Digestive Diseases and Sciences

, Volume 42, Issue 8, pp 1775–1782 | Cite as

Gallstone Dissolution with Oral Bile Acid Therapy Importance of Pretreatment CT Scanning and Reasons for Nonresponse

  • Stephen P. Pereira
  • Martin J. Veysey
  • Colette Kennedy
  • S. Hyder Hussaini
  • Gerard M. Murphy
  • R. Hermon Dowling
Article

Abstract

In patients with cholesterol-rich gallbladderstones and a patent cystic duct, complete stoneclearance rates of 65-90% have been reported with oralbile acids (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy; ESWL).The aims of the present study were to analyzepretreatment gallstone characteristics that predict thespeed and completeness of dissolution with OBAs ±ESWL, and to assess, in patients with incompletedissolution, the reasons for the poor response. Wecompared pretreatment gallstone characteristics in 43patients who became stone-free after a median of 9months OBAs ± ESWL with those in 43 age- andsex-matched patients whose stones failed to dissolveafter two years of treatment. In those with incompletegallstone dissolution, we repeated the oralcholecystogram and computed tomogram (CT) and, in selectedpatients, obtained gallbladder bile by percutaneousfine-needle puncture. In patients who became stone-free,those with stones that were isodense with bile and/or had CT scores of 75 Hounsfield units had thefastest dissolution rates. In the 43 nonresponders, themain causes for treatment failure were impairedgallbladder contractility and acquired stonecalcification. CT-lucent, noncholesterol stones, or failure ofdesaturation of bile with the prescribed bile acids,occurred in a minority. We conclude that thepretreatment CT attenuation score predicts both thespeed and completeness of gallstone dissolution. Inpatients with incomplete stone dissolution, thecombination of oral cholecystography, CT, and analysisof gallbladder bile will determine the underlyingreasons for treatment failure in most, but not all,cases.

CHOLESTEROL SATURATION INDEX COMPUTED TOMOGRAPHY EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY GALLSTONES ORAL BILE ACIDS ORAL CHOLECYSTOGRAPHY 

