UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Surgical resection of sporadic pancreatic neuroendocrine tumors

Authors
James Lee, MD
John Allendorf, MD, FACS
John Chabot, MD
Section Editors
Sally E Carty, MD, FACS
Stanley W Ashley, MD
Deputy Editors
Wenliang Chen, MD, PhD
Diane MF Savarese, MD

INTRODUCTION

Pancreatic neuroendocrine tumors (PNETs) are rare, accounting for less than 3 percent of all pancreatic tumors [1,2]. PNETs exhibit a wide spectrum of clinical behavior that has made classification and staging difficult. While the majority of PNETs are associated with relatively good survival, there can be significant variability in outcomes based on their biological heterogeneity [3-5]. The classification, epidemiology, clinical presentation, localization, and staging of PNETs is discussed separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine tumors (islet-cell tumors)".)

The term “pancreatic neuroendocrine tumor” is preferred to encompass a diverse set of tumors arising in the pancreas that share a common progenitor cell [6]. In the past, PNETs were often referred to as pancreatic “islet cell” tumors or pancreatic “carcinoids”. With time, the term carcinoid has come to mean a very specific group of tumors, predominantly arising in the tubular gastrointestinal tract, which produces only serotonin. However, endocrine tumors of the pancreas can express other hormones or can be biochemically inert. (See "Pathology, classification, and grading of neuroendocrine tumors arising in the digestive system", section on 'Historical evolution'.)

While most PNETs are sporadic, PNETs can also be associated with genetic syndromes. The surgical management of sporadic PNETs is reviewed here. The management of PNETs associated with genetic syndromes is discussed separately. (See "Multiple endocrine neoplasia type 1: Treatment" and "Clinical features, diagnosis, and management of von Hippel-Lindau disease" and "Tuberous sclerosis complex: Management" and "Neurofibromatosis type 1 (NF1): Management and prognosis".)

PREOPERATIVE EVALUATION

Surgical planning must take into account the characteristics of the tumor, as well as the patient’s overall health and wishes. An accurate history and review of pertinent laboratory and prior imaging studies is essential for planning resection of pancreatic neuroendocrine tumors (PNETs).  

Genetic background — The patient’s history and genetic testing help determine whether the tumor is sporadic or associated with a genetic syndrome. This is important because the association of a genetic syndrome, MEN1 for instance, affects the number and extent of primary PNETs, which greatly impacts surgical decision making [7,8]. The management of PNETs associated with genetic syndromes is discussed separately. (See "Multiple endocrine neoplasia type 1: Treatment" and "Clinical features, diagnosis, and management of von Hippel-Lindau disease" and "Tuberous sclerosis complex: Management" and "Neurofibromatosis type 1 (NF1): Management and prognosis".)

                          

