperature of the aortic blood was raised over 43.5°C, and it was impossible to heat the brain over 43°C. On the other hand, the brain temperature could be heated up to 45°C without extreme fall of the blood pressure in the head heating, because the aortic blood remained under 43.5°C at that condition.
In the head heating, the peak frequency of power spectrum of EEG increased as the temperature was raised. High amplitude rhythmic slow wave burst appeared at over 44°C for 30 minutes, which soon changed to a flat pattern.
These findings show that the heat can activate the EEG function parallel to the increase of the temperature, and if the aortic temperature of the animals is remained under 43.5°C, the cerebral functions can be preserved until the temperature of brain reached to 44°C, but in the clinical hyperthermia, it will be safe to keep the brain temperature less than 43°C.

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Response rate of malignant tumors for the treatment of combined radiotherapy and hyperthermia in 1986, from April to December were compared to the earlier results which were already reported.
Sixty percent of 25 superficial tumors showed good response (complete response and partial response more than 50% in size), for 26 deep seated tumors, response rate was 23%. These results are not different from the response rate of the treatment for earlier group of patients, even so many technical improvements were done during this period. Kajira already reported that the response rate of deep seated tumors will go up higher, when it is adjusted by histological findings of X - ray computed tomography of tumors after the treatment.

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[in Japanese]

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With new ferromagnetic implant with low curie point (Ni 70.4%, Cu 29.6%), temperature elevation and distribution in phantom, animal and tumor implanted in rabit were studied. Elevation of temperature both in phantom and muscle in rabit was satisfactory regarding the strength of magnetic field and time reguired to be plateau level. At the curie temperature of 50°C, center of the 4 implants separeted 1.5 cm earch showed 45°C, but in the muscle of rabbit, it reached 42°C. The difference was interpreted by the cooling effect of blood flow in the muscle. Temperature elevation in VX-2 tumor in rabbit was also demonstrated.

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Twenty two patients with primary or secondary liver tumors were treated by radiofrequency hyperthermia (8 MHz) combined with radiation or chemotherapy. Hyperthermia was administered twice a week for 40-60 minutes per session up to a total of 5-48 sessions. Five fractions per week of irradiation (10 MV X ray) at 180-200 cGy or intraarterial chemotherapy using mitomycin C, cis-diamminedichroloplatinum or adriamycine were carried out. Intratumor temperature over 42.5°C were obtained in 9 of 17 patients.
Of the 22 patients treated, 2 (9%) showed complete response, 8 (36%) partial response, 3 (14%) minor response, 7 (32%) no change and 2 (9%) progressive disease. 7 out of 14 tumors, heated over 42.5°C showed complete or partial response but only 1 out of 5 tumors, heated under 42.5°C was responder. Complication observed were thrombocytopenia and leukopenia in 30% of cases.
These results showed that combined treatment of hyperthermia radiation and chemotherapy appear to be useful from of therapy for the patients with liver tumor.

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The histopathological study was performed on 16 human malignant tumors which were treated with thermoradiotherapy. The microscopic examination revealed marked necrosis throughout entire sections in 4 tumors to which irradiation to more than 60 Gy in combination with heating at over 42°C was delivered. In other 7 tumors, a massive coagulation necrosis occupied three fourths of tumor tissues, mainly in the part of the core. The remaining 5 tumors showed only slight histological changes, that is, the area of intratumor necrosis was less than three fourths of an entir tumor section.
A marked destruction of blood vessels appeared in the tumor parenchyma in 13 of the 16 tumors, while in the stroma in only 2 tumors. A condensation of destroyed nuclei was revealed in 11 tumors.
Viable tumor cells surviving after thermoradiotherapy were observed in the central area in 3 tumors, around blood vessels in 2 tumors and in the peripheral zone in 12 tumors. These results indicated that thermoradiotherapy affected the center area of tumors more prominently than the peripheral zone, and provided a rationale for the combined use of a high dose of radiation and hyperthermia in the definitive treatment of bulky tumors.

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Thermotherapy has not yet been firmly established clinically because of the various problems with heating devices and the difficulty in maintaining a proper therapeutic temperature, and much is unknown about its effects on the whole body. We have recently attempted thermotherapy, using an RF heating apparatus, on patients with malignant tumors in the field of gynecology, concomitantly with radiotherapy or chemotherpy, and studied its effects on the whole body, with following results.
The heating apparatus used in the present experiment was a BSD-1000 APAS. Equipped with 8 confronting poles, it can heat the pelvic cavity almost uniformly by using electromagnetic waves of 75 MHz. The subjects were 22 cases treated in the past year, consisting of 10 cases of cervical carcinoma, 2 cases of carcinoma of the uterine body, 3 cases of ovarian carcinoma, 6 cases of vulvar carcinoma, and one uterine sarcoma, in which chemotherapy was concomitantly given in 5 cases and radiotherapy in 16 cases. For the purpose of systemic control, the body weight was measured before and after heating, and the body temperature, blood pressure and pulse rate were continuously measured during the heating process, while the peripheral blood, electrolyte, renal function, and hepatic function were examined throught the term of treatment. In the heating process, parallel to the elevation of body temperature, the pulse rate and systolic pressure increased extremely while the diastolic pressure dropped, but after heating, the blood pressure returned to the pre-heating level after a sudden decline. The decrease of body weight after heating was approximately 500 ml. Other examination findings were almost within the normal range.

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Using KK-47 bladder carcinomas transplanted into the leg of nude mice, hyperthermic tumor destruction was studied in terms of tumor growth curve, histopathological picture and two-wavelength flow cytometric DNA histogram. Local hyperthermia was carried out by immersing the tumor-bearing leg in a water bath at a temperature of 40.0, 43.0, or 43.5°Cfor 10 to 30 minutes. There was no complete tumor response; however, a significant temperature-relating tumor growth inhibition or reduction was obtained for 2 weeks after hyperthermia in each of 40 to 43.5°C hyperthermia groups. The inhibited tumor growth was followed by a logarithmic tumor increase which was similar to that observed at an initial growth phase of control group. By 7 weeks after hyperthermia, these tumors closed to the tumor size of control group. Different degrees of pyknotic necrosis, hemorrhage, congestion and edema suggesting hyperthermic vascular damage were observed as initial histological lesions in the group of 43. 5°C hyperthermia. These findings were daily augmented for 7 days and then the necrotic areas were replaced by the intact tumor tissue for up to 3 weeks after hyperthermia. Flow cytometric studies using a two-wavelength analysis of RNase- and 2N-NCl-treated cells revealed a significant increase in nuclear DNA damage at an early phase of 2 days after 43.5°C hyperthermia when the HCI-treated cells were used, and then it reached a maximum level 2 weeks after hyperthermia.
The results obtained suggested that hyperthermia should be combined with other cancer treatment modalities exerting synergetic or additive antitumor effects.

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Temperature rise of the subcutaneous fat tissue underneath a heating probe and the intravesical space was studied in 21 patients with bladder tumor during RF-heating. There were significant correlations (p<0.01) between the thickness of the subcutaneous fat tissue and the intravesical temperature, and the temperature of the subcutaneous fat tissue. In addition, similar correlations were observed between the mean output power and the intravesical temperature.

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