Skip to main content
SpringerLink
Log in

Pancreatic Neuroendocrine Tumours

  • Chapter
  • First Online:
Evidence-Based Endocrine Surgery

  • 594 Accesses

Abstract

Pancreatic neuroendocrine tumours (pNETs) are relatively rare. While they comprise of only 1–2% of all pancreatic neoplasms [1], they provoke great interest amongst clinicians due to the variety of symptoms with which they present and multiple treatment options. While the overall prognosis of pNETs may be better than their exocrine counterparts, the 5-year survival rate is approximately 55% with localized disease and as low as 15% when the tumours are unresectable [2]. The incidence of pNETs has risen in the last decade, largely contributed to by the improvement of diagnostic imaging and wider use of computer tomography (CT) scanning [3, 4]. This presents clinicians with the opportunity to study the natural history of these tumours in greater detail, allowing us to further define more optimal modalities of treatment for this disease. This chapter highlights several developments and challenges regarding pNETs that have generated much debate amongst hepatobiliary surgeons about the future of treatment of this disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Franked M, Kim MK, Faggiano A, Valk GD. Epidemiology of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2012;26(6):691–703.

    Article  Google Scholar 

  2. Edge SB, Byrd DR, Compton CC, et al., editors. Exocrine and endocrine pancreas. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2010. p. 241–9.

    Google Scholar 

  3. Lawrence B, Gustafsson BI, Chan A, et al. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40:1–18.

    Article  Google Scholar 

  4. Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer. 2008;15:409–27.

    Article  Google Scholar 

  5. Vortmeyer AO, Huang S, Lubensky I, Zhuang Z. Non-islet origin of pancreatic islet cell tumors. J Clin Endocrinol Metab. 2004;89(4):1934–8.

    Article  CAS  Google Scholar 

  6. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011;331(6021):1199–203.

    Article  CAS  Google Scholar 

  7. Chandrasekharappa SC, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–7.

    Article  CAS  Google Scholar 

  8. De Wilde RF, Edil BH, Aruban RH, Maitra A. Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy. Nat Rev Gastroenterol Hepatol. 2012;9(4):199–208.

    Article  Google Scholar 

  9. Toliat MR, Berger W, Ropers HH, Neuhaus P, Wiedenmann B. Mutations in the MEN I gene in sporadic neuroendocrine tumours of gastroenteropancreatic system. Lancet. 1997;350:1223.

    CAS  PubMed  Google Scholar 

  10. Moore PS, et al. Role of disease-causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL. Genes Chromosomes Cancer. 2001;32:177–81.

    Article  CAS  Google Scholar 

  11. Dogeas E, Karagkounis G, Heathy CM, Hirose K, Pawlik TM, Wolfgang CL. Alternative lengthening of telomeres predicts site of origin in neuroendocrine tumor liver metastases. J Am Coll Surg. 2014;218(4):628–35.

    Article  Google Scholar 

  12. Marinoni I, Kurrer AS, Vassella E, Deter M, Rudolph T, Banz V. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology. 2014;146(2):453–60.e5.

    Article  CAS  Google Scholar 

  13. McKenna LR, Edil BH. Update on pancreatic neuroendocrine tumors. Gland Surg. 2014;3(4):258–75.

    PubMed  PubMed Central  Google Scholar 

  14. Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol. 2005;19:783–98.

    Article  CAS  Google Scholar 

  15. Vezzosi D, Bennet A, Fauvel J, et al. Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism. Eur J Endocrinol. 2007;157:75–83.

    Article  CAS  Google Scholar 

  16. Jensen RT, Niederle B, Mitry E, et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology. 2006;84:173–82.

    Article  CAS  Google Scholar 

  17. Gibril F, Jensen RT. Zollinger-Ellison syndrome revisited: diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr Gastroenterol Rep. 2004;6:454–63.

    Article  Google Scholar 

  18. Berna MJ, Hoffmann KM, Long SH, Serrano J, Fibril F, Jensen RT. Serum gastrin in Zollinger-Ellison syndrome: II. Prospective study of gastrin provocative testing in 293 patients from the National Institutes of Health and comparison with 537 cases from the literature. Evaluation of diagnostic criteria, proposal of new criteria, and correlations with clinical and tumoral features. Medicine (Baltimore). 2006;85(6):331–64.

    Article  CAS  Google Scholar 

  19. Soga J, Yakuwa Y. Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. J Hepatobiliary Pancreat Surg. 1998;5:312–9.

    Article  CAS  Google Scholar 

  20. van Beek AP, de Haas ER, van Vloten WA, et al. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eur J Endocrinol. 2004;151:531–7.

