FitSugar

Stretch It: Figure 4 for the Piriformis

FitSugar — Fri, 17 Aug 2007 03:30:00 -0700

Ever feel like you have a sore tight bum, be it from running or sitting for too long? I think being generally tense can lead to over engaging the glute muscles (there’s reason the expression “tight a**” exists).

Here is one of my favorite stretches. It is simple to do and will alleviate some of that deep booty tension you might be feeling. It is called the Figure Four because of the shape of the number with your legs to get into the stretchy. It targets the piriformis, a pear shaped muscle that runs from your sacrum (the back of your pelvis) to the outside of your upper femur (thigh bone).

Here's how to do the Figure 4:

Lie on your back with both legs in the air. Place your right ankle on your thigh above your left knee. See the shape of the number 4? It is there, just upside down.
Reach your right hand through the open space created by your right leg and grab your left hand that is reaching around the outside of your left thigh. Slowly bend your left knee. You should fee a stretch on the outside of your right hip.

Hold the stretch for 15 to 30 seconds.

Variations:

Try to release your pelvis into neutral, by reaching your tail bone toward the floor, creating a little arch in your low back. This should either emphasize the stretch in a different area, or increase the stretch.

To increase the stretch, twist just the pelvis a bit to the left and the stretch should intensify.

Just Released: Three Fitness Video Games For the Wii

FitSugar — Mon, 12 Oct 2009 03:00:47 -0700

Confession: I love playing video games - I especially love them on the Wii because I get to move, jump, and shake myself into a tizzy. Three fitness games were released for the Wii this last week and even though it's not like doing the real deal outside, the games are a fun way to burn calories and whip your bod into shape.

Nintendo Wii Fit Plus ($20) Wii Fit Plus is Nintendo's follow-up to the popular Wii Fit. There are new exercises, balance board games, and strength and yoga activities, as well as targeted exercise routines for things like reducing tummy fat and toning your figure. A great improvement is the addition of a calorie counter - after you complete each exercise the game tells you how many calories you've burned.

To hear about the other two games, continue reading.

From Bad to Worse: The Unhealthiest Fast Food Items

FitSugar — Fri, 25 Sep 2009 03:00:04 -0700

In case you're wondering what not to eat at the major fast food chains, Next Generation Food has made it easy for you with this handy new chart. It's a colorful reminder of what we already know: fast food is not very good for you. However, the figures are still unsettling.

The chart illustrates the bad (Dunkin' Donuts) to the worse (Pizza Hut) and stacks them up against each other in fat, sodium, cholesterol, and calorie content. Here's a small sampling of what you'll see.

An Angry Triple Whopper from Burger King has a whopping 90 grams of fat.
A Mocha Frappuccino from Starbucks contains 500 calories.
A Super Sonic Cheeseburger has 175 mg of cholesterol
A 14-inch Supreme Stuffed Crust Pizza from Pizza Hut has 4,500 mg of sodium

If you can't avoid eating fast food, try these healthier options instead.

Glycemic Index vs. Glycemic Load

FitSugar — Fri, 08 May 2009 12:00:00 -0700

Just when you started to get a handle on the glycemic index (GI) of foods, there's another value to grasp - glycemic load (GL). The GI ranks specific carbohydrates from zero to 100, based on the rate in which they affect your blood sugar levels. A GI of 1 to 55 is low, 56 to 69 is medium, and 70 to 100 is high - these high-ranking foods should be limited.

Glycemic load measures the blood-sugar-raising power per serving of food. Here's the lowdown on the equations used to figure the load. First you multiply the GI of a food by the amount of grams of carbohydrate in a specific serving, and then that number is divided by 100. A glycemic load of 10 or less is low, 11 to 19 is medium, 20 or more is high. If you add up the glycemic load amounts for your entire day, a total GL amount of 80 or less is considered low. Your daily GL shouldn't exceed 120.

Both measurements are useful. Glycemic load helps you select appropriate portion sizes, while glycemic index helps you differentiate between good and bad carbohydrate choices. The lower each number, the less it affects blood sugar levels.

Looking at some food's values may help you understand the two better. So read more.

Food	GI	GL
1 medium apple	38	6
1 small banana	47	8
10 baby carrots	35	2
1 medium baked potato with skin	76	23
1 medium orange	42	5
1 medium pear	38	4
1 cup white rice	64	23
1 cup brown rice	55	18
1 cup regular pasta	44	18
1 cup whole wheat pasta	37	14
1 cup skim milk	32	4
1 oz. cashews	22	2
1 oz. peanuts	14	1
1 oz. jelly beans	78	22
2 tsp sugar	68	7
1 cup lentils	29	5
1 cup kidney beans	28	7
1 cup barley	25	11

If you don't see a specific food on this chart, then go to nutriondata.com, enter the name of a food, and it'll tell you the GL.

Source

What's the Deal With Alcohol and Ibuprofen?

FitSugar — Wed, 04 Mar 2009 10:00:57 -0800

If you wake up with a headache after a night of overindulging, sometimes figuring out what painkiller to take can make the headache even worse. I've heard that it's bad to take acetaminophen (aka Tylenol), because it can lead to liver damage, but take note: you're also not supposed to drink while taking ibuprofen.

Ibuprofen is part of the anti-inflammatory drug family known as NSAIDs, which can cause tears in the stomach lining if taken on an empty tummy. Add alcohol to the mix, and the potential danger is heightened. If you take ibuprofen when drinking more than the recommended amount for women (about two to three drinks), you increase your risk of stomach irritation and bleeding. This is especially true for people who are prone to ulcers.

But wait! Taking Tylenol when you're hungover isn't such a good idea either. To find out why, read more.

Acetaminophen can lead to liver damage if you take it in large doses (that's 4,000 milligrams, or eight extra-strength Tylenol) for more than a couple of days. Heavy drinkers who take acetaminophen and don't eat enough can overtax their livers. However, the risks associated with taking Tylenol after recreational drinking are somewhat blurry. According to The Straight Dope:

I'll spare you the biochemistry, but basically acetaminophen and alcohol in combination overwhelm the liver's ability to remove toxins from your bloodstream. . . . It's not clear from the medical literature what happens if you take acetaminophen after a one-time bender (as opposed to chronic alcohol abuse). But don't substitute some other painkiller - aspirin and ibuprofen can have side effects too. Better to be suffering than dead.

So what's a hungover, headache-plagued gal to do - besides not drinking so much in the first place? Since the jury is still out on the exact effects of combining Advil or Tylenol with booze, probably best just to tough it out. Maybe even try a natural remedy like yoga. Got one that works for you? Share it in the comments.

Source

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

Click the icon to see an image of a CT scan of the chest.

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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Peptic ulcers

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Treatment
Treatment for NSAID-Induced...
Medications
Treatment for Bleeding Ulce...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk with cardiovascular medications

While nonsteroidal anti-inflammatory drugs are the major medications responsible for causing peptic ulcers, drugs taken for cardiovascular disease and its risk factors may also cause ulcers. Recent studies have found an association between increased risk of ulcer and the following drugs:

Spironolactone, a common diuretic used in heart failure
Niacin, a drug used to lower "bad" cholesterol and raise "good" cholesterol
Vitamin K antagonists, commonly prescribed anticoagulants
Dipyridamole, a drug for secondary stroke prevention
Low-dose aspirin, prescribed for both heart attack and stroke prevention

Risk of peptic ulcer increases dramatically when these drugs are used in combination. Considering the millions of people who take these medications to prevent a life-threatening cardiovascular event, their impact on peptic ulcer development could be monumental.

Atypical symptoms of GERD

The burning pain of gastroesophageal reflux disease (GERD) can be confused with that of an ulcer. However, GERD pain typically develops after meals and is relieved by antacids. Elderly patients may have different symptoms that can include loss of appetite, weight loss, anemia, vomiting, or difficulty swallowing. A careful examination may be necessary to diagnose the underlying cause, since GERD and peptic ulcer may coexist.

Adjustments in triple therapy

Peptic ulcers are commonly treated with the triple combination of two antibiotics (amoxicillin and clarithromycin) and a proton-pump inhibitor. Therapy usually lasts for 2 weeks. Recent studies indicate that 1 week may be just as effective. In addition, taking the antibiotics in sequence, rather than at the same time, may work better to eliminate H. pylori, the bacteria responsible for most ulcers.

Healing foods

Milk may not be the ideal food for people with peptic ulcers because it encourages the production of stomach acid. However, certain qualities found in fermented milks and yogurts may actually offer protection against gastric ulcers. Likewise, the phenolic compounds found in virgin olive oil appear to kill many strains of H. pylori, including some that have become resistant to antibiotics. Vegetables contain dietary nitrate, which increases nitric oxide in the gut, causing the mucus layer to thicken. This increases protection against H. pylori invasion.

Protection when taking NSAIDs

People who take NSAIDs for pain control have an immediate increased risk of ulcers. Chronic use increases risk dramatically. Taking a proton-pump inhibitor (PPI) or H2 blocker is necessary to reduce this risk. A review of clinical trials found three PPIs [omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid)] to be more effective than the H2 blocker ranitidine (Zantac). When NSAIDs were discontinued, however, healing rates with ranitidine reached nearly 100%.

Introduction

A peptic ulcer is an open sore or raw area that tends to develop in one of two places:

The lining of the stomach ( gastric ulcer), or
The upper part of the small intestine -- the duodenum ( duodenal ulcers). In the U.S., duodenal ulcers are 3 times more common than gastric ulcers.

A peptic ulcer is an open sore or raw area in the lining of the stomach (gastric) or the upper part of the small intestine (duodenal).

Ulcers average between one-quarter and one-half inch in diameter. They develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.

The two important digestive juices are hydrochloric acid and the enzyme pepsin. Both substances are critical in the breakdown and digestion of starches, fats, and proteins in food. They play different roles in ulcers:

Click the icon to see an image of the stomach.

Hydrochloric acid. A common misbelief is that excess hydrochloric acid, which is secreted in the stomach, is solely responsible for producing ulcers. Patients with duodenal ulcers do tend to have higher-than-normal levels of hydrochloric acid, but most patients with gastric ulcers have normal or lower-than-normal acid levels. Some stomach acid is important for protecting against H. pylori, the bacteria that causes most peptic ulcers. [Note: An exception is ulcers that occur in Zollinger-Ellison syndrome. This is a rare genetic condition in which very high levels of gastrin, a potent acid, are secreted by tumors in the pancreas or duodenum.]
Pepsin. Pepsin is an enzyme that breaks down proteins in food. Since the stomach and duodenum are also composed of protein, they are also susceptible to the actions of pepsin. Pepsin is, then, also important in the formation of ulcers.

Fortunately, the body has a defense system to protect the stomach and intestine against these powerful substances:

The mucous layer, which coats the stomach and duodenum, forms the first line of defense.
Bicarbonate, which the mucous layer secretes, neutralizes the digestive acids.
Hormone-like substances called prostaglandins help dilate the blood vessels in the stomach to ensure good blood flow and protect against injury. Prostaglandins are also believed to stimulate bicarbonate and mucus production.

Disrupting any of these defense mechanisms makes the stomach and intestine lining susceptible to the actions of acid and pepsin, increasing the risk for ulcers.

Causes

Before the discovery of the bacterium Helicobacter (H.) pylori, the stomach was believed to be a sterile environment. However, in 1982 two Australian scientists identified H. pylori as the main cause of stomach ulcers. They showed that inflammation of the stomach and stomach ulcers result from an infection of the stomach caused by the H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Price in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:

H. pylori's corkscrew shape enables it to penetrate the mucous layer of the stomach or duodenum so it can attach itself to the lining.
It survives in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.
H. pylori then produces a number of toxins and factors that can cause inflammation and damage to the lining, leading to ulcers in certain individuals.
It also alters certain immune factors that allow it to evade detection and cause persistent inflammation for a life -- even without invading the mucous membrane.

Even if ulcers do not develop, the bacterium is now considered to be a major cause of active chronic inflammation in the stomach (gastritis) and in the upper part of the small intestine (duodenitis).

It is also strongly linked to stomach (gastric) cancer and possibly other non-intestinal problems.

Factors that Trigger Ulcers in H. pylori Carriers.H. pylori is found in about 25% of people who do not have peptic ulcers. The magnitude of H. pylori infection, particularly in older people, may not always predict the presence or absence of peptic ulcers. Other variables must to be present to actually trigger ulcers. These may include:

Genetic Factors. Some people harbor genetic strains of H. pylori that may make the bacteria more dangerous and increase the risk for ulcers. The most intensively investigated genetic factor is cytotoxin-associated gene A (CagA), which has been associated with both gastric and duodenal ulcers, as well as with stomach cancer. Other genetic types that may also increase bacterial severity are called vacuolating cytotoxin (vacA) and antigen-binding adhesin (BabA) genotypes. Some of these genetic factors may be more or less important for development of ulcers, depending on ethnicity.
Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in the immune response of the intestine, which allow the bacteria to injure the lining.
Lifestyle Factors. Although lifestyle factors such as chronic stress, drinking coffee, and smoking were long believed to be primary causes of ulcers, it is now thought they only increase susceptibility to ulcers in some H. pylori carriers.
Shift Work and Other Causes of Interrupted Sleep. People who work the night shift have a significantly higher incidence of ulcers than day workers. Researchers suspect that frequent interruptions of sleep may weaken the ability of the immune system to protect against endotoxins.

When H. pylori was first identified as the major cause of peptic ulcers, it was found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori- associated ulcers has declined. For example, a 2001 study suggested that about half of ulcers are not caused by H. pylori. Instead, they tend to be caused by regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin and other common pain relievers. Genetic factors or, rarely, Crohn's disease or Zollinger-Ellison syndrome, also cause ulcers.

Some researchers now believe that duodenal ulcers are not caused by H. pylori, but that the presence of the bacteria simply delays healing. This fact, they say, may explain why up to half of cases of acute duodenal perforation show no evidence of H. pylori, and why duodenal ulcers can recur even after H. pylori has been eradicated.

A 2006 study published in the Journal of Biological Chemistry indicates that a protein called decay-accelerating factor (DAF) acts as receptor for H. pylori. Animal studies show that blocking this interaction renders H. pylori harmless to the stomach. Researchers hope the discovery leads to new drugs that can reduce the risk of peptic ulcer.

Long-term use of NSAIDs is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. About 20 million people take prescription NSAIDs regularly, and more than 25 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn), although many others are available. Patients with NSAID-caused ulcers should stop taking these drugs.

There is no doubt NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding is continuous for as long as a patient takes these drugs and may persist for about one year after stopping. Short courses of NSAIDs for temporary pain relief should not cause major problems, because the stomach has time to recover and repair any damage that has occurred.

Specific NSAIDs pose greater or lesser risks for ulcers and bleeding. No NSAIDs, however, even over-the-counter brands, should be used long-term except under a doctor's direction.

Lowest Risk

Medium Risk

Highest Risk

Nabumetone (Relafen)

Etodolac (Lodine)

Salsalate

Sulindac (Clinoril)

Aspirin. Even low-dose ("baby") aspirin (81 mg) may pose some risk

Ibuprofen (Motrin, Advil, Nuprin, Rufen)

Naproxen (Aleve, Naprosyn, Naprelan, Anaprox)

Diclofenac (Voltaren), Tolmetin (Tolectin)

NOTE: Drugs in the medium risk group vary in risk. For example, studies show that naproxen is twice as likely as ibuprofen to be associated with hospitalization from GI bleeding.

Flurbiprofen (Ansaid), Piroxicam (Feldene), Fenoprofen Indomethacin (Indocin), Meclofenamate (Meclomen)

Ketoprofen (Actron, Orudis KT). Note: Ketoprofen is often considered a medium-risk drug, but one study reported that taking the drug in low doses for as little as 1 week causes significant GI injury.

Certain drugs other than NSAIDs may cause or aggravate ulcers, particularly those taken for cardiovascular disease and its risk factors. A review of more than 306,000 primary care patients found that spironolactone, a common diuretic prescribed in heart failure, was associated with a 2.7% increased risk of ulcer or upper GI bleeding. Exacerbation of peptic ulcers is a rare but noted side effect of niacin, a drug that can reduce LDL cholesterol and raise HDL cholesterol. Low-dose aspirin, dipyridamole, and vitamin K antagonists such as Coumadin nearly double the risk of upper GI bleeding. When these drugs are used in combination, the risk soars.

Risk of GI perforation was seen in phase 3 clinical trials of bevacizumab, the first vascular endothelial growth factor agent (VEGF) approved by the FDA. This drug has been shown to increase survival and stop the progression of metastatic colorectal cancer when used in combination with chemotherapy. While the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, the drug must be discontinued.

The least common major cause of peptic ulcer disease is Zollinger-Ellison syndrome (ZES).

Rarely, certain conditions may cause ulceration in the stomach or intestine, including:

Radiation treatments
Bacterial or viral infections
Alcohol abuse
Physical injury
Burns

What is ZES? Zollinger-Ellison syndrome (ZES) is the least common major cause of peptic ulcer disease. In this condition, tumors in the pancreas and duodenum (gastrinomas) produce excessive amounts of gastrin, a hormone that stimulates gastric acid formation. These tumors are usually malignant, so proper and prompt management of the disease is essential.

Another cause of peptic ulcer, although far less common than H. pylori or NSAIDs, is Zollinger-Ellison syndrome. A large amount of excess acid is produced in response to the overproduction of the hormone gastrin, which in turn is caused by tumors on the pancreas or duodenum. These tumors are usually malignant, must be removed and acid production suppressed to relieve the recurrence of the ulcers.

Who Gets ZES? The incidence of ZES in the United States is estimated at 1 case per million people per year, and at 0.1 - 1% among patients with peptic ulcers. The mean age at onset is 45 - 50, and men are affected more often than women.

How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and have no history of NSAID use. Diarrhea may precede ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or the jejunum (the middle section of the small intestine) are signs of ZES. GERD is more prevalent and often more severe in patients with ZES, and can be complicated by ulcerations and strictures of the esophagus.

How Is ZES Treated? Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors and suppressing acid with an intravenous proton-pump inhibitor (Protonix). Previously, removing the stomach was the only option.

Symptoms

Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. Peptic ulcers can occur without dyspepsia or any other gastrointestinal symptom, especially when caused by NSAIDs. Dyspepsia may be persistent or recurrent and can encompass a variety of symptoms in the upper abdomen, including:

Pain or discomfort
Bloating
A feeling of fullness. People with severe dyspepsia are unable to drink as much fluid as people with mild or no dyspepsia.
Hunger and an empty feeling in the stomach, often 1 - 3 hours after a meal
Mild nausea (Vomiting, in fact, may relieve symptoms.)
Regurgitation (sensation of acid backing up into the throat.)
Belching

Ulcer Pain. The pain of ulcers can be either localized in one place or diffuse. The pain is described as a burning, gnawing, or aching in the upper abdomen, or as a stabbing pain penetrating through the gut. The symptoms may vary depending on the location of the ulcer:

Duodenal ulcers often cause a gnawing pain in the upper stomach area several hours after a meal, and the pain is often relieved by eating a meal.
Gastric ulcers may cause a dull, aching pain, often right after a meal; eating does not relieve the pain and may even worsen it. Pain may also occur at night.

Ulcer pain may be particularly confusing or disconcerting when it radiates to the back or to the chest behind the breastbone. In such cases it can be confused with other conditions such as heart attack.

Because ulcers can cause hidden bleeding, patients may experience the symptoms of anemia, including fatigue and shortness of breath.

A sudden onset of severe symptoms may indicate intestinal obstruction, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:

Tarry, black, or bloody stools
Severe vomiting, which may include blood or a substance with the appearance of coffee grounds (a sign of a serious hemorrhage) or entire stomach contents (sign of intestinal obstruction)
Severe abdominal pain with or without vomiting or evidence of blood

Anyone who experiences any of these symptoms should go to the emergency room immediately.

Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds or the presence of black tarry stools may indicate serious bleeding.

Complications

Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life.

Peptic ulcers caused by H. pylori or NSAIDs can be very serious if they hemorrhage or perforate the stomach or duodenum. Up to 15% of people with ulcers experience some degree of bleeding, which can be life-threatening. Ulcers that form where the small intestine joins the stomach can swell and scar, resulting in a narrowing or closing of the intestinal opening. In such cases, the patient will vomit the entire contents of the stomach, and emergency treatment is necessary.

Complications of peptic ulcers cause an estimated 6,500 deaths each year. These figures, however, do not reflect the high number of deaths associated with NSAID use. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori. NSAID-related bleeding and stomach problems may be responsible for as many as 107,000 hospital admissions and 16,500 deaths each year.

Because there are usually no GI symptoms from NSAID ulcers until bleeding begins, doctors cannot predict which patients taking these drugs will develop bleeding. The risk for a poor outcome is highest in people who have had long-term bleeding from NSAIDs, blood clotting disorders, low systolic blood pressure, mental instability, or the presence of another serious, unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.

H. pylori is strongly associated with certain cancers. Some studies have also linked it to a number of non-gastrointestinal illnesses as well, although the evidence is inconsistent.

Stomach Cancers. Stomach cancer, also called gastric cancer, is the second most common cause of cancer worldwide. In developing countries where the rate of H. pylori is very high, the risk of stomach cancer is 6 times higher than in the U.S. An important 2001 study strongly supported previous work that found a causal link between H. pylori infection and stomach cancer. In this study, uninfected people did not develop stomach cancer. However, the stomach cancer rates for H. pylori-associated conditions were 4.7% for nonulcer dyspepsia, 3.4% for gastric ulcers, and 2.2% of stomach polyps. Experts now suggest that H. pylori may be as carcinogenic to the stomach as cigarette smoke is to the lungs.

Eradication of H. pylori may reduce the risk of stomach cancer, but not eliminate it. A Japanese study found that continued risk is associated with degree of mucosal atrophy before H. pylori eradication therapy is started. This is something than can be measured during an endoscopy.

The process most likely starts in childhood. Infection with H. pylori promotes a precancerous condition called atrophic gastritis. This may lead to cancer through the following steps:

The stomach becomes chronically inflamed and loses patches of glands that secrete protein and acid.
Acid protects against carcinogens, substances that cause cancerous changes in cells.
New cells replace destroyed cells, but the new cells do not produce enough acid to protect against carcinogens.
Over time, cancer cells may develop and proliferate in the stomach.

Onset of H. pylori infection in adulthood poses a lower risk, since the development of atrophic gastritis takes years, and an adult is likely to die of other causes first. Other factors, such as specific genetic strains and diets, might also influence a higher risk for stomach cancer. For example, a diet high in salt and low in fresh fruits and vegetables has been associated with a greater risk. Some evidence suggests that the virulent H. pylori strain called cytotoxin-associated gene A (CagA) may also be a particular risk factor for precancerous changes.

Interestingly, people with duodenal ulcers caused by H. pylori appear to have a lower risk of stomach cancer, although scientists do not know why. It may be that different H. pylori strains affect the duodenum and the stomach. Or, the high levels of acid found in the duodenum may help prevent the spread of the bacteria to critical areas of the stomach.

Pancreatic Cancer. H. pylori has recently been linked to pancreatic cancer. The excess risk is high in patients with unoperated gastric ulcers -- 20% after 15 years and 50% after the first hospitalization. Surgery decreased the risk dramatically. Unoperated duodenal ulcers, on the other hand, were not associated with increased risk of pancreatic cancer.

Heart Disease. Some research has reported a very high rate of H. pylori infection in men with coronary artery disease, but more recent work has found no relationship between the bacteria and heart disease. A 2001 study suggested that the only relationship between H. pylori and heart disease may be that people with both tend to be in lower socioeconomic groups. Further studies are needed.

Other Diseases. H. pylori has also been weakly associated with other nonintestinal disorders, including migraine, Raynaud's disease (marked by cold extremities), and some skin disorders, such as chronic hives.

Risk Factors

About 25 million people in the U.S. are expected to develop peptic ulcers at some point in their lives. Peptic ulcer disease affects all age groups, but is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise beginning around age 25 and continues until age 75; gastric ulcers peak at age 55 - 65.

Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas with widespread H. pylori infection. The increased use of proton-pump inhibitor drugs may be responsible for this trend.

H. pylori grows and colonizes only in the intestinal tracts of primates. The bacteria are most likely transmitted directly from person to person. Still, little is yet known about its transmission.

