Skip to main content
SpringerLink
Log in

Helicobacter pylori: the new bug on the (paraffin) block

  • Review Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

A nameless spirillar organism in search of a disease only a few years ago, Helicobacter pylori has seen its fortunes suddenly reversed. After a rapid succession of name changes and some acrimonious disputes across continents, in less than a decade H. pylori has been catapulted to the centre stage of gastroenterological and microbiological research and has topped the most-wanted list of the pharmaceutical industry. The discovery of H. pylori has provided the momentum for the formation of the group that eventually created the Sydney System. Today, H. pylori is increasingly recognized as one of the most prevalent human pathogens worldwide. Its causal association with chronic active gastritis is undisputed and its role in the pathogenesis of peptide ulcer disease, although still poorly understood, is universally accepted. Furthermore, possible connections between chronic H. pylori infection and gastric carcinoma and primary gastric lymphoma are now being explored with increasing alacrity. With a few notable exceptions, pathologists have remained passive spectators of these exciting discoveries and have allowed gastroenterologists and microbiologists to set the pace in the quest for the determinants of gastritis, peptic ulcer and gastric cancer. This article is intended to outline some of the accepted facts on the development, progression, and pathology of H. pylori gastritis and to pose questions about this elusive infection. The authors hope that it might also contribute to stimulate further research, particularly on those aspects that are eminently suited to be addressed by pathologists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alam K, Schubert TT, Bologna SD, Ma CK (1992) Increased density of Helicobacter pylori on antral biopsy is associated with severity of acute and chronic inflammation and likelihood of duodenal ulceration. Am J Gastroenterol 87:424–428

    Google Scholar 

  2. Alpert LC, Graham DY, Evans DJ Jr, Yoshimura HH, Hazell SL, Evans DG, Klein PD (1989) Diagnostic possibilities for Campylobacter pylori infection. Eur J Gastroenterol Hepatol 1:17–26

    Google Scholar 

  3. Alpert LC, Lew GM, Michaletz PA, David L, Graham DY (1989) Comparison of the extent and severity of C. pylori infection between duodenal ulcer patients and age-matched asymptomatic C. pylori-infected subjects. Gastroenterology 96:A10

  4. Bayerdorffer E, Lehn N, Hatz R, Mannes GA, Oertel H, Sauerbruch T, Stolte M (1992) Difference in expression of Helicobacter pylori gastritis in antrum and body. Gastroenterology 102:1575–1582

    Google Scholar 

  5. Burstein M, Monge E, Leon-Baura R, Lozano R, Berendson R, Gilman RH, Legua H, Rodriguez C (1991) Low peptic ulcer and high gastric cancer prevalence in a developing country with a high prevalence of infection by Helicobacter pylori. J Clin Gastroenterol 13:154–156

    Google Scholar 

  6. Carrick J, Lee A, Hazell S, Ralston M, Daskalopoulos G (1989) Campylobacter pylori, duodenal ulcer, and gastric metaplasia: possible role of functional heterotopic tissue in ulcerogenesis. Gut 30:790–797

    Google Scholar 

  7. Chan WY, Hui PK, Chan JKC, Cheung PSY, Ng CS, Sham CH, Gwi E (1991) Epithelial damage by Helicobacter pylori in gastric ulcers. Histopathology 19:47–53

    Google Scholar 

  8. Correa P (1985) Clinical implications of recet developments in gastric cancer pathology and epidemiology. Semin Oncol 12:2–10

    Google Scholar 

  9. Correa P (1988) Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol 5:504–509

    Google Scholar 

  10. Correa P (1992) Human gastric carcinogenesis: a multistep and multifactorial process — First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 52:6735–6740

    Google Scholar 

  11. Correa P, Fox J, Fontham E, Ruiz B, Lin Y, et al (1990) Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks. Cancer 66:2569–2574

    Google Scholar 

  12. Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G, Tannenbaum S, Collazos T, Ruiz B (1990) Gastric precancerous process in a high risk population: cohort follow-up. Cancer Res 50:4737–4740

