Original Article The effect of extracorporeal shock wave lithotripsy in the management of idiopathic gallstones in children Seyed Abdollah Mousavi, Hasan Karami1, Ayub Barzegarnejad2 Departments of Pediatric Surgery, 1Pediatric Gastroenterology, and 2Urology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Address for correspondence: Dr. Seyed Abdollah Mousavi, Department of Pediatric Surgery, Booali Sina Hospital, Pasdaran Boulevard, Sari, Mazandaran Province, Iran. E-mail: [email protected]

ABSTRACT

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Objective: The most common etiology for gallstones in children is hemolytic diseases; however, the prevalence of nonhemolytic gallstones, which are mostly idiopathic, is increasing. Several studies concerning the treatment of gallstones with respect to the influence of extracorporeal shock wave lithotripsy (ESWL) have been conducted in adults, but not to the same extent in children. Therefore, this study attempted to examine the effects of lithotripsy on idiopathic gallstones in children. Materials and Methods: In this study, 12 children, all of whom were under 12 years of age and diagnosed with idiopathic gallstones, were treated with ESWL. The average age of the children examined in this study was 6.5 years (range 3-11 years). Patients were treated with 2500-3000 shockwaves per session. The number of shockwaves was 90 shocks/min and the impulse intensity ranged from 10 to 12 kV. The final goal was the fragmentation of stones in pieces with less than 3 mm in dimension. Patients were followed up for 6-30 months. Results: A total of 12 patients were treated with ESWL for 14 rounds. In three patients, complete fragmentation occurred within the first trial and was cleared. The nine remaining patients underwent ESWL 10 times in which an acceptable change in the gallstone’s condition was not observed. Five of the patients underwent surgery. The chemical composition of the gallstones showed that the dominant element in them was calcium. Conclusions: Our findings show that performing ESWL can be effective in some children. Further studies with larger population are recommended. Furthermore, it seems increasing the voltage intensity and frequency as conducted in adults accompanied with biliary acids prescription can be effective in children.

Website: www.jiaps.com DOI: 10.4103/0971-9261.142010 Quick Response Code:

KEY WORDS: Children, extracorporeal shock wave lithotripsy, gallstone

INTRODUCTION Gallstones in children are less prevalent than in adults, however, in recent decades, the reported number of cases of gallstones in children is gaining increased prevalence.[1] The most common etiology for gallstone in children is hemolytic diseases, whereby in cycle cell anemia, its rampancy reaches to 55%.[2] Several

studies have been conducted concerning the treatment of gallstones. In adults one of the popular treatments was using extracorporeal shock wave lithotripsy (ESWL) due to its relative effect on stones and the progress of laparoscopic surgery. This technique has, however, lost its significance with the exception of particularly rare cases. Due to the hemolytic and pigmented nature of gallstones in children, which resulted in consequent

Cite this article as: Mousavi SA, Karami H, Barzegarnejad A. The effect of extracorporeal shock wave lithotripsy in the management of idiopathic gallstones in children. J Indian Assoc Pediatr Surg 2014;19:218-21. Source of Support: This work was supported by Mazandaran University of Medical Sciences, Conflict of Interest: None declared.

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Mousavi, et al.: Shock wave lithotripsy in children gallstones

relapse, ESWL was not a recommended technique in children. In contrast, idiopathic gallstones are much less common in children and precise statistics concerning them are not available. Due to the incidental findings of idiopathic gallstones in children, finding a group for this study has always remained difficult. As a consequence of this difficulty, there are more articles on ESWL in adults than in children. English journals have only reported two cases where ESWL was used on an 18-month-old baby and a 12-year-old girl.[3,4] Therefore a study regarding the effect of lithiotripsy on children with idiopathic gallstones was made to shed further light on this issue.

