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Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978–2003

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Abstract

Patients with inflammatory bowel disease (IBD) are at increased risk of cholangiocarcinoma (CC), but quantitative data are scant. Furthermore, little is known about the impact of IBD on CC occurrence and prognosis. Based on nationwide population-based registries we compared the incidence and survival of CC patients with and without IBD from 1978 to 2003. We used the National Registry of Patients and the Danish Cancer Registry to identify patients with IBD and CC. From the Civil Registration System we identified population controls. We calculated incidence rates, incidence rate ratios (compared with population controls), and absolute cumulative risks. We also computed median survival in CC patients with and without IBD. 2,725 CC patients were identified. The incidence of CC among the 41,280 IBD patients was 7.6 per 100,000 person years compared with 1.9 per 100,000 among the 412,796 population controls (four-fold increased risk). The 10 year cumulative risk of CC in IBD patients was 0.07%. Sub analyses showed that the increased risk of CC was more pronounced in male IBD patients and in patients with ulcerative colitis. We found a decreasing CC incidence in IBD patients over calendar time. CC patients with IBD were, on average, 15 years younger at cancer diagnosis than IBD-free CC patients, and median survival was 1 month in both groups. In conclusion, the absolute risk of CC in IBD patients was low and the CC incidence decreased over calendar time. The prognosis was equally grave, regardless of the presence of IBD.

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Abbreviations

CC:

Cholangiocarcinoma

CD:

Crohn’s disease

DCR:

Danish Cancer Registry

IBD:

Inflammatory bowel disease

ICD:

International Classification of Diseases

MRR:

Mortality rate ratio

NRP:

National Registry of Patients

UC:

Ulcerative colitis

References

  1. 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;99:895–7.

    Article  PubMed  Google Scholar 

  2. 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;37:806–13.

    Article  PubMed  Google Scholar 

  3. Liu XF, Zhou XT, Zou SQ. An analysis of 680 cases of cholangiocarcinoma from 8 hospitals. Hepatobiliary Pancreat Dis Int. 2005;4:585–8.

    PubMed  Google Scholar 

  4. Weber SM, Jarnagin WR, Klimstra D, DeMatteo RP, Fong Y, Blumgart LH. Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes. J Am Coll Surg. 2001;193:384–91.

    Article  PubMed  CAS  Google Scholar 

  5. Mir-Madjlessi SH, Farmer RG, Sivak MV Jr. Bile duct carcinoma in patients with ulcerative colitis. Relationship to sclerosing cholangitis: report of six cases and review of the literature. Dig Dis Sci. 1987;32:145–54.

    Article  PubMed  CAS  Google Scholar 

  6. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer. 2002;2:10.

    Article  PubMed  Google Scholar 

  7. Klingenberg-Noftz RD, Homann N, Bos I, Bruch HP, Ludwig D. Simultaneous detection of synchronous colonic and biliary carcinoma by abdominal ultrasonography in two patients with ulcerative colitis. Dig Dis Sci. 2004;49:1922–9.

    Article  PubMed  CAS  Google Scholar 

  8. Choi PM, Nugent FW, Zelig MP, Munson JL, Schoetz DJ Jr. Cholangiocarcinoma and crohn’s disease. Dig Dis Sci. 1994;39:667–70.

    Article  PubMed  CAS  Google Scholar 

  9. Chong VF, Heng A. Cholangiocarcinoma complicating ulcerative colitis. Ann Acad Med Singapore. 1993;22:798–801.

    PubMed  CAS  Google Scholar 

  10. Haworth AC, Manley PN, Groll A, Pace R. Bile duct carcinoma and biliary tract dysplasia in chronic ulcerative colitis. Arch Pathol Lab Med. 1989;113:434–6.

    PubMed  CAS  Google Scholar 

  11. Van SW, Fevery J, Vandenbrande P, Desmet V, Ponette E, Kerremans R, et al. Ulcerative colitis, primary sclerosing cholangitis, bile duct carcinoma, and generalized sarcoidosis. Report of a unique association. J Clin Gastroenterol. 1987;9:574–9.

    Google Scholar 

  12. Berman MD, Falchuk KR, Trey C. Carcinoma of the biliary tree complicating crohn’s disease. Dig Dis Sci. 1980;25:795–7.

    Article  PubMed  CAS  Google Scholar 

  13. Wee A, Ludwig J, Coffey RJ Jr, LaRusso NF, Wiesner RH. Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hum Pathol. 1985;16:719–26.

    Article  PubMed  CAS  Google Scholar 

  14. Krause JR, Ayuyang HQ, Ellis LD. Occurrence of three cases of carcinoma in individuals with crohn’s disease treated with metronidazole. Am J Gastroenterol. 1985;80:978–82.

    PubMed  CAS  Google Scholar 

  15. Williams SM, Harned RK. Bile duct carcinoma associated with chronic ulcerative colitis. Dis Colon Rectum. 1981;24:42–4.

    Article  PubMed  CAS  Google Scholar 

  16. Akwari OE, Van Heerden JA, Foulk WT, Baggenstoss AH. Cancer of the bile ducts associated with ulcerative colitis. Ann Surg. 1975;181:303–9.

    Article  PubMed  CAS  Google Scholar 

  17. Mellemkjaer L, Olsen JH, Frisch M, Johansen C, Gridley G, McLaughlin JK. Cancer in patients with ulcerative colitis. Int J Cancer. 1995;60:330–3.

    Article  PubMed  CAS  Google Scholar 

  18. Broome U, Glaumann H, Hellers G, Nilsson B, Sorstad J, Hultcrantz R. Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm. Gut. 1994;35:84–9.