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REFERENCES

  1. 1.
    Bachrach WH, Hofmann AF: Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Dig Dis Sci 27:737–761, 833–856, 1982Google Scholar
  2. 2.
    May GR, Sutherland LR, Shaffer EA: Efficacy of bile acid therapy for gallstone dissolution: A meta-analysis of randomized trials. Aliment Pharmacol Ther 7:139–148, 1993Google Scholar
  3. 3.
    Strasberg SM, Clavien P-A: Cholecystolithiasis: Lithotherapy for the 1990s. Hepatology 16:820–839, 1992Google Scholar
  4. 4.
    Ell C, Schneider HT, Benninger J, Theobaldy S, Friedel N, Rodl W, Wirtz P, Hahn EG: Significance of computed tomography for shock-wave therapy of radiolucent gallbladder stones. Gastroenterology 101:1409–1416, 1992Google Scholar
  5. 5.
    Sackmann M, Pauletzki J, Sauerbruch T, Holl J, Schelling G, Paumgartner G: The Munich gallbladder lithotripsy study: Results of the first 5 years with 711 patients. Ann Intern Med 114:290–296, 1991Google Scholar
  6. 6.
    Elewaut A, Carpe A, Afschrift M, Pauwels W, De Vos M, Barbier F: Results of extracorporeal shock wave lithotripsy of gall bladder stones in 693 patients: A plea for restriction to solitary radiolucent stones. Gut 34:274–278, 1993Google Scholar
  7. 7.
    Bell GD, Dowling RH, Whitney B, Sutor DJ: The value of radiology in predicting gallstone type when selecting patients for medical treatment. Gut 16:359–364, 1975Google Scholar
  8. 8.
    Trotman BW, Petrella EJ, Soloway RD, Sanchez HM, Morris TA, Miller WT: Evaluation of radiographic lucency or opaqueness of gallstones as a means of identifying cholesterol or pigment stones. Correlation of lucency or opaqueness with calcium and mineral. Gastroenterology 68:1563–1566, 1975Google Scholar
  9. 9.
    Rajagopal SU, Keightley A, Bills P, Walters JRF, Murphy GM, Dowling RH: Predictive value of pre-treatment CT scanning vs conventional radiology in determining composition, dissolvability and fragmentability of gallbladder stones (GBS). J Hepatol 9:S211, 1989Google Scholar
  10. 10.
    Brakel K, Lameris JS, Nijs HG, Terpstra OT, Steen G, Blijenberg BC: Predicting gallstone composition with CT: In vivo and in vitro analysis. Radiology 174:337–341, 1990Google Scholar
  11. 11.
    Hickman MS, Schwesinger WH, Bova JD, Kwintin WE: Computed tomography analysis of gallstones: An in vitro study. Arch Surg 121:289–291, 1986Google Scholar
  12. 12.
    Rambow A, Staritz M, Wosiewitz U, Mildenburger P, Thelen M, Meyer zum Buschenfelde KH: Analysis of radiolucent gallstones by computed tomography for in vivo estimation of stone components. Eur J Clin Invest 20:475–478, 1990Google Scholar
  13. 13.
    Walters JRF, Hood KA, Gleeson D, Ellul JPM, Keightley A, Murphy GM, Dowling RH: Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: Pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy. Gut 33:375–380, 1992Google Scholar
  14. 14.
    Caroli A, Del Favero G, Di Mario F, Spigariol F, Scalon P, Meggiato T, Zambelli C, Naccarato R: Computed tomography in predicting gall stone solubility: A prospective trial. Gut 33:698–700, 1992Google Scholar
  15. 15.
    Brink JA, Kammer B, Mueller PR, Balfe DM, Prien EL, Ferrucci JT: Prediction of gallstone composition: Synthesis of CT and radiographic features in vitro. Radiology 190:69–75, 1994Google Scholar
  16. 16.
    Petroni ML, Jazrawi RP, Grundy A, Lanzini A, Pigozzi MG, Biasio A, Heaton KW, Virjee J, Northfield TC: Prospective, multicenter study on value of computerized tomography (CT) in gallstone disease in predicting response to bile acid therapy. Dig Dis Sci 40:1956–1962, 1995Google Scholar
  17. 17.
    Swobodnik W, Hagert MS, Janowitz P, Wenk H: Diagnostic fine needle puncture of the gallbladder with US guidance. Radiology 178:755–758, 1991Google Scholar
  18. 18.
    Hussaini SH, Kennedy C, Pereira SP, Wass JAH, Dowling RH: Ultrasound guided percutaneous fine needle puncture of the gallbladder for studies of bile composition. Br J Radiol 68:271–276, 1995Google Scholar
  19. 19.
    Hussaini SH, Murphy GM, Kennedy C, Besser GM, Wass JAH, Dowling RH: The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gall-bladder stones. Gastroenterology 107:1503–1513, 1994Google Scholar
  20. 20.
