Peptic Ulcer Disease (PUD)

Definition

Epidemiology

• More than 4 million individuals in the United States are treated for PUD each year
• Lifetime risk: ~10% for males, ~4% for females
• Duodenal ulcers are more common than gastric ulcers
• The peak incidence has shifted to older age groups in Western countries
• Still common in Eastern Europe and rising in resource-poor nations
• Robbins & Kumar Basic Pathology

Sites

Etiology and Pathogenesis

The Two Main Causes

• Responsible for >70% of PUD cases globally
• Only 5-10% of infected individuals actually develop ulcers, suggesting host factors and strain variation matter
• Causes chronic gastritis as a background to ulcer development

• In the United States, NSAID use is now becoming the most common cause of gastric ulcers as H. pylori infection rates fall
• Low-dose aspirin use in the aging population is a major contributor
• NSAIDs suppress prostaglandin synthesis, impairing mucosal defense

Other Contributing Factors

Pathology

Duodenal Ulcers

• Most ulcers occur in the first part of the duodenum
• A chronic ulcer penetrates through the mucosa into the muscle coat, causing fibrosis
• Scarring can produce pyloric stenosis
• Anterior duodenal ulcers tend to perforate
• Posterior duodenal ulcers tend to bleed - sometimes by eroding the gastroduodenal artery
• "Kissing ulcers" = both anterior and posterior ulcers present simultaneously

Gastric Ulcers

• Tend to be larger than duodenal ulcers
• Most common on the lesser curve (especially incisura angularis)
• Fibrosis can cause an "hourglass" deformity of the stomach
• Chronic ulcers may erode posteriorly into the pancreas, splenic artery, or rarely the transverse colon
• Important: Unlike duodenal ulcers, gastric ulcers carry a risk of malignancy - every gastric ulcer must be regarded as potentially malignant until proven otherwise with multiple biopsies (up to 10)
• PPIs can heal ulceration associated with gastric cancer but do not treat the malignancy

Histopathology

• Ulcer base is covered with granulation tissue
• Evidence of endarteritis obliterans may be present
• Healing ulcers show epithelial downgrowth that can be misinterpreted as invasion - careful pathological interpretation is needed

Clinical Features

Symptoms

• Epigastric pain - gnawing in character, sometimes radiating to the back; classically intermittent with symptom-free periods
• Eating may relieve discomfort (especially duodenal ulcers)
• Periodicity - symptoms disappear for weeks or months, then return; may correspond to spontaneous healing and re-ulceration
• Vomiting - not prominent unless pyloric stenosis has developed
• Weight change - weight loss common with gastric ulcers; sometimes weight gain
• Bleeding - chronic bleeding may present with microcytic (iron-deficiency) anemia; acute bleeding presents with hematemesis and/or melena

Clinical Examination

• Epigastric tenderness on palpation
• Otherwise unremarkable unless complications (e.g., gastric outlet obstruction) have developed

Investigations / Diagnosis

Gastroduodenoscopy (Upper GI Endoscopy)

• Investigation of choice
• In the stomach: all abnormal lesions must be biopsied; multiple biopsies (up to 10) from a suspected benign gastric ulcer are essential to exclude malignancy
• Antral biopsies + CLO (Campylobacter-like organism) test for H. pylori
• Full inspection including incisura, lesser curve, pylorus, and duodenum

Testing for H. pylori

Complications

1. Hemorrhage - Most common complication; bleeding peptic ulcer accounts for the majority of upper GI bleeds; posterior duodenal ulcers can erode the gastroduodenal artery
2. Perforation - Anterior duodenal ulcers most commonly perforate; presents with sudden severe abdominal pain and peritonitis; management is primarily surgical
3. Penetration - Ulcer erodes into adjacent organ (pancreas, splenic artery, transverse colon) without free perforation
4. Gastric outlet obstruction (pyloric stenosis) - From fibrosis and scarring; presents with vomiting, especially of undigested food

Treatment

Medical Treatment (Mainstay)

• PPIs (e.g., omeprazole, lansoprazole) are the most effective agents - can render a patient achlorhydric
• H2-receptor antagonists (e.g., ranitidine) were historically used; superseded by PPIs but still have a role
• Lifestyle modification: cessation of smoking (reduces relapse), avoid NSAIDs if possible

• Quadruple therapy achieves >90% eradication rates
• Clarithromycin worldwide resistance ranges from 20-35% - local resistance data should guide therapy choice
• After treatment, confirm eradication with urea breath test or stool antigen test

NSAID-Associated Ulcers

• Discontinue NSAID if possible
• If NSAID must be continued: co-prescribe a PPI; consider switching to a selective COX-2 inhibitor
• Test and treat for H. pylori (eradication reduces ulcer recurrence even in NSAID users)

Surgical Treatment

• Reserved for complications: perforation (surgical repair/omental patch), uncontrolled hemorrhage (endoscopic failure), gastric outlet obstruction, and suspected malignancy
• Historically included vagotomy and antrectomy to reduce acid - rarely done now

Recent Evidence

Summary: Key Points

• PUD results from failure of mucosal defenses against acid/pepsin, most often driven by H. pylori or NSAIDs
• Duodenal ulcers are more common; gastric ulcers require biopsy to exclude malignancy
• Classic symptom: intermittent gnawing epigastric pain; symptoms of both types are clinically indistinguishable
• Complications: hemorrhage, perforation, penetration, obstruction
• Treatment: PPI + H. pylori eradication (triple or bismuth quadruple therapy depending on resistance risk)
• Surgery is now reserved for complications; elective surgical treatment is rare