title: Stereotypical Metabolic Response to Endoscopic Retrograde Cholangiopancreatography Show Alterations in Pancreatic Function Regardless of Post-Procedure Pancreatitis.
abstract: OBJECTIVE
  Metabolomics-based diagnosis or prediction of risk may improve patient outcomes and improve understanding of the pathogenesis of acute pancreatitis (AP). Endoscopic retrograde cholangiopancreatography (ERCP) is a risk factor for developing AP. This pilot study examined metabolomes of patients before and after ERCP, hypothesizing that metabolomics could differentiate between patients who did and did not develop post-ERCP pancreatitis, and that biomarkers associated with development of AP could be identified.
  
  
  METHODS
  Patients at high risk for developing post-ERCP pancreatitis were prospectively enrolled at the University of Minnesota from October 2012 to February 2014. Urine and serum samples were collected before ERCP, 2 h after ERCP, and daily thereafter if patients were admitted to the hospital with AP. Pancreatitis severity was calculated with Bedside Index for Severity in Acute Pancreatitis (BISAP) and Modified Glasgow scores. Patients who developed AP (n=9) were matched to patients who did not develop AP (n=18) by age and gender. Urine and serum metabolites were profiled with nuclear magnetic resonance spectroscopy. Partial least squares discriminant analysis (PLS-DA) was performed to detect changes in metabolic profiles associated with development of pancreatitis. Metabolic networks were constructed to probe functional relationships among metabolites.
  
  
  RESULTS
  Of the 113 enrolled patients, 9 developed mild AP according to BISAP and modified Glasglow scores. PLS-DA showed common differences between pre- and post-ERCP metabolic profiles in urine and serum regardless of AP status, characterized by increases in serum and urine ketones and serum glucose. Pre-ERCP lipase levels were somewhat elevated in those who went on to develop AP, though this did not reach statistical significance. Metabolic networks differed between patients with AP and those without after ERCP; however, metabolomics did not identify specific prognostic or diagnostic markers of ERCP-induced AP. Aspartate and asparagine were identified as well-connected hubs in post-ERCP serum networks of cases and were correlated with aspartate transaminase (AST) and white blood cell count levels. These features were not evident in controls. Serum aspartate was elevated in AP patients relative to those without AP after ERCP (P=0.03).
  
  
  CONCLUSIONS
  In this pilot study, ERCP was found to induce global changes in urine and serum metabolomes indicative of alterations in pancreatic function and insulin resistance. This should be taken into consideration in future research on this topic. Post-ERCP serum metabolic networks indicate functional differences surrounding aspartate metabolism between patients with AP and those without. Further study must be done in larger patient populations to test elevated lipase as a prognostic biomarker associated with risk of developing AP and to examine active metabolic mechanisms at work.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Lusczek
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Colling
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Sydne
authors.initials: S
authors.lastname: Muratore
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA.
authors.forename: Darwin
authors.initials: D
authors.lastname: Conwell
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Freeman
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Beilman