Journal of Gastroenterology

, Volume 45, Issue 1, pp 1–8 | Cite as

Eradication of gastric cancer and more efficient gastric cancer surveillance in Japan: two peas in a pod



We provide a historical review and update on current thinking regarding the possibility of elimination of gastric cancer from Japan. Because Helicobacter pylori infection is the cause gastric cancer, its elimination forms the cornerstone of eradication of gastric cancer. However, simply eradicating H. pylori from the entire population will not immediately solve the problem because many patients with H. pylori infections have already developed the precursor lesion, atrophic gastritis. Cure of H. pylori in these high risk patients will only reduce the risk of subsequent cancer. In contrast, treatment of low risk patients will prevent cancer. Thus, to eliminate gastric cancer it is necessary to identify and treat all infected individuals. In addition, those at increased risk for gastric cancer (i.e., atrophic gastritis irrespective of age) should be considered for endoscopic surveillance to identify those cancers that develop at an early stage. We propose that severity and extent of atrophy be used to separate those expected to benefit from endoscopy and annual surveillance from those with little or no potential benefit. We suggest an algorithm for eradicating gastric cancer that incorporates H. pylori and atrophic gastritis testing, H. pylori therapy, and surveillance to institute a program of surveillance restricted to those who could benefit most (i.e., those with moderate or severe atrophy). This will also allow a much closer matching of surveillance capacity and surveillance need making surveillance more clinically- and cost-effective.


