Gastroenterol Clin North Am. 2000 Dec;29(4):885-93, x. Accurate diagnosis of Helicobacter pylori. 13C-urea breath test.

Graham DY, Klein PD. Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA. dgraham@bcm.tmc.edu The preferred schema for management of Helicobacter pylori infection is diagnosis, treatment, and confirmation of cure. The 13C-urea breath test is ideal for active H. pylori infection for those in whom endoscopy is not required (e.g., those in whom cancer is not suspected) because it offers the combination of simplicity, accuracy, reliability, and absence of exposure to radioactivity. New versions of the test also offer increasing simplicity and lower costs. Cas Lek Cesk. 2000 Dec 6;139(24):776-8. [Diagnosis of Helicobacter pylori with the 13C-labeled urea breath test: study methodology]. [Article in Czech] Bures J, Palicka V, Kopcov M, Vorsek V, Rejchrt S, Zivn P. Komplementrn centrum vnitrnho lkarstv 2. intern kliniky LF UK a FN, Hradec Krlov. Helicobacter pylori is one of the most common causes of chronic bacterial infection in humans, and it is associated with many diseases of the upper gastrointestinal tract. The 13C urea breath test (13C-UBT) is a simple, non-invasive and global test for Helicobacter pylori detection. The test reflects the hydrolysis of 13C-labelled urea by Helicobacter pylori urease. The 13CUBT is the gold standard test for Helicobacter pylori infection. Since the original description (in 1987) several modifications of 13C-UBT have been published to simplify and optimise the test. However, neither Standardised European Protocol nor Standard US Protocol were accepted. This paper gives the methodology of the 13C-UBT based on eur own study and on the review of the literature.

Gastroenterol Clin North Am. 2000 Dec;29(4):895-902. Accurate diagnosis of Helicobacter pylori. 14C-urea breath test. Chey WD. University of Michigan Medical Center, Ann Arbor, Michigan, USA. wchey@umich.edu The 14C-urea breath test is an accurate means of identifying the presence of H. pylori infection before and after antimicrobial therapy. Several issues, including out of office analysis, the need for a support structure to perform the test, concerns regarding radiation exposure, and inconsistent reimbursement, have slowed the widespread acceptance of the 14C-urea breath test in clinical practice. Despite these problems, the 14C-urea breath test is simple, rapid, and relatively inexpensive compared with the currently available version of the 13C-urea breath test. As such, the 14C-urea breath test provides an attractive, nonendoscopic means of identifying active H. pylori infection. Ital J Gastroenterol. 1995 Mar;27(2):55-63. The urea breath test: a non-invasive clinical tool for detecting Helicobacter pylori infection. Perri F, Ghoos Y, Hiele M, Andriulli A, Rutgeerts P. Divisione di Gastroenterologia, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy. The urea breath test exploits the urease enzyme of Helicobacter pylori. The hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in the breath. Distribution of urea throughout the stomach prevents sampling errors and allows for semiquantitative assessment of the extent of Helicobacter pylori infection. The urea breath test is very specific and sensitive and can be proposed as the method of choice for detecting Helicobacter pylori infection in ulcer patients before and after eradicating treatment as well as in epidemiological studies. Rev Gastroenterol Mex. 1998 Jul-Sep;63(3):135-42. [Breath tests as a noninvasive diagnostic method in Helicobacter pylori infection].

[Article in Spanish] Di Silvio M, Larisch J, Dibildox M, Almaguer I, Gitler R, Dehesa M, Ramrez-Barba EJ. Centro Mdico Nacional 20 de Noviembre, Universidad Anhuac, Escuela de Medicina. mdisilvio@compuserve.com There are several diagnostic methods for Helicobacter pylori infection, some of them need an endoscopic procedure and biopsy to be performed (invasive) like the rapid urease test, culture and histology. Recently non invasive, specific, sensible, easy to perform and patient's well accepted methods had been developed known as breath test, based on the hydrolysis of labelled urea by Helicobacter pylori urease enzyme, to release ammonia and bicarbonate. Labelled CO2 reaches the bloodstream and the lungs, from where can be collected into the breath for quantification. Labelled urea has to options: 13C stable, non-radioactive and 14C unstable, radioactive. Breath test with 13C is based on the atomic mass difference between 12C and 13C and it is necessary a mass spectrometer and 40 minutes to perform it. Breath test with 14C has 1 uCi (one micro-curie) of radioactivity (1/300 of total radiation received in one year from the environment); the test takes 10 minutes and the samples are read in a beta counter. Both non-invasive tests had demonstrated sensitivity and specificity comparable to established "gold standards" for Helicobacter pylori infection diagnosis. Rev Esp Enferm Dig. 1996 Mar;88(3):202-8. [C13 urea breath test in the diagnosis of Helicobacter pylori infection in the gastric mucosa. Validation of the method]. [Article in Spanish] Prez Garca JI, Pajares Garca JM, Jimnez Alonso I. Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid. Helicobacter pylori has been implicated as an agent in the pathogenesis of antral gastritis, gastric and duodenal ulcer and probably in gastric cancer. The C13 urea breath test is a diagnostic method quick to perform, sensitive, reliable and non invasive. It is based on the presence of Helicobacter pylori urease activity, which permits to detect it in the infected mucosa. A substrate (urea) labelled with Carbon 13 is administered to the patient and exhaled breath is collected to detect the possible catabolism product (CO2 labelled with C13). In the European protocol, patients in fasting condition are given a test meal to delay gastric emptying and five minutes later a solution which contents 100 mg of C13 labelled urea. Breath samples are collected before and 30 minutes after urea was given. In our first year of experience, 363 patients with Helicobacter pylori infection detected by histology or urease were studied by C13 urea breath test, with a sensitivity and specificity of 95 and 96%. False negatives may occur if the test is used after antibiotics and other antiulcer drugs. Its main indication is to monitor eradication therapy after treatment. Its possible use as a quantitative test still remains unclear Arch Pediatr. 1998 Dec;5(12):1359-65. [The 13C-urea breath test in Helicobacter pylori gastric infection in children]. [Article in French] Kalach N, Benhamou PH, Briet F, Raymond J, Dupont C. Unit de gastroentrologie, hpital Saint-Vincent-de-Paul, Paris, France. Helicobacter pylori gastric infection in children is a public health problem. Classical diagnostic tools such as endoscopy are excessively invasive in the usual clinical context. Serology at this age has multiple drawbacks. The urea-13C breath test seems today the most appropriate alternative method. The principle of the test relies upon the indirect detection of H pylori through its high urease activity. The test uses a stable (ie, non radioactive) isotope, which allows its repeated use. The main indications are the detection and the follow-up of H pylori infection. Scand J Gastroenterol Suppl. 1996;215:57-62. Advantages and disadvantages of current diagnostic tests for the detection of Helicobacter pylori. Mgraud F. Laboratoire de Bactriologie Enfants, Hpital Pellegrin, Bordeaux, France.

Current tests used to detect Helicobacter pylori are either invasive (histological detection, culture, the polymerase chain reaction (PCR), smear examination) or non-invasive (serology, 13C-urea breath test). These tests vary in their sensitivity and specificity, and the choice of test will depend on the situation, for example, whether the test is to detect infection or the success of eradication treatment. The accuracy of histological tests depends, to a large degree, on the expertise of the pathologist, while the accuracy of culture can depend on the conditions in which the specimen is transported and processed. When performed under optimal conditions, both techniques give very good results. The PCR test has similar sensitivity and specificity to histological and culture tests but a strict protocol must be followed to avoid contamination with H. pylori DNA. The rapid urease test (with a reading taken 1 hour later) is suitable for diagnosis before treatment but its sensitivity decreases after treatment. Smear examination has limited sensitivity. The urea breath test and serology (specific IgG detected by enzyme-linked immunosorbent assay with purified antigens) have sensitivities close to those using the best of the biopsy methods. Other points to consider when selecting a test are its availability, the rapidity of the results (which can range from a few minutes to 2 weeks), possibilities for retrospective analysis, quantification and the detection of pathogenic properties, the globality of certain tests that present an overall picture of the stomach, thus avoiding errors in sampling, and the cost of the test. Important added value can be gained from certain tests: histology allows evaluation of the status of the mucosa, culture allows strain typing and tests for antibiotic susceptibility, and the breath test can confirm successful eradication without endoscopy. When the diagnostic tests are performed correctly, most of them are highly accurate. Acta Gastroenterol Belg. 1998 Jul-Sep;61(3):336-43. How (who?) and when to test or retest for H. pylori. Burette A. Clinique Edith Cavell, Nouvelle Clinique de la Basilique, Brussels. Several direct/invasive and indirect/non-invasive diagnostic tests are available for the diagnosis of H. pylori infection. Invasive tests require biopsy sampling of the gastric mucosa and include rapid urease test, histology, bacterial culture and polymerase chain reaction technique. Non-invasive tests include the urea breath test and serological assays. This review gives a critical comparative analysis of accuracy, advantages and limitations of the different diagnostic tests including current cost and availability in Belgium. Rapid urease testing (RUT) of gastric biopsy specimens is probably the initial test of choice in patients undergoing endoscopy because of its low cost, rapid availability of results, simplicity and accuracy. Histological examination of gastric biopsy samples should be mandatory at the initial presentation of the patient because it also gives insight on the status of the gastric mucosa (inflammation & premalignant changes). Although not mandatory for primary diagnosis, a biopsy for culture and sensitivity testing should always be obtained when it is available and when endoscopy is undertaken as part of the patient's management. Among the non-invasive tests, the place of serology remains questionable for other than epidemiological purposes. How is H. pylori infection best diagnosed? How many tests are needed in routine clinical practice? The answer will depends on the clinical setting and local availability of the tests. For primary diagnosis in dyspeptic patients-where endoscopy is an important tool--a biopsy-based detection system is appropriate an we recommend the use of at least two diagnostic tests based on different principles, like RUT (with 1 or 2 biopsy specimen/test) and histology (including antrum & corpus biopsies) which are widely available. Alternatively a urea breath test may also be recommended when endoscopy is not required. Post-treatment monitoring seems to be justified in most cases and must always be performed at least 4-6 weeks after completion of therapy. The urea breath test is probably the method of choice for non-invasive testing in this clinical setting. When endoscopy is required, multiple biopsy specimens both from the antrum and the corpus and the use of at least two different diagnostic methods must be performed. Whenever possible, culture should always be done as it is very specific and allows testing of antimicrobial susceptibility which is mandatory in case of treatment failures. Neither the "Test and Treat" nor the "Test and Scope" strategies have been investigated in terms of effectiveness of symptoms relief and cost in Belgium and cannot therefore be recommended at this time. Minerva Med. 2006 Feb;97(1):19-24. [Non-invasive diagnosis of Helicobacter pylori infection in the 2006 clinical practice]. [Article in Italian] Pellicano R, Astegiano M, Smedile A, Bonardi R, Morgando A, Repici A, Rizzetto M. S.C.D.U. Gastro-Epatologia, Azienda Ospedaliera San Giovanni Battista (Molinette), Turin, Italy. rinaldo_pellican@hotmail.com At present, 2 approaches are used to detect Helicobacter pylori (H. pylori): invasive, if based on biopsies taken during endoscopy, and non-invasive, if they do not rely on endoscopic approach. A 3rd option is offered by the string test, that employs an invasive non-endoscopic strategy. The present review attempts to update on the diagnostic non-invasive approaches to patients in the clinical setting. Non-invasive tests include urea breath test (UBT), antigen stool assay,

