Peptic Ulcer Disease

Definition
development of a discrete mucosal defect in the portions of the gastrointestinal tract (gastric or duodenal) exposed to acid and pepsin secretion.

Modified Johnson Classification of peptic ulcers:

• Type I: Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistentiae.

• Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion.

• Type III: In the pyloric channel within 3 cm of pylorus. Associated with acid oversecretion.

• Type IV: Proximal gastroesophageal ulcer

• Type V: Can occur throughout the stomach. Associated with chronic NSAID use (such as aspirin).

Aetiology
Multifactorial
H. pylori infection:

• Associated with 90% of duodenal ulcers and 70–90% of gastric ulcers

• Lifetime risk for PUD in H. pylori–infected people is 10–20%.

• Annual risk of developing duodenal ulcer in H. pylori–infected people is ≤1%.

Ulcerogenic drugs (e.g., NSAIDs)
Hypersecretory syndromes (e.g., Zollinger-Ellison syndrome)
Retained gastric antrum
Less common: Crohn disease, vascular insufficiency, radiation therapy, cancer chemotherapy, smoking
Associated with

• Zollinger-Ellison syndrome (gastrinoma)

• Multiple endocrine neoplasia type 1

• Carcinoid syndrome

• Chronic illness: Crohn disease, chronic obstructive pulmonary disaese (COPD), chronic renal failure, hepatic cirrhosis, cystic fibrosis

• Hematopoietic disorders (rare): Systemic mastocytosis, myeloproliferative disease, hyperparathyroidism, polycythemia rubra vera

Pathophysiology
Multifactorial. Imbalance between aggressive factors (e.g., gastric acid, pepsin, bile salts, pancreatic enzymes) and defensive factors maintaining mucosal integrity (e.g., mucus, bicarbonate, blood flow, prostaglandins, growth factors, cell turnover)


Epidemiology
70% of ulcers occur in patients between the ages of 25 and 64 years.
Ulcer incidence increases with age.
Peptic ulcer: 500,000 new cases/year
Recurrence: 4 million/year
Global incidence rate 0.1–0.19% (1)[A]
Peptic ulcer: 1.8% in the US
Lifetime prevalence is 5–10% for patients not infected with Heliobacter pylori; 10–20% if infected.

Presentation

Symptoms

Episodic gnawing or burning epigastric pain Pain occurring after meals or on empty stomach Nocturnal pain Pain relieved by food intake, antacids, or antisecretory agents Nonspecific dyspeptic complaints: Indigestion, vomiting, loss of appetite, intolerance to fatty foods, and heartburn Alarm features: Anemia, hematemesis, melena, or heme-positive stool may suggest bleeding. Vomiting and early satiety may suggest obstruction. Anorexia or weight loss Persisting upper abdominal pain radiating to the back may suggest penetration. Severe, spreading upper abdominal pain may suggest perforation.

Signs

Epigastric tenderness may be present (absent in at least 30% of older patients). Guaiac-positive stool owing to occult blood loss

Investigation

FBC	Rule out anemia
Fecal occult blood test	GI bleeding
H. Pylori testing	Indications: New-onset PUD, history of PUD, persistent symptoms after empirical antisecretory therapy, gastric mucosa–associated lymphoid tissue (MALT) lymphoma, uninvestigated dyspepsia in patients <50 years of age without alarm symptoms Noninvasive tests: Serology antibody: Most commonly used for testing in primary care but slow to normalize after treatment, so cannot be used to document successful eradication (sensitivity 85%, specificity 79%)] Urea breath test: Identifies active H. pylori infection; also used for posttreatment testing (sensitivity >95%, specificity >90%) Stool antigen: Can be used for screening and posttreatment testing (sensitivity 91%, specificity 94%) Invasive tests: Upper endoscopy with gastric biopsy, which can be evaluated with Steiner stain for direct visualization of organism (sensitivity >95%, specificity >95%) Rapid urease test: Conducted on gastric biopsies (sensitivity 93–97%, specificity 95%)
Imaging	CXR- perforation (free abdominal air) CT
Endoscopy	indications: Patients with suspected peptic ulcers who are >55 years of age, those who have alarm symptoms, and those with ulcers that do not respond to treatment Endoscopic image of gastric ulcer

Management

GI bleeding	IV Fluid, avoid NSAIDs
Acid suppression	PPIs: 1st line Omeprazole 20 mg/d PO; lansoprazole 30 mg/d PO; rabeprazole 20 mg/d PO; esomeprazole 40 mg/d PO; or pantoprazole 40 mg/d PO Administer PPIs before breakfast. H2 blockers: Ranitidine or nizatidine 150 mg PO b.i.d. or 300 mg PO at bedtime
H. pylori eradication regimen	Triple therapy: (8--85% effective) 1.  PPI × 14 days: Omeprazole (Prilosec): 20 mg PO bid or Lansoprazole (Prevacid): 30 mg PO bid or Rabeprazole (Aciphex): 20 mg PO bid or Esomeprazole (Nexium): 40 mg PO qd 2.  Clarithromycin (Biaxin): 500 mg PO bid 3.  Amoxicillin (Amoxil): 1 g PO bid or metronidazole 500 mg PO b.i.d. in patients with allergy to amoxicillin If fail, Bismuth quadruple therapy × 14 days: Bismuth subsalicylate 525 mg PO q.i.d. plus Metronidazole 500 mg PO q.i.d. plus Tetracycline 500 mg PO q.i.d. PPI × 14 days
Surgery	Indications Ulcers that are refractory to treatment patients at high risk for complications (e.g., transplant recipients, patients dependent on steroids or NSAIDs); treatment of perforation bleeding refractory to endoscopic therapy. Options Duodenal ulcers: Truncal vagotomy and drainage (pyloroplasty or gastrojejunostomy), selective vagotomy (preserving the hepatic and/or celiac branches of the vagus) and drainage, highly selective vagotomy (division of only the gastric branches of the vagus, preserving the Latarjet nerve to the pylorus) Gastric ulcers: Partial gastrectomy, Billroth I or II
Patient Education	Stop smoking. Avoid NSAID and aspirin use. Avoid heavy alcohol use. Stress reduction counseling might be helpful in individual cases but is not needed routinely.
Follow-up	Confirm eradication by urea breath test. Acute duodenal ulcer: Monitor clinically Acute gastric ulcer: Confirm healing via endoscopy after 12 weeks if biopsy not done initially to confirm that lesion is benign

Complications
Hemorrhage: Up to 25% of patients (initial presentation in 10%)
Perforation <5% of patients
Gastric outlet obstruction: Up to 5% of duodenal or pyloric channel ulcers; male predilection found
Risk of gastric adenocarcinoma increased in H. pylori–infected patients

Prognosis
After H. pylori eradication:

• Low ulcer relapse rate; if relapse, consider surreptitious use of NSAIDs.

• Reinfection rates <1% per year

• Low risk of rebleeding

• Decreased NSAID ulcer recurrence