1975年から1993年3月までに, 70例82病変の早期胃癌に対して内視鏡治療を施行した. 1.0cm以下の30病変は, いかなる内視鏡治療法を用いても局所根治を得られたが, 1.0cmを越える52病変では, m癌で39病変中8病変・20.5%, sm癌で13病変中5病変・38.5%, 計52病変中13病変・25%に遺残を認め広範囲m癌やsm癌に対する内視鏡治療の限界を感じざるを得ない. 我々の開発したLasertherniaは, 基礎的検討おいてsm～pnにまで効果がおよぶことが確認されている. さらに, ヌードマウスにおける移植ヒト胃癌の検討で化学療法 (5-FU) との併用による相乗効果が示唆されている. 以上よりLaserthermiaは化学療法との併用によりsm癌に対する治療効果が期待できると考え, 1989年より臨床応用を開始した. 1989年以降の治療方法は, 広範囲m癌に対しては可能な限りEMRを繰返し, 遺残を認めた場合はlaser照射などを併用する. sm癌に対しては, 全身的な化学療法を行いつつLaserthermiaを中心とした内視鏡的併用療法を施行する。その結果, 1989年以降の1.0cmを越える病変の遺残率は, m癌の場合30病変中4病変・13.3%, smの場合では8病変中1病変・12.5%と減少しており, Laserthermiaのsm癌に対する治療法としての可能性が示唆された.

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Hyperthermia therapy using Nd-YAG Laser for the treatment of malignant brain tumors have recently developed in neurosurgical field. We have developed new thermal probes for localized laser hyperthermia to the peripheral or infiltrating malignant brain tumor cells immediately after the tumor debulking during the surgery. (1) We have made different sizes of expermental ballon probes, which consisted of laser photofiber covered with photo-scattering materials, latex rubber and thermal sensor. The air injection in the balloon was better than soy bean oil injection. An adequate linear correlation was obtained between the temperature of the probe and that of the balloon surface. (2) In the experiment of local laserthermia applied to swine & rat brains, the temperature of the surrounding brain attached to the balloon could be easily controlled at 42.543.5°C by changing the output power between 5W and 15W. In histological examination, remarkable necrosis and multiple small bleeding as well as autolysis were noticed in the peripheral brain tissue attached to the balloon in the acute stage. The peripheral brain tissue consisted of coagulation necrosis and scattered gliosis in the chronic stage. (3) In the cases of hyperthermia for human glioma xenografts in athymic nude mice at 43.5°C for 20 minutes, remaining tumor tissue attached to the balloon revealed masssive necrosis with small hemorrhage and infiltrating inflammatory cells in the peripheral portion. Although there was no viable tumor cells within 5mm distance from the balloon, tumor necrosis was limited and scattered viable tumor cells were found after hyperthermia at 41.5°C for 20 minutes. (4) Intraoperative laserthermia therapies using balloon probes with Nd : YAG laser for 7 patients with malignant gliomas, 12 patients with metastatic brain tumors and 1 patient with primary malignant lymphoma were successfully performed without any complication during past 2 years. Post operative CT and/or MRI revealed no tumor enhancement or poor enhancement of tumor border. Although follow up of our cases is not so long, this local laserthermia is effective and easy to handle, it might be useful in the treatment of malignant brain tumors including metastatic tumors during surgery.

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温熱療法は悪性腫瘍に対する放射線および化学療法の有効な併用療法として近年注目を浴びている. 今回我々は術前療法として温熱併用放射線, 化学療法を行い, 著効を示した下顎扁平上皮癌の1例を経験したので報告した.
患者は27歳男性. 現病歴 : 1989年8月左下顎智歯部疼痛のため近歯科受診. 智歯周囲炎の診断のもとに抜歯を受けたが, その後開口障害が出現し, 紹介され某大学口腔外科を受診. 慢性下顎骨骨髄炎と診断され, 抗生剤の投与を受けたが症状に変化を認めず, 抜歯窩の生検を受け, 扁平上皮癌と診断された. 1990年7月18日紹介され当科を受診した. 処置および経過 : 腫瘍は左下顎大臼歯部骨体から下顎枝に及び, さらに側頭下窩に深く浸潤していた. 7月30日入院し, 8月2日より放射線照射 (計30Gy), 化学療法 (PEP計60mg, CDDP計20mg), およびマイクロ波加温による温熱療法 (計8回, 各60分) を併用した. 9月20日左全顎部郭清術, 下顎骨半側切除, 下顎から側頭下窩腫瘍切除術, 大胸筋皮弁およびチタンプレートによる再建術を行った.
初診時のCTと術前療法終了時のCTを比較すると下顎枝周囲の腫瘍が著明に縮小し, retromaxillary fat spaceの回復が認められた. また咀嚼筋群の境界明瞭化, 腫瘍内の血管の消失がみられ画像診断上, ほぼ腫瘍が制御されたものと思われた. 摘出物の病理組織学的所見では, 腫瘍のほとんどが線維性組織に置換されており温熱療法併用放射線化学療法の有用性が示唆された.

