What Are Colon and Rectal Cancers?
Colon and rectal cancers (often referred to collectively as colorectal cancer) are malignancies (life-threatening tumors) that develop in the large intestine. This six-foot tube is the last section of the digestive tract, a complex organ system that carries food from the mouth down the esophagus to the stomach and small intestine. There, the processes of digestion occur; the residual undigested material is then carried to the colon and rectum (the large intestine). The waste material is still in liquid form as it passes into the colon at the ileum, the area where the small and large intestines meet. The water is then slowly absorbed as the waste matter travels through the colon and forms into solid feces.

What Are the Symptoms of Colon and Rectal Cancers?
Rectal bleeding can be a symptom of intestinal cancer. Anyone who notices blood in the stools should see a physician promptly. However, blood in bowel movements is not always a serious sign; it is usually caused by conditions other than cancer, including hemorrhoids, minor tears around the rectal or anal areas, or diverticulosis. Other symptoms of colorectal cancer vary widely depending on the location of the cancer within the large intestine. Many patients are even free of symptoms until their tumors are quite advanced.

Tumors in the Cecum and Ascending Colon (Right Colon).
The waste matter in the first portion of the colon is in liquid or semi-liquid form. Tumors that develop here do not change bowel habits or formation of stools. However, they may cause intermittent or chronic bleeding. Although the stools look normal, patients may develop symptoms of anemia and iron deficiency, which includes weakness, fatigue, heart palpitations, shortness of breath, and exercise intolerance.

Tumors in the Transverse Colon
The waste material passes across the upper quadrants of the abdomen (the transverse colon), the intestine absorbs water, and the waste matter becomes more solid. In addition to bleeding, tumors here may cause cramps, gas, partial or complete obstruction, and even perforation of the bowel.

Tumors in the Descending Colon and Rectum (Left Colon).
When tumors partially block the lower intestine, thin, pencil-shaped stools may form. Bowel habits can change. Tumors in the rectum and lowest part of the intestine can cause pain and a feeling of fullness. Defecation may be painful or patients may feel the urge to defecate, but nothing happens. Bleeding from these locations may be brisk and bright red or maroon, but cancer is usually detected before symptoms of chronic anemia develop. It should be noted that stools can turn red after eating certain red foods, such as beets or red licorice. Iron supplements and medications that have bismuth subsalicylate, most commonly Pepto-Bismol, can cause stools to turn black.

Who Gets Colon and Rectal Cancers?

Age and Gender.
Although the incidence of colon cancer has dropped significantly in recent years, about 131,600 people in the U.S. will be diagnosed with either colon or rectal cancer in 1998. Colorectal cancers usually occur in people over 50 and are slightly more common in men. Although a number of more specific risk factors have been identified, about 75% of cases occur without a known predisposing factor.

Family History and Genetic Factors.
Almost a quarter of those under 45 years old and about 15% of everyone who develops colorectal cancer have a genetic risk. People who have a sibling or parent who developed colorectal cancer before age 50 have a significantly higher life-time risk (about 23%) than people whose relatives were free of cancer or did not develop it until after age 60. Recent studies are also finding that people who have close relatives who develop benign adenomatous polyps before age 60 may be at increased risk for colon cancer. This risk is significantly increased, of course, if there are also family members who have had colon or rectal cancer before the age of 60. (Family members of people who develop either colorectal cancer or polyps after age 60 have no risk greater than the general population.)

One of the most important genetic defect identified to date is in the gene known as adenomatous polyposis coli (APC). A protein produced from the APC gene binds with a protein known as beta-catenin. When the APC gene is normal, it helps suppress tumor growth by preventing overproduction of the beta-catenin protein, but in its defective form the mutated APC gene produces high beta-cantenin levels, which in turn, accelerates cell growth leading to polyps. It now appears that, in addition, the beta-catenin protein itself may cause cancerous changes under certain circumstances and become unable to shut down its own production. A common variant of this gene has been found almost exclusively in Ashkenazi Jews that doubles the risk of colorectal cancer in this ethnic group. About 6% of Ashkenazi Jews carry the gene, but the carrier rate rises to about 28% in people who have a family member with colon cancer. This variant is very susceptible to mutation, and the mutated gene promotes the development of a polyp from the cells carrying the gene. In the rare disorder familial adenomatous polyposis (FAP), the APC gene is actually disabled. This causes thousands of polyps to grow in the colon during early adulthood. FAP causes less than 1% of all cases of colorectal cancer; if untreated, however, almost everyone with this condition will develop cancer before the age of 40. A noninherited mutation of the APC gene also occurs in nearly all of those with spontaneous colon cancer.

