Interstitial microwave (915MHz) hyperthermia in conjunction with interstitial irradiation or drugs was performed on 3 recurrent gynecological tumors (2 vaginal wall, 1 parametrium). Two heat treatments were given before and after interstitial irradiation or administration of drugs. The temperature distribution was monitored simultaneously by 2 probes (4 points in each) inserted in the tumors. In 5 of 6 heat treatments, maximum tumor temperature of 42 - 45°C was maintained 60 minutes easily. The difference of maximum and minimum temperature is nearly 5 degree in each heating treatment. Our clinical experience is still limited, however, improvement of local tumor control will be expected with this treatment modality.

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Complex permittivity of agar phantoms and the temperature dependency were examined experimentally and obtained results were discussed from the point of view of developing a standard phantom in the microwave region.
Experimental results showed that an ideal agar phantom which was completely equivalent to the human tissue in the permittivity and was easily handled was not easily made, except at an special frequency range. But agar phantoms which are equivalent to human tissues in the conductivity are easily made in the wide frequency range and easily handled in clinical studies of hyperthermia.

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The use of vinyl chloride sheet 0.08 mm thick with a window in various sizes and shapes can control the temperature distribution in 8 MHz RF-heating using agar phantom model. It may enable a more precise heating area, even in the case of the tumor having various shapes and depth. In addition, excessive heat deposition may be avoided in normal surrounding tissues in RF-heating.

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The effects of thermotolerance on cis-platinum induced-oncogenesis were studied using C3H10T 1/2 cell transformation assay system. Exponentially growing cells were exposed to heat at 44°C or 2 μg/ml of cis-platinum with interval time of incubation at 37°C after a priming heat treatment at 44°C for 1 hr. The thermotolerance was developed and continued over several days. Heat sensitized the cytotoxicity to cis-platinum, depending on interval times between both treatments. At 48 hrs after the priming heat exposure, cells losed the sensitization of cell killing to cis-platinum, but were still thermotolerant. Our results indicated that transformation incidence induced by cis-platinum, of these thermotolerant cells, was the same level as that of non-thermotolerant cells. It is suggested that the oncogenesity by cis-platinum in clinical hyperthermia will not be enhanced during the thermotolerant state of cells.

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The adult mongrel dogs were divided into 2 groups of 8 each infused and not infused physiological saline intraperitoneally. The whole abdomen was heated with 8 MHz radiofrequency capacitive hyperthermia system. The mean increase in total-body temperature under the whole-abdominal hyperthermia was 6.4°C for the saline-infused group and 5.1°C for the non-infused group. The total-body temperature reached 40°C about 50 min after the start of heating in 4 of 5 animals of the saline infused group ; in 3 of the 4 animals died, in which the highest temperature of the peritoneum in the deep abdomen or liver exceeded 43.5°C. The permissible range in heating the visceral organs seemed to be less than 43.5°C in due consideration of the effects of heat on the visceral organs. Changes in the liver were very marked in blood biochemical data and microscopical examination of the visceral organs. It was probable to achieve mild-high total-body temperature about 40°C by means of whole-abdominal hyperthermia within 43.5°C for the permissible temperature of the visceral organs.

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Sarcoma-180腫瘍を大腿部皮下に移植したICRマウスにグルコース(6mg/g)を腹腔内投与し高血糖症を誘発させて,腫瘍部を特異的に低pHにし,グルコースによる温熱増感及び温熱耐性の出現度合を調べた.温熱処理は恒温水槽を用い,43℃,30分間の温熱を加えた後,種々の時間間隔を置いて,2回目の43℃,30分間の温熱を加えた.グルコースの投与後,高血糖症が発生し,腫瘍部は0.3～0.6pHの低下を示したが,正常部は0～0.1pHの減少にとどまり,その回復時間も早かった.温熱処理時のpH低下は腫瘍部も正常部も0.2～0.3pHの低下が起こり,温熱とグルコース投与の併用では,pHの変化は腫瘍部では6.9から6.5へ,正常部では7.2から6.9へ減少し,加温後正常部はすぐに元のpH値に回復したが,腫瘍部の回復時間は遅かった.温熱耐性はグルコース投与群で,加温後6時間目に最大を示し12時間目には消失しているが,グルコース非投与群では12時間目に温熱耐性が最大となり72時間後も温熱耐性の完全な消失を示していなかった.加温後12時間目にグルコース投与群の腫瘍成長速度は4日間も非投与群より遅れ,全加温間隔で1～2日間の遅れが示され,グルコースによる有意な温熱増感が示された.本研究の結果から,グルコース投与により誘発する高血糖症は腫瘍部を選択的に低pHに出来る事が示された.これらの結果から本法は腫瘍部に対し,温熱効果を選択的に増強できることを示唆している.

