http://www.fitsugar.com Happy healthy you. en http://www.fitsugar.com/204593 <a href="http://www.fitsugar.com/204593"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They Sleep--Well:</b> They snooze 2 more hours per week, compared with overweight people, says a study from Eastern Virginia Medical School. Researchers theorize that a lack of shut-eye is linked to lower levels of appetite-suppressing hormones like leptin and higher levels of the appetite-boosting hormone ghrelin.</p> <p><i>Emulate Them:</i> Break it down: Two extra hours of sleep a week is only 17 more minutes a day--a lot more manageable, even for the most packed of schedules. Start there and slowly work toward 8 hours of snooze time a night--the right amount for most adults.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="http://fitsugar.com/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204593#comment sleep prevention 8 secrets 8 secrets of naturally thin people Fri, 20 Apr 2007 03:00:00 -0700 FitSugar http://www.fitsugar.com/204593 http://www.fitsugar.com/204591 <a href="http://www.fitsugar.com/204591"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They're Movers And Shakers:</b> On average, slim people are on their feet an extra 2 1/2 hours per day--which can help burn off 33 pounds a year, according to a study from the Mayo Clinic in Rochester, MN.</p> <p><i>Emulate Them:</i> Try a reality check. Studies have shown that people often overestimate how active they really are, says Gallagher. Most people actually spend 16 to 20 hours a day just sitting. Wear a pedometer on an average day, and see how close you get to the recommended 10,000 steps. Your day should combine 30 minutes of structured exercise with a variety of healthy habits, such as taking the stairs instead of the elevator or mopping the floor with extra vigor. To see how many calories your activities burn, see the exercise calculator at www.caloriecontrol.org.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204591#comment prevention 8 secrets 8 secrets of naturally thin people Thu, 19 Apr 2007 02:00:00 -0700 FitSugar http://www.fitsugar.com/204591 http://www.fitsugar.com/204584 <a href="http://www.fitsugar.com/204584"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 Secrets of Naturally Thin People</a> one by one.</p> <ul> <li><b>They Have A Self-Control Gene:</b> Researchers at Tufts University found that the biggest predictor of weight gain among women in their 50s and 60s was their level of disinhibition, or unrestrained behavior. Women with low disinhibition (in other words, a finely tuned sense of restraint) had the lowest body mass index. High disinhibition (i.e., low restraint) was linked to an adult weight gain of as much as 33 pounds.</p> <p><i>Emulate Them:</i> Prepare for moments when your disinhibition is likely to be higher--such as when you're in a festive atmosphere with a large group of friends. If you're at a party, tell yourself you'll take one of every fourth passed hors d'oeuvre. If you're out at dinner, order an appetizer portion and share dessert. Or if you're stressed--another low-restraint moment--make sure you have a source of crunchy snacks (like fruit or carrot sticks) at the ready.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204584#comment prevention 8 secrets 8 secrets of naturally thin people self control gene Tue, 17 Apr 2007 13:30:00 -0700 FitSugar http://www.fitsugar.com/204584 http://www.fitsugar.com/204580 <a href="http://www.fitsugar.com/204580"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They're Creatures Of Habit:</b> Any dietitian will tell you that a varied diet is good--but too much variety can backfire, says Katz, author of The Flavor Point Diet. Studies have shown that too many tastes and textures encourage you to overeat, he explains. "Thin people have what I call a food groove--the majority of their meals consist of well-planned staples," says Beck. "There are a few surprises thrown in, but for the most part, their diets are fairly predictable."</p> <p><i>Emulate Them:</i> Try to be as consistent as possible with your major meals--have cereal for breakfast, a salad at lunch, and so forth. It's okay to add grilled chicken to the salad one day and tuna the next, but by sticking to a loosely prescribed meal schedule, you limit the opportunities to overindulge.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204580#comment prevention 8 secrets 8 secrets of naturally thin people creatures of habit Mon, 16 Apr 2007 11:45:00 -0700 FitSugar http://www.fitsugar.com/204580 http://www.fitsugar.com/204575 <a href="http://www.fitsugar.com/204575"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They Eat More Fruit:</b> Lean people, on average, have one more serving of fruit and eat more fiber and less fat per day than overweight people, reports a 2006 study published in the Journal of the American Dietetic Association.</p> <p><i>Copy Them:</i> Start tinkering. Examine your diet for ways to add whole fruits (not juices) to your meals and snacks. Aim for two or three servings per day. Sprinkle berries in your cereal or on your yogurt. Add sliced pears to your turkey sandwich, or bake an apple for dessert. Keep a bowl of fruit on your kitchen table or desk to motivate you to think fruit first, vending machine never.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204575#comment prevention 8 secrets 8 secrets of naturally thin people eat more fruit Fri, 13 Apr 2007 03:30:00 -0700 FitSugar http://www.fitsugar.com/204575 http://www.fitsugar.com/204570 <a href="http://www.fitsugar.com/204570"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They Don't Use Food To Cure The Blues:</b> It's not that thin women are immune to emotional eating, says Kara Gallagher, PhD, a weight loss expert based in Louisville. But they tend to recognize when they're doing it and stop.</p> <p><i>Emulate the Naturally thin:</i> Add the word 'Halt' to your vocabulary, says Gallagher. More than just a command (as in stop eating that entire sleeve of cookies), it's an acronym that stands for Hungry, Angry, Lonely, or Tired--the four most common triggers for emotional eating.</p> <p>If you're truly hungry, choose a balanced snack, such as a handful of nuts, to tide you over until your next meal. But if you're angry, lonely, or tired, seek an alternative calorie-free solution to your emotional need. Blow off steam by going for a run or just jumping around--the heartbeat boost will help dissipate your anger. Lonely? Call a friend, e-mail your kid, or walk to the park or mall. Being around others will make you feel more connected to your community (even if you don't bump into anyone you know). If you're tired, for heaven's sake, sleep!</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see secrets one and two <a href="/tag/8+secrets" >here</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204570#comment prevention 8 secrets 8 secrets of naturally thin people Thu, 12 Apr 2007 04:00:00 -0700 FitSugar http://www.fitsugar.com/204570 http://www.fitsugar.com/204558 <a href="http://www.fitsugar.com/204558"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They Realize Hunger Isn't An Emergency:</b> Most of us who struggle with extra pounds tend to view hunger as a condition that needs to be cured--and fast, says Judith S. Beck, PhD, author of the new Beck Diet Solution. "If you fear hunger, you might routinely overeat to avoid it," she says. Thin people tolerate it because they know hunger pangs always come and go, buying them some time.</p> <p><i>Emulate the Naturally Thin:</i> Pick a busy day to purposely delay lunch by an hour or two. Or try skipping an afternoon snack one day. You'll see that you can still function just fine. Then next time you feel those grumbles, you'll hold off before making a beeline for the fridge.</li> </ul> <p>More secrets revealed this week. Did you miss any? You can see all the secrets <a href="/tag/8+secrets" >here</a>.<br /> <a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204558#comment prevention naturally thin 8 secrets 8 secrets of naturally thin people Wed, 11 Apr 2007 02:30:00 -0700 FitSugar http://www.fitsugar.com/204558 http://www.fitsugar.com/204536 <a href="http://www.fitsugar.com/204536"><img width=119 height=160 src='http://media.onsugar.com/files/users/1/12981/15_2007/naturally-thin-secrets.large.jpg'></div></a><p><span class="inline left"></span>We all want to know what those naturally thin people are doing to stay so um, naturally thin. Prevention has discovered that healthy thin people just don't think about food the same way as everyone else. In this 8 part series, I'll reveal <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention's 8 secrets of naturally thin people</a> one by one.</p> <ul> <li><b>They Choose Satisfied Instead of Stuffed:</b> On a fullness scale of 1 to 10, the slim stop eating at a level of 6 or 7, says Jill Fleming, RD, author of <i>Thin People Don't Clean Their Plates</i>. The rest of us may keep going to an 8 or 10. Why? It may be because you mistakenly equate the sensation of fullness with satisfaction and feel deprived if you stop short, says Fleming. Or you may just be used to finishing what's in front of you, regardless of whether you really need it.</p> <p><i>Emulate The Naturally Thin:</i> About halfway through your next meal, put your fork down and, using the 1 to 10 scale, rate your level of fullness. Do it again when you have about five bites left. The goal is to increase your awareness of how satisfied you feel during a meal. (Bonus: It also <a href="203693" >slows down your eating</a>, which allows the sensation of fullness to settle in.)</li> </ul> <p>Look out for the other secrets posted this week. Can't wait? Then check out <a href="http://www.prevention.com/article/0,5778,s1-4-151-647-7894-1,00.html" target="_blank">Prevention.com</a>.</p> <p><a href="http://creative.gettyimages.com/source/home/home.aspx" target="_blank">Source</a></p> http://www.fitsugar.com/204536#comment prevention naturally thin 8 secrets satisfied Tue, 10 Apr 2007 10:15:00 -0700 FitSugar http://www.fitsugar.com/204536 http://www.fitsugar.com/2331791 <a href="http://www.fitsugar.com/2331791"></a><div id="health_topic"> <div id="health_topic_left"> <div class="left_nav_block"> <h3>In This Report</h3> <ul> <li class="indent"><a href="#adamHeading_2" rel="section">Highlights</a></li> <li class="indent"><a href="#adamHeading_3" rel="section">Introduction</a></li> <li class="indent"><a href="#adamHeading_4" rel="section">Causes</a></li> <li class="indent"><a href="#adamHeading_5" rel="section">Symptoms</a></li> <li class="indent"><a href="#adamHeading_6" rel="section">Complications</a></li> <li class="indent"><a href="#adamHeading_7" rel="section">Risk Factors</a></li> <li class="indent"><a href="#adamHeading_8" rel="section">Diagnosis</a></li> <li class="indent"><a href="#adamHeading_9" rel="section">Treatment</a></li> <li class="indent"><a href="#adamHeading_10" rel="section">Treatment for NSAID-Induced...</a></li> <li class="indent"><a href="#adamHeading_11" rel="section">Medications</a></li> <li class="indent"><a href="#adamHeading_12" rel="section">Treatment for Bleeding Ulce...</a></li> <li class="indent"><a href="#adamHeading_13" rel="section">Lifestyle Changes</a></li> <li class="indent"><a href="#adamHeading_14" rel="section">Resources</a></li> <li class="indent"><a href="#adamHeading_15" rel="section">References</a></li> </ul> </div> </div> <div id="health_topic_right"> <div id="health_topic_from_adam"> HEALTH GUIDE REFERENCE FROM A.D.A.M </div> <div id="health_topic_content"> <h3 id="adamHeading_2">Highlights</h3> <p><strong>Risk with cardiovascular medications</strong> </p> <p>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: </p> <ul> <li>Spironolactone, a common diuretic used in heart failure</li> <li>Niacin, a drug used to lower "bad" cholesterol and raise "good" cholesterol</li> <li>Vitamin K antagonists, commonly prescribed anticoagulants</li> <li>Dipyridamole, a drug for secondary stroke prevention</li> <li>Low-dose aspirin, prescribed for both heart attack and stroke prevention</li> </ul> <p>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. </p> <p><strong>Atypical symptoms of GERD</strong> </p> <p>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. </p> <p><strong>Adjustments in triple therapy</strong> </p> <p>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 <em>H. pylori</em>, the bacteria responsible for most ulcers. </p> <p><strong>Healing foods</strong> </p> <p>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 <em>H. pylori</em>, 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 <em>H. pylori</em> invasion. </p> <p><strong>Protection when taking NSAIDs</strong> </p> <p>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%. </p> <h3 id="adamHeading_3">Introduction</h3> <p>A peptic ulcer is an open sore or raw area that tends to develop in one of two places: </p> <ul> <li>The lining of the stomach ( <i>gastric ulcer</i>), or</li> <li>The upper part of the small intestine -- the duodenum ( <i>duodenal ulcers</i>). In the U.S., duodenal ulcers are 3 times more common than gastric ulcers.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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).</div> </div> </div> <p>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. </p> <p>The two important digestive juices are <i>hydrochloric acid</i> and the enzyme <i>pepsin</i>. Both substances are critical in the breakdown and digestion of starches, fats, and proteins in food. They play different roles in ulcers: </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331407" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an image of the stomach.</div> </div> <ul> <li><i>Hydrochloric acid.</i> 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 <i>H. pylori,</i> 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.]</li> <li><i>Pepsin.</i> 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.</li> </ul> <p>Fortunately, the body has a defense system to protect the stomach and intestine against these powerful substances: </p> <ul> <li>The <i>mucous layer,</i> which coats the stomach and duodenum, forms the first line of defense.</li> <li><i>Bicarbonate</i>, which the mucous layer secretes, neutralizes the digestive acids.</li> <li>Hormone-like substances called <i>prostaglandins</i> 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.</li> </ul> <p>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. </p> <h3 id="adamHeading_4">Causes</h3> <p>Before the discovery of the bacterium <i>Helicobacter (H.) pylori</i>, the stomach was believed to be a sterile environment. However, in 1982 two Australian scientists identified <i>H. pylori</i> 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 <em>H. pylori</em> 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: </p> <ul> <li><i>H. pylori's</i> corkscrew shape enables it to penetrate the mucous layer of the stomach or duodenum so it can attach itself to the lining.</li> <li>It survives in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.</li> <li><i>H. pylori</i> then produces a number of toxins and factors that can cause inflammation and damage to the lining, leading to ulcers in certain individuals.</li> <li>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.</li> </ul> <p>Even if ulcers do not develop, the bacterium is now considered to be a major cause of active chronic inflammation in the stomach (<i>gastritis</i>) and in the upper part of the small intestine (<i>duodenitis</i>). </p> <p>It is also strongly linked to stomach (gastric) cancer and possibly other non-intestinal problems. </p> <p><i>Factors that Trigger Ulcers in H. pylori Carriers.</i><i>H. pylori</i> is found in about 25% of people who do <i>not</i> have peptic ulcers. The magnitude of <i>H. pylori</i> 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: </p> <ul> <li>Genetic Factors. Some people harbor genetic strains of <i>H. pylori</i> 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.</li> <li>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.</li> <li>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 <i>H. pylori</i> carriers.</li> <li>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.</li> </ul> <p>When <i>H. pylori</i> 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 <i>H. pylori-</i> associated ulcers has declined. For example, a 2001 study suggested that about half of ulcers are <i>not</i> caused by <i>H. pylori</i>. 