Thursday, September 16, 2010
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Colonoscopy
What is colonoscopy?
Colonoscopy is a procedure that enables an examiner (usually a gastroenterologist) to evaluate the inside of the colon (large intestine or large bowel). The colonoscope is a four foot long, flexible tube about the thickness of a finger with a camera and a source of light at its tip. The tip of the colonoscope is inserted into the anus and then is advanced slowly, under visual control, into the rectum and through the colon usually as far as the cecum, which is the first part of the colon.Why is colonoscopy done?
Colonoscopy may be done for a variety of reasons. Most often it is done to investigate the cause of blood in the stool, abdominal pain, diarrhea, a change in bowel habit, or an abnormality found on colonic X-rays or a computerized tomographic (CT) scan. Individuals with previous history of polyps or colon cancer and certain individuals with a family history of some types of non-colonic cancers or colonic problems that may be associated with colon cancer (such as ulcerative colitis and colonic polyps) may be advised to have periodic colonoscopies because their risks are greater for polyps or colon cancer. How often should one undergo colonoscopy depends on the degree of the risks and the abnormalities found at previous colonoscopies. More recently, it has been recommended that even healthy people at normal risk for colon cancer should undergo colonoscopy at age 50 and every 10 years thereafter, for the purpose of removing colonic polyps before they become cancerous.What bowel preparation is needed for colonoscopy?
If the procedure is to be complete and accurate, the colon must be completely cleaned, and there are several colonoscopy preparations . Patients are given detailed instructions about the cleansing preparation. In general, this consists of drinking a large volume of a special cleansing solution or several days of a clear liquid diet and laxatives or enemas prior to the examination. These instructions should be followed exactly as prescribed or the procedure may be unsatisfactory, and may have to be repeated, or a less accurate alternative test may be performed in its place.What about current medications or diet before colonoscopy?
Most medications should be continued as usual, but some may interfere with the examination. It is best that the physician is informed of all current prescriptions or over-the-counter medications. Aspirin products, blood thinners (warfarin [Coumadin], etc.), arthritis medications, insulin, and iron preparations are examples of medications that may require special instructions. The colonoscopist will also want to be aware of a patient's allergies and any other major illnesses. The colonoscopist should be alerted if, in the past, patients have required antibiotics prior to surgical or dental procedures to prevent infections. Instructions may also be given to avoid certain foods for a couple of days prior to the procedure, such as stringy foods, foods with seeds, or red Jello.What should I expect during colonoscopy?
Prior to colonoscopy, intravenous fluids are started, and the patient is placed on a monitor for continuous monitoring of heart rhythm and blood pressure as well as oxygen in the blood. Medications (sedatives) usually are given through an intravenous line so the the patient becomes sleepy and relaxed, and to reduce pain. If needed, the patient may receive additional doses of medication during the procedure. Colonoscopy often produces a feeling of pressure, cramping, and bloating in the abdomen; however, with the aid of medications, it is generally well-tolerated and infrequently causes severe pain.Patients will lay on their left side or back as the colonoscope is slowly advanced. Once the tip of the colon (cecum) or the last portion of the small intestine (terminal ileum) is reached, the colonoscope is slowly withdrawn, and the lining of the colon is carefully examined. Colonoscopy usually takes 15 to 60 minutes. If the entire colon, for some reason, cannot be visualized, the physician may decide to try colonoscopy again at a later date with or without a different bowel preparation or may decide to order an X-ray or CT of the colon.
What if there are abnormalities detected during colonoscopy?
If an abnormal area needs to be better evaluated, a biopsy forceps is passed through a channel in the colonoscope and a biopsy (a sample of the tissue) is obtained. The biopsy is submitted to the pathology laboratory for examination under a microscope by a pathologist. If infection is suspected, a biopsy may be obtained for culturing of bacteria (and occasionally viruses) or examination under the microscope for parasites. If colonoscopy is performed because of bleeding, the site of bleeding can be identified, samples of tissue obtained (if necessary), and the bleeding controlled by several means. Should there be polyps, (benign growths that can become cancerous) they almost always can be removed through the colonoscope. Removal of these polyps is an important method of preventing colorectal cancer, although the great majority of polyps are benign. None of these additional procedures typically produce pain. Biopsies are taken for many reasons and do not necessarily mean that cancer is suspected.What should I expect post colonoscopy?
Patients will be kept in an observation area for an hour or two post-colonoscopy, until the effects of medications that have been given adequately wear off. If patients have been given sedatives before or during colonoscopy, they may not drive, even if they feel alert. Someone else must drive them home. The patient's reflexes and judgment may be impaired for the rest of the day, making it unsafe to drive, operate machinery, or make important decisions. Should patients have some cramping or bloating, this can be relieved quickly with the passage of gas, and they should be able to eat upon returning home. After the removal of polyps or certain other manipulations, the diet or activities of patients may be restricted for a brief period of time.Prior to the patient's departure from the coloscopic unit, the findings can be discussed with the patient. However, at times, a definitive diagnosis may have to wait for a microscopic analysis of biopsy specimens, which usually takes a few days.
What are the possible complications or alternatives to colonoscopy?
Complications of colonoscopy are rare and usually minor when performed by physicians who have been specially trained and are experienced.Bleeding may occur at the site of biopsy or removal of polyps, but the bleeding is usually minor and self-limited or can be controlled through the colonoscope. It is quite unusual to require transfusions or surgery for post-colonoscopic bleeding. An even less common complication is a perforation or a tear through the colonic wall, but even these perforations do not usually require surgery.
Other potential complications are reactions to the sedatives used, localized irritation to the vein where medications were injected (leaving a tender lump lasting a number of days, which goes away eventually), or complications from existing heart or lung disease. The incidence of all of these, together, is less than one percent.
While these complications are rare, it is important for patients to recognize early signs of a complication so that they may return to their physicians or an emergency room. The colonoscopist who performed the colonoscopy should be contacted if patients notice severe abdominal pain, rectal bleeding of more than half a cup, or fever and chills.
Colonoscopy is the best method available to detect, diagnose, and treat abnormalities within the colon. The alternatives to colonoscopy are quite limited. Barium enema is a less accurate test performed with X-rays. It misses abnormalities more often than colonoscopy, and, if an abnormality is found, a colonoscopy may still be required to biopsy or remove the abnormality. At times, an abnormality or lesion detected with a barium enema is actually stool or residual food in a poorly cleansed colon. Colonoscopy may then be necessary to clarify the issue. Flexible sigmoidoscopy is a limited examination that uses a shorter colonoscope and examines only the last one-third of the colon.
What is virtual colonoscopy?
Another alternative to colonoscopy is virtual colonoscopy. Virtual colonoscopy is a technique that uses computerized tomography (CT) scanning to obtain images of the colon that are similar to the views of the colon obtained by direct observation through colonoscopy. The images are constructed using the CT images so they do not represent true images. They are virtual images.In preparation for virtual colonoscopy, the day before the examination, the colon is cleaned-out using laxatives. During the examination a tube is inserted into the anus and is used to inject air into the colon. The CT scans are then performed with the colon inflated, and the scans are analyzed and manipulated to form a virtual image of the colon. When properly performed, virtual colonoscopy can be effective. It can even find polyps "hiding" behind folds that occasionally are missed by colonoscopy.
Nevertheless, virtual colonoscopy has several limitations.
- Virtual colonoscopy has difficulty identifying small polyps (less than 5 mm in size) that are easily seen at colonoscopy.
