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Gallbladder Motility Before and After Extracorporeal Shock-Wave Lithotripsy
GASTROENTEROLOGY 1989;96:860-3
Gallbladder Motility Before and After Extracorporeal Shock-Wave Lithotripsy U. SPENGLER, M. SACKMANN, T. SAUERBRUCH, G. PAUMGARTNER
J. HOLL,
and
Department of Internal Medicine II. Klinikum Grosshadern. University of Munich. Munich. Federal Republic of Germany
To determine whether extracorporeal shock-wave lithotripsy of gallbladder stones alters gallbladder motility, gallbladder contraction in response to intravenous cholecystokinin was investigated by ultrasound. Twenty-one patients with symptomatic gallstones were studied before and after shock-wave lithotripsy, 12 with and 9 without concomitant litho lytic therapy (combination of ursodeoxycholic acid and chenodeoxycholic acid). Gallbladder emptying was significantly delayed and less complete in both groups of patients before shock-wave treatment (with bile salts: residual volume, 51% ± 10% and half-ejection time, 40 ± 5 min; without bile salts: residual volume, 46% ± 7%; half-ejection time, 30 ± 4 min) compared with healthy controls (residual volume, 15% ± 4%; half-ejection time, 18 ± 2 min). Gallbladder motility was not altered in either group 1 day and 1 yr after lithotripsy. The findings indicate (a) that extracorporeal shockwave lithotripsy has no immediate or long-term adverse effects on gallbladder motility and (b) that the defect of gallbladder motility associated with gallstone disease is not abolished by removal of the stone.
E
xtracorporeal shock-wave lithotripsy (ESWL) with adjuvant oral litholytic therapy has been introduced as a safe and efficient treatment in selected patients with symptomatic gallbladder stones (1). During ESWL parts of the gallbladder wall are located in the shock-wave focal area and may suffer tissue damage. Therefore, gallbladder motility, which may be impaired in gallstone disease (2-6) or during litho lytic therapy with ursodeoxycholic acid (7), could be further impaired by ESWL. Ultrasound provides a sensitive and reproducible method for investigating gallbladder motility (8). Thus, ultrasound was used to study gallbladder contraction induced by intravenous cholecystokinin in patients with gallbladder stones before and after ESWL.
Patients and Methods Twenty-one patients with radiolucent gallbladder stones were selected for ESWL according to previously established criteria (1) and divided into two groups. In group A, gallbladder motility was studied in 5 men and 7 women (aged 18-60 yr) 1 day before ESWL and the day after ESWL. These patients were on oral litho lytic therapy with a combination of ursodeoxycholic and chenodeoxycholic acid (7.5 ± 1.5 mg/kg· day, each bile acid given as a single bedtime dose). This therapy had been started 3 wk before gallbladder motility was assessed. In group B, gallbladder motility was studied in 1 man and 8 women (aged 28-64 yr) before ESWL and after complete disappearance of stone fragments (212-503 days after ESWL treatment). These patients were studied before starting and 3 mo after stopping the adjuvant litholytic therapy. One patient in each group had three stones with maximm;n diameters of <12 mm. All other patients had solitary stones with diameters of <30 mm. Six men and 11 women without signs of hepatobiliary disease (aged 25-63 yr) served as controls. All subjects were studied after an overnight fast at 8 AM. Shock waves were generated by high-current underwater spark discharge and applied as described previously (1). Patients in group A received an average of 1000 shock-wave discharges (range, 430-1500); patients in group B received 1130 discharges (range, 700-1500). Gallbladder volumes were measured every 5 min during intravenous infusion of cholecystokinin (batch No. 8443551; dose, 0.02 U/kg . min; KabiVitrum, Stockholm, Sweden). Volumes were calculated from longitudinal and transverse ultrasonographic transections of the gallbladder using the sum of cylinders method as described by Everson and coworkers (8). Fasting volumes of the gallbladder represented the mean of four volume measurements immediately before starting the cholecystokinin infusion. Gallbladder contraction was characterized by the half-contraction time
Abbreviation used in this paper: ESWL, extracorporeal shockwave lithotripsy. © 1989 by the American Gastroenterological Association 0016-5085/89/$3.50
GALLBLADDER MOTILITY BEFORE AND AFTER ESWL
March 1989
861
Table 1. Gallbladder Contraction in Controls and Patients With Gallstones Before and After Extracorporeal Shock-Wave LithotripsyO Patients with gallstones Group Be
Group Ab Before Fasting volume (mI) Residual volume (mI) Contraction t1l2 (min) a
d
31 ± 5 15.4 ± 4.5" (51% ± 10%)d 40 ± 5"
One year after ESWL
One day after ESWL
Before
25 ± 4 12.1 ± 3.3 (54% ± 11%)
23 ± 6 9.2 ± 1.0· (46% ± 7%)d
47 ± 10
30 ± 4d
17 ± 3 8.2 ± 2.9 (44% ± 13%) 40 ± 16
Controls 16 ± 2 2.1 ± 0.4 (15% ± 4%) 18 ± 2
Group A was studied immediately before and 1 day after shock-wave treatment while taking a combination of chenodeoxycholic and ursodeoxycholic acid. Patients in group B were studied before starting any treatment and 1 yr after ESWL when patients were completely free of stone fragments and had stopped oral bile acids. Results are given as mean ± SEM. b Studied under bile acid therapy. e No bile acid therapy during study. d Significantly different from controls (p < 0.01) .• Significantly different from controls (p < 0.001). Statistical analysis before vs. after extra corporeal shock-wave lithotripsy by Wilcoxon matched-pairs signed-rank test; comparison between group A, group B, and controls by the nonpaired Wilcoxon test.
