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Photodynamic Diagnosis of Gastric Cancer Using 5-Aminolevulinic Acid

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Fluorescence Imaging for Surgeons

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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  19. Namikawa T, Hanazaki K. Clinicopathological features of early gastric cancer with duodenal invasion. World J Gastroenterol. 2009;15(19):2309–13.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan

    Tsutomu Namikawa M.D., Ph.D. & Kazuhiro Hanazaki M.D., Ph.D.

  2. Department of Urology, Kochi Medical School, Nankoku, Japan

    Keiji Inoue M.D., Ph.D. & Taro Shuin M.D., Ph.D.

Authors
  1. Tsutomu Namikawa M.D., Ph.D.
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  2. Keiji Inoue M.D., Ph.D.
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  3. Taro Shuin M.D., Ph.D.
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  4. Kazuhiro Hanazaki M.D., Ph.D.
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Corresponding author

Correspondence to Tsutomu Namikawa 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

Electronic Supplementary Materials

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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)

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Namikawa, T., Inoue, K., Shuin, T., Hanazaki, K. (2015). Photodynamic Diagnosis of Gastric Cancer 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_20

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  • DOI: https://doi.org/10.1007/978-3-319-15678-1_20

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-15677-4

  • Online ISBN: 978-3-319-15678-1

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