Peptic Ulcer Disease

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Background

Gastric and duodenal ulcers usually cannot be differentiated based on history alone, although some findings may be suggestive (see Diagnosis). Epigastric pain is the most common symptom of both gastric and duodenal ulcers. It is characterized by a gnawing or burning sensation and occurs after meals—classically, shortly after meals with gastric ulcer and 2-3 hours afterward with duodenal ulcer.

In uncomplicated peptic ulcer disease (PUD), the clinical findings are few and nonspecific. “Alarm features" that warrant prompt gastroenterology referral[1] include bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia or odynophagia, recurrent vomiting, and family history of GI cancer. Patients with perforated PUD usually present with a sudden onset of severe, sharp abdominal pain. (See Clinical Presentation.)

In most patients with uncomplicated PUD, routine laboratory tests usually are not helpful; instead, documentation of PUD depends on radiographic and endoscopic confirmation. Testing for H pylori infection is essential in all patients with peptic ulcers. Rapid urease tests are considered the endoscopic diagnostic test of choice. Of noninvasive tests, fecal antigen testing is more accurate than antibody testing and is less expensive than urea breath tests. A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome. (See Workup.)

Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD. Endoscopy provides an opportunity to visualize the ulcer, to determine the presence and degree of active bleeding, and to attempt hemostasis by direct measures, if required. Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm features.

Most patients with PUD are treated successfully with cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs), along with the appropriate use of antisecretory therapy. In the United States, the recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy.[1] These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases.[2] Ulcers can recur in the absence of successful H pylori eradication. (See Treatment and Management.)

In patients with NSAID-associated peptic ulcers, discontinuation of NSAIDs is paramount, if it is clinically feasible. For patients who must continue with their NSAIDs, proton pump inhibitor (PPI) maintenance is recommended to prevent recurrences even after eradication of H pylori.[3, 4] Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI. Maintenance therapy with antisecretory medications (eg, H2 blockers, PPIs) for 1 year is indicated in high-risk patients. (See Medication.)

The indications for urgent surgery include failure to achieve hemostasis endoscopically, recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after 2 failed endoscopic attempts), and perforation.

Patients with gastric ulcers are also at risk of developing gastric malignancy.

Anatomy

Because many surgical procedures for peptic ulcer disease (PUD) entail some type of vagotomy, a discussion concerning the vagal innervation of the abdominal viscera is appropriate (see image below). The left (anterior) and the right (posterior) branches of the vagus nerve descend along either side of the distal esophagus. As they enter the lower thoracic cavity, they can communicate with each other through several cross-branches that comprise the esophageal plexus. However, below this plexus, the 2 vagal trunks again become separate and distinct before the anterior trunk branches to form the hepatic, pyloric, and anterior gastric (also termed the anterior nerve of Latarjet) branches. The posterior trunk branches to form the posterior gastric branch (also termed the posterior nerve of Latarjet) and the celiac branch.

The parietal cell mass of the stomach is segmentally innervated by the terminal branches from each of the anterior and posterior gastric branches. These terminal branches are divided during a highly selective vagotomy. The gallbladder is innervated from efferent branches of the hepatic division of the anterior trunk. Consequently, transection of the anterior vagus trunk (performed during truncal vagotomy) can result in a dilated gallbladder with inhibited contractility and subsequent cholelithiasis. The celiac branch of the posterior vagus innervates the entire midgut (with the exception of the gallbladder). Thus, division of the posterior trunk during truncal vagotomy may contribute to postoperative ileus.


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Vagal innervation of stomach.

Pathphysiology

Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. The epithelial cells of the stomach and duodenum secrete mucus in response to irritation of the epithelial lining and as a result of cholinergic stimulation. The superficial portion of the gastric and duodenal mucosa exists in the form of a gel layer, which is impermeable to acid and pepsin. Other gastric and duodenal cells secrete bicarbonate, which aids in buffering acid that lies near the mucosa. Prostaglandins of the E type (PGE) have an important protective role, because PGE increases the production of both bicarbonate and the mucous layer.

In the event of acid and pepsin entering the epithelial cells, additional mechanisms are in place to reduce injury. Within the epithelial cells, ion pumps in the basolateral cell membrane help to regulate intracellular pH by removing excess hydrogen ions. Through the process of restitution, healthy cells migrate to the site of injury. Mucosal blood flow removes acid that diffuses through the injured mucosa and provides bicarbonate to the surface epithelial cells.

Under normal conditions, a physiologic balance exists between gastric acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H pylori infection, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.

The gram-negative spirochete H pylori was first linked to gastritis in 1983. Since then, further study of H pylori has revealed that it is a major part of the triad, which includes acid and pepsin, that contributes to primary peptic ulcer disease. The unique microbiologic characteristics of this organism, such as urease production, allows it to alkalinize its microenvironment and survive for years in the hostile acidic environment of the stomach, where it causes mucosal inflammation and, in some individuals, worsens the severity of peptic ulcer disease.

When H pylori colonizes the gastric mucosa, inflammation usually results. The causal association between H pylori gastritis and duodenal ulceration is now well established in the adult and pediatric literature. In patients infected with H pylori, high levels of gastrin and pepsinogen and reduced levels of somatostatin have been measured. In infected patients, exposure of the duodenum to acid is increased. Virulence factors produced by H pylori, including urease, catalase, vacuolating cytotoxin, and lipopolysaccharide, are well described.

Most patients with duodenal ulcers have impaired duodenal bicarbonate secretion, which has also proven to be caused by H pylori because its eradication reverses the defect[5] . The combination of increased gastric acid secretion and reduced duodenal bicarbonate secretion lowers the pH in the duodenum, which promotes the development of gastric metaplasia (ie, the presence of gastric epithelium in the first portion of the duodenum). H pylori infection in areas of gastric metaplasia induces duodenitis and enhances the susceptibility to acid injury, thereby predisposing to duodenal ulcers. Duodenal colonization by H pylori was found to be a highly significant predictor of subsequent development of duodenal ulcers in one study that followed 181 patients with endoscopy-negative, nonulcer dyspepsia[6] .

Etiology

Peptic ulcer disease (PUD) may be due to any of the following:

H pylori infection

H pylori infection and NSAID use account for most cases of PUD. The rate of H pylori infection for duodenal ulcers in the United States is less than 75% for patients who do not use NSAIDs. Excluding patients who used NSAIDs, 61% of duodenal ulcers and 63% of gastric ulcers were positive for H pylori in one study. These rates were lower in whites than in nonwhites. Prevalence of H pylori infection in complicated ulcers (ie, bleeding, perforation) is significantly lower than that found in uncomplicated ulcer disease.

Drugs

NSAID use is a common cause of PUD. These drugs disrupt the mucosal permeability barrier, rendering the mucosa vulnerable to injury. As many as 30% of adults taking NSAIDs have GI adverse effects. Factors associated with an increased risk of duodenal ulcers in the setting of NSAID use include history of previous peptic ulcer disease, advanced age, female sex, high doses or combinations of NSAIDs, long-term NSAID use, concomitant use of anticoagulants, and severe comorbid illnesses.

A long-term prospective study found that patients with arthritis who were older than 65 years who regularly took low-dose aspirin were at an increased risk for dyspepsia severe enough to necessitate the discontinuation of NSAIDs.[7] This suggests that better management of NSAID use should be discussed with older patients in order to reduce NSAID-associated upper GI events.

Although the idea was initially controversial, most evidence now supports the assertion that H pylori and NSAIDs are synergistic with respect to the development of peptic ulcer disease. A meta-analysis found that H pylori eradication in NSAID-naive users before the initiation of NSAIDs was associated with a decrease in peptic ulcers[8] .

Although the prevalence of NSAID gastropathy in children is unknown, it seems to be increasing, especially in children with chronic arthritis treated with NSAIDs. Case reports have demonstrated gastric ulceration from low-dose ibuprofen in children, even after just 1 or 2 doses[9] .

Corticosteroids alone do not increase the risk for PUD; however, they can potentiate ulcer risk in patients who use NSAIDs concurrently.

The risk of upper GI tract bleeding may be increased in users of the diuretic spironolactone[10] or serotonin reuptake inhibitors with moderate to high affinity for serotonin transporter[11] .

Lifestyle factors

Evidence that tobacco use is a risk factor for duodenal ulcers is not conclusive. Support for a pathogenic role for smoking comes from the finding that smoking may accelerate gastric emptying and decrease pancreatic bicarbonate production. However, studies have produced contradictory findings. In one prospective study of more than 47,000 men with duodenal ulcers, smoking did not emerge as a risk factor.[12] However, smoking in the setting of H pylori infection may increase the risk of relapse of PUD.[13] Smoking is harmful to the gastroduodenal mucosa, and H pylori infiltration is denser in the gastric antrum of smokers.[14]

Ethanol is known to cause gastric mucosal irritation and nonspecific gastritis. Evidence that consumption of alcohol is a risk factor for duodenal ulcer is inconclusive. A prospective study of more than 47,000 men with duodenal ulcer did not find an association between alcohol intake and duodenal ulcer.[12]

Little evidence suggests that caffeine intake is associated with an increased risk of duodenal ulcers.

Severe physiologic stress

Stressful conditions that may cause PUD include burns, CNS trauma, surgery, and severe medical illness. Serious systemic illness, sepsis, hypotension, respiratory failure, and multiple traumatic injuries increase the risk for secondary (stress) ulceration.

Cushing ulcers are associated with a brain tumor or injury and typically are single, deep ulcers that are prone to perforation. They are associated with high gastric acid output and are located in the duodenum or stomach. Extensive burns are associated with Curling ulcers.

Stress ulceration and upper-GI hemorrhage are complications that are increasingly encountered in critically ill children in the intensive care setting. Severe illness and a decreased gastric pH are related to an increased risk of gastric ulceration and hemorrhage.

Hypersecretory states (uncommon)

The following are among hypersecretory states that may, uncommonly, cause PUD:

Physiologic factors

In up to one third of patients with duodenal ulcers, basal acid output (BAO) and maximal acid output (MAO) are increased. In one study, increased BAO was associated with an odds ratio [OR] of up to 3.5, and increased MAO was associated with an OR of up to 7 for the development of duodenal ulcers. Individuals at especially high risk are those with a BAO greater than 15 mEq/h. The increased BAO may reflect the fact that in a significant proportion of patients with duodenal ulcers, the parietal cell mass is increased to nearly twice that of the reference range.[15]

In addition to the increased gastric and duodenal acidity observed in some patients with duodenal ulcers, accelerated gastric emptying is often present. This acceleration leads to a high acid load delivered to the first part of the duodenum, where 95% of all duodenal ulcers are located. Acidification of the duodenum leads to gastric metaplasia, which indicates replacement of duodenal villous cells with cells that share morphologic and secretory characteristics of gastric epithelium. Gastric metaplasia may create an environment that is well suited to colonization by H pylori.

Genetics

More than 20% of patients have a family history of duodenal ulcers, compared with only 5-10% in the control groups. In addition, weak associations have been observed between duodenal ulcers and blood type O. Furthermore, patients who do not secrete ABO antigens in their saliva and gastric juices are known to be at higher risk. The reason for these apparent genetic associations is unclear.

A rare genetic association exists between familial hyperpepsinogenemia type I (a genetic phenotype leading to enhanced secretion of pepsin) and duodenal ulcers. However, H pylori can increase pepsin secretion, and a retrospective analysis of the sera of one family studied before the discovery of H pylori revealed that their high pepsin levels were more likely related to H pylori infection.

Additional etiologic factors

Any of the following may be associated with PUD:

Epidemiology

United States statistics

In the United States, PUD affects approximately 4.5 million people annually. Approximately 10% of the US population has evidence of a duodenal ulcer at some time. Of those infected with H pylori, the lifetime prevalence is approximately 20%. Only about 10% of young persons have H pylori infection; the proportion of people with the infection increases steadily with age.

Overall, the incidence of duodenal ulcers has been decreasing over the past 3-4 decades. Although the rate of simple gastric ulcer is in decline, the incidence of complicated gastric ulcer and hospitalization has remained stable, partly due to the concomitant use of aspirin in an aging population. The hospitalization rate for PUD is approximately 30 patients per 100,000 cases.

The prevalence of PUD has shifted from predominance in males to similar occurrences in males and females. Lifetime prevalence is approximately 11-14% in men and 8-11% in women. Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women. Trends reflect complex changes in risk factors for PUD, including age-cohort phenomena with the prevalence of H pylori infection and the use of NSAIDs in older populations.

International statistics

The frequency of PUD in other countries is variable and is determined primarily by association with the major causes of PUD: H pylori and NSAIDs.[16]

Prognosis

When the underlying cause is addressed, the prognosis is excellent. Most patients are treated successfully with eradication of H pylori infection, avoidance of NSAIDs, and the appropriate use of antisecretory therapy. Eradication of H pylori infection changes the natural history of the disease, with a decrease in the ulcer recurrence rate from 60-90% to approximately 10-20%. However, this is a higher recurrence rate than previously reported, suggesting an increased number of ulcers not caused by H pylori infection.

With regard to NSAID-related ulcers, the incidence of perforation is approximately 0.3% per patient year, and the incidence of obstruction is approximately 0.1% per patient year. Combining both duodenal ulcers and gastric ulcers, the rate of any complication in all age groups combined is approximately 1-2% per ulcer per year.

The mortality rate for PUD, which has decreased modestly in the last few decades, is approximately 1 death per 100,000 cases. If one considers all patients with duodenal ulcers, the mortality rate due to ulcer hemorrhage is approximately 5%. Over the last 20 years, the mortality rate in the setting of ulcer hemorrhage has not changed appreciably despite the advent of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). However, evidence from meta-analyses and other studies has shown a decreased mortality rate from bleeding peptic ulcers when intravenous PPIs are used after successful endoscopic therapy.[17, 18, 19, 20]

Emergency operations for peptic ulcer perforation carry a mortality risk of 6-30%.[21] Factors associated with higher mortality in this setting include the following:

Patient Education

Patients should be warned of known or potentially injurious drugs and agents. Some examples are as follows:

Obesity has been shown to have an association with peptic ulcer disease (PUD), and patients should be counseled regarding benefits of weight loss. Stress reduction counseling might be helpful in individual cases but is not needed routinely.

For excellent patient education resources, visit eMedicineHealth's Esophagus, Stomach, and Intestine Center. In addition, see eMedicineHealth's patient education articles Peptic Ulcers, Heartburn, and Understanding Heartburn/GERD Medications.

History

Obtaining a medical history, especially for peptic ulcer disease, H pylori infection, ingestion of NSAIDs, or smoking, is essential in making the correct diagnosis. Gastric and duodenal ulcers usually cannot be differentiated based on history alone, although some findings may be suggestive.

Epigastric pain is the most common symptom of both gastric and duodenal ulcers. It is characterized by a gnawing or burning sensation and occurs after meals—classically, shortly after meals with gastric ulcer and 2-3 hours afterward with duodenal ulcer. Food or antacids relieve the pain of duodenal ulcers but provide minimal relief of gastric ulcer pain.

Duodenal ulcer pain often awakens the patient at night. About 50-80% of patients with duodenal ulcers experience nightly pain, as opposed to only 30-40% of patients with gastric ulcers and 20-40% of patients with nonulcer dyspepsia (NUD). Pain typically follows a daily pattern specific to the patient. Pain with radiation to the back is suggestive of a posterior penetrating gastric ulcer complicated by pancreatitis.

Patients who develop gastric outlet obstruction as a result of a chronic, untreated duodenal ulcer usually report a history of fullness and bloating associated with nausea and emesis that occurs several hours after food intake. A common misconception is that adults with gastric outlet obstruction present with nausea and emesis immediately after a meal.

Other possible manifestations include the following:

Alarm features that warrant prompt gastroenterology referral[1] include the following:

Physical Examination

In uncomplicated PUD, the clinical findings are few and nonspecific and include the following:

Patients with perforated PUD usually present with a sudden onset of severe, sharp abdominal pain. Most patients describe generalized pain; a few present with severe epigastric pain. As even slight movement can tremendously worsen their pain, these patients assume a fetal position. Abdominal examination usually discloses generalized tenderness, rebound tenderness, guarding, and rigidity. However, the degree of peritoneal findings is strongly influenced by a number of factors, including the size of perforation, amount of bacterial and gastric contents contaminating the abdominal cavity, time between perforation and presentation, and spontaneous sealing of perforation.

These patients may also demonstrate signs and symptoms of septic shock, such as tachycardia, hypotension, and anuria. Not surprisingly, these indicators of shock may be absent in elderly or immunocompromised patients or in those with diabetes. Patients should be asked if retching and vomiting occurred before the onset of pain.

Approach Considerations

Testing for H pylori infection is essential in all patients with peptic ulcers. In most patients with uncomplicated peptic ulcer disease (PUD), routine laboratory tests usually are not helpful. Documentation of PUD depends on radiographic and endoscopic confirmation.

If the diagnosis of PUD is suspected, obtaining CBC count, liver function tests (LFTs), amylase, and lipase may be useful. CBC count and iron studies can help detect anemia, which is an alarm signal that mandates early endoscopy to rule out other sources of chronic GI blood loss.

H pylori Testing

Testing for H pylori infection is essential in all patients with peptic ulcers.

Endoscopic or invasive tests for H pylori include a rapid urease test, histopathology, and culture. Rapid urease tests are considered the endoscopic diagnostic test of choice. The presence of H pylori in gastric mucosal biopsy specimens is detected by testing for the bacterial product urease. Fecal antigen testing identifies active H pylori infection by detecting the presence of H pylori antigens in stools. This test is more accurate than antibody testing and is less expensive than urea breath tests.

Three kits (ie, CLOtest, Hp-fast, Pyloritek) are commercially available for H pylori testing, and each contains a combination of a urea substrate and a pH sensitive indicator. One or more gastric biopsy specimens are placed in the rapid urease test kit. If H pylori is present, bacterial urease converts urea to ammonia, which changes the pH, resulting in a color change.

Urea breath tests detect active H pylori infection by testing for the enzymatic activity of bacterial urease. In the presence of urease produced by H pylori, labeled carbon dioxide (heavy isotope, carbon-13, or radioactive isotope, carbon-14) is produced in the stomach, absorbed into the bloodstream, diffused into the lungs, and exhaled.

Obtain histopathology, often considered the criterion standard to establish a diagnosis of H pylori infection , if the rapid urease test result is negative and a high suspicion for H pylori persists (presence of a duodenal ulcer).

Antibodies (immunoglobulin G [IgG]) to H pylori can be measured in serum, plasma, or whole blood. Results with whole blood tests obtained from finger sticks are less reliable.

Endoscopy

Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD. It is highly sensitive for the diagnosis of gastric and duodenal ulcers, allows for biopsies and cytologic brushings in the setting of a gastric ulcer to differentiate a benign ulcer from a malignant lesion, and allows for the detection of H pylori infection with antral biopsies for a rapid urease test and/or histopathology in patients with PUD. (See the images below.)

At endoscopy, gastric ulcers appear as discrete mucosal lesions with a punched-out smooth ulcer base, which often is filled with whitish fibrinoid exudate. Ulcers tend to be solitary and well circumscribed and usually are 0.5-2.5 cm in diameter. Most gastric ulcers tend to occur at the junction of the fundus and antrum, along the lesser curvature. Benign ulcers tend to have a smooth, regular, rounded edge with a flat smooth base and surrounding mucosa that shows radiating folds. Malignant ulcers usually have irregular heaped-up or overhanging margins. The ulcerated mass often protrudes into the lumen, and the folds surrounding the ulcer crater are often nodular and irregular.


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Gastric ulcer with punched-out ulcer base with whitish fibrinoid exudates.


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Gastric ulcer (lesser curvature) with punched-out ulcer base with whitish exudate.


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Gastric cancer. Note the irregular heaped up overhanging margins.


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Gastric cancer with ulcerated mass.

More than 95% of duodenal ulcers are found in the first part of the duodenum; most are less than 1 cm in diameter.[22] Duodenal ulcers are characterized by the presence of a well-demarcated break in the mucosa that may extend into the muscularis propria of the duodenum (see the images below).


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Gastric cancer with ulcerated mass.


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Duodenal ulcer in a 35-year-old woman who presented with tarry stools and a hemoglobin level of 75 g/L.


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Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena stools. The patient took naproxen on a daily basis.

A meta-analysis has shown that for individuals who undergo endoscopy for dyspepsia, the most common finding is erosive esophagitis (though prevalence was lower when the Rome criteria were used to define dyspepsia) followed by peptic ulcer.[23]

Radiography

In patients presenting acutely, a chest radiograph may be useful to detect free abdominal air when perforation is suspected. On upper GI contrast study with water-soluble contrast, the extravasation of contrast indicates gastric perforation.

Double-contrast radiography performed by an experienced radiologist may approach the diagnostic accuracy of upper GI endoscopy. However, it has been replaced largely by diagnostic endoscopy, when available. An upper GI series is not as sensitive as endoscopy for establishing a diagnosis of small ulcers (< 0.5 cm). It also does not allow for obtaining a biopsy to rule out malignancy in the setting of a gastric ulcer or to assess for H pylori infection in the setting of a gastroduodenal ulcer.

Angiography

Angiography may be necessary in patients with a massive GI bleed in whom endoscopy cannot be performed. An ongoing bleeding rate of 0.5 mL/min or more is needed for the angiography to be able to accurately identify the bleeding source. Angiography can depict the source of the bleeding and can help provide needed therapy in the form of a direct injection of vasoconstrictive agents.

Serum Gastrin Level

A fasting serum gastrin level should be obtained in certain cases to screen for Zollinger-Ellison syndrome. Such cases include the following:

Secretin Stimulation Test

A secretin stimulation test may be required if the diagnosis of Zollinger-Ellison syndrome cannot be made on the basis of the serum gastrin level alone. This test can distinguish Zollinger-Ellison syndrome from other conditions with a high serum gastrin level, such as use of antisecretory therapy with a proton pump inhibitor, renal failure, or gastric outlet obstruction.

Biopsy

A single biopsy offers 70% accuracy in diagnosing gastric cancer, but 7 biopsy samples obtained from the base and ulcer margins increase the sensitivity to 99%. Brush cytology has been shown to increase the biopsy yield, and this method may be useful particularly when bleeding is a concern in a patient with coagulopathy.

Histologic Findings

The histology of gastric ulcer depends on its chronicity. The surface is covered with slough and inflammatory debris. Beneath this neutrophilic infiltration, active granulation with mononuclear leukocytic infiltration and fibrinoid necrosis may be seen. In chronic superficial gastritis, lymphocytes, monocytes, and plasma cells often infiltrate the mucosa and submucosa.

Emergency Department Workup

The ED workup will vary depending on presentation and includes the following:

Approach Considerations

Treatment of peptic ulcers varies depending on the etiology and clinical presentation. The initial management of a stable patient with dyspepsia differs from the management of an unstable patient with upper GI hemorrhage. In the latter scenario, failure of medical management not uncommonly leads to surgical intervention.

Treatment options include empiric antisecretory therapy, empiric triple therapy for H pylori infection, endoscopy followed by appropriate therapy based on findings, and H pylori serology followed by triple therapy for patients who are infected. Breath testing for active H pylori infection may be used.

Endoscopy is required to document healing of gastric ulcers and to rule out gastric cancer. This usually is performed 6-8 weeks after the initial diagnosis of PUD. Documentation of H pylori cure with a noninvasive test, such as the urea breath test or fecal antigen test, is appropriate in patients with complicated ulcers.

Given the current understanding of the pathogenesis of PUD, most patients with PUD are treated successfully with cure of H pylori infection and/or avoidance of NSAIDs, along with the appropriate use of antisecretory therapy. Computer models have suggested that obtaining H pylori serology followed by triple therapy for patients who are infected is the most cost-effective approach; however, no direct evidence from clinical trials provides confirmation.

Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm symptoms, such as dysphagia, recurrent vomiting, weight loss, or bleeding. Age is an independent risk factor for the incidence and mortality from bleeding peptic ulcer, with the risk increasing in persons older than 65 years and increasing further in those older than age 75 years.[24] In one study, at least 2 risk factors (previous duodenal ulcer, H pylori infection, use of ASA/NSAID, and smoking) were present in two thirds of persons with acute gastroduodenal bleeding.[25]

The indications for urgent surgery include failure to achieve hemostasis endoscopically, recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after 2 failed endoscopic attempts), and perforation. Many authorities recommend simple oversewing of the ulcer with treatment of the underlying H pylori infection or cessation of NSAIDs for bleeding PUD. Additional surgical options for refractory or complicated PUD include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.

Bleeding Peptic Ulcers

The principles of management of bleeding peptic ulcers outlined below are equally applicable to both gastric and duodenal ulcers.

Endoscopic therapy

Upper GI bleeding secondary to a bleeding peptic ulcer is a common medical condition. Endoscopic evaluation of the bleeding ulcer can decrease the duration of the hospital stay by identifying patients at low risk for rebleeding. Moreover, endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need for surgery.

Patients can be stratified as having high or low risk for rebleeding depending on the presence or absence of stigmata seen on the initial endoscopic examination.

High-risk stigmata are the following:

Ulcers with such stigmata require endotherapy, while ulcers with a clean base need not be treated endoscopically. In the absence of these stigmata, patients can be discharged home on medical therapy within 48 hours.

Several modalities of endoscopic therapy are available, such as injection therapy, coagulation therapy, hemostatic clips, argon plasma coagulator, and combination therapy.[26] Injection therapy is performed with epinephrine in a 1:10,000 dilution or with absolute alcohol. Thermal endoscopic therapy is performed with a heater probe, bipolar circumactive probe, or gold probe. Pressure is applied to cause coagulation of the underlying artery (coaptive coagulation). Combination therapy with epinephrine injection followed by thermal coagulation appears to be more effective than monotherapy for ulcers with a visible vessel, active hemorrhage, or adherent clot.

Hemoclips have been used successfully to treat an acutely bleeding ulcer by approximating 2 folds and clipping them together. Several clips may need to be deployed to approximate the gastric ulcer folds. In treating high-risk bleeding ulcers, combined therapy with epinephrine and hemoclips seems to be more efficacious than injection alone. However, it is not clear whether hemoclip use or thermal coagulation is more effective in treating an acutely bleeding ulcer; both modalities are used depending on physician experience and equipment availability.

Urgent esophagogastroduodenoscopy (EGD) is the treatment of choice in the setting of a bleeding peptic ulcer for diagnostic and therapeutic reasons. Endoscopy provides an opportunity to visualize the ulcer, to determine the degree of active bleeding, and to attempt hemostasis by direct measures. Primary endoscopic hemostatic therapy (EHT) is successful in about 90% of patients; when this fails, transcatheter embolization may be useful.[27] Medical management usually serves as an adjunct to direct endoscopic therapy.

Risk factors that predict rebleeding following EHT for nonvariceal upper GI bleeding include the following:

These high-risk persons may be considered for initial care in the ICU and follow-up (second-look) endoscopy, especially because many of these factors (advanced age, comorbidities, in-hospital bleeding, rebleeding, hypovolemic shock, need for surgery) are associated with hospital mortality.[30]

Acid suppression

Acid suppression is the general pharmacologic principle of medical management of acute bleeding from a peptic ulcer. Reducing gastric acidity is believed to improve hemostasis primarily through the decreased activity of pepsin in the presence of a more alkaline environment. Pepsin is believed to antagonize the hemostatic process by degrading fibrin clots. By suppressing acid production and maintaining a pH above 6, pepsin becomes markedly less active. Concomitant H pylori infection in the setting of bleeding peptic ulcers should be eradicated, as this lowers the rate of rebleeding.[31, 32]

Two classes of acid-suppressing medications currently in use are histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs).[33] Both classes are available in intravenous and oral preparations. Examples of H2RAs include ranitidine, cimetidine, famotidine, and nizatidine. Examples of PPIs include omeprazole, pantoprazole, lansoprazole, and rabeprazole.

H2RAs are an older class of medications, and in the setting of an actively bleeding duodenal ulcer, their use has been largely superseded by the use of PPIs. Many gastroenterologists assert that intravenous PPI therapy maintains hemostasis more effectively than intravenous H2RA. Thus, intravenous H2RA no longer has a role in the management of bleeding peptic ulcers.[34]

PPIs have a very good safety profile, although attention must continue to be focused on adverse effects, especially with long-term and/or high-dose therapy, such as Clostridium difficile infection, community-acquired pneumonia, hip fracture, and vitamin B12 deficiency.[35] Long-term use of PPIs is also associated with decreased absorption of some medications. PPIs impair gastric secretion of acid; thus, absorption of any medication that depends on gastric acidity, such as ketoconazole and iron salt, is impaired with long-term PPI therapy. In addition, achlorhydria (absence of intragastric acidity) may be associated with iron deficiency anemia, because the ferric form of iron must be converted to the ferrous form by gastric acid. Most iron absorbed is in the ferrous form.

Parenteral PPI administration is indicated after successful endoscopic therapy for ulcers with high-risk signs, such as active bleeding, visible vessels, and adherent clots. Parenteral PPI use before endoscopy is a common practice. Based on intragastric pH data, nonvomiting patients with bleeding ulcers may be treated with oral lansoprazole (120-mg bolus, followed by 30 mg every 3 h).[36] When indicated, intravenous pantoprazole or omeprazole is administered as an 80-mg bolus followed by a continuous 8-mg/h infusion for 72 hours. A study by Chan et al determined that intravenous, standard-dose omeprazole was inferior to high-dose omeprazole in preventing rebleeding after endoscopic therapy for peptic ulcer bleeding.[37] This treatment is changed to oral PPI therapy after 72 hours if no rebleeding occurs.

In a study by Andriulli et al, standard-dose PPI infusion was found to be as effective as a high-dose regimen in reducing the risk of recurrent bleeding following endoscopic hemostasis of bleeding ulcers, according to a study by Andriulli et al. The primary end point was the in-hospital rebleeding rate (determined on repeat endoscopy). Patients with actively bleeding ulcers and those with a nonbleeding visible vessel or an adherent clot were treated with (1) epinephrine injection and/or thermal coagulation, then randomized to receive an intensive regimen of 80-mg PPI bolus, followed by 8 mg/h as continuous infusion for 72 hours, or (2) a standard regimen of a 40-mg PPI bolus daily, followed by saline infusion for 72 hours. After the infusion, all patients were given 20 mg PPI twice daily orally.[38]

In the intensive PPI regimen group, rebleeding recurred in 11.8%, whereas in the standard regimen group, rebleeding recurred in 8.1%. Most of the rebleeding episodes occurred during the initial 72-hour infusion. The duration of hospital stay was less than 5 days for 37.0% in the intensive regimen group and 47.0% in the standard group. There were fewer surgical interventions in the standard group. Five patients in each treatment group died.[38]

A Canadian database (RUGBE) indicated some benefit for parenteral PPI in decreasing rebleed rates.[34] No randomized, controlled trial has provided evidence to support the use of parenteral PPI in this setting, but giving oral PPI both before and after EHT for persons with peptic ulcers with signs of recent hemorrhage can be justified on the grounds of cost-effectiveness.[17]

Whether acid suppression improves therapeutic outcomes of peptic ulcers compared with placebo may be more important than the issues raised above. Many researchers have compared parenteral PPI therapy with placebo, and overall, the results have demonstrated a shorter period of bleeding and a decreased incidence of rebleeding with PPI therapy. Some studies have demonstrated a decreased need for emergency surgery and blood transfusion; however, evidence that parenteral PPI reduces mortality from ulcer bleeding is relatively recent.[18]

H pylori Infection

In the United States, the recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy.[1] These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases.[2] Ulcers can recur in the absence of successful H pylori eradication.

Dual therapies, which are alternative regimens for treating H pylori infection, are usually not recommended as first-line therapy, because of a variable cure rate that is significantly less than the cure rate achieved with triple therapy.

Spouses and H pylori –positive family members of H pylori –positive persons should be considered for testing and treatment of H pylori infection,[39] since mother-to-child transmission may be a major route of H pylori infection.[40]

Triple-therapy regimens

PPI-based triple therapy regimens for H pylori consist of a PPI, amoxicillin, and clarithromycin for 7-14 days. A longer duration of treatment (14 d vs 7 d) appears to be more effective and is currently the recommended treatment. Amoxicillin should be replaced with metronidazole in penicillin-allergic patients only, because of the high rate of metronidazole resistance.[41] In patients with complicated ulcers caused by H pylori, treatment with a PPI beyond the 14-day course of antibiotics and until the confirmation of the eradication of H pylori is recommended.

PPI-based triple therapies are a 14-day regimen as shown below:

Omeprazole (Prilosec): 20 mg PO bid

or

Lansoprazole (Prevacid): 30 mg PO bid

or

Rabeprazole (Aciphex): 20 mg PO bid

or

Esomeprazole (Nexium): 40 mg PO qd

Plus

Clarithromycin (Biaxin): 500 mg PO bid

and

Amoxicillin (Amoxil): 1 g PO bid

Alternative triple-therapy regimens

The alternative triple therapies, also administered for 14 days, are as follows:

Omeprazole (Prilosec): 20 mg PO bid

or

Lansoprazole (Prevacid): 30 mg PO bid

or

Rabeprazole (Aciphex): 20 mg PO bid

or

Esomeprazole (Nexium): 40 mg PO qd

Plus

Clarithromycin (Biaxin): 500 mg PO bid

and

Metronidazole (Flagyl): 500 mg PO bid

Quadruple therapy

Quadruple therapies for H pylori infection are generally reserved for patients in whom the standard course of treatment has failed.

Quadruple treatment includes the following drugs, administered for 14 days:

Consider maintenance therapy with half of the standard doses of H2-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H pylori has not been documented or if an H pylori –negative ulcer is present.

Medical Management of NSAID Ulcers

In 2009, the American College of Gastroenterology (ACG) issued a guideline for prevention of NSAID-related ulcer complications that supports the recommendations in this section.[42] According to the ACG guideline, all patients who are beginning long-term NSAID therapy should first be tested for H pylori. NSAIDs should be immediately discontinued in patients with positive H pylori test results if clinically feasible.

For patients who must continue with their NSAIDs, PPI maintenance is recommended to prevent recurrences even after eradication of H pylori.[3, 4] If NSAIDs must be continued, changing to a COX-2 selective inhibitor is an option. However, use of a traditional NSAID and once-daily PPI is comparable to a selective COX-2 inhibitor with respect to ulcer bleeding in patients with a history of peptic ulcer disease.[43] In general, 6-8 weeks of therapy with a PPI is required for complete healing of a duodenal ulcer.

Active ulcers associated with NSAID use are treated with an appropriate course of PPI therapy and the cessation of NSAIDs. For patients with a known history of ulcer and in whom NSAID use is unavoidable, the lowest possible dose and duration of the NSAID and co-therapy with a PPI or misoprostol are recommended.

Thus, the 2009 ACG guideline recommends that patients who are treated with NSAIDs and also require low-dose aspirin therapy for cardiovascular disease be treated with naproxen plus misoprostol or a PPI. Patients at moderate risk for gastrointestinal complications and at high risk for cardiovascular disease should avoid NSAIDs or COX-2 inhibitors entirely and receive alternative therapy.[42]

Deterrence and prevention

Primary prevention of NSAID-induced ulcers includes the following:

Consider prophylactic or preventive therapy for the following patients:

Prophylactic regimens that have been shown to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analog or a PPI according to the following regimens:

A 2005 study showed that in patients with aspirin-induced ulcer, contrary to popular belief, aspirin plus esomeprazole (Nexium) was superior to clopidogrel (Plavix) in preventing recurrent gastric ulcer bleeding.[44] This was further confirmed in a double-blind randomized study in 2006 by Lai and colleagues.[45]

In a study by Hsu et al, combining esomeprazole and clopidogrel reduced the recurrence of peptic ulcers in patients with atherosclerosis and a history of peptic ulcers more than the use of clopidogrel alone.[46] This combination did not influence the action of clopidogrel on platelet aggregation.

Emergency Department Care

Presentations of peptic ulcer disease and gastritis usually are indistinguishable in the ED, and thus, the management is generally the same. Treatment goals in the acute setting are the relief of discomfort and protection of the gastric mucosal barrier to promote healing. Administer supportive therapy as needed. Most patients with gastritis or peptic ulcer disease do not require acute interventions.

High-risk patients include those with the following characteristics:

Drug treatments

Antacids or a GI cocktail (typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) may be used as symptomatic therapy; however, relief of symptoms with a GI cocktail is not a diagnostic indicator.

Empiric treatment of H pylori is not recommended. Therapy is indicated only after confirmation of infection. These tests are not performed in the ED. Empiric trial of acid suppression in patients younger than 55 years without alarm features may be initiated with PPI for 4-8 weeks. Appropriate follow-up is required to assess response in 2-4 weeks.[47]

Anticholinergic agents are contraindicated.

Bleeding

Massive gastric bleeds are the most difficult complication to treat. Mainstays of resuscitation include the following:

Patients with significant or potentially significant hemorrhage require admission, usually to the intensive care unit.

Surgical Care for Perforated Peptic Ulcer

With the success of medical therapy, surgery has a very limited role in the management of PUD. Elective peptic ulcer surgery has been virtually abandoned. In the 1980s, the number of elective operations for peptic ulcer disease dropped more than 70%, and emergent operations accounted for more than 80%.[49] In general, 5% of bleeding ulcers eventually require operative management. The indications for urgent surgery include the following:

The appropriate surgical procedure depends on the location and nature of the ulcer. Many authorities recommend simple oversewing of the ulcer with treatment of the underlying H pylori infection or cessation of NSAIDs for bleeding PUD. Additional surgical options for refractory or complicated PUD include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.

Only one prospective randomized trial has compared laparoscopic surgery with open surgery for perforated ulcer. The study found that the only difference between the 2 groups was reduced need for analgesia and an increased operative time in the laparoscopic group. Contraindications for laparoscopic repair for perforated peptic ulcer include large perforations, a posterior location of the perforation, and a poor general state of health.[34]

Surgical complications include pneumonia (30%), wound infection, abdominal abscess (15%), cardiac problems (especially in those >70 y), diarrhea (30% after vagotomy), and dumping syndromes (10% after vagotomy and drainage procedures).

To see complete information on Surgical Treatment of Perforated Peptic Ulcer, please go to the main article by clicking here.

Diet

A special diet is not indicated for patients with duodenal ulcers. It is a common-sense approach to avoid any food or beverages that may aggravate symptoms. Although the link between duodenal ulcers and alcohol is inconclusive, moderation of alcohol intake may be recommended for other health reasons.

Complications of Peptic Ulcer Disease

Refractory, symptomatic peptic ulcers, though rare after eradication of H pylori infection and the appropriate use of antisecretory therapy, are a potential complication of PUD. Obstruction is particularly likely to complicate PUD in cases refractory to aggressive antisecretory therapy, H pylori eradication, or avoidance of NSAIDs. Obstruction may persist or recur despite endoscopic balloon dilation. Perforation is also a possibility. Penetration, particularly if not walled off or if a gastrocolic fistula develops, is a potential complication. In addition, ulcer bleeding, particularly in patients with a history of massive hemorrhage and hemodynamic instability, recurrent bleeding on medical therapy, and failure of therapeutic endoscopy to control bleeding is a serious complication.

Patients with gastric ulcers are also at risk of developing gastric malignancy. The risk is approximately 2% in the initial 3 years. One of the important risk factors is related to H pylori infection. H pylori is associated with atrophic gastritis, which, in turn, predisposes to gastric cancer. H pylori infection is associated with gastric lymphoma or mucosa-associated lymphoid tissue (MALT) lymphoma. Normal gastric mucosa is devoid of organized lymphoid tissue. H pylori infection promotes acquisition of lymphocytic infiltration and often the formation of lymphocytic aggregates and follicles from which MALT lymphoma develops. Eradication of H pylori is very important in this group of patients because eradication of H pylori has been shown to cause a remission of MALT lymphoma.

Malignancy should be strongly considered in the case of a persistent nonhealing gastric ulcer. Endoscopic ultrasound examination may be helpful for assessing mucosal invasion or detecting associated adenopathy in such patients. Surgical resection should be considered if evidence of cancerous transformation is present.

Consultations

Surgical consultation is recommended for all patients with bleeding ulcers, especially those patients who are at high risk of significant bleeding. Such ulcers include those that have caused hemodynamic instability, those that are actively bleeding, and those that show a visible vessel on endoscopy.

Long-Term Monitoring

Maintenance therapy with antisecretory medications (eg, H2 blockers, PPIs) for 1 year is indicated in high-risk patients. High-risk patients include those with recurrent ulcers and those with complicated or giant ulcers. If H pylori eradication is not achieved despite repeat treatment, maintenance antisecretory therapy should be recommended.

Consider maintenance therapy with half of the standard doses of H2-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H pylori has not been documented or if an H pylori –negative ulcer is present.

Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely. In this setting, if H pylori is absent, consider a secondary cause of duodenal ulcer, such as Zollinger-Ellison syndrome.

Peptic ulcer rebleeding is extremely rare after H pylori eradication. The use of maintenance antisecretory therapy is not necessary if H pylori eradication has been achieved. However, NSAID use may cause rebleeding even in patients in whom H pylori has been eradicated.[50]

Medication Summary

The goals of pharmacotherapy are to eradicate H pylori infection, to reduce morbidity, and to prevent complications in patients with peptic ulcers. Acid suppression is the general pharmacologic principle of medical management of acute bleeding from a peptic ulcer, using histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs).[33] Both classes are available in intravenous or oral preparations. Discontinuation of NSAIDs is paramount, if it is clinically feasible. For patients who must continue with their NSAIDs, PPI maintenance is recommended to prevent recurrences even after eradication of H pylori.

The recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy. Antacids or a GI cocktail (typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) may be used as symptomatic therapy in the ED. Maintenance treatment with antisecretory medications (eg, H2 blockers, PPIs) for 1 year is indicated in high-risk patients. High-risk patients include those with recurrent ulcers and those with complicated or giant ulcers. If H pylori eradication is not achieved despite repeat treatment, maintenance antisecretory therapy should be recommended. Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely. In this setting, if H pylori is absent, consider a secondary cause of duodenal ulcer, such as Zollinger-Ellison syndrome.

Primary prevention of NSAID-induced ulcers includes avoiding unnecessary use of NSAIDs, using acetaminophen or nonacetylated salicylates when possible, and using the lowest effective dose of an NSAID and switching to less toxic NSAIDs.

Omeprazole (Prilosec)

Clinical Context:  Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump. It usually is given with clarithromycin and amoxicillin (or metronidazole if the patient is allergic to penicillin) if giving proton pump inhibitor–based triple therapy. It might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in long-term NSAID users at high risk.

Lansoprazole (Prevacid)

Clinical Context:  Lansoprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump. It usually is given with clarithromycin and amoxicillin (or metronidazole if the patient is allergic to penicillin) if giving proton pump inhibitor–based triple therapy. It might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in long-term NSAID users at high risk.

Rabeprazole (Aciphex)

Clinical Context:  Rabeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+ ATP pump. It is used for short-term (4-8 wk) treatment and relief of symptomatic erosive or ulcerative gastroesophageal reflux disease. Patients not healed after 8 weeks should consider an additional 8-week course.

Esomeprazole (Nexium)

Clinical Context:  Esomeprazole is an S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. It is used in severe cases and in patients who have not responded to H2 antagonist therapy. Esomeprazole is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers, and it may be used for up to 8 weeks to treat all grades of erosive esophagitis.

Pantoprazole (Protonix)

Clinical Context:  Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the intravenous preparation has only been studied for short-term use (ie, 7-10 d).

Class Summary

PPIs are inhibitors of the gastric H+/K+ -ATPase (proton pump) enzyme system, which catalyzes the exchange of H+ and K+.

Cimetidine (Tagamet)

Clinical Context:  Cimetidine can be used as primary therapy to heal ulcers not associated with H pylori infection. The duration of treatment is 6-8 weeks. A longer treatment course might be required for gastric ulcers.

Famotidine (Pepcid)

Clinical Context:  Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Nizatidine (Axid)

Clinical Context:  Nizatidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Ranitidine (Zantac)

Clinical Context:  Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Class Summary

H2 blocker antihistamine agents are used in the short-term treatment of an active duodenal ulcer and as prophylaxis in the long term.

Amoxicillin (Amoxil, Biomox, Trimox)

Clinical Context:  This is a component of drug combination therapy that effectively treats duodenal ulcer or gastric ulcers associated with H pylori infection. It interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Administer with omeprazole or lansoprazole plus clarithromycin in proton pump inhibitor–based triple therapy.

Clarithromycin (Biaxin)

Clinical Context:  This is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition. This component of drug combination therapy effectively treats duodenal ulcer or gastric ulcers associated with H pylori infection. It interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Administer with omeprazole or lansoprazole plus clarithromycin in proton pump inhibitor–based triple therapy.

Tetracycline (Sumycin)

Clinical Context:  Component of drug combination therapy that effectively treats duodenal ulcer or gastric ulcer associated with H pylori infection. Usually used in combination with bismuth subsalicylate and metronidazole.

Metronidazole (Flagyl, Flagyl ER)

Clinical Context:  This is a component of drug combination therapy that effectively treats duodenal ulcers or gastric ulcers associated with H pylori infection. It is active against various anaerobic bacteria and protozoa. It appears to be absorbed into cells. The intermediate-metabolized compounds formed bind DNA and inhibit protein synthesis, causing cell death.

Class Summary

Antimicrobial agents exert an antibacterial effect on H pylori.

Bismuth subsalicylate (Pepto Bismol, Pink Bismuth, Kaopectate Extra Strength)

Clinical Context:  This is a highly insoluble salt of trivalent bismuth and salicylic acid. Greater than 80% of salicylic acid is absorbed from oral doses of bismuth subsalicylate chewable tablets. It controls diarrhea by reducing fluid secretion into the intestinal lumen, by binding bacterial toxins, or by acting as an antimicrobial agent.

Class Summary

Antidiarrheal agents may have antisecretory and antimicrobial action.

Misoprostol (Cytotec)

Clinical Context:  Misoprostol is a prostaglandin analog that can be used to decrease the incidence of peptic ulcers and complications in long-term NSAID users at high risk.

Sucralfate (Carafate)

Clinical Context:  Sucralfate binds with positively charged proteins in exudates and forms a viscous adhesive substance that protects the GI lining against pepsin, peptic acid, and bile salts. It is used for short-term management of ulcers.

Class Summary

Cytoprotective agents stimulate mucus production and enhance blood flow throughout the lining of the gastrointestinal tract. These agents also work by forming a coating that protects the ulcerated tissue. Examples of cytoprotective agents include misoprostol and sucralfate.

Author

BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Ameesh Shah, MD, Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital

Disclosure: Nothing to disclose.

Andre Hebra, MD, Chief, Division of Pediatric Surgery, Professor of Surgery and Pediatrics, Medical University of South Carolina College of Medicine; Surgeon-in-Chief, Medical University of South Carolina Children's Hospital

Disclosure: Nothing to disclose.

B UK Li, MD, Professor of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Director, Pediatric Fellowships and Gastroenterology Fellowship, Medical Director, Functional Gastrointestinal Disorders and Cyclic Vomiting Program, Medical College of Wisconsin; Attending Gastroenterologist, Children's Hospital of Wisconsin

Disclosure: Nothing to disclose.

Brian James Daley, MD, MBA, FACS, FCCP, CNSC, Professor and Program Director, Department of Surgery, Chief, Division of Trauma and Critical Care, University of Tennessee Health Science Center College of Medicine

Disclosure: Nothing to disclose.

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Chris A Liacouras, MD, Director of Pediatric Endoscopy, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

Daryl Lau, MD, MPH, MSc, FRCP(C), Director of Translational Liver Research, Liver Center, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center; Associate Professor of Medicine, Harvard Medical School

Disclosure: Nothing to disclose.

David Greenwald, MD, Associate Professor of Clinical Medicine, Fellowship Program Director, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Erick F Rivas, MD, PT, Resident Physician, Department of Surgery, Michigan State University College of Human Medicine

Disclosure: Nothing to disclose.

Eugene Hardin, MD, FAAEM, FACEP, Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Faisal Aziz, MD, Assistant Professor of Surgery, Divsion of Vascular and Endovascular Surgery, Department of Surgery, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

George T Fantry, MD, Associate Professor of Medicine, Department of Internal Medicine, Division of Gastroenterology, University of Maryland School of Medicine

Disclosure: Nothing to disclose.

Harsh Grewal, MD, FACS, FAAP, Clinical Professor of Surgery, Temple University School of Medicine; Chief, Division of Pediatric Surgery, Cooper University Hospital

Disclosure: Nothing to disclose.

Jay A Yelon, DO, FACS, Associate Professor of Surgery and Anesthesiology, Program Director, Surgical Critical Care Fellowship, New York Medical College; Chief, Division of Trauma and Surgical Critical Care, Westchester Medical Center

Disclosure: Nothing to disclose.

Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Highfield MRI

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MA, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital

Disclosure: AMGEN Royalty Consulting; Ardelyx Ownership interest Board membership

Juda Zvi Jona, MD, FAAP(s), FACS, EUPSA, Clinical Professor of Surgery, Michigan State University College of Human Medicine; Clinical Professor of Surgery, Northwestern University, The Feinberg School of Medicine; Attending Senior Surgeon, Director of Pediatric Surgery Service, Surgical Executive Committee, Sparrow Hospital

Disclosure: Nothing to disclose.

Mutaz I Sultan, MBChB, Makassed Hospital, Israel

Disclosure: Nothing to disclose.

Philip Shayne, MD, Associate Professor, Program Director and Vice Chair for Education, Department of Emergency Medicine, Emory University School of Medicine

Disclosure: Nothing to disclose.

Robert K Minkes, MD, PhD, Professor of Surgery, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Medical Director and Chief of Surgical Services, Children's Medical Center of Dallas-Legacy Campus

Disclosure: Nothing to disclose.

Sanjeeb Shrestha, MD, Consulting Staff, Division of Gastroenterology, Gastroenterology Care Consultants

Disclosure: Nothing to disclose.

Shane M Devlin, MD, FRCP(C), Clinical Assistant Professor, Department of Internal Medicine, Peter Lougheed Center, University of Calgary, Canada

Disclosure: Nothing to disclose.

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Tri H Le, MD, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Penn State Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Waqar A Qureshi, MD, Associate Professor of Medicine, Chief of Endoscopy, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine and Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Wendi S Miller, MD, Resident Physician, Department of Emergency Medicine, Emory University School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Terence David Lewis, MBBS, FRACP, FRCPC, FACP, Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Noel Williams, MD, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM, Chair, Department of Emergency Medicine, LeConte Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Alan BR Thomson, MD Professor of Medicine, Division of Gastroenterology, University of Alberta, Canada

Alan BR Thomson, MD is a member of the following medical societies: Alberta Medical Association, American College of Gastroenterology, American Gastroenterological Association, Canadian Association of Gastroenterology, Canadian Medical Association, College of Physicians and Surgeons of Alberta, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

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Vagal innervation of stomach.

Gastric ulcer with punched-out ulcer base with whitish fibrinoid exudates.

Gastric ulcer (lesser curvature) with punched-out ulcer base with whitish exudate.

Gastric cancer. Note the irregular heaped up overhanging margins.

Gastric cancer with ulcerated mass.

Gastric cancer with ulcerated mass.

Duodenal ulcer in a 35-year-old woman who presented with tarry stools and a hemoglobin level of 75 g/L.

Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena stools. The patient took naproxen on a daily basis.

Vagal innervation of stomach.

Gastric ulcer with punched-out ulcer base with whitish fibrinoid exudates.

Gastric ulcer (lesser curvature) with punched-out ulcer base with whitish exudate.

Gastric cancer. Note the irregular heaped up overhanging margins.

Gastric cancer with ulcerated mass.

Gross pathology of a gastric ulcer.

Gastric cancer with ulcerated mass.

Duodenal ulcer in a 35-year-old woman who presented with tarry stools and a hemoglobin level of 75 g/L.

Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena stools. The patient took naproxen on a daily basis.