Advertisement

Journal of Gastrointestinal Cancer

, Volume 43, Issue 2, pp 137–147 | Cite as

Risk Factors for Gallbladder Cancer and Cholangiocarcinoma: Similarities, Differences and Updates

  • Tarun RustagiEmail author
  • Constantin A. Dasanu
Review Article

Abstract

Introduction

Far-ranging variation in the incidence of gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in different geographic regions on the globe may reflect the risk factor distribution for these tumors

Methods

The authors give a comprehensive review on the known risk factors for GBC and CCA, and analyze both similarities and differences between the risk factors for the two main types of biliary cancer

Discussion and Conclusion

Leading risk factors for GBC include gallstones, female gender, and advancing age. Primary sclerosing cholangitis, nitrosamine exposure, choledochal cysts, Clonorchis sinensis and Opisthorchis viverrini represent important risk factors for CCA, although a specific risk factor cannot be identified for many patients. While both cancers affect mostly individuals in their sixth decade or older, CCA has a male predominance and GBC—a predilection for females. Although the current level of understanding of the molecular pathogenesis of GBC and CCA at the interface with specific risk factors is significantly lower than for other gastrointestinal malignancies, it continues to evolve and may soon open new avenues for the therapy of biliary cancers.

Keywords

Risk factors Gallbladder Cancer Cholangiocarcinoma Gallstones Liver fluke Cholelithiasis 

Notes

Conflicts of Interest

None

Financial Disclosure

None.

