Abstract
Symptoms of pancreaticobiliary maljunction/choledochal cysts are caused by the obstruction of bile and pancreatic ducts due to protein plugs compacted in the common channel. However, the mechanism of protein plug formation remains unknown. Pancreatic stone protein (PSP) is reported to be a key protein to form protein plugs in chronic pancreatitis. Bile from 13 patients with pancreaticobiliary maljunction and bile from two normal controls were analyzed. Activity of pancreatic enzymes and the concentration of PSP were measured. The mean concentrations of PSP were 76.9 ± 30.9 ng/mL in the bile-duct bile, and 76.9 ± 29.8 ng/mL in the gallbladder bile. PSP was not detected in the controls (P&<0.05). In the bile-duct bile of the patients, trypsin(ogen) was detectable in nine patients, of which seven patients had activated trypsin. In the gallbladder bile, trypsin(ogen) was detectable in 12 patients, of which 9 patients had activated trypsin. Neither activated trypsin nor trypsinogen was detected in the controls. Bile in pancreaticobiliary maljunction patients contained both activated trypsin and PSP. Activated trypsin cleaves soluble PSP and creates insoluble PSP. Protein plugs in pancreaticobiliary maljunction may be formed by assembled insoluble PSP.
Similar content being viewed by others
References
Babbitt DP: Congenital choledochal cysts: New etiological concept based on anomalous relationships of the common bile duct and pancreatic bulb. Ann Radiol (Paris) 12:231–240, 1969
The Japanese Study Group on Pancreaticobiliary Maljunction (JSPBM), The Committee of JSPBM for Diagnostic Criteria: Diagnostic criteria of pancreaticobiliary maljunction. J Hepatobiliary Pancreat Surg 1:219–221, 1994
Kaneko K, Ando H, Umeda T, et al.: A new model for pancreaticobiliary maljunction without bile duct dilatation: Demonstration of cell proliferation in the gallbladder epithelium. J Surg Res 60:115–121, 1996
Kaneko K, Ando H, Ito T, Kasai K, Watanabe Y, Seo T: Increased cell proliferation and transforming growth factor-α (TGF-α) in the gallbladder epithelium of patients with pancreaticobiliary maljunction. Pathol Int 46:253–260, 1996
Kaneko K, Ando H, Watanabe Y, Seo T, Harada T: Pathologic changes in the common bile duct of an experimental model with pancreaticobiliary maljunction without biliary dilatation. Pediatr Surg Int 16:26–28, 2000
Narita H, Hashimoto T, Suzuki T, et al.: Clinical and experimental studies on the activation mechanism of pancreastic enzymes refluxing into the biliary tract with an anomalous pancreatico-biliary ductal junction. Nippon Shonigeka Gakkai Zasshi (Jpn J Pediatr Surg) 26:609–615, 1990
Shimada K, Yanagisawa J, Nakayama F: Increased lysophosphatidylcholine and pancreatic enzyme content in bile of patients with anomalous pancreaticobiliary ductal junction. Hepatology 13:438–444, 1991
Yagi T, Miyoshi Y, Komi N: An activation mechanism of pancreatic proenzymes refluxing into the biliary tract in APBD patients. Shikoku Igakkai Zashhi (Shikoku Med J) 49:106–113, 1993
Yamashiro Y, Sato M, Shimizu T, Oguchi S, Miyano T: How great is the incidence of truly congenital common bile duct dilatation? J Pediatr Surg 28:622–625, 1993
Mizuno M, Kato T, Koyama K: An analysis of mutagens in the contents of the biliary tract in pancreaticobiliary maljunction. Surg Today 26:597–602, 1996
Ando H, Ito T, Nagaya M, Watanabe Y, Seo T, Kaneko K: Pancreaticobiliary maljunction without choledochal cysts in infants and children: Clinical features and surgical therapy. J Pediatr Surg 30:1658–1662, 1995
