Advertisement

Epidemiology of Large Bowel Carcinoid Tumors in the USA: A Population-Based National Study

  • Pooja LalEmail author
  • Mohannad Abou Saleh
  • George Khoudari
  • Mohamed M. Gad
  • Emad Mansoor
  • Gerard Isenberg
  • Gregory S. Cooper
Original Article

Abstract

Background and Aims

Prior studies have shown that about 90% of all carcinoid tumors occur in the GI tract. However, epidemiological studies of these tumors have been limited by small sample size. Our aim was to obtain a more robust epidemiologic survey of large bowel carcinoids (LBC), using population-based data in order to more accurately identify risk factors for these tumors.

Methods

We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with LBC, excluding appendiceal carcinoids, between 1999 and 2018 based on Systematized Nomenclature Of Medicine—Clinical Terms (SNOMED-CT) and evaluated the prevalence of LBC. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors.

Results

Of the 62,817,650 individuals in the database, 4530 were identified to have LBC with an overall prevalence of 7.21/100,000. Individuals with LBC were more likely to be elderly (age > 65) [OR 2.17, CI 2.05–2.31, p < 0.0001], smokers [OR 3.25; 95% CI 3.00–3.53, p < 0.0001], have a history of alcohol use [OR 3.75; 95% CI 3.52–3.99, p < 0.0001], diabetes mellitus (DM) [OR 4.42; 95% CI 4.14–4.72, p < 0.0001], obesity [OR 1.58; 95% CI 1.43–1.74, p < 0.0001], family history of cancer [OR 8.06; 95% CI 7.47–8.71, p < 0.0001], and personal history of ulcerative colitis [OR 6.93; 95% CI 5.55–8.64, p < 0.0001] or Crohn’s disease [OR 6.45; 95% CI 5.24–7.95, p < 0.0001]. The prevalence of LBC was less among Caucasians compared to African–Americans [OR 0.57; 95% CI 0.53–0.61, p < 0.0001]. There was no statistically significant gender-based difference; men versus women [OR 1.02; 95% CI 0.96–1.08, p = 0.47]. The most common presenting symptoms included flushing, diarrhea, nausea, weight loss, and abdominal pain, while the most common GI associations included perforation, obstruction, hemorrhage, intussusception, and volvulus.

Conclusion

This is the largest epidemiological study evaluating the prevalence of LBC. We estimated the prevalence rate of LBC to be 7.21/100,000. The presence of significant risk factors with the clinical picture suspicious for a LBC should warrant thorough evaluation as these tumors can lead to life-threatening complications. Further studies are needed to better understand the mechanism of association between these risk factors and LBC.

Keywords

Neuroendocrine tumors Carcinoid tumors Large bowel carcinoids Epidemiology Prevalence 

Abbreviations

LBC

Large bowel carcinoids

NETs

Neuroendocrine tumors

GI-NETs

Gastrointestinal neuroendocrine tumors

SEER

Surveillance, epidemiology, and end results

HDG

Health data gateway

HITECH

Health information technology for economic and clinical health act

ERG

End results group

TNCS

Third national cancer survey

NCI

National cancer institute

EHR

Electronic health record

ICD

International classification of diseases

OR

Odds ratio

SNOMED-CT

Systematized nomenclature of medical terminology—clinical terms

CI

Confidence interval

Notes

Author’s contribution

PL, MAS, EM, GK, MMG, GI, GSC were involved in study conception and design. PL, MAS, EM, GK, MMG, GI, GSC contributed to acquisition of data. PL, MAS, EM, GK, MMG, GI, GSC helped in analysis and interpretation of data. PL, MAS, EM drafted the manuscript. MAS, EM, GI, GSC contributed to critical revision. PL, MAS, EM, GK, MMG, GI, GSC were involved in statistical analysis. Cooper obtained funding. GI, GSC helped in study supervision.

Funding

Supported in part by the Cleveland Digestive Disease Research Core Center (P30DK097948) and the Case Comprehensive Cancer Center (P30CA43703) (both to Cooper).

Compliance with Ethical Standards

Conflict of interest

There are no potential conflicts (financial, professional, or personal) to disclose by the other authors (Lal, Saleh, Mansoor, Isenberg, Khoudari, Gad).

