Skip to main content

Advertisement

SpringerLink
Log in

Cancer risk in patients with cholelithiasis and after cholecystectomy: a nationwide cohort study

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

This study examined the association of cholelithiasis post-cholecystectomy with subsequent cancers and evaluated the risk of cancer in patients with both cholelithiasis and cholecystectomy.

Methods

The Taiwanese National Health Insurance Research Database was used to identify 15545 newly diagnosed cholelithiasis patients from 2000 to 2010, and 62180 frequency-matched non-cholelithiasis patients. A total of 5850 (37.6 %) with cholelithiasis patients received a cholecystectomy. The risk of developing cancer after cholecystectomy was measured using the Cox proportional-hazards model.

Results

The incidence of developing cancer in the cholelithiasis cohort was 1.52-fold higher than that in the comparison cohort (p < 0.001). Compared with patients aged 20–34 years, patients in older age groups had a higher risk of developing cancer. The hazard ratio (HR) for developing gallbladder, extrahepatic bile duct, pancreatic, liver, stomach, and colorectal cancer was 59.3, 10.7, 3.12, 1.90, 1.71, and 1.36-fold higher for patients with cholelithiasis, respectively. After a cholecystectomy, the HR for developing stomach and colorectal cancer was 1.81-fold and 1.56-fold, respectively. The incidence rate ratio was higher for the first 5 years and over 5 years (5.05 and 4.46, respectively) (95 % confidence interval 4.73–5.39 and 4.11–4.84, respectively) in proximal colon and stomach cancer patients with cholecystectomies.

Conclusions

Cholelithiasis patients have a higher risk of gastrointestinal cancer, particularly of gallbladder and extrahepatic bile duct cancer. Post-cholecystectomy patients have a risk of colorectal and stomach cancer within the first 5 years and persisting after 5 years, respectively. This paper proposes strategies for preventing gastrointestinal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Agrawal S, Jonnalagadda S. Gallstones, from gallbladder to gut: management options for diverse complications. Postgrad Med. 2000;108:143–53.

    CAS  PubMed  Google Scholar 

  2. Huang J, Chang CH, Wang JL, et al. Nationwide epidemiological study of severe gallstone disease in Taiwan. BMC Gastroenterol. 2009;9:63.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Lowenfels AB, Lindstršm CG, Conway MJ, et al. Gallstones and risk of gallbladder cancer. J Natl Cancer Inst. 1985;75:77–80.

    CAS  PubMed  Google Scholar 

  4. Chow WH, Johansen C, Gridley G, et al. Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas. Br J Cancer. 1999;79:640–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Almond HR, Vlahcevic ZR, Bell CC, et al. Bile acid pools, kinetics and biliary lipid composition before and after cholecystectomy. N Engl J Med. 1973;289:1213–6.

    Article  CAS  PubMed  Google Scholar 

  6. Ekbom A, Yuen J, Adami HO, et al. Cholecystectomy and colorectal cancer. Gastroenterology. 1993;105:142–7.

    CAS  PubMed  Google Scholar 

  7. Gustavsson S, Adami HO, Meirik O, et al. Cholecystectomy as a risk factor for gastric cancer. A cohort study. Dig Dis Sci. 1984;29:116–20.

    Article  CAS  PubMed  Google Scholar 

  8. Giovannucci E, Colditz GA, Stampfer MJ. A meta-analysis of cholecystectomy and risk of colorectal cancer. Gastroenterology. 1993;105:130–41.

    CAS  PubMed  Google Scholar 

  9. Reid FD, Mercer PM, Harrison M, et al. Cholecystectomy as a risk factor for colorectal cancer: a meta-analysis. Scand J Gastroenterol. 1996;31:160–9.

    Article  CAS  PubMed  Google Scholar 

  10. Ge Z, Zhao C, Wang Y, et al. Cholecystectomy and the risk of esophageal and gastric cancer. Saudi Med J. 2012;33:1073–9.

    PubMed  Google Scholar 

  11. Tavani A, Rosato V, Di Palma F, et al. History of cholelithiasis and cancer risk in a network of case–control studies. Ann Oncol. 2012;23:2173–8.

    Article  CAS  PubMed  Google Scholar 

  12. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Urbach DR, Stukel TA. Rate of elective cholecystectomy and the incidence of severe gallstone disease. CMAJ. 2005;172:1015–9.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Hung SC, Liao KF, Lai SW, et al. Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study. BMC Gastroenterol. 2011;11:111.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Yu YH, Liao CC, Hsu WH, et al. Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. J Thorac Oncol. 2011;6:32–7.

    Article  PubMed  Google Scholar 

  16. Liang JA, Sun LM, Yeh JJ, et al. Malignancies associated with systemic lupus erythematosus in Taiwan: a nationwide population-based cohort study. Rheumatol Int. 2012;32:773–8.

