Annals of Surgical Oncology

, Volume 22, Issue 8, pp 2685–2699 | Cite as

Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group

  • Simron Singh
  • Chris Dey
  • Hagen Kennecke
  • Walter Kocha
  • Jean Maroun
  • Peter Metrakos
  • Tariq Mukhtar
  • Janice Pasieka
  • Daniel Rayson
  • Corwyn Rowsell
  • Lucas Sideris
  • Ralph Wong
  • Calvin Law
Endocrine Tumors

Abstract

Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers.

Keywords

Sunitinib Everolimus Lanreotide Peptide Receptor Radionuclide Therapy Pancreatic Neuroendocrine Tumor 

Notes

Acknowledgment

Funding for development, including consensus meeting costs and honoraria, and editorial support have been provided through an unrestricted educational grant from Novartis Pharmaceuticals Canada. Writing and editing assistance was provided by Havas Life Toronto.

Disclosure

There are no conflicts of interest.

References

  1. 1.
    Kocha W, Maroun J, Kennecke H, et al. Consensus recommendations for the diagnosis and management of well-differentiated gastroenterohepatic neuroendocrine tumours: a revised statement from a Canadian National Expert Group. Curr Oncol. 2010;17:49–64.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135:1469–92. doi: 10.1053/j.gastro.2008.05.047.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Ellison TA, Edil BH. The current management of pancreatic neuroendocrine tumors. Adv Surg 2012;46:283–96.PubMedCrossRefGoogle Scholar
  4. 4.
    Strosberg JR, Cheema A, Weber J, Han G, Coppola D, Kvols LK. Prognostic validity of a novel American Joint Committee on Cancer Staging Classification for pancreatic neuroendocrine tumors. J Clin Oncol. 2011;29:3044–9. doi: 10.1200/JCO.2011.35.1817 PubMedCrossRefGoogle Scholar
  5. 5.
    Massironi S, Sciola V, Peracchi M, Ciafardini C, Spampatti MP, Conte D. Neuroendocrine tumors of the gastro-entero-pancreatic system. World J Gastroenterol. 2008;14:5377–84.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Jensen RT, Cadiot G, Brandi ML, et al. ENETS Consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95:98–119. doi: 10.1159/000335591.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Kulke MH, Benson AB III, Bergsland E, et al. Neuroendocrine tumors. J Natl Compr Canc Netw. 2012;10:724–64.Google Scholar
  8. 8.
    O’Toole D, Salazar R, Falconi M, et al. Rare functioning pancreatic endocrine tumors. Neuroendocrinology. 2006;84:189–95. doi: 10.1159/000098011.PubMedCrossRefGoogle Scholar
  9. 9.
    Falconi M, Plockinger U, Kwekkeboom DJ, et al. Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology. 2006;84:196–211. doi: 10.1159/000098012.PubMedCrossRefGoogle Scholar
  10. 10.
    Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–3072. doi: 10.1200/JCO.2007.15.4377.PubMedCrossRefGoogle Scholar
  11. 11.
    Halfdanarson TR, Rabe KG, Rubin J, Petersen GM. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis, and recent trend toward improved survival. Ann Oncol. 2008;19:1727–33. doi: 10.1093/annonc/mdn351.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Cukier M, Law C, Liu N, et al. Epidemiology and survival of neuroendocrine tumors in Ontario: a 15-year population-based study [abstract]. J Clin Oncol. 2012;30. Google Scholar
  13. 13.
    Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39:707–12. doi: 10.1097/MPA.0b013e3181ec124e.PubMedCrossRefGoogle Scholar
  14. 14.
    Bosman T, Carneiro F, Hruban R, Theise N. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: IARC Press; 2010. pp. 13–14.Google Scholar
  15. 15.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds). AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010.Google Scholar
  16. 16.
    Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401. doi: 10.1007/s00428-006-0250-1.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Rindi G, Kloppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451:757–62. doi: 10.1007/s00428-007-0452-1.PubMedCrossRefGoogle Scholar
  18. 18.
    Tang L, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with carcinoma of the endocrine pancreas. College of American Pathologists (CAP); 2013. Pancreas Endocrine 3.2.0.1. Google Scholar
  19. 19.
    Chejfec G, Falkmer S, Grimelius L, et al. Synaptophysin: a new marker for pancreatic neuroendocrine tumors. Am J Surg Pathol. 1987;11:241–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV, Kidd M. Chromogranin A: biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol. 2010;17:2427–43. doi: 10.1245/s10434-010-1006-3.PubMedCrossRefGoogle Scholar
  21. 21.
    Taupenot L, Harper KL, O’Connor DT. The chromogranin-secretogranin family. N Engl J Med. 2003;348:1134–49. doi: 10.1056/NEJMra021405.PubMedCrossRefGoogle Scholar
  22. 22.
    Wiedenmann B, Franke WW, Kuhn C, Moll R, Gould VE. Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A. 1986;83:3500–4.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Bridger JM, Kill IR, Lichter P. Association of pKi-67 with satellite DNA of the human genome in early G1 cells. Chromosome Res. 1998;6:13–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Bruno S, Darzynkiewicz Z. Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells. Cell Prolif. 1992;25:31–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Endl E, Gerdes J. The Ki-67 protein: fascinating forms and an unknown function. Exp Cell Res. 2000;257:231–7. doi: 10.1006/excr.2000.4888.PubMedCrossRefGoogle Scholar
  26. 26.
    Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–22. doi: 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9.
  27. 27.
    Klimstra DS, Modlin IR, Adsay NV, et al. Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol. 2010;34:300–13. doi: 10.1097/PAS.0b013e3181ce1447.PubMedCrossRefGoogle Scholar
  28. 28.
    Craig J, Cheung M, Law C, Singh S. Ki-67 index variability in neuroendocrine tumors [abstract]. EMSO. 2012; abstract 1158P 2012. Google Scholar
  29. 29.
    Zerbi A, Falconi M, Rindi G, et al. Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases. Am J Gastroenterol. 2010;105:1421–9. doi: 10.1038/ajg.2009.747.PubMedCrossRefGoogle Scholar
  30. 30.
    Cheslyn-Curtis S, Sitaram V, Williamson RC. Management of nonfunctioning neuroendocrine tumours of the pancreas. Br J Surg. 1993;80:625–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic nonfunctioning tumors. Neuroendocrinology. 2012;95:120–34. doi: 10.1159/000335587.PubMedCrossRefGoogle Scholar
  32. 32.
    White TJ, Edney JA, Thompson JS, Karrer FW, Moor BJ. Is there a prognostic difference between functional and nonfunctional islet cell tumors? Am J Surg. 1994;168:627–9.Google Scholar
  33. 33.
    Bettini R, Partelli S, Boninsegna L, et al. Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor. Surgery. 2011;150:75–82. doi: 10.1016/j.surg.2011.02.022.PubMedCrossRefGoogle Scholar
  34. 34.
    Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res. 2008;14:7798–803. doi: 10.1158/1078-0432.CCR-08-0734.PubMedCrossRefGoogle Scholar
  35. 35.
    Han JH, Kim MH, Moon SH, et al. Clinical characteristics and malignant predictive factors of pancreatic neuroendocrine tumors. Korean J Gastroenterol. 2009;53:98–105.Google Scholar
  36. 36.
    La RS, Sessa F, Capella C, et al. Prognostic criteria in nonfunctioning pancreatic endocrine tumours. Virchows Arch. 1996;429:323–33.CrossRefGoogle Scholar
  37. 37.
    Panzuto F, Nasoni S, Falconi M, et al. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer. 2005;12:1083–92. doi: 10.1677/erc.1.01017.PubMedCrossRefGoogle Scholar
  38. 38.
    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;29:2372–7. doi: 10.1200/JCO.2010.33.0688.PubMedCrossRefGoogle Scholar
