Peptic ulcer disease can involve the stomach or duodenum. Gastric and duodenal ulcers usually cannot be differentiated based on history alone, although some findings may be suggestive (see DDx). Epigastric pain is the most common symptom of both gastric and duodenal ulcers, characterized by a gnawing or burning sensation and that occurs after meals—classically, shortly after meals with gastric ulcers and 2-3 hours afterward with duodenal ulcers.
In uncomplicated peptic ulcer disease, 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 gastrointestinal (GI) cancer. Patients with perforated peptic ulcer disease usually present with a sudden onset of severe, sharp abdominal pain. (See Presentation.)
In most patients with uncomplicated peptic ulcer disease, routine laboratory tests usually are not helpful; instead, documentation of peptic ulcer disease 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 the noninvasive tests, fecal antigen testing is more accurate than antibody testing and is less expensive than urea breath tests but either is reasonable. 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 peptic ulcer disease. 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 peptic ulcer disease 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.)
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 two failed endoscopic attempts), and perforation.
Patients with gastric ulcers are also at risk of developing gastric malignancy.
Because many surgical procedures for peptic ulcer disease 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 two 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 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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Peptic ulcer disease. Vagal innervation of the stomach.
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 nonsteroidal anti-inflammatory drugs (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, bicarbonate, 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]
Peptic ulcer disease may be due to any of the following:
H pylori infection
Drugs
Lifestyle factors
Severe physiologic stress
Hypersecretory states (uncommon)
Genetic factors
H pylori infection
H pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use account for most cases of peptic ulcer disease. 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 peptic ulcer disease. 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, older 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.
A UK retrospective study of patients newly initiated on low-dose aspirin for secondary prevention of cardiovascular events identified risk factors for uncomplicated peptic ulcer disease in these patients that included the following[8] :
Previous history of peptic ulcer disease
Current use of NSAIDs, oral steroid agents, or acid suppressive agents
Tobacco use
Stress
Depression
Anemia
Social deprivation (comprises four census variables used in the Townsend deprivation index[9] : households that lack a car, are overcrowded, not owner-occupied, and have unemployed persons)
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.[10]
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.[11]
Corticosteroids alone do not increase the risk for peptic ulcer disease; 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[12] or serotonin reuptake inhibitors with moderate to high affinity for serotonin transporter.[13]
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.[14] However, smoking in the setting of H pylori infection may increase the risk of relapse of peptic ulcer disease.[15] Smoking is harmful to the gastroduodenal mucosa, and H pylori infiltration is denser in the gastric antrum of smokers.[16]
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.[14]
Little evidence suggests that caffeine intake is associated with an increased risk of duodenal ulcers.
Severe physiologic stress
Stressful conditions that may cause peptic ulcer disease include burns, central nervous system (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-gastrointestinal (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 peptic ulcer disease:
Gastrinoma (Zollinger-Ellison syndrome) or multiple endocrine neoplasia type I (MEN-I)
Antral G cell hyperplasia
Systemic mastocytosis
Basophilic leukemias
Cystic fibrosis
Short bowel syndrome
Hyperparathyroidism
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.[17]
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 the gastric epithelium. Gastric metaplasia may create an environment that is well suited to colonization by H pylori.
Seasonal changes and climate extremes may also affect gastric mucosa and cause damage to the gastric mucosa and its barrier function.[18] In extreme cold climate, Yuan et al noted significantly lower expression of heat shock protein 70 (HSP70) as well as decreased mucosal thickness in the gastric antrum of patients with peptic ulcer disease who were at high risk of bleeding compared to those at low risk of bleeding.
Moreover, compared to extreme hot climate, extreme cold climate was associated with significantly lower levels of occludin, HSP70, nitric oxide synthase (NOS), and epidermal growth factor receptor (EGFR), but no statistically significant differences in these protein expression levels were found between patients at high and low risk of bleeding.[18] The investigators also did not note any significant differences found in the rates of H pylori infection and pH levels of gastric juices between patients at high bleeding risk and low bleeding risk.[18]
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 peptic ulcer disease:
Hepatic cirrhosis
Chronic obstructive pulmonary disease
Allergic gastritis and eosinophilic gastritis
Cytomegalovirus infection
Graft versus host disease
Uremic gastropathy
Henoch-Schönlein gastritis
Corrosive gastropathy
Celiac disease
Bile gastropathy
Autoimmune disease
Crohn disease
Other granulomatous gastritides (eg, sarcoidosis, histiocytosis X, tuberculosis)
Phlegmonous gastritis and emphysematous gastritis
Other infections, including Epstein-Barr virus, HIV, Helicobacter heilmannii, herpes simplex, influenza, syphilis, Candida albicans, histoplasmosis, mucormycosis, and anisakiasis
Chemotherapeutic agents, such as 5-fluorouracil (5-FU), methotrexate (MTX), and cyclophosphamide
Local radiation resulting in mucosal damage, which may lead to the development of duodenal ulcers
Use of crack cocaine, which causes localized vasoconstriction, resulting in reduced blood flow and possibly leading to mucosal damage
The global incidence and prevalence of peptic ulcer disease, along with the associated rates of hospitalizations and mortality, have been in decline over the past couple of decades, attributed in part to complex changes in the risk factors for peptic ulcer disease, including reductions in the prevalence of H pylori infection, the widespread use of antisecretory agents and nonsteroidal anti-inflammatory drugs (NSAIDs), and an aging population.[19]
United States statistics
In the United States, peptic ulcer disease affects approximately 4.6 million people annually, with an estimated 10% of the US population having evidence of a duodenal ulcer at some time.[20] H pylori infection accounts for 90% of duodenal ulcers and 70%-90% of gastric ulcers.[21] The proportion of people with H pylori infection and peptic ulcer disease 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 prevalence of peptic ulcer disease has shifted from predominance in males to similar occurrences in males and females. The lifetime prevalence is approximately 11%-14% in men and 8-11% in women.[20] Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women.
In a systematic search of PubMed, EMBASE, and the Cochrane library, the annual incidence rates of peptic ulcer disease were found to be 0.10-0.19% for physician-diagnosed peptic ulcer disease and 0.03-0.17% when based on hospitalization data.[22] The 1-year prevalence based on physician diagnosis was 0.12-1.50% and that based on hospitalization data was 0.10-0.19%. The majority of studies reported a decrease in the incidence or prevalence of peptic ulcer disease over time.[22]
International statistics
The frequency of peptic ulcer disease in other countries is variable and is determined primarily by association with the major causes of peptic ulcer disease: H pylori and NSAIDs.[23] A 2018 systematic MEDLINE and PubMed review found Spain had the highest annual incidence of all peptic ulcer disease (141.8/100,000 persons), whereas the United Kingdom had the lowest (23.9/100,000 persons).[24] When perforated peptic ulcer disease was assessed, South Korea had the highest annual incidence (4.4/100,000 persons) and the United Kingdom, again, had the lowest (2.2/100,000 persons).[24]
When the underlying cause of peptic ulcer disease is addressed, the prognosis is excellent. Most patients are treated successfully with the eradication of H pylori infection, avoidance of nonsteroidal anti-inflammatory agents (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% to 90% to approximately 10% to 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 peptic ulcer disease, 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%.[20] 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.[25, 26, 27, 28]
Emergency operations for peptic ulcer perforation carry a mortality risk of 6-30%.[29] Factors associated with higher mortality in this setting include the following:
Shock at the time of admission
Renal insufficiency
Delaying the initiation of surgery for more than 12 hours after presentation
Concurrent medical illness (eg, cardiovascular disease, diabetes mellitus
Age older than 70 years
Cirrhosis
Immunocompromised state
Location of ulcer (mortality associated with perforated gastric ulcer is twice that associated with perforated duodenal ulcer.)
In a retrospective population-based study (2001-2014) that evaluated long-term mortality in 234 patients who underwent surgery for perforated peptic ulcer, mortality was 15.2% at 30 days, 19.2% at 90 days, 22.6% at 1 year, and 24.8% at 2 years.[30] When the 30-day mortality data were excluded, 36% of patients died during a median follow-up of 57 months. Independent factors associated with an increased risk of long-term mortality included age older than 60 years and the presence of comorbidities such as active malignancy, hypoalbuminemia, pulmonary disease, cardiovascular disease, and severe postoperative complications during the initial stay.[30]
Patients with peptic ulcer disease should be warned about known or potentially injurious drugs and agents. Some examples are as follows:
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Aspirin
Alcohol
Tobacco
Caffeine (eg, coffee, tea, colas)
Obesity has been shown to have an association with peptic ulcer disease, 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 patient education resources, see Digestive Disorders Center as well as Peptic Ulcer, Heartburn, and GERD and Heartburn Medications.
Obtaining a medical history, especially for peptic ulcer disease, H pylori infection, ingestion of nonsteroidal anti-inflammatory drugs (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:
Dyspepsia, including belching, bloating, distention, and fatty food intolerance
Heartburn
Chest discomfort
Hematemesis or melena resulting from gastrointestinal bleeding. Melena may be intermittent over several days or multiple episodes in a single day.
Rarely, a briskly bleeding ulcer can present as hematochezia.
Symptoms consistent with anemia (eg, fatigue, dyspnea) may be present
Sudden onset of symptoms may indicate perforation.
NSAID-induced gastritis or ulcers may be silent, especially in elderly patients.
Only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.
Alarm features that warrant prompt gastroenterology referral[1] include the following:
In uncomplicated peptic ulcer disease, the clinical findings are few and nonspecific and include the following:
Epigastric tenderness (usually mild)
Right upper quadrant tenderness may suggest a biliary etiology or, less frequently, peptic ulcer disease
Guaiac-positive stool resulting from occult blood loss
Melena resulting from acute or subacute gastrointestinal bleeding
Succussion splash resulting from partial or complete gastric outlet obstruction
Patients with perforated peptic ulcer disease 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.
Testing for H pylori infection is essential in all patients with peptic ulcers. In most patients with uncomplicated peptic ulcer disease, routine laboratory tests usually are not helpful. Documentation of peptic ulcer disease depends on radiographic and endoscopic confirmation.
If the diagnosis of peptic ulcer disease is suspected, obtaining a complete blood cell (CBC) count, liver function tests (LFTs), and levels of 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 gastrointestinal (GI) blood loss.
The 2017 American College of Gastroenterology (ACG) guidelines for the treatment of H pylori infection (HPI) include recommendations for testing for H pylori.[31] (See ACG Guidelines.)
The 2017 ACG guidelines also recommend posttreatment testing to prove eradication of HPI with the use of a urea breath test, fecal antigen test, or biopsy-based testing at least 4 weeks following completion of antimicrobial therapy and after proton pump inhibitors have been withheld for 1-2 weeks.[31]
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.
The American Society for Gastrointestinal Endoscopy (ASGE) released guidelines for sedation and anesthesia in gastrointestinal endoscopy in January 2018.[32] (See ASGE Guidelines.)
Upper gastrointestinal (GI) endoscopy is the preferred diagnostic test in the evaluation of patients with suspected peptic ulcer disease. 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 peptic ulcer disease. (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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Peptic ulcer disease. Gastric ulcer with a punched-out ulcer base and whitish fibrinoid exudates.
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Peptic ulcer disease. Gastric ulcer (lesser curvature) with a punched-out ulcer base with a whitish exudate.
Peptic ulcer disease. Gastric cancer with an 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.[33] 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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Peptic ulcer disease. Gastric cancer with an ulcerated mass.
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Peptic ulcer disease. Endoscopic view of an ulcer (at the upper center) in the wall of the duodenum, the first part of the small intestine. This ulcer....
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Peptic ulcer disease. Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena. The patient took naproxen on ....
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.[34]
In patients presenting acutely, a chest radiograph may be useful to detect free abdominal air when perforation is suspected. On upper gastrointestinal (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 may be necessary in patients with a massive gastrointestinal 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.
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.
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.
The emergency department (ED) workup will vary depending on presentation and includes the following:
Complete blood cell (CBC) count is used to evaluate acute or chronic blood loss.
Electrolytes, blood urea nitrogen (BUN), and creatinine levels are useful tests for critical-appearing patients who require fluid resuscitation.
Type and screen and crossmatched blood for transfusion is indicated in unstable or potentially critical patients.
Activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (INR) are indicated in patients with active bleeding and those on anticoagulants.
Amylase, lipase, and liver transaminase levels can be helpful to rule out other common causes of epigastric pain.
Patients younger than 55 years with no alarm features should be referred for noninvasive testing for H pylori infection in the outpatient setting.[1]
Treatment of peptic ulcers varies depending on the etiology and clinical presentation (see Guidelines). The initial management of a stable patient with dyspepsia differs from the management of an unstable patient with upper gastrointestinal (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 peptic ulcer disease. 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 peptic ulcer disease, most patients with peptic ulcer disease are treated successfully with cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory agents (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.
Endoscopy should be performed 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.[35] In one study, at least two risk factors (previous duodenal ulcer, H pylori infection, use of acetylsalicylic acid (ASA)/NSAID, and smoking) were present in two thirds of persons with acute gastroduodenal bleeding.[36]
The indications for urgent surgery include failure to achieve hemostasis endoscopically, recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after two 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 peptic ulcer disease. Additional surgical options for refractory or complicated peptic ulcer disease include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.
The principles of management of bleeding peptic ulcers outlined below are equally applicable to both gastric and duodenal ulcers.
Endoscopic therapy
Upper gastrointestinal (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.
A large international study demonstrated that following successful endoscopic hemostasis for Forrest IB (oozing) peptic ulcer bleeding, the risk of rebleeding at 72 hours was very low (4.9%) compared with other stigmata of recent hemorrhage, but was similar to that for patients treated with esomeprazole (5.4%) and placebo (4.9%).[37]
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:
Active hemorrhage (90% risk of rebleeding)
A visible vessel (50% risk of rebleeding)
A fresh overlying clot (30% risk of rebleeding)
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.[38] 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.
Another study comprising 108 consecutive patients with high-risk bleeding ulcers at a single institution revealed that an injection of epinephrine alone was equally effective as an injection of epinephrine plus fresh frozen plasma in endoscopic hemostasis.[39] There were no significant differences between the groups regarding recurrent bleeding, surgical rate, blood transfusion, or mortality.
Hemoclips have been used successfully to treat an acutely bleeding ulcer by approximating two 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 the 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.[40] 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:
Failure to use a proton pump inhibitor (PPI) after the endoscopic procedure
Endoscopically demonstrated bleeding, especially peptic ulcer bleeding
EHT monotherapy
Post-EHT use of heparin
Bleeding in a patient with moderate-to-severe liver disease[41]
Pre-endoscopic hemodynamic instability
Comorbid illness
Large ulcer size
Posterior wall duodenal ulcer[42]
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.[43]
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.[44, 45]
Two classes of acid-suppressing medications currently in use are histamine-2 receptor antagonists (H2RAs) and PPIs.[46] 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.[47]
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.[48] 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 used 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).[49] 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.[50] 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. 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.[51]
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.[51]
A Canadian database (RUGBE) indicated some benefit from parenteral PPI in decreasing rebleed rates.[47] 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.[25]
Whether acid suppression improves the 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.[26]
The 2017 American College of Gastroenterology (ACG) guidelines for the treatment of H pylori infection strongly recommend 10-14 days of quadruple therapy with bismuth, a proton pump inhibitor (PPI), tetracycline, and a nitroimidazole).[31] An alternative strongly recommended option is 10-14 days of concomitant PPI, clarithromycin, amoxicillin, and a nitroimidazole.[31] See ACG Guidelines.
In the United States, PPI–based triple therapy was the previous recommendation.[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,[52] since mother-to-child transmission may be a major route of H pylori infection.[53]
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.[54] 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.
Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes of H pylori isolates appear to influence the outcome of triple therapy.[55] CYP2C19 affects peptic ulcer healing, H pylori eradication, and PPI therapeutic efficacy. When a patient’s CYP2C19 genotype is unknown, H pylori eradication may be achieved with fluoroquinolones/metronidazole/clarithromycin-based triple therapies.[55]
PPI-based triple therapies are a 14-day regimen as outlined 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:
PPI, standard dose, or ranitidine 150 mg, PO bid
Bismuth 525 mg PO qid
Metronidazole 500 mg PO qid
Tetracycline 500 mg PO qid
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.
In 2009, the American College of Gastroenterology (ACG) issued a guideline for prevention of nonsteroidal anti-inflammatory agent (NSAID)-related ulcer complications that supports the recommendations in this section.[56] 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. The 2017 ACG guidelines for the treatment of H pylori infection (HPI) have reaffirmed testing for HPI before initiating NSAID therapy.[31]
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 cyclooxygenase (COX)-2 selective inhibitor is an option. However, the use of a traditional NSAID and once-daily proton pump inhibitor (PPI) is comparable to a selective COX-2 inhibitor with respect to ulcer bleeding in patients with a history of peptic ulcer disease.[57] 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.[58] 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.[56]
Deterrence and prevention
Primary prevention of NSAID-induced ulcers includes the following:
Avoid unnecessary use of NSAIDs
Use acetaminophen or nonacetylated salicylates when possible
Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the newer NSAIDs or COX-2 inhibitors, in high-risk patients without cardiovascular disease
Consider prophylactic or preventive therapy for the following patients:
Patients with NSAID-induced ulcers who require chronic, daily NSAID therapy
Patients older than 60 years
Patients with a history of peptic ulcer disease or a complication such as gastrointestinal bleeding
Patients taking concomitant steroids or anticoagulants or patients with significant comorbid medical illnesses
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:
Misoprostol 100-200 mcg PO 4 times per day
Omeprazole 20-40 mg PO every day
Lansoprazole 15-30 mg PO every day
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.[59] This was further confirmed in a double-blind randomized study in 2006 by Lai and colleagues.[60]
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.[61] This combination did not influence the action of clopidogrel on platelet aggregation.
Presentations of peptic ulcer disease and gastritis usually are indistinguishable in the emergency department (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:
Bleeding with hemodynamic instability
Repeated hematemesis or any hematochezia
Failure to clear with gastric lavage
Coagulopathy
Comorbid disease (especially cardiac, pulmonary, or renal)
Advanced age
Drug treatments
Antacids or a gastrointestinal (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 a proton pump inhibitor (PPI) for 4-8 weeks. Appropriate follow-up is required to assess response in 2-4 weeks.[62]
Anticholinergic agents are contraindicated.
Bleeding
Massive gastric bleeds are the most difficult complication to treat. Mainstays of resuscitation include the following:
Establishment of adequate intravenous (IV) access and volume replacement, initially with a crystalloid; in the face of continued hypotension after 2 L, consider blood transfusion.
A central venous catheter to monitor such resuscitation may be considered.
Airway protection with intubation should be considered in the case of massive bleeding.
Nasogastric suction helps to keep the stomach empty and contracted.
IV PPI has been shown to reduce mortality in upper GI bleeds and reduces the incidence of rebleeding and the need for surgical intervention[63] ; emergent surgical or endoscopic intervention may be required
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 peptic ulcer disease. 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%.[64] In general, 5% of bleeding ulcers eventually require operative management. The indications for urgent surgery include the following:
Failure to achieve hemostasis endoscopically
Recurrent bleeding despite endoscopic attempts at achieving hemostasis (many advocate surgery after two failed endoscopic attempts)
Perforation
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 peptic ulcer disease. Additional surgical options for refractory or complicated peptic ulcer disease 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 two 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.[47]
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).
See Surgical Treatment of Perforated Peptic Ulcer for more information.
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.
Refractory, symptomatic peptic ulcers, though rare after eradication of H pylori infection and the appropriate use of antisecretory therapy, are a potential complication of peptic ulcer disease. Obstruction is particularly likely to complicate peptic ulcer disease 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.
Surgical consultation is recommended for all patients with bleeding ulcers, especially those patients who are at a 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.
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.[65]
Perforated and Bleeding Peptic Ulcer Clinical Practice Guidelines (2020)
Perforated and bleeding peptic ulcer clinical practice guidelines were released in January 2020 by the World Society of Emergency Surgery.[66]
Perforated Peptic Ulcer
The recommended biochemical and imaging investigations in the diagnosis of perforated peptic ulcer are as follows:
Suspected gastroduodenal perforation: Routine laboratory studies and arterial blood gas analysis
Acute abdomen from suspected perforated peptic ulcer: CT scanning
Acute abdomen from suspected perforated peptic ulcer: Chest and abdominal radiography as initial diagnostic assessment in the event CT scanning is not immediately available
Acute abdomen from suspected perforated peptic ulcer if free air is not seen on imaging and perforation remains a concern: Imaging with water-soluble contrast (oral or via nasogastric tube)
The recommended targets for resuscitation in unstable patients with a perforated peptic ulcer are as follows:
Rapid resuscitation to reduce mortality
Restoration of physiological parameters with a mean arterial pressure 65 mm Hg or higher, urine output of 0.5 mL/kg/h or greater, and lactate normalization
Use of hemodynamic monitoring (invasive or noninvasive) to optimize fluid/vasopressor therapy, with an individualized resuscitation strategy
Surgical indications and appropriate timing of surgery in patients with perforated peptic ulcer are as follows:
In association with significant pneumoperitoneum, extraluminal contrast extravasation, or signs of peritonitis: Operative treatment strongly recommended
Performing surgery as soon as possible, particularly in patients with delayed presentation or those older than 70 years
The recommended surgical approach (laparoscopic vs open) for perforated peptic ulcer is as follows:
Stable patients: Laparoscopic approach, unless equipment and skilled personnel are not available, in which case an open approach is recommended
Unstable patients: Open surgery
The recommended antimicrobial and antifungal therapy strategies in perforated peptic ulcer are as follows:
Administration of broad-spectrum antibiotics
Microbiological sample collection for analysis for bacterial and fungal pathogens in all patients undergoing surgery, with postanalysis antibiotic therapy adjustment as needed
Antifungal agents not suggested as standard empiric therapy; may be appropriate in high-risk patients, such as those who are immunocompromised, have comorbidities, or are of advanced age
The recommended antimicrobial regimen and duration of therapy in perforated peptic ulcer are as follows:
Initiation of empiric broad-spectrum antibiotics as soon as possible, targeting gram-negative, gram-positive, and anaerobic bacteria
Short course of 3-5 days or until inflammatory markers normalize
Bleeding Peptic Ulcer
The recommended biochemical and imaging/procedural investigations in the diagnosis of suspected bleeding peptic ulcer are as follows:
Blood-typing; hemoglobin, hematocrit, and electrolyte values; and coagulation assessment
Performing endoscopy as soon as possible, particularly in high-risk patients (Management decisions can be guided based on the damage noted from recent hemorrhage during endoscopy, as this can help predict further bleeding risk.)
The recommended parameters for evaluation at emergency department referral and the criteria for defining an unstable patient are as follows:
Rapid, careful medical/surgical evaluation to prevent further bleeding and reduce mortality
Upon emergency department referral, evaluation of signs, symptoms, and laboratory findings to assess stability versus instability
Evaluation according to Rockall and Glasgow-Blatchford scoring systems to assess disease severity and guide therapy
The recommended nonoperative and endoscopic strategies in patients with bleeding peptic ulcer are as follows:
Nonoperative management as first-line management after endoscopy
Endoscopic treatment to achieve hemostasis and to help prevent rebleeding, the need for surgery, and mortality
Administration of pre-endoscopy erythromycin
Initiation of proton-pump inhibitor therapy as soon as possible
Post successful endoscopic hemostasis, high-dose proton-pump inhibitor therapy as a continuous infusion for the first 72 hours
Proton-pump inhibitor therapy for 6-8 weeks following endoscopic treatment (Long-term proton-pump inhibitor therapy is not recommended except in patients with ongoing NSAID use.)
Indications for surgical treatment and the appropriate approach for surgery in patients with bleeding peptic ulcer are as follows:
Surgical hemostasis, or, if equipment and qualified personnel are available, angiographic embolization, after failure of repeated endoscopy
Refractory bleeding peptic ulcer: Surgical intervention with open surgery
Intraoperative endoscopy to facilitate localization of the bleeding site
Indications for antimicrobial therapy and for Helicobacter pylori testing in patients with bleeding peptic ulcer are as follows:
Empirical antimicrobial therapy not recommended
H pylori testing in all patients
If positive for H pylori, eradication therapy recommended
First-line therapy if high clarithromycin resistance detected: Ten-day sequential therapy with four drugs (ie, amoxicillin, clarithromycin, metronidazole, proton-pump inhibitor)
Second-line therapy if first-line failed: Ten-day levofloxacin-amoxicillin triple therapy
Start standard triple therapy after 72-96 hours of intravenous proton-pump inhibitor, for 14-day duration
ASGE Guidelines for Sedation and Anesthesia in Gastrointestinal Endoscopy (2018)
Guidelines for sedation and anesthesia in gastrointestinal endoscopy were released in January 2018 by the American Society for Gastrointestinal Endoscopy (ASGE).[32]
It is recommended that all patients undergoing endoscopic procedures be evaluated to assess their risk of sedation related to preexisting medical conditions.
The combination of an opioid and benzodiazepine is recommended to be a safe and effective regimen for achieving minimal to moderate sedation for upper endoscopy and colonoscopy in patients without risk factors for sedation-related adverse events.
It is suggested to use an appropriate adjunctive agent (eg, diphenhydramine, promethazine, or droperidol) in combination with conventional sedative drugs in select clinical circumstances.
Providers should undergo specific training in the administration of endoscopic sedation and possess the skills necessary for the diagnosis and management of sedation-related adverse events, including rescue from a level of sedation deeper than that intended.
Recommend the routine monitoring of blood pressure, oxygen saturation, and heart rate in addition to clinical observation for changes in cardiopulmonary status during all endoscopic procedures using sedation. Supplemental oxygen administration should be considered for moderate sedation and should be administered during deep sedation. Supplemental oxygen should be administered if hypoxemia is anticipated or develops.
Suggest that capnography monitoring be considered for patients undergoing endoscopy targeting deep sedation. Anesthesia provider–administered sedation should be considered for complex endoscopic procedures or patients with multiple medical comorbidities or at risk for airway compromise.
It is suggested that endoscopists use propofol-based sedation (endoscopist-directed or anesthesia-provider administered) when it is expected to improve patient safety, comfort, procedural efficiency, and/or successful procedure completion.
The 2017 American College of Gastroenterology (ACG) guidelines for the treatment of H pylori infection (HPI) include the following recommendations for testing for H pylori[31] :
All patients with active or past history of peptic ulcer disease (unless previous cure of HPI has been documented), low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, or a history of endoscopic resection of early gastric cancer
Patients with dyspepsia who are undergoing upper endoscopy (gastric biopsy specimens)
Patients on long-term, low-dose aspirin
Patients initiating long-term therapy with nonsteroidal anti-inflammatory agents (NSAIDs)
Patients with unexplained iron deficiency anemia following standard workup
Adults with idiopathic thrombocytopenic purpura
The 2017 ACG guidelines also recommend posttreatment testing to prove eradication of HPI with the use of a urea breath test, fecal antigen test, or biopsy-based testing at least 4 weeks following completion of antimicrobial therapy and after proton pump inhibitors have been withheld for 1-2 weeks.[31]
The guidelines indicate that selection of an HPI management regimen should take into account any previous antibiotic exposure(s). The ACG also includes the following therapeutic strategies for first-line treatment[31] :
10-14 days of bismuth quadruple therapy (bismuth, proton pump inhibitor [PPI], tetracycline, and a nitroimidazole) (strong recommendation), particularly in those with previous macrolide exposure or are penicillin allergic
(Recommended option) 10-14 days of concomitant PPI, clarithromycin, amoxicillin, and a nitroimidazole (strong recommendation)
14 days of clarithromycin triple therapy (clarithromycin, a PPI, and amoxicillin or metronidazole) should be reserved for patients with no previous history of macrolide exposure who live in regions where clarithromycin resistance among H pylori isolates is known to be low (< 15%) (conditional recommendation)
(Suggested option) 5-7 days of sequential therapy with a PPI and amoxicillin, followed by 5-7 days with clarithromycin, a PPI, and a nitroimidazole (conditional recommendation)
(Suggested option) 7 days of a hybrid therapy with a PPI and amoxicillin, followed by 7 days with a PPI, amoxicillin, clarithromycin, and a nitroimidazole (conditional recommendation)
(Suggested option) 10-14 days of levofloxacin triple therapy (levofloxacin, a PPI, and amoxicillin) (conditional recommendation)
(Suggested option) 5-7 days of fluoroquinolone sequential therapy (a PPI and amoxicillin), followed by 5-7 days of a PPI, fluoroquinolone, and nitroimidazole (conditional recommendation)
Salvage treatment if first-line therapy fails and HPI persists include the following options[31] :
Avoid previously used antibiotics, if feasible (strong recommendation)
Preferred for patients who previously received first-line clarithromycin regimens: Bismuth quadruple therapy or levofloxacin salvage regimens (conditional recommendation)
Preferred for patients who previously received first-line bismuth quadruple therapy: Clarithromycin or levofloxacin-containing salvage regimens (conditional recommendation)
Salvage treatment regimens include the following[31] :
(Recommended) Bismuth quadruple therapy or levofloxacin triple therapy for 14 days (strong recommendation)
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).[46] 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.
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) when administering 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.
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) when administering 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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
How are gastric and duodenal ulcers differentiated?What are the “alarm features” of peptic ulcer disease that necessitate immediate referral to a gastroenterologist?How is a diagnosis of peptic ulcer disease (PUD) confirmed?Why is upper GI endoscopy the preferred diagnostic test for peptic ulcer disease (PUD)?How is peptic ulcer disease (PUD) treated?How is NSAID-associated peptic ulcer disease (PUD) treated?When is surgical intervention indicated in in the treatment of peptic ulcer disease (PUD)?What is the anatomy of the vagal innervation of the abdominal viscera and how does it affect surgical procedures for peptic ulcer disease (PUD)?What is the pathogenesis of peptic ulcer disease (PUD)?How do peptic ulcer disease (PUD) occur?What is the role of H pylori infection (HPI) in peptic ulcer disease (PUD)?What is the relationship between H pylori gastritis and duodenal ulceration?What is the etiology of peptic ulcer disease (PUD)?What is the most common cause of peptic ulcer disease (PUD)?Which factors increase the risk of NSAID-related peptic ulcer disease (PUD)?Which factors increase the risk for peptic ulcer disease (PUD) in patients taking low-dose aspirin?Does the combination of H pylori infection (HPI) and NSAID use increase the risk of developing peptic ulcer disease (PUD)?What is the prevalence of NSAID gastropathy in children?Do corticosteroids increase the risk of peptic ulcer disease (PUD)?Does smoking, alcohol, or caffeine increase the risk of peptic ulcer disease (PUD)?Which physiologic stress conditions may cause peptic ulcer disease (PUD)?What are Cushing ulcers?Which patients are at an increased risk for stress ulceration and upper- GI hemorrhage?Which hypersecretory states may cause peptic ulcer disease (PUD)?Which physiologic factors increase the risk of duodenal ulcers?What is the role of accelerated gastric emptying in peptic ulcer disease (PUD)?Does cold climate increase the risk of developing peptic ulcer disease (PUD)?What is the role of genetics in peptic ulcer disease (PUD)?What are the less common causes of peptic ulcer disease (PUD)?What is the prevalence of peptic ulcer disease (PUD) in the US?What is the US incidence of peptic ulcer disease?Is peptic ulcer disease more common in in males or females?What is the international prevalence of peptic ulcer disease?How is peptic ulcer disease treated?What is the incidence of NSAID-related ulcers?What is the mortality rate for peptic ulcer disease?Which factors increase the mortality risk associated with emergency surgery for peptic ulcer perforation?What is the mortality rate for patients undergoing surgery for perforated peptic ulcer?Which agents are potentially injurious to patients with peptic ulcer disease?Which counseling may be beneficial for patients with peptic ulcer disease (PUD)?Which history details suggest peptic ulcer disease (PUD)?How are gastric and duodenal ulcers differentiated?Which pain characteristics suggest duodenal ulcer?What are the symptoms of gastric outlet obstruction?What are the signs and symptoms of peptic ulcer disease (PUD)?What are the alarm features of peptic ulcer disease (PUD) that necessitate immediate referral to a gastroenterologist?Which clinical findings suggest uncomplicated peptic ulcer disease (PUD)?What are the signs and symptoms of perforated peptic ulcer disease (PUD)?How is functional dyspepsia diagnosed?What part of the GI tract is involved in Crohn ulceration?What is Zollinger-Ellison syndrome (ZES)?What are the differential diagnoses for Peptic Ulcer Disease?What is the role of H pylori testing in the diagnosis of peptic ulcer disease (PUD)?Which lab tests should be performed in suspected peptic ulcer disease (PUD)?How is the presence of H pylori detected in peptic ulcer disease (PUD)?Which test finding indicates the presence of H pylori infection?How do urea breath tests detect H pylori infection?What is the role of histopathology in the diagnosis of H pylori infection (HPI)?What is the preferred test for the diagnosis of peptic ulcer disease (PUD)?What is the appearance of duodenal ulcers on endoscopy?What is the most common finding in individuals who undergo endoscopy for dyspepsia?When is a chest X-ray indicated for diagnosis of peptic ulcer disease (PUD)?When is angiography indicated for suspected peptic ulcer disease (PUD)?When should screening for Zollinger-Ellison syndrome (ZES) be performed in patients with peptic ulcer disease (PUD)?When is a secretin simulation test required in in the workup of peptic ulcer disease (PUD)?How accurate is a biopsy in the diagnosis of gastric cancer?What is the histology of gastric ulcers?What testing should be performed in the emergency department (ED) for suspected peptic ulcer disease (PUD)?Which factors determine the treatment of peptic ulcer disease (PUD)?Which treatment options are available for peptic ulcer disease (PUD)?What is the role of endoscopy in the management of peptic ulcer disease (PUD)?Can peptic ulcer disease (PUD) be cured?What factors determine if endoscopy should be performed in the treatment of peptic ulcer disease (PUD)?What are the indications for urgent surgery in peptic ulcer disease (PUD)?How are bleeding peptic ulcers treated?What are the high-risk stigmata in bleeding peptic ulcer?Which endoscopic therapy modalities are available for treating peptic ulcer disease (PUD)?What is the role of hemoclips in the treatment of peptic ulcer disease (PUD)?What is the role of EGD in the treatment of peptic ulcer disease (PUD)?Which risk factors predict rebleeding following endoscopic hemostatic therapy (EHT) in peptic ulcer disease (PUD)?What is the role of acid suppression in the treatment of peptic ulcer disease (PUD)?Which classes of acid-suppressing medications are currently used in the treatment of peptic ulcer disease (PUD)?What is the role of PPIs in the treatment of peptic ulcer disease (PUD)?Is a high-dose PPI regimen more effective than a standard-dose regimen in the treatment of peptic ulcer disease (PUD)?Does parenteral PPI therapy decrease rebleeding in peptic ulcer disease (PUD)?What is the overall efficacy of parenteral PPI therapy in peptic ulcer disease (PUD)?What are the ACG guidelines for the primary treatment of H pylori infection (HPI)?Who should be considered for testing of H pylori infection (HPI)?What are the ACG guidelines for prevention of NSAID-related ulcer complications?How is peptic ulcer disease (PUD) managed when NSAID therapy cannot be discontinued?How are active NSAID-related ulcers treated?What are the 2009 ACG treatment guidelines for peptic ulcer disease (PUD) in patients who require NSAID and low-dose aspirin therapy?How are NSAID-related ulcers prevented?Which patients should be considered for prophylactic therapy for peptic ulcer disease (PUD)?What prophylactic regimen is effective in reducing the risk of NSAID-related ulcers?Is aspirin plus esomeprazole (Nexium) effective in preventing recurrent gastric ulcer bleeding?Is treatment with combined esomeprazole (Nexium) and clopidogrel (Plavix) effective in reducing recurrence of peptic ulcers?What are the treatment goals for peptic ulcer disease (PUD) in the emergency department (ED)?How is high-risk determined in peptic ulcer disease (PUD)?What drug treatments are available for symptomatic treatment of peptic ulcer disease (PUD)?How are massive gastric bleeds managed in patients with peptic ulcer disease (PUD)?When is surgical management of peptic ulcer disease (PUD) indicated?What are the surgical options for the management of peptic ulcer disease (PUD)?When is laparoscopic surgery for perforated ulcer contraindicated?What are the potential complications after surgical treatment of a perforated peptic ulcer?What are the dietary restrictions for patients with peptic ulcer disease (PUD)?What are potential complications of peptic ulcer disease (PUD)?What are the potential health risks of gastric ulcers?What test should be performed in a patient with persistent nonhealing gastric ulcer?When is surgical consultation needed in the treatment of peptic ulcer disease (PUD)?Which maintenance therapy is indicated in high-risk patients with peptic ulcer disease (PUD)?Which maintenance therapies are effective for recurrent, refractory, or complicated ulcers?How common is peptic ulcer rebleeding after H pylori eradication?What are the WSES guidelines for the diagnosis and treatment of bleeding peptic ulcers?What are the WSES guidelines for the diagnosis and treatment of perforated peptic ulcer?What are the ASGE guidelines for sedation and anesthesia in gastrointestinal endoscopy?What are the ACG recommendations for testing for H pylori?What are the ACG guidelines for the treatment of H pylori infection (HPI)?What are the goals of pharmacotherapy for peptic ulcer disease (PUD)?What is the treatment for H pylori infection (HPI)?Can NSAID-induced ulcers be prevented?Which medications in the drug class Proton Pump Inhibitors are used in the treatment of Peptic Ulcer Disease?Which medications in the drug class H2 Receptor Blockers are used in the treatment of Peptic Ulcer Disease?Which medications in the drug class Antimicrobials are used in the treatment of Peptic Ulcer Disease?Which medications in the drug class Antidiarrheal Agents are used in the treatment of Peptic Ulcer Disease?Which medications in the drug class Cytoprotective Agents are used in the treatment of Peptic Ulcer Disease?
BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Philip O Katz, MD, FACP, FACG, Chairman, Division of Gastroenterology, Albert Einstein Medical Center; Clinical Professor of Medicine, Jefferson Medical College of Thomas Jefferson University
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Medtronic<br/>Received income in an amount equal to or greater than $250 from: Torax medical: pfizer consumer, .
Acknowledgements
Faisal Aziz, MD Assistant Professor of Surgery, Divsion of Vascular and Endovascular Surgery, Department of Surgery, Pennsylvania State University College of Medicine
Faisal Aziz, MD is a member of the following medical societies: American College of Surgeons and American Medical Association
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.
Jeffrey Glenn Bowman, MD, MS Consulting Staff, Highfield MRI
Disclosure: Nothing to disclose.
Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
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
Brian James Daley, MD, MBA, FACS, FCCP, CNSC is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Chest Physicians, American College of Surgeons, American Medical Association, Association for Academic Surgery, Association for Surgical Education, Eastern Association for the Surgery of Trauma, Shock Society, Society of Critical Care Medicine, Southeastern Surgical Congress, and Tennessee Medical Association
Disclosure: Nothing to disclose.
Shane M Devlin, MD, FRCP(C) Clinical Assistant Professor, Department of Internal Medicine, Peter Lougheed Center, University of Calgary, Canada
Shane M Devlin, MD, FRCP(C) is a member of the following medical societies: American Gastroenterological Association, Canadian Association of Gastroenterology, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.
Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center
Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency 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
George T Fantry, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association
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
John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract
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
David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, and New York Society for Gastrointestinal Endoscopy
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
Harsh Grewal, MD, FACS, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Pediatric Surgical Association, Association for Surgical Education, Children's Oncology Group, Eastern Association for the Surgery of Trauma, International Pediatric Endosurgery Group, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Laparoendoscopic Surgeons, and SouthwesternSurgical Congress
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.
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
Andre Hebra, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, Children's Oncology Group, Florida Medical Association, International Pediatric Endosurgery Group, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Laparoendoscopic Surgeons,South Carolina Medical Association, Southeastern Surgical Congress, and Southern Medical Association
Disclosure: Nothing to disclose.
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
Juda Zvi Jona is a member of the following medical societies: Alpha Omega Alpha, American Bronchoesophagological Association, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, Association for Academic Surgery, British Association of Paediatric Surgeons, Central Surgical Association, Children's Oncology Group, and International Pediatric Endosurgery Group
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
Daryl Lau, MD, MPH, MSc, FRCP(C) is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association
Disclosure: Nothing to disclose.
Tri H Le, MD Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Penn State Milton S Hershey Medical Center
Tri H Le, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society of Gastrointestinal Endoscopy, and Crohns and Colitis Foundation of America
Disclosure: Nothing to disclose.
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
Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi
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
B UK Li, MD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
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
Chris A Liacouras is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.
Wendi S Miller, MD Resident Physician, Department of Emergency Medicine, Emory University School of Medicine
Wendi S Miller, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Southern Medical Association
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
Robert K Minkes, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, and Phi Beta Kappa
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
Waqar A Qureshi, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Erick F Rivas, MD, PT Resident Physician, Department of Surgery, Michigan State University College of Human Medicine
Erick F Rivas, MD, PT is a member of the following medical societies: American College of Surgeons
Disclosure: Nothing to disclose.
Ameesh Shah, MD Assistant Professor of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital
Ameesh Shah, MD is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition
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
Philip Shayne is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Sanjeeb Shrestha, MD Consulting Staff, Division of Gastroenterology, Gastroenterology Care Consultants
Sanjeeb Shrestha, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Mutaz I Sultan, MBChB Makassed Hospital, Israel
Mutaz I Sultan, MBChB is a member of the following medical societies: American Gastroenterological Association and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
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
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.
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
Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
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
Jay A Yelon, DO, FACS is a member of the following medical societies: American Association for the Surgery of Trauma, American Burn Association, American College of Surgeons, American Trauma Society, Association for Academic Surgery, Eastern Association for the Surgery of Trauma, Pan American Trauma Society, Shock Society, Society of Critical Care Medicine, Southeastern Surgical Congress, and Surgical Infection Society
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Peptic ulcer disease. Gastric cancer with an ulcerated mass.
Peptic ulcer disease. Gastric cancer with an ulcerated mass.
Peptic ulcer disease. Endoscopic view of an ulcer (at the upper center) in the wall of the duodenum, the first part of the small intestine. This ulcer is an open sore. Image courtesy of Science Source | Gastrolab.
Peptic ulcer disease. Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena. The patient took naproxen on a daily basis.
Peptic ulcer disease. Vagal innervation of the stomach.
Peptic ulcer disease. Gastric ulcer with a punched-out ulcer base and whitish fibrinoid exudates.
Peptic ulcer disease. Gastric ulcer (lesser curvature) with a punched-out ulcer base with a whitish exudate.
Peptic ulcer disease. Gastric cancer with an ulcerated mass.
Peptic ulcer disease. Gross pathology specimen of a gastric ulcer.
Peptic ulcer disease. Gastric cancer with an ulcerated mass.
Peptic ulcer disease. Endoscopic view of an ulcer (at the upper center) in the wall of the duodenum, the first part of the small intestine. This ulcer is an open sore. Image courtesy of Science Source | Gastrolab.
Peptic ulcer disease. Duodenal ulcer in a 65-year-old man with osteoarthritis who presented with hematemesis and melena. The patient took naproxen on a daily basis.
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