Who Is Infected with H. pylori? About half the world's adults are infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life, if not treated. The prevalence in children ranges from less than 10% to more than 80%, with the highest infection rates (3 - 10%) in developing countries and the lowest (0.5%) in industrialized nations, where rates continue to decline. Even in industrialized countries, however, infection rates in regions with crowded, unsanitary conditions are equal to those in developing countries.

How Does the Bacteria Pass from Person to Person? It is not entirely clear how the bacteria are transmitted. One study did not find that infected students posed any risk for their classmates. Transmission within families may be the most important route for H. pylori. A 2002 study reported that spouses of people with peptic ulcers are at significantly higher risk for ulcers, suggesting that the bacteria may be transmitted during intimate contact. Some evidence suggests that bacteria may spread during GI tract illness, particularly when vomiting occurs. The bacteria also may be passed in stools. Since H. pylori can live in water, but not apparently in food, the bacteria may also be transmitting through sewage-contaminated water.

Who Is at Risk for Ulcers from H. pylori? Although H. pylori infection is common, ulcers in children are very rare, and only a minority of infected adults develops ulcers. Some known risk factors include smoking, alcohol use, having a relative with peptic ulcers, being male, and the presence of the cytotoxin-associated gene A (CagA). Experts are unable to determine, however, any single factor or group of factors that can determine which infected patients are most likely to develop ulcers.

Between 15 - 25% of patients who have taken NSAIDs regularly will have evidence of one or more ulcers, but in most cases these ulcers are very small. Given the widespread use of NSAIDs, however, the potential total number of people who can develop serious problems may be very large. Long-term NSAID use can damage the stomach and, possibly, the small intestine.

In April 2005, the FDA asked manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes the increased risk for cardiovascular events and GI bleeding in people taking these drugs. (Pharmaceutical companies are trying to develop new COX-2 inhibitors without these dangerous side effects. Early safety studies of the novel COX-2 inhibitor known as CS-706 showed its effect on gastric mucosa to be the same as placebo.)

The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and GI risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Frequent Users of NSAIDs. Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems. Even low-dose aspirin (81 mg) may pose some risk, although the risk is lower than with standard doses. In one 4-year study, 4.5% of regular NSAID users were hospitalized for GI bleeding. The highest risk, however, was found in people who require long-term use of very high-dose NSAIDs, notably patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic stress.

Contributing Factors. Certain factors add to the risk for ulcers in NSAID-users:

Age 65 and older
History of peptic ulcers or upper gastrointestinal bleeding
Other serious ailments, such as congestive heart failure
Use of other medications, such as the anticoagulant warfarin (Coumadin), corticosteroids, or the osteoporosis drug alendronate (Fosamax)
Alcohol abuse
Those infected with H. pylori. A 2002 study reported that the combination of NSAID use and H. pylori posed a 3.5-fold greater risk of ulcers than either factor alone. However, not all studies have reported the higher risk in infected patients.

Stress and Psychological Factors. Although stress is no longer considered a cause of ulcers, studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing. Some experts estimate that social and psychological factors play a contributory role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. Some experts even believe that the anecdotal relationship between stress and ulcers is so strong that treatment of psychological factors is warranted.

Smoking. Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases mucosal blood flow. Results of studies on the actual effect of smoking on ulcers, however, are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of nonsmokers experienced a relapse of their ulcer disease after 1 year, but that all heavy smokers relapsed after 3 months. Other studies have found no increased risk for ulcers in smokers. In any case, any impact of smoking on ulcers does not seem to be affected by the presence of H. pylori.

Tobacco use and exposure may cause an acceleration of coronary artery disease and peptic ulcer disease. It is also linked to reproductive disturbances, esophageal reflux, hypertension, fetal illness and death, and delayed wound healing.

Diagnosis

Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Dyspepsia, however, occurs in 20 - 40% of people who live in industrialized nations, and only about 15 - 25% of these people actually have ulcers. A number of steps are needed to make an accurate diagnosis of ulcers.

The doctor will ask for a thorough report of a patient's dyspepsia and other important symptoms, such as weight loss or fatigue, present and past medication use (especially chronic use of NSAIDs), family members with ulcers, and drinking and smoking habits.

In addition to peptic ulcers, a number of conditions, notably gastroesophageal reflux disease (GERD) and irritable bowel syndrome, cause dyspepsia. Often, however, no cause can be determined. In such cases, the symptoms are referred to collectively as functional dyspepsia.

Peptic ulcer symptoms, particularly abdominal pain and chest pain, may resemble those of other conditions, such as gallstones or heart attack. Certain features may help to distinguish these different conditions. However, symptoms often overlap, and it is impossible to make a diagnosis based on symptoms alone. A number of tests are needed.

The following disorders may be confused with peptic ulcers:

GERD. About half of patients with GERD also have dyspepsia. With GERD or other problems in the esophagus, the main symptom is usually heartburn, a burning pain that radiates up to the throat. It typically develops after meals and is relieved by antacids. The patient may have difficulty swallowing and may experience regurgitation or acid reflux. Elderly patients with GERD are less likely to have these symptoms, but instead may experience loss of appetite, weight loss, anemia, vomiting, or dysphagia (difficulty or painful swallowing). [See In-Depth Report #85: Gastroesophageal Reflux Disease.]
Heart Events. Cardiac pain, such as angina or a heart attack, is more likely to occur with exercise and may radiate to the neck, jaw, or arms. In addition, patients typically have distinct risk factors for heart disease, such as a family history, smoking, high blood pressure, obesity, or high cholesterol. [See In-Depth Report #12: Heart Attack.]
Gallstones. The primary symptom in gallstones is typically a steady gripping or gnawing pain on the right side under the rib cage, which can be quite severe and can radiate to the upper back. Some patients experience pain behind the breastbone. The pain is often precipitated by a fatty or heavy meal, but gallstones almost never cause dyspepsia. [See In-Depth Report #10: Gallstones and Gallbladder Disease.]
Irritable Bowel Syndrome. Irritable bowel syndrome can cause dyspepsia, nausea and vomiting, bloating, and abdominal pain. It occurs more often in women than in men.

Dyspepsia may also occur with gastritis, stomach cancer, or as a side effect of certain drugs, including NSAIDs, antibiotics, iron, corticosteroids, theophylline, and calcium blockers.

When ulcers are suspected, the doctor will prescribe tests to detect bleeding. These may include a rectal exam, a complete blood count, and a fecal occult blood test (FOBT). The FOBT tests for hidden (occult) blood in stools. Typically, the patient is asked to supply up to 6 stool specimens in a specially prepared package. A small quantity of feces is smeared on treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Traditional radiology tests have not yet proven valuable for diagnosing ulcers. However, radiologists in France who performed multidetector computed tomography (MDCT) scans on preoperative patients with proven GI perforations found the technology to be highly accurate in pinpointing the location of the perforations.

Simple blood, breath, and stool tests can now detect H. pylori with a fairly high degree of accuracy. It is not entirely clear, however, which individuals should be screened for H. pylori.

Candidates for Screening. Some doctors currently test for H. pylori only in individuals with dyspepsia who also have high-risk conditions, such as:

Strong indication for ulcers, such as weight loss, anemia, or indications of bleeding
History of active ulcers
Risk factors for stomach cancer or other complications from ulcers

Smokers and those who experience regular and persistent pain on an empty stomach may also be good candidates for screening tests. Some doctors argue that testing for H. pylori may be beneficial for patients with dyspepsia who are regular NSAID users. In fact, given the possible risk for stomach cancer in H. pylori- infected people with dyspepsia, some experts now recommend that any patient with dyspepsia lasting longer than 4 weeks should have a blood test for H. pylori. This is a subject of considerable debate, however.

Specific Screening Tests for H. pylori. The following screening tests used or under investigation for H. pylori:

Breath Test. A simple test called the carbon isotope-urea breath test (UBT) can identify up to 99% of people who harbor H. pylori. Up to 2 weeks before the test, the patient must discontinue taking any antibiotics, bismuth-containing agents such as Pepto-Bismol, and proton-pump inhibitors (PPIs). As part of the test, the patient swallows a special substance containing urea (a compound in mammals metabolized from nitrogen) that has been treated with carbon atoms. If H. pylori is present, the bacteria convert the urea into carbon dioxide, which is detected and recorded in the patient's exhaled breath after 10 minutes.
Blood Tests. Blood tests are used to measure antibodies to H. pylori, with results available in minutes. Diagnostic accuracy is reported at 80 - 90%. One such important test is called enzyme-linked immunosorbent assay (ELISA). An ELISA test of the urine is also showing promise in children.
Stool Test. A test to detect genetic fingerprints of H. pylori in the feces appears to be as accurate as the breath test for initial detection of the bacteria and for detecting recurrences after antibiotic therapy.

It should be noted that such tests are not as accurate as endoscopy, an invasive procedure, which is needed to confirm a diagnosis of H. pylori. The breath and stool tests, however, can be particularly useful after treatment to determine if a patient has been cured.

Test and Treat. Depending on the results of the screening tests, some doctors take the following steps:

Approach for Noninfected Individuals. People who do not have evidence of H. pylori on a blood or breath test are typically given a 4-week course of acid-suppressing medication, usually a PPI such as omeprazole (Prilosec).
Approach for H. pylori-Infected Individuals. Patients with evidence of bacterial infection are given antibiotics. If this does not relieve symptoms, they are given a 6-week course of the PPI omeprazole (Prilosec). (Whether to give antibiotics to infected patients with non-ulcer dyspepsia is controversial and is discussed in the section, What Are the Guidelines for Treating Peptic Ulcers Caused by H. pylori?)

If symptoms persist, endoscopy is usually performed. Endoscopy is an invasive procedure, but is the only procedure in which a biopsy of stomach tissue can be taken, making it the most accurate test.

Experts debate whether endoscopy should be performed on all patients who do not respond to initial medication, since it does not appear to add any useful information on treatment choices, unless there is evidence or suspicion of bleeding or serious complications.

While endoscopy is the gold standard for diagnosing upper GI disorders, because it allows doctors to biopsy the stomach, 3-dimensional CT imaging may also be valuable. Researchers in China compared the results of endoscopy to the results of noninvasive CT imaging performed to diagnose GI disease. They found that the CT imaging correctly diagnosed 50 of 52 cases, including 5 cases of peptic ulcer disease. Three-dimensional CT imaging clearly showed the GI tract lesions. It is currently considered a valuable complement to endoscopy.

Endoscopy is a procedure used to evaluate the esophagus, stomach, and duodenum using a long, thin tube tipped with a tiny video camera (endoscope). When combined with biopsy, endoscopy is the most accurate procedure for detecting the presence of peptic ulcers, bleeding, and stomach cancer, or for confirming the presence of H. pylori.

Appropriate Candidates for Endoscopy. Because endoscopy is invasive and expensive, it is unsuitable for screening everyone with dyspepsia. Most individuals with these symptoms are managed effectively without endoscopy. Endoscopy is usually reserved for patients with dyspepsia who also have risk factors for ulcers, stomach cancer, or both. Such factors include the following:

Having so-called "alarm" symptoms (unexplained weight loss, gastrointestinal bleeding, vomiting, difficulty swallowing, or anemia).
Being over 45 (when the risk for stomach cancer increases).

There is some debate whether patients under 45 with persistent dyspepsia and no alarm symptoms should have endoscopy.

The Procedure. Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center, and typically involves the following:

The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and relax the patient.
The doctor then places the thin, flexible plastic tube into the patient's mouth and down the esophagus into the stomach.
A tiny camera in the endoscope allows the doctor to see the surface of the esophagus, stomach, and duodenum, and to search for abnormalities.
The doctor will remove about 10 small tissue samples (biopsies), which will be tested for H. pylori.

In endoscopy, the doctor places a long, thin, flexible tube (called an endoscope) down the patient's throat and into the stomach and duodenum. A camera and light on the tip of the endoscope enables the doctor to check for abnormalities. Tiny samples may be taken to check for H. pylori bacteria, a cause of many peptic ulcers. If a bleeding ulcer is found, it may be sealed with a burning tool (cauterized) during the procedure.

Note: Some evidence suggests that patients who take PPIs should stop taking the medication 2 weeks before an endoscopy, since it may mask ulcers.

Capsule Endoscopy.Capsule endoscopy involves swallowing a capsule the size of a large vitamin, which contains tiny camera, light source, and radio transmitter. The device takes pictures as it passes through the intestinal tract. At this point, its benefits are limited to the small intestine, so it is unlikely to play a role in the diagnosis of peptic or gastric ulcers. However, capsule endoscopy has the potential to be an important tool for the diagnosis of obscure upper GI bleeding. Patients who have used it have usually found it painless and preferable to conventional endoscopy.

An upper GI (gastrointestinal) series was the standard diagnostic method for peptic ulcers until the introduction of adequate tests for detecting H. pylori. In an upper GI series, the patient drinks a solution containing barium. X-rays are then taken, which may reveal inflammation, active ulcer craters, or deformities and scarring due to previous ulcers. Endoscopy is more accurate, although it is more invasive and expensive.

Click the icon to see an illustrated series detailing treatment of GI bleeding.

Stool tests may show traces of blood that are not visible to the naked eye, and blood tests may reveal anemia in those who have bleeding ulcers. If Zollinger-Ellison syndrome is suspected, blood levels of gastrin should be measured.

Treatment

Antibiotic regimens that eradicate H. pylori can cure peptic ulcers and are now the standard medications used for ulcers in infected individuals who are not taking NSAIDs. Eliminating H. pylori can also cure the rare MALT lymphomas caused by this bacterium. Other drugs, such as proton-pump inhibitors or H2 blockers, are useful for relieving ulcer symptoms.

Patients with Clear Evidence of Ulcers. Antibiotics are clearly indicated for patients who have both ulcers and H. pylori infection. Despite such clear indications, however, European and American studies continue to suggest that many doctors only treat symptoms and not the ulcers themselves. Studies also suggest that most doctors do not counsel patients on the potential dangers of NSAIDs and other drugs that can cause ulcers.

There is considerable debate about whether to test for H. pylori and treat infected patients who have dyspepsia, but no evidence of ulcers.

The best approach for treating dyspepsia is highly controversial. Options include the following:

Test and Treat. This approach involves testing for H. pylori and eradicating the bacteria in infected patients.
Prescribing potent acid-suppressing agents. This approach generally employs a trial of potent acid-suppressing drugs called proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) or esomeprazole (Nexium).

In either case, endoscopy is usually performed if symptoms persist after 4 weeks. Some evidence suggests that PPIs may mask ulcers, so patients taking these drugs may need to discontinue them for 2 weeks before endoscopy.

Arguments for Testing and Treating Patients with Dyspepsia. The argument supporting testing and treating patients with nonulcer dyspepsia is as follows:

Protection against ulcers. Some evidence suggests that antibiotic treatments for infected patients with dyspepsia may prevent ulcers from developing. A 2002 study found that antibiotic regimens to eradicate H. pylori greatly decreased the likelihood of ulcers in infected patients with nonulcer dyspepsia who were chronic NSAID users.
Protection against gastric cancer. Some evidence suggests that eradicating H. pylori may prevent or delay the onset of stomach cancer in people with long-term dyspepsia who are infected with the bacteria. A large 2001 study conducted in Japan, where gastric cancer is especially common, found that such cancers developed in about 3% of infected patients with nonulcer dyspepsia. However, none occurred in dyspeptic patients who were treated with antibiotics for H. pylori.

Arguments against Testing and Treating Patients with Dyspepsia. The arguments against testing and treating are as follows:

Lack of significant effect on symptoms. Studies are mixed on whether antibiotics have much effect on dyspepsia symptoms. In a 2003 study, overall symptom scores after 1 year were not significantly different between dyspeptic patients who were treated for H. pylori and patients who were maintained on PPIs.
Lower rates of H. pylori in the U.S. The number of people with H. pylori infection is declining in the U.S., possibly making the test-and-treat approach too expensive for the number of people it helps.
Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating H. pylori may also have other adverse effects.
Overuse of antibiotics. Concern that such treatments without clear evidence of ulcers will lead to unnecessary antibiotic prescriptions, increasing the risk for side effects. Overuse may also contribute to a growing public health problem -- the emergence of bacteria that are resistant to antibiotics.

The standard treatment regimen for H. pylori uses 2 antibiotics and a PPI. Cure rates after antibiotic treatment range from 70 - 90%. A typical regimen contains three drugs:

A PPI. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). PPIs are important for all types of peptic ulcers, and are a critical partner in antibiotic regimens. They reduce acidity in the intestinal tract, and increase the ability of antibiotics to destroy H. pylori.
Two antibiotics. The standard antibiotics are clarithromycin (Biaxin) and amoxicillin. Some doctors substitute the antibiotic metronidazole (Flagyl) for either clarithromycin or amoxicillin.

This combination treatment is typically taken for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well. A report published in 2006 evaluated a shorter course of treatment using the PPI rabeprazole and 2 antibiotics. They found that a 4-day treatment eliminated H. pylori and was associated with fewer side effects. A study published in 2007 comparing 1- and 2-week treatments with amoxicillin, clarithromycin, and omeprazole for H. pylori eradication found both regimens to be similar in efficacy, safety, and compliance.

Interestingly, an Italian study indicated that giving antibiotics sequentially instead of at the same time may be even more effective. The researchers found that patients who took amoxicillin for 5 days, followed by clarithromycin for 5 days, had higher H. pylori eradication rates (89%) than those who took both antibiotics for 10 days (77%).

A 2007 study showed that eradication rates with this 3-drug regimen could be improved, and side effects reduced, by adding probiotics ("good" bacteria) and the milk protein bovine lactoferrin. These products are often found in yogurts and other forms of fermented milk.

Follow-Up. Follow-up testing for the bacteria should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.

In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate success, nor does persistence of dyspepsia necessarily mean that treatment has failed. Heartburn and other symptoms from GERD, for example, can worsen and require acid-suppressing medication.

Failure. Treatment fails in about 15% of patients, mostly when they fail to adhere to the regimen. Compliance with standard antibiotic regimens may be poor for the following reasons:

The triple-drug regimens are complicated and require many pills. Helicide or two-drug combinations may help offset this problem.
About 30% of patients suffer side effects from the H. pylori regimen. Gastrointestinal problems are very common, and severe diarrhea can occur.

Treatment may also fail if the patients harbor strains of H. pylori that are resistant to the antibiotics. When this happens, different drugs are tried.

Reinfection after Successful Treatment. Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Reinfection with the bacteria is possible, however, in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%.

Weight Gain. Some patients may gain weight.

Gastroesophageal Reflux Disease. Of ongoing interest are reports of a lower incidence of H. pylori in patients with GERD. There are some important unanswered questions associated with this issue:

Is the lower incidence of H. pylori in GERD patients significant, and does the bacteria actually protect against GERD? Studies have not conclusively found any significant risk for GERD in people who are not infected with H. pylori, except possibly in certain regions. In a 2003 study, the absence of H. pylori infection in people with GERD was more pronounced in Asian patients than in those from Europe and North America. That being said, guidelines for eradication of H. pylori infection published in 2007 by the European Helicobacter Study Group state that "Eradication of H. pylori infection does not cause gastroesophageal reflux disease (GERD) or exacerbate GERD, and may prevent peptic ulcer in patients who are naive users of NSAIDs."
Does eliminating the bacteria with antibiotic therapy actually produce GERD in some people? One study observed that patients cured of H. pylori infection were twice as likely to develop GERD as those who remained infected. However, a 2003 analysis of 8 studies reported no higher risk for GERD after antibiotic treatments. In addition, GERD patients did not experience worsening of symptoms. Longer follow-up studies are needed however to determine the long-term consequences, if any.
What is the proper management of people who have GERD and H. pylori infection? Patients with severe GERD usually require on-going therapy with PPIs, which are powerful acid-suppressors. Some evidence suggests that in such patients, the combination of H. pylori and chronic acid suppression may lead to atrophic gastritis, a precancerous condition in the stomach. Guidelines then advocate eliminating the bacteria with antibiotics. There is some concern that once the bacteria are eliminated, however, GERD may worsen, which can pose a risk for Barrett's esophagus, which is also a precancerous condition. On the encouraging side, however, evidence to date does not suggest any higher risk for more serious GERD complications after H. pylori is eliminated.

Effects on Other Gastrointestinal Infections. In children, there is some evidence that H. pylori protects against E. coli and other GI infections, particularly those that cause diarrhea. If this is true, treating infected children for H. pylori should be done only if the bacteria are causing harm.

Click the icon to see an animation on ulcer treatment.

Treatment for NSAID-Induced Ulcers

Preventing Ulcers or Rebleeding Caused by NSAIDs. If NSAID-caused ulcers or bleeding are identified, patients should:

Get tested for H. pylori and, if they are infected, take antibiotics.
Possibly use a PPI. Studies suggest these medications lower the risk for NSAID-caused ulcers, although they do not completely prevent them.

People who still need to take NSAIDs should:

Use the lowest NSAID dose possible.
Try the prescription drugs misoprostol (Cytotec) or Arthrotec. Misoprostol works as well as a PPI, however, it has many side effects. Arthrotec is a combination of misoprostol and the NSAID diclofenac.

A warning to women: misoprostol can induce labor at any stage of pregnancy. Pregnant women should not use the drug.

Healing Existing Ulcers. A number of drugs are used to treat NSAID-caused ulcers. PPIs -- omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium) -- are used most often. Other drugs that may be useful include H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), and ranitidine (Zantac). Sucralfate is another drug used to heal ulcers and reduce the stomach upset caused by NSAIDs.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs, while causing less gastrointestinal distress. However, following numerous reports of cardiovascular events, the FDA banned rofecoxib (Vioxx) and valdecoxib (Bextra) from use in the U.S. Celecoxib (Celebrex) is still available, but patients should discuss with their doctor whether this drug is appropriate and safe for them.

Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac. It may reduce the risk for gastrointestinal bleeding. One study found that patients taking Arthrotec had 65 - 80% fewer ulcers than those who took NSAIDs alone.

Acetaminophen. Acetaminophen (Tylenol, Anacin-3) is the most common alternative to NSAIDs. Acetaminophen is inexpensive and generally safe. It poses far less of a risk of gastrointestinal problems than NSAIDs. It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg); some studies suggest that ulcer risk is increased even in doses exceeding 2 grams (2,000 mg) a day, if the drug is used on a long-term basis. Patients who take high doses of acetaminophen for long periods are also at risk for liver damage, particularly if they drink alcohol. It may pose a small risk for serious kidney complications in people with preexisting kidney disease, although acetaminophen remains the drug of choice for patients with impaired kidney function.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, dependence and abuse have been reported. It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these agents.

Medications

The following drugs are sometimes used in the treatments of peptic ulcers caused by either NSAIDs or H. pylori. They are described in alphabetical order.

Many antacids are available without prescription and are the first drugs recommended to relieve heartburn and mild dyspepsia. They play no major role in either the prevention or healing of ulcers, but help in the following ways:

All rely on various combinations of three basic compounds -- magnesium, calcium, or aluminum -- to neutralize stomach acid.
They may defend the stomach by increasing acid-buffering bicarbonate and mucus secretion.

It is generally believed that liquid antacids work faster and are more potent than tablets, although some evidence suggests that both forms work equally well.

Basic Salts Used in Antacids. There are three basic salts used in antacids:

Magnesium. Magnesium compounds are available in the form of magnesium carbonate, magnesium trisilicate, and, most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of these magnesium compounds is diarrhea.
Calcium. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid-acting antacid, but it can cause constipation. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. Hypercalcemia can lead to kidney failure.
Aluminum. The most common side effect of antacids containing aluminum compounds (Amphogel, Alternagel) is constipation. Maalox and Mylanta are combinations of aluminum and magnesium, which balance the side effects of diarrhea and constipation. People who take large amounts of antacids containing aluminum may be at risk for calcium loss and osteoporosis. Long-term use also increases the risk of kidney stones. People who have recently experienced GI bleeding should not use aluminum compounds.

Interactions with Other Drugs. Antacids can reduce the absorption of a number of drugs. Conversely, some antacids increase the potency of certain drugs. The interactions can be avoided by taking these other drugs 1 hour before or 3 hours after taking the antacid.