    Article  PubMed  Google Scholar 

  17. Cheng CL, Kao YH, Lin SJ, et al. Lai Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20:236–42.

    Article  PubMed  Google Scholar 

  18. Kang JH, Chen YH, Lin HC. Comorbidity profiles among patients with ankylosing spondylitis: a nationwide population-based study. Ann Rheum Dis. 2010;69:1165–8.

    Article  PubMed  Google Scholar 

  19. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012;6:172–87.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Lowenfels AB. Gallstones and the risk of cancer. Gut. 1980;21:1090–2.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Johansen C, Chow WH, Jorgensen T, et al. Risk of colorectal cancer and other cancers in patients with gallstones. Gut. 1996;39:439–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Ho KJ, Lin XZ, Yu SC, Chen JS, Wu CZ. Cholelithiasis in Taiwan. Gallstone characteristics, surgical incidence, bile lipid composition, and role of beta-glucuronidase. Dig Dis Sci. 1995;40:1963–73.

    Article  CAS  PubMed  Google Scholar 

  23. Hung SC, Liao KF, Lai SW, Li CI, Chen WC. Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study. BMC Gastroenterol. 2011;11:111.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Ho KJ, Lin XZ, Yu SC, et al. Cholelithiasis in Taiwan. Gallstone characteristics, surgical incidence, bile lipid composition, and role of beta-glucuronidase. Dig Dis Sci. 1995;40:1963–73.

    Article  CAS  PubMed  Google Scholar 

  25. Yoo EH, Oh HJ, Lee SY. Gallstone analysis using Fourier transform infrared spectroscopy (FT-IR). Clin Chem Lab Med. 2008;46:376–81.

    Article  PubMed  Google Scholar 

  26. Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of gallstone disease in an adult population of Taiwan: an epidemiological survey. J Gastroenterol Hepatol. 2006;21:1737–43.

    Article  PubMed  Google Scholar 

  27. Sheen IS, Liaw YF. The prevalence and incidence of cholecystolithiasis in patients with chronic liver diseases: a prospective study. Hepatology. 1989;9:538–40.

    Article  CAS  PubMed  Google Scholar 

  28. Lagergren J, Ye W, Ekbom A. Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis? Gastroenterology. 2001;121:542–7.

    Article  CAS  PubMed  Google Scholar 

  29. Schernhammer ES, Leitzmann MF, Michaud DS, et al. Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas. Br J Cancer. 2003;88:79–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Shao T, Yang YX. Cholecystectomy and the risk of colorectal cancer. Am J Gastroenterol. 2005;100:1813–20.

    Article  PubMed  Google Scholar 

  31. Goldacre MJ, Abisgold JD, Seagroatt V, et al. Cancer after cholecystectomy: record-linkage cohort study. Br J Cancer. 2005;92:1307–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Altieri A, Pelucchi C, Talamini R, et al. Cholecystectomy and the risk of colorectal cancer in Italy. Br J Cancer. 2004;90:1753–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Fall K, Ye W, Nyren O. Risk for gastric cancer after cholecystectomy. Am J Gastroenterol. 2007;102:1180–4.

    Article  PubMed  Google Scholar 

  34. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454:436–44.

    Article  CAS  PubMed  Google Scholar 

  35. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from China Medical University Hospital (DMR-102-014 and DMR-102-023); the Taiwan Department of Health, Clinical Trial and Research Center for Excellence (DOH102-TD-B-111-004); the Taiwan Department of Health, Cancer Research Center for Excellence (DOH102-TD-C-111-005); and the International Research-Intensive Centers of Excellence, Taiwan (NSC101-2911-I-002-303).

Conflict of interest

All authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and PET Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Yen-Kung Chen

  2. Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Jiann-Horng Yeh

  3. School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

    Yen-Kung Chen & Jiann-Horng Yeh

  4. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan

    Cheng-Li Lin, Chiao-Ling Peng & Fung-Chang Sung

  5. Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan

    Chia-Hung Kao

  6. Department of Public Health, China Medical University, Taichung, Taiwan

    Fung-Chang Sung

  7. Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan

    Ing-Ming Hwang

  8. Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 404, Taiwan

    Chia-Hung Kao

Authors
  1. Yen-Kung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiann-Horng Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng-Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chiao-Ling Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fung-Chang Sung
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ing-Ming Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chia-Hung Kao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chia-Hung Kao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, YK., Yeh, JH., Lin, CL. et al. Cancer risk in patients with cholelithiasis and after cholecystectomy: a nationwide cohort study. J Gastroenterol 49, 923–931 (2014). https://doi.org/10.1007/s00535-013-0846-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-013-0846-6

Keywords

Search

Navigation