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Jan 14 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Halfdanarson TR, Rabe KG, Rubin J, Petersen GM. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol 2008; 19:1727.
  2. Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 2008; 15:409.
  3. Bilimoria KY, Tomlinson JS, Merkow RP, et al. Clinicopathologic features and treatment trends of pancreatic neuroendocrine tumors: analysis of 9,821 patients. J Gastrointest Surg 2007; 11:1460.
  4. Bilimoria KY, Talamonti MS, Tomlinson JS, et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg 2008; 247:490.
  5. Nissen NN, Kim AS, Yu R, et al. Pancreatic neuroendocrine tumors: presentation, management, and outcomes. Am Surg 2009; 75:1025.
  6. Fendrich V, Bartsch DK. Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbecks Arch Surg 2011; 396:299.
  7. Hill JS, McPhee JT, McDade TP, et al. Pancreatic neuroendocrine tumors: the impact of surgical resection on survival. Cancer 2009; 115:741.
  8. Norton JA. Surgery for primary pancreatic neuroendocrine tumors. J Gastrointest Surg 2006; 10:327.
  9. Edil, BH, Ellison, T, Cameron, JL, et al. Even small pancreatic endocrine neoplasms have lymph node metaseasis. Presented at The Pancreas Club meeting, May 2011, Chicago Il.
  10. Scarpa A, Mantovani W, Capelli P, et al. Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010; 23:824.
  11. Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341:635.
  12. Harris AG, O'Dorisio TM, Woltering EA, et al. Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel. Dig Dis Sci 1995; 40:1464.
  13. Abood GJ, Go A, Malhotra D, Shoup M. The surgical and systemic management of neuroendocrine tumors of the pancreas. Surg Clin North Am 2009; 89:249.
  14. Eriksson B, Oberg K. An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol 1993; 32:203.
  15. Fernández-Cruz L, Blanco L, Cosa R, Rendón H. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? World J Surg 2008; 32:904.
  16. Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006; 449:395.
  17. Rindi G, Klöppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007; 451:757.
  18. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010.
  19. Klimstra DS, Modlin IR, Coppola D, et al. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010; 39:707.
  20. Rindi G, Arnold R, Bosman FT, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumours of the Digestive System, 4th ed, Bosman TF, Carneiro F, Hruban RH, Theise ND (Eds), International Agency for Research on cancer (IARC), Lyon 2010. p.13.
  21. Hruban RH, Pitman MB, Klimstra DS. Tumors of the pancreas, ARP/AFIP, Washington, DC 2007. p.422.
  22. Ito H, Abramson M, Ito K, et al. Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience. J Gastrointest Surg 2010; 14:891.
  23. Boninsegna L, Panzuto F, Partelli S, et al. Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. Eur J Cancer 2012; 48:1608.
  24. Klöppel G. Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer 2011; 18 Suppl 1:S1.
  25. Panzuto F, Boninsegna L, Fazio N, et al. Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. J Clin Oncol 2011; 29:2372.
  26. Ferrone CR, Tang LH, Tomlinson J, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol 2007; 25:5609.
  27. Bettini R, Partelli S, Boninsegna L, et al. Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor. Surgery 2011; 150:75.
  28. Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010; 39:735.
  29. Akerström G, Hellman P. Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007; 21:87.
  30. Mansour JC, Chen H. Pancreatic endocrine tumors. J Surg Res 2004; 120:139.
  31. Phan GQ, Yeo CJ, Hruban RH, et al. Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: Review of 125 patients. J Gastrointest Surg 1998; 2:473.
  32. Pitt SC, Pitt HA, Baker MS, et al. Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate? J Gastrointest Surg 2009; 13:1692.
  33. Nguyen SQ, Angel LP, Divino CM, et al. Surgery in malignant pancreatic neuroendocrine tumors. J Surg Oncol 2007; 96:397.
  34. Nomura N, Fujii T, Kanazumi N, et al. Nonfunctioning neuroendocrine pancreatic tumors: our experience and management. J Hepatobiliary Pancreat Surg 2009; 16:639.
