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Management of Gastric Carcinoids (Neuroendocrine Neoplasms)

  • Stomach and Duodenum (J Pisegna, Section Editor)
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Abstract

Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Mainly due to better diagnostics and awareness of this tumor, the observed incidence has increased more than tenfold over the last 30 years. Small (<15–20 mm) localized type I and II lesions that are slowly proliferating (Ki67<2%) can usually be managed conservatively with endoscopic surveillance. Reducing hypergastrinemia by surgical removal of an underlying gastrinoma is important in inhibiting growth and induce reduction of type II lesions, while the specific gastrin receptor antagonist YF476 or gastrin antibodies may become useful for both type I and II lesions. Infiltrating and metastasized tumors and type III lesions require a more aggressive approach with surgical resection and consideration of modalities such as somatostatin analogs, cytotoxics, and peptide receptor targeted treatment.

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References

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

  1. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61–72.

    Article  PubMed  CAS  Google Scholar 

  2. Latta E, Rotondo F, Leiter LA, Horvath E, Kovacs K. Ghrelin- and serotonin-producing gastric carcinoid. J Gastrointest Cancer. 2012;43(2):319–23.

    Article  PubMed  Google Scholar 

  3. Modlin IM, Tang LH. The gastric enterochromaffin-like cell: an enigmatic cellular link. Gastroenterology. 1996;111(3):783–810.

    Article  PubMed  CAS  Google Scholar 

  4. Bordi C. Gastric carcinoids. Ital J Gastroenterol Hepatol. 1999;31 Suppl 2:S94–7.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  6. •• Scherubl H, Cadiot G, Jensen RT, Rosch T, Stolzel U, Kloppel G. Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems? Endoscopy. 2010;42(8):664–71. This provides an up-to-date overview of the lesions and identifies the importance of the pathobiology (growth characteristics/stage of disease) of the lesion for optimal management.

    Article  PubMed  CAS  Google Scholar 

  7. Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010;37(6):594–618.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Arnold R, Kloppel G, Rothmund M. Carcinoid tumors. International symposium on pathology, epidemiology, clinical aspects and therapy. January 13–16, 1994, Munich, Germany. Proceedings. Digestion 1994;55(3): 1–113.

  10. • Spampatti MP, Massironi S, Rossi RE, et al. Unusually aggressive type 1 gastric carcinoid: a case report with a review of the literature. Eur J Gastroenterol Hepatol. 2012;24(5):589–93. This reports the poor prognosis and difficulties with management of a "malignant" Type I tumor, highlighting the potential issues with a "benign" tumor classification.

    Article  PubMed  Google Scholar 

  11. Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  12. Gough DB, Thompson GB, Crotty TB, et al. Diverse clinical and pathologic features of gastric carcinoid and the relevance of hypergastrinemia. World J Surg. 1994;18(4):473–9. discussion 79–80.

    Article  PubMed  CAS  Google Scholar 

  13. Jordan Jr PH, Barroso A, Sweeney J. Gastric carcinoids in patients with hypergastrinemia. J Am Coll Surg. 2004;199(4):552–5.

    Article  PubMed  Google Scholar 

  14. Vannella L, Sbrozzi-Vanni A, Lahner E, et al. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Aliment Pharmacol Ther. 2011;33(12):1361–9.

    Article  PubMed  CAS  Google Scholar 

  15. Modlin IM, Lye KD, Kidd M. Carcinoid tumors of the stomach. Surg Oncol. 2003;12(2):153–72.

    Article  PubMed  Google Scholar 

  16. Ruszniewski P, Delle Fave G, Cadiot G, et al. Well-differentiated gastric tumors/carcinomas. Neuroendocrinology. 2006;84(3):158–64.

    Article  PubMed  CAS  Google Scholar 

  17. Kekilli M, Beyazit Y, Karaman K, et al. Endoscopic and pathological aspects of gastric polyps: a Turkish referral center study. Hepatogastroenterology. 2012;59(116):1147–9.

    PubMed  Google Scholar 

  18. Jianu CS, Fossmark R, Viset T, et al. Gastric carcinoid after long-term use of a proton pump inhibitor. Aliment Pharmacol Ther. 2012, In press.

  19. Saund MS, Al Natour RH, Sharma AM, Huang Q, Boosalis VA, Gold JS. Tumor size and depth predict rate of lymph node metastasis and utilization of lymph node sampling in surgically managed gastric carcinoids. Ann Surg Oncol. 2011;18(10):2826–32. Epub 011 Apr 1.

    Article  PubMed  Google Scholar 

  20. Modlin IM, Latich I, Kidd M, Zikusoka M, Eick G. Therapeutic options for gastrointestinal carcinoids. Clin Gastroenterol Hepatol. 2006;4(5):526–47.

    Article  PubMed  CAS  Google Scholar 

  21. Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242(1):64–73.

    Article  PubMed  Google Scholar 

  22. Merola E, Sbrozzi-Vanni A, Panzuto F, et al. Type I gastric carcinoids: a prospective study on endoscopic management and recurrence rate. Neuroendocrinology. 2012;95(3):207–13. Epub 2011 Jul 30.

    Article  PubMed  CAS  Google Scholar 

  23. Borin JF, Tang LH, Kidd M, et al. Somatostatin receptor regulation of gastric enterochromaffin-like cell transformation to gastric carcinoid. Surgery. 1996;120(6):1026–32.

    Article  PubMed  CAS  Google Scholar 

  24. Fykse V, Sandvik AK, Qvigstad G, Falkmer SE, Syversen U, Waldum HL. Treatment of ECL cell carcinoids with octreotide LAR. Scand J Gastroenterol. 2004;39(7):621–8.

    Article  PubMed  CAS  Google Scholar 

  25. 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):337–42.

    Article  PubMed  CAS  Google Scholar 

  26. •• Jianu CS, Fossmark R, Syversen U, Hauso O, Fykse V, Waldum HL. Five-year follow-up of patients treated for 1 year with octreotide long-acting release for enterochromaffin-like cell carcinoids. Scand J Gastroenterol. 2011;46(4):456–63. Epub 2010 Dec 7. This paper illustrates potential issues with somatostatin analog therapy in gastric NENs, highlighting a rebound growth affect associated with removal of therapy.

    Article  PubMed  Google Scholar 

  27. Boyce M, David O, Darwin K, Mitchell T, Johnston A, Warrington S. Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause dose-dependent, sustained increases in gastric pH compared with placebo and ranitidine in healthy subjects. Aliment Pharmacol Ther. 2012;36(2):181–9.

    Article  PubMed  CAS  Google Scholar 

  28. Kidd M, Siddique ZL, Drozdov I, et al. The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development. Regul Pept. 2010;162(1–3):52–60.

    Article  PubMed  CAS  Google Scholar 

  29. Fossmark R, Sørdal Ø, Jianu CS, Qvigstad G, Boyce M, Waldum HL. Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist YF476 results in regression of tumours and normalisation of serum chromogranin A. Gastroenterology. 2012;142(5):S-15.

    Google Scholar 

  30. • Tieppo C, Betterle C, Basso D, et al. Gastric type I carcinoid: a pilot study with human G17DT immunogen vaccination. Cancer Immunol Immunother. 2011;60(7):1057–60. Epub 2011 May 18. This small, pilot study identified a potential role for a gastrin vaccine in the treatment of gastrin-responsive NENs.

    Article  PubMed  CAS  Google Scholar 

  31. • Spampatti MP, Massironi S, Rossi RE, et al. Unusually aggressive type 1 gastric carcinoid: a case report with a review of the literature. Eur J Gastroenterol Hepatol. 2012;24(5):589–93. This reports the poor prognosis and difficulties with management of a "malignant" Type I tumor, highlighting the potential issues with a "benign" tumor classification.

    Article  PubMed  Google Scholar 

  32. McCarthy DM. Adverse effects of proton pump inhibitor drugs: clues and conclusions. Curr Opin Gastroenterol. 2010;26(6):624–31.

    Article  PubMed  CAS  Google Scholar 

  33. Debelenko LV, Emmert-Buck MR, Zhuang Z, et al. The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology. 1997;113(3):773–81.

    Article  PubMed  CAS  Google Scholar 

  34. D’Adda T, Keller G, Bordi C, Hofler H. Loss of heterozygosity in 11q13-14 regions in gastric neuroendocrine tumors not associated with multiple endocrine neoplasia type 1 syndrome. Lab Invest. 1999;79(6):671–7.

    PubMed  Google Scholar 

  35. Debelenko LV, Zhuang Z, Emmert-Buck MR, et al. Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1-associated and sporadic gastrinomas and pancreatic endocrine tumors. Cancer Res. 1997;57(11):2238–43.

    PubMed  CAS  Google Scholar 

  36. Calender A. Molecular genetics of neuroendocrine tumors. Digestion. 2000;62 Suppl 1:3–18.

    Article  PubMed  CAS  Google Scholar 

  37. Ivo D, Corset L, Desbourdes L, Gaudray P, Weber G. Menin controls the concentration of retinoblastoma protein. Cell Cycle. 2011;10(1):166–8. Epub 2011 Jan 1.

    Article  PubMed  CAS  Google Scholar 

  38. Gagrica S, Brookes S, Anderton E, Rowe J, Peters G. Contrasting behavior of the p18INK4c and p16INK4a tumor suppressors in both replicative and oncogene-induced senescence. Cancer Res. 2012;72(1):165–75. Epub 2011 Nov 11.

    Article  PubMed  CAS  Google Scholar 

  39. Hughes E, Huang C. Participation of Akt, menin, and p21 in pregnancy-induced beta-cell proliferation. Endocrinology. 2011;152(3):847–55. Epub 2011 Jan 14.

    Article  PubMed  CAS  Google Scholar 

  40. Kidd M, Hinoue T, Eick G, et al. Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation. Physiol Genomics. 2004;20(1):131–42.

    Article  PubMed  CAS  Google Scholar 

  41. Mensah-Osman EJ, Veniaminova NA, Merchant JL. Menin and JunD regulate gastrin gene expression through proximal DNA elements. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G783–90. Epub 2011 Aug 18.

    Article  PubMed  CAS  Google Scholar 

  42. Debelenko LV, Emmert-Buck MR, Zhuang Z, et al. The multiple endocrine neoplasia type I gene locus is involved in the pathogenesis of type II gastric carcinoids. Gastroenterology. 1997;113(3):773–81.

    Article  PubMed  CAS  Google Scholar 

  43. Lew EA, Pisegna JR, Starr JA, et al. Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterology. 2000;118(4):696–704.

    Article  PubMed  CAS  Google Scholar 

  44. Modlin IM, Kidd M, Latich I, Zikusoka MN, Shapiro MD. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128(6):1717–51.

    Article  PubMed  Google Scholar 

  45. Campana D, Piscitelli L, Mazzotta E, et al. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. 2005;96(3):187–206.

    PubMed  CAS  Google Scholar 

  46. Ruszniewski P, Ramdani A, Cadiot G, Lehy T, Mignon M, Bonfils S. Long-term treatment with octreotide in patients with the Zollinger-Ellison syndrome. Eur J Clin Invest. 1993;23(5):296–301.

    Article  PubMed  CAS  Google Scholar 

  47. 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  PubMed  CAS  Google Scholar 

  48. 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):1269–74.

    Article  PubMed  Google Scholar 

  49. Richards ML, Gauger P, Thompson NW, Giordano TJ. Regression of type II gastric carcinoids in multiple endocrine neoplasia type 1 patients with Zollinger-Ellison syndrome after surgical excision of all gastrinomas. World J Surg. 2004;28(7):652–8. Epub 2004 Jun 16.

    Article  PubMed  Google Scholar 

  50. Bordi C, Azzoni C, Ferraro G, et al. Sampling strategies for analysis of enterochromaffin-like cell changes in Zollinger-Ellison syndrome. Am J Clin Pathol. 2000;114(3):419–25.

    PubMed  CAS  Google Scholar 

  51. Jensen RT. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med. 1998;243(6):477–88.

    Article  PubMed  CAS  Google Scholar 

  52. Meko JB, Norton JA. Management of patients with Zollinger-Ellison syndrome. Annu Rev Med. 1995;46:395–411.

    Article  PubMed  CAS  Google Scholar 

  53. Stewart W, Traynor JP, Cooke A, et al. Gastric carcinoid: germline and somatic mutation of the neurofibromatosis type 1 gene. Fam Cancer. 2007;6(1):147–52.

    Article  PubMed  CAS  Google Scholar 

  54. Laycock-van Spyk S, Thomas N, Cooper DN, Upadhyaya M. Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis. Hum Genomics. 2011;5(6):623–90.

    Article  PubMed  Google Scholar 

  55. Creutzfeldt W, Stockmann F. Carcinoids and carcinoid syndrome. Am J Med. 1987;82(5B):4–16.

    Article  PubMed  CAS  Google Scholar 

  56. Jensen RT, Norton JA. Carcinoid tumors and the carcinoid syndrome. Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott-Raven Publishers; 1997. p. 1704–23.

    Google Scholar 

  57. Moertel CG, Kvols LK, O’Connell MJ, Rubin J. 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):227–32.

    Article  PubMed  CAS  Google Scholar 

  58. Gilligan CJ, Lawton GP, Tang LH, West AB, Modlin IM. Gastric carcinoid tumors: the biology and therapy of an enigmatic and controversial lesion. Am J Gastroenterol. 1995;90(3):338–52.

    PubMed  CAS  Google Scholar 

  59. Kumashiro R, Naitoh H, Teshima K, Sakai T, Inutsuka S. Minute gastric carcinoid tumor with regional lymph node metastasis. Int Surg. 1989;74(3):198–200.

    PubMed  CAS  Google Scholar 

  60. De Vries EG, Kema IP, Slooff MJ, et al. Recent developments in diagnosis and treatment of metastatic carcinoid tumours. Scand J Gastroenterol Suppl. 1993;200:87–93.

    Article  PubMed  Google Scholar 

  61. Davies MG, O’Dowd G, McEntee GP, Hennessy TP. Primary gastric carcinoids: a view on management. Br J Surg. 1990;77(9):1013–4.

    Article  PubMed  CAS  Google Scholar 

  62. Godwin 2nd JD. Carcinoid tumors. An analysis of 2,837 cases. Cancer. 1975;36(2):560–9.

    Article  PubMed  Google Scholar 

  63. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79(4):813–29.

    Article  PubMed  CAS  Google Scholar 

  64. 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 

  65. Landry CS, Brock G, Scoggins CR, McMasters KM, Martin 2nd RC. A proposed staging system for gastric carcinoid tumors based on an analysis of 1,543 patients. Ann Surg Oncol. 2009;16(1):51–60. Epub 2008 Oct 24.

    Article  PubMed  Google Scholar 

  66. Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40(1):1–18. vii.

    Article  PubMed  Google Scholar 

  67. Hodgson N, Koniaris LG, Livingstone AS, Franceschi D. Gastric carcinoids: a temporal increase with proton pump introduction. Surg Endosc. 2005;19(12):1610–2.

    Article  PubMed  CAS  Google Scholar 

  68. Hassall E, Owen D, Kerr W, Sturby T, Richardson P, El-Serag H. Gastric histology in children treated with proton pump inhibitors long term, with emphasis on enterochromaffin cell-like hyperplasia. Aliment Pharmacol Ther. 2011;33(7):829–36. doi:10.1111/j.365-2036.11.04592.x.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Surgery, Yale University School of Medicine, PO Box 208602, New Haven, CT, USA

    Mark Kidd

  2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Bjorn I. Gustafsson

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Kidd, M., Gustafsson, B.I. Management of Gastric Carcinoids (Neuroendocrine Neoplasms). Curr Gastroenterol Rep 14, 467–472 (2012). https://doi.org/10.1007/s11894-012-0289-x

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