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Early gallstone recurrence rate after successful shock-wave therapy
GASTROENTEROLOGY 1990;98:392-396
LIVER,
PANCREAS,
AND BILIARY
TRACT
Early Gallstone Recurrence Rate After Successful Shock-Wave Therapy MICHAEL SACKMANN, ERNST IPPISCH, TILMAN SAUERBRUCH, JOSEPH HOLL, WALTER BRENDEL, and GUSTAV PAUMGARTNER Department of Medicine II and Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilian-University, Munich, Federal Republic of Germany
Extracorporeal shock-wave lithotripsy combined with adjuvant bile-acid dissolution therapy results in complete clearance of stone fragments in a high percentage of selected patients with radiolucent gallbladder calculi. With the gallbladder in situ, these patients are at risk of stone recurrence. Therefore, the early rate of stone recurrence after successful lithotripsy was evaluated. Fifty-eight of the first 60 consecutive patients who became stone free underwent followup examinations at least 1 yr (range, 12-37 mo; mean t SD, 16 + 6) after discontinuation of adjuvant bile-acid therapy. Five patients reported recurrent biliary pain within 1 yr after lithotripsy, and recurrent gallstones were detected. Fifty-three patients were asymptomatic during the first yr, and no recurrence was detected. Thus, the rate of gallstone recurrence was 9 % within 1 yr. The rate of gallstone recurrence up to 3 yr was estimated by actuarial analysis. The probability of stone recurrence was 11% (k 4%) at 1.5yr, and no further increase was observed up to 3 yr. Gallstone recurrence within 1 yr after successful shock-wave therapy has to be expected in approximately the same percentage of patients as has been reported in earlier postdissolution trials. It causes recurrent biliary pain in most cases.
ased on animal experiments of Brendel and Enders (11, extracorporeal shock-wave lithotripsy combined with bile-acid dissolution therapy has recently been introduced as a novel therapy for gallstone disease (2). In selected patients with 1 to 3 radiolucent stones up to 3 cm in diameter in a functioning gallbladder, it offers an effective alternative to open abdominal surgery, resulting in complete clearance of all stone fragments in a high percentage of patients (3).
B
The future role of this novel gallstone therapy will strongly depend on the rate of stone recurrence and its management. It is not known whether shock-wave therapy will be associated with a rate of stone recurrence similar to or different from that reported in previous postdissolution trials (4-12). Presence or absence of stone recurrence within the first yr may influence the future outcomes of the patients treated successfully by extracorporeal lithotripsy [6,12). The aim of the present study was to assess the rate of early stone recurrence after successful shock-wave lithotripsy. Materials and Methods Patients Fifty-eight of the first 60 consecutive patients with complete clearance of all fragments after extracorporeal shock-wave lithotripsy combined with bile-acid therapy entered the study. Forty-three patients were female and 15 were male. Ages ranged from 25-77 yr (46 of:12, mean * SD). The body mass index ranged from 19.1-36.1 kg/m2 (24.5 f 3.6). Fifty-three patients had been treated for a solitary radiolucent stone, and 5 for 2 or 3 radiolucent stones. The diameter of the largest stone had ranged from 6-29 mm (17 5 6). The time period required for complete clearance of the gallbladder after shock wave lithotripsy ranged from 3 days to 17 mo (2.9 f 3.5 mol. Adjuvant bile-acid litholytic therapy was administered for 2.4-23.8 mo (6.9 5 4.6).
Treatment
of the Gallstones
The gallstones had caused episodes of biliary pain before treatment in all patients. Disintegration of the stones was achieved by a prototype lithotripter (GM 1, Dornier Medizintechnik,
Germering,
F.R.G.). The technique
of gall-
@ 1990 by the American Gastroenterological Association 0016-5065/90/63.00
February 1996
stone disintegration by extracorporeally generated, focused shock waves has been described elsewhere (2.3). Adjuvant bile-acid dissolution therapy consisted of ursodeoxycholic acid and chenodeoxycholic acid, 7.6 f 1.4 mg per kg per day each, administered as a single bedtime dose. The bile acids were started 2 wk before lithotripsy, continued for 3 mo after complete clearance of all fragments, and then withdrawn. Clinical and ultrasonographical follow-up examinations were performed 1 day after lithotripsy, and thereafter within the intervals 1-2, 3-4, 5-8, 9-12, 13-18, and 19-24 mo after lithotripsy to evaluate complete disappearance of all fragments (3). A gallbladder was regarded as stone free if no echogenic foci with or without acoustic shadow could be detected by ultrasonography (curved array transducer, 3.5 MHz or 5.0 MHz LSC 7000 or 9500, Picker, F.R.G., or SAL 77B, Toshiba, Japan] (2.3).
