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Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication

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Abstract

Background

We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa.

Methods

In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acidsecreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acidsecreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index.

Results

After a gradual increase in acidsecreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well.

Conclusions

Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.

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References

  1. Ruiz B, Correa P, Fontham ET, Ramakrishnan T. Antral atrophy, Helicobacter pylori colonization, and gastric pH. Am J Clin Pathol 1996;105:96–101.

    PubMed  CAS  Google Scholar 

  2. Iijima K, Ohara S, Koike T, Sekine H, Shimosegawa T. Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender. Scand J Gastroenterol 2004;39:709–716.

    Article  PubMed  CAS  Google Scholar 

  3. Svendsen JH, Svendsen CD, Christiansen PM. Gastric cancer risk in achlorhydric patients. A long-term follow-up study. Scand J Gastroenterol 1986;21:16–20.

    Article  PubMed  CAS  Google Scholar 

  4. El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997;113:15–24.

    Article  PubMed  CAS  Google Scholar 

  5. Gutierrez O, Melo M, Segura AM, Angel A, Genta RM, Graham DY. Cure of Helicobacter pylori infection improves gastric acid secretion in patients with corpus gastritis. Scand J Gastroenterol 1997;32:664–668.

    Article  PubMed  CAS  Google Scholar 

  6. Yasunaga Y, Shinomura Y, Kanayama S, Yabu M, Nakanishi T, Miyazaki Y, et al. Improved fold width and increased acid secretion after eradication of the organism in Helicobacter pylori associated enlarged fold gastritis. Gut 1994;35:1571–1574.

    Article  PubMed  CAS  Google Scholar 

  7. Tucci A, Poli L, Tosetti C, Biasco G, Grigioni W, Varoli O, et al. Reversal of fundic atrophy after eradication of Helicobacter pylori. Am J Gastroenterol 1998;93:1425–1431.

    Article  PubMed  CAS  Google Scholar 

  8. El-Omar EM, Oien K, Murray LS, El-Nujumi A, Wirz A, Gillen D, et al. Increased prevalence of precancerous change in relatives of gastric cancer patients: critical role of H. pylori. Gastroenterology 2000;188:22–30.

    Article  Google Scholar 

  9. Annibale B, Aprile MR, D’ambra G, Caruana P, Bordi C, Delle Fave G. Cure of Helicobacter pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL-cell hyperplasia. Aliment Pharmacol Ther 2000;14:625–634.

    Article  PubMed  CAS  Google Scholar 

  10. Iijima K, Sekine H, Koike T, Imatani A, Ohara S, Shimosegawa T. Long-term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria. Aliment Pharmacol Ther 2004;19:1181–1188.

    Article  PubMed  CAS  Google Scholar 

  11. Sekine H, Iijima K, Koike T, Abe Y, Imatani A, Kato K, et al. Regional differences in the recovery of gastric acid secretion after Helicobacter pylori eradication: evaluations with Congo red chromoendoscopy. Gastrointest Endosc 2006;64:678–685.

    Article  PubMed  Google Scholar 

  12. Tatsuta M, Saegusa T, Okuda S. Studies on gastritis in upper portion of stomach by endoscopic Congo red test. Endoscopy 1973;5:61–69.

    Article  Google Scholar 

  13. Tatsuta M, Ishii H, Ichii M, Noguchi S, Okuda S, Taniguchi H. Chromoendoscopic observations on extension and development of fundal gastritis and intestinal metaplasia Gastroenterology 1985;88:70–74.

    PubMed  CAS  Google Scholar 

  14. Tatsuta M, Okuda S. Location, healing, and recurrence of gastric ulcers in relation to fundal gastritis. Gastroenterology 1975;69:897–902.

    PubMed  CAS  Google Scholar 

  15. Toth E, Sjolund K, Thorsson O, Thorlacius H. Evaluation of gastric acid secretion at endoscopy with a modified Congo red test. Gastrointest Endosc 2002;56:254–259.

    Article  PubMed  Google Scholar 

  16. Toth E, Sjolund K, Lindstrom. Chronic atrophic fundic gastritis diagnosed by a modified Congo red test. Endoscopy 1995;27:654–658.

