Peptic Ulcer Disease - Clinical Tree

If anyone should consider removing half of my good stomach to cure a small ulcer in my duodenum, I would run faster than he. Charles H. Mayo (1865–1939

In the era of Helicobacter pylori doing a gastrectomy for peptic ulcer is like doing a lobectomy for pneumonia. Asher Hirshberg

I

Occurrence

1.
Lifetime risk—10%
2.
US prevalence—2%
3.
Age
- a.
  Duodenal ulcers are more common in younger patients.
- b.
  Gastric ulcer incidence peaks at age 55–65 years.
4.
Male predominance for both types
5.
Risk factors
- a.
  Nonsteroidal antiinflammatory drug (NSAID) use
  - (1)
    Chronic users have 25% prevalence rate of peptic ulcer.
  - (2)
    Risk for adverse gastrointestinal events is three times that of healthy control subjects (>60 years, risk increases to five times normal).
- b.
  Cigarette smokers are twice as likely to experience development of peptic ulcer disease as nonsmokers.
- c.
  Stressful life events
  - (1)
    Burn injury—Curling ulcer, can be in stomach, duodenum, or jejunum
  - (2)
    Head injury—Cushing ulcer

II

Presentation and Evaluation

Differential: pancreatitis, celiac disease, gastric malignancy, biliary disease, gastroparesis

A

Symptoms

1.
Abdominal pain (80% of cases)—epigastric, burning, may radiate to the back (uncommon)
- a.
  Gastric ulcer—with eating
- b.
  Duodenal ulcer—2–3 hours postprandial, relieved by food; also at night
2.
Nausea, bloating
3.
Weight loss
4.
Complicated disease—worsening abdominal pain, hematemesis, melena

B

Physical Examination

1.
Epigastric tenderness
2.
Complicated disease—tachycardia, hypotension, peritonitis, older patient, persistent vomiting, jaundice, palpable mass

C

Laboratory Studies

1.
Positive Helicobacter pylori tests
2.
Complicated disease—decreased hemoglobin, acidosis, or metabolic alkalosis (gastric outlet obstruction with vomiting)

D

Definitive Diagnosis

Differential diagnosis: nonulcerative dyspepsia, gastric neoplasia, biliary disease, inflammatory/neoplastic disorder of pancreas

1.
Esophagogastroduodenoscopy (EGD)—90% sensitivity, direct visualization of ulcer; the gold standard
2.
Upper gastrointestinal series (with air and barium contrast)—75%–80% accurate, filling defect in wall

E

Modified Johnson Classification

1.
Type I—lesser curvature (60% of gastric ulcers)
2.
Type II—synchronous ulcers in gastric body and duodenum (most common in first portion of duodenum)
3.
Type III—prepyloric
4.
Type IV—near gastroesophageal junction
5.
Type V—related to NSAIDs, can be located anywhere, but typically greater curvature