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A 49-year-old man with advanced esophageal cancer was admitted to our hospital to have an operation. X-ray examination of the esophagus showed a ulcerative and localized type tumor located in middle to middle third of the esophagus. The tumor was measured 5.5cm in vertical extension. Endoscopic biopsy revealed moderately differentiated squamous cell carcinoma. We performed preoperative treatment using hyperthermochemoradiotherapy. Subtotal esophagectomy was carried out after preoperative treatment. Histological study of the surgical specimen revealed no cancer cells in the lesion, so preoperative hyperthemochemoradiotherapy was markedly effective. Nevertheless this patient died of liver metastasis 32 months after operation. To improve the survival time, the more sophisticated multimodality therapy is expected.

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A case of recurrent rectal cancer who survived more than 5 years following thermo-radiotherapy was presented. A 76-year-old male patient with unresectable recurrent rectal cancer in the perineum was treated with radiation therapy combined with hyperthermia. Total radiation dose was 66Gy/2Gy, and an 8MHzRF capacitive heating device was used for reginal hyperthermia. Although the recurrent tumor showed complete regresion 4 months after the combined therapy, a small marginal recurrence behind sacrum was noted on CT scan. Thermoradiation therapy was performed again for the recurrent tumor. Total radiation dose for the tumor was 50Gy/2Gy, and a 430MHz microwave hyperthermia system was used for local hyperthermia. An average intratumoral temperature was 43.0°C. In terms of toxicity, radiation skin ulcer was noted in the hip region 4 years after the initial treatment. He died of pulumonary infection 5 years and 8months after the combined treatment. At autopsy, neither residual tumor nor distant metastasis was demonstrated. Hyperthermia combined with radiation therapy seems effective in the treatment of locally recurrent rectal cancer.

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Combined treatment with local hyperthermia, radiation and chemotherapy was performed for a young female with a retrovesical tumor histologically diagnosed as an undifferentiated mesenchymal tumor.
The patient was 17 years old and had suffered from left flank pain since October 1991. Computed tomography and magnetic resonance imaging revealed a large retrovesical tumor. She was operated in December 1991, but the tumor was not resected completely due to adhesion to the pelvis. After the operation, she received intra-arterial infusion of cisplation, doxorubicin, and mitomycin C, and thereafter received Lineac irradiation to a total dose of 50.4 grays. Hyperthermia of the pelvis was conducted from March 1991 to December 1993 for 26 sessions as an outpatient using a Thermotron RF-8.
The tumor decreased markedly in size after this combination of hyperthermia, chemotherapy, and radiation. The patient is currently well and is receiving hyperthermia, chemotherapy, and radiation. The patient is currently well and is receiving hyperthermia once a month.
This case indicates that combined local hyperthermia, chemotherapy, and radiation is useful for the treatment of retrovesical tumors.