Another inherited colon cancer, hereditary nonpolyposis colorectal cancer (HNPCC), causes about 5% of all colorectal cancers. This abnormality occurs in genes that error-check DNA; people who inherit the abnormal gene have an extremely high risk of developing colon cancer. People who inherit the HNPCC are also often prone to other cancers, including uterine cancer and possibly breast cancer.

It should be noted, however, that in some cases of hereditary colon cancer, the responsible genetic abnormalities have not yet been identified.

Alcohol and Smoking.
A recent study found that people who both drink alcohol and smoke are at least three times more likely to develop colorectal cancer than people who neither smoke nor drink. People with diets rich in vegetables and fruits who drink moderately do not seem to have an increased risk, but the risk of colorectal cancer for smokers is higher than for nonsmokers and increases the more and longer a person smokes.

Weight and Height.
A 1998 study showed that obesity, weight gain, and large weight changes are all associated with the development of polyps in the colon and rectum. Obesity seems to increase risk particularly if excess body weight is concentrated around the waist. Lifestyle factors, such as a high fat diet and a lack of physical exercise, may provide one link between weight gain and colon cancer. A recent survey found that taller men (73 inches or more) also had a higher risk than shorter men (68 inches or less) did.

Other Medical Conditions.
Experiencing constipation at least weekly and using laxatives is associated with an increased risk for colon cancer. Certain intestinal disorders increase risk, including ulcerative colitis and inflammatory bowel disease. People with diabetes, particularly men, also may have a slightly increased risk for colon cancer. Polyps in the colon increase risk, even if they are benign. People who have had ureterosigmoidostomy, a surgical procedure to correct a birth defect in the bladder or to treat some bladder cancers, have a 5% to 10% chance of developing colon cancer 15 to 30 years after the operation, because tumors may develop near the site of the implant chronically exposed to urine and feces.

Environmental Factors.
Asbestos workers and those exposed to high levels of radiation have a higher risk for colorectal cancer. A recent study also found an association between high exposure to electrical fields and colorectal cancer.

Stress.
In one study, people suffering stressful events experienced three to five times the risk of colon caner compared to those not undergoing unusual stress. (Work stress seemed to be particularly harmful.) Some tumor formation in laboratory animals has been shown to be affected by stress, but there is no firm evidence that stress contributes to cancer in humans.

Family History and Genetic Testing.
A family history of colon cancer is an extremely important factor in estimating risk. The recent discovery of the variant APC gene in people of Ashkenazi Jewish descent has caused great concern in this population. Experts do not recommend genetic screening in people in this group who do not have a family history of colon cancer. Some believe that even in Ashkenazi Jews who have a family history of colon cancer, genetic screening is probably not necessary, since other screening tests and preventive procedures are already in place for people who have an inherited risk. Genetic testing results are not always accurate; a result that indicates the presence of the gene does not necessarily mean that cancer will develop and a negative result does not always mean a person is safe from the cancer. Tests for the FAP and HNPCC genes pose similar issues.

Screening Tests.
Screening is extremely important to detect premalignant polyps and early colorectal cancers in order to allow their removal. If cancer is discovered early with screening tests, survival rate is as high as 90%, survival rates are much lower for those whose cancers are not diagnosed until symptoms such as obstruction or anemia develop. Fewer than 20% of American adults are screened for colorectal cancer, and according to two separate 1997 surveys, many primary care physicians use the screening tests inappropriately; sigmoidoscopy is especially underused. Only a minority of adults over 49 (mostly in the upper socioeconomic group) has regular screening tests that could detect a cancer early enough for curative treatment. A survey reported that many people weren't screened because they were too embarrassed and revealed that they would rather lose months off their life than face these tests. Those who had already had the tests were willing to have them again if they saved one additional day of their lives. [For general screening guidelines, see Box below.]

Digital Rectal Examination.
The digital rectal examination may detect tumors in the rectum and lower intestine as well as prostate cancer in men. The doctor inserts a lubricated-gloved finger into the patient's rectum and feels for lumps or other abnormalities. The exam is quick and painless but embarrassing for some and far from infallible.

