Now hyperthermia is widely used to treat clinical malignancies. In this articles, the history, the principle, the techniques and the clinical results of hyperthermia treatment were reviewed, and prospects of it were also mentioned. At present, methods of deep heating have to be improved, the possibility of non-invasive thermometry has to be considered, heat sensitivity needs to be defined and a practical concept of thermal dose has to be worked out. The recent wide clinical use of hyperthermia will no doubt lead to well-defined clinical trials which will bring with them important biological answers to hyperthermia-related problems. The design of large multicenter randomised clinical trial is therefore encouraged in order to evaluate the effects of hyperthermia for primary treatment of a malignancy as well as supplementary studies on metastatic and/or recurrent malignancy. The clinical results of combination of hyperthermia and irradiation for the patients with carcinoma of the esophagus are also presented herein.

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A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of TNF against L-M cells in incubation for 12 h at 38.5 and 40°C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37°C. And, it was also shown to be ralated to an accelerated turnover rate of TNF receptor complex under elevated temperatures rather than to changes in number of cell receptors or binding strength.
As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i. v. administration of TNF at 1, 000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40°C), whereas TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i. v. administration of TNF three times at 100 or 300 units/mouse together with hyperthermia (40°C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively ; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth.
A clearly synergistic inhibition of metastatic tumor growth by combined administration of TNF (300 units) and hyperthermia (40°C, 30 min) was also observed in BALB/c mice previously given injections of 1 × 10⁶ Meth-A (F₁₅) cells/mouse via tail vein, neither of which alone resulted in significant inhibition.
The results suggest that combination therapy including TNF and hyperthermia may be of value in the treatment of malignancy in human patients.

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We present a newly type applicator using a re-entrant resonant cavity for deep and concentrated hyperthermia. In this system, a human body is placed between the gap of the re-entrant resonant cavity, and is heated by standing wave electromagnetic fields.
From the results of computer simulations using a three layers disk phantom, that is, fat-muscle-fat model, it is shown that the deep and local tumor may be heated effectively without generating any hotspot or edge effects as in the case of RF capacitive heating method.

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Various type of 25 refractory tumors (16 : shallow-seated tumors, 9 : deep-seated tumors) were treated with radiotherapy and RF capacitive heating using HEH-500. Heating state, acute toxity and clinical result were analysed as follows.
Mean maximum intratumor temperature over 42°C and 41-42°C could be obtained in 9 (36%) and 8 (32%) respectively. Bulky shallow-seated tumors in the flat portion were capable of getting good heating state. But the temperatures of deep-seated tumors in the pelvis and lung could not be reached 42°C. In the rugged portions such as neck, supraclavicular region and chest wall after radical mastectomy, heatings tend to be unstable due to complaining of hot spot. The frequency of painful hot spot which was the cause of power limiting factor decreased from 81% to 41% by using large water bolus. Acute toxicity occured in 15 cases (12 : burns, 3 : subcutaneous indurations). There were no serious complications. Tumor response was evaluated by tumor shrinkage and complete responses were observed in 28% (7/ 25), partial responses in 40% (10/25) and no responses in 32% (8/25). Therefore the heating device (HEH -500) is thus suitable for heating of shallow-seated bulky tumors. It is considered that further improvement of applicators and boluses and increasing power of machine are necessary in order to heat deepseated tumors and other various site of tumors properly.

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The effects of general anesthesia on changes in temperature of the tissue heated in hyperthermic treatment were investigated in 9 rabbits. The thermosensitive tissue of the preoptic area and anterior hypothalamus (PO/AH) was locally heated by Argon Laser irradiation guided with glass fiber (0.4 mm in diameter). After local heating of PO/AH at 45 mW for 10 min under unanesthesia, PO/AH was locally heated at 45, 63, 90, 125 mW for 10 min under anesthesia with sodium pentobarbital (2.5 mg/kg/hr i.v.) in each rabbit. The heat loss responses of increase in ear skin temperature (Tea') by vasodilatation and increase in respiratory rate (RR) for evaporative heat loss were induced by local heating of PO/AH, and temperatures of the rectum (Tre) and brain (Tbr) at 10 mm apart from the irradiated center decreased following these heat loss responses in unanesthetic condition. But under anesthesia, unchanging Tre and increase in Tbr were observed because of no heat loss responses induced by local heating of PO/AH. Under unanesthesia, changes in Tea', RR, Tre and Tbr at 45 mW were +5.48 ± 0.57 °C, +56 ± 9min^-1, -0.33 ± 0.04 °C and -0.47 ± 0.08 °C, respectively. Under anesthesia, the changes in Tea', RR, Tre and Tbr at 45 mW were +0.22 ± 0.19 °C, +8 ± 2 min^-1, +0.01 ± 0.03 °C and +0.17 ± 0.06 °C, respectively. Furthermore, changes in Tea', RR, Tre and Tbr at 63, 90 and 125 mW were -0.45±0.25 °C, +12±2 min^-1, -0.02±0.03 °C and +0.19±0.04 °C, respectively. In cases of all values obtained under anesthesia, there were significant differences to compare with each value under unanesthesia.
Heat loss responses are likely to be induced in hyperthermic treatment, and these responses act on decreasing of core temperature. This phenomenon is obvious disadvantage to hyperthermic treatment under unanesthesia. One disadvantage is that the excess heat energy should be supplied to keep the temperature of the target tissue at the effective level. And the other is that the tissue temperature is variable depending on change in temperature of circulating blood as well as change in blood flow of the tissue. Inhibiting heat loss responses of thermoregulation with anesthesia is significantly effective in hyperthermic treatment. But the greatest attention should be paied to the temperature of heated tissue and heat load in the time course of hyperthermic treatment, since the unpredictable tissue damage might be caused by excess heating in consequence of inhibited physiological functions under anesthesia.

