There exsists several evidences supporting that hyperthermia may be useful as a new modality of cancer treatment. The details of the mechanisms of thermal cell killing are not clarified yet. In in vitro studies, however, it has been demonstrated that (1) cell in radioresistant S phase are thermosensitive, (2) thermal cell killing is enhanced by lowering medium pH, and (3) a transient thermotolerance is induced by hyperthermic treatment. The data suggest that the primary target of thermal cell killing may include the plasma membrane and/or chromatin. On the other hand, it has been reported that many chemical agents enhance cellular thermosensitivity. These agents are called as “hyperthermic sensitizers”. In this report, the author introduces several hyperthermic sensitizers, such as (1) inhibitors of polyamine synthesis, (2) inhibitors of poly (ADP-ribose) synthesis, (3) hypoxic cell sensitizers, (4) SH-compounds and its modifying agents, (5) anaesthetics, and (6) chemical agents modifying membrane ion-transports. Chemotherapeutic agents, which have anti-tumor toxicity by themselves, are not included in these groups. Hyperthermic sensitizers would be helpful to analize the mechanisms of thermal cell killing, and also have some possibility to be utilized in clinical hyperthermia.
The future prospects of hyperthermic sensitizers are discussed.

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We have designed a multiple helical array applicator operating at 2450 MHz microwave in order to extend the homogenous heating area. The applicator consists of seven helical antennas. Six of them are disposed on a circle and the remaining one in the center. The power of microwave irradiated from each antenna in sequence is fixed at 180W and the total power is determined by changing the cycle-off time between irradiation.
The temperature distributions in the phantom containing 2% agar and 0.9% NaCl were measured by thermography. The heating area on a phantom surface increased as much as 4 times in the multiple applicator compared with a single one. Another special feature of this applicator is that various heat patterns desired could be obtained by selecting some of antennas.
It is considered that a multiple applicator developed by us is useful for the heating of superficial tumors with wide extension.

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A dynamic (perfused) phantom, which could model the convection of circulation, was made and temperature distributions were investigated to know their dependence on flow rate. Sponge (polyurethane foam) was packed in an acrylic box and perfused with 0.22% saline solution driven by gravity. Steady state condition, which meant the equilibrium of heat deposition with heat loss due to conduction and convection, was achieved. The state was essential to simulate the temperature data in patients for hyperthermia. After the steady states were reached at the flow rate of 1.0 1.5 and 2.0ml/cm₂/min., tenperatures on perpendicular and parallel planes to the flow were measured by moving thermocouple probes to obtain temperature-rise distributions. Temperature rises got lower with increasing flow rates but normalized distributions little depended upon the flow rate. The steady state temperature distribution on depth was comparable with the specific absorption rate (SAR) distributions but the relation could not hold good throughout the phantom due to the skew of distribution. The perfused phantom could model the effects of circulation to a certain degree but the improvement of the system is necessary to make use of it in clinical situation.

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A combined therapy of irradiation and an 8 MHz radiofrequency hyperthermia with/without chemoembolization, using microencapsulated mitomycin C, was carried out in a total of 10 patients with advanced renal tumors. Previous therapies had been unsuccessful in these patients, or surgical interventions had not been indicated because the disease was too advanced or the presence of other complications. Chemoembolization was performed in 7 of the 10 patients before the combined treatment of irradiation and hyperthermia. They were irradiated with 1.8 to 2.0 Gy, 5 times a week, or 2.0 to 4.0 Gy twice a week. As a treatment plan, hyperthermia was performed twice a week within one hour after each irradiation, totally 10 sessions in 5 weeks. Intratumoral temperature was kept at more than 42.5°C. Clinical efficacy was evaluated by CT, ultrasound and biochemical data. Partial tumor regression, defined as a regression of 50% or more, was attained in one of the 10 cases. Minimal response, defined as a regression of 25 to 50%, was observed in 2 cases. The side effects of mild skin burns and anorexia were observed in approximately 50% of the cases. After the treatment, subcutaneous fat tissue induration occurred in one patient whose subdermal fat tissue was 18 mm thick.

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Several studies indicated that hyperthermia was effective in the treatment of human and animal tumors. But this hyperthermic effects are strongly influenced by the conditions of tissue blood flow.
We investigated the effectiveness of Degradable Starch Microsphere (D.S.M.) embolization combined with hyperthermia in the treatment of VX2 carcinoma. These microspheres temporarily obstructed blood flow at the precapillary arteriole levels. In our study, the blood flow in tumors was inhibited longer than in normal muscle tissues and during heating, the temperature of tumors was increased by D.S.M. embolization. The tumor growth was inhibited and the damages of nomal muscle were not so remarkable by these combined treatment.

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We investigated the acute heat injury induced by whole body hyperthermia (WBH) with microwave, and protective effect of indomethacin and methylpredonisolone on its injury. When mouse was subjected to WBH with 2450MHz microwave (rectal temperature, 43.5°C, 30 min), hematocrit (Ht) and water content in small intestine increased considerably 24hr after the treatment. It might result from leak out of water into an intestinal tract due to intestinal lesion by WBH.
The activity of acid phosphatase (AcP), transaminase (GOT, GPT) in plasma increased remarkably after WBH. All lactate dehydrogenase (LDH) isozymes (LD₁LD₅) and creatine phosphokinase (CPK) isozymes (BB and MM) also increased by WBH.
These data were considered to reflect a destructive changes in parenchymatous organs such as liver, skeletal muscle, kidney and lung. When indomethacin (0.3mg/mouse) was administered i.p. 510hr before WBH, hyperthermia-induced leak out of water into small intestine, and the increase of Ht and AcP activity were partially inhibited, but not of GOT and GPT. Indomethacin also inhibited the increase of LD₁LD₄ of LDH isozymes and MM type of CPK isozymes.
Methylpredonisolone had a similar protective effect on the acute heat injury. From these results, it would be hopeful that effective hyperthermia could be performed by protecting normal tissue with these drugs.

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At the National Cancer Center Hospital, Tokyo, BSD-1000 (APAS) was introduced into clinical practice in February 1982, followed by Thermotron RF-8 in January 1983.
Comparisons were made between both devices about various treatment parameters including the percentage of effective hyperthermia which a temperature elevation to more than 42°C, and a concomitant increase in body temperature.
Tumors of the lower extremity, effective hyperthermia rate was 93% (37/40) with APAS as against 60% (6/10) with Thermotron RF-8.
Upper abdominal tumors, effective hyperthermia rate was 37% (19/51) with APAS and 81% (25/31) with Thermotron RF-8. Tumor of the pelvic cavity, the effective hyperthermia rate was 95% (61/65) with APAS as against 40% (12/30) with Thermotron RF-8.
The increase in pulse rate and body temperature was greater with APAS. It appears that with APAS, systemic stress caused by the increase in pulse rate and body temperature might possibly be a limiting factor, while with Thermotron local intense pains that tend to be felt by patients with a thick subcutaneous fat tissue may possibly be a limiting factor that interfere with successful performance of hyperthermia.

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