Согласительные рекомендации ENETS(Европейское общество по нейроэндокринным опухолям) по ведению больных с нейроэндокринными опухолями ЖКТ: функционирующие нейроэндокринные опухоли поджелудочной железы

Панкреатические нейроэндокринные опухоли (П-НЭО) представлены как функционирующими опухолями, так и новообразованиями без определенной функциональной активности [1–4]. Нефункционирующие П-НЭО часто секретируют панкреатический полипептид (ПП), хромогранин А, нейроспецифическую энолазу (НСЭ), хорионический гонадотропин (ХГ), кальцитонин, нейротензин и другие пептиды, обычно не проявляются клиническими симптомами и в связи с этим считаются нефункционирующими опухолями [2, 3, 5–7]. В этой части рекомендаций рассматриваются только функционирующие П-НЭО. Отдельно обсуждаются две группы: наиболее часто встречающиеся опухоли (инсулинома и гастринома) и другие опухоли (подробно описанные и реже встречающиеся), так называемые редкие функционирующие П-НЭО (см. таблицу) [1–4].

1. Robert T. Jensen, Guillaume Cadiot, Maria L. Brandi, Wouter W. de Herder, Gregory Kaltsas, Paul Komminoth, Jean-Yves Scoazec, Ramon Salazar, Alain Sauvanet, Reza Kianmanesh и др. // Neuroendocrinology. 2012; 95: 98–119

2. Oberg K. Pancreatic endocrine tumors. Semin. Oncol. 2010; 37: 594–618.

3. Metz D.C., Jensen R.T. Gastrointestinal neuroendocrine tumors: Pancreatic endocrine tumors. Gastroenterology 2008; 135: 1469–1492.

4. Kulke M.H., Anthony L.B., Bushnell D.L. et al. NANETS Treatment Guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010; 39: 735–752.

5. Ekeblad S. Islet cell tumours. Adv. Exp. Med. Biol. 2010; 654: 771–789.

6. O’Toole D., Salazar R., Falconi M. et al. Rare functioning pancreatic endocrine tumors. Neuroendocrinology 2006; 84: 189–195.

7. Falconi M., Plockinger U., Kwekkeboom D.J. et al. Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology 2006; 84: 196–211.

8. Kaltsas G., Androulakis I.I., de Herder W.W. et al. Paraneoplastic syndromes secondary to neuroendocrine tumours. Endocr. Relat. Cancer. 2010; 17: R173–R193.

9. Jensen R.T., Niederle B., Mitry E. et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology 2006; 84: 173–182.

10. Ellison E.C., Johnson J.A. The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr. Probl. Surg. 2009; 46: 13–106.

11. Roy P., Venzon D.J., Shojamanesh H. et al. Zollinger-Ellison syndrome: clinical presentation in 261 patients. Medicine (Baltimore) 2000; 79: 379–411.

12. Jensen R.T., Berna M.J., Bingham M.D. et al. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies. Cancer 2008; 113(suppl): 1807–1843.

13. Gibril F., Schumann M., Pace A. et al. Multiple endocrine neoplasia type 1 and ZollingerEllison syndrome. A prospective study of 107 cases and comparison with 1,009 patients from the literature. Medicine (Baltimore). 2004; 83: 43–83.

14. Vanderveen K., Grant C. Insulinoma. Cancer Treat. Res. 2010; 153: 235–252.

15. Guettier J.M., Gorden P. Insulin secretion and insulin-producing tumors. Expert Rev Endocrinol. Metab. 2010; 5: 217–227.

16. De Herder W.W., Niederle B., Scoazec J.Y. et al. Well-differentiated pancreatic tumor/carcinoma: insulinoma. Neuroendocrinology 2006; 84: 183–188.

17. Anlauf M., Garbrecht N., Henopp T. et al. Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinicopathological and epidemiological features. Wld Med. J. 2006; 12: 5440–5446.

18. Kloppel G., Anlauf M. Gastrinoma – morphological aspects. Wien Klin. Wochenschr. 2007; 119: 579–584.

19. Gibril F., Jensen R.T. Advances in evaluation and management of gastrinoma in patients with Zollinger-Ellison syndrome. Curr. Gastroenterol. Rep. 2005; 7: 114–121.

20. Anlauf M., Perren A., Meyer C.L. et al. Precursor lesions in patients with multiple endocrine neoplasia type 1 associated duodenal gastrinomas. Gastroenterology 2005; 128: 1187–1198.

21. Bosman F.T., Carneiro F., Hruban R.H., Theise N.D. World Health Organization classification of tumors and genetics of the digestive system, ed 1. Lyon, IARC, 2010.

22. 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.

23. Edge S.B., Byrd D.R., Compton C.C. et al. AJCC Cancer Staging Manual, ed. 1. New York, Springer, 2010.

24. 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: 627–635.

25. Ekeblad S., Skogseid B., Dunder K. et al. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin. Cancer Res. 2008; 14: 7798–7803.

26. Pape U.F., Jann H. Muller Nordhorn J. et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 2008; 113: 256–265.

27. Zhao Y.P., Zhan H.X., Zhang T.P. et al. Surgical management of patients with insulinomas: result of 292 cases in a single institution. J. Surg. Oncol. 2011; 103: 169–174.

28. Casadei R., Ricci C., Rega D. et al. Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? A single-center experience. Pancreas 2010; 39: 825–828.

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: 1421–1429.

30. Niederle M.B., Hackl M., Kaserer K. et al. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr. Relat. Cancer 2010; 17: 909–918.

31. Klimstra D.S., Modlin I.R., Coppola D. et al. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 2010; 39: 707–712.

32. Weber H.C., Venzon D.J., Lin J.T. et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology 1995; 108: 1637–1649.

33. Banasch M., Schmitz F. Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. Wien. Klin. Wschr. 2007; 119: 573–578.

34. Thom A.K., Norton J.A., Axiotis C.A. et al. Location, incidence and malignant potential of duodenal gastrinomas. Surgery 1991; 110: 1086–1093.

35. Stabile B.E., Morrow D.J., Passaro E. Jr. The gastrinoma triangle: operative implications. Am. J. Surg. 1984; 147: 25–31.

36. Pipeleers-Marichal M., Kloppel G. Gastrinomas in MEN-1. N. Engl. J. Med. 1990; 323:349.

37. MacFarlane M.P., Fraker D.L., Alexander H.R. et al. A prospective study of surgical resection of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery 1995; 118: 973–980.

38. Garbrecht N., Anlauf M., Schmitt A. et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr. Relat. Cancer 2008; 15: 229– 241.

39. Isidori A.M., Kaltsas G.A., Grossman A.B. Ectopic ACTH syndrome. Front Horm. Res. 2006; 35: 143–156.

40. Hoffmann K.M., Furukawa M., Jensen R.T. Duodenal neuroendocrine tumors: classification, functional syndromes, diagnosis and medical treatment. Best. Pract. Res. Clin. Gastroenterology 2005; 19: 675–697.

41. Levy Bohbot N., Merle C., Goudet P. et al. Prevalence, characteristics and prognosis of MEN-1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterology Clin. Biol. 2004; 28: 1075– 1081.

42. Yu F., Venzon D.J., Serrano J. et al. Prospective study of the clinical course, prognostic factors and survival in patients with longstanding Zollinger-Ellison syndrome. J. Clin. Oncol. 1999; 17: 615–630.

43. Jensen R.T. Natural history of digestive endocrine tumors; in Mignon M, Colombel JF (eds): Recent Advances in Pathophysiology and Management of Inf lammatory Bowel Diseases and Digestive Endocrine Tumors. Paris, Libbey Eurotext, 1999; 192–219.

44. Gibril F., Venzon D.J., Ojeaburu J.V. et al. 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: 5282–5293.

45. Jensen R.T. Zollinger-Ellison syndrome; in Doherty GM, Skogseid B (eds): Surgical Endocrinology: Clinical Syndromes. Philadelphia, Lippincott Williams & Wilkins, 2001, 291–344.