  39. 39.
    Singh S, et al. [Abstract] The role of Ki-67 in the prognosis and management of neuroendocrine (NET) patients in a multidisciplinary cancer center. Gastrointestinal Cancers Symposium, 2012; (suppl 4; abstr 184).Google Scholar
  40. 40.
    Noone TC, Hosey J, Firat Z, Semelka RC. Imaging and localization of islet cell tumours of the pancreas on CT and MRI. Best Pract Res Clin Endocrinol Metab. 2005;19:195–211. doi: 10.1016/j.beem.2004.11.013.PubMedCrossRefGoogle Scholar
  41. 41.
    Rockall AG, Reznek RH. Imaging of neuroendocrine tumours (CT/MR/US). Best Pract Res Clin Endocrinol Metab. 2007;21:43–68. doi: 10.1016/j.beem.2007.01.003.PubMedCrossRefGoogle Scholar
  42. 42.
    Sundin A, Vullierme MP, Kaltsas G, Plockinger U. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. Neuroendocrinology. 2009;90:167–83. doi: 10.1159/000184855.PubMedCrossRefGoogle Scholar
  43. 43.
    Figueiredo FA, Giovannini M, Monges G, et al. Pancreatic endocrine tumors: a large single-center experience. Pancreas. 2009;38:936–40. doi: 10.1097/MPA.0b013e3181b365db.PubMedCrossRefGoogle Scholar
  44. 44.
    Jhala NC, Jhala DN, Chhieng DC, Eloubeidi MA, Eltoum IA. Endoscopic ultrasound-guided fine-needle aspiration: a cytopathologist’s perspective. Am J Clin Pathol. 2003;120:351–67. doi: 10.1309/MFRF-J0XY-JLN8-NVDP.PubMedCrossRefGoogle Scholar
  45. 45.
    Kocjan G. Fine-needle aspiration cytology of the pancreas: a guide to the diagnostic approach. Coll Antropol. 2010;34:749–56.PubMedGoogle Scholar
  46. 46.
    Pais SA, Al-Haddad M, Mohamadnejad M, et al. EUS for pancreatic neuroendocrine tumors: a single-center, 11-year experience. Gastrointest Endosc. 2010;71:1185–93. doi: 10.1016/j.gie.2009.12.006.PubMedCrossRefGoogle Scholar
  47. 47.
    Teunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer. 2011;18(Suppl 1):S27–S51. doi: 10.1530/ERC-10-0282.PubMedCrossRefGoogle Scholar
  48. 48.
    Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85. doi: 10.1158/1078-0432.CCR-09-1759.CrossRefGoogle Scholar
  49. 49.
    Vinik AI, Woltering EA, Warner RR, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39:713–34. doi: 10.1097/MPA.0b013e3181ebaffd.PubMedCrossRefGoogle Scholar
  50. 50.
    Krausz Y, Freedman N, Rubinstein R, et al. 68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with (1)(1)(1)In-DTPA-octreotide (OctreoScan(R)). Mol Imaging Biol. 2011;13:583–93. doi: 10.1007/s11307-010-0374-1.PubMedCrossRefGoogle Scholar
  51. 51.
    Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med. 2006;36:228–47. doi: 10.1053/j.semnuclmed.2006.03.007.PubMedCrossRefGoogle Scholar
  52. 52.
    Singh S, Law C. Chromogranin A: A sensitive biomarker for the detection and posttreatment monitoring of gastroenteropancreatic neuroendocrine tumors. Expert Rev Gastroenterol Hepatol. 2012;6:313–34. doi: 10.1586/egh.12.15.PubMedCrossRefGoogle Scholar
  53. 53.
    Yao JC, Pavel M, Phan AT, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011;96:3741–9. doi: 10.1210/jc.2011-0666.PubMedCrossRefGoogle Scholar
  54. 54.
    Oberg K. Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 2011;18(Suppl 1):S17–S25. doi: 10.1530/ERC-10-0280.PubMedCrossRefGoogle Scholar
  55. 55.
    55.Panzuto F, Severi C, Cannizzaro R, et al. Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors. J Endocrinol Invest. 2004;27:6–11.PubMedCrossRefGoogle Scholar
  56. 56.
    Raines D, Chester M, Diebold AE, et al. A prospective evaluation of the effect of chronic proton pump inhibitor use on plasma biomarker levels in humans. Pancreas. 2012;41:508–11. doi: 10.1097/MPA.0b013e318243a0b6.PubMedCrossRefGoogle Scholar
  57. 57.
    Rustagi S, Warner RR, Divino CM. Serum pancreastatin: the next predictive neuroendocrine tumor marker. J Surg Oncol. 2013;108:126–8. doi: 10.1002/jso.23359.PubMedCrossRefGoogle Scholar
