colon cancer

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Key Terms: Adenocarcinoma, Adjuvant therapy, Anastomosis, Anemia, Carcinogens, Electolytes, Epithelium, Lymphatics, Lymph nodes, Malignant, Metastasis, Mutation, Occult blood, Polyps, Radical resection, Resect, Sacrum.

Definition

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 intestine. Malignant cells have lost normal control mechanisms governing growth. These cells may invade surrounding local tissue or they may spread throughout the body and invade other organ systems.

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.

Description

The colon is a tubular organ beginning in the right lower abdomen. 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 bloodstream. 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 carrying 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. The colon is responsible for the preservation of fluid and electrolytes as it propels the increasingly solid waste toward 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 gain 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.

By the time the primary tumor is originally detected it is usually larger than one cm (about 3/8 in) in size and has over one 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.

Demographics

There are at least 100,000 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. A 2003 study reported that for unknown reasons, women are more likely to have advanced colon cancer at diagnosis than men. Nearly 57,000 people died from colon and rectal cancer in the United States in 2003. In recent years the incidence of this disease has decreased 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. Twenty percent of people are thought to have genetic predisposition, meaning their genes carry a trigger for the disease. 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

Causes of colon cancer often are environmental in sporadic cases (80%) and sometimes genetic (20%). Since malignant cells have a changed genetic makeup, this means that in 80% of cases, the environment spontaneously induces change, whereas those born with a genetic predisposition are either destined to get the cancer or less environmental exposure can induce the cancer. Exposure to agents in the environment that may induce mutation is the process of carcinogenesis and is caused by agents known as carcinogens (cancer-causing agents). Specific carcinogens have been difficult to identify; however, dietary factors seem to be involved.

Colon cancer is more common in industrialized nations. Diets high in fat, red meat, total calories, and alcohol seem to predispose people to the disease. Diets high in fiber appear to decrease risk. High-fiber diets may help lessen 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. Two-thirds of all cases occur after age 50 and the average age for those who develop the disease is 62.

There is also a slight increase risk for colon cancer in the individual who smokes.

Patients who suffer from inflammatory diseases of the colon known as ulcerative colitis and Crohn's colitis are also at increased risk.

Researchers know there is a genetic link to many cases of colon cancer, those called familial cases. This is the type of colon cancer that tends to run in families. In late 2003, a team of researchers identified the specific location on a human chromosome by analyzing blood samples from 53 families in which at least one member had a colon cancer or precancerous colon polyp. At least 200 genes exist on the location of chromosome 9, however, so the research will continue to identify the particular gene responsible for the cancer.

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.

Symptoms

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
• constipation
• 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.

If a tumor develops in the colon, it will begin to cause symptoms as it reaches a certain size. The symptoms are caused by the tumor blocking the opening in the colon. In addition, the tumor commonly oozes blood that is lost in the stool. (Often, this blood is not visible.) This results in anemia and chronic fatigue. Weight loss is a late symptom, often implying substantial obstruction or the presence of systemic disease.

Diagnosis

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. To visualize the colon epithelium, clinicians use 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 three 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 colon lining is accomplished using a scope or endoscope. The physician introduces the instrument through the rectum. 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.

A procedure called virtual colonoscopy has been developed but debate continues on whether or not it is effective as colonoscopy. Virtual colonoscopy refers to the use of imaging, usually with computed tomography (CT) scans or magnetic resonance imaging (MRI) to produce images of the colon. Studies in late 2003 showed that virtual colonoscopy was as effective as colonoscopy for screening purposes and it offered the advantage of being less invasive and less risky. However, many physicians were unwilling to accept it as a replacement for colonoscopy, particularly since some patients might still require the regular colonoscopy as a follow-up to the virtual procedure if a polyp or abnormality is found that requires biopsy.

Unlike the indirect visualizations of the colon (the BE and the DCBE), the endoscopic screenings 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 at normal risk over 50 years of age:

• yearly fecal occult blood test
• flexible sigmoidoscopy at age 50
• flexible sigmoidoscopy repeated every 5 years
• double contrast barium enema every five years
• colonoscopy every 10 years The American Gastroenterologial Association revised its screening guidelines in 2003 to recommend that people with two or more first-degree relatives with colorectal cancer or a first-degree relative with colon or rectal cancer before age 60 should have a screening colonoscopy beginning at age 40 or beginning 10 years prior to the age of the earlier colon cancer diagnosis in their family (whichever is earliest). Those with a first-degree relative diagnosed with colon cancer after age 60 or two second-degree relative with colon or rectal cancer should begin screening at age 40 with one of the methods listed above, such as annual sigmoidoscopy.

Evaluation of Patients With Symptoms

If patients have symptoms that could possibly be related to colon cancer, the entire colon will be examined. The combination of a flexible sigmoidoscopy and DCBE may be performed, but the preferred evaluation of the entire colon and rectum is a complete colonoscopy. Colonoscopy allows direct visualization, photography, and the opportunity to obtain a biopsy of any abnormality visualized. If, for technical reasons, the entire colon is not visualized endoscopically, a DCBE 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 to exclude any sampling errors.

If the patient 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 the cancer has spread to the lung, the CAT scan will evaluate potential spread to the liver as well as any local spread 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 also will be performed.

Treatment Team

The surgeon and the medical oncologist each have a role in therapy that is dictated by the degree of progression of the disease. A radiation oncologist may also play a role on the team; however, radiation treatment is rare in colon cancer.

Clinical Staging, Treatments, and Prognosis

Clinical Staging

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. 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.

Treatments

Surgery

Surgical removal of the involved segment of colon (colectomy) along with its blood supply and regional lymph nodes is the primary therapy for colon cancer. Usually, the partial colectomies are separated into right, left, transverse, or sigmoid sections based on the blood supply. The removal of the blood supply at its origin along with the regional lymph nodes that accompany it ensures 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 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 rare, occurring 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 is risky and cannot be performed. 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 hook-up at a later, safer date, or the colostomy may be permanent. In most cases, emergent colostomies are not reversed and are permanent.

RADIATION 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.

