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  • Title: Etanercept, a TNF-alpha binding agent, is ineffective in the prevention of post-ERCP pancreatitis in canines.
    Author: Buscaglia JM, Simons BW, Prosser BJ, Ruben DS, Giday SA, Magno P, Clarke JO, Shin EJ, Kalloo AN, Kantsevoy SV, Gabrielson KL, Jagannath SB.
    Journal: JOP; 2008 Jul 10; 9(4):456-67. PubMed ID: 18648137.
    Abstract:
    CONTEXT: 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. DESIGN: Endoscopic retrograde pancreatography (ERP)-induced injury was performed in dogs using a previously established endoscopic model of post-ERCP pancreatitis. ANIMALS: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.
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