(t 1l2 ), which was calculated by linear regression analysis from the linear part of the contraction curves, and by the residual volume expressed both in milliliters and percentage of the fasting volume. Data before and after ESWL were analyzed by the Wilcoxon matched-pairs signed-rank test. Comparison between group A, group B, and controls was performed by the nonpaired Wilcoxon test. A p value of < 0.05 was considered statistically significant. Results are given as mean ± SEM.
Results There was no difference in fasting volume of the gallbladder between patients with gallstones who did not receive bile acid treatment and healthy controls. By contrast, patients with gallstones who were undergoing litho lytic therapy had significantly larger fasting volumes (Table 1, p < 0 .01). After starting the cholecystokinin infusion, gallbladder volume decreased and reached a plateau within 60 min in all groups (Figure 1). However, gallbladder contraction was slower and less complete in both groups of patients with gallstones than in the controls. The difference in gallbladder volume was statistically significant for each measurement taken at 2:20 min after starting the cholecystokinin infusion. Gallbladder emptying appeared to be even more sluggish in patients receiving oral litholytic bile acid treatment (group A), although this small difference was not statistically significant. After ESWL, gallbladder contractility was similar to pretreatment contractility for both groups of patients with gallstones (Figure 1). Contraction halftimes as well as residual volumes were not significantly altered by ESWL, whereas differences in these contraction parameters were evident between patients with gallstones and healthy controls (Table 1).
The time required for clearance of stone fragments was 7-250 days in group Band 2-530 days for those 9 patients of group A who were free of fragments at termination of the study. However, no correlation could be detected between gallbladder motility and the time required for stone disappearance.
Discussion This study demonstrates that ESWL treatment of gallbladder stones with up to 1500 shock-wave
100 Volume
20 Mean ±SEM o+-~--~~----~~--~~~--~~~
o
5
10
15
20 25 30
35 40
45 50
55 60
Minutes
Figure 1. Gallbladder emptying in response to intravenous cholecystokinin. Gallbladder volumes (mean ± SEM) of the two groups of patients with gallstones and the control subjects (A) during the cholecystokinin infusion. Volumes are expressed as a percentage of fasting volume (%FV) . Patients in group A were studied before (_) and 1 day after (0) ESWL under a combined therapy with ursodeoxycholic acid and chenodeoxycholic acid. Patients in group B were without oral litholytic therapy at the time of the study, which was performed before (e) and repeated 1 yr after (0) ESWL and complete disappearance of fragments. Asterisks indicate levels of significance versus controls (*p < 0.05, **p < 0.01 , ** *p < 0.001; Wilcoxon test) .
862
discharges has no immediate or long-term adverse effects on gallbladder motility. This indicates that ESWL does not inflict tissue damage on gallbladder walls that leads to further functional impairment. Indeed, histologic examination of gallbladders removed surgically 3 mo after ESWL has not revealed any changes that can be attributed to shock waves (9).
GASTROENTEROLOGY Vol. 96, No.3
SPENGLER ET AL.
