J Korean Med Sci.  2024 Jan;39(4):e21. 10.3346/jkms.2024.39.e21.

Risk of Pancreatic Cancer After Acute Pancreatitis: A Retrospective Analysis of the Korean National Sample Cohort

• Jeong SH
• Hurh K
• Park EC
• Leigh Jh
• Kim SH
• Jang SI

• KMID: 2551964
• DOI: http://doi.org/10.3346/jkms.2024.39.e21

Abstract

Background
Acute pancreatitis may increase the risk of pancreatic cancer, although this association remains unclear. Therefore, we aimed to investigate this association.
Methods
We retrospectively analyzed the 2002–2019 Korean National Health Insurance ServiceNational Sample Cohort using 1:3 propensity score matching for sex and age (acute pancreatitis, n = 4,494; matched controls, n = 13,482). We calculated the hazard ratio (HR) for pancreatic cancer risk in patients with acute pancreatitis using Cox proportional hazards regression.
Results
Acute pancreatitis was significantly associated with an increased risk of pancreatic cancer throughout the study period (adjusted HR, 7.56 [95% confidence interval, 5.00– 11.41]), which persisted for 2, 2–5, and > 5 years post-diagnosis (19.11 [9.60–38.05], 3.46 [1.35–8.33], and 2.73 [1.21–6.15], respectively). This pancreatitis-related pancreatic cancer risk became insignificant beyond 10 years of follow-up (1.24 [0.24–6.49]). Furthermore, this risk notably increased as the number of recurrent acute pancreatitis episodes increased (1 episode: 5.25 [3.31–8.33], 2 episodes: 11.35 [6.38–20.19], ≥ 3 episodes: 24.58 [13.66–44.26]).
Conclusion
Following an acute pancreatitis diagnosis, the risk of pancreatic cancer increases significantly in the initial years, with a rapid increase further accentuated with recurrent acute pancreatitis episodes. Additional study is needed to evaluate whether this increased risk of carcinogenesis is attributed to accumulated inflammation.

Keyword

Pancreatic Cancer; Acute Pancreatitis; Acute Recurrent Pancreatitis; Risk Factor

Figure

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  Fig. 1 Kaplan–Meier survival curves for patients with acute pancreatitis and matched controls.

Reference

1. Hong S, Won YJ, Park YR, Jung KW, Kong HJ, Lee ES, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2017. Cancer Res Treat. 2020; 52(2):335–350. PMID: 32178489.

2. Committee of the Korean clinical practice guideline for pancreatic cancer and National Cancer Center, Korea. Korean clinical practice guideline for pancreatic cancer 2021: a summary of evidence-based, multi-disciplinary diagnostic and therapeutic approaches. Pancreatology. 2021; 21(7):1326–1341. PMID: 34148794.

3. Li S, Tian B. Acute pancreatitis in patients with pancreatic cancer: timing of surgery and survival duration. Medicine (Baltimore). 2017; 96(3):e5908. PMID: 28099352.

4. Bhatia M, Wong FL, Cao Y, Lau HY, Huang J, Puneet P, et al. Pathophysiology of acute pancreatitis. Pancreatology. 2005; 5(2-3):132–144. PMID: 15849484.

5. McKay CJ, Glen P, McMillan DC. Chronic inflammation and pancreatic cancer. Best Pract Res Clin Gastroenterol. 2008; 22(1):65–73. PMID: 18206813.

6. Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic pancreatitis and pancreatic cancer risk: a systematic review and meta-analysis. Am J Gastroenterol. 2017; 112(9):1366–1372. PMID: 28762376.

7. Malka D, Hammel P, Maire F, Rufat P, Madeira I, Pessione F, et al. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut. 2002; 51(6):849–852. PMID: 12427788.

8. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. N Engl J Med. 1993; 328(20):1433–1437. PMID: 8479461.

9. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013; 144(6):1252–1261. PMID: 23622135.

10. Carrière C, Young AL, Gunn JR, Longnecker DS, Korc M. Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the Nestin cell lineage. PLoS One. 2011; 6(11):e27725. PMID: 22140463.

11. Carrière C, Young AL, Gunn JR, Longnecker DS, Korc M. Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras. Biochem Biophys Res Commun. 2009; 382(3):561–565. PMID: 19292977.

12. Duell EJ, Casella DP, Burk RD, Kelsey KT, Holly EA. Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and CCR5, and risk of pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2006; 15(4):726–731. PMID: 16614115.

13. Goldacre MJ, Wotton CJ, Yeates D, Seagroatt V, Collier J. Liver cirrhosis, other liver diseases, pancreatitis and subsequent cancer: record linkage study. Eur J Gastroenterol Hepatol. 2008; 20(5):384–392. PMID: 18403939.

14. Park BK, Seo JH, Son KJ, Choi JK. Risk of pancreatic cancer after acute pancreatitis: a population-based matched cohort study. Pancreatology. 2023; 23(5):449–455. PMID: 37230893.

15. Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol. 2017; 46(2):e15. PMID: 26822938.

16. Kirkegård J, Cronin-Fenton D, Heide-Jørgensen U, Mortensen FV. Acute pancreatitis and pancreatic cancer risk: a nationwide matched-cohort study in Denmark. Gastroenterology. 2018; 154(6):1729–1736. PMID: 29432727.

17. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373–383. PMID: 3558716.

18. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson Comorbidity Index predicted in-hospital mortality. J Clin Epidemiol. 2004; 57(12):1288–1294. PMID: 15617955.

19. Hariharan D, Saied A, Kocher HM. Analysis of mortality rates for pancreatic cancer across the world. HPB. 2008; 10(1):58–62. PMID: 18695761.

20. Kim KH, Park EC, Hahm MI. The gap between physicians and the public in satisfaction with the National Health Insurance system in Korea. J Korean Med Sci. 2012; 27(6):579–585. PMID: 22690087.

21. Rasouliyan L, Plana E, Aguado J. Considerations in the use of propensity scores in observational studies. In : Poster presented at the 2016 PhUSE Annual Conference; 2016 October 9-12; Barcelona, Spain.

22. Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014; 33(7):1242–1258. PMID: 24122911.

23. Somogyi L, Martin SP, Venkatesan T, Ulrich CD 2nd. Recurrent acute pancreatitis: an algorithmic approach to identification and elimination of inciting factors. Gastroenterology. 2001; 120(3):708–717. PMID: 11179245.

24. Rijkers AP, Bakker OJ, Ahmed Ali U, Hagenaars JCJP, van Santvoort HC, Besselink MG, et al. Risk of pancreatic cancer after a primary episode of acute pancreatitis. Pancreas. 2017; 46(8):1018–1022. PMID: 28797012.

25. Chung SD, Chen KY, Xirasagar S, Tsai MC, Lin HC. More than 9-times increased risk for pancreatic cancer among patients with acute pancreatitis in Chinese population. Pancreas. 2012; 41(1):142–146. PMID: 21946811.

26. Sadr-Azodi O, Oskarsson V, Discacciati A, Videhult P, Askling J, Ekbom A. Pancreatic cancer following acute pancreatitis: a population-based matched cohort study. Am J Gastroenterol. 2018; 113(11):1711–1719. PMID: 30315287.

27. Sun Y, Jin J, Zhu A, Hu H, Lu Y, Zeng Y, et al. Risk factors for recurrent pancreatitis after first episode of acute pancreatitis. Int J Gen Med. 2022; 15:1319–1328. PMID: 35173470.

28. Munigala S, Almaskeen S, Subramaniam DS, Bandi S, Bowe B, Xian H, et al. Acute pancreatitis recurrences augment long-term pancreatic cancer risk. Am J Gastroenterol. 2023; 118(4):727–737. PMID: 36473072.

29. Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology. 2015; 149(6):1490–1500.e1. PMID: 26299411.

30. Whitcomb D, Greer J. Germ-line mutations, pancreatic inflammation, and pancreatic cancer. Clin Gastroenterol Hepatol. 2009; 7(11):Suppl. S29–S34. PMID: 19896094.

31. Jin G, Hong W, Guo Y, Bai Y, Chen B. Molecular mechanism of pancreatic stellate cells activation in chronic pancreatitis and pancreatic cancer. J Cancer. 2020; 11(6):1505–1515. PMID: 32047557.

32. Talamini G, Falconi M, Bassi C, Mastromauro M, Salvia R, Pederzoli P. Chronic pancreatitis: relationship to acute pancreatitis and pancreatic cancer. JOP. 2000; 1(3):Suppl. 69–76.

33. Bansal P, Sonnenberg A. Pancreatitis is a risk factor for pancreatic cancer. Gastroenterology. 1995; 109(1):247–251. PMID: 7797022.

34. Im MY, Lee SY. Risk factors for heavy episodic drinking among Korean adults: differences by gender and age. J Korean Acad Soc Home Care Nurs. 2015; 22(2):265–279.

35. Jeong YW, Kim EY. A study on factors related to smoking experience by sex: using the National Health and Nutrition Examination Survey (KNHANES IV-VII, 2007-2018). J Health Info Stat. 2021; 46(3):352–361.

36. Go VL, Gukovskaya A, Pandol SJ. Alcohol and pancreatic cancer. Alcohol. 2005; 35(3):205–211. PMID: 16054982.

37. Talamini G, Bassi C, Falconi M, Sartori N, Salvia R, Rigo L, et al. Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci. 1999; 44(7):1303–1311. PMID: 10489910.

38. Zheng Z, Zheng R, He Y, Sun X, Wang N, Chen T, et al. Risk factors for pancreatic cancer in China: a multicenter case-control study. J Epidemiol. 2016; 26(2):64–70. PMID: 26441209.

39. He Y, Zheng R, Li D, Zeng H, Zhang S, Chen W. Pancreatic cancer incidence and mortality patterns in China, 2011. Chin J Cancer Res. 2015; 27(1):29–37. PMID: 25717223.

40. Lowenfels AB, Maisonneuve P. Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol. 2006; 20(2):197–209. PMID: 16549324.

41. Yadav D, O'connell M, Papachristou GI. Natural history following the first attack of acute pancreatitis. Am J Gastroenterol. 2012; 107(7):1096–1103. PMID: 22613906.

42. Luo W, Tao J, Zheng L, Zhang T. Current epidemiology of pancreatic cancer: challenges and opportunities. Chin J Cancer Res. 2020; 32(6):705–719. PMID: 33446994.

43. Preziosi G, Oben JA, Fusai G. Obesity and pancreatic cancer. Surg Oncol. 2014; 23(2):61–71. PMID: 24746917.

44. Kim DM, Kim KH. The changes in obesity prevalence and dietary habits in Korean adults by residential area during the last 10 years—based on the 4th (2007-2009) and the 7th (2016-2018) Korea National Health and Nutrition Examination Survey Data. Korean J Community Nutr. 2021; 26(1):37–47.

45. Ekbom A, McLaughlin JK, Karlsson BM, Nyrén O, Gridley G, Adami HO, et al. Pancreatitis and pancreatic cancer: a population-based study. J Natl Cancer Inst. 1994; 86(8):625–627. PMID: 8145277.

46. Karlson BM, Ekbom A, Josefsson S, McLaughlin JK, Fraumeni JF Jr, Nyrén O. The risk of pancreatic cancer following pancreatitis: an association due to confounding? Gastroenterology. 1997; 113(2):587–592. PMID: 9247480.

47. Lee WS, Kim MY, Kim SW, Paik CN, Kim HO, Park YM. Fatal pancreatic panniculitis associated with acute pancreatitis: a case report. J Korean Med Sci. 2007; 22(5):914–917. PMID: 17982246.

48. Youn GJ, Chung WC, Lee JM, Paik CN, Oh JH, Jung SH. The etiologic evaluation of acute pancreatitis in a general hospital of Seoul-Gyeonggi Province in Korea. Korean J Gastroenterol. 2017; 70(4):190–197. PMID: 29060957.

49. Park E. Evaluating the Consistency of Health Insurance Claim Disease Code and Medical Record and Improvement Plan. Wonju, Korea: Health Insurance Review & Assessment Service;2017.