Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Surgical management of pancreatic endocrine tumors

Nature Reviews Clinical Oncology volume 6, pages 419–428 (2009)Cite this article

Abstract

Pancreatic endocrine tumors (PETs) are uncommon but clinically challenging and fascinating tumors with an annual incidence of 1 per 100,000 people. PETs present as either functional pancreatic tumors or as nonfunctional pancreatic tumors. Functional tumors are commonly associated with a specific hormonal syndrome directly related to a hormone secreted by the tumor, such as Zollinger–Ellison syndrome or organic hyperinsulinism. Nonfunctional tumors do not secrete a hormone resulting in a pathologic syndrome of clinical symptoms. The natural history of PETs is highly variable. Small, benign neoplasms, such as 90% of all insulinomas, are readily curable by surgical resection; however, most other functional and all nonfunctional pancreatic tumors have a much less favorable prognosis. Patients with completely resected tumors generally have a good prognosis, and an aggressive surgical approach in patients with advanced disease may also prolong survival. Many features of the management of pancreatic endocrine tumors, such as timing and extent of resection, and the use of laparoscopic procedures, are currently under debate. This Review describes the current status of surgical treatment for pancreatic endocrine tumors, and discusses the new developments in this field.

Key Points

  • Pancreatic endocrine tumors (PETs) represent an important subset of pancreatic neoplasms

  • The only potentially curative option for patients with PETs is complete surgical resection, as has been shown for insulinomas, gastrinomas, and nonfunctioning PETs

  • The rationale for surgical resection is clear; if the condition is untreated, the natural history of malignant PETs is one of slow but gradual progression, with the development of liver metastases and death of patients

  • An aggressive surgical approach may lead to long-term survival in patients with malignant PETs

  • Although long-term cure is rare, significant long-term palliation can be achieved

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Image of a resected pancreatic endocrine tumor.
Figure 2: Enucleation of two insulinomas in a 14-year-old patient with MEN1.
Figure 3: Image of a resected duodenal gastrinoma and pancreatic gastrinoma.
Figure 4: Nonfunctioning PET (arrow) in a pancreatic specimen from a patient with MEN1.

Similar content being viewed by others

References

  1. Metz, D. C. & Jensen, R. T. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135, 1469–1492 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Öberg, K. & Eriksson, B. Endocrine tumors of the pancreas. Best Pract. Res. Clin. Gastroenterol. 19, 753–781 (2005).

    Article  PubMed  Google Scholar 

  3. Danforth, D. N. Jr, Gorden, P. & Brennan, M. F. Metastatic insulin-secreting carcinoma of the pancreas: clinical course and the role of surgery. Surgery 96, 1027–1037 (1984).

    PubMed  Google Scholar 

  4. Weber, H. C. et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology 108, 1637–1649 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Yu, F. 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. 17, 615–630 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Fendrich, V. et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors. Ann. Surg. 244, 845–851 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hochwald, S. et al. Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups. J. Clin. Oncol. 20, 2633–2642 (2002).

    Article  PubMed  Google Scholar 

  8. Bartsch, D. K. et al. (2005). Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann. Surg. 242, 757–764.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Doherty, G. M. et al. Lethality of multiple endocrine neoplasia type I. World J. Surg. 22, 581–587 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Halfdanarson, T. R., Rubin, J., Farnell, M. B., Grant, C. S. & Petersen, G. M. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr. Relat. Cancer 15, 409–427 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Service, F. J. Hypoglycemic disorders. N. Engl. J. Med. 332, 1144–1152 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Whipple, A. O. & Frantz, V. K. Adenomas of the islet cells with hyperinsulinism: a review. Ann. Surg. 101, 1299–1335 (1935).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Roy, P. et al. Zollinger-Ellison syndrome: clinical presentation in 261 patients. Medicine 79, 379–411 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Fendrich, V., Langer, P., Waldmann, J., Bartsch, D. K. & Rothmund, M. The management of sporadic and MEN-1-gastrinomas. Br. J. Surg. 94, 1331–1341 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Bartsch, D. K. et al. Management of non-functioning islet cell carcinomas. World J. Surg. 24, 1418–1424 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Kouvaraki, M. A. et al. Surgical treatment of non-functioning pancreatic islet cell tumors. J. Surg. Oncol. 89, 170–185 (2005).