Our data suggest that patients with symptomatic gallbladder stones have impaired gallbladder motility. This is in agreement with several other reports (2-6) that describe poorly functioning gallbladders in patients with gallstones. Shaffer et al. (2), applying 99IDTc-hepatoiminodiacetic acid scintigraphy, have shown slower gallbladder emptying in a subgroup of patients with gallstones. In a larger study, Forgacs and coworkers (5) have demonstrated that gallbladder contraction in response to a Lundh meal or cholecystokinin-octapeptide infusion was diminished and less complete for patients with gallstones. In some studies, gallbladder contraction appeared to be further reduced by treatment with ursodeoxycholic acid or chenodeoxycholic acid (5,7). In our patients taking oral bile acids there was a similar trend, which did not reach statistical significance. To our knowledge this study is the first to show that nonsurgical removal of calculi does not reverse the defect of gallbladder motility in patients with gallstone disease. Thus, our data propose that the presence of biliary calculi, per se, has only little effect on gallbladder motility. The cause of altered gallbladder motility in cholecystolithiasis remains unexplained. Data from experimental animals on lithogenic diets suggest that gallbladder motility may be impaired early in the pathogenesis of gallstones (10,11). In vitro studies of muscle strips from gallbladders of patients with cholecystolithiasis indicate that there is a defect in muscle contraction in noncontractors (12). Furthermore, poor responses of gallbladders to cholecystokinin, in vivo, have been shown to correlate with decreased gallbladder smooth muscle cholecystokinin-receptor densities measured in vitro after cholecystectomy in patients with cholecystolithiasis (13). Moreover, fibrosis and increased thickness of the gallbladder wall secondary to gallstone disease may also play a role. Although no alterations of the gallbladder wall could be detected by ultrasound, chronic cholecystitis with fibrosis might well be present at the histologic level and could have impaired gallbladder emptying in our patients with symptomatic gallstones. Whatever the cause of the motility defect, its persistence after ESWL may have important consequences. Although secretion of lithogenic bile is a prerequisite for cholesterol precipitation (14), its presence does not necessarily result in stone forma-
tion (15,16), indicating that additional factors contribute to the development of cholesterol gallstones. Bile stasis in a poorly functioning gallbladder could provide conditions that are favorable for crystal formation, nucleation, and growth of cholesterol stones (15-19). In humans, clinical conditions such as long-term parenteral nutrition (20), pregnancy, or contraceptive steroids (21,22) create an increased risk of gallstone formation and are associated with both an increase in biliary cholesterol saturation and prolonged retention of bile in the gallbladder. As the motility defect of the gallbladder shown in our study persisted after stone disappearance, it may be an important factor in gallstone recurrence after ESWL. Stone removal by cholecystotomy has been abandoned because of high recurrence rates (23). Bile salt litholytic therapy has an average recurrence rate of 10% per year over the first 5 yr after successful dissolution of the stones and discontinuation of therapy (24,25). It may be reasonable to expect a slightly smaller recurrence rate in the patients that we have selected for ESWL as they are predominantly patients with solitary stones. The risk of stone recurrence may be less in patients with solitary stones than in patients with multiple stones (26,27). Follow-up studies after ESWL will reveal the exact recurrence rates after ESWL and will hopefully clarify whether patients with poorly functioning gallbladders actually have a higher risk of reforming gallstones.
References 1. Sauerbruch T, Delius M, Paumgartner G, et al. Fragmentation of gallstones by extra corporeal shock waves. N Engl J Med 1986;314:818-22. 2. Shaffer EA, McOrmond P, Duggan H. Quantitative cholescintigraphy: assessment of gallbladder filling and emptying and duodenogastric reflux. Gastroenterology 1980;79:899-906. 3. Fischer RS, Stelzer F, Rock E, Malmud LS. Abnormal gallbladder emptying in patients with gallstones. Dig Dis Sci 1982;27:1019-24. 4. Thompson J, Fried GM, Ogden WD, et al. Correlation between release of cholecystokinin and contraction of the gallbladder in patients with gallstones. Ann Surg 1982;195:670-5. 5. Forgacs IC, Masey MN, Murphy GM, Dowling RH. Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying. Gastroenterology 1984;87:299-307. 6. Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology 1985;88:787-91. 7. Howard P, Murphy GM, Dowling RH. Effects of chenodeoxy (CDCA) and ursocholic acids (UCA) on gallbladder (GB) emptying (abstr). Gut 1985;26:A1124. 8. Everson GT, Braverman DZ, Johnson ML, Kern F. A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 1980; 79:40-6. 9. Sackmann M, Delius M, Sauerbruch T, et al. Shock-wave
March 1989
10.
