Gastric cancer

Cancer developing from the lining of the stomach.

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Epidemiology

• 4th M/C malignancy worldwide
• 2nd M/C cancer-related deaths worldwide

↓ Incidence of gastric cancer:

• Successful reduction of H. pylori infections
• Changes in food preservation, such as less pickling of vegetables, and less smoking and processing of meat
• Greater availability of fresh fruits and vegetables

Gastric cancer survival rates:

• Earlier detection
• Better treatment options

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Classification

• Adenocarcinoma (M/C, 90%): Columnar glandular epithelium
• Lymphoma (3-5%): B-lymphocytes (B-cells)
  • Mucosa-associated lymphoid tissue (MALT) lymphoma
  • DLBCL (diffuse large B cell lymphoma)
• Carcinoid tumour: G-cells in stomach
• Leiomyosarcoma: Smooth muscle cells

Lauren’s histopathologic classification (M/C):

• Intestinal (with intercellular junctions) (M/C)
  • Mass lesions: Polyploid tumours/ulcers (glands/tubules lined by epithelium resembling the intestinal mucosa)
• Diffuse (without intercellular junctions)
  • No mass lesions
  • Poor prognosis

World Health Organization (WHO) classification:

• Adenocarcinoma
• Signet ring-cell carcinoma
• Undifferentiated carcinoma

Japanese classification:

For early gastric cancer (Cancer limited to mucosa and submucosa with/without lymph node involvement (T1 & any N)

Bormann classification (4 basic growth patterns):

Indiacted for advanced gastric cancer

1. Polypoid (type I)
2. Fungating (type II)
3. Ulcerated (type III)
4. Diffusely infiltrative (type IV): Linitis plastica appearance (worst prognosis)

Molecular subtypes

• Subtype 1: Microsatellite instability (MSI) (best prognosis)
• Subtype 2: EBV associated
• Subtype 3: Chromosomal instability (CIN)
• Subtype 4: Genomic instability (GS) (worst prognosis)

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Etiology

Etiology is multifactorial, although infection with Helicobacter pylori is the primary cause.

Infectious:

• H. pylori infection (M/C, 80% cases)
  • Gastric cancer is one of a few types of neoplasms directly linked to an infectious agent.
  • Also MALT lymphoma
  • Protective against gastro-esophageal reflux (GERD) and esophageal adenocarcinoma
• Epstein-Barr virus (EBV) (5-16% cases)
  • ~90% in gastric lymphoepitheliomas (carcinomas with lymphoid stroma)

Environmental:

• Tobacco (11% cases)
• Moderate-high alcohol consumption (39% ↑ risk)
• High salt diet
  • Salt erodes mucosal barrier of stomach → inflammation → ↑ gastritis and carcinogenic effects of known gastric carcinogens like N-methyl-N-nitro-N-nitrosoguanidine (MNNG)
• Processed & smoked meat
• Fresh fruits and vegetables ↓ incidence

Host factors:

• Male (2x more likely)
• Old age
• Blood group A (20% more cases)
  • Blood group O associated with ↑ risk of peptic ulcers
• Diet high in smoked/salty foods

Family history/hereditary (5-10% cases):

• Hereditary familial gastric cancer:
  • Hereditary diffuse gastric cancer (HDGC)
  • Gastric adenocarcinoma & proximal polyposis of the stomach (GAPPS)
  • Familial intestinal gastric cancer (FIGC)
• Other hereditary cancer syndromes:
  • Hereditary non-polyposis colon cancer (HNPCC, 13% lifetime risk, predominantly intestinal type, 1–3% of all GC)
    • CDH1 gene mutation (encodes E-cadherin)
    • Autosomal dominant conditions that cause diffuse, poorly differentiated GC, which infiltrates into stomach wall and causes thickening of the wall without forming a distinct mass.
  • Familial adenomatous syndrome (FAP, 10% risk)
  • Peutz Jeghers syndrome (PJS, 29% risk)
  • Juvenile polyposis syndrome (JPS, 21%)
  • Li-Fraumeni syndrome
  • Hereditary breast and ovarian cancer syndrome
  • Phosphatase & tensin homolog (PTEN) or hamartoma tumor (Cowden’s) syndrome

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Pathophysiology

Prolonged precancerous process takes place, with well-defined sequential stages:

(Initiated & sustained by infection with H pylori)

Chronic active gastritis
↓
Chronic atrophic gastritis
↓
Intestinal metaplasia
(Complete/small intestinal type → incomplete/colonic intestinal type
↓
Dysplasia or intraepithelial neoplasia
↓
Invasive carcinoma

Spread:

• DIRECT SPREAD
  • Spleen, diaphragm, omentum, transverse colon, liver, lung
• PERITONEAL SPREAD
  • Kruckenberg tumour: Ovary
  • Blummer shelf tumour: Pouch of Douglas
  • Sister Mary Joseph node: Periumbilical region
    • Also found in:
      • Gastric cancer
      • Colon cancer
      • Pancreatic cancer
      • Gynaecological cancer
• LYMPHATIC SPREAD
  • Virchow node: Left supraclavicular lymph node
  • Irish node: Left anterior axillary lymph node
• HEMATOGENOUS SPREAD

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Presentation

• Epigastric pain
• Anaemia
• Fatigue
• Early satiety
• Anorexia
• Dysphagia
• Vomiting

Dermatological signs:

• Lesser Trelat sign: Multiple seborrhoeic keratosis
• Tripe palms: Hyperkeratotic palms
• Sister Mary Joseph nodules: Periumbilical metastasis
• Irish nodules: Left axillary LN
• Troisier sign: Clinical finding of a hard and enlarged left supraclavicular node (Virchow node)

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Diagnosis

Screening:

• Contrast radiography and endoscopy
• Serum pepsinogen levels
• H. pylori serology
  • ELISA or HelicoTest
  • Benchmark urea breath test (UBT)
• Serum trefoil factor 3

EGD + biopsy:

Best initial diagnostic for any elderly patient with dysphagia

Imaging:

• Upper GI seies “Barium roentgenogram”
  • Series of radiographs used to examine the gastrointestinal tract for abnormalities
• Endoscopic ultrasound (EUS)
• CT scan

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Management

• Eradication of H pylori infection

Dietary changes:

• Increase fresh fruits & vegetables
• Reduce salt consumption

Surgical management:

• No metastasis: Subtotal or total gastrectomy
• Metastasis: Palliative surgery

Chemoradiation:

• 5-FU or leucovorin

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Prognosis

Early gastric cancer:

• 5-year survival rate: 90%

Late gastric cancer:

• Average 5-year survival rate: <20%
  • Mainly because of late diagnosis, because the early stages are clinically silent

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