The 2 major etiological factors for PUD are Helicobacter pylori infection and the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs). Currently, 70% of all gastric ulcers occurring in the United States can be attributed to H pylori infection. In addition to an increase in acid secretion, H pylori also predisposes patients to PUD by disrupting mucosal integrity. The bacterium's spiral shape and flagella facilitate its penetration into the mucous layer and its attachment to the epithelial layer. Subsequently, it releases phospholipase and proteases, which cause further mucosal damage. A cytotoxin-associated gene (cag A) has been isolated in approximately 65% of the bacteria. The products of this gene are associated with more severe gastritis, gastric ulcer, gastric cancer, and lymphoma.

Cigarette smoking can affect gastric mucosal defense adversely. Cigarette smoking is believed to play a facultative role in H pylori infection, that is, people who smoke tend to develop frequent and recurrent ulcers and their ulcers are more resistant to therapy. No evidence indicates that dietary habits or alcohol consumption predisposes individuals to gastric ulcer.

NSAID-induced ulcers account for approximately 26% of gastric ulcers, and they are believed to be secondary to a decrease in prostaglandin production resulting from the inhibition of cyclooxygenase. The topical effects of NSAIDs are superficial gastric erosions and petechial lesions. However, the risk of gastroduodenal ulcer is not diminished with parental or rectal use of NSAIDs indicating injury occurring from the systemic effect of NSAIDs on the gastrointestinal mucosa. The greatest risk of developing an ulcer occurs during the first 3 months of NSAID use; thereafter, the risk decreases but continues to be present. Whether concurrent H pylori infection and NSAID use are synergistic in producing gastric ulcers remains unclear. Recent accumulating evidence indicates that patients with H pylori infection may be twice as likely to get a bleeding peptic ulcer.

Selective COX-2 (cyclooxygenase) inhibitors, like celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra), have been shown to cause gastroduodenal ulcers at a rate comparable to placebo (4%). In the Celecoxib Long-term Arthritis Safety Study (CLASS), they found a significantly lower incidence of symptomatic ulcers in patients taking celecoxib for the initial 6 months as compared to patients taking ibuprofen or diclofenac. Currently, the only US Food and Drug Administration (FDA)- approved COX-2 inhibitor available is celecoxib, as rofecoxib and valdecoxib were withdrawn from the market by the FDA because of increased cardiovascular risk.

Other medications that predispose patients to gastroduodenal ulcers include potassium chloride, chemotherapeutic agents, and bisphosphonates. A rare cause of PUD is Zollinger-Ellison syndrome (i.e.: gastrinoma). The hallmark of Zollinger-Ellison syndrome is the profound hypersecretion of gastric acid. Significant disruption of the mucosal integrity often results in multiple duodenal and gastric ulcers.

The mortality rate is approximately 1 case per 100,000 persons, based on the 1979 estimates from the United States. The mortality rate is higher in patients older than 75 years, which can be attributable to a high rate of NSAID use in this age group. The other high-risk groups include people with chronic renal insufficiency and diabetes. Gastric ulcers are also associated with considerable morbidity related to chronic epigastric pain, nausea, vomiting, and anemia.

• Gastric and duodenal ulcers usually cannot be differentiated based on history alone.
• Classic gastric ulcer pain is described as pain occurring shortly after meals, for which antacids provide minimal relief.
• The pain from gastric ulcer is typically located in the epigastrium; however, it can also be perceived in the right upper quadrant and elsewhere.
• Duodenal ulcer pain often occurs hours after meals and at night. Pain is characteristically relieved with food or antacids.
• Pain with radiation to the back is suggestive of a posterior penetrating gastric ulcer complicated by pancreatitis.
• Patients with bleeding gastric ulcers may give a history of hematemesis, melena, or episodes of presyncope.

• Epigastric tenderness may or may not be present.
• Right upper quadrant tenderness may suggest a biliary etiology or, less frequently, PUD.
• In the presence of gastric outlet obstruction, abdominal distension and succussion splash may be found.
• A palpable mass should raise the suggestion of a gastric malignancy.
• Involuntary guarding is indicative of peritonitis secondary to gastric perforation.
• Patients should be checked for melena, which is indicative of bleeding from a gastroduodenal ulcer.

Other tests include H pylori testing: A strong relationship exists between PUD and H pylori infection. Therefore, to prevent recurrence of ulcer disease, diagnosing and eradicating H pylori infection is important. H pylori infection can be diagnosed using various invasive or noninvasive methods.

In patients with bleeding PUD, volume resuscitation with IV fluid and blood products is the most important initial therapy. An intravenous proton pump inhibitor (PPI) is started. This is followed by checking for acute anemia, thrombocytopenia, or coagulopathy, which needs correction with vitamin K or fresh frozen plasma.