11.
12.
13.
14.
15. 16.
17.
18.
19.
lithotripsy of gallbladder stones: the first 175 patients. N Engl J Med 1988;318:393-7. Fridhandler TM, Davison JS, Shaffer EA. Defective gallbladder contractility in the ground squirrel and prairie dog during early stages of cholesterol gallstone formation. Gastroenterology 1983;85:830-6. Pellegrini CA, Ryan T, Broderick W, Way LW. Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. Gastroenterology 1986;90:143-9. Zhu X-G, Greeley GH, Newmann J, Wiener J, Fagan q, Thompson JC. Correlation of in vitro measurements of contractility of the gallbladder with in vivo ultrasonographic findings in patients with gallstones. Surg Gynecol Obstet 1985;161:470-2. Upp JR, Nealon WH, Singh P, et al. Correlation of cholecystokinin receptors with gallbladder contractility in patients with gallstones. Ann Surg 1987;205:641-7. Admirand WH, Small DM. The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest 1968;47: 1043-51. Sedaghat A, Grundy SM. Cholesterol crystal and the formation of cholesterol gallstones. N Engl J Med 1980;302:1274-7. Holzbach RT, March M, Olzewski M, Holan K. Cholesterol solubility in bile; evidence that supersaturated bile is frequent in healthy man. J Clin Invest 1973;52:1467-79. LaMorte W, Schoetz D, Birkitt D, Williams L. The role of the gallbladder in the pathogenesis of cholesterol gallstones. Gastroenterology 1979;77:580-92. Holan KR, Holzbach RT, Hermann RE, Cooperman AM, Claffey WJ. Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology 1979;77: 611-7. Doty JE, Pitt HA, Kuchenbecker SL, DenBesten L. Impaired
GALLBLADDER MOTILITY BEFORE AND AFTER ESWL
20. 21.
22. 23. 24. 25. 26.
27.
863
gallbladder emptying before gallstone formation in the prairie dog. Gastroenterology 1983;85:168-74. Holzbach RT. Gallbladder stasis: consequence of lbng-term parenteral hyperalimentation and risk factor for cholelithiasis. Gastroenterology 1983;84:1055-7. Everson G, McKinley C, Lawson M, et al. Gallbladder function in the human female: effect of the ovulatoty cycle, pregnancy, and contraceptive steroids. Gastroenterology 1982;82:711-9. Braverman DZ, Johnson ML, Kern F. Effects of pregnllncy and contraceptive steroids on gallbladder function. N Engl J Med 1980;302:362--4. Norrby S, Schiinebeck J. Long-term results with cholecystolithotomy. Acta Chir Scand 1970;136:711-3. Lanzini A, Jazrawi RP, Kupfer RM, Maudgal DP, Joseph AEA, Northfield TC. Gallstone recurrence after medical dissolution. An overestimated threat? J HepatoI1986;3:241-6. O'Donnell LDJ, Heaton KW. Recurrence and re-recutrence of gallstones after medical dissolution: a longterm fdllow up. Gut 1988;29:655-8. Villanova N, Bazzoli F, Frabboni R, Morselli Labate AM, Roda E, Barbara L. Gallstone recurrence after successful oral bile acid treatment: a three year follow-up and evaluation of long-term postdissolution treatment (abstr). Gastroenterology 1987;92:1787. Hood K, Gleeson D, Ruppin D, Dowling RH. Can gallstone recurrence be prevented? The BritishlBelgian post-dissolution trial (abstr). Gastroenterology 1988;94:548A.
Received March 18, 1988. Accepted September 30, H188. Address requests for reprints to: U. Spengler, M.D., Department of Internal Medicine II, Klinikum Grosshadern, Marchidhistrasse 15, D-8000 Munich 70, Federal Republic of Germany.
