Journal of Gastroenterology

, Volume 48, Issue 12, pp 1332–1342 | Cite as

Magnifying narrow-band imaging of surface maturation in early differentiated-type gastric cancers after Helicobacter pylori eradication

  • Masaaki KobayashiEmail author
  • Satoru Hashimoto
  • Ken Nishikura
  • Ken-ichi Mizuno
  • Manabu Takeuchi
  • Yuichi Sato
  • Yoichi Ajioka
  • Yutaka Aoyagi
Original Article—Alimentary Tract



Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. The endoscopic features of these cancers may be modified by controlling inflammation. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis.


Distinctive NBI-ME characteristics were examined retrospectively in intramucosal or minimally submucosal and differentiated-type adenocarcinomas from a successful eradication group (42 patients, 50 lesions) and a non-eradicated control group (44 patients, 50 lesions) matched in age and sex. A “gastritis-like” appearance under NBI-ME was characterized by uniform papillae and/or tubular pits with a whitish border, regular or faint microvessels and unclear demarcation, resembling the adjacent noncancerous mucosa. Histological differentiation at the luminal surface of the cancer was evaluated according to Ki-67 immunoreactivity restricted at the middle or lower portion of the tubules. NBI-ME alteration was prospectively confirmed in 29 patients (30 lesions) after eradication therapy.


The frequency of a “gastritis-like” appearance was 44 % (22/50) for the eradication group, which was significantly higher than the 4 % (2/50) for the control group (p < 0.001). In the eradication group, the “gastritis-like” appearance was significantly correlated with histological surface differentiation (p < 0.001). In the prospective study, NBI-ME showed changes to heterogeneous papillary microstructures in 43 % (10/23) of the lesions after successful eradication at short-term follow-up.


Identification of surface maturation under NBI-ME offers a promising approach for accurate diagnosis of early gastric cancers after successful eradication.


Gastric cancer Helicobacter pylori Eradication Narrow-band imaging Magnifying endoscopy 



This work was supported in part by the Japan Society for the Promotion of Science KAKENHI Grant Number 24591025.