Grant Support

None

References

  1. 1.
    Carriaga MT, Henson DE. Liver, gallbladder, extrahepatic bile ducts, and pancreas. Cancer. 1995;75(1 Suppl):171–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Hamrick Jr RE, Liner FJ, Hastings PR, Cohn Jr I. Primary carcinoma of the gallbladder. Ann Surg. 1982;195(3):270–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Yamaguchi K, Chijiiwa K, Ichimiya H, Sada M, Kawakami K, Nishikata F, et al. Gallbladder carcinoma in the era of laparoscopic cholecystectomy. Arch Surg. 1996;131(9):981–4. discussion 985.PubMedCrossRefGoogle Scholar
  4. 4.
    A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. N Engl J Med. 1991;324(16):1073–8.CrossRefGoogle Scholar
  5. 5.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.PubMedCrossRefGoogle Scholar
  6. 6.
    Diehl AK. Epidemiology of gallbladder cancer: a synthesis of recent data. J Natl Cancer Inst. 1980;65(6):1209–14.PubMedGoogle Scholar
  7. 7.
    Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis. 1994;14(2):109–14.PubMedCrossRefGoogle Scholar
  8. 8.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. CA Cancer J Clin. 2006;56(2):106–30.PubMedCrossRefGoogle Scholar
  9. 9.
    Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33(6):1353–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol. 2004;40(3):472–7.PubMedCrossRefGoogle Scholar
  11. 11.
    West J, Wood H, Logan RF, Quinn M, Aithal GP. Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer. 2006;94(11):1751–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Welzel TM, McGlynn KA, Hsing AW, O’Brien TR, Pfeiffer RM. Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra-and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst. 2006;98(12):873–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol. 2002;37(6):806–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer. 2002;2:10.PubMedCrossRefGoogle Scholar
  15. 15.
    Jepsen P, Vilstrup H, Tarone RE, Friis S, Sorensen HT. Incidence rates of intra-and extrahepatic cholangiocarcinomas in Denmark from 1978 through 2002. J Natl Cancer Inst. 2007;99(11):895–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Rajagopalan V, Daines WP, Grossbard ML, Kozuch P. Gallbladder and biliary tract carcinoma: a comprehensive update, Part 1. Oncology. 2004;18(7):889–96.PubMedGoogle Scholar
  17. 17.
    Shaib YH, El-Serag HB, Davila JA, Morgan R, McGlynn KA. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case–control study. Gastroenterology. 2005;128(3):620–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Chapman RW. Risk factors for biliary tract carcinogenesis. Ann Oncol. 1999;10 Suppl 4:308–11.PubMedCrossRefGoogle Scholar
  19. 19.
    Ben-Menachem T. Risk factors for cholangiocarcinoma. Eur J Gastroenterol Hepatol. 2007;19(8):615–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Lazaridis KN, Gores GJ. Cholangiocarcinoma. Gastroenterology. 2005;128(6):1655–67.PubMedCrossRefGoogle Scholar
  21. 21.
    Welzel TM, Mellemkjaer L, Gloria G, Sakoda LC, Hsing AW, El Ghormli L, et al. Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: a nationwide case–control study. Int J Cancer. 2007;120(3):638–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Hsing AW, Gao YT, Han TQ, Rashid A, Sakoda LC, Wang BS, et al. Gallstones and the risk of biliary tract cancer: a population-based study in China. Br J Cancer. 2007;97(11):1577–82.PubMedCrossRefGoogle Scholar
  23. 23.
    Ahrens W, Timmer A, Vyberg M, Fletcher T, Guenel P, Merler E, et al. Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case–control study. Eur J Gastroenterol Hepatol. 2007;19(8):623–30.PubMedCrossRefGoogle Scholar
  24. 24.
    Donato F, Gelatti U, Tagger A, Favret M, Ribero ML, Callea F, et al. Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case–control study in Italy. Cancer Causes Control. 2001;12(10):959–64.PubMedCrossRefGoogle Scholar
  25. 25.
    Okuda K, Kubo Y, Okazaki N, Arishima T, Hashimoto M. Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases. Cancer. 1977;39(1):232–46.PubMedCrossRefGoogle Scholar
  26. 26.
    Su CH, Shyr YM, Lui WY, P’Eng FK. Hepatolithiasis associated with cholangiocarcinoma. Br J Surg. 1997;84(7):969–73.PubMedCrossRefGoogle Scholar
  27. 27.
