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Colorectal Cancer for the PA Exam

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Colorectal Cancer for the Physician Assistant Licensing Exam
  • Epidemiology:
    • Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States.
    • The incidence increases after age 50, leading to screening recommendations for adults starting at this age.
    • It affects both males and females equally.
  • Risk Factors:
    • Dietary factors: Diets high in red and processed meats, low in fiber, and high in alcohol increase risk.
    • Family history: A first-degree relative with CRC or adenomatous polyps increases risk, particularly if diagnosed before age 60.
    • Hereditary syndromes:
    • Familial adenomatous polyposis (FAP): Caused by a mutation in the APC gene, leading to hundreds of polyps and a near 100% risk of CRC.
    • Lynch syndrome (HNPCC): Caused by mutations in DNA mismatch repair genes (MLH1, MSH2, etc.), leading to a high lifetime CRC risk.
    • Inflammatory bowel disease: Chronic inflammation in ulcerative colitis and Crohn’s disease increases the risk of dysplasia and carcinoma.
    • Smoking, obesity, and a sedentary lifestyle are modifiable risk factors.
  • Pathogenesis:
    • CRC primarily arises from adenomatous polyps through the adenoma-carcinoma sequence, a multistep process of accumulated mutations (e.g., APC, KRAS, TP53).
Colorectal cancer adenocarcinoma pathway
    • Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes leads to an alternative carcinogenic pathway, particularly in Lynch syndrome.
    • Sporadic CRC makes up the majority of cases and typically follows the adenoma-carcinoma sequence, while hereditary CRC is linked to genetic mutations (e.g., APC, MMR genes).
  • Symptoms and Clinical Presentation:
    • Early-stage CRC is often asymptomatic, which is why routine screening is crucial.
    • Right-sided colon cancer: More likely to present with vague symptoms such as iron deficiency anemia (due to chronic occult bleeding), fatigue, and weight loss.
    • Left-sided colon cancer: Typically presents with changes in bowel habits, hematochezia, and signs of obstruction.
    • Rectal cancer: May cause rectal bleeding, tenesmus, and a feeling of incomplete defecation.
    • Systemic symptoms (e.g., weight loss, anorexia) and more advanced signs like liver metastasis can occur in later stages.
  • Screening:
    • Colonoscopy is the gold standard for both CRC screening and diagnosis. It can detect and remove polyps, preventing progression to cancer.
    • Other methods:
    • Fecal immunochemical test (FIT): Detects occult blood in the stool.
    • CT colonography: Noninvasive imaging to visualize the colon and rectum.
    • Screening should begin at age 45 for average-risk individuals. Patients with a family history of CRC should start earlier.
  • Diagnosis:
    • Colonoscopy with biopsy is used to confirm the diagnosis.
    • Pathology usually shows adenocarcinoma, which makes up over 95% of CRC cases.
    • CT scans are used for staging and detecting metastasis, especially to the liver and lungs.
    • Carcinoembryonic antigen (CEA) is a tumor marker useful in monitoring treatment and recurrence.
  • Treatment:
    • Surgical resection is the main treatment for localized disease. Types of surgery depend on tumor location (e.g., hemicolectomy, sigmoidectomy).
    • Chemotherapy is used for advanced stages (stage III or IV), often combined with drugs like 5-fluorouracil (5-FU) and oxaliplatin.
    • In metastatic CRC, palliative chemotherapy can prolong survival and improve symptoms.
  • Prognosis:
    • Prognosis depends on the stage at diagnosis:
    • Stage I: 5-year survival >90%.
    • Stage IV: 5-year survival <10%.
  • Prevention:
    • Lifestyle changes such as a high-fiber diet, reduced intake of processed and red meats, and regular exercise help lower CRC risk.
    • Regular screening and removal of polyps during colonoscopy are essential preventive measures.
Key Points
  • Colorectal cancer arises from adenomatous polyps, with progression driven by mutations in key genes like APC, KRAS, and TP53.
  • Microsatellite instability (MSI) is an alternative pathway seen in Lynch syndrome, caused by defective mismatch repair genes.
  • Colonoscopy is the gold standard for screening and diagnosis, and routine screening is recommended starting at age 45.
  • Right-sided CRC often presents with anemia, while left-sided CRC presents with changes in bowel habits or hematochezia.
  • Surgical resection is the primary treatment for localized disease, and chemotherapy is added for advanced or metastatic stages.
  • Prevention includes dietary changes, regular screening, and polyp removal.