    Google Scholar 

  13. Cover TL, Cao P, Lind CD, Tham KT, Blaser MJ (1993) Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. Infect Immun 61:5008–5012

    Google Scholar 

  14. Crabtree JE, Taylor JD, Wyatt JI, Heatley RV, Shallcross TM, Tompkins DS, Rathbone BJ (1991) Mucosal IgG recognition of Helicobacter pylori 120 kDa protein, peptic ulceration, and gastric pathology. Lancet 338:332–335

    Google Scholar 

  15. Dehesa M, Dooly CP, Cohen H, Fitzgibbons PL, Perez-Perez GI, Blaser MJ (1991) High prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic Hispanics. J Clin Microbiol 29:1128–1131

    Google Scholar 

  16. Dixon MF (1991) Helicobacter pylori and peptic ulceration: histopathological aspects. J Gastroenterol Hepatol 6:125–130

    Google Scholar 

  17. Dixon M (1993) Acid, ulcers, and H. pylori. Lancet 342:384–385

    Google Scholar 

  18. Dixon MF, Wyatt JI, Burke DA, Rathbone BJ (1988) Lymphocytic gastritis — relationship to Campylobacter pylori infection. J Pathol 154:125–132

    Google Scholar 

  19. Doglioni C, Wotherspoon A, Moschini A, de Boni M, Isaacsson PG (1992) High incidence of primary gastric lymphoma in northeastern Italy. Lancet 339:834–835

    Google Scholar 

  20. Eaton KA, Brooks CL, Morgan DR, Krakowka S (1991) Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect Immun 59:2470–2475

    Google Scholar 

  21. Feng Y-Y, Wang Y (1988) Campylobacter pylori in patients with gastritis, peptic ulcer, and carcinoma of the stomach in Lanzhou, China. Lancet i:1055–1056

    Google Scholar 

  22. Figura N, Guglielmetti P, Rossolini A, Barberi A, Cusi G, Musmanno RA, Russi M, Quaranta S (1989) Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol 27:225–226

    Google Scholar 

  23. Fiocca R, Villani L, De Giacomo C, Perego M, Trespi E, Solcia E (1989) Morphological evidence of Campylobacter pylori pathogenicity in chronic gastritis and peptic ulcer. Acta Gastroenterol Belg 52:324–335

    Google Scholar 

  24. Fiocca R, Villani L, Luinetti O, Gianatti A, Perego M, Alvisi C, Turpini F, Solcia E (1992) Helicobacter colonization and histopathological profile of chronic gastritis in patients with or without dyspepsia, mucosal erosion and peptic ulcer: a morphological approach to the study of ulcerogenesis in man. Virchows Arch [A] 420:489–498

    Google Scholar 

  25. Forman D, Sitas F, Newell DG, Stacey AR, Boreham J, et al (1990) Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China. Int J Cancer 46:608–611

    Google Scholar 

  26. Forman D, Newell DG, Fullerton F, Yarnell JWG, Stacey AR, Wald N, Sitas F (1991) Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. B M J 302:1302–1305

    Google Scholar 

  27. Fox JG, Correa P, Taylor NS, Zavala D, Fontham E, Janney F, Rodriquez E, Hunter F, Diavolitsis S (1989) Campylobacter pylori-associated gastritis and immune response in a population at increased risk of gastric carcinoma. Am J Gastroenterol 84:775–781

    Google Scholar 

  28. Genta RM (1992) Counting angels and bacteria: the quest for a unifying theory of ulcerogenesis. Am J Clin Pathol 98:549–551

    Google Scholar 

  29. Genta RM (1994) The pathology of Helicobacter pylori infection. Adv Pathol 7:443–465

    Google Scholar 

  30. Genta RM, Graham DY (1993) Lack of biologically significant correlation between inflammatory responses and density of H. pylori infection. Acta Gastroenterologica Belgica; 56, 111A

  31. Genta RM, Hamner HW (1994) The significance of lymphoid follicles in the diagnosis of gastric biopsies. Arch Pathol Lab Med 118:740–743