Radiation also is used in the treatment of patients with metastatic disease. It is particularly useful in shrinking metastatic colon cancer to the brain.

CHEMOTHERAPY 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 of the cancer from chemotherapy.) Another agent, levamisole, (which seems to stimulate the immune system), may be substituted for leucovorin. These protocols reduce rate of recurrence by about 15% and reduce mortality by about 10%. The regimens do have some toxicity but usually are tolerated fairly well.

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. If the cancer is detected early, surgical removal of the tumor can lead to complete cure in 75%–90% of patients.

Prognosis

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 crucial.

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 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 or 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.

The Colon Cancer Alliance offers internet online support at the following web page: .

Clinical Trials

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.

Prevention

There is not an absolute method for 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.

People who turn age 50, and all of those with a history of colon cancer in their families, should speak with their physicians about the most recent screening recommendations from physician and cancer organizations. They should watch for symptoms and attend all recommended screenings to increase the likelihood of catching colon cancer early.

Special Concerns

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 with the colonoscope and may need surgical removal because of their pre-malignant nature.

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.

Resources

Books

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., PhD, John C. Carey MD, Michael J. Bamshad MD, and Raymond L. White, PhD. Medical Genetics. 2nd ed. St. Louis: Mosby, 1999.

Periodicals

"Colon Cancer; Facts to Know." NWHRC Health Center December 15, 2003.

Golden, William E., and Robert H. Hopkins. "Colon Cancer Screening 2003." Internal Medicine News 36 (December 1, 2003): 46.

Greenlee, Robert T., MPH, Mary Beth Hill-Harmon, Taylor Murray, and Michael Thun. "Cancer Statistics 2001." CA: A Cancer Journal for Clinicians 51, no. 1 (January-February 2001).

"Professional Organization Recommends Standard Colonoscopy Over Virtual." Biotech Week December 31, 2003: 422.

"Researchers Discover New Genetic Link to Common Colon Cancer." Genomics & Genetics Weekly November 7, 2003: 29.

Saltz, Leonard, et al. "Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer." The New England Journal of Medicine 343, no. 13 (September 28, 2000).

"Study Shows Virtual Colonoscopy as Effective as Traditional Colonoscopy." Biotech Week December 31, 2003.

Wachter, Kerri. "Reasons Unclear for Later Colon Cancer Diagnosis in Women: Regional or Distant Disease More Likely." Internal Medicine News 36 (December 1, 2003).

Organizations

American Cancer Society. (800) ACS-2345. .

Cancer Information Service of the NCI. (1-800-4-CANCER). .

Colon Cancer Alliance. .

National Cancer Institute Cancer Trials. . .

—Richard A. McCartney, M.D.; Teresa G. Odle

Colorectal cancer is a malignant neoplasm that affects the larger, lower portion of the intestinal tract. About two-thirds of such cancers occur in the colon, mainly in the sigmoid portion, and one-third occur in the rectum or at the recto-sigmoid junction. The third-leading cause of cancer morbidity and the second leading cause of cancer mortality, colorectal cancer has recently declined among white persons in the United States but is almost 50 percent higher, and rising, among African Americans. Hispanics have only half the mortality rate of non-Hispanic white persons. An estimated 135,400 new cases and 56,700 deaths are anticipated during 2001 in the United States. Risk factors for the disease include being older and male; having had polyps, inflammatory bowel disease, or previous other cancers; being physically inactive and obese; consuming excessive alcohol; and a low fiber diet. Five-year survival has recently been 62 percent among white persons and 53 percent among African Americans.

Worldwide, colorectal cancer amounts to about one-tenth of all cancers—almost 600,000 of the6.35 million cases of cancer that occur. Migrants to the United States tend to develop colorectal cancer rates that are similar to those among long-term residents of their adoptive country—even during the first generation or within twenty years of living in the United States. This relatively rapid change suggests the importance of lifestyle in the causation of the disease. This inference is further supported by the fact that colorectal cancer rates throughout the world tend to be substantially higher in urban areas than in rural areas in various countries.

Polyps in the colon, particularly multiple polyps and those exceeding 1.0 cm in diameter frequently precede the occurrence of malignant neoplasm; they therefore constitute a major risk factor.

Control measures include diet, screening, and treatment. It appears that a low fat diet that includes large amounts of vegetables and fruit reduces the risk of colorectal cancer, although the evidence is equivocal, especially as to the extent of reduction. Efforts to control the disease (e.g., the National Colorectal Cancer Awareness Month, supported by the Centers for Disease Control and Prevention of the United States Public Health Services), have recently been emphasizing screening by digital rectal examination (DRE), which is used to detect malignancies that can be reached by that means: the fecal occult blood test (FOBT); and sigmoidoscopy. Barium enemas and proctoscopy have also been used for screening, as well as diagnostically. In 1999 only two-fifths of the American people over fifty years of age had ever received the FOBT or sigmoidoscopy, the latter term including a colonoscopy, which reaches farther into the colon, and a proctoscopy, which extends only into the rectum. The FOBT is recommended annually after age fifty and sigmoidoscopy every five years. Sigmoidoscopy is particularly intended to disclose polyps which may evolve into cancer as well as malignancies that are already present. Both tests are somewhat awkward for patients, but are now recognized as important tools for controlling colorectal cancer. In several trials, biennial screening with FOBT among persons forty-five to eighty years of age reduced mortality from colorectal cancer by 15 to 21 percent; among persons over forty-five years of age, sigmoidoscopy reduced mortality in the distal colon by 59 to 79 percent.

The Office of Public Health and Science of the United States Department of Health and Human Services has set, as a goal for 2010, reduction of the colorectal mortality rate (age-adjusted) from 12.8 per 100,000 (in 1995) to 8.8 per 100,000.

(SEE ALSO: Cancer; Foods and Diet; Lifestyle; Screening)

Bibliography

Massachusetts Medical Society (2000). Morbidity & Mortality Weekly Report 50.

Schottenfold, D., and Fraumeni, J. E., Jr., eds. (1996). Cancer Epidemiology and Prevention, 2nd edition. New York: Oxford University Press.