- Virtual colonoscopy has great difficulty identifying flat cancers or premalignant lesions that are not protruding, that is, are not polyp-like.
- Virtual colonoscopy does not allow removal of polyps that are found. Thirty to forty percent of people have colon polyps. If polyps are found by virtual colonoscopy, then colonoscopy must be done to remove the polyps. Therefore, many individuals having virtual colonoscopy will have to undergo a second procedure, colonoscopy.
- Virtual colonoscopy exposes individuals to a moderate amount of radiation.
- Virtual colonoscopy does not allow the use of the newer techniques that are being developed to differentiate between abnormal lesions that need to be biopsied or removed and those that don't. (See section "What's new in colonoscopy?" that follows.)
What's new in colonoscopy?
There are several new developments in colonoscopy. Most of these center around improving the detection of difficult-to-identify lesions-- small ones (for example, small polyps) and flat ones--as well as the ability to determine at the time of colonoscopy whether or not smaller polyps and lesions need to be biopsied or removed because they may contain premalignant or malignant tissue. This is important because many of these lesions are not premalignant or malignant, and a lot of time and money is spent removing them and sending them for microscopic examination unnecessarily.High resolution images that allow better detection of flat lesions have become standard on most colonoscopes. Magnification of the images also may improve the detection of the lesions.
Narrow-band imaging uses a special wavelength of light that enhances the pattern of tiny blood vessels that lie just below the lining of the colon. The pattern of these vessels is different in normal, premalignant and malignant tissue. Determination of the pattern allows lesions, particularly premalignant and malignant flat lesions, to be identified more easily and also allows a decision to be made as to whether or not the lesion should be biopsied or removed at the time of colonoscopy without waiting for the results of the microscopic examination.
Chromoendoscopy uses dyes (stains) that are sprayed on the colon lining to differentiate normal lining from neoplastic (benign, premalignant, and malignant) tissues and determine which lesions should be removed or biopsied.
Fluorescence endoscopy uses fluorescein-labelled chemicals either sprayed on the lining of the colon or injected intravenously. The chemicals are taken up by abnormal cells (premalignant and malignant) of the colon's lining more than the normal cells, and special lighting make the areas of abnormal cells clearer to see so they can be biopsied or removed completely. Confocal laser endoscopy uses a particular wavelength of light that penetrates the lining of the fluorescein-stained colon for several millimeters. Abnormal cells may be more clearly identified than with fluorescein staining alone.
There are even colonoscopes and accessories that allow a retrograde view of the colon in addition to the antegrade view from the tip of the colonoscope. Thus, images are obtained in two, 180 degree-opposed directions in order to identify lesions that might be hiding behind folds in the lining of the colon that would be missed by a standard, forward-viewing colonoscope. There are even attempts to develop a self-advancing colonoscope.
Most of these newer colonoscopic techniques, with the exception of high resolution imaging, are still considered experimental. Which one(s) will ultimately turn out to be valuable adjuncts to colonoscopy has yet to be determined.
REFERENCE: eMedicine.com. Colonoscopy.
<http://emedicine.medscape.com/article/1819350-overview>
Previous contributing author and editor: Medical Author: Eric Lee, M.D.
Medical Reviewing Author/Editor: Dennis Lee, M.D.
<http://emedicine.medscape.com/article/1819350-overview>
Previous contributing author and editor: Medical Author: Eric Lee, M.D.
Medical Reviewing Author/Editor: Dennis Lee, M.D.
Colon Cancer (Colorectal Cancer)
What is cancer?
Cancer is a group of more than 100 different diseases. They affect the body's basic unit, the cell. Cancer occurs when cells become abnormal and divide without control or order. Like all other organs of the body, the colon and rectum are made up of many types of cells. Normally, cells divide to produce more cells only when the body needs them. This orderly process helps keep us healthy.If cells keep dividing when new cells are not needed, a mass of tissue forms. This mass of extra tissue, called a growth or tumor, can be benign or malignant.
Benign tumors are not cancer. They can usually be removed and, in most cases, they do not come back. Most important, cells from benign tumors do not spread to other parts of the body. Benign tumors are rarely a threat to life.
Malignant tumors are cancer. Cancer cells can invade and damage tissues and organs near the tumor. Also, cancer cells can break away from a malignant tumor and enter the bloodstream or lymphatic system. This is how cancer spreads from the original (primary) tumor to form new tumors in other parts of the body. The spread of cancer is called metastasis.
When cancer spreads to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if colon cancer spreads to the liver, the cancer cells in the liver are colon cancer cells. The disease is metastatic colon cancer (it is not liver cancer).
What is cancer of the colon and rectum?
The colon is the part of the digestive system where the waste material is stored. The rectum is the end of the colon adjacent to the anus. Together, they form a long, muscular tube called the large intestine (also known as the large bowel). Tumors of the colon and rectum are growths arising from the inner wall of the large intestine. Benign tumors of the large intestine are called polyps. Malignant tumors of the large intestine are called cancers. Benign polyps do not invade nearby tissue or spread to other parts of the body. Benign polyps can be easily removed during colonoscopy and are not life-threatening. If benign polyps are not removed from the large intestine, they can become malignant (cancerous) over time. Most of the cancers of the large intestine are believed to have developed from polyps. Cancer of the colon and rectum (also referred to as colorectal cancer) can invade and damage adjacent tissues and organs. Cancer cells can also break away and spread to other parts of the body (such as liver and lung) where new tumors form. The spread of colon cancer to distant organs is called metastasis of the colon cancer. Once metastasis has occurred in colorectal cancer, a complete cure of the cancer is unlikely.
What are the causes of colon cancer?
Doctors are certain that colorectal cancer is not contagious (a person cannot catch the disease from a cancer patient). Some people are more likely to develop colorectal cancer than others. Factors that increase a person's risk of colorectal cancer include high fat intake, a family history of colorectal cancer and polyps, the presence of polyps in the large intestine, and chronic ulcerative colitis.Diet and colon cancer
Diets high in fat are believed to predispose humans to colorectal cancer. In countries with high colorectal cancer rates, the fat intake by the population is much higher than in countries with low cancer rates. It is believed that the breakdown products of fat metabolism lead to the formation of cancer-causing chemicals (carcinogens). Diets high in vegetables and high-fiber foods such as whole-grain breads and cereals may rid the bowel of these carcinogens and help reduce the risk of cancer.
Colon polyps and colon cancer
Doctors believe that most colon cancers develop in colon polyps. Therefore, removing benign colon polyps can prevent colorectal cancer. Colon polyps develop when chromosome damage occurs in cells of the inner lining of the colon. Chromosomes contain genetic information inherited from each parent. Normally, healthy chromosomes control the growth of cells in an orderly manner. When chromosomes are damaged, cell growth becomes uncontrolled, resulting in masses of extra tissue (polyps). Colon polyps are initially benign. Over years, benign colon polyps can acquire additional chromosome damage to become cancerous.
Ulcerative colitis and colon cancer
Chronic ulcerative colitis causes inflammation of the inner lining of the colon. For further information, please read the Ulcerative Colitis article. Colon cancer is a recognized complication of chronic ulcerative colitis. The risk for cancer begins to rise after eight to 10 years of colitis. The risk of developing colon cancer in a patient with ulcerative colitis also is related to the location and the extent of his or her disease.