    Article  PubMed  Google Scholar 

  17. Grant, C. S. Surgical management of malignant islet cell tumors. World J. Surg. 17, 498–503 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Lo, C. Y. et al. Islet cell carcinoma of the pancreas. World J. Surg. 20, 878–883 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. Fendrich, V., Bartsch, D. K., Langer, P., Zielke, A. & Rothmund, M. Diagnosis and therapy in 40 patients with insulinoma [German]. Dtsch. Med. Wochenschr. 129, 941–946 (2004).

    Article  CAS  PubMed  Google Scholar 

  20. Rothmund, M. et al. Surgery for benign insulinoma: an international review. World J. Surg. 14, 393–398 (1990).

    Article  CAS  PubMed  Google Scholar 

  21. Udelsman, R. et al. Pancreaticoduodenectomy for selected pancreatic endocrine tumors. Surg. Gynecol. Obstet. 177, 269–278 (1993).

    CAS  PubMed  Google Scholar 

  22. Hirshberg, B. et al. Malignant insulinoma: spectrum of unusual clinical features. Cancer 104, 264–272 (2005).

    Article  PubMed  Google Scholar 

  23. Michalski, C. W., Weitz, J. & Büchler, M. W. Surgery insight: surgical management of pancreatic cancer. Nat. Clin. Pract. Oncol. 4, 526–535 (2007).

    Article  PubMed  Google Scholar 

  24. Hirshberg, B. et al. Blind distal pancreatectomy for occult insulinoma, an inadvisable procedure. J. Am. Coll. Surg. 194, 761–764 (2002).

    Article  PubMed  Google Scholar 

  25. Grama, D. et al. Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation and surgical treatment. World J. Surg. 16, 611–618 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Norton, J. A. & Jensen, R. T. Resolved and unresolved controversies in the surgical management of patients with Zollinger–Ellison syndrome. Ann. Surg. 240, 757–773 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Thompson. N. W. Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic–duodenal disease. Results in the treatment of 40 patients with Zollinger–Ellison syndrome, hypoglycaemia or both. J. Intern. Med. 243, 495–500 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Fendrich, V. & Langer, P. Minimally invasive surgery for pancreatic endocrine tumours. Br. J. Surg. 94, 1187–1188 (2007).

    Article  CAS  PubMed  Google Scholar 

  29. Gagner, M., Pomp, A. & Herrera, M. F. Early experience with laparoscopic resections of islet cell tumors. Surgery 120, 1051–1054 (1996).

    Article  CAS  PubMed  Google Scholar 

  30. Langer, P. et al. Minimal-invasive operative treatment of organic hyperinsulinism [German]. Dtsch. Med. Wochenschr. 130, 514–518 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Fernandez-Cruz, L. & Cesar-Borges, G. Laparoscopic strategies for resection of insulinomas. J. Gastrointest. Surg. 10, 752–760 (2006).

    Article  PubMed  Google Scholar 

  32. Carrere, N., Abid, S., Julio, C. H., Bloom, E. & Pradère, 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. 31, 375–382 (2007).

    Article  PubMed  Google Scholar 

  33. Mabrut, J. Y. et al. Laparoscopic pancreatic resection: results of a multicenter European study of 127 patients. Surgery 137, 597–605 (2005).

    Article  PubMed  Google Scholar 

  34. Kooby, D. A. et al. Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches. Ann. Surg. 248, 438–446 (2008).

    PubMed  Google Scholar 

  35. Assalia, A. & Gagner, M. Laparoscopic pancreatic surgery for islet cell tumors of the pancreas. World J. Surg. 28, 1239–1247 (2004).