serology, and ''doctor's tests''. The choice of the methods depends on the situation, for example, the clinical circumstances, the diagnostic accuracy, the costs of the testing strategy, and the availability of the tests in the respective area. According to European guidelines, UBT and antigen stool assay are recommended in patients without alarm symptoms or under 45 years of age, at low risk of malignancy in the test and treat strategy. Confirmation of H. pylori eradication following treatment should be tested by UBT; the stool antigen assay is the alternative if the former is not available. Best Pract Res Clin Gastroenterol. 2007;21(2):299-313. Diagnosis of Helicobacter pylori: invasive and non-invasive tests. Ricci C, Holton J, Vaira D. Gastroenterology Unit, University of Brescia, Italy. Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (e.g. histological examination, culture and rapid urease test) and by non-invasive techniques, such as serology, the urea breath test, urine/blood or detection of H. pylori antigen in stool specimen. Some non-invasive tests, such as the urea breath test and the stool antigen test, detect active infection: these are called 'active tests'. Non-invasive tests (e.g. serology, urine, near-patient tests) are markers of exposure to H. pylori but do not indicate if active infection is ongoing; these are 'passive tests'. Noninvasive test-and-treat strategies are widely recommended in the primary care setting. The choice of appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness. Ann Ital Med Int. 2005 Jan-Mar;20(1):23-7. [Non-invasive analyses for the diagnosis of Helicobacter pylori infection. A critical review of the literature]. [Article in Italian] Vaira D, Gatta L, Ricci C, Bernabucci V, Cavina M, Miglioli M. Dipartimento di Medicina Interna e Gastroenterologia, Universit degli Studi, Policlinico S. Orsola-Malpighi di Bologna. vairadin@med.unibo.it Helicobacter pylori (H. pylori) infection may be diagnosed by means of invasive techniques requiring endoscopy and biopsy (histological examination, rapid urease test, culture, polymerase chain reaction) and by non-invasive techniques (urea breath test, detection of specific antibodies in the serum or urine, detection of the H. pylori antigen in a stool specimen). Some noninvasive tests detect active infection e.g. the urea breath test and the stool antigen test and are called active tests. Other non-invasive tests are markers of exposure to H. pylori (e.g. serology or urine) but do not indicate whether active infection is ongoing and are called passive tests. Non-invasive tests and treatment strategies are widely recommended in primary care settings and the choice of the appropriate test depends on the pre-test probability of infection, the characteristics of the test being used and its cost-effectiveness. The available non-invasive tests are reviewed in this article. Rev Gastroenterol Disord. 2004 Winter;4(1):1-6. Non-invasive tests for the diagnosis of H. pylori infection. Vakil N, Vaira D. University of Wisconsin Medical School, Milwaukee, Wisconsin, USA. Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (eg, histological examination, culture, polymerase chain reaction) and by non-invasive techniques such as serology, urea breath test, urine/blood test, or detection of H. pylori antigen in stool specimen. Some non-invasive tests, such as the urea breath test and the stool antigen test, detect active infection; these are called "active tests." Non-invasive tests (eg, serology) are markers of exposure to H. pylori but do not indicate if active infection is ongoing; these are called "passive tests." Noninvasive test-and-treat strategies are widely recommended in primary care settings. The choice of an appropriate test depends on the pre-test probability of infection, the characteristics of the test being used, and the cost-effectiveness of the test. This article reviews available non-invasive tests.