In This paper we clarified the efficacy of thermochemotherapy using several anti-cancer agents such as MMC and 5'-DFUR in experimental animal models. The effective anti-tumor effect which was estimated by the rate of shrinkage of tumor and histopathological changes were observed. Especially, liposome MMC were advantageous type of agent with heating compared with native MMC. The intratumor concentration of these agents were examined to clarify the mechanism of enhancement of anti-tumor effect. These results suggest that the concentration of anticancer agent was affected with the dose of agent, the route and timing to administrate. For example several different results about the concentration of 254S were reported previously. Therefore when thermochemotherapy are performed, it is important to determine the exact dose of agent and timing to administrate.
On the other hand clinically randomized control study is need to prove the efficacy of thermochemotherapy, but actually it is impossible to perform this study due to the difference of patient's general condition, primary tumor present site and interruption of treatment by side effects. Therefore in this study matched control study was used for gastric cancer, pancreas cancer and colonic cancer to evaluate the efficacy of this therapy. The advantageous efficacy was demonstrated on the point of the shrinkage of tumor, life span, performance status and alleviation of pain and tumor histopathological changes. In addition of this results, sixty nine patients out of 90 (77%) had no side effect.
In conclusion that thermochemotherapy is one of the useful therapy for cancer in multi-disciplinary approach.

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What kinds of instruments are required in the future ?
(1) Instruments for simultaneous thermotherapy and radiotherapy.
Simultaneous thermotherapy and radiotherapy achieve the most effective antitumor effect. As normal tissue sensitivity is also increased, selective radiotherapy and thermotherapy delivery to the tumor is necessary. We obtained good results in treating pancreatic and esophageal cancers with simultaneous thermotherapy and radiotherapy.
(2) Instruments effecting at least 45 C in tumors only.
This treatment is only effective for small tumors at 2-3 cm, in which case thermotherapy alone may be an effective teratment.
(3) Instruments effective for lung cancer.
Apart from surgery, other treatments for lung cancer are ineffective.
Some Japanese facilities are experimenting with combined Rf capacitive thermotherapy and radiotherapy for lung cancer.
Although the result is better than radiotherapy alone, a satisfactory level has not been reached. RF capacitive heating is not the best suited delivery system for lung cancer. Instruments that achieve effective hyperthermia in lung cancer await development.
The future of thermotherapy depends on the development of effective instruments, for which the responsibility of engineers is great.

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Non-invasive temperature imaging methods using proton MRI were reviewed with respect to the temperature-dependent parameters, thermal equilibrium magnetization (with the effect of proton density) (M₀'), spin-lattice relaxation time (T₁), spin-spin relaxation time (T₂), diffusion coefficient (D) and proton chemical shift (δ). Although the temperature relations of M₀', T₁, T₂ and D of the water proton are clear in pure water (-0.36% /°C for M₀', 2.2% /°C for T₁, T₂ andD at 40°C), it was observed that the temperature relations have remarkable differences in tissues. On the other hand, it was found that the temperature relation of the proton chemical shift are similar (of the order of - 0.01 ppm/°C) between pure water and the different tissues. In addition, the proton chemical shift is the only parameter derived from the signal frequency, and therefore can be detected independently from the other parameters. For these reasons, the proton chemical shift method is deemed superior. The author and his colleagues have proposed two different temperature imaging modalities, the spectroscopic imaging (SI) and phase mapping (PM) methods, using the water proton chemical shift. The typical images of temperature distribution changes in an anesthetized rat obtained by the SI and PM methods were exhibitied. The PM method for temperature imaging during focused ultrasound sonication was introduced as a state-of-the-art technique for non-invasive temperature monitoring during thermotherapy.

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マイトマイシンCおよびシスプラチンとその誘導体と温熱の併用効果を, ヒト悪性黒色腫と大腸の腺癌由来の培養細胞の多細胞スフェロイドと単層培養で比較検討した.薬剤と温熱の併用効果は, 同じ細胞でも多細胞スフェロイドでは単層培養と明らかに異なっていた.その理由としてはスフェロイド内の微小環境が併用効果に影響をおよぼすこと, スフェロイド内の薬剤分布が内部と外側で異なっていることなどが考えられた.このような結果は温熱化学療法の研究において, 多細胞スフェロイドを使用した研究が, 基礎と臨床を結びつけるきわめて有益な情報を提供することを示唆する.

