Intra-arterial infusion chemotherapy is widely used for inoperable metastatic liver cancer but the rate of success is not necessary high. To these patients, we used combined RF hyperthermia and intra-arterial infusion chemotherapy. If the temperature increase by external hyperthermia is insufficient, the effect of application of both modalities maybe small. A beagle male dog 13 kg weight, was operated under general anesthesia to open abdominal cavity and insert a catheter in the hepatic artery. External heating was preceded with Thermotro RF-8 and maintained the liver temperature 41.5°C for 5 minutes. Then saline which was exchanged in a 70°C water bath was infused at the speed of 400 ml/h for 10 minutes, 6 minutes after the infusing, the liver temperature was elevated by 1.5°C. Hot water infusing alone considerably high water temperature and fast infusing speed were necessary but when using both modalities the increase of liver temperature was easily achieved.

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From December 1982 through September 1990, 27 patients with 32 tumors were treated with thermochemotherapy. Of the 32 tumors, 19 were locally recurrent tumors, 11 distant metastases, and 2 peritoneal disseminations. Employung two types of heating devices (8MHz capacitive RF, 430MHz microwave), hyperthermia was administered once or twice weekly, for 30-60 minutes per session, up to total sessions of 2-15 (mean = 6.4 ± 3.8). In some sessions, anticancer drugs were administered intraveneously or in-traarterially immediately before or simultaneously with hyperthermia. The number of thermochemitherapy sessions was 1-6 (mean = 3.0 ± 1.5). Of the 32 tumors treated, 2 (6%) showed CR, 13 (41 %) PR, 11 (34%) NC, and 6 (19%) PD. The better the tumor response was, the higher local control rate was achieved. The survival rate of patients who achieved CR or PR was higher than that of patients who showed NC or PD. Tumor volume, depth of tumor, average tumor temperature, minimum tumor temperature, the numer of effective heat sessions and varieties of anticancer drugs used were shown to affect the tumor response by multivariate analysis. On the other hand, radiotherapy or chemotherapy history did not affect the tumor response. As almost all the tumors treated were considered to be refractory to radiotherapy or chemotherapy, the tumor responses obtained with thermochemotherapy seemed very encouraging. The expanded trials are warranted to reveal the effectiveness of thermochemotherapy.

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We demonstrated an in vivo antitumor effect of thermochemotherapy using CDDP in BALB/c mice with Meth-A fibrosarcoma. The mice were divided into the following four groups : control, heat alone, CDDP alone and CDDP + heat. To assess the antitumor effect of treatment, immunostaining using anti-bromodeoxyuridine monoclonal antibody was employed. This was performed immediately, 3 hours, 6hours, 24 hours and 72 hours after treatment. Local hyperthermia was produced with a halogen lamp (43°C, 30min.). CDDP was administered intraperitoneally at a dose of 5mg/kg immediately prior to heating the tumor. Tumor temperature was measured with a thermistor placed at the center of the tumor.
The CDDP + heat group demonstrated a marked decrease of S phase tumor cells compared to other groups. This decrease of S phase cells started immediately after heating and persisted for a long period. In addition, the periphery of the tumor which initially appeared not to be injured demonstrated a prolonged decrease of S phase cells. Thus, thermochemotherapy using CDDP affected cell cycle progression of the tumor cells which appeared morphologically normal. These result suggest that the cytotoxicity of CDDP is activated by use in combination with hyperthemia and prevents cell cycle progression of tumor cells to the S phase.

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The paper is concerned with the new gel phantoms which can be used to visualize the high temperature region in a three-dimensional way. For the performance test or the maintenance of electromagnetic equipments for hyperthermia, it is desired to examine or check the three-dimensional pattern of the temperature distribution in the human body. In order to visualize the temperature distribution easily, the synthetic paste phantom has been used. The phantom is fabricated by dissolving the Polyvinyl Alcohol (PVA) into water and adding by a small amount of the surface active agent such as polyethylen glycol. The region whose temperature exceeds a certain value (clouding point) becomes white and opaque due to segregation of the agent. Thus the heated region whose temperature exceeds the clouding point can be visualized in the three-dimensional way. But the synthetic paste phantom has a serious problem of convection due to the temperature rise, because the phantom is a viscous fluid.
The new gel phantoms are transparent below the clouding point and the region which exceeds the clouding point becomes white and opaque. But convection due to the temperature rise does not occur in these phantoms. We have examined many kinds of high molecular gels to find suitable ones for the phantom. The materials we have found for the phantom materials are polyacrylamide and gellan gum. They show a good transparency to observe the white and opaque region from the outside and have high melting points. The clouding point can be controlled by changing the kind and concentration of the agent or by adding ionic materials such as a salt. The electrical properties of those phantoms can be adjusted to show the same properties as biological tissues by adding an appropriate amount of ionic material such as a salt. The newly developed phantoms may be quite useful for hyperthermia, because they enable us to observe the temperature region above 42.5°C in a three-dimensional way.

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The effectiveness of regional capacitive hyperthermia was investigated in 10 patients with benign prostate hyperplasia using Thermotron RF-8. All the subjects previously been treated with drugs such as cernitin pollen extract, chlor-madinone acetate or a-blockers for more than 6 months and various complications such as neurogenic bladder, prostatitis and neuralgia were observed in 6 patients. Treatment was in the outpatient clinic and without anesthesia. The lower pelvic area was heated 1 -2 times a week for a total of 2-10 treatments. Each treatment lasted about 60 min. during which period the rectal temperature could be raised to higher than 42°C for 20 - 40 min. in all patients except one. The therapeutic effects were as follows : prostate size was reduced in 6 out of 10 cases and significant improvement in urination was observed in 9 patients as judged by subjective symptoms and uroflowmetry. No serious adverse effects were observed, although hardened subcutaneous fatty layers were noticed in 2 cases and hematospermia in 1 case. Capacitive hyperthermia may thus be useful for treating outpatients with prostatic hypertrophy.

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Combined therapy with intravesical instillation of hydroxypropylcellulose- doxorubicin and local hyperthermia was performed in 11 patients with recurrent and multiple bladder carcinomas. The stage of the cancer before treatment was T1 in 4 cases, carcinoma in situ in 2 cases and T2 in 5 cases. Among the 11 cases, 7 cases had severe complications such as cardiac disease and pulmonary emphysema. Hydroxypropylcellulose-doxorubicin was instilled into the bladder, and then local hyperthermia was applied by means of capacitive heating using Thermotron RF-8. Therapeutic effect was as follows : complete response in 6 cases, partial response in 4 cases, and no response in 1 case. All 11 cases are alive as of this report with a survival duration ranging from 8 to 45 months. Adverse effects seen were induration of subcutaneous fatty tissue in 5 cases and first degree burns in 2 cases. There was no systemic adverse effect in the 11 patients treated.

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