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. </p> <p>Some researchers now believe that duodenal ulcers are not caused by <em>H. pylori</em>, 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 <em>H. pylori</em>, and why duodenal ulcers can recur even after <em>H. pylori</em> has been eradicated. </p> <p>A 2006 study published in the <em>Journal of Biological Chemistry</em> indicates that a protein called decay-accelerating factor (DAF) acts as receptor for <em>H. pylori</em>. Animal studies show that blocking this interaction renders <em>H. pylori</em> harmless to the stomach. Researchers hope the discovery leads to new drugs that can reduce the risk of peptic ulcer. </p> <p>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. </p> <p>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. </p> <p>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. </p> <table border="1" cellpadding="3" cellspacing="0"> <tr> <td valign="top" colspan="3" /></tr> <tr> <td valign="top"> <p><b>Lowest Risk</b> </p> </td> <td valign="top"> <p><b>Medium Risk</b> </p> </td> <td valign="top"> <p><b>Highest Risk</b> </p> </td> </tr> <tr> <td valign="top"> <p>Nabumetone (Relafen) </p> <p>Etodolac (Lodine) </p> <p>Salsalate </p> <p>Sulindac (Clinoril) </p> </td> <td valign="top"> <p>Aspirin. Even low-dose ("baby") aspirin (81 mg) may pose some risk </p> <p>Ibuprofen (Motrin, Advil, Nuprin, Rufen) </p> <p>Naproxen (Aleve, Naprosyn, Naprelan, Anaprox) </p> <p>Diclofenac (Voltaren), Tolmetin (Tolectin) </p> <p>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. </p> </td> <td valign="top"> <p>Flurbiprofen (Ansaid), Piroxicam (Feldene), Fenoprofen Indomethacin (Indocin), Meclofenamate (Meclomen) </p> <p>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. </p> </td> </tr> </table> <p>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. </p> <p>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. </p> <p>The least common major cause of peptic ulcer disease is Zollinger-Ellison syndrome (ZES). </p> <p>Rarely, certain conditions may cause ulceration in the stomach or intestine, including: </p> <ul> <li>Radiation treatments</li> <li>Bacterial or viral infections</li> <li>Alcohol abuse</li> <li>Physical injury</li> <li>Burns</li> </ul> <p><em>What is ZES?</em> 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. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <p><em>Who Gets ZES?</em> 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. </p> <p><em>How Is ZES Diagnosed?</em> ZES should be suspected in patients with ulcers who are not infected with <i>H. pylori</i> 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. </p> <p><em>How Is ZES Treated?</em> 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. </p> <h3 id="adamHeading_5">Symptoms</h3> <p><i>Dyspepsia.</i> The most common symptoms of peptic ulcer are known collectively as <i>dyspepsia</i>. 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: </p> <ul> <li>Pain or discomfort</li> <li>Bloating</li> <li>A feeling of fullness. People with severe dyspepsia are unable to drink as much fluid as people with mild or no dyspepsia.</li> <li>Hunger and an empty feeling in the stomach, often 1 - 3 hours after a meal</li> <li>Mild nausea (Vomiting, in fact, may relieve symptoms.)</li> <li>Regurgitation (sensation of acid backing up into the throat.)</li> <li>Belching</li> </ul> <p><i>Ulcer Pain.</i> 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: </p> <ul> <li>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.</li> <li>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.</li> </ul> <p>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. </p> <p>Because ulcers can cause hidden bleeding, patients may experience the symptoms of anemia, including fatigue and shortness of breath. </p> <p>A sudden onset of severe symptoms may indicate intestinal obstruction, perforation, or hemorrhage, all of which are emergencies. Symptoms may include: </p> <ul> <li>Tarry, black, or bloody stools</li> <li>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)</li> <li>Severe abdominal pain with or without vomiting or evidence of blood</li> </ul> <p>Anyone who experiences any of these symptoms should go to the emergency room immediately. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <h3 id="adamHeading_6">Complications</h3> <p>Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life. </p> <p>Peptic ulcers caused by <i>H. pylori</i> 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. </p> <p>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 <i>H. pylori.</i> NSAID-related bleeding and stomach problems may be responsible for as many as 107,000 hospital admissions and 16,500 deaths each year. </p> <p>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. </p> <p><i>H. pylori</i> 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. </p> <p><i>Stomach Cancers.</i> Stomach cancer, also called <i>gastric</i> cancer, is the second most common cause of cancer worldwide. In developing countries where the rate of <i>H. pylori</i> 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 <i>H. pylori</i> infection and stomach cancer. In this study, uninfected people did not develop stomach cancer. However, the stomach cancer rates for <i>H. pylori-</i>associated conditions were 4.7% for nonulcer dyspepsia, 3.4% for gastric ulcers, and 2.2% of stomach polyps. Experts now suggest that <i>H. pylor</i>i may be as carcinogenic to the stomach as cigarette smoke is to the lungs. </p> <p>Eradication of <em>H. pylori</em> 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 <em>H. pylori</em> eradication therapy is started. This is something than can be measured during an endoscopy. </p> <p>The process most likely starts in childhood. Infection with <i>H. pylori</i> promotes a precancerous condition called <i>atrophic gastritis</i>. This may lead to cancer through the following steps: </p> <ul> <li>The stomach becomes chronically inflamed and loses patches of glands that secrete protein and acid.</li> <li>Acid protects against carcinogens, substances that cause cancerous changes in cells.</li> <li>New cells replace destroyed cells, but the new cells do not produce enough acid to protect against carcinogens.</li> <li>Over time, cancer cells may develop and proliferate in the stomach.</li> </ul> <p>Onset of <i>H. pylori</i> 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 <i>H. pylori</i> strain called cytotoxin-associated gene A (CagA) may also be a particular risk factor for precancerous changes. </p> <p>Interestingly, people with duodenal ulcers caused by <i>H. pylori</i> appear to have a <i>lower</i> risk of stomach cancer, although scientists do not know why. It may be that different <i>H. pylori</i> 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. </p> <p><i>Pancreatic Cancer. H. pylori</i> 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. </p> <p><i>Heart Disease.</i> Some research has reported a very high rate of <i>H. pylori</i> 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 <em>H. pylori</em> and heart disease may be that people with both tend to be in lower socioeconomic groups. Further studies are needed. </p> <p><i>Other Diseases. H. pylori</i> 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. </p> <h3 id="adamHeading_7">Risk Factors</h3> <p>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. </p> <p>Peptic ulcers are less common than they once were. Research suggests that ulcer rates have even declined in areas with widespread <em>H. pylori</em> infection. The increased use of proton-pump inhibitor drugs may be responsible for this trend. </p> <p><i>H. pylori</i> 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. </p> <p><i>Who Is Infected with H. pylori?</i> About half the world's adults are infected with <i>H. pylori.</i> 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. </p> <p><i>How Does the Bacteria Pass from Person to Person?</i> 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 <i>H. pylori</i>. 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 <i>H. pylori</i> can live in water, but not apparently in food, the bacteria may also be transmitting through sewage-contaminated water. </p> <p><i>Who Is at Risk for Ulcers from H. pylori?</i> Although <i>H. pylori</i> 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. </p> <p>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. </p> <p>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.) </p> <p>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. </p> <p><i>Frequent Users of NSAIDs.</i> 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. </p> <p><em>Contributing Factors</em>. Certain factors add to the risk for ulcers in NSAID-users: </p> <ul> <li>Age 65 and older</li> <li>History of peptic ulcers or upper gastrointestinal bleeding</li> <li>Other serious ailments, such as congestive heart failure</li> <li>Use of other medications, such as the anticoagulant warfarin (Coumadin), corticosteroids, or the osteoporosis drug alendronate (Fosamax)</li> <li>Alcohol abuse</li> <li>Those infected with <i>H. pylori</i>. A 2002 study reported that the combination of NSAID use and <em>H. pylori</em> 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.</li> </ul> <p><i>Stress and Psychological Factors.</i> 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 <i>H. pylori</i> or NSAIDs. Some experts even believe that the anecdotal relationship between stress and ulcers is so strong that treatment of psychological factors is warranted. </p> <p><i>Smoking.</i> 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 <i>H. pylori</i>. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <h3 id="adamHeading_8">Diagnosis</h3> <p>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. </p> <p>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. </p> <p>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. </p> <p>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. </p> <p>The following disorders may be confused with peptic ulcers: </p> <ul> <li><i>GERD.</i> 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 <em>In-Depth Report</em> #85: <a href="/2331708" >Gastroesophageal Reflux Disease</a><em>.</em>]</li> <li><i>Heart Events.</i> 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 <em>In-Depth Report</em> #12: <a href="/2331144" >Heart Attack</a><em>.</em>]</li> <li><i>Gallstones.</i> 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 <em>In-Depth Report</em> #10: <a href="/2331795" >Gallstones and Gallbladder Disease</a><em>.</em>]</li> <li><i>Irritable Bowel Syndrome.</i> Irritable bowel syndrome can cause dyspepsia, nausea and vomiting, bloating, and abdominal pain. It occurs more often in women than in men.</li> </ul> <p>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. </p> <p>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. </p> <p>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. </p> <p>Simple blood, breath, and stool tests can now detect <i>H. pylori</i> with a fairly high degree of accuracy. It is not entirely clear, however, which individuals should be screened for <i>H. pylori.</i> </p> <p><i>Candidates for Screening.</i> Some doctors currently test for <i>H. pylori</i> only in individuals with dyspepsia who also have high-risk conditions, such as: </p> <ul> <li>Strong indication for ulcers, such as weight loss, anemia, or indications of bleeding</li> <li>History of active ulcers</li> <li>Risk factors for stomach cancer or other complications from ulcers</li> </ul> <p>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 <i>H. pylori</i> may be beneficial for patients with dyspepsia who are regular NSAID users. In fact, given the possible risk for stomach cancer in <i>H. pylori-</i> infected people with dyspepsia, some experts now recommend that <i>any</i> patient with dyspepsia lasting longer than 4 weeks should have a blood test for <i>H. pylori</i>. This is a subject of considerable debate, however. </p> <p><i>Specific Screening Tests for H. pylori.</i> The following screening tests used or under investigation for <i>H. pylori:</i> </p> <ul> <li>Breath Test. A simple test called the carbon isotope-urea breath test (UBT) can identify up to 99% of people who harbor <i>H. pylori</i>. 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 <i>urea</i> (a compound in mammals metabolized from nitrogen) that has been treated with carbon atoms. If <em>H. pylori</em> is present, the bacteria convert the urea into carbon dioxide, which is detected and recorded in the patient's exhaled breath after 10 minutes.</li> <li>Blood Tests. Blood tests are used to measure antibodies to <i>H. pylori</i>, 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.</li> <li>Stool Test. A test to detect genetic fingerprints of <i>H. pylori</i> 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.</li> </ul> <p>It should be noted that such tests are not as accurate as endoscopy, an invasive procedure, which is needed to confirm a diagnosis of <i>H. pylori</i>. The breath and stool tests, however, can be particularly useful after treatment to determine if a patient has been cured. </p> <p><i>Test and Tre</i>at<i>.</i> Depending on the results of the screening tests, some doctors take the following steps: </p> <ul> <li>Approach for Noninfected Individuals. People who do not have evidence of <i>H. pylori</i> on a blood or breath test are typically given a 4-week course of acid-suppressing medication, usually a PPI such as omeprazole (Prilosec).</li> <li>Approach for <i>H. pylori-</i>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 <i>H. pylori</i>?)</li> </ul> <p>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. </p> <p>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. </p> <p>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. </p> <p>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 <i>H. pylori</i>. </p> <p><i>Appropriate Candidates for Endoscopy.</i> 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: </p> <ul> <li>Having so-called "alarm" symptoms (unexplained weight loss, gastrointestinal bleeding, vomiting, difficulty swallowing, or anemia).</li> <li>Being over 45 (when the risk for stomach cancer increases).</li> </ul> <p>There is some debate whether patients under 45 with persistent dyspepsia and no alarm symptoms should have endoscopy. </p> <p><i>The Procedure.</i> Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center, and typically involves the following: </p> <ul> <li>The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and relax the patient.</li> <li>The doctor then places the thin, flexible plastic tube into the patient's mouth and down the esophagus into the stomach.</li> <li>A tiny camera in the endoscope allows the doctor to see the surface of the esophagus, stomach, and duodenum, and to search for abnormalities.</li> <li>The doctor will remove about 10 small tissue samples (biopsies), which will be tested for <i>H. pylori</i>.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <p>Note: Some evidence suggests that patients who take PPIs should stop taking the medication 2 weeks before an endoscopy, since it may mask ulcers. </p> <p><i>Capsule Endoscopy.</i>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. </p> <p>An upper GI (gastrointestinal) series was the standard diagnostic method for peptic ulcers until the introduction of adequate tests for detecting <i>H. pylori</i>. 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. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331807" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an illustrated series detailing treatment of GI bleeding.</div> </div> <p>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. </p> <h3 id="adamHeading_9">Treatment</h3> <p>Antibiotic regimens that eradicate <i>H. pylori</i> can cure peptic ulcers and are now the standard medications used for ulcers in infected individuals who are not taking NSAIDs. Eliminating <i>H. pylori</i> 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. </p> <p><i>Patients with Clear Evidence of Ulcers.</i> Antibiotics are clearly indicated for patients who have both ulcers and <i>H. pylori</i> 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. </p> <p>There is considerable debate about whether to test for <i>H. pylori</i> and treat infected patients who have dyspepsia, but no evidence of ulcers. </p> <p>The best approach for treating dyspepsia is highly controversial. Options include the following: </p> <ul> <li>Test and Treat. This approach involves testing for <i>H. pylori</i> and eradicating the bacteria in infected patients.</li> <li>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).</li> </ul> <p>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. </p> <p><i>Arguments for Testing and Treating Patients with Dyspepsia.</i> The argument supporting testing and treating patients with nonulcer dyspepsia is as follows: </p> <ul> <li>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 <i>H. pylori</i> greatly decreased the likelihood of ulcers in infected patients with nonulcer dyspepsia who were chronic NSAID users.</li> <li>Protection against gastric cancer. Some evidence suggests that eradicating <i>H. pylori</i> 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 <i>H. pylori</i>.</li> </ul> <p><i>Arguments against Testing and Treating Patients with Dyspepsia.</i> The arguments against testing and treating are as follows: </p> <ul> <li>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 <i>H. pylori</i> and patients who were maintained on PPIs.</li> <li>Lower rates of <i>H. pylori</i> in the U.S. The number of people with <i>H. pylori</i> infection is declining in the U.S., possibly making the test-and-treat approach too expensive for the number of people it helps.</li> <li>Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that <i>H. pylori</i> in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating <i>H. pylori</i> may also have other adverse effects.</li> <li>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.</li> </ul> <p>The standard treatment regimen for <em>H. pylori</em> uses 2 antibiotics and a PPI. Cure rates after antibiotic treatment range from 70 - 90%. A typical regimen contains three drugs: </p> <ul> <li>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 <em>H. pylori</em>.</li> <li>Two antibiotics. The standard antibiotics are clarithromycin (Biaxin) and amoxicillin. Some doctors substitute the antibiotic metronidazole (Flagyl) for either clarithromycin or amoxicillin.</li> </ul> <p>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 <em>H. pylori</em> and was associated with fewer side effects. A study published in 2007 comparing 1- and 2-week treatments with amoxicillin, clarithromycin, and omeprazole for <em>H. pylori</em> eradication found both regimens to be similar in efficacy, safety, and compliance. </p> <p>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%). </p> <p>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. </p> <p><i>Follow-Up.