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ORIGINAL ARTICLE
Year : 2021  |  Volume : 26  |  Issue : 4  |  Page : 228-233
 

Asymptomatic cholelithiasis in children: Management dilemma


Department of Pediatric Surgery, Park Medical Research and Welfare Society, Kolkata, West Bengal, India

Date of Submission15-Apr-2020
Date of Decision26-Apr-2020
Date of Acceptance08-May-2020
Date of Web Publication12-Jul-2021

Correspondence Address:
Prof. Kuntal Bhaumik
Indira Kunj, 3rd Floor, 38/39, Bangur Avenue, Block – D, Kolkata - 700 055, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.JIAPS_107_20

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   Abstract 


Aims and Objectives: The incidence of cholelithiasis is now increasing in children. Besides hemolytic diseases, there are also nonhemolytic conditions and idiopathic group. A large number of children belong to asymptomatic group who do not present with gallstone-related symptoms. There is no consensus in the management of these children. The aim of this study is to evaluate the role of elective cholecystectomy in asymptomatic cases to prevent complications which leads to more morbidity.
Materials and Methods: One hundred and seventy-eight children were treated over a period of 12 years and they were divided into two groups according to their age at presentation. Sixty-four children below 5 years belonged to Group A and 114 children between 5 and 12 years belonged to Group B. About 71.8% of children of Group A and 49.1% of children of Group B were asymptomatic. Cholecystectomy was advised in all cases of Group B and all symptomatic cases of Group A. In Group A asymptomatic cases, ursodeoxycholic acid (UDCA) was given for 6–12 months and followed up.
Results: Laparoscopic cholecystectomy was performed in all cases except in five cases where conversion to open surgery was done as there was gross adhesions due to previous laparotomy. Of 46 asymptomatic cases of Group A, the stone disappeared in seven cases, 12 children developed symptoms, and there was no change in 27 patients. Stone reappeared again in three of seven children who were managed by cholecystectomy. Cholecystectomy was also performed in 12 cases that developed symptoms. In the rest of the 27 children, cholecystectomy was advised after 1 year trial of UDCA. Cholecystectomy was advised in both symptomatic and asymptomatic cases of Group B. Sixteen of 56 asymptomatic cases did not agree for cholecystectomy and 12 of them returned with complications. Endoscopic retrograde cholangio-pancreaticography (ERCP) and stone extraction was performed in four cases. In all the acute cases, cholecystectomy was performed after a period of conservative management.
Conclusion: UDCA can be tried in the smaller age group below 5 years, but there is a chance of recurrent stone formation. Elective laparoscopic cholecystectomy should be the choice in all asymptomatic cases to prevent complications.


Keywords: Asymptomatic cholelithiasis, cholelithiasis, laparoscopic cholecystectomy


How to cite this article:
Bhaumik K. Asymptomatic cholelithiasis in children: Management dilemma. J Indian Assoc Pediatr Surg 2021;26:228-33

How to cite this URL:
Bhaumik K. Asymptomatic cholelithiasis in children: Management dilemma. J Indian Assoc Pediatr Surg [serial online] 2021 [cited 2021 Jul 30];26:228-33. Available from: https://www.jiaps.com/text.asp?2021/26/4/228/321080





   Introduction Top


Cholecystitis and cholelithiasis in children are not uncommon nowadays. It is debatable whether the incidence is increasing or it is the result of increasing use of ultrasonography (USG) to find the cause of pain in the abdomen in children. The biliary tract cannot be ignored as a possible source of pain in the abdomen. Gallstones that do not cause gallstone-related symptoms and are diagnosed incidentally are asymptomatic gallstones. At that time, a dilemma starts whether to operate or not in these cases as there are no symptoms. On the one hand, Mayo advocates that innocent gallstones are a myth,[1] and on the other hand, long-term follow-up studies from the others have consistently shown that only a small minority of asymptomatic gallstones lead to development of symptoms or complications.[2] This study aims to evaluate the role of elective cholecystectomy in asymptomatic cholelithiasis to prevent complications which leads to more morbidity.