  35. Hung JS, Chang MC, Lee PH, Tien YW. Is surgery indicated for patients with symptomatic nonfunctioning pancreatic neuroendocrine tumor and unresectable hepatic metastases? World J Surg 2007; 31:2392.
  36. Bruzoni M, Parikh P, Celis R, et al. Management of the primary tumor in patients with metastatic pancreatic neuroendocrine tumor: a contemporary single-institution review. Am J Surg 2009; 197:376.
  37. Norton JA, Kivlen M, Li M, et al. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg 2003; 138:859.
  38. Schurr PG, Strate T, Rese K, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience. Ann Surg 2007; 245:273.
  39. Abu Hilal M, McPhail MJ, Zeidan BA, et al. Aggressive multi-visceral pancreatic resections for locally advanced neuroendocrine tumours. Is it worth it? JOP 2009; 10:276.
  40. Franko J, Feng W, Yip L, et al. Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 2010; 14:541.
  41. Chu QD, Hill HC, Douglass HO Jr, et al. Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas. Ann Surg Oncol 2002; 9:855.
  42. Kazanjian KK, Reber HA, Hines OJ. Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg 2006; 141:765.
  43. Birnbaum DJ, Turrini O, Vigano L, et al. Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study. Ann Surg Oncol 2015; 22:1000.
  44. Birnbaum DJ, Gaujoux S, Cherif R, et al. Sporadic nonfunctioning pancreatic neuroendocrine tumors: prognostic significance of incidental diagnosis. Surgery 2014; 155:13.
  45. Bahra M, Jacob D, Pascher A, et al. Surgical strategies and predictors of outcome for malignant neuroendocrine tumors of the pancreas. J Gastroenterol Hepatol 2007; 22:930.
  46. Fischer L, Kleeff J, Esposito I, et al. Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 2008; 95:627.
  47. Bonney GK, Gomez D, Rahman SH, et al. Results following surgical resection for malignant pancreatic neuroendocrine tumours. A single institutional experience. JOP 2008; 9:19.
  48. Norton JA, Harris EJ, Chen Y, et al. Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection. Arch Surg 2011; 146:724.
  49. Oberg K, Ferone D, Kaltsas G, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biotherapy. Neuroendocrinology 2009; 90:209.
  50. Plöckinger U, Rindi G, Arnold R, 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 2004; 80:394.
  51. Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 2000; 190:432.
  52. Sarmiento JM, Heywood G, Rubin J, et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003; 197:29.
  53. Dixon E, Pasieka JL. Functioning and nonfunctioning neuroendocrine tumors of the pancreas. Curr Opin Oncol 2007; 19:30.
  54. Gomez-Rivera F, Stewart AE, Arnoletti JP, et al. Surgical treatment of pancreatic endocrine neoplasms. Am J Surg 2007; 193:460.
  55. Allendorf JD, Schrope BA, Lauerman MH, et al. Postoperative glycemic control after central pancreatectomy for mid-gland lesions. World J Surg 2007; 31:164.
  56. DiNorcia J, Ahmed L, Lee MK, et al. Better preservation of endocrine function after central versus distal pancreatectomy for mid-gland lesions. Surgery 2010; 148:1247.
  57. Warshaw AL. Conservation of the spleen with distal pancreatectomy. Arch Surg 1998; 123:550.
  58. Warshaw AL. Distal pancreatectomy with preservation of the spleen. J Hepatobiliary Pancreat Sci 2010; 17:808.
  59. Falconi M, Zerbi A, Crippa S, et al. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol 2010; 17:1621.
  60. Crippa S, Bassi C, Warshaw AL, et al. Middle pancreatectomy: indications, short- and long-term operative outcomes. Ann Surg 2007; 246:69.
  61. Müller MW, Friess H, Kleeff J, et al. Middle segmental pancreatic resection: An option to treat benign pancreatic body lesions. Ann Surg 2006; 244:909.
  62. Adham M, Giunippero A, Hervieu V, et al. Central pancreatectomy: single-center experience of 50 cases. Arch Surg 2008; 143:175.
  63. Hirono S, Tani M, Kawai M, et al. A central pancreatectomy for benign or low-grade malignant neoplasms. J Gastrointest Surg 2009; 13:1659.
  64. Sudo T, Murakami Y, Uemura K, et al. Middle pancreatectomy with pancreaticogastrostomy: a technique, operative outcomes, and long-term pancreatic function. J Surg Oncol 2010; 101:61.