  58. 58.
    Kvols LK, Brendtro KL. The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas. 2010;39:705–6. doi: 10.1097/MPA.0b013e3181eb7451.PubMedCrossRefGoogle Scholar
  59. 59.
    Lee LC, Grant CS, Salomao DR, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery. 2012;152:965–74. doi: 10.1016/j.surg.2012.08.038.PubMedCrossRefGoogle Scholar
  60. 60.
    Libutti SK, Inabnet WB III. Force or stratagem? Surgery. 2012;152:975–6. doi: 10.1016/j.surg.2012.08.061.PubMedCrossRefGoogle Scholar
  61. 61.
    Crippa S, Bassi C, Salvia R, Falconi M, Butturini G, Pederzoli P. Enucleation of pancreatic neoplasms. Br J Surg. 2007;94:1254–9. doi: 10.1002/bjs.5833.PubMedCrossRefGoogle Scholar
  62. 62.
    Hellman P, Goretzki P, Simon D, Dotzenrath C, Roher HD. Therapeutic experience of 65 cases with organic hyperinsulinism. Langenbecks Arch Surg. 2000;385:329–36.PubMedCrossRefGoogle Scholar
  63. 63.
    63.Park BJ, Alexander HR, Libutti SK, et al. Operative management of islet cell tumors arising in the head of the pancreas. Surgery. 1998;124:1056–61.PubMedCrossRefGoogle Scholar
  64. 64.
    Rothmund M, Angelini L, Brunt LM, et al. Surgery for benign insulinoma: an international review. World J Surg. 1990;14:393–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Muller MW, Friess H, Kleeff J, et al. Is there still a role for total pancreatectomy? Ann Surg. 2007;246:966–74. doi: 10.1097/SLA.0b013e31815c2ca3.PubMedCrossRefGoogle Scholar
  66. 66.
    Smith JK, Ng SC, Hill JS, et al. Complications after pancreatectomy for neuroendocrine tumors: a national study. J Surg Res. 2010;163:63–8. doi: 10.1016/j.jss.2010.04.017.PubMedCrossRefGoogle Scholar
  67. 67.
    Abu HM, McPhail MJ, Zeidan BA, Jones CE, Johnson CD, Pearce NW. Aggressive multi-visceral pancreatic resections for locally advanced neuroendocrine tumours. is it worth it? JOP. 2009;10:276–9.Google Scholar
  68. 68.
    Bonney GK, Gomez D, Rahman SH, et al. Results following surgical resection for malignant pancreatic neuroendocrine tumours: a single institutional experience. JOP. 2008;9:19–25.Google Scholar
  69. 69.
    69.Chen H, Hardacre JM, Uzar A, Cameron JL, Choti MA. Isolated liver metastases from neuroendocrine tumors: does resection prolong survival? J Am Coll Surg. 1998;187:88–92.PubMedCrossRefGoogle Scholar
  70. 70.
    Dousset B, Saint-Marc O, Pitre J, Soubrane O, Houssin D, Chapuis Y. Metastatic endocrine tumors: medical treatment, surgical resection, or liver transplantation. World J Surg. 1996;20:908–14.PubMedCrossRefGoogle Scholar
  71. 71.
    Fendrich V, Langer P, Celik I, et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors. Ann Surg. 2006;244:845–51. doi: 10.1097/01.sla.0000246951.21252.60.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Hodul PJ, Strosberg JR, Kvols LK. Aggressive surgical resection in the management of pancreatic neuroendocrine tumors: when is it indicated? Cancer Control. 2008;15:314–21.PubMedGoogle Scholar
  73. 73.
    Kleine M, Schrem H, Vondran FW, Krech T, Klempnauer J, Bektas H. Extended surgery for advanced pancreatic endocrine tumours. Br J Surg. 2012;99:88–94. doi: 10.1002/bjs.7681.PubMedCrossRefGoogle Scholar
  74. 74.
    Norton JA, Kivlen M, Li M, Schneider D, Chuter T, Jensen RT. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 2003;138:859–66. doi: 10.1001/archsurg.138.8.859.PubMedCrossRefGoogle Scholar
  75. 75.
    Sarmiento JM, Que FG, Grant CS, Thompson GB, Farnell MB, Nagorney DM. Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomes of an aggressive approach. Surgery. 2002;132:976–82. doi: 10.1067/msy.2002.128615.PubMedCrossRefGoogle Scholar
  76. 76.
    Sasson AR, Hoffman JP, Ross EA, Kagan SA, Pingpank JF, Eisenberg BL. En bloc resection for locally advanced cancer of the pancreas: is it worthwhile? J Gastrointest Surg. 2002;6:147–57.PubMedCrossRefGoogle Scholar