</i> 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. </p> <p>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. </p> <p><i>Failure.</i> 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: </p> <ul> <li>The triple-drug regimens are complicated and require many pills. Helicide or two-drug combinations may help offset this problem.</li> <li>About 30% of patients suffer side effects from the <i>H. pylori</i> regimen. Gastrointestinal problems are very common, and severe diarrhea can occur.</li> </ul> <p>Treatment may also fail if the patients harbor strains of <i>H. pylori</i> that are resistant to the antibiotics. When this happens, different drugs are tried. </p> <p><i>Reinfection after Successful Treatment</i>. 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 <i>H. pylori</i> is very high and sanitary conditions are poor. In such regions, reinfection rates are 6 - 15%. </p> <p><i>Weight Gain.</i> Some patients may gain weight. </p> <p><i>Gastroesophageal Reflux Disease.</i> Of ongoing interest are reports of a lower incidence of <i>H. pylori</i> in patients with GERD. There are some important unanswered questions associated with this issue: </p> <ul> <li>Is the lower incidence of <i>H. pylori </i> 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 <i>not</i> infected with <i>H. pylori,</i> except possibly in certain regions. In a 2003 study, the absence of <i>H. pylori</i> 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 <em>H. pylori</em> infection published in 2007 by the European Helicobacter Study Group state that "Eradication of <em>H. pylori</em> infection does not cause gastroesophageal reflux disease (GERD) or exacerbate GERD, and may prevent peptic ulcer in patients who are naive users of NSAIDs."</li> <li>Does eliminating the bacteria with antibiotic therapy actually produce GERD in some people? One study observed that patients cured of <i>H. pylori</i> 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.</li> <li>What is the proper management of people who have GERD and <i>H. pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i> is eliminated.</li> </ul> <p><i>Effects on Other Gastrointestinal Infections.</i> In children, there is some evidence that <i>H. pylori</i> protects against <em>E. coli</em> and other GI infections, particularly those that cause diarrhea. If this is true, treating infected children for <em>H. pylori</em> should be done only if the bacteria are causing harm. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331781" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an animation on ulcer treatment.</div> </div> <h3 id="adamHeading_10">Treatment for NSAID-Induced Ulcers</h3> <p><i>Preventing Ulcers or Rebleeding Caused by NSAIDs.</i> If NSAID-caused ulcers or bleeding are identified, patients should: </p> <ul> <li>Get tested for <em>H. pylori</em> and, if they are infected, take antibiotics.</li> <li>Possibly use a PPI. Studies suggest these medications lower the risk for NSAID-caused ulcers, although they do not completely prevent them.</li> </ul> <p>People who still need to take NSAIDs should: </p> <ul> <li>Use the lowest NSAID dose possible.</li> <li>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.</li> </ul> <p>A warning to women: misoprostol can induce labor at any stage of pregnancy. Pregnant women should not use the drug. </p> <p><i>Healing Existing Ulcers</i>. 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. </p> <p><i>COX-2 Inhibitors (Coxibs).</i> 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. </p> <p><i>Arthrote</i>c<i>.</i> 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. </p> <p><em>Acetaminophen.</em> 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. </p> <p><i>Tramadol.</i> 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. </p> <h3 id="adamHeading_11">Medications</h3> <p>The following drugs are sometimes used in the treatments of peptic ulcers caused by either NSAIDs or <i>H. pylori</i>. They are described in alphabetical order. </p> <p>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: </p> <ul> <li>All rely on various combinations of three basic compounds -- magnesium, calcium, or aluminum -- to neutralize stomach acid.</li> <li>They may defend the stomach by increasing acid-buffering bicarbonate and mucus secretion.</li> </ul> <p>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. </p> <p><i>Basic Salts Used in Antacids.</i> There are three basic salts used in antacids: </p> <ul> <li>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.</li> <li>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.</li> <li>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.</li> </ul> <p><i>Interactions with Other Drugs.</i> 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. </p> <table border="1" cellpadding="3" cellspacing="0"> <tr> <td valign="top" colspan="2" /></tr> <tr> <td valign="top"> <p><b>Drugs that are absorbed less well if taken with antacids</b> </p> </td> <td valign="top"> <p><b>Drugs that are made more potent by antacids</b> </p> </td> </tr> <tr> <td valign="top"> <p>Tetracycline </p> <p>Ciprofloxacin (Cipro) </p> <p>Propranolol (Inderal) </p> <p>Captopril (Capoten) </p> <p>Ranitidine (Zantac) </p> <p>Famotidine (Pepcid AC) </p> </td> <td valign="top"> <p>Valproic acid </p> <p>Sulfonylureas </p> <p>Quinidine </p> <p>Levodopa </p> </td> </tr> </table> <p><i>H. pylori</i> 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. </p> <ul> <li>Amoxicillin is the most common form of penicillin. It is inexpensive, but many people are allergic to it.</li> <li>Clarithromycin (Biaxin) is a macrolide and is the most expensive antibiotic used against <i>H. pylori</i>. 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.</li> <li>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.</li> <li>Ciprofloxacin (Cipro), a fluoroquinolone, is also sometimes used in ulcer regimens.</li> <li>Metronidazole (Flagyl) was the mainstay in initial combination regimens for <i>H. pylori.</i> As with clarithromycin, however, there continues to be growing bacterial resistance to the drug. Today, about 25 - 35% of <i>H. pylori</i> bacteria are metronidazole-resistant.</li> </ul> <p><i>Side Effects of Antibiotics.</i> </p> <ul> <li>The most common side effects of nearly all antibiotics are gastrointestinal problems such as cramps, nausea, vomiting, and diarrhea.</li> <li>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.</li> <li>Some drugs, including certain over-the-counter medications, interact with antibiotics; patients should report to all medications they are taking to their doctor.</li> <li>Antibiotics double the risk of vaginal infections in women.</li> </ul> <p>Compounds that contain bismuth are often used in the three-drug antibiotic regimens. They destroy the cell walls of <i>H. pylori</i> 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. </p> <p>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 <em>H. pylori</em> were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however. </p> <p>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: </p> <ul> <li><i>Famotidine (Pepcid AC).</i> 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.</li> <li><i>Cimetidine (Tagamet).</i> 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.</li> <li><i>Ranitidine (Zantac).</i> 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.</li> </ul> <p>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: </p> <ul> <li>92% and 88% with esomeprazole 40 mg and 20 mg (vs 74% with ranitidine).</li> <li>87% and 84% with omeprazole 40 mg and 20 mg (vs 64% with ranitidine).</li> <li>And 73 - 74% and 66 - 69% with lansoprazole 30 mg and 15 mg (vs 50 - 53% with ranitidine).</li> <li>However, healing rates with ranitidine reached nearly 100% when NSAIDs were discontinued.</li> </ul> <p><i>Nizatidine (Axid).</i> Nizatidine is nearly free of side effects and drug interactions. </p> <p><i>Long-Term Concerns.</i> 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 <i>H. pylori</i> infection. More research is needed. However, the following concerns are real: </p> <ul> <li>Liver damage. This is more likely with ranitidine than other H2 blockers, but is rare in any event.</li> <li>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.</li> <li>Increased risk for pneumonia in hospitalized patients.</li> <li>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.</li> </ul> <p>Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major intestinal toxicity of NSAIDs. </p> <p><i>Actions against Ulcers.</i> 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. </p> <p><i>Side Effects.</i> </p> <ul> <li>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.</li> <li>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.</li> </ul> <p><i>Actions against Ulcers.</i> 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. </p> <p>PPIs can be used either as part of a multidrug regimen for <em>H. pylori</em> 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. </p> <p><i>Standard Brands.</i> 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: </p> <ul> <li>Omeprazole (generic, Prilosec OTC)</li> <li>Esomeprazole (Nexium)</li> <li>Lansoprazole (Prevacid)</li> <li>Rabeprazole (Aciphex)</li> </ul> <p><i>Possible Adverse Effects.</i> </p> <ul> <li>Side effects are uncommon, but may include headache, diarrhea, constipation, nausea, and itching.</li> <li>Pregnant women and nursing mothers should avoid taking PPIs, although recent studies suggest that these drugs do not increase the risk of birth defects.</li> <li>PPIs may interact with certain drugs, such as antiseizure agents (such as phenytoin), antianxiety drugs (such as diazepam), and blood thinners (such as warfarin).</li> <li>Long-term use of high-dose PPIs may produce vitamin B12 deficiency, but studies are needed to confirm this risk.</li> <li>In theory, long-term use of PPIs by people with <i>H. pylori</i> 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.</li> </ul> <p>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. </p> <h3 id="adamHeading_12">Treatment for Bleeding Ulcers</h3> <p>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. </p> <p>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. </p> <p>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. </p> <p>Between 10 - 20% of patients require more invasive procedures for bleeding, usually major abdominal surgery. </p> <p>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. </p> <p><i>Endoscopy for Diagnosing Bleeding Ulcers and Determining Risk of Rebleeding.</i> 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 <i>stigmata</i>, which indicate a higher or lower risk of rebleeding. </p> <p>Such features include the following: </p> <ul> <li>Low risk (5 -15%) for bleeding: flat dot; a clean or white base.</li> <li>High risk (30 - 50%) for bleeding: swollen but nonbleeding blood vessels; blood clots that adhere to ulcers.</li> <li>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.</li> <li>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.</li> </ul> <p><i>Endoscopy as Treatment.</i> 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). </p> <p>The following is a typical endoscopy procedure: </p> <ul> <li>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.</li> <li>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.</li> <li>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.</li> </ul> <p>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. </p> <p>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. </p> <p>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. </p> <p><i>Other Medical Considerations.</i> Certain agents may be warranted after endoscopy: </p> <ul> <li>Patients who harbor the <i>H. pylori</i> 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 <i>H. pylori</i> immediately after endoscopy is warranted in most patients infected with the bacteria.</li> <li>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.</li> </ul> <p>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. </p> <p><i>Surgical Approaches.</i> 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. </p> <p><i>Major Surgical Procedures.</i> There are a number of surgical procedures aimed at long-term relief of ulcer complications. These include: </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331788" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an illustrated series detailing a gastrectomy procedure.</div> </div> <ul> <li>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.</li> <li>Antrectomy, in which the lower part of the stomach is removed. This part manufactures the hormone responsible for stimulation of digestive juices.</li> <li>Pyloroplasty, which enlarges the opening into the small intestine so that stomach contents can pass into it more easily.</li> </ul> <p>Antrectomy and pyloroplasty are usually performed with vagotomy. </p> <h3 id="adamHeading_13">Lifestyle Changes</h3> <p>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. </p> <p><i>Fruits and Vegetables.</i> 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: </p> <ul> <li>In one study, apples and yams appeared to be especially helpful.</li> <li>Apples, celery, cranberries, onions, red wine, and green and black tea are also high in natural chemicals known as flavonoids, which appear to inhibit <i>H. pylori</i> growth and have many other health benefits. Cranberry juice specifically may have properties that help prevent <i>H. pylori</i> from infecting the intestinal lining.</li> <li>Grapefruit has antioxidant properties that may help heal ulcers.</li> <li>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.</li> <li>Laboratory experiments suggest that sulforaphone, a compound found in broccoli and broccoli sprouts, may be lethal to even drug-resistant strains of <i>H. pylori.</i></li> <li>Tea has chemicals that may help protect against cancers in the stomach and esophagus.</li> </ul> <p><i>Milk.</i> 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. </p> <p><i>Coffee and Carbonated Beverages.</i> 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 <i>H. pylori</i> infection. </p> <p><i>Spices and Peppers.</i> 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. </p> <p><i>Garlic.</i> 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 <i>H. pylori</i> and, in high amounts, can cause considerable GI distress. </p> <p><em>Olive Oil.</em> 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. </p> <p><i>Vitamins.</i> Although no vitamins have been shown to protect against ulcers, <i>H. pylori</i> appears to impair absorption of vitamin C, which may play a role in the higher risk of stomach cancer. </p> <p>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. </p> <p>Stress relief programs have not been shown to promote ulcer healing, but they may have other health benefits. </p> <p>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. </p> <h3 id="adamHeading_14">Resources</h3> <ul> <li><a href="http://digestive.niddk.nih.gov/" target="_blank">http://digestive.niddk.nih.gov</a> -- National Digestive Diseases Information Clearinghouse</li> <li><a href="http://www.gastro.org/" target="_blank">www.gastro.org</a> -- American Gastroenterological Association</li> <li><a href="http://www.acg.gi.org/" target="_blank">www.acg.gi.org</a> -- American College of Gastroenterology</li> </ul> <h3 id="adamHeading_15">References</h3> <p>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. <em>Am J. Gastroenterol</em>. 2007;102(5):951-956. </p> <p>Guyton JR, Bays HE. Safety considerations with niacin therapy. <em>Am J Cardiol</em>. 2007;99(6A):22C-31C. </p> <p>Hainaux B, Agneessens E, Bertinotti R, et al. Accuracy of MDCT in predicting site of gastrointestinal tract perforation. <em>Am J Roentgenol</em>. 2006;187(5):1179-1183. </p> <p>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. <em>BMS</em>. 2006;333(7571):726. Epub 2006 Sept 19. </p> <p>Hobsley M, Tovey F, Horton J. Precise role of H. pylori in duodenal ulceration. <em>World J Gastroenterol</em>. 2006;12(40):6413-6419. </p> <p>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. <em>Pharmacoepidemiol Drug Saf</em>. 2007 Feb 26 [Epub ahead of print]. </p> <p>Jansson EA, Petersson J, Reinders C, et al. Protection from nonsteroidal anti-inflammatory (NSAID)-induced gastric ulcers by dietary nitrate. <em>Free Radic Biol Med</em>. 2007;41(4):510-518. </p> <p>Keefer L, Stepanski EJ, Ranjbaran Z, Benson LM, Keshavarzian A. An initial report of sleep disturbance in inactive inflammatory bowel disease. <em>J Clin Sleep Med</em>. 2006;2(4):409-416. </p> <p>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. <em>Dig Dis Sci</em>. 2007 May 19 [Epub ahead of print]. </p> <p>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. <em>Int J Cancer</em>. 2007;120(2):368-372. </p> <p>Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastrict III Consensus Report. <em>Gut</em>. 2007;56(6):772-781. </p> <p>Miki K, Urita Y, Ishikawa F, et al. Effect of Bifidobacterium bifidum fermented milk on Helicobacter pylori and serum pepsinogen levels in humans. <em>J Dairy Sci</em>. 2007;90(6):2630-2640. </p> <p>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. <em>Dig Dis Sci</em>. 2007;52(2):442-450. </p> <p>Moore ML. Misoprostol-is more research needed? <em>J Perinat Educ</em>. 2002;11(3):43-47. </p> <p>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. <em>Dig Dis Sci</em>. 