Journal ofHepatology, 1992; 16: 102-10.~ ©1992 Elsevier Scientific Publishers Ireland Ltd. All rights reserved. 0168-827802/$05.0(

102

HEPAT 01149

Low early gallstone recurrence rate after successful extracorporeal lithotripsy in patients with solitary stones G. Pelletier a, R. Capdeville b, H. M o s n i e r c, J.M. R a y m o n d d, J. D e l m o n t e, J. M o r e a u x b, M. G u i v a r c h c, M. A m o u r e t t i d, F.X. Caroli e, V.G. Levy f a n d J.P. Etienne a aDepartment of Gastroenterology, H6pital de Bic~tre, Le Kremlin Bic~tre, bDepartment of Radiology and Surgery, Centre mkdicochirurgical de la Porte de Choisy, Paris, CDepartment of Surgery, H6pital Foch, Suresnes, dDepartment of Gastroenterology, H6pital du Haut Lev~que, Bordeaux-Pessac, CDepartment of Gastroenterology, H6pital de Cimiez, Nice and fDepartment of Gastroenterology, H6pital Saint-Antoine, Paris, France (Received 6 May 1991)

Piezoelectric lithotripsy with the EDAP LT-01 machine combined with adjuvant bile acid therapy results in complete clearance of radiolucent gallstones in selected patients. We assessed stone recurrence rate in 84 patients with complete clearance of stone fragments and followed up at least 12 months after cessation of bile acid therapy (mean 17 months, range 12-33). Fifty-four patients had a solitary stone and 30 multiple stones. Bile acid therapy was continued for 3 months after complete fragment stones clearance which was ascertained by two consecutive ultrasound examinations. Stone recurrence was assessed by ultrasonography at 6 and 12 months, and then at least once a year. Gallstone recurrence occurred in 5 patients (6%) between 9 and 12 months with no further recurrence up to 33 months. The rate of recurrence at one year was 3.7% in patients with a solitary stone and 10% in patients with multiple stones. Only one patient with stone recurrence had recurrent biliary pain. We concluded that early gallstone recurrence rate after successful lithotripsy seems to be low in patients with solitary stones.

Key words."Gallstone; Bile acid therapy; Shock-wave lithotripsy

Extracorporeal lithotripsy combined with bile acid therapy has recently been introduced as a treatment of gallstone disease. It is a safe and effective treatment in selected patients, especially in patients with solitary radiolucent stones up to 20mm in diameter (1-3). A drawback of this non-surgical treatment of gallstones is that with the gallbladder in place there is a risk of recurrence. Stone recurrence rate after successful bile acid therapy alone has been estimated at approximatively 10% per year over the first years (4,5). Extracorporeal lithotripsy is a recent therapy and whether the recurrence rate after successful lithotripsy is the same as in dissolution trials, has only been investigated in one preliminary study from Germany (6). Since the future role of extracorporeal lithotripsy in the treatment of gallstones will strongly depend on the stone recurrence rate, we report the early recurrence rate observed after

successful treatment of radiolucent gallstones with a combination of piezoelectric lithotripsy and bile acid therapy.

Patients and Methods

Eighty-four patients were followed for at least I year after complete clearance of gallstones and bile acid withdrawal. There were 57 females (68%) and 27 males. Age ranged from 8 to 88 years (mean: 55.7). All patients had been treated for symptomatic radiolucent gallstones. Fifty-four had solitary stones and 30 multiple stones (2-6). Patients had been treated in 5 medical centers with the same protocol (3). Extracorporeal lithotripsy was

Correspondence to: Gilles Pelletier, Service de gastroent6rologie, H6pital de Bit&re, 78 Rue du G+n6ral Leclerc, 94275 Le Krernlin-Bic~tre Cedex, France.

103

GALLSTONE RECURRENCE AFTER LITHOTRIPSY 20

performed using the piezoelectric lithotripter EDAP LT01. Adjuvant bile acid therapy (combination of chenodeoxycholic acid and ursodeoxycholic acid, 7-8 mg/kg/ day each) was continued 3 months after complete clearance of stones. Duration of bile acid therapy ranged from 3 to 29 months (mean: 9.6). The complete clearance of all fragments was ascertained by two consecutive ultrasound examinations. Follow-up investigations after stone clearance consisted of clinical and ultrasound examinations at 6 and 12 months, and thereafter at least once a year. Ultrasonography was performed earlier if biliary pain occurred. The way to treat recurrent gallstones was not defined in the protocol, due to the absence of agreement in the literature. The cumulative proportion of gallstone recurrence was calculated by the actuarial life-table method.