Stool Examination for Occult Blood.
Blood in bowel movements is not always visible; in which case it is called occult blood. Fecal occult blood tests (FOBT) are used to detect this hidden blood. The most common method using FOBT is called the quaiac-based test. The patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on specially treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue. Because the reaction depends on the presence of iron in the blood, patients should not take iron supplements or eat red meats, which are rich in iron, several days before the test. During this period, they should also avoid eating certain raw fruit and vegetables, including cauliflower, horseradish, radishes, melons, and turnips, which contain the chemical peroxidase and can cause a positive test reaction even if no blood is present. People should delay the test if they are experiencing bleeding from other causes, such as menstruation, hemorrhoids, gingivitis, or urinary infections.

Aspirin and other NSAIDs can cause minor bleeding and should not be taken for a week before the test. Vitamin C and foods rich in this vitamin may cause a false negative reaction and should be avoided a few days before the test. A positive result to the test that shows the presence of hidden blood, however, is still no cause for alarm; about 20% to 30% of people with occult blood have noncancerous polyps or other conditions, such as gastritis, and only 5% to 10% actually have cancer. Any abnormal result requires further tests. Some experts also argue that the test misses too many cancers and should not be relied on. Controversy has been on-going as to whether this test is too inaccurate to be very beneficial, both in missing cancers and in showing false positive results that lead to invasive and expensive tests, most of which turn out to be unnecessary. Large recent studies, however, are proving that this simple test does indeed save lives, reducing the risk of dying from colon cancer by 15% to 18%; one study reported that it reduced colon cancer morality rate by a third, but some experts question these high results. Accuracy is improved with the addition of another test called HemeSelect, although it adds to the expense. Compliance is also a major problem. Patients are asked to perform the tests at home and send the test cards to the laboratory; only 35% to 50% of patients actually follow through. Occult-blood tests that give results at home are available but are extremely inaccurate. In one large study, these tests failed to detect advanced cancer in about 62% of cases, although they may detect some early cancers.

Colonoscopy, Sigmoidoscopy, and Other Techniques Used to Visualize the Colon.
If a digital rectal examination or occult blood tests show signs of trouble, several methods to visualize the colon are available, including sigmoidoscopy, colonoscopy, or a double-contrast barium enema. Sigmoidoscopy can only view the rectum and the left side of the colon, while colonoscopy and barium enemas allow a view of the entire large intestine. Individuals should discuss with their physician the risks and benefits of these screening procedures. Some controversy exits over how often people without risk factors for cancer should be screened and which detection method should be used for them [see Box, below]. Both flexible sigmoidoscopy and colonoscopy involve snaking a fiberoptic tube through regions of the rectum and colon to view the walls of the intestine. During either procedure, the physician is able to remove polyps or other abnormalities revealed by these procedures. Sigmoidoscopy lasts about 10 minutes and may be mildly uncomfortable, but it is not painful. This procedure has been found to reduce the risk of fatal cancers in the rectal and sigmoid area by 60%. It should also be noted that sigmoidoscopy would miss right-colon cancer, which has dramatically increased in African American men in recent years. About 72% of hereditary nonpolyposis colorectal cancers are out of the view of a sigmoidoscope. When a whole view of the colon is indicated, either colonoscopy or a barium enema is required. Colonoscopy is more expensive and requires a sedative, although it is still performed on an outpatient bases. The double-contrast barium enema, which uses an x-ray image, is the less expensive alternative for viewing the entire colon, but it is also not as accurate, and if any polyps or abnormalities are revealed on x-ray, a colonoscopy is then required to remove suspicious tissue. A colonoscopy also avoids the risk of radiation, although it should be noted that even a colonoscopy does not detect all cancers. Studies have reported a 76% to 90% decrease in colorectal cancers in people who were regularly screened with colonoscopy and who had all colonic polyps removed during the procedure, even those that were benign. In addition, no deaths were reported from cancers that were detected during screening. Theoretically, then, examinations every three years with colonoscopy with removal of any polyps could wipe out nearly all colorectal cancers. Some risk for perforation or other complications exist, however, and most polyps found during an examination are not cancerous. It is difficult, therefore, to justify the high cost of colonoscopy for most people, particularly those without a family history and who have a healthy lifestyle.