Current estimates of the cumulative incidence of colon cancer associated with ulcerative colitis are 2.5% at 10 years, 7.6% at 30 years, and 10.8% at 50 years. Patients at higher risk of cancer are those with a family history of colon cancer, a long duration of colitis, extensive colon involvement, and those with primary sclerosing cholangitis (PSC).
Since the cancers associated with ulcerative colitis have a more favorable outcome when caught at an earlier stage, yearly examinations of the colon often are recommended after eight years of known extensive disease. During these examinations, samples of tissue (biopsies) can be taken to search for precancerous changes in the lining cells of the colon. When precancerous changes are found, removal of the colon may be necessary to prevent colon cancer.
Genetics and colon cancer
A person's genetic background is an important factor in colon cancer risk. Among first-degree relatives of colon cancer patients, the lifetime risk of developing colon cancer is 18% (a threefold increase over the general population in the United States).
Even though family history of colon cancer is an important risk factor, majority (80%) of colon cancers occur sporadically in patients with no family history of colon cancer. Approximately 20% of cancers are associated with a family history of colon cancer. And 5 % of colon cancers are due to hereditary colon cancer syndromes. Hereditary colon caner syndromes are disorders where affected family members have inherited cancer-causing genetic defects from one or both of the parents.
Chromosomes contain genetic information, and chromosome damages cause genetic defects that lead to the formation of colon polyps and later colon cancer. In sporadic polyps and cancers (polyps and cancers that develop in the absence of family history), the chromosome damages are acquired (develop in a cell during adult life). The damaged chromosomes can only be found in the polyps and the cancers that develop from that cell. But in hereditary colon cancer syndromes, the chromosome defects are inherited at birth and are present in every cell in the body. Patients who have inherited the hereditary colon cancer syndrome genes are at risk of developing large number of colon polyps, usually at young ages, and are at very high risk of developing colon cancer early in life, and also are at risk of developing cancers in other organs.
FAP (familial adenomatous polyposis) is a hereditary colon cancer syndrome where the affected family members will develop countless numbers (hundreds, sometimes thousands) of colon polyps starting during the teens. Unless the condition is detected and treated (treatment involves removal of the colon) early, a person affected by familial polyposis syndrome is almost sure to develop colon cancer from these polyps. Cancers usually develop in the 40s. These patients are also at risk of developing other cancers such as cancers in the thyroid gland, stomach, and the ampulla (the part where the bile ducts drain into the duodenum just beyond the stomach).
AFAP (attenuated familial adenomatous polyposis) is a milder version of FAP. Affected members develop less than 100 colon polyps. Nevertheless, they are still at very high risk of developing colon cancers at young ages. They are also at risk of having gastric polyps and duodenal polyps.
HNPCC (hereditary nonpolyposis colon cancer) is a hereditary colon cancer syndrome where affected family members can develop colon polyps and cancers, usually in the right colon, in their 30s to 40s. Certain HNPCC patients are also at risk of developing uterine cancer, stomach cancer, ovarian cancer, and cancers of the ureters (the tubes that connect the kidneys to the bladder), and the biliary tract (the ducts that drain bile from the liver to the intestines).
MYH polyposis syndrome is a recently discovered hereditary colon cancer syndrome. Affected members typically develop 10-100 polyps occurring at around 40 years of age, and are at high risk of developing colon cancer.
What are the symptoms of colon cancer?
Symptoms of colon cancer are numerous and nonspecific. They include fatigue, weakness, shortness of breath, change in bowel habits, narrow stools, diarrhea or constipation, red or dark blood in stool, weight loss, abdominal pain, cramps, or bloating. Other conditions such as irritable bowel syndrome (spastic colon), ulcerative colitis, Crohn's disease, diverticulosis, and peptic ulcer disease can have symptoms that mimic colorectal cancer. For more information on these conditions, please read the following articles: Irritable Bowel Syndrome, Ulcerative Colitis, Crohn's Disease, Diverticulosis, and Peptic Ulcer Disease.Colon cancer can be present for several years before symptoms develop. Symptoms vary according to where in the large bowel the tumor is located. The right colon is spacious, and cancers of the right colon can grow to large sizes before they cause any abdominal symptoms. Typically, right-sided cancers cause iron deficiency anemia due to the slow loss of blood over a long period of time. Iron deficiency anemia causes fatigue, weakness, and shortness of breath. The left colon is narrower than the right colon. Therefore, cancers of the left colon are more likely to cause partial or complete bowel obstruction. Cancers causing partial bowel obstruction can cause symptoms of constipation, narrowed stool, diarrhea, abdominal pains, cramps, and bloating. Bright red blood in the stool may also indicate a growth near the end of the left colon or rectum.
What tests can be done to detect colon cancer?
When colon cancer is suspected, either a lower GI series (barium enema x-ray) or colonoscopy is performed to confirm the diagnosis and to localize the tumor.A barium enema involves taking x-rays of the colon and the rectum after the patient is given an enema with a white, chalky liquid containing barium. The barium outlines the large intestines on the x-rays. Tumors and other abnormalities appear as dark shadows on the x-rays. For more information, please read the Lower Gastrointestinal Series (Barium Enema) article.
Colonoscopy is a procedure whereby a doctor inserts a long, flexible viewing tube into the rectum for the purpose of inspecting the inside of the entire colon. Colonoscopy is generally considered more accurate than barium enema x-rays, especially in detecting small polyps. If colon polyps are found, they are usually removed through the colonoscope and sent to the pathologist. The pathologist examines the polyps under the microscope to check for cancer. While the majority of the polyps removed through the colonoscopes are benign, many are precancerous. Removal of precancerous polyps prevents the future development of colon cancer from these polyps. For more information, please read the Colonoscopy article.
If cancerous growths are found during colonoscopy, small tissue samples (biopsies) can be obtained and examined under the microscope to confirm the diagnosis. If colon cancer is confirmed by a biopsy, staging examinations are performed to determine whether the cancer has already spread to other organs. Since colorectal cancer tends to spread to the lungs and the liver, staging tests usually include chest x-rays, ultrasonography, or a CAT scan of the lungs, liver, and abdomen.
Sometimes, the doctor may obtain a blood test for CEA (carcinoembyonic antigen). CEA is a substance produced by some cancer cells. It is sometimes found in high levels in patients with colorectal cancer, especially when the disease has spread.
How can colon cancer be prevented?
Unfortunately, colon cancers can be well advanced before they are detected. The most effective prevention of colon cancer is early detection and removal of precancerous colon polyps before they turn cancerous. Even in cases where cancer has already developed, early detection still significantly improves the chances of a cure by surgically removing the cancer before the disease spreads to other organs. Multiple world health organizations have suggested general screening guidelines.
Digital rectal examination and stool occult blood testing
It is recommended that all individuals over the age of 40 have yearly digital examinations of the rectum and their stool tested for hidden or "occult" blood. During digital examination of the rectum, the doctor inserts a gloved finger into the rectum to feel for abnormal growths. Stool samples can be obtained to test for occult blood (see below). The prostate gland can be examined at the same time.
An important screening test for colorectal cancers and polyps is the stool occult blood test. Tumors of the colon and rectum tend to bleed slowly into the stool. The small amount of blood mixed into the stool is usually not visible to the naked eye. The commonly used stool occult blood tests rely on chemical color conversions to detect microscopic amounts of blood. These tests are both convenient and inexpensive. A small amount of stool sample is smeared on a special card for occult blood testing. Usually, three consecutive stool cards are collected. A person who tests positive for stool occult blood has a 30% to 45% chance of having a colon polyp and a 3% to 5% chance of having a colon cancer. Colon cancers found under these circumstances tend to be early and have a better long-term prognosis.
It is important to remember that having stool tested positive for occult blood does not necessarily mean the person has colon cancer. Many other conditions can cause occult blood in the stool. However, patients with a positive stool occult blood should undergo further evaluations involving barium enema x-rays, colonoscopies, and other tests to exclude colon cancer, and to explain the source of the bleeding. It is also important to realize that stool which has tested negative for occult blood does not mean the absence of colorectal cancer or polyps. Even under ideal testing conditions, at least 20% of colon cancers can be missed by stool occult blood screening. Many patients with colon polyps are tested negative for stool occult blood. In patients suspected of having colon tumors, and in those with high risk factors for developing colorectal polyps and cancer, flexible sigmoidoscopies or screening colonoscopies are performed even if the stool occult blood tests are negative.
Flexible sigmoidoscopy and colonoscopy
Beginning at age 50, a flexible sigmoidoscopy screening tests is recommended every three to five years. Flexible sigmoidoscopy is an exam of the rectum and the lower colon using a viewing tube (a short version of colonoscopy). Recent studies have shown that the use of screening flexible sigmoidoscopy can reduce mortality from colon cancer. This is a result of the detection of polyps or early cancers in people with no symptoms. If a polyp or cancer is found, a complete colonoscopy is recommended. The majority of colon polyps can be completely removed by colonoscopy without open surgery. Recently doctors are recommending screening colonoscopies instead of screening flexible sigmoidoscopies for healthy individuals starting at ages 50-55. Please read the Colon Cancer Screening article.
Patients with a high risk of developing colorectal cancer may undergo colonoscopies starting at earlier ages than 50. For example, patients with family history of colon cancer are recommended to start screening colonoscopies at an age 10 years before the earliest colon caner diagnosed in a first-degree relative, or five years earlier than the earliest precancerous colon polyp discovered in a first-degree relative. Patients with hereditary colon cancer syndromes such as FAP, AFAP, HNPCC, and MYH are recommended to begin colonoscopies early. The recommendations differ depending on the genetic defect, for example in FAP; colonoscopies may begin during teenage years to look for the development of colon polyps. Patients with a prior history of polyps or colon cancer may also undergo colonoscopies to exclude recurrence. Patients with a long history (greater than 10 years) of chronic ulcerative colitis have an increased risk of colon cancer, and should have regular colonoscopies to look for precancerous changes in the colon lining.
Genetic counseling and testing
Blood tests are now available to test for FAP, AFAP, MYH, and HNPCC hereditary colon cancer syndromes. Families with multiple members having colon cancers, members with multiple colon polyps, members having cancers at young ages, and having other cancers such as cancers of the ureters, uterus, duodenum, etc., should be referred for genetic counseling followed possibly by genetic testing. Genetic testing without prior counseling is discouraged because of the extensive family education that is involved and the complicated nature of interpreting the test results.
The advantages of genetic counseling followed by genetic testing include: (1) identifying family members at high risk of developing colon cancer to begin colonoscopies early; (2) identifying high risk members so that screening may begin to prevent other cancers such as ultrasound tests for uterine cancer, urine examinations for ureter cancer, and upper endoscopies for stomach and duodenal cancers; and (3) alleviating concern for members who test negative for the hereditary genetic defects.
Diet and colon cancer to prevent colon cancer
People can change their eating habits by reducing fat intake and increasing fiber (roughage) in their diet. Major sources of fat are meat, eggs, dairy products, salad dressings, and oils used in cooking. Fiber is the insoluble, nondigestible part of plant material present in fruits, vegetables, and whole-grain breads and cereals. It is postulated that high fiber in the diet leads to the creation of bulky stools which can rid the intestines of potential carcinogens. In addition, fiber leads to the more rapid transit of fecal material through the intestine, thus allowing less time for a potential carcinogen to react with the intestinal lining. For additional information, please read the Colon Cancer Prevention article.
What are the treatments and survival for colon cancer?
Surgery is the most common treatment for colorectal cancer. During surgery, the tumor, a small margin of the surrounding healthy bowel, and adjacent lymph nodes are removed. The surgeon then reconnects the healthy sections of the bowel. In patients with rectal cancer, the rectum is permanently removed. The surgeon then creates an opening (colostomy) on the abdomen wall through which solid waste in the colon is excreted. Specially trained nurses (enterostomal therapists) can help patients adjust to colostomies, and most patients with colostomies return to a normal lifestyle.The long-term prognosis after surgery depends on whether the cancer has spread to other organs (metastasis). The risk of metastasis is proportional to the depth of penetration of the cancer into the bowel wall. In patients with early colon cancer which is limited to the superficial layer of the bowel wall, surgery is often the only treatment needed. These patients can experience long-term survival in excess of 80%. In patients with advanced colon cancer, wherein the tumor has penetrated beyond the bowel wall and there is evidence of metastasis to distant organs, the five-year survival rate is less than 10%.
In some patients, there is no evidence of distant metastasis at the time of surgery, but the cancer has penetrated deeply into the colon wall or reached adjacent lymph nodes. These patients are at risk of tumor recurrence either locally or in distant organs. Chemotherapy in these patients may delay tumor recurrence and improve survival.
Chemotherapy is the use of medications to kill cancer cells. It is a systemic therapy, meaning that the medication travels throughout the body to destroy cancer cells. After colon cancer surgery, some patients may harbor microscopic metastasis (small foci of cancer cells that cannot be detected). Chemotherapy is given shortly after surgery to destroy these microscopic cells. Chemotherapy given in this manner is called adjuvant chemotherapy. Recent studies have shown increased survival and delay of tumor recurrence in some patients treated with adjuvant chemotherapy within five weeks of surgery. Most drug regimens have included the use of 5-flourauracil (5-FU). On the other hand, chemotherapy for shrinking or controlling the growth of metastatic tumors has been disappointing. Improvement in the overall survival for patients with widespread metastasis has not been convincingly demonstrated.
Chemotherapy is usually given in a doctor's office, in the hospital as a outpatient, or at home. Chemotherapy is usually given in cycles of treatment periods followed by recovery periods. Side effects of chemotherapy vary from person to person, and also depend on the agents given. Modern chemotherapy agents are usually well tolerated, and side effects are manageable. In general, anticancer medications destroy cells that are rapidly growing and dividing. Therefore, red blood cells, platelets, and white blood cells are frequently affected by chemotherapy. Common side effects include anemia, loss of energy, easy bruising, and a low resistance to infections. Cells in the hair roots and intestines also divide rapidly. Therefore, chemotherapy can cause hair loss, mouth sores, nausea, vomiting, and diarrhea.
Radiation therapy in colorectal cancer has been limited to treating cancer of the rectum. There is a decreased local recurrence of rectal cancer in patients receiving radiation either prior to or after surgery. Without radiation, the risk of rectal cancer recurrence is close to 50%. With radiation, the risk is lowered to approximately 7%. Side effects of radiation treatment include fatigue, temporary or permanent pelvic hair loss, and skin irritation in the treated areas.
Other treatments have included the use of localized infusion of chemotherapeutic agents into the liver, the most common site of metastasis. This involves the insertion of a pump into the blood supply of the liver which can deliver high doses of medicine directly to the liver tumor. Response rates for these treatments have been reported to be as high as eighty percent. Side effects, however, can be serious. Additional experimental agents considered for the treatment of colon cancer include the use of cancer-seeking antibodies bound to cancer-fighting drugs. Such combinations can specifically seek and destroy tumor tissues in the body. Other treatments attempt to boost the immune system, the bodies' own defense system, in an effort to more effectively attack and control colon cancer. In patients who are poor surgical risks, but who have large tumors which are causing obstruction or bleeding, laser treatment can be used to destroy cancerous tissue and relieve associated symptoms. Still other experimental agents include the use of photodynamic therapy. In this treatment, a light sensitive agent is taken up by the tumor which can then be activated to cause tumor destruction.
What is the follow-up care for colon cancer?
Follow-up exams are important after treatment for colon cancer. The cancer can recur near the original site or in a distant organ such as the liver or lung. Follow-up exams include a physical examination by the doctor, blood tests of liver enzymes, chest x-rays, CAT scans of the abdomen and pelvis, colonoscopies, and blood CEA levels. Abnormal liver enzymes may indicate growth of liver metastasis. CEA levels may be elevated before surgery and become normal shortly after the cancer is removed. Slowly rising CEA level may indicate cancer recurrence. A CAT scan of the abdomen and pelvis can show tumor recurrence in the liver, pelvis, or other areas. Colonoscopy can show recurrence of polyps or cancer in the large intestine.In addition to checking for cancer recurrence, patients who have had colon cancer may have an increased risk of cancer of the prostate, breast, and ovary. Therefore, follow-up examinations should include these areas.
What does the future hold for patients with colorectal cancer?
Colon cancer remains a major cause of death and disease, especially in the western world. A clear understanding of the causes and course of the disease is emerging. This has allowed for recommendations regarding screening for and prevention of this disease. The removal of colon polyps helps prevent colon cancer. Early detection of colon cancer can improve the chances of a cure and overall survival. Treatment remains unsatisfactory for advanced disease, but research in this area remains strong and newer treatments continue to emerge. New and exciting preventive measures have recently focused on the possible beneficial effects of aspirin or other anti-inflammatory agents. In trials, the use of these agents has markedly limited colon cancer formation in several experimental models. Other agents being evaluated to prevent colon cancer include calcium, selenium, and vitamins A, C, and E. More studies are needed before these agents can be recommended for widespread use by the public to prevent colon cancer.Colon Cancer At A Glance
- Colorectal cancer is a malignant tumor arising from the inner wall of the large intestine.
- Colorectal cancer is the third leading cause of cancer in males and fourth in females in the U.S.
- Risk factors for colorectal cancer include heredity, colon polyps, and long-standing ulcerative colitis.
- Most colorectal cancers develop from polyps. Removal of colon polyps can prevent colorectal cancer.
- Colon polyps and early cancer can have no symptoms. Therefore regular screening is important.
- Diagnosis of colorectal cancer can be made by barium enema or by colonoscopy with biopsy confirmation of cancer tissue.
- Treatment of colorectal cancer depends on the location, size, and extent of cancer spread, as well as the age and health of the patient.
- Surgery is the most common treatment for colorectal cancer.
Rheumatoid Arthritis (RA)
Medical Editor: Melissa Conrad Stöppler, MD
- What is rheumatoid arthritis (RA)?
- What causes rheumatoid arthritis?
- What are the symptoms and signs of rheumatoid arthritis?
- How is rheumatoid arthritis diagnosed?
- How is rheumatoid arthritis treated?
- "First-line" medications
- "Second-line" or "slow-acting" drugs
- Newer treatments
- Other treatments
- Future treatments
- Rheumatoid Arthritis (RA) At A Glance
- Pictures of Rheumatoid Arthritis - Slideshow
- Patient Discussions: Rheumatoid Arthritis - Early Symptoms
- Find a local Rheumatologist in your town
What is rheumatoid arthritis (RA)?
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Rheumatoid arthritis can also cause inflammation of the tissue around the joints, as well as in other organs in the body. Autoimmune diseases are illnesses that occur when the body's tissues are mistakenly attacked by their own immune system. The immune system contains a complex organization of cells and antibodies designed normally to "seek and destroy" invaders of the body, particularly infections. Patients with autoimmune diseases have antibodies in their blood that target their own body tissues, where they can be associated with inflammation. Because it can affect multiple other organs of the body, rheumatoid arthritis is referred to as a systemic illness and is sometimes called rheumatoid disease.While rheumatoid arthritis is a chronic illness, meaning it can last for years, patients may experience long periods without symptoms. However, rheumatoid arthritis is typically a progressive illness that has the potential to cause joint destruction and functional disability.
In some people with rheumatoid arthritis, chronic inflammation leads to the destruction of the cartilage, bone, and ligaments, causing deformity of the joints. Damage to the joints can occur early in the disease and be progressive. Moreover, studies have shown that the progressive damage to the joints does not necessarily correlate with the degree of pain, stiffness, or swelling present in the joints.
Rheumatoid arthritis is a common rheumatic disease, affecting approximately 1.3 million people in the United States, according to current census data. The disease is three times more common in women as in men. It afflicts people of all races equally. The disease can begin at any age, but it most often starts after 40 years of age and before 60 years of age. In some families, multiple members can be affected, suggesting a genetic basis for the disorder.
What is rheumatoid arthritis (RA)?
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Rheumatoid arthritis can also cause inflammation of the tissue around the joints, as well as in other organs in the body. Autoimmune diseases are illnesses that occur when the body's tissues are mistakenly attacked by their own immune system. The immune system contains a complex organization of cells and antibodies designed normally to "seek and destroy" invaders of the body, particularly infections. Patients with autoimmune diseases have antibodies in their blood that target their own body tissues, where they can be associated with inflammation. Because it can affect multiple other organs of the body, rheumatoid arthritis is referred to as a systemic illness and is sometimes called rheumatoid disease.While rheumatoid arthritis is a chronic illness, meaning it can last for years, patients may experience long periods without symptoms. However, rheumatoid arthritis is typically a progressive illness that has the potential to cause joint destruction and functional disability.
In some people with rheumatoid arthritis, chronic inflammation leads to the destruction of the cartilage, bone, and ligaments, causing deformity of the joints. Damage to the joints can occur early in the disease and be progressive. Moreover, studies have shown that the progressive damage to the joints does not necessarily correlate with the degree of pain, stiffness, or swelling present in the joints.
Rheumatoid arthritis is a common rheumatic disease, affecting approximately 1.3 million people in the United States, according to current census data. The disease is three times more common in women as in men. It afflicts people of all races equally. The disease can begin at any age, but it most often starts after 40 years of age and before 60 years of age. In some families, multiple members can be affected, suggesting a genetic basis for the disorder.
How is rheumatoid arthritis diagnosed?
The first step in the diagnosis of rheumatoid arthritis is a meeting between the doctor and the patient. The doctor reviews the history of symptoms, examines the joints for inflammation and deformity, the skin for rheumatoid nodules, and other parts of the body for inflammation. Certain blood and X-ray tests are often obtained. The diagnosis will be based on the pattern of symptoms, the distribution of the inflamed joints, and the blood and X-ray findings. Several visits may be necessary before the doctor can be certain of the diagnosis. A doctor with special training in arthritis and related diseases is called a rheumatologist.The distribution of joint inflammation is important to the doctor in making a diagnosis. In rheumatoid arthritis, the small joints of the hands, wrists, feet, and knees are typically inflamed in a symmetrical distribution (affecting both sides of the body). When only one or two joints are inflamed, the diagnosis of rheumatoid arthritis becomes more difficult. The doctor may then perform other tests to exclude arthritis due to infection or gout. The detection of rheumatoid nodules (described above), most often around the elbows and fingers, can suggest the diagnosis.
