Colorectal Cancer

Colorectal Cancer

 

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 ≥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

Diagnosis

  • Imaging studies
    • Colonoscopy
    • Barium study
  • 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

Disease Monitoring

  • Carcinoembryonic antigen
    • Elevated titer preoperatively predicts tumor recurrence
    • Pre-operative and post-operative monitoring for changes in concentration
  • 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

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

See Also