46. Maton P.N., Gardner J.D., Jensen R.T. Cushing’s syndrome in patients with Zollinger-Ellison syndrome. N. Engl. J. Med. 1986; 315: 1–5.

47. Cadiot G., Vuagnat A., Doukhan I. et al. Prognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. Gastroenterology 1999; 116: 286–293.

48. Norton J.A., Jensen R.T. Resolved and unresolved controversies in the surgical management of patients with ZollingerEllison syndrome. Ann. Surg. 2004; 240: 757–773.

49. Goh B.K., Chow P.K., Tan Y.M. et al. Validation of five contemporary prognostication systems for primary pancreatic endocrine neoplasms: results from a single institution experience with 61 surgically treated cases. ANZ J. Surg. 2011; 81: 79–85.

50. London J.F., Shawker T.H., Doppman J.L. et al. Zollinger– Ellison syndrome: prospective assessment of abdominal US in the localization of gastrinomas. Radiol. 1991; 178: 763–767.

51. Mathur A., Gorden P., Libutti S.K. Insulinoma. Surg. Clin. N. Am. 2009;89:1105–1121.

52. Jonkers Y.M., Claessen S.M., Perren A. et al. DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients. Endocr. Relat. Cancer. 2007; 14: 769–779.

53. Norton J.A., Fang T.D., Jensen R.T. Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J. Nat. Compr. Cancer 2006; 4: 148–153.

54. Goudet P., Murat A., Cardot Bauters C. et al. Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). Wld J. Surg. 2009; 33: 1197– 1207.

55. Goudet P., Murat A., Binquet C. et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) cohort study among 758 patients. Wld J. Surg. 2010; 34: 249–255.

56. Gibril F., Chen Y. J., Schrump D.S. et al. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J. Clin. Endocrinol. Metab.2003; 88: 1066–1081.

57. Krenning E.P., Bakker W.H., Kooij P.P. et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe1octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J. Nucl. Med. 1992; 33: 652–658.

58. Osefo N., Ito T., Jensen R.T. Gastric acid hypersecretory states: recent insights and advances. Curr. Gastroenterol. Rep. 2009; 11: 433–441.

59. Berna M.J., Hoffmann K.M., Serrano J. et al. Serum gastrin in Zollinger-Ellison syndrome. I. Prospective study of fasting serum gastrin in 309 patients from the National Institutes of Health and comparison with 2,229 cases from the literature. Medicine (Baltimore) 2006; 85: 295–330.

60. Corleto V.D., Annibale B., Gibril F. et al. Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome? Aliment. Pharmacol. Ther. 2001; 15: 1555–1561.

61. Arnold R. Diagnosis and differential diagnosis of hypergastrinemia. Wien. Klin. Wschr. 2007; 119: 564–569.

62. Roy P., Venzon D.J., Feigenbaum K.M. et al. Gastric secretion in Zollinger-Ellison syndrome: correlation with clinical expression, tumor extent and role in diagnosis – a prospective NIH study of 235 patients and review of the literature in cases. Medicine (Baltimore) 2001; 80: 189–222.

63. Benya R.V., Metz D.C., Venzon D.J. et al. Zollinger–Ellison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia type 1. Am. J. Med. 1994; 97: 436–444.

64. Cadiot G., Houillier P., Allouch A. et al. Oral calcium tolerance test in the early diagnosis of primary hyperparathyroidism and multiple endocrine neoplasia type 1 in patients with the Zollinger-Ellison syndrome. Groupe de Recherche et d’Etude du Syndrome de Zollinger-Ellison. Gut. 1996; 39: 273–278.

65. Wynick D., Williams S.J., Bloom S.R. Symptomatic secondary hormone syndromes in patients with established malignant pancreatic endocrine tumors. N. Engl. J. Med. 1988; 319: 605–607.