Abnormal antibodies can be found in the blood of people with rheumatoid arthritis. An antibody called "rheumatoid factor" can be found in 80% of patients. Citrulline antibody (also referred to as anticitrulline antibody, anticyclic citrullinated peptide antibody, and anti-CCP) is present in most people with rheumatoid arthritis. It is useful in the diagnosis of rheumatoid arthritis when evaluating cases of unexplained joint inflammation. A test for citrulline antibodies is most helpful in looking for the cause of previously undiagnosed inflammatory arthritis when the traditional blood test for rheumatoid arthritis, rheumatoid factor, is not present. Citrulline antibodies have been felt to represent the earlier stages of rheumatoid arthritis in this setting. Another antibody called the "antinuclear antibody" (ANA) is also frequently found in people with rheumatoid arthritis.
A blood test called the sedimentation rate (sed rate) is a measure of how fast red blood cells fall to the bottom of a test tube. The sed rate is used as a crude measure of the inflammation of the joints. The sed rate is usually faster during disease flares and slower during remissions. Another blood test that is used to measure the degree of inflammation present in the body is the C-reactive protein. Blood testing may also reveal anemia, since anemia is common in rheumatoid arthritis, particularly because of the chronic inflammation.
The rheumatoid factor, ANA, sed rate, and C-reactive protein tests can also be abnormal in other systemic autoimmune and inflammatory conditions. Therefore, abnormalities in these blood tests alone are not sufficient for a firm diagnosis of rheumatoid arthritis.
Joint X-rays may be normal or only show swelling of soft tissues early in the disease. As the disease progresses, X-rays can show bony erosions typical of rheumatoid arthritis in the joints. Joint X-rays can also be helpful in monitoring the progression of disease and joint damage over time. Bone scanning, a radioactive procedure, can also be used to demonstrate the inflamed joints. MRI scanning can also be used to demonstrate joint damage.
The American College of Rheumatology has developed a system for classifying rheumatoid arthritis that is primarily based upon the X-ray appearance of the joints. This system helps medical professionals classify the severity of your rheumatoid arthritis.
Stage I
- no damage seen on X-rays, although there may be signs of bone thinning
- on X-ray, evidence of bone thinning around a joint with or without slight bone damage
- slight cartilage damage possible
- joint mobility may be limited; no joint deformities observed
- atrophy of adjacent muscle
- abnormalities of soft tissue around joint possible
- on X-ray, evidence of cartilage and bone damage and bone thinning around the joint
- joint deformity without permanent stiffening or fixation of the joint
- extensive muscle atrophy
- abnormalities of soft tissue around joint possible
- on X-ray, evidence of cartilage and bone damage and osteoporosis around joint
- joint deformity with permanent fixation of the joint (referred to as ankylosis)
- extensive muscle atrophy
- abnormalities of soft tissue around joint possible
- Class I: completely able to perform usual activities of daily living
- Class II: able to perform usual self-care and work activities but limited in activities outside of work (such as playing sports, household chores)
- Class III: able to perform usual self-care activities but limited in work and other activities
- Class IV: limited in ability to perform usual self-care, work, and other activities
How is rheumatoid arthritis treated?
There is no known cure for rheumatoid arthritis. To date, the goal of treatment in rheumatoid arthritis is to reduce joint inflammation and pain, maximize joint function, and prevent joint destruction and deformity. Early medical intervention has been shown to be important in improving outcomes. Aggressive management can improve function, stop damage to joints as monitored on X-rays, and prevent work disability. Optimal treatment for the disease involves a combination of medications, rest, joint-strengthening exercises, joint protection, and patient (and family) education. Treatment is customized according to many factors such as disease activity, types of joints involved, general health, age, and patient occupation. Treatment is most successful when there is close cooperation between the doctor, patient, and family members.Two classes of medications are used in treating rheumatoid arthritis: fast-acting "first-line drugs" and slow-acting "second-line drugs" (also referred to as disease-modifying antirheumatic drugs or DMARDs). The first-line drugs, such as aspirin and cortisone (corticosteroids), are used to reduce pain and inflammation. The slow-acting second-line drugs, such as gold, methotrexate, and hydroxychloroquine (Plaquenil), promote disease remission and prevent progressive joint destruction, but they are not anti-inflammatory agents.
The degree of destructiveness of rheumatoid arthritis varies among affected individuals. Those with uncommon, less destructive forms of the disease or disease that has quieted after years of activity ("burned out" rheumatoid arthritis) can be managed with rest and pain and anti-inflammatory medications alone. In general, however, function is improved and disability and joint destruction are minimized when the condition is treated earlier with second-line drugs (disease-modifying antirheumatic drugs), even within months of the diagnosis. Most people require more aggressive second-line drugs, such as methotrexate, in addition to anti-inflammatory agents. Sometimes these second-line drugs are used in combination. In some cases with severe joint deformity, surgery may be necessary.
"First-line" medications
Acetylsalicylate (aspirin), naproxen (Naprosyn), ibuprofen (Advil, Medipren, Motrin), and etodolac (Lodine) are examples of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are medications that can reduce tissue inflammation, pain, and swelling. NSAIDs are not cortisone. Aspirin, in doses higher than those used in treating headaches and fever, is an effective anti-inflammatory medication for rheumatoid arthritis. Aspirin has been used for joint problems since the ancient Egyptian era. The newer NSAIDs are just as effective as aspirin in reducing inflammation and pain and require fewer dosages per day. Patients' responses to different NSAID medications vary. Therefore, it is not unusual for a doctor to try several NSAID drugs in order to identify the most effective agent with the fewest side effects. The most common side effects of aspirin and other NSAIDs include stomach upset, abdominal pain, ulcers, and even gastrointestinal bleeding. In order to reduce gastrointestinal side effects, NSAIDs are usually taken with food. Additional medications are frequently recommended to protect the stomach from the ulcer effects of NSAIDs. These medications include antacids, sucralfate (Carafate), proton-pump inhibitors (Prevacid and others), and misoprostol (Cytotec). Newer NSAIDs include selective Cox-2 inhibitors, such as celecoxib (Celebrex), which offer anti-inflammatory effects with less risk of stomach irritation and bleeding risk.Corticosteroid medications can be given orally or injected directly into tissues and joints. They are more potent than NSAIDs in reducing inflammation and in restoring joint mobility and function. Corticosteroids are useful for short periods during severe flares of disease activity or when the disease is not responding to NSAIDs. However, corticosteroids can have serious side effects, especially when given in high doses for long periods of time. These side effects include weight gain, facial puffiness, thinning of the skin and bone, easy bruising, cataracts, risk of infection, muscle wasting, and destruction of large joints, such as the hips. Corticosteroids also carry some increased risk of contracting infections. These side effects can be partially avoided by gradually tapering the doses of corticosteroids as the individual achieves improvement in symptoms. Abruptly discontinuing corticosteroids can lead to flares of the disease or other symptoms of corticosteroid withdrawal and is discouraged. Thinning of the bones due to osteoporosis may be prevented by calcium and vitamin D supplements. For further information on corticosteroids, please read the article on prednisone.