MATERIALS AND METHODS Patients under study were aged less than 12 years, who expressed nonspecific abdominal pain, and were referred to a gastroenterologist from March 2010 till September 2012. These patients were found to have gallstones after ultrasonography examinations but did not convey any gastrointestinal symptoms relating to inflammation of gallbladder. To identify the gallstone being idiopathic biochemical blood examinations including hemoglobin, reticulocyte, electrophoresis, aspartate aminotransferase (AST), alanine aminotransferase(ALT), glucose 6 phosphate dehydrogenase (G6PD), seruloplasmin, and direct coombs were measured. Sweat test and stool examinations (for parasite) were also taken. Results with negative readings had gallstones labeled as idiopathic. Identifying the gallstone number and its size was done by one expert ultrasonographist and one instrument in all patients. All idiopathic gallstones with diameters 3 mm or larger were added to this study. Plain abdomen radiography was taken from all the patients to identify the level of calcification. Prior to ESWL, medical history, and physical examinations were taken. In the blood examination, coagulation tests and liver function tests were normal. The exclusion criteria involved hemolytic anemia, history of septicemia or long time treatment with furosemide, hyper alimentation, ileal resection, and cystic fibrosis disease. Also, patients with liver diseases were excluded from this study. Thus 12 patients entered our study (3 boys and 9 girls). The average age was 6.5 years (range 3-11 years). The average diameter of the gallstone was 6 mm (range 2-11 mm) and nearly 66% of the patients had more than one gallstone [Table 1]. ESWL was conducted after explaining the benefits and possible consequences and with the written consent form of either parent. The patients were completely conscious and no sedatives were injected. The instrument being used was of the Triple Focus PIEZOLITH 3000, Germany. The patient was placed in

Table 1: Patients and stone characteristics Characteristic Patients Female/male (n) Age (years) mean Range Weight (kg) mean Range Stones number Solitary 2 3 >3 Diameter range, mm

Total 12 9/3 6.8 3-11 20.2 13.5-34 4 3 3 2 2-11

the left lateral position. For optimal contact between the lithotripter head and the surface of the body, ultrasound gel was used. The number of shockwaves per session differed from 2500 to 3000 and each time took 25 to 30 min. Its speed was 90 shocks/min and intensity of impulse varied from 10 to 12 kV. Our final goal was to crumble the gallstone to pieces to less than 3 mm in size so that according to the diameter of cystic duct, it could exit the gallbladder. If no stones or residual fragments were found after fragmentation, the patient was moved into the right, lateral, and supine positions to shift any hidden concretions so that they could be localized. Ultrasonography was repeated after ESWL if it was deemed necessary and with the patient’s consent, 2 weeks after ESWL was conducted. The patients were followed up for 6-30 months.

RESULTS In total, 12 patients were treated in 14 sessions of ESWL. The patient’s cooperation during the therapy was relatively good and there was no need for sedation. The number of shockwaves differed from 2500 to 3000 in each session (average: 2760). In three patients, a complete fragmentation was accomplished in the first attempt and was cleared. The number and size of gallstones in this group was in order from 1 to 3 mm (average: 2.25 mm) and from 3 to 10 mm (average: 5.7 mm). The average number of shockwaves in this group was 3100. Except in patient number 2 who had mild colic pain and diarrhea after ESWL that continued for one week, the remaining patients with 6-18 months follow up were fine. The remaining nine patients were treated with ESWL 11 times in total in which the average hits were 3283 for each person. With control ultrasonography, an acceptable change in the gallstone size was not observed. With the exception of two patients, the rest did not accept a repeated ESWL. Due to nonspecific abdominal pain, five of them were treated with laparoscopic cholecystectomy and the pain reduced considerably after the surgery [Table 2]. Number, diameter, color, and chemical composition of

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Mousavi, et al.: Shock wave lithotripsy in children gallstones Table 2: Details of ESWL and stones in 12 patients with gallstone Age (years)

Sex

6 11 3 6 7 11 4 9 5 6 6 5

M F F F M M F F F F F F

Weight (kg)

Number of stones and size (mm)

Sessions of ESWL

Shock waves (n)

US after ESWL N (size mm)

21 30 13.5 14.5 22 34 15 17 14 22 20 17

1 (10) 2 (6, 6) 3 (4, 5, 8) Multi (2-3) Multi (3-9) 2 (3, 11) 1 (10) 1 (9) 3 (6, 7, 8) 2 (3, 3) 3 (3, 5, 5) 1(10)

1 1 1 1 2 1 1 2 1 1 1 1

2700 3000 2700 2700 3000 3000 2500 3000 2500 3000 2500 3000

Clear Clear Clear Same Same Same Multiple 4 (2-5)* 3 (5, 6, 7)* 1 (6)* Same* 1 (7mm)*

Associated disease

PCK and nephrocalcinosis Bilateral VUR

Renal stones Hydrocephaly and shunt

*Operation, PCK: Poly cystic kidney, VUR: Vesicouretral reflux, US: Ultrasonography

gallstones were determined. Gallstones were analyzed for the determination of cholesterol (CHOD-PAP), bilirubin (DCA), calcium (arsenazo), and phosphorous (phosphometric UV) concentrations. Measurements were performed by commercial kits (Pars Azmoon, Tehran, Iran) using a biochemical analyzer (Biotecnica, Roma, Italy) in accordance with the instructions by the manufacturers. Oxalate was determined (enzymatic method) with a commercial kit (Darman Kav, Tehran, Iran) using a spectrophotometer (Clima, Madrid, Spain). The chemical composition of only the stones that were removed surgically is shown in [Table 3] and the dominant element is calcium. Two of these patients had radiopaque kidney stones and one of them was resistant to ESWL. The second patient had a poly-cystic kidney, along with height and weight growth retardation. All the patients were under observation for 6-30 months, except for case numbers 4-7, the remaining patients were without stone.