   Materials and Methods Top


One hundred and seventy-eight patients were treated over the period of the past 12 years (January 2008 to December 2019). There were 83 males and 95 females. The mean age at presentation was 6 years and 3 months (range: 6 months to 12 years). The diagnosis of cholelithiasis was based on the abdominal USG. The patients were divided into two groups according to the age at presentation. Those patients presented below 5 years belong to Group A (64 patients) and the patients who presented between 5 and 12 years belong to Group B (114 patients).

Group A (<5 years)

Eighteen patients were symptomatic and 46 patients were asymptomatic at presentation. Only two patients had hemolytic disease. Five patients received total parenteral nutrition (TPN) in infancy. Three patients had a history of septicemia. Three patients had short bowel due to intestinal resection earlier who also received TPN. Two patients had a history of umbilical catheterization. Total asymptomatic patients in Group A were 46 of 64 (71.87%). In the symptomatic group, eight children presented with typical right upper abdominal pain, nausea, and vomiting and three of them had fever also. Ten children presented with nonspecific pain in the abdomen [Table 1]. Cholecystectomy was performed in all symptomatic cases once the acute phase has subsided. In all asymptomatic cases, ursodeoxycholic acid (UDCA) was given from 6 months to 1 year and follow-up was done by USG every 3–6 months. UDCA was administered at a dose of 10 mg/kg/day.
Table 1: Clinical presentations

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Group B (5–12 years)

Fifty-eight patients are symptomatic and 56 patients are asymptomatic at presentation. Nine patients had thalassemia, two patients had hereditary spherocytosis, and one child had sickle cell disease. Six patients received TPN in infancy without any surgery. Seven patients had a history of septicemia and two patients were operated for intestinal atresia and three were operated for necrotizing enterocolitis in the neonatal period. These five children also received TPN in the postoperative period. Total asymptomatic cases in Group B were 56 of 114 (49.12%). In the symptomatic group, 28 children presented with typical right upper abdominal pain along with nausea and vomiting. Twelve children presented with acute pain in the abdomen due to acute cholecystitis with or without pancreatitis. All of them had fever, nausea, and vomiting along with deranged liver function test (LFT). Eighteen children had nonspecific pain in the abdomen [Table 1]. Cholecystectomy was performed in all the symptomatic cases once the acute phase was over. Operation was also advised in all asymptomatic cases.


   Results Top


All the patients underwent elective cholecystectomy once the acute phase had subsided. Laparoscopic cholecystectomy was performed in most of the cases except in four cases where conversion to open surgery was done as there were gross adhesions due to the previous laparotomy, and in three cases, combined cholecystectomy and splenectomy was performed as there was massive splenomegaly. No major complications were reported in all elective cholecystectomies.

Of 46 asymptomatic cases in Group A who were treated with UDCA, seven patients reported to be lumen-free gallbladder in the follow-up USG after 6 months to 1 year. Twelve patients developed symptoms in the follow-up. Nine patients presented with acute cholecystitis, two patients presented with acute pancreatitis, and one patient presented with obstructive jaundice due to choledocholithiasis. Hence, the stone disappeared in 7 of 46 patients (15.2%) in 1-year follow-up. These seven patients were followed up for a period of 1 to 6 years, and in three of them, the stone appeared again and cholecystectomy was performed. Twelve of 46 patients (26%) developed symptoms. In the rest of the 27 patients, as there was no change after 1-year trial of UDCA, cholecystectomy was advised. Parents of 22 patients readily agreed for cholecystectomy, but five patients lost in follow-up.

Sixteen of 56 asymptomatic cases in Group B did not agree for cholecystectomy at that moment, of which 12 patients came with complications and four patients lost in follow-up. Three patients came with acute pancreatitis. Six patients came with acute cholecystitis including two cases of empyema and three patients returned with obstructive jaundice due to choledocholithiasis.

In all the acute cases, cholecystectomy was performed after a period of conservative management. ERCP, sphincterotomy, and stone extraction were performed in four cases who presented with obstructive jaundice due to choledocholithiasis, and thereafter, cholecystectomy was performed. Two patients developed acute pancreatitis in the post-ERCP period. All the specimens sent for histopathological examination which revealed chronic cholecystitis in 146 cases, acute cholecystitis in 24 cases, and acute on chronic cholecystitis in 8 cases.


