Skip to main content

Advertisement

SpringerLink
Log in

A Clinical Perspective on Gastric Neuroendocrine Neoplasia

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series of international consensus statements defining the biology and management strategies for the disease. Overall, gastric NETs are categorized as well-differentiated or poorly differentiated neoplasms. Well-differentiated gastric NETs are enterochromaffin-like (ECL) cell tumors subclassified into three types based on their relationship to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment of type 1 and type 2 tumors depends on the size and invasiveness of the tumor, whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant aggressive surgical resection. The disease-specific 5-year survival ranges from about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated gastric NECs. Elucidation of the precise biology of a gastric NET is critical to diagnosis and delineation of a type-specific management strategy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Modlin IM, Lye KD, Kidd M: Carcinoid tumors of the stomach. Surg Oncol 2003;12(2):153–172.

    Article  PubMed  Google Scholar 

  2. Rindi G, Solcia E: Endocrine hyperplasia and dysplasia in the pathogenesis of gastrointestinal and pancreatic endocrine tumors. Gastroenterol Clin North Am 2007;36(4):851–865, vi.

    Article  PubMed  Google Scholar 

  3. Nilsson O, Van Cutsem E, Delle Fave G, et al.: Poorly differentiated carcinomas of the foregut (gastric, duodenal and pancreatic). Neuroendocrinology 2006;84(3):212–215.

    Article  CAS  PubMed  Google Scholar 

  4. Rindi G, Luinetti O, Cornaggia M, et al.: Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology 1993;104(4):994–1006.

    CAS  PubMed  Google Scholar 

  5. Washington MK, Tang LH, Berlin J, et al.: Protocol for the examination of specimens from patients with neuroendocrine tumors (carcinoid tumors) of the stomach. Arch Pathol Lab Med 2010;134(2):187–191.

    PubMed  Google Scholar 

  6. • Klimstra DS, Modlin IR, Coppola D, et al.: The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010;39(6):707–712. This paper provides elucidation of the protean contentions and controversies that surround the nomenclature and classification of neuroendocrine tumors.

    Article  PubMed  Google Scholar 

  7. Carney JA, Go VL, Fairbanks VF, et al.: The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med 1983;99(6):761–766.

    CAS  PubMed  Google Scholar 

  8. Rindi G, Bordi C, Rappel S, et al.: Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg 1996;20(2):168–172.

    Article  CAS  PubMed  Google Scholar 

  9. Namikawa T, Kobayashi M, Okabayashi T, et al.: Primary gastric small cell carcinoma: report of a case and review of the literature. Med Mol Morphol 2005;38(4):256–261.

    Article  PubMed  Google Scholar 

  10. Modlin IM, Kidd M, Lye KD: Biology and management of gastric carcinoid tumours: a review. Eur J Surg 2002;168(12):669–683.

    Article  CAS  PubMed  Google Scholar 

  11. Borch K, Ahren B, Ahlman H, et al.: Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 2005;242(1):64–73.

    Article  PubMed  Google Scholar 

  12. Schindl M, Kaserer K, Niederle B: Treatment of gastric neuroendocrine tumors: the necessity of a type-adapted treatment. Arch Surg 2001;136(1):49–54.

    Article  CAS  PubMed  Google Scholar 

  13. Modlin IM, Kidd M, Latich I, et al.: Current status of gastrointestinal carcinoids. Gastroenterology 2005;128(6):1717–1751.

    Article  PubMed  Google Scholar 

  14. Solcia E, Klöppel G, Sobin LH, eds.: Histological Typing of Endocrine Tumors. Berlin: Springer; 2000.

  15. DeLellis RA, Lloyd RV, Heitz PU, eds.: World Health Organization Classification of Tumors, Pathology and Genetics of Tumors of Endocrine Organs. Lyon: IARC Press; 2004.

    Google Scholar 

  16. Ruszniewski P, Delle Fave G, Cadiot G, et al.: Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 2006;84(3):158–164.

    Article  CAS  PubMed  Google Scholar 

  17. Edge S, Byrd D, Carducci M, eds.: AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2009.

    Google Scholar 

  18. Modlin IM, Lye KD, Kidd M: A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem? Am J Gastroenterol 2004;99(1):23–32.

    Article  PubMed  Google Scholar 

  19. Lawrence B, Gustafsson BI, Chan AK, et al.: The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinology and Metabolism Clinics of North America;In Press.

  20. Li AF, Hsu CY, Li A, et al.: A 35-year retrospective study of carcinoid tumors in Taiwan: differences in distribution with a high probability of associated second primary malignancies. Cancer 2008;112(2):274–283.

    Article  PubMed  Google Scholar 

  21. Hauso O, Gustafsson BI, Kidd M, et al.: Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer 2008;113(10):2655–2664.

