We reviewed international publications printed in English before April, 2002. The pathophysiology of peptic ulcer is based on research work published in major scientific journals such as Cell, Nature, Science, Gastroenterology, and Proc Natl Acad Sci USA. The efficacy of eradication therapies is based on results of large-scale randomised trials. The recommended treatments for H pylori infection is based on the Maastricht-2 2000 Consensus Report. The management of NSAID-associated ulcers is
SeminarPeptic-ulcer disease
Introduction
For more than a century, peptic ulcer disease has been a major cause of morbidity and mortality. The pathophysiology of peptic ulcer disease has centred on an imbalance between aggressive and protective factors in the stomach. 20 years have elapsed since Marshall and Warren's discovery of the link between a bacterium called at that time Campylobacter pylori and peptic ulcer disease.1 This finding was initially received with scepticism and disbelief. Now there is much evidence to support the idea that Helicobacter pylori infection is a prerequisite for duodenal and gastric ulcers.2, 3 Nevertheless, much about the relation between H pylori and peptic ulcer remains to be learned. The rapid emergence of antimicrobial resistance has important implications for management of these ulcers.
Although hospital admissions for uncomplicated peptic ulcers in developed countries had begun to decrease by the 1950s,4, 5 there was a striking rise in admissions for ulcer haemorrhage and perforation among elderly people.4, 5, 6 This increase has been attributed to the increased use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin.4, 6 The widespread use of NSAIDs has led to an epidemic of ulcer complications. In the USA, prescribed NSAIDs account for about 25% of all reported adverse drug reactions. An estimated 16 500 patients with arthritis die from the gastrointestinal toxicity of NSAIDs every year.7 A better understanding of the mechanisms by which NSAIDs damage the stomach has led to the development of potent anti-ulcer agents and, recently, highly selective cyclo-oxygenase (COX)-2 inhibitors. Although there is evidence from large-scale clinical trials that these agents reduce the gastrointestinal toxicity of NSAIDs, whether these findings will translate into clinical benefits is unclear.
Researchers have previously identified several risk factors for the development of NSAID-associated ulcers.8 However, whether H pylori infection modifies the risk of ulcer in patients taking NSAIDs has generated many conflicting data.9 With the reduction in frequency of uncomplicated peptic ulcers, the proportion of ulcers not related to H pylori or NSAIDs has increased. Recent data from the USA suggest that the association between H pylori and ulcer disease is not as strong as previously reported.10 The pendulum seems to swing from enthusiasm for the idea that peptic-ulcer disease is an infectious disease, to a more cautious view that H pylori has a causative role in peptic-ulcer disease. Ulcers not associated with H pylori or NSAIDs–ie, non-NSAID non-H pylori ulcers–have attracted considerable attention.
Section snippets
Duodenal ulcers
Although there is much evidence to implicate H pylori in the development of duodenal ulcer, the underlying mechanisms remain unclear. The fact that duodenal ulcer can be effectively treated by acid suppression strongly suggests that duodenal ulcer is largely a disease of acid hypersecretion. However, the general view is that acid hypersecretion is only part of the equation in pathogenesis of duodenal ulcer; it is the imbalance between duodenal acid load and the buffering capacity of the
Gastric ulcers
Long before the discovery of H pylori, patterns of gastritis associated with duodenal ulcers were known to be different from those associated with gastric ulcers.33 Duodenal ulcer is associated with an antrum-predominant gastritis, whereas gastric ulcer is associated with a diffuse or a corpus-predominant gastritis.34 This last gastric phenotype is linked with low acid output, gastric atrophy, and adenocarcinoma. This pattern is consistent with the negative association between duodenal ulcer
NSAID-induced gastric injury
For the past three decades, investigators have been working on how NSAIDs damage the gastrointestinal tract. Some of these mechanisms have helped our understanding of the development of NSAIDs with lower ulcerogenic risk or prophylactic agents that reduce the toxicity of existing NSAIDs.
