Changes in gastric ECL cells and parietal cells after long-term administration of high-dose omeprazole to patients with Barrett's esophagus.
OBJECTIVE
Long-term administration of PPI causes hyperplastic changes of the gastric parietal cells; however, the detailed mechanism remains to be clarified. We administered high-dose omeprazole to patients with Barrett's esophagus for 2 years, and investigated changes in gastric ECL (Enterochromaffin-like) cells using endoscopic biopsy specimens to clarify the etiology of hyperplasia of the parietal cells.


METHODS
The subjects were 69 patients who were diagnosed as having Barrett's esophagus (39 males, 30 females). We established two groups, an omeprazole-treated group and a ranitidine-treated group. Upper digestive tract endoscopy was performed before administration, and 12 and 24 months after the start of administration. Biopsy was performed in the greater curvature of the gastric body. The ECL/parietal cell counts and the grade of hyperplasia of the gastric mucosa were determined under a microscope. In addition, the fasting serum gastrin level was measured, and statistical analysis was performed.


RESULTS
In the omeprazole-treated group, the ECL cell count was markedly increased 12 months after the start of administration, but was lower than the pretreatment value 24 months after the start of administration. The parietal and ECL cell counts significantly increased. Furthermore, there were no changes in mucosa thickness. The fasting serum gastrin level significantly increased. In the ranitidine-treated group, there was no increase in the ECL cell count, and the parietal cell count was decreased. There was no significant increase in mucosa thickness. The fasting serum gastrin level increased, although the rate of increase was markedly smaller than that in the omeprazole-treated group.


CONCLUSIONS
Not the direct pharmacological actions of PPI but hypergastrinemia-associated secondary changes may be etiologically involved in hyperplasia of the parietal cells related to long-term administration of PPI.
Nishi
Takayuki
T
Department of Surgery, School of Medicine, Tokai University, Kanagawa, Japan. ann.nishi@nifty.com
Makuuchi
Hiroyasu
H
Weinstein
Wilfred M
WM
D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005755:Gastrins / Q000378:metabolism; D005773:Gastroscopy; D006801:Humans; D006965:Hyperplasia; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D054328:Proton Pump Inhibitors; D013997:Time Factors
D000897:Anti-Ulcer Agents; D005755:Gastrins; D054328:Proton Pump Inhibitors; D009853:Omeprazole