    Chijiiwa K, Yamashita H, Yoshida J, Kuroki S, Tanaka M. Current management and long-term prognosis of hepatolithiasis. Arch Surg. 1995;130(2):194–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen MF. Peripheral cholangiocarcinoma (cholangiocellular carcinoma): clinical features, diagnosis and treatment. J Gastroenterol Hepatol. 1999;14(12):1144–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Lee CC, Wu CY, Chen GH. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma? J Gastroenterol Hepatol. 2002;17(9):1015–20.PubMedCrossRefGoogle Scholar
  30. 30.
    Yamamoto K, Tsuchiya R, Ito I, et al. A study of cholangiocarcinoma coexisting with hepatolithiasis. Jpn J Gastroenterol Surg. 1984;17:601.CrossRefGoogle Scholar
  31. 31.
    Kinami Y, Noto H, Miyazaki I, et al. A study of hepatolithiasis associated with cholangiocarcinoma. Acta Hepatol Jpn. 1978;19:573.CrossRefGoogle Scholar
  32. 32.
    Paraskevopoulos JA, Dennison AR, Ross B, Johnson AG. Primary carcinoma of the gallbladder: a 10-year experience. Ann R Coll Surg Engl. 1992;74(3):222–4.PubMedGoogle Scholar
  33. 33.
    Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118(7):1591–602.PubMedCrossRefGoogle Scholar
  34. 34.
    Maringhini A, Moreau JA, Melton 3rd LJ, Hench VS, Zinsmeister AR, DiMagno EP. Gallstones, gallbladder cancer, and other gastrointestinal malignancies. An epidemiologic study in Rochester, Minnesota. Ann Intern Med. 1987;107(1):30–5.PubMedGoogle Scholar
  35. 35.
    Zatonski WA, Lowenfels AB, Boyle P, Maisonneuve P, de Mesquita HB Bueno, Ghadirian P, et al. Epidemiologic aspects of gallbladder cancer: a case–control study of the SEARCH Program of the International Agency for Research on Cancer. J Natl Cancer Inst. 1997;89(15):1132–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Ghadirian P, Simard A, Baillargeon J. A population-based case–control study of cancer of the bile ducts and gallbladder in Quebec, Canada. Rev Épidémiol Santé Publique. 1993;41(2):107–12.PubMedGoogle Scholar
  37. 37.
    Chow WH, Johansen C, Gridley G, Mellemkjaer L, Olsen JH, Fraumeni Jr JF. Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas. Br J Cancer. 1999;79(3–4):640–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol. 2003;4(3):167–76.PubMedCrossRefGoogle Scholar
  39. 39.
    Glenn F, Hays DM. The scope of radical surgery in the treatment of malignant tumors of the extrahepatic biliary tract. Surg Gynecol Obstet. 1954;99(5):529–41.PubMedGoogle Scholar
  40. 40.
    Sahani D, Prasad SR, Tannabe KK, Hahn PF, Mueller PR, Saini S. Thorotrast-induced cholangiocarcinoma: case report. Abdom Imaging. 2003;28(1):72–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Ishikawa Y, Wada I, Fukumoto M. Alpha-particle carcinogenesis in Thorotrast patients: epidemiology, dosimetry, pathology, and molecular analysis. J Environ Pathol Toxicol Oncol. 2001;20(4):311–5.PubMedGoogle Scholar
  42. 42.
    Taylor GN, Lloyd RD, Mays CW, Angus W, Miller SC, Shabestari L, et al. Plutonium- or americium-induced liver tumors and lesions in beagles. Health Phys. 1991;61(3):337–47.PubMedCrossRefGoogle Scholar
  43. 43.
    Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51(6):349–64.PubMedCrossRefGoogle Scholar
  44. 44.
    Pandey M, Shukla VK. Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. Eur J Cancer Prev. 2003;12(4):269–72.PubMedCrossRefGoogle Scholar
  45. 45.
    Darby SC, Whitley E, Howe GR, Hutchings SJ, Kusiak RA, Lubin JH, et al. Radon and cancers other than lung cancer in underground miners: a collaborative analysis of 11 studies. J Natl Cancer Inst. 1995;87(5):378–84.PubMedCrossRefGoogle Scholar
  46. 46.
    Ellis EF, Gordon PR, Gottlieb LS. Oral contraceptives and cholangiocarcinoma. Lancet. 1978;1(8057):207.PubMedCrossRefGoogle Scholar
  47. 47.
    Broden G, Bengtsson L. Biliary carcinoma associated with methyldopa therapy. Acta Chir Scand Suppl. 1980;500:7–12.PubMedGoogle Scholar
  48. 48.
    Lowenfels AB, Norman J. Isoniazid and bile duct cancer. JAMA. 1978;240(5):434–5.PubMedCrossRefGoogle Scholar
  49. 49.
    Milne R, Vessey M. The association of oral contraception with kidney cancer, colon cancer, gallbladder cancer (including extrahepatic bile duct cancer) and pituitary tumours. Contraception. 1991;43(6):667–93.PubMedCrossRefGoogle Scholar
  50. 50.
    The WHO Collaborative Study of neoplasia and steroid contraceptives. Combined oral contraceptives and gallbladder cancer. Int J Epidemiol. 1989;18(2):309–14.CrossRefGoogle Scholar
  51. 51.
