title: The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA).
abstract: OBJECTIVE
  To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy.
  
  
  METHODS
  The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source.
  
  
  RESULTS
  Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body.
  
  
  CONCLUSIONS
  ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan. Electronic address: keiji@kochi-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Urology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Division of Urology, National Hospital Organizarion Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Department of UroOncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Oyama
authors.affiliation: Department of UroOncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan.
authors.forename: Munehisa
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine Institute of Medical Science, 2-174 Edobashi Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Urology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Graduate School of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
authors.affiliation: Department of Urology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
authors.affiliation: Division of Urology, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu-shi, Tokyo 183-8524, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nagase
authors.affiliation: Department of Urology, Hiroshima University Faculty of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Department of Biostatistics, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Yoichi M
authors.initials: YM
authors.lastname: Ito
authors.affiliation: Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D003287:Contrast Media / Q000008:administration & dosage; D003558:Cystoscopy / Q000009:adverse effects / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects; D025321:Surgery, Computer-Assisted / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery*
chemical_list: D003287:Contrast Media; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid (5-ALA); Carcinoma in situ (CIS); Non-muscle invasive bladder cancer (NMIBC); Photodynamic diagnosis (PDD); The advanced medical technology