66. Chiang H.C., O’Dorisio T.M., Huang S.C. et al. Multiple hormone elevations in patients with Zollinger-Ellison syndrome: prospective study of clinical significance and of the development of a second symptomatic pancreatic endocrine tumor syndrome. Gastroenterol. 1990; 99: 1565–1575.

67. Vinik A.I., Woltering E.A., Warner R.R. et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas 2010; 39: 713–734.

68. O’Toole D., Grossman A., Gross D. et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: biochemical markers. Neuroendocrinology 2009; 90: 194–202.

69. Rehfeld J.F., Gingras M.H., Bardram L. et al. The ZollingerEllison syndrome and mismeasurement of gastrin. Gastroenterol. 2011; 140: 1444–1453.

70. Weber H.C., Venzon D.J., Jensen R.T. et al. Studies on the interrelation between ZollingerEllison syndrome, Helicobacter pylori and proton pump inhibitor therapy. Gastroenterol. 1997; 112: 84–91.

71. Jensen R.T. Consequences of long-term proton pump blockade: highlighting insights from studies of patients with gastrinomas. Basic Clin. Pharmacol. Toxicol. 2006; 98: 4–19.

72. Oh D.S., Wang H.S., Ohning G.V. et al. Validation of a new endoscopic technique to assess acid output in Zollinger– Ellison syndrome. Clin. Gastroenterol. Hepatol. 2006; 4: 1467– 1473.

73. Berna M.J., Hoffmann K.M., Long S.H. et al. 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: 331– 364.

74. Mignon M., Jais P., Cadiot G. et al. Clinical features and advances in biological diagnostic criteria for Zollinger-Ellison syndrome; in Mignon M, Jensen RT (eds): Endocrine Tumors of the Pancreas: Recent Advances in Research and Management. Series. Front Gastrointest Res. Basel, Karger, 1995; 23: 223–239.

75. Frucht H., Howard J.M., Slaff J.I. et al. Secretin and calcium provocative tests in the Zollinger-Ellison syndrome: a prospective study. Ann. Intern. Med. 1989; 111: 713–722.

76. Gibril F., Jensen R.T. Zollinger-Ellison syndrome revisited: diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr. Gastroenterol. Rep. 2004; 6: 454–463.

77. Goldman J.A. Blanton W.P., Hay D.W. et al. Case report: false-positive secretin stimulation test for gastrinoma associated with the use of proton pump inhibitor therapy. Clin. Gastroenterol. Hepatol. 2009; 7: 600–602.

78. Niederle B. Hypergastrinemia – diagnosis and treatment. Wien. Klin. Wschr. 2007; 119: 561–563.

79. De Herder W.W., O’Toole D., Rindi G. et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine tumors. Part 1. Stomach, duodeneum and pancreas. Neuroendocrinology 2006; 84: 151–216.

80. Berna M.J., Annibale B., Marignani M. et al. A prospective study of gastric carcinoids and enterochromaffin-like cells changes in multiple endocrine neoplasia type 1 and ZollingerEllison syndrome: identification of risk factors. J. Clin. Endocrinol. Metab. 2008; 93: 1582–1591.

81. Norton J.A., Cornelius M.J., Doppman J.L. et al. Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome and multiple endocrine neoplasia type I: a prospective study. Surgery 1987; 102: 958–966.

82. Waldmann J., Fendrich V., Habbe N. et al. Screening of patients with multiple endocrine neoplasia type 1 (MEN-1): a critical analysis of its value. Wld J. Surg. 2009; 33: 1208–1218.

83. Norton J.A., Venzon D.J., Berna M.J. et al. Prospective study of surgery for primary hyperaparathyroidism in multiple endocrine neoplasia type 1, and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPT. Ann. Surg. 2008; 247: 501–510.

84. Jensen R.T. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J. Intern. Med. 1998; 243: 477–488.

85. Brandi M.L., Gagel R.F., Angeli A. et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J. Clin. Endocrinol. Metab. 2001; 86: 5658–5671.

86. Thakker R.V. Multiple endocrine neoplasia type 1 (MEN1). Best. Pract. Res. Clin. Endocrinol. Metab. 2010; 24: 355–370.