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放射線腫瘍学会 (JASTRO), 温熱療法研究グループ参加施設より集められた子宮癌の温熱療法症例を分析し温熱療法の意義を検討した.111例のうち, 扁平上皮癌III期40例, IVa期18例および術後または照射後再発40例, 計98例について検討した.放射線治療は基本的な方法にて行われ, 温熱療法はThermotronRF-8, Thermox1000, BSD1000, ERS100A, HMS-020を用いて週1～2回, 計5～10回行われた.IIIb期ではCR58%, PR35%で奏功率は93%, IVa期ではCR39%, PR55%で奏功率は94%であった.累積5年生存率はIIIb期で65.2%, IVa期で37.3%であった.再発例では外部加温28例で50% (14/28), 腔内加温12例で100% (12/12) の奏功率であった.腔内加温は腫瘍が小さい症例に行われ, 44～45℃と高い腫瘍温度が得られた事が良好な結果をもたらしたと考えられた.子宮頸癌IIIb期, IVa期, 再発例の放射線治療に温熱療法を併用する事は, 局所制御率の改善により生存率の向上に寄与すると考えられた.
JASTRO温熱療法研究グループによる子宮頸癌の温熱併用放射線治療症例を分析した.IIIb期40例では, CR58%, PR35%, 奏功率93%であり, 5年累積生存率は65.2%, CR例では80.5%であった.IVa期18例ではCR39%, PR55%, 奏功率94%であり, 5年累積生存率は37.3%, CR例では40%であった.再発40例では奏功率は外部加温で50%, 腔内加温で100%であり, 扁平上皮癌と腺癌との間に差は認められなかった.比較研究ではないため明確な結論は出せないが, 子宮頸癌IIIb期, IVa期, 再発例に対しての放射線と温熱の併用は, 局所の制御率を増強させ, 生存率も延長させる可能性が示唆された.

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末期癌患者を対象に, 米国製遠赤外線全身温熱加温器 (RHD 2002) を用い, 遠赤外線全身温熱療法を行い, 4回 (1クール) 以上の治療を終了した112例について治療効果を判定した.効果判定には, UICC criteriaとSystemic criteriaの2つの評価方法を用いた.又, QOLの改善をアンケート方式により3段階で評価した.結果, UICC criteriaでは75%の有効, Systemic criteriaでは, 81.3%の有効を認め, QOL評価では最高, 良好の合計が78.5%であった.
従来より広く行われているUICC criteriaによる評価は, 全身状態や血清学的改善 (腫瘍マーカー等) による評価を加えていないために, 治療効果の全容と必ずしも一致していない.しかし, 今回我々が検討したSystemic criteriaによる評価方法は, Karnofsky Indexを加えるなど全身状態の変化をより正しく反映し, 遠赤外線全身温熱療法の効果判定に適していると思われた.
当センターで遠赤外線全身温熱療法を行った112例についての効果判定の結果, 従来よりのUICC criteriaでのCR+PRが75%であるのに対してSystemic criteriaでは81.3%であった.後者はKarnofsky Indexなどの全身状態の評価を含み, 全身温熱療法の効果をより反映した評価基準であることが示唆された.

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Hsp72 is one of the stress proteins induced transcriptionally by various stressors such as heat, UV, ionizing radiation and DNA damaging agents. Many studies have shown a positive relationship between thermosensitivity/thermotolerance and heat shock proteins. On the other hand, cisplatin (cis-diamminedichloroplatinum (II)) is one of the chemotherapeutic agents which are widely effective against human cancers. The cytotoxicity of cisplatin is believed to be due to the formation of DNA adducts, which include mainly inter-and intra-strand DNA crosslinks. Many investigators have shown the cytotoxic effect of cisplatin enhanced by combination with hyperthermia. There are two possible modes of the interaction between hyperthermia and cisplatin. One is an increase of the drug uptake by hyperthermia, which may cause much more DNA damage in cells. The other is that hyperthermia may inhibit the repair of cisplatin-induced DNA damage as is the case in the combination of ionizing radiation and hyperthermia.
In the present study, we show the accumulation of hsp72 induced by cisplatin and the suppression of hsp72 accumulation by the combined treatment with hyperthermia and cisplatin, suggesting the third possible mode of interaction between hyperthermia and cisplatin which cisplatin suppresses the heat-induced hsp72 accumulation. These results suggest that the synergistic cytotoxic enhancement by the combination of hyperthermia and cisplatin may be dependent on the suppression of heat-induced hsp72 accumulation by cisplatin.

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A non-contact microwave applicator was able to succesfully heat the posterior part of the retina near the optic disc of rabbits. The calculated temperature coincided with the actual measurment. The conventional Lagendijk type applicat does not heat sufficiently the posterior part of the retina. Our system cooled the anterior part of the eyeball of rabbits with water bolus. Microwave frequency was 2450MHz. The eyeball SAR (Specific Absorption Rate) distribution and its circumferential temperatures (boundary conditions) were measured using thermistors resistant to microwave irradiation (ACT). The temperature distribution in an eyeball sagital cross section was calculated using the finite element method. Calculated results were obtained from the SAR profile and boundary conditions. The calculated temperature at the midpoint of the eyeball was almost the same with the value measured by the ACT. The temperature of posterior part of the retina increased moderately. This method appears promising for safe and effective hyperthermic therapy of retinoblastoma.

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