Advertisement

Photodynamic Diagnosis of Gastric Cancer Using 5-Aminolevulinic Acid

  • Tsutomu NamikawaEmail author
  • Keiji Inoue
  • Taro Shuin
  • Kazuhiro Hanazaki

Abstract

5-Aminolevulinic acid (ALA) is a protoporphyrin IX precursor and a new-generation photosensitive substance for photodynamic diagnosis (PDD). Fluorescence navigation by PDD provides good visualization and detection of gastric cancer lesions, and might be particularly useful for intestinal type gastric cancer. PDD using ALA is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Another promising application for this modality is in diagnosing peritoneal metastasis during preoperative staging laparoscopy wherein it could provide useful information for the selection of therapeutic modality.

Keywords

Photodynamic diagnosis 5-Aminolevulinic acid Gastric cancer Protoporphyrin IX Adenocarcinoma Adenoma Endoscopy Endoscopic submucosal dissection Gastrectomy Photosensitizer 

Supplementary material

Video 20.1

Our ALA-PDD system revealed a slightly elevated lesion in this patient with a distinct margin demarcated by an intense fluorescent signal. This lesion was pathologically diagnosed as well-differentiated adenocarcinoma confined to the mucosal layer. (WMV 14365 kb)

References

  1. 1.
    Kelty CJ, Brown NJ, Reed MW, Ackroyd R. The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosis. Photochem Photobiol Sci. 2002;1(3):158–68.CrossRefPubMedGoogle Scholar
  2. 2.
    Inoue K, Karashima T, Kamada M, Shuin T, Kurabayashi A, Furihata M, et al. Regulation of 5-aminolevulinic acid-mediated protoporphyrin IX accumulation in human urothelial carcinomas. Pathobiology. 2009;76(6):303–14.CrossRefPubMedGoogle Scholar
  3. 3.
    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 nonmuscle invasive bladder cancer. Cancer. 2012;118(4):1062–74.CrossRefPubMedGoogle Scholar
  4. 4.
    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(3):213–7. Epub 2013.CrossRefPubMedGoogle Scholar
  5. 5.
    Hinnen P, de Rooij FW, van Velthuysen ML, Edixhoven A, van Hillegersberg R, Tilanus HW, et al. Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus. Br J Cancer. 1998;78(5):679–82.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    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(3):294–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Lam S, Palcic B, McLean D, Hung J, Korbelik M, Profio AE. Detection of early lung cancer using low dose Photofrin II. Chest. 1990;97(2):333–7.CrossRefPubMedGoogle Scholar
  8. 8.
    von Holstein CS, Nilsson AM, Andersson-Engels S, Willén R, Walther B, Svanberg K. Detection of adenocarcinoma in Barrett’s oesophagus by means of laser induced fluorescence. Gut. 1996;39(5):711–6.CrossRefGoogle Scholar
  9. 9.
    Loh CS, Vernon D, MacRobert AJ, Bedwell J, Bown SG, Brown SB. Endogenous porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the gastrointestinal tract. J Photochem Photobiol B. 1993;20(1):47–54.CrossRefPubMedGoogle Scholar
  10. 10.
    Krieg RC, Messmann H, Rauch J, Seeger S, Knuechel R. Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. Photochem Photobiol. 2002;76(5):518–25.CrossRefPubMedGoogle Scholar
  11. 11.
    Utsuki S, Miyoshi N, Oka H, Miyajima Y, Shimizu S, Suzuki S, et al. Fluorescence-guided resection of metastatic brain tumors using a 5-aminolevulinic acid-induced protoporphyrin IX: pathological study. Brain Tumor Pathol. 2007;24(2):53–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Fukuhara H, Inoue K, Satake H, Tamura K, Karashima T, Yamasaki I, et al. Photodynamic diagnosis of positive margin during radical prostatectomy: preliminary experience with 5-aminolevulinic acid. Int J Urol. 2011;18(8):585–91.CrossRefPubMedGoogle Scholar
  13. 13.
    Mayinger B, Neidhardt S, Reh H, Martus P, Hahn EG. Fluorescence induced with 5-aminolevulinic acid for the endoscopic detection and follow-up of esophageal lesions. Gastrointest Endosc. 2001;54(5):572–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  15. 15.
    Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer. 2013;16(1):1–27.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Sano T, Sasako M, Kinoshita T, Maruyama K. Recurrence of early gastric cancer. Follow-up of 1475 patients and review of the Japanese literature. Cancer. 1993;72(11):3174–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Namikawa T, Kobayashi M, Kitagawa H, Okabayashi T, Sugimoto T, Kuratani Y, et al. Differentiated adenocarcinoma with a gastric phenotype in the stomach: difficulties in clinical and pathological diagnoses. Clin J Gastroenterol. 2009;2(4):268–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Okabayashi T, Kobayashi M, Nishimori I, Sugimoto T, Namikawa T, Onishi S, et al. Clinicopathological features and medical management of early gastric cancer. Am J Surg. 2008;195(2):229–32.CrossRefPubMedGoogle Scholar
  19. 19.
