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Longitudinal Study of Comorbidities and Clinical Outcomes in Persons with Gallstone Disease Using Electronic Health Records

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

Gallstone disease (GSD) is common and leads to significant morbidity, mortality, and health care utilization in the USA. We examined comorbidities and clinical outcomes among persons with GSD using electronic health records (EHR).

Methods

In this retrospective study of 1,381,004 adults, GSD was defined by ICD-9 code 574 or ICD-10 code K80 using Optum® longitudinal EHR from January 2007 to March 2021. We obtained diagnosis, procedure, prescription, and vital sign records and evaluated associations between demographics, comorbidities, and medications with cholecystectomy, digestive cancers, and mortality.

Results

Among persons with GSD, 30% had a cholecystectomy and were more likely to be women, White, and younger, and less likely to have comorbidities, except for obesity, gastroesophageal reflux disease (GERD), abdominal pain, hyperlipidemia, and pancreatitis. Among persons with GSD, 2.2% had a non-colorectal digestive cancer diagnosis during follow-up and risk was 40% lower among persons with a cholecystectomy. Non-colorectal digestive cancer predictors included older age, male sex, non-White race-ethnicity, lower BMI, other cancers, diabetes, chronic liver disease, pancreatitis, GERD, and abdominal pain. Among persons with GSD, mortality was 15.1% compared with 9.7% for the whole EHR sample. Persons with a cholecystectomy had 40% lower mortality risk and mortality predictors included older age, male sex, Black race, lower BMI, and most comorbidities.

Conclusions

In this EHR analysis of persons with GSD, 30% had a cholecystectomy. Mortality was higher compared with the whole EHR sample. Persons with cholecystectomy were less likely to have non-colorectal digestive cancer or to die.

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References

  1. Unalp-Arida A, Ruhl C. Increasing gallstone disease prevalence and associations with gallbladder and biliary tract mortality in the US. Hepatology. 2023;77(6):1882-1895. doi: https://doi.org/10.1097/HEP.0000000000000264.

    Article  PubMed  Google Scholar 

  2. Peery AF, Crockett SD, Murphy CC, Jensen ET, Kim HP, Egberg MD, Lund JL, Moon AM, Pate V, Barnes EL, Schlusser CL, Baron TH, Shaheen NJ, Sandler RS. Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021. Gastroenterology. 2022;162(2):621-644.

    Article  PubMed  Google Scholar 

  3. Admirand WH, Small DM. The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest. 1968;47(5):1043-1052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Moschetta A, Bookout AL, Mangelsdorf DJ. Prevention of cholesterol gallstone disease by FXR agonists in a mouse model. Nat Med. 2004;10(12):1352-1358.

    Article  CAS  PubMed  Google Scholar 

  5. Wang HH, Portincasa P, Mendez-Sanchez N, Uribe M, Wang DQ-H. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology. 2008;134(7):2101-2110.

    Article  CAS  PubMed  Google Scholar 

  6. Ellington TD, Momin B, Wilson RJ, Henley SJ, Wu M, Ryerson AB. Incidence and Mortality of Cancers of the Biliary Tract, Gallbladder, and Liver by Sex, Age, Race/Ethnicity, and Stage at Diagnosis: United States, 2013 to 2017. Cancer Epidemiol Biomarkers Prev. 2021;30(9):1607-1614.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nogueira L, Freedman ND, Engels EA, Warren JL, Castro F, Koshiol J. Gallstones, cholecystectomy, and risk of digestive system cancers. Am J Epidemiol. 2014;179(6):731-739.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Grimaldi CH, Nelson RG, Pettitt DJ, Sampliner RE, Bennett PH, Knowler WC. Increased mortality with gallstone disease: results of a 20-year population-based survey in Pima Indians. Ann Intern Med. 1993;118(3):185-190.

    Article  CAS  PubMed  Google Scholar 

  9. Schmidt M, Småstuen MC, Søndenaa K. Increased cancer incidence in some gallstone diseases, and equivocal effect of cholecystectomy: a long-term analysis of cancer and mortality. Scand J Gastroenterol. 2012;47(12):1467-1474.

    Article  PubMed  Google Scholar 

  10. Liu Y, He Y, Li T, **e L, Wang J, Qin X, Li S. Risk of primary liver cancer associated with gallstones and cholecystectomy: a meta-analysis. PLoS One. 2014;9(10):e109733.

