Methods have been sought for the in vivo marking of tiny papillary tumors of the bladder and flat urothelial lesions such as dysplasia or carcinoma in situ, which can easily be missed during conventional endoscopy under white light. A new procedure is reported for the fluorescence detection of urothelial dysplasia and early bladder cancer. The method 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 fluorescing agent. The mean ratio of fluorescence intensity between urothelial cancer and normal epithelium was found to be 17:1. Fluorescence excitation was achieved by violet light from a krypton ion laser (lambda = 406.7 nm) or from a xenon arc lamp with a bandpass filter system (lambda = 375-440 nm). Both light sources proved to be of equal suitability for fluorescence excitation. Fluorescence microscopy revealed that the PPIX fluorescence is strictly limited to the urothelium. It could not be detected from the submucosa or muscle of the bladder. Bladder wall biopsies were taken from 90 patients with suspicion of bladder cancer under fluorescence view. The fluorescence detection proved to be of high sensitivity (98%). No serious side effects which would preclude further clinical testing, especially no cutaneous photoreaction, were observed. Tumor-associated fluorescence induced by topical ALA application offers new perspectives in the diagnosis and treatment of bladder cancer. In case of suspicious or positive urine cytologic findings, ALA fluorescence cystoscopy may be useful for detecting the precise site of the malignancy. The procedure might be helpful in complete resection or coagulation of urothelial neoplasms. Due to this, diminishing recurrence rates are expected. However, this hypothesis has to be studied in prospective clinical trials.

PURPOSE:Cystectomy is indicated after unsuccessful transurethral resection and intravesical treatment of superficial bladder cancer. As an alternative, whole bladder photodynamic therapy was done.MATERIALS AND METHODS:In 21 patients the bladder was irradiated with laser light at a wavelength of 630 nm. after intravenous injection of a synthetic porphyrin mixture.RESULTS:Of the 21 patients 12 attained complete remission with a mean disease-free interval of 18.0 months (range 3 to 42), 3 with partial remission were rendered disease-free with transurethral resection or neodymium:YAG laser coagulation and 6 underwent cystectomy.CONCLUSIONS:In patients with refractory superficial bladder cancer the bladder can be preserved by use of photodynamic therapy.

A total of 149 patients with 152 ureteral stones were treated with intraureteral lithotripsy by Dye-laser (83.55 %), Alexandrite-laser (41.27 %), electrohydraulic lithotripsy adapted for use in the ureter (25.16 %) or neodymium: YAG laser with optomechanic coupling (3.2 %). The Dye-laser has an automatic pulse shut-off mechanism with spectral analysis of the reflected laser beam, so that effective laser pulses can only be released by contact with a stone. Most (127 of 83.5 %) of the stones could be completely fragmented, so that no further treatment was necessary. In 16 cases (10.5 %) the stone was too hard for fragmentation and had to be removed by alternative techniques. Intraureteral lithotripsy is a save and effective method of treating ureteral stones that cannot be reached or have not been treated successfully by schockwave lithotripsy. No significant differences in outcome were found between the different lasers or electro-hydraulic lithotripsy. In selected cases endoscopic treatment may be recommended as treatment of first choice.

Following transurethral resection of bladder cancer, the fate of patients is clearly related to the presence or absence of precancerous or malignant lesions in the remaining mucosa. We report on a new procedure for in situ diagnosis of these flat, hardly visible urothelial lesions. The method is based on tumor-selective accumulation of endogenous protoporphyrin IX following intravesical instillation of 5-aminolevulinic acid. On excitation with violet light even tiny papillary tumors, dysplastic lesions and carcinoma in situ are bright fluorescing red. In 15 patients 26 neoplastic lesions had been diagnosed only by protoporphyrin IX fluorescence. False-negative results have not yet been observed. In 84% of 285 evaluable specimens the fluorescence findings corresponded correctly with the microscopic findings. It is expected that photodynamic diagnosis will become a matter of routine in detection of bladder cancer.

Objectives. Tiny papillary tumors and flat urothelial lesions such as dysplasia or carcinoma in situ can easily be missed during routine cystoscopy. Various methods for in vivo detection of fluorescing agents (preferentially localized in malignant tissue) have been developed. Most of them are based on systemically administered synthetic porphyrin compounds and require sensitive detection devices and image processing units for fluorescence visualization. The usefulness of intracellularly accumulated endogenous protoporphyrin IX (PPIX), induced by 5-aminolevulinic acid (ALA), for diagnosis of early bladder cancer and the correlation with cystoscopic, microscopic, and fluorescence findings was investigated.Methods. ALA was instilled intravesically in 68 patients, followed by fluorescence cystoscopy with violet light from a krypton ion laser that produced fluorescence excitation. There were 299 biopsies obtained from fluorescing and nonfluorescing areas of the bladder.Results. ALA-induced fluorescence could be easily observed with the naked eye during cystoscopy under violet light illumination. All tumor lesions were sharply marked with brightly shining red fluorescence. Correlation of fluorescence and microscopic findings gave a sensitivity of 100% and a specificity of 68.5%. There were 26 malignant or precancerous lesions that were missed during routine cystoscopy but were detected only by ALA-induced fluorescence.Conclusions. Labeling of urothelial lesions by PPIX fluorescence induced by intravesically instilled ALA seems to be a promising diagnostic procedure for malignant lesions that are difficult to visualize with standard cystoscopy.

If transurethral resection and intravesical treatment with BCG or chemotherapeutic agents are unsuccessful in recurrent flat multifocal superficial bladder cancer, cystectomy is considered to be indicated. A whole-bladder photodynamic therapy (PDT) was carried out in 23 patients in this worst-case situation, in 19 of whom minimum follow-up of 3 months has been possible. In 5 patients with carcinoma in situ and in 14 patients with flat papillary tumors covering nearly the whole bladder, Photofrin or Photosan-3 was applied intravesically. Irradiation of the bladder followed about 48 h, later with a light dose of 15 J/cm2 or 30 J/cm2 at a wave length of 630 nm. In 12 patients complete remission was achieved; 7 patients showed no evidence of disease over a follow-up period of 3-31 months (median 16.3 months). One patient was lost to follow-up. In 7 patients recurrent disease or residual tumor was observed following PDT, but these were easily managed by transurethral resection or Nd:YAG laser coagulation. In 4 patients PDT failed and cystectomy was carried out. Systemic progression was not observed. PDT has to be regarded as an alternative to cystectomy in the treatment of refractory superficial bladder cancer.

Following transurethral resection of bladder cancer, the fate of patients is clearly related to the presence or absence of precancerous or malignant lesions in the remaining mucosa. We report on a new procedure for in situ diagnosis of these flat, hardly visible urothelial lesions. The method is based on tumor-selective accumulation of endogenous protoporphyrin IX following intravesical instillation of 5-aminolevulinic acid. On excitation with violet light even tiny papillary tumors, dysplastic lesions and carcinoma in situ are bright fluorescing red. In 15 patients 26 neoplastic lesions had been diagnosed only by protoporphyrin IX fluorescence. False-negative results have not yet been observed. In 84% of 285 evaluable specimens the fluorescence findings corresponded correctly with the microscopic findings. It is expected that photodynamic diagnosis will become a matter of routine in detection of bladder cancer.