Treatment of the Dunning Prostate Rat Tumor R3327-AT1 with Pulsed High Energy Ultrasound Shock Waves (PHEUS): Growth Delay and Histomorphologic Changes

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Abstract
We are interested in the interaction of pulsed high energy shock waves (PHEUS) on soft tissues treated in situ to evaluate its potential for therapeutic use. The experimental apparatus built by us was adapted from a lithotripter designed for clinical use. For the present studies we used the R3327-AT1 Dunning prostate tumor growing s.c. in the thigh of Copenhagen rats. The treatments consisted of four groups of eight animals each who received 500 or 2000 pulses at 1 or 5 Hz. Sham-treated tumor bearing animals served as controls (n = 11). During each PHEUS treatment, petechial bleeding of the skin at the point of entry and exit of sound appeared. Sonication at a repetition rate of five Hz seemed to induce more macroscopic damage in terms of hematomas and skin effects. The cytotoxic effects of PHEUS to tumor tissue were sufficient to induce a significant delay (p less than 0.05) in tumor growth but no clear-cut dose relationship was established. Histological studies revealed widespread early rupture of the fine vasculature with extravasation of erythrocytes. By 72 hr., in PHEUS treated tumors, a large necrosis was seen within the central zone which was never observed in sham-treated tumors. Our results clearly indicate that PHEUS has a cytotoxic potential. The observation of a rapid onset of hemostasis, stark hemorrhage and necrosis in the treatment field would suggest that vascular damage is an important contributing factor.