trypsinogen and Constriction--Pathologic

Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to compare them with CA19-9 and CEA.. The study consisted of 84 patients with either PSC or cholangiocarcinoma or both referred for liver transplantation or other liver surgery. The serum concentrations were determined by time-resolved immunofluorometric assays.. Forty-six patients were transplanted due to PSC; in 3 of the explanted livers cholangiocarcinoma was found incidentally. All transplanted patients had severe biliary strictures together with cirrhosis or pre-cirrhosis. Twenty-nine of 38 patients with cholangiocarcinoma were candidates for intervention. In all, 8 patients had both PSC and cholangiocarcinoma. Receiver-operating characteristics curve analysis showed that serum trypsinogen-2 had the highest accuracy in differentiating between cholangiocarcinoma and PSC. The area under the curve (AUC) value was 0.804 for trypsinogen-2 and 0.613 for CA19-9. Serum trypsinogen-2 also showed the highest accuracy for differentiation between PSC and PSC with simultaneous cholangiocarcinoma with an AUC value of 0.759.. Our results suggest that serum trypsinogen-2 is a most useful marker for diagnosing patients with cholangiocarcinoma, and it is superior to serum CA19-9 and CEA.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; CA-19-9 Antigen; Cholangiocarcinoma; Constriction, Pathologic; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Receptors, Cell Surface; Sensitivity and Specificity; Trypsin; Trypsinogen

Intracellular Ca(2+)-changes not only participate in important signaling pathways but have also been implicated in a number of disease states including acute pancreatitis. To investigate the underlying mechanisms in an experimental model mimicking human gallstone-induced pancreatitis, we ligated the pancreatic duct of Sprague-Dawley rats and NMRI mice for up to 6 h and studied intrapancreatic changes including the dynamics of [Ca(2+)](i) in isolated acini. In contrast to bile duct ligation, pancreatic duct obstruction induced intra-pancreatic trypsinogen activation, leukocytosis, hyperamylasemia, and pancreatic edema and increased lung myeloperoxidase activity. Although resting [Ca(2+)](i) in isolated acini rose by 45% to 205 +/- 7 nmol, the acetylcholine- and cholecystokinin (CCK)-stimulated calcium peaks as well as the amylase secretion declined, but neither the [Ca(2+)](i)-signaling pattern nor the amylase output in response to the Ca(2+)-ATPase inhibitor thapsigargin nor the secretin-stimulated amylase release were impaired by pancreatic duct ligation. On the single cell level pancreatic duct ligation reduced the percentage of cells in which submaximal secretagogue stimulation was followed by a physiological response (i.e. Ca(2+) oscillations) and increased the percentage of cells with a pathological response (i.e. peak plateau or absent Ca(2+) signal). Moreover, it reduced the frequency and amplitude of Ca(2+) oscillation as well as the capacitative Ca(2+) influx in response to secretagogue stimulation. Serum pancreatic enzyme elevation as well as trypsinogen activation was significantly reduced by pretreatment of animals with the calcium chelator BAPTA-AM. These experiments suggest that pancreatic duct obstruction rapidly changes the physiological response of the exocrine pancreas to a Ca(2+)-signaling pattern that has been associated with premature digestive enzyme activation and the onset of pancreatitis, both of which can be prevented by administration of an intracellular calcium chelator.

Topics: Adenosine Triphosphatases; Amylases; Animals; Calcium; Chelating Agents; Cholecystokinin; Constriction, Pathologic; Egtazic Acid; Flow Cytometry; Male; Mice; Pancreas; Pancreatic Diseases; Pancreatic Ducts; Rats; Rats, Sprague-Dawley; Signal Transduction; Thapsigargin; Time Factors; Trypsinogen

Authors report two cases of childhood chronic pancreatitis, causing severe symptoms and common bile duct stenosis with cholestasis. Both patients had to be operated on. Chronic pancreatitis with calcification led to significant common bile duct stenosis in a 13 years old girl. After ERCP a double bypass procedure was performed (Wirsungo-jejunostomy and hepatico-jejunostomy). During 42 months follow-up the patient remained pain- and symptom-free gaining 16 kilograms. In a 9 years old girl severe stenosis of the intrapancreatic common bile duct and a small duct type chronic pancreatitis with extensive fibrosis was found. Treatment was Roux-en-Y hepatico-jejunostomy. Thirty-four months after the operation she is symptom-free with normal enzyme parameters. Authors report results of genetic investigations performed on registered chronic pancreatitis children and their families in Hungary, including the two operated cases. Two of the 5 patients were hereditary type, despite negative family history. Cationic trypsinogen gene R122H (R117H) mutation were detected in both patients. Chronic non-hereditary pancreatitis is a very rare disease in childhood but may cause severe secondary conditions requiring surgery.

Topics: Adolescent; Biliary Tract Surgical Procedures; Child; Cholestasis; Chronic Disease; Common Bile Duct; Constriction, Pathologic; Female; Fibrosis; Humans; Hungary; Male; Mutation; Pancreatitis; Trypsinogen