History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer

Abstract

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.

Keywords: Antiquity; Atrophic gastritis; Duodenal ulcer; Epidemiology; Gastric cancer; Gastric ulcer; Gastritis; Helicobacter pylori; Medical history; Ulcer surgery.

Figure 1

Admissions for gastric ulcer and duodenal ulcer in 12 London hospitals associated with a medical school presented as mean rates per 10000 admissions in each of five year periods plotted as the moving average of three consecutive time periods. Adapted from[1] with permission. GU: Gastric ulcer; DU: Duodenal ulcer.

Figure 2

Examples of the relation of the site of a peptic ulcer and its relation to the extent and severity of corpus gastritis/gastric atrophy. The number of cases sampled for each ulcer site are shown. The control group consisted of 158 individuals without a peptic ulcer. Adapted from[13] with permission. N: Normal; SG: Superficial gastritis; A: Atrophy.

Figure 3

Prevalence of atrophic gastritis/atrophy in the early twentieth century. Example of studies in the United States and Europe showing the high prevalence of atrophic gastritis/atrophy as evidenced by the age-related prevalence of achlorhydria (from[17], with permission).

Figure 4

Comparison of the prevalence of intestinal metaplasia on gastric antral biopsies in two areas of Japan and in one area in Minnesota, United States. Adapted from[47] with permission.

Figure 5

Autopsy data from Europe showing the proportion of adults (i.e., 10 or older) from large autopsy studies in which the presence of an ulcer or ulcer scar was specifically examined showing the increase in the incidence of duodenal ulcer in the latter part of the 19^th and early 20^th century. Data from refererence[48].

Figure 6

Health, height, and welfare: Britain between 1700 and 1980 based on the human development index which is a composite statistic of life expectancy, education, and income indices used to rank human development. A score below 0.5 signifies low development and 0.8 or greater, high development. Data from[59].

Figure 7

Changes in the incidence of gastric cancer and Helicobacter pylori infection among Japanese men age 65-69 during the latter half of the 20^th century (Constance Wang and David Y Graham, unpublished observations). From reference[86], with permission. Hp: Helicobacter pylori.

Figure 8

In this 65 years old cohort the change in gastric incidence occurred without a change in the prevalence of Helicobacter pylori. A: Model showing that gastric ulcer and gastric cancer were present and relatively common until the early 20^th century when changes in the pattern of gastritis and also the prevalence of Helicobacter pylori (H. pylori) infection separately led to a reduction in incidence. In contrast, the change in the pattern of gastritis and new diagnostic modalities led to ascendance of duodenal ulcer until the rise was overtaken by the fall in H. pylori prevalence (the scale is arbitrary); B: The same results shown in relation to the underlying pathology, atrophic pangastritis which manifests clinically as gastric ulcer or cancer and non-atrophic gastritis which manifests as duodenal ulcer.