Skip to main content

Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan

Journal of Gastroenterology volume 45, pages 234–243 (2010)Cite this article

Abstract

Background

There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan.

Methods

We examined the epidemiology of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified random sampling method.

Results

A total of 2,845 individuals received treatment for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21% patients with NF-PETs and occurred more frequently as tumor size increased (>2 cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical examination in 24% patients. In 2005, an estimated 4,406 patients received treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%; midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph node metastases occurred more frequently as tumor size increased (>1 cm). The frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in 44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1% of patients with foregut GI-NETs had type A gastritis.

Conclusion

Our results show there are large differences in GEP-NETs between Japan and Western nations, primarily due to differences in the presence of MEN-1 in NF-PETs and the location, symptomatic status, and prevalence of malignancy in GI-NETs.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Berge T, Linell F. Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A. 1976;84:322–30.

    Google Scholar 

  2. Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.

    Article  PubMed  Google Scholar 

  3. Eriksson B, Oberg K. Neuroendocrine tumours of the pancreas. Br J Surg. 2000;87:129–31.

    Article  CAS  PubMed  Google Scholar 

  4. Lam KY, Lo CY. Pancreatic endocrine tumour. A 22-year clinico-pathological experience with morphological, immunohistochemical observation and a review of the literature. Eur J Surg Oncol. 1997;23:36–42.

    Article  CAS  PubMed  Google Scholar 

  5. Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology. 1968;55:677–86.

    CAS  PubMed  Google Scholar 

  6. Plöckinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology. 2004;80:394–424.

    Article  PubMed  Google Scholar 

  7. Oberg K, Astrup L, Eriksson B, Falkmer SE, Falkmer UG, Gustafsen J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part I: general overview. Acta Oncol. 2004;43:617–25.

    Google Scholar 

  8. Oberg K, Astrup L, Eriksson B, Falkmer SE, Falkmer UG, Gustafsen J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II: specific NE tumour types. Acta Oncol. 2004;43:626–36.

    Google Scholar 

  9. Quaedvlieg PF, Visser O, Lamers CB, Janssen-Heijen ML, Taal BG. Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol. 2001;12:1295–300.

    Article  CAS  PubMed  Google Scholar 

  10. Tomassetti P, Campana D, Piscitelli L, Casadei R, Nori F, Brocchi E, et al. Endocrine tumors of the ileum: factors correlated with survival. Neuroendocrinology. 2006;83:380–6.

    Article  CAS  PubMed  Google Scholar 

  11. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  CAS  PubMed  Google Scholar 

  12. Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res. 1999;18:133–41.

    CAS  PubMed  Google Scholar 

  13. Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005;103:1587–95.

    Article  PubMed  Google Scholar 

  14. Ito T, Tanaka M, Sasano H, Osamura YR, Sasaki I, Kimura W, et al. Preliminary results of a Japanese nationwide survey of neuroendocrine gastrointestinal tumors. J Gastroenterol. 2007;42:497–500.

    Article  PubMed  Google Scholar 

  15. Ohno Y. The nationwide epidemiological survey manual for investigating the number of patients and clinico-epidemiological features of intractable diseases. Tokyo: Japanese Ministry of Health and Welfare; 1998 (in Japanese).

  16. Phan AT, Yao JC. Neuroendocrine tumors: novel approaches in the age of targeted therapy. Oncology (Williston Park). 2008;22:1617–23.

    Google Scholar 

  17. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, 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;26:3063–72.

    Article  PubMed  Google Scholar 

  18. Levi F, Te VC, Randimbison L, Rindi G, La Vecchia C. Epidemiology of carcinoid neoplasms in Vaud, Switzerland, 1974–97. Br J Cancer. 2000;83:952–5.

    Article  CAS  PubMed  Google Scholar 

  19. Oberg K. Diagnosis and treatment of carcinoid tumors. Expert Rev Anticancer Ther. 2003;3:863–77.

    Article  PubMed  Google Scholar 

  20. Pape UF, Berndt U, Müller-Nordhorn J, Böhmig M, Roll S, Koch M, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 2008;15:1083–97.

    Article  PubMed  Google Scholar 

  21. Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92.

    Article  CAS  PubMed  Google Scholar 

  22. Bettini R, Boninsegna L, Mantovani W, Capelli P, Bassi C, Pederzoli P, et al. Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol. 2008;19:903–8.

    Article  CAS  PubMed  Google Scholar 

  23. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–68.

    Article  CAS  PubMed  Google Scholar 

  24. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;9:934–59.

