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Source: Davis LE, Sun W, Medina PJ. Colorectal Cancer. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. Accessed August 1, 2012.

  • Malignant neoplasm involving colon, rectum, and anal canal

  • Studies suggest development of colorectal cancer related to:
    • Dietary factors
    • Lifestyle factors
    • Physical and genetic susceptibilities

  • Multistep process of genetic and phenotypic alterations of normal bowel epithelium structure and function leading to unregulated cell growth, proliferation, and tumor development.
  • Features of colorectal tumorigenesis include:
    • Genomic instability
    • Activation of oncogene pathways
    • Mutational inactivation of tumor-suppressor genes
    • Activation of growth factor pathways
  • Adenocarcinomas account for >90% of tumors of large intestine.

  • Third leading cause of cancer-related deaths for men and women in United States.
  • Median age at diagnosis is 70 years.

  • Primary prevention aimed at populations at highest risk.
  • Secondary prevention aimed at preventing malignancy in population already manifesting initial disease process.
    • Includes procedures ranging from colonoscopic removal of precancerous polyps detected during screening colonoscopy to total colectomy for high-risk individuals (e.g., familial adenomatous polyposis [FAP]).
  • Screening techniques
    • Fecal occult blood testing (FOBT)
    • Flexible sigmoidoscopy: not able to evaluate entire bowel
    • Total colonic examination
      • Colonoscopy
      • Double-contrast barium enema
    • United States screening guidelines for average-risk individuals include annual occult fecal blood testing starting at age 50 years and examination of colon every 5 or 10 years, depending on procedure.

  • Elevated risk
    • Physical inactivity and elevated BMI
    • Alcohol intake: stronger association for men than women
    • Tobacco use
    • Western diet
    • Clinical risk factors
      • Type 2 diabetes, independent of BMI and physical activity
      • Chronic inflammatory diseases
        • Ulcerative colitis
        • Crohn’s disease
    • Genetic susceptibility
      • Hereditary (10% of cases)
        • FAP
        • Hereditary nonpolyposis colorectal cancer (HNPCC)
      • Familial (20% of cases)
        • First-degree relatives have 2–4 times increased risk as compared to general population.
  • Reduced risk
    • Risk-to-benefit considerations unresolved:
      • Regular aspirin and NSAID use associated with risk reduction of 30–50%.
      • Exogenous postmenopausal oral hormone replacement therapy reduces risk by about 20%.
      • Vitamin D and calcium appear to interact synergistically to protect against adenoma recurrence and colorectal cancer.

  • Signs and symptoms can be extremely varied, subtle, and nonspecific.
  • Patients with early-stage colorectal cancer often asymptomatic, and lesions usually detected by screening procedures.
  • Approximately 19% of patients present with metastatic disease.
    • Most common site of metastasis is liver, followed by lungs and bones.

Signs and Symptoms

  • Blood in stool most common sign.
  • Any change in bowel habits
  • Vague abdominal discomfort
  • Abdominal distension
  • Nausea
  • Vomiting
  • Fatigue (if anemia is severe)

Means of Confirmation and Diagnosis

  • Pathologic examination of surgical specimens

Laboratory Tests

  • Complete blood count (CBC): iron deficiency anemia from blood loss
  • Guaiac stool test: positive if blood in stool
  • Carcinoembryonic antigen (CEA): elevated in most patients
  • Metabolic panel: Liver function test (LFT) elevated ...

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