Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.
BACKGROUND
The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent.


METHODS
We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR).


RESULTS
In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001).


CONCLUSIONS
Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.
Department of Surgery, Royal College of Surgeons, Connolly Hospital, Blanchardstown, Dublin, Ireland.
Ayman O
AO
Nasr
Mary F
MF
Dillon
Susie
S
Conlon
Paul
P
Downey
Gang
G
Chen
Adrian
A
Ireland
Eamon
E
Leen
David
D
Bouchier-Hayes
Thomas N
TN
Walsh
D000818:Animals; D000863:Antacids / Q000008:administration & dosage; D001471:Barrett Esophagus / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004383:Duodenogastric Reflux / Q000150:complications* / Q000503:physiopathology; D004385:Duodenostomy; D066246:ErbB Receptors / Q000378:metabolism; D004946:Esophagostomy; D004947:Esophagus / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005743:Gastrectomy; D005744:Gastric Acid / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D000863:Antacids; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D054328:Proton Pump Inhibitors; D066246:ErbB Receptors