    Zhou YM, Yin ZF, Yang JM, Li B, Shao WY, Xu F, et al. Risk factors for intrahepatic cholangiocarcinoma: a case–control study in China. World J Gastroenterol. 2008;14(4):632–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Grainge MJ, West J, Solaymani-Dodaran M, Aithal GP, Card TR. The antecedents of biliary cancer: a primary care case–control study in the United Kingdom. Br J Cancer. 2009;100(1):178–80.PubMedCrossRefGoogle Scholar
  53. 53.
    Welzel TM, Graubard BI, El-Serag HB, Shaib YH, Hsing AW, Davila JA, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case–control study. Clin Gastroenterol Hepatol. 2007;5(10):1221–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Shaib YH, El-Serag HB, Nooka AK, Thomas M, Brown TD, Patt YZ, et al. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a hospital-based case–control study. Am J Gastroenterol. 2007;102(5):1016–21.PubMedCrossRefGoogle Scholar
  55. 55.
    Mitacek EJ, Brunnemann KD, Hoffmann D, Limsila T, Suttajit M, Martin N, et al. Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand. Carcinogenesis. 1999;20(1):133–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Hardell L, Bengtsson NO, Jonsson U, Eriksson S, Larsson LG. Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria—an epidemiological investigation. Br J Cancer. 1984;50(3):389–97.PubMedCrossRefGoogle Scholar
  57. 57.
    Sawanyawisuth K. Genes and cholangiocarcinoma. Southeast Asian J Trop Med Public Health. 2009;40(4):701–12.PubMedGoogle Scholar
  58. 58.
    Konstantinidis IT, Deshpande V, Genevay M, Berger D, Fernandez-del Castillo C, Tanabe KK, et al. Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: a single-institution experience. Arch Surg. 2009;144(5):441–7. discussion 447.PubMedCrossRefGoogle Scholar
  59. 59.
    Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, et al. Gallbladder cancer (GBC): 10-year experience at memorial Sloan-Kettering cancer centre (MSKCC). J Surg Oncol. 2008;98(7):485–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Scott TE, Carroll M, Cogliano FD, Smith BF, Lamorte WW. A case–control assessment of risk factors for gallbladder carcinoma. Dig Dis Sci. 1999;44(8):1619–25.PubMedCrossRefGoogle Scholar
  61. 61.
    Henson DE, Albores-Saavedra J, Corle D. Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates. Cancer. 1992;70(6):1498–501.PubMedCrossRefGoogle Scholar
  62. 62.
    Strom BL, Soloway RD, Rios-Dalenz JL, Rodriguez-Martinez HA, West SL, Kinman JL, et al. Risk factors for gallbladder cancer. An international collaborative case–control study. Cancer. 1995;76(10):1747–56.PubMedCrossRefGoogle Scholar
  63. 63.
    Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4(9):695–706.PubMedCrossRefGoogle Scholar
  64. 64.
    Miquel JF, Covarrubias C, Villaroel L, Mingrone G, Greco AV, Puglielli L, et al. Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris. Gastroenterology. 1998;115(4):937–46.PubMedCrossRefGoogle Scholar
  65. 65.
    Watanapa P, Watanapa WB. Liver fluke-associated cholangiocarcinoma. Br J Surg. 2002;89(8):962–70.PubMedCrossRefGoogle Scholar
  66. 66.
    Watanapa P. Cholangiocarcinoma in patients with opisthorchiasis. Br J Surg. 1996;83(8):1062–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Shin HR, Lee CU, Park HJ, Seol SY, Chung JM, Choi HC, et al. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case–control study in Pusan, Korea. Int J Epidemiol. 1996;25(5):933–40.PubMedCrossRefGoogle Scholar
  68. 68.
    Kim YI. Liver carcinoma and liver fluke infection. Arzneimittelforschung. 1984;34(9B):1121–6.PubMedGoogle Scholar
  69. 69.
    Kurathong S, Lerdverasirikul P, Wongpaitoon V, Pramoolsinsap C, Kanjanapitak A, Varavithya W, et al. Opisthorchis viverrini infection and cholangiocarcinoma. A prospective, case–controlled study. Gastroenterology. 1985;89(1):151–6.PubMedGoogle Scholar
  70. 70.
    Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin DM. Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand. Trop Med Int Health. 2004;9(5):588–94.PubMedCrossRefGoogle Scholar
  71. 71.
    Lim MK, Ju YH, Franceschi S, Oh JK, Kong HJ, Hwang SS, et al. Clonorchis sinensis infection and increasing risk of cholangiocarcinoma in the Republic of Korea. Am J Trop Med Hyg. 2006;75(1):93–6.PubMedGoogle Scholar
  72. 72.
    Lun ZR, Gasser RB, Lai DH, Li AX, Zhu XQ, Yu XB, et al. Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis. 2005;5(1):31–41.PubMedCrossRefGoogle Scholar
  73. 73.
