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Gastro-entero-pancreatic Neuroendocrine Tumors

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Abstract

The understanding of the structure and functioning of the neuroendocrine system has engendered impressive developments since the late nineteenth century, along with corresponding changes in its nomenclature. Assumptions about a distinct role began to be expressed, initially by the German physiologist Heidenhain and subsequently by the Russian physician Kulchitsky, after the localisation in the intestine of individual cells or populations of cells having secretory vesicles with chromophilic properties staining. In this chapter, the classification, epidemiology, characteristics and therapeutic approaches of gastro-entero-pancreatic neuroendocrine tumors are reported in detail.

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Notes

  1. 1.

    This is because there are endocrine cells (parathyroid gland cells) that do not express APUD behaviour and exocrine cells (Lieberkühn’s Paneth cells) that surprisingly express APUD behaviour; additionally, it is well known that the neuroendocrine cells of the gastrointestinal tract have an endodermal, rather than exodermal, embryologic origin [20].

References

  1. Modlin IM, Champaneria MC, Bornschein J, et al. Evolution of the diffuse neuroendocrine system- clear cells and cloudy origins. Neuroendocrinology. 2006;84(2):69–82.

    Article  CAS  PubMed  Google Scholar 

  2. Drozdov I, Modlin IM, Kidd M, et al. From Leningrad to London: the saga of Kultschitzky and the legacy of the enterochromaffin cell. Neuroendocrinology. 2009;89(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  3. De Herder WW, Rehfeld JF, et al. A short history of neuroendocrine tumours and their peptide hormones. Best Pract Res Clin Endocrinol Metab. 2015; https://doi.org/10.1016/j.beem.2015.10.004.

  4. Heidenhain R. Untersuchungen über den Bau der Labdrusen. Arch Mikrosk Anat. 1870;6:368–406.

    Article  Google Scholar 

  5. Public domain; http://resource.nlm.nih.gov/101418204

  6. Kulchitsky N. Zur Frage über den Bau des Darmkanals. Arch Mikrosk Anat. 1897;49:7–35.

    Article  Google Scholar 

  7. Public domain; http://rusk.ru/newsdata.php?idar=175371

  8. Ciaccio MC. Sopra speciali cellule granulose della mucosa intestinale. Arch Ital Embriol. 1907;6:498–582.

    Google Scholar 

  9. Ciaccio MC. Sur une nouvelle espece cellulaire dans les glande de Lieberkühn. C R Soc Biol (Paris). 1906;60:76.

    Google Scholar 

  10. Masson P. La glande endocrine de l’intestin chez l’homme. C R Hebd Seances Acad Sci. 1914;158:59–61.

    Google Scholar 

  11. Hamperl H. Was sind argentaffine Zellen? Virchows Arch. 1932;286:811–33.

    Article  Google Scholar 

  12. Feyrter F. Über diffuse endokrine epithelial Organe. Leipzig, Germany: JA Barth (Pbls); 1938.

    Google Scholar 

  13. Carvalheira AF, Welsch U, Pearse AG. Cytochemical and ultrastructural observations on the argentaffin and argyrophil cells of the gastro-intestinal tract in mammals, and their place in the APUD series of polypeptide-secreting cells. Histochemie. 1968;14(1):33–46.

    Article  CAS  PubMed  Google Scholar 

  14. Pearse AG. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of this concept. J Histochem Cytochem. 1969;17:303–13.

    Article  CAS  PubMed  Google Scholar 

  15. Pearse AG. The APUD cell concept and its implications in pathology. Pathol Annu. 1974;9:27–41.

    CAS  PubMed  Google Scholar 

  16. Langley K. The neuroendocrine concept today. Ann NY Acad Science. 1994;733:1–17.

    Article  CAS  Google Scholar 

  17. De Lellis RA. The neuroendocrine system and its tumors: an overview. Am J Clin Pathol. 2001;115(S1):S5–16.

    Google Scholar 

  18. Kino SR. Ch. 10: Neuroendocrine system and neuroendocrine neoplasia. In: Kini SR, editor. Colo Atlas of differential diagnosis in exfoliative and aspiration cytopathology. 2nd ed. Philadelphia, PA: Wolters-Kluwer Lippincott Williams & Wilkins Section III (Fine Needle Aspiration Cytopathology); 2011. p. 349–69.