"Second-line" or "slow-acting" drugs
(Disease-modifying anti-rheumatic drugs or DMARDs)
While "first-line" medications (NSAIDs and corticosteroids) can relieve joint inflammation and pain, they do not necessarily prevent joint destruction or deformity. Rheumatoid arthritis requires medications other than NSAIDs and corticosteroids to stop progressive damage to cartilage, bone, and adjacent soft tissues. The medications needed for ideal management of the disease are also referred to as disease-modifying antirheumatic drugs or DMARDs. They come in a variety of forms and are listed below. These "second-line" or "slow-acting" medicines may take weeks to months to become effective. They are used for long periods of time, even years, at varying doses. If maximally effective, DMARDs can promote remission, thereby retarding the progression of joint destruction and deformity. Sometimes a number of DMARD second-line medications are used together as combination therapy. As with the first-line medications, the doctor may need to try different second-line medications before treatment is optimal.Recent research suggests that patients who respond to a DMARD with control of the rheumatoid disease may actually decrease the known risk (small but real) of lymphoma (cancer of lymph nodes) that exists from simply having rheumatoid arthritis. The various available DMARDs are reviewed next. Hydroxychloroquine (Plaquenil) is related to quinine and is also used in the treatment of malaria. It is used over long periods for the treatment of rheumatoid arthritis. Possible side effects include upset stomach, skin rashes, muscle weakness, and vision changes. Even though vision changes are rare, people taking Plaquenil should be monitored by an eye doctor (ophthalmologist).
Sulfasalazine (Azulfidine) is an oral medication traditionally used in the treatment of mild to moderately severe inflammatory bowel diseases, such as ulcerative colitis and Crohn's colitis. Azulfidine is used to treat rheumatoid arthritis in combination with anti-inflammatory medications. Azulfidine is generally well tolerated. Common side effects include rash and upset stomach. Because Azulfidine is made up of sulfa and salicylate compounds, it should be avoided by people with known sulfa allergies.
Methotrexate has gained popularity among doctors as an initial second-line drug because of both its effectiveness and relatively infrequent side effects. It also has an advantage in dose flexibility (dosages can be adjusted according to needs). Methotrexate is an immune-suppression drug. It can affect the bone marrow and the liver, even rarely causing cirrhosis. All people taking methotrexate require regular blood tests to monitor blood counts and liver function.
Gold salts have been used to treat rheumatoid arthritis throughout most of the past century. Gold thioglucose (Solganal) and gold thiomalate (Myochrysine) are given by injection, initially on a weekly basis, for months to years. Oral gold, auranofin (Ridaura), was introduced in the 1980s. Side effects of gold (oral and injectable) include skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white cell count. Those receiving gold treatment are regularly monitored with blood and urine tests. Oral gold can cause diarrhea. These gold drugs have lost favor because of the availability of more effective treatments, and many companies no longer manufacture them.
D-penicillamine (Depen, Cuprimine) can be helpful in selected cases of progressive forms of rheumatoid arthritis. Side effects are similar to those of gold. They include fever, chills, mouth sores, a metallic taste in the mouth, skin rash, kidney and bone marrow damage, stomach upset, and easy bruising. People taking this medication require routine blood and urine tests. D-penicillamine can rarely cause symptoms of other autoimmune diseases and is no longer commonly used for the treatment of rheumatoid arthritis.
Immunosuppressive medicines are powerful medications that suppress the body's immune system. A number of immunosuppressive drugs are used to treat rheumatoid arthritis. They include methotrexate (Rheumatrex, Trexall) as described above, azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). Because of potentially serious side effects, immunosuppressive medicines (other than methotrexate) are generally reserved for those who have very aggressive disease or those with serious complications of rheumatoid inflammation, such as blood vessel inflammation (vasculitis). The exception is methotrexate, which is not frequently associated with serious side effects and can be carefully monitored with blood testing. Methotrexate has become a preferred second-line medication as a result.
Immunosuppressive medications can depress bone-marrow function and cause anemia, a low white cell count, and low platelet counts. A low white count can increase the risk of infections, while a low platelet count can increase the risk of bleeding. Methotrexate rarely can lead to liver cirrhosis and allergic reactions in the lung. Cyclosporine can cause kidney damage and high blood pressure. Because of potentially serious side effects, immunosuppressive medications are used in low doses, usually in combination with anti-inflammatory agents.
Newer treatments
Newer "second-line" drugs for the treatment of rheumatoid arthritis include leflunomide (Arava) and the "biologic" medications etanercept (Enbrel), infliximab (Remicade), anakinra (Kineret), adalimumab (Humira), rituximab (Rituxan), abatacept (Orencia), golimumab (Simponi), certolizumab pegol (Cimzia), and tocilizumab (Actemra). Each of these medications can increase the risk for infections, and the development of any infections should be reported to the health-care professional when taking these newer second-line drugs.Leflunomide (Arava) is available to relieve the symptoms and halt the progression of the disease. It seems to work by blocking the action of an important enzyme that has a role in immune activation. Arava can cause liver disease, diarrhea, hair loss, and/or rash in some people. It should not be taken just before or during pregnancy because of possible birth defects and is generally avoided in women who might become pregnant.
Newer medications that represent a novel approach to the treatment of rheumatoid arthritis are products of modern biotechnology. These are referred to as the biologic medications or biological response modifiers. In comparison with traditional DMARDs, the biologic medications have a much more rapid onset of action and can have powerful effects on stopping progressive joint damage. In general, their methods of action are also more directed, defined, and targeted.
Etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol are biologic medications that intercept a messenger protein in the joints (tumor necrosis factor or TNF) that promotes inflammation of the joints in rheumatoid arthritis. These TNF-blockers intercept TNF before it can act on its natural receptor to "switch on" the process of inflammation. This effectively blocks the TNF inflammation messenger from recruiting the cells of inflammation. Symptoms can be significantly, and often rapidly, improved in those using these drugs. Etanercept must be injected subcutaneously once or twice a week. Infliximab is given by infusion directly into a vein (intravenously). Adalimumab is injected subcutaneously either every other week or weekly. Golimumab is injected subcutaneously on a monthly basis. Certolizumab pegol is injected subcutaneously every two to four weeks. Each of these medications is being evaluated by doctors in practice to determine what role they may have in treating patients in various stages of rheumatoid arthritis. Research has shown that biological response modifiers also prevent the progressive joint destruction of rheumatoid arthritis. They are currently recommended for use after other second-line medications have not been effective. The biological response modifiers (TNF-inhibitors) are expensive treatments. They are also frequently used in combination with methotrexate and other DMARDs. Furthermore, it should be noted that the TNF-blocking biologics all are more effective when combined with methotrexate. These medications should be avoided by persons with significant congestive heart failure or demyelinating diseases (such as multiple sclerosis) because they can worsen these conditions.
Anakinra is another biologic treatment that is used to treat moderate to severe rheumatoid arthritis. Anakinra works by binding to a cell messenger protein (IL-1, a proinflammatory cytokine). Anakinra is injected under the skin daily. Anakinra can be used alone or with other DMARDs. The response rate of anakinra does not seem to be as high as with other biologic medications.
Rituximab (rituxan) is an antibody that was first used to treat lymphoma, a cancer of the lymph nodes. Rituxan can be effective in treating autoimmune diseases like rheumatoid arthritis because it depletes B-cells, which are important cells of inflammation and in the production of abnormal antibodies that are common in these conditions. Rituxan is now available to treat moderate to severely active rheumatoid arthritis in patients who have failed treatment with the TNF-blocking biologics. Preliminary studies have shown that Rituxan was also found to be beneficial in treating severe rheumatoid arthritis complicated by blood vessel inflammation (vasculitis) and cryoglobulinemia. Rituximab (Rituxan) is an intravenous infusion given in two doses, two weeks apart, approximately every six months.
