Journal of Gastroenterology

, Volume 32, Issue 6, pp 801–807

Carcinoma of the gallbladder and anomalous arrangement of the pancreaticobiliary ductal system: Cell kinetic studies of gallbladder epithelial cells

  • Yang Yang
  • Hideki Fujii
  • Yoshiro Matsumoto
  • Koichi Suzuki
  • Akira Kawaoi
  • Koichi Suda
Liver, Pancreas, and Biliary Tract


Anomalous arrangement of the pancreatic-obiliary ductal system (AAPB), a congenital anomaly defined as a union of the pancreatic and biliary ducts located outside the duodenal wall, is a newly designated disease entity, and is frequently found in adult patients with gallbladder carcinoma (GBX). In the present study, the relationship of AAPB and GBX was investigated. We studied 27 patients with GBX and AAPB, 34 patients with AAPB and without GBX, and as a control group, 56 patients without AAPB (10 with GBX, 24 with cholecystolithiasis, and 22 with normal gallbladder). Tissue sections from cancerous and non-cancerous mucosa of the gallbladder of all of these patients were stained for proliferating cell nuclear antigen (PCNA), Ki-67 nuclear antigen, and bromodeoxyuridine (BrdU). The Ki-67 labeling index (Ki-67-LI), PCNA labeling index (PCNA-LI), and BrdU labeling index (BrdU-LI) of the noncancerous mucosa in the patients with AAPB and/or GBX were significantly higher than those in the patients without GBX and AAPB (P<0.01). These indices of the noncancerous mucosa in the patients with AAPB and GBX were significantly higher than those in the patients with either AAPB or GBX (P<0.05). Cell proliferation in the gallbladder epithelia was accelerated in patients with AAPB. Consequently, AAPB appears to be an important risk factor for the occurrence of GBX.