Gallbladder Motility Before and After Extracorporeal Shock-Wave Lithotripsy U. SPENGLER, M. SACKMANN, T. SAUERBRUCH, G. PAUMGARTNER
J. HOLL,
and
Department of Internal Medicine II. Klinikum Grosshadern. University of Munich. Munich. Federal Republic of Germany
To determine whether extracorporeal shock-wave lithotripsy of gallbladder stones alters gallbladder motility, gallbladder contraction in response to intravenous cholecystokinin was investigated by ultrasound. Twenty-one patients with symptomatic gallstones were studied before and after shock-wave lithotripsy, 12 with and 9 without concomitant litho lytic therapy (combination of ursodeoxycholic acid and chenodeoxycholic acid). Gallbladder emptying was significantly delayed and less complete in both groups of patients before shock-wave treatment (with bile salts: residual volume, 51% ± 10% and half-ejection time, 40 ± 5 min; without bile salts: residual volume, 46% ± 7%; half-ejection time, 30 ± 4 min) compared with healthy controls (residual volume, 15% ± 4%; half-ejection time, 18 ± 2 min). Gallbladder motility was not altered in either group 1 day and 1 yr after lithotripsy. The findings indicate (a) that extracorporeal shockwave lithotripsy has no immediate or long-term adverse effects on gallbladder motility and (b) that the defect of gallbladder motility associated with gallstone disease is not abolished by removal of the stone.
E
xtracorporeal shock-wave lithotripsy (ESWL) with adjuvant oral litholytic therapy has been introduced as a safe and efficient treatment in selected patients with symptomatic gallbladder stones (1). During ESWL parts of the gallbladder wall are located in the shock-wave focal area and may suffer tissue damage. Therefore, gallbladder motility, which may be impaired in gallstone disease (2-6) or during litho lytic therapy with ursodeoxycholic acid (7), could be further impaired by ESWL. Ultrasound provides a sensitive and reproducible method for investigating gallbladder motility (8). Thus, ultrasound was used to study gallbladder contraction induced by intravenous cholecystokinin in patients with gallbladder stones before and after ESWL.
Patients and Methods Twenty-one patients with radiolucent gallbladder stones were selected for ESWL according to previously established criteria (1) and divided into two groups. In group A, gallbladder motility was studied in 5 men and 7 women (aged 18-60 yr) 1 day before ESWL and the day after ESWL. These patients were on oral litho lytic therapy with a combination of ursodeoxycholic and chenodeoxycholic acid (7.5 ± 1.5 mg/kg· day, each bile acid given as a single bedtime dose). This therapy had been started 3 wk before gallbladder motility was assessed. In group B, gallbladder motility was studied in 1 man and 8 women (aged 28-64 yr) before ESWL and after complete disappearance of stone fragments (212-503 days after ESWL treatment). These patients were studied before starting and 3 mo after stopping the adjuvant litholytic therapy. One patient in each group had three stones with maximm;n diameters of <12 mm. All other patients had solitary stones with diameters of <30 mm. Six men and 11 women without signs of hepatobiliary disease (aged 25-63 yr) served as controls. All subjects were studied after an overnight fast at 8 AM. Shock waves were generated by high-current underwater spark discharge and applied as described previously (1). Patients in group A received an average of 1000 shock-wave discharges (range, 430-1500); patients in group B received 1130 discharges (range, 700-1500). Gallbladder volumes were measured every 5 min during intravenous infusion of cholecystokinin (batch No. 8443551; dose, 0.02 U/kg . min; KabiVitrum, Stockholm, Sweden). Volumes were calculated from longitudinal and transverse ultrasonographic transections of the gallbladder using the sum of cylinders method as described by Everson and coworkers (8). Fasting volumes of the gallbladder represented the mean of four volume measurements immediately before starting the cholecystokinin infusion. Gallbladder contraction was characterized by the half-contraction time
Abbreviation used in this paper: ESWL, extracorporeal shockwave lithotripsy. © 1989 by the American Gastroenterological Association 0016-5085/89/$3.50
GALLBLADDER MOTILITY BEFORE AND AFTER ESWL
March 1989
861
Table 1. Gallbladder Contraction in Controls and Patients With Gallstones Before and After Extracorporeal Shock-Wave LithotripsyO Patients with gallstones Group Be
Group Ab Before Fasting volume (mI) Residual volume (mI) Contraction t1l2 (min) a
d
31 ± 5 15.4 ± 4.5" (51% ± 10%)d 40 ± 5"
One year after ESWL
One day after ESWL
Before
25 ± 4 12.1 ± 3.3 (54% ± 11%)
23 ± 6 9.2 ± 1.0· (46% ± 7%)d
47 ± 10
30 ± 4d
17 ± 3 8.2 ± 2.9 (44% ± 13%) 40 ± 16
Controls 16 ± 2 2.1 ± 0.4 (15% ± 4%) 18 ± 2
Group A was studied immediately before and 1 day after shock-wave treatment while taking a combination of chenodeoxycholic and ursodeoxycholic acid. Patients in group B were studied before starting any treatment and 1 yr after ESWL when patients were completely free of stone fragments and had stopped oral bile acids. Results are given as mean ± SEM. b Studied under bile acid therapy. e No bile acid therapy during study. d Significantly different from controls (p < 0.01) .• Significantly different from controls (p < 0.001). Statistical analysis before vs. after extra corporeal shock-wave lithotripsy by Wilcoxon matched-pairs signed-rank test; comparison between group A, group B, and controls by the nonpaired Wilcoxon test.
