Endocrinol Metab 2004;89(4):1934–1938.

7. Klimstra DS. Nonductal neoplasms of the pancreas. Mod Pathol 2007; 20(1):S94–S112.

8. Wick MR, Graeme-Cook FM. Pancreatic neuroendocrine neoplasms: a current summary of

diagnostic, prognostic, and differential diagnostic information. Am J Clin Pathol 2001;115:S28–S45.

9. Halfdanarson TR, Rabe KG, Rubin J, et al. Pancreatic neuroendocrine tumors (PNETs): incidence,

prognosis and recent trend toward improved survival. Ann Oncol 2008;19(10):1727–1733.

10. De Wilde RF, Edil BH, Hruban RH, et al. Well-differentiated pancreatic neuroendocrine tumors:

from genetics to therapy. Nat Rev Gastroenterol Hepatol 2012;9(4):199–208.

11. Kimura W, Kuroda A, Morioka Y. Clinical pathology of endocrine tumors of the pancreas. Analysis

of autopsy cases. Dig Dis Sci 1991;36(7):933–942.

12. Klimstra DS, Perren A, Oberg K, et al. Pancreatic endocrine tumors: non-functioning tumors and

microadenomas. In: DeLellis RA, Lloyd RV, Heitz PU, et al., eds. Pathology and Genetics of Tumours

of Endocrine Organs. Lyon, France: IARC Press; 2004:201–204.

13. Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology

1968;55:677–686.

14. Eriksson B, Oberg K. Neuroendocrine tumors of the pancreas. Br J Surg 2000;87:129–131.

15. Frankel WL. Update on pancreatic endocrine tumors. Arch Pathol Lab Med 2006;130(7):963–966.

16. Rindi G, de Herder WW, O’Toole D, et al. Consensus guidelines for the management of patients

with digestive neuroendocrine tumors: why such guidelines and how we went about it.

Neuroendocrinology 2006;84(3):155–157.

17. Strosberg JR, Cheema A, Weber JM, et al. Relapse-free survival in patients with nonmetastatic,

surgically resected pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging

classifications. Ann Surg 2012; 256(2):321–325.

18. Hochwald SN, Zee S, Conlon KC, 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

2002;20(11):2633–2642.

19. Capella C, Heitz PU, Hafler H, et al. Revised classification of neuroendocrine tumours of the lung,

pancreas and gut. Virchows Arch 1995;425(6):547–560.

20. La Rosa S, Sessa F, Capella C, et al. Prognostic criteria in nonfunctioning pancreatic endocrine

tumours. Virchows Arch 1996;429(6):323–333.

21. Pelosi G, Bresaola E, Bogina G, et al. Endocrine tumors of the pancreas: Ki-67 immunoreactivity on

paraffin sections is an independent predictor for malignancy: a comparative study with

proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index,

and other clinicopathologic variables. Hum Pathol 1996;27(11):1124–1134.

22. Boninsegna L, Panzuto F, Partelli S, et al. Malignant pancreatic neuroendocrine tumour: lymph

node ratio and Ki-67 are predictors of recurrence after curative resections. Eur J Cancer

2012;48(11):1608–1615.

23. Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and

treatment of neuroendocrine tumors. Pancreas 2013;42(4):557–577.

24. Goldin SB, Aston J, Wahi MM. Sporadically occurring functional pancreatic endocrine tumors:

review of recent literature. Curr Opin Oncol 2008; 20(1):25–33.

25. McLeod MK, Vinik AI. Calcitonin immunoreactivity and hypercalcitoninemia in two patients with

sporadic, nonfamilial, gastroenteropancreatic neuroendocrine tumors. Surgery 1992;111(5):484–

488.

26. Howard JM, Gohara AF, Cardwell RJ. Malignant islet cell tumor of the pancreas associated with

high plasma calcitonin and somatostatin levels. Surgery 1989;105(2 Pt 1):227–229.

27. Mao C, Carter P, Schaefer P, et al. Malignant islet cell tumor associated with hypercalcemia.

Surgery 1995;117(1):37–40.

28. Aniszewski JP, Young WF Jr, Thompson GB, et al. Cushing syndrome due to ectopic

adrenocorticotropic hormone secretion. World J Surg 2001;25(7):934–940.

29. Mukai K, Grotting JC, Greider MH, et al. Retrospective study of 77 pancreatic endocrine tumors

using the immunoperoxidase method. Am J Surg Pathol 1982;6(5):387–399.

30. Tomita T, Kimmel JR, Friesen SR, et al. Pancreatic polypeptide in islet cell tumors. Morphologic

1444

and functional correlations. Cancer 1985;56(7):1649–1657.