Drugs that are absorbed less well if taken with antacids

Drugs that are made more potent by antacids

Tetracycline

Ciprofloxacin (Cipro)

Propranolol (Inderal)

Captopril (Capoten)

Ranitidine (Zantac)

Famotidine (Pepcid AC)

Valproic acid

Sulfonylureas

Quinidine

Levodopa

H. pylori is usually highly sensitive to certain antibiotics, particularly amoxicillin, and to antibiotics in the macrolide class, such as clarithromycin. Either type of agent serves effectively as a second antibiotic in a three-drug regimen. Other antibiotics that are sometimes used include tetracycline, metronidazole, and ciprofloxacin.

Amoxicillin is the most common form of penicillin. It is inexpensive, but many people are allergic to it.
Clarithromycin (Biaxin) is a macrolide and is the most expensive antibiotic used against H. pylori. It is very effective, but there is growing bacterial resistance to this drug. Resistance rates tend to be higher in women and increase with age. Researchers fear that resistance will increase as more people use the drug.
Tetracycline is effective, but this medicine has unique side effects, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration. Pregnant women cannot take tetracycline.
Ciprofloxacin (Cipro), a fluoroquinolone, is also sometimes used in ulcer regimens.
Metronidazole (Flagyl) was the mainstay in initial combination regimens for H. pylori. As with clarithromycin, however, there continues to be growing bacterial resistance to the drug. Today, about 25 - 35% of H. pylori bacteria are metronidazole-resistant.

Side Effects of Antibiotics.

The most common side effects of nearly all antibiotics are gastrointestinal problems such as cramps, nausea, vomiting, and diarrhea.
Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare, but severe -- even life-threatening -- anaphylactic shock.
Some drugs, including certain over-the-counter medications, interact with antibiotics; patients should report to all medications they are taking to their doctor.
Antibiotics double the risk of vaginal infections in women.

Compounds that contain bismuth are often used in the three-drug antibiotic regimens. They destroy the cell walls of H. pylori bacteria. The only bismuth compound available in the U.S. has been bismuth subsalicylate (Pepto-Bismol), although a drug combination of the H2 blocker ranitidine and bismuth citrate (Tritec) has been released. High doses can cause vomiting and depression of the central nervous system, but the doses given for ulcer patients rarely cause side effects.

H2 blockers interfere with acid production by blocking histamine, a substance produced by the body that encourages acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.

Four H2 blockers are currently available over-the-counter in the U.S.: famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac), and nizatidine (Axid). All have good safety profiles and few side effects. There are some differences between these drugs:

Famotidine (Pepcid AC). Famotidine is the most potent H2 blocker. The most common side effect is headache, which occurs in 4. 7% of people who take it. Famotidine is virtually free of drug interactions, but it may have significant adverse effects in patients with kidney problems.
Cimetidine (Tagamet). Cimetidine has few side effects; about 1% of people taking cimetidine experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, including phenytoin, theophylline, and warfarin. Long-term use of excessive doses (more than 3 grams a day) may cause impotence or breast enlargement in men. These problems resolve after the drug is discontinued.
Ranitidine (Zantac). Ranitidine interacts with very few drugs. In one study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people younger than age 60, but there was no difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of people who take it.

That being said, a literature review of clinical trials showed that the PPIs are more effective than the H2 blockers in healing ulcers in people who take NSAIDs. After 8 weeks of treatment, healing rates of both gastric and duodenal ulcers were:

92% and 88% with esomeprazole 40 mg and 20 mg (vs 74% with ranitidine).
87% and 84% with omeprazole 40 mg and 20 mg (vs 64% with ranitidine).
And 73 - 74% and 66 - 69% with lansoprazole 30 mg and 15 mg (vs 50 - 53% with ranitidine).
However, healing rates with ranitidine reached nearly 100% when NSAIDs were discontinued.

Nizatidine (Axid). Nizatidine is nearly free of side effects and drug interactions.

Long-Term Concerns. In most cases, these H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs, be sure to tell your doctor about any other drugs you are taking. There are also some concerns about possible long-term effects -- for example, that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who also have untreated H. pylori infection. More research is needed. However, the following concerns are real:

Liver damage. This is more likely with ranitidine than other H2 blockers, but is rare in any event.
Kidney-related complications. With famotidine, adverse effects on the central nervous system in patients with even moderate kidney insufficiency have been reported, resulting in anxiety, depression, and mental disturbances.
Increased risk for pneumonia in hospitalized patients.
Ulcer perforation and bleeding. Some experts are concerned that the use of acid-blocking drugs may actually increase the risk for serious complications by masking the ulcer's symptoms.

Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major intestinal toxicity of NSAIDs.

Actions against Ulcers. Misoprostol can reduce formation of ulcers in the upper small intestine by two-thirds and in the stomach by three-fourths. It does not neutralize or reduce acid, so although the drug is helpful for preventing NSAID-induced ulcers, it is not useful in healing existing ulcers.

Side Effects.

Diarrhea and other gastrointestinal problems are severe enough to cause 20% of patients to stop taking the drug. Taking misoprostol after meals should minimize these effects. One study indicated that taking the drug 2 - 3 times a day, instead of the standard regimen of 4 times, may prove to be just as effective and cause fewer side effects.
Misoprostol can induce abortion or cause birth defects and should not be taken by pregnant women. If pregnancy occurs during treatment, the drug should be discontinued at once and the doctor contacted immediately.

Actions against Ulcers. PPIs are the drugs of choice for managing patients with peptic ulcers from any cause. They suppress the production of stomach acid by blocking the gastric acid pump -- the molecule in the stomach glands that is responsible for acid secretion.

PPIs can be used either as part of a multidrug regimen for H. pylori or alone for preventing and healing NSAID-caused ulcers. One retrospective study found that adding a PPI to diclofenac therapy reduced hospitalization for ulcers by 60%. They are also useful in treating ulcers caused by Zollinger-Ellison syndrome. Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18 - 20% of people of Asian descent.

Standard Brands. Most PPIs are available by prescription as oral drugs. There is no evidence that one brand of PPI works better than another. Brands approved for ulcer prevention and treatment include:

Omeprazole (generic, Prilosec OTC)
Esomeprazole (Nexium)
Lansoprazole (Prevacid)
Rabeprazole (Aciphex)

Possible Adverse Effects.

Side effects are uncommon, but may include headache, diarrhea, constipation, nausea, and itching.
Pregnant women and nursing mothers should avoid taking PPIs, although recent studies suggest that these drugs do not increase the risk of birth defects.
PPIs may interact with certain drugs, such as antiseizure agents (such as phenytoin), antianxiety drugs (such as diazepam), and blood thinners (such as warfarin).
Long-term use of high-dose PPIs may produce vitamin B12 deficiency, but studies are needed to confirm this risk.
In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in stomach cancer with long-term use of these drugs.

Sucralfate (Carafate) seems to work by adhering to the ulcer crater and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. Sucralfate has an ulcer-healing rate similar to that of H2 blockers. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate does interact with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline.

Treatment for Bleeding Ulcers

When a patient comes to the hospital with bleeding ulcers, endoscopy is usually performed. This procedure is critical for the diagnosis, determination of treatment options, and treatment of bleeding ulcers.

In high-risk patients or those with evidence of bleeding, options include watchful waiting with medical treatments or surgery. The first critical steps for massive bleeding are to stabilize the patient and support vital functions with fluid replacement and possibly blood transfusions. People on NSAIDs should discontinue them, if possible.

Depending on the intensity of the bleeding, patients can be released from the hospital within a day or kept up to 3 days after endoscopy. Bleeding stops spontaneously in about 70 - 80% of patients, but about 30% of patients who come to the hospital for bleeding ulcers need surgery. Endoscopy is the surgical procedure most often used for treating bleeding ulcers and patients at high-risk for rebleeding. It is usually combined with medications, such as epinephrine and intravenous proton-pump inhibitors.

Between 10 - 20% of patients require more invasive procedures for bleeding, usually major abdominal surgery.

Endoscopy is important for both diagnosing and treating bleeding ulcers. The doctor first places a thin, flexible plastic tube called an endoscope into the patient's mouth and down the esophagus into the stomach.

Endoscopy for Diagnosing Bleeding Ulcers and Determining Risk of Rebleeding. With endoscopy, doctors are able to detect the signs of bleeding, such as active spurting or oozing of blood from arteries. Endoscopy can also detect specific features in the ulcers referred to as stigmata, which indicate a higher or lower risk of rebleeding.

Such features include the following:

Low risk (5 -15%) for bleeding: flat dot; a clean or white base.
High risk (30 - 50%) for bleeding: swollen but nonbleeding blood vessels; blood clots that adhere to ulcers.
According to one study, if patients with these high-risk features are untreated, their risk for rebleeding after endoscopy ranges from about 10% on the first day after endoscopy to about 3% by the third day. Identifying and treating patients with stigmata can reduce these risks. Other factors that increase the risk for rebleeding include bleeding disorders, very low blood pressure, other serious medical conditions, and bleeding that started after hospitalization.
After endoscopy, high-dose PPI therapy has been shown to significantly reduce the rate of rebleeding, need for surgery, and death from hemorrhage. The medication may be given intravenously, but studies show that oral PPI therapy is probably just as effective.

Endoscopy as Treatment. Endoscopy is usually used to treat bleeding from visible vessels that are less than 2 mm in diameter. This approach also appears to be very effective in preventing rebleeding in patients whose ulcers are not bleeding, but who have high-risk features (swollen blood vessels or clots adhering to ulcers).

The following is a typical endoscopy procedure:

The surgeon passes a probe through an endoscopic tube and applies electricity, heat, or small clips to coagulate the blood and stop the bleeding. This procedure also causes fluid buildup, which helps to compress the blood vessels.
In high-risk cases, the doctor may inject epinephrine (commonly known as adrenaline) directly into the ulcer to enhance the effects of the heating process. Epinephrine activates the process leading to blood coagulation, narrows the arteries, and enhances blood clotting.
Intravenous (IV) administration of a PPI (usually omeprazole or pantoprazole) significantly prevents rebleeding and appears to be cost-effective. In one study, the use of IV PPIs reduced the risk of bleeding from 23% to 7%. (Oral PPIs are also effective, but studies are needed to compare their effectiveness versus IV PPIs.) A PPI may also be useful for initial bleeding episodes when endoscopy is unsuccessful, inappropriate, or unavailable.

Intravenous H2 blockers are often used, but a major analysis reported no benefit in bleeding duodenal ulcers, although they may be effective in gastric ulcers.

Endoscopy is effective in controlling bleeding in more than 85% of appropriate candidates. If rebleeding occurs, a repeat endoscopy is effective in about 75% of patients. Those who fail to respond require major abdominal surgery. The most serious complication from endoscopy is perforation of the stomach or intestinal wall, which occurred in about 1.4% of patients in a large 2002 study.

While endoscopy and clipping are routine treatment for bleeding ulcers in the U.S., a Korean study found little difference in outcomes between clipping (plus H2 therapy) and oral PPI therapy alone. In a randomized test of 129 patients, hemostasis (end of bleeding) was achieved in 93.5% of patients after clipping and 92.5% of patients on oral PPIs at 24 hours. The rate of rebleeding was 6.9% with clipping and 7.5% with PPIs.

Other Medical Considerations. Certain agents may be warranted after endoscopy:

Patients who harbor the H. pylori bacteria, even when the bleeding has been caused by NSAID use, should be treated with antibiotic therapy to eliminate the bacteria. Triple therapy, including antibiotics, to eliminate H. pylori immediately after endoscopy is warranted in most patients infected with the bacteria.
Somatostatin (a hormone used to prevent bleeding in cirrhosis) is also useful for reducing persistent peptic ulcer bleeding or the risk of recurrence. Researchers are investigating adding other therapies, such as fibrin glue, a blood clotting factor. To date, no therapy has proven to be more effective than current treatments.

Major abdominal surgery for bleeding ulcers is now generally performed only when endoscopy fails or is not appropriate. Certain emergencies may require surgical repair, such as when an ulcer perforates the wall of the stomach or intestine, causing sudden intense pain and life-threatening infection.

Surgical Approaches. The standard major surgical approach uses a wide abdominal incision and standard surgical instruments (called open surgery). Laparoscopic techniques employ small abdominal incisions and the insertion of tubes that contain miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers. Surgery is not effective for upper GI ulceration caused by chronic NSAID use.

Major Surgical Procedures. There are a number of surgical procedures aimed at long-term relief of ulcer complications. These include:

Click the icon to see an illustrated series detailing a gastrectomy procedure.

Vagotomy, in which the vagus nerve is cut to interrupt messages from the brain that stimulate acid secretion in the stomach. This surgery may impair stomach emptying. A recent variation that cuts only parts of the nerve may reduce this complication.
Antrectomy, in which the lower part of the stomach is removed. This part manufactures the hormone responsible for stimulation of digestive juices.
Pyloroplasty, which enlarges the opening into the small intestine so that stomach contents can pass into it more easily.

Antrectomy and pyloroplasty are usually performed with vagotomy.

Lifestyle Changes

In the past, it was common practice to tell people suffering from peptic ulcers to consume small, frequent amounts of bland foods. Exhaustive research conducted since that time has shown that a bland diet is not effective in reducing the incidence or recurrence of ulcers, and that eating numerous small meals throughout the day is no more effective than eating three meals a day. Large amounts of food should still be avoided, because stretching the stomach can result in painful symptoms.

Fruits and Vegetables. The good news is that a diet rich in fiber may cut the risk of developing ulcers in half and speed healing of existing ulcers. Fiber found in fruits and vegetables is particularly protective; vitamin A contained in many of these foods may increase the benefit. Some studies on associations between specific food chemicals and ulcers are as follows:

In one study, apples and yams appeared to be especially helpful.
Apples, celery, cranberries, onions, red wine, and green and black tea are also high in natural chemicals known as flavonoids, which appear to inhibit H. pylori growth and have many other health benefits. Cranberry juice specifically may have properties that help prevent H. pylori from infecting the intestinal lining.
Grapefruit has antioxidant properties that may help heal ulcers.
Studies on rats have found that dietary nitrate increases nitric oxide in the gut and causes the mucus layer to thicken. Pretreatment with nitrate provided dramatic protection against diclofenac-induced ulcers. High levels of dietary nitrate are found in many vegetables.
Laboratory experiments suggest that sulforaphone, a compound found in broccoli and broccoli sprouts, may be lethal to even drug-resistant strains of H. pylori.
Tea has chemicals that may help protect against cancers in the stomach and esophagus.

Milk. Milk actually encourages the production of acid in the stomach, although moderate amounts (2 - 3 cups a day) appear to do no harm. Animal studies show that a milk protein called bovine alpha-lactalbumin protects against gastric ulcers caused by stress. Certain probiotics, which are "good" bacteria added to yogurt and other fermented milk drinks, may also have gastric protective qualities.

Coffee and Carbonated Beverages. Coffee (both caffeinated and decaffeinated), soft drinks, and fruit juices with citric acid increase stomach acid production. Although no studies have proven that any of these drinks contribute to ulcers, consuming more than 3 cups of coffee per day may increase susceptibility to H. pylori infection.

Spices and Peppers. Studies conducted on spices and peppers have yielded conflicting results. The rule of thumb is to use these substances moderately, and to avoid them if they irritate the stomach.

Garlic. Some studies suggest that high amounts of garlic may have some protective properties against stomach cancer, although a recent study concluded that it offered no benefits against H. pylori and, in high amounts, can cause considerable GI distress.

Olive Oil. Studies from Spain have shown that phenolic compounds in virgin olive oil may have strong bactericidal activity against 8 strains of H. pylori, 3 of which are resistant to antibiotics.

Vitamins. Although no vitamins have been shown to protect against ulcers, H. pylori appears to impair absorption of vitamin C, which may play a role in the higher risk of stomach cancer.

Some evidence exists that exercise may help reduce the risk for ulcers in some people. In one study, exercise was associated with a lower risk for duodenal, but not gastric, ulcers in men. In this study, exercise appeared to have no effect on ulcer development in women.

Stress relief programs have not been shown to promote ulcer healing, but they may have other health benefits.

Melatonin is a hormone found in the brain that is normally associated with sleep. Researchers have observed that the GI tract is rich in melatonin, and that the hormone may have properties that help prevent ulcers, reduce acid secretion, and improve blood flow. It is not known whether this would benefit people with peptic ulcers, but it appears to warrant some research. In the U.S., melatonin is classified as a dietary supplement and not a drug, so its quality and effectiveness are uncontrolled. The U.S. is the only developed nation that does not regulate this agent.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology

References

deBortoli M, Leonardi G, Ciancia E, et al. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J. Gastroenterol. 2007;102(5):951-956.

Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007;99(6A):22C-31C.

Hainaux B, Agneessens E, Bertinotti R, et al. Accuracy of MDCT in predicting site of gastrointestinal tract perforation. Am J Roentgenol. 2006;187(5):1179-1183.

Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMS. 2006;333(7571):726. Epub 2006 Sept 19.

Hobsley M, Tovey F, Horton J. Precise role of H. pylori in duodenal ulceration. World J Gastroenterol. 2006;12(40):6413-6419.

Goer A, Gothe H, Schiffhorst G, Sterzel A, Grass U, Haussler B. Comparison of the effects of diclofenac or other non-steroidal anti-inflammatory drugs (NSAIDs) and dicolfenac or other NSAIDs in combination with proton pump inhibitors (PPI) on hospitalization due to peptic ulcer disease. Pharmacoepidemiol Drug Saf. 2007 Feb 26 [Epub ahead of print].

Jansson EA, Petersson J, Reinders C, et al. Protection from nonsteroidal anti-inflammatory (NSAID)-induced gastric ulcers by dietary nitrate. Free Radic Biol Med. 2007;41(4):510-518.

Keefer L, Stepanski EJ, Ranjbaran Z, Benson LM, Keshavarzian A. An initial report of sleep disturbance in inactive inflammatory bowel disease. J Clin Sleep Med. 2006;2(4):409-416.

Kim JI, Cheung DY, Cho SH, et al. Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding peptic ulcer: a prospective, randomized, controlled trial. Dig Dis Sci. 2007 May 19 [Epub ahead of print].

Luo J, Nordenvall C, Nyren O, Adami HO, Permert J, Ye W. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007;120(2):368-372.

Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastrict III Consensus Report. Gut. 2007;56(6):772-781.

Miki K, Urita Y, Ishikawa F, et al. Effect of Bifidobacterium bifidum fermented milk on Helicobacter pylori and serum pepsinogen levels in humans. J Dairy Sci. 2007;90(6):2630-2640.

Moberly JB, Harris SI, Diff DS, et al. A randomized, double-blind, one-week study comparing the effects of a novel COX-2 inhibitor and naproxen on the gastric mucosa. Dig Dis Sci. 2007;52(2):442-450.

Moore ML. Misoprostol-is more research needed? J Perinat Educ. 2002;11(3):43-47.

Murthy S, Keyvani L, Leeson S, Targownik LE. Intravenous versus high-dose oral proton pump inhibitor therapy after endoscopic hemostasis of high-risk lesions in patients with acute nonvariceal upper gastrointestinal bleeding. Dig Dis Sci. 2007;63(11):773-775.

Pietroiusti A, Forlini A, Magrini A, et al. Shift work increases the frequency of duodenal ulcer in H. pylori infected workers. Occup Environ Med. 2006;63(11):773-775.

Pilotto A, Franceschi M, Leandro G, et al. Clinical features of reflux esophagitis in older people: a study of 840 consecutive patients. J Am Geriatr Soc. 2006;54(10):1537-1542.

Romero C, Medina E, Vargas J, Brenes M, De Castro A. In vitro activity of olive oil polyphenols against Helicobacter pylori. J Agric Food Chem. 2007;55(3):680-688.

Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol. 2007;14(6):1860-1869.

Simon-Rudler M, Massard J, Bernard-Chabert B, et al. Continuous infusion of high-dose omeprazole is more effective than standard-dose omeprazole in patients with high-risk peptic ulcer bleeding: a retrospective study. Aliment Pharmacol Ther. 2007;25(:949-954.

Take S, Mizuno M, Ishiki K, et al. Baseline gastric mucosal atrophy is a risk factor associated with the development of gastric cancer after Helicobacter pylori eradication therapy in patients with peptic ulcer disease. J Gastroenterol. 2007;42(suppl 17):21-27.

Ushida Y, Shimokawa Y, Toida T, Matsui H, Takase M. Bovine alpha-lacalbumin stimulates mucus metabolism in gastric mucosa. J Dairy Sci. 2007;90(2):541-546.

Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med. 2007;146(:556-563.

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Yeomans ND, Svedberg LD, Naesdal J. Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use? Int J Clin Pract. 2006;60(11):1401-407.

Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F. Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER study. Gut. 2007;56(4):475-479.

Review Date:
6/22/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Melanoma and other skin cancers

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Melanoma
Nonmelanoma Skin Cancer
Precancerous Skin Condition...
Causes
Risk Factors
Prevention
Screening
Diagnosis
Staging
Treatment for Melanoma
Treatment for Nonmelanoma S...
Prognosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk factors

According to a report in the Archives of Dermatology, marathon runners are more likely than the general population to develop skin changes that increase the risk for melanoma.

Prevention

A study published in The Lancet indicates that the best ways to avoid sun damage are to reduce the time you spend in the sun and to wear a hat and clothing to protect as much of your skin as possible. Fabrics that are thick and tightly woven offer the best protection.

The U.S. Food and Drug Administration has approved a new type of sunscreen that may more effectively block UVA than products currently available in the United States. UVA light penetrates the skin deeper than other forms of sunlight. Exposure to UVA is believed to contribute to skin cancers. The new sunscreen, called Anthelios SX, is available over the counter.

Screening

A study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they understand their personal risk factors for melanoma and know where to go to have such an exam. The study emphasizes the importance of skin cancer awareness and education.

One-time melanoma screening for adults over age 50 seems to be as cost-effective as other nationally recommended cancer screening programs, according to a report in the Archives of Dermatology. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology. The earlier melanoma is diagnosed and treated, the greater your chances of survival.

Introduction

Skin cancer is cancer that starts in the skin. Skin cancers are divided into two major groups:

Nonmelanoma, which includes basal cell cancer and squamous cell cancer
Melanoma, the deadliest form of skin cancer

Different skin cancers start in different layers or cells of the skin. To understand how skin cancer develops, it is useful to know something about the skin.

The Skin. The skin is the largest organ in the body and consists of layers.

The outermost layer of the skin is called the epidermis. It is only about 20 cells deep, roughly as thick as a sheet of paper.
The dermis ranges in thickness from 1 - 4 millimeters (about 1/32 - 1/8 inch). The dermis contains tiny blood and lymph vessels, which increase in number deeper in the skin.

The skin is the largest organ of the body. The skin and its derivatives (hair, nails, sweat, and oil glands) make up the integumentary system. One of the main functions of the skin is protection. It protects the body from external factors, such as bacteria, chemicals, and temperature. The skin contains secretions that can kill bacteria, and the pigment melanin provides a chemical pigment defense against ultraviolet light that can damage skin cells. The skin also helps control body temperature.

Melanocytes. A layer of cells between the epidermis and the dermis, called melanocytes, produces a brown-black skin pigment ( melanin) that determines skin and hair color. Melanin also helps protect against the damaging rays of the sun.

As a person ages, melanocytes often proliferate, forming concentrated clusters that appear on the surface as small, dark, flat, or dome-shaped spots, which are usually harmless moles or liver spots.

When cell proliferation occurs in a controlled and contained manner, the resulting lesion is benign and is commonly referred to as a mole or nevus.
Sometimes, however, pigment cells grow out of control and become a cancerous and life-threatening melanoma.

Click the icon to see an image of melanin.

Melanoma

At first, melanoma cells are found in the epidermis and top layers of the dermis. However, once they grow downward into the dermis, the cancer can come into contact with lymph and blood vessels. The thicker the melanoma, the greater the likelihood that it could spread to distant sites.

Removal of the lesion before it reaches the deeper layers of the skin is important for achieving a cure.

Superficial Spreading Melanoma. Superficial spreading melanoma is the most common and most curable. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.

Nodular Melanoma. Nodular melanoma appears as a fast-growing brown or black lump, and its characteristics do not always fit the definitions described above. It is important to check for this type of melanoma because it is associated with an outbreak of other tumors.