DISCUSSION The first article regarding the role of lithotripsy in treating gallstones was published in 1988 by Heberer et al., who conducted ESWL on 250 patients.[5] They claimed that 80% of the patients were free of stone for one year and 10% reported relapse. It was from then that the role of ESWL in treatment of gallstone was distinguished in an exaggerated manner and several articles were published in this context. Four years later, Stoller et al. suggested that ESWL should be performed on patients with the following conditions: the number of gallstones should not be more than three, their size should be 0.5-3 cm, contraction of gallbladder must be at least 20% after a fatty meal, and calcification should be minimal. Therefore only 10-15% of the patients became candidates.[6] With the salient progresses of laparoscopic surgeries, the role of ESWL gradually became more limited. In 2004, after 10 years of study, Adamek et al. reached the conclusion that using ESWL in selected cases, such as in patients 220

Table 3: Composition of stones in operated patients Patient’s Color number

Composition (%)

8

Black

9

‘’

10 11

‘’ ‘’

12

Brown

Ca (60), Ammonia (1), Oxalate (30), Phosphate (5) Ca (70), Ammonia (1), Oxalate (20), Phosphate (5) Ca (70), Ammonia (2), Phosphate (20), mg (2) Ca (74), Ammonia (3), Oxalate (15), Phosphate (2) Ca (7), Cholesterol (60), Bill (30), Phosphate (3)

whose surgery is dangerous, this could be a suitable choice. Because the pursuit showed that 59.9% of the patients were free of any stone, the prevalence of cholecystectomy decreased by 19.5%.[7] Following this by studying 304 patients with choledochal stones larger than 1.5 cm, which could not exit using endoscopic methods, Chang et al. performed ESWL and concluded that with this measure, in 90% of the patients, the gallstone would exit.[8] Therefore the role of ESWL as gallstone tended to choledochal stone and then stone of pancreatic duct.[9] As we know the cause and kind of gallstone in children is different from adults, the cause for gallstone in adults and of the cholesterol kind are mostly unknown. However, in children, hemolytic diseases are most common and prominent in ages under 10 years, and are composed of calcium carbonate with black pigment. Also from non hemolytic causes, one may additionally mention dehydration, septicemia, long treatment with furosemide, cystic fibrosis, and ileal resection. However, in some reports it is mentioned that with take care of stone due hyper alimentation hyper alimentation, recovery happens naturally but unfortunately the consequences cannot be easily predicted.[1] All studies on cholesterol stones have been done on adults. In children we can only refer to two reports. One is an 18-month-old baby with radiopaque choledochal stone and the other a 12-year-old girl with radiolucent gallstone who was treated with oral bile acids and ESWL.[3,4]

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Mousavi, et al.: Shock wave lithotripsy in children gallstones

Because the size of gallstone in children is small, diagnosing opaque or non opaque stone with a simple radiography is not reliable. But in the patients who underwent surgery, it is shown that the dominant element was calcium, however, only one case was opaque. Likewise in our study, a meaningful relation was not found between the gallstone being or not being opaque and the effect of ESWL. In other studies and in greater populations of adults, the amount of success of ESWL in opaque was less than lucent stones.[10,11] Emptying, as well as residual and fasting volume of the gallbladder influence the outcome of ESWL. But it is difficult to determine on children. The other problem encountered in performing ESWL of gallbladder is mobility and floating of stones in bill and motion of liver during respiration. The measure of success rate in this method of treatment in similar articles (adults) is quite different and depends on the kind of gallstone, number, place, times, and impulse intensity using bilious acids and the time of follow up, changes. However, the success rate was stated as 72-90%, but relapse is reported from 10% to 50%.[5,11] Also in a 34-month follow up, 36% of the patients eventually had operations due to presenting symptoms.[7] Additionally in our study, 25% success was attained with one session of ESWL and without bile acids therapy, however, our follow up was short (6-30 months). Because of having little specimen, the relation between the size and number of gallstone with recovery scale could not be examined. However, in an experimental study, Arends et al. found that to crumble gallstone, the size is more important than the number.[12] A number of rare and serious complications have been reported following ESWL. These occur infrequently and appear to be limited in number. Accurate targeting achieved by the third-generation lithotripter is responsible for reducing collateral tissue damage and minimizing complications.[8] The significant point in our study is the easy tolerance of the child during ESWL and that there was no need for sedation. The amount of side effect was 10% in which a 6-year-old boy, with a 1 cm gallstone, was cleaned after one session of ESWL but 6 h later acquired biliary colic and the day after, diarrhea. The symptoms were mild and completely treated with dicyclomine syrup for one week. In the Meiser’s study, the complication rates was 31% and generally were biliary colic.[13] In most studies, the number of shockwaves per session was 500 reaching a voltage of 16 kV. But in our study because of little experience concerning children, the frequency was at the maximum 3000 per session and reached a maximum of 12 kV. In total, it can be concluded that ESWL can be effective in some children. It seems, if we could increase the voltage intensity, frequency, and also increase the number of sessions like in adults in a larger population

