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Pancreatic Cancer Following Acute Pancreatitis: A Population-based Matched Cohort Study

The American Journal of Gastroenterologyvolume 113pages17111719 (2018) | Download Citation




Acute pancreatitis is linked to pancreatic cancer, but the direction of this association is not fully elaborated.


This was a population-based cohort study including all Swedish residents diagnosed with a first-time episode of acute pancreatitis between 1997 and 2013 and corresponding matched pancreatitis-free individuals from the general population. Hazard ratios for the association between acute pancreatitis and pancreatic cancer were estimated using multivariable Cox regression models.


Overall, 49,749 individuals with acute pancreatitis and 138,750 matched individuals without acute pancreatitis were followed up for 1,192,134 person-years (median 5.3 years). A total of 769 individuals developed pancreatic cancer, of whom 536 (69.7%) had a history of acute pancreatitis. The risk of pancreatic cancer was substantially increased during the first few years after a diagnosis of acute pancreatitis but declined gradually over time, reaching a level comparable to the pancreatitis-free population after >10 years of follow-up. In those with non-gallstone-related acute pancreatitis, the risk of pancreatic cancer declined to a level comparable to the pancreatitis-free population only when follow-up time was censored for a second episode of acute pancreatitis or a diagnosis of chronic pancreatitis. Increasing number of recurrent episodes of acute pancreatitis was associated with increased risk of pancreatic cancer.


These findings imply a delay in the diagnosis of pre-existing pancreatic cancer, if clinically presented as acute pancreatitis. Any association between non-gallstone-related acute pancreatitis and pancreatic cancer in the long-term (>10 years) could be mediated through recurrent acute pancreatitis or chronic pancreatitis.

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  1. 1.

    Li S, Tian B. Acute pancreatitis in patients with pancreatic cancer: timing of surgery and survival duration. Medicine. 2017;96:e5908.

  2. 2.

    Lee ES, Lee JM. Imaging diagnosis of pancreatic cancer: a state-of-the-art review. World J Gastroenterol. 2014;20:7864–77.

  3. 3.

    Frampas E, Morla O, Regenet N, et al. A solid pancreatic mass: tumour or inflammation? Diagn Interv Imaging. 2013;94:741–55.

  4. 4.

    Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1252–61.

  5. 5.

    Munigala S, Kanwal F, Xian H, et al. Increased risk of pancreatic adenocarcinoma after acute pancreatitis. Clin Gastroenterol Hepatol. 2014;12:1143–50 e1.

  6. 6.

    McKay CJ, Glen P, McMillan DC. Chronic inflammation and pancreatic cancer. Best Pract Res Clin Gastroenterol. 2008;22:65–73.

  7. 7.

    Ekbom A, McLaughlin JK, Nyren O. Pancreatitis and the risk of pancreatic cancer. N Engl J Med. 1993;329:1502–3.

  8. 8.

    Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, et al. Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands. Int J Cancer. 1992;52:17–23.

  9. 9.

    Kalapothaki V, Tzonou A, Hsieh CC, et al. Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. Cancer Causes Control. 1993;4:375–82.

  10. 10.

    Fernandez E, La Vecchia C, Porta M, et al. Pancreatitis and the risk of pancreatic cancer. Pancreas. 1995;11:185–9.

  11. 11.

    Hassan MM, Bondy ML, Wolff RA, et al. Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol. 2007;102:2696–707.

  12. 12.

    Bracci PM, Wang F, Hassan MM, et al. Pancreatitis and pancreatic cancer in two large pooled case-control studies. Cancer Causes Control. 2009;20:1723–31.

  13. 13.

    Duell EJ, Lucenteforte E, Olson SH, et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012;23:2964–70.

  14. 14.

    Ekbom A, McLaughlin JK, Karlsson BM, et al. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst. 1994;86:625–7.

  15. 15.

    Karlson BM, Ekbom A, Josefsson S, et al. The risk of pancreatic cancer following pancreatitis: an association due to confounding? Gastroenterology. 1997;113:587–92.

  16. 16.

    Kirkegard J, Cronin-Fenton D, Heide-Jorgensen U, et al. Acute pancreatitis and pancreatic cancer risk: a nationwide matched-cohort study in Denmark. Gastroenterology. 2018;154:1729–36.

  17. 17.

    Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, et al. The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol. 2009;24:659–67.

  18. 18.

    Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.

  19. 19.

    Razavi D, Ljung R, Lu Y, et al. Reliability of acute pancreatitis diagnosis coding in a National Patient Register: a validation study in Sweden. Pancreatology. 2011;11:525–32.

  20. 20.

    The Swedish National Board of Health and Welfare. Swedish Causes of Death Register - Bortfall och kvalitet i dödsorsaksregistret. Accessed 6 August 2012.

  21. 21.

    Statistics Sweden. Register of Total Population. Accessed 6 August 2012.

  22. 22.

    Statistics Sweden. The Swedish Register of Education. Accessed 6 August 2012.

  23. 23.

    Sadr-Azodi O, Andren-Sandberg A, Orsini N, et al. Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study. Gut. 2012;61:262–7.

  24. 24.

    Vrieling A, Bueno-de-Mesquita HB, Boshuizen HC, et al. Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2010;126:2394–403.

  25. 25.

    Michaud DS, Giovannucci E, Willett WC, et al. Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA. 2001;286:921–9.

  26. 26.

    Rijkers AP, Bakker OJ, Ahmed Ali U, et al. Risk of pancreatic cancer after a primary episode of acute pancreatitis. Pancreas. 2017;46:1018–22.

  27. 27.

    Working Party of the British Society of G, Association of Surgeons of Great B, Ireland. et al. UK guidelines for the management of acute pancreatitis. Gut. 2005;54(Suppl 3):iii1–9.

  28. 28.

    Tenner S, Baillie J, DeWitt J, et al. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108:1400–15. 1416.

  29. 29.

    Working Group IAPAPAAPG. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13:e1–15.

  30. 30.

    Cho JH, Choi JS, Hwang ET, et al. Usefulness of scheduled follow-up CT in discharged patients with acute pancreatitis. Pancreatology. 2015;15:642–6.

  31. 31.

    Lowenfels AB, Maisonneuve P, DiMagno EP, et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst. 1997;89:442–6.

  32. 32.

    Raimondi S, Lowenfels AB, Morselli-Labate AM, et al. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 2010;24:349–58.

  33. 33.

    Carriere C, Young AL, Gunn JR, et al. Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the nestin cell lineage. PLoS ONE. 2011;6:e27725.

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Author information


  1. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    • Omid Sadr-Azodi MD, PhD
    • , Johan Askling MD, PhD
    •  & Anders Ekbom MD, PhD
  2. Department of Surgery, Eskilstuna County Hospital, Eskilstuna, Sweden

    • Omid Sadr-Azodi MD, PhD
  3. Center for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden

    • Omid Sadr-Azodi MD, PhD
  4. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    • Viktor Oskarsson MD, PhD
  5. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    • Andrea Discacciati PhD
  6. Department of Surgery, Västerås County Hospital, Västerås, Sweden

    • Per Videhult MD


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Guarantor of the article

Sadr Azodi, Omid

Specific author contributions

Study planning: All authors. Data collection: OSA. Interpretation of data: All authors. Statistical analysis: OSA, AD. Drafting the manuscript: OSA, VO. Critical revision of the manuscript for important intellectual content: All authors. All authors have approved the final draft.

Financial support

This study was supported by grants from the Swedish Society of Medicine, the Centre for Clinical Research Sörmland, Uppsala University and Uppsala-Örebro Research Council. None of the funders had any role in the study design, collection, analysis, interpretation or writing of the manuscript.

Potential competing interests

The authors declare that they have no potential competing interests.

Corresponding author

Correspondence to Omid Sadr-Azodi MD, PhD.

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