An update on the pathogenesis and treatment of cholesterol gallstones.
The primum movens in cholesterol gallstone formation is hepatic cholesterol 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 crystallization-promoting factors), increased proportions of hydrophobic bile salts, increased mucin secretion, and rapid nucleation/crystallization of cholesterol from cholesterol-enriched biliary vesicles; (ii) multiple motility defects: impaired gallbladder contractility in vitro and gallbladder stasis in vivo, delayed intestinal transit. A genetic predisposition (together with environmental factors) might also be important. 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 significant surgical risk, alternative non-invasive therapies include: (i) oral litholysis of small stones by bile salts, (ii) fragmentation of 1-3 medium-sized stones by extracorporeal shock-wave lithotripsy, and (iii) topical dissolution of multiple stones by methyl tertbutyl ether. A major disadvantage of all non-surgical therapies, however, is the 50% recurrence rate of stones at 5 years. A number of prokinetic agents can improve gallbladder and/or intestine transit, two important contributing factors in gallstone disease. In selected patients, administration of these agents might enhance the clearance of cholesterol crystals/gallstones or might impede/delay gallstone formation and recurrence.
Portincasa
P
P
Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands.
van de Meeberg
P
P
van Erpecum
K J
KJ
Palasciano
G
G
VanBerge-Henegouwen
G P
GP
D002769:Cholelithiasis / Q000737:chemistry / Q000503:physiopathology* / Q000628:therapy; D002784:Cholesterol / Q000378:metabolism; D005704:Gallbladder / Q000503:physiopathology; D005772:Gastrointestinal Transit; D006801:Humans
D002784:Cholesterol