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In recent years, hyperthermia has been used to treat malignant tumors, and attempts have been made to improve its therapeutic efficacy. However, since the highest temperature currently used in whole clinical body hyperthermia is around 42°C, its therapeutic efficacy still remains less than satisfactory. Generally, the safety limit for the highest temperature for the body is thought to be around 42°C. However, the critical temperature for cell lethality is considered to be around 43°C, and cell lethality is remarkably increased by elevating temperatures above 43°C. Rapid tumor cell killing can be achieved by maintaining the body temperature at 43°C for 90 mintues.
In our present experiment, 5 Japamese monkeys were kept under hyperthermia maintained at 43°C for 90 minutes. After the experiment, 4 monkeys survived, and no abnormal findings were noted. Systolic arterial pressure was significantly elevated as the body temperature rose to 42°C and declined somewhat aftef reaching 43°C. Thereafter systolic pressure remained at 110-123 mmHg. The heart rate increased with rising body temperature and remained the highest when the temperature was at 43°C for 90 min. With normalization of the temperature, the heart rate dropped to 170 beats/min, but was still higher than the preheating level. According to a blood gas analysis, PaO2 was persistency elevated above 400 mmHg during hyperthermia. In serum electrolytes, the K ion was elevated during hyperthermia then declined below the preheating level after normalization of the temperature.
Although there are species differences between man an monkey, our results suggest potential clinical applications for hyperthermia at 43°C, which will contribute to a dramatic increase in its therapeutic efficacy.

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Two patients with primary lung carcinoma were treated by local hyperthermia combined with radiotherapy at the National Medical Center Hospital. We used 8MHz radiofrequency (RF) capacitive heating equipment. Hyperthermia was administered locally once a week or twice a week after irradiation, for 60 minutes. Radiotherapy was performed in fractions of 2 Gy per day, 5 days a week to 60 Gy. Tumor temperature was continuously measured by thermocouples inserted into tumors through endoclosed catheters, while thermal distributions with tumors and surrounding normal tissues were obtained. Thermometry results were as follows. (1) The maximum temperatures arround the vertebral bones or the inside of the ribs were about 41°C. (2) The maximum temperatures of the normal lung tissues were about 41°C. (3) The maximum tumor temperatures were 42-44°C.
Each cases showed PRb when the tumor response was assessed by tumor size measurement on CT scan. But histopathological examinations demonstrated more effectiveness of the tumor tissues, almost cancer cells showed the fibrotic or necrotic changes. But degenerated cancer cells were partially remaining especially in the tumor tissues which were localized around the vertebral bones or the inside of the ribs. This is the most important problem with the heating to the lung tumors.
Complications were not seen in this treatment.
This preliminary results suggest the effectiveness of RF capacitive heating combined with irradiation for lung carcinomas.

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The temperature dependency of complex permittivity of biological tissues was measured and much information could be derived from a series of preliminary experimental results.
The temperature coefficient of conductivity was larger than tht of dielectric constant and fairly large temperature coefficients were observed in fatty tissues rather than nonfatty tissues. Although it depends on the frequency of a heating equipment, real-time control of the equipment may be required to keep the best condition for the treatment (e. g. a desirable temperature pattern). This also means that the temperature dependency must be taken into consideration in the computation of temperature distributions for planning of the treatment. The temperature dependency of the permittivity may be utilized for noninvasive temperature monitoring in the active imaging, but at the same time, it is undesirable in a passive method such as microwave radiomtry.

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Heating experiments on phantoms and miniature pigs were made by using two lens applicators and a waveguide applicator fed by the 430MHz microwave heating system (HTS-100, producted by Tokyo Keiki Co., Ltd.). Temperature distributions of agar phantoms and miniature pigs were measured at regular intervals during heating. As the results of these experiments, the followings are obtained.
1. The results of effective heating depth varying with a focal length confirm lens effect.
2. Using a four-aperture lens applicator and miniature pigs, the heating depth of 6cm and it almost doubles that of the ordinary waveguide applicators. The heating area is 12cm x 6cm at 4cm depth.
3. Dielectric properties of miniature pig buttocks are nearly equal to these of the agar phantom containing 0.35% NaCl and 0.05% NaN₃.

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The effects of an internally placed metallic bar on the thermal distribution in agar phantom by RF hyperthermia were studied. There was no hot spot when the metallic-bar was parallel to both electrodes, whereas hot spots were there in both edges of the bar if the bar was perpendicular to the electrodes. In the clinical application of RF hyperthermia, we treated one patient with recurrent sacral tumor (synovial sarcoma) who had metallic bar implants in his lumbosacral region. As we applied the electrodes parallel to the metallic implants, he could receive RF hyperthermia safely and effectively fourteen times without any complication. It is important to give careful considerations to spatial relation of electrodes and metal when treating patients who have metallic implants.

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