Patient Follow-up After cessation of adjuvant bile acid therapy, followup investigations of the stone-free patients consisting of clinical examination and abdominal ultrasonography were made 6 and 12 mo later, and thereafter at least once a yr. In addition, the patients were asked to contact the investigators in case of biliary pain to obtain an earlier ultrasonography. The 58 patients were followed for at least 12 mo (range 12-38; mean 5 SD, 18 + 6) after withdrawal of bile acids. Two of the first 60 consecutive patients were abroad and were not reexamined by ultrasonography after cessation of the adjuvant bile acid therapy. They denied biliary pain at a recent interview. These 2 patients were excluded from the study. Recurrence of gallbladder stones was defined as the ultrasonographic detection of any echogenic object with acoustic shadow or gravity dependence. For the management of recurrent stones, the patients could opt for cholecystectomy or nonsurgical treatment. All patients with recurrent stones preferred nonsurgical therapy. Follow-up examinations of patients with recurrent stones consisted of the described procedures and were obtained every 3 mo.
Statistical Analysis Results are expressed as means + SD or as ranges. Actuarial analysis was performed according to the method of Kaplan and Meier (13).
Results Of the 58 patients followed for at least 1 yr after discontinuation of bile-acid therapy, 5 patients (9%) reported recurrence of biliary pain within 1 yr, and 1 patient at 14 mo. Ultrasonography revealed recurrent stones in each of these 6 patients with gallstone recurrence [Table 1). The recurrent stones had a maximum diameter of 3-4 mm and were multiple (2 or more] (Figure 1). Four of the 6 patients with recurrent stones had been treated for a single stone, and 2 for 2
GALLSTONE RECURRENCE
AFTER LITHOTRIPSY
393
Table 1. Characteristics of the Patients With Early Gallstone Recurrence After Successful Shock-Wave Therapy Patient no.
Age (yrl Sex No. of previous stones Stone size (mm] Period until stone free after ESWL (mo) Detection of recurrent stones after stopping bile acids (mo) No. of recurrent stones Diameter of largest recurrent stone [mm]
10
2
3
4
5
6b
39 F 1 14
77 M 1 14
37 F 1 17
41 M 2 22
32 F 1 24
41 F 3 9
2.4
2.7
3.7
17.2
1.3
13.2
4.4 2
5.3 2
6.5 6
8.9 N
12.4 5
14.1 N
3
3
4
4
4
3
‘Patient with second recurrence of gallstones. bPatient with recurrent gallstones detected more than 1 yr after cessation of bile-acid therapy. ESWL, extracorporeal shock-wave lithotripsy; N, numerous stones.
