Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett's oesophagus.
BACKGROUND
There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO).


OBJECTIVE
To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO.


METHODS
A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student-t test and the U-Mann-Whitney test were used for quantitative and ordinal variables.


RESULTS
Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed.


CONCLUSIONS
The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis.
Lanas
A
A
Service of Digestive Diseases, University Hospital, Instituto Aragonés de Ciencias de la Salud, CIBERehd, Zaragoza, Spain. alanas@unizar.es
Ortego
J
J
Sopeña
F
F
Alcedo
J
J
Barrio
E
E
Bujanda
L
L
Cosme
A
A
Bajador
E
E
Parra-Blanco
A
A
Ferrandez
A
A
Piazuelo
E
E
Quintero
E
E
Pique
J M
JM
D017209:Apoptosis / Q000187:drug effects*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013030:Spain; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D054328:Proton Pump Inhibitors; D013450:Sulfones; C116926:rofecoxib