References

  1. 1.
    Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.CrossRefGoogle Scholar
  2. 2.
    Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–868.CrossRefGoogle Scholar
  3. 3.
    Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma): current concepts. Hematol Oncol Clin N Am. 2007;21:395–407.CrossRefGoogle Scholar
  4. 4.
    Obendorfer S. Karzinoide tumoren des dunndarms. Frankf Z Pathol. 1907;1:425–432.Google Scholar
  5. 5.
    Kloppel G, Anlauf M. Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2005;19:507–517.CrossRefGoogle Scholar
  6. 6.
    Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128:1717–1751.CrossRefGoogle Scholar
  7. 7.
    Dierdorf SF. Carcinoid tumor and carcinoid syndrome. Curr Opin Anaesthesiol. 2003;16:343–347.CrossRefGoogle Scholar
  8. 8.
    Yao JC, Hassan M, Phan A, et al. One hundred years after ‘carcinoid’: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–3072.CrossRefGoogle Scholar
  9. 9.
    Ito T, Igarashi H, Nakamura K, et al. Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis. J Gastroenterol. 2015;50:58–64.CrossRefGoogle Scholar
  10. 10.
    Hallet J, Law CH, Cukier M, Saskin R, Liu N, Singh S. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015;121:589–597.CrossRefGoogle Scholar
  11. 11.
    Godwin JD. Carcinoid tumors: an analysis of 2837 cases. Cancer. 1975;36:560–569.CrossRefGoogle Scholar
  12. 12.
    Modlin IM, Sandor A. An analysis of 8305 carcinoid tumors. Cancer. 1997;79:813–829.CrossRefGoogle Scholar
  13. 13.
    Gore R, Berlin JW, Mehta UK, Newmark GM, Yaghmai V. GI carcinoid tumours: appearance of the primary and detecting metastases. Best Pract Res Clin Endocrinol Metab. 2005;19:245–263.CrossRefGoogle Scholar
  14. 14.
    Arnold R. Introduction: definition, historical aspects, classification, staging, prognosis and therapeutic options. Best Pract Res Clin Endocrinol Metab. 2005;19:491–505.Google Scholar
  15. 15.
    Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005;103:1587–1595.CrossRefGoogle Scholar
  16. 16.
    Altman DG. Practical Statistics for Medical Research. Boca Raton: CRC Press; 1990.Google Scholar
  17. 17.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–959.CrossRefGoogle Scholar
  18. 18.
    Hemminki K, Li X. Incidence trends and risk factors of carcinoid tumors. Cancer. 2001;92:2204–2210.CrossRefGoogle Scholar
  19. 19.
    Norheim I, Oberg K, Theodorsson-Norheim E, et al. Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival. Ann Surg. 1987;206:115.CrossRefGoogle Scholar
  20. 20.
    Haselkorn T, Whittemore AS, Lilienfeld DE. Incidence of small bowel cancer in the United States and worldwide: geographic, temporal, and racial differences. Cancer Causes Control. 2005;16:781–787.CrossRefGoogle Scholar
  21. 21.
    Mocellin S, Nitti D. Gastrointestinal carcinoid: epidemiological and survival evidence from a large population-based study (n = 25,531). Ann Oncol. 2013;24:3040–3044.CrossRefGoogle Scholar
  22. 22.
    Maggard MA, O’Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg. 2004;240:117.CrossRefGoogle Scholar
  23. 23.
    Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Risk factors associated with neuroendocrine tumors: a US-based case–control study. Int J Cancer. 2008;123:867–873.CrossRefGoogle Scholar
  24. 24.
    Chow WH, Linet MS, McLaughlin JK, Hsing AW, Chien HT, Blot WJ. Risk factors for small intestine cancer. Cancer Causes Control. 1993;4:163–169.CrossRefGoogle Scholar
  25. 25.
    Chen CC, Neugut AI, Rotterdam H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Canc Epidemiol Biomark Prev. 1994;3:205–207.Google Scholar
  26. 26.
    Kaerlev L, Teglbjaerg PS, Sabroe S, et al. The importance of smoking and medical history for development of small bowel carcinoid tumor: a European population-based case–control study. Cancer Causes Control. 2002;13:27–34.CrossRefGoogle Scholar
  27. 27.
    Feldman JM, Plonk JW, Bivens CH, Lebovitz HE. Glucose intolerance in the carcinoid syndrome. Diabetes. 1975;24:664–671.CrossRefGoogle Scholar
  28. 28.
    Szabo GG, Barta Z, Kerekes L, Szakáll S. Association of carcinoid tumor of the appendix and Crohn disease (case report and review of the literature). Orv Hetil. 1999;140:1635–1639.Google Scholar
  29. 29.
    Le Marc’hadour F, Bost F, Peoc’h M, Roux JJ, Pasquier D, Pasquier B. Carcinoid tumour complicating inflammatory bowel disease. A study of two cases with review of the literature. Pathol Res Pract. 1994;190:1185–1192.CrossRefGoogle Scholar
  30. 30.
    Barhoum M, Hutchins L, Fonseca VA. Intractable hypercalcemia due to a metastatic carcinoid secreting parathyroid hormone-related peptide and interleukin-6: response to octreotide. Am J Med Sci. 1999;318:203–205.Google Scholar
  31. 31.
    Kasprzak A, Przewoźna M, Surdyk-Zasada J, Zabel M. The expression of selected neuroendocrine markers and of anti-neoplastic cytokines (IL-2 and IL-12) in lung cancers. Folia Morphol (Warsz). 2003;62:497–499.Google Scholar
  32. 32.
    McCluggage WG, McConnell L, Sloan JM, Ellis PK, Irwin ST. Small intestinal ulceration secondary to carcinoid tumour arising in a Meckel’s diverticulum. J Clin Pathol. 1999;52:72–74.CrossRefGoogle Scholar
  33. 33.
    Krishnamurthy S, Dayal Y. Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. Am J Surg Pathol. 1997;21:327–333.CrossRefGoogle Scholar
  34. 34.
    Abou Saleh M, Mansoor E, Anindo M, Isenberg G. Prevalence of small intestine carcinoid tumors: a US population-based study 2012–2017. Dig Dis Sci. 2018. (Epub ahead of print). doi:  https://doi.org/10.1007/s10620-018-5402-z.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineCleveland Clinic FoundationClevelandUSA
  2. 2.Division of Gastroenterology and HepatologyCleveland Clinic FoundationClevelandUSA
  3. 3.Division of Gastroenterology and Liver DiseaseCase Western Reserve UniversityClevelandUSA
  4. 4.University Hospitals Cleveland Medical CenterClevelandUSA

Personalised recommendations