~Colorectal Cancer

~Colorectal Cancer
Reprinted with permission of Life Extension®.
According to the Centers for Disease Control and Prevention, cancer of the colon and rectum affects nearly 150,000 Americans each year, with one out of every 20 individuals at risk for developing colorectal cancer at some point in their lifetime. It is the second most frequently diagnosed malignancy in the United States, causing approximately 56,000 deaths annually. However, early detection of colorectal cancer dramatically increases survival. For example, 92% of patients who receive early treatment are still alive after 5 years compared to 64% survival when adjacent organs or lymph nodes are affected. Only 7% of patients are alive after 5 years if the cancer is carried to distant organs (Dashwood 1999).

Anatomy

The colon and rectum are organs of the digestive system located in the abdomen between the small intestine and the anus. Together, the colon and rectum make up the large intestine or large bowel. Because of their close proximity cancers of the two organs are often discussed together under the name colorectal cancer.

The colon initiates at the juncture between the small intestine and the large intestine, called the ileocecal sphincter (valve). The colon takes several paths. First, the ascending colon travels up vertically on the right side of the abdomen, then the transverse colon extends across the abdomen, and finally, the descending colon leads down vertically on the left side of the body. At this point, the sigmoid (S-shaped) colon extends to the rectum. The rectum is the last section of the large intestine and leads to the anus.

Functions

The colon and rectum have several major functions. The colon maintains the body's water balance by absorbing water and minerals from food and transporting them into the bloodstream. Additionally, the colon moves its contents by muscular contraction into the sigmoid colon and finally into the rectum. The rectum stores fecal matter until it is eliminated from the body.

Colorectal Cancer Development

In a healthy body, the cell cycle is the natural mechanism that regulates the creation, growth, and death of cells. It is this mechanism that regulates cell division, allowing the creation of new tissue as older cells die off. When normal cell regulators malfunction and cells do not die off at the proper rate, there is a failure of cell death (apoptosis) and cell growth goes unchecked. If, as a result, cancer begins to develop, cells divide without control, accumulating into a mass of extra tissue called a malignant tumor. As a tumor grows, it elicits new capillary growth (angiogenesis) from surrounding normal tissues and diverts blood supply and nutrients away from the tissue to feed itself. Unregulated angiogenesis can facilitate the growth of cancer throughout the body.

Cancer cells have the ability to leave the original tumor site, travel to distant locations, and recolonize. This process is called metastasis and occurs in organs such as the liver, lungs, or bones. Both the bloodstream and lymphatic system (the network connecting lymph nodes throughout the body) serve as vehicles for traveling cancer. Although these traveling cancer cells do not always survive beyond the original tumor site, if they do survive, these cancer cells will attach, begin to proliferate, and create other tumors in each new location. A person with untreated or treatment-resistant cancer will eventually die of the disease when vital organs such as the liver or lungs are invaded, overtaken, and destroyed. (Metastasis will be discussed in further detail later in the protocol.)

The exact cause of colorectal cancer is unknown. However, it is believed that most colorectal cancers develop from polyps , more specifically adenomas . Adenomas are benign (noncancerous) growths arising from the mucosa or inner mucus lining of the colon and rectum and are believed to have the potential to become malignant (cancerous) given enough time. Polyps can occur at any age, although people over age 60 have a much more significant risk, about 40%, of developing colon polyps. Colorectal carcinomas may occur anywhere in the large intestine.

Once a colorectal cancer is established and becomes invasive, it may penetrate deep into the walls of the colon and eventually spread to the lymph nodes. Later on, these malignant cells can metastasize ( spread) to the liver, lungs, brain, or other organs, and result in organ failure or reduced resistance to infection and, ultimately, death. However, the latest medical and surgical treatments offer a good chance for a cure if the cancer is diagnosed in its early stages.

Colorectal Cancer Screening and Detection

Once polyps are removed, they are sent to the laboratory for analysis. A pathologist determines if the polyps are cancerous by microscopic examination. Colorectal cancer found in this early stage, before symptoms develop, is the most curable form, and it is for this reason that screening in asymptomatic individuals is so important.