(t 1l2 ), which was calculated by linear regression analysis from the linear part of the contraction curves, and by the residual volume expressed both in milliliters and percentage of the fasting volume. Data before and after ESWL were analyzed by the Wilcoxon matched-pairs signed-rank test. Comparison between group A, group B, and controls was performed by the nonpaired Wilcoxon test. A p value of < 0.05 was considered statistically significant. Results are given as mean ± SEM.
Results There was no difference in fasting volume of the gallbladder between patients with gallstones who did not receive bile acid treatment and healthy controls. By contrast, patients with gallstones who were undergoing litho lytic therapy had significantly larger fasting volumes (Table 1, p < 0 .01). After starting the cholecystokinin infusion, gallbladder volume decreased and reached a plateau within 60 min in all groups (Figure 1). However, gallbladder contraction was slower and less complete in both groups of patients with gallstones than in the controls. The difference in gallbladder volume was statistically significant for each measurement taken at 2:20 min after starting the cholecystokinin infusion. Gallbladder emptying appeared to be even more sluggish in patients receiving oral litholytic bile acid treatment (group A), although this small difference was not statistically significant. After ESWL, gallbladder contractility was similar to pretreatment contractility for both groups of patients with gallstones (Figure 1). Contraction halftimes as well as residual volumes were not significantly altered by ESWL, whereas differences in these contraction parameters were evident between patients with gallstones and healthy controls (Table 1).
The time required for clearance of stone fragments was 7-250 days in group Band 2-530 days for those 9 patients of group A who were free of fragments at termination of the study. However, no correlation could be detected between gallbladder motility and the time required for stone disappearance.
Discussion This study demonstrates that ESWL treatment of gallbladder stones with up to 1500 shock-wave
100 Volume
20 Mean ±SEM o+-~--~~----~~--~~~--~~~
o
5
10
15
20 25 30
35 40
45 50
55 60
Minutes
Figure 1. Gallbladder emptying in response to intravenous cholecystokinin. Gallbladder volumes (mean ± SEM) of the two groups of patients with gallstones and the control subjects (A) during the cholecystokinin infusion. Volumes are expressed as a percentage of fasting volume (%FV) . Patients in group A were studied before (_) and 1 day after (0) ESWL under a combined therapy with ursodeoxycholic acid and chenodeoxycholic acid. Patients in group B were without oral litholytic therapy at the time of the study, which was performed before (e) and repeated 1 yr after (0) ESWL and complete disappearance of fragments. Asterisks indicate levels of significance versus controls (*p < 0.05, **p < 0.01 , ** *p < 0.001; Wilcoxon test) .
862
discharges has no immediate or long-term adverse effects on gallbladder motility. This indicates that ESWL does not inflict tissue damage on gallbladder walls that leads to further functional impairment. Indeed, histologic examination of gallbladders removed surgically 3 mo after ESWL has not revealed any changes that can be attributed to shock waves (9).
GASTROENTEROLOGY Vol. 96, No.3
SPENGLER ET AL.