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  11. Kiu KT, Chen HL, Huang MT, Sung CW, Liaw YP, Chang CC, Wang YH, Chen HA. Outcome Analysis of Patients with Gallstone Disease Receiving Cholecystectomy: A Population-Based Cohort Study. Digestion. 2017;95(2):132-139.

    Article  PubMed  Google Scholar 

  12. Shabanzadeh DM, Sorensen LT, and Jorensen T. Association between screen-detected gallstone disease and cancer in a cohort study. Gastroenterology. 2017;152(8):1965-1974.

    Article  PubMed  Google Scholar 

  13. Zheng Y, Xu M, Heianza Y, Ma W, Wang T, Sun D, Albert CM, Hu FB, Rexrode KM, Manson JE, Qi L. Gallstone disease and increased risk of mortality: Two large prospective studies in US men and women. J Gastroenterol Hepatol. 2018;33(11):1925-1931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang Y, **e LF, Lin J. Gallstones and cholecystectomy in relation to risk of liver cancer. Eur J Cancer Prev. 2019;28(2):61-67.

    Article  CAS  PubMed  Google Scholar 

  15. Huang D, Lee J, Song N, Cho S, Choe S, Shin A. Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea. J Cancer Prev. 2020;25(3):164-172.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhao X, Wang N, Sun Y, Zhu G, Wang Y, Wang Z, Zhang Y, Cheng K, Wang G, Wu S, Wang L. Screen-detected gallstone disease and risk of liver and pancreatic cancer: The Kailuan Cohort Study. Liver Int. 2020;40(7):1744-1755.

    Article  PubMed  Google Scholar 

  17. Luo X, Yang W, Joshi AD, Wu K, Simon TG, Yuan C, ** L, Long L, Kim MN, Lo CH, Liu X, Abrams TA, Wolpin BM, Chan AT, Giovannucci EL, Zhang X. Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts. Br J Cancer. 2022;127(6):1069-1075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ruhl C, Everhart J. Gallstone disease is associated with increased mortality in the United States. Gastroenterology. 2011;140(2):508-516.

    Article  PubMed  Google Scholar 

  19. Shabanzadeh DM, Sørensen LT, Jørgensen T. Gallstone disease and mortality: a cohort study. Int J Public Health. 2017;62(3):353-360.

    Article  PubMed  Google Scholar 

  20. Lin KJ and Schneeweiss S. Considerations for the analysis of longitudinal electronic health records linked to claims data to study the effectiveness and safety of drugs. Clin Pharmacol Ther. 2016;100(2):147-159.

    Article  CAS  PubMed  Google Scholar 

  21. Betteridge JD. Framework for Smart Electronic Health Record-Linked Predictive Models to Optimize Care for Complex Digestive Diseases. Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD; March 2015. Internet: https://apps.dtic.mil/sti/pdfs/ADA614941.pdf. Accessed August, 2023.

  22. Anderson AJ, Click B, Ramos-Rivers C, Babichenko D, Koutroubakis IE, Hartman DJ, Hashash JG, Schwartz M, Swoger J, Barrie AM, Dunn MA. Development of an inflammatory bowel disease research registry derived from observational electronic health record data for comprehensive clinical phenoty**. Dig Dis Sci. 2016;61(11):3236-3245.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Corey KE, Kartoun U, Zheng H, Shaw SY. Development and validation of an algorithm to identify nonalcoholic fatty liver disease in the electronic medical record. Dig Dis Sci. 2016;61(3):913-919.

    Article  PubMed  Google Scholar 

  24. Baldwin-Hunter BL, Knotts RM, Leeds SD, Rubenstein JH, Lightdale CJ, Abrams JA. Use of the electronic health record to target patients for non-endoscopic Barrett’s esophagus screening. Dig Dis Sci. 2019;64(12):3463-3470.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ananthakrishnan AN, Cai T, Savova G, Cheng SC, Chen P, Perez RG, Gainer VS, Murphy SN, Szolovits P, **a Z, Shaw S. Improving case definition of Crohn’s disease and ulcerative colitis in electronic medical records using natural language processing: a novel informatics approach. Inflamm Bowel Dis. 2013;19(7):1411-1420.

