Challenges in the Management of Peptic Ulcer Disease

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1).Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel's diverticulum.1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3% 1 ; both rates are declining.3 The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%. 4The lifetime prevalence of peptic ulcers has been decreasing in highincome countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.1,3 Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, or both.A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers.H. pylori-specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury.The mucosal inflammatory response is at least partially determined by polymorphisms in the host's cytokine genes.1,4 NSAIDs inhibit the production of cyclooxygenase-1derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.1,5 Less common causes of peptic ulcers include gastrinoma,