Peptic Ulcer Disease

GENERAL PRINCIPLES

Definition

Peptic ulcer disease (PUD) consists of mucosal breaks in the stomach and duodenum when corrosive effects of acid and pepsin overwhelm mucosal defense mechanisms.

Etiology

• Helicobacter pylori, a spiral, Gram-negative, urease-producing bacillus, is responsible for at least half of all PUD and the majority of ulcers that are not due to NSAIDs.

• PUD can develop in 15%-25% of chronic NSAID and aspirin users. Past history of PUD, age gt;60 years, concomitant corticosteroid or anticoagulant therapy, high-dose or multiple NSAID therapy, and presence of serious comorbid medical illnesses increase risk for PUD.⁶⁵

• A gastrin-secreting tumor or gastrinoma accounts for lt;1% of all peptic ulcers.

• Gastric cancer or lymphoma may manifest as a gastric ulcer.

• When none of these etiologies are evident, PUD is designated idiopathic. Most idiopathic PUD could be due to undiagnosed H. pylori or undetected NSAID use.

• Cigarette smoking doubles the risk for PUD; it delays healing and promotes recurrence.

DIAGNOSIS

Clinical Presentation

• Epigastric pain or dyspepsia may be presenting symptoms; however, symptoms are not always predictive of the presence of ulcers. Epigastric tenderness may be elicited on abdominal palpation. Ten percent may present with a complication (see Complications).

• The presence of alarm symptoms (weight loss, early satiety, bleeding, anemia, persistent vomiting, epigastric mass, and lack of response to PPI) should prompt an EGD to assess for PUD or other diagnoses including gastric cancer.

Diagnostic Testing

• Endoscopy is the gold standard for diagnosis of peptic ulcers because it allows direct visualization and tissue sampling for H.

• Stool H. pylori antigen testing has good sensitivity and specificity for the diagnosis of H. pylori infection and can confirm eradication of H. pylori after treatment.

• Serum H. pylori antibody testing may identify previous or current infection, but both false negative and false positive results are possible. Since the antibody remains detectable as long as 18 months after successful eradication it cannot be used to document successful treatment.

• Rapid urease assay (e.g., Campylobacter-Iike organism [CLO] test) and histopathologic examination of endoscopic biopsy specimens diagnose H. pylori in patients undergoing endoscopy but may be falsely negative in patients on PPI therapy.

• Carbon-labeled urea breath testing is the most accurate noninvasive test for diagnosis, with sensitivity and specificity of 95%; it is often used to document successful eradication after therapy of H. pylori infection.⁶⁶

TREATMENT

Medications

• Regardless of etiology, acid suppression forms the mainstay of therapy of PUD. Gastric ulcers are typically treated for 12 weeks and duodenal ulcers for 8 weeks.

• Oral PPI or H₂RA therapy will suffice in most instances. Dosage adjustment of H₂RAs is necessary in renal insufficiency. Cimetidine can impair metabolism of many drugs, including warfarin anticoagulants, theophylline, and phenytoin.

• H. pylori is a carcinogen and thus should be eradicated in any patient that tests positive. H. pylori is treated with a combination of acid suppression and antibiotics. Several regimens are available (Table 18-3).^67,68 Quadruple therapy with a PPI, bismuth, metronidazole, and tetracycline has replaced clarithromycin-based triple therapy as first-line. Patients that have had previous exposure to macrolides should not be treated with clarithromycin-based regimens, and those with fluoroquinolone exposure should not be treated with levofloxacin-based regimens. Eradication should be documented with an H.

TABLE 18-3

REGIMENS USED FOR ERADICATION OF HELICOBACTER PYLORI

Medications and Doses Comments

and PPI^a for another 5-7 d

Duration of therapy: 10-14 days unless otherwise stated. When using salvage regimens after initial treatment failure, choose drugs that have not been used before.

^aStandard doses for PPI: omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, rabeprazole 20 mg, all twice a day. Esomeprazole is used as a single 40-mg dose once a day.

• NSAIDs and aspirin should be avoided when possible; if continued, maintenance PPI therapy and/or a mucosal protective agent (misoprostol, 400-800 #956;g#8725;d) is recommended.⁶⁹

• Sucralfate coats the eroded mucosal surface without blocking acid secretion and can be used as an adjunct to PPI when foregut mucosa is severely ulcerated. Side effects include constipation and reduction of bioavailability of certain drugs (e.g., cimetidine, digoxin, fluoroquinolones, phenytoin, and tetracycline) when administered concomitantly.

• Antacids can be useful as supplemental therapy for pain relief in PUD.

• Nonpharmacologic measures: Cessation of cigarette smoking should be encouraged. Alcohol in high concentrations can damage the gastric mucosal barrier, but no evidence exists to link alcohol with ulcer recurrence.

Surgical Management

Surgery is still occasionally required for intractable symptoms, GI bleeding refractory to endoscopic therapy, Zollinger-Ellison syndrome, and complicated PUD (i.e., perforation, gastric outlet obstruction). Surgical options vary depending on the location of the ulcer and the presence of complications.

SPECIAL CONSIDERATIONS

• Zollinger-Ellison syndrome is caused by a gastrin-secreting non-#946; islet cell tumor of the pancreas or duodenum. Multiple endocrine neoplasia type I can be associated with this syndrome in one-quarter to one-third of patients.⁷⁰ The resultant hypersecretion of gastric acid can cause multiple PUD in unusual locations, ulcers that fail to respond to standard medical therapy, or recurrent PUD after surgical therapy. Diarrhea and GERD symptoms are common.

• Gastric acid output is typically gt;15 mEq/L, and gastric pH is lt;1.0. A fasting serum gastrin level while off acid suppression for at least 5 days serves as a screening test in patients who make gastric acid; a value gt;1000 pg/mL is seen in 90% of patients with Zollinger-Ellison syndrome.

Complications

• GI bleeding (see Cardiac Patients and Gastrointestinal Bleeding section).

• Gastric outlet obstruction can occur with ulcers close to the pyloric channel and can manifest as nausea and vomiting, sometimes several hours after meals. Plain abdominal radiographs can show a dilated stomach with an air-fluid level. NG suction can decompress the stomach while fluids and electrolytes are repleted intravenously. Recurrence is common, and endoscopic balloon dilation or surgery is often necessary for definitive correction.

• Perforation occurs infrequently and usually necessitates emergent surgery. Perforation may occur in the absence of previous symptoms of PUD. A plain upright radiograph of the abdomen may demonstrate free air under the diaphragm. CT scan is usually diagnostic.

• Pancreatitis can result from ulcers in the posterior wall of the stomach or duodenal bulb penetrating the pancreas. The pain becomes severe and continuous, radiates to the back, and is no longer relieved by antisecretory therapy. Serum amylase may be elevated. CT scanning is usually diagnostic. Surgery is often required.

Monitoring/Follow-Up

• Repeat EGD or upper GI series should be performed 8-12 weeks after initial diagnosis of all gastric ulcers to document healing; nonhealing ulcers should be biopsied to evaluate for a malignant ulcer.

• Duodenal ulcers are almost never malignant; therefore, documentation of healing is unnecessary in the absence of symptoms.