The application of 5-aminolevulinic acid-induced fluorescence for cystoscopic diagnosis and treatment of bladder carcinoma

Summary 

Purpose

To investigate the clinical application of 5-aminolevulinic acid (ALA) assisted fluorescence cystoscopy for early detection of bladder carcinoma and completely transurethral resection.

Method

ALA-assisted fluorescence cystoscopy was performed on 51 cases of anodynia haematuria. Fluorescence cystoscopy was performed with a D-Light system 2–3h after intravesical instillation of 5-ALA. Biopsy was performed in fluorescence positive regions and/or the fluorescence negative regions with an abnormal gross appearance under a white light. Thirty-two biopsies were subjected to frozen sectioning and the fluorescence distributions were analyzed with a confocal fluorescence microscopy and PpIX fluorescence contents in different tissues were quantified. Transurethral resection was performed in fluorescence positive regions.

Results

Red fluorescence (fluorescence positive) was found in 47 cases, among them 40 urothelial carcinomas and seven benign lesions confirmed by pathological examination; fluorescence negative was found in four cases of benign lesions. The sensitivity of fluorescence cystoscope for the diagnosis of bladder carcinoma was 97.1% (68/70) with a false-positive rate of 23.6% (21/89). Micro-fluorescence positive regions were found near the tumor or at distant region in 19 cases of transitional cell carcinoma with two carcinoma in situ unidentifiable with white light, and were confirmed of the existence of malignancy by biopsy. ALA-induced PpIX fluorescence was mainly distributed on the surface layer of the tissue and PpIX fluorescence was fairly weak in the deep tissue. Fluorescence quantization showed that the fluorescence intensity of the surface layer of the tissue was 5–10 fold higher than deep tissue, which was correlated with the grade of tumor (G₃>G_1–2), but the mean fluorescence intensity in tumor tissue was significantly higher than that of benign lesions.

Conclusion

ALA-assisted fluorescence cystoscope offers a simple photodynamic diagnosis approach for the diagnosis of bladder carcinoma, in particular, flat and small malignant lesions.

Keywords: Bladder carcinoma, Photodynamic diagnosis, Fluorescence cystoscope, Biopsy, 5-Aminolevulinic acid, Transurethral resection, Confocal fluorescence microscopy