2007;63(11):773-775. </p> <p>Pietroiusti A, Forlini A, Magrini A, et al. Shift work increases the frequency of duodenal ulcer in H. pylori infected workers. <em>Occup Environ Med</em>. 2006;63(11):773-775. </p> <p>Pilotto A, Franceschi M, Leandro G, et al. Clinical features of reflux esophagitis in older people: a study of 840 consecutive patients. <em>J Am Geriatr Soc</em>. 2006;54(10):1537-1542. </p> <p>Romero C, Medina E, Vargas J, Brenes M, De Castro A. In vitro activity of olive oil polyphenols against Helicobacter pylori. <em>J Agric Food Chem</em>. 2007;55(3):680-688. </p> <p>Saif MW, Elfiky A, Salem RR. Gastrointestinal perforation due to bevacizumab in colorectal cancer. <em>Ann Surg Oncol</em>. 2007;14(6):1860-1869. </p> <p>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. <em>Aliment Pharmacol Ther</em>. 2007;25(:949-954. </p> <p>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. <em>J Gastroenterol</em>. 2007;42(suppl 17):21-27. </p> <p>Ushida Y, Shimokawa Y, Toida T, Matsui H, Takase M. Bovine alpha-lacalbumin stimulates mucus metabolism in gastric mucosa. <em>J Dairy Sci</em>. 2007;90(2):541-546. </p> <p>Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. <em>Ann Intern Med</em>. 2007;146(:556-563. </p> <p>Verhamme K, Mosis G, Dieleman J, Stricker B, Sturkenboom M. Spironolactone and risk of upper gastrointestinal events: population-based case-control study. <em>BMJ</em>. 2006;333(7563):330. Epub 2006 Jul 13. </p> <p>Yeomans ND, Svedberg LD, Naesdal J. Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use? <em>Int J Clin Pract</em>. 2006;60(11):1401-407. </p> <p>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. <em>Gut.</em> 2007;56(4):475-479. </p> <div id="health_topic_footer"> Review Date:<br /> 6/22/2007<br /> Reviewed By:<br /> Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.<br /> <div style="margin:10px 0px;"> <div style="float:left;margin:0px 10px 5px 0;"> </div> <div style="margin-bottom:5px;"> A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC&#39;s <a href="http://webapps.urac.org/healthwebsiteaccreditation/default.asp?id=878843645" target="_blank">accreditation program</a> 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.&#39;s <a href="http://www.adam.com/EditorialPolicy.html" target="_blank">editorial policy</a>, <a href="http://www.adam.com/About_ADAM/Editorial/process.html" target="_blank">editorial process</a> and <a href="http://www.adam.com/PrivacyStatement.html" target="_blank">privacy policy</a>. 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). </div> <div style="font-weight:bold">A.D.A.M. 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Any duplication or distribution of the information contained herein is strictly prohibited. </div> <div align="center"><a href="http://www.adam.com" target="_blank">adam.com</a></div> </div> </div> </div> </div> </div> <div class="clear"></div> http://www.fitsugar.com/2331791#comment In-Depth Report Wed, 08 Oct 2008 17:35:38 -0700 FitSugar http://www.fitsugar.com/2331791 http://www.fitsugar.com/2331708 <a href="http://www.fitsugar.com/2331708"></a><div id="health_topic"> <div id="health_topic_left"> <div class="left_nav_block"> <h3>In This Report</h3> <ul> <li class="indent"><a href="#adamHeading_2" rel="section">Highlights</a></li> <li class="indent"><a href="#adamHeading_3" rel="section">Introduction</a></li> <li class="indent"><a href="#adamHeading_4" rel="section">Causes</a></li> <li class="indent"><a href="#adamHeading_5" rel="section">Risk Factors</a></li> <li class="indent"><a href="#adamHeading_6" rel="section">Symptoms</a></li> <li class="indent"><a href="#adamHeading_7" rel="section">Complications</a></li> <li class="indent"><a href="#adamHeading_8" rel="section">Barrett's Esophagus</a></li> <li class="indent"><a href="#adamHeading_9" rel="section">Diagnosis</a></li> <li class="indent"><a href="#adamHeading_10" rel="section">Treatment</a></li> <li class="indent"><a href="#adamHeading_11" rel="section">Prevention</a></li> <li class="indent"><a href="#adamHeading_12" rel="section">Medications</a></li> <li class="indent"><a href="#adamHeading_13" rel="section">Surgery</a></li> <li class="indent"><a href="#adamHeading_14" rel="section">Resources</a></li> <li class="indent"><a href="#adamHeading_15" rel="section">References</a></li> </ul> </div> </div> <div id="health_topic_right"> <div id="health_topic_from_adam"> HEALTH GUIDE REFERENCE FROM A.D.A.M </div> <div id="health_topic_content"> <h3 id="adamHeading_2">Highlights</h3> <p><b>New Research</b> </p> <ul> <li><em>Obesity and GERD</em>. Increased weight in women is linked to more frequent GERD symptoms, according to the Nurses' Health Study, which included 10,545 female participants. Overweight and obese women were two to three times more likely to have frequent symptoms than women of normal weight. GERD symptoms decreased nearly 40% in women whose body mass index (BMI) dropped by more than 3.5, compared to women whose BMI remained the same.</li> <li><em>Proton-Pump Inhibitors and Bone Fracture</em>. Long-term use of PPIs may increase the risk of hip fractures in older adults, according to a study in the <em>Journal of the American Medical Association</em>. People taking high doses of PPIs for more than a year were 2.6 times as likely to fracture a hip as those who were not taking the drug. The authors suggested that the stomach acids blocked by PPIs may be needed to absorb calcium, or the drugs may interfere with the body's natural process of breaking down and rebuilding bones.</li> <li><i>PPIs and H2 Blockers in Children.</i> Otherwise healthy children who take PPI inhibitors or H2 blockers may be at increased risk for intestinal and respiratory infections, according to a study of 186 children with GERD. The rate of gastroenteritis and community-acquired pneumonia significantly increased in children who were taking these medications when researchers compared the 4 months before and after enrollment in the study.</li> </ul> <p><strong>New Approval</strong> </p> <ul> <li><i>Proton-Pump Inhibitor Approved for Adolescents.</i> Esomeprazole (Nexium) delayed-release capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. Research shows that this medication reduces heartburn symptoms in adolescents.</li> </ul> <h3 id="adamHeading_3">Introduction</h3> <p>Gastroesophageal reflux disease (GERD) is a condition in which acids from the stomach move backward into the esophagus (an action called reflux). <i>Reflux</i> occurs if the muscular actions in the esophagus or other protective mechanisms fail. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331695" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an animation about heartburn.</div> </div> <p>The hallmark symptoms of GERD are: </p> <ul> <li><i>Heartburn</i>: a burning sensation in the chest and throat.</li> <li><i>Regurgitation</i>: a sensation of acid backed up in the esophagus.</li> </ul> <p>Although acid is a primary factor in damage caused by GERD, other products of the digestive tract, including pepsin and bile, can also be harmful. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">Heartburn is a condition in which the acidic stomach contents back up into the esophagus, causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux that causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.</div> </div> </div> <p>The esophagus, commonly called the <i>food pipe</i>, is a narrow muscular tube about nine-and-a-half inches long. It begins below the tongue and ends at the stomach. The esophagus is narrowest at the top and bottom; it also narrows slightly in the middle. The esophagus consists of three basic layers: </p> <ul> <li>An outer layer of fibrous tissue.</li> <li>A middle layer containing smoother muscle.</li> <li>An inner membrane, which contains numerous tiny glands.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331343" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an image of the esophagus.</div> </div> <p>When a person swallows food, the esophagus moves it into the stomach through the action of peristalsis, wave-like muscle contractions. In the stomach, the starch, fat, and protein in food are broken down by acid and various enzymes, notably hydrochloric acid and pepsin. The lining of the stomach has a thin layer of mucous that protects it from these fluids. </p> <p>If acid and enzymes back up into the esophagus, however, its lining offers only a weak defense. The esophagus is protected using specific muscles and other factors. </p> <p>The most important structure protecting the esophagus may be the <i>lower esophageal sphincter</i> (<i>LES</i>). The LES is a band of muscle around the bottom of the esophagus where it meets the stomach. </p> <ul> <li>The LES opens after a person swallows to let food enter the stomach and then immediately closes to prevent regurgitation of the stomach contents, including gastric acid.</li> <li>The LES maintains this pressure barrier until food is swallowed again.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331407" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an image of the stomach.</div> </div> <p>If the pressure barrier is not sufficient to prevent regurgitation and acid backs-up (reflux), then peristaltic action of the esophagus serves as an additional defense mechanism and pushes the contents back down into the stomach. </p> <p><i>Esophagitis.</i> In most people, GERD symptoms are short-lived and occur infrequently. In about 20% of cases, however, the condition becomes chronic. When the acid causes irritation or inflammation, the condition is called <i>esophagitis</i>. If the damage becomes extensive and injures the esophagus, the disorder is known as <i>erosive esophagitis.</i> </p> <p><i>Non-Erosive Esophageal Reflux Disease.</i> Symptoms of gastroesophageal reflux disease can occur without any signs of inflammation or injury to the esophagus. This condition is also referred to as non-erosive esophageal reflux disease (NERD). NERD rarely progresses to full-blown GERD. Patients with NERD have no signs of inflammation or erosion in the esophagus, but they experience certain symptoms of GERD, such as burning sensations behind the breastbone for at least 3 months. Researchers suggest that nerves lying near the surface of the lining become exposed to acid that has penetrated the layers. The nerves then trigger prolonged and painful symptoms in response. </p> <p><i>Barrett's Esophagus.</i> A small percentage of patients with GERD may eventually develop Barrett's esophagus, a serious complication of GERD that results in precancerous changes in the tissue lining the esophagus. </p> <p><em>Eosinophilic Esophagitis.</em> This is a distinct disorder characterized by difficult or painful swallowing. It can occur along with GERD. The lining of the esophagus develops furrows and rings. This condition can be treated with swallowed fluticasone propionate, the active ingredient in some asthma medications. </p> <h3 id="adamHeading_4">Causes</h3> <p>Anyone who eats a large amount of acidic foods can have mild and temporary heartburn. This is especially true when lifting, bending over, or taking a nap after eating a large meal high in fatty, acidic foods. Persistent GERD, however, may be due to various conditions, including abnormal biologic or structural factors. </p> <p>The band of muscle tissue called the LES is responsible for closing and opening the lower end of the esophagus and is essential for maintaining a pressure barrier against contents from the stomach. It is a complex area of smooth muscles and various hormones. If it weakens and loses tone, the LES cannot close up completely after food empties into the stomach. In such cases, acid from the stomach backs up into the esophagus. Dietary substances, drugs, and nervous system factors can weaken the LES and impair its function. </p> <p>A study showed that more than half of GERD patients had abnormal nerve or muscle function in the stomach. These abnormalities cause <i>impaired motility</i>, which is the inability of muscles to act spontaneously. The stomach muscles do not contract normally, which causes delays in stomach emptying, increasing the risk for acid back-up. </p> <p>Some studies suggest that most people with atypical GERD symptoms (such as hoarseness, chronic cough, or the feeling of having a lump in the throat) may have specific abnormalities in the esophagus. (In one study, such abnormalities appeared in 73% of patients who had atypical symptoms.) </p> <p><i>Motility Abnormalities.</i> Problems in spontaneous muscle action (<i>peristalsis</i>) in the esophagus commonly occur in GERD, although it is not clear if such occurrences are a cause or result of long-term effects of GERD. </p> <p><i>Adult-Ringed Esophagus.</i> This condition is characterized by an esophagus with multiple rings and persistent trouble with swallowing (including getting food stuck in the esophagus). It occurs mostly in men. </p> <p>The <i>hiatus</i> is a small hole in the diaphragm through which the esophagus passes into the stomach. It normally fits very snugly, but it may weaken and enlarge. When this happens, part of the stomach muscles may protrude into it, producing a condition called <i>hiatal hernia</i>. It is very common, occurring in over half of people over 60 years old, and is rarely serious. Until recent years, it was believed that most cases of persistent heartburn were caused by a hiatal hernia. Hiatal hernia may impair LES muscle function. Studies have failed to confirm evidence, however, that it is a common cause of GERD, although its presence may increase GERD symptoms in patients with both conditions. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">A hiatal hernia occurs when part of the stomach protrudes up into the chest through the sheet of muscle called the diaphragm. This may result from a weakening of the surrounding tissues and may be aggravated by obesity or smoking.</div> </div> </div> <p>Studies indicate that 31 - 43% of reflux may be hereditary. An inherited risk exists in many cases of GERD, possibly because of inherited muscular or structural problems in the stomach or esophagus. Genetic factors may play an especially strong role in susceptibility to Barrett's esophagus, a precancerous condition caused by very severe GERD. </p> <p>At least half of people with asthma also have GERD. Some experts speculate that the coughing and sneezing accompanying asthmatic attacks cause changes in pressure in the chest that can trigger reflux. Certain asthma drugs that dilate the airways may relax the LES and contribute to GERD. On the other hand, GERD has been associated with a number of other upper respiratory problems and may be a cause of asthma, rather than a result. </p> <p>Crohn's disease is a chronic ailment that causes inflammation and injury in the colon and other parts of the gastrointestinal tract, including the esophagus. Other disorders that may affect areas that can contribute to GERD include diabetes, any gastrointestinal disorder, peptic ulcers, lymphomas, and cancer. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331322" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an image of inflammatory bowel disease.</div> </div> <p><i>Helicobacter Pylori</i>, also called <i>H. pylori</i>, is a bacterium found in the mucous membranes and is now known to be a major cause of peptic ulcers. Antibiotics used to eradicate <i>H. pylori</i> are now accepted treatment for curing ulcers. Of some concern, however, are studies indicating that <i>H. Pylori</i> may actually protect against GERD by reducing stomach acid. Furthermore, curing ulcers by eliminating the bacteria might actually trigger GERD in some people. Studies are mixed, however, on whether patients with cured <i>H. Pylori</i> infections are at risk for GERD. An analysis of 8 studies reported no higher risk for GERD after antibiotic treatments, nor was GERD any worse in patients who already had it. Seven of the 8 studies, however, were conducted only 2 months after antibiotic treatment. Longer follow-up studies are needed to determine long-term consequences, if any. </p> <p>In any case, the bacteria should be eradicated in infected patients with existing GERD who are taking ongoing acid suppressing agents. There is some evidence that the combination of <i>H. pylori</i> and chronic acid suppression in these patients can lead to atrophic gastritis, a precancerous condition in the stomach. </p> <p>In some cases, the esophagus appears normal, but GERD symptoms are present. This may indicate an over-reaction of the immune system to irritants that are introduced into the esophagus. In such cases, the immune system reacts with an exaggerated (or hyper-reactive) response, triggering the release of certain factors that end up causing inflammation and possibly injury. (This event is similar to the asthmatic response in the airways.) </p> <p><i>NSAIDs.