  77. 77.
    Bold RJ, Charnsangavej C, Cleary KR, et al. Major vascular resection as part of pancreaticoduodenectomy for cancer: radiologic, intraoperative, and pathologic analysis. J Gastrointest Surg. 1999;3:233–43.PubMedCrossRefGoogle Scholar
  78. 78.
    Kouvaraki MA, Solorzano CC, Shapiro SE, et al. Surgical treatment of nonfunctioning pancreatic islet cell tumors. J Surg Oncol. 2005;89:170–85. doi: 10.1002/jso.20178.PubMedCrossRefGoogle Scholar
  79. 79.
    Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004;8:935–49. doi: 10.1016/j.gassur.2004.09.046.PubMedCrossRefGoogle Scholar
  80. 80.
    Cusati D, Zhang L, Harmsen WS, et al. Metastatic nonfunctioning pancreatic neuroendocrine carcinoma to liver: surgical treatment and outcomes. J Am Coll Surg. 2012;215:117–24. doi: 10.1016/j.jamcollsurg.2012.05.002.PubMedCrossRefGoogle Scholar
  81. 81.
    81.Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg. 2000;190:432–45.PubMedCrossRefGoogle Scholar
  82. 82.
    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;31:2392–7. doi: 10.1007/s00268-007-9264-3.PubMedCrossRefGoogle Scholar
  83. 83.
    Saxena A, Chua TC, Perera M, Chu F, Morris DL. Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review. Surg Oncol. 2012;21:e131–41. doi: 10.1016/j.suronc.2012.05.001.PubMedCrossRefGoogle Scholar
  84. 84.
    Mayo SC, de Jong MC, Bloomston M, et al. Surgery versus intraarterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Ann Surg Oncol. 2011;18:3657–65. doi: 10.1245/s10434-011-1832-y.PubMedCrossRefGoogle Scholar
  85. 85.
    Elias D, Sideris L, Liberale G, et al. Surgical treatment of peritoneal carcinomatosis from well-differentiated digestive endocrine carcinomas. Surgery. 2005;137:411–6. doi: 10.1016/j.surg.2004.11.007.PubMedCrossRefGoogle Scholar
  86. 86.
    Elias D, David A, Sourrouille I, et al. Neuroendocrine carcinomas: optimal surgery of peritoneal metastases (and associated intraabdominal metastases). Surgery. 2014;155:5–12. doi: 10.1016/j.surg.2013.05.030.PubMedCrossRefGoogle Scholar
  87. 87.
    Kianmanesh R, Ruszniewski P, Rindi G, et al. ENETS consensus guidelines for the management of peritoneal carcinomatosis from neuroendocrine tumors. Neuroendocrinology. 2010;91:333–40. doi: 10.1159/000286700.PubMedCrossRefGoogle Scholar
  88. 88.
    Steinmuller 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. doi: 10.1159/000111037.PubMedCrossRefGoogle Scholar
  89. 89.
    Kulke MH, Bendell J, Kvols L, Picus J, Pommier R, Yao J. Evolving diagnostic and treatment strategies for pancreatic neuroendocrine tumors. J Hematol Oncol. 2011;4:29. doi: 10.1186/1756-8722-4-29.PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Lewis MA, Hobday TJ. Treatment of neuroendocrine tumor liver metastases. Int J Hepatol. 2012;973–946. doi: 10.1155/2012/973946.
  91. 91.
    Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980;303:1189–94. doi: 10.1056/NEJM198011203032101.PubMedCrossRefGoogle Scholar
  92. 92.
    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;22:4762–771. doi: 10.1200/JCO.2004.04.024.PubMedCrossRefGoogle Scholar
  93. 93.
    Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326:519–23. doi: 10.1056/NEJM199202203260804.PubMedCrossRefGoogle Scholar
  94. 94.
    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. doi: 10.1002/cncr.25425.PubMedCrossRefGoogle Scholar
  95. 95.
    Mitry E, Baudin E, Ducreux M, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer. 1999;81:1351–5. doi: 10.1038/sj.bjc.6690325.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Hainsworth JD, Spigel DR, Litchy S, Greco FA. Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. J Clin Oncol. 2006;24:3548–54. doi: 10.1200/JCO.2005.05.0575.PubMedCrossRefGoogle Scholar
