Gastric Cancer for the USMLE Step 3 Exam
Gastric Cancer for the USMLE Step 3 Exam
Gastric Cancer
- Epidemiology:
- Gastric cancer is the fifth most common cancer worldwide but has a declining incidence in many countries.
- Highest prevalence is in East Asia (especially Japan and Korea), with lower rates in North America and Europe.
- The most common histological type is adenocarcinoma, accounting for >90% of gastric malignancies.
- Risk Factors:
- Helicobacter pylori infection is the most significant risk factor, leading to chronic gastritis and atrophic changes.
- Diet: High salt intake, smoked foods, and nitrosamines increase risk.
- Smoking and alcohol consumption are associated with higher incidence.
- Genetic factors: Family history and hereditary syndromes like hereditary diffuse gastric cancer (mutations in the CDH1 gene).
- Medical conditions: Chronic atrophic gastritis, intestinal metaplasia, pernicious anemia, and gastric polyps (especially adenomatous polyps) predispose to cancer.
- Pathogenesis:
- Intestinal type adenocarcinoma: Arises from chronic inflammation leading to intestinal metaplasia and dysplasia.
- Diffuse type adenocarcinoma: Characterized by a poorly cohesive cell pattern (signet ring cells). More aggressive and associated with CDH1 mutations.
- Precancerous lesions: Chronic H. pylori infection leads to a multistep process (superficial gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → carcinoma).
- Symptoms and Clinical Presentation:
- Often asymptomatic in early stages, contributing to delayed diagnosis.
- Weight loss and abdominal pain are the most common symptoms.
- Other symptoms include nausea, dysphagia, early satiety, and melena.
- Advanced disease may present with hematemesis, ascites, or signs of metastasis (e.g., Virchow's node, Sister Mary Joseph nodule).
- Paraneoplastic syndromes such as acanthosis nigricans or Leser-Trélat sign may occur.
- Diagnosis:
- Upper endoscopy with biopsy is the gold standard for diagnosis, enabling direct visualization and histopathological evaluation.
- Endoscopic ultrasound (EUS) helps in staging by assessing tumor depth and local lymph node involvement.
- CT scan of the abdomen and pelvis is used to detect distant metastases.
- Staging follows the TNM system (Tumor, Node, Metastasis):
- T: Depth of tumor invasion.
- N: Lymph node involvement.
- M: Presence of distant metastases.
- Treatment:
- Surgical resection is the mainstay of treatment for localized disease:
- Subtotal gastrectomy: For distal tumors.
- Total gastrectomy: For proximal or diffuse tumors.
- Lymph node dissection is performed alongside surgery to remove potentially affected nodes.
- Neoadjuvant chemotherapy is often used in resectable disease to shrink tumors and improve outcomes.
- Adjuvant chemotherapy and/or radiation are employed postoperatively for patients with residual disease or high-risk features.
- For advanced or metastatic disease, palliative chemotherapy is used to prolong survival and alleviate symptoms.
- Targeted therapies: HER2-positive tumors may respond to trastuzumab, while PD-1 inhibitors (e.g., pembrolizumab) may benefit those with high microsatellite instability (MSI) or PD-L1 expression.
- Prognosis:
- Prognosis depends on the stage at diagnosis:
- Early-stage gastric cancer has a 5-year survival rate of >90% with appropriate treatment.
- Advanced-stage or metastatic gastric cancer has a poor prognosis, with a 5-year survival rate below 20%.
- Recurrence is common, particularly in advanced disease, often within 2 years after surgery.
- Prevention:
- Screening programs in high-incidence regions (e.g., Japan, Korea) using endoscopy have improved early detection rates and survival.
- Eradication of H. pylori infection can significantly reduce the risk of gastric cancer, especially in high-risk individuals.
- Dietary modifications, such as reducing salt and smoked food intake, are also recommended as preventive measures.
Key Points
- Gastric adenocarcinoma is the most common type of gastric cancer, with H. pylori infection being a major risk factor.
- Upper endoscopy with biopsy is the diagnostic gold standard, with staging using the TNM system.
- Surgery with lymph node dissection is the main treatment for localized disease, supplemented by chemotherapy and radiation.
- Neoadjuvant and adjuvant therapies improve survival in advanced stages, while palliative chemotherapy is used for metastasis.
- Prognosis is poor for advanced gastric cancer, highlighting the importance of early detection through screening and H. pylori eradication.