    Article  PubMed  CAS  Google Scholar 

  17. Thirlby RC, Patterson DJ, Kozarek RA. Prospective comparison of Congo red and sham feeding testing to determine vagal innervation of the stomach. Am J Surg 1992;163:533–536.

    Article  PubMed  CAS  Google Scholar 

  18. Peetsalu A, Peetsalu M. Interpretation of postvagotomy endoscopic Congo-red test results in relation to ulcer recurrence 5 to 12 years after operation. Am J Surg 1998;175:472–476.

    Article  PubMed  CAS  Google Scholar 

  19. Rohrer GV, Welsh JD. Correlative study: gastric secretion and histology. Gastroenterology 1967;52:185–191.

    PubMed  CAS  Google Scholar 

  20. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. Cancer Res 1992;52:6735–6740.

    PubMed  CAS  Google Scholar 

  21. Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G, et al. Gastric precancerous process in a high risk population: cohort follow-up. Cancer Res 1990;50:4737–4740.

    PubMed  CAS  Google Scholar 

  22. Anti M, Armuzzi A, Gasbarrini A, Gasbarrini G. Importance of changes in epithelial cell turnover during Helicobacter pylori infection in gastric carcinogenesis. Gut 1998;43Suppl 1:S27–S32.

    PubMed  Google Scholar 

  23. 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;38:177–181.

    Article  PubMed  CAS  Google Scholar 

  24. Yabuki N, Sasano H, Tobita M, Imatani A, Hoshi T, Kata K, et al. Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma. Am J Pathol 1997;151:821–829.

    PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. 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;40:337–344.

    Article  PubMed  Google Scholar 

  27. Yoshimura T, Shimoyama T, Tanaka M, Sasaki Y, Fukuda S, Munakata A. Gastric mucosal inflammation and epithelial cell turnover are associated with gastric cancer in patients with Helicobacter pylori infection. J Clin Pathol 2000;53:532–536.

    Article  PubMed  CAS  Google Scholar 

  28. Sung JJY, Lin SR, Ching JYL, Zhou LY, To KF, Wang RT, et al. Atrophy and intestinal metaplasia one year after cure of H. pylori infection: randomized study. Gastroenterology 2000;119:4–14.

    Article  Google Scholar 

  29. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, et al. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med 2001;134:380–386.

    PubMed  CAS  Google Scholar 

  30. Annibale B, Giulio ED, Caruana P, Lahner E, Capurso G, Bordi C, et al. The long-term effects of cure of Helicobacter pylori infection on patients with atrophic body gastritis. Aliment Pharmacol Ther 2002;16:1723–1731.

    Article  PubMed  CAS  Google Scholar 

  31. Ito M, Haruma K, Kamada T, Mihara M, Kim S, Kitadai Y, et al. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther 2002;16:1449–1456.

    Article  PubMed  CAS  Google Scholar 

  32. Kokkola A, Sipponen P, Rautelin H, Härkönen M, Kosunen TU, Haapiainen R, et al. The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia. Aliment Pharmacol Ther 2002;16:515–520.

    Article  PubMed  CAS  Google Scholar 

  33. Mera R, Fontham ETH, Bravo LE, Bravo JC, Piazuelo B, Camargo MC, et al. Long term follow up of patients treated for Helicobacter pylori infection. Gut 2005;54:1536–1540.

    Article  PubMed  CAS  Google Scholar 

  34. 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;36:346–350.

    Article  PubMed  CAS  Google Scholar 

  35. El-Zimaity HMT, Graham DY, Genta RM, Lechago J. Sustained increase in gastric antral epithelial cell proliferation despite cure of Helicobacter pylori infection. Am J Gastroenterol 2000;95:930–935.

    Article  PubMed  CAS  Google Scholar 

  36. Ierardi E, Francavilla A, Balzano T, Traversa A, Principi M, Monno RA, et al. Effect of Helicobacter pylori eradication on gastric epithelial proliferation: relationship with ras oncogene p21 expression. Ital J Gastroenterol Hepatol 1997;29:214–219.