Experimental screening and diagnostic methods under investigation include filling the colon with liquid and viewing it using ultrasound. This has been effective in some cases, but its value is inconsistent and not yet fully proven. Another promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. The procedure involves pumping air into the colon and scanning it using computed tomography (CT). The procedure is very safe, takes only 10 minutes, and can identify most polyps that are larger than half an inch. It is also potentially less expensive than colonoscopy. As with barium enemas, however, colonoscopy is required if suspicious areas are found, which may occur frequently with CT procedure, since it erroneously identifies a high number of nonexistent polyps.

Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).
Since the enzymes cyclooxygenases (COX1 and COX2) are thought to promote the development of colorectal cancers through production of prostaglandins, it is intriguing to speculate that drugs that inhibit these enzymes may retard the growth of these cancers. Aspirin and other so-called nonsteroidal anti-inflammatory drugs (NSAIDs) are such drugs. In addition to aspirin many are available, including ibuprofen (Motrin, Advil, Nuprin, Rufen) and naproxen (Aleve). Studies are finding that taking aspirin or other NSAIDs at doses similar to those taken by arthritic patents for pain protection confers protection against colon cancer, although lower doses (325 mg a day) do not appear to offer protection. One study reported that a suppository containing the NSAID indomethacin caused regression of rectal polyps in people with familial adenomatous polyposis. The NSAID sulindac, commonly used for arthritis, causs regression of adenomatous polyps. The drug is effective in reducing polyp size in people with familial adenomatous polyposis, although the polyps resume progression when the drug is stopped. The drug may also prove to be useful for people with noninherited polyps. It should be noted that NSAIDs, even in low doses, can cause gastrointestinal bleeding and ulcers in some people. New aspirin-like drugs, including celecoxib (Celebra) and another (Vioxx) are being developed to target cyclooxygenase 2 (COX2). Such drugs may allow high doses without the accompanying gastrointestinal side effects, thereby possibly conferring protection against colon cancer.

General Guidelines for Screening for Colon and Rectal Cancers.
*People at age 50 and over who have no symptoms and no family history of colon cancer (or possibly also no family history of benign polyps) should have an annual digital rectal exam (DRE) and fecal occult blood test (FOBT). Every five years they should have flexible sigmoidoscopy. Experts generally recommend follow-up colonoscopy if sigmoidoscopy reveals multiple polyps, polyps that show precancerous signs, or polyps larger than 11 millimeters. If such polyps are present, even if they are benign, colonoscopy should be repeated a year later. If polyps are not present, then patients should continue to have a sigmoidoscopy every five years. A barium enema or colonoscopy should replace sigmoidoscopy every five to ten years.

*People who have no symptoms but have one or more close relatives with colon cancer (and possibly a family history of benign colorectal polyps) should begin the same screening regimen with a barium enema or colonoscopy every five years beginning at age 40 or ten years before the youngest case in the family, whichever is earlier.

*People with a history of familial adenomatous polyposis (FAP) should have a DRE and colonoscopy beginning at age 10. Those with hereditary nonpolyposis colorectal carcinoma (HNPCC) should have the same tests performed beginning in adolescence. In both groups the tests should be repeated every three years if there are no polyps and every year if polyps are present. Consider genetic testing.

*Adults at any age without a family history but with symptoms of colon cancer (including rectal bleeding, pain, anemia) should have a DRE, FOBT, and colonoscopy or barium enema; if results are negative these patients should be tested every three to five years. If polyps are present they should have a repeat colonoscopy the following year.

*People with predisposing intestinal problems such as ulcerative colitis or Crohn's disease should consider annual screening with colonoscopy beginning as early as age 25.

Vitamins and Other Nutrients.
Studies on benefits of vitamin supplements for protection against colorectal cancer have been discouraging. A 1994 study of patients who have been treated for colorectal cancer found that after fur years there was absolutely no difference in the rate of recurring cancer between those who took antioxidants C,E, and beta carotene and those who took no supplements. The B vitamins folic acid and B12 convert the amino acid homocysteine to methionine, a chemical that protects certain genes that help prevent cells from becoming malignant. Folic acid, which is found in beans, citrus fruits, and green vegetables, has been found to be protective in some studies. Carotenoids are nutrients that seem to be particularly important. Studies have found that the carotenoid lycopene, found in red fruits and vegetables, may protect against colon and bladder cancer. Sulphoraphane is a cancer-fighting nutrient found in broccoli, cauliflower, and other similar vegetables. Eating foods that contain these nutrients is the best way to lower the risk for colon cancer. Foods that contain valuable nutrients can be identified by colors: dark green (broccoli, spinach, kale, collard greens, mustard greens); red (red pepper, tomatoes, watermelon, and pink grapefruit); and yellow-orange (carrots, pumpkin, sweet potatoes, oranges, tangerines). People should strive to eat five to nine daily servings of fruits and vegetables. Green tea may also have protective substances.