Lentigo Maligna. Lentigo maligna (sometimes called Hutchinson's freckle) usually occurs in elderly people and is marked by flat, mottled, tan-to-brown freckle-like spots with irregular borders. These lesions often appear on the face or other sun-exposed areas and typically enlarge slowly for 5 - 15 years before cancer appears.

Acral Lentiginous Melanoma. Although rare, acral lentiginous melanoma is the most common melanoma among African and Asian populations. It commonly appears as a dark patch on the palms, soles, fingers, toes, under fingernails or toenails, or in mucous membranes.

Melanoma cells usually spread first through the lymph vessels or glands. Melanoma cells can also spread by way of blood vessels to various organs, spreading cancer to the liver, lungs, brain, or other sites.

Melanomas tend to grow in stages:

Most melanomas tend to be flat initially and spread laterally across the skin surface as they grow. At this early stage, which can last 1 - 5 years or longer, removal of the growth has an excellent chance of curing the melanoma. Still, there is a chance that some of these melanomas are invasive, and they should be treated aggressively.
Lesions that become raised or dome-shaped over at least part of their surface indicate that downward growth has occurred. In some cases, this growth is very rapid, occurring over a period of weeks to months.

Any suspicious lesion should be checked immediately, particularly if it has grown quickly or is partially flat and partially raised.

Common sites of melanoma in men include:

Head
Middle of the body (trunk)
Neck

Common sites of melanoma in women include:

Arms
Legs

However, any area of the skin may be affected. You may not notice melanomas if they appear on areas that are difficult to examine, such as the scalp or the back.

Less common sites for melanoma include:

Fingers
Palms
Soles of the feet
Genitals
Lips
Under the fingernails or toenails

The presence of a dark lesion under the nail that runs into the adjoining skin and doesn't heal may signal melanoma.

Rarely, melanomas appear in the mouth, in the iris of the eye, or in the retina at the back of the eye, where they may be detected during dental or eye examinations.

Click the icon to see an image of melanoma.

Nonmelanoma Skin Cancer

The two other types of skin cancers are called basal cell cancer and squamous cell cancer. These are nonmelanoma skin cancers.

Basal cell cancer starts in the lowest part of the epidermis in round cells called basal cells. Basal cell is the most common form of skin cancer. It occurs in about 800,000 - 900,000 people every year.

Basal cell cancer usually develops later in life in areas that have received the most sun exposure, such as the head, neck, back, and especially the nose. However, some basal cell cancers appear in areas not exposed to the sun.

Basal cell cancers have many different appearances:

They usually appear as a round area of thickened skin that does not change color or cause pain or itching.
Very slowly, the lesion spreads out and develops a slightly raised edge, which may be translucent and smooth. Infrequently, basal cell cancers resemble malignant melanomas in color.
Eventually, the center becomes hollowed and covered with a thin skin, which can become sore and open.
A form known as aggressive-growth basal cell cancer resembles a scar with a hard base. This type is more likely to spread and must be treated very aggressively.

Basal cell cancer is a cancerous (malignant) skin tumor involving basal skin cells. Basal cell skin cancers usually occur on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation. Once a suspicious lesion is found, a biopsy is needed to prove the diagnosis of basal cell cancer. Treatment varies depending on the size, depth, and location of the cancer.

Basal cell cancers are sometimes hard to tell from benign skin conditions. For instance, occasionally they arise in unexposed skin, where they may mimic an ordinary mole, cyst, or pimple. They may be particularly difficult to distinguish from benign cysts when they occur near the eyes.

Usually, basal cells grow slowly. They are rarely deadly. Most basal cell cancers need not be treated as an emergency, although late treatment can cause disfigurement, so they should be removed as early as possible.

Basal cell cancers that are most likely to spread include those that are larger than 1 centimeter, scar-like, and those located on the cheek, nose, neck, earlobe, eyelid, or temple.

Some studies have shown that people with basal cell cancer may be at higher risk for second cancers, including melanoma, cancer of the lip, salivary glands, larynx, lung, breast, and kidney, and non-Hodgkin's lymphoma. Those at higher risk for such cancers appear to be men and anyone diagnosed before 60 with basal cell cancer.

Squamous cell cancer develops from flat, scale-like skin cells called keratinocytes, which lie under the top layer of the epidermis. Most squamous cell cancers occur on sun-exposed areas, especially the forehead, temple, ears, neck, and back of the hands. People who have spent considerable time sunbathing may develop them on their lower legs.

Types of squamous cell cancer:

Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of this type of cancer. The cancer has not spread. Cancer areas appear as large reddish patches (often over 1 inch) that are scaly and crusted.
Invasive squamous cell carcinoma is highly likely to spread (metastasize). The skin cancer lesions can grown rapidly (over months) or slowly (over years). Eventually they become ulcerated.

Click the icon to see an image of squamous cell cancer.

Prompt treatment is desirable because squamous cell cancers are more likely to spread to local lymph nodes than basal cell cancer. Squamous cell cancers most likely to spread include:

Deep lesions, those larger than 2 cm in diameter, or patches with poorly defined margins
Recurrent lesions
Squamous cell cancer on neck, earlobe, eyelid, lips, or temple
Squamous cell cancer that develops in ulcers
Squamous cell cancer that develops on skin areas that have been previously treated with radiation or exposed to cancer-killing chemicals

People with squamous cell cancers seem to be at higher risk for other cancers, including melanoma, lung cancer, non-Hodgkin's lymphoma, bladder cancer, leukemia, testicular and prostate cancer in men, and breast cancer in women.

Precancerous Skin Conditions

Actinic (Solar) Keratosis. Actinic keratosis (also called solar keratosis) is a precancerous skin lesion caused by too much sun exposure. Such lesions can turn into cancer, but not always.

Actinic keratoses occur after years of sun exposure. They appear predominantly on sun-exposed skin, such as the face, neck, back of the hands and forearms, upper chest, and upper back. Men may develop keratoses along the rim of the ear.

Actinic keratoses have the following characteristics:

Lesions typically occur on the surface of the skin and have a sandpaper-like feel. In fact, they are sometimes more easily felt than seen.
Most lesions are pink and even flesh-colored. Some are red or brown, scaly, and tender. At times, they can resemble melanomas; even dermatologists may have trouble telling the two apart.
They can range in size from microscopic to several inches in diameter.

Keratoacanthomas. Keratoacanthomas closely resemble squamous cell cancers, but they are not malignant. The majority occur in sun-exposed skin, usually on the hands or face. They are typically skin colored or slightly red when they first develop, but their appearance typically changes:

In the early stages, keratoacanthomas are smooth, red, and dome shaped.
Within a few weeks, they can grow rapidly, usually to 1 or 2 centimeters. Some reach the size of a quarter in less than a month and can be rather disfiguring.
They eventually stop growing and become crater-like with a surrounding outer rim of tissue and sometimes have a crusty interior.

Most will spontaneously get better within 1 year, but they almost always scar after healing. Also about 25% develop into squamous cell cancers, most frequently in older people and in sun-exposed areas. Removal by surgery (sometimes by radiation) is recommended. They may also be treated with 5-fluorouracil, either as a cream or injections.

Causes

You cannot overestimate the role of the sun as the most important cause of prematurely aging skin (called photoaging ) and skin cancers.

Long-term repetitive and cumulative exposure to sunlight appears to be responsible for the vast majority of undesirable consequences of aging skin, including basal cell and squamous cell cancers.

Melanoma is more likely to be caused by intense exposure to sunlight in early life.

UVA and UVB Radiation. When sunlight penetrates the top layers of the skin, ultraviolet (UVA or UVB) radiation strikes the DNA inside the skin cells and damages it.

UVB is the main type of radiation responsible for sunburns. It primarily affects the outer skin layers. This type of ultraviolet light is most intense at midday when sunlight is brightest.
UVA penetrates more deeply and efficiently. Unlike UVB, window glass does not filter out UVA rays.

Damaging Effects of UV Radiation. Both UVA and UVB rays cause damage, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders, and cancer, although the mechanisms are not yet fully clear. The following are some ways in which cancer may develop and some defensive actions that the skin uses to defend itself against DNA damage.

Oxidation and Antioxidants. The effects of UV radiation are implicated in the production of oxidants, also called free radicals. Free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter the DNA. This contributes to the aging process and sometimes to cancer.
Defective DNA Repair and Protective Enzymes. Some skin cancers are caused by a breakdown in the body's mechanisms that help repair DNA damage. For example, xeroderma pigmentosum (XP) is a rare genetic disease in which the body cannot repair damage caused by ultraviolet light. Normally, a number of enzymes in the skin help protect against this damage.
Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune system cells attack developing cancer cells at the very earliest stages. However, certain substances in the skin, particularly a chemical called urocanic acid, can suppress such immune factors when exposed to sunlight.

Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are very severely damaged. Apoptosis in the skin kills off cells harmed by UVA so that they do not turn cancerous. The peeling after sunburn is the result of these dead skin cells. However, some gene defects or other factors interfere with apoptosis. If this occurs, damaged cells can continue to spread, resulting in skin cancer.

A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental assaults (particularly sunlight).

Mutations in Genes that Regulate Cell Growth. Noninherited mutations in a number of genes that block tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.

Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may be a viable treatment path.
P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.
Genetic mutations that regulate Ku70 and Ku80 proteins may disrupt processes that repair strands of DNA.
Researchers are also studying mutations in a gene that encodes for a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and may account for many sporadic (non-inherited) cases of melanoma.
Of further interest are mutations in genes that regulate Fas proteins, which are involved in apoptosis, a natural process of cell self-destruction. When apoptosis goes awry in melanoma cells, proliferation can become rampant.

CDKN2A Mutations. Mutations in a gene regulator called CDKN2A are the most common causes of inherited melanoma, which is still very uncommon. Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A, although it is not clear if knowing the results of the test would benefit people carrying the gene.

Variations in the Melanocortin-1 Receptor Gene. One study found that the greater the number of variations from normal in a gene called the melanocortin-1 receptor gene, the greater the risk for melanoma. The gene plays an important role in determining if a person has red hair, fair skin, and sensitivity to UV radiation. Interestingly, people who had olive and darker skin and who carried one or more variations of the gene had a higher than average risk for melanoma.

Aging may weaken the body's ability to fend off impending cancers, including melanomas. As a person ages, they lose Langerhans cells that help fight off early skin cancers. The number of these immune cells decreases with age, possibly setting the stage for skin cancers in later life.

Risk Factors

In the United States, the rate of melanoma is rising more rapidly than any other cancer. According to the American Cancer Society, about 59,940 persons will be diagnosed with melanoma in 2007. More than 8,000 people will die from the cancer.

Survival rates have been improving, however, and the increase in melanomas has occurred principally with thin, less aggressive forms of the disease. Some experts believe this is due to the increased awareness from effective public programs and earlier diagnosis.

A risk factor is anything that increases your chance of getting a disease. The following factors increase your risk for skin cancer:

Age over 40
Being male
Fair skin
Too much exposure to sunlight and ultraviolet radiation
Personal history of skin cancer
Family history of skin cancer
Smoking
Certain chronic or severe skin problems
Certain medical conditions or treatments that affect your immune system
Exposure to chemicals or radiation

Melanoma in Adults. Melanoma is most common in people over 40, and the incidence increases significantly as people get older. Before age 40, melanomas are slightly more common in women than men, but after age 40 men are more often affected. Men are also more likely to have invasive and fatal melanoma than are women, although some research suggests that the higher rates are only because men fail to seek a diagnosis of suspicious skin changes before they become dangerous. The rate in women levels off somewhat between age 45 and 60; researchers speculate that menopause could have some sort of protective effect during those years.

Melanoma in Children. Melanoma is rare in children under age 10. Among children ages 10 - 14 the incidence is only 0.3 per 100,000. Between ages 14 - 19, it is still very rare, 1.3 per 100,000. Parents, then, should not be unduly alarmed by every minor skin imperfection in their children. Nevertheless, melanoma is as serious in children as in adults, and early detection is still critical.

Skin cancer is associated with both duration and intensity of sun exposure. Risk of melanoma increases with excessive sun exposure during the first 10 - 18 years of life. Sunburns are also dangerous, with five or more sunburns doubling the risk of developing cancer. Cancer typically arises many years later.

Marathon runners are more likely than the general population to develop skin changes that increase your risk for melanoma. That's because marathon runners spend a lot of time outdoors. The study findings are published in the Archives of Dermatology.

Tanning Devices. Tanning beds and sunlamps increase the risk for developing melanoma, according to a 2005 review of epidemiologic studies. Previous findings have suggested that women who use tanning devices more than once a month significantly increase their melanoma risk. Women in their 20s, as well as blondes and redheads, are especially at risk.

Ethnic Groups and Complexion. People with light skin, blue, gray, or green eyes, red or blond hair, and lots of freckles are at highest risk for developing melanoma. The risk increases for those who are easily sunburned and rarely tan, particularly if they live close to the equator where sunlight is most intense. Darker ethnic groups or those with swarthy complexions are not immune, however.

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). Tanning and Sunburn Risk People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning Risk
I	Always burns, never tans, sensitive to sun exposure.
II	Burns easily, tans minimally.
III	Burns moderately, tans gradually to light brown.
IV	Burns minimally, always tans well to moderately brown.
V	Rarely burns, tans profusely to dark.
VI	Never burns, deeply pigmented, least sensitive.

Australia has the highest melanoma rate in the world. In the United States the rate is highest in California, Florida, and Texas. The disease is by no means limited to such sunny states and countries, however. In general, the risks are highest in regions where the population tends to be blonde and fair-skinned. Norway, for example, has had the highest rate of melanoma in Europe, and rates are soaring in the UK, particularly among men, perhaps because Britons are increasingly vacationing in sunny climates.

Melanoma. Individuals who have been diagnosed with melanoma are at increased risk for a second primary melanoma. According to one 2003 study, the risk over time for developing a second melanoma is 1% in the first year after diagnosis, 2.1% at 5 years, 3.2% at 10 years, and 5.3% at 20 years. The risk is especially higher in older men and in those with first melanomas on the upper body and face.

People with family members who have or had melanoma should also be considered at high risk and examined on a regular basis.

Nonmelanoma Skin Cancers. Nonmelanoma skin cancers, including basal and squamous cell carcinomas, increase the risk of dying from other cancers, including melanoma itself, lung cancer, non-Hodgkin's lymphoma, bladder cancer, and leukemia as well as testicular and prostate cancers (in men) and breast cancer (in women).

Psoriasis. Psoriasis increases the risk for squamous cell carcinoma, but studies conflict on whether it has any effect on melanoma. One study, in fact, reported a lower risk. Nevertheless, there is some evidence that long-term treatment for psoriasis using UVA radiation (PUVA) may increase the risk for melanoma. In one study, there was a significantly higher risk even with relatively few treatments. In one study, invasive melanoma had occurred in 2.8% of patients 15 or more years after the initial treatment.

Moles (Nevi) and Other Dark Blemishes. Certain moles and dark blemishes increase the risk for skin cancer. Any mole ( nevus) or other blemish that seems new, changing, or unusual in any way should be evaluated by a health care professional.

Some specific moles or dark blemishes that are risk factors for melanoma include:

Freckles. Freckles typically appear in children on sun-exposed areas and are usually evenly brown or tan. The more freckles a person develops as a child, the greater the risk for melanoma in adulthood.
Dysplastic (or Atypical) Nevi. About 30% of the population has moles called dysplastic nevi, or atypical moles. They are larger than ordinary moles (most are 5 mm across, about the size of a pencil eraser, or larger), have irregular borders, and are various shades or colors. Individuals who have dysplastic nevi plus a family history of melanoma (a syndrome known as FAMM) are at a high risk for developing melanoma at an early age (younger than 40). The risk for those with atypical moles and no family history of melanoma is less clear.
Large birthmarks (giant congenital nevi). Very large birthmarks more than 8 inches across are major risk factors for melanoma. In such cases, cancer usually appears by age 10. Medium-sized congenital nevi do not appear to increase the risk for melanoma. Whenever possible, very large birthmarks should be removed during infancy. Experts disagree, however, about whether small birthmarks need to be removed. Parents should watch any birthmark for changes.

The more moles one has the higher the risk that one of them will become cancerous, although the danger is still very small. A 2003 study estimated that the risk for a single mole to develop into melanoma by age 80 is 1 in 3,164 in men and 1 in 10,800 for women.

The risk is higher, however, with atypical moles. One study of people with melanoma indicated that the presence of even one atypical mole doubled the normal risk.

Some skin blemishes can look like -- but are not -- melanoma. Noncancerous moles typically have the following characteristics:

They generally remain small with clearly defined, regular borders, and uniform coloration. Some have a regular stippled or net-like pattern of pigmentation, however, and may even resemble early melanoma.
They typically first appear during childhood, puberty, or young adulthood. They may naturally grow, darken, or increase in number at certain times of life, such as adolescence or pregnancy.

Examples of moles or blemishes that may resemble skin cancer include:

Blue nevus. A benign mole that may easily be mistaken for melanoma. It is a blue-black, smooth, raised nodule and commonly occurs on the buttocks, hands, or feet.

Liver Spots. Liver spots are usually evenly brown or tan sun-induced lesions that are universal signs of aging. Occurring most noticeably on the hands and face, these harmless blemishes tend to enlarge and darken over time.

Spindle Cell (Spitz) Nevus. Children may develop a benign lesion called a spindle cell (or Spitz) nevus. The mole is firm, raised, and pink or reddish-brown. It may be smooth or scaly and usually appears on the face, particularly the cheeks. It is not harmful, but it may be difficult to differentiate from a melanoma, even for experts.

Non-Hodgkin's Lymphoma. Survivors of either non-Hodgkin's lymphoma or melanoma face a higher risk for the other malignancy. These may have common causes, such as exposure to UV radiation or shared genetic factors.

Human papillomavirus (HPV). Genital warts (human papillomavirus, or HPV) may also increase the risk of squamous cell cancer in the genital and anal areas and around fingernails.

Immunosuppression. Skin cancer risk is increased in persons whose immune systems are suppressed because of certain medications, organ transplantation, or medical conditions such as AIDS. Melanoma has also developed in patients who received heart transplants from donors who had the disease. Immune-suppressing drugs used to treat autoimmune disorders may also increase the risk of skin cancer. Potential skin cancer risks have been associated with the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic).

Rheumatoid arthritis. Despite previous concerns, the rheumatoid arthritis drug etanercept (Enbrel) does not raise the risk for developing squamous cell skin cancer. The findings are reported in the Archives of Dermatology. Etanercept works by blocking tumor necrosis factor (TNF), an immune system chemical messenger that is involved in inflammatory processes and diseases.

Occupational exposure to radiation, such as in health care or industrial settings, may increase the risk for melanoma. Airline pilots, too, are at increased risk for melanoma. It is uncertain, however, whether this higher risk is from excessive exposure to ionizing radiation at high altitudes or because they have more opportunity to spend time in sunny regions. Experts disagree over whether frequent flyers are also at increased jeopardy.

Prevention

The best way to lower the risk your risk of skin cancer is to protect your skin from the sun and UV light.

Wear sunscreen. The use of sunscreens is complex, and everyone should understand how and when to use them. Follow instructions closely and reapply as directed after swimming or sweating. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Many parents are now taking effective steps to protect their children, although experts worry that they are relying too much on sunscreen and less on other protective measures. Adolescents are at special risk for sun-related cancers because, according to a 2002 study, most of them do not take protective measures when out in the sun. According to the study, boys are less likely to use sunscreen than girls, but girls are more likely to get sunburn and use tanning salons more often.

The best way to prevent skin damage in any case is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. Do not rely on sunscreen alone for sun protection. Also wear protective clothing and sunglasses.
Avoid exposure particularly during the hours of 10 a.m. to 4 p.m., when UV rays are the strongest.
Clouds and haze do not protect you from the sun and in some cases may intensify UVB rays.
Avoid reflective surfaces such as water, sand, concrete, and white-painted areas.
UV intensity depends on the angle of the sun, not heat or brightness. The dangers are greater the closer to the start of summer.
Skin burns faster at higher altitudes. One study suggested that an average complexioned person burns in 6 minutes at 11,000 feet at noon compared to 25 minutes at sea level.
Avoid sun lamps, tanning beds, and tanning salons. The machines use mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon are as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning.

Wear protective clothing, sunglasses, and a hat to shield your face from the sun's rays. Special clothing can block out UV rays and is rated using sun protection factor (SPF) ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however.

Everyone, including children, should wear hats with wide brims. (Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.)
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays when in the sun.

Click the icon to see a depiction of sun protection.

When choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, and benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. And many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little.

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis.

Calculating the SPF. SPF is a ratio based on the amount of UVB radiation needed to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11
Moderate: SPF 12 through 29
High: 30+

Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.

SPF Levels by Age Group. Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. All young children should be well-covered with clothing, sunglasses, and hats. Children should be kept out of the sun during peak sunlight periods. Do not use sunscreens on babies younger than 6 months without consulting a doctor.

Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.

Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. Apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen every day, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however. Sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include:

Until recently, many sunscreens blocked only or predominantly blocked UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Studies then may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may stay out too long during peak sunlight hours. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. A 2002 study found that people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. A later study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure.

Underexposure to sunlight. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems such as:

Vitamin D deficiency. The body makes vitamin D through a chemical reaction to UVB sunlight. Too many sun-protection measures may increase the risk for developing vitamin D deficiency. Vitamin D helps prevent rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. (Warning: Vitamin D is poisonous when taken in high doses.) People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin.
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from seasonal affective disorder (SAD), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary.

A study published in 1994 in the New England Journal of Medicine found that persons with a history of nonmelanoma skin cancer who ate a low-fat diet were much less likely to develop actinic keratosis, a precancerous skin condition.

However, the low-fat diet did not appear to have any effect on the development of basal cell cancer.

Chemoprevention is the use of a substance to prevent or reduce your risk of cancer. Certain drugs have been used to help block the development of skin cancers, including melanoma. For example, a medicine called imiquimod is approved to prevent skin cancer in certain individuals. This medicine prompts the immune system to fight off foreign substances, including cancer cells. Chemopreventive agents under investigation and showing promise for skin cancer include:

Nonsteroidal anti-inflammatory drugs
Difluoromethylornithine (DFMO)
Catechins (phytochemicals found in certain foods)
Anti-aging drugs called retinoids (vitamin A derivatives)

Retinoids have been shown to prevent nonmelanoma skin cancer in patients with basal cell nevus syndrome, xeroderma pigmentosum, and transplanted organs. Oral retinoids include isotretinoin and acitretin. They may also prevent the development of squamous cell carcinoma in patients who are taking such medicines to treat psoriasis.

Early animal studies had suggested that cholesterol-lowering statins or fibrates may reduce the risk of skin cancer, but human studies have produced inconsistent results. A review of several studies has concluded that such drugs do not decrease your risk of melanoma. The findings are published in the Journal of the National Cancer Institute.

Researchers are also studying chemopreventative compounds that target genetic mechanisms in the skin. They may prove to be beneficial ingredients in creams or lotions used to prevent skin cancers on a molecular level. They include cytokine interleukin-12 and T4 endonuclease 5 (T4N5).

Studies have shown that mice with round-the-clock access to an exercise wheel developed skin cancer more slowly when exposed to UVB. Their tumors were also fewer in number and smaller. Analysis of the data suggested that exercise might trigger the death of the developing cancer cells faster than they can grow. Exercise also made the mice lose weight, and the number of tumors decreased as fat disappeared.

Antioxidants are chemicals or drugs that help prevent cell damage from unstable molecules called free radicals. Antioxidants promote to protect the skin include vitamins C and E, and coenzyme Q10 (CoQ10).

Studies suggest that vitamin E creams, particularly those made from a type of Vitamin E called alpha tocopherol, decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also shown that such creams reduce UV-related skin cancer.

Vitamin C is a very potent antioxidant. It is also called ascorbic acid. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts reduced skin swelling and protected immune factors from sunlight.

Selenium in the form of L-selenomethionine has protected against sun damage and even delayed skin cancer in animal studies. It is not known if such benefits apply to people.

Click the icon to read about the antioxidant selenium.

Antioxidant Skin Creams. There are wide claims about the benefits of antioxidants for wrinkles when used in skin creams. However, to date, only vitamin E, C, and selenium-based skin products have been shown to help reduce sun damage to the skin. However, most available brands contain very low concentrations of these antioxidants. In addition, the antioxidants are also not well absorbed by the skin, so the effect may be short-term.

