Peptic Ulcer Disease Workup

Updated: Apr 26, 2021
  • Author: BS Anand, MD; Chief Editor: Philip O Katz, MD, FACP, FACG  more...
  • Print

Approach Considerations

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.

Hung et al conducted a retrospective study of 830 records of patients hospitalized for bleeding peptic ulcers and found that 19% of patients were not tested for H pylori. Further analysis revealed that failure to test for H pylori within 60 days of endoscopy was associated with increased risk of rebleeding or death within 1 year. [32]

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. [33] (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 the completion of antimicrobial therapy and after proton pump inhibitors have been withheld for 1-2 weeks. [33]

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. [34] (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.

Peptic ulcer disease. Gastric ulcer with a punched Peptic ulcer disease. Gastric ulcer with a punched-out ulcer base and whitish fibrinoid exudates.
Peptic ulcer disease. Gastric ulcer (lesser curvat Peptic ulcer disease. Gastric ulcer (lesser curvature) with a punched-out ulcer base with a whitish exudate.
Peptic ulcer disease. Gastric cancer. Note the irr Peptic ulcer disease. Gastric cancer. Note the irregular heaped-up overhanging margins.
Peptic ulcer disease. Gastric cancer with an ulcer 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. [35] 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).

Peptic ulcer disease. Gastric cancer with an ulcer Peptic ulcer disease. Gastric cancer with an ulcerated mass.
Peptic ulcer disease. Endoscopic view of an ulcer 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- 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.

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. [36]



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.


Serum Gastrin Level

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

  • Patients with multiple ulcers

  • Ulcers occurring distal to the duodenal bulb

  • Strong family history of peptic ulcer disease

  • Peptic ulcer associated with diarrhea, steatorrhea, or weight loss

  • Peptic ulcer not associated with H pylori infection or use of nonsteroidal anti-inflammatory agents

  • Peptic ulcer associated with hypercalcemia or renal stones

  • Ulcer refractory to medical therapy

  • Ulcer recurring after surgery


Secretin Stimulation Test

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


Biopsy and Histologic Findings


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

Histologic findings

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


Emergency Department Workup

The 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]