United States Department of Health and Human Services (2000). Healthy People 2010. Washington, DC: USDHHS Office of Public Health and Science.

— LESTER BRESLOW

Colon cancer is the second leading cause of cancer death in the United States, occurring in approximately 5 percent of the population and resulting in roughly 55,000 deaths annually. New cases of colorectal cancer are diagnosed in approximately 90 per 100,000 people annually. The majority of cases occur in individuals older than age fifty. Of those who suffer from colorectal malignancy, an estimated 40 percent will die from the disease.

Colon cancer-related health-care costs, consisting of outpatient visits, hospitalizations, hospice and home health care, medications, and physician services, exceed $5 billion per year. This figure does not include the indirect costs of wages lost and reduced productivity.

Developing Cancer

The colon, also known as the large intestine, is the final portion of the digestive tract and consists of a tube (called the lumen) lined by specialized cells called colonic epithelial cells. These cells are constantly reproducing in a regulated manner, but when the growth and division of colonic epithelial cells becomes unregulated, colon cancer may result.

Cancer is a form of unregulated cell growth in which growing cells invade surrounding tissue. Such a growth is said to be malignant. Colon cancer results when there are certain changes in the genes that control normal cell replication. In most cases, when cell growth becomes abnormal, a visible growth (lesion) protrudes into the colon's lumen and is termed an adenomatous polyp (or adenoma). The polyp is not yet cancerous but may become so, at which point it is called carcinoma. This process, in which normal tissue becomes cancerous, is known as the adenoma-carcinoma sequence and may take between ten and fifteen years.

Major Genes Involved

The genes altered in the adenoma-carcinoma sequence normally play a role in regulating the cell cycle, controlling the division and turnover of epithelial cells. DNA mutations result in a loss of function of the gene and subsequent unregulated cell growth. While many genes have been studied, the ones most commonly associated with the majority of colon cancers are APC, p53 and K-ras.

Colorectal cancer may develop in an individual who has a strong inherited risk. This occurs, for example, in patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC). These patients will usually have a specific genetic alteration.

Apc

The Adenomatous Polyposis Coli (APC) gene is found on chromosome 5 and is a tumor suppressor gene. Both alleles of the gene must be inactivated for tumor growth to occur. In the normal cell, the APC gene plays a role in regulating the cycle of cellular division and replication, as well as in cell-to-cell communication, thereby suppressing tumor development. Mutations of APC result in a loss of gene function, thus allowing unregulated cellular proliferation. APC mutations are found in the majority of common colon polyps and cancers and in patients with FAP, and they may be one of the earliest genetic alterations in the adenoma-carcinoma sequence.

K-Ras

The K-ras gene plays an active role in cellular signaling and promoting cell growth. The normal gene exists in both an active and inactive form. However, in the abnormal state, the active form predominates and results in a continually growth-stimulated state.

P53

The normal p53 gene is responsible for regulating cells with damaged DNA by directing abnormal cells either to halt the cycle of cell division or to die as the result of a process called apoptosis. Like APC, the p53 gene is a tumor suppressor. With the p53 mutation, the gene no longer functions, and this permits the uninhibited proliferation of cells that may have damaged DNA. p53 mutations are seen in more than half of colorectal cancers.

Familial Adenomatous Polyposis (FAP)

FAP is characterized by the presence of hundreds or thousands of colonic polyps, and it accounts for less than 1 percent of colon cancers. Affected individuals are at increased risk of colorectal polyps and malignancy, and they usually develop polyps by age thirty-five and cancer by age forty. Because endoscopic removal of all the polyps is impossible, patients are usually advised to consider colectomy at a relatively young age. In addition to occurring in the colon, polyps occur in the upper digestive tract, and a variety of tumors may develop outside the gastrointestinal tract. Because mutations in the APC gene can be identified in most cases, genetic testing is now available for affected families.

FAP is inherited as an autosomal dominant disorder with 95 percent penetrance, meaning 95 percent of those who inherit one mutated APC gene will develop FAP. At the cellular level, the APC mutation is actually recessive: As long as there is one copy that is not mutated, the cell cycle will remain controlled.

The apparent paradox of a recessive gene causing a dominant disorder is resolved when we consider how a gene defect predisposes a person to cancer. Of the many millions of cells lining the colon, it is highly likely that some will undergo spontaneous mutation in one of the two copies of the APC gene.

For a person not affected by the APC gene, a spontaneous mutation of one allele will not lead to cancer, because the other gene copy remains intact. However, for a person affected who inherits one mutated copy of the APC gene, each of the cells lining the colon begins with one bad gene copy. Any mutation to the remaining good copy will cause the cell to lose control of its cell cycle and begin the process of polyp development. Given the number of cells involved, it is almost inevitable that this will occur in some of them. Hence FAP is a dominant condition.

Hereditary Nonpolyposis Colon Cancer

HNPCC is an autosomal dominant disorder that may be responsible for up to 5 percent of colon cancers. The genetic mutation leading to the abnormality is the mutation of DNA mismatch repair genes. Individuals with this mutation have up to an 80 percent chance of developing colon cancer. At least five genes are involved in this syndrome.

Malignancy in patients with HNPCC occurs at a younger age than in the general population, is more often located in the proximal colon (the portion nearest the small intestine), and may be associated with multiple tumors. HNPCC also carries an increased risk of tumors of the endometrium, ovaries, stomach, small intestine, bile ducts, bladder, renal pelvis, and ureters. Genetic testing is useful for HNPCC families.

Genetic Testing

Genetic testing may benefit patients and families affected by an inherited colon cancer syndrome. The genetic mutations in FAP and HNPCC can often be characterized. If a family member with colon cancer has an identified genetic abnormality, other family members can be tested to see if they have the same abnormality.

If the mutated gene is not found, the abnormal gene was not inherited and the family member is not at increased risk of developing cancer. Because screening (i.e., colon examination) is more frequently performed for those with FAP and HNPCC than others, genetic testing can be useful for determining who would benefit from intense surveillance.