High-Fiber
Diets high in fiber appear to reduce risk. A recent study identified the fatty-acid butyrate--a byproduct of fiber fermentation--as a possible agent for this protection. Fiber also reduces the time it takes food to pass through the large intestine, thereby decreasing exposure of the intestinal wall to carcinogens in food. Fiber also increases the bulk of stools, thus decreasing the concentration of carcinogens in waste matter; it also removes bile acids which can cause mutations in healthy cells. In one study people on high-fiber diets showed no decrease in the number of new polyps, but it did indicate that such diets might prevent polyps from becoming larger and therefore more dangerous.

Fat and Protein Intake.
A number of studies have found an association between saturated fats (animal fats and tropical oils) and colon cancer. Some experts believe that it is only the particular type of fatty acid found in red meat, not all animal fat, that raises the risk for colon cancer, although one animal study conducted in Texas did not confirm this risk. Just cooking meat, particularly by barbecuing it, increases the amount of carcinogens (although one study found that marinating chicken in almost any liquid except water appears to limit the amount of carcinogens produced by barbecues). Fish oil consumption appears to lower risk and monounsaturated oil (olive oil) may be weakly protective. In other studies of people under 67 years old, the amounts of fat and protein were less important than the total number of calories consumed; the higher the energy intake, the greater the risk for developing colon cancer. In older adults, high calorie intake did not make any significant difference. It should be noted, however, that most studies on dietary habits rely on personal recollection and bias. More scientific studies are needed, but until results are in the best advice is to avoid fatty foods and cut down on red meat and increase intake of fiber-rich fresh fruits and vegetables.

Dairy Products and Calcium.
Some studies have reported that calcium intake protects against colon cancer and may even offset some of the risks from fats. One study found that colorectal patients who took multivitamins, calcium, and vitamin E together or separately had a lower rate of recurrence of polyps than those who did not take these supplements. A recent major analysis of studies found no association between calcium intake and protection, however, although milk itself, particularly fermented milk (buttermilk, yogurt), may have compounds that help protect against colon cancer. May dairy products are fortified with vitamin D, which has also been associated with protection from colon cancer. It should be noted that many studies report little or no protection from any of these foods and nutrients; the benefits, if any, are probably very modest.

Selenium.
Selenium is a trace element in meats, whole grains, egg yolks, fish, and some other foods, such as Brazil nuts. In one study, people who took daily selenium supplement of 200 micrograms for more than four years had half the rate of lung, colon, rectal, and prostate cancer as those who did not. The study had limitations, however, and high amounts can be toxic, causing hypothyroidism and hair and nail loss. Experts are working on a synthetic form that may be effective and safe in high doses.

Coffee.
Studies conducted in a number of countries have found that drinking four or more cups of coffee a day is associated with a lower risk for colorectal cancer.

Exercise.
A recent major survey found that men who exercise even moderately (equal to about an hour of running per week) reduced their chance for colon cancer. The most active group had half the risk of colon cancer of those who didn't exercise. Many other studies have demonstrated the protective effects of regular exercise.

Estrogen.
Studies have indicated that hormone replacement therapy, with or without progesterone, cuts the risk of colon cancer by over a third to a half. (Estrogen may increase the risk for other cancers, including uterine, breast, and ovarian, and women should discuss their own individual risk factors with their physician.) Use of oral contraceptives also may protect against the development of colon cancer. It should be recognized that these findings repreliminary and need to be confirmed by other studies before being regarded as proven.

A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments.

Determining Prognosis after Diagnosis.

Staging.
Unlike many other cancers, the size of the tumor is not a major factor in determining the outcome of colorectal cancer. Of greater importance is how far the cancer has spread. To determine this, physicians will assign a stage to the tumor. There are several methods for staging. The older system, known as Dukes', categorized four basic stages: A, B, C, and D. A more recent system refers to these stages as I, II, III, and IV, and divides the categories slightly differently. In Stage A or I, the tumor has gone no deeper than the mucous layer at the surface of intestinal wall. The five-year survival at this point is more than 90%. (The term "five-year survival" means that patients have lived at least five years since diagnosis.) If the tumor has gone to Stage B or II, it has penetrated into or through the intestinal wall but has not reached the lymph nodes, and give-year survival ranges from 70% to 85%. In Stage C or III, the lymph nodes are involved, and the survival rate drops to 65% or below. In Stage D or IV, the tumor has metastasized and spread to other organs, usually the liver first, and the disease is generally considered incurable.