or 3 stones (Table 1). The 6 patients received a repeated course of bile-acid therapy with chenodeoxycholic acid and ursodeoxycholic acid. In 5 cases, shock-wave lithotripsy was also repeated without the need for any sedative or analgesic medication (lithotripter MPL 9000, Dornier). Fifty-two of the 58 patients studied have not experienced recurrent biliary pain, and no recurrent stones were detected. The 6 patients with recurrent stones have been followed for l-15 mo after detection of the recurrent stones. In 1 patient, complete dissolution of recurrent stones was observed by ultrasonography 3 mo after the start of repeated bile-acid therapy. The bile acids were continued for an additional 3 mo and then stopped. In this patient, a second recurrence (3 small stones of 2-3 mm] was observed 7 mo thereafter. Litholytic therapy was administered again, and again resulted in disappearance of the recurrent stones within 3 mo. In 3 of the other 5 patients, the size or number of the recurrent stones had decreased at a recent follow-up examination. The 2 remaining patients reported noncompliance with bile acid therapy, and no diminution of size or number of the recurrent stones was observed. To estimate the stone recurrence rate up to 2-3 yr, actuarial analysis was performed because not all patients have been followed for that period. The estimated probability of stone recurrence was 9 + 3% at 1.0 yr, and 11 * 4% at 1.5 yr. Thereafter, the recurrence rate showed no further increase up to 3 yr (Figure 2). Discussion The rate of postlithotripsy gallstone recurrence cannot be predicted from previous postdissolution trials because shock-wave therapy could influence
394 SACKMANN ET AL
GASTROENTEROLOGY Vol. 98, No, 2
Figure 1.Ultrasonography of the gallbladder of a patient (patient no. 5, Table 1)with a single radiolucent gallbladder stone (diameter 24 mm) before shock-wave therapy (A), 24 h after shock-wave therapy with multiple small stone fragments (B), at complete clearance of all fragments 1.8 mo later (C), and at the detection of tiny recurrent stones 12.4mo after ceesation of adjuvant bile-acid therapy 0)
stone formation through its effects on gallbladder function such as mucin production or motility. In addition, small residual fragments undetectable by ultrasonography could act as a nidus for stone formation. If shock-wave therapy does not affect mechanisms promoting stone formation, the recurrence rate should be comparable to that reported in earlier
Figure 2. Actuarial analysis of the probability of gallstone recurrence after successful shock-wave therapy in 58 patients. The 58 patients were followed for at least 12 mo. Each tick marks the Bnal follow-up investigation of a patient without stone recurrence.
T
#-+v
$ “J a’
postdissolution studies. Shock-wave therapy itself does not seem to alter gallbladder motor function (14). The present results indicate that early gallstone recurrence after successful lithotripsy occurs in about the same percentage of patients as that reported in postdissolution trials. The recurrence rate of 9% within the first yr in the current study is at the lower end of
01
0.5 I
1.0 1
1.5 I
Follow-up
2.0
2.5
( years
)
I
1
,
58
58
58
29 Patients
12 at risk
6
3.0 I
3.5 I
I
8
4
0
GALLSTONE RECURRENCE
February 1990
range of values from previous postdissolution The latter have reported a recurrence rate of 9%-15% and l3%-23% at 1 and 2 yr, respectively (4-6,9). For studies with variable follow-up periods, the
trials.
life-table
analysis
gives
the
most
accurate
estimation
(4,15). The results of actuarial analysis of the present data on the recurrence rate for up to 3 yr (Figure 2) are also at the lower end of the range of values reported in previous postdissolution studies (4-6,9). Recently, evidence has been reported that the recurrence rate may be lower in patients with single stones than in patients with multiple stones (lo-12,16). This could have influenced the recurrence rate observed in the present study because the majority of our patients had been treated for solitary gallstones. Therefore, the patients selected for lithotripsy are not representative of the occurrence of stones in the general population. In the present study, 4 of 53 patients treated for a single stone and 2 of 5 patients treated for 2-3 stones showed early stone recurrence. This very preliminary observation also suggests a higher recurrence rate in patients with multiple stones. Studies are needed to elucidate possible differences in bile-cholesterol saturation and nucleation time and in gallbladder motor function in patients with different numbers of stones. The observation that