Other Risk Factors

In addition to the well-described genetic syndromes of FAP and HNPCC, other factors that place an individual at increased risk include a personal or family history of colon cancer and the presence of inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease). Population studies support an association between the development of colon cancer and a high-fat, low-fiber diet, although a cause-and-effect relationship has not been proved.

Prevention

Inhibiting the development of polyps and cancers, finding and removing premalignant polyps, and testing individuals at high risk may reduce colon cancer-related morbidity and mortality. Colon cancer occurs less commonly in individuals whose diets are high in calcium and folate, who take multivitamins, and who maintain high-fiber and low-fat diets.

Non-steroidal anti-inflammatory medications like aspirin may reduce the numbers of polyps, particularly in families with FAP. Colonoscopy can identify polyps that may be premalignant and can facilitate polyp removal. It is recommended that all individuals have a colonoscopy at age fifty. Highrisk patients, such as those with inflammatory bowel disease, FAP, or HNPCC, should have screening initiated at an earlier age and repeat exams at shorter time intervals.

Bibliography

Giardiello, Francis M., Jill D. Brensinger, and Gloria M. Petersen. "AGA Technical Review on Hereditary Colorectal Cancer and Genetic Testing." Gastroenterology 121 (2001): 198-213.

Yamada, Tadataka, et al., eds. Textbook of Gastroenterology, 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1999.

Internet Resource

"The Burden of Gastrointestinal Diseases." American Gastrointestinal Association. May 2001. http://www.gastro.org/pdf/burden-report.pdf.

—David E. Loren and Michael L. Kochman

Colorectal cancer
Classification and external resources
Diagram of the lower gastrointestinal tract
ICD-10	C18-C20/C21
ICD-9	153.0-154.1
ICD-O:	M8140/3 (95% of cases)
OMIM	114500
DiseasesDB	2975
MedlinePlus	000262
eMedicine	med/413 med/1994 ped/3037

Colorectal cancer, commonly known as bowel cancer, is a cancer from uncontrolled cell growth in the colon, rectum, or appendix. Symptoms typically include rectal bleeding and anemia which are sometimes associated with weight loss and changes in bowel habits.

Most colorectal cancer occurs due to lifestyle and increasing age with only a minority of cases associated with underlying genetic disorders. It typically starts in the lining of the bowel and if left untreated, can grow into the muscle layers underneath, and then through the bowel wall. Screening is effective at decreasing the chance of dying from colorectal cancer and is recommended starting at the age of 50 and continuing until a person is 75 years old. Localized bowel cancer is usually diagnosed through sigmoidoscopy or colonoscopy.

Cancers that are confined within the wall of the colon are often curable with surgery while cancer that has spread widely around the body is usually not curable and management then focuses on extending the person's life via chemotherapy and improving quality of life. Colorectal cancer is the fourth most commonly diagnosed cancer in the world, but it is more common in developed countries.^[1] Around 60% of cases were diagnosed in the developed world.^[1] It is estimated that worldwide, in 2008, 1.23 million new cases of colorectal cancer were clinically diagnosed, and that it killed 608,000 people.^[1]

Contents 1 Signs and symptoms 2 Cause 2.1 Inflammatory bowel disease 2.2 Genetics 3 Pathogenesis 4 Diagnosis 4.1 Pathology 5 Prevention 5.1 Lifestyle 5.2 Medication 5.3 Screening 6 Management 6.1 Surgery 6.2 Chemotherapy 6.3 Biological therapies 6.4 Radiation 6.5 Palliative care 7 Prognosis 7.1 Follow-up 8 Epidemiology 9 Society and culture 9.1 Notable cases 10 Research 11 References 12 External links

Signs and symptoms

The symptoms and signs of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, weight loss, fever, loss of appetite, and nausea or vomiting in someone over 50 years old.^[2] While rectal bleeding or anemia are high risk features in those over the age of 50,^[3] other commonly descripted symptoms include weight loss and change in bowel habit are typically only concerning if associated with bleeding.^[3][4]

Cause

Greater than 75-95% of colon cancer occurs in people with little or no genetic risk.^[5][6] While some risk factors such as older age and male gender cannot be changed many can.^[6] A high fat, alcohol or red meat intake are risk factors for colorectal cancer as is obesity, smoking and a lack of physical exercise.^[5] The risk for alcohol appears to increase at greater than one drink per day.^[7]

Inflammatory bowel disease

People with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are at increased risk of colon cancer.^[8] The risk is greater the longer a person has had the disease,^[9] and the worse the severity of inflammation.^[10] In these high risk groups both prevention with aspirin and regular colonoscopies are recommended. ^[9] People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.^[10] In those with Crohn's disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years.^[10] In those with ulcerative colitis approximately 20% develop tumors within the first 10 years.^[10]

Genetics

Those with a family history in two or more first degree relatives have a two to three fold greater risk of disease and this group accounts for about 20% of all cases.^[6]A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer.^[6] Other syndromes that are strongly associated include: Gardner syndrome,^[11] and familial adenomatous polyposis (FAP) in which cancer nearly always occurs and is the cause of 1% of cases.^[12]

Pathogenesis

Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of mutations in the Wnt signaling pathway that artificially increase signaling activity. The mutations can be inherited or are acquired, and must probably occur in the intestinal crypt stem cell.^[13][14] The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein is a "brake" on the accumulation of β-catenin protein; without APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of genes that are normally important for stem cell renewal and differentiation but when inappropriately expressed at high levels can cause cancer. While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its degradation, or they have mutation(s) in other genes with function analogous to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.^[15]

Beyond the defects in the Wnt-APC-beta-catenin signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from an adenoma into an invasive carcinoma. (Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is.)^[15]

Other apoptotic proteins commonly deactivated in colorectal cancers are TGF-β and DCC (Deleted in Colorectal Cancer). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named SMAD is.^[15] DCC commonly has deletion of its chromosome segment in colorectal cancer.^[16]

Some genes are oncogenes - they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF,^{[disambiguation needed ]} and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important, with a primary KRAS mutation generally leading to a self-limiting hyperplastic or borderline lesion, but if occurring after a previous APC mutation it often progresses to cancer.^[17] PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.^[15]

Diagnosis

Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor).