In later stages, colorectal cancer can cause symptoms such as blood in the stool, changes in normal bowel habits, narrowing of the stool, abdominal pain, weight loss, or constant fatigue. Symptoms associated in right-sided, ascending colon tumors include fatigue, weakness, and anemia, or iron deficiency of unknown origin. These lesions can become very large without causing any obstructive symptoms because stool in the ascending colon is relatively liquid and can continue to pass through even significantly narrowed lumens. Ascending colon lesions often project into the lumen and ulcerate, causing chronic blood loss and resulting in symptoms of palpitations and possible angina pectoris, as well as fatigue. Any adult with chronic iron deficiency of unknown origin should have a thorough visualization of the entire bowel via colonoscopy.

Symptoms of an obstruction are often the first indication of cancer located in the left descending colon. Since stool in this location is more solidly formed, its passage can become blocked from moving into the rectum by a growing tumor. Such symptoms include changes in bowel habits (constipation and/or diarrhea), crampy left lower quadrant (abdomen) pain, and even perforation. Barium enema x-rays of left-sided lesions often reveal characteristic annular, constricting lesions.

When a patient with symptoms comes in for an examination, the doctor may perform x-rays of the colon and rectum via a barium enema or a colonoscopy to look for tumors. The physician will take tissue samples of any growths that are found. These samples are examined in the laboratory to determine if they are cancerous.

Digital Rectal Exam. In this examination, a doctor puts a gloved finger into the patient's rectum to find any growths. This exam is simple to do and is not painful. However, because this examination can find less than 10% of colorectal cancers, it must be used along with another screening test.

Fecal Occult Blood Testing (FOBT). A fecal occult blood test (stool guaiac or Hemoccult test) detects the presence of occult (not visible to the naked eye and only detectable by chemical means) blood in the stool. This type of bleeding may occur anywhere along the digestive tract, but it is most likely to originate in the colon. Physicians usually recommend an annual fecal occult blood test for all adults beginning at age 50. If you have a higher risk because of a personal or family history of colorectal cancer or polyps, your physician may suggest that your fecal occult blood testing should begin earlier.

The fecal occult blood test is a simple chemical test of three consecutive stool samples, each of which is sent to the laboratory for analysis. It is not recommended that red meat or fish be consumed prior to this test as this can cause a false-positive reading for blood. It is also suggested that all drugs and substances that can interfere with the test (such as vitamin C, which can cause a false-negative reading; horseradish, fresh broccoli, turnips, and cauliflower, which can give a false-positive reading; anticoagulants, aspirin, or arthritis medicine, which can cause leakage of blood into the intestinal tract; and oxidizing drugs such as topical iodine, bromides, boric acid, and reserpine, which can also cause a false-positive reading) be discontinued prior to the test.

Note: It is important to discuss all drugs, supplements, and dietary regimens with your physician.

The fecal occult blood test can be positive in many different situations including colorectal cancer, esophagitis, gastritis, stomach cancer, ulcerative colitis, and hemorrhoids. It can also be positive when a person has been taking aspirin or other medications that irritate the digestive tract.

Flexible Sigmoidoscopy. A flexible sigmoidoscope, a short, flexible, lighted tube connected to a tiny video camera, enables a physician to examine the inside of the large intestine from the rectum through the sigmoid or descending colon when inserted into the rectum. The scope inflates the large intestine by blowing air into the rectum and colon providing a clear image of the inside lining of the colorectal area, which is then transmitted back to a monitor for viewing. Usually a sigmoidoscopy can be performed by a trained, primary care physician without sedation in the practitioner's office.

The colon and rectum must be completely empty for flexible sigmoidoscopy to be thorough and safe. Therefore, 12-24 hours before the procedure, the patient will be instructed to drink only clear liquids. A liquid diet is one containing fat-free bouillon or broth, gelatin, strained fruit juice, water, plain coffee, plain tea, or diet soda. Prior to the procedure, a patient may also be given an enema, which is a liquid solution that washes out the intestines.