   Discussion Top


Increased incidence of cholelithiasis in children is due to the increasing use of USG to investigate the cause of pain in the abdomen and increasing use of TPN, frusemide, and phototherapy in infants[3] and also increased the incidence of obesity in children.[4] A population-based study estimated the prevalence of gallstones and biliary sludge in children at 1.9% and 1.46%, respectively.[5] The prevalence of gallstones among obese children and adolescents is 2%.[6] Studies have shown a bimodal distribution, with a small peak in infancy and a steadily increasing incidence from early adolescence.[5] In our study, 64 children (35.95%) presented below 5 years. Prior to puberty, the sex ratio is almost equal similar to our study.

Children may present with stone or sludge. Unlike adults, black pigment stones are common (48%). Other types of stones found are calcium carbonate stones (24%),[7] cholesterol stones (21%),[8],[9] brown pigment stones (3%), and protein dominant stones (3%). Black pigment stones are commonly found in hemolytic disorders and can also develop with parenteral nutrition. Microliths are gallstones <3 mm which may lead to biliary colic and pancreatitis and are difficult to diagnose by USG. Biliary sludge is made up of precipitates of cholesterol monohydrate crystals, calcium bilirubinate, calcium phosphate, and calcium salts of fatty acids which are embedded in biliary mucin to form sludge.[10] It is commonly associated with prolonged fasting, TPN, sickle cell disease, and the use of ceftriaxone. It may resolve spontaneously or may progress to the development of gallstone, and if persists, it may give rise to complications.[11] In this series, 14 children (7.9%) presented with biliary sludge and 174 children (92.1%) presented with definite stone. Three of our patients with biliary sludge resolved spontaneously and two patients presented with acute cholecystitis. In 12 children, there were cholesterol stones that are in the higher age group and in 166 children (93.25%), there were pigmented stones.

Contrary to earlier belief hemolytic disease is no longer a prerequisite for gallstone formation. There are also nonhemolytic conditions and idiopathic group.[5],[12] Almost 20%–30% is due to hemolytic diseases such as thalassemia, sickle cell disease, and hereditary spherocytosis. About 40%–50% is due to nonhemolytic conditions which include hepatobiliary disease, obesity,[13] prolonged TPN, abdominal surgery, trauma, ileal resection, Crohn's disease, and sepsis. Biliary pseudolithiasis or reversible cholelithiasis is found with the use of ceftriaxone.[14] Progressive familial intrahepatic cholestasis type 3 can predispose to gallstone. Defect in ABCB4 gene is seen in children with recurrent cholestasis and cholesterol gallstone.[15] Around 30%–40% cases are idiopathic.[12] In this series, 14 children (7.9%) had a hemolytic disease. There was a history of TPN in 19 children, of which eight had a history of previous abdominal surgery. Ten children had a history of septicemia and two had a history of umbilical catheterization. Eighteen children were obese at presentation. Hence, in this series, 49 children (27.5%) were in the nonhemolytic group and 115 children (64.6%) were in the idiopathic group [Table 2].
Table 2: Etiology of cholelithiasis

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Although approximately 80% of adults are asymptomatic, retrospective studies have found that 33%–40% of children are asymptomatic.[10],[16] Gallstones in infancy are usually asymptomatic but occasionally can present with pain, jaundice, and sepsis.[11] In a study by St-Vil et al., 11 of 13 cases were asymptomatic and detected by USG,[17] but in another series by Debray et al., 6 of 40 cases had isolated gallstones and asymptomatic and 34 had bile duct obstruction and symptomatic.[18] Children with gallstones may present with acute pain in the right upper quadrant of the abdomen along with nausea and vomiting which are the most common presentations[10] or may present with nonspecific abdominal pain. Older children usually localize the pain better, whereas younger children present with nonspecific symptoms.[5] In our study, only 18 children in Group A presented with symptoms, among which eight children presented with typical symptoms and 10 presented with nonspecific pain in the abdomen. Among the 58 older children (Group B), 28 presented with typical symptoms, 18 presented with nonspecific pain in the abdomen, and 12 presented with acute pain in the abdomen due to acute cholecystitis with or without pancreatitis. Hence, cholelithiasis should be kept in mind also in nonspecific abdominal pain.

