AN UPDATE ON THE PATHOGENESIS AND TREATMENT OF CHOLESTEROL GALLSTONES

The primum movens in cholesterol gallstone formation is hepatic choles terol hypersecretion and chronic supersaturation of bile. A cascade of events will then include: (i) multiple biochemical defects: increased total biliary proteins (and qualitative shift to cholesterol crystall ization-promoting factors), increased proportions of hydrophobic bile salts, increased mucin secretion, and rapid nucleation/crystallization of cholesterol from cholesterol-enriched biliary vesicles; iii) multi ple motility defects: impaired gallbladder contractility in vitro and gallbladder stasis in vivo, delayed intestinal transit. A genetic pred isposition (together with environmental factors) might also be importa nt. Therapy should be offered to patients with symptomatic gallstones. Cholecystectomy remains the only radical therapy for cholelithiasis. For a subgroup of patients with symptomatic, uncomplicated cholesterol stones who are unwilling to undergo surgery, or who have a significan t surgical risk, alternative non-invasive therapies include: (i) oral litholysis of small stones by bile salts, (ii) fragmentation of 1-3 me dium-sized stones by extracorporeal shock-wave lithotripsy, and (iii) topical dissolution of multiple stones by methyl tertbutyl ether. A ma jor disadvantage of all non-surgical therapies, however, is the 50% re currence rate of stones at 5 years. A number of prokinetic agents can improve gallbladder and/or intestine transit, two important contributi ng factors in gallstone disease. In selected patients, administration of these agents might enhance the clearance of cholesterol crystals/ga llstones or might impede/delay gallstone formation and recurrence.