    Google Scholar 

  32. Genta RM, Graham DY (1994) Comparison of biopsy sites for the histopathologic diagnosis of Helicobacter pylori: a topographic study of H. pylori density and distribution. Gastrointest Endosc 40:342–345

    Google Scholar 

  33. Genta RM, Lew G, Graham DY (1993) Systematic analysis of changes in gastric mucosa following eradication of Helicobacter pylori. Mod Pathol 6:281–289

    Google Scholar 

  34. Genta RM, Hamner HW, Graham DY (1993) Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution and response to triple therapy. Hum Pathol 24:577–583

    Google Scholar 

  35. Genta RM, Hamner HW, Graham DY (1993) Systematic analysis of the inflammatory responses in patients with different expression of H. pylori infection. Mod Pathol 6:46A

    Google Scholar 

  36. Genta RM, Huberman RM, Graham DY (1993) The microscopic topography of Helicobacter pylori in patients with different expressions of the infection. Acta Gastroenterologica Belgica; 56, 124A

  37. Genta RM, Robason GO, Graham DY (1994) Simultaneous visualization of Helicobacter pylori and gastric morphology: a new stain. Hum Pathol 25:221–226

    Google Scholar 

  38. Go MF, Lew GM, Lichtenberger LM, Genta RM, Graham DY (1993) Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy. Am J Gastroenterol 88:1362–1365

    Google Scholar 

  39. Go MF, Tran L, Chan KY Versalovic J, Koeuth T, Graham DY, Lupski JR (1993) REP-PCR DNA fingerprint analysis reveals gastroduodenal disease-specific clusters of H. pylori strains. Am J Gastroenterol 88:1591A

    Google Scholar 

  40. Goodwin CS, Armstrong JA, Chilvers T, et al (1989) Transfer of Campylobacter pylori and Campylobacter mustelae to Helicobacter gen. nov. as Helicobacter pylori comb. nov. and Helicobacter mustelae comb. nov., respectively. Int J Syst Bacteriol 39:397–405

    Google Scholar 

  41. Graham DY (1989) Campylobacter pylori and peptic ulcer disease. Gastroenterology 96 [Suppl]:615–625

    Google Scholar 

  42. Graham DY (1991) Helicobacter pylori: its epidemiology and its role in duodenal ulcer disease. J Gastroenterol Hepatol 6:97–105

    Google Scholar 

  43. Graham DY (1991) Helicobacter pylori in human populations: the present and predictions of the future based on the epidemiology of polio. Helicobacter pylori 1990. In: Proceedings of the Second International Symposium on Helicobacter pylori. H Menge, M Gregor, GNJ Tytgat, BJ Marshall, CAM McNulty (eds) Springer, Berlin, pp. 97–102

    Google Scholar 

  44. Graham DY (1993) Pathogenic mechanisms leading to Helicobacter pylori-induced inflammation. Eur J Gastroenterol Hepatol 4 [Suppl 2]:S9-S16

    Google Scholar 

  45. Graham DY (1993) Treatment of peptic ulcer caused by Helicobacter pylori. N Engl J Med 328:349–350

    Google Scholar 

  46. Graham DY, Klein PD, Evans DJ, Evans DG, Alpert LC, Opekun AR, Boutton TW (1987) Campylobacter pyloridis detected noninvasively by the 13C-urea breath test. Lancet i:1174–1177

    Google Scholar 

  47. Graham DY, Adam E, Klein PD, Evans DJ Jr, Evans DG, Hazell SL, Alpert LC, Michaletz PA, Yoshimura HH (1989) Epidemiology of Campylobacter pylori. Gastroenterol Clin Biol 13:84B-88B

    Google Scholar 

  48. Graham DY, Malaty HM, Evans DG, Evans DJ Jr, Klein PD, Adam E (1991) Epidemiology of Helicobacter pylori in an asymptomatic population in the United States: effect of age, race and socioeconomic status. Gastroenterology 100:1495–1501

