Journal of Gastroenterology

, Volume 45, Issue 2, pp 234–243 | Cite as

Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan

  • Tetsuhide Ito
  • Hironobu Sasano
  • Masao Tanaka
  • R. Yoshiyuki Osamura
  • Iwao Sasaki
  • Wataru Kimura
  • Koji Takano
  • Takao Obara
  • Miyuki Ishibashi
  • Kazuwa Nakao
  • Ryuichiro Doi
  • Akira Shimatsu
  • Toshirou Nishida
  • Izumi Komoto
  • Yukio Hirata
  • Kazuhiko Nakamura
  • Hisato Igarashi
  • Robert T. Jensen
  • Bertram Wiedenmann
  • Masayuki Imamura
Original Article—Liver, Pancreas, and Biliary Tract



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


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.


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.


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.


Neuroendocrine tumor Endocrine pancreatic tumor Gastrointestinal neuroendocrine tumors Nationwide survey Epidemiology 



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


  1. 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. 2.
    Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRefPubMedGoogle Scholar
  3. 3.
    Eriksson B, Oberg K. Neuroendocrine tumours of the pancreas. Br J Surg. 2000;87:129–31.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 5.
    Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology. 1968;55:677–86.PubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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. 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. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 13.
    Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005;103:1587–95.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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).Google Scholar
  16. 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. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Oberg K. Diagnosis and treatment of carcinoid tumors. Expert Rev Anticancer Ther. 2003;3:863–77.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 21.
    Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 23.
    Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–68.CrossRefPubMedGoogle Scholar
  24. 24.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;9:934–59.CrossRefGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 34.
    Gibril F, Jensen RT. Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours. Dig Liver Dis. 2004;36:S106–20.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Tetsuhide Ito
    • 1
  • Hironobu Sasano
    • 2
  • Masao Tanaka
    • 3
  • R. Yoshiyuki Osamura
    • 4
  • Iwao Sasaki
    • 5
  • Wataru Kimura
    • 6
  • Koji Takano
    • 7
  • Takao Obara
    • 8
  • Miyuki Ishibashi
    • 9
  • Kazuwa Nakao
    • 10
  • Ryuichiro Doi
    • 11
  • Akira Shimatsu
    • 12
  • Toshirou Nishida
    • 13
  • Izumi Komoto
    • 14
  • Yukio Hirata
    • 15
  • Kazuhiko Nakamura
    • 1
  • Hisato Igarashi
    • 1
  • Robert T. Jensen
    • 16
  • Bertram Wiedenmann
    • 17
  • Masayuki Imamura
    • 14
  1. 1.Department of Medicine and Bioregulatory Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of PathologyTohoku University School of MedicineSendaiJapan
  3. 3.Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of PathologyTokai University School of MedicineKanagawaJapan
  5. 5.Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
  6. 6.Course of Organ Functions and Controls, Department of Gastroenterological and General SurgeryYamagata University School of MedicineYamagataJapan
  7. 7.Department of Nephrology and EndocrinologyUniversity of Tokyo Faculty of MedicineTokyoJapan
  8. 8.Department of Endocrine SurgeryTokyo Women’s Medical UniversityTokyoJapan
  9. 9.Department of MedicineTakatsu General HospitalKawasakiJapan
  10. 10.Division of Endocrinology and Metabolism, Department of Medicine and Clinical ScienceKyoto University Graduate School of MedicineKyotoJapan
  11. 11.Department of SurgeryKyoto UniversityKyotoJapan
  12. 12.Clinical Research InstituteNational Hospital Organization Kyoto Medical CenterKyotoJapan
  13. 13.Department of SurgeryOsaka University Graduate School of MedicineOsakaJapan
  14. 14.Department of SurgeryOsaka Saiseikai Noe HospitalOsakaJapan
  15. 15.Department of Clinical and Molecular EndocrinologyTokyo Medical and Dental University Graduate SchoolTokyoJapan
  16. 16.Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  17. 17.Department of Hepatology and GastroenterologyUniversity Medicine BerlinBerlinGermany

Personalised recommendations