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Peptic ulcers

Highlights

New Research:

  • Aspirin and other NSAIDs can lead to ulcers, but patients who require these medications on a long-term basis can reduce their risk of ulcers by taking drugs in the proton pump inhibitor (PPI) group, such as omeprazole (Prilosec). A new study shows that famotidine (Pepcid -- an H2 blocker) can also protect people who are taking low-dose aspirin for cardiovascular prevention, at least in the short-term.
  • Research finds that laparoscopic surgery for a perforated peptic ulcer is comparable in safety with open surgery, and results in less pain after the procedure.

Overview:

  • A peptic ulcer is an open sore or raw area that tends to develop in one of two places:
    • The lining of the stomach (gastric ulcer)
    • The upper part of the small intestine -- the duodenum (duodenal ulcer)
  • Ulcers develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.
  • In 1982 two Australian scientists identified the bacteria H. pylori as the main cause of stomach ulcers.
  • Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing.
  • Certain drugs other than NSAIDs may aggravate ulcers.

Risk Factors Include:

  • Only about 10 - 15% of people infected with H. pylori develop peptic ulcer disease. Other factors must also be present to trigger ulcers.
  • Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems.
  • Although stress is no longer considered to be a cause of ulcers, some studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing.

Introduction

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

  • The lining of the stomach (gastric ulcer)
  • The upper part of the small intestine -- the duodenum (duodenal ulcer)

In the U.S., duodenal ulcers are three times more common than gastric ulcers.

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

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

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

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

Click the icon to see an image of the stomach.

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

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

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

Causes

In 1982 two Australian scientists identified H. pylori as the main cause of stomach ulcers. They showed that inflammation of the stomach, and stomach ulcers, result from an infection of the stomach caused by H. pylori bacteria. This discovery was so important that the researchers were awarded the Nobel Prize in Medicine in 2005. The bacteria appear to trigger ulcers in the following way:

  • H. pylori's corkscrew shape enables it to penetrate the mucus layer of the stomach or duodenum so that it can attach itself to the lining. The surfaces of the cells lining the stomach contain a protein, called decay-accelerating factor, which acts as a receptor for the bacterium.
  • H. pylori survives in the highly acidic environment by producing urease, an enzyme that generates ammonia to neutralize the acid.
  • H. pylori then produces a number of toxins and factors that can cause inflammation and damage to the stomach and intestinal lining, leading to ulcers in certain individuals.
  • It also alters certain immune factors that allow it to evade detection by the immune system and cause persistent inflammation -- even without invading the mucus membrane.

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

H. pylori is also strongly linked to stomach cancer and possibly other non-intestinal problems.

Factors that Trigger Ulcers in H. pylori Carriers. Only around 10 to 15% of people who are infected with H. pylori develop peptic ulcer disease. H. pylori infections, particularly in older people, may not always predict whether there are peptic ulcers. Other variables must also be present to actually trigger ulcers. These may include:

  • Genetic Factors. Some people harbor strains of H. pylori that contain genes that may make the bacteria more dangerous, and increase the risk for ulcers. How important these genetic factors are in the development of ulcers depends on a person's ethnicity.
  • Immune Abnormalities. Some experts suggest that certain individuals have abnormalities in their intestinal immune response, which allow the bacteria to injure the lining.
  • Lifestyle Factors. Although lifestyle factors such as chronic stress, drinking coffee, and smoking were long believed to be primary causes of ulcers, it is now thought that they only increase susceptibility to ulcers in some H. pylori carriers.
  • Shift Work and Other Causes of Interrupted Sleep. People who work the night shift have a significantly higher incidence of ulcers than day workers. Researchers suspect that frequent interruptions of sleep may weaken the immune system's ability to protect against harmful bacterial substances.

When H. pylori was first identified as the major cause of peptic ulcers, it was found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. As more people are being tested and treated for the bacteria, however, the rate of H. pylori- associated ulcers has declined. Currently, H. pylori are found in about 50% of people with peptic ulcer disease.

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

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Long-term use of NSAIDs is the second most common cause of ulcers, and the rate of NSAID-caused ulcers is increasing. More than 30 million people take prescription NSAIDs regularly, and more than 30 billion tablets of over-the-counter brands are sold each year in the U.S. alone. The most common NSAIDs are aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn), although many others are available.