87. Service F.J., Natt N., Thompson G.B. et al. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J. Clin. Endocrinol. Metab. 1999; 84: 1582–1589.

88. Marsk R., Jonas E., Rasmussen F. et al. Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden. Diabetologia 2010; 53: 2307–2311.

89. Patti M.E., Goldfine A.B. Hypoglycaemia following gastric bypass surgery – diabetes remission in the extreme? Diabetologia 2010; 53: 2276–2279.

90. Van Bon A.C., Benhadi N., Endert E. et al. Evaluation of endocrine tests. D: the prolonged fasting test for insulinoma. Neth. J. Med. 2009; 67: 274–278.

91. Hirshberg B., Livi A., Bartlett D.L. et al. Forty-eight-hour fast: the diagnostic test for insulinoma. J. Clin. Endocrinol. Metab. 2000; 85: 3222–3226.

92. 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.

93. Sundin A., Vullierme M.P., Kaltsas G. et al. ENETS guidelines for the standards of care in patients with neuroendocrine tumours: radiological examinations in patients with neuroendocrine tumours. Neuroendocrinology 2009; 90: 183.

94. Kwekkeboom D.J., Krenning E.P., Scheidhauer K. et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: somatostatin receptor imaging with 111In-pentetreotide. Neuroendocrinology 2009; 90: 184–189.

95. Sundin A., Garske U., Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract. Res. Clin. Endocrinol. Metab. 2007; 21: 69–85.

96. Rockall A.G., Reznek R.H. Imaging of neuroendocrine tumours (CT/MR/US). Best Pract. Res. Clin. Endocrinol. Metab. 2007; 21: 43–68.

97. Morrow E.H., Norton J.A. Surgical management of ZollingerEllison syndrome; state of the art. Surg. Clin. N. Am. 2009; 89: 1091–1103.

98. Fraker D.L., Norton J.A., Alexander H.R. et al. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann. Surg. 1994; 220: 320–330.

99. Norton J.A., Fraker D.L., Alexander H.R. et al. Surgery increases survival in patients with gastrinoma. Ann. Surg. 2006; 244: 410–419.

100. Norton J.A., Alexander H.R., Fraker D.L. 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: 617–626.

101. Lebtahi R., Cadiot G., Sarda L. et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J. Nucl. Med. 1997; 38: 853–858.

102. Doppman J.L., Miller D.L., Chang R. et al. Gastrinomas: localization by means of selective intraarterial injection of secretin. Radiology 1990; 174: 25–29.

103. Termanini B., Gibril F., Reynolds J.C. et al. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology 1997; 112: 335–347.

104. Alexander H.R., Fraker D.L., Norton J.A. et al. Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome. Ann. Surg. 1998; 228: 228–238.

105. Anderson M.A. Carpenter S., Thompson N.W. et al. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am. J. Gastroenterol. 2000; 95: 2271–2277.

106. Ruszniewski P., Amouyal P., Amouyal G. et al. Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. Surgery 1995; 117: 629–635.

107. Patel K.K., Kim M.K. Neuroendocrine tumors of the pancreas: endoscopic diagnosis. Curr. Opin. Gastroenterol. 2008; 24: 638–642.

108. Guettier J.M., Kam A., Chang R. et al. Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience. J. Clin. Endocrinol. Metab. 2009; 94: 1074–1080.

109. Morganstein D.L., Lewis D.H., Jackson J. et al. The role of arterial stimulation and simultaneous venous sampling in addition to cross-sectional imaging for localisation of biochemically proven insulinoma. Eur. Radiol. 2009; 19: 2467–2473.

110. Gibril F., Reynolds J.C., Doppman J.L. et al. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas: a prospective study. Ann. Intern. Med. 1996; 125: 26–34.

111. Gibril F., Jensen R.T. Diagnostic uses of radiolabelled somatostatin-receptor analogues in gastroenteropancreatic endocrine tumors. Dig. Liver. Dis. 2004; 36: S106– S120.

112. Akerstrom G., Hellman P. Surgery on neuroendocrine tumours. Best. Pract. Res. Clin. Endocrinol. Metab. 2007; 21: 87–109.

113. Srirajaskanthan R., Kayani I., Quigley A.M. et al. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPAoctreotide scintigraphy. J. Nucl. Med. 2010; 51: 875–882.

114. Putzer D., Gabriel M., Henninger B. et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3octreotide PET in comparison to CT and bone scintigraphy. J. Nucl. Med. 2009; 50: 1214–1221.

115. Ambrosini V., Nanni C., Zompatori M. et al. 68Ga-DOTANOC PET/CT in comparison with CT for the detection of bone metastasis in patients with neuroendocrine tumours. Eur. J. Nucl. Med. Mol. Imaging 2010; 37: 722–727.

116. Dudczak R., Traub Weidinger T. PET and PET/CT in endocrine tumours. Eur. J. Radiol. 2010; 73: 481–493.

117. Buchmann I., Henze M., Engelbrecht S. et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur. J. Nucl. Med. Mol. Imaging 2007; 34: 1617–1626.

118. Gabriel M., Decristoforo C., Kendler D. et al. 68Ga-DOTATyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J. Nucl. Med. 2007; 48: 508–518.

119. Ruf J., Heuck F., Schiefer J. et al. Impact of multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors. Neuroendocrinology 2010; 91: 101–109.

120. Cadiot G., Lebtahi R., Sarda L. et al. Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Gastroenterology 1996; 111: 845–854.

121. Dromain C., De Baere T., Lumbroso J. et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J. Clin. Oncol. 2005; 23: 70–78.

122. Gibril F., Doppman J.L., Reynolds J.C. et al. Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and MRI in their detection, their frequency, location and effect of their detection on management. J. Clin. Oncol. 1998; 16: 1040–1053.

123. Lebtahi R., Cadiot G., Delahaye N. et al. Detection of bone metastases in patients with endocrine gastroenteropancreatic tumors: bone scintigraphy compared with somatostatin receptor scintigraphy. J. Nucl. Med. 1999; 40: 1602–1608.

124. Bhate K., Mok W.Y., Tran K. et al. Functional assessment in the multimodality imaging of pancreatic neuroendocrine tumours. Minerva Endocrinol. 2010;35: 17–25.

125. Thomas Marques L., Murat A., Delemer B. et al. Prospe ctive endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am. J. Gastroenterol. 2006; 101: 266–273.

126. Triponez F., Goudet P., Dosseh D. et al. Is surgery beneficial for MEN1 patients with small (! or = 2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. Wld J. Surg. 2006; 30: 654–662.

127. Figueiredo F.A., Giovannini M., Monges G. et al. Pancreatic endocrine tumors: a large single-center experience. Pancreas 2009; 38: 936–940.

128. Christ E., Wild D., Forrer F. et al. Glucagon-like peptide-1 receptor imaging for localization of insulinomas. J. Clin. Endocrinol. Metab. 2009; 94: 4398–4405.

129. Kauhanen S., Seppanen M., Minn H. et al. Clinical PET imaging of insulinoma and β-cell hyperplasia. Curr. Pharm. Des. 2010; 16: 1550–1560.

130. Chetty R. An overview of practical issues in the diagnosis of gastroenteropancreatic neuroendocrine pathology. Arch. Pathol. Lab. Med. 2008; 132: 1285–1289.

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

132. Kloppel G., Couvelard A., Perren A. et al. ENETS guidelines for the standards of care in patients with neuroendocrine tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology 2009; 90:166.

133. Capelli P., Martignoni G., Pedica F. et al. Endocrine neoplasms of the pancreas: pathologic and genetic features. Arch. Pathol. Lab. Med. 2009; 133: 350–364.

134. Schmitt A.M., Anlauf M., Rousson V. et al. WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors. Am. J. Surg. Pathol. 2007; 31: 1677–1682.

135. 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: 824–833.

136. La Rosa S., Klersy C., Uccella S. et al. Improved histologic and clinicopathologic criteria for prognostic evaluation of pancreatic endocrine tumors. Hum. Pathol. 2009; 40: 30–40.

137. Casadei R., Ricci C., Pezzilli R. et al. Value of both WHO and TNM classification systems for patients with pancreatic endocrine tumors: results of a single-center series. Wld J. Surg. 2009; 33: 2458–2463.

138. Klimstra D.S., Modlin I.R., Adsay N.V. 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: 300–313.

139. Walker F.M., Lehy T., Bernuau D.G. et al. Detection of gastrin mRNA in human antral mucosa and digestive endocrine tumors by in situ hybridization: a correlative study with immunocytochemistry and electron microscopy. J. Histochem. Cytochem. 1992; 40: 1363–1372.

140. Toumpanakis C.G., Caplin M.E. Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Am. J. Gastroenterol. 2008; 103: 729–732.

141. Anlauf M., Bauersfeld J., Raffel A. et al. Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am. J. Surg. Pathol. 2009; 33: 339–346.

142. Henopp T., Anlauf M., Schmitt A. et al. Glucagon cell adenomatosis: a newly recognized disease of the endocrine pancreas. J. Clin. Endocrinol. Metab. 2009; 94: 213–217.

143. Fendrich V., Waldmann J., Bartsch D.K. et al. Surgical management of pancreatic endocrine tumors. Nat. Rev. Clin. Oncol. 2009; 6: 419–428.

144. Zerbi A., Capitanio V., Boninsegna L. et al. Surgical treatment of pancreatic endocrine tumours in Italy: results of a prospective multicentre study of 262 cases. Langenbecks Arch. Surg. 2011; 396: 313–321.

145. Abood G.J., Go A., Malhotra D. et al. The surgical and systemic management of neuroendocrine tumors of the pancreas. Surg. Clin. North. Am. 2009; 89: 249–266.

146. Lorenz K., Dralle H. Surgical treatment of sporadic gastrinoma. Wien. Klin. Wschr. 2007; 119: 597–601.

147. Bartsch D.K., Langer P., Rothmund M. Surgical aspects of gastrinoma in multiple endocrine neoplasia type 1. Wien. Klin. Wschr. 2007; 119: 602–608.

148. Norton J.A., Fraker D.L., Alexander H.R. et al. Surgery to cure the Zollinger-Ellison syndrome. N. Engl. J. Med. 1999; 341: 635–644.

149. Tonelli F., Fratini G., Nesi G. et al. Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias. Ann. Surg. 2006; 244: 61–70.

150. Norton J.A., Alexander H.R., Fraker D.L. 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. 2001; 234: 495–506.

151. Franz R.C., Penzhorn H.O. Is total gastrectomy still a viable option in the management of patients with the ZollingerEllison syndrome? S. Afr. J. Surg. 2007; 45: 58–60.

152. Fishbeyn V.A., Norton J.A., Benya R.V. et al. Assessment and prediction of long-term cure in patients with ZollingerEllison syndrome: the best approach. Ann. Intern. Med. 1993; 119: 199–206.

153. 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.

154. Sugg S.L., Norton J.A., Fraker D.L. et al. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann. Surg. 1993; 218: 138–144.

155. Grobmyer S.R., Vogel S.B., McGuigan J.E. et al. Reoperative surgery in sporadic ZollingerEllison Syndrome: longterm results. J. Am. Coll. Surg. 2009; 208: 718–722.

156. Norton J.A., Alexander H.A., Fraker D.L. et al. Possible primary lymph node gastrinomas: occurrence, natural history and predictive factors: a prospective study. Ann. Surg. 2003; 237: 650–659.

157. Norton J.A., Jensen R.T. Role of surgery in Zollinger-Ellison syndrome. J. Am. Coll. Surg. 2007; 205: S34–S37.

158. Fendrich V., Langer P., Waldmann J. et al. Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas. Br. J. Surg. 2007; 94: 1331–1341.