Antioxidant Pills. One small study found that taking a combination of vitamins C and E supplements by mouth may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins alone does not appear to have the same effect.

Other Natural Substances. The following natural substances have antioxidant properties and are being tried for sun-protection:

Both green and black tea appear to have properties that may provide some protection against skin cancers and photoaging. A 2001 study using extracts of topical green tea suggested that it might protect against ultraviolet damage. Green tea skin care products are now available, but their quality is unregulated.
Ginger also appears to have some sun protective qualities.
Silymarin, a substance found in the milk thistle family (which includes artichokes), may prevent UVB-promoted cancers in animals.
Garlic has been shown to protect animals against UVB damage. Whether these results may be applied to humans, and what quantities of garlic might be beneficial, is still unknown.

Warning Note: A wide range of herbal products may contribute to dermatological problems. Some Chinese herbal creams have been found to contain corticosteroids. Mercury or arsenic contaminants have been found in some Ayurvedic therapies. In addition, several oral herbal remedies used for medical or emotional conditions may produce irritation in reaction to sunlight (photosensitivity). They include, but are not limited to, St. John's wort, kava, and yohimbe.

Screening

Education and prevention programs have led to improved screening for skin cancer, which in turn has improved diagnosis and survival rates for melanoma. For example, a study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they were aware of personal risk factors and where they could go to have an exam performed.

Skin cancers may have many different appearances. They can be small, shiny, or waxy, scaly and rough, firm and red, crusty or bleeding, or have other features. Itching, tenderness, scaling, bleeding, crusting, or sores can signal potentially cancerous changes in any mole.

A mnemonic device, ABCDE, is used to describe several features that help to distinguish skin cancer from noncancerous growths.

Asymmetry (A). Skin cancers usually grow in an irregular, asymmetric fashion. That means one half of the abnormal skin area is different than the other half.
Border Irregularity (B). Noncancerous lesions generally have clearly defined borders. Melanoma lesions often have notched or indistinct borders that may signal ongoing growth and spread of the cancer.
Color Variation (C). One of the earliest signs of melanoma may be the appearance of various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. Occasionally, lesions are flesh colored or surrounded by redness or lighter areas of depigmentation.
- Pink or red areas may result from inflammation of blood vessels within the skin.
- Blue areas reflect pigment in the deeper layers of the skin.
- White areas can arise from dead cancerous tissue.
Diameter (D). A diameter of 6 millimeters or larger (about the size of a pencil eraser) is worrisome. Melanomas start out small; by the time a lesion has grown this large, other abnormalities will most likely be present. A doctor should examine any suspicious lesion, no matter what size it is.
Evolution (E). A lesion that is growing or changing deserves evaluation.

The ABCDE plan is a general guide. It will not help detect the early stages of nodular melanoma and may also miss amelanotic melanoma, which is not pigmented.

You should keep in mind that the most important warning sign of melanoma is a new or changing skin lesion, regardless of size or color. Changes that occur over a short period of time (particularly over a few weeks) are most worrisome.

Anyone with risk factors for skin cancer should check the entire body about once a month. People who regularly check moles on their skin may have a lower risk of developing advanced melanoma.

Experts suggest drawing a map of the body, indicating locations of moles, areas of discoloration, lumps, or other blemishes. Whenever a person conducts a self-examination, they should compare their body to the map to check for new lesions, lumps, or moles and for changes in shape, color, and size.

Some experts have defined three specific body areas to look for skin cancers, including melanomas:

Areas visible to anyone, such as the arms or face -- about 60% of melanomas are found on such areas.
Areas usually covered with clothing and visible only to the patients or their partners -- about 34% of melanomas are detected in these areas.
Hidden areas such as the scalp, buttock folds, and mouth -- about 6% of melanomas, usually more advanced, are found here.

Ask a partner to help you check these areas. Turn on a hair dryer to separate hair and examine the scalp.

Some experts recommend that everyone, especially those with a high risk of developing melanoma, have a dermatologist perform a whole body skin exam. Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology.

High-risk people include those with a personal or family history of melanoma and individuals with atypical nevi (irregular moles that are also larger than normal).

Such people should protect themselves from overexposure to sunlight and have a medical examination of the entire skin surface every 3 - 12 months, with the frequency depending on risk factors. Doctors may take photographs of any moles at each visit and compare them with previous photos for any changes.

Examinations for Patients Previously Treated for Melanoma. People who have had melanoma and have been treated successfully are at risk for recurrence or a second primary melanoma. Based on recurrence rates by cancer stage, a team of researchers suggested the following guidelines for being reexamined by the doctor after treatment:

Stage I patients: Yearly exam
Stage II patients: Every 6 months for years 1 and 2 and annually thereafter
Stage III patients: Every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 to 5

All patients should be checked annually after year 5. These are guidelines only and may be changed, depending on individual patient characteristics.

Some studies also suggest that regular screening of family members of people with melanoma could prevent a number of serious cases. A 2007 report in the Archives of Dermatology has called for expanded melanoma screening programs. The study found that one-time melanoma screening for adults over age 50 seems to be as cost-effective as other recommended cancer screenings. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

An experienced doctor should first rule out benign conditions that resemble melanoma, such as a noncancerous mole called a melanocytic nevi.

In rare instances, a melanoma will be difficult to detect. For example, an uncommon form, called a myxoid melanoma, may be mistaken for a benign skin disorder known as a myxoid fibrohistiocytic lesion. Other opinions from a second pathologist, computerized image processing or advanced staining techniques, may help to confirm the diagnosis.

A study published in the Archives of Internal Medicine has found that melanoma tends to be diagnosed at a later stage in persons who are not light-skinned. The study involved nearly 50,000 patients with melanoma, and included Caucasians, Hispanics, Asian/Pacific Islanders, African-Americans, and American Indians.

Some doctors now use dermoscopy (also called dermatoscopy or epiluminescence microscopy). This technique uses a handheld scope-like device that enhances the suspected lesion. It is still not clear if such devices are any better than the naked eye of a trained professional. Of interest, however, was a 2002 study suggesting that it was very useful in identifying possible melanomas in suspicious nail abnormalities and therefore avoiding many painful biopsies in this area. A 2004 study confirmed that adding dermoscopy to conventional naked-eye examination leads to fewer biopsies than using naked-eye examination alone.

A recently developed Australian device (the Solarscan) may improve detection. It is shaped like a hair dryer and takes an image of the suspicious lesion; it then reads the image and compares it with a databank of melanoma images to help determine if it is cancerous. It can also store the image of the lesion and compare it for changes with later images taken at subsequent check ups. The device is not yet used in the United States. It still requires FDA approval. Testing is under way to confirm its accuracy.

A skin biopsy is the removal of skin tissue for examination under a microscope. The exact type of biopsy depends on how deep the lesion has penetrated the skin.

Shave biopsy uses a thin surgical blade to shave off the top layers of skin. The doctor may use this type of biopsy to diagnose basal cell cancer.
Punch biopsy uses a round, cookie-cutter-like tool. It is used to take a deeper sample skin.
Incisional and excisional biopsies remove tumors that have grown deep into the skin. An incisional biopsy cuts out part of the tumor. An excisional biopsy removes the entire tumor. These biopsies are used to diagnose melanoma.

All of the above-mentioned biopsies can be done using local anesthesia.

A lymph node biopsy helps the doctor determine whether cancer has spread to one or more lymph nodes.

A procedure called sentinel lymph node (SLN) biopsy is now recommended for cancers that are thicker than 1 millimeter and generally unnecessary for those thinner than 0.75 millimeter, unless they are ulcerated. Although some evidence suggests this procedure may improve survival, no clinical trials have proven to date that this procedure improves the outlook in persons with melanoma.

Sentinel node biopsy is a technique that helps determine if a cancer has spread. When a cancer has been detected, often the next step is to find the lymph node closest to the tumor site and retrieve it for analysis. The concept of the "sentinel" node, or the first node to drain the area of the cancer, allows a more accurate staging of the cancer, and leaves unaffected nodes behind to continue the important job of draining fluids. The procedure involves the injection of a dye (sometimes mildly radioactive) to pinpoint the lymph node which is closest to the cancer site. Sentinel node biopsy is used to stage many kinds of cancer, including melanoma.

This procedure involves the following:

A tiny amount of a tracer, either a radioactively labeled substance (radioisotope) or a blue dye, is injected into the tumor site.
These substances then flow through the lymph system into the sentinel node, the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed and biopsied.

The results of the biopsy can help doctors decide whether or not to remove other lymph nodes:

If the sentinel node and others shows signs of cancer then the nearby lymph nodes are removed.
If they do not, then the remainder of the lymph nodes will likely be cancer-free, and further surgery is not needed.

If melanoma has been diagnosed, the doctor will perform other tests to see if the cancer has spread, such as a chest x-ray.

Blood tests that show high levels of lactate dehydrogenase suggest that the cancer has spread. Blood tests to assess liver function and other factors to help determine specific sites where the cancer may appear.

Advanced imaging techniques, such as computed tomography (CT) or positron emission tomography (PET), may also be used. PET is particularly accurate. One study reported that PET was able to diagnose melanoma that had spread even when other tests, including CT, did not. PET can also be very accurate for identifying recurrent melanomas.

Biomarkers are specific substances that are linked to cancer. Blood tests to detect biomarkers may be used to identify microscopic cancers if sentinel node biopsy results are uncertain. Researchers are continually investigating other biomarkers that may indicate whether the cancer had spread or how severe it is, which would help determine whether treatments should be more or less aggressive.

A number of proteins and other factors detected in blood tests are showing promise as markers for microscopic metastasis. Examples include antibodies to MART-1, Melan-A, tyrosinase, and microphthalmia transcription factor (Mitf). Combinations of some of these factors may improve detection rates.

Staging

Staging is the process used to determine the size of the tumor and where and how far it has spread. When a cancer spreads, it’s said to have metastasized. Staging helps the health care team plan for appropriate treatment.

Basal cell cancer is rarely staged, because it doesn't usually spread to other organs. However, it may be staged if it's very, very large.
Squamous cell cancer may be staged in persons who have a high risk of the cancer spreading.
Melanoma is always staged.

Health professionals have come up with various methods for staging the cancer. This report uses the TNM staging system recommended by American Joint Committee on Cancer.

T = tumor. T is followed by a number to indicate thickness.
N = node. N is followed by numbers to indicate the number of lymph nodes involved.
M = metastasis. Metastasis is the spread of cancer to far away sites.

In addition a stage will include whether the melanoma is ulcerated or not, an indication of severity. Ulceration is determined if skin layers over the tumor appear indistinct under the microscope.

In general, the thicker the lesion and the farther the cancer has spread, the higher the assigned stage. The higher the stage, the worse the long-term outlook.

The earliest melanomas, which do not penetrate beneath the surface of the skin and are known as melanoma in situ, are highly curable and are called stage 0 or not given a stage.
Melanomas less than 4 mm thick suggest Stage I or II cancers, and the next step is to attempt to determine if they have spread or are likely to spread to the lymph nodes.
Melanomas that are over 4 mm thick indicated later stages. In such cases, the lymph nodes are sometimes removed to attempt to prevent the cancer from spreading, although about 70% of these melanomas have already spread.

Specific stages are as follows:

Stage I. Cure rates are excellent with surgical removal, since they are least likely to have spread.

Stage 1A. Tumor has not spread to the nodes. It is less than 1 mm and is not ulcerated.
Stage IB. Tumor has not spread to the nodes. It is less than 1 mm, but is ulcerated, or the tumor is between 1.01 and 2 mm but is not ulcerated.

Stage II. Melanomas can be cured, but the success rate lags behind that of Stage I because a small number of cancer cells may have spread to distant sites. In addition to surgery, other forms of therapy may be recommended.

Stage IIA. Tumor has not spread to the nodes. It is between 1.01 and 2 mm and is ulcerated, or it is 2.01 to 4 mm without ulceration.
Stage IIB. Tumor has not spread to the nodes. It is between 2.01 and 4 mm and is ulcerated or greater than 4 mm without ulceration.

Stage III. Survival rate is lower than earlier stages.

Stage IIIA. Tumor has spread to 1 node and it is up to 4 mm without ulceration. Sentinel biopsy has detected microscopic evidence of tumor cells in the node (micrometastasis).
Stage IIIB. Tumor is up to 4 mm without ulceration and has spread to one node or there is evidence of micrometastasis in two nodes.
Stage IIIC. Tumor is any thickness and ulceration may or may not be present. It has spread to 2 or 3 nodes. Additional "satellite" melanomas on the skin more than 2 cm (about an inch) from the original lesion may be present; these are sometimes called "metastases in transit."

Treatment for Melanoma

Treatment for melanoma depends on various factors, including:

The site of the original lesion
The stage of the cancer
The patient's age and general health

Treatment options include:

Surgery to remove the melanoma cancer cells
Chemotherapy
Immunotherapy
Radiation therapy
Palliative therapy

Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the diagnosis biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.

Mohs micrographic surgery is a technique used to remove very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.

The amount of tissue removed depends on the size, depth, and degree of invasion:

Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk of recurrence.
Thicker lesions require wider surgical cuts.

It used to be customary to remove a large area, regardless of the stage of cancer. This potentially disfiguring approach has been abandoned because studies have shown that excising wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.

Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond, removing them may reduce the chance of recurrence and help patients live longer.

Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible and prolong survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.

Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate residual cancer cells after standard surgery for lentigo maligna melanomas, an atypical form of melanoma that has a wide surface and is difficult to treat.

Recurrence rates are very high with lentigo maligna after conservative surgery. Although this is a very slowly progressive condition, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should discuss with their doctor carefully staged surgery to remove all diseased tissue with as little cosmetic harm as possible.

Chemotherapy is often used to treat recurrent or metastatic melanomas. This type of therapy is not intended as a cure but can prolong life and improve its quality.

Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.

Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones most often used.
Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some low-level activity against melanoma.

Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which works best.

Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction.
Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy may preserve fertility in some women.
Rarely, secondary cancers such as leukemia.
Problems in concentration, motor function, and memory, which may be long-term.

Treating Side Effects

Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs and most patients who take more powerful drugs.

Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and so requires fewer injections.

Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.

Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for metastasized or recurrent melanoma that occurs on the arm or leg. It does not appear to be useful for preventing metastasis after a first occurrence of melanoma in one of these locations.

This technique involves the following:

The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
Anticancer drugs are added to the blood in doses up to 10 times the standard doses.
The blood is then heated to enhance the drug's potency.
The chemo-infused blood is then sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
Adverse effects occur in less than 1% of cases and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.

In addition to arms and legs, perfusion techniques have been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.

Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain persons with melanoma.

Cytokines. Cytokines are small proteins that play an important role in the body's immune response. Certain cytokines called interferons are used as a therapy for metastatic melanoma. These medicines are usually given along with chemotherapy or other immunotherapies, or both.

A number of cytokines and combinations are being investigated. They include:

Interferon alpha-2b (Intron) is the only FDA approved immunotherapy for late stage melanoma. The most common side effects are fatigue, depression, and flu-like symptoms, which can be severe. Starting an antidepressant, such as paroxetine (Paxil), several weeks before interferon therapy may help prevent depression.
Pegylated interferon and natural human interferon are long-acting forms are under investigation. One study showed that low-dose natural interferon after chemotherapy increased the 5-year relapse-free survival rate.
Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with metastatic melanoma. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable and nearly always reversible.
Granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine, Sargramostim) is an injectable cytokine under study. The drug boosts production of immune cells in the blood and bone marrow. An inhaled form of the drug is being tested for melanoma that has spread to the lungs.
T-cell therapy uses white blood cells, called tumor-infiltrating lymphocytes (TIL), that taken from the patient. The cells are modified so they better fight cancer and are then reinjected back into the patient. T-cell therapy is showing promising results, especially for patients with advanced melanoma who have failed to respond to other treatments.

A chemical called histamine is a powerful inhibitor of reactive oxygen species, ROS, which may inactivate immune cells that fight cancer. Researchers are investigating to see if it can be used along with interleukin-2 cytokine therapy. In one study, the added benefits of histamine were modest except in patients with liver metastatic; in these patients, survival improved by 129 days, which was significant.

Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are uniquely expressed by melanoma cells.

Many therapeutic melanoma vaccines are in advanced stages of development, but none is approved for use in the United States.

There are two basic types of therapeutic vaccines:

Autologous vaccines
Allogenic vaccines

Sometimes a combination of the two are used. In this case, it's called a hybrid.

Autologous vaccines are made from the patient's own cancer cells. This produces a very specific immune response that can target the patient's cancer precisely. Oncophage (HSPPC-96) and M-Vax are autologous vaccines for melanoma that have shown promise in early clinical trials. One problem with the autologous approach is that there is no way to scientifically assess outcome or even guarantee repeated success since each vaccine is unique to the individual patient. This approach is also appropriate only for select patients.

Allogenic vaccines are made in a laboratory using cells from someone other than the patient. They may be made from proteins from tumor cells, genetic material, or even bacteria. One such vaccine is Canvaxin. Early studies showed this vaccine increased survival rates in some patients with Stage 3 melanoma. However, a later trial was halted because the vaccine did not appear to improve make such patients live any longer.

Vaccine immunotherapy requires the body to build up its own defenses. It can take months before beneficial effects occur, but when they do, tumor reduction is much more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.

Antisense Compounds. Antisense compounds can prevent defective cancer genes from being translated into proteins that cause abnormal cell proliferation.

Monoclonal Antibodies (MAb). Antibodies are natural substances produced by immune cells that home in and destroy cancer cells. Scientists are identifying specific antibodies that may attack melanoma cells and cloning them to create monoclonal antibodies. MAbs have shown promise for other cancers and are now being tested for melanoma, often in combination with vaccines and other forms of immunotherapy.

In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in some cases, however.

In some patients with tumors less than 3 cm deep, however, radiation may help slow down metastasis when combined with a super-heating process using microwaves.
Brachytherapy, in which radioactive seeds are implanted close to the tumor, has also been used with success for melanoma of the eye.
Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
Radiotherapy using a so-called gamma knife (very focused gamma radiation) is also effective for cancer that has metastasized to the brain, in some cases halting the growth and, in rare situations, even eliminating it.

The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgical removal of metastatic tumors may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.

Patients should ask their doctor's about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.

Tetracyclines. Chemically modified tetracyclines, a common antibiotic, have been shown to modify metalloproteinase, an enzyme in the skin that promotes skin cancers, including melanoma.

Anti-Angiogenesis Agents. An anti-angiogenesis drug is one that blocks the formation of new blood vessels. The growth of new blood vessels helps cancer cells grow and spread. The anti-angiogenesis drug thalidomide (Thalomid) is approved for treatment of melanoma but requires special prescribing precautions. This drug had gained notoriety in the 1960s because of devastating birth defects in the children of women who took it during pregnancy. Scientists are investigating drugs that are chemically similar to thalidomide but have fewer side effects.

Curcumin. The yellow spice found in turmeric and curry powders may contain cancer-fighting properties. In a preliminary laboratory study, curcumin stopped the growth of melanoma cells. It is far too early, however, to recommend curcumin for clinical use.

Treatment for Nonmelanoma Skin Cancer

A number of options are available for treating nonmelanoma skin cancer, including surgery, cryosurgery, phototherapy, radiation, and topical 5-fluorouracil.

For any skin cancer and for some keratoses that require removal, surgery is the first treatment. It is usually one of the following:

Excisional Surgery. This is the surgical removal of the cancerous lesion.

Curettage and Electrodesiccation. This procedure involves scraping away of the cancerous tissue followed by electric cauterization to stop the bleeding.

Mohs Micrographic Surgery. Mohs surgery is a meticulous procedure used for skin cancers at high risk for recurrence or becoming invasive. The technique removes very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete. A human skin substitute (Apligraf) is applied to the surgical area. It helps speed up wound healing to achieve a better cosmetic effect.

Good candidates for Mohs surgery include:

Persons with squamous cell cancer
Persons with basal cell cancer greater than 1 cm (about half an inch)
Persons with basal cell cancer on the face, ear, or neck
Young people with skin cancer

Mohs surgery saves more healthy tissue than other procedures and is highly effective. It results in a 99% cure rate for primary tumors and a 95% cure rate for recurrent ones. It can be safely performed in the doctor's office. Complications are uncommon but can include bleeding and infection.

Lasers. Laser surgery may be useful for certain basal cells and for keratoses that appear on the lips, although it is not clear whether lasers offer any advantages over other surgical treatments. Lasers do not appear to be very effective for thick or tough squamous cell cancers.

Cryosurgery removes skin cancer cells or actinic keratoses by freezing the affected tissue with liquid nitrogen. Studies have shown that cyrosurgery can be used to remove even wide areas of actinic keratoses and that it may be more successful over the long term than treatment with 5-fluorouracil, the standard drug. Cryosurgery also appears to reduce the risk for squamous cell cancer in these patients.

A head-to-head comparison of a freezing technique with Mohs micrographic surgery in patients with basal cell cancer reported similar recurrence rates with each approach. Over 85% of the patients with the freezing technique were satisfied with the appearance of the area afterwards. Five-year recurrence rates were only 2.1%.

Cryotherapy achieves good cosmetic results for many patients. However, it may cause blistering and ulceration, leading to pain and infection, as well as harmless, but undesirable, skin-color changes.

In unusual cases where the skin cancer may be in an inoperable position (such as the eyelid or the tip of the nose) or if cancer has recurred multiple times, radiation therapy may be indicated. Radiation is directed at the tumor. It may take 1 - 4 weeks with treatments performed several times a week. One technique being investigated for basal and squamous cell cancer uses radiation implants (brachytherapy) and custom-made molds to specifically target the radiation to the cancer site. Studies suggest that this treatment is very effective with few complications.

Topical phototherapy with the drug aminolevulinic acid (ALA) is a nonsurgical method that is proving to be a good choice for treating actinic keratoses and nonmelanoma skin cancers. The technique involves shining blue light onto the cancer area after that patient has taken ALA. ALA accumulates in the skin cells. When the cells are exposed to intense light, the chemical causes them to die. This approach allows precise targeting of one or more lesions, leaving healthy skin unaffected.

It does not penetrate deeper than the epidermis (the top layer of the skin), so it does not produce scarring or changes in skin color, as cryotherapy or other more invasive treatments do.

It can cause pain and irritation, including stinging, itching, and burning, but in one study only 3% of patients stopped using it for these reasons. In a 2002 study, the procedure was more painful for patients with actinic keratoses than for those with nonmelanoma skin cancers. It was also painful when large areas were affected, and men experienced more pain than women.

ALA Phototherapy for Actinic Keratoses. Phototherapy works best on flat lesions performed in two treatments, and is more effective for clearing lesions on the face than those on the scalp. Phototherapy can also treat multiple lesions at the same time instead of sequentially, as in cryotherapy. Studies suggest that it may work as well as cryotherapy and achieve better cosmetic results. (More patients report burning and itching with phototherapy, however.) Phototherapy is also equal to topical 5-fluorouracil in effectiveness and achieving a satisfactory appearance.

ALA Phototherapy for Nonmelanoma Skin Cancers. In patients with squamous cell cancer-in-situ and basal cell cancer, phototherapy has been equal to cryotherapy, with superior healing and appearance afterward. A 2003 study reported that it was more effective than topical 5-fluorouracil for patients with Bowen's disease, and there were fewer side effects.

Some studies have shown that about 10% of patients using phototherapy have a recurrence within 1 year. These recurrence rates are higher than with surgery and other standard treatments. Longer-term studies are required before ALA phototherapy can be recommended for most patients with nonmelanoma skin cancers.

Chemical peeling, or exfoliation, is useful for solar keratoses on the face, especially in people with fair, dry skin. Alpha-hydroxy acids, for example, are being investigated for keratoses. Dermabrasion, which "sands" the skin, may also be effective, although scarring is possible. A 2002 study found laser resurfacing to treat severe sun damage on the face; however, it may not prevent nonmelanoma skin cancers.

A number of medications are being used for keratoses and some may be helpful for skin cancers as well. Besides cryotherapy, 5-fluorouracil is the other most commonly used treatment for actinic keratoses. Other medications are also available.