Patients with NSAID-caused ulcers should stop taking these drugs. However, patients who require these medications on a long-term basis can reduce their risk of ulcers by taking drugs in the proton pump inhibitor (PPI) group, such as omeprazole (Prilosec). A new study shows that famotidine (Pepcid -- an H2 blocker) can also protect people who are taking low-dose aspirin for cardiovascular prevention, at least in the short-term.

There is no doubt that NSAIDs increase the risk of ulcers and gastrointestinal (GI) bleeding. The risk of bleeding continues for as long as a patient takes these drugs and may persist for about 1 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.

Some NSAIDs pose greater risks than others for ulcers and bleeding. No NSAID, even an over-the-counter brand, should be used long-term without a doctor's supervision.

Other Causes

Certain drugs other than NSAIDs may aggravate ulcers. These include warfarin (Coumadin) -- an anticoagulant that increases the risk of bleeding, oral corticosteroids, some chemotherapy drugs, spironolactone, and niacin.

Bevacizumab, a drug used to treat colorectal cancer, may increase the risk of GI perforation. Although the benefits of bevacizumab outweigh the risks, GI perforation is very serious. If it occurs, patients must stop taking the drug.

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

  • Radiation treatments
  • Bacterial or viral infections
  • Alcohol abuse
  • Physical injury
  • Burns

Zollinger-Ellison Syndrome (ZES)

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

Cause of peptic ulcers

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 cancerous and must be removed. Acid production should also be suppressed to prevent ulcers from returning.

Who Gets ZES? An estimated 1 person per million per year gets ZES. The incidence is 0.1 - 1% among patients with peptic ulcers. Typically the disease starts in people ages 45 - 50, and men are affected more often than women.

How Is ZES Diagnosed? ZES should be suspected in patients with ulcers who are not infected with H. pylori and who have no history of NSAID use. Diarrhea may occur before ulcer symptoms. Ulcers occurring in the second, third, or fourth portions of the duodenum or in the jejunum (the middle section of the small intestine) are signs of ZES. Gastroesophageal reflux disease (GERD) is more common, and often more severe in patients with ZES. Complications of GERD include ulcers and narrowing (strictures) of the esophagus.

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

Symptoms

Dyspepsia. The most common symptoms of peptic ulcer are known collectively as dyspepsia. However, peptic ulcers can occur without dyspepsia or any other gastrointestinal symptom, especially when they are caused by NSAIDs. Dyspepsia may be persistent or recurrent and can lead to a variety of upper abdominal symptoms, including:

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

Many patients with the above symptoms do not have peptic ulcer disease or any other diagnosed condition. In that case, they have what is called functional dyspepsia.

Ulcer Pain. Some symptoms are similar to those of gastric ulcers, although not everyone with these symptoms has an ulcer. The pain of ulcers can be in one place, or it can be diffuse (all over the abdomen). The pain is described as a burning, gnawing, or aching in the upper abdomen, or as a stabbing pain penetrating through the gut. The symptoms may vary depending on the location of the ulcer:

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

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

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

Emergency Symptoms

Severe symptoms that begin suddenly may indicate a blockage in the intestine, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:

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

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

Ulcer emergencies

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

Complications

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

Bleeding and hemorrhage

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

Complications of peptic ulcers cause an estimated 6,500 deaths each year. These figures, however, do not reflect the high number of deaths associated with NSAID use. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori.

Because there are often 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 another serious and unstable medical condition. Populations at greatest risk are the elderly and those with other serious conditions, such as heart problems.

Stomach Cancer and Other Conditions Associated with H. pylori

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

Stomach Cancers. Stomach cancer, also called gastric cancer, is the second most common type of cancer worldwide. In developing countries where the rate of H. pylori is very high, the risk of stomach cancer is six times higher than in the U.S. Evidence now suggests that H. pylori may be as carcinogenic to the stomach as cigarette smoke is to the lungs.

Eradication of H. pylori may reduce the risk of stomach cancer, but not eliminate it. The patient's risk depends on how much damage the mucus membranes sustained before H. pylori treatment was started. The damage can be measured during an endoscopy.

