Skip to main content
SpringerLink
Log in

Photodynamic Detection of Lymph Node Metastases in Gastrointestinal Cancer by Using 5-Aminolevulinic Acid

  • Chapter
Fluorescence Imaging for Surgeons

  • 1179 Accesses

Abstract

Lymph node (LN) metastasis is common in gastrointestinal cancer patients and serves as an important prognostic indicator. Fluorescence detection using 5-aminolevulinic acid (5-ALA) is a new approach to attain rapid evaluation of LN metastasis during surgery. Administration of excessive 5-ALA produces selective accumulation of fluorescent protoporphyrin IX (PpIX) in cancer cells. Here, we introduce recent advances in the fluorescence detection of LN metastases of gastrointestinal cancer by using 5-ALA.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kitagawa Y, Kitano S, Kubota T, Kumai K, Otani Y, Saikawa Y, et al. Minimally invasive surgery for gastric cancer–toward a confluence of two major streams: a review. Gastric Cancer. 2005;8(2):103–10. PubMed PMID: 15864717.

    Article  PubMed  Google Scholar 

  2. Koeda K, Nishizuka S, Wakabayashi G. Minimally invasive surgery for gastric cancer: the future standard of care. World J Surg. 2011;35(7):1469–77. PubMed PMID: 21476116.

    Article  PubMed  Google Scholar 

  3. Nicholl M, Bilchik A. Is routine use of sentinel node biopsy justified in colon cancer? Ann Surg Oncol. 2008;15(1):1–3. PMID: 17929100.

    Article  PubMed  Google Scholar 

  4. Cohen AM, Kelsen D, Saltz L, Minsky BD, Nelson H, Farouk R, et al. Adjuvant therapy for colorectal cancer. Curr Probl Surg. 1997;34(8):601–76. PubMed PMID: 9251585.

    Article  CAS  PubMed  Google Scholar 

  5. Yun M, Lim JS, Noh SH, Hyung WJ, Cheong JH, Bong JK, et al. Lymph node staging of gastric cancer using (18)F-FDG PET: a comparison study with CT. J Nucl Med. 2005;46(10):1582–8. PubMed PMID: 16204706.

    PubMed  Google Scholar 

  6. Kim S-K, Kang K, Lee J, Kim H, Chang H, Choi J, et al. Assessment of lymph node metastases using 18F-FDG PET in patients with advanced gastric cancer. Eur J Nucl Med Mol Imaging. 2006;33(2):148–55.

    Article  PubMed  Google Scholar 

  7. Mukai K, Ishida Y, Okajima K, Isozaki H, Morimoto T, Nishiyama S. Usefulness of preoperative FDG-PET for detection of gastric cancer. Gastric Cancer. 2006;9(3):192–6.

    Article  PubMed  Google Scholar 

  8. Kim EY, Lee WJ, Choi D, Lee SJ, Choi JY, Kim B-T, et al. The value of PET/CT for preoperative staging of advanced gastric cancer: comparison with contrast-enhanced CT. Eur J Radiol. 2011;79(2):183–8.

    Article  PubMed  Google Scholar 

  9. Mejia A, Waldman SA. Previstage™ GCC test for staging patients with colorectal cancer. Expert Rev Mol Diagn. 2008;8(5):571–8.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13(16):4807–16. PubMed PMID: 17699859.

    Article  CAS  PubMed  Google Scholar 

  11. Le Frere-Belda MA, Bats AS, Gillaizeau F, Poulet B, Clough KB, Nos C, et al. Diagnostic performance of one-step nucleic acid amplification for intraoperative sentinel node metastasis detection in breast cancer patients. Int J Cancer. 2012;130(10):2377–86. PubMed PMID: 21780107.

    Article  PubMed  Google Scholar 

  12. Ishizuka M, Abe F, Sano Y, Takahashi K, Inoue K, Nakajima M, et al. Novel development of 5-aminolevulinic acid (ALA) in cancer diagnoses and therapy. Int Immunopharmacol. 2011;11(3):358–65. PubMed PMID: 21144919.

    Article  CAS  PubMed  Google Scholar 

  13. Berlin NI, Neuberger A, Scott JJ. The metabolism of delta-aminolevulinic acid. 2. Normal pathways, studied with the aid of 14C. Biochem J. 1956;64(1):90–100. PubMed PMID: 13363810, Pubmed Central PMCID: 1199694.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Van Hillegersberg R, Van den Berg JW, Kort WJ, Terpstra OT, Wilson JH. Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. Gastroenterology. 1992;103(2):647–51. PubMed PMID: 1386052.

