FLUORESCENCE CYSTOSCOPY FOLLOWING INTRAVESICAL INSTILLATION OF 5-AMINOLEVULINIC ACID - A NEW PROCEDURE WITH HIGH-SENSITIVITY FOR DETECTION OF HARDLY VISIBLE UROTHELIAL NEOPLASIAS

Methods have been sought for the in vivo marking of tiny papillary tum ors of the bladder and flat urothelial lesions such as dysplasia or ca rcinoma in situ, which can easily be missed during conventional endosc opy under white light. A new procedure is reported for the fluorescenc e detection of urothelial dysplasia and early bladder cancer. The meth od is based on intravesical application of 5-aminolevulinic acid (ALA) . ALA if applied exogenously induces accumulation of protoporphyrin IX (PPIX) in the urothelium of the bladder. PPIX is an intensively red f luorescing agent. The mean ratio of fluorescence intensity between uro thelial cancer and normal epithelium was found to be 17:1. Fluorescenc e excitation was achieved by violet light from a krypton ion laser (la mbda = 406.7 nm) or from a xenon are lamp with a bandpass filter syste m (lambda = 375-440 nm). Both light sources proved to be of equal suit ability for fluorescence excitation. Fluorescence microscopy revealed that the PPIX fluorescence is strictly limited to the urothelium. It c ould not be detected from the submucosa or muscle of the bladder. Blad der wall biopsies were taken from 90 patients with suspicion of bladde r cancer under fluorescence view. The fluorescence detection proved to be of high sensitivity (98%). No serious side effects which would pre clude further clinical testing, especially no cutaneous photoreaction, were observed. Tumor-associated fluorescence induced by topical ALA a pplication offers new perspectives in the diagnosis and treatment of b ladder cancer. In case of suspicious or positive urine cytologic findi ngs, ALA fluorescence cystoscopy may be useful for detecting the preci se site of the malignancy. The procedure might be helpful in complete resection or coagulation of urothelial neoplasms. Due to this, diminis hing recurrence rates are expected. However, this hypothesis has to be studied in prospective clinical trials.