    Parkin DM, Srivatanakul P, Khlat M, Chenvidhya D, Chotiwan P, Insiripong S, et al. Liver cancer in Thailand. I. A case–control study of cholangiocarcinoma. Int J Cancer. 1991;48(3):323–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Haswell-Elkins MR, Mairiang E, Mairiang P, Chaiyakum J, Chamadol N, Loapaiboon V, et al. Cross-sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand. Int J Cancer. 1994;59(4):505–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Honjo S, Srivatanakul P, Sriplung H, Kikukawa H, Hanai S, Uchida K, et al. Genetic and environmental determinants of risk for cholangiocarcinoma via Opisthorchis viverrini in a densely infested area in Nakhon Phanom, northeast Thailand. Int J Cancer. 2005;117(5):854–60.PubMedCrossRefGoogle Scholar
  76. 76.
    Choi D, Lim JH, Lee KT, Lee JK, Choi SH, Heo JS, et al. Cholangiocarcinoma and Clonorchis sinensis infection: a case–control study in Korea. J Hepatol. 2006;44(6):1066–73.PubMedCrossRefGoogle Scholar
  77. 77.
    Lee TY, Lee SS, Jung SW, Jeon SH, Yun SC, Oh HC, et al. Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case–control study. Am J Gastroenterol. 2008;103(7):1716–20.PubMedCrossRefGoogle Scholar
  78. 78.
    Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang YY, et al. Epidemiology of cholangiocarcinoma: an update focusing on risk factors. Cancer Sci. 2010 Mar;101(3):579–85.PubMedCrossRefGoogle Scholar
  79. 79.
    Nagaoka T, Ohkawa S, Ito Y, Tamai S, Tarao K, Sugimasa Y, et al. A case of minute cholangiocellular carcinoma which was found in the follow-up periods of liver cirrhosis and was indistinguishable from hepatocellular carcinoma on hepatic angiography. Nippon Shokakibyo Gakkai Zasshi. 1991;88(6):1369–74.PubMedGoogle Scholar
  80. 80.
    Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, et al. Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis. Cancer. 2000;88(11):2471–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Lu H, Ye MQ, Thung SN, Dash S, Gerber MA. Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients. Chin Med J. 2000;113(12):1138–41.PubMedGoogle Scholar
  82. 82.
    Hsing AW, Zhang M, Rashid A, McGlynn KA, Wang BS, Niwa S, et al. Hepatitis B and C virus infection and the risk of biliary tract cancer: a population-based study in China. Int J Cancer. 2008;122(8):1849–53.PubMedCrossRefGoogle Scholar
  83. 83.
    Liu XF, Zou SQ, Qiu FZ. Pathogenesis of cholangiocarcinoma in the porta hepatis and infection of hepatitis virus. Hepatobiliary Pancreat Dis Int. 2003;2(2):285–9.PubMedGoogle Scholar
  84. 84.
    Okuda K, Nakanuma Y, Miyazaki M. Cholangiocarcinoma: recent progress. Part 1: epidemiology and etiology. J Gastroenterol Hepatol. 2002;17(10):1049–55.PubMedCrossRefGoogle Scholar
  85. 85.
    Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, et al. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. Cancer Sci. 2004;95(7):592–5.PubMedCrossRefGoogle Scholar
  86. 86.
    El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, et al. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. Hepatology. 2009;49(1):116–23.PubMedCrossRefGoogle Scholar
  87. 87.
    Lee CH, Chang CJ, Lin YJ, Yeh CN, Chen MF, Hsieh SY. Viral hepatitis-associated intrahepatic cholangiocarcinoma shares common disease processes with hepatocellular carcinoma. Br J Cancer. 2009;100(11):1765–70.PubMedCrossRefGoogle Scholar
  88. 88.
    Nath G, Singh H, Shukla VK. Chronic typhoid carriage and carcinoma of the gallbladder. Eur J Cancer Prev. 1997;6(6):557–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Shukla VK, Singh H, Pandey M, Upadhyay SK, Nath G. Carcinoma of the gallbladder—is it a sequel of typhoid? Dig Dis Sci. 2000;45(5):900–3.PubMedCrossRefGoogle Scholar
  90. 90.
    Dutta U, Garg PK, Kumar R, Tandon RK. Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder. Am J Gastroenterol. 2000;95(3):784–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Matsukura N, Yokomuro S, Yamada S, Tajiri T, Sundo T, Hadama T, et al. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res. 2002;93(7):842–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Metz DC. Helicobacter colonization of the biliary tree: commensal, pathogen, or spurious finding? Am J Gastroenterol. 1998;93(10):1996–8.PubMedGoogle Scholar
  93. 93.
    Fukuda K, Kuroki T, Tajima Y, Tsuneoka N, Kitajima T, Matsuzaki S, et al. Comparative analysis of Helicobacter DNAs and biliary pathology in patients with and without hepatobiliary cancer. Carcinogenesis. 2002;23(11):1927–31.PubMedCrossRefGoogle Scholar