    Google Scholar 

  19. Day R, Salzet M. The neuroendocrine phenotype, cellular plasticity, and the search for genetic switches: redefining the diffuse neuroendocrine system. Neuroendoc Letters. 2002;23:447–51.

    Google Scholar 

  20. Andrew A, Kramer B, Rawdon BB. The origin of gut and pancreatic neuroendocrine (APUD) cells the last word? J Pathol. 1998;186:117–8.

    Article  CAS  PubMed  Google Scholar 

  21. De Lellis RA, Tischler AS. The dispersed neuroendocrine cell system. In: Kovacs K, Asa SL, editors. Functional endocrine pathology. 2nd ed. Blackwell Scientific: Malden, MA; 1998. p. 529–49.

    Google Scholar 

  22. Modlin IM, Öberg K, Chung DC, et al. Gastroenteropancreatic neuro-endocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  CAS  PubMed  Google Scholar 

  23. Klöppel G. Classification and pathology of gastroenteropancreatic neuro-endocrine neo-plasms. Endoc Rel Cancer. 2011;18(S1):S1–16.

    Article  Google Scholar 

  24. Klimstra DS, Modlin IR, Coppola D. The pathologic classification of neuro-endocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39:707–12.

    Article  PubMed  Google Scholar 

  25. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–59.

    Article  PubMed  Google Scholar 

  26. Warner RR. Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. Gastroenterology. 2005;128:1668–84.

    Article  PubMed  Google Scholar 

  27. Schimmack S, Svejda B, Lawrence B, et al. The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors. Langenbeck's Arch Surg. 2011;396:273–98.

    Article  Google Scholar 

  28. Langhans T. Über einen Drüsenpolyp im Ileum. Virchow Arch Pathol Anat. 1867;38:550–60.

    Article  Google Scholar 

  29. Lubarsch O. Über den primären Krebs des Ileums, nebst Bemerkungen über das gleichzeitige Vorkommen von Krebs und Tuberkulose. Virchow Arch Pathol Anat. 1888;111:280–317.

    Article  Google Scholar 

  30. Ransom W. A case of primary carcinoma of the ileum. Lancet. 1890;2:1020–3.

    Article  Google Scholar 

  31. Williams ED, Sandler M. The classification of carcinoid tumor. Lancet. 1963;1:238–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kerström G, Hellman P, Hessman O. Midgut carcinoid tumors: surgical treatment and prognosis. Best Pract Res Clin Gastroenterol. 2005;19:717–28.

    Article  PubMed  Google Scholar 

  33. Plöckinger U, Couvelard A, Falconi M, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumors: well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma. Neuroendocrinology. 2008;87:20–30.

    Article  PubMed  CAS  Google Scholar 

  34. Ramage JK, Goretzki PE, Manfredi R, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumors: well-differentiated colon and rectum tumor/carcinoma. Neuroendocrinology. 2008;87:31–9.

    Article  CAS  PubMed  Google Scholar 

  35. Givi B, Pommier SJ, Thompson AK, et al. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery. 2006;140:891–7.

    Article  PubMed  Google Scholar 

  36. Steinmüller T, Kianmanesh R, Falconi M, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2008;87:47–62.

    Article  PubMed  CAS  Google Scholar 

  37. Vogl TJ, Naguib NN, Zangos S, et al. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol. 2009;72:517–28.

    Article  PubMed  Google Scholar 

  38. Kamat PP, Gupta S, Ensor JE, et al. Hepatic arterial embolization and chemoembolization in the management of patients with large-volume liver metastases. Cardiovasc Intervent Radiol. 2008;31:299–307.

    Article  PubMed  Google Scholar 

  39. Ruszniewski P, Malka D. Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. Digestion. 2000;62(Suppl 1):79–83.

    Article  PubMed  Google Scholar 

  40. King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008;113:921–9.

    Article  PubMed  Google Scholar 

  41. Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol. 2008;31:271–9.

    Article  PubMed  Google Scholar 

  42. Ruszniewski P, Ish-Shalom S, Wymenga M, et al. Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide. Neuroendocrinology. 2004;80:244–51.

    Article  CAS  PubMed  Google Scholar 

  43. Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumors. Aliment Pharmacol Ther. 2010;31:169–88.

    CAS  PubMed  Google Scholar 

  44. Eriksson B, Klöppel G, Krenning E, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumors—well-differentiated jejunal-ileal tumour/carcinoma. Neuroendocrinology. 2008;87:8–19.

    Article  CAS  PubMed  Google Scholar 

  45. Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27:4656–63.

    Article  CAS  PubMed  Google Scholar 

  46. Öberg K. Interferon in the management of neuroendocrine GEP tumors. Digestion. 2000;62(Suppl 1):92–7.

    Article  PubMed  Google Scholar 

  47. Eriksson B, Öberg K. An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol. 1993;32:203–8.

    Article  CAS  PubMed  Google Scholar 

  48. 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;68:227–32.

    Article  CAS  PubMed  Google Scholar 

  49. Moertel CG, Johnson CM, McKusick MA, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. 1994;120:302–9.

    Article  CAS  PubMed  Google Scholar 

  50. Mani MA, Shroff RT, Jacobs C, et al. A phase II study of irinotecan and cisplatin for metastatic or unresectable high-grade neuroendocrine carcinoma [abstract]. J Clin Oncol. 2008;26(Suppl)

    Google Scholar 

  51. Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumors? Cancer Chemother Pharmacol. 2007;59:637–42.

    Article  CAS  PubMed  Google Scholar 

  52. Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004;22:4762–71.

    Article  CAS  PubMed  Google Scholar 

  53. Fjallskog ML, Janson ET, Falkmer UG, et al. Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors. Neuroendocrinology. 2008;88:53–8.

    Article  PubMed  CAS  Google Scholar 

  54. Moertel CG, Lefkopoulos M, Lipsitz S, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326:519–23.

    Article  CAS  PubMed  Google Scholar 

  55. Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011;117:268–75.

    Article  CAS  PubMed  Google Scholar 

  56. Kulke MH, Stuart K, Enzinger PC, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006;24:401–6.

    Article  CAS  PubMed  Google Scholar 

  57. Eriksson B, Annibale B, Bajetta E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: chemotherapy in patients with neuroendocrine tumors. Neuroendocrinology. 2009;90:214–9.

    Article  CAS  PubMed  Google Scholar 

  58. Yao JC, Phan A, Hoff PM, et al. Targeting vascular endothelial growth factor in advanced carcinoid tumour: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol. 2008;26:1316–23.

    Article  CAS  PubMed  Google Scholar 

  59. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–13.

    Article  CAS  PubMed  Google Scholar 

  60. Yao JC, Lombard-Bohas C, Baudin E, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010;28:69–76.

    Article  CAS  PubMed  Google Scholar 

  61. Yao JC, Shah MH, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Patrick DL, Ferketich SL, Frame PS, et al. Symptom management in cancer: pain, depression, and fatigue. J Natl Cancer Inst. 2003;95:1110–7.

    PubMed  Google Scholar 

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  1. Nuclear Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Georgios S. Limouris

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  1. Nuclear Medicine, Medical School National and Kapodistrian University of Athens, Athens, Greece

    Georgios S. Limouris

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Limouris, G.S. (2021). Gastro-entero-pancreatic Neuroendocrine Tumors. In: Limouris, G.S. (eds) Liver Intra-arterial PRRT with 111In-Octreotide. Springer, Cham. https://doi.org/10.1007/978-3-030-70773-6_3

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  • DOI: https://doi.org/10.1007/978-3-030-70773-6_3

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