Translational research for acute pancreatitis - Which results have really influenced our therapy?

Abstract

Acute pancreatitis is a common disease characterized by acinar cell destruction and acute inflammatory changes of the pancreas that lead to a systemic inflammatory response. A major research effort has been undertaken to unravel the underlying pathophysiology and to identify possible therapeutic targets. Still, only very few findings have influenced our clinical practice in the treatment of acute pancreatitis. Pancreatic microcirculation and capillary blood flow have long been suspected to play a major role in the course of the disease. It therefore seemed tempting to speculate that manipulation of the vasoconstrictor endothelin or its antagonist nitrogen monoxide could positively influence the outcome. We had to acknowledge, however, that these mechanisms take place very early in the disease course and that only prophylactic applications show an effect; this is useful in the setting of pancreas transplantation and endoscopic retrograde cholangiopancreatography but not applicable for clinical use in the therapy of acute pancreatitis. Research then focused on later pathophysiological stages of the disease, mainly on the process of adhesion and extravasation of leukocytes into the pancreatic tissue. Here, integrins and adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) were investigated in detail. A monoclonal antibody to ICAM-1 showed promising results in experimental models but was never further evaluated in the clinical setting. Hemodilution and fluid resuscitation was recognized to be an important therapeutic tool in acute pancreatitis. Here, initial experimental studies favored colloid solutions, and especially dextrans for isovolemic fluid resuscitation. It was recognized only later that colloid solutions are not effective and may even increase mortality in critically ill patients. Therefore, goal-directed infusion of Ringer's lactate solution at a moderate infusion rate to optimize volume status and hemoconcentration in acute pancreatitis is now advocated. In summary, out of the numerous experimental and translational studies, only very few have really influenced our daily clinical practice. Further research is therefore needed to find more specific and effective therapeutic agents for the treatment of acute pancreatitis.