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 that is responsible for carrying ingested nutrients into the body. The waste left after the small intestine has finished absorbing 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 in 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 is originally detected, it is usually larger than 0.4in (1 cm) in size and has over one million cells. This amount of growth itself is estimated to take about three to 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 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 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 seem 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 also is a slight increased 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 usually 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
• 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
• 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.

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 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 five 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 is spread to the lung, and the CAT scan will evaluate potential spread to the liver as well as any local spread of the primary tumor. If the patient has neurological 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

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, the stage of the cancer 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.

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 5-fluorouracil, (5FU) combined with leucovorin for a period of six to 12 months. 5FU is an antimetabolite, and leucovorin 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 two to three months to disease-free survival, and prolonged overall survival by a little over two months.

Alternative treatment

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.

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

About 15% of patients present with stage I disease and 85–90% survive. Stage II represents 20–30% of cases and 65–75% survive. Thirty to forty percent comprise the stage III presentation of which 55% survive. The remaining 20–25% present with stage IV disease and are rarely cured.

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. 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.