title: Etanercept, a TNF-alpha binding agent, is ineffective in the prevention of post-ERCP pancreatitis in canines.
abstract: BACKGROUND
  The incidence of post-ERCP pancreatitis is 1-22%. It continues to be a difficult problem for endoscopist and patient. Uncovering an agent that may be used to prevent its occurrence is critical.
  
  
  OBJECTIVE
  The aim of our study was to investigate the role of etanercept in the prevention of post-ERCP pancreatitis.
  
  
  METHODS
  Endoscopic retrograde pancreatography (ERP)-induced injury was performed in dogs using a previously established endoscopic model of post-ERCP pancreatitis.
  
  
  METHODS
  Eight study dogs underwent ERP: 4 were pre-treated with etanercept one day before the procedure and 4 were untreated. In addition, three control dogs not undergoing ERP were also studied.
  
  
  METHODS
  Serum levels of amylase, lipase, and TNF-alpha, as well as the ratio of urinary trypsinogen activation peptide (TAP) and urinary creatinine, were measured before and after ERP. Necropsy was performed on post-operative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system.
  
  
  RESULTS
  Eight study dogs developed mild to moderate clinical pancreatitis with hyperamylasemia (11,538+/-4,065 U/L vs. 701+/-157 U/L; post-ERP peak levels vs. baseline values: P<0.001) and hyperlipasemia (3,637+/-2,333 U/L vs. 246+/-125 U/L; P=0.003). Mean total injury score was significantly elevated in study dogs compared to control dogs (6.16+/-1.85 vs. 1.06+/-0.49; P=0.001). There were escalating total injury scores concordant with more elaborate methods of endoscopically-induced injury although the trend did not reach the statistical significance (P=0.223). When comparing untreated to etanercept-treated dogs, there were no significant differences in serum amylase levels (P=0.903), serum lipase levels (P=0.771), TAP/creatinine urinary ratio (P=0.912), and pancreatic injury score (P=0.324).
  
  
  CONCLUSIONS
  Etanercept is ineffective in prevention of mild to moderate post-ERCP pancreatitis in canines. ERP-induced pancreatic injury can be used as a reliable animal model for studies investigating therapy and prevention of post-ERCP pancreatitis.
authors.affiliation: Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21205, USA. jbuscaglia@jhmi.edu
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Buscaglia
authors.forename: Brian W
authors.initials: BW
authors.lastname: Simons
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Prosser
authors.forename: Dawn S
authors.initials: DS
authors.lastname: Ruben
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Giday
authors.forename: Priscilla
authors.initials: P
authors.lastname: Magno
authors.forename: John O
authors.initials: JO
authors.lastname: Clarke
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Shin
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Kalloo
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Kantsevoy
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gabrielson
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Jagannath
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects* / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D000068800:Etanercept; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood; D009842:Oligopeptides / Q000652:urine; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007074:Immunoglobulin G; D009842:Oligopeptides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C080396:trypsinogen activation peptide; D008049:Lipase; D000681:Amylases; D000068800:Etanercept