Gastric premalignant conditions

Gastric premalignant conditions (GPMCs) are histological abnormalities of the gastric mucosa that increase the risk for gastric adenocarcinoma. These conditions include atrophic gastritis, gastric intestinal metaplasia (GIM), gastric dysplasia, and certain gastric epithelial polyps (GEPs). The most common cause is chronic Helicobacter pylori infection. While often asymptomatic, some patients may experience nonspecific symptoms such as dyspepsia, epigastric pain, or early satiety. Diagnosis is established through esophagogastroduodenoscopy (EGD) with biopsies for histopathological evaluation. Management is guided by the severity and extent of the condition and primarily involves treating the underlying cause, such as eradicating H. pylori. Endoscopic surveillance is recommended for patients with high-risk features to assess for progression to gastric dysplasia or early gastric adenocarcinoma. Dysplastic lesions are managed with periodic endoscopic surveillance or endoscopic resection. Early detection and management are crucial for preventing invasive gastric adenocarcinoma.

• Prevalence in individuals undergoing EGD and gastric biopsies
  • Atrophic gastritis: ∼ 15% in the US ^[1][2]
  • Gastric intestinal metaplasia: 5–15% in Western populations ^[1]
  • Gastric dysplasia: 0.5–3.75% in Western populations ^[1]
• Increased prevalence in certain groups, including: ^[1][3][4]
  • Racial and ethnic groups with higher gastric cancer prevalence
  • First-generation immigrants from regions with high gastric cancer prevalence (e.g., East Asia, Eastern Europe)

Epidemiological data refers to the US, unless otherwise specified.

• Chronic H. pylori infection: most common cause of GPMCs ^[1]
• Autoimmune gastritis (AIG)
• Risk factors for gastric premalignant conditions include: ^[1]
  • First-degree relative with gastric cancer
  • Male sex
  • Tobacco use
  • Heavy alcohol use
  • Dietary factors (e.g., high intake of salted, smoked, and/or nitrate-preserved foods; low intake of fresh fruits and vegetables)

H. pylori mainly colonizes the gastric antrum.

• Pathogenesis: a stepwise sequence known as the Correa cascade ^[1]
• Persistent H. pylori infection: chronic inflammation of the gastric body → local destruction of gastric mucosa (via cytotoxins such as ammonia) → ↓ production of mucins and atrophy of the gastric glands → hypochlorhydria → hypergastrinemia and epithelial metaplasia → epithelial dysplasia → ↑ risk of gastric adenocarcinoma ^[5][6]
• Dietary factors: oral and gastric bacteria metabolize nitrates present in food to nitrites → nitrites form carcinogenic N-nitroso compounds in an acidic environment → epithelial metaplasia → ↑ risk of gastrointestinal cancer ^[7]

• Typically asymptomatic ^[1]
• When present, symptoms may include:
  • Dyspepsia
  • Epigastric discomfort
  • Early satiety
  • Nausea, vomiting
  • Features of associated complications, e.g.:
    • Anemia (e.g., pallor, fatigue) due to iron deficiency and/or vitamin B₁₂ deficiency
    • Overt or occult gastrointestinal bleeding due to erosions or gastroduodenal ulcers
    • Small intestinal bacterial overgrowth due to achlorhydria ^[8]

The diagnosis of GPMCs requires endoscopic evaluation and biopsies.

EGD and biopsies ^[1][2]

• Indication: individuals with suspected GPMC and relevant risk factors
• Procedure: advanced endoscopic imaging techniques preferred (e.g., high-definition white light endoscopy)
• Biopsies: Systematic biopsies using the Sydney protocol and targeted biopsies of visible mucosal abnormalities should be obtained.
• Histopathological evaluation
  • H. pylori testing
  • Factors used for risk stratification include:
    • Location, severity, and extent of mucosal abnormalities
    • Subtype of gastric intestinal metaplasia (i.e., complete, incomplete, or mixed)
    • Grade of gastric dysplasia (i.e., indeterminate, low-grade, high-grade)

Laboratory studies ^[1][2]

• CBC
  • Anemia: due to micronutrient deficiencies or blood loss
  • Microcytosis: suggests iron deficiency
  • Macrocytosis: suggests vitamin B₁₂ deficiency
• Noninvasive H. pylori testing
• Iron studies
• Vitamin B₁₂ levels
• Serology for AIG if autoimmune gastritis is suspected
• Biomarkers (e.g., serum pepsinogen isoforms, gastrin) are not recommended for screening or surveillance.

Microscopy findings

• Chronic inflammation → granulocytic infiltrations in the mucosa, lymphocytic infiltrations in the submucosa
• Mucosal thinning
• Loss of glands
• Epithelial metaplasia
  • (Pseudo)pyloric: replacement of parietal and chief cells in oxyntic glands by mucus-secreting cells, which are usually present in the pyloric region
  • Intestinal: replacement of epithelial cells in the oxyntic or antral mucosa by intestinal epithelium cells (e.g., goblet cells)
• Possible detection of H. pylori (gram-negative, rod-shaped bacteria)
• G-cell hyperplasia (common in AIG)

Patterns of affliction

• AIG: Lesions are confined to the gastric corpus and fundus.
• H. pylori-associated atrophic gastritis: Lesions first manifest in the gastric antrum (predominant), then spread to corpus and fundus.

• Reactive gastropathy
• Chronic gastritis (e.g., NSAID-related, bile reflux)
• Granulomatous gastritis
• Eosinophilic gastritis
• Lymphocytic gastritis
• Giant hypertrophic gastritis
• Portal hypertensive gastropathy
• See also “Causes of dyspepsia.”

The differential diagnoses listed here are not exhaustive.

General principles ^[1][2]

• Treat H. pylori infection if present
• Confirm eradication with H. pylori eradication confirmation testing
• Correct nutritional deficiencies if present, e.g.:
  • Iron therapy for iron deficiency
  • Vitamin B₁₂ replacement therapy
• Encourage lifestyle modifications that reduce symptoms and disease progression, e.g.:
  • Smoking cessation
  • Reduced alcohol use
  • Dietary adjustments (e.g., avoidance of trigger foods, reduced salt intake, increased intake of fresh fruit and vegetables)
  • Avoidance of; medications associated with reactive gastritis (e.g., NSAIDs)
  • See “Nonpharmacological recommendations” in “Treatment of dyspepsia” for details.

Symptom management ^[9]

Provide symptomatic relief of dyspepsia and epigastric discomfort as needed.

• PPIs
• H₂ receptor blockers
• Antacids
• Sucralfate
• See “Antacids and acid suppression medications” for dosages.

Avoid coadministration of sucralfate with PPIs or H₂ receptor blockers because sucralfate requires an acidic environment for activation.

Management of gastric dysplasia ^[1]

• Lesions with visible margins: endoscopic resection
• Lesions with nonvisible margins
  • Treat gastric inflammation, if present.
  • Refer for periodic endoscopic surveillance (e.g., every 3–6 months for high-grade dysplasia, every 6–12 months for low-grade dysplasia). ^[1]

• Gastric adenocarcinoma ^[1]
• Gastrointestinal bleeding or perforation
• Nutritional deficiencies (e.g., iron deficiency, vitamin B₁₂ deficiency)
• Small intestinal bacterial overgrowth

We list the most important complications. The selection is not exhaustive.