Diagnosis of colorectal cancer is via tumor biopsy typically done during sigmoidoscopy or colonoscopy.^[6] The extent of the disease is then usually determined by a CT scan of the chest, abdomen and pelvis.^[6] There are other potential imaging test such as PET and MRI which may be used in certain cases.^[6] Colon cancer staging is done next and based on the TNM system which is determined by how much the initial tumor has spread, if and where lymph nodes are involved and, and if and how many metastasis there are.^[6]

Pathology

The pathology of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma which accounts for 95% of cases. Other, rarer types include lymphoma and squamous cell carcinoma.

Cancers on the right side (ascending colon and cecum) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces, and presents with symptoms such as anemia. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring.

Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces) - mucinous (colloid) adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery - "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated.^[18]

Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive. This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.

• 

  Gross appearance of a colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor located above the label).

• 

  Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopy in the setting of Crohn's disease.

• 

  Micrograph of an invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image.

• 

  Histopathologic image of colonic carcinoid stained by hematoxylin and eosin.

• 

  Micrograph of a tubular adenoma (left of image), a type of colonic polyp and a precursor of colorectal cancer. Normal colorectal mucosa is seen on the right. H&E stain.

• 

  thumb|Micrograph of a colorectal villous adenoma. These lesions are considered pre-cancerous. H&E stain.

Prevention

Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.

Lifestyle

Current dietary recommendations to prevent colorectal cancer include increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat.^[19][20] The evidence for fiber and fruits and vegetables however is poor.^[20] Physical activity can moderately reduce the risk of colorectal cancer.^[21]

Medication

Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk.^[22] However it is not recommended in those at average risk.^[23] There is tentative evidence for calcium supplementation but it is not sufficient to make a recommendation.^[24] Vitamin D intake and blood levels are associated with a lower risk of colon cancer.^[25][26]

Screening

More than 80% colorectal cancers arise from adenomatous polyps making this cancer amenable to screening. The three main screening tests are fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Fecal occult blood testing of the stool is typically recommended every two years and can be either guaiac based or immunochemical. In the United States screening is recommended between the age of 50 and 75 years with sigmoidoscopy every 5 years and colonoscopy every 10 years.^[27] Virtual colonoscopy via a CT scan aspears as good as standard colonoscopy but is expensive and associated with radiation exposure.^[6] It is believed that screening has the potential to reduce colorectal cancer deaths by 60%.^[28]

Management

The treatment of colorectal cancer depends on how advanced it is.^[29] When colorectal cancer is caught early surgery can be curative.^[6] However, when it is detected at later stages (metastases are present), this is less likely and treatment is often directed more at extending life and keeping people comfortable.^[6]

Surgery

For people with localized cancer the preferred treatment is complete surgical removal with the attempt of achieving a cure. This can either be done by an open laporotomy or sometimes laparoscopically. If there are only a few metastases in the liver or lungs they may also be removed. Sometimes chemotherapy is used before surgery to shrink the cancer before attempting to remove it. The two most common sites of recurrence if it occurs is in the liver and lungs.^[6]

Chemotherapy

Chemotherapy may be used in addition to surgery in certain cases^[6] as adjuvant therapy. If cancer has entered the lymph nodes adding the chemotherapy agents fluorouracil, or capecitabine increases life expectancy. If the lymph nodes do not contain cancer the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this case a couple of different chemotherapy medications are used.^[6] Chemotherapy drugs common in advanced economies, combinations and availability which vary with regulation and location, for advanced colorectal cancer are fluorouracil, capecitabine, UFT, leucovorin, irinotecan, oxaliplatin.^[30] Cimetidine, a generic anti-ulcer drug, is known to suppress vascular E-selectin expression and prevent hematogenous metastasis when cancer cells react with sialyl Lewis a/x antibodies CA19-9 and CSLEX1^[31] in the majority of advanced colorectal cancers.^[32]

Biological therapies

Antibody based biological treatments like Bevacizumab (Avastin), Cetuximab (Erbitux) and Panitumumab (Vectibix) are available, typically with or after combinations of chemotherapy drugs in advanced colon cancer.

Radiation

While a combination of radiation and chemotherapy may be useful for rectal cancer,^[6] its use in colon cancer is not routine due to the sensitivity of the bowels to radiation.^[33]

Palliative care

In people with incurable colorectal cancer, palliative care can be considered for improving quality of life. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction.^[34] Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.^[35]

Prognosis

In Europe the 5 year survival for colorectal cancer is less than 60%.^[6] In the developed world about a third of people who get the disease die from it.^[6]

Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection is about 5 times that of late stage cancers. For example, patients with a tumor that has not breached the muscularis mucosa (TNM stage Tis, N0, M0) have an average 5-year survival of 100%, while those with an invasive cancer, i.e. T1 (within the submucosal layer) or T2 (within the muscular layer) cancer have an average 5-year survival of approximately 90%. Those with a more invasive tumor, yet without node involvement (T3-4, N0, M0) have an average 5-year survival of approximately 70%. Patients with positive regional lymph nodes (any T, N1-3, M0) have an average 5-year survival of approximately 40%, while those with distant metastases (any T, any N, M1) have an average 5-year survival of approximately 5%.^[36]

According to the American Cancer Society statistics in 2006,^[37] over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.^[38]

Follow-up

The aims of follow-up are to diagnose, in the earliest possible stage, any metastasis or tumors that develop later, but did not originate from the original cancer (metachronous lesions).

The U.S. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer.^[39][40] A medical history and physical examination are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen blood level measurements follow the same timing, but are only advised for patients with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example, patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, a polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.

