EFFECT OF THE SOMATOSTATIN ANALOG OCTREOTIDE ON GASTRIC-MUCOSAL FUNCTION AND HISTOLOGY DURING 3 MONTHS OF PREOPERATIVE TREATMENT IN PATIENTS WITH ACROMEGALY

Objective: To study the effects of the somatostatin analog octreotide on gastric mucosal function and histology during short-term (3 months) preoperative treatment in patients with acromegaly. Design: Open desi gn clinical study. Methods: 10 patients were studied before treatment: with octreotide (pre-tx), on day 1 of 300 mu g octreotide/day (d300), after 1 week on 300 (w300), 600 (w600) or 1500 (w1500) mu g octreotid e/day, and after an additional 2.5 months on 1500 mu g octreotide/day (M3). An 8 h gastrin profile was obtained and ambulatory intragastric 23 h pH-metry carried out at the indicated time points. Gastroscopy wa s performed at pre-tx and M3 and multiple mucosal biopsy specimens tak en. Results: The mean serum gastrin concentration at first declined du ring octreotide therapy to a nadir at w1500, then recovered despite on going therapy (probably in response to reduced gastric acidity) and wa s similar to pre-tx values at M3 (mean+/-S.E. 87+/-26, 50+/-11 and 98/-46 ng/l for pre-tx, w1500 and M3 respectively; P<0.05, pre-tx vs w15 00). Gastric acidity had also declined at d300 (P<0.05, d300 vs pre-tx ), then recovered (despite the increase in the octreotide dose), but d eclined again at M3 (mean pH (95% confidence interval): 2.4 (1.7-3.2), 3.3 (2.4-4.3), 2.6 (1.8-3.5, n=8) and 2.9 (1.6-4.2, n=7) at pre-tx, d 300, w1500 and M3 respectively). The gastrin concentration at M3, alth ough similar to pre-tx values, remained inadequately low for the reduc ed gastric acidity. The reduction in gastric acidity was marked during the daytime (0900-2200 h; P<0.01, d300 vs pre-tx and P=0.028, M3 vs p re-tx). However, while the stimulated postprandial gastric acid secret ion was reduced at d300 (P<0.01, d300 vs pre-tx) and at M3 (n=7; P=0.0 27, M3 vs pre-tx), fasting and preprandial acidity was not affected. D uring the night, gastric acidity was reduced from 2200 to 0300h, but t he reduction was less marked than during the daytime. Paradoxically, t he physiological intermittent late nocturnal reduction in acidity ('pH peaks' (0300-0800 h)) was abolished rather than enhanced. No patient acquired new Helicobacter pylori infection. The mean gastritis scores for antrum and body (n=8, Sidney classification) increased marginally from 1.7 to 1.9 (chronicity) and from 0.7 to 0.9 (atrophy), while the activity score was slightly reduced from 1.2 to 1.0. Conclusions: Thre e months of preoperative octreotide treatment profoundly and persisten tly altered gastric mucosal function (gastrin suppression, reduced aci dity), but caused only minor variations in the pre-existing gastritis scores.