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Activated Pancreatic Enzyme and Pancreatic Stone Protein (PSP/reg) in Bile of Patients with Pancreaticobiliary Maljunction/Choledochal Cysts

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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.

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References

  1. 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

    CAS  Google Scholar 

  2. 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

    Article  Google Scholar 

  3. 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

    Article  CAS  Google Scholar 

  4. 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

    Article  CAS  Google Scholar 

  5. 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

    Article  CAS  Google Scholar 

  6. 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

    Google Scholar 

  7. 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

    Article  CAS  Google Scholar 

  8. 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

    CAS  Google Scholar 

  9. 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

    Article  CAS  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. 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

    Article  CAS  Google Scholar 

  12. Kaneko K, Ando H, Ito T, et al.: Protein plugs cause symptoms in patients with choledochal cysts. Am J Gastroenterol 92:1018–1021, 1997

    CAS  PubMed  Google Scholar 

  13. de Caro A, Multigner L, Dagorn JC, Sarles H: The human pancreatic stone protein. Biochimie 70:1209–1214, 1988

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  Google Scholar 

  15. 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

    Article  CAS  Google Scholar 

  16. 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

    Article  CAS  Google Scholar 

  17. Ganong WF: Review of Medical Physiology, 20th ed. New York, McGraw–Hill, 2001

    Google Scholar 

  18. Rinderknecht H: Activation of pancreatic zymogens: Normal activation, premature intrapancreatic activation, protective mechanisms against inappropriate activation. Dig Dis Sci 31:314–321, 1986

    Article  CAS  Google Scholar 

  19. Kimura K, Tsugawa C, Ogawa K, et al.: Choledochal cyst: Etiological considerations and surgical management in 22 cases. Arch Surg 113:159–163, 1978

    Article  CAS  Google Scholar 

  20. 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

    CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

  22. 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

    Article  CAS  Google Scholar 

  23. Davenport M, Stringer MD, Howard ER: Biliary amylase and congenital choledochal dilatation. J Pediatr Surg 30:474–477, 1995

    Article  CAS  Google Scholar 

  24. Samuel M, Spitz L: Choledochal cyst: Varied clinical presentations and long-term results of surgery. Eur J Pediatr Surg 6:78–81, 1996

    Article  CAS  Google Scholar 

  25. 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

    Article  CAS  Google Scholar 

  26. 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

    PubMed  Google Scholar 

  27. 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

    Article  CAS  Google Scholar 

  28. Konok GP, Thompson AG: Pancreatic ductal mucosa as a protective barrier in the pathogenesis of pancreatitis. Am J Surg 117:18–23, 1969

    Article  CAS  Google Scholar 

  29. 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

    Article  CAS  Google Scholar 

  30. Yamasaki S, Miyoshi Y, Komi N: Immunohistochemical studies on enterokinase producing cells in the biliary tract. Jpn J Surg 21:600–605, 1991

    Article  CAS  Google Scholar 

  31. 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)

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Correspondence to Kenitiro Kaneko.

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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

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  • DOI: https://doi.org/10.1007/s10620-004-9599-7

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