Gallstones during Octreotide Therapy

Abstract

Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide, but the reported prevalence of cholecystolithiasis in patients treated with octreotide is variable and little is known about gallstone incidence, composition, pathogenetic mechanisms, dissolvability, and primary prevention. Octreotide treatment apart, in industrialised societies most GBS are mixed in composition, cholesterol-rich (arbitrarily >70% cholesterol by weight), radiolucent (70%), and, given a patent cystic duct (70%). dissolvable in bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) + chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes supersaturated with cholesterol (as the molar ratio of cholesterol to phospholipids in biliary vesicles approaches 1 :I, the vesicles become unstable); (2) there is an imbalance between proand anti-nucleating factors, which favors cholesterol crystal precipitation; and (3) there is stasis within the GB as a result of altered motor function and/or excess mucus that traps the crystals. These changes may be associated with altered (4) biliary bile acid composition (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid composition (arachidonyl-rich lecithin acting as a substrate for mucosal prostaglandin synthesis which, in turn, may influence both gallbladder motility, and mucus glycoprotein synthesis and secretion). During octreotide treatment, meal-stimulated cholecystokinin (CCK) release is impaired leading to GB hypomotility, but little is known about the effects of octreotide on biliary cholesterol saturation, crystal nucleation time, mucus glycoprotein concentration, bile acid or phospholipid fatty acid composition. Most, but not all, reports suggest that the prevalence of GBS in octreotide-treated patients is considerably greater than that in age-, sex-, and weight-matched controls, but proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent before, but developed during, therapy is not always available. Furthermore, there are few data on analysis of GBS composition in patients developing stones during treatment, although initial reports suggest that octreotideassociated GBS are also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment. Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized computerized tomography scanning of the GB, predict stone composition and dissolvability: GBS with scores of less than 100 HU are cholesterol-rich and dissolve well with oral bile acid treatment. However, preliminary results in 11 acromegalic patients treated with 200 to 600 pg octreotide/d for 29 to 68 months show that the HU scores range from 23 to 490 (mean f SEM, 116 it 41). suggesting that at least four of these 11 patients have noncholesterol stones. Gallstone dissolvability is being assessed by studying the response to oral UDCA (10 mg . kg-kg-‘&‘). Liquid test meal-stimulated immunoreactive CCK release and gallbladder contraction are also being measured before and during treatment, as are biliary bile acid and lipid composition, cholesterol saturation indices, and crystal nucleation times in samples of fasting bile obtained by ultrasound-guided skinny-needle aspiration of the GB. Only after establishing the relative contributions of these different pathogenetic mechanisms will we be in a position to plan, logically, prophylactic measures to prevent octreotide-induced GBS formation. Copyright 61 1992 by W.B. Saunders Company