postlithotripsy recurrence was associated with recurrence of biliary pain differs from previous postdissolution trials, which have reported recurrence of biliary pain in only a minority of patients with stone recurrence (8-l&17). In this context, it should be emphasized that all of the present patients had biliary colic before lithotripsy. It is possible that more patients with frequent and severe attacks of biliary pain were treated than have been entered into dissolution trials. The recurrent stones could also be different from the previous stones in their propensity to cause symptoms because of the fact that all recurrent stones were small and multiple. At the time of detection, the recurrent stones were multiple and of quite homogenous size. It cannot be determined from the present study whether multiple tiny residual stone fragments undetectable by ultrasonography provided the nidus for the recurrent stones or the recurrent stones represent denovo formation. The factors determining stone recurrence are still unknown. Recently it was suggested that a stone-free interval of about 9 mo after cessation of bile acids may have predictive value for the absence of future stone recurrence (6,121. Therefore, presence or absence of stone recurrence within the first yr may predict the future outcome of the patients treated successfully by shock-wave lithotripsy. However, the early rate of recurrence may not be adequate to assess long-term recurrence, which should be evaluated by appropriate studies (4,5). of the
recurrence
rate
AFTER LITHOTRIPSY
395
No medication to prevent stone recurrence was used in the present study. Convincing data that would favor prophylaxis of gallstone formation using lowdose bile-acid therapy are lacking, or are only available as preliminary reports (8,9,11,12,16,18). At the time of detection, the recurrent stones in the present study had diameters of less than 5 mm. The recurrent stones were not rapidly dissolved by a repeated course of bile acids except in 1 case in which a second recurrence developed. Recently, it has been shown that sludge could be a precursor of recurrent stones (19). In our patients, earlier and more frequent follow-up examinations after complete clearance of stone fragments might have detected the formation of sludge before the appearance of recurrent stones. In the treatment of recurrent stones, efficacy of repeated bile-acid therapy could be enhanced by additional treatment with shock waves. Future studies are required to evaluate the benefit of such an approach. Our postlithotripsy study shows that early recurrence of gallbladder stones after successful treatment by extracorporeal shock-wave lithotripsy must be expected in a percentage of patients comparable with that reported in previous postdissolution trials. Thus, shock-wave therapy itself does not seem to have a major influence on factors promoting early stone recurrence.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
Brendel W. Enders G. Shock waves for gallstones: animal studies [letter). Lancet 1983;1:1054. Sauerbruch T, Delius M, Paumgartner G, Ho11J. Wess 0, Weber W. Hepp W, Brendel W. Fragmentation of gallstones by extracorporeal shock waves. N Engl J Med 1986;314:818-22. Sackmann M, Delius M, Sauerbruch T, Ho11 J, Weber W, Ippisch E, Hagelauer U, Wess 0, Hepp W, Brendel W, Paumgartner G. Shock-wave lithotripsy of gallbladder stones. The first 175 patients. N Engl J Med 1988;318:393-7. Lanzini A, Jazrawi RP, Kupfer RM, Maudgal DP, Joseph AE, Northfield TC. Gallstone recurrence after medical dissolution: an overestimated threat? J Hepatol1986;3:241-6. O’Donell LDJ, Heaton KW. Recurrence and re-recurrence of gall stones after medical dissolution: a long-term follow-up. Gut 1988;29:655-8. Hood K, Gleeson D, Ruppin DC, Dowling RH, and the British/ Belgian Gallstone Study Group. The British/Belgian Gallstone Study Group’s (BBSG) postdissolution trial (abstr]. Gut 1987;28: 470. Toulet J, Rousselet J, Viteau J-M, Duchon Y, Pagniez R, Samain B, Vienne J-L. Recidives et prevention des recidives apres dissolution de la lithiase vesiculaire par I’acide chenodesoxycholique chez 22 patients. Gastroenterol Clin Biol1983;7:605-9. Schoenfield LJ, Marks JW, for the National Cooperative Gallstone Study Group. Update on results of the national cooperative gallstone study: chenodiol after partial gallstone dissolution and gallstone recurrence after dissolution. In: Barbara L, Dowling RH, Hofmann AF, Roda E. eds. Recent advances in bile acid research. New York: Raven, 1985:267-71. Marks JW, Lan SP. and the National Cooperative Gallstone
396 SACKMANN
10.
11.
12.
13. 14.
15.
ET AL.
