Advertisement

Photodynamic Diagnosis Mediated by 5-Aminolevulinic Acid for Urinary Bladder Cancer

  • Keiji InoueEmail author
  • Hideo Fukuhara
  • Taro Shuin

Abstract

5-Aminolevulinic acid (ALA) is an endogenous natural amino acid, and has recently been attracting attention as a new-generation photosensitive substance for photodynamic diagnosis (PDD). In the urology field, ALA-mediated PDD (ALA-PDD) has already been approved for the intraoperative diagnosis of non-muscle invasive bladder cancer (NMIBC) as a novel fluorescence-guided navigation technology approved in Europe and United States, whereas in Japan, ALA is waiting for approval as a photosensitizer for bladder cancer. Moreover, ALA-PDD is also clinically applied for the diagnosis of upper urinary tract cancer, prostate cancer, and renal cancer. This chapter outlines ALA-PDD for urinary bladder cancer.

Keywords

5-Aminolevulinic acid (ALA) Photodynamic diagnosis (PDD) Protoporphyrin IX (PpIX) Fluorescence cystoscopy Non-muscle invasive bladder cancer (NMIBC) Transurethral resection of bladder tumor (TURBT) 

Supplementary material

Video 30.1

There were multiple papillary tumors. ALA-PDD could show red fluorescence of these tumors themselves and also the outskirts of these tumors. In particular, a tiny and flat lesion could be detected only by ALA-PDD in the right posterior wall of urinary bladder. Moreover, the floating of a lot of bladder cancer cells with PDD-fluorescence (MP4 87,401 kb) could be detected.

Video 30.2

In TURB, bladder tumor is scraped with the looped type of electrical scalpel under the cystoscopic observation. TURB under ALA-PDD enable to confirm the correct surgical margin by navigation of red fluorescence. The residual lesions with red fluorescence at the resected margin could be resected additionally and exactly (MP4 201,878 kb)