Key words

anomalous arrangement of pancreatic-obiliary ductal system (AAPB) carcinoma of gallbladder immunohistochemical staining proliferating cell nuclear antigen (PCNA) Ki-67 nuclear antigen bromodeoxyuridine (BrdU) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Babbitt DP. Congenital choledochal cyst: New etiological concept based on anomalous relationships of common bile duct and pancreatic bulb. Ann Radiol 1969;12:231–241.PubMedGoogle Scholar
  2. 2.
    The Japanese Study Group on Pancreaticobiliary Maljunction. Diagnostic criteria of pancreaticobiliary maljunction. J Hep Bil Pancr Surg 1994;1:219–221.CrossRefGoogle Scholar
  3. 3.
    Alonso-Lej F, Rever WB, Pessagno DJ. Congenital choledochal cyst with a report of two and an analysis of 94 cases. Int Abstr Surg 1959;108:1–23.PubMedGoogle Scholar
  4. 4.
    Kimura K, Ohto M, Ino T, et al. Congenital cystic dilatation of the common bile duct. Relationship to anomalous pancreatic biliary ductal union. AJR Am J Roentgenol 1977;128:571–577.PubMedGoogle Scholar
  5. 5.
    Komi N, Takehara J, Kunitomo K. Choledochal cyst: Anomalous arrangement of the pancreaticobiliary ductal system and biliary malignancy. J Gastroenterol Hepatol 1989;4:63–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Kinoshita H, Nagata E, Kobayashi Y, et al. Carcinoma of the gallbladder with an anomalous connection between the choledochus and the pancreatic duct; report of ten cases and review of the literature in Japan. Cancer 1984;54:762–769.PubMedCrossRefGoogle Scholar
  7. 7.
    Matsumoto Y, Uchida K, Honjo I, et al. Congenital cystic dilatation of the common bile duct as a cause of primary bile duct stone. Am J Surg 1977;134:346–352.PubMedCrossRefGoogle Scholar
  8. 8.
    Kimura K, Ohto M, Saisho H, et al. Association of gallbladder carcinoma and anomalous pancreatico-biliary ductal union. Gastroenterology 1985;89:1258–1265.PubMedGoogle Scholar
  9. 9.
    Hasumi A, Sugaya H, Aoki H, et al. Pancreaticobiliary maljunction and biliary duct cancer (in Japanese). J Biliary Tract Pancreas 1995;16:753–757.Google Scholar
  10. 10.
    Suda K, Miyano T, Konuma I, et al. An anomalous pancreaticocholedochal-ductal junction in cases of biliary tract carcinoma. Cancer 1983;52:2083–2088.CrossRefGoogle Scholar
  11. 11.
    Matsumoto Y, Fujii H, Aoyama H, et al. Surgical treatment of primary carcinoma of the gallbladder based on the histologic analysis of 48 surgical specimens. Am J Surg 1992;163:239–245.PubMedCrossRefGoogle Scholar
  12. 12.
    Hanada K, Itoh M, Fujii K, et al. Pathology and cellular kinetics of gallbladder with an anomalous junction of the pancreaticobiliary duct. Am J Gastroenterol 1996;91:1007–1011.PubMedGoogle Scholar
  13. 13.
    Miyachi K, Fritzler MJ, Tan EM. Autoantibodies to a nuclear antigen in proliferating cells. J Immunol 1978;121:2228–2234.PubMedGoogle Scholar
  14. 14.
    Hall PA, Levision DA, Woods AL, et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 1990;162:285–294.PubMedCrossRefGoogle Scholar
  15. 15.
    Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710–1715.PubMedGoogle Scholar
  16. 16.
    Cattoretti G, Becker MHG, Key G, et al. Monoclonal antibodies produced against recombinant parts of the Ki-67 molecule (MIB-1 to 3) stain proliferating cells in formalin-fixed, paraffin-embedded microwave-processed tissues (abstract). Histochem J 1992;24:611.Google Scholar
  17. 17.
    Darmon E, Pincu-Hornstein A, Rosen P. A rapid and simple invitro method for evaluating human colorectal epithelial cell proliferation. Arch Pathol Lab Med 1990;114:855–857.PubMedGoogle Scholar
  18. 18.
    Kozumi I, Kodama T. A case report and the etiology of choledochal cystic dilation (in Japanese). J Tokyo Med Assoc 1916;30:1413–1423.Google Scholar
  19. 19.
    Yotsuyanagi S. Contributions to aetiology and pathogeny of idiopathic cystic dilatation of common bile duct with report of three cases: New aetiologic theory. Gann 1936;30:601–650.Google Scholar
  20. 20.
    Fujita T, Shimada H, Nakagawara G. Cell kinetic study of the gallbladder epithelium with special reference to the pancreaticobiliary maljunction. J Hep Bil Pancr Surg 1944;1:229–235.CrossRefGoogle Scholar
  21. 21.
    Yamaguchi K, Enjoji M. Carcinoma of the gallbladder: A clinicopathology of 103 patients and a newly proposed staging Cancer 1988;62:1425–1432.PubMedCrossRefGoogle Scholar
  22. 22.
    Duarte I, Llamos O, Domke H, et al. Metaplasia and precursor lesions of gallbladder carcinoma: Frequency, distribution and probability of detection in routine histologic samples. Cancer 1933;72:1878–1884.CrossRefGoogle Scholar
  23. 23.
    Irwin ST, Morisson JE. Congenital cyst of common bile duct containing stones and undergoing cancerous change. Br J Surg 1944;32:319–621.CrossRefGoogle Scholar
  24. 24.
    Matsumoto Y, Uchida K, Honjo I, et al. Clinicopathological classification of congenital cystic dilatation of the common bile duct. Am J Surg 1977;134:569–574.PubMedCrossRefGoogle Scholar
  25. 25.
    Funabiki T, Sugie K, Matsubara T, et al. Bile acids and biliary carcinoma in pancreaticobiliary maljunction. Keio J Med 1991;40:118–122.PubMedGoogle Scholar
  26. 26.
    Gratzner HG. Monoclonal antibody to 5-bromo- an 5-introdeoxyuridine: A new reagent for detection of DNA replication. Science 1982;218:475.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Yang Yang
    • 1
    • 2
  • Hideki Fujii
    • 1
    • 2
  • Yoshiro Matsumoto
    • 1
    • 2
  • Koichi Suzuki
    • 1
    • 2
  • Akira Kawaoi
    • 1
    • 2
  • Koichi Suda
    • 1
    • 2
  1. 1.Department of SurgeryYamanashi Medical UniversityNakakoma, YamanashiJapan
  2. 2.Department of PathologyYamanashi Medical UniversityNakakoma, YamanashiJapan

Personalised recommendations