Abatacept (Orencia) is a biologic medication that blocks T-cell activation. Orencia is now available to treat adult patients who have failed treatment with a traditional DMARD or TNF-blocking biologic medication. Abatacept (Orencia) is an intravenous infusion given monthly.
Tocilizumab (Actemra) has recently been approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Tocilizumab (Actemra) is the first approved biologic medication that blocks interleukin-6 (IL-6), which is a chemical messenger of the inflammation of rheumatoid arthritis. Tocilizumab (Actemra) is an intravenous infusion given monthly.
While biologic medications are often combined with traditional DMARDs in the treatment of rheumatoid arthritis, they are generally not used with other biologic medications because of the unacceptable risk for serious infections.
The Prosorba column therapy involves pumping blood drawn from a vein in the arm into an apheresis machine, or cell separator. This machine separates the liquid part of the blood (the plasma) from the blood cells. The Prosorba column is a plastic cylinder about the size of a coffee mug that contains a sand-like substance coated with a special material called Protein A. Protein A is unique in that it binds unwanted antibodies from the blood that promote the arthritis. The Prosorba column works to counter the effect of these harmful antibodies. The Prosorba column is indicated to reduce the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients with long-standing disease who have failed or are intolerant to disease-modifying antirheumatic drugs (DMARDs). The exact role of this treatment is being evaluated by doctors, and it is not commonly used currently.
Other treatments
There is no special diet for rheumatoid arthritis. One hundred years ago, it was touted that "night-shade" foods, such as tomatoes, would aggravate rheumatoid arthritis. This is no longer accepted as true. Fish oil may have anti-inflammatory beneficial effects, but so far this has only been shown in laboratory experiments studying inflammatory cells. Likewise, the benefits of cartilage preparations remain unproven. Symptomatic pain relief can often be achieved with oral acetaminophen (Tylenol) or over-the-counter topical preparations, which are rubbed into the skin. Antibiotics, in particular the tetracycline drug minocycline (Minocin), have been tried for rheumatoid arthritis recently in clinical trials. Early results have demonstrated mild to moderate improvement in the symptoms of arthritis. Minocycline has been shown to impede important mediator enzymes of tissue destruction, called metalloproteinases, in the laboratory as well as in humans.The areas of the body other than the joints that are affected by rheumatoid inflammation are treated individually. Sjogren's syndrome (described above, see symptoms) can be helped by artificial tears and humidifying rooms of the home or office. Medicated eyedrops, cortisporine ophthalmic drops (Restasis), are also available to help the dry eyes in those affected. Regular eye checkups and early antibiotic treatment for infection of the eyes are important. Inflammation of the tendons (tendinitis), bursae (bursitis), and rheumatoid nodules can be injected with cortisone. Inflammation of the lining of the heart and/or lungs may require high doses of oral cortisone.
Proper, regular exercise is important in maintaining joint mobility and in strengthening the muscles around the joints. Swimming is particularly helpful because it allows exercise with minimal stress on the joints. Physical and occupational therapists are trained to provide specific exercise instructions and can offer splinting supports. For example, wrist and finger splints can be helpful in reducing inflammation and maintaining joint alignment. Devices such as canes, toilet seat raisers, and jar grippers can assist in the activities of daily living. Heat and cold applications are modalities that can ease symptoms before and after exercise.
Surgery may be recommended to restore joint mobility or repair damaged joints. Doctors who specialize in joint surgery are orthopedic surgeons. The types of joint surgery range from arthroscopy to partial and complete replacement of the joint. Arthroscopy is a surgical technique whereby a doctor inserts a tube-like instrument into the joint to see and repair abnormal tissues.
Total joint replacement is a surgical procedure whereby a destroyed joint is replaced with artificial materials. For example, the small joints of the hand can be replaced with plastic material. Large joints, such as the hips or knees, are replaced with metals.
Finally, minimizing emotional stress can help improve the overall health in people with rheumatoid arthritis. Support and extracurricular groups provide those with rheumatoid arthritis time to discuss their problems with others and learn more about their illness.
Future treatments
Scientists throughout the world are studying many promising areas of new treatment approaches for rheumatoid arthritis. These areas include treatments that block the action of the special inflammation factors, such as tumor necrosis factor (TNFalpha) and interleukin-1 (IL-1), as described above. Many other drugs are being developed that act against certain critical white blood cells involved in rheumatoid inflammation. Also, new NSAIDs with mechanisms of action that are different from current drugs are on the horizon.Better methods of more accurately defining which patients are more likely to develop more aggressive disease are becoming available. Recent antibody research has found that the presence of citrulline antibodies in the blood (see above, in diagnosis) has been associated with a greater tendency toward more destructive forms of rheumatoid arthritis.
Studies involving various types of the connective tissue collagen are in progress and show encouraging signs of reducing rheumatoid disease activity. Finally, genetic research and engineering is likely to bring forth many new avenues for earlier diagnosis and accurate treatment in the near future. Gene profiling, also known as gene array analysis, is being identified as a helpful method of defining which people will respond to which medications. Studies are under way that are using gene array analysis to determine which patients will be at more risk for more aggressive disease. This is all occurring because of improvements in technology. We are at the threshold of tremendous improvements in the way rheumatoid arthritis is managed.
Rheumatoid Arthritis (RA) At A Glance
- Rheumatoid arthritis is an autoimmune disease that can cause chronic inflammation of the joints and other areas of the body.
- Rheumatoid arthritis can affect people of all ages.
- The cause of rheumatoid arthritis is not known.
- Rheumatoid arthritis is a chronic disease, characterized by periods of disease flares and remissions.
- In rheumatoid arthritis, multiple joints are usually, but not always, affected in a symmetrical pattern.
- Chronic inflammation of rheumatoid arthritis can cause permanent joint destruction and deformity.
- Damage to joints can occur early and does not correlate with the severity of symptoms.
- The "rheumatoid factor" is an antibody that can be found in the blood of 80% of people with rheumatoid arthritis.
- There is no known cure for rheumatoid arthritis.
- The treatment of rheumatoid arthritis optimally involves a combination of patient education, rest and exercise, joint protection, medications, and occasionally surgery.
- Early treatment of rheumatoid arthritis results in better outcomes.
The Arthritis Foundation (http://www.arthritis.org)
P.O. Box 19000
Atlanta, Georgia 30326
(or contact your local chapter)
For additional information, please contact:
National Arthritis and Musculoskeletal and Skin Diseases Clearinghouse
Box AMS
Bethesda, Maryland 20892
301-495-4484
Additional resources from WebMD Boots UK on Rheumatoid Arthritis
REFERENCES:
Koopman, William, et al., eds. Clinical Primer of Rheumatology. Philadelphia: Lippincott Williams & Wilkins, 2003.
Ruddy, Shaun, et al., eds. Kelley's Textbook of Rheumatology, Philadelphia: W.B. Saunders Co., 2000.
Koopman, William, et al., eds. Clinical Primer of Rheumatology. Philadelphia: Lippincott Williams & Wilkins, 2003.
Ruddy, Shaun, et al., eds. Kelley's Textbook of Rheumatology, Philadelphia: W.B. Saunders Co., 2000.
this article access from http://www.medicinenet.com/rheumatoid_arthritis/discussion-1.htm
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