title: Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.
abstract: BACKGROUND
  We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA).
  
  
  METHODS
  Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated.
  
  
  RESULTS
  The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively.
  
  
  CONCLUSIONS
  We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use.
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Anai
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Onishi
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Kuwada
authors.initials: K
authors.lastname: Masaomi
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tatsumi
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Miyake
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
authors.affiliation: Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan. Electronic address: kiyokun@naramed-u.ac.jp.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011524:Protoporphyrins / Q000652:urine*; D012680:Sensitivity and Specificity; D013053:Spectrophotometry; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid; Photodynamic detection; Spectrophotometer; Urinary cytology