|
Colorectal cancer ranks third in cancer incidence and second in cancer-associated mortality in the United States, making primary prevention, screening, diagnosis, and therapy of concern to most physicians who care for adults.
EPIDEMIOLOGY AND SIGNS AND SYMPTOMS OF COLON CANCER
In the United States, an estimated 140,000 new cases of colorectal cancer are diagnosed each year, with approximately 55,000 deaths related to the disease. The overall lifetime risk is approximately 5% for the general population. Men have a slightly higher age-adjusted death rate than women. The incidence of colorectal cancer increases with age, beginning to rise after 40 years of age and then significantly after 55 years of age.
Worldwide, colorectal cancer rates vary depending on geographic location. The United States (with a rate of 14 per 100,000 population) is near the upper end of a broad range. Rates in Australia and several European countries are higher (up to 30 per 100,000 in the Czech Republic), whereas rates in most Asian and South American countries are much lower (3 per 100,000 in Ecuador). Environmental factors are suggested to play a role because persons from an area of low incidence assume a. significantly higher risk when they migrate to areas of high incidence.
ETIOLOGY OF COLON CANCER
The current hypothesis is that most colorectal cancers arise from preexisting benign adenomatous polyps that undergo sequential malignant transfor
mation. Adenomas are neoplastic lesions that display abnormal cellular differentiation and are of varying architecture, size, and shape. Histologically, adenomas can be classified as:
- Tubular (80% to 85% of all adenomas)
- Tubulovillous (8% to 16%)
- Villous (3% to 15%)
Although adenomatous polyps are considered to be premalignant lesions, only approximately 5% are estimated to develop into cancer.
Factors associated with malignant transformation are:
- Increasing size (<1% of polyps <1 cm diameter develop into frank malignancies, whereas approximately 10% of those larger than 2 cm will)
- Villous histology
At the molecular level, neoplastic and malignant transformations are believed to be caused by an accumulation of damage to the DNA of the mucosal cells of the colon. Two key events are believed to be the activation of the ras oncogene and the inactivation of one or more of the so-called tumor-suppressor genes (e.g., APC, dcc, and p53). The DNA damage can be caused by endogenous agents (e.g., oxidizing and alkylating products of cellular metabolism) or exogenous agents (e.g., carcinogens, viruses, and radiation).
Cancers can initially be confined to the mucosa (carcinoma in situ) and then progress to the submucosa, muscularis propria, and adjacent tissues. Once the cancer invades past the mucosa, it can metastasize to regional lymph nodes and distant sites. Invasive cancer involving the rectum differs from other colon cancers in that local recurrences after resection are more common.
RISK FACTORS OF COLON CANCER
A number of risk factors are associated with the development of colorectal cancer:
- History of adenomatous polyps
- Inflammatory bowel disease (greater in ulcerative colitis than Crohn's disease)
- Familial's disorders (familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer)
- Personal history of another malignancy (ovarian,endometrial, breast)
- Family history of colon cancer in first-degree relatives
A number of studies have looked at dietary and lifestyle risk factors, with conflicting and inconclusive results. The strongest positive associations are as follows:
- High animal fat consumption (red meat)
- Low fiber consumption (lack of fruits and vegetables)
- Obesity
- Ethanol
- Refined sugar
- Cigarette smoking
There is the suggestion that regular use of aspirin may lower the incidence of colorectal cancer. Additionally, because high animal fat consumption and low fiber consumption is associated with increased risk, a number of studies have attempted to determine if certain dietary habits can be protective. Strong evidence indicates that increased dietary fiber may significantly reduce colon cancer risk, although prospective data are lacking.
CLINICAL MANIFESTATIONS OF COLON CANCER
HISTORY
Most neoplastic colorectal lesions present without symptoms. Symptoms generally occur in more advanced disease. For this reason, screening (see later) is advocated for the detection of neoplasms in asymptomatic patients. When present, the most common symptoms of colorectal cancer are:
- GI bleeding (may be occult and variably associated with iron-deficiency anemia)
- Change in bowel habits (narrowed caliber of stool, chronic diarrhea, constipation)
- Abdominal pain
- Anorexia/weight loss (generally late, with advanced metastatic cancers)
PHYSICAL EXAMINATION FOR COLON CANCER
In a manner similar to the history, patients with colorectal cancer generally have few specific physical examination findings. A mass may be found on external palpation of the abdomen or on digital rectal examination, but this is uncommon.
DIAGNOSTIC EVALUATION
The main studies used for screening and diagnosis of colorectal cancer are as follows
- Fecal occult blood test
- Barium enema
- Sigmoidoscopy
- Colonoscopy
COLON CANCER TREATMENT
The overall management of colorectal cancer involves both primary prevention, by reducing the potential risk factors listed earlier, and secondary prevention, by screening to detect and treat asymptomatic cancers and premalignant precursors. Multiple guidelines exist for the surveillance of colorectal cancer using the methods just listed Polyps and carcinoma in situ are detected and then subsequently cured by excisional biopsy with sigmoidoscopy or colonoscopy. If invasive cancer is detected, the next step is to determine the local extent of the tumor and the presence of metastatic disease. Abdominal CT is generally of use for this staging.
Colectomy is the treatment modality of choice for invasive colon cancer. Adjuvant therapy with chemotherapy and/or radiation therapy is added if the clinical situation warrantsgenerally, if there are nodal metastases. Colon cancer with nodal metastases is generally treated with postoperative 5-fluorouracil (5-FU) and levamisole. Because of the higher risk of local recurrences, rectal cancers characterized by invasion through the muscularis, with or without nodal disease and all tumors with nodal involvement are treated with surgery plus postoperative 5-FU and high-dose pelvic irradiation.
Once colorectal neoplasms are discovered and treated, monitoring for recurrence must be maintained because the patient is now at higher than average risk for future neoplasms. This includes patients who are discovered to have benign polyps as well as those with malignant disease.
Colorectal cancers are believed to arise from malignant transformation of benign adenomatous pcslps
-Environmental and dietary factors are believed to play a role in the development of colorectal neoplasms and primary prevention maybe possible:
Fecal occult -blood testing, sigmoidoscopy,, barium enema;and ;cofonoscopy: are .the commonly available screening and dlagnostic tests.
Early detection via screening, the intensity of which is tailored to relative risk, may result in signlficant decreases in mortality.
Surgery, followed by chemotherapy and/or radiation for more extensive disease, is the therapy of choice for invasive disease.
|