Routine PET or ultrasound scanning, chest X-rays, complete blood count or liver function tests are not recommended.^[39][40] These guidelines are based on recent meta-analyses showing intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%.^[41][42][43]

Epidemiology

Age-standardized death from colorectal cancer per 100,000 inhabitants in 2004.^[44]

no data   <2.5   2.5-5   5-7.5   7.5-10   10-12.5   12.5-15

15-17.5   17.5-20   20-22.5   22.5-25   25-27.5   >27.5

Globally greater than 1 million people get colorectal cancer yearly^[6] resulting in about 0.5 million deaths.^[45] As of 2008 it is the second most common cause of cancer in women and the third most common in men^[46] with it being the fourth most common cause of cancer death after lung, stomach, and liver cancer.^[47] It is more common in developed than developing countries.^[45]

Society and culture

In the United States March is colorectal cancer awareness month.^[28]

Notable cases

Main article: List of people diagnosed with colorectal cancer

• Corazon Aquino, former president of the Philippines^[48]
• Pope John Paul II^[49]
• Ronald Reagan^[50]
• Harold Wilson, former Prime Minister of the United Kingdom^[51]

Research

• Bowel & Cancer Research
• Mouse models of colorectal and intestinal cancer

References

1. ^ ^{a b c} http://globocan.iarc.fr/
2. ^ al.], edited by Tadataka Yamada ; associate editors, David H. Alpers ... [et (2008). Principles of clinical gastroenterology. Chichester, West Sussex: Wiley-Blackwell. pp. 381. ISBN 9781405169103. http://books.google.ca/books?id=Zo7QcUjz0PYC&pg=PA381. 
3. ^ ^{a b} Astin, M; Griffin, T, Neal, RD, Rose, P, Hamilton, W (2011 May). "The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review". The British journal of general practice : the journal of the Royal College of General Practitioners 61 (586): 231–43. doi:10.3399/bjgp11X572427. PMC 3080228. PMID 21619747. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3080228. 
4. ^ Adelstein, BA; Macaskill, P, Chan, SF, Katelaris, PH, Irwig, L (2011 May 30). "Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review.". BMC gastroenterology 11: 65. PMID 21624112. 
5. ^ ^{a b} Watson, AJ; Collins, PD (2011). "Colon cancer: a civilization disorder.". Digestive diseases (Basel, Switzerland) 29 (2): 222–8. PMID 21734388. 
6. ^ ^{a b c d e f g h i j k l m n o p q r} Cunningham, D; Atkin, W, Lenz, HJ, Lynch, HT, Minsky, B, Nordlinger, B, Starling, N (2010 Mar 20). "Colorectal cancer.". Lancet 375 (9719): 1030–47. doi:10.1016/S0140-6736(10)60353-4. PMID 20304247. http://pingpong.ki.se/public/pp/public_courses/course08879/published/0/resourceId/0/content/Colon%20cancer.pdf. 
7. ^ Fedirko, V; Tramacere, I, Bagnardi, V, Rota, M, Scotti, L, Islami, F, Negri, E, Straif, K, Romieu, I, La Vecchia, C, Boffetta, P, Jenab, M (2011 Sep). "Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies.". Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 22 (9): 1958–72. PMID 21307158. 
8. ^ Jawad, N; Direkze, N, Leedham, SJ (2011). "Inflammatory bowel disease and colon cancer.". Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 185: 99–115. PMID 21822822. 
9. ^ ^{a b} Xie, J; Itzkowitz, SH (2008 Jan 21). "Cancer in inflammatory bowel disease.". World journal of gastroenterology : WJG 14 (3): 378–89. PMID 18200660. 
10. ^ ^{a b c d} Triantafillidis, JK; Nasioulas, G, Kosmidis, PA (2009 Jul). "Colorectal cancer and inflammatory bowel disease: epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies.". Anticancer research 29 (7): 2727–37. PMID 19596953. 
11. ^ Juhn, E; Khachemoune, A (2010). "Gardner syndrome: skin manifestations, differential diagnosis and management.". American journal of clinical dermatology 11 (2): 117–22. PMID 20141232. 
12. ^ Half, E; Bercovich, D, Rozen, P (2009 Oct 12). "Familial adenomatous polyposis.". Orphanet journal of rare diseases 4: 22. PMID 19822006. 
13. ^ Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M (1993). "Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis". Nature 363 (6429): 558–61. doi:10.1038/363558a0. PMID 8505985. 
14. ^ Srikumar Chakravarthi, Baba Krishnan, Malathy Madhavan (1999). "Apoptosis and expression of p53 in colorectal neoplasms". Indian J Med Res 86 (7): 95–102. 
15. ^ ^{a b c d} Markowitz SD, Bertagnolli MM (December 2009). "Molecular Origins of Cancer: Molecular Basis of Colorectal Cancer". N. Engl. J. Med. 361 (25): 2449–60. doi:10.1056/NEJMra0804588. PMC 2843693. PMID 20018966. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2843693. 
16. ^ Mehlen P, Fearon ER (August 2004). "Role of the dependence receptor DCC in colorectal cancer pathogenesis". J. Clin. Oncol. 22 (16): 3420–8. doi:10.1200/JCO.2004.02.019. PMID 15310786. 
17. ^ Vogelstein, B.; Kinzler, K. W. (2004). "Cancer genes and the pathways they control". Nature Medicine 10 (8): 789–799. doi:10.1038/nm1087. PMID 15286780.  edit
18. ^ Pathology atlas
19. ^ Campos, FG; Logullo Waitzberg, AG, Kiss, DR, Waitzberg, DL, Habr-Gama, A, Gama-Rodrigues, J (2005 Jan-Feb). "Diet and colorectal cancer: current evidence for etiology and prevention.". Nutricion hospitalaria : organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 20 (1): 18–25. PMID 15762416. 
20. ^ ^{a b} Doyle, VC (2007 May-Jun). "Nutrition and colorectal cancer risk: a literature review.". Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates 30 (3): 178-82; quiz 182-3. PMID 17568255. 
21. ^ Harriss, DJ; Atkinson, G, Batterham, A, George, K, Cable, NT, Reilly, T, Haboubi, N, Renehan, AG, Colorectal Cancer, Lifestyle, Exercise And Research, Group (2009 Sep). "Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity.". Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 11 (7): 689–701. PMID 19207713. 