Flexible sigmoidoscopy takes 10-20 minutes. During the procedure, a feeling of pressure and slight cramping may occur in the lower abdomen. Once the air leaves the colon, these symptoms will dissipate. If anything unusual is found in the rectum or colon, such as a polyp or inflamed tissue, the physician can remove a biopsy (piece of tissue), using an instrument inserted into the scope, and send it to a laboratory for testing. Bleeding and puncture of the colon are possible complications of sigmoidoscopy. However, such complications are very uncommon.

Physicians may use the procedure to find the cause of diarrhea, abdominal pain, or constipation. They also use it to look for early signs of cancer in the descending colon and rectum. With flexible sigmoidoscopy, the physician can see bleeding, inflammation, abnormal growths, and ulcers in the descending colon and rectum. A flexible sigmoidoscopy is not sufficient to detect polyps or cancer in the ascending or transverse colon (two-thirds of the colon).

A sigmoidoscopy has been proven to reduce the incidence and mortality of colon cancer through early detection. A flexible sigmoidoscopy, however, is not an adequate method of screening in hereditary colon cancer, as two-thirds of lesions develop beyond the colorectal area viewed by sigmoidoscopy. In these cases, colonoscopy should be used. A flexible sigmoidoscopy can detect about 65-75% of polyps and 40-65% of colorectal cancers (Okamoto et al. 2002).

Colonoscopy. Colonoscopy remains the gold standard for visualizing and diagnosing unexplained changes in bowel habits, performing biopsies, and removing colon polyps. A colonoscopy is similar to sigmoidoscopy in its ability to enable a physician to see inflamed tissue, abnormal growths, ulcers, and bleeding. However, colonoscopy provides a means of visually examining the entire large intestine from the lowest part, the rectum, all the way up through the colon to the lower end of the small intestine, whereas sigmoidoscopy only allows for a partial examination of the large intestine.

As with sigmoidoscopy, colonoscopy requires the colon and rectum to be completely empty. Therefore, 24 hours before the procedure, the patient will be instructed to drink only clear liquids. During this 24-hour period, strong saline-based laxatives are administered to thoroughly clean the lining of the colon. In some instances, a patient may also be given an enema, which is a liquid solution that washes out the intestines.

Colonoscopy consists of the insertion of a long, flexible, lighted tube connected to a tiny video camera, called a colonoscope, into the rectum. The colonoscope is slowly guided into the colon. The scope bends and also blows air into the colon (which inflates the colon, allowing for improved viewing) and transmits an image of the inside of the colon to a monitor for the physician's careful examination of the colon lining. Pain medication and a mild sedative may be administered to ensure comfort and relaxation during the examination.

If there are any abnormal findings, such as a polyp or inflamed tissue, they will be removed by the passing of small instruments through the scope. These tissues (biopsy) will then be sent to a laboratory for testing. If bleeding is found in the colon, the physician can pass a laser, heater probe, or electrical probe or inject special medicines through the scope to stop the bleeding. Most colonoscopies are performed on an outpatient basis with minimal inconvenience and discomfort.

Bleeding and puncture of the colon are possible complications of colonoscopy. However, such complications are uncommon.

Barium Enema. The use of the double contrast barium enema has declined in recent years in favor of colonoscopy, despite the lower cost of the barium enema. There are several reasons for the decreased use of the barium enema as a diagnostic tool: reduced sensitivity of this test in detecting polyps of less than 1 cm, reduced sensitivity in detecting polyps in areas where a single lumen is not detectable (i.e., sigmoid, rectosigmoid, hepatic, and splenic flexures), and patient comfort and compliance issues. Despite these limitations, when a colonoscopy is not possible, the double contrast barium enema combined with a flexible sigmoidoscopy is an acceptable alternative. A barium enema cannot be used for the surveillance of familial polyps, familial colon cancer, and inflammatory bowel disease, when attention to small details of the colonic mucosa is required and the likelihood of biopsy or polyp removal is high.

A barium enema is an x-ray test used to examine the colon and rectum of the lower digestive tract. Because these internal organs are normally not visible on x-rays, barium is inserted by enema into the rectum and colon to enhance visibility. The barium will temporarily coat the inside lining of the rectum and colon, allowing the outline of these organs to be visible on the x-ray pictures. This test is useful for diagnosing cancers and diverticula (small pouches that may form in the intestinal wall).

As with sigmoidoscopy and the colonoscopy, the barium enema requires the colon and rectum to be completely empty. Therefore, before the procedure, the patient will be instructed to drink only clear liquids. Milk or milk products should not be consumed.

The x-ray for this test is actually taken as a video by a large camera positioned over the abdomen immediately after the enema has begun. Usually the room will be darkened during the procedure so that the doctor can observe the x-rays on a monitor and pick out a few freeze-frame pictures to save and develop for a closer look later.

A major reason to avoid barium enemas is the large amount of radiation needed to view the lower abdominal region of the body. Radiation damages cellular DNA, causing mutations that can lead to cancer later in life.

Virtual Colonoscopy. An emerging technology referred to as virtual colonoscopy uses computer-generated images of the colon constructed from data obtained during an abdominal computed tomographic examination (CT scan). A CT scan is a specialized x-ray technique that produces many layers of detailed pictures. Sometimes magnetic resonance imaging (MRI) is substituted for CT. In an MRI, the patient passes through a tunnel surrounded by a powerful magnet. A computer tracks the magnetism and produces a picture of the tissues being studied. These images simulate the effect of a conventional colonoscopy. As with the colonoscopy, patients must take laxatives before the procedure, and the colon is insufflated with air just prior to the radiographic examination. The risk with a CT virtual colonoscopy is the large amount of radiation delivered to the body.

Genetic Tests. Detection of DNA mutations in the stool identifies genes that can later lead to colorectal cancer. In a study published in Exact Sciences and presented at the Digestive Disease Week Annual Conference (May 2002), the association of certain DNA mutations with advanced colonic polyps was examined to determine their potential utility as targets for stool-based mutated human DNA screening assays. The study found 91% positive identification of one or more of 19 gene mutations known to be associated with colorectal cancer including K-Ras, APC, and p53, which had been previously identified in tissue specimens from randomly selected advanced colonic polyps, 1 cm in diameter or greater.

New methods of screening patients for colorectal cancer depend on the identification of mutated or otherwise altered DNA in stool samples. Stool-based assays for mutated human DNA that can identify these mutations may significantly increase the identification of patients with potentially premalignant advanced colonic polyps for evaluation and treatment by colonoscopy.

A study in the January 2002 New England Journal of Medicine reports that mutations in the adenomatous polyposis coli (APC), the gene that initiates colorectal tumors, theoretically provide an optimal marker for detecting colorectal tumors. The study concludes that mutations can be detected in fecal DNA from patients with relatively early colorectal tumors. This feasibility study suggests a new approach for the early detection of colorectal neoplasms (Traverso et al. 2002). However, results from large-scale population studies on the sensitivity and specificity of such markers have not been reported as yet.

Abnormal Screening Findings

In the laboratory, pathologists can evaluate the specimen for abnormal growth. If there is a tumor, it may be benign (noncancerous) or malignant (cancerous). If a patient is diagnosed with cancer, professionals will form a treatment team to determine the best course of action. This team may include medical and radiation oncologists (physicians who specialize in diagnosing and treating cancer), a surgeon, and a gastroenterologist (a physician who specializes in treating the digestive system).

Prognostic and Predictive Factors

Once cancer is diagnosed, there are several tests performed on lymph node or tumor tissue that can be useful in determining prognosis and assessing the type of treatment that will be most effective for the specific type of colorectal cancer. There are several important predictive factors such as the presence of tumor markers and genetic mutations.

However, the prognosis of colon cancer is clearly related to the degree of the tumor's penetration of the bowel wall and the presence or absence of nodal involvement. Therefore, these two characteristics form the basis for all staging systems developed for this disease.

Continued . . .


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