    Maton PN, Murphy GM, Dowling RH: Ursodeoxycholic acid treatment of gallstones: dose response studies and a possible mechanism of action. Lancet 2:1297–1301, 1977Google Scholar
  21. 21.
    Hofmann AF: Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol 29(suppl 204):1–15, 1994Google Scholar
  22. 22.
    Hofmann AF, Grundy SM, Lachin JM, Lan SP, Baum RA, Hanson RF, Hersh T, Hightower NC Jr, Marks JW, Mekhjian H, Shaefer RA, Soloway RD, Thistle JL, Thomas FB, Tyor MP: Pre-treatment lipid composition in white patients with gallstones in the National Cooperative Gallstone Study. Gastroenterology 83:738–752, 1982Google Scholar
  23. 23.
    Tazuma S, Sasaki H, Mizuno S, Sagawa H, Hashiba S, Horiuchi I, Kajiyama G: Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile. Gastroenterology 97:173–178, 1989Google Scholar
  24. 24.
    Podda M, Zuin M, Battezzati PM, Ghezzi C, DeFazio C, Dioguardi ML: Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: A comparison with ursodeoxycholic acid alone. Gastroenterology 96:222–229, 1989Google Scholar
  25. 25.
    Baron RL, Rohrmann CA Jr, Lee SP, Shuman WP, Teefey SA: CT evaluation of gallstones in vitro: Correlation with chemical analysis. Am J Roentgen 151:1123–1128, 1988Google Scholar
  26. 26.
    Bova JG, Schwesinger WH, Kurtin WE: In vivo analysis of gallstone composition by computed tomography. Gastrointest Radiol 17:253–256, 1992Google Scholar
  27. 27.
    Marzio L, Innocenti P, Genovesi N, Di Felice F, Napolitano AM, Constantini R, Di Giandomenico E: Role of oral cholecystography, real-time ultrasound, and CT in evaluation of gallstones and gallbladder function. Gastrointest Radiol 17:257–261, 1992Google Scholar
  28. 28.
    Gleeson D, Ruppin DC, Saunders A, Murphy GM, Dowling RH: Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones. Q J Med 76:711–729, 1990Google Scholar
  29. 29.
    Schoenfield LJ, Lachin GM, National Cooperative Gallstone Study Group: Chenodiol (chenodeoxycholic acid) for dissolution of gallstones: The National Cooperative Gallstone Study—a controlled trial of efficacy and safety. Ann Intern Med 95:257–282, 1981Google Scholar
  30. 30.
    Rothstein RD, Brugge WR, Malet PF: Effect of extracorporeal shock wave lithotripsy and ursodeoxycholic acid on gallbladder motility. Dig Dis Sci 38:1712–1717, 1993Google Scholar
  31. 31.
    Sackmann NM, Eder H, Spengler U, Pauletzki J, Holl J, Paumgartner G, Sauerbruch T: Gallbladder emptying is an important factor in fragment disappearance after shock wave lithotripsy. J Hepatol 17:62–66, 1993Google Scholar
  32. 32.
    Portincasa P, Di Ciaula A, Baldassarre G, Palmieri V, Gentile A, Cimmino A, Palasciano G: Gallbladder motor function in gallstone patients: Sonographic and in vitro studies on the role of gallstones, smooth muscle function and gallbladder wall inflammation. J Hepatol 21:430–440, 1994Google Scholar
  33. 33.
    Forgacs IC, Maisey MN, Murphy GM, Dowling RH: Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying. Gastroenterology 87:299–307, 1984Google Scholar
  34. 34.
    Festi D, Frabboni R, Bazzoli F, Sangermano A, Ronchi M, Rossi L, Parini P, Orsini M, Primerano AM, Mazzella G, Aldini R, Roda E: Gallbladder motility in cholesterol gallstone disease: Effect of ursodeoxycholic acid administration and gallstone dissolution. Gastroenterology 99:1779–1785, 1990Google Scholar
  35. 35.
    Pauletzki J, Sailer C, Klüppelberg U, von Ritter C, Neubrand M, Holl J, Sauerbruch T, Sackmann M, Paumgartner G: Gallbladder emptying determines early gallstone clearance after shock-wave lithotripsy. Gastroenterology 107:1496–1502, 1994Google Scholar
  36. 36.
    Janowitz P, Wechsler JG, Janowitz A, Kuhn K, Swobodnik W, Ditschuneit H: Nucleation time, cholesterol saturation index, and biliary bile acid pattern: A comparison in responders and nonresponders to systemic litholysis with bile acids. Scand J Gastroenterol 26:367–373, 1991Google Scholar
  37. 37.
    Bateson MC, Bouchier IAD, Trash DB, Maudgal DP, Northfield TC: Calcification of radiolucent gallstones during treatment with ursodeoxycholic acid. Br Med J 283:645–646, 1981Google Scholar
  38. 38.
    Raedsch R, Stiehl A, Czygan P: Ursodeoxycholic acid and gallstone calcification. Lancet 2:1296, 1981 (letter)Google Scholar
  39. 39.