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Take S, Mizuno M, Ishiki K, Nagahara Y, Yoshida T, Yokota K, et al. The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol. 2005;100:1037–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Wu CY, Kuo KN, Wu MS, Chen YJ, Wang CB, Lin JT. Early Helicobacter pylori eradication decreases risk of gastric cancer in patients with peptic ulcer disease. Gastroenterology. 2009;137:1641–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Mabe K, Takahashi M, Oizumi H, Tsukuma H, Shibata A, Fukase K, et al. Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer? World J Gastroenterol. 2009;15:4290–7.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Fukase K, Kato M, Kikuchi S, Inoue K, Uemura N, Okamoto S, Japan Gast Study Group, 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Kamada T, Hata J, Sugiu K, Kusunoki H, Ito M, Tanaka S, et al. Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan. Aliment Pharmacol Ther. 2005;21:1121–6.PubMedCrossRefGoogle Scholar
  6. 6.
    de Vries AC, Kuipers EJ, Rauws EA. Helicobacter pylori eradication and gastric cancer: when is the horse out of the barn? Am J Gastroenterol. 2009;104:1342–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Yamamoto K, Kato M, Takahashi M, Haneda M, Shinada K, Nishida U, et al. Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori. Helicobacter. 2011;16:210–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Matsuo T, Ito M, Tatsugami M, Boda T, Takata S, Tanaka S, et al. Gastric cancer development after Helicobacter pylori eradication therapy: a new form of gastric neoplasia. Digestion. 2012;85:61–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Yao K, Anagnostopoulos GK, Ragunath K. Magnifying endoscopy for diagnosing and delineating early gastric cancer. Endoscopy. 2009;41:462–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Dinis-Ribeiro M, Areia M, de Vries AC, Marcos-Pinto R, Monteiro-Soares M, O’Connor A, MAPS Participants, et al. Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED). Endoscopy. 2012;44:74–94.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Nagahama T, Yao K, Maki S, Yasaka M, Takaki Y, Matsui T, et al. Usefulness of magnifying endoscopy with narrow-band imaging for determining the horizontal extent of early gastric cancer when there is an unclear margin by chromoendoscopy (with video). Gastrointest Endosc. 2011;74:1259–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;3:87–97.CrossRefGoogle Scholar
  13. 13.
    Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma, 3rd English Edition. Gastric Cancer. 2011;14:101–12.CrossRefGoogle Scholar
  14. 14.
    Lauwers GY, Carneiro F, Graham DY, Curado MP, Franceschi S, Montgomery E, et al. Gastric carcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of tumours of the digestive system. 4th ed. Lyon: IARC Press; 2010. p. 48–58.Google Scholar
  15. 15.
    Kobayashi M, Takeuchi M, Ajioka Y, Hashimoto S, Sato A, Narisawa R, et al. Mucin phenotype and narrow-band imaging with magnifying endoscopy for differentiated-type mucosal gastric cancer. J Gastroenterol. 2011;46:1064–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaise M, Kato M, Urashima M, Arai Y, Kaneyama H, Kanzazawa Y, et al. Magnifying endoscopy combined with narrow-band imaging for differential diagnosis of superficial depressed gastric lesions. Endoscopy. 2009;41:310–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Yagi K, Nozawa Y, Endou S, Nakamura A. Diagnosis of early gastric cancer by magnifying endoscopy with NBI from viewpoint of histological imaging: mucosal patterning in terms of white zone visibility and its relationship to histology. Diagn Ther Endosc. 2012;. doi: 10.1155/2012/954809.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–81.PubMedCrossRefGoogle Scholar
  19. 19.
    Kobayashi M, Watanabe H, Ajioka Y, Honma T, Asakura H. Effect of K-ras mutation on morphogenesis of colorectal adenomas and early cancers: relationship to distribution of proliferating cells. Hum Pathol. 1996;27:1042–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Nozawa Y, Nishikura K, Ajioka Y, Aoyagi Y. Relationship between alpha-methylacyl-coenzyme: a racemase expression and mucin phenotype in gastric cancer. Hum Pathol. 2012;43:878–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Kato M, Kaise M, Yonezawa J, Toyoizumi H, Yoshimura N, Yoshida Y, et al. Magnifying endoscopy with narrow-band imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study. Gastrointest Endosc. 2010;72:523–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Ezoe Y, Muto M, Uedo N, Doyama H, Yao K, Oda I, et al. Magnifying narrowband imaging is more accurate than conventional white-light imaging in diagnosis of gastric mucosal cancer. Gastroenterology. 2011;141:2017–25.PubMedCrossRefGoogle Scholar
  23. 23.
    Kobayashi M, Narisawa R, Sato Y, Takeuchi M, Aoyagi Y. Self-limiting risk of metachronous gastric cancers after endoscopic resection. Dig Endosc. 2010;22:169–73.PubMedCrossRefGoogle Scholar
  24. 24.
    Endoh Y, Tamura G, Watanabe H, Ajioka Y, Motoyama T. The common 18-base pair deletion at codons 418–423 of the E-cadherin gene in differentiated-type adenocarcinomas and intramucosal precancerous lesions of the stomach with the features of gastric foveolar epithelium. J Pathol. 1999;189:201–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Endoh Y, Tamura G, Motoyama T, Ajioka Y, Watanabe H. Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach. Hum Pathol. 1999;30:826–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Noffsinger AE, Miller MA, Cusi MV, Fenoglio-Preiser CM. The pattern of cell proliferation in neoplastic and nonneoplastic lesions of ulcerative colitis. Cancer. 1996;78:2307–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Mikami T, Yoshida T, Akino F, Motoori T, Yajima M, Okayasu I. Apoptosis regulation differs between ulcerative colitis–associated and sporadic colonic tumors. Am J Clin Pathol. 2003;119:723–30.PubMedCrossRefGoogle Scholar
  28. 28.
    Lynch DA, Mapstone NP, Clarke AMT, Sobala GM, Jackson P, Morrison L, et al. Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy. Gut. 1995;36:346–50.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Cahill RJ, Kilgallen C, Beattie S, Hamilton H, O’Morain C. Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma. Gut. 1996;38:177–81.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Scotiniotis IA, Rokkas T, Furth EE, Rigas B, Shiff SJ. Altered gastric epithelial cell kinetics in Helicobacter pylori-associated intestinal metaplasia: implication for gastric carcinogenesis. Int J Cancer. 2000;85:192–200.PubMedGoogle Scholar
  31. 31.
    Shiotani A, Iishi H, Ishiguro S, Tatsuta M, Nakae Y, Merchant JL. Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation and paramalignant lesions. J Gastroenterol. 2005;40:337–44.PubMedCrossRefGoogle Scholar
  32. 32.
    Iijima K, Koike T, Sekine H, Abe Y, Asanuma K, Ara N, et al. Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. J Gastroenterol. 2009;44:47–55.PubMedCrossRefGoogle Scholar
  33. 33.
    Ito M, Tanaka S, Takata S, Oka S, Imagawa S, Ueda H, et al. Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up. Aliment Pharmacol Ther. 2005;21:559–66.PubMedCrossRefGoogle Scholar
  34. 34.
    Kato M, Asaka M, Ono S, Nakagawa M, Nakagawa S, Shimizu Y, et al. Eradication of Helicobacter pylori for primary gastric cancer and secondary gastric cancer after endoscopic mucosal resection. J Gastroenterol. 2007;42(Suppl 17):16–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Masaaki Kobayashi
    • 1
    Email author
  • Satoru Hashimoto
    • 1
  • Ken Nishikura
    • 2
  • Ken-ichi Mizuno
    • 1
  • Manabu Takeuchi
    • 3
  • Yuichi Sato
    • 3
  • Yoichi Ajioka
    • 4
  • Yutaka Aoyagi
    • 3
  1. 1.Department of EndoscopyNiigata University Medical and Dental HospitalNiigataJapan
  2. 2.Division of Molecular and Functional PathologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  3. 3.Division of GastroenterologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  4. 4.Division of Molecular and Diagnostic PathologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

Personalised recommendations