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The 915 MHz microwave hyperthermia system Clini-therm Mark IX was introduced in Hokkaido university hospital in September 1986 and 33 patients were treated using this system until july 1987. Hyperthermia was given once or twice weekly for 60 minutes at 43 °C using direct contact applicators. In most of the cases hyperthermia was combined with radiation therapy. Other combined therapies were chemotherapy and I-131 therapy.
The materials evaluated were 18 patients who had more than 6 fractions of hyperthermia, more than 3 months' follow-up period and were combined with irradiation. Tumor volume response were : CR= 28%, PRa=39%, PRb=11%, NC=22%.
In analysis of intratumoral temperature, the tumor edge temperature and the uniformity of heating were correlated with the tumor response, which suggests the minimum intratumoral temperature is important for the evaluation of hyperthermic effect to the tumors.On the other hand the maximum intratumoral temperature appeared to be correlated with heat-induced toxicities.

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マイクロ波を用いた局所温熱療法における加温用アプリケータとして, 従来から用いられてきた導波管型アプリケータに比して加温深度の大きな電波レンズ型アプリケータの実用化を試みた.加温に用いる周波数は430MHzであり, 電波レンズ型アプリケータの開口の大きさは212mm ×80mmである.アプリケータの開口面には, 脱着容易な水バッグが一体化して装着されており, 表面冷却が行われる.さらに, 内部には冷却水が循環しており, これによりアプリケータが小型化されると共に, 加温媒質とのインピーダンス整合がとられる.なお, アプリケータ内部に挿入された金属板は可動できるよう工夫されており, これにより焦点距離すなわち加温深度が変化でき, 加温パターンも変化できる構造となっている.
従来から用いられている導波管型アプリケータと共に放射電界強度の実測を行った結果, 導波管型アプリケータに比べて2倍程度の深さまで加温の範囲が広がることが判明した.理論解析結果およびファントム加温実験から今回試作・開発した電波レンズ型アプリケータを用いると, ハイパーサーミアに有効な温度範囲は深さ約60mmとなった.

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温熱療法においては, 表在性あるいは浅在性腫瘍の局所加温を比較的容易に行うことの出来るマイクロ波加温装置の開発が望まれている.この目的のために, 筆者らは電波レンズ型アプリケータを採用して比較的深い部分の加温が可能なマイクロ波加温装置 (HTS-100) を試作・開発した。本装置はマイクロ波電力発生装置, 表面冷却装置, 温度計測装置, 加温制御システム並びにアプリケータ保持装置の5つの要素で構成されており, 信頼性, 操作性, 安全性等の臨床治療上重要な点を考慮して, 小型で実用性の高い装置として完成させた.本装置はマイクロ波加温装置に必要となる諸要素・諸機能をすべて備えており, 動物実験のみならず今後の臨床応用にも十分耐える実用的な加温装置と言える.

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温熱療法の有用性が高まるにつれ,身体各所の悪性腫瘍に対する種々の加温の工夫がなされている.我々は表在性悪性腫瘍に対して8 MHzのRF誘電加温装置が使用可能なアプリケーターを試作した.試作品は2枚の電極を直角に対向させたもので,本アプリケーターでRF誘電加温を試みたところ,電極間の距離の最も短い部分が最も高温で,距離が長くなるに従って段階的に温度が低下するという予測に反し,電極によって構成される三角形のほぼ中心が最も高温となるという結果が得られた.これにより,RF誘電加温が従来は電極を平行に対向させもっぱら深部加温に用いられたのに対し,表在性で突出した腫瘍の加温にも有用であることが示唆された.遺憾ながら提示した症例は4回(2回/W)施行したところで肺転移にて死亡したため治療効果の判定は不能であった,しかし,我々の試作したアプリケーターは,顔面を含めた頭頚部,外陰部,四肢などの悪性腫瘍に対しての誘電加温の際に高い有用性を持つものと考える.現在は角度を90度に固定せず,様々な形状に対応できるよう角度可変型のアプリケーターを試作し,その加温特性について検討中である.

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