Therapy should be directed toward histamine release, i.e.: H2 blockers, such as cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid). These agents selectively block the H2 receptors in the parietal cells. All H2 blockers are comparable in efficacy and, when used in twice- daily doses for a period of 8 weeks, have a healing rate of higher than 70%. PPIs are drugs that covalently bind and irreversibly inhibit the H+/K+ adenosine triphosphatase (ATPase) pump, effectively inhibiting acid release. Omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium) given in daily or twice-daily doses for 4 weeks heal 80-100% of gastric ulcers if H pylori infection is not present or has been eradicated.

All PPIs seem to have equal efficacy. The PPI should preferentially be taken on an empty stomach to allow maximum inhibition of H+/K+ pumps. Prilosec binds irreversibly with the H+/K+ pumps and suppresses acid secretion. This inhibition is at its maximum in 24-48 hours, and when Prilosec is stopped, the secretory activity gradually returns to normal in the next 2-3 days.

Mucosal protectants, such as bismuth and sucralfate, can also be effective in healing gastric ulcers; however, they are not as effective as H2 blockers. Patients taking NSAIDs should discontinue them if possible. If discontinuing NSAIDs is not possible, omeprazole at 40 mg/d should be given concurrently. However, only misoprostol (Cytotec) has been shown to be cytoprotective when taken with NSAIDs. The use of misoprostol is limited because of its adverse effects, including diarrhea and abdominal pain observed in 14-40% of patients, and because it is administered in doses 4 times a day.

H pylori eradication: Multiple regimens have been evaluated for the eradication of H pylori infection; however, triple therapy consistently has been shown to eradicate the organism more than 90% of the time. The 5 different regimens approved by American College of Gastroenterology are as follows (all 5 regimens are given for a total of 2 wk): Bismuth, metronidazole, and tetracycline qid with H2 blockers bid; Bismuth, metronidazole, and tetracycline bid with a PPI (Helidac); Prevacid, amoxicillin, and clarithromycin bid (PrevPac); Prilosec, metronidazole, and clarithromycin bid; Ranitidine, bismuth, and clarithromycin with amoxicillin, metronidazole, or tetracycline bid.

Upper GI bleeding secondary to a bleeding peptic ulcer is a common medical condition. Endoscopic evaluation of the bleeding ulcer can decrease the duration of the hospital stay by identifying patients at low risk for rebleeding. Moreover, endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need for surgery. Patients can be stratified as high or low risk for rebleeding depending on the presence or absence of stigmata during their initial endoscopic examination. High-risk stigmata are active hemorrhage (90% risk of rebleeding), a visible vessel (50% risk of rebleeding), or a fresh overlying clot (30% risk of rebleeding). In the absence of these stigmata, patients can be discharged home on medical therapy within 48 hours. Ulcers with stigmata (i.e.: visible vessel, oozing, overlying blood clot) require endotherapy, while ulcers with a clean base crater need not be treated endoscopically.

Several modalities of endotherapy are available, such as injection therapy, coagulation therapy, hemostatic clips, argon plasma coagulator, and combination therapy. Injection therapy is performed with epinephrine in a 1:10,000 dilution or with absolute alcohol. Thermal endotherapy is performed with a heater probe, bipolar circumactive probe, or gold probe. Pressure is applied to cause coagulation of the underlying artery (coaptive coagulation). Combination therapy with epinephrine injection followed by thermal coagulation appears to be more effective than monotherapy for ulcers with a visible vessel, active hemorrhage, or adherent clot.

Other indications for surgical therapy are ulcer perforation, gastric outlet obstruction, giant gastric ulcer, and a transfusion requirement of more than 6 units in 24 hours.

Distal gastrectomy with Billroth I (gastroduodenostomy) or Billroth II (gastrojejunostomy) is the preferred procedure for these complications. The surgery involves the removal of both the ulcer (mostly on the lesser curvature) and the diseased antrum. Medical therapy for gastric ulcer has shifted from antisecretory therapy to antimicrobial therapy; however, surgical therapy relies on acid reduction with vagotomy. Although vagotomy may be unnecessary, truncal or selective vagotomy is performed routinely.

Patients with gastric ulcers are also at risk of developing gastric malignancy. The risk is approximately 2% in the initial 3 years. One of the important risk factors is related to H pylori infection. H pylori is associated with atrophic H pylori infection is associated with gastric lymphoma or mucosa-associated lymphoid tissue (MALT) lymphoma. The normal gastric mucosa is devoid of organized lymphoid tissue. H pylori infection promotes acquisition of lymphocytic infiltration and often forms lymphocytic aggregates and follicles from which MALT lymphoma develops. Eradication of H pylori is very important in this group of patients because eradication of H pylori has been shown to cause a remission of MALT lymphoma.

Problems also arise because of a failure to document the eradication of H pylori with UBT, fecal stool antigen, or repeat upper endoscopy with biopsy in a patient with bleeding PUD. This usually stems from a failure to use a multidrug regimen to eradicate the infection.

Another area of concern is the failure to consider other, nongastrointestinal etiologies for epigastric pain, including myocardial infarction and abdominal aortic aneurysm.