1. Erosions or not in GERD? The potential role of esophageal cell kinetics
- Author
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CALABRESE, CARLO, FABBRI, ANNA, CENACCHI, GIOVANNA, TRERE', DAVIDE, SCIALPI, CARLO, DERENZINI, MASSIMO, MIGLIOLI, MARIO, DI FEBO, GIULIO, Zahlane D, Calabrese C, Fabbri A, Cenacchi G, Trere D, Scialpi C, Zahlane D, Derenzini M, Miglioli M, and Di Febo G.
- Abstract
Gastro-oesophageal reflux is an almost universal daily occurrence, but only a small percentage of the population develops gastro-oesophageal reflux disease (GORD) and, among them, a small number develop erosive oesophagitis (ERD) or one of its complications. It is well accepted that the pathophysiology of GORD is related to failure of antireflux mechanisms but several phenomena are not fully explained on the basis of this sequence. There is no apparent relation between damage and the amount and quality of refluxate. It is not known why the same amount of refluxate determines GORD in one patient and not in another.2 It is also unclear whether there is a relation between these unexplained questions and the possible influence of proliferative responses of epithelial proliferating cells to damage. Hence we evaluated cell proliferation of the oesophageal epithelium using Ki67 immunostaining in normal subjects and in patients with GORD, with or without erosions. Thirty five subjects were enrolled: nine were healthy voluntary controls with normal pH testing and normal endoscopic, histological, and ultrastructural patterns. Twenty six patients were affected by GORD, defined as frequent heartburn for at least a year, and abnormal 24 hour pH, histological, and ultrastructural parameters. Of these 26 patients, 13 had a normal appearing oesophageal mucosa at endoscopy (NERD) while 13 had ERD. All subjects underwent gastroscopy; six biopsies were obtained within the lower 5 cm of the oesophagus from areas of macroscopically intact oesophageal mucosa. The presence of oesophagitis was graded according to the Los Angeles classification. pH parameters were not statistically different between NERD and ERD. At transmission electron microscopy (TEM), all patients with GORD, with or without erosions, showed ultrastructural signs of damage, defined by the presence of dilation of intercellular spaces (>0.74 µm). No significant differences were observed between the two groups. For assessment of the proliferative activity of epithelial cells, we used the immunohistochemical approach based on the Ki67 marker of cell proliferation which provides an accurate estimate of the cell growth fraction. Ki67-labelling index (LI) ranged from 8.9% to 74.4% among all patients (mean (SD) 33.5 (19.7)%; median 27.8%). Mean Ki67-LI values for the three groups of patients (normal, NERD, and ERD) were 62.2%, 29.8%, and 17.2%, respectively, and the difference among the groups was significant (p
- Published
- 2005