    Article  Google Scholar 

  21. Ghaferi AA, Chojnacki KA, Long WD, Cameron JL, Yeo CJ. Pancreatic VIPomas: subject review and one institutional experience. J Gastrointest Surg. 2008;12(2):382–93.

    Article  Google Scholar 

  22. Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135(5):1469–92.

    Article  CAS  Google Scholar 

  23. Kloppel G. Tumour biology and histopathology of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21:15–31.

    Article  Google Scholar 

  24. Viudez A, De Jesus-Acosta A, Carvalho FL, Vera R, Marti-Algarra S, Ramirez N. Pancreatic neuroendocrine tumors: challenges in an underestimated disease. Crit Rev Oncol Hematol. 2016;101:193–206.

    Article  CAS  Google Scholar 

  25. Vinik A, Casellini C, Perry RR, Feliberti E, Vingan H. Diagnosis and management of pancreatic neuroendocrine tumors. 2015.

    Google Scholar 

  26. Sundin A. Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2012;26(6):803–18.

    Article  Google Scholar 

  27. Caramel C, Domain C, De Baere T, Boulet B, Schlumberger M, Ducreux M, et al. Endocrine pancreatic tumours: which are the most useful MRI sequences? Eur Radiol. 2010;20(11):2618–27.

    Article  Google Scholar 

  28. Anderson MA, Carpenter S, Thompson NW, Nostrant TT, Elta GH, Scheiman JM. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumours of the pancreas. Am J Gastroenterol. 2000;95(9):2271–7.

    Article  CAS  Google Scholar 

  29. Atiq M, Bhutan MS, Bektas M, Lee JE, Gong Y, Tamm EP. EUS-FNA for pancreatic neuroendocrine tumors: a tertiary cancer center experience. Dig Dis Sci. 2012;57(3):791–800.

    Article  CAS  Google Scholar 

  30. Kimura W, Tezuka K, Hirai I. Surgical management of pancreatic neuroendocrine tumors. Surg Today. 2011;41(10):1332–43.

    Article  Google Scholar 

  31. Casadei R, Monari F, Buscemi S, et al. Total pancreatectomy: indications, operative technique, and results: a single centre experience and review of literature. Updates Surg. 2010;62:41–6.

    Article  Google Scholar 

  32. Falconi M, Zerbi A, Crippa S, et al. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol. 2010;17:1621–7.

    Article  Google Scholar 

  33. Du ZY, Chen S, Han BS, et al. Middle segmental pancreatectomy: a safe and organ-preserving option for benign and low-grade malignant lesions. World J Gastroenterol. 2013;19:1458–65.

    Article  CAS  Google Scholar 

  34. Hackett T, Hinz U, Fritz S, Strobel O, Schneider L, Hartwig W, et al. Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections. Langenbecks Arch Surg. 2011;396(8):1197–203.

    Article  Google Scholar 

  35. Cauley CE, Pitt HA, Ziegler KM, Nakeeb A, Schmidt CM, Zyromski NJ, et al. Pancreatic enucleation: improved outcomes compared to resection. J Gastrointest Surg. 2012;16(7):1347–53.

    Article  CAS  Google Scholar 

  36. Al-Kurd A, Chapchay K, Grozinsky-Glasberg S, Mazeh H. Laparoscopic resection of pancreatic neuroendocrine tumors. World J Gastroenterol. 2014;20(17):4908–16.

    Article  Google Scholar 

  37. Jilesen AP, van Eijck CH, Busch OR, van Gulik TM, Gouma DJ, van Dijkum EJ. Postoperative outcomes of enucleation and standard resections in patients with a pancreatic neuroendocrine tumor. World J Surg. 2016;40(3):715–28.

    Article  Google Scholar 

  38. Triponez F, Goudet P, Dosseh D, Cougard P, Bauters C, Murat A, et al. Is surgery beneficial for MEN1 patients with small (< = 2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg. 2006;30(5):654–62. discussion 663-4

    Article  Google Scholar 

  39. Machado MC. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. Clinics (Sao Paulo). 2012;67(Suppl 1):145–8.

    Article  Google Scholar 

  40. Lowney JK, Frisella MM, Lairmore TC, Doherty GM, et al. Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size. Surgery. 1998;124(6):1043–8. discussion 1048-9

    Article  CAS  Google Scholar 

  41. Norton JA, Alexander HR, Fraker DL, Venzon DJ, Gibril F, Jensen RT. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg. 2001;234(4):495–506.

    Article  CAS  Google Scholar 

  42. Gibril F, Venzon DJ, Ojeaburu JV, Bashir S, Jensen RT. Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form. J Clin Endocrinol Metab. 2001;86(11):5282–93.

    Article  CAS  Google Scholar 

  43. Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A. Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg. 2006;243(2):265–72.

    Article  Google Scholar 

  44. Niina Y, Fujimori N, Nakamura T, Igarashi H, Oono T, Nakamura K, et al. The current strategy for managing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1. Gut Liver. 2012;6(3):287–94.

    Article  CAS  Google Scholar 

  45. Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95(2):98–119.

    Article  CAS  Google Scholar 

  46. Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735–52.

    Article  Google Scholar 

  47. Cusati D, Zhang L, Harmsen WS, Hu A, Farnell MB, Nagorney DM, et al. Metastatic nonfunctioning pancreatic neuroendocrine carcinoma to liver: surgical treatment and outcomes. J Am Coll Surg. 2012;215(1):117–24; discussion 124-5.

    Article  Google Scholar 

  48. Sarmiento HM, Heywood G, Rubin J, Ilstrup DM, Nargoney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29–37.

    Article  Google Scholar 

  49. Bettini R, Mantovani W, Boninsegna L, Crippa S, Capelli P, Bassi C. Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas. Dig Liver Dis. 2009;41(1):49–55.

    Article  CAS  Google Scholar 

  50. Taner T, Atwell TD, Zhang L, Oberg TN, Harmsen WS, Slettedahl SW, et al. Adjunctive radiofrequency ablation of metastatic neuroendocrine cancer to the liver complements surgical resection. HPB (Oxford). 2013;15(3):190–5.

    Article  Google Scholar 

  51. Akyildiz HY, Mitchell J, Milas M, Siperstein A, Berber E. Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery. 2010;148(6):1288–93; discussion 1293.

    Article  Google Scholar 

  52. Akahori T, Sho M, Tanaka T, et al. Significant efficacy of new transcatheter arterial chemoembolization technique for hepatic metastases of pancreatic neuroendocrine tumors. Anticancer Res. 2013;33:3355–8.

    PubMed  Google Scholar 

  53. Strosberg JR, Choi J, Cantor AB, et al. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13:72–8.

    Article  Google Scholar 

  54. Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer. 2005;104:1590–602.

    Article  Google Scholar 

  55. Ito T, Igarashi H, Jensen RT. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances. J Gastroenterol. 2012;47:941–60.

    Article  CAS  Google Scholar 

  56. Cao CQ, Yan TD, Bester L, et al. Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases. Br J Surg. 2010;97:537–43.

    Article  CAS  Google Scholar 

  57. Bonney GK, Gomez D, Rahman SH, Verbeke CS, Prasad KR, Toogood GJ, Lodge JP, Menon KV. Results following surgical resection for malignant pancreatic neuroendocrine tumours. A single institutional experience. JOP. 2008;9(1):19–25.

    PubMed  Google Scholar 

  58. Toumpanakis C, Caplin ME. Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors. Semin Oncol. 2013;40(1):56–68.

    Article  CAS  Google Scholar 

  59. Eriksson B, Annibale B, Bajetta E, Mitry E, Pavel M, Platania M, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: chemotherapy in patients with neuroendocrine tumors. Neuroendocrinology. 2009;90(2):214–9.

    Article  CAS  Google Scholar 

  60. Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004;22(23):4762–71.

    Article  CAS  Google Scholar 

  61. Yao JC, Shah MH, Ito T, Bohas CL, Wolin ED, Cutsem EV, et al. Everolimus for advanced pancreatic neuroendocrine tumours. N Engl J Med. 2011;364:514–23.

    Article  CAS  Google Scholar 

  62. Raymond E, Dahan L, Raoul J, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–13.

    Article  CAS  Google Scholar 

  63. Horsch D, Ezziddin S, Haug A, Gratz KF, Dukelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. Recent Results Cancer Res. 2013;194:457–65.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hepatobiliary Surgery, National University Hospital Singapore, Singapore, Singapore

    C. Chew & G. K. Bonney

Authors
  1. C. Chew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. K. Bonney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. K. Bonney .

Editor information

Editors and Affiliations

  1. Division of Endocrine Surgery, National University Hospital, Singapore, Singapore

    Rajeev Parameswaran

  2. Department of Endocrine Surgery, SGPGI Hospital, Lucknow, India

    Amit Agarwal

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media Singapore

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chew, C., Bonney, G.K. (2018). Pancreatic Neuroendocrine Tumours. In: Parameswaran, R., Agarwal, A. (eds) Evidence-Based Endocrine Surgery. Springer, Singapore. https://doi.org/10.1007/978-981-10-1124-5_36

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-1124-5_36

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-1123-8

  • Online ISBN: 978-981-10-1124-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation