Induction of controlled prostatic tissue necrosis by bacille Calmette-Gu�rin derivatives

Abstract

Intraprostatic administration of live bacille Calmette-Guérin (BCG) in humans has been found to produce tumor necrosis; unfortunately, the number of severity of complications have made its clinical use prohibitive. Previous studies have shown that soluble and microparticulate components present in the supernatants obtained after centrifugation of a reconstituted BCG preparation exhibit similar immunogenicity to the one shown by live bacteria. The supernatants, however, are not associated with disseminated infection of the progressive regional tissue destruction observed with the use of viable vaccine. Experiments were conducted to determine the effect of intraprostatic injection of BCG and its supernatants. Adult dogs, after positive conversion to protein purified derivative (PPD), were randomly assigned to three groups. Under direct vision and with digital rectal control, intraprostatic injections of various agents were given as follows: group I, normal saline; group II, live BCG; group III, 200 micrograms of BCG supernatants. Two months later the animals were sacrificed, and the prostates removed in toto and submitted for a thorough histological examination. Extensive but variable tissue necrosis was noted in groups II and III. No histological alterations were present in group I. The histological picture of the animals receiving BCG supernatants conclusively demonstrated circumscribed necrosis of the gland. Side effects and complications were present in animals receiving live BCG but conspicuously absent in the ones receiving supernatants. The observed effectiveness and safety of BCG supernatants for intraprostatic administration in an experimental system may lead to a simple, safe, and efficacious therapeutic modality for localized carcinoma of the prostate in humans.