and or accompany ESWL with prescription of bile acids in respect to the difference of idiopathic gallstones in children, we can reach interesting conclusions.

ACKNOWLEDGMENTS The authors would like to thank Manoochehr Biglari and Abbas Aramideh for their cooperation in writing this text.

Footnotes Implication for health policy/practice/research/medical education In respect of ESWL influence, several studies concerning the treatment of gallstones have been conducted in adults but much less in children. Therefore, the present study aims to investigate the influence of ESWL in children with gallstone who were aged below 12 years. It may open a new window to treatment of idiopathic gallstones in children.

REFERENCES 1. Holcomb GW, Andrews WS. Gallbladder disease and hepatic infection. Pediatric Surgery. 6th ed. Philadelphia: Mosby; 2006. p. 1635-40. 2. Yamataka A, Kato Y, Miyano T. Billiary tract disorders and portal hypertension. Ashcraft Pediatric Surgery. 5th ed. Philadelphia: Saunders; 2010. p. 574-5. 3. Sokal EM, De Bilderling G, Clapuyt P, Opsomer RJ, Buts JP. Extracorporeal shock-wave lithotripsy for calcified lower choledocholithiasis in an 18-month-old boy. J Pediatr Gastroenterol Nutr 1994;18:391-4. 4. Ziegenhagen DJ, Wedel S, Kruis W, Zehnter E. Successful extracorporeal lithotripsy of gallbladder stones in a 12 year-old girl. Padiatr Padol 1993;28:55-6. 5. Heberer G, Paumgartner G, Sauerbruch T, Sackmann M, Krämling HJ, Delius M. et al. A retrospective analysis of 3 year’s experience of an interdisciplinary approach to gallstone disease including shock-waves. Ann Surg. 1988 Sep;208:274-8. 6. Stoller J. Treating Gallstones without Surgery, A review of alternative therapies. Can Fam Physician 1992;38:549-52. 7. Adamek HE, Rochlitz C, Von Bubnoff AC, Schilling D, Riemann JF. Predictions and associations of cholecystectomy in patients with cholecystolithiasis treated with extracorporeal shock wave lithotripsy. Dig Dis Sci 2004;49:1938-42. 8. Chang WH, Chu CH, Wang TE, Chen MJ, Lin CC. Outcome of simple use of mechanical lithotripsy of difficult common bile duct stone. World J Gastroenterol 2005;11:593-9. 9. Tandan M, Reddy DN. Extracorporeal shock wave lithotripsy for pancreatic and large common bile duct stones. World J Gastroenterol 2011;17:4365-71. 10. Soehendra N, Nam VC, Binmoeller KF, Koch H, Bohnacker S, Schreiber HW. Pulverisation of calcified and non-calcified gall bladder stones: Extracorporeal shock wave lithotripsy used alone. Gut 1994;35:417-22. 11. Mulagha E, Fromm H. Extracorporeal shock wave lithotripsy of gallstones revisited: Current status and future promises. J Gastroenterol Hepatol 2000;15:239-43. 12. Arends TW, Nemcek AA, Rege RV, Nahrwold DL. The effect of volume and number on fragmentation of gallstones by lithotripsy. J Surg Res 1990;48:279-83. 13. Meiser G, Heinerman M, Lexer G, Boeckl O. Aggressive extracorporeal shock wave lithotripsy of gall bladder stones within wider treatment criteria: Fragmentation rate and early results. Gut 1992;33:277-81.

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The effect of extracorporeal shock wave lithotripsy in the management of idiopathic gallstones in children.

The most common etiology for gallstones in children is hemolytic diseases; however, the prevalence of nonhemolytic gallstones, which are mostly idiopa...
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