    Tint GS, Salen G, Colalillo A, Graber D, Verga D, Speck J, Shefer S: Ursodeoxycholic acid: A safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med 97:351–356, 1982Google Scholar
  40. 40.
    Lirussi F, Passera D, Iemmolo RM, Nassuato G, Okolicsanyi L: Clinical, ultrasonographic, and roentgenographic study in 134 asymptomatic gallstone carriers: Is oral ursodeoxycholic acid treatment worthwhile? Scand J Gastroenterol 28:267–273, 1993Google Scholar
  41. 41.
    Dumont M, Erlinger S, Uchman S: Hypercholeresis induced by ursodeoxycholic acid and 7-ketolithocholic acid in the rat: possible role of bicarbonate transport. Gastroenterology 79:82–89, 1980Google Scholar
  42. 42.
    Whiting MJ, Jarvinen V, Watts JMcK: Chemical composition of gallstones resistant to dissolution therapy with chenodeoxycholic acid. Gut 21:1077–1081, 1980Google Scholar
  43. 43.
    Freilich HS, Malet PF, Schwartz JS, Soloway RD, National Cooperative Gallstone Study Group: Chemical and morphologic characteristics of cholesterol gallstones that failed to dissolve on chenodiol: The National Cooperative Gallstone Study. Gastroenterology 91:713–718, 1986Google Scholar
  44. 44.
    Bazzoli F, Festi D, Mazzella G, Frabboni R, Zagari RM, Fossi S, Pozzato P, Sotilli S, Simoni P, Roda A, Roda E: Acquired gallstone opacification during cholelitholytic treatment with chenodeoxycholic, ursodeoxycholic, and tauroursodeoxycholic acids. Am J Gastroenterol 90:978–981, 1995Google Scholar
  45. 45.
    Sarva R, Farivar S, Fromm H, Poller W: Study of the sensitivity and specificity of computerised tomography in the detection of calcified gallstones which appear radiolucent by conventional roentgenography. Gastrointest Radiol 6:165–167, 1981Google Scholar
  46. 46.
    Lirussi F, Nassuato G, Passera D, Toso S, Zalunardo B, Monica F, Virgilio C, Frasson F, Okolicsanyi L: Gallstone (GS) characteristics and gallbladder emptying in an elderly resident population. Gut 35(suppl 4):A109, 1994Google Scholar
  47. 47.
    Plaisier PW, Brakel K, van der Hul RL, Bruining HA: Radiographic features of oral cholecystograms of 448 symptomatic gallstone patients: Implications for nonsurgical therapy. Eur J Radiol 18:57–60, 1994Google Scholar
  48. 48.
    Lanzini A, Facchinetti D, Northfield TC: Maintenance of hepatic bile acid secretion rate during overnight fasting by bedtime bile acid administration. Gastroenterology 95:1029–1035, 1988Google Scholar
  49. 49.
    Zuin M, Petroni ML, Grandinetti G, Crosignani A, Bertolini E, Battezzati PM, Podda M: Comparison of effects of chenodeoxycholic and ursodeoxycholic acid and their combination on biliary lipids in obese patients with gallstones. Scand J Gastroenterol 26:257–262, 1991Google Scholar
  50. 50.
    Galatola G, Jazrawi RP, Northfield TC: Low dose ursodeoxycholic acid at bedtime and at mealtimes: Effect on mass of lipids within the gallbladder and on gallstone dissolution rate. Eur J Gastroenterol Hepatol 4:301–306, 1992Google Scholar
  51. 51.
    Mizuno S, Tazuma S, Kajiyama G: Stabilization of biliary lipid particles by ursodeoxycholic acid: Prolonged nucleation time in human gallbladder bile. Dig Dis Sci 38:684–693, 1993Google Scholar
  52. 52.
    Tudyka J, Wechsler JG, Kratzer W, Mason R, Janowitz P, Maier C, Adler G: The effect of ursodeoxycholic acid on nucleation time in patients with solitary or multiple gallbladder stones. Am J Gastroenterol 89:1206–1210, 1994Google Scholar
  53. 53.
    Mazzella G, Bazzoli F, Festi D, Ronchi M, Aldini R, Roda A, Grigolo B, Simoni P, Villanova N, Roda E: Comparative evaluation of chenodeoxycholic and ursodeoxycholic acids in obese patients: Effects on biliary lipid metabolism during weight maintenance and weight reduction. Gastroenterology 101:490–496, 1991Google Scholar
  54. 54.
    Sackmann M, Pauletzki J, Aydemir U, Holl J, Sauerbruch T, Hasford J, Paumgartner G: Efficacy and safety of ursodeoxycholic acid for dissolution of gallstone fragments: comparison with the combination of ursodeoxycholic acid and chenodeoxycholic acid. Hepatology 14:1136–1141, 1991Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • Stephen P. Pereira
  • Martin J. Veysey
  • Colette Kennedy
  • S. Hyder Hussaini
  • Gerard M. Murphy
  • R. Hermon Dowling

There are no affiliations available

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