ABSTRACT
BACKGROUND AND AIMS: Low-grade erosive esophagitis (i.e. Los Angeles grade A) is the most predominant type of esophagitis in Japan. It is unclear whether all the mucosal breaks detected by conventional endoscopy are indicative of esophageal mucosal erosion. Hospital-based, cross-sectional, cross-over, observational study was assigned to investigate the value of magnifying endoscopy for diagnosis of erosive esophagitis. METHODS: From August to December 2006, 178 consecutive patients with upper gastrointestinal symptoms were enrolled at three university hospitals and one national medical center in western Japan. Before endoscopy, all participants were requested to answer questionnaires concerning their symptoms. Experienced endoscopists performed an endoscopic diagnosis of each patient first with a conventional standard view and then with a magnifying view. Endoscopic diagnostic concordance between conventional and magnifying endoscopic view for erosive esophagitis was calculated. Relationship between a variety of symptoms and erosive esophagitis was also evaluated. RESULTS: Erosive esophagitis was identified using conventional and magnifying endoscopy in 14.6% and 17.4% of patients, respectively. Eleven false-negative and six false-positive diagnoses using conventional endoscopy occurred among the 178 enrolled patients. The weighted kappa value of diagnostic concordance for erosive esophagitis between the two endoscopic views was 0.76. The prevalence of erosive esophagitis in patients with reflux-, dysmotility-, and ulcer-like symptoms was 20.7%, 24.1%, and 15.2%, respectively. CONCLUSIONS: Magnifying endoscopy did not significantly improve the diagnostic sensitivity of erosive esophagitis over non-magnifying, conventional endoscopy. Erosive esophagitis was frequently identified in patients that did not have reflux symptoms.
Subject(s)
Esophagitis/pathology , Esophagoscopy/methods , Image Enhancement , Aged , Cross-Over Studies , Cross-Sectional Studies , Esophageal Motility Disorders/etiology , Esophageal Motility Disorders/pathology , Esophagitis/complications , False Negative Reactions , False Positive Reactions , Female , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/pathology , Humans , Japan , Male , Middle Aged , Mucous Membrane/pathology , Peptic Ulcer/etiology , Peptic Ulcer/pathology , Predictive Value of Tests , Severity of Illness IndexABSTRACT
Helicobacter pylori infection increases the risk of hyperplastic polyps and gastric cancer, but the mechanisms remain to be elucidated. H. pylori was recently shown to transactivate epidermal growth factor receptor (EGFR) through metalloprotease stimulation. The present study was designed to investigate the effect of interleukin-8 (IL-8) induced by H. pylori infection on EGFR transactivation and epithelial cell growth. H. pylori Sydney strain 1 (SS1) having wild-type cag(+)A was used. Phospho-EGFR assay was performed by immunoprecipitation using anti-human EGFR and anti-phosphotyrosine antibodies. DNA synthesis was evaluated by [3H]thymidine uptake using the human gastric cancer cell line, KATO III. H. pylori induced EGFR phosphorylation, and a disintegrin and metalloproteinase (ADAM) inhibitor, KB-R7785, completely suppressed EGFR phosphorylation. IL-8 also induced EGFR phosphorylation, while anti-IL-8 and anti-IL-8 receptor (CXCR1) neutralizing antibodies suppressed EGFR phosphorylation. [(3)H]Thymidine uptake analysis demonstrated that H. pylori increased DNA synthesis in gastric epithelial cells, and tyrosine kinase inhibitor, MEK inhibitor, and ADAM inhibitor suppressed the DNA synthesis induced by H. pylori. H. pylori-stimulated IL-8 accelerates processing of EGFR ligands through ADAM activation, and cleaved EGFR ligands bind and stimulate EGFR in paracrine and autocrine manners to induce cell proliferation. This may be one of the mechanisms of hyperplastic polyp and gastric cancer development in H. pylori-infected gastric mucosa.