    PubMed  Google Scholar 

  15. Schoenfeld N, Epstein O, Lahav M, Mamet R, Shaklai M, Atsmon A. The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders. Cancer Lett. 1988;43(1–2):43–8. PubMed PMID: 3203329.

    Article  CAS  PubMed  Google Scholar 

  16. Dailey HA, Smith A. Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase. Biochem J. 1984;223(2):441–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B. 1992;14(4):275–92. PubMed PMID: 1403373.

    Article  CAS  PubMed  Google Scholar 

  18. Peng Q, Warloe T, Berg K, Moan J, Kongshaug M, Giercksky KE, et al. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer. 1997;79(12):2282–308. PubMed PMID: 9191516.

    Article  CAS  PubMed  Google Scholar 

  19. Murayama Y, Harada Y, Imaizumi K, Dai P, Nakano K, Okamoto K, et al. Precise detection of lymph node metastases in mouse rectal cancer by using 5-aminolevulinic acid. Int J Cancer. 2009;125(10):2256–63. PubMed PMID: 19569177.

    Article  CAS  PubMed  Google Scholar 

  20. Kriegmair M, Baumgartner R, Knuchel R, Stepp H, Hofstadter F, Hofstetter A. Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. J Urol. 1996;155(1):105–9. discussion 9–10, PubMed PMID: 7490803.

    Article  CAS  PubMed  Google Scholar 

  21. Jichlinski P, Forrer M, Mizeret J, Glanzmann T, Braichotte D, Wagnieres G, et al. Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: preliminary results. Lasers Surg Med. 1997;20(4):402–8. PubMed PMID: 9142679.

    Article  CAS  PubMed  Google Scholar 

  22. Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery. 1998;42(3):518–25. discussion 25–6, PubMed PMID: 9526986.

    Article  CAS  PubMed  Google Scholar 

  23. 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(3):577–82. PubMed PMID: 12168102.

    CAS  PubMed  Google Scholar 

  24. Mayinger B, Reh H, Hochberger J, Hahn EG. Endoscopic photodynamic diagnosis: oral aminolevulinic acid is a marker of GI cancer and dysplastic lesions. Gastrointest Endosc. 1999;50(2):242–6. PubMed PMID: 10425420.

    Article  CAS  PubMed  Google Scholar 

  25. 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(12):5421–7. PubMed PMID: 23225446.

    CAS  PubMed  Google Scholar 

  26. Harada K, Harada Y, Beika M, Koizumi N, Inoue K, Murayama Y, et al. Detection of lymph node metastases in human colorectal cancer by using 5-aminolevulinic acid-induced protoporphyrin IX fluorescence with spectral unmixing. Int J Mol Sci. 2013;14(11):23140–52. PubMed PMID: 24284403, Pubmed Central PMCID: 3856110.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Koizumi N, Harada Y, Murayama Y, Harada K, Beika M, Yamaoka Y, et al. Detection of metastatic lymph nodes using 5-aminolevulinic acid in patients with gastric cancer. Ann Surg Oncol. 2013;20(11):3541–8. PubMed PMID: 23846777.

    Article  PubMed  Google Scholar 

  28. Kato S, Kawamura J, Kawada K, Hasegawa S, Sakai Y. Fluorescence diagnosis of metastatic lymph nodes using 5-aminolevulinic acid (5-ALA) in a mouse model of colon cancer. J Surg Res. 2012;176(2):430–6. PubMed PMID: 22221602.

    Article  CAS  PubMed  Google Scholar 

  29. Takizawa H, Kondo K, Toba H, Kenzaki K, Sakiyama S, Tangoku A. Fluorescence diagnosis of lymph node metastasis of lung cancer in a mouse model. Oncol Rep. 2009;22(1):17–21. PubMed PMID: 19513499.

    PubMed  Google Scholar 

  30. Asai J, Harada Y, Beika M, Takenaka H, Katoh N, Takamatsu T. Photodynamic diagnosis of metastatic lymph nodes using 5-aminolevulinic acid in mouse squamous cell carcinoma. J Dermatol Sci. 2014;74:171.

