Cancer, Colorectal

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. http://accesspharmacy.com/content.aspx?aid=8008586. 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 ...