Elsevier

Urology

Volume 44, Issue 6, December 1994, Pages 836-841
Urology

Adult urology
Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid*

https://doi.org/10.1016/S0090-4295(94)80167-3Get rights and content

Abstract

Objectives.

Tiny papillary tumors and flat urothelial lesions such as dysplasiaor 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.

References (21)

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    All three abovementioned key elements have been investigated to some extent before, however, scarcely so in cell lines of NMSC, and frequently the published observations have not been consequently linked to resistance [20–22]. Tumor tissues often show increased PpIX accumulation compared to their healthy counterparts, e.g., liver [23], gastrointestinal [24], bladder [25] or brain tissue [26], and also in skin: In a direct comparison between a squamous cell carcinoma cell line and healthy, virus-immortalized keratinocytes, neoplastic cells produced more PpIX from the precursor 5-ALA than healthy cells [20]. Likely candidates for 5-ALA uptake are genes of the solute carrier transporter (SLC) family, especially the SLC6, SLC15 and SLC36 subfamilies due to molecular structure similarity of 5-ALA to endogenous substrates of these transporters [27].

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*

This study was supported by the Bundesministeriumfar Forschung and Technologie (German government) and Friedrich-Baur Stiftung (University of Munich).

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