    Namikawa T, Hanazaki K. Clinicopathological features of early gastric cancer with duodenal invasion. World J Gastroenterol. 2009;15(19):2309–13.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Namikawa T, Hanazaki K. Mucin phenotype of gastric cancer and clinicopathology of gastric-type differentiated adenocarcinoma. World J Gastroenterol. 2010;16(37):4634–9.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Kabashima A, Yao T, Maehara Y, Tsuneyoshi M. Relationship between biological behavior and phenotypic expression in undifferentiated-type gastric carcinomas. Gastric Cancer. 2005;8(4):220–7.CrossRefPubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    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.CrossRefPubMedGoogle Scholar
  24. 24.
    Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histoclinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.PubMedGoogle Scholar
  25. 25.
    Hagiya Y, Endo Y, Yonemura Y, Takahashi K, Ishizuka M, Abe F, et al. Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro. Photodiagnosis Photodyn Ther. 2012;9(3):204–14.CrossRefPubMedGoogle Scholar
  26. 26.
    Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T, et al. Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation. PLoS One. 2012;7(11):e50082.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Inoue K, Fukuhara H, Kurabayashi A, Furihata M, Tsuda M, Nagakawa K, et al. Photodynamic therapy involves an antiangiogenic mechanism and is enhanced by ferrochelatase inhibitor in urothelial carcinoma. Cancer Sci. 2013;104(6):765–72.CrossRefPubMedGoogle Scholar
  28. 28.
    Rodriguez L, Batlle A, Di Venosa G, MacRobert AJ, Battah S, Daniel H, et al. Study of the mechanisms of uptake of 5-aminolevulinic acid derivatives by PEPT1 and PEPT2 transporters as a tool to improve photodynamic therapy of tumours. Int J Biochem Cell Biol. 2006;38(9):1530–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Novotny A, Xiang J, Stummer W, Teuscher NS, Smith DE, Keep RF. Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus. J Neurochem. 2000;75(1):321–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Döring F, Walter J, Will J, Föcking M, Boll M, Amasheh S, et al. Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998;101(12):2761–7.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    el-Sharabasy MM, el-Waseef AM, Hafez MM, Salim SA. Porphyrin metabolism in some malignant diseases. Br J Cancer. 1992;65(3):409–12.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Navone NM, Polo CF, Frisardi AL, Andrade NE, Battle AM. Heme biosynthesis in human breast cancer–mimetic “in vitro” studies and some heme enzymic activity levels. Int J Biochem. 1990;22(12):1407–11.CrossRefPubMedGoogle Scholar
  33. 33.
    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.PubMedGoogle Scholar
  34. 34.
    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.CrossRefPubMedGoogle Scholar
  35. 35.
    Robey RW, Steadman K, Polgar O, Bates SE. ABCG2-mediated transport of photosensitizers: potential impact on photodynamic therapy. Cancer Biol Ther. 2005;4(2):187–94.CrossRefPubMedGoogle Scholar
  36. 36.
    Namikawa T, Kobayashi M, Kitagawa H, Okabayashi T, Dabanaka K, Okamoto K, et al. Early gastric cancer with widespread duodenal invasion within the mucosa. Dig Endosc. 2010;22(3):223–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Namikawa T, Kitagawa H, Iwabu J, Okabayashi T, Sugimoto T, Kobayashi M, et al. Clinicopathological properties of the superficial spreading type early gastric cancer. J Gastrointest Surg. 2010;14(1):52–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Cao Y, Liao C, Tan A, Gao Y, Mo Z, Gao F. Meta-analysis of endoscopic submucosal dissection versus endoscopic mucosal resection for tumors of the gastrointestinal tract. Endoscopy. 2009;41(9):751–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Abe S, Oda I, Suzuki H, Nonaka S, Yoshinaga S, Odagaki T, et al. Short- and long-term outcomes of endoscopic submucosal dissection for undifferentiated early gastric cancer. Endoscopy. 2013;45(9):703–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Abe N, Takeuchi H, Ooki A, Nagao G, Masaki T, Mori T, et al. Recent developments in gastric endoscopic submucosal dissection: towards the era of endoscopic resection of layers deeper than the submucosa. Dig Endosc. 2013;25 Suppl 1:64–70.CrossRefPubMedGoogle Scholar
  41. 41.
    Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9(3):215–21.CrossRefPubMedGoogle Scholar
  42. 42.
    Cardona K, Zhou Q, Gönen M, Shah MA, Strong VE, Brennan MF, et al. Role of repeat staging laparoscopy in locoregionally advanced gastric or gastroesophageal cancer after neoadjuvant therapy. Ann Surg Oncol. 2013;20(2):548–54.CrossRefPubMedGoogle Scholar
  43. 43.
    Karanicolas PJ, Elkin EB, Jacks LM, Atoria CL, Strong VE, Brennan MF, et al. Staging laparoscopy in the management of gastric cancer: a population-based analysis. J Am Coll Surg. 2011;213(5):644–51.CrossRefPubMedGoogle Scholar
  44. 44.
    Muntean V, Mihailov A, Iancu C, Toganel R, Fabian O, Domsa I, et al. Staging laparoscopy in gastric cancer. Accuracy and impact on therapy. J Gastrointestin Liver Dis. 2009;18(2):189–95.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Tsutomu Namikawa
    • 1
    Email author
  • Keiji Inoue
    • 2
  • Taro Shuin
    • 2
  • Kazuhiro Hanazaki
    • 1
  1. 1.Department of SurgeryKochi Medical SchoolNankokuJapan
  2. 2.Department of UrologyKochi Medical SchoolNankokuJapan

Personalised recommendations