</i> Nonsteroidal anti-inflammatory drugs (NSAIDs), common causes of peptic ulcers, may also cause GERD and increase severity in people who already have GERD. In a 3-year study of 25,000 people, NSAID users were twice as likely to have GERD symptoms as non-users. Symptoms did not become evident until after about 6 months of regular use. There are dozens of NSAIDs, including over-the-counter aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve), as well as prescription anti-inflammatory medicines. A person with GERD who takes the occasional aspirin or other NSAID will not necessarily experience adverse effects. This is especially true if there are no risk factors or indications of ulcers. Acetaminophen (Tylenol), which is NOT an NSAID, is a good alternative for those who want to relieve mild pain. It does not, however, relieve inflammation. </p> <p><i>Other Drugs</i>. Many other drugs can cause GERD, including but not limited to the following: calcium channel blockers (used to treat high blood pressure and angina), anticholinergics (used in drugs that treat urinary tract disorders, allergies, and glaucoma), beta adrenergic agonists (used for asthma and obstructive lung diseases), dopamine (used in Parkinson's disease), bisphosphonates (used to treat osteoporosis), sedatives, antibiotics, potassium, or iron pills. </p> <p>Weakened peristaltic movement in the esophagus may contribute to GERD. If the mucous membrane is impaired, even a normal amount of acid can harm the esophagus. Pressure on the abdomen caused by obesity and also wearing tight clothing can contribute to acid backing up into the esophagus. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331696" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an image of peristalsis.</div> </div> <h3 id="adamHeading_5">Risk Factors</h3> <p>GERD occurs monthly in about half of American adults. People of all ages are susceptible to GERD. Elderly people with GERD tend to have a more serious condition than younger people. </p> <p><i>Eating Pattern.</i> Anyone who eats a heavy meal and subsequently lies on the back or bends over from the waist is at risk for an attack of heartburn. Anyone who snacks at bedtime is at high risk for heartburn. </p> <p><i>Pregnancy.</i> Pregnant women are particularly vulnerable to heartburn in their third trimester as the growing uterus puts increasing pressure on the stomach. Heartburn in such cases is often resistant to dietary interventions and even antacids. </p> <p><i>Obesity.</i> A number of studies suggest that obesity contributes to GERD and may increase the risk for erosive esophagitis in GERD patients. The Nurses' Health Study found that being overweight or obese significantly increased GERD symptoms in women. The higher a woman's body mass index (BMI), the study found, the more frequent were her symptoms. Women who lost weight in the study saw a decrease in their symptoms. Research suggests that the prevalence of GERD symptoms among obese patients has been underreported. Other researchers have reported that increased BMI is associated with a higher risk for cancer of the esophagus (esophageal adenocarcinoma). </p> <p><i>Respiratory Diseases.</i> People with asthma are at very high risk for GERD. One study indicated that patients with chronic obstructive pulmonary diseases (e.g., emphysema or chronic bronchitis) were more likely to have GERD. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">Chronic obstructive pulmonary disease (COPD) refers to chronic lung disorders that result in blocked air flow in the lungs. The two main COPD disorders are emphysema and chronic bronchitis, the most common causes of respiratory failure. Emphysema occurs when the walls between the lung's air sacs become weakened and the sacs get enlarged and filled with too much air. Damage from COPD is usually permanent and irreversible.</div> </div> </div> <p><i>Smoking.</i> Increasing evidence indicates that smoking raises the risk for GERD. Studies suggest that smoking reduces LES muscle function, increases acid secretion, impairs muscle reflexes in the throat, and damages protective mucous membranes. Smoking reduces salivation, which helps neutralize acid. Whether it is the smoke, nicotine, or both that triggers GERD is unknown. Some people who use nicotine patches to quit smoking, for example, experience heartburn, but it is not clear if it's the nicotine or stress that produces acid back-up. </p> <p><i>Alcohol Use.</i> Alcohol has mixed effects on GERD. It relaxes the LES muscles and, in high amounts, may irritate the mucous membrane of the esophagus. All alcoholic beverages increase stomach acid levels. A combination of heavy alcohol use and smoking increases the risk for esophageal cancer. (Small amounts of alcohol, however, may actually protect the mucosal layer.) </p> <p>In general, overweight Caucasian males over 40 are at highest risk for complications, notably Barrett's esophagus. Others at high risk for severe symptoms, inflammation, or both include: </p> <ul> <li>People who use nonsteroidal anti-inflammatory drugs (NSAIDs). Studies suggest that certain NSAID users are at higher risk for GERD, including older adults, women, alcohol and tobacco users, and patients with asthma, hiatal hernia, or obesity. One study reported that NSAIDs put people at risk for ulcers but not for erosive esophagitis or strictures. Interestingly, NSAIDs are being studied for protection <i>against</i> Barrett's esophagus.</li> <li>People with hiatal hernia</li> </ul> <p>GERD is very common in children of all ages, but it is usually mild. Heartburn has been reported in 1.8% of 3-year-olds and in 5.2% of young people 10 - 17 years old. Children with the following conditions are at higher risk for severe GERD: </p> <ul> <li>Neurologic impairments</li> <li>Food allergies</li> <li>Scoliosis</li> <li>Cyclic vomiting</li> <li>Cystic fibrosis</li> <li>Problems in the lungs, ear, nose, or throat</li> <li>Any medical condition affecting the digestive tract</li> </ul> <p><em>Symptoms in Children.</em> A physician should examine any child who has the following symptoms as soon as possible, because they may indicate complications such as anemia, failure to gain weight, or respiratory problems. Symptoms of severe GERD in infants and small children may include: </p> <ul> <li>Chronic coughing</li> <li>Frequent infections</li> <li>Wheezing</li> <li>Gasping or frequent cessation in breathing while asleep (called sleep apnea). However, one study found no association between GERD and apneas in premature infants.</li> <li>Frequent vomiting in infants. About half of all infants up to 3 months old regurgitate milk at least once a day. Some simply spit up; others vomit large amounts after feedings. Vomiting in infants and older children is rarely a sign of GERD. In infants it usually resolves by age one. Severe vomiting -- particularly if it is bilious (green colored) -- always requires a doctor's visit, since it could be a symptom of severe obstruction.</li> <li>Having to burp babies very frequently during and after feeding.</li> </ul> <p>Babies and children may experience these symptoms without having GERD. An Australian study suggested that many infants who have normal irritability may be treated inappropriately for reflux disorders. </p> <p><i>Feeding Problems.</i> Feeding problems may be more severe than previously thought in children with GERD. In one study, children who had GERD and problems swallowing tended to refuse food and were late in eating solids. They also cried more and reacted more negatively in general than non-GERD babies. Such behaviors negatively affected the mothers as well. These findings were supported in an earlier study which reported that children at 1 year who had GERD in infancy were no longer spitting up, but still tended to have negative dining experiences ("too slow," "upsetting"). However, these children were at no greater risk for respiratory illnesses than other 1-year-old children. </p> <p><i>Associations with Asthma and Infections in the Upper Airways.</i> In addition to asthma, GERD is associated with other upper airway problems, including ear infections and sinusitis. Some experts argue that the association with common childhood infections and asthma is unfounded, since GERD is normal in most children. </p> <p><i>Dental Erosion.</i> GERD can cause irreversible loss of tooth enamel. Based on a 2002 study, some experts suggest checking for GERD in children with dental erosions. In the study, no child <i>without</i> GERD experienced loss of tooth enamel. </p> <p><i>Rare Complications in Infants.</i> Although GERD is very common, the following complications are very rare and only occur in certain cases: </p> <ul> <li>Failure to thrive</li> <li>Feeding problems and severe vomiting may cause anemia</li> <li>Acid back-up may be inhaled into the airways and cause pneumonia</li> </ul> <p>The infant's life may be in danger if acid reflux causes spasms in the larynx severe enough to block the airways. In fact, some experts believe this action may contribute to sudden infant death syndrome (SIDS). More research is needed to determine whether this association is valid. </p> <p><em>Managing GERD in Infancy.</em> Here are some hints on managing GERD in infants: </p> <ul> <li>During and after feeding, infants should be positioned vertically and burped frequently.</li> <li>If a baby with GERD is fed formula, the mother should ask the doctor how to thicken it in order to prevent splashing up from the stomach.</li> <li>Parents of infants with GERD should discuss the baby's sleeping position with their pediatrician. Experts strongly recommend that all healthy infants sleep on their backs to help prevent sudden infant death syndrome (SIDS). For babies with GERD, however, lying on the back may obstruct the airways. In one study, infants with gastroesophageal reflux who spent prolonged periods of time in infant seats, including car seats, had more reflux than those who spent waking time on their stomachs. If the physician recommends that babies with GERD sleep on their stomachs, parents should be sure that their infant's mattress is very firm, possibly tilted up at the head, and that there are no pillows. The baby's head should be turned so that the mouth and nose are completely unobstructed.</li> <li>Because food allergies may trigger GERD in children, parents may want to discuss a dietary plan with their physician that starts the child on formulas using non-allergenic proteins, and then incrementally adds other foods until symptoms are triggered.</li> </ul> <p><em>Managing GERD in Children.</em> The same drugs used in adults may be tried in children with chronic GERD. While some drugs are available over the counter, they should not be given to children without physician supervision. </p> <ul> <li>Milder medications, such as antacids, are used first.</li> <li>H2 blockers may be tried next. They are available over the counter and include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). The FDA has issued a warning on Pepcid AC for adults with kidney problems.</li> <li>Proton-pump inhibitors (PPIs), such as omeprazole (Prilosec) and lansoprazole (Prevacid), are even more powerful agents that suppress the production of stomach acid. Delayed-release esomeprazole (Nexium) capsules have been approved for use in children ages 12 - 17 for the short-term treatment of GERD. One study found that esomeprazole (Nexium) in either a 20 or 40 mg dose once a day significantly reduced heartburn symptoms in adolescents. PPIs appear to be safe and effective even for children as young as 1 year old who fail the less intensive therapies. However, a 2006 study found that otherwise healthy children who were treated with H2 blockers and PPIs had an increased risk of developing respiratory and intestinal infections.</li> </ul> <p>Surgical fundoplication involves wrapping the upper curve of the stomach (fundus) around the esophagus. The goal of this surgical technique is to strengthen the LES. Until recently, surgery was the primary treatment for children with severe complications from GERD because older drug therapies had severe side effects, were ineffective, or had not been designed for children. However, with the introduction of proton-pump inhibitor drugs, some children may be able to avoid surgery. Surgical fundoplication can be performed laparoscopically through small incisions. In one study, of 238 children from 5 months to 16 years of age who underwent laparoscopic fundoplication, all but 9 were symptom free at least 5 years after the surgery. A 2006 study found that children who underwent antireflux surgery before age 4 were less likely to be hospitalized again, or to have reflux-related events such as pneumonia and esophagitis after the surgery. </p> <h3 id="adamHeading_6">Symptoms</h3> <p><i>Heartburn.</i> Heartburn is the primary symptom of GERD. It is a burning sensation that radiates up from the stomach to the chest and throat. Heartburn is most likely to occur in connection with the following activities: </p> <ul> <li>After a heavy meal</li> <li>Bending over</li> <li>Lifting</li> <li>Lying down, particularly on the back</li> </ul> <p>According to one study, nearly three-quarters of patients with frequent GERD symptoms experience them at night. Patients with nighttime GERD also tend to experience more severe pain than those whose symptoms occur at other times. One study found that patients with nighttime pain reported levels of severity that were similar to those reported in angina and heart failure. </p> <p>The severity of heartburn does not necessarily indicate actual injury in the esophagus. For example, Barrett's esophagus, which causes precancerous changes in the esophagus, may trigger few symptoms, especially in elderly people. On the other hand, people can suffer severe heartburn without the presence of damage to the esophagus. </p> <p><i>Dyspepsia.</i> Up to half of GERD patients have <i>dyspepsia,</i> a syndrome consisting of the following: </p> <ul> <li>Pain and discomfort in the upper abdomen</li> <li>Fullness in the stomach</li> <li>Nausea after eating</li> </ul> <p>People can have dyspepsia without having GERD. </p> <p><i>Regurgitation.</i> Regurgitation is the feeling of acid backing up in the throat. Sometimes acid regurgitates as far as the mouth and can be experienced as a "wet burp." Uncommonly, it may come out forcefully as vomit. </p> <p>Many patients with GERD do not experience heartburn or regurgitation. Elderly patients with GERD often have less typical symptoms than do younger people. Instead symptoms may appear in other locations. </p> <p><i>Chest Sensations or Pain.</i> Patients may have the sensation that food is trapped behind the breastbone. Chest pain is a common symptom of GERD. It is very important to differentiate it from chest pain caused by heart conditions, such as angina and heart attack. </p> <p><i>Symptoms in the Throat.</i> Less commonly, GERD may produce symptoms that occur in the throat: </p> <ul> <li>Acid laryngitis. A condition that includes hoarseness, dry cough, the sensation of having a lump in the throat, and the need to repeatedly clear the throat.</li> <li>Trouble swallowing (<i>dysphagia</i>). In severe cases, patients may even choke or food may become trapped in the esophagus, causing severe chest pain. This may indicate a temporary spasm that narrows the tube, or it could also be an indication of serious esophageal damage or abnormalities.</li> <li>Chronic sore throat</li> <li>Persistent hiccups</li> </ul> <p><i>Coughing and Respiratory Symptoms.</i> Asthmatic symptoms, such as coughing and wheezing, may occur. In fact, in one study, GERD alone accounted for 41.1% of cases of chronic cough in nonsmoking patients. The incidence was even higher when GERD and asthma were combined. </p> <p><i>Chronic Nausea and Vomiting.</i> Nausea that persists for weeks or even months and is not attributable to a common cause of stomach upset may be a symptom of acid reflux. In rare cases, vomiting can occur as often as once a day. All other causes of chronic nausea and vomiting should be ruled out, including ulcers, stomach cancer, obstruction, and pancreas or gallbladder disorders. </p> <h3 id="adamHeading_7">Complications</h3> <p>Nearly everyone has an attack of heartburn at some point in their lives. In the vast majority of cases the condition is temporary and mild, causing only transient discomfort. If patients develop persistent gastroesophageal reflux disease with frequent relapses, however, and it remains untreated, serious complications may develop over time. They can include the following: </p> <ul> <li>Erosive esophagitis (severe inflammation in the esophagus)</li> <li>Severe narrowing (<i>stricture</i>) of the esophagus</li> <li>Barrett's esophagus</li> <li>Problems in other areas, including the teeth, throat, and airways leading to the lungs</li> </ul> <p>Older people are at higher risk for complications from persistent GERD. The following conditions also put individuals at risk for recurrent and serious GERD: </p> <ul> <li>The esophagus is very inflamed.</li> <li>Initial symptoms are severe.</li> <li>Symptoms persist in spite of treatments that successfully heal the esophagus.</li> <li>There are severe underlying muscular abnormalities.</li> </ul> <p>Erosive esophagitis develops in chronic GERD patients when acid causes enough irritation and inflammation to produce extensive injuries in the esophagus. Some studies have suggested that overweight Caucasian males with GERD are at highest risk for this condition. In anyone, however, the longer and more severe the GERD condition, the higher the risk for erosive esophagitis. </p> <p><i>Bleeding.</i> In one study, bleeding occurred in more than 8% of patients with erosive esophagitis (severe inflammation of the esophagus), which is associated with GERD. In very severe cases, the patient may detect dark-colored, tarry stools (indicating the presence of blood) or may vomit blood, particularly if ulcers have developed in the esophagus. This is a sign of severe damage and requires immediate attention. </p> <p>Sometimes long-term bleeding can result in iron-deficiency anemia and may even require emergency transfusions. This condition can occur without heartburn or other warning symptoms, or even obvious blood in the stools. </p> <p><i>Barrett's Esophagus (BE) and Esophageal Cancer.</i> In some cases, BE develops as an advanced stage of erosive esophagitis. BE results in abnormal cellular changes in the esophagus that, in turn, put a patient at risk for esophageal cancer. There are many issues involved with BE, however, including its prevalence and true severity, that are unresolved. </p> <p>Of note, GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms. </p> <p>If the esophagus becomes severely injured over time, narrowed regions called <i>strictures</i> can develop, which may impair swallowing (dysphagia). Food may even become blocked in some cases. Stretching procedures or surgery may be required to restore normal swallowing. Paradoxically, strictures may actually prevent other GERD symptoms by helping to keep acid from traveling up the esophagus. </p> <p><i>Asthma.</i> Asthma and GERD often occur together. Studies report that reflux disorder coincides with 32 - 80% of asthma cases. Some theories for the causal connection between GERD and asthma are as follows: </p> <ul> <li>Acid leaking from the lower esophagus in GERD stimulates the <i>vagus nerves</i>, which run through the gastrointestinal tract. These stimulated nerves trigger the nearby airways in the lung to constrict, which causes asthma symptoms.</li> <li>Acid back-up that reaches the mouth may be inhaled into the airways (<i>aspirated</i>). Here, the acid triggers a reaction in the airways that causes asthma symptoms.</li> </ul> <p>There is some evidence that asthma causes GERD. In contrast, some evidence suggests that GERD causes asthma. Some clinical trials report that treating GERD in patients who also have asthma reduces symptoms of both conditions. Not all such patients report improved asthma symptoms with GERD treatments, and these treatments do not appear to have much effect on actual lung function. One study suggested that this approach works in asthmatic individuals who tended to be overweight and to have severe GERD in the lower part of the esophagus. </p> <p><i>Other Respiratory and Airway Conditions.</i> Current studies indicate an association between GERD and various upper respiratory problems that occur in the sinuses, ear and nasal passages, and airways of the lung. People with GERD appear to have an above-average risk for chronic bronchitis, chronic sinusitis, emphysema, pulmonary fibrosis (lung scarring), and recurrent pneumonia. If a person inhales fluid from the esophagus (aspirates) into the lungs, serious pneumonia can occur. It is not yet known whether treatment of GERD would also reduce the risk for these respiratory conditions. </p> <p>Dental erosion (the loss of the tooth's enamel coating) is a very common problem among GERD patients, including children. It results from the acid backing up into the mouth and eroding the enamel. </p> <p>An estimated 20 - 60% of patients with GERD have atypical symptoms in the throat (hoarseness, sore throat) without any significant heartburn. A failure to diagnose and treat GERD may lead to persistent throat conditions such as chronic laryngitis, hoarseness, difficulty in speaking, sore throat, cough, constant throat clearing, and granulomas (soft, pink bumps) on the vocal cords. </p> <p>GERD commonly occurs with obstructive sleep apnea, a condition in which breathing stops temporarily but repeatedly during sleep. It is not clear which condition is responsible for the other, but GERD is particularly severe when both conditions occur together. One study reported that spasms in the vocal cords caused by acid reflux may block the flow of air and cause sleep apnea in adults. On the other hand, other research suggests that the disordered breathing in sleep apnea alters pressure in the chest area and causes GERD. Both conditions may also have risk factors in common, such as sleeping on the back. Studies suggest that in such patients GERD can be markedly improved with a continuous positive airway pressure (CPAP) device, which opens the airways and is the standard treatment for severe sleep apnea. </p> <h3 id="adamHeading_8">Barrett's Esophagus</h3> <p><i>Barrett's esophagus</i> (BE) is a serious condition in which changes occur in the cells that line the lower esophagus and cause the cells to become abnormal and precancerous. Barrett's esophagus is categorized as either long-segment or short-segment disease: </p> <ul> <li>Long-segment BE occurs when abnormal cells affect 3 cm or more of the esophagus. This condition occurs in about 3 - 7% of GERD patients. It is associated with a more severe condition.</li> <li>Short-segment BE affects less than 3 cm of the esophagus and is found in about 10 - 17% of GERD patients.</li> </ul> <p>About 10% of patients with symptomatic GERD have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. Some studies suggest that individuals at highest risk for BE are obese white males over the age of 50 with persistent GERD who drink alcohol. However, a number of studies have reported no relationship between alcohol use or being male and overweight with BE. Such studies have also reported no higher risk in smokers or relatives of BE patients. Only the persistence of symptoms suggested a higher risk. Nevertheless, not all patients with BE have either esophagitis or symptoms of GERD. </p> <p>The true prevalence of BE, in fact, is not entirely clear, since studies suggest that significantly more than half of people with BE have no GERD symptoms at all. BE, then, is likely to be much more prevalent and probably less harmful than is currently believed. (BE that occurs without symptoms can only be identified in clinical trials or in autopsies, so it is difficult to determine the true extent.) Some evidence suggests that the presence of specific immune factors may be involved in determining the development of BE. </p> <p>The rate of esophageal cancer has been rising steadily at about 2% a year in white men. The American Cancer Society estimates that there will be 15,560 new cases of esophageal cancer and 13,940 deaths from the disease in 2007. Esophageal cancer is also very difficult to cure. The 5-year survival rate for all stages of esophageal cancer is 17% in white patients, and 12% in African-American patients. Most cases of esophageal cancer start with BE, with less than half of the cases developing with any symptoms. Of note, only a minority of BE patients develop cancer. Some evidence suggests that acid reflux may contribute to the development of cancer in BE. Researchers have speculated that exposure to extra acid in people with Barrett's esophagus produces more of an enzyme called NOX5-S, which may put stress on cells, leading to DNA damage. </p> <p>Evidence suggests that asymptomatic BE is quite common in the general population, and if true, BE would pose far less of a threat than is now believed. (GERD itself poses no significant risk for esophageal cancer. One study reported an annual incidence of 6.5 cancer cases per 10,000 people with regular GERD symptoms.) </p> <p>Barrett's esophagus is diagnosed using endoscopy, a procedure that involves inserting a tube down the throat so that the physician can view the esophagus. </p> <p><i>Monitoring High-Risk GERD Patients.</i> Some experts recommend a one-time screening test for BE using endoscopy in high-risk patients (such as Caucasian overweight men) with chronic GERD. </p> <p><i>Monitoring Patients with Barrett's Esophagus for Cancer.</i> Periodic endoscopy is recommended for detecting early cancer in patients who have been diagnosed with Barrett's esophagus. In an important 2002 study, 5-year survival was 73% in BE patients whose cancer was detected with endoscopy screening and was 0% in patients who were not regularly screened. </p> <p>To date, no treatments can reverse the cellular damage done after Barrett's esophagus has developed, although some procedures are showing promise. </p> <p><i>Medications.</i> Some evidence suggests that a combination of proton-pump inhibitors to suppress acid, coupled with anti-inflammatory COX-2 inhibitors, might be a promising approach. </p> <ul> <li>Proton-Pump Inhibitors. Some experts recommend very aggressive treatments to reduce acid reflux using high-dose proton-pump inhibitors. The standard agent has been omeprazole (Prilosec). Newer oral PPIs include lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). Even when drugs relieve symptoms completely, the condition usually recurs within months after the drugs are discontinued. In chronic cases, drugs may need to be taken throughout a patient's life. These agents provide no protection against Barrett's esophagus. Still, there is some evidence that acid reflux may contribute to the development of cancer in BE, although it is not yet known if acid blockers have any protective effects against cancer in these patients.</li> <li>COX-2 (cyclooxygenase-2) inhibitors reduce inflammation and pain, as do well-known agents such as aspirin and ibuprofen, but COX-2 inhibitors may pose less of a risk for peptic ulcers and bleeding. Some early evidence suggests they may be protective against cancerous changes in patients with Barrett's esophagus. However, Vioxx and Bextra have been withdrawn from the market due to their association with an increased risk of heart attack. Celebrex remains available, but must be used with caution, especially by patients with cardiovascular risk factors. Also, research is mixed on the benefits of NSAIDs for esophageal cancer. Some studies have found that they may decrease the risk of developing or dying from esophageal cancer. However, a 2007 study indicated that a small dose of Celebrex did not prevent the progression of cancer in Barrett's esophagus patients.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <p><i>Procedures to Remove the Mucous Lining.</i> Various techniques or devices have been developed to remove (ablate) the mucous lining of the esophagus. The intention is to remove early cancerous or precancerous tissue and allow regrowth of new and hopefully healthy tissue in the esophagus. Such techniques include photodynamic therapy (PDT) or laser, electrical, or heat probes. </p> <p>Studies on the use of these ablation techniques combined with aggressive use of proton-pump inhibitors or surgical treatments are very encouraging. Some of these techniques may eventually even offer potential cures. At this time, they can be very effective in removing harmful tissue, although the benefits do not last in all patients. In one study, an average of 5.6 years after anti-GERD surgery and laser treatment, only a third of patients showed no evidence of renewed precancerous cell growth. These procedures also have complications, such as possible problems swallowing, that patients should discuss with their physician. </p> <p><i>Esophagectomy.</i> Esophagectomy is the surgical removal of all or part of the esophagus. Patients with Barrett's esophagus, who are otherwise healthy, are candidates for this procedure if endoscopy shows developing cancer. After esophageal removal, in total or in part, a new conduit for foods and fluids must be established to replace the absent esophagus. Alternatives include the stomach, colon, and part of the small intestine called the jejunum. The stomach is the optimal choice. </p> <h3 id="adamHeading_9">Diagnosis</h3> <p>If a patient suffers from <i>chronic</i> heartburn, chances are good the patient also has GERD. (Occasional heartburn does not necessarily indicate the presence of GERD.) The following is the general diagnostic approach: </p> <ul> <li>A physician can usually make an easy diagnosis of GERD if the patient finds relief from persistent heartburn and acid regurgitation after taking antacids for short periods.</li> <li>If the diagnosis is uncertain but the physician still suspects GERD, a drug trial using a proton-pump inhibitor medication, such as omeprazole (Prilosec) identifies 80 - 90% of people with the conditions. This class of medication blocks stomach acid secretion.</li> </ul> <p>Laboratory or more invasive tests, including endoscopy, may be required if the diagnosis is still uncertain, if atypical symptoms are present, if Barrett's esophagus is suspected, or if complications, such as signs of bleeding or difficulty in swallowing, are present. Some of these tests are described below. </p> <p>A barium swallow radiograph (x-ray) is useful for identifying structural abnormalities and erosive esophagitis (severe inflammation). When taking this test, the patient drinks a solution containing barium, then x-rays are taken. This test can show stricture, active ulcer craters, hiatal hernia, erosion, or other abnormalities. The test cannot reveal mild irritation. </p> <p>Upper endoscopy, also called <i>esophagogastroduodenoscopy</i> or <i>panendoscopy</i>, is more accurate than a barium-swallow radiograph. It is also more invasive and expensive. It is widely used in GERD, including for identifying and grading severe esophagitis, for periodic monitoring of patients with Barrett's esophagus or for screening people at high risk, or when other complications are suspected. It is also now employed as part of various surgical techniques. </p> <p><i>Endoscopy to Diagnose GERD.</i> Endoscopy may be performed either in a hospital or in a doctor's office: </p> <ul> <li>First, the patient should eat nothing for at least 6 hours before the procedure.</li> <li>The doctor administers a local anesthetic using an oral spray and an intravenous sedative to suppress the gag reflex and to relax the patient.</li> <li>Next, the physician places an endoscope (a thin flexible plastic tube containing a tiny camera) into the patient's mouth and down the esophagus. The procedure does not interfere with breathing. It may be slightly uncomfortable for some patients; others are able to sleep through it.</li> <li>Once the endoscope is in place, the tiny camera allows the physician to see the surface of the esophagus and to search for abnormalities, including hiatal hernia and damage to the mucous lining.</li> <li>The physician performs a biopsy (the removal and microscopic examination of small tissue sections). The biopsy may detect tissue injury indicative of GERD. It may also be used to detect cancer or other conditions, such as yeast (<i>Candida albicans</i>) or viral infections (e.g., herpes simplex and cytomegalovirus). Such infections are more likely to occur in people with impaired immune systems.</li> <li>Complications from the procedure are uncommon. If they occur, complications are almost always mild and typically include minor bleeding from the biopsy site or irritation where medications were injected.</li> </ul> <p>If a patient has moderate-to-severe GERD symptoms and the procedure reveals injury in the esophagus, usually no further tests are needed to confirm a diagnosis. The test is not foolproof, however. A visual view misses about half of esophageal abnormalities. </p> <p><em>Capsule Endoscopy.</em> Capsule endoscopy was first approved for use in 2001. A new version of this pill-sized camera, renamed PillCam, was approved by the FDA in 2004. PillCam reduces the imaging time previously required by the original capsule endoscopy technique. The PillCam capsule contains tiny video cameras on both ends. After the patient swallows the capsule, a series of 2600 color pictures are transmitted to a recording device where they can be downloaded and interpreted by a doctor. A newer version of the PillCam takes 14 frames per second as opposed to the 4 frames per second of the original device. The newer PillCam is superior in visualizing the entire esophagus and in identifying GERD. The entire procedure takes 20 minutes. The capsule is naturally passed through the digestive system within 24 hours. Capsule endoscopy may provide a more attractive and less invasive alternative for patients than traditional endoscopy. However, while capsule endoscopy is useful as a screening device for diagnosing esophageal conditions such as GERD and Barrett's esophagus, traditional endoscopy is still required for gathering tissue samples or removing polyps. </p> <p>The (ambulatory) pH monitor examination may be employed to determine acid back-up. It is useful when endoscopy has not detected damage to the mucous lining in the esophagus, but GERD symptoms are present. pH monitoring may be used when patients have not found relief from medicine or surgery. The traditional trans-nasal catheter diagnostic procedure involved inserting a tubular probe through the nose and down to the esophagus. The tube was left in place for 24 hours. This test was irritating to the throat, and uncomfortable and awkward for most patients. </p> <p>A new method, known as the Bravo pH test, uses a small capsule-sized data transmitter that is temporarily attached to the wall of the esophagus during endoscopy. The capsule records pH levels and transmits these data to a pager-sized receiver worn by the patient. Patients can continue their usual diet and activity schedule during the 24 - 48-hour monitoring period. After a few days, the capsule detaches from the esophagus, passes through the digestive tract, and is eliminated through a bowel movement. </p> <p>Manometry is a technique that measures muscular pressure. It employs a tube containing various openings, which is placed through the esophagus. As the muscular action of the esophagus exerts pressure on the tube in various locations, a computer connected to the tube measures it. It is useful for the following situations: </p> <ul> <li>To determine if a GERD patient would benefit from surgery by measuring pressure exerted by the lower esophageal sphincter muscles (LES).</li> <li>To detect impaired stomach motility (an inability of the muscles to contract normally), which cannot be surgically corrected with standard procedures.