Current issues in prevention of NSAID ulcers
Various prophylactic strategies to reduce the gastric toxicity of NSAIDs have been investigated. These strategies include concurrent treatment with histamine-2 receptor antagonists (H2RA), misoprostol, PPIs, and recently, substitution of conventional NSAIDs by selective COX-2 inhibitors. Although there are data showing that these agents reduce gastroduodenal ulceration, whether these findings would translate into clinical benefits deserves careful consideration (panel 2).
Non-NSAID, non-H pylori ulcers
The decline in prevalence of H pylori infection in developed countries has changed the pattern of peptic ulcer disease. In one retrospective study from the USA in ulcer patients who did not use NSAIDs, H pylori-negative ulcers were found in 47% of white patients and 22% of non-white patients.102 In a meta-analysis of duodenal ulcer trials in the USA, 20% of patients had ulcer recurrence within 6 months after the eradication of H pylori.10 This finding contrasts with results from Asia where the
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References (105)
- et al.
Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration
Lancet
(1984) Epidemiology of peptic ulcer disease
Clin Gastroenterol
(1984)Helicobacter pylori and non-steroidal anti-inflammatory drugs
Gastroenterol Clin North Am
(2001)- et al.
Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials
Am J Gastroenterol
(1998) - et al.
Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease
Gastroenterology
(1995) - et al.
Effect of Helicobacter pylori on gastric somatostatin in duodenal ulcer disease
Lancet
(1992) - et al.
A mechanism by which Helicobacter pylori infection of the antrum contributes to the development of duodenal ulcer
Gastroenterology
(1996) - et al.
Campylobacter pylori and duodenal ulcers: the gastrin link
Lancet
(1989) - et al.
Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells
Gastroenterology
(1997) - et al.
Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells
Gastroenterology
(1997)
24-hour gastric pH and extent of duodenal gastric metaplasia in Helicobacter pylori-positive patients
Gastroenterology
Duodenal bicarbonate secretion: eradication of Helicobacter pylori and duodenal structure and function in humans
Gastroenterology
Water extract of Helicobacter pylori inhibits duodenal mucosal alkaline secretion in anesthetized rats
Gastroenterology
Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa
Gastroenterology
Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori
Gastroenterology
Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model
Gastroenterology
The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies
Gastroenterology
Randomized study of two “rescue” therapies for Helicobacter pylori-infected patients after failure of standard triple therapies
Am J Gastroenterol
Gastric mucosal hemorrhage in dogs. Effects of acid, aspirin, and alcohol
Gastroenterology
Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product
Lancet
Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat
Gastroenterology
Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years
Gastroenterology
Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration
Cell
A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats
Gastroenterology
Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat
Gastroenterology
The mucoid cap over superficial gastric damage in the rat. A high-pH microenvironment dissipated by nonsteroidal antiinflammatory drugs and endothelin
Gastroenterology
Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage
Gastroenterology
Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration
Gastroenterology
The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes
J Biol Chem
NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2
Gastroenterology
Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice
Gastroenterology
Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer
Gastroenterology
Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study
Lancet
Infection of Helicobacter pylori in gastric adaptation to continued administration of aspirin in humans
Gastroenterology
Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis
Lancet
Randomised trial of eradication of Helicobacter pylori before starting non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers
Lancet
Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial
Lancet
NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease
JAMA
Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter pylori Study Group
Gut
Time trends of physician visits and treatment patterns of peptic ulcer disease in the United States
Arch Intern Med
Recent trends in admissions and mortality due to peptic ulcer in England: increasing frequency of haemorrhage among older subjects
Gut
Epidemiology of NSAID-induced GI complications
J Rheumatol
Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs
N Engl J Med
Perturbations in gastric physiology in Helicobacter pylori duodenal ulcer: are they all epiphenomena?
Helicobacter
Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis
J Clin Pathol
Impaired proximal duodenal mucosal bicarbonate secretion in patients with duodenal ulcer
N Engl J Med
Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer
Proc Natl Acad Sci USA
Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors
Proc Natl Acad Sci USA
Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori.
Proc Natl Acad Sci USA
Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion
Science
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