    Google Scholar 

  49. Graham DY, Go MF, Evans DJ Jr (1992) Review article: urease, gastric ammonium/ammonia, and Helicobacter pylori — the past, the present, and recommendations for future research. Aliment Pharmacol Ther 6:659–669

    Google Scholar 

  50. Graham DY, Lew GM, Malaty HM, Evans DG, Evans DJ Jr, Klein PD, Alpert LC, Genta RM (1992) Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology 102:493–496

    Google Scholar 

  51. Haenszel W, Kurihara M, Segi Mitsuo, Lee RKC (1972) Stomach cancer among Japanese in Hawaii. J Natl Cancer Inst 49:969–988

    Google Scholar 

  52. Hansson LE, Engstrand L, Nyrén O, et al (1993) Helicobacter pylori infection: independent risk indicator of gastric carcinoma. Gastroenterology 105:1098–1103

    Google Scholar 

  53. Haot J, Berger F, Andre C, Moulinier B, Mainguet P, Lambert R (1989) Lymphocytic gastritis versus varioliform gastritis. A historical series revisited. J Pathol 158:19–22

    Google Scholar 

  54. Hentsche E, Brandstatter G, Dragosics B, et al (1993) Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer. N Engl J Med 328:308–312

    Google Scholar 

  55. Hessey SJ, Spencer J, Whatt JI, Sohala G, Rathbone BJ, Axons ATR, Dixon MF (1990) Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. Gut 31:603–610

    Google Scholar 

  56. Hui PK, Chan WY, Cheung PS, Chan JKC, Ng CS (1992) Pathologic changes of gastric mucosa colonized by Helicobacter pylori. Hum Pathol 23:548–556

    Google Scholar 

  57. Hussell T, Isaacson PG, Crabtree JE, Spencer J (1993) The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 342:571–574

    Google Scholar 

  58. Isaacson PG, Wright DH (1984) Extranodal malignant lymphoma arising from mucosa-associated lymphoid tissue. Cancer 53:2515–2524

    Google Scholar 

  59. Joossens JV, Geboers J (1984) Diet and environment in the etiology of gastric cancer. In: Frontiers in gastrointestinal cancer. Levin B, Riddell RH (eds) Elsevier, New York, pp. 167–183

    Google Scholar 

  60. Kjoller M, Fischer A, Justesen T (1991) Transport conditions and number of biopsies necessary for culture of Helicobacter pylori. Eur J Clin Microbiol Infect Ds 10:166–167

    Google Scholar 

  61. Malaty HM, Evans DG, Evans DJ Jr, Graham DY (1993) Helicobacter pylori infection in Hispanics: comparison with blacks and whites of similar age and socioeconomic class. Gastroenterology (in press)

  62. Marshall BJ (1983) Unidentified curved bacilli on gastric epithelium in chronic active gastritis. Lancet i:1273–1274

    Google Scholar 

  63. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ (1985) Attempt to fulfil Koch's postulates for pyloric campylobacter. Med J Aust 142:436–439

    Google Scholar 

  64. Morris A, Nicholson G (1987) Ingestion of Campylobacter pyloridis causes gastritis and raises fasting gastric pH. Am J Gastroenterol; 82:192–199

    Google Scholar 

  65. Nomura A, Stemmermann GN, Chyou P-H, Kato I, Perez-Perez GI, Blaser MJ (1991) Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 325:1132–1136

    Google Scholar 

  66. Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J, Chang Y (1991) Helicobacter pylori infection in intestinal-and diffuse-type gastric adenocarcinomas. J Natl Cancer Inst 83:640–643

    Google Scholar 

  67. Price AB (1991) The Sydney System: histological division. J Gastroenterol Hepatol 6:209–222

    Google Scholar 

  68. Price AB, Levi J, Dolby JM, Dunscombe PL, Smith A, Clark J, Stephenson ML (1985) Campylobacter pyloridis in peptic ulcer disease: microbiology, pathology, and scanning electron microscopy. Gut 26:1183–1188

