Enhancement of antitumor effect of hyperthermia with glucose administration in murine mammary carcinoma.

Antitumor effects of hyperthermia are enhanced by lowering the pH in the tumor tissue with administration of glucose. This decreased pH in the tumor tissue with glucose administration was determined using mouse experimental tumors. 31P-MRS microelectrodes were used for the measurement of pH. By using these two measurement methods, time course change in the tumor tissue was determined in the controls and the groups treated with 6 g/kg of intraperitoneal glucose. The determination of pH with 31P-MRS was calculated from the chemical shift of the peak of creatine phosphate (Pcr) and that of inorganic phosphate (Pi). Following glucose administration, the tumor tissue showed a decrease of 0.3 pH units with the microelectrode method, but did not show any significant decrease in pH with the MRS determination. This finding suggested that 31P-MRS showed intracellular pH (pHi) due to the localization of Pi and that the microelectrode indicated interstitial or extracellular pH (pHe). The ATP/Pi ratio obtained in tumor tissue 24 h after heat treatment (with, without glucose) was correlated with tumor inhibition.

Relevance of a new impedance matching, or subtrap, method for the reduction of pain during hyperthermia.

Capacitive heating is widely used in hyperthermic treatment of human malignancies. However, the pain on the body surface or thermoesthesia in the subcutaneous fatty layer may prevent an elevation of temperature in the tumors. Impedance matching is improved by a subtrap method entailing the application of two copper plates (10 x 850 x 0.06 mm) as a subtrap circuit to each of two capacitive electrodes. In a clinical trial the Tmax, Tave, Tmin for the subtrap method were all higher in comparison with those for the conventional technique (42.5 +/- 0.7 degrees C, 41.9 +/- 1.0 degrees C, 41.3 +/- 1.1 degrees C vs. 41.1 +/- 1.5 degrees C, 40.6 +/- 1.3 degrees C, 40.0 +/- 1.3 degrees C). Although the maximal radiofrequency (RF) power applied to patients was higher with the subtrap method (875 +/- 189 W vs. 763 +/- 200 W), the incidence of surface pain was reduced dramatically. It is concluded that the subtrap method substantially improves the RF capacitive heating of deep-seated tumors.

Studies on hyperthermia combined with arterial blockade for treatment of tumors: (Part I) effectiveness of hyperthermia combined with arterial ligation.

Arterial ligation was combined with hyperthermia in rabbits with VX2 tumors implanted in the leg. For seven days after arterial ligation, blood flow was decreased and the pH was low in both normal muscle and tumor tissue. The temperature of normal muscle and tumor tissue increased faster and reached a higher level on heating immediately after ligation than without ligation. The antitumor effect of hyperthermia was stronger immediately after ligation than two or seven days afterwards. However, damage to normal muscle was severe with this combination therapy, so a better method of therapeutic arterial blockade is needed.

Studies on hyperthermia combined with arterial therapeutic blockade for treatment of tumors: (Part III) effectiveness of hyperthermia combined with arterial chemoembolization using degradable starch microspheres on advanced liver cancer.

Arterial chemoembolization using degradable starch microspheres and adriamycin was combined with hyperthermia to treat advanced liver cancer. The prolonged peak adriamycin level in hepatic venous blood suggested that the drug persisted for longer in the liver after injection containing microspheres. Heating efficiency was increased more in tumor tissue than in normal liver tissue after embolization. This combined therapy was performed in eight patients with advanced liver cancer and was effective in three (complete or partial remission). The mean survival time was 25 weeks and there were no severe side effects. This combined therapy may be useful for liver cancer.

Studies on hyperthermia combined with arterial blockade for treatment of tumors: (Part II) effectiveness of hyperthermia combined with arterial embolization using degradable starch microspheres.

The efficacy of temporary arterial embolization using degradable starch microspheres combined with hyperthermia was investigated in rabbits bearing VX2 tumors. Microsphere injection caused a marked decrease of tumor blood flow and pH. During heating, there was a marked increase of the maximum temperature in tumor tissue compared with normal muscle. Tumor growth was suppressed 330% times at 3 weeks after hyperthermia alone and 270% times following combined treatment with microspheres and hyperthermia. Damage to normal muscle tissue was mild. In conclusion, this combination therapy may be useful for causing selective tumor damage and reducing the effect on normal tissues.

New technique for mediastinal temperature measurement in hyperthermic cancer treatment: balloon catheter in the azygos vein.

The temperature in the mediastinum during hyperthermia is difficult to determine accurately. We measured the temperature in the azygos vein, using a new technique, and compared the measurements with temperatures in the oesophagus. Eight patients with mediastinal tumours resulting from lung cancer or oesophageal cancer were given hyperthermo-radiotherapy. The temperatures in the azygos vein and in the oesophagus were measured before and during blockage of the blood flow of the azygos vein using an angiographic balloon catheter. None of the patients had complications as a result of these procedures, and hyperthermia by capacitative heating was safely performed. The temperature in the azygos vein increased by a mean of 1.7 degrees C (0.2-2.8 degrees C) after blockage of the blood flow. The temperature in the oesophagus was 0.83 +/- 1.09 degrees C (mean +/- SD) higher than that in the azygos vein. Measurement of the temperature in the azygos vein gives a more accurate estimate of mediastinal temperature than does oesophageal temperature but it is an invasive procedure.