Gastric cancer

Epidemiology

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Etiology

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Exogenous risk factors

• Diet rich in nitrates and/or salts (e.g., dried foods, foods preserved by curing or smoking) and low in fresh vegetables containing antioxidants t
  • Bacteria are believed to convert ingested nitrates into carcinogenic nitrites.
• H. pylori infection
• Nicotine use
• Epstein-Barr virus

Endogenous risk factors

• Gastric conditions
  • Chronic atrophic gastritis and associated pernicious anemia
  • Achlorhydria (e.g., due to Ménétrier disease)
  • Gastric ulcers

Pathophysiology

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Two major histologic types

• Intestinal Type
  • Resembles colonic adenocarcinoma; forms glandular structures.
  • Located typically on the lesser curvature of the antrum/pylorus.
  • Strong association with H. pylori, smoking, and nitrosamines.
• Diffuse Type
  • Not associated with H. pylori.
  • Signet Ring Cells: Mucin-filled cells with nucleus pushed to the periphery.
  • Linitis Plastica: “Leather bottle” stomach due to diffuse infiltration and thickening of the stomach wall (loss of distensibility).
  • Younger patients; worse prognosis.

Clinical features

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• Paraneoplastic syndromes
  • Leser-Trélat sign
  • Malignant acanthosis nigricans

Diagnostics

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Pathology

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Gastric adenocarcinoma

• Accounts for ∼ 95% of cases
• Most commonly located on the lesser curvature

Lauren classification of gastric adenocarcinoma

• Intestinal type gastric carcinoma
  • Typically localized
  • Polypoid, glandular formation
  • Similar to an ulcerative lesion with clear raised margins
  • Commonly located on the lesser curvature
  • Must be differentiated from peptic gastric ulcers by biopsy
• Diffuse type gastric carcinoma
  • No clear border
  • Spreads earlier in the course of disease
  • Infiltrative growth
  • Diffuse spread in the gastric wall
  • Linitis plastica: gastric wall thickening and leather bottle appearance
  • Composed of signet ring cells: round cells filled with mucin, with a flat nucleus in the cell periphery
  • Associated with E-cadherin mutation
    • E-cadherin is a family of calcium-dependent glycoproteins that facilitate cell-to-cell adhesion at adherens junctions. Link to the actin cytoskeleton via catenin and vinculin.
    • Due to its role in cell adhesion and differentiation, E-cadherin protects against tumor formation. Low expression is associated with poorer prognosis (e.g., increased depth of invasion or severe lymph node involvement).

Treatment

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Complications

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Postgastrectomy complications

Dumping syndrome

• Definition: rapid gastric emptying as a result of defective gastric reservoir function, impaired pyloric emptying mechanisms, or anomalous postsurgery gastric motor function

Early dumping

• Pathophysiology: dysfunctional or bypassed pyloric sphincter → rapid emptying of undiluted hyperosmolar chyme into the small intestine → fluid shift to the intestinal lumen → small bowel distention → vagal stimulation → increased intestinal motility
• Clinical features
  • Occur within 15–30 minutes after meal ingestion
  • Include nausea, vomiting, diarrhea, and cramps
  • Vasomotor symptoms such as sweating, flushing, and palpitations
• Management
  1. Dietary Modifications (First-line; highly effective in most pts):
     • Eat small, frequent meals (e.g., 6 small meals/day).
     • Avoid liquids during meals (postpone fluids for ≥ 30–40 mins after solid food).
     • High-protein, high-fat, low-carbohydrate diet; strictly avoid simple sugars.
     • Lie down for 30 mins after meals to slow gastric transit & reduce vasomotor symptoms.
  2. Acarbose (Second-line for late dumping):
     • Alpha-glucosidase inhibitor; delays carb digestion to minimize postprandial glucose spike & insulin surge.
  3. Octreotide (Somatostatin analog) (For severe/refractory cases):
     • Inhibits insulin and GI vasoactive peptides, slows gastric emptying & intestinal transit.
  4. Reconstructive Surgery (Last resort):
     • Conversion of Billroth I/II to Roux-en-Y (rarely required).

Late dumping

• Pathophysiology: dysfunctional pyloric sphincter → rapid emptying of glucose-containing chyme into the small intestine → quick reabsorption of glucose → hyperglycemia → excessive release of insulin → hypoglycemia and release of catecholamines
• Clinical features
  • Occur hours after meal ingestion
  • Include signs of hypoglycemia (e.g., hunger, tremor, lightheadedness)
  • GI discomfort
• Management
  • Dietary modifications
  • Second-line treatment: octreotide
  • Third-line treatment: surgery