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Author: Alexandre F Migala, DO, Staff Physician, Department of Emergency Medicine, Denton Regional Medical Center

Alexandre F Migala is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Osteopathic Association, Association of Military Osteopathic Physicians and Surgeons, and Texas Medical Association

Coauthor(s): Hildegardo Costa, MD, Fellow in Pediatric Gastroenterology and Nutrition, Instructor, Department of Pediatrics, State University of New York Health Sciences Center at Brooklyn; Richard D Warren, MD, Staff Physician, Department of Emergency Medicine, Darnall Army Community Hospital

Editors: Jorge Vargas, MD, Professor, Department of Pediatrics, Division of Pediatric Gastroenterology, University of California at Los Angeles School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; B U K Li, MD, Professor of Pediatrics, Division of Gastroenterology and Nutrition, Children's Hospital of Wisconsin, Medical College of Wisconsin; Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health; Steven M Altschuler, MD, President and CEO, Children's Hospital Foundation, Children's Hospital of Philadelphia

Author and Editor Disclosure

Synonyms and related keywords: cholelithiasis, gallstones, biliary colic, cholecystitis, choledocholithiasis, gall bladder calculi, gallbladder, chronic calculous cholecystitis, cystic duct, acute cholecystitis, biliary obstruction, cholangitis, biliary pancreatitis, chronic abdominal pain, stomach pain

Background

Gallbladder calculi are relatively uncommon in children. However, the incidence of cholelithiasis has been increasing recently. Children may harbor cholesterol gallstones, black- or brown-pigmented stones, or mixed-type gallstones. A study by Stringer et al demonstrated a high incidence of calcium carbonate stones in children that are exceptionally rare in the adult population.

Pathophysiology

Complications that occur in adults with this condition may also occur in children. Cholelithiasis primarily affects the gallbladder. Gallstones may cause irritation and inflammation of the gallbladder mucosa, resulting in chronic calculous cholecystitis and symptoms of biliary colic. If a stone obstructs the cystic duct, acute cholecystitis can occur, with distension of the gallbladder wall and the possibility of necrosis and spillage of gallbladder contents. With migration of gallstones from the gallbladder, through the cystic duct, and into the main biliary ductal system, more ominous complications may occur. These include choledocholithiasis, biliary obstruction with or without cholangitis, and biliary pancreatitis.

Frequency

United States

Currently, the incidence of cholelithiasis in children is estimated to be 0.15-0.22%. This number seems to be increasing, and the true number of affected children may have always been underestimated because patients with cholelithiasis can present with a nonspecific abdominal pain. Another factor that may be adding to the increasing incidence is the rise in teenage pregnancies. The frequency of cholelithiasis in children with sickle cell disease is almost double that of the general population.

The incidence of patients with identified gallstones who eventually develop symptoms is relatively low. A 1992 National Institutes of Health consensus conference on gallstones concluded that approximately 10% of patients with gallstones will develop symptoms in the first 5 years after diagnosis. In 1995, The Group for Epidemiology and Prevention of Cholelithiasis reported that initially asymptomatic patients with cholelithiasis had a 25.8% probability of developing symptoms within 10 years and a yearly incidence of 0.5-3% after 10 years.

Mortality/Morbidity

The morbidity and mortality associated with gallstones are more commonly associated with cholecystitis or ascending cholangitis. Cholelithiasis may lead to morbidity as chronic abdominal pain, which can be incapacitating.

Race

Although no racial predilection exists, individuals of certain ethnic heritage have been identified to be at higher risk for developing gallstones, particularly the Pima Indians of North America and Scandinavians.

Sex

The frequency of cholelithiasis in children is significantly greater in females than in males and is comparable to the adult ratio, with up to 4:1 female predominance.



History

Gallstones in children are most commonly an incidental finding, but strongly consider them during the workup of those with nonspecific intermittent abdominal pain with risk factors. Also, consider cholelithiasis in those with jaundice and low-grade elevations of transaminases and transpeptidase. Older children may be able to localize their pain to the right upper quadrant (RUQ).

Physical

Perform a complete physical examination in children. Include auscultation, visualization, and lastly, palpation in the abdominal examination. Pain in the RUQ is common. A Murphy sign (expiratory arrest with palpation in the RUQ) is thought to be pathognomonic. Also, note hepatomegaly and splenomegaly because they may be a clue to venous congestion or hemolytic processes that may predispose a patient to gallstones.

Causes

The causes of cholelithiasis are multiple and relate to the risk factors. Trauma, sepsis, prolonged total parenteral nutrition (TPN), hepatobiliary disease, hemolytic diseases, abdominal surgery, and pregnancy all may lead to an increased incidence of gallstones in the pediatric population. In addition, acute renal failure, prolonged fasting, low-calorie diets, and rapid weight loss have been identified to increase the incidence of gallstones. Sickle cell disease has been identified as an independent risk factor associated with an increase in the frequency of cholelithiasis. Biliary pseudolithiasis has been identified with the use of certain medications, primarily ceftriaxone.



Cholecystitis
Cholestasis
Gallbladder Disease
Jaundice, Neonatal
Pancreatitis and Pancreatic Pseudocyst

Other Problems to be Considered

Biliary dyskinesia
Biliary pseudolithiasis



Lab Studies

  • The workup of cholelithiasis in pediatric patients is similar to that in adults. The goal is to demonstrate evidence of gall bladder or biliary tract disease.
  • Liver function test (LFT) and CBC results are typically within reference ranges. Abnormalities suggest infection or obstruction, or both.
  • All laboratory results in simple cholelithiasis should be within reference ranges. They are of use in identifying a more complex disease process, including biliary obstruction and cholecystitis.

Imaging Studies

  • Use of kidney-ureter-bladder (KUB) plain radiography in these patients is often fruitless because many stones are not visible. However, it may be beneficial in identifying small-bowel obstruction or free air under the diaphragm.
  • Ultrasonography of the right upper quadrant (RUQ) is the study of choice for these patients. Ultrasonography can be used to identify the location of the stone, gallbladder wall thickening, and pericholecystic fluid, and a sonographic Murphy sign aids in diagnosis of the disease process.
  • Radionuclide scanning, such as scanning with iminodiacetic acid (IDA) derivatives (eg, hepatoiminodiacetic acid [HIDA], diisopropyl iminodiacetic acid [DISIDA], and para-isopropyliminodiacetic acid [PIPIDA] scanning), are also used to assess gall bladder function, its ability to harbor and concentrate bile, and perhaps more importantly, its motility response to cholecystokinin or a fatty meal by quantifying the ejection fraction.
  • In children with suspected hepatobiliary complications, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) can help delineate the anatomy of the extrahepatic and intrahepatic biliary tract, identify the presence of ductal stones, and provide a therapeutic mode of removing a stone or decompressing the biliary tract. ERCP in the pediatric population has been associated with the same frequency of success and complications as in adults. As a noninvasive alternative, the MRCP has demonstrated promise in the evaluation of choledocholithiasis but is less available at many institutions.



Medical Care

  • Treatment for simple cholelithiasis is symptomatic.
  • One option for nonsurgical management of gallstone disease is the use of ursodeoxycholic acid. One study demonstrated a 56% reduction in biliary pain after 3 months of therapy and a mean dissolution of gallstones in 59% of cases after 12 months of treatment with 10 mg/kg/d of ursodeoxycholic acid. The primary disadvantage with this approach is the incidence of recurrent gallstones, approximately 25% within 5 years. The nonsurgical option is currently only indicated for patients either unfit or unwilling to undergo surgical intervention and has not been recommended in the pediatric population.
  • The number of pediatric cholecystectomies in symptomatic patients has increased.
  • Removal of a stone in an asymptomatic patient is not standard practice.
  • Admission may be required for observation with nasogastric tube placement.

Surgical Care

  • The number of gallbladders removed in patients with symptomatic stones is increasing.
  • Removal of the gallbladder in those who are asymptomatic is not the standard treatment.
  • Laparoscopic cholecystectomies are now being routinely performed in children and are accepted as the criterion standard for the treatment of symptomatic cholelithiasis. Laparoscopic cholecystectomy with intraoperative cholangiography has demonstrated promise as an alternative to ERCP in patients with obstructive common bile duct stones (choledocholithiasis).
  • Endoscopic cholecystotomy has been demonstrated to be ameliorating.

Consultations

Consultation with a general surgeon is appropriate in symptomatic patients with stones and evidence of cholecystitis.

Diet

A decrease in the consumption of fatty foods and controlled reduction in weight may be effective in some patients.

Activity

Leitzmann et al have demonstrated in a prospective cohort study that symptomatic gallstones in men were reduced by approximately 20% with increased exercise. This reduction may be extrapolated to the pediatric population.



Spontaneous resolution without specific treatment is most commonly observed.

Drug Category: Gallstone solubilizers

These agents are indicated for the treatment of radiolucent noncalcified gallbladder stones.