    Article  PubMed  CAS  Google Scholar 

  19. 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;128:620–6.

    Article  PubMed  Google Scholar 

  20. Mellemkjaer L, Johansen C, Gridley G, Linet MS, Kjaer SK, Olsen JH. Crohn’s disease and cancer risk (Denmark). Cancer Causes Control. 2000;11:145–50.

    Article  PubMed  CAS  Google Scholar 

  21. Broome U, Lofberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology. 1995;22:1404–8.

    PubMed  CAS  Google Scholar 

  22. Persson PG, Karlen P, Bernell O, Leijonmarck CE, Brostrom O, Ahlbom A, et al. Crohn’s disease and cancer: a population-based cohort study. Gastroenterology. 1994;107:1675–9.

    PubMed  CAS  Google Scholar 

  23. Ekbom A, Helmick C, Zack M, Adami HO. Extracolonic malignancies in inflammatory bowel disease. Cancer. 1991;67:2015–9.

    Article  PubMed  CAS  Google Scholar 

  24. Welzel TM, Mellemkjaer L, Gloria G, Sakoda LC, Hsing AW, Ghormli LE, et al. Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: a nationwide case-control study. Int J Cancer. 2007;120:638–41.

    Article  PubMed  CAS  Google Scholar 

  25. Schrumpf E, Fausa O, Elgjo K, Kolmannskog F. Hepatobiliary complications of inflammatory bowel disease. Semin Liver Dis. 1988;8:201–9.

    Article  PubMed  CAS  Google Scholar 

  26. Jacobsen BA, Fallingborg J, Rasmussen HH, Nielsen KR, Drewes AM, Puho E, et al. Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a population-based study, 1978–2002. Eur J Gastroenterol Hepatol. 2006;18:601–6.

    Article  PubMed  Google Scholar 

  27. 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;32:1042–5.

    Article  PubMed  CAS  Google Scholar 

  28. Frank L. Epidemiology. When an entire country is a cohort. Science. 2000;287:2398–9.

    Article  PubMed  CAS  Google Scholar 

  29. Danish National Board of Health. 8th & 10th Revision of the World Health Organisations Classification of Diseases. Copenhagen: National Board of Health; 1986.

  30. Storm HH, Michelsen EV, Clemmensen IH, Pihl J. The Danish cancer registry–history, content, quality and use. Dan Med Bull. 1997;44:535–9.

    PubMed  CAS  Google Scholar 

  31. 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;98:873–5.

    Article  PubMed  Google Scholar 

  32. Jensen AB, Larsen M, Gislum M, Skriver MV, Jepsen P, Norgaard B, et al. Survival after colorectal cancer in patients with ulcerative colitis: a nationwide population-based Danish study. Am J Gastroenterol. 2006;101:1283–7.

    Article  PubMed  Google Scholar 

  33. Larsen M, Mose H, Gislum M, Skriver MV, Jepsen P, Norgard B, et al. Survival after colorectal cancer in patients with crohn’s disease: a nationwide population-based Danish follow-up study. Am J Gastroenterol. 2007;102:163–7.

    Article  PubMed  Google Scholar 

  34. Fonager K, Sorensen HT, Rasmussen SN, Moller-Petersen J, Vyberg M. Assessment of the diagnoses of crohn’s disease and ulcerative colitis in a Danish hospital information system. Scand J Gastroenterol. 1996;31:154–9.

    Article  PubMed  CAS  Google Scholar 

  35. Olsson R, Danielsson A, Järnerot G, Lindström E, Lööf L, Rolny P, et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterol. 1991;100:1319–23.

    CAS  Google Scholar 

  36. Vind I, Riis L, Jess T, Knudsen E, Pedersen N, Elkjaer M, et al. Increasing incidences of inflammatory bowel disease and decreasing surgery rates in Copenhagen city and county, 2003–2005: a population-based study from the Danish crohn colitis database. Am J Gastroenterol. 2006;101:1274–82.

    Article  PubMed  Google Scholar 

  37. Zoepf T, Jakobs R, Arnold JC, Apel D, Riemann JF. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol. 2005;100:2426–30.

    Article  PubMed  CAS  Google Scholar 

  38. Luciani MG, Campregher C, Fortune JM, Kunkel TA, Gasche C. 5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint. Gastroenterology. 2007;132:221–35.

    Article  PubMed  CAS  Google Scholar 

  39. Larsson SC, Giovannucci E, Wolk A. Long-term aspirin use and colorectal cancer risk: a cohort study in Sweden. Br J Cancer. 2006;95:1277–9.

    Article  PubMed  CAS  Google Scholar 

  40. 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;5:1221–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark

    Rune Erichsen, Peter Jepsen & Henrik Toft Sørensen

  2. Department of Medicine V, Aarhus University Hospital, 8000, Aarhus C, Denmark

    Rune Erichsen & Hendrik Vilstrup

  3. Clinical Epidemiology Unit, Karolinska University Hospital, Solna, Sweden

    Anders Ekbom

Authors
  1. Rune Erichsen
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  2. Peter Jepsen
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  3. Hendrik Vilstrup
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  4. Anders Ekbom
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  5. Henrik Toft Sørensen
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Correspondence to Rune Erichsen.

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Erichsen, R., Jepsen, P., Vilstrup, H. et al. Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978–2003. Eur J Epidemiol 24, 513–520 (2009). https://doi.org/10.1007/s10654-009-9365-4

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  • DOI: https://doi.org/10.1007/s10654-009-9365-4

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