    Google Scholar 

  69. Recavarren-Arce S, Leon-Barua R, Cok J, Berendson R, Gilman RH, Ramirez-Ramos A, Rodriquez C, Spira WM (1991) Helicobacter pylori and progressive gastric pathology that predisposes to gastric cancer. Scand J Gastroenterol 26:51–57

    Google Scholar 

  70. Rosh JR, Kurfist LA, Benkov KJ, Toor AH, Bottone EJ, Le-Leiko NS (1992) Helicobacter pylori and gastric lymphonodular hyperplasis in children. Am J Gastroenterol 87:135–139

    Google Scholar 

  71. Scott N, Lansdown M, Diament R, Rathbone B, Murday V, Wyatt JI, McMahon M, Dixon MF, Quirke P (1990) Helicobacter gastritis and intestinal metaplasia in a gastric cancer family. Lancet i:728

    Google Scholar 

  72. Sipponen P (1992) Natural history of gastritis and its relationship to peptic ulcer disease. Digestion 51 [suppl 1]:70–75

    Google Scholar 

  73. Sipponen P, Hyvarinen H (1993) Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer. Scand J Gastroenterol [Suppl] 196:3–6

    Google Scholar 

  74. Siurala M, Sipponen P, Kekki M (1985) Chronic gastritis: dynamic and clinical aspects. Scand J Gastroenterol 20 [suppl 109]:69–76

    Google Scholar 

  75. Smoot DT, Rosenthal LE, Mobley HL, Iseri O, Zhu SM, Resau JH (1990) Development of a human stomach explant organ culture system to study the pathogenesis of Helicobacter pylori. Digestion 46:46–54

    Google Scholar 

  76. Solcia E, Villani L, Luinetti O, Fiocca R (1993) Proton pump inhibitors, enterochromaffin-like cell growth and Helicobacter pylori gastritis. Aliment Pharmacol Ther 7P (Suppl 1):25–28

    Google Scholar 

  77. Stolte M, Eidt S (1989) Lymphoid follicles in antral mucosa: immune response to Campylobacter pylori? J Clin Pathol 42:1269–1271

    Google Scholar 

  78. Warren JR (1983) Unidentified curved bacilli on gastric epithelium in chronic active gastritis. Lancet i:1273–1274

    Google Scholar 

  79. Wotherspoon A, Oritz-Hidalgo C, Diss T, Falzon MR, Isaacson PG (1991) Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 338:1175–1176

    Google Scholar 

  80. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG (1993) Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–578

    Google Scholar 

  81. Wyatt JI, Rathbone BJ (1988) Immune response of the gastric mucosa to Campylobacter pylori. Scand J Gastroenterol 23 [suppl 142]:44–49

    Google Scholar 

  82. Wyatt JI, Rathbone BJ, Sobala GM, Shallcross T, Heatley RV, Axon AT, Dixon MF (1990) Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation. J Clin Pathol 43:981–986

    Google Scholar 

  83. Yoshimura HH, Evans DG, Graham DY (1993) DNA-DNA hybridization demonstrates apparent genetic differences between Helicobacter pylori from patients with duodenal ulcer and asymptomatic gastritis. Dig Dis Sci 38:1128–1131

    Google Scholar 

  84. Zuckerberg LR, Ferry JA, Southern JF, Harris NL (1990) Lymphoid infiltrates of the stomach. Evaluation of histologic criteria for the diagnosis of low-grade gastric lymphoma on endoscopic biopsy specimens. Am J Surg Pathol 14:1087–1099

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pathology, Medicine, Microbiology and Immunology, Veterans Affairs Medical Center, and Baylor College of Medicine, TX 77030, Houston, Texas, USA

    R. M. Genta

  2. Departments of Medicine and Molecular Virology, Veterans Affairs Medical Center and Baylor College of Medicine, TX 77030, Houston, Texas, USA

    D. Y. Graham

Authors
  1. R. M. Genta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Y. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Genta, R.M., Graham, D.Y. Helicobacter pylori: the new bug on the (paraffin) block. Vichows Archiv A Pathol Anat 425, 339–347 (1994). https://doi.org/10.1007/BF00189571

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00189571

Keywords

Search

Navigation