22. ^ Cooper, K; Squires, H, Carroll, C, Papaioannou, D, Booth, A, Logan, RF, Maguire, C, Hind, D, Tappenden, P (2010 Jun). "Chemoprevention of colorectal cancer: systematic review and economic evaluation.". Health technology assessment (Winchester, England) 14 (32): 1–206. doi:10.3310/hta14320. PMID 20594533. 
23. ^ Agency for Healthcare Research and Quality (2010/2011). "Aspirin or Nonsteroidal Anti-inflammatory Drugs for the Primary Prevention of Colorectal Cancer". United States Department of Health & Human Services. http://www.ahrq.gov/clinic/pocketgd1011/gcp10s2.htm. 
24. ^ Weingarten, MA; Zalmanovici, A, Yaphe, J (2008 Jan 23). "Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps.". Cochrane database of systematic reviews (Online) (1): CD003548. PMID 18254022. 
25. ^ Ma, Y; Zhang, P, Wang, F, Yang, J, Liu, Z, Qin, H (2011 Oct 1). "Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies.". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29 (28): 3775–82. PMID 21876081. 
26. ^ Yin, L; Grandi, N, Raum, E, Haug, U, Arndt, V, Brenner, H (2011 Jul-Aug). "Meta-analysis: Serum vitamin D and colorectal adenoma risk.". Preventive medicine 53 (1-2): 10–6. doi:10.1016/j.ypmed.2011.05.013. PMID 21672549. 
27. ^ "Screening for Colorectal Cancer". U.S. Preventive Services Task Force. 2008. http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm. 
28. ^ ^{a b} He, J; Efron, JE (2011). "Screening for colorectal cancer.". Advances in surgery 45: 31–44. PMID 21954677. 
29. ^ Stein, A; Atanackovic, D, Bokemeyer, C (2011 Sep). "Current standards and new trends in the primary treatment of colorectal cancer.". European journal of cancer (Oxford, England : 1990) 47 Suppl 3: S312-4. PMID 21943995. 
30. ^ none (2010 Oct). "Chemotherapy of metastatic colorectal cancer.". Prescrire Int. 19 (109): 219-224. http://www.ncbi.nlm.nih.gov/pubmed/21180382. 
31. ^ Kannagi, R. (May-June 2007). "Carbohydrate Antigen Sialyl Lewis a – Its Pathophysiological Significance and Induction Mechanism in Cancer Progression.". Chang Gung Med J No. 3 30 (3): 204. http://memo.cgu.edu.tw/cgmj/3003/300301.pdf. 
32. ^ Matsumoto S, Imaeda Y, Umemoto S, Kobayashi K, Okamoto T (january 2002). "Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells.". Br J Cancer 86: 161–167. doi:10.1038/sj.bjc.6600048. PMID 19671906. http://www.nature.com/bjc/journal/v86/n2/abs/6600048a.html. 
33. ^ authors, editors, Vincent T. DeVita, Jr., Theodore S. Lawrence, Steven A. Rosenberg ; associate scientific advisors, Robert A. Weinberg, Ronald A. DePinho ; with 421 contributing (2008). DeVita, Hellman, and Rosenberg's cancer : principles & practice of oncology (8th ed. ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. pp. 1258. ISBN 9780781772075. http://books.google.ca/books?id=NF90HzUFPjgC&pg=PA1258. 
34. ^ Wasserberg N, Kaufman HS (December 2007). "Palliation of colorectal cancer". Surg Oncol 16 (4): 299–310. doi:10.1016/j.suronc.2007.08.008. PMID 17913495. 
35. ^ Amersi F, Stamos MJ, Ko CY (July 2004). "Palliative care for colorectal cancer". Surg. Oncol. Clin. N. Am. 13 (3): 467–77. doi:10.1016/j.soc.2004.03.002. PMID 15236729. 
36. ^ Box 3-1, Page 107 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6. 
37. ^ http://www.cancer.org/docroot/PRO/content/PRO_1_1_Cancer_Statistics_2006_Presentation.asp
38. ^ Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M (April 2006). "Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies". Br. J. Cancer 94 (7): 982–99. doi:10.1038/sj.bjc.6603033. PMC 2361241. PMID 16538219. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2361241. 
39. ^ ^{a b} NCCN Clinical Practice Guidelines in Oncology - Colon Cancer (version 1, 2008: September 19, 2007).
40. ^ ^{a b} Desch CE, Benson AB 3rd, Somerfield MR, et al.; American Society of Clinical Oncology (2005). "Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline" (PDF). J Clin Oncol 23 (33): 8512–9. doi:10.1200/JCO.2005.04.0063. PMID 16260687. http://jco.ascopubs.org/cgi/reprint/JCO.2005.04.0063v1.pdf. 
41. ^ Jeffery M, Hickey BE, Hider PN (2002). Jeffery, Mark. ed. "Follow-up strategies for patients treated for non-metastatic colorectal cancer". Cochrane Database Syst Rev (1): CD002200. doi:10.1002/14651858.CD002200. PMID 11869629. CD002200. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002200/frame.html. 
42. ^ Renehan AG, Egger M, Saunders MP, O'Dwyer ST (2002). "Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials". BMJ 324 (7341): 831–8. doi:10.1136/bmj.324.7341.813. PMC 100789. PMID 11934773. http://www.bmj.com/cgi/reprint/324/7341/813. 
43. ^ Figueredo A, Rumble RB, Maroun J, et al.; Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care. (2003). "Follow-up of patients with curatively resected colorectal cancer: a practice guideline". BMC Cancer 3: 26. doi:10.1186/1471-2407-3-26. PMC 270033. PMID 14529575. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=270033. 
44. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
45. ^ ^{a b} Merika, E; Saif, MW, Katz, A, Syrigos, K, Morse, M (2010 Sep-Oct). "Review. Colon cancer vaccines: an update.". In vivo (Athens, Greece) 24 (5): 607–28. PMID 20952724. 
46. ^ Jemal, A; Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D (2011-02-04). "Global cancer statistics". CA: a cancer journal for clinicians 61 (2): 69–90. doi:10.3322/caac.20107. PMID 21296855. 
47. ^ WHO (February 2010). "Cancer". World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/. Retrieved 2011-01-05. 
48. ^ http://www.abs-cbnnews.com/storypage.aspx?StoryID=112887
49. ^ "Pope John Paul II". ABC News Online. http://www.abc.net.au/news/indepth/pope/timeline.htm. 
50. ^ "Reagan turns 90". BBC News: Americas. 6 February 2001. http://news.bbc.co.uk/2/hi/americas/1156513.stm. 
51. ^ Daily Mail

