trypsinogen and Gallstones

Acute pancreatitis (AP) is an important cause of morbidity and mortality worldwide and the annual incidence appears to be increasing. It presents as a mild self-limiting illness in 80% of patients. However, one-fifth of these develop a severe complicated life-threatening disease requiring intensive and prolonged therapeutic intervention. Alcohol and gallstone disease remain the commonest causes of AP but metabolic abnormalities, obesity and genetic susceptibility are thought be increasingly important aetiological factors. The prompt diagnosis of AP and stratification of disease severity is essential in directing rapid delivery of appropriate therapeutic measures. In this review, the range of diagnostic and prognostic assays, severity scoring systems and radiological investigations used in current clinical practice are described, highlighting their strengths and weaknesses. Increased understanding of the complex pathophysiology of AP has generated an array of new potential diagnostic assays and these are discussed. The multidisciplinary approach to management of severe pancreatitis is outlined, including areas of controversy and novel treatments.

Topics: Acute Disease; Alcohol Drinking; Amylases; Autolysis; Gallstones; Genetic Predisposition to Disease; Humans; Hypercalcemia; Hyperlipidemias; Lipase; Obesity; Pancreatitis; Prognosis; Trypsin; Trypsinogen

Topics: Abdominal Pain; Alcohol Drinking; Chronic Disease; Diabetes Mellitus; Fibrosis; Gallstones; Humans; Hypercalcemia; Hyperlipidemias; Malabsorption Syndromes; Mutation; Pancreas; Pancreatitis; Risk Factors; Smoking; Trypsin; Trypsinogen

To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP.. Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis.. Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification.. Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis.

Topics: Adult; Aged; Amylases; Biomarkers; Carboxypeptidase B; Case-Control Studies; Catheterization; Chi-Square Distribution; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy, Laparoscopic; Colorimetry; Enzyme-Linked Immunosorbent Assay; Female; Gallstones; Humans; Linear Models; Male; Middle Aged; Odds Ratio; Pancreas; Pancreatitis; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Trypsin; Trypsinogen

Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2(-/-) mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca(2+) concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury induced by endoscopic retrograde cholangiopancreatography (ERCP). This reduction in pancreatitis severity is observed when the pepducin is given before or 2 h after bile acid infusion but not when it is given 5 h after bile acid infusion. Conversely, P2pal-18S increases the severity of secretagogue-induced pancreatitis. In vitro studies indicate that P2pal-18S protects acinar cells against bile acid-induced injury/death, but it does not alter bile acid-induced intracellular zymogen activation. These studies are the first to report the effects of an effective PAR2 pharmacological inhibitor on pancreatic acinar cells and on the severity of experimental pancreatitis. They raise the possibility that a pepducin such as P2pal-18S might prove useful in the clinical management of patients at risk for developing severe biliary pancreatitis such as occurs following ERCP.

Topics: Acinar Cells; Animals; Bile Acids and Salts; Biliary Tract Diseases; Calcium; Calcium Signaling; Ceruletide; Cholangiopancreatography, Endoscopic Retrograde; Chymotrypsinogen; Coloring Agents; Enzyme Activation; Enzyme Precursors; Gallstones; Indicators and Reagents; Lipopeptides; Mice; Mice, Inbred C57BL; Mice, Knockout; Pancreatitis; Propidium; Receptor, PAR-2; Trypsinogen

Topics: Adult; Aged; Female; Gallstones; Hepatitis, Alcoholic; Humans; Male; Middle Aged; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay; Trypsin; Trypsinogen