Gastric Cancer for the ABIM
Gastric Cancer for the American Board of Internal Medicine
Overview
- Gastric cancer primarily refers to adenocarcinoma, which originates from the gastric mucosa. It is a leading cause of cancer-related deaths worldwide.
- Two main histologic subtypes:
- Intestinal type: Associated with environmental factors, forms gland-like structures, and follows a more predictable progression.
- Diffuse type: Poorly differentiated, lacks glandular formation, and is characterized by a more aggressive course and signet-ring cells on histology.
Epidemiology
- High prevalence in East Asia (Japan, South Korea, China) and Eastern Europe.
- Incidence in Western countries has decreased, but the proportion of proximal gastric cancer (cardia) has increased.
- Male predominance, typically diagnosed between ages 60 and 80.
Risk Factors
- Helicobacter pylori infection: A major risk factor due to chronic gastritis and subsequent intestinal metaplasia.
- Diet: High intake of smoked, salted, or pickled foods. Low consumption of fruits and vegetables.
- Smoking: Increases risk, particularly for proximal gastric cancer.
- Alcohol consumption: Particularly associated with higher cancer risk.
- Genetics:
- Hereditary diffuse gastric cancer (HDGC): Associated with CDH1 gene mutations, confers a high risk of diffuse-type gastric cancer.
- Familial adenomatous polyposis (FAP) and Lynch syndrome: Increase the risk of gastric cancer.
- Atrophic gastritis and pernicious anemia: Cause chronic inflammation and increase cancer risk.
- Epstein-Barr virus (EBV): Implicated in a minority of gastric cancers, particularly in the diffuse type.
Pathophysiology
- Gastric cancer develops through a multistep process, beginning with chronic gastritis, progressing to atrophy, intestinal metaplasia, dysplasia, and finally adenocarcinoma.
- The intestinal type arises from precancerous lesions like intestinal metaplasia and is more associated with environmental factors.
- The diffuse type often lacks these precursor lesions and is associated with genetic mutations such as CDH1, which encodes E-cadherin, leading to loss of cellular adhesion.
Clinical Presentation
- Early stages of gastric cancer are often asymptomatic, leading to delayed diagnosis.
- Nonspecific symptoms in early disease include:
- Dyspepsia, early satiety, nausea, and epigastric discomfort.
- As the disease progresses:
- Weight loss and anorexia.
- Abdominal pain that is persistent and unrelieved by antacids.
- Dysphagia may occur with proximal or cardia tumors.
- Signs of metastatic disease:
- Virchow’s node: Left supraclavicular lymph node enlargement.
- Sister Mary Joseph nodule: Periumbilical nodule indicating peritoneal spread.
- Blumer’s shelf: Palpable mass on rectal examination indicating pelvic metastasis.
- Krukenberg tumor: Ovarian metastasis, often seen in diffuse-type gastric cancer.
Diagnosis
Endoscopy
- Esophagogastroduodenoscopy (EGD) with biopsy is the gold standard for diagnosis.
- Biopsy is necessary for histopathological confirmation.
- Screening: High-risk populations (e.g., Japan, South Korea) undergo routine endoscopic screening, leading to earlier detection and better outcomes.
Imaging
- CT scan of the chest, abdomen, and pelvis is used to assess for distant metastasis and staging.
- Endoscopic ultrasound (EUS): Critical for determining the depth of tumor invasion and local nodal involvement.
- PET/CT: May be used in selected cases to evaluate metastatic disease.
- Laparoscopy: Performed in advanced cases to assess peritoneal metastases that may be missed by imaging.
Tumor Markers
- Carcinoembryonic antigen (CEA) and CA 19-9: May be elevated in advanced disease but lack sensitivity and specificity for screening or diagnosis.
Staging
- TNM system:
- T: Tumor invasion (depth of wall penetration).
- N: Regional lymph node involvement.
- M: Distant metastasis (e.g., liver, lungs, peritoneum).
- Accurate staging is critical for treatment planning and prognosis.
Management
Surgical Treatment
- Surgical resection is the only curative option for gastric cancer.
- Distal gastrectomy: For tumors in the distal two-thirds of the stomach.
- Total gastrectomy: For diffuse-type cancer or tumors involving the proximal stomach (cardia or fundus).
- D2 lymphadenectomy: Involves the removal of regional lymph nodes to improve survival.
- Palliative surgery: May be performed in advanced cases to alleviate symptoms like obstruction or bleeding.
Chemotherapy
- Neoadjuvant chemotherapy: Used before surgery to shrink the tumor and improve resectability.
- Common regimens include FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel).
- Adjuvant chemotherapy: Given postoperatively to eliminate residual microscopic disease and reduce recurrence risk.
- Chemoradiation: May be combined with surgery in selected cases, particularly in locally advanced disease.
Targeted Therapy
- HER2-positive gastric cancer: Treated with trastuzumab in combination with chemotherapy.
- Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab) may be used in advanced disease with high PD-L1 expression or microsatellite instability (MSI).
Palliative Care
- In metastatic or unresectable disease, focus shifts to symptom management and improving quality of life.
- Palliative chemotherapy: Prolongs survival in metastatic disease.
- Palliative radiation: Used for pain control or to stop bleeding from the tumor.
- Biliary stenting: For biliary obstruction caused by tumor compression.
- Pain management: May require opioids for adequate relief.
Prognosis
- Prognosis depends on the stage at diagnosis.
- Localized disease: 5-year survival rate of around 70%.
- Advanced disease: Poor prognosis, with 5-year survival <20% for metastatic disease.
- Early detection through screening significantly improves outcomes, especially in high-risk populations.
Prevention
- Helicobacter pylori eradication: Reduces the risk of gastric cancer, especially in high-prevalence areas.
- Dietary modifications: Increase consumption of fresh fruits and vegetables, reduce intake of smoked and salted foods.
- Smoking cessation and moderation of alcohol intake can lower the risk.
Key Points
- Gastric adenocarcinoma is the most common type of gastric cancer, with two major subtypes: intestinal and diffuse.
- Major risk factors include H. pylori infection, smoking, a diet high in smoked and pickled foods, and genetic syndromes (e.g., CDH1 mutations).
- Early gastric cancer is often asymptomatic, with nonspecific symptoms such as dyspepsia, early satiety, and weight loss presenting in more advanced stages.
- Endoscopy with biopsy is the gold standard for diagnosis, and CT scan is essential for staging and metastasis evaluation.
- Surgical resection remains the mainstay of treatment for curative intent, with chemotherapy used in neoadjuvant and adjuvant settings.
- Prognosis is poor for advanced gastric cancer, highlighting the importance of early detection, especially in high-risk populations.