Our data suggest that patients with symptomatic gallbladder stones have impaired gallbladder motility. This is in agreement with several other reports (2-6) that describe poorly functioning gallbladders in patients with gallstones. Shaffer et al. (2), applying 99IDTc-hepatoiminodiacetic acid scintigraphy, have shown slower gallbladder emptying in a subgroup of patients with gallstones. In a larger study, Forgacs and coworkers (5) have demonstrated that gallbladder contraction in response to a Lundh meal or cholecystokinin-octapeptide infusion was diminished and less complete for patients with gallstones. In some studies, gallbladder contraction appeared to be further reduced by treatment with ursodeoxycholic acid or chenodeoxycholic acid (5,7). In our patients taking oral bile acids there was a similar trend, which did not reach statistical significance. To our knowledge this study is the first to show that nonsurgical removal of calculi does not reverse the defect of gallbladder motility in patients with gallstone disease. Thus, our data propose that the presence of biliary calculi, per se, has only little effect on gallbladder motility. The cause of altered gallbladder motility in cholecystolithiasis remains unexplained. Data from experimental animals on lithogenic diets suggest that gallbladder motility may be impaired early in the pathogenesis of gallstones (10,11). In vitro studies of muscle strips from gallbladders of patients with cholecystolithiasis indicate that there is a defect in muscle contraction in noncontractors (12). Furthermore, poor responses of gallbladders to cholecystokinin, in vivo, have been shown to correlate with decreased gallbladder smooth muscle cholecystokinin-receptor densities measured in vitro after cholecystectomy in patients with cholecystolithiasis (13). Moreover, fibrosis and increased thickness of the gallbladder wall secondary to gallstone disease may also play a role. Although no alterations of the gallbladder wall could be detected by ultrasound, chronic cholecystitis with fibrosis might well be present at the histologic level and could have impaired gallbladder emptying in our patients with symptomatic gallstones. Whatever the cause of the motility defect, its persistence after ESWL may have important consequences. Although secretion of lithogenic bile is a prerequisite for cholesterol precipitation (14), its presence does not necessarily result in stone forma-
tion (15,16), indicating that additional factors contribute to the development of cholesterol gallstones. Bile stasis in a poorly functioning gallbladder could provide conditions that are favorable for crystal formation, nucleation, and growth of cholesterol stones (15-19). In humans, clinical conditions such as long-term parenteral nutrition (20), pregnancy, or contraceptive steroids (21,22) create an increased risk of gallstone formation and are associated with both an increase in biliary cholesterol saturation and prolonged retention of bile in the gallbladder. As the motility defect of the gallbladder shown in our study persisted after stone disappearance, it may be an important factor in gallstone recurrence after ESWL. Stone removal by cholecystotomy has been abandoned because of high recurrence rates (23). Bile salt litholytic therapy has an average recurrence rate of 10% per year over the first 5 yr after successful dissolution of the stones and discontinuation of therapy (24,25). It may be reasonable to expect a slightly smaller recurrence rate in the patients that we have selected for ESWL as they are predominantly patients with solitary stones. The risk of stone recurrence may be less in patients with solitary stones than in patients with multiple stones (26,27). Follow-up studies after ESWL will reveal the exact recurrence rates after ESWL and will hopefully clarify whether patients with poorly functioning gallbladders actually have a higher risk of reforming gallstones.
References 1. Sauerbruch T, Delius M, Paumgartner G, et al. Fragmentation of gallstones by extra corporeal shock waves. N Engl J Med 1986;314:818-22. 2. Shaffer EA, McOrmond P, Duggan H. Quantitative cholescintigraphy: assessment of gallbladder filling and emptying and duodenogastric reflux. Gastroenterology 1980;79:899-906. 3. Fischer RS, Stelzer F, Rock E, Malmud LS. Abnormal gallbladder emptying in patients with gallstones. Dig Dis Sci 1982;27:1019-24. 4. Thompson J, Fried GM, Ogden WD, et al. Correlation between release of cholecystokinin and contraction of the gallbladder in patients with gallstones. Ann Surg 1982;195:670-5. 5. Forgacs IC, Masey MN, Murphy GM, Dowling RH. Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying. Gastroenterology 1984;87:299-307. 6. Pomeranz IS, Shaffer EA. Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology 1985;88:787-91. 7. Howard P, Murphy GM, Dowling RH. Effects of chenodeoxy (CDCA) and ursocholic acids (UCA) on gallbladder (GB) emptying (abstr). Gut 1985;26:A1124. 8. Everson GT, Braverman DZ, Johnson ML, Kern F. A critical evaluation of real-time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 1980; 79:40-6. 9. Sackmann M, Delius M, Sauerbruch T, et al. Shock-wave
March 1989
10.
11.
12.
13.
14.
15. 16.
17.
18.
19.
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Received March 18, 1988. Accepted September 30, H188. Address requests for reprints to: U. Spengler, M.D., Department of Internal Medicine II, Klinikum Grosshadern, Marchidhistrasse 15, D-8000 Munich 70, Federal Republic of Germany.