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To evaluate the efficacy of intra-arterial chemotherapy combined with hyperthermia for malignant liver tumors, our cooperative study group carried out a randomized clinical trial of intra-arterial chemotherapy alone and intraarterial chemotherapy combined with hyperthermia. Fifteen patients were registered by telephone contact and allocated at random to groups treated with either intra-arterial chemotherapy alone or combined therapy. Patients were treated with combined chemotherapy of 5-fluorouracil (5-FU), epirubucin (EPIR), mitomycin C (MMC) by hepatic infusion using a subcutaneously implanted reservoir. Hyperthermia (8MHz radiofrequency) was usually performed for 40-60 min every week, and intra-arterial chemotherapy was performed immediately before hyperthermia. Therapeutic effects were evaluated by examining the changes in tumor size on computed tomography, and/or intratumor low density areas on posttreatment computed tomography. There were no favorable responses obtained in the patients treated with intra-arterial chemotherapy alone. Among patients treated with combined therapy, PRh was observed in one patient with hepatocellular carcinoma, PR in one patient with hepatocellular carcinoma and two patients with metastatic liver cancer, These results suggest that intraarterial chemotherapy combined with hyperthermia may be a useful modality for the treatment of either non-resectable hepatocellular carcinoma or metastatic liver cancer.

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ドラッグデリバリー技術を応用し, 細胞レベルでの加熱を目的とした磁性微粒子であるマグネトリポソームを開発し, その発熱特性について検討した. マグネトリポソームはマグネタイト微粒子にリン脂質二重膜を被覆して調製した. このマグネトリポソームは交番磁場中で発熱し, その発熱特性は微粒子の粒径に依存し, 平均粒径約40nmの場合に最大の発熱量を示した. また, このマグネトリポソームを適用した温熱療法に対するシミュレーションも行った. シミュレーションは癌組織周りの血流を考慮した同心円状モデルによって行った. 直径6cmの癌組織を42℃以上に保つためには組織1m³当り200kWの熱量が必要であった. これを磁界22.8kA/m (286Oe), 周波数240kHzの条件でマグネトリポソームが目的の癌組織に0.74mg/cm³_組織吸着していることに相当する.

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大腸癌株化細胞WiDr細胞に対する温熱あるいは温熱と制癌剤の殺細胞効果および細胞動態に及ぼす影響をcolony assayとflow cytometryを用いて検討した. さらに, 温熱により生じたG2M期蓄積細胞をcell sortingの方法で無菌的に取り出して, そのviabilityを検討した. WiDr細胞に対する温熱の細胞障害性は44℃で著明であった. flow cytometryを用いた細胞動態の解析では温度の上昇につれてG2M期細胞が増加し, とくに44℃加温では48時間後にもG2M期蓄積が認められた. MMC併用加温後のG2M期細胞の蓄積比率は加温単独におけるよりも高率であった. G0G1期細胞およびG2M期細胞のsurviving fractionは加温温度の上昇につれて低下したが, その程度はG2M期細胞で著明であった. また, MMC併用加温におけるsurviving fractionの低下は単独加温におけるよりも著明であった. 以上より, 加温後に出現するG2M期細胞の蓄積は細胞障害を示しており, G2M期細胞の蓄積比率は抗腫瘍効果あるいは感受性判定の有用な指標になると思われる.

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The authors developed and evaluated the performance, using a phantom, of a new capacitive heating applicator designed for the “parallel method” of applying clinical simultaneous radiohyperthermotherapy (SRH) in which electron beam irradiation is provided from above an external capacitive heating applicator for the treatment of superficial and shallow-seated tumors. The trial applicator was made to fulfill the following conditions : (1) use of an electrode plate which does not affect the electron beam depth dose, (2) a uniform tickness to maintain flatness of the electron beam, (3) an attachment site between the electrode and lead wire at the electrode margin to avoid entering the irradiation field, and (4) cooling function to enhance therapeutic gain factor and avoid damage to normal skin tissue. This applicator consisted of a 0.1-mm-thick copper electrode and a 5-mm-thick cooling chamber. The depth of the 80% dose of the new applicator was 21 mm with a 9-MeV electron beam and 36 mm with a 15-MeV electron beam, which was comparable to the effect of a conventional irradiation bolus. The temperature distribution produced by the trial applicator was symmetrical on both the right and left from the center of the applicator. The 50% specific absorption rate region was a width of 6.4 cm at a depth of 1 cm from the phantom surface and a width of 2.8 cm at a depth of 3 cm. There have been no previous reports on the development of an external capacitive heating applicator designed for the SRH of superficial and shallow-seated tumors; this is the first report. SRH of these tumors can be performed simply, noninvasively and repeatedly by means of this new applicator.

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