  97. 97.
    Sorbye H, Wekin S, Langer S, et al. Ki-67 Proliferative Index Predicts Response to Chemotherapy and Survival in 252 Patients with High-Grade Gastrointestinal Neuroendocrine Carcinoma (WHO G3) (abstract). North American Neuroendocrine Society Symposium, Abstract C36 2012.Google Scholar
  98. 98.
    Welin S, Sorbye H, Sebjornsen S, Knappskog S, Busch C, Oberg K. Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer. 2011;117:4617–22. doi: 10.1002/cncr.26124.PubMedCrossRefGoogle Scholar
  99. 99.
    Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–23. doi: 10.1056/NEJMoa1009290.PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    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. doi: 10.1056/NEJMoa1003825.PubMedCrossRefGoogle Scholar
  101. 101.
    101.Ricke J, Klose KJ, Mignon M, Oberg K, Wiedenmann B. Standardisation of imaging in neuroendocrine tumours: results of a European Delphi process. Eur J Radiol. 2001;37:8–17.PubMedCrossRefGoogle Scholar
  102. 102.
    A randomized, double-blind, placebo-controlled study of lanreotide antiproliferative response in patients with gastroenteropancreatic neuroendocrine tumors (CLARINET). The European Cancer Congress; 2013.Google Scholar
  103. 103.
    Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26:2124–30. doi: 10.1200/JCO.2007.15.2553.PubMedCrossRefGoogle Scholar
  104. 104.
    Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology. 2009;90:220–6. doi: 10.1159/000225951.PubMedCrossRefGoogle Scholar
  105. 105.
    Sowa-Staszczak A, Pach D, Stefanska A, et al. Can treatment using radiolabelled somatostatin analogue increase the survival rate in patients with nonfunctioning neuroendocrine pancreatic tumours? Nucl Med Rev Cent East Eur. 2011;14:73–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Villard L, Romer A, Marincek N, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol. 2012;30:1100–6. doi: 10.1200/JCO.2011.37.2151.PubMedCrossRefGoogle Scholar
  107. 107.
    Gulenchyn KY, Yao X, Asa SL, Singh S, Law C. Radionuclide therapy in neuroendocrine tumours: a systematic review. Clin Oncol R Coll Radiol. 2012;24:294–308. doi: 10.1016/j.clon.2011.12.003.PubMedCrossRefGoogle Scholar
  108. 108.
    108.Arnold R, Rinke A, Klose KJ, et al. Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial. Clin Gastroenterol Hepatol. 2005;3:761–71.PubMedCrossRefGoogle Scholar
  109. 109.
    Fjallskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19:35–42. doi: 10.1385/MO:19:1:35.PubMedCrossRefGoogle Scholar
  110. 110.
    Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72. doi: 10.1016/S1470-2045(07)70410-2.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Simron Singh
    • 1
  • Chris Dey
    • 2
  • Hagen Kennecke
    • 3
  • Walter Kocha
    • 4
  • Jean Maroun
    • 5
  • Peter Metrakos
    • 6
  • Tariq Mukhtar
    • 7
  • Janice Pasieka
    • 8
  • Daniel Rayson
    • 9
  • Corwyn Rowsell
    • 10
  • Lucas Sideris
    • 11
  • Ralph Wong
    • 12
  • Calvin Law
    • 1
  1. 1.Department of Medicine, Odette Cancer Centre – Sunnybrook HospitalUniversity of TorontoTorontoCanada
  2. 2.Department of Medical Imaging, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  3. 3.BC Cancer AgencyVancouverCanada
  4. 4.London Regional Cancer CentreLondonCanada
  5. 5.The Ottawa HospitalOttawaCanada
  6. 6.McGill University Health CentreRoyal Victoria HospitalMontrealCanada
  7. 7.Havas Life TorontoTorontoCanada
  8. 8.Department Surgery and OncologyUniversity of CalgaryCalgaryCanada
  9. 9.Queen Elizabeth II Health Sciences CenterHalifaxCanada
  10. 10.Sunnybrook Health Sciences CentreTorontoCanada
  11. 11.Hopital Maisonneuve-RosemontMontrealCanada
  12. 12.St. Boniface General HospitalWinnipegCanada

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