  65. Shikano T, Nakao A, Kodera Y, et al. Middle pancreatectomy: safety and long-term results. Surgery 2010; 147:21.
  66. Zhou J, Dong M, Kong F, et al. Central pancreatectomy for benign tumors of the neck and body of the pancreas: report of eight cases. J Surg Oncol 2009; 100:273.
  67. Lavu H, Knuth JL, Baker MS, et al. Middle segment pancreatectomy can be safely incorporated into a pancreatic surgeon's clinical practice. HPB (Oxford) 2008; 10:491.
  68. Roggin KK, Rudloff U, Blumgart LH, Brennan MF. Central pancreatectomy revisited. J Gastrointest Surg 2006; 10:804.
  69. Sauvanet A, Partensky C, Sastre B, et al. Medial pancreatectomy: a multi-institutional retrospective study of 53 patients by the French Pancreas Club. Surgery 2002; 132:836.
  70. Christein JD, Smoot RL, Farnell MB. Central pancreatectomy: a technique for the resection of pancreatic neck lesions. Arch Surg 2006; 141:293.
  71. King J, Kazanjian K, Matsumoto J, et al. Distal pancreatectomy: incidence of postoperative diabetes. J Gastrointest Surg 2008; 12:1548.
  72. Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 2008; 135:1469.
  73. DiNorcia J, Schrope BA, Lee MK, et al. Laparoscopic distal pancreatectomy offers shorter hospital stays with fewer complications. J Gastrointest Surg 2010; 14:1804.
  74. DiNorcia J, Lee MK, Reavey PL, et al. One hundred thirty resections for pancreatic neuroendocrine tumor: evaluating the impact of minimally invasive and parenchyma-sparing techniques. J Gastrointest Surg 2010; 14:1536.
  75. Solorzano CC, Lee JE, Pisters PW, et al. Nonfunctioning islet cell carcinoma of the pancreas: survival results in a contemporary series of 163 patients. Surgery 2001; 130:1078.
  76. Bettini R, Mantovani W, Boninsegna L, et al. Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas. Dig Liver Dis 2009; 41:49.
  77. Keutgen XM, Nilubol N, Glanville J, et al. Resection of primary tumor site is associated with prolonged survival in metastatic nonfunctioning pancreatic neuroendocrine tumors. Surgery 2016; 159:311.
  78. Howard TJ, Stabile BE, Zinner MJ, et al. Anatomic distribution of pancreatic endocrine tumors. Am J Surg 1990; 159:258.
  79. Thompson GB, Service FJ, van Heerden JA, et al. Reoperative insulinomas, 1927 to 1992: an institutional experience. Surgery 1993; 114:1196.
  80. Jackson JE. Angiography and arterial stimulation venous sampling in the localization of pancreatic neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2005; 19:229.
  81. Carty SE, Jensen RT, Norton JA. Prospective study of aggressive resection of metastatic pancreatic endocrine tumors. Surgery 1992; 112:1024.
  82. Modlin IM, Lewis JJ, Ahlman H, et al. Management of unresectable malignant endocrine tumors of the pancreas. Surg Gynecol Obstet 1993; 176:507.
  83. McEntee GP, Nagorney DM, Kvols LK, et al. Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery 1990; 108:1091.
  84. Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol 2005; 19:783.
  85. de Herder WW, Niederle B, Scoazec JY, et al. Well-differentiated pancreatic tumor/carcinoma: insulinoma. Neuroendocrinology 2006; 84:183.
  86. Jensen RT, Berna MJ, Bingham DB, Norton JA. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 2008; 113:1807.
  87. Fishbeyn VA, Norton JA, Benya RV, et al. Assessment and prediction of long-term cure in patients with the Zollinger-Ellison syndrome: the best approach. Ann Intern Med 1993; 119:199.
  88. 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.
  89. Ehehalt F, Saeger HD, Schmidt CM, Grützmann R. Neuroendocrine tumors of the pancreas. Oncologist 2009; 14:456.
  90. Jensen RT, Niederle B, Mitry E, et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology 2006; 84:173.
  91. Yao JC, Eisner MP, Leary C, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol 2007; 14:3492.
  92. Smith SL, Branton SA, Avino AJ, et al. Vasoactive intestinal polypeptide secreting islet cell tumors: a 15-year experience and review of the literature. Surgery 1998; 124:1050.
  93. Chu QD, Al-kasspooles MF, Smith JL, et al. Is glucagonoma of the pancreas a curable disease? Int J Pancreatol 2001; 29:155.
  94. House MG, Yeo CJ, Schulick RD. Periampullary pancreatic somatostatinoma. Ann Surg Oncol 2002; 9:869.