Medication	Skin Conditions Affected	Oral or Topical		Comments
5-Fluorouracil	Actinic keratoses, Bowen's disease and small nonmelanoma skin cancers.		Topical cream (Efudex, Fluoroplex) or injected gel containing 5-FU and epinephrine (AccuSite).	5-Fluorouracil (5-FU) removes actinic keratoses and is useful for some patients with a large number of lesions. It requires twice daily application for 3 - 4 weeks. It can cause significant redness, irritation, swelling, and crusting, which takes 2 - 4 weeks to heal. Newer preparations are reducing these side effects. It is still unclear if this medication protects against recurrent keratoses or future skin cancer. Of concern is the possibility that (5-FU) will clear the top of a skin cancer and obscure the rest of the cancer that lies beneath the surface of the skin. A 10-year 2003 study of patients with Bowen's disease reported that 5-FU was safe and effective, with only 2 out of 26 cancers recurring.
Diclofenac and hyaluronan (Solaraze)	Actinic keratoses (approved). Investigated for basal cell.		Topical gel applied twice a day.	Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). When used to treat actinic keratoses, it is delivered to the skin with hyaluronan, a water-seeking molecule that helps maintain skin tension. It has modest effects and when healing occurs, it may not be evident for at least a month after treatment ends. However, it causes less irritation than 5-FU and may be useful for some people.
Imiquimod (Aldara)	FDA approved for the treatment of superficial basal cell cancer. Previously approved for treating actinic keratoses. Investigated for Bowen's disease and squamous cell cancer.		Imiquimod is a topical cream.	Imiquimod triggers the production of immune factors that help fight cell proliferation. Aldara should be used only when surgery for basal cell cancer is inappropriate. It is not approved for use on the face.
Alpha-Interferons	Basal cell cancer, squamous cell cancer.		Require injections administered three times a week.	Interferons are immune factors that are being used to treat a number of serious conditions. Alpha-interferon injections may be effective against skin cancers that are hard to treat using conventional surgical measures. Cosmetic results reported to be good or very good by 83% of patients.

Prognosis

Virtually all basal and squamous type skin cancers can be cured if treated early.

The outlook for melanoma depends on when it is diagnosed.

If melanoma is detected in its earliest form, the 5-year survival rate is 99%. Other localized forms of melanoma have very favorable outlooks.

If the cancer is found after the melanoma has spread, the 5-year survival rate drops.

If melanoma spreads to nearby areas (regional metastatic), the rate is 65%.
If melanoma has spread to distant areas of the body, the survival rate is 15%.

In general, after patients are treated for melanoma, the longer they remain free of cancer recurrence following treatment the better the chance of remaining disease-free. However, relapses are not uncommon in those whose initial melanoma was large.

Anyone who has recovered from melanoma should be especially strict about adhering to preventive guidelines and remain vigilant for suspicious lesions, since the risk for developing a new melanoma is increased even if the first one was successfully cured. Such relapses may occur years after the original diagnosis.

Resources

www.aad.org -- American Academy of Dermatology
www.cancer.org -- American Cancer Society
www.asds.net -- American Society for Dermatologic Surgery
www.mpip.org -- Melanoma Patients' Information Page
www.cancer.gov -- National Cancer Institute
www.nccn.org -- National Comprehensive Cancer Network
www.skincancer.org -- The Skin Cancer Foundation
www.epa.gov/sunwise/uvindex.html -- UV index information

References

Ambros-Rudolph CM, Hofmann-Wellenhof R, Richtig E, et al. Malignant melanoma in marathon runners. Arch Dermatol. 2006;142:1471-1474.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, GA: American Cancer Society; 2007.

Chemotherapy for Inoperable Liver Metastases from Ocular Melanoma. NCI Cancer Bulletin. November 30, 2004;1(46):7.

Dale KM, Coleman CI, Henyan NN et al. Statins and Cancer Risk: A Meta-Analysis. JAMA. 2006;295:74-80.

Delavalle RP. Melanoma chemoprevention. Program presented at: Annual meeting of the American Academy of Dermatology. March 3, 2006; San Diego, CA.

Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005;23(10):2346-2357.

Early Detection and Surgery for Melanoma in Lymph Nodes May Increase Survival. NCI Cancer Bulletin. May 17, 2005;2(20):2.

Freeman SR, Drake AL, Heilig LF, et al. Statins, Fibrates, and Melanoma Risk: a Systematic Review and Meta-analysis. J Natl Cancer Inst. 2006;98:1538-46.

Gallagher RP, Spinelli JJ, Lee TK. Tanning beds, sunlamps, and risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2005;14(3):562-566.

Lautenschlager S, Wulf HC, Pittelkow MR. Photoprotection. The Lancet [early online publication]. May 3, 2007.

Lebwohl M. Cutaneous oncology. Program presented at: Annual meeting of the American Academy of Dermatology; March 7, 2006; San Diego, CA.

Michna L, Wagner GC, Lou YR, XE JG, Peng QY, Lin Y, Carlson K, Shih WJ, Conney AH, Lu XP. Inhibitory effects of voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis. May 2006.

Pennie M, Soon S, Risser J, et al. Melanoma outcomes for medicare patients. Arch Dermatol. 2007; 143:488-494.

Response to Immunotherapy for Melanoma Tied to Autoimmunity. NCI Cancer Bulletin. February 21, 2006;3(: 4.

Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. 2005;104(4):879-890.

Treatment for Metastatic Ocular Melanoma. NCI Cancer Bulletin. March 7, 2006;3(10):8.

Veierod MB, Weiderpass E, Thorn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst. 2003;95(20):1530-1538.

Weinstock MA. Cutaneous melanoma: public health approach to early detection. Dermatologic Therapy. 2006;19(1):26-31.

Review Date:
6/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Scoliosis

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prognosis
Symptoms
Diagnosis
Treatment
Managing Scoliosis
Braces
Surgery
Treatment for Adult Scolios...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Diagnosing Scoliosis

Scoliosis is diagnosed typically in children 10 - 15 years of age. However, only about 1% of cases actually require treatment. There is a large female preponderance for larger curves that do require treatment.

Defining Scoliosis

Nonstructural scoliosis is a simple side-to-side curve of the spine. Structural scoliosis adds to that simple curve a rotation of the vertebrae, resulting in a twisting of the spine.

Causes

In about 80% of scoliosis cases, the cause is unknown (idiopathic scoliosis). Research has not been able to identify any genetic abnormality that would make a person susceptible to developing scoliosis.

Treatment with Bracing

Bracing has long been the standard treatment to prevent progression of the curvature of scoliosis. However, patient compliance has been a problem, especially for younger patients. Newer braces are now more comfortable and can be worn discretely under the clothing, thus improving patient compliance and treatment results.

Introduction

Scoliosis is the abnormal curvature of the spine. While the normal spine has gentle natural curves that round the shoulders and make the lower back curve inward, scoliosis typically involves a three-dimensional deformity of the spinal column and rib cage. To varying degrees, the spine curves from side-to-side, and some of the spinal bones may rotate slightly, making the hips or shoulders appear uneven. It may develop in the following way:

As a single primary side-to-side curve (resembling the letter C), or
As two curves (a primary curve along with a compensating secondary curve that forms an S shape).

Scoliosis most commonly develops in the area between the upper back (the thoracic area) and lower back (lumbar area). It may also occur only in the upper or lower back. The doctor attempts to define scoliosis by the following characteristics:

The shape of the curve
Its location
Its direction
Its magnitude
Its causes, if possible

Click the icon to see an image of scoliosis.

The severity of scoliosis is determined by the extent of the spinal curvature and the angle of the trunk rotation (ATR) and is usually measured in degrees. Curves of less than 20 degrees are considered mild and account for 80% of scoliosis cases. Curves that progress beyond 20% require medical attention. Such attention, however, usually involves periodic monitoring to make sure the condition is not becoming worse.

Scoliosis affects about 2 - 3% of the population (about 6 million people in the United States). It can occur in adults but is more commonly diagnosed for the first time in children aged 10 - 15 years. About 10% of the adolescent population has some degree of scoliosis, but less than 1% develops scoliosis that requires treatment. The condition also tends to run in families. Among persons with relatives that have scoliosis, about 20% develop the condition.

Among adults, previous reports have indicated a prevalence of scoliosis of up to 32%. But a recent study of 75 healthy adults aged 60 years and older with no known history of scoliosis or prior spine surgery suggested a rate of 68%. However, scoliosis was not linked to physical or social impairment in this population.

Scoliosis is often categorized by the shape of the curve, usually as either structural or nonstructural.

Structural scoliosis. In addition to the spine curving from side to side, the vertebrae rotate, twisting the spine. As it twists, one side of the rib cage is pushed outward so that the spaces between the ribs widen and the shoulder blade protrudes (producing the rib-cage deformity, or hump). The other half of the rib cage is twisted inward, compressing the ribs.
Nonstructural scoliosis. The curve does not twist but is a simple side-to-side curve.

Other abnormalities of the spine that may occur alone or in combination with scoliosis include hyperkyphosis (an abnormal exaggeration in the backward rounding of the upper spine) and hyperlordosis (an exaggerated forward curving of the lower spine, also called swayback).

Click the icon to see an image of kyphosis.

The location of a structural curve is defined by the location of the apical vertebra. This is bone at the highest point (the apex) in the spinal hump. This particular vertebra also undergoes the most severe rotation during the disease process.

The direction of the curve in structural scoliosis is determined by whether the convex (rounded) side of the curve bends to the right or left. For example, a doctor will diagnose a patient as having right thoracic scoliosis if the apical vertebra is in the thoracic (upper back) region of the spine, and the curve bends to the right.

The magnitude of the curve is determined by taking measurements of the length and angle of the curve on an x-ray view.

Vertebrae. The spine is a column of small bones, or vertebrae, that support the entire upper body. The column is grouped into three sections of vertebrae:

Cervical (C) vertebrae are the 7 spinal bones that support the neck.
Thoracic (T) vertebrae are the 12 spinal bones that connect to the rib cage.
Lumbar (L) vertebrae are the 5 lowest and largest bones of the spinal column. Most of the body's weight and stress falls on the lumbar vertebrae.

Each vertebra can be designated by using a letter and number; the letter reflects the region (C=cervical, T=thoracic, and L=lumbar), and the number signifies its location within that region. For example, C4 is the fourth bone down in the cervical region, and T8 is the eighth thoracic vertebra.

Below the lumbar region is the sacrum, a shield-shaped bony structure that connects with the pelvis at the sacroiliac joints. At the end of the sacrum are 2 - 4 tiny, partially fused vertebrae known as the coccyx or "tail bone."

The Spinal Column and its Curves. Altogether, the vertebrae form the spinal column. In the upper trunk the column normally has a gentle outward curve (kyphosis) while the lower back has a reverse inward curve (lordosis).

The Disks. Vertebrae in the spinal column are separated from each other by small cushions of cartilage known as intervertebral disks. Inside each disk is a jelly-like substance called the nucleus pulposus, which is surrounded by a tough, fibrous ring called the annulus fibrosis. The disk is 80% water. This structure makes the disk both elastic and strong. The disks have no blood supply of their own, relying instead on nearby blood vessels to keep them nourished.

Processes. Each vertebra in the spine has a number of bony projections, known as processes. The spinal and transverse processes attach to the muscles in the back and act like little levers, allowing the spine to twist or bend. The particular processes form the joints between the vertebrae themselves, meeting together and interlocking at the zygapophysial joints (more commonly known as facet or z joints).

Spinal Canal. Each vertebra and its processes surround and protect an arch-shaped central opening. These arches, aligned to run down the spine, form the spinal canal, which encloses the spinal cord, the central trunk of nerves that connects the brain with the rest of the body.

Click the icon to see an image of the spine.

Click the icon to see an image of the sacrum.

Click the icon to see an image of the curves of the spine.

Click the icon to see an image of an intervertebral disk.

Click the icon to see an image of the spinal canal.

Causes

In 80% of patients, the cause of scoliosis is unknown. Such cases are called idiopathic scoliosis. (Idiopathic means without a known cause.) Idiopathic scoliosis may be due to multiple, poorly understood inherited factors, most likely from the mother's side. However, the severity often varies widely among family members who have the condition, suggesting that other factors must be present.

Researchers have not been able to identify the specific genetic abnormalities that make a young person susceptible to spinal distortion. Inherited physical abnormalities, problems in coordination, abnormalities in the central nervous system, and other inherited factors may play some role either alone or in combination with other conditions to produce scoliosis.

Physical Abnormalities. Researchers are investigating possible physical abnormalities that may cause imbalances in bones or muscles that would lead to scoliosis. Among them are the following:

Imbalances in Muscles around the Vertebrae. Some research suggests that imbalances in the muscles around the vertebrae may make children susceptible to spinal distortions as they grow.
High Arches. One study showed a higher incidence of abnormally high arches in the feet in people with idiopathic scoliosis, suggesting that altered balance may be a factor in certain cases.

Problems in Coordination. Some experts are looking at inherited defects in perception or coordination that may cause asymmetrical growth in the spine of some children with scoliosis.

Genetic Abnormalities in the Central Nervous System. Genetic defects that cause altered processing in the brain may play a role in producing abnormalities in the growing spine. For example, research has implicated low levels of melatonin, a hormone secreted in the pineal gland in brain. Melatonin is involved with sleep and growth. Researchers speculate that genetic factors that cause reduced blood levels of melatonin may adversely affect muscle tone and development during sleep, perhaps contributing to scoliosis.

Other Biologic Factors. Several other biologic factors are being investigated for some contribution to scoliosis:

Abnormalities in collagen, the critical structural protein found in muscles and bones. Enzymes known as matrix metalloproteinases are involved in the repair and remodeling of collagen. Researchers have found high levels of the enzymes in the disks of patients with scoliosis, which suggests that the enzymes may contribute to curve progression. Elevated levels of the enzymes can cause abnormalities in components in the spinal disks, contributing to disk degeneration.
A possible defective gene responsible for production of fibrillin, an important component of connective tissue, which makes up bones and muscles.
Abnormalities in a protein called platelet calmodulin that binds to calcium. This protein acts like a tiny muscle and pulls clots together. Measuring levels of this protein may eventually help predict whether scoliosis will worsen.

Congenital scoliosis is caused by inborn spinal deformities that may result in the development of absent or fused vertebrae. Kidney problems, particularly having only one kidney, often coincide with congenital scoliosis. The condition usually becomes evident at either age 2 or between ages 8 and 13 as the spine begins to grow more quickly, putting additional stress on the abnormal vertebrae. It is essential to diagnose and monitor such curvatures as early as possible, since they can progress quickly. Early surgical treatment -- before age 5 -- may be important in many of these patients to prevent serious complications.

Adult scoliosis has two primary causes:

Progression of childhood scoliosis.
Degenerative lumbar scoliosis. Degenerative lumbar scoliosis is a condition that typically develops after age 50. With this condition, the lower spine is affected, usually due to disk degeneration. Osteoporosis, a serious problem in many older adults, is not a risk factor for new-onset scoliosis, but it can be a contributing factor. In most cases, however, it is not known why scoliosis occurs in adults.

Scoliosis may be a result of various conditions that affect bones and muscles associated with the spinal column. They include the following:

Muscle paralysis.
Muscle deterioration from diseases such as muscular dystrophy, polio, or cerebral palsy.
Injury to the spinal cord.
Tumors, growths, or other small abnormalities on the spinal column. For example, syringomyelia, a disorder in which cysts form along the spine, can cause scoliosis. These spinal abnormalities may play a larger role in causing some cases of scoliosis than previously thought.
Familial dysautonomia, a rare disorder in Jewish children of Ashkenazi descent. (Only about 500 cases have been reported.)
Stress fractures and hormonal abnormalities that affect bone growth in young, competitive athletes.
Birth defects, including spina bifida (an open spinal cord) and myelomeningocele (a hernia of the central nervous system).
Turner syndrome, a genetic disease in females that affects physical and reproductive development.
Other diseases that can cause scoliosis are Marfan syndrome, Aicardi syndrome, Friedreich ataxia, Albers-Schonberg disease, rheumatoid arthritis, Cushing syndrome, and osteogenesis imperfecta.

Spina bifida is a congenital disorder (birth defect) in which the backbone and spinal canal do not close before birth. In severe cases, this can result in the spinal cord and its covering membranes protruding out of an affected infant's back. Spina bifida may also be nearly inconsequential, or may be repairable through surgery.

Nonstructural scoliosis is usually not a serious problem, since the curve is side to side. It can develop from a number of physical problems, including the following:

Unequal leg length. Injury, a shortened Achilles tendon, or other structural in-born problems can cause this very common condition. Unequal leg length rarely causes any problems and in most cases requires no treatment other than a lift in one of the shoes to equalize the length.
Muscle spasms.

Risk Factors

Risk Factors for Initial Scoliosis. Idiopathic scoliosis, the most common form, occurs most often during the growth spurt right before and during adolescence. (Between 12 - 21% of idiopathic cases occur in children ages 3 - 10 years, and less than 1% in infants.) Mild curvature (under 20 degrees) occurs about equally in girls and boys, but curve progression is 10 times more likely to occur in girls. Being taller than average at earlier ages may put some girls at risk, but other factors must be present to produce scoliosis. A risk factor that affects females is a delayed onset of menstruation, which can prolong the growth spurt period, thus increasing the possibility for the development of scoliosis.

Risk Factors for Curvature Progression. Once scoliosis is diagnosed, it is very difficult to predict who is at highest risk for curve progression. About 2 - 4% of all adolescents develop curvature of 10 degrees or more, but only about 0.3 - 0.5% of teenagers have curves greater than 20 degrees, which requires some medical attention.

People with certain medical conditions that affect the joints and muscles are at higher risk for scoliosis. These conditions include rheumatoid arthritis, muscular dystrophy, polio, and cerebral palsy. Children who receive organ transplants (kidney, liver, heart) are also at increased risk.

In one study, idiopathic scoliosis occurred in about 5% of close family members of children with the condition.

Scoliosis may be evident in young athletes, with a prevalence of 2 - 24%. The highest rates are observed among dancers, gymnasts, and swimmers. The scoliosis may have been due in part to loosening of the joints, delay in puberty onset (which can lead to weakened bones), and stresses on the growing spine. There have also been other isolated reports of a higher risk for scoliosis in young athletes who engage vigorously in sports that put an uneven load on the spine. These include figure skating, dance, tennis, skiing, and javelin throwing, among other sports. In most cases, the scoliosis is minor, and everyday sports do not lead to scoliosis. Exercise has many benefits for people both young and old and may even help patients with scoliosis.

Prognosis

In general, the severity of the scoliosis depends on the degree of the curvature and whether it threatens vital organs, specifically the lungs and heart.

Mild Scoliosis (less than 20 degrees). Mild scoliosis is not serious and requires no treatment other than monitoring.
Moderate Scoliosis (between 25 and 70 degrees). It is still not clear whether untreated moderate scoliosis causes significant health problems later on. Some studies have found no difference in either back pain or survival rates in adult untreated patients versus the general population. In one study, adults with moderate scoliosis had normal lung function, although they had difficulty exercising. (This low exercise tolerance might have been because many patients with scoliosis do not engage in regular physical activity.)
Severe Scoliosis (over 70 degrees). If the curvature exceeds 70 degrees, the severe twisting of the spine that occurs in structural scoliosis can cause the ribs to press against the lungs, restrict breathing, and reduce oxygen levels. The distortions may also affect the heart and possibly cause dangerous changes.
Very Severe Scoliosis (Over 100 degrees). Eventually, if the curve reaches over 100 degrees, both the lungs and heart can be injured. Patients with this degree of severity are susceptible to lung infections and pneumonia. Curves greater than 100 degrees increase mortality rates, but this problem is very uncommon in America.

Some experts argue that simply measuring the degree of the curve may not identify patients in the moderate and severe groups who are at greatest risk for lung problems. Other factors (spinal flexibility, the extent of asymmetry between the ribs and the vertebrae) may be more important in predicting severity in this group.

Scoliosis is associated with osteopenia, a condition characterized by loss of bone mass. About 27 - 38% of adolescent girls who have scoliosis also have osteopenia. Some experts recommend measuring bone mineral density when a patient is diagnosed with scoliosis. The amount of bone loss may help predict how severely the spine will curve. Preventing and treating osteopenia may help limit further curve progression.

If not treated, osteopenia can later develop into osteoporosis. Osteoporosis is a more serious loss of bone density that is common among postmenopausal women. Adolescents who have scoliosis are at increased risk of developing osteoporosis later in life. [See In-Depth Report#18: Osteoporosis.]

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

After 20 years or more, scoliosis patients who were previously treated with surgery experience small but significant physical impairment, (mainly mild back problems), compared to their peers without scoliosis. In one study, 65% of patients reported some low back pain compared to 47% of people without a history of scoliosis. In general it was mild, although 45% of patients reported having to take days off from work compared to 19% of nonscolosis patients. In another study, only 1.5% of the scoliosis group had severe debilitating back pain. In general, the quality of life was similar, however. Pain also did not play a major role in social limitations.

The following are some possible causes of later back problems in people with a history of treated scoliosis:

Spinal fusion disease. Patients who are surgically treated with fusion techniques lose flexibility and may experience weakness in back muscles due to injuries during surgery.
Disk degeneration and low back pain. With disk degeneration, the disks between the vertebrae may become weakened and rupture. In some patients, years after the original surgeries, particularly with the first generation of the Harrington rods, the weight of the instrumentation can cause disk and joint degeneration severe enough to require surgery. Treatment may involve removal of the old instrumentation and extension of the fusion into the lower back. Still, most patients do not experience significant back pain from these problems.
Height loss.
Scarred regions. Pain can occur from old scars in the incision areas.
Lumbar flatback. This condition is most often the result of a scoliosis surgical procedure called the Harrington technique, which eliminated lordosis (the inward curve in the lower back). Adult patients with flatback syndrome tend to stoop forward. They may experience fatigue and back and even neck pain.
Rotational trunk shift (uneven shoulders and hips).

Evidence suggests that previous treatment with braces may also cause mild back pain and more days off, but problems appear to be less than with surgery. In one study, dysfunction was comparable to people without a history of scoliosis.

Pain in adult-onset or untreated childhood scoliosis often develops because of posture problems that cause uneven stresses on the back, hips, shoulders, necks, and legs. In one study conducted 20 years after growth had stopped, two-thirds of adults who had lived with curvatures of 20 - 55 degrees reported they experienced back pain. Other studies have reported that adults with a history of scoliosis tend to have chronic and more back pain than the general population.

Nearly all individuals with untreated scoliosis at some point develop spondylosis, an arthritic condition in the spine. The joints become inflamed, the cartilage that cushions the disks may thin, and bone spurs may develop. If the disk degenerates or the curvature progresses to the point that the spinal vertebrae begin pressing on the nerves, pain can be very severe and may require surgery. Even surgically treated patients are at risk for spondylosis if inflammation occurs in vertebrae around the fusion site.

Emotional Impact in Childhood. The emotional impact of scoliosis, particularly on young girls or boys during their most vulnerable years, should not be underestimated. Adults who have had scoliosis and its treatments often recall significant social isolation and physical pain. Follow-up studies of children who had scoliosis without having strong family and professional support often report significant behavioral problems. Fortunately, current treatments are solving many of the problems that previous generations had to deal with, including unsightly bracing and extremely painful surgeries with little pain control.

Emotional Effects in Adults. Of some concern are growing numbers of adults with scoliosis. This group experiences considerable problems in general health, social functioning, emotional and mental health, as well as pain.

Older people with a history of treated scoliosis may carry negative emotional events into adulthood that have their roots in their early experiences with scoliosis. Many studies have reported that patients who were treated for scoliosis have limited social activities and a poorer body image in adulthood. Some patients with a history of scoliosis have reported a slight negative effect on their sexual life. Pain appears to be only a minor reason for such limitation.

Women who have been successfully treated for scoliosis have only minor or no additional risks at all for complications during pregnancy and delivery. A history of scoliosis also does not endanger the child. Pregnancy itself, even multiple pregnancies, does not increase the risk for curve progression. Women who have severe scoliosis that restricts the lungs, however, should be monitored closely.

Some evidence suggests a slightly higher risk for breast cancer and leukemia in patients who had multiple x-rays. Risks are highest in patients who had the largest radiation exposure, such as those who had been surgically treated.

Patients who simply received x-ray series for untreated idiopathic scoliosis or scoliosis caused by uneven length legs or hip abnormalities have a very low risk for future complications.