III

Pathogenesis

1.
Focal defect in gastric or duodenal mucosa, extending to submucosa or deeper ( Fig. 25.1 )
2.
Increased gastric acid production
- a.
  Acid produced by parietal cells, located mostly in corpus of stomach
  - (1)
    Stimulated by acetylcholine from branches of vagus nerve in response to smell, taste, and sight of food (cephalic phase of acid secretory response)
  - (2)
    Stimulated by gastrin from G cells in antrum in response to amino acids in lumen (gastric phase)
    - (a)
      Gastric distension also stimulates acetylcholine and gastrin release.
  - (3)
    Histamine , released from enterochromaffin-like cells (basal acid secretion), mediates large portion of parietal cell stimulation in response to acetylcholine and gastrin release.
  - (4)
    Inhibited by somatostatin, released from D cells in response to antral acidification
- b.
  Zollinger-Ellison syndrome is characterized by pancreatic, duodenal, or nodal gastrinoma, leading to increased gastrin secretion.
  - (1)
    Cases are 80% sporadic and 20% inherited (most common tumor associated with multiple endocrine neoplasia type 1, tend to be multiple tumors; see Chapter 62 ).
  - (2)
    Diarrhea is most common symptom.
  - (3)
    Peptic ulcer disease is present in 90% of patients with Zollinger-Ellison syndrome.
  - (4)
    It is diagnosed by increased gastrin levels (can be falsely increased with proton-pump inhibitor [PPI] use) and confirmed by secretin stimulation test (increase of 200 pg/mL serum gastrin after 2 units/kg intravenous secretin bolus)
  - (5)
    Fifty percent are malignant.
  - (6)
    Surgical enucleation of gastrinoma is curative in 60% of patients.
  - (7)
    Most are found in gastrinoma triangle (junction of second and third portions of duodenum, junction of cystic and common bile ducts, junction of head and neck of pancreas).
  - (8)
    Preoperative localization is by computed tomography scan, transabdominal ultrasound, endoscopic ultrasound, or octreotide scan (gastrinoma cells contain type 2 somatostatin receptors, which bind radiolabeled somatostatin analogue with high affinity). In rare situations, angiography with selective venous sampling may be used.
  - (9)
    Intraoperative localization—exploration of gastrinoma triangle/pancreas, longitudinal duodenotomy, sampling of lymph nodes (portal, peripancreatic, celiac). Intraoperative ultrasound is helpful in identifying the lesion.
- c.
  Duodenal ulcers, concurrent duodenal and gastric ulcers (Johnson type II), and prepyloric gastric ulcers (Johnson type III) are associated with increased acid production.
3.
Weakened mucosal defenses
- a.
  Defenses consist of mucosal barrier, bicarbonate secretion, and healthy epithelial cell barrier.
- b.
  Mediators of defense system include prostaglandins and nitric oxide.
  - (1)
    NSAIDs inhibit prostaglandin production.
  - (2)
    Cigarette smoking inhibits prostaglandin and bicarbonate production.
- c.
  Gastric outlet obstruction causes increased exposure of gastric mucosa to acid and can overwhelm defenses.
- d.
  Gastric ulcers along the lesser curvature (Johnson type I), near the gastroesophageal junction (Johnson type IV), and those associated with pills (Johnson type V) are associated with weakened defenses.

IV

Helicobacter Pylori

1.
Characteristics
- a.
  Oxidase-positive, catalase-positive, microaerophilic gram-negative rod
2.
Associations
- a.
  Associated with 90% of duodenal ulcers and 70%–90% of gastric ulcers (85% of peptic ulcers overall)
3.
Fifty percent of adults worldwide and 33% of adults in the United States are infected.
4.
Associated, although not causally, with gastric cancer and mucosa-associated lymphoid tissue lymphoma
5.
Predisposes to ulcer formation by both increasing acid production and weakening defenses
- a.
  Local alkalinization of antrum leading to increased acid production
  - (1)
    To survive in acidic environment, H. pylori possesses urease, which converts urea to ammonia and bicarbonate.
  - (2)
    Increased bicarbonate → inhibition of D cells → decreased somatostatin production → less inhibition of G cells → hypergastrinemia → increased acid in stomach
- b.
  Colonization of duodenum leading to decreased bicarbonate production
  - (1)
    Antral epithelial metaplasia of the duodenum secondary to increased acidity
  - (2)
    Leads to further decrease in bicarbonate production
- c.
  Production and release of toxins (vacA, CagA) and cytokines (interleukin-8)
6.
Diagnosis of infection
- a.
  Endoscopic biopsy, if endoscopy is otherwise indicated
  - (1)
    Histologic analysis to directly visualize organisms (gold standard)
    - (a)
      Benign features: smooth, regular, rounded edges
    - (b)
      Concerning features (suggestive of malignancy): ulcerated mass protruding into lumen, thickened/irregular ulcer margins
  - (2)
    Rapid urease test (CLOtest)—sensitivity of 80%–95%, specificity of 95%–100%; do not use if patient taking PPI/antibiotics
- b.
  Serologic test—test of choice when endoscopy not indicated; “scar” remains after eradication following treatment; sensitivity of 80%, specificity of 90%
- c.
  Fecal antigen test—for active infection and to confirm cure
- d.
  Urea breath test—gold standard to confirm cure after 4 weeks of treatment
  - (1)
    Ingest urea labeled with ¹³ C, which is converted to CO ₂ by urease and exhaled as ¹³ CO ₂
- e.
  Culture only with treatment failure, when antibiotic resistance is suspected, or when ulcer has concerning features
7.
Treatment of known infection
- a.
  “Triple therapy” (amoxicillin, clarithromycin, and PPI) for eradication of infection
  - (1)
    Adequate for eradication in 90%
  - (2)
    May substitute metronidazole for amoxicillin
  - (3)
    Levofloxacin for resistant strains

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