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

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

When H. pylori infection starts in adulthood it poses a lower risk for cancer, because it takes years for atrophic gastritis to develop, and an adult is likely to die of other causes first. Other factors, such as specific strains of H. pylori and diet, might also influence the 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 H. pylori strain that carries the cytotoxin-associated gene A (CagA) may also be a particular risk factor for precancerous changes.

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

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

Risk Factors

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

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

Risk Factors for H. pylori

H. pylori bacteria are most likely transmitted directly from person to person. Yet little is known about exactly how these bacteria are transmitted.

Who Is Infected with H. pylori? About 20% of people under age 40 and 50% of those over age 60 are infected with H. pylori. The bacteria are nearly always acquired during childhood and persist throughout life if not treated. The prevalence in children is around 0.5% in industrialized nations, where rates continue to decline. Even in industrialized countries, however, infection rates in regions with crowded, unsanitary conditions are equal to those in developing countries.

How Do the Bacteria Pass from Person to Person? It is not entirely clear how the bacteria are transmitted. Suggested, but not clearly proven methods of transmission include: intimate contact, GI tract illness (particularly when vomiting occurs), and contact with oral secretions. The bacteria may also be passed in stools. Because H. pylori can live in water, but apparently not in food, the bacteria may also be transmitted through sewage-contaminated water.

Who Is at Risk for Ulcers from H. pylori? Although H. pylori infection is common, ulcers in children are very rare, and only a small percentage of infected adults develop ulcers. Some known risk factors include smoking, alcohol use, having a relative with peptic ulcers, being male, and having the cytotoxin-associated gene A (CagA). Experts do not know of any single factor or group of factors that can determine which infected patients are most likely to develop ulcers.

Risk Factors for NSAID-Induced Ulcers

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

The FDA has asked manufacturers of prescription NSAIDs and the COX-2 inhibitor celecoxib (Celebrex) to include with their products a boxed warning emphasizing 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 new COX-2 inhibitor CS-706 showed it to have the same effects on gastric mucosa as a placebo.)

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

Frequent Users

NSAIDs. Anyone who uses NSAIDs regularly is at risk for gastrointestinal problems. Even low-dose aspirin (81 mg) may pose some risk, although the risk is lower than with standard doses. The highest risk is among people who require long-term use of very high-dose NSAIDs, especially patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic stress.

The use of COX-2 inhibitors may decrease the risk of uncomplicated ulcers, but these medications do not seem to reduce the risk of more serious events, such as bleeding or perforation.

Contributing Factors. Certain factors may increase the risk for ulcers in NSAID users:

  • Age 65 and older
  • History of peptic ulcers or upper gastrointestinal bleeding
  • Other serious ailments, such as congestive heart failure
  • Use of other medications, such as the anticoagulant warfarin (Coumadin), corticosteroids, or the osteoporosis drug alendronate (Fosamax)
  • Alcohol abuse
  • H. pylori infection

Other Risk Factors for Ulcers from H. pylori or NSAIDs

Stress and Psychological Factors. Although stress is no longer considered a cause of ulcers, studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing. Some even believe that the anecdotal relationship between stress and ulcers is so strong that people with ulcers should be treated for psychological conditions.

Smoking. Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases mucosal blood flow. However, the results of studies on the actual effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. Other studies have found no increased risk for ulcers in smokers. In any case, H. pylori does not seem to affect the impact of smoking on ulcers.

Tobacco and vascular disease

Tobacco use and exposure may accelerate coronary artery disease and peptic ulcer disease. It is also linked to reproductive problems, esophageal reflux, hypertension, fetal illness and death, and delayed wound healing.

Diagnosis

Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Symptoms of dyspepsia occur in 20 - 25% of people who live in industrialized nations, but only about 15 - 25% of those with dyspepsia actually have ulcers. A number of steps are needed to accurately diagnose ulcers.

Medical and Family History

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 NSAID use), family members with ulcers, and drinking and smoking habits.

Ruling out Other Disorders

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

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

The following disorders may be confused with peptic ulcers:

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

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

Noninvasive Tests for Gastrointestinal (GI) Bleeding

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

Traditional radiology tests have not yet proven valuable for diagnosing ulcers.

Tests to Detect H. pylori

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

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

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

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

Tests for Diagnosing H. pylori. The following tests are used to diagnose H. pylori infection. Testing may also be done after treatment to ensure that the bacteria have been completely eliminated.

  • Breath Test. A simple test called the carbon isotope-urea breath test (UBT) can identify up to 99% of people who have H. pylori. Up to 2 weeks before the test, the patient must stop taking any antibiotics, bismuth-containing medications such as Pepto-Bismol, and proton pump inhibitors (PPIs). As part of the test, the patient swallows a special substance containing urea (a waste product the body produces as it breaks down protein) that has been treated with carbon atoms. If H. pylori are present, the bacteria convert the urea into carbon dioxide, which is detected and recorded in the patient's exhaled breath after 10 minutes. This test can also be used to confirm that H. pylori have been fully treated.
  • Blood Tests. Blood tests are used to measure antibodies to H. pylori, and the results are available in minutes. Diagnostic accuracy is reported to be 80 - 90%. One such important test is called enzyme-linked immunosorbent assay (ELISA). An ELISA test of the urine is also showing promise for diagnosing H. pylori in children.
  • Stool Test. A test to detect the genetic fingerprints of H. pylori in the feces appears to be as accurate as the breath test for initially detecting the bacteria, and for detecting recurrences after antibiotic therapy. This test can also be used to confirm that the H. pylori infection has been fully treated.
  • The most accurate way to identify the presence of H. pylori is by taking a tissue biopsy from the lining of the stomach. The only way to do this is with endoscopy. It is an invasive procedure, but it is the most accurate test. However, many patients are treated for H. pylori based on the three noninvasive tests listed above.

Endoscopy

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

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

  • "Alarm" symptoms (unexplained weight loss, gastrointestinal bleeding, vomiting, difficulty swallowing, or anemia). Patients with these symptoms generally have an endoscopy before treatment.
  • Over age 55 (when the risk for stomach cancer increases)
  • Failure to respond to medical treatment of H. pylori, if present

Experts disagree about whether endoscopy should be performed on all patients who do not respond to initial medication, unless there is evidence or suspicion of bleeding or serious complications, because it does not appear to add any useful information about treatment choices. There is also some debate about whether patients under age 45 who have persistent dyspepsia but no alarm symptoms should have an endoscopy.

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

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

Upper GI Series

An upper GI series was the standard method for diagnosing peptic ulcers until endoscopy and tests for detecting H. pylori were introduced. 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 also more invasive and expensive.

GI bleeding - series

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

Other Laboratory Tests

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

Treatment

Deciding which treatment is best for patients with symptoms of dyspepsia or peptic ulcer disease depends on a number of factors. An endoscopy to identify any ulcers and test for H. pylori probably gives the best guidance for treatment. However, dyspepsia is such a common reason for a doctor's visit that many people are treated initially based on their symptoms and blood or breath H. pylori test results. This approach (called test and treat) is considered an appropriate option for most patients. Patients who do not have any evidence of bleeding or other alarm symptoms, and who are over age 55 should have an endoscopy performed first.

Approach to Patients Who Are Not Taking NSAIDs

If an endoscopy is performed soon after the patient first visits a doctor for symptoms, treatment is based on the results of the endoscopy:

  • If an ulcer is seen and the patient is infected with H. pylori, treatment for the infection is started, followed by 4 to 8 weeks of treatment with a proton pump inhibitor. Most patients will improve with this treatment.
  • If an ulcer is seen but H. pylori is not present, patients are usually treated with proton pump inhibitors for 8 weeks.
  • If no ulcer is seen and the patient is not infected with H. pylori, the first treatment attempt will usually be with proton pump inhibitors. These patients do not need antibiotics to treat H. pylori. Other possible causes of their symptoms should also be considered.

As mentioned above, most patients who do not have risk factors for additional complications are treated without first having an endoscopy. The decision of which treatment to use is based on the types of symptoms patients have, and on the results of their H. pylori blood or breath tests.

Patients who are not infected with H. pylori are given a diagnosis of functional (non-ulcer) dyspepsia. These patients are most commonly given 4 to 8 weeks of a proton pump inhibitor. If this dose is not effective, occasionally doubling the dose will relieve symptoms. If there is still no symptom relief, patients may have an endoscopy. However, it is unlikely that an ulcer is present. In this group of patients, symptoms may not fully improve.

  • Patients who test positive for H. pylori infection will receive an antibiotic regimen that eradicates H. pylori. Those who have an ulcer are more likely to respond to such treatment. Unfortunately, because an endoscopy is not performed before treatment in the test and treat strategy, patients who do not have an ulcer are also treated with antibiotics. Even if they are positive for H. pylori, these patients are less likely to have a full response.
  • When the test and treat approach is used, those who do not respond to treatment, or whose symptoms return relatively quickly, will often need an upper endoscopy.

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

  • Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against GERD, which in severe cases can be a risk factor for cancer of the esophagus. Eliminating H. pylori may also have other adverse effects.
  • Overuse of antibiotics. There is concern that using antibiotics when there is no clear evidence of ulcers will lead to unnecessary antibiotic prescriptions and increase the risk for side effects. Overuse may also contribute to a growing public health problem -- the emergence of antibiotic-resistant bacteria.
  • Because the number of people infected with H. pylori is declining in the United States, and therefore the number of people being helped by this approach is declining, the test and treat approach is becoming expensive.

Antibiotic and Combination Drug Regimens for the Treatment of H. pylori

Reported cure rates for H. pylori range from 70 - 90% after antibiotic treatment. The standard treatment regimen uses two antibiotics and a PPI:

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

Patients typically take this combination treatment for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well.

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

In most cases, drug treatment relieves ulcer symptoms. However, symptom relief does not always indicate treatment success, just as persistent dyspepsia does not necessarily mean that treatment has failed. Heartburn and other GERD symptoms can get worse and require acid-suppressing medication.

Failure. Treatment fails in about 15% of patients, typically when they do not follow their prescribed treatment. Compliance with standard antibiotic regimens may be poor for the following reasons:

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

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

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

Treatment of NSAID-induced ulcers

If patients are diagnosed with NSAID-caused ulcers or bleeding, they should:

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

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

People with chronic pain may try a number of other medications to minimize the risk of ulcers associated with NSAIDs.

  • COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs and cause less gastrointestinal distress. Although the use of COX-2 inhibitors may decrease uncomplicated ulcers, they do not seem to reduce the incidence of more serious gastrointestinal events. Also, following numerous reports of cardiovascular events with COX-2 inhibitors, only Celecoxib (Celebrex) is still available. (Regular NSAIDs also increase the risk of cardiovascular events.)
  • Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac. It may reduce the risk for gastrointestinal bleeding. This drug can cause miscarriage at any stage of pregnancy and therefore should not be used during pregnancy.
  • Acetaminophen.Acetaminophen (Tylenol, Anacin-3) is the most common alternative to NSAIDs. It is inexpensive and generally safe. Acetaminophen poses far less of a gastrointestinal risk than NSAIDs. Until recently, the recommended maximum daily dose was 4 grams (4,000 mg). An FDA advisory panel in June 2009 recommended lowering the maximum daily dose. Patients who take high doses of acetaminophen for long periods of time are also at risk for liver damage, particularly if they drink alcohol. Acetaminophen also may pose a small risk for serious kidney complications in people with preexisting kidney disease, although it remains the drug of choice for patients with impaired kidney function.
  • Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. However, dependence and abuse have been reported. Tramadol can cause nausea, but it 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 medications.
  • If patients need to continue taking NSAIDs, they should use the lowest possible dose.

The American College of Gastroenterology has recently made recommendations about the prevention of ulcers in patients using NSAIDs. A patient's physician must consider whether they are at high, moderate, or low risk for gastrointestinal and cardiovascular problems. Depending on your risk factors, your doctor may recommend any NSAID, naproxen only, a COX-2 inhibitor, one of these, or none of the three. Some patients take either a proton pump inhibitor or misoprostol along with their NSAID. Before starting a patient on long-term NSAID therapy, a physician should consider testing for H. pylori.

Gastroenterology

Click the icon to see an animation on ulcer treatment.

Medications

The following drugs are sometimes used to treat peptic ulcers caused by either NSAIDs or H. pylori.

Antacids

Many antacids are available without a prescription, and they are the first drugs recommended to relieve heartburn and mild dyspepsia. Antacids are not effective for preventing or healing ulcers, but they can help in the following ways:

  • They neutralize stomach acid with various combinations of three basic compounds -- magnesium, calcium, or aluminum.
  • They may protect the stomach by increasing bicarbonate and mucus secretion. (Bicarbonate is an acid-buffering substance.)

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

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

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

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

Drug Interactions with Antacids (such as Maalox, Mylanta)

Drugs that are not absorbed as well if taken with antacids

Drugs that are made more potent by antacids

Tetracycline

Ciprofloxacin (Cipro)

Propranolol (Inderal)

Captopril (Capoten)

Ranitidine (Zantac)

Famotidine (Pepcid AC)

Valproic acid

Sulfonylureas

Quinidine

Levodopa

Antibiotics

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

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

Side Effects of Antibiotics.

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

Bismuth

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

Proton Pump Inhibitors (PPIs)

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

PPIs can be used either as part of a multidrug regimen for H. pylori, or alone for preventing and healing NSAID-caused ulcers. They are also useful for treating ulcers caused by Zollinger-Ellison syndrome. They are considered to be more effective than H2 blockers.

Some people carry a gene that reduces the effectiveness of PPIs. This gene is present in 18 - 20% of people of Asian descent.

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

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

Possible Adverse Effects.

  • Side effects are uncommon, but may include headache, diarrhea, constipation, nausea, and itching.
  • Pregnant women and nursing mothers should avoid taking PPIs. Although recent studies suggest that these drugs do not increase the risk of birth defects, their safety during pregnancy is not yet proven.
  • PPIs may interact with certain drugs, including antiseizure medications (such as phenytoin), anti-anxiety drugs (such as diazepam), and blood thinners (such as warfarin).
  • Long-term use of high-dose PPIs may produce vitamin B12 deficiency, but more studies are needed to confirm this risk.

In theory, long-term use of PPIs by people with H. pylori may reduce acid secretion enough to cause atrophic gastritis (chronic inflammation of the stomach), a risk factor for stomach cancer. Long-term use of PPIs may also mask the symptoms of stomach cancer and delay diagnosis. At this time, however, there have been no reports of an increase in the incidence of stomach cancer with long-term use of these drugs.

H2 Blockers

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 proton pump inhibitors and antibiotic regimens against H. pylori were developed. These drugs cannot cure ulcers, but they are useful in certain cases. They are effective only for duodenal ulcers, however.

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

  • Famotidine (Pepcid AC). Famotidine is the most potent H2 blocker. The most common side effect is headache, which occurs in 4. 7% of people who take it. Famotidine is virtually free from drug interactions, but it may have significant adverse effects in patients with kidney problems.
  • Cimetidine (Tagamet). Cimetidine has few side effects. However, 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 erectile dysfunction or breast enlargement in men. These problems go away after the drug is discontinued.
  • Ranitidine (Zantac). Ranitidine interacts with very few drugs. In one study, ranitidine provided more pain relief and healed ulcers more quickly than cimetidine in people younger than age 60, but there was no difference in older patients. A common side effect of ranitidine is headache, which occurs in about 3% of people who take it.

PPIs are more effective than H2 blockers at healing ulcers in people who take NSAIDs. Treatment effectiveness for PPIs is between 65 and 100%, versus 50 and 85% for H2 blockers, depending on which specific drugs are being used.

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

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

  • Liver damage. This is more likely with ranitidine than with the other H2 blockers, but it is rare with any of these drugs.
  • Kidney-related central nervous system complications. With famotidine, adverse effects on the central nervous system (such as anxiety, depression, and mental disturbances) have been reported in patients with even moderate kidney problems.
  • Increased risk for pneumonia in hospitalized patients, as well as in the community.
  • 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 ulcer symptoms.
FDA Warning for Famotidine (Pepcid AC)

Famotidine is removed from the body primarily by the kidney. This can pose a danger to people with kidney problems. The U.S. Food and Drug Administration (FDA) and Health Canada are now advising physicians 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.

Misoprostol

Misoprostol (Cytotec) increases prostaglandin levels in the stomach lining, which protects against the major gastrointestinal side effects of NSAIDs.

Actions against ulcers. Misoprostol can reduce the risk of NSAID-induced 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 for healing existing ulcers.

Side Effects.

  • Because misoprostol can induce miscarriage or cause birth defects, pregnant women should not take it. If pregnancy occurs during treatment, the drug should be stopped at once and the doctor contacted immediately.
  • 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 two to three times a day, instead of the standard regimen of four times, may prove to be just as effective and cause fewer side effects.

Sucralfate

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.

Surgery

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

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

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

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

Endoscopy for Treating or Preventing Bleeding Ulcers

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

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

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

The following is a typical endoscopy procedure:

  • The physician passes a probe through an endoscopic tube and applies electricity, heat, or small clips to coagulate the blood and stop the bleeding. This procedure also causes fluid buildup, which helps to compress the blood vessels.
  • In high-risk cases, the doctor may inject epinephrine (commonly known as adrenaline) directly into the ulcer to enhance the effects of the heating process. Epinephrine activates the process leading to blood coagulation, narrows the arteries, and enhances blood clotting.
  • Intravenous (IV) administration of a PPI (usually omeprazole or pantoprazole) significantly prevents rebleeding and appears to be cost-effective. (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.

Endoscopy is effective at controlling bleeding in most 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.

Other Medical Considerations. Certain medications may be needed after endoscopy:

  • Patients who harbor the H. pylori bacteria, even when the bleeding has been caused by NSAID use, should be treated with antibiotic therapy to eliminate the bacteria. Most patients infected with the bacteria need triple therapy, including antibiotics, to eliminate H. pylori immediately after endoscopy.
  • 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 been proven to be more effective than current treatments.

Major Abdominal Surgery

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

Surgical Approaches. The standard major surgical approach (called open surgery) uses a wide abdominal incision and standard surgical instruments. Laparoscopic techniques use small abdominal incisions, through which are inserted tubes that contain miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers. Research finds that laparoscopic surgery for a perforated peptic ulcer is comparable in safety with open surgery, and results in less pain after the procedure.

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

Gastrectomy - series

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

Antrectomy and pyloroplasty are usually performed with vagotomy.

Lifestyle Changes

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

Fruits and Vegetables. The good news is that a diet rich in fiber may cut the risk of developing ulcers in half and speed the 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.

Milk. Milk actually encourages the production of acid in the stomach, although moderate amounts (2 - 3 cups a day) appear to do no harm. Certain probiotics, which are "good" bacteria added to yogurt and other fermented milk drinks, may protect the gastrointestinal system.

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

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

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

Olive Oil. Studies from Spain have shown that phenolic compounds in virgin olive oil may be effective against eight strains of H. pylori, three of which are antibiotic-resistant.

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

Exercise

Some evidence suggests that exercise may help reduce the risk for ulcers in some people.

Stress Relief

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

Resources

References

Bertleff M, Helm JA, Bemelman WA, van der Ham AC, van der Harst E, Oei HI, et al. Randomized clinical trial of laparoscopic versus open repair of the perforated peptic ulcer: The LAMA Trial. World J Surg. 2009;33(7):1368-1373.

Chey WD, Wong BC. Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808-1825.

Grainek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med. 2008;359(9):928-937.

Kim JI, Cheung DY, Cho SH, et al. Oral proton pump inhibitors are as effective as endoscopic treatment for bleeding peptic ulcer: a prospective, randomized, controlled trial. Dig Dis Sci. 2007;52(12):3371-3376.

Lanza FL, Chan FK, Quigley EM. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-738.

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

Malagelada J-R, KuipersMartin EJ, Blaser J. Acid Peptic Disease: Clinical manifestations, Diagnosis, Treatment, and Prognosis. In: Goldman: Cecil Medicine, 23rd ed. Philadelphia, PA: WB Saunders, 2007.

Mercer DW, Robinson EK. Stomach. In: Townsend: Sabiston Textbook of Surgery, 18th ed. Philadelphia, PA: WB Saunders, 2007.

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

Ramakrishnan K, Salinas RC. Peptic ulcer disease. Am Fam Physician. 2007;76(7):1005-1012.

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

Taha AS, McCloakwy C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): A phase III, randomized, double-blind, placebo-controlled trial. Lancet. 2009:doi: 10.1016/S0140-6736(09)61246-0.

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


Review Date: 7/17/2009
Reviewed By: Reviewed by: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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