Causes and Risk Factors
Around 80% of gastric ulcers and 90% of duodenal ulcers are caused by H pylori. H pylori is very common in both developed and developing countries. Although estimates indicate around 50% or more of the adult US population is colonized with H pylori, only between 10% and 20% of people carrying H pylori will have a peptic ulcer during their lifetime. Additionally, around 5% to 10% of people in the United States not infected with H pylori will have a peptic ulcer at some point in their lives.
This means that over 25 million people in the United States will develop a peptic ulcer at some point in their lifetime.
An ulcer is an open sore or raw area that most commonly develops in one of 2 places:
In the United States, duodenal ulcers are 3 times more common than gastric ulcers.
A peptic ulcer is an open sore or raw area in the lining of the stomach (gastric) or the upper part of the small intestine (duodenal).
Ulcers average between one-quarter and one-half inch in diameter. They develop when digestive juices produced in the stomach, intestines, and digestive glands damage the lining of the stomach or duodenum.
The 2 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:
Fortunately, the body has a defense system to protect the stomach and intestines against these 2 powerful substances:
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.
In 1982, two Australian scientists identified the gram-negative bacterium 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:
Even if ulcers do not develop, H pylori bacteria are considered to be a major cause of active chronic inflammation in the stomach (gastritis) and the upper part of the small intestine (duodenitis).
H pylori are 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 lead to peptic ulcers. Other factors must also be present to actually trigger ulcers, including:
When H pylori were first identified as the major cause of peptic ulcers, these bacteria were found in 90% of people with duodenal ulcers and in about 80% of people with gastric ulcers. However, as more people are being tested and treated for the bacteria, the rate of H pylori- associated ulcers has declined.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Long-term use of NSAIDs such as aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn) is the second most common cause of ulcers. NSAIDs also increase the risk for gastrointestinal (GI) bleeding. The risk of bleeding continues for as long as a patient takes these drugs and may last 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. To lower risk, the medicine should be taken in the lowest effective dose for the shortest possible time.
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), or in the histamine receptor-2 blocker group, such as famotidine (Pepcid). Misoprostol (Cytotec) has been approved for the prevention of NSAID-related ulcer disease in patients with high risk of ulcer complications.
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.
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 for many cancer patients 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 ulcers in the stomach or intestine, including:
Zollinger-Ellison Syndrome (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.
A large amount of 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 sometimes cancerous and must be removed. Acid production should also be suppressed to prevent ulcers from returning.
An estimated 1 out of every 1 million people per year gets ZES. The incidence is 0.1% to 1% among patients with peptic ulcers. Typically the disease starts in people, ages 45 to 50, and men are affected more often than women.
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.
Peptic ulcers associated with ZES are typically persistent and difficult to treat. Treatment consists of removing the tumors or administering chemotherapy if surgery is not possible, and suppressing acid with a high dose PPI such as pantoprazole (Protonix). In the past, removing the stomach was the only treatment option.
The most common symptoms of peptic ulcer are known collectively as dyspepsia, or symptoms of indigestion. However, peptic ulcers can occur without dyspepsia or any other gastrointestinal symptoms, especially when they are caused by NSAIDs.
The most common peptic ulcer symptoms are:
Other dyspepsia symptoms include:
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.
Older patients are less likely to have symptoms than younger patients. A lack of symptoms may delay diagnosis, which may put older patients at greater risk for severe complications.
Recurrent abdominal pain and other gastrointestinal symptoms are common in children, and it is becoming the norm for pediatricians to screen for H pylori infection in children with these symptoms. However, researchers have not been able to confirm a link between regular abdominal pain and H pylori infection in children.
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 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:
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 a heart attack. The reverse is also true: pain from serious heart conditions may be confused with ulcer pain and not addressed properly.
Because ulcers can cause hidden bleeding, patients may experience symptoms of anemia, including fatigue and shortness of breath.
Severe symptoms that begin suddenly may indicate a blockage in the intestine, perforation, or hemorrhage, all of which are emergencies. Symptoms may include:
Anyone who experiences any of these symptoms should go to the emergency room immediately.
Peptic ulcers may lead to emergency situations. Severe abdominal pain, with or without evidence of bleeding, may indicate 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.
Most people with severe ulcers experience significant pain and sleeplessness, which can have a dramatic and adverse impact on their quality of life.
Peptic ulcer complications can also have a major effect on a person's healthcare costs.
Bleeding (Hemorrhage) and Perforation
Peptic ulcers caused by H pylori or NSAIDs can be very serious if they cause hemorrhage or perforate the stomach or duodenum.
Bleeding is the most common complication of peptic ulcer. Up to 15% of people with ulcers experience some degree of bleeding, which can be life-threatening. Ulcers caused by NSAIDs are more likely to cause hemorrhage. Rapid bleeding can lead to death and is considered a medical emergency (see Treatment section).
An ulcer may penetrate all the way through the gastric or duodenal wall, and cause a perforation. Gastric content may be spilled into the abdominal cavity. The ulcer can also penetrate into nearby organs such as the liver or the pancreas. Both of these problems may require emergency surgery.
A rare but serious problem may occur when ulcers form where the small intestine joins the stomach. Swelling and scarring from the ulcer may lead to narrowing or closing of this opening. In such cases, the patient will vomit the entire contents of the stomach, and emergency treatment is needed.
Complications of peptic ulcers cause an estimated 6,500 deaths each year.
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 cancer, also called gastric cancer, is the third leading cause of cancer death 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 United States. Evidence now suggests that H pylori may be as carcinogenic (cancer producing) to the stomach as cigarette smoke is to the lungs.
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:
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 be a particular risk factor for precancerous changes.
Although the evidence is mixed, some research suggests that early elimination of H pylori may reduce the risk of stomach cancer to that of the general population. It is important to follow patients after treatment for a long period of time.
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.
H pylori also is weakly associated with other non-intestinal disorders, including migraine headache, Raynaud disease (which causes cold hands and feet), and skin disorders such as chronic hives.
Men with gastric ulcers may face a higher risk for pancreatic cancer. Duodenal ulcers do not seem to pose the same risk.
About 10% of people in the United States are expected to develop peptic ulcers at some point in their lives. Peptic ulcer disease affects all age groups, but it is rare in children. Men have twice the risk of ulcers as women. The risk of duodenal ulcers tends to rise starting at age 25, and continuing until age 75. The risk peaks between ages 55 and 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. Treatments have also led to a reduction in the rate of H pylori complications that require a hospital stay.
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.
About 50% of the world's population is 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.
It is not entirely clear how the bacteria are transmitted. Suggested, but not clearly proven, methods of transmission include:
Although H pylori infection is common, ulcers in children are very rare, and only 5% to 10% of H pylori-infected adults develop ulcers. Some factors that may explain why certain infected patients get ulcers include:
Experts do not know what factor or factors actually increase the risk of developing an ulcer.
Risk Factors for NSAID-Induced Ulcers
Between 15% and 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 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 Food and Drug Administration (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.
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 requirements.
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 higher doses. The highest risk is among people who use very high-dose NSAIDs over a long period of time (more than the typical 1 to 2 weeks), especially patients with rheumatoid arthritis. Other people who take high doses of NSAIDs include those with chronic low back pain, fibromyalgia, and chronic headaches.
Compared to NSAIDs, COX-2 inhibitors may pose less risk for uncomplicated ulcers, but these medications do not seem to reduce the risk of more serious events, such as bleeding or perforation.
Certain factors may increase the risk for ulcers in NSAID users:
Other Risk Factors for Ulcers from H pylori or NSAIDs
Stress and Psychological Factors
Although stress is no longer considered a cause of ulcers, some studies still suggest that stress may predispose a person to ulcers or prevent existing ulcers from healing.
Smoking increases acid secretion, reduces prostaglandin and bicarbonate production, and decreases 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.
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.
Peptic ulcers are always suspected in patients with persistent dyspepsia (bloating, belching, and abdominal pain). Symptoms of dyspepsia occur in 20% to 25% of people who live in industrialized nations, but only about 15% to 25% of those with dyspepsia actually have ulcers. It takes several steps to accurately diagnose ulcers.
Medical and Family History
The doctor will ask for a thorough report of a patient's dyspepsia, as well as:
Ruling out Other Disorders
Many other conditions, including gastroesophageal reflux disease (GERD) and irritable bowel syndrome, cause dyspepsia.
Peptic ulcer symptoms, particularly abdominal pain and chest pain, may resemble the symptoms of other conditions, including:
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 is then exposed to hydrogen peroxide. If blood is present, the paper turns blue.
Tests to Detect H pylori
Simple blood, breath, and stool tests can detect H pylori with a fairly high degree of accuracy.
Experts recommend testing for H pylori in all patients with peptic ulcer, because it is such a common cause of this condition.
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.
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. However, this is a subject of considerable debate.
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.
Endoscopy (also called esophagogastroduodenoscopy or EGD) 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. Endoscopy is usually reserved for patients with dyspepsia who also have risk factors or history of ulcers, stomach cancer, or both.
Endoscopy is usually recommended for:
Patients under age 50 who do not have alarm symptoms may be tested non-invasively for H pylori and treated for the infection if they test positive.
The decision about whether endoscopy should be performed on patients who do not respond to initial medication should be individualized. Endoscopy may be recommended for patients with gastric ulcers who continue to have symptoms despite treatment, or for those who have ulcers without a clear cause. It should also be done before surgery is considered.
Endoscopy may be performed in a hospital, doctor's office, or outpatient surgery center. It typically involves the following:
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 ulcers, or deformities and scarring due to previous ulcers. Endoscopy is more accurate than an upper GI series, although it is also more invasive and expensive.
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.
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 have evidence of bleeding or other alarm symptoms, or who are over age 50 should have an endoscopy performed first.
Treatment 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:
Most patients who do not have risk factors for complications are treated without first having an endoscopy. The type of treatment is decided based on a patient's symptoms, and on the results of 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 PPI. If this dose is not effective, doubling the dose will occasionally 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.
There is considerable debate about whether to test for H pylori and treat infected patients who have dyspepsia but no clear evidence of ulcers, in part because H. pylori in the intestinal tract protects against GERD and possibly other conditions. There is also concern about the overuse of antibiotics, which can contribute to the emergence of antibiotic-resistant bacteria.
Antibiotic and Combination Drug Regimens for the Treatment of H pylori
The established treatment for H pylori infection is a combination of antibiotics plus a PPI. Current standard therapy includes three medicines, two antibiotics plus a PPI, called triple therapy. Quadruple therapy refers to four medicines, in various combinations. For any of these regimens, the medicines may be taken in stages, one after another. This is called sequential therapy. Medicines may also be taken at the same time. This is called concomitant therapy. Due to the growing resistance to certain antibiotics and areas where standard therapy cure rates are somewhat low, various combinations and timing of medications are now under study.
Reported cure rates for H pylori range from 70% to 90% after triple therapy regimen (antibiotics plus PPI) treatment. Eradication rates are higher for when bismuth subsalicylate (Pepto-Bismol) is added to the regimen. The standard treatment regimen uses two antibiotics and a PPI:
Patients typically take combination treatment for 10 to 14 days. A 7-day regimen is another option, but some research suggests that 14 days of therapy with antibiotics and PPIs is more effective at eradicating H pylori. When quadruple therapy (without bismuth) is taken at the same time (concomitant therapy), cure rates appear similar to when the medicines are taken sequentially.
Combination products are available.
Follow-up testing to check that the bacteria have been eliminated 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.
Treatment fails in about 10% to 20% of patients, typically when they do not follow their prescribed treatment. Compliance with standard antibiotic regimens may be poor for the following reasons:
Treatment may also fail if patients harbor strains of H pylori that are resistant to antibiotics. When this happens, different drugs are tried.
Re-infection after Successful Treatment
Studies in developed countries indicate that once the bacteria are eliminated, recurrence rates are below 1% per year. Re-infection 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, re-infection rates are 6% to 15%.
Treatment of NSAID-induced ulcers
If patients are diagnosed with NSAID-caused ulcers or bleeding, they should:
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.
In addition to medications to treat the NSAID-caused ulcer, people with chronic pain may replace the original NSAID with one of these alternatives:
The American College of Gastroenterology has made recommendations about the prevention of ulcers in patients using NSAIDs. Doctors should consider whether their patients are at high, moderate, or low risk for gastrointestinal and cardiovascular problems. Depending on a patient's risk factors, the doctor may recommend any NSAID, naproxen only, a COX-2 inhibitor, one of these, or none of the three.
Some patients take either a PPI or misoprostol along with their NSAID. Before starting a patient on long-term NSAID therapy, the physician should consider testing for H pylori.
The following drugs are sometimes used to treat peptic ulcers caused by either NSAIDs or H pylori.
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:
Liquid antacids are thought to work faster and more effectively 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:
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.
H pylori may be treated with the following antibiotics:
Side Effects of Antibiotics
Probiotics and yeasts can help minimize gastrointestinal side effects.
Compounds that contain bismuth inhibit the growth of H pylori bacteria by complex mechanisms. The most common bismuth compound available in the United States has been bismuth subsalicylate (Pepto-Bismol). High doses of bismuth 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. Additionally, they have direct effects on H pylori urease production. They are well tolerated during short term use.
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% to 20% of people who are of Asian descent.
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:
Possible Adverse Effects
Side effects of PPIs are uncommon, but may include headache, diarrhea, constipation, abdominal pain, nausea, and itching.
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 (histamine receptor-2 blockers) interfere with acid production by blocking histamine, a substance produced by the body that stimulates acid secretion in the stomach. H2 blockers were the standard treatment for peptic ulcers until PPIs and antibiotic regimens against H pylori were developed. H2 blockers cannot cure H pylori related ulcers, but they are useful in certain cases.
Four H2 blockers are currently available over-the-counter in the United States:
All 4 drugs have good safety profiles, similar effectiveness and few side effects. There are some differences in side effects between these drugs:
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 drugs are used.
In most cases, H2 blockers have good safety profiles and few side effects. Because H2 blockers can interact with other drugs (such as theophylline, warfarin, phenytoin and lidocaine), be sure to tell your doctor about any other medications 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 to prove this risk.
However, the following concerns are well documented:
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 66%, and in the stomach by 75%. 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.
Sucralfate (Carafate) seems to work by adhering to the ulcer and protecting it from further damage by stomach acid and pepsin. It also promotes the defensive processes of the stomach. 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, ketoconazole, fluoroquinolones, and tetracycline.
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% to 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 PPIs.
Around 10% to 20% of patients require more invasive procedures for bleeding, such as angiography with embolization or major abdominal surgery.
Endoscopy for Diagnosing or Treating Bleeding Ulcers
Endoscopy is important for both diagnosing and treating bleeding ulcers.
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 sticking to ulcers). Endoscopic treatment includes epinephrine injection, thermocoagulation, application of clips and banding procedures.
The following is a typical endoscopic treatment procedure:
Endoscopy is effective at controlling bleeding in most people who are good candidates for the procedure. Rebleeding occurs in about 10% to 20% of patients. If rebleeding occurs, a repeat endoscopy is effective in about 75% of patients. Those who fail to respond will need to have an angiogram with embolization or 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:
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.
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 miniature cameras and instruments. Laparoscopic techniques are increasingly being used for perforated ulcers, and are thought to be comparable in safety to open surgery. Laparoscopic surgery also 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:
Antrectomy and pyloroplasty are usually performed with vagotomy.
In the past, it was common practice to tell people with peptic ulcers to consume small amounts of bland foods frequently throughout the day. Research conducted since that time has shown that a bland diet is not effective at reducing the incidence or recurrence of ulcers, and that eating numerous small meals throughout the day is no more effective than eating 3 meals a day. Large amounts of food should still be avoided, however, because stretching the stomach can result in painful symptoms.
Some evidence suggests that exercise may help reduce the risk for ulcers in some people.
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