    Article  PubMed  Google Scholar 

  22. Cao L, Mizoshita T, Tsukamoto T, et al.: Development of carcinoid tumors of the glandular stomach and effects of eradication in Helicobacter pylori-infected Mongolian gerbils. Asian Pac J Cancer Prev 2008;9(1):25–30.

    PubMed  Google Scholar 

  23. Waldum HL, Sandvik AK, Idle JR: Gastrin is the most important factor in ECL tumorigenesis. Gastroenterology 1998;114(5):1113–1115.

    Article  CAS  PubMed  Google Scholar 

  24. Nakata K, Aishima S, Ichimiya H, et al.: Unusual multiple gastric carcinoids with hypergastrinemia: report of a case. Surg Today 2010;40(3):267–271.

    Article  PubMed  Google Scholar 

  25. Poynter D, Pick CR, Harcourt RA, et al.: Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat. Gut 1985;26(12):1284–1295.

    Article  CAS  PubMed  Google Scholar 

  26. Thomson AB, Sauve MD, Kassam N, et al.: Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 2010;16(19):2323–2330.

    Article  CAS  PubMed  Google Scholar 

  27. Graham DY, Genta RM: Long-term proton pump inhibitor use and gastrointestinal cancer. Curr Gastroenterol Rep 2008;10(6):543–547.

    Article  PubMed  Google Scholar 

  28. Kuipers EJ: Proton pump inhibitors and gastric neoplasia. Gut 2006;55(9):1217–1221.

    Article  CAS  PubMed  Google Scholar 

  29. Jensen RT: Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med 1998;243(6):477–488.

    Article  CAS  PubMed  Google Scholar 

  30. • Berna MJ, Annibale B, Marignani M, et al.: A prospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors. J Clin Endocrinol Metab 2008;93(5):1582–1591. This prospective multinational series provides clinicopathological correlation between MEN-I and neoplastic transformation in ECL cells.

    Article  CAS  PubMed  Google Scholar 

  31. Bordi C, Yu JY, Baggi MT, et al.: Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases. Cancer 1991;67(3):663–672.

    Article  CAS  PubMed  Google Scholar 

  32. Strosberg J, Coppola D, Klimstra D, et al.: The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas 2010;39(6):799–800.

    Article  PubMed  Google Scholar 

  33. Kim BS, Oh ST, Yook JH, et al.: Typical carcinoids and neuroendocrine carcinomas of the stomach: differing clinical courses and prognoses. Am J Surg 2010;200(3):328–333.

    Article  PubMed  Google Scholar 

  34. Waldum HL, Rorvik H, Falkmer S, et al.: Neuroendocrine (ECL cell) differentiation of spontaneous gastric carcinomas of cotton rats (Sigmodon hispidus). Lab Anim Sci 1999;49(3):241–247.

    CAS  PubMed  Google Scholar 

  35. Maempel FZ, Modlin I: Diagnosis and management of gastric carcinoid tumour with hepatic metastases. Br J Surg 1978;65(7):516–520.

    Article  CAS  PubMed  Google Scholar 

  36. Kulke MH, Anthony LB, Bushnell DL, et al.: NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010;39(6):735–752.

    Article  PubMed  Google Scholar 

  37. Karaca C, Turner BG, Cizginer S, et al.: Accuracy of EUS in the evaluation of small gastric subepithelial lesions. Gastrointest Endosc 2010;71(4):722–727.

    Article  PubMed  Google Scholar 

  38. • Gladdy RA, Strong VE, Coit D, et al.: Defining surgical indications for type I gastric carcinoid tumor. Ann Surg Oncol 2009;16(11):3154–3160. This paper retrospectively analyzes a relatively large series comparing surgical versus endoscopic resection of small gastric carcinoids, and suggests a similar outcome following either treatment approach.

    Article  PubMed  Google Scholar 

  39. Eckhauser FE, Lloyd RV, Thompson NW, et al.: Antrectomy for multicentric, argyrophil gastric carcinoids: a preliminary report. Surgery 1988;104(6):1046–1053.

    CAS  PubMed  Google Scholar 

  40. Hoshino M, Omura N, Yano F, et al.: Usefulness of laparoscope-assisted antrectomy for gastric carcinoids with hypergastrinemia. Hepatogastroenterology 2010;57(98):379–382.

    PubMed  Google Scholar 

  41. Ozao-Choy J, Buch K, Strauchen JA, et al.: Laparoscopic antrectomy for the treatment of type I gastric carcinoid tumors. J Surg Res 2010;162(1):22–25.

    Article  PubMed  Google Scholar 

  42. Kidd M, Tang LH, Modlin IM, et al.: Gastrin-mediated alterations in gastric epithelial apoptosis and proliferation in a mastomys rodent model of gastric neoplasia. Digestion 2000;62(2–3):143–151.

    Article  CAS  PubMed  Google Scholar 

  43. Kidd M, Modlin IM, Black JW, et al.: A comparison of the effects of gastrin, somatostatin and dopamine receptor ligands on rat gastric enterochromaffin-like cell secretion and proliferation. Regul Pept 2007;143(1–3):109–117.

    Article  CAS  PubMed  Google Scholar 

  44. Khuroo MS, Khuroo NS: Treatment of type I gastric neuroendocrine tumors with somatostatin analogs. J Gastroenterol Hepatol 2010;25(3):548–554.

    Article  CAS  PubMed  Google Scholar 

  45. Fykse V, Sandvik AK, Waldum HL: One-year follow-up study of patients with enterochromaffin-like cell carcinoids after treatment with octreotide long-acting release. Scand J Gastroenterol 2005;40(11):1269–1274.

    Article  PubMed  Google Scholar 

  46. Grozinsky-Glasberg S, Kaltsas G, Gur C, et al.: Long-acting somatostatin analogues are an effective treatment for type 1 gastric carcinoid tumours. Eur J Endocrinol 2008;159(4):475–482.

    Article  CAS  PubMed  Google Scholar 

  47. Campana D, Nori F, Pezzilli R, et al.: Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs. Endocr Relat Cancer 2008;15(1):337–342.

    Article  CAS  PubMed  Google Scholar 

  48. Ruszniewski P, Ramdani A, Cadiot G, et al.: Long-term treatment with octreotide in patients with the Zollinger-Ellison syndrome. Eur J Clin Invest 1993;23(5):296–301.

    Article  CAS  PubMed  Google Scholar 

  49. Annibale B, Delle Fave G, Azzoni C, et al.: Three months of octreotide treatment decreases gastric acid secretion and argyrophil cell density in patients with Zollinger-Ellison syndrome and antral G-cell hyperfunction. Aliment Pharmacol Ther 1994;8(1):95–104.

    Article  CAS  PubMed  Google Scholar 

  50. Manfredi S, Pagenault M, de Lajarte-Thirouard AS, et al.: Type 1 and 2 gastric carcinoid tumors: long-term follow-up of the efficacy of treatment with a slow-release somatostatin analogue. Eur J Gastroenterol Hepatol 2007;19(11):1021–1025.

    Article  PubMed  Google Scholar 

  51. Lawrence B, Gustaffson B, Kidd M, et al.: New Pharmacologic Therapies for Gastroenteropancreatic Neuroendocrine Tumors. North American Clinics of Gastroenterology 2010;in press.

  52. Moertel CG, Kvols LK, O’Connell MJ, et al.: Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer 1991;68(2):227–232.

    Article  CAS  PubMed  Google Scholar 

  53. Mitry E, Baudin E, Ducreux M, et al.: Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer 1999;81(8):1351–1355.

    Article  CAS  PubMed  Google Scholar 

  54. Kulke MH, Wu B, Ryan DP, et al.: A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors. Dig Dis Sci 2006;51(6):1033–1038.

    Article  CAS  PubMed  Google Scholar 

  55. Modlin IM, Lye KD, Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97(4):934–959.

    Article  PubMed  Google Scholar 

  56. Rindi G, Azzoni C, La Rosa S, et al.: ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: prognostic evaluation by pathological analysis. Gastroenterology 1999;116(3):532–542.

    Article  CAS  PubMed  Google Scholar 

  57. Rappel S, Altendorf-Hofmann A, Stolte M: Prognosis of gastric carcinoid tumours. Digestion 1995;56(6):455–462.

    Article  CAS  PubMed  Google Scholar 

  58. Landry CS, Brock G, Scoggins CR, et al.: A proposed staging system for gastric carcinoid tumors based on an analysis of 1,543 patients. Ann Surg Oncol 2009;16(1):51–60.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Maria-Theresia Svejda provided support with figure illustration. Ben Lawrence was partially supported by the Murray Jackson Clinical Fellowship, Genesis Oncology Trust, Auckland, New Zealand. Mark Kidd is supported by National Institutes of Health grant DK080871.

Disclosure

Conflicts of interest: B. Lawrence—none; M. Kidd—none; B. Svejda—none; I. Modlin—none.

Author information

Authors and Affiliations

  1. Gastrointestinal Pathobiology Group, Yale University School of Medicine, PO Box 208602, New Haven, CT, 06520, USA

    Ben Lawrence, Mark Kidd, Bernhard Svejda & Irvin Modlin

Authors
  1. Ben Lawrence
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Kidd
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernhard Svejda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irvin Modlin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irvin Modlin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lawrence, B., Kidd, M., Svejda, B. et al. A Clinical Perspective on Gastric Neuroendocrine Neoplasia. Curr Gastroenterol Rep 13, 101–109 (2011). https://doi.org/10.1007/s11894-010-0158-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-010-0158-4

Keywords

Search

Navigation