Gastric Carcinoma: Types, Etiology, Gross Features, and Treatment

Overview

• Yamada's Textbook of Gastroenterology, 7th ed.
• Harrison's Principles of Internal Medicine, 22nd ed.

Classification / Types

1. Lauren Classification (1965 - Most Widely Used)

• Sabiston Textbook of Surgery, Biological Basis of Modern Surgical Practice

2. WHO Classification (2019)

1. Tubular adenocarcinoma - Most common (45-64%); corresponds to Lauren intestinal type
2. Papillary adenocarcinoma - Rare (2.7-9.9%); well-differentiated but higher liver metastasis rate and poor survival
3. Poorly cohesive adenocarcinoma (including signet ring cell carcinoma) - 20-54% of cases; corresponds to Lauren diffuse type; lower sensitivity to chemoradiotherapy
4. Mucinous adenocarcinoma - Rare (2.1-8.1%); glandular structures with interstitial mucin or nests of signet ring cells surrounded by mucin
5. Mixed-pattern adenocarcinoma - 6-22%; contains both glandular and signet ring cell components; poorer prognosis than single-component tumors

• Yamada's Textbook of Gastroenterology, 7th ed.

3. TCGA Molecular Classification (2014)

• Sabiston Textbook of Surgery

Etiology and Risk Factors

Environmental / Acquired Factors

• H. pylori infection: The most important modifiable risk factor. ~50% of all humans are infected, but only a small subset develop cancer. High-risk strains drive intestinal metaplasia via the Correa cascade (normal mucosa → chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma). H. pylori eradication significantly reduces gastric cancer risk, supported by RCT evidence.
• Diet: High intake of nitrates from dried, smoked, and salted foods. Refrigeration (since 1920s) has correlated with decreased incidence in Western countries.
• EBV (Epstein-Barr Virus): Associated with a distinct subtype (~10% of all gastric cancers); characterized by dense lymphoid stroma and good prognosis.
• Chronic inflammation / atrophic gastritis: Especially autoimmune gastritis causing achlorhydria.
• Obesity and acid reflux: Promotes adenocarcinoma of the gastroesophageal junction (GEJ) -- incidence of proximal/GEJ cancers has been rising in Western high-HDI countries even as distal cancers decline.
• Gastric microbiome: Gastric cancer patients show higher overall bacterial load; the spectrum beyond H. pylori may contribute.
• Harrison's Principles of Internal Medicine, 22nd ed.

Genetic / Hereditary Factors

• Sabiston Textbook of Surgery, Harrison's Principles of Internal Medicine

Gross Features: Borrmann Classification (1926)

• Yamada's Textbook of Gastroenterology, Sabiston Textbook of Surgery

Early vs Advanced Gastric Cancer

• Early gastric cancer (EGC): Confined to mucosa or submucosa regardless of lymph node status; associated with high cure rates.
• Advanced gastric cancer: Invades muscularis propria or beyond. In Western countries, ~75% of patients present with perigastric lymph node spread or distant metastases at diagnosis.

• Type I: Protruding
• Type IIa: Superficially elevated
• Type IIb: Flat
• Type IIc: Superficially depressed
• Type III: Excavated

Treatment Management

A. Early Gastric Cancer (EGC)

• Endoscopic mucosal resection (EMR): For non-ulcerated lesions confined to mucosa
• Endoscopic submucosal dissection (ESD): Preferred for larger or ulcerated EGC; allows en bloc resection
  • Japanese expanded ESD criteria: (1) Mucosal intestinal-type of any size without ulceration; (2) Mucosal intestinal-type <3 cm with ulceration; (3) Submucosal intestinal-type <3 cm with submucosal invasion <500 μm
  • En bloc resection rates >90%; local recurrence <3%
  • Risk of perforation ~2-6% (managed conservatively with clips)

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease

B. Resectable / Locally Advanced Gastric Cancer - Surgery

• Subtotal gastrectomy: For distal tumors
• Total gastrectomy: For proximal tumors or diffuse-type disease
• Lymphadenectomy extent (JGCA definitions):
  • D1: Perigastric nodes only
  • D1+: D1 + selected regional nodes
  • D2: Extended nodal dissection (recommended by NCCN for experienced centers)
  • NCCN recommends modified D2 (without routine distal pancreatectomy or splenectomy) to reduce morbidity while maintaining survival benefit
  • Minimum 16 lymph nodes recommended for pathologic analysis; >30 is desirable

• Sabiston Textbook of Surgery

C. Perioperative Chemotherapy (Standard of Care for Resectable Disease)

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease

D. Adjuvant Chemoradiation

E. Targeted Therapy and Immunotherapy

• Current Surgical Therapy, 14th ed., Sabiston Textbook of Surgery

F. Intraperitoneal (IP) Chemotherapy

• HIPEC (Hyperthermic Intraperitoneal Chemotherapy): Used for patients with peritoneal metastases or high-risk of microscopic peritoneal residual after resection. Meta-analysis shows significantly reduced risk of death (OR 0.60) vs surgery alone. Most benefit in stage III-IV with serosal invasion or lymph node metastases.

G. Palliative Treatment (Advanced / Unresectable Disease)

• Debulking surgery
• Bypass procedures for gastric outlet obstruction
• Endoscopic laser therapy or alcohol injection for tumor debulking
• Endoscopic stenting
• Systemic chemotherapy (FLOT, FOLFOX, XP/XELOX regimens)
• Best supportive care
• Yamada's Textbook of Gastroenterology

H. Prevention

• H. pylori eradication in high-risk individuals (first-degree relatives of gastric cancer patients, prior early-stage gastric cancer) - reduces subsequent cancer incidence
• Prophylactic gastrectomy for CDH1 germline mutation carriers
• Surveillance endoscopy with Cambridge/Bethesda protocol biopsies for those declining prophylactic gastrectomy (HDGC)
• Dietary modification: reduce smoked, salted, nitrate-rich foods; increase fresh fruits and vegetables

Summary at a Glance