    Article  CAS  PubMed  Google Scholar 

  31. Tsutsumi S, Kuwano H, Morinaga N, Shimura T, Asao T. Animal model of para-aortic lymph node metastasis. Cancer Lett. 2001;169(1):77–85. PubMed PMID: 11410328.

    Article  CAS  PubMed  Google Scholar 

  32. Fisher ER, Swamidoss S, Lee CH, Rockette H, Redmond C, Fisher B. Detection and significance of occult axillary node metastases in patients with invasive breast cancer. Cancer. 1978;42(4):2025–31. PubMed PMID: 213191.

    Article  CAS  PubMed  Google Scholar 

  33. Cochran AJ, Wen DR, Morton DL. Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study. Am J Surg Pathol. 1988;12(8):612–8. PubMed PMID: 3041850.

    Article  CAS  PubMed  Google Scholar 

  34. Trojani M, de Mascarel I, Bonichon F, Coindre JM, Delsol G. Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. Br J Cancer. 1987;55(3):303–6. PubMed PMID: 3552017, Pubmed Central PMCID: 2001759.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. European Assessment Report – Gliolan. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000744/human_med_000807.jsp&mid=WC0b01ac058001d124

  36. Dalton JT, Yates CR, Yin D, Straughn A, Marcus SL, Golub AL, et al. Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer. J Pharmacol Exp Ther. 2002;301(2):507–12. PubMed PMID: 11961050.

    Article  CAS  PubMed  Google Scholar 

  37. 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(3):313–9. PubMed PMID: 9372622.

    Article  CAS  PubMed  Google Scholar 

  38. Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res. 1997;68(1):31–7. PubMed PMID: 9126192.

    Article  CAS  PubMed  Google Scholar 

  39. Hinnen P, de Rooij FW, Terlouw EM, Edixhoven A, van Dekken H, van Hillegersberg R, et al. Porphyrin biosynthesis in human Barrett’s oesophagus and adenocarcinoma after ingestion of 5-aminolaevulinic acid. Br J Cancer. 2000;83(4):539–43. PubMed PMID: 10945504, Pubmed Central PMCID: 2374652.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Bjorkman DJ, Samowitz WS, Brigham EJ, Peterson BJ, Straight RC. Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. Lasers Surg Med. 1991;11(3):263–70. PubMed PMID: 1861565.

    Article  CAS  PubMed  Google Scholar 

  41. Jones BB, Jessop LD, Samowitz WS, Bjorkman DJ. Computer-assisted fluorescence identification of colon cancer in rats. Am J Gastroenterol. 1993;88(10):1724–8. PubMed PMID: 8213714.

    CAS  PubMed  Google Scholar 

  42. Gao X, Cui Y, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22(8):969–76. PubMed PMID: 15258594.

    Article  CAS  PubMed  Google Scholar 

  43. Garini Y, Young IT, McNamara G. Spectral imaging: principles and applications. Cytometry A. 2006;69(8):735–47. PubMed PMID: 16969819.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 456 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Takeo Minamikawa Ph.D., Yoshinori Harada M.D., Ph.D. & Tetsuro Takamatsu M.D., Ph.D.

Authors
  1. Takeo Minamikawa Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshinori Harada M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tetsuro Takamatsu M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuro Takamatsu M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Section of Minimally Invasive Surgery, Department of General and Vascular Surgery, The Bariatric and Metabolic Institute, Cleveland Clinic Florida, FL, USA; Oncological Surgical Division, Division of Surgical Research, Department of Surgery, Hospital de Clinicas Buenos Aires, University of Buenos Aires, Buenos Aires, Argentina

    Fernando D. Dip

  2. Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research; Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Takeaki Ishizawa

  3. Hepato-Biliary-Pancreatic Surgery; Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan

    Norihiro Kokudo

  4. Department of General Surgery, Section of Minimally Invasive Surgery; Department of General and Vascular Surgery, The Bariatric and Metabolic Institute, Cleveland Clinic Florida, Weston, Florida, USA

    Raul J. Rosenthal

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Minamikawa, T., Harada, Y., Takamatsu, T. (2015). Photodynamic Detection of Lymph Node Metastases in Gastrointestinal Cancer by Using 5-Aminolevulinic Acid. In: Dip, F., Ishizawa, T., Kokudo, N., Rosenthal, R. (eds) Fluorescence Imaging for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-15678-1_28

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15678-1_28

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15677-4

  • Online ISBN: 978-3-319-15678-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation