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Figure 6. Schematic showing rationale for carbon-14 urea breath testing.

Peak radioactivity in the breath is reached in approximately 10—20 minutes. The breath sample is captured in a non-diffusible balloon or trapping solution. The sample is then counted by liquid scintillation and reported as carbon-14 activity per mmole of CO2 in the breath. Results can usually be classified as definitely positive or definitely negative. A small number of cases show detectable radioactivity that falls below the abnormal threshold and are considered indeterminate.

A number of medications can interfere with the examination. Treatment with antibiotics or bismuth-containing preparations in the previous month can give a false negative result related to suppression of H. pylori growth. Proton pump inhibitors suppress H. pylori growth and may interfere with the diffusion of carbon dioxide across the gastric mucosal surface. This results in a false negative test in over one third of patients and therefore the agent should be discontinued for at least 7-14 days prior to performing the examination. Sucralfate can also suppress active H. pylori for up to one week. Antacids and H2 antagonists are usually stopped as well, though they probably have little effect on test results. Gastric surgery can cause a false negative result if the isotope empties too rapidly from the stomach. False posi tive results are rare, but occasionally bacterial overgrowth from species other than H. pylori will metabolize the labeled urea.

Techniques are now available for using urea labeled with non-radioactive car-bon-13, though the radioactive format is still the most widely available. The non-radioactive method requires a standardized meal, a larger dose of urea and more specialized equipment (mass spectrometer or laser spectroscope).

Clinical

The accuracy of diagnosing PUD from history is poor. The diagnosis is confirmed in only 50% of those in whom it is suspected. After excluding ulcers related to nonsteroidal antiiflammatory drugs (NSAIDs), the vast majority of duodenal and gastric ulcers are caused by chronic infection with H. pylori. With standard treatment regimens such as a one-month treatment with an H2 receptor antagonist or a proton pump inhibitor, there is a high rate of ulcer relapse (50 to 90%) after acute ulcer healing. Eradication of the organism dramatically alters the natural history of PUD with a marked decrease in ulcer recurrence. Highly effective (>90%) eradication of H. pylori is achieved with 7-10 days of a triple drug regimen (bismuth or a proton pump inhibitor and two antibiotics—clarithromycin and either metronidazole or amoxicillin). Adherence to such complex regimens is variable and side effects are not infrequent.

The traditional approach to the diagnosis of PUD has included either an upper GI series or endoscopy to document an ulcer. Determination of H. pylori status followed by eradication therapy of patients found to be H. pylori positive may be a rational and cost-effective approach to the investigation and management of patients with suspected PUD (Fig. 7). With a "test and treat" approach, a positive H. pylori breath test removes the need for endoscopy if no "alarm" features (anemia, evidence of bleeding, weight loss or early satiety) are present. Due to the increased risk of malignancy in older patients, this approach should be confined to those less than 50 years of age. A small number (20-30%) of patients with H. pylori infection and non-ulcer dyspepsia also appear to benefit from eradication therapy, though this remains controversial.

H. pylori has been associated with a two- to threefold increase in risk for gastric cancer. Studies are in progress to determine if H. pylori eradication will alter the risk of malignancy. Gastric maltoma, a lymphoproliferative disorder of gastric mucosal associated lymphoid tissue (MALT), is related to infection with H. pylori. Eradication of H. pylori in early stages of this low-grade tumor may lead to complete remission. Surgical resection and chemotherapy are also effective treatment modalities. If a non-operative approach to management is chosen then these patients need to be followed very closely.

If peptic ulcer disease is uncomplicated, i.e., no evidence of bleeding, perforation or obstruction, then documentation that eradication has been successful is felt to be unnecessary. The success of eradication should be confirmed in all those with complications, taking care to avoid medications that can give a false negative examination.

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