Kaneko K, Ando H, Ito T, et al.: Protein plugs cause symptoms in patients with choledochal cysts. Am J Gastroenterol 92:1018–1021, 1997
de Caro A, Multigner L, Dagorn JC, Sarles H: The human pancreatic stone protein. Biochimie 70:1209–1214, 1988
Hayakawa T, Naruse S, Kitagawa M, et al.: Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis. Pancreas 10:137–142, 1995
Graf R, Schiesser M, Scheele GA, et al.: A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. J Biol Chem 276:21028–21038, 2001
Katsuzaki T, Tatemichi N, Takeichi C, et al.: Enzyme immunoassay for specific analysis of pancreatic stone proteins in human pancreatic juice. J Clin Lab Anal 6:375–378, 1992
Ganong WF: Review of Medical Physiology, 20th ed. New York, McGraw–Hill, 2001
Rinderknecht H: Activation of pancreatic zymogens: Normal activation, premature intrapancreatic activation, protective mechanisms against inappropriate activation. Dig Dis Sci 31:314–321, 1986
Kimura K, Tsugawa C, Ogawa K, et al.: Choledochal cyst: Etiological considerations and surgical management in 22 cases. Arch Surg 113:159–163, 1978
Okada A, Oguchi Y, Kamata S, Ikeda Y, Kawashima Y, Saito R: Common channel syndrome: Diagnosis with endoscopic retrograde cholangiopancreatography and surgical management. Surgery 93:634–642, 1983
Todani T, Watanabe Y, Fujii T, Uemura S: Anomalous arrangement of the pancreaticobiliary ductal system in patients with a choledochal cyst. Am J Surg 147:672–676, 1984
Iwai N, Yanagihara J, Tokiwa K, Shimotake T, Nakamura K: Congenital choledochal dilatation with emphasis on pathophysiology of the biliary tract. Ann Surg 215:27–30, 1992
Davenport M, Stringer MD, Howard ER: Biliary amylase and congenital choledochal dilatation. J Pediatr Surg 30:474–477, 1995
Samuel M, Spitz L: Choledochal cyst: Varied clinical presentations and long-term results of surgery. Eur J Pediatr Surg 6:78–81, 1996
Aoki T, Tsuchida A, Kasuya K, Endo M, Kitamura K, Koyanagi Y: Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct? Jpn J Clin Oncol 31:107–111, 2001
Hara H, Morita S, Sako S, et al.: Relationship between types of common channel and development of biliary tract cancer in pancreaticobiliary maljunction. Hepatogastroenterology 49:322–325, 2002
Xiao X, Li H, Wang Q, Tong S: Abnormal pancreatic isoamylases in the serum of children with choledochal cyst. Eur J Pediatr Surg 13:26–30, 2003
Konok GP, Thompson AG: Pancreatic ductal mucosa as a protective barrier in the pathogenesis of pancreatitis. Am J Surg 117:18–23, 1969
White TT, Allan BJ: Intrapancreatic activation of proteases in the etiology of pancreatitis and cancer of the pancreas. Med Clin North Am 58:1305–1310, 1974
Yamasaki S, Miyoshi Y, Komi N: Immunohistochemical studies on enterokinase producing cells in the biliary tract. Jpn J Surg 21:600–605, 1991
Shibata T, Hayakawa T, Kondo T, et al.: Analysis of pancreatic enzymes in the bile of congenital choledochal cyst with anomalous pancreaticobiliary ductal union. Nippon Shokakibyo Gakkai Zasshi (Jpn J Gastroenterol) 86:1513–1518 (in Japanese)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ochiai, K., Kaneko, K., Kitagawa, M. et al. Activated Pancreatic Enzyme and Pancreatic Stone Protein (PSP/reg) in Bile of Patients with Pancreaticobiliary Maljunction/Choledochal Cysts. Dig Dis Sci 49, 1953–1956 (2004). https://doi.org/10.1007/s10620-004-9599-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-004-9599-7