Pediatric gallstones

definition ,etiology ,types ,Choledocholithiasis وBlack Pigment Gallstones وpresentation و,diagnosis ,differential diagnosis, management ,prognosis ,

1. Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah ,UAE [email protected] Pediatric Gallstones (Cholelithiasis)

2. Cholelithiasis Involves the presence of gallstones which are concretions that form in the biliary tract, usually in the gallbladder . 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 2

3. Choledocholithiasis Refers to the presence of 1 or more gallstones in the common bile duct (CBD). 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 3

4. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 4 Types of gallstones Children may present with: Black pigment Cholesterol Calcium carbonate Protein-dominant Brown pigment stones . Typically, only one type of stone forms at any given time.

5. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 5 Black Pigment Gallstones http://www.gallstones-treatments.com/black-pigment-gallstones-symptonscauses-treatment/

6. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 6 Make up 48% of gallstones in children. F ormed when bile becomes supersaturated with calcium bilirubinate, Commonly formed in hemolytic disorders Can develop with parenteral nutrition . Black Pigment Gallstones (Cont.)

7. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 7 Cholesterol gallstones Healthline

8. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 8 Brown pigment gallstones Google Sites

9. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 9 Calcium carbonate gallstones Rare in adults More common in children, accounting for 24% of gallstones in children

10. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof. Dr. Saad S Al Ani 10 Remember Pain in the right upper quadrant (RUQ) of the abdomen is common .

11. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof. Dr. Saad S Al Ani 11 Remember (Cont.) A Murphy sign (expiratory arrest with palpation in the RUQ) is thought to be pathognomonic.

12. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 12 Remember (Cont.) Ultrasonography of the RUQ is the study of choice in patients with uncomplicated cholelithiasis.

13. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 13 The distribution of gallstone types in children differs from the adult population, black pigment stones being the most common type in children. Remember (Cont.) Cholesterol stones being the most common type of stone in adults

14. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 14 Gallstone formation

15. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 15 Black pigment stones M ake up 48% of gallstones in children . Are the calcium salt of unconjugated bilirubin . ( when bile becomes supersaturated with calcium bilirubinate) C ommonly formed in hemolytic disorders A lso develop with parenteral nutrition.

16. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 16 Calcium carbonate stones Are rare in adults Are more common in children, accounting for 24% of gallstones in children.   Stringer MD, Soloway RD, Taylor DR, Riyad K, Toogood G. Calcium carbonate gallstones in children.  J Pediatr Surg . 2007 Oct. 42(10): 1677-82

17. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 17 Cholesterol stones Formed from cholesterol supersaturation of bile A re composed of 70-100% cholesterol (with an admixture of protein, bilirubin, and carbonate .) Account for most gallstones in adults M ake about 21% of stones in children Stringer MD, Taylor DR, Soloway RD. Gallstone composition: are children different?.  J Pediatr . 2003 Apr. 142(4):435-40 Koivusalo A, Pakarinen M, Gylling H, Nissinen MJ. Relation of cholesterol metabolism to pediatric gallstone disease: a retrospective controlled study.  BMC Gastroenterol . 2015 Jun 30. 15:74. 

18. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 18 Brown pigment stones Accounting for only 3% of gallstones in children F orm in the presence of biliary stasis and bacterial infection. C omposed of calcium bilirubinate and the calcium salts of fatty acids Occur more often in the bile ducts than in the gallbladder

19. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 19 Protein-dominant stones The remaining portion of gallstones in children consists of protein-dominant stones Make up about 5% of gallstones in these patients.

20. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 20 Microliths Are gallstones smaller than 3 mm Can form within the intrahepatic and extrahepatic biliary tree M ay lead to biliary colic, cholecystitis, and pancreatitis C an persist after cholecystectomy

21. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 21 Biliary sludge I s made up of precipitates of: c holesterol monohydrate crystals c alcium bilirubinate c alcium phosphate c alcium carbonate c alcium salts of fatty acids A re embedded in biliary mucin

22. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 22 Pathophysiology

23. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 23 Pathophysiology Cholelithiasis primarily affects the gallbladder May cause irritation of the gallbladder mucosa, resulting in: Chronic calculous cholecystitis Symptoms of biliary colic.

24. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 24 Pathophysiology (Cont.) If a gallstone obstructs the cystic duct: Acute cholecystitis  distension of the gallbladder wall Necrosis and spillage of bile

25. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 25 Pathophysiology (Cont.) If gallstones migrate from the gallbladder into the cystic duct and main biliary ductal system, further complications can occur, such as: Choledocholithiasis biliary obstruction with or without cholangitis Gallstone pancreatitis  

26. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 26 Etiology

27. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 27 Common predisposing factors 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 Aug. 28 (4):623-35 Hemolytic disease Trauma Hepatobiliary disease Ileal resection Obesity Crohn disease Prolonged parenteral nutrition Sepsis Abdominal surgery Pregnancy

28. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 28 Less prominent risk factors Acute renal failure Prolonged fasting Low-calorie diets Rapid weight loss Use of certain medications, primarily ceftriaxone  Biliary pseudolithiasis, or reversible cholelithiasis Prince JS, Senac MO Jr. Ceftriaxone-associated nephrolithiasis and biliary pseudolithiasis in a child.  Pediatr Radiol . 2003 Sep. 33(9):648-51

29. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 29 Genetic conditions P rogressive familial intrahepatic cholestasis type 3  gallstone formation. Defects in the in the  ABCB4  gene  recurrent cholestasis and cholesterol gallstones Nakken KE, Labori KJ, Rodningen OK, et al. ABCB4 sequence variations in young adults with cholesterol gallstone disease.  Liver Int . 2009 May. 29(5):743-7

30. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 30 Epidemiology The prevalence of gallstones and biliary sludge in children at 1.9% and 1.46%, respectively(*) The morbidity and mortality associated with gallstones are more commonly associated with cholecystitis or ascending cholangitis . * Wesdorp I, Bosman D, de Graaff A, Aronson D, van der Blij F, Taminiau J. Clinical presentations and predisposing f after puberty, the frequency of cholelithiasis is significantly greater in females than in males and is comparable to the adult ratio of 4:1 female predominance. actors of cholelithiasis and sludge in children.  J Pediatr Gastroenterol Nutr . 2000 Oct. 31(4):411-7.

31. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 31 Epidemiology No racial predilection Higher risk for developing gallstones, in the Pima Indians of North America and Scandinavians

32. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 32 Epidemiology (Cont.) Prior to puberty, the sex ratio of gallstones in children appears to be equal . After puberty, the frequency of gallstones is significantly greater in females than in males

33. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 33 Epidemiology (Cont.) Approximately 20-40% of all pediatric gallstone disease can be attributable to hemolytic disease.   (1) 1..Currò G, Meo A, Ippolito D, Pusiol A, Cucinotta E. Asymptomatic cholelithiasis in children with sickle cell disease: early or delayed cholecystectomy?.  Ann Surg . 2007 Jan. 245(1):126-9

34. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 34 Epidemiology (Cont.) Concerning sickle cell disease: The frequency of cholelithiasis in is almost double that of the general population.   [1] Pigmented gallstones occur in~ 50 % by age 22 years. 1.Alonso MH. Gall bladder abnormalities in children with sickle cell disease: management with laparoscopic cholecystectomy.  J Pediatr . 2004 Nov. 145(5):580-1

35. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 35 Epidemiology (Cont.) The frequency of cholelithiasis in children with sickle cell disease is almost double that of the general population.   (1,2) 1.Kaechele V, Wabitsch M, Thiere D, 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 . 2006 Jan. 42(1):66-70. 2.Alonso MH. Gall bladder abnormalities in children with sickle cell disease: management with laparoscopic cholecystectomy.  J Pediatr . 2004 Nov. 145(5):580-1

36. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 36 Epidemiology (Cont.)   Pigmented gallstones occur in approximately 50% of children with sickle cell disease by age 22 years. Approximately 20-40% of all pediatric gallstone disease can be attributable to hemolytic disease.   (1) 1.Currò G, Meo A, Ippolito D, Pusiol A, Cucinotta E. Asymptomatic cholelithiasis in children with sickle cell disease: early or delayed cholecystectomy?.  Ann Surg . 2007 Jan. 245(1):126-9

37. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 37 Prognosis Is favourable for simple cholelithiasis > 10 years is the period between the discovery of stones in asymptomatic patients and the development of symptoms https:// emedicine.medscape.com/article/927522-overview#a6

38. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 38 Presentation

39. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 39 History Only 33-40% of children are asymptomatic . ( approximately 80% of adults with gallstones were historically believed to be asymptomatic ,) In symptomatic patients : T he most common presenting symptom is right upper quadrant abdominal pain N ausea and vomiting . may be accompanied the pain

40. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 40 In the presence of nonspecific, intermittent abdominal pain in children with risk factors, gallstones must be considered as a possible cause. Risk factors include: C hronic hemolysis O besity I leal disease F amily history of childhood gallstones P arenteral nutrition . History (cont.)

41. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 41 Physical Examination Pain in the RUQ is common . Murphy sign (expiratory arrest with palpation in the RUQ) is pathognomonic H epatomegaly and splenomegaly ? Obesity ?

42. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 42 Diagnostic Considerations Biliary dyskinesia Biliary pseudolithiasis Choledochal cyst

43. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 43 Differential Diagnoses Cholestasis Neonatal Jaundice Pediatric Cholecystitis Pediatric pancreatitis and pancreatic pseudocyst

44. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 44 Workup

45. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 45 Approach Considerations The goal is to demonstrate evidence of gall bladder or biliary tract disease . Laboratory tests should include: Complete blood count Gamma- glutamyltransferase (GGT)  Amylase Urinalysis Direct and indirect bilirubin Alkaline phosphatase Transaminase levels

46. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 46 Imaging in Cholelithiasis Ultrasonography of the RUQ is the study of choice in patients with uncomplicated cholelithiasis . Plain radiography , radionuclide scanning , and cholangiopancreatography can also play a role in the assessment of cholelithiasis.

47. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 47 Ultrasonography Ultrasonography can be used to identify : T he location of the stone G allbladder wall thickening T he presence of gallbladder sludge P ericholecystic fluid

48. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 48 Ultrasonography of the RUQ www.meddean.luc.edu US findings: Thick GB wall Stones in GB Absence of echoes posterior to the calculi "Shadowing"

49. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 49 Abdominal plain radiography Abdominal plain radiography in pediatric patients with cholelithiasis is seldom useful , because gallstones, with the exception of calcium carbonate stones, are not radio-opaque .

50. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 50 Abdominal plain radiography (Cont.) Radiography may be beneficial in: Identifying small-bowel obstruction , or F ree air under the diaphragm.

51. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 51 Radionuclide Scanning A ssess gallbladder filling and bile excretion, particularly in response to cholecystokinin or a fatty meal

52. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr . Saad S Al Ani 52 Cholangiopancreatography M agnetic resonance cholangiopancreatography (MRCP ) (1)   or endoscopic retrograde cholangiopancreatography (ERCP) can help: Delineate the anatomy of the extrahepatic and intrahepatic biliary tract Identify the presence of ductal stones P rovide a therapeutic mode of removing a stone or decompressing the biliary tract In children with suspected hepatobiliary complications (2) 1.Dalton SJ, Balupuri S, Guest J. Routine magnetic resonance cholangiopancreatography and intra-operative cholangiogram in the evaluation of common bile duct stones.  Ann R Coll Surg Engl . 2005 Nov. 87(6):469-70 2.Rocca R, Castellino F, Daperno M, et al. Therapeutic ERCP in paediatric patients.  Dig Liver Dis . 2005 May. 37(5):357-62

53. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 53 Treatment

54. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 54 General consideration Treatment for simple cholelithiasis is symptomatic. Surgical removal of asymptomatic gallstones is currently not standard practice.

55. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 55 Asymptomatic Patients Periodic clinical and ultra-sonographic surveillance is appropriate for asymptomatic cholelithiasis . Al-Salem AH, Issa H. Laparoscopic cholecystectomy in children with sickle cell anemia and the role of ERCP.  Surg Laparosc Endosc Percutan Tech . 2012 Apr. 22(2):139-42

56. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 56 Asymptomatic Patients Children with sickle cell anemia, laparoscopic cholecystectomy is currently recommended for asymptomatic gallstones, (potential complications of cholelithiasis are more common in children with sickle cell anemia) Al-Salem AH, Issa H. Laparoscopic cholecystectomy in children with sickle cell anemia and the role of ERCP.  Surg Laparosc Endosc Percutan Tech . 2012 Apr. 22(2):139-42

57. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 57 Symptomatic Patients Laparoscopic cholecystectomy is currently the criterion standard in the treatment of symptomatic cholelithiasis It is safe and effective in children, with a low rate of postoperative complications. Siddiqui S, Newbrough S, Alterman D, Anderson A, Kennedy A Jr. Efficacy of laparoscopic cholecystectomy in the pediatric population.  J Pediatr Surg . 2008 Jan. 43(1):109-13; discussion 113

58. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 58 Diet usage for prevention The followings may be effective in preventing the development of cholesterol stones. D ecrease in the consumption of fatty foods C ontrolled weight reduction in patients with obesity 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 Aug. 28 (4):623-35

59. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 59 Complications Cholecystitis A scending cholangitis

60. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 60 If migration of gallstones into the main biliary ductal system occur, more ominous complications may occur, including: Choledocholithiasis Biliary obstruction with or without cholangitis Gallstone ileus Biliary hepatitis B iliary pancreatitis. Complications (cont.)

61. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 61 Summary Spontaneous resolution without specific treatment is most commonly observed in asymptomatic cholelithiasis

62. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 62 Summary (cont.) S ome medications may be beneficial, such as ursodeoxycholic acid for the treatment of radiolucent, noncalcified gallbladder stones . ( not been approved by the US Food and Drug Administration for use in pediatric patients .)

63. Management algorithm for gallstones in children 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 63 http://indianpediatrics.net/nov2010/nov-945-953.htm

64. 29/11/2017 Pediatric gallstones (Cholelithiasis) Prof.Dr. Saad S Al Ani 64 Thank you