Group. Low-dose chenodiol to prevent gallstone recurrence after dissolution therapy. Ann Intern Med 1984;100:376-81. Bazzoli F, Mazzella G, Frabboni R. Villanova N, Monti F, Festi D. Roda E, Barbara L. Gallstone recurrence after successful oral bile acid therapy. In: Barbara L, Dowling RH, Hofmann AF, Roda E, eds. Recent advances in bile acid research. New York: Raven, 1985:277-g. Villanova N, Bazzoli F, Frabboni R, Mazzella G, Morselli Labate AM, Barbara L, Roda E. Gallstone recurrence after successful oral bile acid treatment: a follow-up study and evaluation of long term post-dissolution treatment (abstr). Gastroenterology 1987;92:1789. Dowling RH, Gleeson DC, Hood KA. Ruppin DC, and the British-Belgian Gallstone Study Group. Gallstone recurrence and postdissolution management. In: Paumgartner G. Stiehl A, Gerok W, eds. Bile acids and the liver. Lancaster: MTP Press, 1987355-67. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. Spengler II, Sackmann M, Sauerbruch T, Ho11 J, Paumgartner G. Gallbladder motility before and after extracorporeal shock wave lithotripsy. Gastroenterology 1989;96:860-3. Northfield TC, Lanzini A. Jazrawi R, Kupfer R, Maudgal DP. Gallstone dissolution rate and recurrence rate during and after
GASTROENTEROLOGY
18.
17. 18.
19.
Vol. 98, No. 2
bile acid therapy. In: Barbara L, et al., eds. Recent advances in bile acid research. New York: Raven, 1985:289-302. Hood K, Gleeson D, Ruppin D, Dowling H. Can gallstone recurrence be prevented?: the British/Belgian post-dissolution trial (abstr). Gastroenterology 1988;94:A548. Ruppin DC, Dowling RH. Is recurrence inevitable after gallstone dissolution by bile-acid treatment? Lancet 1982;1:181-5. Tint GS, Salen G, Chazen D. Symptomatic gallstones are likely to reoccur after dissolution with ursodeoxycholic acid (UDCA) but this may be prevented by low-dose LJDCA (abstr). Gastroenterology 1987;92:1787. Lee SP, Maher K. Nicholls JF. Origin and fate of biliary sludge. Gastroenterology 1988:94:170-6.
Received October 17.1988. Accepted June 2,1989. Address requests for reprints to: Dr. Michael Sackmann, Dept. of Medicine II, Klinikum Grosshadern, University of Munich, D-8000 Munich 70, Federal Republic of Germany. Supported by the Korber Foundation. The authors are indebted to J. Pedrazzoli for help in data computerization, to U. Aydemir. I. Koch, and C. Geis for help in actuarial analysis, and to R. Jiirgensmeyer for secretarial help.
LIVER,
PANCREAS,
AND BILIARY
TRACT
Early Gallstone Recurrence Rate After Successful Shock-Wave Therapy MICHAEL SACKMANN, ERNST IPPISCH, TILMAN SAUERBRUCH, JOSEPH HOLL, WALTER BRENDEL, and GUSTAV PAUMGARTNER Department of Medicine II and Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilian-University, Munich, Federal Republic of Germany
Extracorporeal shock-wave lithotripsy combined with adjuvant bile-acid dissolution therapy results in complete clearance of stone fragments in a high percentage of selected patients with radiolucent gallbladder calculi. With the gallbladder in situ, these patients are at risk of stone recurrence. Therefore, the early rate of stone recurrence after successful lithotripsy was evaluated. Fifty-eight of the first 60 consecutive patients who became stone free underwent followup examinations at least 1 yr (range, 12-37 mo; mean t SD, 16 + 6) after discontinuation of adjuvant bile-acid therapy. Five patients reported recurrent biliary pain within 1 yr after lithotripsy, and recurrent gallstones were detected. Fifty-three patients were asymptomatic during the first yr, and no recurrence was detected. Thus, the rate of gallstone recurrence was 9 % within 1 yr. The rate of gallstone recurrence up to 3 yr was estimated by actuarial analysis. The probability of stone recurrence was 11% (k 4%) at 1.5yr, and no further increase was observed up to 3 yr. Gallstone recurrence within 1 yr after successful shock-wave therapy has to be expected in approximately the same percentage of patients as has been reported in earlier postdissolution trials. It causes recurrent biliary pain in most cases.
ased on animal experiments of Brendel and Enders (11, extracorporeal shock-wave lithotripsy combined with bile-acid dissolution therapy has recently been introduced as a novel therapy for gallstone disease (2). In selected patients with 1 to 3 radiolucent stones up to 3 cm in diameter in a functioning gallbladder, it offers an effective alternative to open abdominal surgery, resulting in complete clearance of all stone fragments in a high percentage of patients (3).
B
The future role of this novel gallstone therapy will strongly depend on the rate of stone recurrence and its management. It is not known whether shock-wave therapy will be associated with a rate of stone recurrence similar to or different from that reported in previous postdissolution trials (4-12). Presence or absence of stone recurrence within the first yr may influence the future outcomes of the patients treated successfully by extracorporeal lithotripsy [6,12). The aim of the present study was to assess the rate of early stone recurrence after successful shock-wave lithotripsy. Materials and Methods Patients Fifty-eight of the first 60 consecutive patients with complete clearance of all fragments after extracorporeal shock-wave lithotripsy combined with bile-acid therapy entered the study. Forty-three patients were female and 15 were male. Ages ranged from 25-77 yr (46 of:12, mean * SD). The body mass index ranged from 19.1-36.1 kg/m2 (24.5 f 3.6). Fifty-three patients had been treated for a solitary radiolucent stone, and 5 for 2 or 3 radiolucent stones. The diameter of the largest stone had ranged from 6-29 mm (17 5 6). The time period required for complete clearance of the gallbladder after shock wave lithotripsy ranged from 3 days to 17 mo (2.9 f 3.5 mol. Adjuvant bile-acid litholytic therapy was administered for 2.4-23.8 mo (6.9 5 4.6).
Treatment
of the Gallstones
The gallstones had caused episodes of biliary pain before treatment in all patients. Disintegration of the stones was achieved by a prototype lithotripter (GM 1, Dornier Medizintechnik,
Germering,
F.R.G.). The technique
of gall-
@ 1990 by the American Gastroenterological Association 0016-5065/90/63.00
February 1996
stone disintegration by extracorporeally generated, focused shock waves has been described elsewhere (2.3). Adjuvant bile-acid dissolution therapy consisted of ursodeoxycholic acid and chenodeoxycholic acid, 7.6 f 1.4 mg per kg per day each, administered as a single bedtime dose. The bile acids were started 2 wk before lithotripsy, continued for 3 mo after complete clearance of all fragments, and then withdrawn. Clinical and ultrasonographical follow-up examinations were performed 1 day after lithotripsy, and thereafter within the intervals 1-2, 3-4, 5-8, 9-12, 13-18, and 19-24 mo after lithotripsy to evaluate complete disappearance of all fragments (3). A gallbladder was regarded as stone free if no echogenic foci with or without acoustic shadow could be detected by ultrasonography (curved array transducer, 3.5 MHz or 5.0 MHz LSC 7000 or 9500, Picker, F.R.G., or SAL 77B, Toshiba, Japan] (2.3).
Patient Follow-up After cessation of adjuvant bile acid therapy, followup investigations of the stone-free patients consisting of clinical examination and abdominal ultrasonography were made 6 and 12 mo later, and thereafter at least once a yr. In addition, the patients were asked to contact the investigators in case of biliary pain to obtain an earlier ultrasonography. The 58 patients were followed for at least 12 mo (range 12-38; mean 5 SD, 18 + 6) after withdrawal of bile acids. Two of the first 60 consecutive patients were abroad and were not reexamined by ultrasonography after cessation of the adjuvant bile acid therapy. They denied biliary pain at a recent interview. These 2 patients were excluded from the study. Recurrence of gallbladder stones was defined as the ultrasonographic detection of any echogenic object with acoustic shadow or gravity dependence. For the management of recurrent stones, the patients could opt for cholecystectomy or nonsurgical treatment. All patients with recurrent stones preferred nonsurgical therapy. Follow-up examinations of patients with recurrent stones consisted of the described procedures and were obtained every 3 mo.
Statistical Analysis Results are expressed as means + SD or as ranges. Actuarial analysis was performed according to the method of Kaplan and Meier (13).