    Article  PubMed  Google Scholar 

  36. Norton, J. A. et al. Surgery to cure the Zollinger–Ellison syndrome. N. Engl. J. Med. 341, 635–644 (1999).

    Article  CAS  PubMed  Google Scholar 

  37. Norton, J. A. 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. 239, 617–625 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Delcore, R. Jr, Cheung, L. Y. & Friesen, S. R. Characteristics of duodenal wall gastrinomas. Am. J. Surg. 160, 621–623 (1990).

    Article  PubMed  Google Scholar 

  39. Ellison, E. C. et al. 50-year appraisal of gastrinoma: recommendations for staging and treatment. J. Am. Coll. Surg. 202, 897–905 (2006).

    Article  PubMed  Google Scholar 

  40. Zogakis, T. G. et al. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann. Surg. 238, 42–48 (2003).

    PubMed  PubMed Central  Google Scholar 

  41. Thodiyil, P. A., El-Masry, N. S. & Williamson, R. C. Achieving eugastrinaemia in Zollinger–Ellison syndrome: resection or enucleation? Dig. Surg. 18, 118–123 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Stadil, F., Bardram, L., Gustafsen, J. & Efsen, F. Surgical treatment of the Zollinger–Ellison syndrome. World J. Surg. 17, 463–467 (1993).

    Article  CAS  PubMed  Google Scholar 

  43. Norton, J. A. et al. Surgery increases survival in patients with gastrinoma. Ann. Surg. 244, 410–419 (2006).

    PubMed  PubMed Central  Google Scholar 

  44. Sugg, S. L. et al. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann. Surg. 218, 138–144 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Thompson, N. W., Pasieka, J. & Fukuuchi, A. Duodenal gastrinomas, duodenotomy, and duodenal exploration in the surgical management of Zollinger-Ellison syndrome. World J. Surg. 17, 455–462 (1993).

    Article  CAS  PubMed  Google Scholar 

  46. Norton, J. A. Surgery and prognosis of duodenal gastrinoma as a duodenal neuroendocrine tumor. Best Pract. Res. Clin. Gastroenterol. 19, 699–704 (2005).

    Article  PubMed  Google Scholar 

  47. Anlauf, M. et al. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features. World J. Gastroenterol. 12, 5440–5446 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mignon, M. & Cadiot, G. Diagnostic and therapeutic criteria in patients with Zollinger–Ellison syndrome and multiple endocrine neoplasia type 1. J. Intern. Med. 243, 489–494 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. MacFarlane, M. P. et al. Prospective study of surgical resection of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery 118, 973–979 (1995).

    Article  CAS  PubMed  Google Scholar 

  50. Skogseid, B. et al. Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J. Clin. Endocrinol. Metab. 73, 281–287 (1991).

    Article  CAS  PubMed  Google Scholar 

  51. Norton, J. A. et al. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger–Ellison syndrome. Ann. Surg. 234, 495–505 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tonelli, F. et al. Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias. Ann. Surg. 244, 61–70 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Imamura, M. et al. New pancreas-preserving total duodenectomy technique. World J. Surg. 29, 203–207 (2005).

    Article  PubMed  Google Scholar 

  54. Dralle, H. et al. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors. World J. Surg. 28, 1248–1260 (2004).

    Article  PubMed  Google Scholar 

  55. Sarmiento, J. M. et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J. Am. Coll. Surg. 197, 29–37 (2003).

    Article  PubMed  Google Scholar 

  56. Evans, D. B. et al. Nonfunctioning islet cell carcinoma of the pancreas. Surgery 114, 1175–1181 (1993).

    CAS  PubMed  Google Scholar 

  57. Akerström, G., Hessman, O. & Skogseid, B. Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1. Langenbecks Arch. Surg. 386, 558–569 (2002).

    Article  PubMed  Google Scholar 

  58. Langer, P. et al. Prospective evaluation of imaging procedures for the detection of pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. World J. Surg. 28, 1317–1322 (2004).

