Colorectal cancer is second only to lung cancer as a cause of cancer-related deaths in the U.S.

Epidemiology

• Incidence - 34/100,000, according to U.S. SEER (Surveillance Epidemiology and End Results) database
• Age - usually greater than or equal to 50 years
• Sex - males > females

Risk Factors

• Diet high in animal fats (Western diet)
• Patients with metabolic syndrome
• Hereditary syndromes (autosomal dominant transmission)
  • Familial adenomatous polyposis (FAP)
    • Rare condition where patients present with 100s to 1000s of adenomatous polyps
  • Hereditary nonpolyposis colorectal cancer (HNPCC) (Lynch syndrome)
    • Extra colorectal cancers also occur, especially endometrial cancer
  • Hamartomatous polyps
    • Peutz Jeghers syndrome
    • Juvenile polyposis
    • Cowden syndrome
• Other
  • Ureterosigmoidostomy - can develop more than 15 years post procedure

Pathophysiology

• Most colorectal cancers arise from adenomatous polyps; although a subset may develop from hyperplastic polyps, especially large, right-sided ones
• Villous adenomas become malignant three times more frequently than tubular adenomas
• Adenocarcinoma is the usual cell type - only considered malignant if it penetrates into the submucosa
• Other tumors are uncommon
  • Lymphomas, endocrine and mesenchymal tumors

Clinical Presentation

• Symptoms vary with tumor location - most are located in sigmoid colon and rectum
  • Cecal and ascending colon - tumors may be very large without obstructing
    • Anemia is a common presenting symptom
  • Descending and transverse colon - tumors tend to obstruct and cause annular lesions (apple core or napkin ring) with abdominal pain and bloating
  • Rectosigmoid - hematochezia, tenesmus and narrowing of stool caliber

Prevention

• Aspirin and other NSAIDs
  • Suppress cell proliferation by inhibiting prostaglandin synthesis
  • Effects increase with duration of use
• Diets rich in fruit and vegetables
  • Reduce risk
  • Do not reduce incidence of subsequent adenomas in a patient with prior adenoma removal
• Estrogens
  • May decrease insulin-like growth factor 1 or bile acid synthesis

Diagnosis

• Laboratory testing
  • Histology
    • Genetic changes in tumors
      • Mostly used for the evaluation of HNPCC (Lynch syndrome)
      • Microsatellite instability (MSI) can occur both with HNPCC and in sporadic colorectal cancer
      • BRAF and MLH1 methylation
        • BRAF gene encodes a serine-threonine kinase and plays a role in the mitogen-activated protein kinase signaling pathway
        • Commonly seen in sporadic unstable colorectal cancer; has not been reported in Lynch-associated cancers
        • Its presence strongly supports sporadic colon cancer
        • Similarly, MLH1 methylation is commonly seen in sporadic microsatellite unstable colorectal cancer and has only rarely been reported in Lynch-associated cancers
  • Germline testing for inherited colorectal cancer syndromes of affected individuals and family members
• Imaging studies
  • Colonoscopy
  • Barium study

Disease Monitoring

• Carcinoembryonic antigen
  • Elevated titer preoperatively predicts tumor recurrence
  • Pre-operative and post-operative monitoring for changes in concentration
• Circulating tumor cell count - in metastatic tumors, monitor disease progression and response to therapy
• Others
  • CA 19-9 is not recommended
  • p53 - not enough data to recommend its use

Disease Screening

• Rationale - since tumor progression is sequential in polyps, locating tumors earlier will allow more cures
• Early colonoscopy for family history of hereditary cancers
• Hemoccult for stool blood
  • 50% of documented colon cancers have a negative fecal occult blood test (FOBT)
    • If patient is at risk, consider sigmoidoscopy or colonoscopy even in the presence of a negative fecal occult blood test
  • Positive FOBT mandates further testing
• Colonoscopy - current recommendation
  • Every 10 years beginning after age 50