Photodynamic Therapeutic Effect during 5-Aminolevulinic Acid-Mediated Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumors.

Abstract

Photodynamic diagnosis-assisted transurethral resection of bladder tumors (PDD-TURBT) enhances detection of elusive lesions compared to standard white light-transurethral resection of bladder tumors (WL-TURBT). If minimal light exposure during PDD-TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD-TURBT. Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and N ε -hexanoyl-lysine was performed on 69 patients who underwent 5-aminolevulinic acid-mediated PDD-TURBT and 28 patients who underwent WL-TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM-UC-3 cells treated with 5-aminolevulinic acid using instruments similar to those used in PDD-TURBT and evaluated intracellular ROS production and phototoxicity. Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and N ε -hexanoyl-lysine within the PDD-TURBT group. In T24 and UM-UC-3 cells treated with 5-aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose-dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential. Although the irradiation energy used in PDD-TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD-TURBT.