Role of gastrin-peptides in Barrett's and colorectal carcinogenesis

Table 3 Clinico-epidemiologic studies exploring the effects of proton pump inhibitors use in human beings

Ref.	Population studied	Treatment, dose and duration	Effects on gastrin levels	Physiopathological effects
Brunner et al[35]	143 patients with duodenal or stomach ulcer and GERD	Omeprazole 40 mg/d 1-5 yr	Plasma gastrin levels increased 4-fold after 4 mo of therapy	Hyperplasia of argyrophil cells from oxyntic mucosa; No increase in dysplasia or neoplasia rates was observed
Klinkenberg-Knol et al[37]	91 GERD patients	Omeprazole 20-40 mg/d 5 yr	Median serum gastrin levels increased from 60 to 162 ng/L and reached a plateau during maintenance treatment	Esophagitis symptoms ameliorated; Gastric hyperplasia rates increased from 2.5% at the beginning of the study to 20% at last biopsy
Nemeth et al[39]	10 patients with oesophagitis	Omeprazole 20 mg/d 6-8 wk	Plasma levels of amidated gastrins increased from 18 to 48 pmol/L; Antral levels of progastrin increased 6-fold while amidated gastrins and G-Gly remain unaltered	Not assessed
Wang et al[42]	82 BE patients; 13 GERD patients	All patients were on PPI therapy, once or twice daily during a median time of 74 mo	The median serum gastrin levels (40 pmol/L) was not related to the degree of dysplasia in BE	Higher serum gastrin levels were associated with high grade dysplasia and adenocarcinoma
Creutzfeldt et al[53]	74 patients with esophagitis or peptic ulcer	Omeprazole 40 mg/d 1-5 yr	Plasma gastrin levels increased 4-fold in 23% of patients	Patients with higher serum gastrin levels developed hyperplasia of the gastric argyrophil cells; This hyperplasia may not necessary be related to high gastrin levels
Kuipers et al[54]	177 GERD patients	105 patients treated with omeprazole 20-40 mg/d 5 yr; 72 patients treated with fundoplication	Not assessed	Patients treated with omeprazole and infected with H.pylori infection are at increased risk of atrophic gastritis
Lamberts et al[55]	74 peptic ulcer patients	Omeprazole 48 mo	Median gastrin levels moderately increased after 3 mo of therapy and reached a plateau during maintenance treatment	Significant argyrophil cell hyperplasia

GERD: Gastroesophageal reflux disease; G-Gly: Glycine-extended gastrins; BE: Barrett’s esophagus; PPI: Proton pump inhibitors.