Critical issues in the pathophysiology and management of peptic ulcer disease.
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OBJECTIVE: To discuss some of the critical issues in the pathophysiology and management of peptic ulcer disease. OPINION: Peptic ulcer disease has multiple causes, although gastric acid has traditionally been considered the primary aggressive factor. Helicobacter pylori infection is established as a major causative factor, but some aspects of the mechanisms by which H. pylori causes peptic ulceration remain unclear. Treatment with proton pump inhibitors (PPIs) is the most effective means of healing peptic ulcers. In addition to healing a higher proportion of ulcers than H2-receptor antagonists, PPIs provide faster healing and relief of symptoms. The ability of PPIs to produce effective and sustained inhibition of gastric acid secretion suggests that they may also become the treatment of choice for gastric ulcers caused by non-steroidal anti-inflammatory drugs. However, eradication of H. pylori infection is more effective than maintenance therapy with antisecretory agents in reducing the rate of recurrence of peptic ulcers initially healed using antisecretory therapy. H. pylori eradication is therefore the optimal, and almost certainly the most cost-effective, approach to the long-term management of patients with peptic ulcer disease. Despite the fact that 90-95% of patients with demonstrable duodenal ulceration are probably infected with H. pylori, it is recommended that, in routine clinical practice, infection is diagnosed before eradication therapy is instituted. H. pylori testing 4-6 weeks after the completion of eradication therapy is also recommended to check that the infection has been successfully cured. For routine clinical practice, the highly sensitive and specific rapid urease test is probably the most useful diagnostic approach. The most appropriate H. pylori eradication regimen remains to be defined. However, 1-2 weeks of treatment with a combination of a PPI and two antimicrobial agents achieves eradication rates in excess of 90%, which are similar to those attained using standard triple therapy, but with the advantage of better patient compliance and greater tolerability. Preliminary evidence also suggests that H. pylori eradication prevents the recurrence of peptic ulcer bleeding, although further studies are required. CONCLUSION: H. pylori eradication by 1-2 weeks' treatment with a combination of a PPI and two antimicrobial agents appears to be the optimal (and probably the most cost-effective) approach to the long-term management of patients with peptic ulcer disease, and represents a major advance in the management of such patients.