Laparoscopic cholecystectomy is the gold standard in the treatment of symptomatic cholelithiasis. It is a very safe procedure and has a low rate of postoperative complication.[19],[20] However, there is no consensus about the management of asymptomatic gallstones. There are two options – either wait-and-watch policy with medical management by UDCA or routine cholecystectomy in all cases. The disadvantage of expectant treatment is that there may be development of complications which leads to more morbidity, whereas by routine cholecystectomy, we can avoid those complications.

UDCA decreases biliary cholesterol saturation by 40%–60% by inhibition of cholesterol absorption in the intestine and cholesterol secretion in the bile. UDCA decreases the toxicity of bile acids which can damage cell membranes and cause cholestasis. In one study, one hundred and seventeen patients were treated with UDCA; in eight children, the dissolution of gallstones was observed, but the cholelithiasis recurred in three of them.[21] Another study demonstrated resolution of clinical discomfort in 83.7% of patients who received UDCA for a median period of 13 months. However, complete disappearance is observed in only 7.2% and cholelithiasis recurred in 50% of these patients.[16] In another study by Gamba et al., 15 children with cholelithiasis were treated with UDCA for 1 year. Stones disappeared completely in only two cases but returned later in both.[22] In our series, UDCA was given to all 46 asymptomatic cases of Group A, but only in seven children (15.2%), the stone disappeared and again reappeared in three children. Hence, UDCA is ineffective in the dissolution of gallstones, but it had a positive effect on the symptoms.

There are some studies on asymptomatic gallstones, but most of these are related to adult population and from the Western countries. In a study of 123 cases over 15 years by Gracie and Ransohoff, at 5, 10, and 15 years of follow-up, 10%, 15%, and 18% became symptomatic.[23] According to the Italian group for epidemiology and prevention of cholelithiasis study,[24] the annual complication rate of initially asymptomatic patients was even less (0.3%–1.2%). In a study by Friedman and Raviola over a 20-year period, only 18% patients developed biliary pain.[25] According to the National Institute of Health Consensus Conference Report, 10% of patients developed symptoms during the first 5 years and 20% by 20 years.[26] Schmidt et al. showed no long-term risk of symptoms or adverse events.[27] Behari and Kapoor in a review article of asymptomatic in a 24 years controlled follow-up of patients with silent summarized all the studies from the West and concluded that progression from asymptomatic to symptomatic disease is relatively low, ranging from 10% to 25% over a period of 5–15 years.[2]

There are, unfortunately, very few studies on the natural history of asymptomatic gallstones in children. Bruch et al. followed 41 asymptomatic children for 21 months, of which 50% remained asymptomatic, 32% experienced a definite improvement in symptoms, and 18% had continued symptoms.[28] Wesdorp et al. followed up 82 children for a mean period of 4.6 years and also substantiated this observation.[5] In two different studies of cholelithiasis in infancy by St-Vil et al. and Debray et al., a spontaneous resolution was reported in 50% cases of cholelithiasis and 30% cases of choledocholithiasis. They advised cholecystectomy in symptomatic cholelithiasis and asymptomatic cholelithiasis persisting beyond 12 months and radio-opaque calculi.[17],[18] In a study of 18 cases of pediatric cholelithiasis, they suggested operation for all because of the expectancy of long life for children, expectant management may not be safe.[29] In a review article by Poddar where he reviewed 61 relevant articles with gallstone disease in children and concluded that asymptomatic gallstones or gallstones with atypical symptoms may be observed as the natural history is benign.[11] Although we have treated 24 acute cases, histological evidence of inflammation was present in all the operated cases. Other studies also reported structural alterations in the majority of cases.[21],[29] There are some risk factors where there is a high risk of progression from asymptomatic to symptomatic disease in children like the presence of three or more stones, presence of floating stones,[13],[30] calculi >2 cm in diameter and calculi <3 mm, and patent cystic duct and obesity.[2] Cumulative lifetime risk of developing gallbladder carcinoma is also higher as gall stone (GS)appears at a very early age in children and this is an indication of prophylactic cholecystectomy in asymptomatic cholelithiasis in children.[31]

