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• W2002192108 abstract "We read with great interest the recent paper by Hung et al1Hung L.C.T. Ching J.Y.L. Sung J.J.Y. Ka–Fai T. Hui A.J. Wong V.W.S. Leong R.W.L. Chan H.L.Y. Wu J.C.Y. Leung W.K. Lee Y.T. Chung S.C.S. Chan F.K.L. Long-term outcome of Helicobacter pylori–negative idiopathic bleeding ulcers a prospective cohort study.Gastroenterology. 2005; 128: 1845-1850Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar regarding the long-term outcome of H pylori–negative idiopathic bleeding ulcers. The authors presented evidence that the incidence of H pylori–negative idiopathic ulcers is increasing in Hong Kong, in contrast with what reported for noncomplicated peptic ulcer in Europe,2Arents N.L.A. Thijs J.C. Van Zwet A.A. Kleibeuker J.H. Does the declining prevalence of Helicobacter pylori unmask patients with idiopathic peptic ulcer disease? Trends over an 8 years period.Eur J Gastroenterol Hepatol. 2004; 16: 779-783Crossref PubMed Scopus (45) Google Scholar, 3Arroyo M.T. Forne M. de Argila C.M. Feu F. Arenas J. de la Vega J. Garrigues V. Mora F. Castro M. Bujanda L. Cosme A. Castiella A. Gisbert J.P. Hervas A. Lanas A. The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe.Helicobacter. 2004; 9: 249-254Crossref PubMed Scopus (67) Google Scholar underlying the need for similar studies in Western countries. Although we agree with most of these conclusions, we think that some points remain controversial and may benefit from additional reflections. The first point of doubt regards the definition of the H pylori–negative status. The authors considered as “idiopathic H pylori–negative” those patients with negative urease test and histology and no history of aspirin or NSAIDs assumption. Among them, there were a number of patients with histologically determined gastric damage considered a sign of past H pylori infection. In this context, we feel that the possibility of false-negative cases due to H pylori infection “clearing” should be considered. Indeed, while the authors state that none of the H pylori–negative patients received proton pump inhibitors (PPIs) before endoscopy (albeit the time from suspension of drugs to endoscopy is not reported), they do not mention exclusion of antibiotics use in patients eventually classified as “idiopathic H pylori–negative,” despite these drugs being reported as associated with a quarter of apparently H pylori–negative ulcers.4Gisbert J.P. Blanco M. Mateos J.M. Fernandez-Salazar L. Fernandez-Bermejo M. Cantero J. Pajares J.M. H pylori-negative duodenal ulcer prevalence and causes in 774 patients.Dig Dis Sci. 1999; 44: 2295-2302Crossref PubMed Scopus (79) Google Scholar Interestingly, the authors report that “idiopathic H pylori–negative” patients accounted for some 19% of the study population, but for up to 42% of those who bled in hospital. These patients were older, and some 29% of them died within 6 months due to their underlying medical conditions. One may well speculate that in such a population (old, critically ill, inpatients) the use not only of antisecretory drugs or NSAIDs, but also of antibiotics is a common event, which may have lead to apparent H pylori clearing and to an overestimation of the actual incidence of idiopathic cases, especially in patients in whom histological traces of past infection have been found. In this subpopulation the addition of 13C urea breath test ad/or of H pylori IgG serology, could be advisable, at least after ulcer healing, to effectively rule out the possibility of missed H pylori infection. A second, maybe more intriguing issue, regards the need to evaluate gastric acid secretion in patients with H pylori–negative bleeding peptic ulcer to rule out hypersecretory states either gastrin driven, such as Zollinger–Ellison syndrome (ZES) or idiopathic. The authors’ study protocol indeed included evaluation of gastric acid secretion to rule out ZES only in those patients with more than 4 ulcers, ulcers at atypical sites, or refractory cases, which was never the case in the study population. In our experience, the risk of bleeding in patients with gastric acid hypersecretion is 6,5-folds higher,5Capurso G. Annibale B. Osborn J. D’Ambra G. Martino G. Lahner E. Delle Fave G. Occurence and relapse of bleeding from duodenal ulcer respective roles of acid secretion and Helicobacter pylori infection.Aliment Pharmacol Ther. 2001; 15: 821-829Crossref PubMed Scopus (17) Google Scholar and the number and site of those ulcers is not different from those of patients with normal acid output. Moreover, while in early studies “atypical ulcers” were frequent issues in the presentation of ZES patients, more recent studies have pointed out that up to 2/3 of ZES patients have a typical, solitary, ulcer only.6Jensen R.T. Gardner J.D. Gastrinoma.in: Go V.L.W. Di Magno E.P. Gardner J.D. Lebenthal E. Reber H.A. Scheele G.A. The Pancreas biology, pathobiology and disease. Raven Press, New York1993: 931-978Google Scholar Indeed, while bleeding is present in a quarter of ZES patients at diagnosis, the most common misdiagnosis in these patients remains “idiopathic peptic ulcer disease,” reported in 71% of cases.7Roy P.K. Venzon D.J. Shojamanesh H. Abou-Saif A. Peghini P. Dopp J.L. Gibril F. Jensen R.T. Zollinger-Ellison sindrome. Clinical presentation in 261 patients.Medicine. 2000; 79: 379-411Crossref PubMed Scopus (267) Google Scholar Interestingly, since the widespread introduction of very effective drugs such as PPIs, the referral rate for suspected ZES has dramatically decreased, with a consequent fall in the annual rate of diagnoses of some 40% in both our referral center in Italy and at the NIH in the US.8Corleto V.D. Annibale B. Gibril F. Angeletti S. Serrano J. Venzon D.J. Delle Fave G. Jensen R.T. Does the widespread use of proton pump inhibitors masl, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?.Aliment Pharmacol Ther. 2001; 15: 1555-1561Crossref PubMed Scopus (72) Google Scholar These findings suggest a possible delay in the diagnosis of gastrinoma, with a consequent shift toward a more advanced stage, which could be overcome by the awareness of physicians, in suspecting the diagnosis. In this scenario, in the population described by Hung et al, as PPIs were reported to be discontinued after 8 weeks in “idiopathic H pylori–negative” ulcer patients, a simple determination of fasting gastrin at that time could have been used as a screening test, eventually followed, in patients with hypergastrinemia, by the evaluation of intragastric pH, which is virtually always <2 in ZES. In conclusion, we feel that as the actual prevalence of H pylori is likely to fall in the next years, and more complicated or uncomplicated peptic lesions may eventually be classified as “idiopathic,” the importance of careful exclusion of the infection, and of even rare causes of disease, such as ZES, by simple and cheap tests should be highlighted. Long-term Outcome of Helicobacter pylori–Negative Idiopathic Bleeding Ulcers: A Prospective Cohort StudyGastroenterologyVol. 128Issue 7PreviewBackground & Aims: Helicobacter pylori-negative idiopathic ulcers are increasingly recognized. The secular trend and long-term outcome of this condition are unknown. Methods: We prospectively studied consecutive patients with bleeding gastroduodenal ulcers from January to December 2000. The incidence and etiology of ulcers during this period were compared with that between September 1997 and August 1998. H pylori–negative idiopathic ulcers were defined as negative tests for H pylori, no exposure to analgesics within 4 weeks, and absence of other risk factors for ulcers. Full-Text PDF" @default.
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