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Sporadic Pancreatic Endocrine Tumors

  • Volker Fendrich
  • Detlef K. Bartsch
Reference work entry
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Abstract

Pancreatic endocrine neoplasias (pNENs) are uncommon but fascinating tumors with an annual incidence of 1 per 100,000 people. pNENs present as either functional tumors, causing specific hormonal syndromes like Zollinger-Ellison syndrome (ZES) or organic hyperinsulinism, or as pancreatic endocrine nonfunctional tumors (NF-pNENs). The natural history of pNENs is highly variable. Ninety percent of all insulinomas or small NF-pNENs are readily curable by surgical resection. Most other functional and late detected NF-pNENs have a less favorable chance for cure. Patients with completely resected tumors generally have a good prognosis, and an aggressive surgical approach combined with conservative treatment options in patients with advanced disease often results in long-term survival.

Keywords

Neuroendocrine tumors of the pancreas Insulinoma Gastrinoma Pancreatic endocrine nonfunctional tumors Surgical therapy 
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References

  1. 1.
    Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT. Vienna consensus conference participants. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103:153–71.CrossRefGoogle Scholar
  2. 2.
    Baumann T, Rottenburger C, Nicolas G, Wild D. Gastroenteropancreatic neuroendocrine tumours (GEP-NET) – Imaging and staging. Best Pract Res Clin Endocrinol Metab. 2016;30:45–57.CrossRefGoogle Scholar
  3. 3.
    Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92.CrossRefGoogle Scholar
  4. 4.
    Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, de Wilde RF, Maitra A, Hicks J, Demarzo AM, Shi C, Sharma R, Laheru D, Edil BH, Wolfgang CL, Schulick RD, Hruban RH, Tang LH, Klimstra DS, Iacobuzio-Donahue CA. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am J Surg Pathol. 2012;36:173–84.CrossRefGoogle Scholar
  5. 5.
    Christ E, Wild D, Ederer S, Béhé M, Nicolas G, Caplin ME, Brändle M, Clerici T, Fischli S, Stettler C, Ell PJ, Seufert J, Gloor B, Perren A, Reubi JC, Forrer F. Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study. Lancet Diabetes Endocrinol. 2013;1:115–22.CrossRefGoogle Scholar
  6. 6.
    Ruf J, Schiefer J, Furth C, Kosiek O, Kropf S, Heuck F, Denecke T, Pavel M, Pascher A, Wiedenmann B, Amthauer H. 68Ga-DOTATOC PET/CT of neuroendocrine tumors: spotlight on the CT phases of a triple-phase protocol. J Nucl Med. 2011;52:697–704.CrossRefGoogle Scholar
  7. 7.
    Pavel M, O’Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, Krenning E, Knigge U, Salazar R, Pape UF, Öberg K. Vienna consensus conference participants. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103:172–85.CrossRefGoogle Scholar
  8. 8.
    De Herder WW, Lamberts SW. Somatostatin and somatostatin analogues: diagnostic and therapeutic uses. Curr Opin Oncol. 2002;14:53–7.CrossRefGoogle Scholar
  9. 9.
    Toumpanakis C, Kim MK, Rinke A, Bergestuen DS, Thirlwell C, Khan MS, Salazar R, Oberg K. Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. Neuroendocrinology. 2014;99:63–74.CrossRefGoogle Scholar
  10. 10.
    Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, Dickson J, Caplin M, Ell PJ. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112:2447–55.CrossRefGoogle Scholar
  11. 11.
    Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007;48:736–43.CrossRefGoogle Scholar
  12. 12.
    Fendrich V, Bartsch DK, Langer P, Zielke A, Rothmund M. Diagnosis and therapy in 40 patients with insulinoma. Dtsch Med Wochenschr. 2004;129:941–6.CrossRefGoogle Scholar
  13. 13.
    Mathur A, Gorden P, Libutti SK. Insulinoma. Surg Clin North Am. 2009;89:1105–21.CrossRefGoogle Scholar
  14. 14.
    Whipple AO. Adenomas of the islet cells with hyperinsulinism. Ann Surg. 1935;101:1299.CrossRefGoogle Scholar
  15. 15.
    Fendrich V, Waldmann J, Bartsch DK, Langer P. Surgical management of pancreatic endocrine tumors. Nat Rev Clin Oncol. 2009;6:419–28.CrossRefGoogle Scholar
  16. 16.
    Dedieu A, Rault A, Collet D, Masson B, Sa CA. Laparoscopic enucleation of pancreatic neoplasm. Surg Endosc. 2011;25:572–6.CrossRefGoogle Scholar
  17. 17.
    Zhao YP, Zhan HX, Zhang TP, Cong L, Dai MH, Liao Q, Cai LX. Surgical management of patients with insulinomas: result of 292 cases in a single institution. J Surg Oncol. 2011;103:169–74.CrossRefGoogle Scholar
  18. 18.
    Mehrabi A, Hafezi M, Arvin J, Esmaeilzadeh M, Garoussi C, Emami G, Kössler-Ebs J, Müller-Stich BP, Büchler MW, Hackert T, Diener MK. A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: it’s time to randomize. Surgery. 2015;157:45–55.CrossRefGoogle Scholar
  19. 19.
    Carrere N, Abid S, Julio CH, Bloom E, Pradere B. Spleen-preserving distal pancreatectomy with excision of splenic artery and vein: a case-matched comparison with conventional distal pancreatectomy with splenectomy. World J Surg. 2007;31:375–82.CrossRefGoogle Scholar
  20. 20.
    Öberg K, Eriksson B. Endocrine tumors of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19:753–81.CrossRefGoogle Scholar
  21. 21.
    Oberg K, Modlin IM, De Herder W, Pavel M, Klimstra D, Frilling A, Metz DC, Heaney A, Kwekkeboom D, Strosberg J, Meyer T, Moss SF, Washington K, Wolin E, Liu E, Goldenring J. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015;16:e435–46.CrossRefGoogle Scholar
  22. 22.
    Tamburrino D, Spoletini G, Partelli S, Muffatti F, Adamenko O, Crippa S, Falconi M. Surgical management of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab. 2016;30:93–102.CrossRefGoogle Scholar
  23. 23.
    Gagner M. Early experience with laparoscopic resections of islet cell tumors. Surgery. 1996;120:1051–4.CrossRefGoogle Scholar
  24. 24.
    Fernández-Cruz L, Molina V, Vallejos R, Jiménez Chavarria E, López-Boado MA, Ferrer J. Outcome after laparoscopic enucleation for non-functional neuroendocrine pancreatic tumours. HPB (Oxford). 2012;14:171–6.CrossRefGoogle Scholar
  25. 25.
    Langer P, Bartsch DK, Fendrich V, Kann PH, Rothmund M, Zielke A. Minimal-invasive operative treatment of organic hyperinsulinism. Dtsch Med Wochenschr. 2005;130:508–13.CrossRefGoogle Scholar
  26. 26.
    Lopez CL, Albers MB, Bollmann C, Manoharan J, Waldmann J, Fendrich V, Bartsch DK. Minimally invasive versus open pancreatic surgery in patients with multiple endocrine neoplasia type 1. World J Surg. 2016;40:1729–36.CrossRefGoogle Scholar
  27. 27.
    Eckhardt S, Schicker C, Maurer E, Fendrich V, Bartsch DK. Robotic-assisted approach improves vessel preservation in spleen-preserving distal pancreatectomy. Dig Surg. 2016;33:406–13.CrossRefGoogle Scholar
  28. 28.
    Zhan Q, Deng XX, Han B, Liu Q, Shen BY, Peng CH, Li HW. Robotic-assisted pancreatic resection: a report of 47 cases. Int J Med Robot. 2013;9:44–51.CrossRefGoogle Scholar
  29. 29.
    Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955;142:709–23.CrossRefGoogle Scholar
  30. 30.
    Stabile BE, Morrow DJ, Passaro E. The gastrinoma triangle: operative implications. Am J Surg. 1987;209:550.Google Scholar
  31. 31.
    Yu F, Venzon DJ, Serrano J, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol. 1999;17:615–30.CrossRefGoogle Scholar
  32. 32.
    Roy P, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome: clinical presentation in 261 patients. Medicine. 2000;79:379–411.CrossRefGoogle Scholar
  33. 33.
    Jensen RT, Gardner JD. Gastrinoma. In: VLW G, Di Magno EP, Gardner JD, editors. The pancreas: biology, pathobiology and disease. 2nd ed. New York: Raven Press; 1993. p. 931.Google Scholar
  34. 34.
    Norton JA, Fraker DL, Alexander HR, et al. Surgery increases survival in patients with gastrinoma. Ann Surg. 2006;244:410–9.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Norton JA, Alexander HR, Fraker DL, et al. Does the use of routine duodenotomy (DUODX) affect rate of cure, development of liver metastases, or survival in patients with Zollinger-Ellison syndrome? Ann Surg. 2004;239:617–23.CrossRefGoogle Scholar
  36. 36.
    Bartsch DK, Waldmann J, Fendrich V, Boninsegna L, Lopez CL, Partelli S, Falconi M. Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma. Br J Surg. 2012;99:1234–40.CrossRefGoogle Scholar
  37. 37.
    Zogakis TG, Gibril F, Libutti SK, et al. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann Surg. 2003;238:42–8.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Chastain MA. The glucagonoma syndrome: a review of its features and discussion of new perspectives. Am J Med Sci. 2001;321:306–20.CrossRefGoogle Scholar
  39. 39.
    Pavel M, O’Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, Krenning E, Knigge U, Salazar R, Pape UF, Öberg K. Vienna consensus conference participants. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103:172–85.CrossRefGoogle Scholar
  40. 40.
    Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer. 2015;121:1172–86.CrossRefGoogle Scholar
  41. 41.
    Mayo SC, Herman JM, Cosgrove D, Bhagat N, Kamel I, Geschwind JF, Pawlik TM. Emerging approaches in the management of patients with neuroendocrine liver metastasis: role of liver-directed and systemic therapies. J Am Coll Surg. 2013;216:123–34.CrossRefGoogle Scholar
  42. 42.
    Vilchez V, Gedaly R. Liver transplantation for the treatment of neuroendocrine liver metastases. Best Pract Res Clin Endocrinol Metab. 2016;30:141–7.CrossRefGoogle Scholar
  43. 43.
    Brabander T, Teunissen JJ, Van Eijck CH, Franssen GJ, Feelders RA, de Herder WW, Kwekkeboom DJ. Peptide receptor radionuclide therapy of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2016;30:103–14.CrossRefGoogle Scholar
  44. 44.
    Strosberg J, Wolin E, Chasen B. 177Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours: results of the phase III NETTER-1 trial. ESMO. 2015;Abstr LBA6.Google Scholar
  45. 45.
    van Vliet EI, van Eijck CH, de Krijger RR, Nieveen van Dijkum EJ, Teunissen JJ, Kam BL, de Herder WW, Feelders RA, Bonsing BA, Brabander T, Krenning EP, Kwekkeboom DJ. Neoadjuvant treatment of nonfunctioning pancreatic neuroendocrine tumors with [177Lu-DOTA0,Tyr3]Octreotate. J Nucl Med. 2015;56:1647–53.CrossRefGoogle Scholar
  46. 46.
    Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P. CLARINET investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371:224–33.CrossRefGoogle Scholar
  47. 47.
    Rinke A, Krug S. Neuroendocrine tumours – medical therapy: biological. Best Pract Res Clin Endocrinol Metab. 2016;30:79–91.CrossRefGoogle Scholar
  48. 48.
    Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K. RAD001 in advanced neuroendocrine tumors, third trial (RADIANT-3) study group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–23.CrossRefGoogle Scholar
  49. 49.
    Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–13.CrossRefGoogle Scholar
  50. 50.
    Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014;120:2814–23.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of SurgeryUniversity Hospital Marburg and GiessenMarburgGermany
  2. 2.Klinik für Visceral- Thorax- und GefäßchirurgieUniversitätsklinikum Gießen und Marburg, BaldingerstraßeMarburgGermany

Section editors and affiliations

  • Raul A. Urrutia
    • 1
  • Markus W. Büchler
    • 2
  • John Neoptolemos
    • 3
  1. 1.Mayo Clinic Cancer CenterMayo ClinicRochesterUSA
  2. 2.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
  3. 3.Division of Surgery and OncologyUniversity of LiverpoolLiverpoolUK

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