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Helicobacter pylori, a carcinogen of gastric cancer

Author: Ngoc Tran, M.D., M.S.

Last revised: 25 January 2022

Some information below is from the Nobel Prize lecture given by J. Robin Warren in 2005. (The Nobel Prize: J. Robin Warren - Nobel Lecture [Accessed 25 January 2022])


First discovery of Helicobacter pylori (H. pylori) in gastric and pyloric ulcers, precancer lesions in the stomach
  • Before the era of flexible endoscope (i.e., pre-1970s), there was no good quality stomach biopsy; thus, description of gastric pathological features was limited.
  • Robin Warren, an Australian pathologist, was interested in gastric pathology and began his study of Whitehead's description and classification of active gastritis. (J Clin Pathol 1972;25:1)
  • In 1979 flexible endoscope was available at his institution, thus Warren was able to examine good quality gastric biopsies from patients with gastritis.
  • Warren observed histological changes described by Whitehead and found an unusual blue line on the surface of the inflamed gastric tissue.
  • On high magnification of this surface, he observed numerous small, curved bacilli. (Lancet 1983;1:1273)
  • At that time, the Warthin-Starry silver stain was successfully utilized to detect spirochetes but there were not many other stains available for detecting bacteria in tissue; Warren experimented with the gastritis tissue and this silver stain and found small, curved, spiral bacilli attached to the mucosal surface.
  • To learn more about these bacteria he then examined the biopsies under electron microscopy and found that the bacteria resembled Campylobacter.
  • Although he was unsure about the significance, from then on he always documented this finding in his pathology reports.
  • In approximately half of the gastric biopsies, he found an association between the presence of this bacterium and histological gastritis in a severe and active form.
Points of disbelief from specialists
  • It was argued that these bacteria were caused by gastritis and not vice versa.
  • "If it is true, why were they not recognized before?"
  • Scientists of the time believed that the stomach was sterile because its acid would likely kill all the gastric bacteria.
  • These disbeliefs came from the lack of a clinicohistopathological correlation study.
A clinical trial study establishing the causal relationship between H. pylori and duodenal ulcer
  • The clinical importance of this association was revealed when a gastroenterologist named Barry Marshall joined Warren to conduct a blinded clinical trial; in order to test their hypothesis they obtained gastric biopsies (including normal gastric antrum tissue) from a hundred outpatients to determine if there was a presence of the bacteria in the normal tissue.
  • In addition to histologic examination, the tissues were cultured using Campylobacter techniques.
  • The trial resulted in unexpected findings (Lancet 1984;1:1311):
    • Bad breath and burping were related only to gastritis or bacteria.
    • The bacterium was found to present in 100% of duodenal ulcer and 77% in gastric ulcer. This means that duodenal ulcer was strongly related to this infection.
    • A new species was identified - Helicobacter pylori.
  • After the trial, these findings were published. (Lancet 1984;1:1311)
Inventing assays for detecting H. pylori and the first introduction of triple therapy
  • Marshall did additional work such as inventing CLOtest, serology and breath test, and triple therapy for duodenal ulcers in 1984.
  • Marshall and Arthur Morris used Koch's postulates to prove the strong causal relationship between H. pylori and duodenal ulcer. (Med J Aust 1985;142:436)
More studies exploring and supporting the causal relationship between H. pylori and gastric cancer
Effect of H. pylori eradication on gastric cancer treatment and prevention
  • H. pylori eradication can cure 60 - 80% of low stage MALT lymphoma that does not contain a t(11,18) translocation. (Gut 2017;66:6, Gut 2012;61:507)
  • Early gastric cancers that are limited to mucosa and submucosa can be prevented from metachronous gastric cancers by H. pylori eradication. (N Engl J Med 2018;378:1085)
  • H. pylori eradication therapy reduced 9.2% of gastric cancers in Japan, as demonstrated over 4 years of national insurance coverage for this therapy. (Helicobacter 2017;22:e12415)
Microscopic (histologic) images

Images hosted on other servers:

H. pylori in a gastric biopsy (H&E stain)

Warthin-Starry stain highlights H. pylori in a gastric biopsy

Videos

Helicobacter: the ease and difficulty of a new discovery

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