31. Vagefi PA, Razo O, Deshpande V, et al. Evolving patterns in the detection and outcomes of

pancreatic neuroendocrine neoplasms: the Massachusetts general hospital experience from 1977 to

2005. Arch Surg 2007;142(4):347–354.

32. Brodi C, Oberg K, Papotti M, et al. Pancreatic endocrine tumors: poorly differentiated endocrine

carcinoma. In: DeLellis RA, Lloyd RV, Heitz PU, et al., eds. Pathology and Genesis of Tumors of

Endocrine Organs. Lyon, France: IARC Press; 2004:207–208.

33. Jiao Y, Shi C, Edil BH, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered

in pancreatic neuroendocrine tumors. Science 2011;331(6021):1199–203.

34. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed

by global genomic analyses. Science 2008; 321(5897):1801–1806.

35. Zhang J, Francois R, Iyer R, et al. Current understanding of the molecular biology of pancreatic

neuroendocrine tumors. J Natl Cancer Inst 2013; 105(14):1005–1017.

36. Marinoni I, Kurrer AS, Vassella E, et al. Loss of DAXX and ATRX are associated with chromosome

instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology

2014;146(2):453–460.

37. Qian ZR, Ter-Minassian M, Chan JA, et al. Prognostic significance of MTOR pathway component

expression in neuroendocrine tumors. J Clin Oncol 2013;31(27):3418–3425.

38. Marx S, Spiegel AM, Skarulis MC, et al. Multiple endocrine neoplasia type 1: clinical and genetic

topics. Ann Intern Med 1998;129(6):484–494.

39. Toumpanakis CG, Caplin ME. Molecular genetics of gastroenteropancreatic neuroendocrine tumors.

Am J Gastroenterol 2008;103(3):729–732.

40. Lairmore TC, Piersall LD, DeBenedetti MK, et al. Clinical genetic testing and early surgical

intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg

2004;239(5):637–645; discussion 645–647.

41. Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: epidemiology and

prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 2008;15(2):409–427.

42. Speisky D, Duces A, Bièche I, et al. Molecular profiling of pancreatic neuroendocrine tumors in

sporadic and Von Hippel-Lindau patients. Clin Cancer Res 2012;18(10):2838–2849.

43. Johannessen CM, Reczek EE, James MF, et al. The NF1 tumor suppressor critically regulates TSC2

and mTOR. Proc Natl Acad Sci U S A 2005;102(24):8573–8578.

44. Starker LF, Carling T. Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Curr

Opin Oncol 2009;21(1):29–33.

45. Heaphy CM, de Wilde RF, Jiao Y, et al. Altered telomeres in tumors with ATRX and DAXX

mutations. Science 2011;333(6041):425.

46. Passacantilli I, Capurso G, Archibugi L, et al. Combined therapy with RAD001 e BEZ235 overcomes

resistance of PET immortalized cell lines to mTOR inhibition. Oncotarget 2014;5(14):5381–5391.

47. Muniraj T, Vignesh S, Shetty S, et al. Pancreatic neuroendocrine tumors. Dis Mon 2013;59(1):5–19.

48. Panzuto F, Severi C, Cannizzaro R, et al. Utility of combined use of plasma levels of chromogranin

A and pancreatic plypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors. J

Endocrinol Invest 2004;27(1):6–11.

49. Baudin E, Gigliotti A, Ducreux M, et al. Neuron-specific enolase and chromogranin A as markers of

neuroendocrine tumours. Br J Cancer 1998;78(8):1102–1107.

50. Tamm EP, Kim EE, Ng CS. Imaging of neuroendocrine tumors. Hematol Oncol Clin North Am

2007;21(3):409–432; vii.

51. Ichikawa T, Peterson MS, Federle MP, et al. Islet cell tumor of the pancreas: biphasic CT versus MR

imaging in tumor detection. Radiology 2000;216(1):163–171.

52. Vick C, Zech CJ, Hopfner S, et al. Imaging of neuroendocrine tumors of the pancreas. Radiologe

2003;43(4):293–300.

53. King AD, Ko GT, Yeung VT, et al. Dual phase spiral CT in the detection of small insulinomas of the

pancreas. Br J Radiol 1998;71(841):20–23.

54. Van Hoe L, Gryspeerdt S, Marchal G, et al. Helical CT for the preoperative localization of islet cell

tumors of the pancreas: value of arterial and parenchymal phase images. AJR Am J Roentgenol

1445

1995;165(6):1437–1439.