  94. 94.
    Kobayashi T, Harada K, Miwa K, Nakanuma Y. Helicobacter genus DNA fragments are commonly detectable in bile from patients with extrahepatic biliary diseases and associated with their pathogenesis. Dig Dis Sci. 2005;50(5):862–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Murata H, Tsuji S, Tsujii M, Fu HY, Tanimura H, Tsujimoto M, et al. Helicobacter bilis infection in biliary tract cancer. Aliment Pharmacol Ther. 2004;20 Suppl 1:90–4.PubMedCrossRefGoogle Scholar
  96. 96.
    Roa I, Ibacache G, Carvallo J, Melo A, Araya J, De Aretxabala X, et al. Microbiological study of gallbladder bile in a high risk zone for gallbladder cancer. Rev Med Chil. 1999;127(9):1049–55.PubMedGoogle Scholar
  97. 97.
    Lee SS, Kim MH, Lee SK, Jang SJ, Song MH, Kim KP, et al. Clinicopathologic review of 58 patients with biliary papillomatosis. Cancer. 2004;100(4):783–93.PubMedCrossRefGoogle Scholar
  98. 98.
    Taguchi J, Yasunaga M, Kojiro M, Arita T, Nakayama T, Simokobe T. Intrahepatic and extrahepatic biliary papillomatosis. Arch Pathol Lab Med. 1993;117(9):944–7.PubMedGoogle Scholar
  99. 99.
    Wistuba II, Miquel JF, Gazdar AF, Albores-Saavedra J. Gallbladder adenomas have molecular abnormalities different from those present in gallbladder carcinomas. Hum Pathol. 1999;30(1):21–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Okamoto M, Okamoto H, Kitahara F, Kobayashi K, Karikome K, Miura K, et al. Ultrasonographic evidence of association of polyps and stones with gallbladder cancer. Am J Gastroenterol. 1999;94(2):446–50.PubMedCrossRefGoogle Scholar
  101. 101.
    Voyles CR, Smadja C, Shands WC, Blumgart LH. Carcinoma in choledochal cysts. Age-related incidence. Arch Surg. 1983;118(8):986–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Song HK, Kim MH, Myung SJ, Lee SK, Kim HJ, Yoo KS, et al. Choledochal cyst associated the with anomalous union of pancreaticobiliary duct (AUPBD) has a more grave clinical course than choledochal cyst alone. Korean J Intern Med. 1999;14(2):1–8.PubMedGoogle Scholar
  103. 103.
    Lipsett PA, Pitt HA, Colombani PM, Boitnott JK, Cameron JL. Choledochal cyst disease. A changing pattern of presentation. Ann Surg. 1994;220(5):644–52.PubMedCrossRefGoogle Scholar
  104. 104.
    Scott J, Shousha S, Thomas HC, Sherlock S. Bile duct carcinoma: a late complication of congenital hepatic fibrosis. Case report and review of literature. Am J Gastroenterol. 1980;73(2):113–9.PubMedGoogle Scholar
  105. 105.
    Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet. 2005;366(9493):1303–14.PubMedCrossRefGoogle Scholar
  106. 106.
    Pisano G, Donlon JB, Platell C, Hall JC. Cholangiocarcinoma in a type III choledochal cyst. Aust N Z J Surg. 1991;61(11):855–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Kale IT, Kuzu MA. Porta choledochal fistula: an unusual complication of a cholangiocarcinoma arising from a type I choledochal cyst. Eur J Surg Oncol. 1997;23(2):188–9.PubMedGoogle Scholar
  108. 108.
    Bova JG, Dempsher CJ, Sepulveda G. Cholangiocarcinoma associated with a type 2 choledochal cyst. Gastrointest Radiol. 1983;8(1):41–3.PubMedCrossRefGoogle Scholar
  109. 109.
    Robertson JF, Raine PA. Choledochal cyst: a 33-year review. Br J Surg. 1988;75(8):799–801.PubMedCrossRefGoogle Scholar
  110. 110.
    de Vries JS, de Vries S, Aronson DC, Bosman DK, Rauws EA, Bosma A, et al. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani’s classification. J Pediatr Surg. 2002;37(11):1568–73.PubMedCrossRefGoogle Scholar
  111. 111.
    Ohtsuka T, Inoue K, Ohuchida J, Nabae T, Takahata S, Niiyama H, et al. Carcinoma arising in choledochocele. Endoscopy. 2001;33(7):614–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc. 2003;57(4):541–5.PubMedCrossRefGoogle Scholar
  113. 113.
    Chijiiwa K, Kimura H, Tanaka M. Malignant potential of the gallbladder in patients with anomalous pancreaticobiliary ductal junction. The difference in risk between patients with and without choledochal cyst. Int Surg. 1995;80(1):61–4.PubMedGoogle Scholar
  114. 114.
    Funabiki T, Matsubara T, Ochiai M, Marugami Y, Sakurai Y, Hasegawa S, et al. Surgical strategy for patients with pancreaticobiliary maljunction without choledocal dilatation. Keio J Med. 1997;46(4):169–72.PubMedCrossRefGoogle Scholar
  115. 115.
