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In the Caucasian adult population of western countries, the decreasing prevalence of ulcer disease in the duodenum (first part) and its increasing prevalence in the esophagus (lower one-third), has been observed during the last four decades. [1,2,3,4]The relationship of Helicobacter pylori (H. pylori) prevalence in the population (in relation to time), to this paradigm shift, has been discussed here.
Duodenal ulcer (DU): origin, peak and decline
Till 1823, DU did not have a formal place in medical text books.[5] In the latter half of the 19th century, sporadic cases of DU on autopsy or the operating table (presenting with hematemesis or perforation), were reported.[6,7] In the beginning of the 20th century, a single study reported 1000 cases of peptic ulcer (529 DU)[8] and a book for the surgical treatment of DU was published.[9] The advent of barium meal x-rays (1914)[10] and fibre-optic endoscopy (1958),[11] for the precise diagnosis of DU, enabled proper documentation of the “epidemic” of DU in the 20th century.[12] In the adult Caucasian population of North America and Europe, the decreasing prevalence of DU has been noted during the last four decades (1961 – 2000).[1,2,3,13]
Aetiology of duodenal ulcer
In the beginning of the 20th century, DU was considered multifactorial - stress (hurry-worry), spices (curry), and smoking were convicted as major causes.[12,14,15] “No acid, no ulcer” (Schwarz 1910)[16] was recognised early in the development of this entity.[16] With the development of the augmented histamine test (1953),[17] for the accurate measurement of maximal acid output (MAO), the size of the parietal cell mass (PCM) was estimated.[18] A greater PCM, with higher MAO was blamed in about 50% of DU patients.[19,20] Accelerated healing of DU within a few weeks, with H2-receptor antagonists (1972)[21] or proton pump inhibitors (PPI) (1983)[22] compared to placebo, further emphasised the importance of acidpepsin in the aetiology of DU. In male DU patients from a developing country (like India), the values of MAO are significantly lower than those of patients from developed countries,[17,20] as H. pylori is present in the gastric body mucosa for several decades (prior to DU) in the former, compared to only a few years in the latter.[23]
A major breakthrough in our understanding of the etiology of DU, was the Nobel-prize winning discovery of H. pylori in the antral mucosal biopsy of humans, on upper gastroduodenal endoscopy (1983).[24] Antral gastritis (predominant) due to H.pylori, is the most important aetiological factor for DU: (i) as about 90% of DU patients had H. pylori in the antral mucosal biopsy,[25,26] (ii) following the eradication of H. pylori from the gastric mucosa, annual DU recurrence reduced to about 10% compared to 90% following healing with acid suppression treatment,[27,28] (iii) failure to eradicate H. pylori resulted in a higher recurrence rate of DU[28] (iv) treatment with antibiotics for eradication of H. pylori accelerates DU healing, compared to H2-receptor antagonists or proton pump inhibitors alone.[29] Antral mucosal damage decreases somatostatin secretion from the delta cells, which is an inhibitor of G cell secreting gastrin, resulting in hypergastrinaemia and an increased PCM, as gastrin is a trophic hormone.[30]
The major mode of H. pylori transmission is the faeco-oral route.[23] In developing countries, exposure to H. pylori occurs frequently and early in life (with poor sanitation) whilst it occurs occasionally and later in life in developed countries (with good sanitation).[23,24,25,26,27,28,29,30,31] Birth-cohort (individuals born during the same period) risks emphasised that babies born between 1870 and1900 had the highest risk of DU and that the cohort phenomenon began at an age below 5 years.[32] In the latter half of the 20th century (1961-2000), with continuous improvement in sanitation, the exposure to H.pylori is infrequent.[13,33,34,35,36] The annual exposure to H. pylori in adult individuals is estimated to be 0.5% in developed countries compared to 10% indeveloping countries.[37] The rate of acquisition was four fold greater in African Americans than in Caucasians.[31] H. pylori
infection causes of DU in only about 62% of patients at present,[13,36] in contrast to the 95% of patients in developed countries noted earlier (1985-1990).[27,28]
Esophageal ulcer: Origin, increase and peak
An ulcer in the lower one-third of the esophageal mucosa, due to gastroesophageal reflux of acid-pepsin, was observed in the early 20th century.[38,39,40,41,42] During the last four decades of the 20th century, a gradual increase in gastroesophageal reflux disease (GERD) - erosions, ulcer, stricture and its complications (Barrett’s esophagus and esophageal adenocarcinoma) has been noted in the Caucasian adult population of developed countries.[43,44] Amongst Asians, the incidence of esophageal ulcer and its complications is low, as the values of MAO are low, due to H. pylori exposure early in life.[20,45,46,47,48]er, even in the few affluent Asian countries (Japan, Singapore, Malaysia), such an increase in esophageal ulcers with endoscopic esophagitis was reported, in the beginning of the 21st century.[45,46,49,50,51]
Aetiology of esophageal ulcer
Esophageal ulcer with esophagitis was earlier linked to hiatus hernia but it was soon realised that it occurs even in the absence of the same.[52,53] Esophageal damage in the presence of hiatus hernia is usually severe and refractory to medical treatment.