Tumor Markers.
Carcinoembryonic antigen (CEA) is a tumor marker, a protein that is found in high levels in blood samples when advanced colon cancer is present. It is not an accurate screening test for colon cancer because it is also elevated in people with other cancers or certain noncancerous health conditions. In addition, CEA levels rise only after the cancer has reached late Stage II. In general, physicians use this tumor marker before surgery to help determine the patient's prognosis. After an operation, it is used to determine whether the procedure has fully removed the cancer and, later, it may be helpful in detecting recurrence of the cancer and as one measure of response to treatment. The presence of a defective p53 gene is a marker for very poor prognosis in patients with advanced colon cancer. (In its normal state, the gene is important for regulation of cell growth.) Other sensitive markers under investigation are cancer antigen 19-9 (CA19-9), matrix metalloproteinase-9 (MMP-9) RNA, HER-2/neu oncoprotein, and CD44.

At this time, the five-year survival rate for those undergoing surgery for colon cancer is as high as 90% for cancers that have not spread to the lymph nodes. When cancer has spread, survival ranges from 69% to 27% depending on the number of nodes affected. Unfortunately, because many cancers are detected at later stages, the overall survival is currently abut 50%. Age is not a factor in treatment success; good survival rates are achieved in the elderly as well as in young people. Chances for survival are less if the intestine is obstructed or perforated. If cancer has spread beyond the intestine (but not beyond the lymph nodes that drain from it), the outlook is better if three or less lymph nodes are involved. It is important to note that treatment can prolong life ever when cancer has spread.

An estimated 56,000 Americans are expected to die from colon or rectal cancer in 1998; only lung cancer is responsible for more cancer deaths. On the positive side, over the past 20 years the mortality rate from colorectal cancers has dropped by 25% in women and 13% in men. While the mortality rate from colorectal cancers has declined in whites, it has risen in African Americans, who now have a 50% higher chance of dying from the disease than whites have. It should be noted that when the two groups are compared at the same socioeconomic and educational levels, then the incidence is higher in whites. One reason then for the overall lower survival rate in African Americans is undoubtedly later detection due to limited access to care. Recent studies have also shown, however, that right-sided colon cancer, which is harder to detect, has increased sharply in the past decade in African American men.

Surgical removal of the colon or rectal tumor along with any affected surrounding tissue is the standard treatment for potentially curable colorectal cancers. Chemotherapy (drug therapy) and radiation are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.

Local Excision or Polypectomy.
Early cancers that have not invaded the mucous membrane of the intestine and precancerous polyps may be removed by a colonoscopy. During the procedure a tube is inserted through the rectum into the colon and the tumor or polyp is cut out. Slightly larger areas may need to be removed using abdominal surgery, a procedure known as a segmental resection. When the cancer is in these early stages, surgery cures almost all patients and there are minimal side effects from the treatment. For early-stage rectal cancer, a treatment called electrocoagulation that destroys tumors using high frequency electric current is being tested.

Surgery.
Once the cancer has gone beyond the mucous membrane and has penetrated into or through the intestinal wall, an operation known as colectomy is the standard treatment of colon and rectal cancers. This involves removing the cancerous part of the intestine and nearby lymph nodes and then reconnecting the intestine using what is known as anastomosis. If the surgeon cannot sew the ends together because of infection or obstruction, an opening called a stoma will be made through the abdominal wall to which the colon is connected for elimination of feces (colostomy). It may have one opening (single-barreled) or there may be two loops opening through the skin (double-barreled). Usually the colostomy is temporary and can be reversed by a second operation. However, in about a third of cases, the cancer occurs in the lower part of the rectum where between 70% and 80% of cancers have spread beyond the rectal wall. In such cases, a radical resection is required, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed. In these cases, the colostomy is permanent and the patient requires a colostomy bag. An alternative technique called coloanal anastomosis reconstructs the area to avoid the need for colostomy, and may be appropriate in selected patients.

