title: Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone disease.
abstract: OBJECTIVE
  Gallstone formation is a common problem in neonates on prolonged courses of total parenteral nutrition (TPN). The authors hypothesized that the use of cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would prevent gallstone formation in a high-risk group of patients with TPN.
  
  
  METHODS
  A prospective, randomized, blinded, controlled trial of neonates who were on a prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to receive CCK vs placebo. Patients remained on the study until taking more than 50% of energy enterally. Children were recalled between 2 and 4 years after completing TPN for ultrasonographic examination of their hepatobiliary tree.
  
  
  RESULTS
  Neonates (38 studied) required a mean (+/-SD) of 33 +/- 16 days of TPN. Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was not effective in preventing the formation of gallstones (3 stones in infants receiving CCK, P = .51). Diagnosis (P = .56), birth weight (P = .54), gestational age (P = .18), and duration of TPN (P = .53) did not correlate with gallstone formation. To address the management of these stones, all 4 were placed on a prolonged course of ursodeoxycholic acid (mean duration, 11.6 +/- 5.4 months). Two additional infants (not in the original study) with TPN-associated gallstone disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were performed every 6 months. No patient achieved any degree of stone dissolution. One patient underwent cholecystectomy for symptomatology.
  
  
  CONCLUSIONS
  Total parenteral nutrition-associated gallstones were detected in 10% of children, and most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not effective in preventing TPN-associated gallstones. In addition, the use of ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods will be needed to address the prevention and treatment of these stones.
authors.affiliation: Section of Pediatric Surgery, CS Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI 48109, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Tsai
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Strouse
authors.forename: Robert A
authors.initials: RA
authors.lastname: Drongowski
authors.forename: Saleem
authors.initials: S
authors.lastname: Islam
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D042882:Gallstones / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D011446:Prospective Studies; D012844:Sincalide / Q000627:therapeutic use*; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D005765:Gastrointestinal Agents; D014580:Ursodeoxycholic Acid; D012844:Sincalide