Chapter 61: Colorectal Cancer

INTRODUCTION

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

PATHOPHYSIOLOGY

• 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.

PREVENTION AND SCREENING

• 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.

CLINICAL MANIFESTATIONS

• 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.

DIAGNOSIS

• 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 (T_1–4), presence and extent of lymph node involvement (N_0–2), 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 (T_...