Rates for recurring rectal cancer are still high, about 28%, if surgery is used alone, although some medical centers that use a new technique known as total mesorectal excision (TME) are reporting average recurrence rates as low as 5%. TME removes the entire wall of the rectum in one intact unit. It also helps to preserve nerve function and to reduce the risks for sexual dysfunction and bladder complications, which often occur after rectal surgery. Other side effects of colon surgery include diarrhea, irregular bowel movements, and a sense of urinary urgency. Most patients do not experience fecal incontinence. Research is ongoing to discover effective combinations and the best sequences of surgical, radiation, and chemotherapeutic treatments to improve survival and reduce recurrence rates.

Drug Therapy.
Chemotherapy uses drugs that kill cancer cells throughout the body. It is not beneficial when used as the sole therapy for colorectal cancers, but certain drug combinations may prolong life when given after surgery. Chemotherapy administered in this way is known as adjuvant therapy. The object of this treatment is to knock out any cancer cells that surgery may have missed and prevent recurrence. Adjuvant chemotherapy is particularly effective for Stage III patients. Some do not recommend it for Stage II patients, unless they are at high risk for recurrence, because patients at this stage usually have a more favorable prognosis, so the benefits of adjuvant therapy may not offset the adverse drug effects. High risk Stage II cancers that might benefit from adjuvant therapy are those that have obstructed the bowel, perforated the intestinal wall, or adhered to structures outside the intestine.

Adjuvant therapy using 5-fluorouracil (5-FU) with levamisole or with leucovorin appears to be the best current treatment for reducing recurrence rates and improving survival. Leucovorin, also called folinic acid, a form of the B vitamin folic acid, is particularly effective in combination with 5-FU, and a recent study reported a 25% reduction in mortality rate with the use of these drugs. At the present time, common adjuvant drug therapy after surgery consists of three to 12 months of 5-FU combined either with levamisole or leucovorin. Semustine and vincristine are drugs that have also been used in combination with fluorouracil but are not as effective. 5-FU is given intravenously at present, but oral preparations are currently being tested in clinical trails.

A number of treatments known as immunotherapy are under investigation. These approaches use the body's own disease fighters to attack the cancer. Immunotherapy attempts to enhance defense systems or to aim them at tumor cells. Of particular interest is the antibody 17-A, which attacks a protein located in colon cancer cells. In one study of patients with Stage III cancer, use of the antibody after surgery improved long-term survival and reduced recurrence of the cancer. Side effects of this treatment are malaise, low-grade fever and chills, and gastrointestinal distress. Other experimental therapies include interleukin-2(IL-2), which stimulates white blood cells to attack and destroy cancer tissue, interferon, and vaccines that use genetic materials from cancer factors to launch an immune attack.

Radiation.
Radiation treatment is particularly important for patients with rectal cancer in late Stages II and III, because cancer tends to recur near the site of the original cancer in 30% to 40% of these patients. Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered externally by an x-ray machine, by passing radioactive pellets through thin plastic tubes inserted into the intestine, or by implanting tiny radiation seeds directly into the tumor. New computer imaging techniques providing 3-dimensional pictures of the cancerous area are allowing precise targeting of radiation to the tumor. Combining radiation with chemotherapy after surgery extends disease-free intervals and ever survival. This regimen is very toxic, but the side effects may be outweighed by longer symptom free time.

Until recently, radiation used after surgery has been the standard procedure to achieve further benefits. Recently, however, studies are showing that, in some cases, the use of radiation before surgery, known as neoadjuvant radiation therapy, is showing survival and recurrence reduction rates equal to or even, in some cases, better than postoperative radiation. Preoperative radiation allows lower doses than postoperative radiation to achieve he same effectiveness. Radiation therapy is also being used during surgery, a technique called intra-operative radiotherapy (IORT), which allows the surgeon to move healthy tissue out of the path of the radiation beam. Side effects of radiation tend to progress as treatment continues; they include fatigue, bowel movement problems, incontinence, diarrhea, and skin irritation around the anus. Long-term complications include an increased risk for bowel obstruction, blood clotting problems, and hip and pelvic fractures.

To detect recurring cancer after treatment has been completed, periodic sigmoidoscopy, CEA blood tests, and barium enemas or colonoscopies are performed. One study reported that aggressive testing, including yearly colonoscopy, ultrasound every six months, and annual CT scans, tended to pick up recurrence earlier but did not significantly reduce the mortality rate.

Patients with colostomies must learn how to care for the stoma and keep the area sanitary. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which has a special glue to stick to the skin. Adjusting to cancer is difficult enough. The psychologic burdens of dealing with a permanent colostomy and other side effects of treatment only add to the distress. Men tend to have more emotional difficulties dealing with permanent colostomies than women do. In one study, the four major concerns after treatment were the following: (1) fear of being unable to care for themselves; (2) leakage from the pouch, odor, and gas; (3) other health problems; and (4) recurrence of cancer. The potential side effects of sexual and bowel dysfunction for colorectal patients can also be devastating. Colon cancer patients without a colostomy are at lower risk for these problems than patients with rectal cancer whose sphincter muscles are affected, but no one is immune to the psychologic repercussions of cancer and its consequences. Cancer affects the emotional life of all patients, and positive emotions play a strong role in recovery. It is very important to discuss all aspects of treatment that affect the quality of life and to seek support groups or therapy that will help the patient.

Treatment of Recurrent and Metastasized Colon Cancer.

The treatment for metastasized cancer (Stage IV) is intended to make the patient comfortable, reduce the risk of developing complications, and if possible, prolong life, since a cure is unlikely. Surgery to remove or bypass obstructions in the intestine may be performed. It may be possible to remove tumors surgically from areas to which the cancer has spread, such as the liver, ovaries, and lung. The liver is the first and most common site to which colon cancer spreads. If the tumors in the liver are operable, a cure rate of up 20% has been reported and survival is enhanced in many. Physicians have attempted to target liver tumors using chemotherapy administered with implanted pumps. It is possible to shrink swollen painful livers this way, but to date it is not clear whether survival rates are improved. Other investigative techniques used to destroy liver tumors include cryosurgery (which freezes the cancer tissue), radiation, and embolization.

Chemotherapy and radiation are generally used to reduce symptoms in advanced cancer; at late stages, they rarely prolong life. In addition to its use in adjuvant therapy, 5-fluorouracil (5-FU) is also used to treat metastatic colon cancer. Only about 20% of patients gain a significant benefit. Irinotecan (Campto or CPT-11) inhibits an enzyme essential for cell division; it is one of the first drugs developed specifically for colon cancer in 30 years and has recently been approved. In three studies, the drug reduced tumor size for sic months in 13% of patients with advanced cancer. Side effects include diarrhea, sometimes very severe, and a drop in white blood cells (leukopenia.) Patients who have previously responded to 5-FU are likely to respond better to irinotecan than those who had a poor response to 5-FU. Tomudex is a similar drug. Other drugs being tested include methotrexate, carmustine, lemustine, and tegafur. One interesting study reported that in mice the use of vitamin E or another antioxidant pyrrolidinedithiocarbamate (PDTC) enhanced the cell-killing properties of 5-FU. Side effects of chemotherapy may include nausea and vomiting, fatigue, diarrhea, and partial hair loss. Timing of drug administration when the patient's metabolism most effectively processes the medications may help decrease side effects by allowing lower dosage. Studies are promising.

American Cancer Society
1599 Clifton Road, NE
Atlanta, GA 30329

call (800) ACS-2345 or (404) 320-3333 or on the Internet (http://www.cancer.org)

In addition to offering information, the ACS has a number of educational programs and informational materials. Call the American Cancer Society for local chapters of the American Cancer Society.

National Cancer Institute

The NCI has help line open during working hours:  call (800) 4-CANCER or (800) 422-6237. The NCI offers free information on all aspects of cancer. It also offers CancerFax. This excellent service provides immediate free faxes on the latest detailed information for cancer treatment for both patients and physicians. Also included in the information packet is a complete list of U.S. cancer centers and hospitals. Call (301-402-5874) and request code #200008 for patient information or #100008 for physician information on colon cancer; and #200076 for patient information or #100076 for physician information on rectal cancer. For information on prevention, request #304731 and for screening, 3304726. To use this service, the call must be made directly from a fax machine.

United Ostomy Association
36 Executive Park
Suite 120
Irvine, CA 92614-6744;

Call (800) 826-0826) or (714) 660-8624

This organization refers people to local support group chapters. They offer many free publications about ostomy care and management and have also a subscription to bimonthly magazine Ostomy Quarterly.

Internet Sites

The best site for colon cancer is http://cancer.med.upenn.edu/disease/colon/. The general site is called Oncolink and it provides excellent links and in-depth free information. Included in their information links for colon cancer are the National Cancer Institute's patient and physician information sheets. They also provide abstracts of the latest research.

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Modified November 12, 1999 - Four M Engineering, Inc