Drug NameUrsodiol (Actigall, Ursodamor, Ursofalk, Ursogal)
DescriptionAlso called ursodeoxycholic acid. Indicated for radiolucent noncalcified gallbladder stones <20 mm in diameter when conditions preclude cholecystectomy.
Suppresses hepatic cholesterol synthesis and secretion and also inhibits intestinal absorption. It appears to have little inhibitory effect on synthesis and secretion into bile of endogenous bile acids and does not appear to affect secretion of phospholipids into bile. After repeated doses, reaches steady-state bile concentrations in about 3 wk.
Cholesterol is insoluble in aqueous media, but it can be solubilized in at least 2 different ways in the presence of dihydroxy bile acids. In addition to solubilizing cholesterol in micelles, ursodiol acts by dispersing cholesterol as liquid crystals in aqueous media. The overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs.
The various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing bile, thus resulting in bile conducive to cholesterol stones dissolution.
Although not approved by the FDA, ursodiol has been used in combination with chenodeoxycholic acid and in conjunction with extracorporeal shock-wave lithotripsy for the dissolution of gallstones.
Available in 250-mg and 300-mg caps. An extemporaneous liquid formulation may be compounded for pediatric use.
Adult Dose8-10 mg/kg/d PO divided bid/tid
Pediatric DoseNot established; limited data exist; administer as in adults
ContraindicationsDocumented hypersensitivity; calcified cholesterol stones; radiopaque stones; radiolucent bile pigment stones; required cholecystectomy (eg, unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, biliary-gastrointestinal fistula)
InteractionsDecreased effect with aluminum-containing antacids, cholestyramine, colestipol, clofibrate, and PO contraceptives
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsUrsodiol has not been associated with liver damage; however, a metabolite (lithocholic acid, a naturally occurring bile acid and ursodiol metabolite) is known to be liver toxic and congenital or acquired sulfation deficiency may increase the risk; monitor liver enzymes at baseline and as clinically indicated thereafter

Drug Category: Anti-inflammatory agents

These agents decrease inflammatory responses and systemically interfere with events leading to inflammation.

Drug NameDiclofenac (Voltaren, Cataflam)
DescriptionDesignated chemically as 2-[(2,6-dichlorophenyl) amino] benzene acetic acid, monosodium salt, with an empirical formula of C14 H10 Cl2 NO2 NA. One of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. Believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Can cause hepatotoxicity; hence, liver enzymes should be monitored in the first 8 wk of treatment.
Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Delayed-release, enteric-coated form is diclofenac sodium, and immediate release form is diclofenac potassium. Has relatively low risk for bleeding GI ulcers.
Adult Dose25 mg PO bid/tid
If well tolerated, increase by 25 or 50 mg at weekly intervals until satisfactory response is obtained or total daily dose of 150-200 mg PO is reached
Higher doses generally do not increase effectiveness
Pediatric Dose<12 years: Not established
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity; do not administer into CNS or give to patients with peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or those at high risk of bleeding
InteractionsCoadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding) may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsPregnancy category D during third trimester; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts rarely occur and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia is present

Drug NameIndomethacin (Indocin)
DescriptionRapidly absorbed. Metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.
Adult Dose25-50 mg PO bid/tid
75 mg SR PO bid; not to exceed 200 mg/d
Pediatric Dose<2 years: Not established
>2 years: 1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d
ContraindicationsDocumented hypersensitivity; GI bleeding or renal insufficiency
InteractionsCoadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsPregnancy category D during third trimester; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur; discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia is present



Further Inpatient Care

  • Treat patients with simple cholelithiasis on an outpatient basis because spontaneous resolution without treatment is the rule.
  • Patients with symptomatic stones require cholecystectomy.
  • In patients with sickle cell disease, successful operative management requires appropriate perioperative management, with emphasis on adequate hydration, oxygenation, and consideration for possible exchange transfusion to reduce the percentage of hemoglobin S or transfusion to a hemoglobin greater than 10 g/dL.

In/Out Patient Meds

  • In adolescents, Robinul may be used while in the hospital, and Bentyl is effective in many patients on an outpatient basis. Although not widely used and not recommended for patients younger than 12 years, if administered early, indomethacin has been reported to reverse the inflammatory changes associated with acute calculous cholecystitis, and diclofenac has been reported to reduce progression rates to acute calculous cholecystitis.

Deterrence/Prevention

  • Regular exercise and proper body weight management (gradual weight reduction if overweight) have demonstrated benefit in reducing the incidence of developing gallstones.

Complications

  • Complications of concern include cholecystitis and ascending cholangitis.
  • With migration of gallstones from the gallbladder, through the cystic duct, and into the main biliary ductal system, more ominous complications may occur, including choledocholithiasis, biliary obstruction with or without cholangitis, gallstone ileus, biliary hepatitis, and biliary pancreatitis.

Prognosis

  • The prognosis for simple cholelithiasis is favorable.
  • The lag time between the discovery of stones in asymptomatic patients and development of symptoms is estimated at more than 10 years.

Patient Education



Medical/Legal Pitfalls

  • Failure to use ultrasonography: Use of radiography in these patients is often fruitless because many stones are not visible.
  • Failure to rule out cholecystitis

Special Concerns

  • Consider gallstones in populations at risk other than the classic high-risk population. Patients with sickle cell disease who have recently traveled to foreign countries are at risk for enteric parasites.



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Cholelithiasis excerpt

Article Last Updated: Jun 19, 2006