Photodynamic therapy using 5‐aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5‐aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low‐invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5‐aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low‐energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low‐invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5‐aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment‐resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5‐aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer.

BACKGROUND: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5‐aminolevulinic acid (ALA) (ALA‐PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA‐PDD (PDD‐TURBT) for nonmuscle invasive bladder cancer.METHODS: Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA‐induced fluorescence with the pathological result. PDD‐TURBT was performed in 99 completely resectable cases corresponding to 210 ALA‐PDD cases. To evaluate the abilities of PDD‐TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT.RESULTS: The diagnostic accuracy and capability of ALA‐PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA‐PDD. The recurrence‐free survival rate in the cases that underwent PDD‐TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD‐TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence‐free survival. All procedures were well tolerated by all patients without any severe adverse events.CONCLUSIONS: This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA‐PDD and PDD‐TURBT are remarkably helpful in detection and intraoperative navigation programs. Cancer 2012;. © 2011 American Cancer Society.

Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases.

Purpose: The purpose of this study was to clarify the regulatory mechanism of protoporphyrin IX (PpIX) synthesis mediated by 5-aminolevulinic acid (ALA) in human urothelial carcinoma (UC), leading to improved accuracy in photodynamic diagnosis and therapy using ALA. Experimental Design: PpIX accumulation in cultured UC cells after incubation for 1–5 h with 0.5–5 mM ALA was analyzed by fluorescence analysis using fluorescence microscopy and flow cytometry technique. Results: PpIX fluorescence mediated by ALA was increased, and the intensity of PpIX fluorescence was time-dependently increased in UC cells compared to noncancerous cells. The distribution of endogenous PpIX fluorescence primarily coincided with mitochondria, and then increased at a specific perinuclear region in the cells during the time of incubation. The ALA-mediated PpIX synthesis in UC cells was suppressed by β-alanine, an inhibitor of β-transporters of cell membrane, and carbonylcyanide p-trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, the ALA-mediated PpIX accumulation was increased by deferoxamine, an iron chelator, manganese and nitric oxide, which is contributed to PpIX metabolism by inhibiting ferrochelatase activity, generated by a nitric oxide-generating reagent NOC-18. As observed above, ALA-mediated PpIX synthesis in human UC cells was regulated by the process of ALA uptake, ALA conversion to PpIX and metabolism of accumulated PpIX to heme. Conclusions: This shows that the suppression of ferrochelatase increased PpIX accumulation in UC cells using small amount of ALA, thus leading to an improved clinical practicability of photodynamic diagnosis and therapy.