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.
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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.
Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.
Eriksson B, Oberg K. Neuroendocrine tumours of the pancreas. Br J Surg. 2000;87:129–31.
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.
Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology. 1968;55:677–86.
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.
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.
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.
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.
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.
Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.
Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res. 1999;18:133–41.
Soga J. Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005;103:1587–95.
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.
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).
Phan AT, Yao JC. Neuroendocrine tumors: novel approaches in the age of targeted therapy. Oncology (Williston Park). 2008;22:1617–23.
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.
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.
Oberg K. Diagnosis and treatment of carcinoid tumors. Expert Rev Anticancer Ther. 2003;3:863–77.
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.
Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92.
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.
Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858–68.
Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;9:934–59.
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.
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.
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.
Korman MG, Hansky J, Strickland RG. Progressive increase in the functional G cell mass with age in atrophic gastritis. Gut. 1973;14:549–51.
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.
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.
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.
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.
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.
Gibril F, Jensen RT. Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours. Dig Liver Dis. 2004;36:S106–20.
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.
The authors are most grateful to the doctors who responded to the questionnaires.
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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
- Neuroendocrine tumor
- Endocrine pancreatic tumor
- Gastrointestinal neuroendocrine tumors
- Nationwide survey