    Elnemr A, Ohta T, Kayahara M, Kitagawa H, Yoshimoto K, Tani T, et al. Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer. Hepatogastroenterology. 2001;48(38):382–6.PubMedGoogle Scholar
  116. 116.
    Sugiyama M, Atomi Y. Anomalous pancreaticobiliary junction without congenital choledochal cyst. Br J Surg. 1998;85(7):911–6.PubMedCrossRefGoogle Scholar
  117. 117.
    de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341(18):1368–78.PubMedCrossRefGoogle Scholar
  118. 118.
    Claessen MM, Vleggaar FP, Tytgat KM, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 2009;50(1):158–64.PubMedCrossRefGoogle Scholar
  119. 119.
    Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Loof L, Danielsson A, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002;36(3):321–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99(3):523–6.PubMedCrossRefGoogle Scholar
  121. 121.
    de Groen PC. Cholangiocarcinoma in primary sclerosing cholangitis: who is at risk and how do we screen? Hepatology. 2000;31(1):247–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Bergquist A, Glaumann H, Persson B, Broome U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case–control study. Hepatology. 1998;27(2):311–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33.PubMedCrossRefGoogle Scholar
  124. 124.
    Wiesner RH. Current concepts in primary sclerosing cholangitis. Mayo Clin Proc. 1994;69(10):969–82.PubMedGoogle Scholar
  125. 125.
    Rosen CB, Nagorney DM, Wiesner RH, Coffey Jr RJ, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991;213(1):21–5.PubMedCrossRefGoogle Scholar
  126. 126.
    Broome U, Olsson R, Loof L, Bodemar G, Hultcrantz R, Danielsson A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38(4):610–5.PubMedCrossRefGoogle Scholar
  127. 127.
    Chalasani N, Baluyut A, Ismail A, Zaman A, Sood G, Ghalib R, et al. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case–control study. Hepatology. 2000;31(1):7–11.PubMedCrossRefGoogle Scholar
  128. 128.
    Stauffer MH, Sauer WG, Dearing WH, Baggenstoss AH. The spectrum of cholestatic hepatic disease. JAMA. 1965;191:829–37.PubMedCrossRefGoogle Scholar
  129. 129.
    Ham JM. Tumors of biliary epithelium and ulcerative colitis. Ann Surg. 1968;168(6):1088–93.PubMedCrossRefGoogle Scholar
  130. 130.
    Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. Scand J Gastroenterol. 1997;32(10):1042–5.PubMedCrossRefGoogle Scholar
  131. 131.
    Yachimski P, Pratt DS. Cholangiocarcinoma: natural history, treatment, and strategies for surveillance in high-risk patients. J Clin Gastroenterol. 2008;42(2):178–90.PubMedCrossRefGoogle Scholar
  132. 132.
    Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a meta-analysis. Br J Cancer. 2007;96(9):1457–61.PubMedGoogle Scholar
  133. 133.
    Rai A, Mohapatra SC, Shukla HS. A review of association of dietary factors in gallbladder cancer. Indian J Cancer. 2004;41(4):147–51.PubMedGoogle Scholar
  134. 134.
    Pandey M, Shukla VK. Diet and gallbladder cancer: a case–control study. Eur J Cancer Prev. 2002;11(4):365–8.PubMedCrossRefGoogle Scholar
  135. 135.
    Serra I, Yamamoto M, Calvo A, Cavada G, Baez S, Endoh K, et al. Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Int J Cancer. 2002;102(4):407–11.PubMedCrossRefGoogle Scholar
  136. 136.
    Rai A, Mohapatra SC, Shukla HS. Correlates between vegetable consumption and gallbladder cancer. Eur J Cancer Prev. 2006;15(2):134–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Sheth S, Bedford A, Chopra S. Primary gallbladder cancer: recognition of risk factors and the role of prophylactic cholecystectomy. Am J Gastroenterol. 2000;95(6):1402–10.PubMedCrossRefGoogle Scholar
  138. 138.
    Liang HP, Cheung WK, Su FH, Chu FY. Porcelain gallbladder. J Am Geriatr Soc. 2008;56(5):960–1.PubMedCrossRefGoogle Scholar
  139. 139.
    Towfigh S, McFadden DW, Cortina GR, Thompson Jr JE, Tompkins RK, Chandler C, et al. Porcelain gallbladder is not associated with gallbladder carcinoma. Am Surg. 2001;67(1):7–10.PubMedGoogle Scholar
  140. 140.
    Stephen AE, Berger DL. Carcinoma in the porcelain gallbladder: a relationship revisited. Surgery. 2001;129(6):699–703.PubMedCrossRefGoogle Scholar
  141. 141.
    Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, et al. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology. 1998;28(4):921–5.PubMedCrossRefGoogle Scholar
  142. 142.
    Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst. 1997;89(18):1360–5.PubMedCrossRefGoogle Scholar
  143. 143.