-- - D - -

- Multiple

stones

Solitary

stones

Q

."h

15

:

10%

/

O-

--

--0-

--

--0

/ /

.Q

5

/

/

3.7%

I

Follow-up Patients

at r i s k

30

54

(months) 15 26

7 Multiple 13 S o l i t a r y

Fig. 1. Probability of gallstone recurrence after successful extracorporeal lithotripsy (life table analysis).

(95% confidence limits 1-11%) at i and 2 years. At 1 year, only two recurrences were observed in the 54 patients with a solitary gallstone (3.7%) and 3 recurrences occurred in the 30 patients who had multiple stones (10%). Recurrent stones were multiple in 3 patients and their size ranged from 1 to 5mm. Only 1 patient (20%) complained of recurrent biliary pain. All other patients with recurrent gallstones were asymptomatic. The patient with symptoms was treated by cholecystectomy, and the 4 asymptomatic patients received a second

Results

Eighty-four patients were followed for at least 1 year, 41 for 18 months and 20 for 2 years after cessation of bile acid therapy. Follow-up ranged from 12 to 33 months (mean: 17 months). Five gallstone recurrences were observed between 9 and 12 months (6%) with no further recurrence (Table 1). The recurrence rate was estimated by actuarial life table analysis (Fig. 1). The estimated probability of gallstone recurrence was 6%

TABLE 1 Characteristics of patients with stone recurrence Patients

Age (years) Sex Previous stones Number Stone size (mm) Period until stone clearance after lithotripsy (months) Recurrent stones Detection of recurrent stones after cessation of bile acids (months) Number Size (mm) Symptoms Treatment after recurrence

I

2

3

4

5

55 F

57 M

68 F

65 F

52 F

1 15

I I1

4 5-6

3 3-18

2 6

29

6

4

9

I

9 1 3 0

12 4 2-3 0

12 N I-3 +

12 I 3 0

12 2 5 0

BA

BA

CH

BA

BA

N = numerous; BA = bile acid therapy; CH = cholecystectomy.

stones stones

104 course of bile acid therapy. Redissolution was achieved in Patient 2 after 6 months of treatment.

Discussion The enthusiasm regarding nonsurgical treatment of gallstone disease has been tempered by the risk of recurrence. There are many reports concerning the risk of recurrence after complete clearance following bile acid therapy alone and the first studies suggested that gallstone recurrence was almost inevitable once dissolution therapy was stopped (7,8). However, these studies should be treated with caution since the diagnosis of complete clearance of gallstones and the decision to stop dissolution therapy were based on oral cholecystography. It is now recognized that oral cholecystography can miss very small stones (9,10). When bile acids were discontinued, these small residual stones become large enough to be detected and were counted as recurrences. Ultrasonography is a more sensitive technique for diagnosing small stones (9,10) and to diagnose complete clearance of gallstones, 2 consecutive normal ultrasound examinations are now recommended (5). In our study, a first ultrasound examination showed apparent stone clearance in 4 patients, but a second ultrasound examination performed while patients were still under bile acid therapy showed that small fragments persisted. These patients were considered as having 'pseudorecurrences' and were not entered in this report. These 4 patients emphasize the risk of an overestimation of the stone recurrence rate if stone clearance is not ascertained by two consecutive ultrasound examinations and as a result more recently published studies on post-dissolution recurrence are probably more reliable. Studies show that the higher risk of recurrence occurs in patients whose stone dissolution is most recent. In patients with no recurrence at 2.5 or 5 years, there was no reappearance of stones by the end of the study (11-13). In two recent studies, the recurrence rate was approximatively 10% per year in the first years with a plateau at 40-50% by 4-5 years (11,13). Will the recurrence rate following successful combination of extracorporeal lithotripsy and bile acid therapy be the same? One could hypothesize that it would be higher. Indeed two factors could increase the recurrence rate: (1) the alteration of gallbladder motor function by shock-waves; (2) multiple residual fragments induced by lithotripsy which could act as nidus for stone formation. In fact, the Paumgartner group, using an electrohydrau-