Click the icon to see an image of an x-ray.

Symptoms

Scoliosis is usually painless. The curvature itself may often be too subtle to be noticed, even by observant parents. Some parents may notice abnormal posture in their growing child that includes:

A tilted head that does not line up over the hips
A protruding shoulder blade
One hip or shoulder that is higher than the other, causing an uneven hem or shirt line
An uneven neckline
Leaning more to one side than the other
In developing girls, breasts appearing to be of unequal size
One side of the upper back being higher than the other when the child bends over, knees together, with the arms dangling down

Scoliosis may be suspected when one shoulder appears to be higher than the other, there is a curvature in the spine, or the pelvis appears to be tilted. The treatment of scoliosis can involve the use of a brace or surgery. Treatment is determined by the cause of the scoliosis, the size and location of the curve, and the stage of bone growth of the patient.

With more advanced scoliosis, fatigue may occur after prolonged sitting or standing. Scoliosis caused by muscle spasms or growths on the spine can sometimes cause pain. Nearly always, however, mild scoliosis produces no symptoms, and the condition is usually detected by the pediatrician or during a school screening test.

Diagnosis

The severity of scoliosis and need for treatment is usually determined by two factors:

The extent of the spinal curvature. (Scoliosis is diagnosed when the curve measures 11 degrees or more.)
The angle of the trunk rotation (ATR).

Both are measured in degrees. These two factors are usually related. For example, a person with a spinal curve of 20 degrees will usually have a trunk rotation (ATR) of 5 degrees. These two measurements, in fact, used to be the cutoff for recommending treatment. However, the great majority of 20-degree curves do not get worse. Patients do not usually need medical attention until the curve reaches 30 degrees, and the ATR is 7 degrees.

Adam's Forward Bend Test. The screening test used most often in schools and in the offices of pediatricians and primary care doctors is called the Adam's forward bend test.

The child bends forward dangling the arms, with the feet together and knees straight. The curve of structural scoliosis is more apparent when bending over. In a child with scoliosis, the examiner may observe an imbalanced rib cage, with one side being higher than the other, or other deformities.

The forward bend test is used most often in schools and doctor's offices to screen for scoliosis. During the test, the child bends forward with the feet together and knees straight while dangling the arms. Any imbalances in the rib cage or other deformities along the back could be a sign of scoliosis.

The forward bend test, however, is not sensitive to abnormalities in the lower back, a very common site for scoliosis. Because the test misses about 15% of scoliosis cases, many experts do not recommend it as the sole method for screening for scoliosis.

Other Physical Tests.

The patient walks on the toes, then the heels, and then jumps up and down on one foot. Such activities indicate leg strength and balance.
The doctor will check leg length and look for tight tendons in the back of the leg, which may cause an uneven leg length or other back problems.
The doctor will also check for neurologic impairment by testing reflexes, nerve sensation, and muscle function.

Proper diagnosis is important. A misjudgment can lead to unnecessary x-rays and stressful treatments in children not actually at risk for progression. Unfortunately, although measurements of curves and rotation are useful, no test exists yet to determine whether a curve will progress.

Inclinometer (Scoliometer). An inclinometer, also known as a Scoliometer, measures distortions of the torso. The procedure is as follows:

The patient bends over, arms dangling and palms pressed together, until a curve can be observed in the upper back (thoracic area).
The Scoliometer is placed on the back and measures the apex (the highest point) of the upper back curve.
The patient continues bending until the curve can be seen in the lower back (lumbar area). The apex of this curve is also measured.
Measurements are repeated twice, with the patient returning to a standing position between repetitions.
If results show a deformity, x-rays probably need to be performed to determine the extent.

Some experts believe the Scoliometer would make a useful device for widespread screening. Scoliometers, however, indicate rib cage distortions in more than half of children who turn out to have very minor or no sideways curves. They are therefore not accurate enough to guide treatment.

Currently, x-rays are the most cost-effective method for diagnosing scoliosis. Experts hope that accurate, noninvasive diagnostic techniques will eventually be developed to replace some of the x-rays used to monitor the progression of scoliosis. To date, imaging techniques under investigation appear to be fairly accurate for detecting scoliosis in the upper back (the thoracic region), but not scoliosis in the lower back (the lumbar region).

X-Rays. If screening indicates scoliosis, the child may be sent to a specialist who takes an initial x-ray and monitors the child every few months using repeated x-rays. X-rays are essential for an accurate diagnosis of scoliosis in that they:

Reveal the degree and severity of scoliosis.
Identify any other spinal abnormalities, including kyphosis (hunchback) and hyperlordosis (swayback).
Help the doctor determine whether skeletal growth has reached maturity.
X-rays taken when patients are bending forward can also help differentiate between structural and nonstructural scoliosis. Structural curves persist when a person bends over, and nonstructural curves tend to disappear. (Muscle spasms or spinal growths may sometimes cause nonstructural scoliosis that shows a curve on bending.)
Children and young adolescents who have mild curves and in older adolescents who have more severe curvatures but whose growth has stopped or slowed need x-rays every few months to detect increasing severity. Young people who are diagnosed with scoliosis should keep their x-rays indefinitely in case they develop back problems later in adulthood and need to be re-examined.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is an advanced imaging procedure that does not use radiation, as x-rays do. It is expensive, however, and not generally used for an initial diagnosis. MRI can, nevertheless, identify spinal cord and brain stem abnormalities, which some studies indicate may be more prevalent than previously believed in children with idiopathic scoliosis. It also may be particularly useful before surgery for detecting defects that could lead to potential complications.

Click the icon to see an image of a MRI scan.

Because frequent x-rays may be required for young children with scoliosis, parents should be sure that x-ray technicians take all necessary protective measures. Experts are concerned about the long-term effects of radiation on sensitive young organs, particularly about a possible increase in the risk for cancer. Studies have reported an increased risk for cancer in women and men who, because of scoliosis, had been exposed to diagnostic x-rays in their childhood and adolescence.

X-ray techniques have become safer in recent years, and technicians can reduce the hazards with the following simple measures:

Directing x-ray beams through the patient from back to front, rather than the reverse.
Using x-ray filters that absorb some of the beam.
Using fast film to reduce exposure by two to six times.
Placing lead aprons or shields over parts of the body that are not being x-rayed.

There are various methods for determining and classifying the extent of the curve.

Cobb Method. The technique known as the Cobb method nearly always calculates the degree of the curve.

On an x-ray of the spine, the examiner draws two lines: One line extends out and up from the edge of the top vertebrae of the curve. The second line extends out and down from the bottom vertebrae.
The technician then draws a perpendicular line between the two lines.
Measuring the intersecting angle determines the degree of curvature.

The Cobb method is limited because it cannot fully determine the flexibility or the three-dimensional aspect of the spine. It is not as effective, then, in defining spinal rotation or kyphosis. It also tends to over-estimate the curve. Other diagnostic tools are needed then to make a more accurate diagnosis.

Classifying the Curve.Classification of the curve allows the doctor to identify patterns that can help determine treatments, particularly specific surgical techniques. The following are examples:

King Classification. The King classification classifies scoliotic curves as one of five patterns, which can help determine surgical treatments. It has limitations, however, and is not very useful for advanced surgical techniques.
Lenke Classification. Lenke classification takes more features of the curve into consideration and is proving to be more reliable. This includes six curve patterns plus additional factors that modify each of these curves.

Three-Dimensional Modeling Techniques. Advanced computer modeling techniques are able to create three dimensional images using x-rays or other two-dimensional images. They allow doctors to observe the spinal distortions and eventually could reduce the number of x-rays currently needed to monitor scoliosis and help surgeons determine optimal surgical procedures.

Even if the curve is accurately calculated, it still remains difficult to predict whether the scoliosis will progress. A recent report indicates that measuring the nerve conduction activity of the muscles supporting the spine may help predict subsequent progression in children with scoliosis. In addition, computer models are being used to better predict risk. One approach requires measuring 21 radiographic and clinical indicators and entering them into a computer program. The technique takes less than 20 minutes per patient, and studies found it to be up to 80% accurate in determining progression of curvature.

One way of predicting whether or not the curvature will progress is knowing when the child will stop growing:

If the child has years to grow, then the spine has more time to progress.
If the child will stop growing within a year, then progression should be very slight. (However, some progression continues in nearly 70% of curves even after the spine has matured.)

Knowing the child's age is, of course, the first step in estimating the end of growth. In addition, other methods can help predict the end of the growth stage. One method is called the Risser sign, which grades the amount of bone in the area at the top of the hipbone. A low grade indicates that the skeleton still has considerable growth; a high grade means that the child has nearly stopped growing and the curve is unlikely to progress much further. The Risser scale differs between genders, and, in boys, a high grade does not always signify the end of progression.

Screening programs for scoliosis, which began in the 1940s, are now mandatory in middle or high schools in many states, but there is considerable debate over whether screening should be routine.

Arguments Against Routine Screening. The U.S. Preventive Services Task Force does not recommend routine screening to detect adolescent scoliosis for the following reasons:

Screening tests are not accurate and depend too much on the skill of the examiner.
Schools often refer children with minor curves who are not at any risk for a progressive or serious condition to doctors, and such over-referrals add considerably to the costs of the health system. In one major study, 94% of the children referred to a doctor by the school did not require treatment. (Over 2,000 children were screened in order to find only 5 children who did need treatment.)
A long-term study of untreated patients with late-onset scoliosis indicates that these patients are productive and functional at a high level at 50-year follow-up. Patients with scoliosis have no greater danger for significant lung problems than the general population until their curves reach 60 - 100 degrees, making early screening unnecessary.

Experts against screening argue that such programs result in early treatments that either will not prevent curve progression and surgery or are unnecessary in the first place since curvatures often do not progress at all.

Arguments for Routine Screening. The American Academy of Orthopaedic Surgeons recommends that girls be screened twice, at ages 10 and 12, and that boys be screened once, at 13 or 14. The American Academy of Pediatrics recommends, however, scoliosis screening at ages 10, 12, 14, and 16 years. (In one study, over 40% of high school sophomores with newly diagnosed scoliosis had shown no signs of the disorder in earlier screening tests.) Other experts make the following arguments for universal screening:

Universal screening is useful for producing information on scoliosis that may eventually lead to knowledge of its cause and ways to prevent it.
Braces have proven to be effective, and early treatment can be important.
Without screening, the chances are slim that children with scoliosis will be diagnosed at an early stage if parents rely only on examinations by a family doctor or pediatrician. Such doctors often do not even look at backs and, if they do, they tend to use only the forward bend test, which is not accurate.

Some experts argue that widespread screening would be cost effective if schools had reasonable guidelines for determining which children should see a doctor for further testing. The following are some suggested guidelines for determining the need for a doctor referral:

Children should be sent to a doctor only if they have a 30-degree curve. (A 20-degree curve with a 5-degree trunk rotation has been the criteria for recommending treatment, although up to 80% of 20-degree curves do not get worse.)
Children with curves between 20 and 30 degrees should be screened every 6 months.

Such guidelines would detect about 95% of all genuinely serious cases while referring only 3% of all children tested for follow-up, thereby cutting costs without jeopardizing children.

Treatment

The treatments for scoliosis are not always straightforward. Some young people do not need treatment at all -- only careful observation. When treatment is warranted, several options, including braces and different surgical procedures, can help.

The general rule of thumb for treating scoliosis is to monitor the condition if the curve is less than 20 degrees. Curves greater than 25 degrees, or those that progress by 10 degrees while being monitored, may require treatment. Whether scoliosis is treated immediately or simply monitored is not an easy decision, however. The percentage of cases that will progress more than 5 degrees can be as low as 5% in certain cases or as high as 50 - 90%, depending on the severity of the curve or other predisposing factors:

Age. In general, the older the child the less likely the curve will progress. Scoliosis in a child under 10, for example, is more likely to progress than scoliosis in an adolescent. Experts estimate that curves less than 19 degrees will progress 10% in girls ages 13 - 15 years and 4% in children older than 15. (In some rare, severe cases, a curve may worsen even after a child has received treatment and stopped growing because of the weight of the body pressing against the abnormal curve.)

Gender. Girls have a higher risk for progression than boys.

Location of the Curvature. Thoracic curves, those in the upper spine, are more likely to progress than thoracolumbar curves or lumbar curves, those of the middle to lower spine.

Severity of the Curvature. The higher the degree of curvature the more likely the chance of progression and the more likely the lungs will be affected. Some experts argue that the degree of the curve alone may not identify patients with moderate and severe scoliosis who are at greatest risk for complications and therefore need treatment. For example, spinal flexibility and the extent of asymmetry between the ribs and the vertebrae may be more important than the curve degree in predicting severity in this group.

Presence of Other Health Conditions. Children in poor health may suffer more from stressful scoliosis treatments than other children. On the other hand, children who have existing conditions and are predispose to lung and heart problems may warrant immediate, aggressive treatment.

For example, a young man of 18 who has a curvature of 30 degrees may require no treatment because his growth has probably almost stopped, and his gender puts him at lower risk. A young girl of 10, however, with the same curvature requires immediate treatment.

In general, the following criteria are used to determine whether a patient should receive braces and conservative therapies or surgery:

Braces tend to be used in children with curvatures between 25 - 40 degrees who still will be growing significantly.
Surgery is suggested for patients with curvatures over 50 degrees, in untreated patients, or when braces have failed. In adults, scoliosis rarely progresses beyond 40 degrees, but surgery may be required if the patient is in a great deal of pain or if the scoliosis causes neurologic problems.

The choice may not be so straightforward in certain cases, and patients should discuss all options with their doctor.

In Children and Adolescents. After a mild curve is detected, a more difficult step is required: predicting whether the curve will progress into a more serious condition. Although as many as 3 in every 100 teenagers have a condition serious enough to need at least observation, progression is highly variable and individual.

In a study of patients whose curves did progress after diagnosis, 34% progressed more than 10 degrees, 18% progressed more than 20 degrees, and 8% progressed more than 30 degrees. Doctors cannot rely on any definitive risk factors for curve progression to predict with any certainty which patients will need aggressive treatment. Some evidence suggests the following factors may help determine patients at lower or higher risk:

Being female, particularly if taller than average.
Being younger at the onset of scoliosis.
Having a greater angle of curvature. For example, at 20 degrees, only about 20% of curves progress. Young people diagnosed with a 30-degree curve, however, have a risk for progression of 60%. With a curve of 50 degrees, the risk is 90%.
Curvatures caused by congenital scoliosis (spinal problems present at birth). These may progress rapidly.
Treatment with growth hormone. (Studies are mixed on whether this treatment poses any significant risk, although strict monitoring is still essential in young patients being given growth hormone.)

Curvatures may be less likely to progress in girls whose scoliosis was low in the back and whose spine was out of balance by more than an inch. Height also comes into play. For example, a shorter-than-average girl of 14 with low-back scoliosis of 25 - 35 degrees but whose spine is imbalanced by over an inch would have almost no risk. The same degree of curvature in the chest region of a tall 10-year old girl whose spine was in balance, however, would almost certainly progress.

In Adults. In rare cases, unrecognized or untreated scoliosis in youth may progress into adulthood, with the following curvatures posing low to high risk:

Curvatures under 30 degrees almost never progress
Predicting progression at curves around 40 degrees is not clear
Curvatures over 50 degrees are at great risk for progression

Managing Scoliosis

Exercise has many health benefits and is important for maintaining strength and muscle tone and stabilizing weight. Stretching exercises may be beneficial in children whose scoliosis is due to uneven leg lengths or a shortened tendon.

Strengthening the Muscles That Turn the Torso. A promising approach focuses on training and strengthening the muscles that turn the torso. Studies using specific equipment (MedX Torso Rotation machine) are showing promise. In a 2003 study, 16 of the 20 patients experienced curve reduction, and no curves progressed. In an earlier study, patients increased strength from 12 - 40%. One girl with a severe lumbar curve required surgery, but the remaining 11 patients had no progression of curvature, and 4 of the patients experienced a reduction in their curvature. Treatment did not involve braces. Clinical trials using this approach are underway. Exercising the torso to build muscle strength is important, in any case, in conjunction with braces.

ASCO Scoliosis Treatment Method. ASCO Scoliosis Treatment Method is a Russian approach that consists of isometric and stretching exercises, vibration, spinal manipulation, and electrical muscle stimulation. Some U.S. centers are reporting success in halting curve progression, but more research is needed to determine possible benefits.

Biofeedback. Researchers have investigated biofeedback on the premise that people receiving a signal to improve posture when slumping may, in some cases, reduce their spinal deformities. (Some experts believe that braces work only because the young patients self-correct their curves by retraining their posture to avoid the discomfort of the brace.)

Chiropractic Care. Several case reports suggest that chiropractic manipulation of the spine may help stop progression of mild curves. However, no rigorous studies have proved this. One small study reported no benefits from chiropractic in girls with spinal curves less than 20 degrees. (About 80% of such curves will not progress significantly without any treatment.)

Airway Ventilation at Night. Some research has focused on the use of airway systems, such as nasal continuous positive airflow pressure, for patients with severe scoliosis and reduced lung capacity. Patients use such systems during the night to force air into the upper airways and into the lungs. In one study, the use of these devices reduced hospitalization and improved lung function, shortness of breath, and fatigue. Such systems also can treat sleep apnea, a common sleep disorder.

Breathing Exercises. Breathing exercises may help improve lung function in children with scoliosis, and signs of lung problems.

When a difference in leg lengths causes secondary scoliosis, adding lifts to the heels may decrease a mild curvature. In one study, this practice reduced the curvature by an average of 5.3 to 7.5 degrees. (Curvatures were all less than 20 degrees.) Patients with the greatest curvature experienced some muscle pain, fatigue, and even nausea during the first few days they were using the lifts, but these symptoms eased within 10 days.

Braces

A brace can prevent further progression of moderate curves of (24 - 40 degrees). However, a brace will almost never reverse an existing curve and is only used to stop progression. One study reported overall success rates of around 74%, but results vary widely depending on the length of time the brace is worn, the type of brace, and the severity of the curve. The great majority of subjects in scoliosis studies are girls. Limited data suggest that in boys compliance rates are low, and braces are not effective.

Compliance with wearing a brace correlates strongly with success rate. In analysis of 34 patients, the compliance rate for the patients whose curve progressed by more than 5 degrees was 62%, while the compliance rate for the patients who did not progress was 85%.

In overweight patients with adolescent idiopathic scoliosis, braces appear to be less effective than in those who are not overweight. In one 10-year multicenter retrospective study, overweight patients were about three times more likely to have an unsuccessful result with braces than were people of normal weight.

A brace is one type of treatment for scoliosis. The brace works by exerting pressure on the back and ribs to push the spine in a straighter position. The brace usually fits snugly around the torso and can come in many styles. In a child who is still growing, bracing is usually recommended to help slow the progression of the curve. The brace is usually worn full-time until the growth of the bones has stopped.

Many experts have questioned whether a brace is any better than nature in halting curvature progress. Early studies found that braces were successful in halting progression in only half of cases (the same rate as no treatment at all). In recent years, however, braces have improved. Many now fit under the arms and can be worn under clothing, so that patients are much more likely to use them for longer periods during the day, which greatly affects their success rates.

Wearing the brace for the prescribed time is difficult but essential for any success. A team approach, with several health professionals involved, is beneficial and often necessary to support the patient through the bracing process. An orthopedic surgeon interprets the x-rays, assesses the potential progression of the scoliosis, and plans the treatment with the patient and family. If a brace is used, an orthotist measures and fits the patient with the device. A physical therapist tailors an exercise program best suited for the patient. A nurse may also coordinate the treatment plans and provide physical and emotional support.

Milwaukee Brace. A full torso brace called the Milwaukee brace was the standard treatment until a decade ago. It is still used particularly for high curves.

The device contains a wide flat bar in front and two smaller ones in back. These bars attach to a ring around the neck that has rests for the chin and back of the head. One study determined that correcting the curve occurs best if the patient lies on their chest when wearing the brace. Some researchers suggest that increasing the tension on the chest straps might add benefit. The brace is also periodically adjusted for growth.

The brace needs to be worn 23 hours a day, with relief during bathing and exercise only. Compliance is a major problem. In one study, only 15% of patients wore the Milwaukee brace as directed. It is a particularly difficult brace to endure wearing; one woman who had worn it for 7 years during adolescence remembered being invisible during her school years, ignored and shunned by other children.

The Boston and TLSO Braces. Molded braces called thoracolumbar-sacral orthoses (TLSOs), most often the Boston brace, come up to beneath the underarms and can be fitted close to the skin so they do not show beneath clothing. It appears to be effective for mid-back and lower curves. In one study, treatment was judged successful in 61% of adolescents who wore Boston braces, and success correlated with wearing the brace more than 18 hours a day. Wearing the brace for 16 hours a day may still be beneficial, although the risk for curve progression is significantly higher the less time the brace is worn. These braces have problems; they are hot, reduce lung capacity by nearly 20%, and cause mild, temporary changes in kidney function.

The Charleston Bending Brace. The Charleston Bending Brace is worn only at night. Some doctors question its value, although it appears to be suitable for small, flexible curves. In a 2002 study, it was equally effective as the Boston brace. Other studies have reported success rates of 56 - 66% in patients who wore the brace as directed. Still, more than 10% of the patients using either brace eventually needed surgery.

Additional Braces in Development. New braces are being developed in an attempt to improve compliance and results. Some examples are:

The Providence brace is a computer-fitted device that is worn only at night. It is specifically designed for the individual curvature abnormalities, and early studies are showing promise.
A bracing method called the SpineCor uses adjustable bands and a cotton vest that allows flexibility. A 2003 study reported that after 2 years, the brace corrected the curve by 5 degrees in more than half the patients, while 38% were stabilized and only 7% had curvature that worsened by more than 5 degrees. A recent trial of 24 girls with idiopathic scoliosis compared the SpineCor with a TLSO-type brace. The study indicated that the SpineCor did not halt curvature progression associated with idiopathic scoliosis during the pubertal growth spurt whereas the TLSO device did.
The custom-fitted TriaC brace exerts pressure in specific areas of the back to allow greater comfort and flexibility. It may be less conspicuous than some of the older braces.

Studies are needed to determine if these or other new braces provide any additional value.

According to a 2003 study, compliance in wearing the brace averages 65% (although it varied from 8 - 90%). Patients were apt to wear them at night but often wore them sporadically during the day. The quality of life can vary by the type of brace worn. In one study, patients who had the Milwaukee brace reported greater impairment than patients with the Boston, TSLO, or Charleston braces. The choice of brace should be one that will be the most effective for a particular patient with the lowest impact on quality of life. Young people often refuse to wear braces, even the newer models, and emotional support from the family and professionals is extremely important to help a child accept the process and sustain compliance. On a positive note, one study reported that brace treatment did not negatively affect the self images of the adolescents who had to wear them.

For children who require braces, an exercise program helps boost well being, improves compliance with treatment, and keeps muscles in tone so that the transition period after brace removal is easier.

An exercise and physical therapy program is important to maintain or achieve the following:

Chest mobility.
Proper breathing. In one study, young girls who wore the Boston brace and performed aerobic exercises for 30 minutes four times a week experienced improved lung function, whereas lung function declined in girls who did not exercise.
Muscle strength (especially in the abdominal muscles).
Flexibility in the spine. One small study showed that patients who performed exercises improving flexibility in the torso experienced less spinal twisting and had improved curvature.
Correct posture. Practicing correct posture, especially in front of a mirror, is an extremely important part of any physical therapy program. A patient who is accustomed to a curved spine may have the sensation of being crooked when first taught to properly align the spine. Practicing in front of a mirror provides a reality check.
Patients must also learn to conduct daily activities while wearing the brace. Patients tend to comply with physical therapy in the period when the brace is first being used. They typically stop exercising when they have gotten used to the brace, however, and resume exercising only near the time the brace is being removed. Patients who don't stay with the program throughout the duration of brace use experience a weakening in the back at the time of removal.

Surgery

The goals of scoliosis surgery are threefold:

Straighten the spine as much as possible in a safe manner
Balance the torso and pelvic areas
Maintain correction

It takes a two-part process to accomplish these goals:

Fusing (joining together) the vertebrae along the curve
Supporting these fused bones with instrumentation (steel rods, hooks, and other devices) attached to the spine

There are many surgical variations that use different instruments, procedures, and surgical approaches to treat scoliosis. All of the operations require meticulous skill. In most cases, success depends less on the type of operation than on the skill and experience of the surgeon. The cause of scoliosis often determines the type of procedure. Parents of patients or adult patients should not be shy in asking the surgeon and hospital about their experience with the specific procedures being considered.