    Article  PubMed  Google Scholar 

  26. Unalp-Arida A, Ruhl CE. The Burden of Gallstone Disease in the United States Population. Available at: https://doi.org/10.1101/2022.07.08.22277386. Accessed August, 2023.

  27. Sung H, Hyun N, Leach CR, Yabroff KR, Jemal A. Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States. JAMA. 2020;324(24):2521-2535.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Myers CA, Slack T, Martin CK, Broyles ST, Heymsfield SB. Regional disparities in obesity prevalence in the United States: A spatial regime analysis. Obesity (Silver Spring). 2015;23(2):481-487.

    Article  PubMed  Google Scholar 

  29. Polubriaginof FCG, Ryan P, Salmasian H, Wells Shapiro A, Perotte A, Safford MM, Hripcsak G, Smith S, Tatonetti NP, Vawdrey DK. Challenges with quality of race and ethnicity data in observational databases. J Am Med Inform Assoc. 2019;26(8-9):730-736.

    Article  PubMed  PubMed Central  Google Scholar 

  30. National Institute of Diabetes and Digestive and Kidney Diseases. NIDDK Strategic Plan for Research. Dec. 2021. Available at: https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/niddk-strategic-plan-for-research. Accessed August, 2023.

  31. Dupont B, Dejardin O, Bouvier V, Piquet MA, Alves A. Systematic Review: Impact of Social Determinants of Health on the Management and Prognosis of Gallstone Disease. Health Equity. 2022;6(1):819-835.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rudasill SE, Dillon D, Karunungan K, Mardock AL, Hadaya J, Sanaiha Y, Tran Z, Benharash P. The obesity paradox: Underweight patients are at the greatest risk of mortality after cholecystectomy. Surgery. 2021;170(3):675-681.

    Article  PubMed  Google Scholar 

  33. Chang VW, Langa KM, Weir D, Iwashyna TJ. The obesity paradox and incident cardiovascular disease: A population-based study. PLoS One. 2017;12(12):e0188636. doi: https://doi.org/10.1371/journal.pone.0188636. eCollection 2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Curcic IB, Berkovic MC, Kuna L, Roguljic H, Smolic R, Varzic SC, Jukic LV, Smolic M. Obesity Paradox in Chronic Liver Diseases: Product of Bias or a Real Thing? J Clin Transl Hepatol. 2019;7(3):275-279.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Li Y, Li C, Wu G, Yang W, Wang X, Duan L, Niu L, Chen J, Zhang Y, Zhou W, Liu J, Hong L, Fan D. The obesity paradox in patients with colorectal cancer: a systematic review and meta-analysis. Nutr Rev. 2022;80(7):1755-1768.

    Article  PubMed  Google Scholar 

  36. Kumar S, Mahmud N, Goldberg DS, Datta J, Kaplan DE. Disentangling the obesity paradox in upper gastrointestinal cancers: Weight loss matters more than body mass index. Cancer Epidemiol. 2021;72:101912. doi: https://doi.org/10.1016/j.canep.2021.101912.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Helen Corns for programming assistance with survival figure creation.

Funding

The work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN275201700074U and 75N94022F00050).

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Authors and Affiliations

  1. Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Two Democracy Plaza, Room 6009, 6707 Democracy Blvd., Bethesda, MD, 20892-5458, USA

    Aynur Unalp-Arida

  2. Social & Scientific Systems, Inc., a DLH Holdings Corp company, 8757 Georgia Avenue, 12th floor, Silver Spring, MD, 20910, USA

    Jane S. Der & Constance E. Ruhl

Authors
  1. Aynur Unalp-Arida
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  2. Jane S. Der
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  3. Constance E. Ruhl
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Contributions

Study concept and design: AUA, JSD, and CER. Analysis and interpretation of data: AUA, JSD, and CER. Drafting of the manuscript: JSD and CER. Critical revision of the manuscript for important intellectual content: AUA. All authors approve the final version of the manuscript and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Constance E. Ruhl.

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Unalp-Arida, A., Der, J.S. & Ruhl, C.E. Longitudinal Study of Comorbidities and Clinical Outcomes in Persons with Gallstone Disease Using Electronic Health Records. J Gastrointest Surg 27, 2843–2856 (2023). https://doi.org/10.1007/s11605-023-05861-z

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  • DOI: https://doi.org/10.1007/s11605-023-05861-z

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