    Article  PubMed  Google Scholar 

  59. Plöckinger, U. et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80, 394–424 (2004).

    Article  PubMed  Google Scholar 

  60. European Neuroendocrine Tumor Society [online],

  61. Solorzano, C. C. et al. Nonfunctioning islet all carcinoma of the pancreas: survival results in a contemporary series of 163 patients. Surgery 130, 1078–1085 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Touzios, J. G. et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann. Surg. 241, 776–783 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dousset, B. et al. Metastatic endocrine tumors: medical treatment, surgical resection, or liver transplantation. World J. Surg. 20, 908–914 (1996).

    Article  CAS  PubMed  Google Scholar 

  64. Que, F. G., Nagorney, D. M., Batts, K. P., Linz, L. J. & Kvols, L. K. Hepatic resection for metastatic neuroendocrine carcinomas. Am. J. Surg. 169, 36–42 (1995).

    Article  CAS  PubMed  Google Scholar 

  65. Chen, H., Hardacre, J. M., Uzar, A., Cameron, J. L. & Choti, M. A. Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? J. Am. Coll. Surg. 187, 88–92 (1998).

    Article  CAS  PubMed  Google Scholar 

  66. Chamberlain, R. S. et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? J. Am. Coll. Surg. 190, 432–435 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Nave, H., Mössinger, E., Feist, H., Lang, H. & Raab, H. Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years. Surgery 129, 170–175 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Sarmiento, J. M. et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J. Am. Coll. Surg. 197, 29–37 (2003).

    Article  PubMed  Google Scholar 

  69. Moertel, C. G. Karnofsky memorial lecture: An odyssey in the land of small tumors. J. Clin. Oncol. 5, 1502–1522 (1987).

    Article  CAS  PubMed  Google Scholar 

  70. Thompson, G. B., van Heerden, J. A., Grant, C. S., Carney, J. A. & Ilstrup, D. M. Islet cell carcinomas of the pancreas: a twenty-year experience. Surgery 104, 1011–1017 (1988).

    CAS  PubMed  Google Scholar 

  71. Que, F. G., Sarmiento, J. M. & Nagorney, D. M. Hepatic surgery for metastatic gastrointestinal neuroendocrine tumors. Cancer Control 9, 67–79 (2002).

    Article  PubMed  Google Scholar 

  72. Pascher, A. et al. Endocrine tumours of the gastrointestinal tract. Transplantation in the management of metastatic endocrine tumours. Best Pract. Res. Clin. Gastroenterol. 19, 637–648 (2005).

    Article  PubMed  Google Scholar 

  73. Rosenau, J. et al. Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumours. Transplantation 73, 386–394 (2002).

    Article  CAS  PubMed  Google Scholar 

  74. Service, F. J., McMahon, M. M., O'Brien, P. C. & Ballard, D. J. Functioning insulinoma--incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin. Proc. 66, 711–719 (1991).

    Article  CAS  PubMed  Google Scholar 

  75. Gullo, L. et al. Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study. Am. J. Gastroenterol. 98, 2435–2439 (2003).

    Article  PubMed  Google Scholar 

  76. Grant, C. S. Insulinoma. Best Pract. Res. Clin. Gastroenterol. 19, 783–798 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Fendrich, V. et al. Operative management and long-term survival in patients with neuroendocrine tumors of the pancreas-experience with 144 patients [German]. Dtsch Med. Wochenschr. 132, 195–200 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Philipps University, Marburg, Germany

    Volker Fendrich, Jens Waldmann, Detlef K. Bartsch & Peter Langer

Authors
  1. Volker Fendrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jens Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Detlef K. Bartsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Volker Fendrich.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fendrich, V., Waldmann, J., Bartsch, D. et al. Surgical management of pancreatic endocrine tumors. Nat Rev Clin Oncol 6, 419–428 (2009). https://doi.org/10.1038/nrclinonc.2009.82

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2009.82

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing