Cancer of the colon is the disease characterized by the development of malignant cells in the lining or epithelium of the first and longest portion of the large
Synonyms for the colon include the large bowel or the large intestine. The rectum is the continuation of the large intestine into the pelvis that terminates in the anus.
The colon is a tubular organ beginning in the right lower aspect of the abdomen. Anatomically, it ascends on the right side of the abdomen, traverses from right to left in the upper abdomen, descends vertically down the left side, takes an S-shaped curve in the lower left abdomen, and then flows into the rectum as it leaves the abdomen for the pelvis. These portions of the colon are named separately though they are part of the same organ.
- cecum, the beginning of the colon
- ascending colon, the right vertical ascent of the colon
- transverse colon, the portion traversing from right to left
- descending colon, the left vertical descent of the colon
- sigmoid colon, the s-shaped segment of colon above the pelvis
These portions of the colon are recognized anatomically based on the arterial blood supply and venous and lymphatic drainage of these segments of the colon. Lymph, a protein-rich fluid that bathes the cells of the body, is transported in small channels known as lymphatics that run alongside the veins of the colon. Lymph nodes are small filters through which the lymph travels on its way back to the blood stream. Cancer can spread elsewhere in the body by invading the lymph and vascular systems. Therefore, these anatomic considerations become very important in the treatment of colon cancer.
The small intestine is the continuation of the upper gastrointestinal tract responsible for the transport of ingested nutrients into the body. The waste left after the small intestine has completed absorption of nutrients amounts to a few liters, (about the same as quart), of material per day and is directly delivered to the colon, (at the cecum), for processing. Physiologically, the colon is responsible for the preservation of fluid and electrolytes as it propels the increasingly solid waste towards the rectum and anus for excretion.
When cells lining the colon become malignant, they first grow locally and may invade partially or totally through the wall of the bowel and even into adjacent structures and organs. In the process, the tumor can penetrate and invade the lymphatics or the capillaries locally and it gains access to the circulation. As the malignant cells work their way to other areas of the body, they again become locally invasive in the new area to which they have spread. These tumor deposits, originating from the colon primary tumor, are then known as metastases. If metastases are found in the regional lymph nodes from the primary, they are known as regional metastases, or regional nodal metastases. If they are distant from the primary tumor, they are known as distant metastases. The patient with distant metastases has systemic disease. Thus the cancer originating in the colon begins locally and, given time, can become systemic in its extent.
By the time the primary tumor is originally detected it is usually larger than one cm, (about 3/8 inches), in size and has over a million cells. This amount of growth itself is estimated to take about three-seven years. Each time the cells double in number, the size of the tumor quadruples. Thus like most cancers, the part that is identified clinically is later in the progression than would be desired and screening becomes a very important endeavor to aid in earlier detection of this disease.
There are about 94, 000 cases of colon cancer diagnosed per year in the United States. Together, colon and rectal cancers account for 10% of cancers in men and 11% of cancers in women. It is the second most common site-specific cancer affecting both men and women. (Lung cancer is the first affecting both men and women, breast is the leader in women and prostate the leader in men). Nearly 48, 000 people died from colon cancer in the United States in 2000. In recent years the incidence of this disease is decreasing very slightly, as has the mortality rate. It is difficult to tell if the decrease in mortality reflects earlier diagnosis, less death related to the actual treatment of the disease, or a combination of both factors.
Cancer of the colon is thought to arise sporadically in about 80% of those who develop the disease. 20% of cases are thought to have genetic predisposition that ranges from familial syndromes affecting 50% of the off-spring of a mutation carrier, to a risk of 6% when there is just a family history of colon cancer occurring in a first degree relative. Development of colon cancer at an early age, or at multiple sites, or recurrent colon cancer suggests a genetically transmitted form of the disease as opposed to the sporadic form.
Causes and symptoms
Causes of colon cancer are probably environmental in the sporadic cases, (80%), and genetic in the heredity predisposed cases (20%). Since malignant cells have a
Colon cancer is more common in industrialized nations and diets high in fat, red meat, total calories, and alcohol seem to predispose. Diets high in fiber are associated with a decreased risk. The mechanism for protection by high-fiber diets may be related to less exposure of the colon lining to carcinogens from the environment, as the transit time through the bowel is faster with a high-fiber diet than it is with a low fiber diet.
Age plays a definite role in the predisposition to colon cancer. Colon cancer is uncommon before age 40. This incidence increases substantially after age 50 and doubles with each succeeding decade.
There is also a slight increase risk for colon cancer in the individual who smokes.
As for genetic predisposition, on chromosome 5, there is a gene called the APC gene associated with the familial adenomatous polyposis syndrome. There are multiple different mutations that occur at this site, yet they all cause a defect in tumor suppression that results in early and frequent development of colon cancer. This genetic aberration is transmitted to 50% of offspring and each of those affected will develop colon cancer, usually at an early age. There is another syndrome, hereditary non-polyposis colon cancer (also known as Lynch syndrome), related to mutations in any of four genes responsible for DNA mismatch repair. In patients with colon cancer, the p53 gene is mutated 70% of the time. When the p53 gene is mutated and ineffective, cells with damaged DNA escape repair or destruction. This allows for the damaged cell to perpetuate itself, and continued replication of the damaged DNA may lead to tumor development. Though these syndromes have a very high incidence of colon cancer, family history without the syndrome is also a substantial risk factor. When considering first-degree relatives, history of one with colon cancer raises the baseline risk of 2% to 6%. (Most physicians think that this baseline is about 4%.) The presence of a second raises the risk to 17%.
The development of polyps of the colon almost always precedes the development of colon cancer by five or more years. Polyps are benign growths of the colon lining. They can be unrelated to cancer, precancerous, or malignant. Polyps, when identified, are removed for diagnosis. If the polyps are benign, the patient should undergo careful surveillance for the development of more polyps or the development of colon cancer.
Colon cancer causes symptoms related to its local presence in the large bowel or by its effect on other organs if it has spread. These symptoms may occur alone or in combination:
- a change in bowel habit
- blood in the stool
- bloating, persistent abdominal distention
- a feeling of fullness even after having a bowel movement
- narrowing of the stool—so-called ribbon stools
- persistent, chronic fatigue
- abdominal discomfort
- unexplained weight loss
- and, very rarely, nausea and vomiting
Most of these symptoms are caused by the physical presence of the tumor mass in the colon. Similar symptoms can be caused by other processes; these are not absolutely specific to colon cancer. The key is recognizing that the persistence of these types of symptoms without ready explanation should prompt the individual to seek medical evaluation.
Many of the symptoms are understood by remembering that the colon is a tubular conduit. If a tumor
Of all of the major cancers, only colorectal cancer can be prevented by screening. In all other cancers (breast and prostate, for example), screening tests look for small, malignant lesions. Screening for colorectal cancers, however, is the search for pre-malignant, benign polyps. This screening can be close to 100% effective in preventing cancer development, not just in detecting small cancers.
Screening involves physical exam, simple laboratory tests, and the visualization of the lining of the colon. The ways to visualize the colon epithelium are with x rays (indirect visualization), and endoscopy (direct visualization).
The physical examination involves the performance of a digital rectal exam (DRE). The DRE includes manual examination of the rectum, anus and the prostate. During this examination, the physician examines the anus and the surrounding skin for hemorrhoids, abscesses, and other irregularities. After lubricating the gloved finger and anus, the examiner gently slides the finger into the anus and follows the contours of the rectum. The examiner notes the tone of the anus and feels the walls and the edges for texture, tenderness and masses as far as the examining finger can reach. At the time of this exam, the physician checks the stool on the examining glove with a chemical to see if any occult (invisible), blood is present. At home, after having a bowel movement, the patient is asked to swipe a sample of stool obtained with a small stick on a card. After 3 such specimens are on the card, the card is then easily chemically tested for occult blood also. (The stool analysis mentioned here is known as a fecal occult blood test, or FOBT, and, while it can be helpful, it is not 100% accurate—only about 50% of cancers are FOBT-positive.) These exams are accomplished as an easy part of a routine yearly physical exam.
Proteins are sometimes produced by cancers and these may be elevated in the patient's blood. When this occurs, the protein produced is known as a tumor marker. There is a tumor marker for some cancers of the colon; it is known as carcinoembryonic antigen, or CEA. Unfortunately, this protein may be made by other adenocarcinomas as well, or it may not be produced by a particular colon cancer. Therefore, screening by chemical analysis for CEA has not been helpful. CEA has been helpful when used in a follow-up role for patients treated for colon cancer if their tumor makes the protein.
Indirect visualization of the colon may be accomplished by placing barium through the rectum and filling the colon with this compound. Barium produces a white contrast image of the lining of the colon on x ray and thus the contour of the lining of the colon may be seen. Detail can be increased if the barium utilized is thinned and air also introduced. These studies are known as the barium enema (BE), and the double contrast barium enema (DCBE).
Direct visualization of the lining of the colon is accomplished using a scope or endoscope. The physician introduces the instrument through the rectum and passes it proximally, visualizing the colon epithelium in the process. Older, shorter scopes were rigid. Today, utilizing fiberoptic technology, the scopes are flexible and can reach much farther. If the left colon only is visualized, it is called flexible sigmoidoscopy. When the entire colon is visualized, the procedure is known as colonoscopy.
Unlike the indirect visualizations of the colon (the BE and the DCBE), the endoscopic screeenings allow the physician to remove polyps and biopsy suspicious tissue. (A biopsy is a removal of tissue for examination by a pathologist.) For this reason, many physicians prefer endoscopic screening. All of the visualizations, the BE, DCBE, and each type of endoscopy require pre-procedure preparation (evacuation) of the colon.
The American Cancer Society has recommended the following screening protocol for those of normal risk over 50 years of age:
- yearly DRE with occult blood in stool testing
- flexible sigmoidoscopy at age 50
- flexible sigmoidoscopy repeated every 5 years
Many physicians, however, recommend full colon-oscopy every five to seven years. Screening evaluations should start sooner for patients who have predisposing factors, such as family history, history of polyps, or a familial syndrome.
Evaluation of patients with symptoms
For those whose symptoms prompt them to visit their physician, and if their symptoms could possibly be related to colon cancer, the entire colon will be inspected. The combination of a flexible sigmoidoscopy and double contrast barium enema may be performed but the preferred evaluation of the entire colon and rectum is that of complete colonoscopy. Colonoscopy allows direct visualization, photography, as well as the opportunity to obtain a biopsy of any abnormality visualized. If, for technical reasons, the entire colon is not visualized endoscopically, a double contrast barium enema should complement the colonoscopy.
The diagnosis of colon cancer is actually made by the performance of a biopsy of any abnormal lesion in the colon. When a tumor growth is identified, it could be either a benign polyp (or lesion) or a cancer; the biopsy resolves the issue. The endoscopist may take many samples so as to exclude any sampling errors.
If the patient presents with advanced disease, or has advanced disease at the time of diagnosis, areas where the tumor has spread (such as the liver) may be amenable to biopsy. Such biopsies are usually obtained using a special needle under local anesthesia.
Once a diagnosis of colon cancer has been established by biopsy, in addition to the physical exam, studies will be performed to assess the extent of the disease. Blood studies include a complete blood count, liver function tests, and a CEA. Imaging studies will include a chest x ray and a CAT scan (computed tomography scan) of the abdomen. The chest x ray will determine if there is spread to the lung, the CAT scan will evaluate potential spread to the liver as well as any local invasive characteristics of the primary tumor. If the patient has any neurologic symptoms, a CAT scan of the brain will be performed, and if the patient is experiencing bone pain, a bone scan will also be performed.
The surgeon and the medical oncologist each have a role in therapy that is dictated by the degree of progression
Clinical staging, treatments, and prognosis
Once the diagnosis has been confirmed by biopsy, the clinical stage of the cancer is assigned. Using the characteristics of the primary tumor, its depth of penetration through the bowel, and the presence or absence of regional or distant metastases, stage is derived. Often, the depth of penetration through the bowel or the presence of regional lymph nodes can't be assigned before surgery.
Colon cancer is assigned stages I through IV, based on the following general criteria:
- Stage I: the tumor is confined to the epithelium or has not penetrated through the first layer of muscle in the bowel wall.
- Stage II: the tumor has penetrated through to the outer wall of the colon or has gone through it, possibly invading other local tissue.
- Stage III: Any depth or size of tumor associated with regional lymph node involvement.
- Stage IV: any of previous criteria associated with distant metastasis.
With many cancers other than colon cancer, staging plays an important pre-treatment role to best determine treatment options. In colon cancer, almost all colon cancers are treated with surgery first, regardless of stage. Colon cancers through Stage III, and even some Stage IV colon cancers, are treated with surgery first, before any other treatments are considered.
Surgical removal of the involved anatomic segment of colon (colectomy) along with its blood supply and regional lymph nodes is the primary therapy for colon cancer. Usually, on the basis of the blood supply, the partial colectomies are separated into right, left, transverse, or sigmoid. The removal of the blood supply at its origin along with the regional lymph nodes that accompany it assures an adequate margin of normal colon on either side of the primary tumor. When the cancer lies in a position such that the blood supply and lymph drainage lies between two of the major vessels, both vessels are taken to assure complete radical resection, or removal (extended radical right or left colectomy). If the primary tumor penetrates through the bowel wall, any tissue adjacent to the tumor extension is also taken if feasible.
Surgery is used as primary therapy for stages I through III colon cancer unless there are signs that local invasion will not permit complete removal of the tumor, as may occur in advanced stage III tumors. However, this circumstance is very rare, and occurs in less than 2% of all colon cancer cases.
After the resection is completed, the ends of the remaining colon are reconstructed; the hook-up is called an anastomosis. Once healing has occurred, there may be a slight increase in the frequency of bowel movements. This effect usually lasts only for several weeks. Most patients go on to develop completely normal bowel function.
Occasionally, the anastomosis would be risky and cannot be performed. (Most commonly, this occurs when the bowel could not be adequately evacuated in an emergency circumstance due to bowel obstruction.) When the anastomosis cannot be performed, a colostomy is performed instead. A colostomy is performed by bringing the end of the colon through the abdominal wall and sewing it to the skin. The patient will have to wear an appliance (a bag) to manage the stool. The colostomy may be temporary and the patient may undergo a hookup at a later, safer date, or the colostomy may be permanent. In most cases, emergent colostomies are not reversed and are permanent.
Radiation therapy is used as an adjunct to surgery if there is concern about potential for local recurrence post-operatively and the area of concern will tolerate the radiation. For instance, if the tumor invaded muscle of the abdominal wall but was not completely removed, this area would be considered for radiation. Radiation has significant dose limits when residual bowel is exposed to it because the small and large intestine do not tolerate radiation well.
Chemotherapy is useful for patients who have had all identifiable tumor removed and are at risk for recurrence (adjuvant chemotherapy). Chemotherapy may also be used when the cancer is stage IV and is beyond the scope of regional therapy, but this use is rare.
Adjuvant therapy is considered in stage II disease with deep penetration or in stage III patients. Standard therapy is treatment with fluorouracil, (5FU) combined with leucovorin for a period of 6 to 12 months. 5FU is an antimetabolite and leukovorin improves the response rate. (A response is a temporary regression
Similar chemotherapy may be administered for stage IV disease or if a patient progresses and develops metastases. Results show response rates of about 20%. Unfortunately, these patients eventually succumb to the disease, and this chemotherapy may not prolong survival or improve quality of life in Stage IV patients. Clinical trials have now shown that the results can be improved with the addition of another agent to this regimen. Irinotecan does not seem to increase toxicity but it improved response rates to 39%, added 2-3 months to disease-free survival, and prolonged overall survival by a little over two months.
Prognosis is the long-term outlook or survival after therapy. Overall, about 50% of patients treated for colon cancer survive the disease. As expected, the survival rates are dependent upon the stage of the cancer at the time of diagnosis, making early detection a very worthwhile endeavor.
About 15% of patients present with stage I disease and 85-90% survive. Stage II represents 20-30% of cases and 65-75% survive. 30-40% comprise the stage III presentation of which 55% survive. The remaining 20-25% present with stage IV disease and are very rarely cured.
Alternative and complementary therapies
Alternative therapies have not been studied in a large-scale, scientific way. Large doses of vitamins, fiber, and green tea are among therapies tried. Avoiding cigarettes and alcohol may be helpful. Before initiating any alternative therapies, the patient is wise to consult his/her physician to be sure that these therapies do not complicate or interfere with the established therapy.
Coping with cancer treatment
For those with familial syndromes causing colon cancer, genetic counseling may be appropriate. Psychological counseling may be appropriate for anyone having trouble coping with a potentially fatal disease. Local cancer support groups may be helpful and are often identified by contacting local hospitals or the American Cancer Society.
Clinical trials are scientific studies in which new therapies are compared to current standards in an effort to identify therapies that give better results.
Agents being tested for efficacy in patients with advanced disease include oxaliplatin and CPT-11. Please see reference below for current information available from the National Cancer Institute regarding these clinical trials.
There is not an absolute way of preventing colon cancer. Still, there are steps an individual can take to dramatically lessen the risk or to identify the precursors of colon cancer so that it does not manifest itself. The patient with a familial history can enter screening and surveillance programs earlier than the general population. High-fiber diets and vitamins, avoiding obesity, and staying active lessen the risk. Avoiding cigarettes and alcohol may be helpful. By controlling these environmental factors, an individual can lessen risk and to this degree prevent the disease.
By undergoing appropriate screening when uncontrollable genetic risk factors have been identified, an individual may be rewarded by the identification of benign polyps that can be treated as opposed to having these growths degenerate into a malignancy.
Polyps are growths of the epithelium of the colon. They may be completely benign, premalignant or cancerous. The association of colon cancers in patients with certain types of polyps is such that it is thought that many polyps begin as a benign growth and later acquire malignant characteristics. There are two types of polyps, pedunculated and sessile. This terminology comes from their appearance; those that are pedunculated are on a stalk like a mushroom, and the sessile polyps are broad based and have no stalk. Unless a pedunculated polyp gets large, malignant potential is very small. This type may also be easily removed at colonoscopy, by a snaring technique. (A snare is like a lasso introduced through the endoscope to encircle the polyp at its base and amputate it.) The sessile polyp is also known as a villous adenoma and as many as 1/3 of these harbor a malignancy. Therefore, the villous adenoma is considered premalignant. Sessile polyps may or may not be able to be managed
Polyps commonly present with occult blood in the stool. Since they are associated with the development of cancer, patients who have developed polyps need to enter a program of careful surveillance.
There is an occasional patient who develops a pattern of metastatic disease that is isolated to either the liver or the lung and the deposit appears to be solitary. When patients have this type of pattern of metastatic disease, especially if there has been a long interval between the primary management and the development of metastasis, they may be considered for surgical resection of the isolated metastasis to effect a cure. In carefully selected patients, long-term survival approaching 20% has been achieved.
When a patient has developed metastatic cancer in the liver alone, a technique of administering chemotherapy directly to the liver is sometimes considered. This is called hepatic arterial infusion and requires the placement of a special device into the artery supplying the liver. This method of utilizing chemotherapy has been helpful in carefully selected patients only, and currently is not used as a cure.
Abelhoff, Martin, MD, James O. Armitage MD, Allen S. Lichter MD, and John E. Niederhuber MD. Clinical Oncology Library. Philadelphia: Churchill Livingstone, 1999.
Jorde, Lynn B., Ph.D., John C. Carey MD, Michael J. Bamshad MD, and Raymond L. White, Ph.D. Medical Genetics, Second Edition. St. Louis: Mosby, 1999.
Kirkwood, John M., MD, Michael T. Lotze MD, Joyce M.Yasko Ph.D. Current Cancer Therapeutics, Third Edition. Philadelphia: Churchill Livingstone, 1998
Greenlee, Robert T., Ph.D., MPH, Mary Beth Hill-Harmon, MSPH, Taylor Murray, and Michael Thun, MD, MS. "Cancer Statistics 2001." CA: A Cancer Journal for Clinicians, Volume 51 No. 1 (Jan/Feb 2001).
Saltz, Leonard, et al. "Irinotecan plus Fluorouracil and Leucov-orin for Metastatic Colorectal Cancer." The New England Journal of Medicine Volune 343, No. 13 (September 28, 2000).
American Cancer Society. (800) ACS-2345. <http://www.cancer.org>.
Cancer Information Service of the NCI. (1-800-4-CANCER).<http://wwwicic.nci.nih.gov>.
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Richard A. McCartney, M.D.
—Type of cancer beginning in glandular epithelium.
—surgical reconnection of the ends of the bowel after removal of a portion of the bowel.
—The condition caused by too few circulating red blood cells, often manifested in part by fatigue.
—Substances in the environment that cause cancer, presumably by inducing mutations, with prolonged exposure.
—Cells composing the lining of an organ.
—Channels that are conduits for lymph.
—cellular filters through which lymphatics flow.
—Cells that have been altered such that they have lost normal control mechanisms and are capable of local invasion and spread to other areas of the body.
—Site of invasive tumor growth that originated from a malignancy elsewhere in the body.
—A change in the genetic make up of a cell that may occur spontaneously or be environmentally induced.
—Presence of blood that cannot be seen with the naked eye.
—Localized growths of the epithelium that can be benign, precancerous, or harbor malignancy.
—Surgical resection that takes the blood supply and lymph system supplying the organ along with the organ.
—to remove surgically.
—Posterior bony wall of the pelvis.
—Throughout the body.
Table Of Contents
- Causes and symptoms
- Treatment team
- Clinical staging, treatments, and prognosis
- Coping with cancer treatment
- Clinical trials
- Special concerns
- Adjuvant therapy
- Lymph nodes
- Occult blood
- Radical resection