Gastric Cancer for the USMLE Step 2 Exam
Gastric Cancer for the USMLE Step 2 Exam
Overview
- Gastric adenocarcinoma is the most common form of gastric cancer, originating from the gastric mucosa. It has two main subtypes:
- Intestinal type: Associated with chronic inflammation, forming glandular structures.
- Diffuse type: Poorly differentiated, characterized by signet-ring cells and a more aggressive course.
Epidemiology
- High prevalence in East Asia (Japan, South Korea) and Eastern Europe.
- More common in men, usually diagnosed between ages 60 and 80.
- The incidence of proximal gastric cancer (involving the cardia) has increased in Western countries.
Risk Factors
- Helicobacter pylori (H. pylori) infection: Major risk factor due to chronic inflammation and progression to intestinal metaplasia.
- Diet: High intake of smoked, salted, or pickled foods increases the risk.
- Smoking and alcohol: Both contribute to gastric cancer risk.
- Genetic factors:
- Hereditary diffuse gastric cancer (HDGC): Caused by mutations in the CDH1 gene, associated with diffuse-type cancer.
- Lynch syndrome and familial adenomatous polyposis (FAP) increase the risk.
- Atrophic gastritis and pernicious anemia are associated with higher risk.
Pathophysiology
- Gastric cancer develops through a progression from chronic gastritis to atrophy, intestinal metaplasia, dysplasia, and finally adenocarcinoma.
- Intestinal-type adenocarcinoma follows this sequence.
- Diffuse-type is linked to CDH1 mutations, leading to loss of E-cadherin function, impairing cell adhesion and promoting tumor spread.
Clinical Presentation
- Early-stage disease is usually asymptomatic, leading to delayed diagnosis.
- Nonspecific symptoms include:
- Dyspepsia, nausea, and early satiety.
- Weight loss, anorexia, and epigastric pain in advanced disease.
- Signs of metastasis:
- Virchow’s node: Enlarged left supraclavicular lymph node.
- Sister Mary Joseph nodule: Periumbilical mass, indicating peritoneal metastasis.
- Krukenberg tumor: Ovarian metastasis, common in diffuse-type cancer.
Diagnosis
Endoscopy
- Esophagogastroduodenoscopy (EGD) with biopsy is the gold standard for diagnosis.
- Endoscopic screening is routine in high-risk populations (e.g., Japan, South Korea).
Imaging
- CT scan of the chest, abdomen, and pelvis is used to assess tumor spread and staging.
- Endoscopic ultrasound (EUS): Useful for assessing tumor depth and local lymph node involvement.
Tumor Markers
- Carcinoembryonic antigen (CEA) and CA 19-9: May be elevated in advanced disease but are nonspecific.
Staging
- Staging is based on the TNM system:
- T: Depth of tumor invasion.
- N: Involvement of regional lymph nodes.
- M: Presence of distant metastasis.
Management
Surgery
- Surgical resection is the only curative option.
- Distal gastrectomy: For distal tumors.
- Total gastrectomy: For diffuse or proximal tumors.
- D2 lymphadenectomy: Involves removal of regional lymph nodes to improve survival.
Chemotherapy and Radiation
- Neoadjuvant chemotherapy: Given before surgery to shrink tumors and improve resectability.
- Common regimens include FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel).
- Adjuvant chemotherapy: Given after surgery to reduce recurrence risk.
- Chemoradiation: Used in locally advanced cases to improve survival.
Palliative Care
- For advanced or unresectable gastric cancer:
- Palliative chemotherapy can prolong survival.
- Palliative radiation may control symptoms such as bleeding or pain.
Prevention
- H. pylori eradication: Reduces the risk of gastric cancer.
- Dietary changes: Increasing intake of fresh fruits and vegetables may lower the risk.
Key Points
- Gastric adenocarcinoma is the most common form of gastric cancer, divided into intestinal and diffuse subtypes.
- Major risk factors include H. pylori infection, diets high in smoked or salted foods, and genetic mutations (e.g., CDH1).
- Early gastric cancer is usually asymptomatic; advanced disease presents with weight loss, anorexia, and signs of metastasis (e.g., Virchow’s node).
- Endoscopy with biopsy is the gold standard for diagnosis, with CT scanning used for staging.
- Surgical resection is the main curative treatment, with chemotherapy and radiation used as adjuncts in advanced cases.