In our series, total asymptomatic cases are 102 of 178 (57.3%), more number of asymptomatic cases are seen in the younger age group (Group A). UDCA is not very effective in these cases. Twelve children developed complications in the follow-up in Group A including one case of choledocholithiasis and two cases of acute pancreatitis. In Group B also, 12 of 16 cases who did not agree for cholecystectomy presented with complications. Pediatric ERCP is a very challenging procedure due to the small caliber of the bile duct in children and it had to be performed in four cases when we continued medical management or parents did not agree for operation. Acute pancreatitis is also a serious complication which we encountered in five cases. Post-ERCP acute pancreatitis was also managed in two cases. Hence, we could avoid these complications by doing routine cholecystectomy in all these cases. By definition, a procedure is considered appropriate if the health benefits exceed its health risks by a sufficiently wide margin, thus making the procedure worth performing.[32]


   Conclusion Top


Taking into consideration of the fact that there may be complications such as acute cholecystitis, cholangitis, acute pancreatitis, and obstructive jaundice due to choledocholithiasis, laparoscopic cholecystectomy presumed to be the choice in asymptomatic cholelithiasis >5 years. As the onset of gallstone is at a younger age, there is an increased lifetime risk of developing complications. UDCA can be tried in the smaller age group <5 years but should not be used for >1 year and should be followed up even after dissolution, as there is a chance of recurrent stone formation. Surgeons should discuss with the parents regarding the choice of treatment and the risks involved in expectant treatment and take decision.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Mayo WJ. Innocent gallstones – A myth. JAMA 1911;54:1021-4.  Back to cited text no. 1
    
2.
Behari A, Kapoor VK. Asymptomatic Gallstones (AsGS) - To Treat or Not to? Indian J Surg 2012;74:4-12.  Back to cited text no. 2
    
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Mehta S, Lopez ME, Chumpitazi BP, Mazziotti MV, Brandt ML, Fishman DS. Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease. Pediatrics 2012;129:e82-8.  Back to cited text no. 4
    
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Wesdorp I, Bosman D, de Graaff A, Aronson D, van der Blij F, Taminiau J. Clinical presentations and predisposing factors of cholelithiasis and sludge in children. J Pediatr Gastroenterol Nutr 2000;31:411-7.  Back to cited text no. 5
    
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Kaechele V, Wabitsch M, Thiere D, Kessler AL, Haenle MM, Mayer H, et al. Prevalence of gallbladder stone disease in obese children and adolescents: Influence of the degree of obesity, sex and pubertal development. J Pediatr Gastroenterol Nutr 2008;42:66-70.  Back to cited text no. 6
    
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Stringer MD, Soloway RD, Taylor DR, Riyad K, Toogood G. Calcium carbonate gall stones in children. J. Pediatr Surg 2007;42:1677-82.  Back to cited text no. 7
    
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Stringer MD, Taylor DR, Soloway RD. Gallstone composition: Are children different? J Pediatr 2003;142:435-40.  Back to cited text no. 8
    
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Koivusalo A, Pakarinen M, Gylling H, Nissinen MJ. Relation of cholesterol metabolism to pediatric gallstone disease: A retrospective controlled study. BMC Gastroenterol 2015;15:74.  Back to cited text no. 9
    
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Svensson J, Makin E. Gallstone disease in children. Semin Pediatr Surg 2012;21:255-65.  Back to cited text no. 10
    
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Poddar U. Gall stone disease in children. Indian Pediatr 2010;47:945-53.  Back to cited text no. 11
    
12.
Schweizer P, Lenz MP, Kirschner HJ. Pathogenesis and symptomatology of cholelithiasis in childhood. A prospective study. Dig Surg 2000;17:459-67.  Back to cited text no. 12
    
13.
Bonfrate L, Wang DQ, Garruti G, Portincasa P. Obesity and the risk and prognosis of gallstone disease and pancreatitis. Best Pract Res Clin Gastroenterol 2014;28:623-35.  Back to cited text no. 13
    
