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INTRODUCTION

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  • Colorectal cancer (CRC) is a malignant neoplasm involving the colon, rectum, and anal canal.

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PATHOPHYSIOLOGY

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  • Development of a colorectal neoplasm is a multistep process of genetic and phenotypic alterations of normal bowel epithelium structure and function leading to dysregulated cell growth, proliferation, and tumor development.

  • Features of colorectal tumorigenesis include genomic instability, activation of oncogene pathways, mutational inactivation or silencing of tumor-suppressor genes, DNA mismatch repairs, and activation of growth factor pathways.

  • Adenocarcinomas account for about 85% of tumors of the large intestine.

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PREVENTION AND SCREENING

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  • Primary prevention is aimed at preventing CRC in an at-risk population. Trials with celecoxib in people with familial adenomatous polyposis (FAP) showed reduction in size and number of polyps after 6 to 9 months of treatment, but there is a lack of long-term benefit.

  • Secondary prevention is aimed at preventing malignancy in a population that has already manifested an initial disease process. Secondary prevention includes procedures ranging from colonoscopic removal of precancerous polyps detected during screening colonoscopy to total colectomy for high-risk individuals (eg, FAP)

  • Current US guidelines for average-risk individuals include annual occult fecal blood testing starting at age 50 years and examination of the colon every 5 or 10 years, depending on the procedure.

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CLINICAL MANIFESTATIONS

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  • Signs and symptoms of CRC can be extremely varied, subtle, and nonspecific. Early-stage CRC is often asymptomatic and detected by screening procedures.

  • Blood in the stool is the most common sign; however, any change in bowel habits, vague abdominal discomfort, or abdominal distention may be a warning sign. Less common signs and symptoms include nausea, vomiting, and, if anemia is severe, fatigue.

  • Twenty percent of patients present with metastatic disease most commonly in the liver, lung, and bones.

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DIAGNOSIS

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  • Perform a physical examination and obtain a careful personal and family history. Evaluate entire large bowel by colonoscopy.

  • Obtain baseline laboratory tests: complete blood cell count, international normalized ratio (INR), activated partial thromboplastin time, liver and renal function tests, and serum carcinoembryonic antigen (CEA). Serum CEA serves as a marker for monitoring CRC response to treatment, but it is too insensitive and nonspecific to be used as a screening test for early-stage CRC.

  • Radiographic imaging studies may include chest radiographs, bone scan, chest and abdominal computed tomography scans, positron emission tomography, ultrasonography, and magnetic resonance imaging.

  • Determine CRC stage at diagnosis to predict prognosis and develop treatment options. Stage is based on size of the primary tumor (T1–4), presence and extent of lymph node involvement (N0–2), and presence or absence of distant metastases (M).

    • ✓ Stage I disease involves tumor invasion of the submucosa (T1) or muscularis propria (T2) and negative lymph nodes.

    • ✓ Stage II disease involves tumor invasion through the muscularis propria into pericolorectal tissues (T3), or penetration to ...

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