Results Of the 58 patients followed for at least 1 yr after discontinuation of bile-acid therapy, 5 patients (9%) reported recurrence of biliary pain within 1 yr, and 1 patient at 14 mo. Ultrasonography revealed recurrent stones in each of these 6 patients with gallstone recurrence [Table 1). The recurrent stones had a maximum diameter of 3-4 mm and were multiple (2 or more] (Figure 1). Four of the 6 patients with recurrent stones had been treated for a single stone, and 2 for 2
GALLSTONE RECURRENCE
AFTER LITHOTRIPSY
393
Table 1. Characteristics of the Patients With Early Gallstone Recurrence After Successful Shock-Wave Therapy Patient no.
Age (yrl Sex No. of previous stones Stone size (mm] Period until stone free after ESWL (mo) Detection of recurrent stones after stopping bile acids (mo) No. of recurrent stones Diameter of largest recurrent stone [mm]
10
2
3
4
5
6b
39 F 1 14
77 M 1 14
37 F 1 17
41 M 2 22
32 F 1 24
41 F 3 9
2.4
2.7
3.7
17.2
1.3
13.2
4.4 2
5.3 2
6.5 6
8.9 N
12.4 5
14.1 N
3
3
4
4
4
3
‘Patient with second recurrence of gallstones. bPatient with recurrent gallstones detected more than 1 yr after cessation of bile-acid therapy. ESWL, extracorporeal shock-wave lithotripsy; N, numerous stones.
or 3 stones (Table 1). The 6 patients received a repeated course of bile-acid therapy with chenodeoxycholic acid and ursodeoxycholic acid. In 5 cases, shock-wave lithotripsy was also repeated without the need for any sedative or analgesic medication (lithotripter MPL 9000, Dornier). Fifty-two of the 58 patients studied have not experienced recurrent biliary pain, and no recurrent stones were detected. The 6 patients with recurrent stones have been followed for l-15 mo after detection of the recurrent stones. In 1 patient, complete dissolution of recurrent stones was observed by ultrasonography 3 mo after the start of repeated bile-acid therapy. The bile acids were continued for an additional 3 mo and then stopped. In this patient, a second recurrence (3 small stones of 2-3 mm] was observed 7 mo thereafter. Litholytic therapy was administered again, and again resulted in disappearance of the recurrent stones within 3 mo. In 3 of the other 5 patients, the size or number of the recurrent stones had decreased at a recent follow-up examination. The 2 remaining patients reported noncompliance with bile acid therapy, and no diminution of size or number of the recurrent stones was observed. To estimate the stone recurrence rate up to 2-3 yr, actuarial analysis was performed because not all patients have been followed for that period. The estimated probability of stone recurrence was 9 + 3% at 1.0 yr, and 11 * 4% at 1.5 yr. Thereafter, the recurrence rate showed no further increase up to 3 yr (Figure 2). Discussion The rate of postlithotripsy gallstone recurrence cannot be predicted from previous postdissolution trials because shock-wave therapy could influence
394 SACKMANN ET AL
GASTROENTEROLOGY Vol. 98, No, 2
Figure 1.Ultrasonography of the gallbladder of a patient (patient no. 5, Table 1)with a single radiolucent gallbladder stone (diameter 24 mm) before shock-wave therapy (A), 24 h after shock-wave therapy with multiple small stone fragments (B), at complete clearance of all fragments 1.8 mo later (C), and at the detection of tiny recurrent stones 12.4mo after ceesation of adjuvant bile-acid therapy 0)
stone formation through its effects on gallbladder function such as mucin production or motility. In addition, small residual fragments undetectable by ultrasonography could act as a nidus for stone formation. If shock-wave therapy does not affect mechanisms promoting stone formation, the recurrence rate should be comparable to that reported in earlier
Figure 2. Actuarial analysis of the probability of gallstone recurrence after successful shock-wave therapy in 58 patients. The 58 patients were followed for at least 12 mo. Each tick marks the Bnal follow-up investigation of a patient without stone recurrence.
T
#-+v
$ “J a’
postdissolution studies. Shock-wave therapy itself does not seem to alter gallbladder motor function (14). The present results indicate that early gallstone recurrence after successful lithotripsy occurs in about the same percentage of patients as that reported in postdissolution trials. The recurrence rate of 9% within the first yr in the current study is at the lower end of
01
0.5 I
1.0 1
1.5 I
Follow-up
2.0
2.5
( years
)
I
1
,
58
58
58
29 Patients
12 at risk
6
3.0 I
3.5 I
I
8
4
0
GALLSTONE RECURRENCE
February 1990
range of values from previous postdissolution The latter have reported a recurrence rate of 9%-15% and l3%-23% at 1 and 2 yr, respectively (4-6,9). For studies with variable follow-up periods, the
trials.
life-table
analysis
gives
the
most
accurate
estimation
(4,15). The results of actuarial analysis of the present data on the recurrence rate for up to 3 yr (Figure 2) are also at the lower end of the range of values reported in previous postdissolution studies (4-6,9). Recently, evidence has been reported that the recurrence rate may be lower in patients with single stones than in patients with multiple stones (lo-12,16). This could have influenced the recurrence rate observed in the present study because the majority of our patients had been treated for solitary gallstones. Therefore, the patients selected for lithotripsy are not representative of the occurrence of stones in the general population. In the present study, 4 of 53 patients treated for a single stone and 2 of 5 patients treated for 2-3 stones showed early stone recurrence. This very preliminary observation also suggests a higher recurrence rate in patients with multiple stones. Studies are needed to elucidate possible differences in bile-cholesterol saturation and nucleation time and in gallbladder motor function in patients with different numbers of stones. The observation that postlithotripsy recurrence was associated with recurrence of biliary pain differs from previous postdissolution trials, which have reported recurrence of biliary pain in only a minority of patients with stone recurrence (8-l&17). In this context, it should be emphasized that all of the present patients had biliary colic before lithotripsy. It is possible that more patients with frequent and severe attacks of biliary pain were treated than have been entered into dissolution trials. The recurrent stones could also be different from the previous stones in their propensity to cause symptoms because of the fact that all recurrent stones were small and multiple. At the time of detection, the recurrent stones were multiple and of quite homogenous size. It cannot be determined from the present study whether multiple tiny residual stone fragments undetectable by ultrasonography provided the nidus for the recurrent stones or the recurrent stones represent denovo formation. The factors determining stone recurrence are still unknown. Recently it was suggested that a stone-free interval of about 9 mo after cessation of bile acids may have predictive value for the absence of future stone recurrence (6,121. Therefore, presence or absence of stone recurrence within the first yr may predict the future outcome of the patients treated successfully by shock-wave lithotripsy. However, the early rate of recurrence may not be adequate to assess long-term recurrence, which should be evaluated by appropriate studies (4,5). of the
recurrence
rate
AFTER LITHOTRIPSY
395
No medication to prevent stone recurrence was used in the present study. Convincing data that would favor prophylaxis of gallstone formation using lowdose bile-acid therapy are lacking, or are only available as preliminary reports (8,9,11,12,16,18). At the time of detection, the recurrent stones in the present study had diameters of less than 5 mm. The recurrent stones were not rapidly dissolved by a repeated course of bile acids except in 1 case in which a second recurrence developed. Recently, it has been shown that sludge could be a precursor of recurrent stones (19). In our patients, earlier and more frequent follow-up examinations after complete clearance of stone fragments might have detected the formation of sludge before the appearance of recurrent stones. In the treatment of recurrent stones, efficacy of repeated bile-acid therapy could be enhanced by additional treatment with shock waves. Future studies are required to evaluate the benefit of such an approach. Our postlithotripsy study shows that early recurrence of gallbladder stones after successful treatment by extracorporeal shock-wave lithotripsy must be expected in a percentage of patients comparable with that reported in previous postdissolution trials. Thus, shock-wave therapy itself does not seem to have a major influence on factors promoting early stone recurrence.
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Received October 17.1988. Accepted June 2,1989. Address requests for reprints to: Dr. Michael Sackmann, Dept. of Medicine II, Klinikum Grosshadern, University of Munich, D-8000 Munich 70, Federal Republic of Germany. Supported by the Korber Foundation. The authors are indebted to J. Pedrazzoli for help in data computerization, to U. Aydemir. I. Koch, and C. Geis for help in actuarial analysis, and to R. Jiirgensmeyer for secretarial help.