4 Bile acid dissolution therapy of gallbladder stones HANS FROMM MAURO MALAVOLTI
BACKGROUND
AND PATHOPHYSIOLOGICAL
CONSIDERATIONS
Oral gallstone dissolution treatment with ursodeoxycholic acid (UDCA, 3a,7B-dihydroxy,SB-cholanic acid), or a combination of this bile acid with chenodeoxycholic acid (CDCA, 3a,7o-dihydroxy,SB-cholanic acid) has become established therapy for selected patients with gallstones (Fromm, 1986; Fromm and Malavolti, 1988; Salen et al, 1990). The treatment finds its main clinical applications both as bile acid therapy per se and in combination with extracorporeal shockwave lithotripsy (ESWL) (Albert and Fromm, 1990; Sackmann et al, 1991). In either case, the bile acid treatment is directed at the correction of the pathophysiological abnormalities underlying cholesterolcholelithiasis(Grundyet al, 1972;NorthfieldandHofmann, 1975; Bachrach and Hofmann, 1982). Biliary hypersecretion of cholesterol is suppressed, with consequent desaturation of the bile and re-establishment of its ability to solubilize cholesterol. In addition to this therapeutic effect, the bile acids appear to decrease the nucleating activity of the bile, as has been demonstrated in patients with gallstones treated with UDCA (Jtingst, 1989). The success of cholelitholytic therapy is principally a function of patient selection. Depending on whether oral cholelitholytic therapy is carried out without or with ESWL, the gallstone characteristics to be observed are very different. The selection criteria for these two clinical uses are, therefore, discussed separately. PATIENT
SELECTION
AND EFFICACY
General comments Only gallstone patients with biliary symptoms are considered eligible for treatment. The choice of gallstone treatment should be individualized according to the patient’s needs, symptoms and signs, and should involve the following principles and considerations. First, the patient’s preference is a most important subjective element in the selection process. Because, usually, more than one treatment option is applicable in a particular case, Baillihe’s Clinical GastroenterologyVol. 6, No. 4, November 1992 ISBN 0-7020-1625-X
689 Copyright 0 1992, by Baillitre Tindall All rights of reproduction in any form reserved
690
H.
FROMM
AND
M.
MALAVOLTI
the pros and cons of the available treatment modalities need to be discussed with the patient. It is not uncommon that a patient chooses medical therapy over surgery, in spite of being advised that operative treatment is either necessary or offers the best therapeutic solution. Second, objective patient selection criteria, based upon the severity of symptoms, as well as gallstone and gallbladder characteristics, have evolved which allow relatively reliable predictions concerning the risks and outcome of the different treatment methods. Proper counselling of the patient, therefore, requires the physician to be familiar with the selection criteria for the different treatment options for gallstones. Patient selection for dissolution therapy without ESWL Gallstone characteristics
Bile acid therapy, if used alone, i.e. without ESWL, offers a competitive success rate only for small cholesterol stones. The best results are obtained in the I OS-cm size category or if the cholesterol content of the gallstones is very high, as indicated by their buoyancy during oral cholecystography (OCG). These stones dissolve in > 70% of the cases within 1 year (Tint et al, 1982; Fromm et al, 1983a). However, the dissolution rate is low, i.e.
BACKGROUND
AND PATHOPHYSIOLOGICAL
CONSIDERATIONS
Oral gallstone dissolution treatment with ursodeoxycholic acid (UDCA, 3a,7B-dihydroxy,SB-cholanic acid), or a combination of this bile acid with chenodeoxycholic acid (CDCA, 3a,7o-dihydroxy,SB-cholanic acid) has become established therapy for selected patients with gallstones (Fromm, 1986; Fromm and Malavolti, 1988; Salen et al, 1990). The treatment finds its main clinical applications both as bile acid therapy per se and in combination with extracorporeal shockwave lithotripsy (ESWL) (Albert and Fromm, 1990; Sackmann et al, 1991). In either case, the bile acid treatment is directed at the correction of the pathophysiological abnormalities underlying cholesterolcholelithiasis(Grundyet al, 1972;NorthfieldandHofmann, 1975; Bachrach and Hofmann, 1982). Biliary hypersecretion of cholesterol is suppressed, with consequent desaturation of the bile and re-establishment of its ability to solubilize cholesterol. In addition to this therapeutic effect, the bile acids appear to decrease the nucleating activity of the bile, as has been demonstrated in patients with gallstones treated with UDCA (Jtingst, 1989). The success of cholelitholytic therapy is principally a function of patient selection. Depending on whether oral cholelitholytic therapy is carried out without or with ESWL, the gallstone characteristics to be observed are very different. The selection criteria for these two clinical uses are, therefore, discussed separately. PATIENT
SELECTION
AND EFFICACY
General comments Only gallstone patients with biliary symptoms are considered eligible for treatment. The choice of gallstone treatment should be individualized according to the patient’s needs, symptoms and signs, and should involve the following principles and considerations. First, the patient’s preference is a most important subjective element in the selection process. Because, usually, more than one treatment option is applicable in a particular case, Baillihe’s Clinical GastroenterologyVol. 6, No. 4, November 1992 ISBN 0-7020-1625-X
689 Copyright 0 1992, by Baillitre Tindall All rights of reproduction in any form reserved
690
H.
FROMM
AND
M.
MALAVOLTI
the pros and cons of the available treatment modalities need to be discussed with the patient. It is not uncommon that a patient chooses medical therapy over surgery, in spite of being advised that operative treatment is either necessary or offers the best therapeutic solution. Second, objective patient selection criteria, based upon the severity of symptoms, as well as gallstone and gallbladder characteristics, have evolved which allow relatively reliable predictions concerning the risks and outcome of the different treatment methods. Proper counselling of the patient, therefore, requires the physician to be familiar with the selection criteria for the different treatment options for gallstones. Patient selection for dissolution therapy without ESWL Gallstone characteristics
Bile acid therapy, if used alone, i.e. without ESWL, offers a competitive success rate only for small cholesterol stones. The best results are obtained in the I OS-cm size category or if the cholesterol content of the gallstones is very high, as indicated by their buoyancy during oral cholecystography (OCG). These stones dissolve in > 70% of the cases within 1 year (Tint et al, 1982; Fromm et al, 1983a). However, the dissolution rate is low, i.e.