    PubMed  CAS  Google Scholar 

  37. Guarner J, Bartlett J, Seitz R, Whistler T, Herrera-Goepfert R, Mohar A, et al. Cell proliferation and inflammation on biopsy samples with multifocal atrophic gastritis before and after 1 year after Helicobacter pylori eradication. Arch Pathol Lab Med 2005;129:1451–1456.

    PubMed  Google Scholar 

  38. Cahill RJ, Xia H, Kilgallen C, Beattie S, Hamilton H, O’Morain C. Effect of eradication of Helicobacter pylori infection on gastric epithelial cell proliferation. Dig Dis Sci 1995;40:1627–1631.

    Article  PubMed  CAS  Google Scholar 

  39. Brenes F, Ruiz B, Correa P, Hunter F, Rhamakrishnan T, Fontham E, et al. Helicobacter pylori causes hyperproliferation of the gastric epithelium: pre- and post-eradication indices of proliferating cell nuclear antigen. Am J Gastroenterol 1993;88:1870–1875.

    PubMed  CAS  Google Scholar 

  40. Yamagata S, Masuda H, Ishimori A, Inoue A. Wada T. Gastric secretion stimulated by gastrin-like AOC-tetrapeptid. Tohoku J Exp Med 1970;101:103–107.

    Article  PubMed  CAS  Google Scholar 

  41. Abernethy RJ, Gillespie IE, Lawrie JH, Forrest APM, Payne RA, Barabas A, et al. Pentagastrin as a stimulant of maximal gastric acid response in man, a multicenter pilot study. Lancet 1967;1:291–295.

    Google Scholar 

  42. Malfertheiner P, Fry LC, Monkemuller K. Can gastric cancer be prevented by Helicobacter pylori eradication? Best Pract Res Clin Gastroenterol 2006;20:709–719.

    Article  PubMed  Google Scholar 

  43. Tepes B, Kavcic B, Zaletel LK, Gubina M, Ihan A, Poljak M, et al. Two- to four-year histological follow-up of gastric mucosa after Helicobacter pylori eradication. J Pathol 1999;188:24–29.

    Article  PubMed  CAS  Google Scholar 

  44. Kikuchi T, Kato K, Ohara S, Sekine H, Arikawa T, Suzuki T, et al. The relationship between persistent secretion of RANTES and residual infiltration of eosinophils and memory T lymphocytes after Helicobacter pylori eradication. J Pathol 2000;192:243–250.

    Article  PubMed  CAS  Google Scholar 

  45. Ioachin HL, Hajdu C, Giancotti FR, Dorsett B. Lymphoid proliferations and lymphomas associated with gastric metaplasia, dysplasia, and carcinoma. Hum Pathol 1999;30:833–842.

    Article  Google Scholar 

  46. Tsutsumi Y, Nagura H, Watanabe K. Immune aspects of intestinal metaplasia of the stomach: an immunohistochemical study. Virchows Arch 1984;403:345–359.

    Article  CAS  Google Scholar 

  47. Wallace JL, Cucala M, Mugridge K, Parente L. Secretagoguespecific effects of interleukin-1 on gastric acid secretion. Am J Physiol 1991;261:G559–G564.

    PubMed  CAS  Google Scholar 

  48. Beales IL, Calam J. Interleukin 1 beta and tumor necrosis factor alpha inhibit acid secretion in cultured rabbit parietal cells by multiple pathways. Gut 1998;42:227–234.

    Article  PubMed  CAS  Google Scholar 

  49. Ozawa K, Kato S, Sekine H, Koike T, Minora T, Iinuma K, et al. Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection. J Gastroenterol 2005;40:236–246.

    Article  PubMed  Google Scholar 

  50. Uemura N, Mukai T, Okamoto S, Yamaguchi S, Mashiba H, Taniyama K, et al. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomarkers Prev 1997;6:639–642.

    PubMed  CAS  Google Scholar 

  51. 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;21:1121–1126.

    Article  PubMed  CAS  Google Scholar 

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Iijima, K., Koike, T., Sekine, H. et al. Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication. J Gastroenterol 44, 47–55 (2009). https://doi.org/10.1007/s00535-008-2270-x

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  • DOI: https://doi.org/10.1007/s00535-008-2270-x

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