Oral 5-Aminolaevulinic Acid-Guided Photodynamic Diagnosis of Upper and Lower Tract Transitional Cell Carcinoma: A Feasibility Study

Abstract

Introduction and Objective: Photodynamic diagnosis (PDD) using 5-Amino levulinic acid (ALA) has been reported to decrease the recurrences of nonmuscle invasive bladder tumor on surveillance by enhancing their initial diagnosis and treatment. There are several impediments, however, to the application of this technology in the upper tract urothelial lesions, including optimal method of photosensitizer delivery and its uptake; safety of photosensitizing agents; methods of observation; and subsequent destruction of tumor. This report and accompanying video demonstrate the feasibility of using oral 5-ALA in diagnosing upper and lower tract urothelial tumors. Methods: A prospective pilot study was performed to assess the feasibility of PDD using oral 5-ALA for urothelial tumors. About 20 mg/kg ALA was dissolved in 50 mL of water and the contents mixed with 50–100 mL of orange juice for flavor. The mixture was given orally 3–4 h before the planned observation. A standard white light flexible ureteroscopy was first performed using 7.5F (Uretero-Fiberscopes KARL STORZ Flex-X for PDD). Endoscopic observation was then done using D-light system (Karl Storz, Tuttlingen, Germany) to detect fluorescence using a xenon arc lamp with a blue light with a wavelength of 380–440 nm. Biopsies were carried out for all suspicious areas noting if lesions were detected by white or blue light, or both. Biopsies and tumor ablation of suspicious fluorescent lesions were then carried out under white light. Ablation was done with a curative intent. Holmium laser (365 μ) power levels for ablation ranged from 1 to 1.2 J, and the pulse frequencies ran from 12 to 15 Hz. For ablation, the laser fiber was directed at and placed in close approximation to the tumor without touching the tissue. Results: Photodynamic-guided observation of the upper tract in four patients showed additional multiple biopsies proven transitional cell carcinoma (TCC) besides obvious exophytic lesions seen using white light.1,2 Four of the five additional positive biopsies were low-grade tumors with one high-grade tumor. This included even those areas not seen on white light. Additional fluorescence around the tumor edge passed off as normal on white light was biopsied and confirmed as tumor. Post tumor ablation no further fluorescence was seen. The degree of observation as assessed by an experienced endoscopist (S.G.K.) was as good as seen in the bladder tumors using intravesical photosensitizers. Additional bladder biopsies from fluorescent areas also proved to be tumor. There were no technical problems and none of the patients had any side effects. All patients were discharged on the following postoperative day. PDD ureteroscopy was also helpful in follow-up of urinary tract-TCC confirming recurrent TCC both in the upper tract and bladder, not obvious on white light. Conclusions: PDD and subsequent treatment of upper tract urothelial tumors using oral 5-ALA is safe and feasible with additional advantages of detecting lesions not observed on conventional white light endoscopy. We would like to thank the staff and nurses at Scottish PDT center in Dundee. We declare that there were no commercial associations that might create a conflict of interest in connection with this article. None of the authors had any competing financial interests. Runtime of video: 4 mins 13 secs