© 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY nature publishing group ORIGINAL CONTRIBUTIONS 2287 PANCREAS AND BILIARY TRACT INTRODUCTION Acute pancreatitis (AP) is a common acute inlammatory proc- ess with a highly variable clinical course that is manifested by systemic inlammation and multiple organ failure in the 10–20% of patients who experience a severe disease course (1). Common early complications of severe AP include intravascular volume depletion, hemoconcentration, hypotension, acute kidney injury, acute lung injury, and shock (1–3). A shared trait among these complications is increased systemic vascular permeability with extravasation of luids and protein into tissues, also known as vas- cular leak syndrome (4,5). he dynamic, time-dependent nature of AP and the inluence of disease-modifying factors require the Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation, Is Associated With Persistent Organ Failure in Patients With Acute Pancreatitis From the United States and Germany David C. Whitcomb, MD, PhD 1,2 , Venkata Muddana, MD 1 , Christopher J. Langmead, PhD 3 , Frank D. Houghton Jr, PhD 1 , Annett Guenther, MSc 4 , Patricia K. Eagon, PhD 1 , Julia Mayerle, MD 4 , Ali A. Aghdassi, PhD 4 , F. Ulrich Weiss, PhD 4 , Anna Evans, BA 1 , Janette Lamb, PhD 1 , Gilles Clermont, MD 5,6 , Markus M. Lerch, MD 4 and Georgios I. Papachristou, MD 1,6 OBJECTIVES: Patients with severe acute pancreatitis (AP) typically develop vascular leak syndrome, resulting in hemoconcentration, hypotension, pulmonary edema, and renal insufficiency. Angiopoietin-1 (Ang-1) and 2 (Ang-2) are autocrine peptides that reduce or increase endothelial permeability, respectively. The aim of this study was to determine whether Ang-1 and/or Ang-2 levels are predictive biomarkers of persistent organ failure ( > 48 h) and prolonged hospital course. METHODS: Banked serum from 28 patients enrolled in the Severity of Acute Pancreatitis Study at the University of Pittsburgh Medical Center (UPMC) and 58 controls was analyzed for Ang-1 and Ang-2 levels. Separately, serum from 123 patients and 103 controls at Greifswald University (GU), Germany was analyzed for Ang-2 levels. Angiopoietin levels were measured by enzyme-linked immunosorbent assay. RESULTS: In all, 6 out of 28 UPMC patients (21%) and 14 out of 123 GU patients (13%) developed persistent organ failure and were classified as severe AP. Ang-2 was significantly higher on admission in patients who developed persistent organ failure compared with those who did not in UPMC (3,698 pg/ml vs. 1,001 pg/ml; P = 0.001) and GU (4,945 pg/ml vs. 2,631 pg/ml; P = 0.0004) cohorts. After data scaling, admission Ang-2 levels showed a receiver-operator curve of 0.81, sensitivity 90%, and specificity 67% in predicting persistent organ failure. In addition, Ang-2 levels remained significantly higher in severe AP compared with mild AP patients until day 7 (days 2 – 4: P < 0.005; day 7: P < 0.02). Ang-1 levels were not significantly different between mild and severe AP patients on admission. CONCLUSIONS: Elevated serum Ang-2 levels on admission are associated with and may be a useful biomarker of predicting persistent organ failure and ongoing endothelial cell activation in AP. Am J Gastroenterol 2010; 105:2287–2292; doi:10.1038/ajg.2010.183; published online 11 May 2010 1 Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania, USA; 2 Departments of Cell Biology and Physiology and Department of Human Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; 3 Department of Computer Science, Carnegie Mellon University , Pittsburgh, Pennsylvania, USA; 4 Department of Medicine A, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany; 5 Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; 6 Veterans Affairs Pittsburgh Health System, Pittsburgh, Pennsylvania, USA. Correspondence: David C. Whitcomb, MD, PhD, Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh and UPMC, Room 401.4, 3708 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA. E-mail: whitcomb@pitt.edu Received 10 December 2009; accepted 1 April 2010