</li> <li>To determine if impaired peristalsis or other motor abnormalities are causing chest pain in people with GERD who have these symptoms.</li> </ul> <p><i>Blood and Stool Tests.</i> Stool tests may show traces of blood that are not visible. Blood tests for anemia should be performed if bleeding is suspected. </p> <p><i>Bernstein Test.</i> For patients with chest pain in which the diagnosis is uncertain, a procedure called the Bernstein test may be useful, although it is rarely used. A tube is inserted through the patient's nasal passage. Then solutions of hydrochloric acid and saline are administered separately into the esophagus. If the acid infusion causes symptoms and the saline solution does not, then a diagnosis of GERD is established. </p> <p>Because many illnesses share similar symptoms, careful analysis and consideration of the patient's history is key to an accurate diagnosis. The following are only a few of the conditions that could accompany or resemble GERD. </p> <p><i>Dyspepsia.</i> The most common disorder confused with GERD is dyspepsia, which is defined as pain or discomfort in the upper abdomen without heartburn. Specific symptoms may include a feeling of fullness (particularly early in the meal), bloating, and nausea. Dyspepsia can be a symptom of GERD, but does not always occur with GERD. The drug metoclopramide (Reglan) helps stomach emptying and may be helpful for this condition. </p> <p><i>Angina and Chest Pain.</i> About 600,000 people come to emergency rooms each year with chest pains. More than 100,000 of these people are believed to actually have GERD. Chest pain from both GERD and from severe angina can occur after a heavy meal. In general, a heart problem is probably not responsible for the pain if it is worse at night and does not occur after exercise. It should be noted that the two conditions often coexist. In fact, there is some theory that in patients with coronary artery disease, acid reflux may actually trigger angina. In such cases, experts believe that acid in the esophagus may activate nerves that temporarily impair blood flow to the heart. </p> <p><i>Asthma</i>. Because asthma and GERD commonly occur together, physicians must be sure that each disorder is diagnosed accurately. </p> <p><i>Other Diseases.</i> Many gastrointestinal diseases (e.g., inflammatory bowel disease, ulcers, intestinal cancers) can cause GERD, but they are often easily identified, since they have other symptoms and affect other areas of the intestinal tract. </p> <h3 id="adamHeading_10">Treatment</h3> <p>Acid suppression continues to be the mainstay for treating GERD. The aim of drug therapy is to reduce the amount of acid present and improve any abnormalities in muscle function of the lower esophageal sphincter (LES), the esophagus, or the stomach. </p> <p>Most cases of gastroesophageal reflux are mild and can be managed with lifestyle changes and over-the-counter medications and antacids. </p> <p>Patients with moderate-to-severe symptoms that do not respond to lifestyle measures, or who are diagnosed at a late stage may be started on more or less potent agents depending on their complications at diagnosis. Experts argue, however, about the best way to initiate drug treatment for GERD in most of these patients. The two major treatment options are known as the step-up and step-down approaches: </p> <ul> <li><i>Step-up</i>. With a step-up drug approach the patient first tries an H2 blocker drug, which is available over the counter. These drugs include famotidine (Pepcid AC), cimetidine (Tagamet HB), ranitidine (Zantac 75), and nizatidine (Axid AR). If the condition fails to improve, therapy is "stepped up" to the more powerful proton-pump inhibitors, usually omeprazole (Prilosec).</li> <li><i>Step-down</i>. A step-<i>down</i> approach first uses a more potent agent, most often a proton-pump inhibitor (PPI), such as omeprazole (Prilosec). When patients have been symptom-free for 2 months or longer, they are then "stepped down" to a half-dose. If symptoms do not recur, the drug is withdrawn. If symptoms recur, the patient is put on high-dose H2 blockers. In one study using this step-down approach, 58% of patients remained symptom-free after a year, with 27% not using any medications at all. Some physicians argue that the step-down approach should be used for most patients with moderate-to-severe GERD.</li> </ul> <p>Recent guidelines indicate that PPIs should be the first drug treatment, and that these drugs should be given once a day for approximately 8 weeks. Even when symptoms are completely relieved by medication, they usually return within a few months after drug treatment has stopped. Long-term maintenance may be necessary. </p> <p>If neither approach relieves symptoms, the physician should look for other conditions. Endoscopy and other tests might be used to confirm GERD and rule out other disorders. In some cases, bile, not acid, may be responsible for symptoms, so that acid-reducing or blocking agents would not be helpful. (Bile is a fluid that is present in the small intestine and gallbladder.) </p> <p>Surgery may be indicated under certain circumstances: </p> <ul> <li>If lifestyle changes and drug treatments have failed</li> <li>In patients with other medical complications</li> <li>In younger people with chronic GERD, who face a lifetime of expense and inconvenience with maintenance drug treatment</li> </ul> <p>Some physicians are recommending surgery as the treatment of choice for many more patients with chronic GERD, particularly since minimally invasive surgical procedures are becoming more widely available, and since only surgery improves regurgitation. Furthermore, persistent GERD appears to be much more serious than was previously believed, and the long-term safety of acid suppression using medication is still uncertain. </p> <p>Nevertheless, anti-GERD procedures have many complications and high failure rates (ranging from 30% at 5 years to 63% at 10 years) and, as with medications, current surgical procedures cannot cure GERD. About 15% of patients still require anti-GERD medications after surgery. Furthermore, about 40% of surgical patients are at risk for new symptoms after surgery (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Finally, evidence -- notably an important 2002 Swedish study -- now strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus. New procedures may improve current results, but at this time patients should consider surgical options very carefully with both a surgeon and their primary doctor. </p> <h3 id="adamHeading_11">Prevention</h3> <p>People with heartburn should first try lifestyle and dietary changes. In one study, 44% of patients who experienced symptoms of gastroesophageal reflux disease (GERD) reported improvement after changing their diet. Some suggestions are the following: </p> <ul> <li>Avoid or reduce consumption of foods and beverages that contain caffeine, chocolate, peppermint, spearmint, and alcohol. Both caffeinated and decaffeinated coffees increase acid secretion.</li> <li>Avoid all carbonated drinks, because they increase the risk for GERD.</li> <li>Although physicians often advise patients with GERD to cut down on fatty foods, many studies have found no evidence that a low-fat or high-fat meal makes any difference in symptom exacerbation. One small study, however, found that the frequency of GERD symptoms increased with a high-fat compared to a low-fat diet. Better studies are needed to confirm this. In any case, as a rule, it is always wise to avoid saturated fats (which are from animal products), and cut down on all fats if one is overweight.</li> <li>Choose low-fat or skim dairy products, poultry, or fish. Increasing protein may help strengthen muscles in the muscle valve.</li> <li>Consume whole-grain products rich in selenium, which may have some protective role against dangerous cell changes in Barrett's esophagus.</li> <li>Eat a diet rich in fruits and vegetables, although it's best to avoid acidic vegetables and fruits (e.g., oranges, lemons, grapefruit, pineapple, tomatoes).</li> </ul> <p>Patients who have trouble swallowing should avoid tough meats, vegetables with skins, doughy bread, and pasta. </p> <p>Nearly three-quarters of patients with frequent GERD symptoms have them at night. Patients with nighttime GERD also tend to experience severe pain. It is very important to take preventive measures before going to sleep. Some suggestions for preventing acid reflux at night are as follows: </p> <ul> <li>After meals, take a walk or, at the very least, remain upright.</li> <li>Avoid bedtime snacks. In general, avoid eating for at least 2 hours prior to bedtime.</li> <li>When going to bed, try lying on the left side rather than on the right. The stomach is located higher than the esophagus when a person sleeps on the right side, which can put pressure on the lower esophageal sphincter (LES), increasing the risk for fluid back-up.</li> <li>Sleep in a tilted position to help keep acid in the stomach at night. To do this, raise the bed at an angle using 4- to 6-inch blocks at the head of the bed and use a wedge-support to elevate the top half of the body. (Extra pillows that only raise the head actually increase the risk for reflux.)</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">A reflux board is prescribed for use in children who have gastroesophageal reflux. A board tilts the child upward while he is lying in bed to prevent the stomach contents from going back into the esophagus and mouth, and possibly into the lungs.</div> </div> </div> <ul> <li>Quitting smoking is essential.</li> <li>People who are overweight should try to reduce food intake and exercise to lose weight.</li> <li>People with GERD should avoid tight clothing, particularly around the abdomen.</li> <li>If possible, GERD patients should avoid nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Motrin, Advil), or naproxen (Aleve), among others. Tylenol (acetaminophen) is a good alternative pain reliever.</li> </ul> <p>Although gum chewing is commonly believed to increase the risk for GERD symptoms, one study reported it might be helpful. Because saliva helps neutralize acid and contains a number of other factors that protect the esophagus, chewing gum 30 minutes after a meal has been found to help relieve heartburn and even protect against damage caused by GERD. Chewing on anything at all can help since it stimulates saliva production. </p> <h3 id="adamHeading_12">Medications</h3> <p>Antacids neutralize digestive acids and are the primary drugs for mild symptoms. They are best used alone for relief of occasional and unpredictable episodes of heartburn. They all work by neutralizing the acid in the stomach. They may also stimulate the defensive systems in the stomach by increasing bicarbonate and mucous secretion. Many antacids are available without a prescription and are the first drugs recommended to relieve heartburn and mild symptoms. Despite the many brands, they all rely on various combinations of three basic ingredients: magnesium, calcium, or aluminum. </p> <p><i>Magnesium</i>. Magnesium salts are available in the form of magnesium carbonate, magnesium trisilicate, and most commonly, magnesium hydroxide (Milk of Magnesia). The major side effect of magnesium salts is diarrhea. Magnesium salts offered in combination products with aluminum (Mylanta and Maalox) balance the side effects of diarrhea and constipation. </p> <p><i>Calcium</i>. Calcium carbonate (Tums, Titralac, and Alka-2) is a potent and rapid acting antacid that can cause constipation. These antacids are actually sources of calcium. There have been rare cases of hypercalcemia (elevated levels of calcium in the blood) in people taking calcium carbonate for long periods of time. This can lead to kidney failure and is very dangerous. None of the other antacids has this side effect. </p> <p><i>Aluminum</i>. Aluminum salts (Amphogel, Alternagel) are also available. The most common side effect of antacids containing aluminum salts is constipation. People who take large amounts of antacids that contain aluminum may also be at risk for calcium loss, which can lead to osteoporosis. </p> <div class="ADAMInlineGraphic"> <div class="ADAMInlineFull"><br /> <div class="ADAMTextBox">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.</div> </div> </div> <p>It is generally believed that liquid antacids work faster and are more potent than tablets, although evidence suggests that they all work equally well. Antacids can interact with a number of drugs in the intestines by reducing their absorption. These drugs include tetracycline, ciprofloxacin (Cipro), propranolol (Inderal), captopril (Capoten), and H2 blockers. Interactions can be avoided by taking the drugs 1 hour before or 3 hours after taking the antacid. Long-term use of nearly any antacid increases the risk for kidney stones. </p> <p>H2 blockers impede acid production by blocking or antagonizing the actions of histamine, a chemical found in the body that encourages acid secretion in the stomach. They are available over the counter and provide symptom relief in about half of GERD patients. It takes 30 - 90 minutes for them to work, but the benefits last for hours. The drugs are usually taken at bedtime. Some people may need to take them twice a day. </p> <p>H2 blockers inhibit acid secretion for 6 - 24 hours and are very useful for people who need persistent acid suppression. They may also prevent heartburn episodes in people who are able to predict its occurrence. In some studies, H2 blockers improved asthmatic symptoms in people who have both conditions. A 2001 study suggested, however, that they rarely provide complete symptom relief for chronic heartburn and dyspepsia and they have done little to reduce office visits to physicians for GERD. </p> <p><i>Brands.</i> Four H2 blockers are currently available in the U.S.: </p> <ul> <li>Famotidine (Pepcid AC). Famotidine (Pepcid AC, Pepcid Oral) is the most potent H2 blocker. The most common side effect of famotidine is headache, which occurs in 4.7% of people who take it. Famotidine is virtually free of drug interactions, but the FDA has issued a warning on its use in patients with kidney problems.</li> <li>Cimetidine (Tagamet, Tagamet HB). Cimetidine (Tagamet) is the oldest H2 blocker. It has few side effects; approximately 1% of people taking it will experience mild temporary diarrhea, dizziness, rash, or headache. Cimetidine interacts with a number of commonly used medications, such as 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.</li> <li>Ranitidine (Zantac, Zantac 75, Zantac Efferdose, Zantac injection, Zantac Syrup). Ranitidine (Zantac) interacts with very few drugs. In a recent study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people less than 60 years old, but there was no difference in older patients. A common side effect associated with ranitidine is headache, which occurs in about 3% of the people who take it.</li> <li>Nizatidine Capsules (Axid AR, Axid Capsules, Nizatidine Capsules). Nizatidine (Axid) is nearly free of side effects and drug interactions. A controlled-release form is proving to help alleviate nighttime GERD symptoms.</li> </ul> <table border="0" cellpadding="3" cellspacing="0"> <tr> <td valign="top"> <p>Famotidine is excreted primarily by the kidney. This can pose a danger to people with kidney problems. Physicians are now being advised by the U.S. Food and Drug Administration (FDA) and Health Canada to reduce the dose and increase the time between doses in patients with kidney failure. Use of the drug in those with impaired kidney function can affect the central nervous system and may result in anxiety, depression, insomnia or drowsiness, and mental disturbances. </p> </td> </tr> </table> <p><i>Drug Combinations.</i> </p> <ul> <li>Over-the-counter antacids and H2 blockers: This combination may be the best approach for many people who experience heartburn after eating. Both classes of drugs are effective in relieving GERD, but have different timing. Antacids work within a few minutes but are short-acting, while H2 blockers take longer but have long-lasting benefits. Pepcid AC combined with an antacid (calcium carbonate and magnesium) is now available as Pepcid Complete.</li> <li>Proton-pump inhibitors and H2 blockers: Physicians sometimes recommend a nighttime dose of an H2 blocker for people who are taking proton-pump inhibitors twice a day. This is based on the belief that adding the H2 blocker will prevent a rise in acid reflux at night. An important 2002 study, however, reported no additional benefits from the nighttime H2 blocker. Some experts recommended an H2 blocker in patients who are on proton-pump inhibitors only to prevent breakthrough symptoms, such as before a heavy meal.</li> </ul> <p><i>Long Term Complications.</i> In most cases, these agents have good safety profiles and few side effects. H2 blockers can interact with other drugs, although some less so than others. In all cases, however, the physician should be made aware of any other drugs a patient is taking. More research is needed. Anyone with kidney problems should use famotidine only under the direction of a physician. </p> <p><i>Concerns and Limitations.</i> Some experts are concerned that the use of acid-blocking drugs in people with peptic ulcers may mask ulcer symptoms and increase the risk for serious complications. </p> <p>These agents provide no protection against Barrett's esophagus. In fact, of concern are reports that long-term acid suppression with these drugs may cause cancerous changes in the stomach in patients who are infected with <i>H. pylori</i>. Research on this question is still ongoing. </p> <p>Proton-pump inhibitors (PPIs) suppress the production of stomach acid and work by inhibiting the molecule in the stomach glands that is responsible for acid secretion, which is called the <i>gastric acid pump</i>. According to recent guidelines, initial drug treatment should be with PPIs once daily for about 8 weeks. </p> <p>The standard agent has been omeprazole (Prilosec), which is now available over the counter without a prescription. Newer prescription oral PPIs include esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix). </p> <p>Studies report significant relief from PPIs in most patients with heartburn. PPIs are effective for healing erosive esophagitis and may also be helpful in patients with chronic laryngitis that is suspected to be caused by GERD. The newer agents provide quicker symptom relief compared to omeprazole. However, a comparison study suggested that, to date, esomeprazole (Nexium) is the only newer oral PPI to show any significant advantage over omeprazole (Prilosec). All PPIs are more effective than the H2 blockers. </p> <p>In addition to relieving most common symptoms, including heartburn, proton-pump inhibitors also have the following advantages: </p> <ul> <li>They are effective in relieving chest pain and laryngitis caused by GERD.</li> <li>They may also reduce acid reflux that typically occurs during strenuous exercise.</li> </ul> <p>Patients with impaired esophageal muscular action are still likely to experience acid breakthrough and reflux at night. Proton-pump inhibitors also may have little or no effect on regurgitation or asthmatic symptoms. Some experts believe, however, that they should be the first drugs of choice, even for patients with milder symptoms. At this time, these drugs are recommended for the following patients: </p> <ul> <li>Those with moderate symptoms that do not respond to H2 blockers</li> <li>Those with severe symptoms</li> <li>Those who have respiratory complications</li> <li>Those who have persistent nausea</li> <li>Those who have esophageal injury</li> </ul> <p>These agents have no affect against non-acid reflux, such as bile back-up. </p> <p><i>Adverse Effects.</i> Proton-pump inhibitors may pose the following concerns: </p> <ul> <li>Side effects are uncommon but may include headache, diarrhea, constipation, nausea, and itching.</li> <li>Proton-pump inhibitors should be avoided by pregnant women and nursing mothers, although recent studies suggest that they do not pose an increased risk of birth defects.</li> <li>They may interact with certain drugs, such as anti-seizure agents (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin).</li> <li>Long-term use of high-dose PPIs may produce vitamin B12 deficiencies, but studies are needed to confirm whether there is any significant risk. High-dose PPIs used over the long-term also may increase the risk of hip fracture in older adults, according to one study.</li> </ul> <p>There is some evidence that acid reflux may contribute to the higher risk of cancer in BE, but it is not yet confirmed whether acid-blockers have any protective effects against cancer in these patients. In fact, the long-term use of proton-pump inhibitors by people with <i>H. pylori</i> may, in theory at least, reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach). This condition is a risk factor for stomach cancer. To compound concerns, long-term use of PPIs may mask symptoms of stomach cancer and so delay a diagnosis. To date, however, there have been no reports of an increased risk of stomach cancer with the long-term use of these drugs. </p> <p>Sucralfate (Carafate) protects the mucous lining in the gastrointestinal tract. It seems to work by sticking to an ulcer crater and protecting it from damage due to stomach acid and pepsin. It may be helpful for maintenance therapy in people with mild-to-moderate GERD. Other than constipation, which occurs in 2.2% of patients, the drug has few side effects. Sucralfate interacts with a wide variety of drugs, however, including warfarin, phenytoin, and tetracycline. </p> <p>Most drugs used for GERD have no effect on non-acid reflux, such as back-up of bile. Baclofen, known as a gamma-amino butyric acid agonist, is commonly used to reduce muscle spasms. Investigators are now showing that it can reduce both acid and non-acid reflux episodes (as much as 70% in one study) and increase LES pressure, an important factor for preventing back-up. </p> <h3 id="adamHeading_13">Surgery</h3> <p>The standard surgical treatment for GERD is <i>fundoplication</i>. The goal of this procedure is twofold: </p> <ul> <li>To increase LES pressure and, therefore, prevent acid back-up (reflux)</li> <li>To repair any present hiatal hernia</li> </ul> <p>There are two primary approaches: </p> <ul> <li>Open Nissen fundoplication (the more invasive technique)</li> <li>Laparoscopic fundoplication</li> </ul> <p>In general, the overall long-term benefits of these procedures are similar. Some studies report that more than 90% of patients are free of heartburn after the operation and satisfied with their choice, even after 5 years. Fundoplication relieves GERD-induced coughs and some other respiratory symptoms in up to 85% of patients. (Its effect on asthma associated with GERD, however, is unclear.) It may enhance stomach emptying and improve peristalsis in about half of patients. (It may actually <i>cause</i> abnormal peristalsis in about 14% of patients, although in such cases the problem does not appear to be very significant.) </p> <p>Still, it has other significant limitations and postoperative problems. For example, the results of one 2003 survey suggested that 18% of surgical patients still required anti-GERD medications and 38% had new symptoms (e.g., gas, bloating, trouble swallowing), with most occurring more than a year after surgery. Other studies have reported similar results. Also, fundoplication does not cure GERD. Finally, evidence from a 2002 Swedish study strongly suggests that the procedure does not reduce the risk for esophageal cancer in high-risk patients, such as those with Barrett's esophagus. </p> <p><i>Candidates.</i> Fundoplication is recommended for patients whose condition includes one or more of the following: </p> <ul> <li>Esophagitis (inflamed esophagus)</li> <li>Symptoms that persist or are recurrent in spite of anti-reflux drug treatment</li> <li>Strictures</li> <li>Failure to gain or maintain weight (children)</li> </ul> <p>Fundoplication has little benefit for patients with impaired stomach motility (an inability of the muscles to move spontaneously). </p> <p><i>The Open Nissen Fundoplication Procedure.</i> Until recently, most fundoplication procedures for GERD have been the 360° Nissen fundoplication. This is called an <i>open</i> procedure because it requires wide surgical incisions. </p> <ul> <li>With this procedure, the physician wraps the upper part of the stomach (<i>fundus</i>) completely around the esophagus to form a collar-like structure.</li> <li>The collar places pressure on the LES and prevents stomach fluids from backing up into the esophagus.</li> <li>Open fundoplication requires a 6- to 10-day hospital stay.</li> </ul> <div class="ADAMInlineGraphic"> <div class="ADAMInlineTnail" style="float: left;"><a href="/2331736" ></a></div> <div class="ADAMTextBox" style="float: left; width: 330px;"></p> <p>Click the icon to see an illustrated series detailing gastroesophageal reflux surgery.</div> </div> <p><i>Laparoscopic Fundoplication.</i> The standard invasive fundoplication procedure has been replaced in many cases by a less invasive fundoplication procedure that uses <i>laparoscopy</i>. In the operation: </p> <ul> <li>Tiny incisions are made in the abdomen.</li> <li>Small instruments and a tiny camera are inserted into tubes, through which the surgeon can view the region.</li> <li>The surgeon creates a collar using the fundus, although the area is smaller to work with.</li> </ul> <p>When performed by experienced surgeons, the procedure shows results that are equal to those of standard open fundoplication, but with faster recovery time. </p> <p>Overall, laparoscopic fundoplication appears to be safe and effective in people of all ages, even babies. Laparoscopy is more difficult to perform in certain patients, including those who are obese, who have a short esophagus, or who have a history of previous surgery in the upper abdominal area. It may also be less successful in relieving atypical symptoms of GERD, including cough, abnormal chest pain, and choking. In about 8% of laparoscopies, it is necessary to convert to open surgery during the procedure because of unforeseen complications. </p> <p><i>Other Variations.</i> There are now a number of variants of fundoplication procedures. Examples include the following: </p> <ul> <li>Toupet fundoplication employs only a partial wrap, as does a Thal fundoplication. Partial fundoplication procedures may be more effective in patients with poor or no esophageal motility (spontaneous muscle contraction). Those with normal motility may do better with the full-circle wrap.</li> <li>Others use a very short and "floppy" Nissen full wrap.</li> </ul> <p>Many surgeons report that such limited fundoplications result in earlier feeding and discharge from the hospital and a lower incidence of complications (trouble swallowing, gas bloating, gagging) than the full Nissan fundoplication. A British study, however, reported no significant differences in swallowing problems. </p> <p><i>Postoperative Problems and Complications after Fundoplication.</i> Postoperative problems can include a delay in intestinal functioning causing bloating, gagging, and vomiting. These side effects usually resolve in a few weeks. A 2003 study suggested, however, that 38% of patients develop such symptoms, and most occur more than a year after the procedures. If symptoms persist or if they start weeks or months after surgery, particularly if vomiting is present, then surgical complications are likely. Complications include the following: </p> <ul> <li>An excessively wrapped fundus. This is fairly common and can cause difficulty swallowing (dysphagia), as well as gagging, gas, bloating, or an inability to burp. (A follow-up procedure that dilates the esophagus using an inflated balloon may help correct dysphagia, although it cannot treat other symptoms.)</li> <li>Bowel obstruction</li> <li>Wound infection</li> <li>Injury to nearby organs</li> <li>Respiratory complications, such as a collapsed lung. These are uncommon, particularly with laparoscopic fundoplication.</li> <li>Muscle spasms after swallowing food. This can cause intense pain, and patients may require a liquid diet, sometimes for weeks. This is a rare complication in most patients, but it can be very high in children with neurologic abnormalities. Such children are already at very high risk for GERD.</li> </ul> <p><i>Reasons for Treatment Failure.</i> Long-term failure rates after fundoplication are 30% after 5 years and 63% after 10 years. Hiatal herniation is the most common reason for surgical failure and the need for a repeat fundoplication. Other common reasons for reoperation include breakdown, slippage, and excessive tightness of the wrap. Surgeon experience can lessen complication risks. Some studies have reported that repeat operations after open procedures occur in 9 - 30% of cases and 13% after laparoscopy. (Repeat surgery usually has good results.) </p> <p>A number of treatments that make use of endoscopy are being used or investigated for increasing LES pressure and preventing reflux, as well as for treating severe GERD and its complications. </p> <p><i>Transoral Flexible Endoscopic Suturing.</i> Transoral flexible endoscopic suturing (sometimes referred to as Bard's procedure) uses a tiny device at the end of the endoscope that acts like a miniature sewing machine. It places stitches in two locations near the LES, which are then tied to tighten the valve and increase pressure. There is no incision and no need for general anesthesia. </p> <p><i>Radiofrequency.</i> Radiofrequency energy generated from the tip of a needle (sometimes called the Stretta procedure) heats and destroys tissue in the problem spots in the LES. Either the resulting scar tissue strengthens the muscle, or the heat kills the nerves that caused the malfunction. Patients may experience some chest or stomach pain afterwards. Few serious side effects have been reported, although there have been reports of perforation, hemorrhage, and even death. A recent study reported that 81% of patients remained symptom-free for up to 3 years following the Stretta procedure. </p> <p><i>Implants.</i> In 2003, the FDA approved the Enteryx procedure as a treatment option for people who have persistent symptoms of GERD and who regularly take and respond to PPIs. In 2005, however, the manufacturer of Enteryx (Boston Scientific), voluntarily removed Enteryx from clinical use due to problems related to the difficult injection technique. </p> <p><i>Techniques to Stop Bleeding.</i> Endoscopic ablation treatment of bleeding involves using a probe passed through the endoscopic tube, which applies electricity or heat to coagulate blood and stop the bleeding. </p> <p><i>Dilation Procedures.</i> Strictures (abnormally narrowed regions) may need to be dilated (opened) with endoscopy. Dilation may be performed by inflating a balloon in the passageway. About 30% of patients who need this procedure require a series of dilation treatments over a long duration in order to fully open the passageway. Long-term use of proton-pump inhibitors may reduce the duration of treatments. </p> <p>One study also suggested that dilation may help correct swallowing problems that can occur after fundoplication. In the study dilation improved dysphagia in 67% of the surgical patients who had experienced it. </p> <p>A recent advance is the development of small-caliber upper endoscopy, which does not require sedation and can be performed in the physician's office. </p> <h3 id="adamHeading_14">Resources</h3> <ul> <li><a href="http://digestive.niddk.nih.gov" target="_blank">http://digestive.niddk.nih.gov</a> -- National Digestive Diseases Information Clearinghouse</li> <li><a href="http://www.gastro.org/" target="_blank">www.gastro.org</a> -- American Gastroenterological Association</li> <li><a href="http://www.acg.gi.org/" target="_blank">www.acg.gi.org</a> -- American College of Gastroenterology</li> <li><a href="http://www.asge.org/" target="_blank">www.asge.org</a> -- American Society for Gastrointestinal Endoscopy</li> <li><a href="http://www.ssat.com/" target="_blank">www.ssat.com</a> -- Society for Surgery of the Alimentary Tract</li> <li><a href="http://www.naspgn.org/" target="_blank">www.naspgn.org</a> -- North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition</li> <li><a href="http://www.reflux.org/" target="_blank">www.reflux.org</a> -- Pediatric/Adolescent Gastroesophageal Reflux Association</li> <li><a href="http://www.iffgd.org/" target="_blank">www.iffgd.org</a> -- International Foundation for Functional Gastrointestinal Disorders</li> </ul> <h3 id="adamHeading_15">References</h3> <p>DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. <em>Am J Gastroenterol.</em> 2005;100(1):190-200. </p> <p>Deviere J, Costamagna G, Neuhause H, Voderholzer W, Louis H, Tringali A, et al. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial. <em>Gastroenterology</em>. 2005;128(3):532-540. </p> <p>Esposito C, Montupet P, van Der Zee D, Settimi A, Paye-Jaouen A, Centonze A, Bax NK. Long-term outcome of laparoscopic Nissen, Toupet, and Thal antireflux procedures for neurologically normal children with gastroesophageal reflux disease. <em>Surg Endosc</em>. 2006 Jun;20(6):855-8. Epub 2006 May 12. Accessed June 2, 2006. </p> <p>Gilger MA, Yeh C, Chiang J, Dietrich C, Brandt ML, El-Serag HB. Outcomes of surgical fundoplication in children. <em>Clin Gastroenterol Hepatol</em>. 2004;2(11):978-984. </p> <p>Gold BD, Schelman JM, Sabesin SM, Vitat P. Updates on the management of upper gastrointestinal disorders in primary care setting:NSAID-related gastropathies and pediatric reflux disease. <em>The Journal of Family Practice</em>. March 2007;56(3):S1-S11. </p> <p>Hirano I, Richter JE, and the Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. <em>American Journal of Gastroenterology. 2007;102:668-685.</em><em /> </p> <p>Kim CY, O'Rourke RW, Chang EY, Jobe BA. Unsedated small-caliber upper endoscopy: an emerging diagnostic and therapeutic technology. <em>Surg Innov</em>. 2006 Mar;13(1):31-9. </p> <p>Koslowsky B, Jacob H, Eliakim R, Adler SN. PillCam ESO in esophageal studies: improved diagnostic yield of 14 frames per second (fps) compared with 4 fps. <em>Endoscopy</em>. 2006 Jan;38(1):27-30. </p> <p>Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings,and response to treatment with fluticasone propionate. <em>Gastrointest Endosc</em>. 2006 Jan;63(1):3-12. </p> <p>Rudolph CD, Mazur LJ, Liptak GS, Baker RD, Boyle JT, Colletti RB, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. <em>J Pediatr Gastroenterol Nutr</em>. 2001;32 Suppl 2: S1-S31. </p> <div id="health_topic_footer"> Review Date:<br /> 5/22/2007<br /> Reviewed By:<br /> Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.<br /> <div style="margin:10px 0px;"> <div style="float:left;margin:0px 10px 5px 0;"> </div> <div style="margin-bottom:5px;"> A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). 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