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Wikimedia Commons has media related to: Colorectal cancer

• Colorectal cancer at the Open Directory Project

v d e Digestive system · Digestive disease · Gastroenterology (primarily K20–K93, 530–579) Upper GI tract Esophagus Esophagitis (Candidal, Herpetiform) · rupture (Boerhaave syndrome, Mallory-Weiss syndrome) · UES (Zenker's diverticulum) · LES (Barrett's esophagus) · Esophageal motility disorder (Nutcracker esophagus, Achalasia, Diffuse esophageal spasm, Gastroesophageal reflux disease (GERD)) · Laryngopharyngeal reflux (LPR) · Esophageal stricture · Megaesophagus Stomach Gastritis (Atrophic, Ménétrier's disease, Gastroenteritis) · Peptic (gastric) ulcer (Cushing ulcer, Dieulafoy's lesion) · Dyspepsia · Pyloric stenosis · Achlorhydria · Gastroparesis · Gastroptosis · Portal hypertensive gastropathy · Gastric antral vascular ectasia · Gastric dumping syndrome · Gastric volvulus Lower GI tract: Intestinal/ enteropathy Small intestine/ (duodenum/jejunum/ileum) Enteritis (Duodenitis, Jejunitis, Ileitis) — Peptic (duodenal) ulcer (Curling's ulcer) — Malabsorption: Coeliac · Tropical sprue · Blind loop syndrome · small bowel bacterial overgrowth syndrome  · Whipple's · Short bowel syndrome · Steatorrhea · Milroy disease · bile acid malabsorption Large intestine (appendix/colon) Appendicitis · Colitis (Pseudomembranous, Ulcerative, Ischemic, Microscopic, Collagenous, Lymphocytic) · Functional colonic disease (IBS, Intestinal pseudoobstruction/Ogilvie syndrome) — Megacolon/Toxic megacolon · Diverticulitis/Diverticulosis Large and/or small Enterocolitis (Necrotizing) · IBD (Crohn's disease) — vascular: Abdominal angina · Mesenteric ischemia · Angiodysplasia — Bowel obstruction: Ileus · Intussusception · Volvulus · Fecal impaction — Constipation · Diarrhea (Infectious) · Intestinal adhesions Rectum Proctitis (Radiation proctitis) · Proctalgia fugax · Rectal prolapse · Anismus Anal canal Anal fissure/Anal fistula · Anal abscess  · Anal dysplasia  · Pruritus ani GI bleeding/BIS Upper (Hematemesis, Melena) · Lower (Hematochezia) Accessory Liver Hepatitis (Viral hepatitis, Autoimmune hepatitis, Alcoholic hepatitis) · Cirrhosis (PBC) · Fatty liver (NASH) · vascular (Budd-Chiari syndrome, Hepatic veno-occlusive disease, Portal hypertension, Nutmeg liver) · Alcoholic liver disease · Liver failure (Hepatic encephalopathy, Acute liver failure) · Liver abscess (Pyogenic, Amoebic) · Hepatorenal syndrome · Peliosis hepatis Gallbladder Cholecystitis · Gallstones/Cholecystolithiasis · Cholesterolosis · Rokitansky-Aschoff sinuses · Postcholecystectomy syndrome · Porcelain gallbladder Bile duct/ other biliary tree Cholangitis (PSC, Secondary sclerosing cholangitis, Ascending) · Cholestasis/Mirizzi's syndrome · Biliary fistula · Haemobilia · Gallstones/Cholelithiasis common bile duct (Choledocholithiasis, Biliary dyskinesia) · Sphincter of Oddi dysfunction Pancreatic Pancreatitis (Acute, Chronic, Hereditary, Pancreatic abscess) · Pancreatic pseudocyst · Exocrine pancreatic insufficiency · Pancreatic fistula Abdominopelvic Hernia Diaphragmatic (Congenital) · Hiatus Inguinal (Indirect, Direct) · Umbilical · Femoral · Obturator · Spigelian lumbar (Petit's, Grynfeltt-Lesshaft) undefined location (Incisional · Internal hernia) Peritoneal Peritonitis (Spontaneous bacterial peritonitis) · Hemoperitoneum · Pneumoperitoneum M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

v d e Tumors: digestive system neoplasia (C15–C26/D12–D13, 150–159/211) GI tract Upper GI tract Esophagus Squamous cell carcinoma · Adenocarcinoma Stomach Gastric carcinoma · Signet ring cell carcinoma · Gastric lymphoma (MALT lymphoma) · Linitis plastica Lower GI tract Small intestine Duodenal cancer (Adenocarcinoma) Appendix Carcinoid · Pseudomyxoma peritonei Colon/rectum colorectal polyp: Peutz-Jeghers syndrome · Juvenile polyposis syndrome · Familial adenomatous polyposis/Gardner's syndrome · Cronkhite–Canada syndrome neoplasm: Adenocarcinoma · Familial adenomatous polyposis · Hereditary nonpolyposis colorectal cancer Anus Squamous cell carcinoma Upper and/or lower Gastrointestinal stromal tumor · Krukenberg tumor (metastatic) Accessory Liver malignant: Hepatocellular carcinoma (Fibrolamellar) · Hepatoblastoma benign: Hepatocellular adenoma · Cavernous hemangioma hyperplasia: Focal nodular hyperplasia · Nodular regenerative hyperplasia Biliary tract bile duct: Cholangiocarcinoma · Klatskin tumor gallbladder: Gallbladder cancer Pancreas exocrine pancreas: Adenocarcinoma · Pancreatic ductal carcinoma cystic neoplasms: Serous microcystic adenoma · Intraductal papillary mucinous neoplasm · Mucinous cystic neoplasm · Solid pseudopapillary neoplasm Pancreatoblastoma Peritoneum Primary peritoneal carcinoma · Peritoneal mesothelioma · Desmoplastic small round cell tumor M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

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