14.
Prince JS, Senac MO Jr. Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis in a child. Pediatr Radiol 2003;33:648-51.  Back to cited text no. 14
    
15.
Nakken KE, Labori KJ, Rødningen OK, Nakken S, Berge KE, Eiklid K, et al. ABCB4 sequence variations in young adults with cholesterol gallstone disease. Liver Int 2009;29:743-7.  Back to cited text no. 15
    
16.
Kennedy M. Pediatric Gallstones (Cholelithiasis). November, 2015. Available from: http://emedicine.medscape.com. [Last accessed on 2020 Mar 20].  Back to cited text no. 16
    
17.
St-Vil D, Yazbeck S, Luks FI, Hancock BJ, Filiatrault D, Youssef S. Cholelithiasis in newborns and infants. J Pediatr Surg 1992;27:1305-7.  Back to cited text no. 17
    
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Debray D, Pariente D, Gauthier F, Myara A, Bernard O. Cholelithiasis in infancy: A study of 40 cases. J Pediatr 1993;122:385-91.  Back to cited text no. 18
    
19.
Bonnard A, Seguier-Lipszyc E, Liguory C, Benkerrou M, Garel C, Malbezin S, et al. Laparoscopic approach as primary treatment of common bile duct stones in children. J Pediatr Surg 2005;40:1459-63.  Back to cited text no. 19
    
20.
Siddiqui S, Newbrough S, Alterman D, Anderson A, Kennedy A Jr. Efficacy of laparoscopic cholecystectomy in the pediatric population. J Pediatr Surg 2008;43:109-13.  Back to cited text no. 20
    
21.
Della Corte C, Falchetti D, Nebbia G, Calacoci M, Pastore M, Francavilla R, et al. Management of cholelithiasis in Italian children: A national multicenter study. World J Gastroenterol 2008;14:1383-8.  Back to cited text no. 21
    
22.
Gamba PG, Zancan L, Muraca M, Vilei M T, Talenti E, Midrio P, et al. Is there a place for medical treatment in children with gallstones? J Pediatr Surg 1997;32:476-8.  Back to cited text no. 22
    
23.
Gracie WA, Ransohoff DF. The natural history of silent gall stones: The innocent gallstone is not a myth. N Engl J Med 1982;307:798-800.  Back to cited text no. 23
    
24.
Attili AF, De Santis A, Capri R, Repice AM, Maselli S. The natural history of gallstones: The GREPCO experience. The GREPCO Group. Hepatology 1995;21:655-60.  Back to cited text no. 24
    
25.
Friedman GD, Raviola CA, Fireman B. Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization. J Clin Epidemiol 1989;42:127-36.  Back to cited text no. 25
    
26.
NIH Consensus development panel on gall stones and laparoscopic cholecystectomy. JAMA 1993;269:1018-24.  Back to cited text no. 26
    
27.
Schmidt M, Hausken T, Glambek I, Schleer C, Eide GE, Søndenaa K. A 24-year controlled follow-up of patients with silent gallstones showed no long-term risk of symptoms or adverse events leading to cholecystectomy. Scand J Gastroenterol 2011;46:949-54.  Back to cited text no. 27
    
28.
Bruch SW, Ein SH, Rocchi C, Kim PC. The management of nonpigmented gallstones in children. J Pediatr Surg 2000;35:729-32.  Back to cited text no. 28
    
29.
Deepak J, Agarwal P, Bagdi RK, Subramanian B, Kumar M, Ramasundaram M, et al. Laparoscopic cholecystectomy for cholelithiasis in children. J Indian Assoc Pediatr Surg 2009;14: 204-6.  Back to cited text no. 29
    
30.
Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T. The natural history of cholelithiasis: The National Cooperative Gallstone Study. Ann Intern Med 1984;101:171-5.  Back to cited text no. 30
    
31.
Kapoor VK. Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer–the case against. Indian J Gastroenterol 2006;25:152-4.  Back to cited text no. 31
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32.
Quintana JM, Aróstegui I, Cabriada J, López de Tejada I, Perdigo L. Predictors of improvement in health-related quality of life in patients undergoing cholecystectomy. Br J Surg 2003;90:1549-55.  Back to cited text no. 32
    



 
 
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