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–403.CrossRefPubMedGoogle Scholar
  3. 3.
    Matsuda A, Matsuda T, Shibata A, Katanoda K, Sobue T, Nishimoto H, et al. Cancer incidence and incidence rates in Japan in 2007: a study of 21 population-based cancer registries for the monitoring of cancer incidence in Japan (MCIJ) project. Jpn J Clin Oncol. 2013;43:328–36.CrossRefPubMedGoogle Scholar
  4. 4.
    Cogliano VJ, Baan R, Straif K, Grosse Y, Lauby-Secretan B, El Ghissassi F, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst. 2011;103:1827–39.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Ferrís J, Berbel O, Alonso-López J, Garcia J, Ortega JA. Environmental non-occupational risk factors associated with bladder cancer. Actas Urol Esp. 2013;37:579–86.PubMedGoogle Scholar
  6. 6.
    Malik Z, Lugaci H. Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. Br J Cancer. 1987;56:589–95.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Kriegmair M, Baumgartner R, Knuechel R, Steinbach P, Ehsan A, Lumper W, et al. Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid. Urology. 1994;44:836–41.CrossRefPubMedGoogle Scholar
  8. 8.
    Fukuhara H, Inoue K, Kuno T, Kamei M, Shimamoto T, Fukata S, et al. Photodynamic diagnosis of positive margin during radical prostatectomy: preliminary experience with 5-aminolevulinic acid. Int J Urol. 2011;18:585–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Inoue K, Ashida S, Fukuhara H, Iiyama T, Miyamura M, Kurabayashi K, et al. Application of 5-aminolevulinic acid (ALA) mediated photodynamic diagnosis (PDD) to robot-assisted laparoscopic radical prostatectomy (RALP). Urology. 2013;82:1175–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Hoda MR, Popken G. Surgical outcomes of fluorescence-guided laparoscopic partial nephrectomy using 5-aminolevulinic acid-induced protoporphyrin IX. J Surg Res. 2009;154:220–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Inoue K, Karashima T, Kamada M, Kurabayashi A, Ohtsuki Y, Shuin T. Clinical experience with intravesical instillations of 5-aminolevulinic acid (5-ALA) for the photodynamic diagnosis using fluorescence cystoscopy for bladder cancer. Nippon Hinyokika Gakkai Zasshi. 2006;97:719–29.PubMedGoogle Scholar
  12. 12.
    Inoue K, Kuno T, Fukuhara H, Hamaguchi T, Fukata S, Karashima T, et al. Clinical experience with transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD). Nippon Hinyokika Gakkai Zasshi. 2009;100:661–70.PubMedGoogle Scholar
  13. 13.
    Inoue K, Fukuhara H, Shimamoto T, Kamada M, Iiyama T, Miyamura M, et al. Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for non-muscle invasive bladder cancer. Cancer. 2012;118:1062–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Kausch I, Sommerauer M, Montorsi F, Stenzl A, Jacqmin D, Jichlinski P, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol. 2010;57:595–606.CrossRefPubMedGoogle Scholar
  15. 15.
    Mowatt G, N’Dow J, Vale L, Nabi G, Boachie C, Cook JA, et al. Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: systematic review and meta-analysis. Int J Technol Assess Health Care. 2011;27:3–10.CrossRefPubMedGoogle Scholar
  16. 16.
    Burger M, Grossman HB, Droller M, Schmidbauer J, Hermann G, Drăgoescu O, et al. Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol. 2013;64:846–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Rink M, Babjuk M, Catto JW, Jichlinski P, Shariat SF, Stenzl A, et al. Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature. Eur Urol. 2013;64:624–38.CrossRefPubMedGoogle Scholar
  18. 18.
    Zaak D, Hungerhuber E, Schneede P, Stepp H, Frimberger D, Corvin S, et al. Role of 5-aminolevulinic acid in the detection of urothelial premalignant lesions. Cancer. 2002;95:1234–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Hungerhuber E, Stepp H, Kriegmair M, Stief C, Hofstetter A, Hartmann A, et al. Seven years’ experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology. 2007;69(2):260–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Denzinger S, Burger M, Walter B, Knuechel R, Roessler W, Wieland WF, et al. Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acidinduced fluorescence diagnosis: 8-year results of prospective randomized study. Urology. 2007;69:675–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Rick K, Sroka R, Stepp H, Kriegmair M, Huber RM, Jacob K, et al. Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood. J Photochem Photobiol B. 1997;40:313–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Popken G, Schultze-Seemann W, Seiler KU, Birkel M, Wetterauer U. Intravesical administration of 5-aminolevulinic acid (5-ALA). Safety and pharmacokinetics of 5-ALA and its metabolite protoporphyrin IX. Eur J Clin Pharmacol. 2000;56:241–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Filbeck T, Wimmershoff MB, Pichlmeier U, Karrer S, Wieland WF, Szeimies RM, et al. No generalized skin phototoxicity after intravesical application of 5-aminolevulinic acid for fluorescence diagnosis of superficial bladder cancer. Urol Int. 2000;64:126–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Witjes JA, Redorta JP, Jacqmin D, Sofras F, Malmström PU, Riedl C, et al. Hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: review of the evidence and recommendations. Eur Urol. 2010;57:607–14.CrossRefPubMedGoogle Scholar
  25. 25.
    European Association of Urology. Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and CIS). European Association of Urology Guidelines. 2013 edition, pp. 10–16.Google Scholar
  26. 26.
    Guideline for the management of nonmuscle invasive bladder cancer: (Stages Ta, T1, and Tis). Chapter 1: the management of bladder cancer: diagnosis and treatment recommendations. 2007 Update, pp. 14–15.Google Scholar
  27. 27.
    Friesen SA, Hjortland GO, Madsen SJ, Hirschberg H, Engebraten O, Nesland JM, et al. 5-Aminolevulinic acid-based photodynamic detection and therapy of brain tumors (review). Int J Oncol. 2002;21:577–82.PubMedGoogle Scholar
  28. 28.
    Csanády M, Kiss JG, Iván L, Jóri J, Czigner J. ALA (5-aminolevulinic acid)-induced protoporphyrin IX fluorescence in the endoscopic diagnostic and control of pharyngo-laryngeal cancer. Eur Arch Otorhinolaryngol. 2004;26:262–6.CrossRefGoogle Scholar
  29. 29.
    Namikawa T, Inoue K, Uemura S, Shiga M, Maeda H, Kitagawa H, et al. Photodynamic diagnosis using 5-aminolevulinic acid during gastrectomy for gastric cancer. J Surg Oncol. 2014;109:213. doi: 10.1002/jso.23487.CrossRefPubMedGoogle Scholar
  30. 30.
    Kishi K, Fujiwara Y, Yano M, Inoue M, Miyashiro I, Motoori M, et al. Staging laparoscopy using ALA-mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer. J Surg Oncol. 2012;106:294–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Murayama Y, Ichikawa D, Koizumi N, Komatsu S, Shiozaki A, Kuriu Y, et al. Staging fluorescence laparoscopy for gastric cancer by using 5-aminolevulinic acid. Anticancer Res. 2012;32:5421–7.PubMedGoogle Scholar
  32. 32.
    Messmann H, Knüchel R, Endlicher E, Hauser T, Szeimies RM, Kullmann F, et al. Photodynamic diagnosis of gastrointestinal precancerous lesions after sensitization with 5-aminolevulinic acid. A pilot study. Dtsch Med Wochenschr. 1998;123:515–21.CrossRefPubMedGoogle Scholar
  33. 33.
    Baumgartner R, Huber RM, Schulz H, Stepp H, Rick K, Gamarra F, et al. Inhalation of 5-aminolevulinic acid: a new technique for fluorescence detection of early stage lung cancer. J Photochem Photobiol B. 1996;36:169–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Baas P, Triesscheijn M, Burgers S, van Pel R, Stewart F, Aalders M. Fluorescence detection of pleural malignancies using 5-aminolaevulinic acid. Chest. 2006;129:718–24.CrossRefPubMedGoogle Scholar
  35. 35.
    Andikyan V, Kronschnabl M, Hillemanns M, Wang X, Stepp H, Hillemanns P. Fluorescence diagnosis with 5-ALA thermogel of cervical intraepithelial neoplasia. Gynakol Geburtshilfliche Rundsch. 2004;44:31–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Fritsch C, Ruzicka T. Fluorescence diagnosis and photodynamic therapy in dermatology from experimental state to clinic standard methods. J Environ Pathol Toxicol Oncol. 2006;25:425–39.CrossRefPubMedGoogle Scholar
  37. 37.
    Muroi C, Fandino J, Coluccia D, Berkmann S, Fathi AR, Landolt H. 5-Aminolevulinic acid fluorescence-guided surgery for spinal meningioma. World Neurosurg. 2013;80:223. pii: S1878-8750(12)01450-7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of UrologyKochi Medical SchoolNankokuJapan

Personalised recommendations