Gastric cancer Surveillance Pepsinogen Helicobacter pylori Natural history 


  1. 1.
    Graham DY, Lu H, Yamaoka Y. African, Asian or Indian enigma, the East Asian Helicobacter pylori: facts or medical myths. J Dig Dis. 2009;10:77–84.CrossRefPubMedGoogle Scholar
  2. 2.
    Hoffman FL. The mortality from cancer throughout the world. Newark: Prudential Press; 1915.Google Scholar
  3. 3.
    von den Velden R. Ueber vorkommen und mandgel der freien salzsaure in magensaft bei gastrektasie. Deutsches Arch Klin Med. 1879;23:369–99.Google Scholar
  4. 4.
    Faber K. Gastritis and its consequences. Paris: Oxford University Press; 1935.Google Scholar
  5. 5.
    Comfort MW. Gastric acidity before and after development of gastric cancer: its etiologic, diagnostic and prognostic significance. Ann Intern Med. 1951;36:1331–48.Google Scholar
  6. 6.
    Warren RJ, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273–5.Google Scholar
  7. 7.
    Comfort MW, Vanzant FR. Gastric acidity in carcinoma of the stomach. Am J Surg. 1934;26:447–56.CrossRefGoogle Scholar
  8. 8.
    Shay H, Gershon-Cohen J, Fels SS. Gastric anacidity: its physiologic and clinical significance and its management. Am J Dig Dis. 1941;8:115–23.Google Scholar
  9. 9.
    Berkson J, Butt HR, Comfort MW. Occurrence of gastric cancer in persons with achlorhydria and with pernicious anemia. Proc Staff Meet Mayo Clin. 1956;31:583–96.PubMedGoogle Scholar
  10. 10.
    Faber K. Chronic gastritis: its relation to achylia and ulcer. Lancet. 1927;2:902–7.Google Scholar
  11. 11.
    Massarrat S. Konjetzny: a German surgeon of the past century and his pioneering hypothesis of a bacterial aetiology for gastritis, peptic ulcer and gastric cancer. Z Gastroenterol. 2005;43:411–3.CrossRefPubMedGoogle Scholar
  12. 12.
    Cheli R, Perasso A, Giacosa A. Gastritis: a clinical review. Berlin: Springer; 1987.Google Scholar
  13. 13.
    Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M. A model for gastric cancer epidemiology. Lancet. 1975;2:58–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Kokkola A, Kosunen TU, Puolakkainen P, Sipponen P, Harkonen M, Laxen F, et al. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS. 2003;111:619–24.CrossRefPubMedGoogle Scholar
  15. 15.
    Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis: associations according to severity of disease. Epidemiology. 2009;20:569–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Ekstrom AM, Held M, Hansson LE, Engstrand L, Nyren O. Helicobacter pylori in gastric cancer established by CagA immunoblot as a marker of past infection. Gastroenterology. 2001;121:784–91.CrossRefPubMedGoogle Scholar
  17. 17.
    Graham DY, Sung JY. Helicobacter pylori. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran’s gastrointestinal and liver disease. Pathophysiology, diagnosis, management. 7th ed. Philadelphia: WB Saunders; 2006. p. 1049–66.Google Scholar
  18. 18.
    Cardenas VM, Mulla ZD, Ortiz M, Graham DY. Iron deficiency and Helicobacter pylori infection in the United States. Am J Epidemiol. 2006;163:127–34.CrossRefPubMedGoogle Scholar
  19. 19.
    Dholakia KR, Dharmarajan TS, Yadav D, Oiseth S, Norkus EP, Pitchumoni CS. Vitamin B12 deficiency and gastric histopathology in older patients. World J Gastroenterol. 2005;11:7078–83.PubMedGoogle Scholar
  20. 20.
    DuBois S, Kearney DJ. Iron-deficiency anemia and Helicobacter pylori infection: a review of the evidence. Am J Gastroenterol. 2005;100:453–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Hershko C, Lahad A, Kereth D. Gastropathic sideropenia. Best Pract Res Clin Haematol. 2005;18:363–80.CrossRefPubMedGoogle Scholar
  22. 22.
    Tan HJ, Goh KL. Changing epidemiology of Helicobacter pylori in Asia. J Dig Dis. 2008;9:186–9.PubMedGoogle Scholar
  23. 23.
    Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: a model. Gastroenterology. 1997;113:1983–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Ohata H, Kitauchi S, Yoshimura N, Mugitani K, Iwane M, Nakamura H, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer. 2004;109:138–43.CrossRefPubMedGoogle Scholar
  25. 25.
    Snaith A, El-Omar EM. Helicobacter pylori: host genetics and disease outcomes. Expert Rev Gastroenterol Hepatol. 2008;2:577–85.CrossRefPubMedGoogle Scholar
  26. 26.
    Graham DY, Uemura N. Natural history of gastric cancer after Helicobacter pylori eradication in Japan: after endoscopic resection, after treatment of the general population, and naturally. Helicobacter. 2006;11:139–43.CrossRefPubMedGoogle Scholar
  27. 27.
    Graham DY, Shiotani A. The time to eradicate gastric cancer is now. Gut. 2005;54:735–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Graham DY, Shiotani A, El-Zimaity HM. Chromoendoscopy points the way to understanding recovery of gastric function after Helicobacter pylori eradication. Gastrointest Endosc. 2006;64:686–90.CrossRefPubMedGoogle Scholar
  29. 29.
    Graham DY. Gastric cancer surveillance or prevention plus targeted surveillance. Jpn J Helicobacter Res. 2009;10:9–14.Google Scholar
  30. 30.
    Rugge M, Correa P, Di Mario F, El-Omar E, Fiocca R, Geboes K, et al. OLGA staging for gastritis: a tutorial. Dig Liver Dis. 2008;40:650–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Graham DY, Kato M, Asaka M. Gastric endoscopy in the 21st century: appropriate use of an invasive procedure in the era of non-invasive testing. Dig Liver Dis. 2008;40:497–503.CrossRefPubMedGoogle Scholar
  32. 32.
    Miki K, Morita M, Sasajima M, Hoshina R, Kanda E, Urita Y. Usefulness of gastric cancer screening using the serum pepsinogen test method. Am J Gastroenterol. 2003;98:735–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Urita Y, Hike K, Torii N, Kikuchi Y, Kanda E, Sasajima M, et al. Serum pepsinogens as a predicator of the topography of intestinal metaplasia in patients with atrophic gastritis. Dig Dis Sci. 2004;49:795–801.CrossRefPubMedGoogle Scholar
  34. 34.
    El-Zimaity HM, Ota H, Graham DY, Akamatsu T, Katsuyama T. Patterns of gastric atrophy in intestinal type gastric carcinoma. Cancer. 2002;94:1428–36.CrossRefPubMedGoogle Scholar
  35. 35.
    Oi M, Oshida K, Sugimura S. The location of gastric ulcer. Gastroenterology. 1959;36:45–56.PubMedGoogle Scholar
  36. 36.
    Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;1:87–97.CrossRefGoogle Scholar
  37. 37.
    Kimura K. Chronological transition of the fundic-pyloric border determined by stepwise biopsy of the lesser and greater curvatures of the stomach. Gastroenterology. 1972;63:584–92.PubMedGoogle Scholar
  38. 38.
    Hebbel R. The topography of chronic gastritis in otherwise normal stomachs. Am J Pathol. 1949;25:125–41.PubMedGoogle Scholar
  39. 39.
    Watabe H, Mitsushima T, Yamaji Y, Okamoto M, Wada R, Kokubo T, et al. Predicting the development of gastric cancer from combining Helicobacter pylori antibodies and serum pepsinogen status: a prospective endoscopic cohort study. Gut. 2005;54:764–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Cancer incidence and incidence rates in Japan in 1986: estimates based on data from nine population-based cancer registries. The Research Group for Population-based Cancer Registration in Japan. Jpn J Clin Oncol. 1991;21:318–23.Google Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  1. 1.Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of MedicineHoustonUSA
  2. 2.Hokkaido University School of MedicineSapporoJapan

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