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  1. What is the burden of disease?

    1. Fourth most common cancer in the United States and second leading cause of death from cancer

    2. About 135,430 diagnoses in 2017, with about 50,260 deaths each year

    3. Americans have a 5% lifetime risk of developing colorectal cancer; 85% of cases occur after age 50

    4. 80–95% of colorectal cancers arise from adenomatous polyps, with advanced adenomas defined as those ≥ 1 cm in diameter or those < 1cm in diameter containing at least 25% villous features, high-grade dysplasia, or carcinoma

      1. Adenomas are found in 20–53% of adults by age 50.

      2. The risk of cancer varies by size

        1. Adenomas ≤ 5mm make up 45–71% of detected adenomas; 7–16% are advanced, and up to 0.05% are malignant

        2. Adenomas 6–9 mm make up 21–23% of detected adenomas; 10–34% are advanced, and up to 0.2% are malignant

        3. Adenomas ≥ 1 cm make up 8–22% of detected adenomas; while all are advanced based on size, 37–54% have additional advanced histopathological features, and 3.2–11% are malignant

  2. Is it possible to identify a high-risk group that might especially benefit from screening (Tables 2-2 and 2-3)?

    1. 20% of colorectal cancers occur in patients with specific risk factors.

      1. History of either colorectal cancer or adenomatous polyps in a first-degree relative, especially if diagnosed before age 60

      2. Personal history of adenomatous polyps

      3. Long-standing ulcerative colitis

    2. 6% occur in patients with rare genetic syndromes, such as familial polyposis or hereditary nonpolyposis colorectal cancer (HNPCC).

      1. Colorectal cancer develops in 80% of patients with HNPCC by age 50 years.

      2. The mutation associated with HNPCC also increases the risk of cancer of the uterus, ovary, ureter, renal pelvis, stomach, small bowel, and bile duct.

      3. Patients with familial polyposis have diffuse colonic polyps at an early age, and colorectal cancer will develop without intervention.

    3. The remaining colorectal cancers occur sporadically.

  3. What is the quality of the screening test?

    1. Guaiac-based FOBT

      1. Two distinct samples of 3 different stools are applied to 6 test card panels.

      2. If Hb is present, a blue color appears when hydrogen peroxide is added.

      3. False-negative tests can occur if the patient has ingested > 250 mg of vitamin C, and false-positive tests occur with use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and ingestion of red meat since this test detects hemoglobin from any source.

      4. “Low sensitivity” tests, such as Hemoccult II have a sensitivity of 25–38% and specificity of 98%.

      5. “High sensitivity” tests, such as Hemoccult SENSA, have a sensitivity of 64–80% and specificity of 87–90%.

      6. Annual screening detected 49% of cancers; biannual screening detected 27–39% of cancers.

      7. A single panel test after a DRE has a sensitivity of 9% and should never be considered an adequate screening test for colorectal cancer.

    2. Fecal immunochemical test (FIT)

      1. Uses an antibody specific to human Hb but has not been standardized.

      2. For detecting colorectal cancer, sensitivity ranges from 73% to 88%, with specificities of 90–96%; the sensitivity is 24% for detecting advanced adenomas.

    3. Stool DNA test

      1. Expensive compared to the other stool tests

      2. For detecting colorectal ...

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