55. Semelka RC, Cumming MJ, Shoenut JP, et al. Islet cell tumors: comparison of dynamic contrastenhanced CT and MR imaging with dynamic gadolinium enhancement and fat suppression.

Radiology 1993;186(3):799–802.

56. Termanini B, Gibril F, Reynolds JC, et al. Value of somatostatin receptor scintigraphy: a

prospective study in gastrinoma of its effect on clinical management. Gastroenterology

1997;112(2):335–347.

57. Meko JB, Doherty GM, Siegel BA, et al. Evaluation of somatostatin-receptor scintigraphy for

detecting neuroendocrine tumors. Surgery 1996;120(6):975–983; discussion 983–984.

58. Kisker O, Bartsch D, Weinel RJ, et al. The value of somatostatin-receptor scintigraphy in newly

diagnosed endocrine gastroenteropancreatic tumors. J Am Coll Surg 1997;184(5):487–492.

59. Schirmer WJ, O’Dorisio TM, Schirmer TP, et al. Intraoperative localization of neuroendocrine

tumors with 125I-TYR(3)-octreotide and a hand-held gamma-detecting probe. Surgery

1993;114(4):745–751; discussion 751–752.

60. Modlin IM, Tang LH. Approaches to the diagnosis of gut neuroendocrine tumors: the last word

(today). Gastroenterology 1997;112(2):583–590.

61. Krausz Y, Bar-Ziv J, de Jong RB, et al. Somatostatin-receptor scintigraphy in the management of

gastroenteropancreatic tumors. Am J Gastroenterol 1998;93(1):66–70.

62. Frilling A, Malago M, Martin H, et al. Use of somatostatin receptor scintigraphy to image

extrahepatic metastases of neuroendocrine tumors. Surgery 1998;124(6):1000–1004.

63. Kwekkeboom DJ, Krenning EP. Somatostatin receptor imaging. Semin Nucl Med 2002;32(2):84–91.

64. Anderson MA, Carpenter S, Thompson NW, et al. Endoscopic ultrasound is highly accurate and

directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol

2000;95(9):2271–2277.

65. McLean AM, Fairclough PD. Endoscopic ultrasound in the localisation of pancreatic islet cell

tumours. Best Pract Res Clin Endocrinol Metab 2005; 19(2):177–193.

66. Glover JR, Shorvon PJ, Lees WR. Endoscopic ultrasound for localisation of islet cell tumours. Gut

1992;33(1):108–110.

67. Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic

ultrasonography. N Engl J Med 1992;326(26):1721–1726.

68. Thompson NW, Czako PF, Fritts LL, et al. Role of endoscopic ultrasonography in the localization of

insulinomas and gastrinomas. Surgery 1994; 116(6):1131–1138.

69. Proye C, Malvaux P, Pattou F, et al. Noninvasive imaging of insulinomas and gastrinomas with

endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery 1998;124(6):1134–

1143; discussion 1143–1144.

70. Mertz H, Gautam S. The learning curve for EUS-guided FNA of pancreatic cancer. Gastrointest

Endosc 2004;59(1):33–37.

71. Grover AC, Skarulis M, Alexander HR, et al. A prospective evaluation of laparoscopic exploration

with intraoperative ultrasound as a technique for localizing sporadic insulinomas. Surgery

2005;138(6):1003–1008; discussion 1008.

72. Zeiger MA, Shawker TH, Norton JA. Use of intraoperative ultrasonography to localize islet cell

tumors. World J Surg 1993;17(4):448–454.

73. Norton JA, Shawker TH, Doppman JL, et al. Localization and surgical treatment of occult

insulinomas. Ann Surg 1990;212(5):615–620.

74. Vinik AI, Moattari AR, Cho K, et al. Transhepatic portal vein catheterization for localization of

sporadic and MEN gastrinomas: a ten-year experience. Surgery 1990;107(3):246–255.

75. Pedrazzoli S, Pasquali C, Miotto D, et al. Transhepatic portal sampling for preoperative localization

of insulinomas. Surg Gynecol Obstet 1987; 165(2):101–106.

76. Vinik AI, Delbridge L, Moattari R, et al. Transhepatic portal vein catheterization for localization of

insulinomas: a ten-year experience. Surgery 1991; 109(1):1–11; discussion 111.

77. Fraker DL, Norton JA. Localization and resection of insulinomas and gastrinomas. JAMA

1988;259(24):3601–3605.

78. Imamura M, Takahashi K, Adachi H, et al. Usefulness of selective arterial secretin injection test for

1446