    Article  Google Scholar 

  25. Landry CS, Brock G, Scoggins CR, McMasters KM, Martin RC 2nd. Proposed staging system for colon carcinoid tumors based on an analysis of 2,459 patients. J Am Coll Surg. 2008;207:874–81.

    Article  PubMed  Google Scholar 

  26. Triponez F, Goudet P, Dosseh D, Cougard P, Bauters C, Murat A, et al. Is surgery beneficial for MEN1 patients with small (< or =2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg. 2006;30:654–62.

    Article  PubMed  Google Scholar 

  27. Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Risk factors associated with neuroendocrine tumors. A U.S.-based case-control study. Int J Cancer. 2008;123:867–73.

    Article  CAS  PubMed  Google Scholar 

  28. Korman MG, Hansky J, Strickland RG. Progressive increase in the functional G cell mass with age in atrophic gastritis. Gut. 1973;14:549–51.

    Article  CAS  PubMed  Google Scholar 

  29. Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E. Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg. 1996;20:168–72.

    Article  CAS  PubMed  Google Scholar 

  30. Panzuto F, Nasoni S, Falconi M, Corleto VD, Capurso G, Cassetta S, et al. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer. 2005;12:1083–92.

    Article  PubMed  Google Scholar 

  31. Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008;113:256–65.

    Article  PubMed  Google Scholar 

  32. Modlin IM, Latich I, Zikusoka M, Kidd M, Eick G, Chan AK. Gastrointestinal carcinoids: the evolution of diagnostic strategies. J Clin Gastroenterol. 2006;40:572–82.

    Article  PubMed  Google Scholar 

  33. Kvols LK, Brown ML, O’Connor MK, Hung JC, Hayostek RJ, Reubi JC, et al. Evaluation of a radiolabeled somatostatin analog (I-123 octreotide) in the detection and localization of carcinoid and islet cell tumors. Radiology. 1993;187:129–33.

    CAS  PubMed  Google Scholar 

  34. Gibril F, Jensen RT. Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours. Dig Liver Dis. 2004;36:S106–20.

    Article  CAS  PubMed  Google Scholar 

  35. Termanini B, Gibril F, Reynolds JC, Doppman JL, Chen CC, Stewart CA, et al. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology. 1997;112:335–47.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are most grateful to the doctors who responded to the questionnaires.

Author information

Authors and Affiliations

  1. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Tetsuhide Ito, Kazuhiko Nakamura & Hisato Igarashi

  2. Department of Pathology, Tohoku University School of Medicine, Sendai, Japan

    Hironobu Sasano

  3. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masao Tanaka

  4. Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan

    R. Yoshiyuki Osamura

  5. Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan

    Iwao Sasaki

  6. Course of Organ Functions and Controls, Department of Gastroenterological and General Surgery, Yamagata University School of Medicine, Yamagata, Japan

    Wataru Kimura

  7. Department of Nephrology and Endocrinology, University of Tokyo Faculty of Medicine, Tokyo, Japan

    Koji Takano

  8. Department of Endocrine Surgery, Tokyo Women’s Medical University, Tokyo, Japan

    Takao Obara

  9. Department of Medicine, Takatsu General Hospital, Kawasaki, Japan

    Miyuki Ishibashi

  10. Division of Endocrinology and Metabolism, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Kazuwa Nakao

  11. Department of Surgery, Kyoto University, Kyoto, Japan

    Ryuichiro Doi

  12. Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Akira Shimatsu

  13. Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Toshirou Nishida

  14. Department of Surgery, Osaka Saiseikai Noe Hospital, Osaka, Japan

    Izumi Komoto & Masayuki Imamura

  15. Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan

    Yukio Hirata

  16. Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Robert T. Jensen

  17. Department of Hepatology and Gastroenterology, University Medicine Berlin, Charité, Campus Virchow Klinikum, Berlin, Germany

    Bertram Wiedenmann

Authors
  1. Tetsuhide Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hironobu Sasano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masao Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Yoshiyuki Osamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iwao Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wataru Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Koji Takano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takao Obara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miyuki Ishibashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kazuwa Nakao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ryuichiro Doi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akira Shimatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Toshirou Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Izumi Komoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yukio Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kazuhiko Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hisato Igarashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Robert T. Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Bertram Wiedenmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Masayuki Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsuhide Ito.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ito, T., Sasano, H., Tanaka, M. et al. Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol 45, 234–243 (2010). https://doi.org/10.1007/s00535-009-0194-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-009-0194-8

Keywords

  • Neuroendocrine tumor
  • Endocrine pancreatic tumor
  • Gastrointestinal neuroendocrine tumors
  • Nationwide survey
  • Epidemiology