Gastric Cancer

Detailed Overview

The intestinal type is strongly associated with environmental factors, specifically Helicobacter pylori infection, and progresses through a well-defined cascade from chronic gastritis to atrophy, intestinal metaplasia, dysplasia, and finally carcinoma. The diffuse type is poorly differentiated, highly infiltrative (linitis plastica), and often associated with genetic mutations (CDH1). Because early gastric cancer is typically asymptomatic, most cases in Western countries are diagnosed at advanced stages with a poor prognosis.

Epidemiology & Demographics

It is the 5th most common cancer worldwide. Incidence is highly variable geographically, being extremely high in East Asia (Japan, Korea) and Eastern Europe. It is twice as common in men as in women.

Etiological Mechanism

The predominant etiology for the intestinal type is chronic infection with Helicobacter pylori. Other causes include dietary factors, autoimmune gastritis, and genetic syndromes.

Primary Causes

Helicobacter pylori Infection

Dietary Factors (high salt, smoked foods, nitrates)

Epstein-Barr Virus (EBV) (10% of cases)

Hereditary Diffuse Gastric Cancer (CDH1 mutation)

• H. pylori Infection: The strongest known risk factor, increasing risk by 6-fold.
• Smoking: Increases risk by roughly 50%.
• Diet: High intake of preserved, salted, or smoked foods containing nitrites, and low intake of fresh fruits.
• Pernicious Anemia: Autoimmune destruction of parietal cells leads to achlorhydria and increased cancer risk.

Correa's cascade describes the development of the intestinal type: H. pylori causes chronic active gastritis. Over decades, this leads to loss of gastric glands (atrophic gastritis). The stomach lining is replaced by intestinal-type epithelium (intestinal metaplasia) as a defense mechanism. DNA damage accumulates, leading to dysplasia and adenocarcinoma. Diffuse gastric cancer lacks intercellular adhesions due to loss of E-cadherin expression (often due to CDH1 mutation). This allows signet-ring cells to diffusely infiltrate the gastric wall, causing marked thickening and rigidity (linitis plastica or 'leather bottle' stomach).

Characteristic Clinical Presentation

• Early Satiety: Feeling full after eating only a small amount of food, especially common in diffuse type (rigid stomach).
• Epigastric Pain: Vague upper abdominal discomfort that may mimic peptic ulcer disease but is not fully relieved by antacids.
• Weight Loss: Unexplained and significant weight loss due to decreased intake and tumor consumption.
• Nausea and Vomiting: Occurs especially if the tumor is obstructing the pylorus.

Physical Examination Signs

• Palpable epigastric mass (late sign)
• Virchow's Node (Left supraclavicular lymphadenopathy)
• Sister Mary Joseph Nodule (Periumbilical metastatic nodule)
• Blumer's Shelf (Palpable metastatic mass in the pouch of Douglas on digital rectal exam)

• Gastric Outlet Obstruction: Tumors near the pylorus block food passage, causing intractable vomiting.
• Gastrointestinal Bleeding: Chronic occult bleeding leading to severe anemia, or acute hematemesis.
• Malignant Ascites: Peritoneal carcinomatosis leading to fluid accumulation and massive abdominal distention.

Diagnostic Criteria & Guidelines

Diagnosis requires Esophagogastroduodenoscopy (EGD) with multiple biopsies of suspicious lesions or ulcers. Any gastric ulcer requires biopsy to rule out malignancy (unlike duodenal ulcers). Staging requires CT of the chest, abdomen, and pelvis, and Endoscopic Ultrasound (EUS) to assess depth.

Differential Diagnosis

• Peptic Ulcer Disease
• Gastric Lymphoma (MALToma)
• Gastrointestinal Stromal Tumor (GIST)
• Menetrier's Disease

Laboratory Tests & Biomarkers

• Complete Blood Count: Microcytic anemia due to iron deficiency from chronic bleeding.
• Tumor Markers (CEA, CA 19-9): May be elevated, but lack sensitivity for screening; used for monitoring recurrence.
• Mismatch Repair (MMR) and HER2: Biopsy is tested to guide targeted immunotherapy and chemotherapy.

Imaging Modalities & Findings

• EGD:
• CT Abdomen/Pelvis:
• Diagnostic Laparoscopy:

• Stage I
  Tumor limited to mucosa/submucosa. Excellent prognosis if resected.
• Stage II/III
  Invasion into muscularis or serosa, and positive regional lymph nodes.
• Stage IV
  Distant metastasis (liver, peritoneum, lungs).

Second-Line & Adjunctive Therapy

For metastatic or unresectable disease: Palliative systemic chemotherapy (FOLFOX). Add Trastuzumab if HER2-positive. Add Nivolumab if PD-L1 CPS >= 5.

Surgical & Procedural Management

Gastrectomy. Distal tumors require subtotal gastrectomy with Roux-en-Y reconstruction. Proximal or diffuse tumors require total gastrectomy with esophagojejunostomy. D2 lymphadenectomy is the standard of care for curative intent.

Recommended Lifestyle Changes

• Small, frequent meals post-gastrectomy to manage dumping syndrome.
• Dietary modifications to reduce nitrites/salt and increase fresh fruits/vegetables.
• Vitamin B12 injections are permanently required after total gastrectomy.

Patient Counseling & Advice

Warn the patient about 'dumping syndrome' after stomach removal—rapid emptying of food into the intestine causing cramps, sweating, and diarrhea. Emphasize that dietary habits must permanently change.

Follow-Up & Monitoring Schedule

History and physical, CEA/CA 19-9 testing, and CT scans every 3-6 months for the first 2 years, then every 6-12 months up to 5 years. Endoscopy is usually repeated at 1 year post-op.

Preventive Strategies

Eradication of H. pylori with antibiotic therapy. Mass endoscopic screening in high-risk countries (e.g., Japan, South Korea) has dramatically reduced mortality by catching Stage I disease. Prophylactic total gastrectomy is recommended for patients with confirmed CDH1 genetic mutations.

Highly dependent on stage. 5-year survival for localized stage I is >70%. However, overall 5-year survival in the US is around 32% because most cases present at Stage III or IV.