G. PELLETIER et al. lic device, showed that shockwave therapy itself does not alter gallbladder motility (14) and that early recurrence was not higher than in post-dissolution trials (6). In our study the recurrence rate within 1 year using a piezoelectric generator, observed in patients with multiple stones, was approximately the same as has been reported in patients treated by bile acids alone (10%). On the other hand, the recurrence rate in patients with solitary stones seemed to be lower. Only two patients (3.7%) had recurrent stones within 12 months with no further recurrence up to 33 months. Some postdissolution studies had already suggested that patients with solitary gallstones had a lower recurrence rate than patients with multiple stones (12,15,16). If confirmed by further studies with longer follow-up, this low recurrence rate in patients with solitary gallstones is an important result for the future role of extracorporeal lithotripsy in the treatment of gallstones. Indeed the highest efficacy of this new technology is obtained in patients with solitary stones (1-3). If most of these patients can expect to stay free of recurrence, they would represent a good indication for extracorporeal lithotripsy. The only previous report on recurrence after successful extracorporeal lithotripsy is the Sackmann et al. study (6). They observed 58 patients for at least 1 year, after bile acids were discontinued (mean 18 months). They reported a probability of stone recurrence of 9 ___ 3% at 1 year and ! 1 -I- 4% at 1.5 years with no further increase up to 3 years. In this preliminary study the recurrence rate in patients with solitary stones also seems to be lower than in patients with multiple stones (respectively 4/53 and 2/5). Surprisingly, in the Sackmann et al. study, all patients with stone recurrence had recurrent biliary pain. In our study, most of our patients (80%) with recurrent stones were asymptomatic. In our study the low rate of symptoms in patients with stone recurrence is in accordance with previous post-dissolution trials (7,11). The management of patients whose gallstones recurred is still under discussion. Thistle suggested treatment only if patients are symptomatic (5). Our preliminary post-lithotripsy study shows that the early recurrence rate seems to be low, especially in patients with solitary stones. If our results are confirmed by further studies, they support the use of extracorporeal lithotripsy in selected patients with symptomatic gallstones. In this respect piezoelectric lithotripsy offers some advantages. It is especially well tolerated and can be performed in an outpatient basis. Larger series showed its safety and efficacy (3,17).

GALLSTONE RECURRENCE AFTER LITHOTRIPSY

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105 10 Shapero TF, Rosen IE, Wilson SR, Fisher MM. Discrepancy between ultrasound and oral cholecystography in the assessment of gallstone dissolution. Hepatology 1982; 2: 587-90. 11 Lanzini A, Jazrawi RP, Kupfer RM, et al. Gallstone recurrence after medical dissolution. An overestimated threat? J Hepatol 1986; 3: 241-6. 12 Dowling RH, Gleeson DC, Hood KA, Ruppin DC. British-Belgian gallstone study group: gallstone recurrence and postdissolution management. In: Paumgartner G, Stiehl A, Gerok W, eds. Bile Acids and the Liver. Lancaster, England: MTP Press, 1987; 355-67. 13 O'Donnell LDJ, Heaton KW. Recurrence and re-recurrence of gallstones after medical dissolution: a longterm follow-up. Gut 1988; 29: 655-58. 14 Spengler U, Sackmann M, Sauerbruch T, Holl J, Paumgartner G. Gallbladder motility before and after extracorporeal shock-wave lithotrypsy. Gastroenterology 1989; 96: 860-3. 15 Scholz DG, McCullough JE, Petersen BT, Thistle JL. Gallstone recurrence following complete dissolution with oral bile acid therapy or methyl tert-butyl ether. Hepatology 1988; 8:1372 (abstractl. 16 Villanova N, Bazzoli F, Taroni, F et al. Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study and evaluation of long term postdissolution treatment. Gastroenterology 1989; 97: 726-31. 17 Ell C, Kerzel W, Schneider HT, et al. Piezoelectric lithotripsy stone disintegration and follow-up results in patients with symptomatic gallbladder stones. Gastroenterology 1990; 99: 1439-44.