Surgery is usually recommended for the following children and adolescents with idiopathic scoliosis:

All young people whose curve exceeds 50 degrees.
Growing children whose curve has gone beyond 40 degrees. (There is still some debate, however, about whether all children with curves of 40 degrees should have surgery.)
Older children who have surgery tend to experience improved well-being from the changes in their appearance, even if they have no actual improved physical functioning.

Surgery may be required for the following children at as early an age as possible.

Those whose scoliosis is due to inborn abnormalities. (The younger they are when surgery is performed the better their chances for success.)
Children with multiple physical handicaps.

Procedures will differ depending on whether a child has idiopathic scoliosis, or scoliosis due to muscle and nerve disorders (such as muscular dystrophy or cerebral palsy). In the latter cases, children also need a team approach to reduce their risks for serious complications.

Before the operation, a doctor conducts a complete physical examination to determine leg lengths, muscle strength, lung function, and any postural abnormalities. The patient receives training in deep breathing and effective coughing to avoid lung congestion after the operation. The patient should also receive training in turning over in bed in a single movement (called log-rolling) before the operation. Psychologic intervention using cognitive-behavioral methods that help young patients cope may be very helpful in reducing anxiety and pain after surgery.

Patients are encouraged to donate their own blood before the operation for use in possible transfusions. The patient should have no sunburn, rashes, or sores on the back before the operation, which could increase the risk for infection.

Most scoliosis operations involve fusing the vertebrae. The instruments and devices used to support the fusion vary, however.

In the fusion procedure, the surgeon will:

Slice flaps to expose the backs of the vertebrae that lie along the curve.
Remove the bony outgrowths along the vertebrae that allow the spine to twist and bend.
Lay matchstick-sized bone grafts vertically across the exposed surface of each vertebra, being careful that they touch adjoining vertebrae.
Fold the flaps back to their original position, covering the bone grafts.
These grafts will regenerate, grow into the bone, and fuse the vertebrae together.

Depending upon the severity and responsiveness to other treatment, a doctor may recommend surgery for scoliosis. Surgery involves correcting the curve (although not all the way) and fusing the bones in the curve together. The surgeon lays bone grafts across the exposed surface of each vertebra. These grafts will regenerate, grow into the bone, and fuse the vertebrae together. The bones are held in place with one or two metal rods held down with hooks and screws, helping to support the fusion of the vertebrae.

Graft Materials. A surgeon takes bone grafts from the patient's hip, ribs, spine, or other bones (called autografts). This is the best quality bone. However, because autografts are taken directly from the scoliosis patient, the operation is longer and the patient experiences more pain afterward. Researchers are investigating allografts, bone grafts taken from another person or a cadaver. This would reduce the pain and duration of the operation. Allografts, however, pose an increased risk for infection from the donor.

Some surgical centers now perform spinal fusions in adults using a biologically-manufactured human bone protein instead of bone grafts. RhBMP-2 (INFUSE Bone Graft) contains a bone morphogenetic protein (BMP) that helps the body grow its own bone. A surgeon inserts the protein into a pair of thimble-like cages, which are implanted between the spinal vertebrae. The cages help stabilize the spine, while the protein prompts new bone growth. Doctors hope that this new procedure can eliminate the pain of autografts and the risk of infection of allografts. Results from preliminary studies have been promising. BMP treatments are currently approved only for adults.

Healing. The healed fusions harden in a straightened position to prevent further curvature, leaving the rest of the spine flexible. It takes about 3 months for the vertebrae to fuse substantially, although 1 - 2 years are required before fusion is complete. Fusion stops growth in the spine, but most growth occurs in the long bones of the body (such as in the legs), anyway. Patients will most likely gain height from both growth in the legs and from the straighter spine. Patients may walk at a slightly slower pace after fusion, but balance may improve, and sports activities are not restricted after the procedure.

Harrington Procedure. Until 10 years ago, the standard instruments used in fusion procedures were those of the Harrington procedure, first developed in the 1960s:

To support the fusion of the vertebrae, the surgeon uses a steel rod, extending from the bottom to the top of the curve. (More than one rod may be used depending on the type of curve and whether outward curvature of the spine is present.)
The rod is attached by hooks that are suspended from pegs inserted into the bone.
Similar to changing a tire, the steel rod is jacked up and then locked into place to support the spine securely. The surgeon is then ready to fuse the vertebrae together.
After this operation, patients must wear a full body cast and lie in bed for 3 - 6 months until fusion is complete enough to stabilize the spine.
After 1 - 2 years, the steel rod is not really necessary, but it is almost always left in place unless infection or other complications occur.

The Harrington procedure is very difficult to undergo, particularly for young people, and although the operation can achieve a correction of the curve of over 50%, studies have reported a loss in this correction of between 10 - 25% over time. The procedure does not correct the rotation of the spine and, therefore, does not improve an existing rib hump that was caused by the rotation. The operation does not interfere with normal pregnancies and deliveries later in life.

Certain complications may occur from this procedure:

About 40% of Harrington patients have a condition called the flat back syndrome, because the procedure eliminates normal lordosis (the inward curving of the lower back). Flat back syndrome from the Harrington procedure does not cause any immediate pain. In later years, however, the disks may collapse below the fusion, making it difficult to stand erect, and the condition can cause significant pain and emotional distress.
Studies have reported that 5 - 7 years after their surgery, between a fifth and a third of patients who had the Harrington procedure experienced low back pain. (In one study, only 3% had experienced back pain before surgery.) In such cases, however, the pain was not severe enough to interfere with normal activities and did not require additional surgery.
Children younger than age 11 whose skeleton is immature and who have the Harrington procedure have a fairly high risk for a specific curve progression called the crankshaft phenomenon. This condition occurs when the front of the fused spine continues to grow after the procedure. The spine cannot grow longer, so it twists and develops a curvature. In one study that followed patients for 5 - 16 years, crankshaft curve progression was moderate, however, with the Cobb angle averaging 9 degrees and rotation averaging 7 degrees.

Cotrel-Dubousset Procedure. The Cotrel-Dubousset procedure not only corrects the curve but also may help correct rotation, and it does not cause flat back syndrome.

With this procedure, a surgeon cross links parallel rods for better stability in holding the fused vertebrae. Improvement in correction averaged 66% in one study, with a later correction loss reported to be 5%. (Other studies have reported loss of curvature correction at less than 2%.) Over 95% of patients reported the results to be good or very good (only 86% of patients who had the Harrington procedure experienced the same levels of satisfaction). Patients often go home in 5 days and may be back in school in 3 weeks.

Complication rates are similar to the Harrington procedure but with some differences:

Operation time and blood loss are greater than with the Harrington procedure.
Cotrel-Dubousset and other procedures that are designed to reverse the rotation of the spine have less risk for flat back syndrome, but they have a higher risk for spinal imbalance than the Harrington procedure.
Failure rates are about 25% after 10 years, which is very high. Experts hope that the advances in current scoliosis procedures will help reduce the long-term adverse effects.

The Texas Scottish-Rite Hospital (TSRH) Instrumentation. The Texas Scottish-Rite Hospital (TSRH) instrumentation is similar to the Cotrel-Dubousset procedure in that it uses parallel rods and other devices that reverse rotation as well as improve curvature. TSRH, however, uses smooth rods and hooks that are designed to make removal or adjustment easier later on if complications arise. Complications are similar to the Cotrel-Dubousset procedure.

Additional Forms of Instrumentation. Other instrumentation procedures have refined the hardware used in the Harrington and Cotrel-Dubousset operations.

After surgeons developed Luque instrumentation to help maintain normal lordosis, experts hoped that bracing would not be needed afterward. Several studies showed, however, that without braces, correction was lost after this operation, and the procedure may have a higher risk for spinal cord injury than other standard procedures. Luque instrumentation is used primarily in people whose scoliosis is due to problems of nerves and muscles, such as in children with cerebral palsy.
Wisconsin segmental spine instrumentation (WSSI) is as safe as the Harrington rod and nearly as strong as the Luque instrumentation.
The Dorsal Dynamic Spondylodesis (DDS) system, under testing in Germany, is a semirigid system that allows for greater flexibility of the spine.

Instrumentation for Anterior Approach. The anterior approach, in which the surgeon performs the operation by opening the chest wall, requires specific hardware. Halm-Zielke instrumentation, for example, uses TSRH instrumentation with bone grafts constructed from ribs to prop open the spaces between the disks. It allows true three-dimensional curve correction. However, it does not solve specific problems with this approach -- higher risks for kyphosis (an outward curve) and pseudoarthrosis (a false joint at the fusion site). Variants using two rod systems, fusion cages, or other instruments appear to improve this procedure.

Posterior Approach (Through the Back). Many surgeons use a posterior approach for scoliosis, which reaches the surgical area by opening the back of the patient. It has been the gold standard for decades and is generally used with Harrington instrumentation. The posterior approach has advantages and disadvantages:

Advantages. Surgeons are familiar with it, so fusion rates are excellent, curve correction is good, and it has few complications.
Disadvantages. Preadolescent children are at risk for the crankshaft phenomenon (a worsening of the curve) later on. (Newer posterior instrumentation, such as the Isola instrumentation, may prevent this occurrence.) The posterior approach also does not always correct hypokyphosis (the loss of normal outward curvature) in the thoracic (upper) spine. The procedure is not always effective for curves in the thoracolumbar region (where the upper and lower spine meet) and may cause spinal abnormalities there.

Anterior Approach (Through the Front). Increasingly, surgeons are using the anterior approach, in which the surgeon performs the operation through the chest wall (called a thoracotomy). With the anterior approach, the surgeon makes an incision in the chest, deflates the lung, and removes a rib in order to reach the spine. This rib can be used during the operation as a strut to support the spine. It also may be repositioned within the patient until it is used for bone grafting during fusion.

The anterior approach also has its advantages and disadvantages:

Advantages. Because the frontal approach allows the procedure to be performed higher up in the spine than with standard procedures, the patient may have a lower risk for lower-back injury later on. In addition, transfusion rates are much lower with the anterior approach. With increasing experience, the anterior approach is as effective as the posterior approach.
Disadvantages. It is a more recent procedure than the posterior approach, and, among inexperienced surgeons, carries a higher risk for complications than in the more standard posterior approach. One study noted poorer lung function 2 years after surgery than with the posterior approach, possibly because the wide chest incision impairs the chest muscles, which can affect lung function afterward. Anterior instrumentation poses a risk for hyperkyphosis (exaggerated outward curvature) and a higher risk for pseudoarthrosis, a painful condition in which a false joint develops at the fusion site. Hardware failure rates may also be higher in the anterior approach than in the posterior approach. Increasing experience and newer hardware designs are reducing many of these problems.

The Combined Anterior-Posterior Approach. The combination approach uses an anterior approach first, which allows better correction of the problems. The fusion part of the operation is done with the posterior approach. This is a very long and complex procedure. It appears to be safe, however, and is proving to be useful, even in very young patients, for preventing the crankshaft phenomenon. It also may correct large rigid curves and specific severe curves in the thoracic spine.

Researchers are evaluating new approaches to treating thoracic scoliosis in adolescents and children. Researchers in Germany are studying the effects of implanting a vertical expandable prosthetic titanium rib. This implant expands the thoracic cavity, thereby correcting the curvature and allowing spinal, thoracic, and lung growth. Early experience with 15 children showed improvement of thoracic insufficiency syndrome and ability to sit, in addition to greatly improvement cosmetic appearance.

Researchers in the U.S. recently compared the radiographic and clinical outcomes and pulmonary function in patients treated with either anterior thoracoscopic or traditional posterior surgery. The anterior thoracoscopic surgery uses a video-assisted anterior approach and recently developed spinal instrumentation. There were 28 patients in the thoracoscopic group (average, 14.6 years of age) and 23 patients in the posterior fusion group (average, 14.3 years of age). The researchers found no significant differences between the groups in terms of kyphosis, coronal balance, or tilt angle. Advantages of the anterior thoracoscopic approach include the need for fewer vertebral levels fused, less blood loss, and lower transfusion rate, yet the operative time was nearly 2 times longer than for the posterior approach.

While both of these new treatments have shown some early positive results, more research will be needed to determine their true value.

Complication rates are high (nearly 10%) with any of these procedures, including the standard Harrington method and the newer Cotrel-Dubousset procedure.

Complications for all procedures include allergic reactions to anesthesia and the following:

Bleeding. Standard procedures increase the risk for major blood loss during the procedure. Patients are encouraged to donate blood before the operation for use in possible transfusions. Children sometimes require more than one transfusion following surgery. Researchers are investigating various methods for reducing the need for transfusions.

In one study, patients received erythropoietin (rhEPO) before the procedure. RhEPO is a hormone that acts in the bone marrow to increase the production of red blood cells. Patients who received this hormone, particularly those with idiopathic scoliosis, needed fewer transfusions and spent less time in the hospital than those who did not receive rhEPO.

Newer endoscopic techniques are reducing the need for transfusions.

Postoperative Pain. Some pain always follows these procedures, requiring intravenous administration of potent painkillers right after the operation (endoscopic procedures may require only mild pain relievers). Of some concern is a study suggesting that the use of NSAIDs, or nonsteroidal anti-inflammatory drugs (aspirin, Motrin, Advil), for pain relief right after fusion may increase the risk for fusion failure. Until more research is conducted, these common painkillers should not be routinely used immediately after surgery.

Infection. Infection is always a risk with any operation. One study reported changes in the immune system for about 3 weeks after surgery, which indicated a greater risk for infection. Researchers recommended being very vigilant for signs of infection, including in the pancreas and urinary tract. Doctors also recommend antibiotics, given by injection for 2 - 5 days after surgery and by mouth for 1 - 2 weeks longer.

Nerve Damage. Patients often worry about neurologic injuries, but the risk is actually very low. In general, nerve injury occurs in 1% of patients, with the risk highest in adults. If neurologic damage occurs, it most often causes muscle weakness. Paralysis is very rare and can be prevented using monitoring techniques during the operation. Nearly all monitoring procedures use a so-called wake-up test, in which the patient is brought out of anesthesia during or at the end of the procedure and assessed for sensations to be sure no injury has occurred. One simple method is to wake patients up in the middle of their operations and ask them to wiggle their toes. More sophisticated methods measure the electrical activity of the spinal cord; if the monitor indicates a fall in electrical response and possible injury, the surgeon adjusts his techniques to avoid further damage to the spinal cord.

Pseudoarthrosis. If the fusion fails to heal, pseudoarthrosis, a painful condition in which a false joint develops at the site, may develop. In one study, teenagers who smoked and heavier adolescents (over 154 pounds) who had hyperkyphosis (hunchback) were at higher risk for this complication. The anterior approach may pose a higher risk for pseudoarthrosis. One study reported that pseudoarthrosis may be undiagnosed, and rates may average 20% after surgery, therefore acting as a major contributor to post-surgery pain.

Disk Degeneration and Low Back Pain. Fusion in the lumbar area produces great stress on the lower back and eventually can cause disk degeneration. Loss of trunk mobility, balance, and muscle strength from surgical treatments can also cause lower back pain and chronic problems in future years. Patients who are surgically treated with fusion techniques lose flexibility; their back muscles may be weakened if they were injured during surgery. In most cases, however, the consequences are mild to moderate.

Lung Function. Some patients may develop serious lung problems after surgery. These complications are highest in children whose scoliosis is due to neuromuscular problems, such as spina bifida, cerebral palsy, or muscular dystrophy. Lung problems can occur up to 1 week after surgery. Lung function may not become completely normal until 1 - 2 months after surgery.

Other Complications. Other problems can include, but are not limited to, the following:

Hooks dislodging or a fused vertebra fracturing
Gallstones
Pancreatitis (inflammation of the pancreas). Among adolescents, this complication tends to occur more often among those who are older or who have a lower body mass index.
Intestinal obstruction

Click the icon to see an image of gallstones.

Patients must perform breathing and coughing exercises shortly after the procedure and continue them through the recovery process to rid the lungs of congestion. The patient is usually able to sit up the day after the operation, and most patients can move on their own within a week. A brace may be necessary, depending on the procedure. With the anterior approach in the upper back, patients may have some trouble with activities involving the arms and hands -- such as tying shoes and cutting food. In one study, however, occupational therapy using stretching and strengthening exercises allowed for full resumption of daily activities, including dressing, bathing, and grooming, within 3 months.

Patients are often concerned that surgery will stiffen their backs, but most cases of scoliosis affect the upper back, which has only limited movement, so that patients do not notice much difference. It may take a year or more for muscle strength to return. In some cases, the operation cannot completely correct the curve, and one leg may be shorter than the other. Heel lifts may help in this case.

Patients may need a corrective procedure called revision or salvage surgery, usually for one of these reasons:

Failure of the previous procedure
Curvature progression around the fusion site
Disk degeneration
Poor posture alignment

Minimally invasive surgery is an alternative to spinal fusion. These types of surgeries use a few small incisions and cause less scarring than standard open approaches that require wide cuts. However, these surgeries are limited to certain patients and are not yet as frequently performed as spinal fusion surgeries.

Endoscopy. In endoscopy, the surgeon makes small incisions and inserts tubes that contain tiny instruments and cameras through the incisions in order to view and execute the procedure. In most cases, the procedure occurs in two stages:

First, the surgeon uses the anterior approach to remove disk material and loosen the spine.
They follow with a posterior for fusion and instrumentation.

Recovery after surgery is rapid. Most patients are out of bed 2 days after surgery. Endoscopy causes fewer and smaller scars, and an easier recovery, than more invasive surgical approaches.

However, the endoscopic procedure for scoliosis is complicated, and few surgeons are trained to perform it. The surgery is generally used only for single curves in the upper back or for patients with a curve in the upper back and a compensating curve in the lower back. Some surgeons are now able to operate on areas below the diaphragm, including the lumbar spine. The patients must still wear a brace for 3 months after surgery. Long-term studies are required to compare results to those of standard procedures.

Growing Rod Technique. This technique is used for very young children in whom bracing has not helped. Instead of doing spinal fusion, doctors surgically insert a rod into the patient’s back. Additional surgeries are performed every 6 months to extend the rod so that the spine can continue to grow. Some growing rod techniques use a single rod, while others use two rods. Studies suggest that dual rods are stronger than single rods, which may help provide better spinal stability and correction.

Vertebral Body Stapling. Vertebral body stapling is an experimental technique that may prevent curve progression in some young patients with curves less than 50 degrees. It involves stapling the convex (outer) curve of the anterior spine (the side of the spine facing the chest), which helps stabilize and reduce progression of the inner (concave) curve. The procedure uses a special metal device that is clamp-shaped at body temperature but can be straightened when subjected to cold temperatures and inserted into the spine. When warmed up, the staple returns to its clamp shape and supports the spine.

Treatment for Adult Scoliosis

Adults who were surgically treated for scoliosis in their youth are at risk for disk degeneration and spinal fusion failure. In most adults with previous scoliosis, moderate exercise is not harmful and is extremely important for maintaining healthy supportive muscles and preventing disk degeneration. However, people who have only one or two mobile lumbar vertebrae below the area that was fused during surgery should avoid activity or exercise that causes excessive twisting on the spine. Some experts believe this may accelerate spinal degeneration.

In most cases of adult scoliosis, nonsurgical care is preferred if possible. This can include patient education, exercises, and medical treatments. Braces are not useful.

One center reported that epidural steroid injections were a beneficial alternative to surgery in patients with degenerative lumbar scoliosis.

Candidates for Surgery. In general, pain is the most common reason for surgery in adult scoliosis. Surgery may be recommended in the following cases:

Curvatures over 50 degrees with persistent pain.
Surgery is almost always recommended for adults with curvatures over 60 degrees.
Progressive mid and low back curve or low back curve with persistent pain.
Reduced heart and lung function. Most surgeons, however, will not operate on adults with severely impaired lung function and heart failure. Once this has occurred, surgery will not help improve lung capacity and may cause the condition to worsen, at least temporarily.
Significant deformity is present. Adults should not expect to achieve a completely straight spine, however. There is a high risk for nerve damage if the spine is over-corrected, and adult spines are less flexible than children's are. Usually, however, the correction achieves an acceptable cosmetic improvement.

Surgeons prefer to operate on adults under 50 years old, although surgery may be appropriate in some older people.

Standard Scoliosis Procedures in Adult Scoliosis. The procedures involve the following depending on whether the patient had been treated previously or not:

In patients who have not had previous treatment and who have degenerative lumbar scoliosis, the procedure is often a diskectomy (removal of the diseased disks) followed by scoliosis procedures (instrumentation and fusion).
In patients with previously treated scoliosis, the only remedy is removal of the old instrumentation, extension of the fusion, and implementation of new instrumentation and bone grafts.

Surgical procedures in adult scoliosis are complex and undertaken only after careful consideration and all nonsurgical methods have been exhausted. Adults have a much higher risk than children for complications, including pneumonia, infection, poor wound healing, and persistent pain. In addition, procedures in adults often involve fusion in lumbar and sacral areas (the low back), which can cause several complications. Some experts believe that the risks of operations in this area nearly always outweigh any benefits in adults. Most studies on adults have also reported low success rates.

Others argue that without an operation, the back will become unstable and painful. In addition, most studies on adults report on procedures using the old Harrington instrumentation techniques. Advances in instrumentation are increasing success rates in adults.

In a recent study, for example, adults who underwent anterior fusion and instrumentation had excellent results. In another study of newer generation instrumentation, 87% of adult patients reported satisfaction.

Wedge Osteotomy. Researchers are investigating wedge osteotomy in patients with mature spines, as corrective surgery and as an alternative to braces. In this procedure, a surgeon cuts wedges of bone from the concave side of the curve. The surgeon then straightens the spine by inserting a temporary rod and closing the cut sections. The patient needs to wear a brace and restrict activity for about 12 weeks or until the bone has healed. The patient can resume normal activities when a surgeon removes the rod, and the spine is mobile.

Resources

www.scoliosis.org -- National Scoliosis Foundation
www.srs.org -- Scoliosis Research Society
www.scoliosis-assoc.org - - Scoliosis Association
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.ispine.com -- Information on the spine

References

Akbarnia BA, Marks DS, Boachie-Adjei O, Thompson AG, Asher MA. Dual growing rod technique for the treatment of progressive early-onset scoliosis: a multicenter study. Spine. 2005;30(17 Suppl):S46-S57.

Helenius I, Jalanko H, Remes V, Sairanen H, Salminen S, Holmberg C, et al. Scoliosis after solid organ transplantation in children and adolescents. Am J Transplant. 2006;6(2):324-330.

Hell AK, Campbell RM, Hefti F. The vertical expandable prosthetic titanium rib implant for the treatment of thoracic insufficiency syndrome associated with congenital and neuromuscular scoliosis in young children. J Pediatr Orthop B. 2005;14:287-293.

Hung VW, Qin L, Cheung CS, Lam TP, Ng BK, Tse YK, et al. Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2005;87(12):2709-2716.

Lee WT, Cheung CS, Tse YK, Guo X, Qin L, Lam TP, et al. Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls. Osteoporos Int. 2005;16(12):1924-1932.

Lonner BS, Kondrachov D, Siddiqi F, Hayes V, Charf C. Thoracoscopic spinal fusion compared with posterior spinal fusion for the treatment of thoracic adolescent idiopathic scoliosis. J Bone Joint Surg. 2006;88A:1022-1034.

Luhmann SJ, Bridwell KH, Cheng I, Imamura T, Lenke LG, Schootman M. Use of bone morphogenetic protein-2 for adult spinal deformity. Spine. 2005;30(17 Suppl):S110-S117.

Thompson GH, Akbarnia BA, Kostial P, Poe-Kochert C, Armstrong DG, Roh J, et al. Comparison of single and dual growing rod techniques followed through definitive surgery: a preliminary study. Spine. 2005;30(18):2039-2044.

Yuan N, Fraire JA, Margetis MM, Skaggs DL, Tolo VT, Keens TG. The effect of scoliosis surgery on lung function in the immediate postoperative period. Spine. 2005;30(19):2182-2185.

Review Date:
4/6/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

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