The relationship of H. pylori infection of gastric mucosa and esophageal ulceration is complex and controversial. .
Absence of H. pylori in the gastric mucosa and esophageal ulcer:
(i) Lack of Exposure
In serum, H. pylori antibody (HPA) prevalence was 50%, at age 5 years in developing countries and at age 50 years in developed countries.[54,55] With continuous improvement of sanitation in developed countries during the last four decades, the prevalence of H.pylori in the gastric mucosa is decreasing and the lifetime risk of exposure is only about 10%.[37] The decreasing prevalence of duodenal ulcer and gastric carcinoma and the increasing prevalence of endoscopic esophagitis and its complications, also indicate the decreasing exposure to H. pylori.[34,35,56,57,58]
In developed countries, the increased prevalence of esophageal ulcer is at present restricted to the Caucasian adult population,[59] as the prevalence of H. pylori antibody (IgG) in the serum is low in whites (26.2%) but high in non- Caucasians (non-Hispanic African Americans: 52.7%, Mexican Americans 61.6%).]59] Furthermore, during a 12-year follow up, the disappearance of H pylori was 50% in Caucasians and only 4% in African Americans .[31]
(ii) Following eradication therapy
Absence of H. pylori in the gastric mucosa may also result following successful eradication therapy. Eradication of H. pylori from the gastric mucosa resulted in a higher prevalenceof endoscopic esophagitis compared to control subjects.[60] During a 3-year follow-up, of the 286 patients who received H. pylori eradication therapy or no therapy, the prevalence of reflux esophagitis was 18% and 0.3% respectively.[60] Similar observations of endoscopic esophagitis have been made in patients of DU in whom H. pylori eradication was achieved.[61]
Absence of H. pylori in the gastric mucosa (either from lack of exposure or eradication therapy) results in increased acid in the stomach; H. pylori causes diminished acid output initially by secreting a protein inhibitor, and later through chronic corpus gastritis.[50,62,63,64,65]ce of corpus gastritis results in higher volume and concentration of gastric juice in the gastric lumen, causing greater esophageal damage resulting in esophageal ulcer.[32] The prevalence of H. pylori was lower in short segment Barrett’s esophagus (18.7%) and zero in long segment Barrett’s oesophagus.[50] These observations suggest that the absence of H. pylori corpus gastritis may increase the incidence of esophageal ulcer and its complications.[60,61]
Presence of H. pylori and/or corpus gastritis and esophageal ulcer
(i) Presence of H. pylori
In patients with esophagitis and control subjects, the presence of H.pylori infection in the gastric mucosa was not different, indicating H.pylori (alone) in the gastric mucosa does not affect the incidence of esophageal ulcer.[65] However a negative association between H.pylori prevalence and esophagitis was observed in subjects over 60 years.[66] In contrast, when H. pylori infection was reported on histology, rapid urease test, H. pylori antibody (IgG) in serum, the prevalence of H. pylori was significantly lower in GERD patients (30%) compared to control subjects (71.2%) indicating that the presence pf H.pylori chronic gastritis is important in reducing the incidence of esophageal ulcer.[50,65,67]
(ii) Evidence of corpus gastritis
The prevalence of chronic corpus gastritis and its severity was lower in GERD patients than in control subjects.[65] The corpus gastritis was associated with a 54% reduced risk of endoscopic oesophagitis.[65] Furthermore, the prevalence of CagA positivity in the serum was 42.3% in control subjects, 38.9% in GERD patients, 13.3% in Barrett’s esophagus and 0% in esophageal adenocarcinoma indicating that the presence of the pathogenic H. pylori in the gastric mucosa causing corpus gastritis, protects against the development of GERD complications.[68,69]
Conclusions
Antral gastritis (predominant) due to H. pylori infection causes hypergastrinemia and greater parietal cell mass (with higher values of acid output) and is the cause of DU – a disease of the 20th century. In contrast, the absence of H. pylori in the gastric mucosa with improved sanitation, results in increased acid output in the stomach (in the absence of corpus gastritis), precipitating peptic esophageal ulcer - a disease of the 21st century. This paradigm shift of ulceration from the duodenum to the esophagus, observed recently in developed countries, results from the differences of H. pylori prevalence in the gastric mucosa of the population, in relation to time (with improvedsanitation). Such a shift is likely to extend to developing countries in the 21st century, with assumed improvement in sanitation and hygiene.
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