    Adami HO, Chow WH, Nyren O, Berne C, Linet MS, Ekbom A, et al. Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst. 1996;88(20):1472–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Wistuba II, Sugio K, Hung J, Kishimoto Y, Virmani AK, Roa I, et al. Allele-specific mutations involved in the pathogenesis of endemic gallbladder carcinoma in Chile. Cancer Res. 1995;55(12):2511–5.PubMedGoogle Scholar
  145. 145.
    Wistuba II, Gazdar AF, Roa I, Albores-Saavedra J. p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study. Hum Pathol. 1996;27(4):360–5.PubMedCrossRefGoogle Scholar
  146. 146.
    Masuhara S, Kasuya K, Aoki T, Yoshimatsu A, Tsuchida A, Koyanagi Y. Relation between K-ras codon 12 mutation and p53 protein overexpression in gallbladder cancer and biliary ductal epithelia in patients with pancreaticobiliary maljunction. J Hepatobiliary Pancreat Surg. 2000;7(2):198–205.PubMedCrossRefGoogle Scholar
  147. 147.
    Hidaka E, Yanagisawa A, Seki M, Takano K, Setoguchi T, Kato Y. High frequency of K-ras mutations in biliary duct carcinomas of cases with a long common channel in the papilla of Vater. Cancer Res. 2000;60(3):522–4.PubMedGoogle Scholar
  148. 148.
    Hanada K, Tsuchida A, Iwao T, Eguchi N, Sasaki T, Morinaka K, et al. Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct. Am J Gastroenterol. 1999;94(6):1638–42.PubMedCrossRefGoogle Scholar
  149. 149.
    Isa T, Tomita S, Nakachi A, Miyazato H, Shimoji H, Kusano T, et al. Analysis of microsatellite instability, K-ras gene mutation and p53 protein overexpression in intrahepatic cholangiocarcinoma. Hepatogastroenterology. 2002;49(45):604–8.PubMedGoogle Scholar
  150. 150.
    Ohashi K, Nakajima Y, Kanehiro H, Tsutsumi M, Taki J, Aomatsu Y, et al. Ki-ras mutations and p53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology. 1995;109(5):1612–7.PubMedCrossRefGoogle Scholar
  151. 151.
    Terada T, Nakanuma Y, Sirica AE. Immunohistochemical demonstration of MET overexpression in human intrahepatic cholangiocarcinoma and in hepatolithiasis. Hum Pathol. 1998;29(2):175–80.PubMedCrossRefGoogle Scholar
  152. 152.
    Aishima SI, Taguchi KI, Sugimachi K, Shimada M, Tsuneyoshi M. c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma. Histopathology. 2002;40(3):269–78.PubMedCrossRefGoogle Scholar
  153. 153.
    Tannapfel A, Weinans L, Geissler F, Schutz A, Katalinic A, Kockerling F, et al. Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver. Dig Dis Sci. 2000;45(2):317–24.PubMedCrossRefGoogle Scholar
  154. 154.
    Diamantis I, Karamitopoulou E, Perentes E, Zimmermann A. p53 protein immunoreactivity in extrahepatic bile duct and gallbladder cancer: correlation with tumor grade and survival. Hepatology. 1995;22(3):774–9.PubMedCrossRefGoogle Scholar
  155. 155.
    Ahrendt SA, Rashid A, Chow JT, Eisenberger CF, Pitt HA, Sidransky D. p53 overexpression and K-ras gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. J Hepatobiliary Pancreat Surg. 2000;7(4):426–31.PubMedCrossRefGoogle Scholar
  156. 156.
    Suto T, Sugai T, Nakamura S, Funato O, Nitta H, Sasaki R, et al. Assessment of the expression of p53, MIB-1 (Ki-67 antigen), and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic bile duct. Cancer. 1998;82(1):86–95.PubMedCrossRefGoogle Scholar
  157. 157.
    Rizzi PM, Ryder SD, Portmann B, Ramage JK, Naoumov NV, Williams R. p53 Protein overexpression in cholangiocarcinoma arising in primary sclerosing cholangitis. Gut. 1996;38(2):265–8.PubMedCrossRefGoogle Scholar
  158. 158.
    Nehls O, Gregor M, Klump B. Serum and bile markers for cholangiocarcinoma. Semin Liver Dis. 2004;24(2):139–54.PubMedCrossRefGoogle Scholar
  159. 159.
    Tannapfel A, Benicke M, Katalinic A, Uhlmann D, Kockerling F, Hauss J, et al. Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver. Gut. 2000;47(5):721–7.PubMedCrossRefGoogle Scholar
  160. 160.
    Taniai M, Higuchi H, Burgart LJ, Gores GJ. p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma. Gastroenterology. 2002;123(4):1090–8.PubMedCrossRefGoogle Scholar
  161. 161.
    Momoi H, Okabe H, Kamikawa T, Satoh S, Ikai I, Yamamoto M, et al. Comprehensive allelotyping of human intrahepatic cholangiocarcinoma. Clin Cancer Res. 2001;7(9):2648–55.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of ConnecticutFarmingtonUSA
  2. 2.Division of Hematology and OncologySaint Francis Hospital and Medical CenterHartfordUSA

Personalised recommendations