159. Fernandez Cruz L., Blanco L., Cosa R. et al. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? Wld J. Surg. 2008; 32: 904–917.

160. Espana Gomez M.N., Velazquez Fernandez D., Bezaury P. et al. Pancreatic insulinoma: a surgical experience. Wld J. Surg. 2009; 33: 1966–1970.

161. Richards M.L., Thompson G.B., Farley D.R. et al. Setting the bar for laparoscopic resection of sporadic insulinoma. Wld J. Surg. 2011; 35: 785–789.

162. Isla A., Arbuckle J.D., Kekis P.B. et al. Laparoscopic management of insulinomas. Br. J. Surg. 2009; 96: 185–190.

163. Krudy A.G., Doppman J.L., Jensen R.T. et al. Localization of islet cell tumors by dynamic CT: comparison with plain CT, arteriography, sonography and venous sampling. Am. J. Roentgenol. 1984; 143: 585–589.

164. Gimm O., Konig E., Thanh P.N. et al. Intraoperative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injection. Langenbecks Arch. Surg. 2007; 392: 679–684.

165. Elias D., Goere D., Leroux G. et al. Combined liver surgery and RFA for patients with gastroenteropancreatic endocrine tumors presenting with more than 15 metastases to the liver. Eur. J. Surg. Oncol. 2009; 35: 1092–1097.

166. Fendrich V., Michl P., Habbe N. et al. Liverspecific therapies for metastases of neuroendocrine pancreatic tumors. Wld J. Hepatol. 2010; 2: 367–373.

167. Kianmanesh R., Sauvanet A., Hentic O. et al. Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors: a safe approach for radical resection. Ann. Surg. 2008; 247: 659–665.

168. Hodul P., Malafa M., Choi J. et al. The role of cytoreductive hepatic surgery as an adjunct to the management of metastatic neuroendocrine carcinomas. Cancer Control 2006; 13: 61–71.

169. Desai K.K., Khan M.S., Toumpanakis C. et al. Management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Minerva Gastroenterol. Dietol. 2009; 55: 425–443.

170. Reddy S.K., Clary B.M. Neuroendocrine liver metastases. Surg. Clin. N. Am. 2010; 90: 853–861.

171. Akyildiz H.Y., Mitchell J., Milas M. et al. Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery 2010; 148: 1288–1293.

172. Modlin I.M., Pavel M., Kidd M. et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol. Ther. 2010; 31: 169–188.

173. Nieto J.M., Pisegna J.R. The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome. Expert. Opin. Pharmacother. 2006; 7: 169–175.

174. Auernhammer C.J., Goke B. Medical treatment of gastrinomas. Wien. Klin. Wschr. 2007; 119: 609–615.

175. Baldwin C.M., Keam S.J. Rabeprazole: a review of its use in the management of gastric acid-related diseases in adults. Drugs 2009; 69: 1373–1401.

176. Wilcox C.M., Hirschowitz B.I. Treatment strategies for Zollinger–Ellison syndrome. Expert Opin. Pharmacother. 2009; 10: 1145–1157.

177. Metz D.C., Sostek M.B., Ruszniewski P. et al. Effects of esomeprazole on acid output in patients with Zollinger– Ellison syndrome or idiopathic gastric acid hypersecretion. Am. J. Gastroenterol. 2007; 102: 2648–2654.

178. Morocutti A., Merrouche M., Bjaaland T. et al. An openlabel study of rabeprazole in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion. Aliment Pharmacol. Ther. 2006; 24: 1439–1444.

179. Metz D.C., Comer G.M., Soffer E. et al. Threeyear oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions. Aliment Pharmacol. Ther. 2006; 23: 437–444.

180. Yang Y.X., Metz D.C. Safety of proton pump inhibitor exposure. Gastroenterology 2010; 139: 1115–1127.

181. Ito T., Jensen R.T. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr. Gastroenterol. Rep. 2010; 12: 448–457.

182. Termanini B., Gibril F., Sutliff V.E. III et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am. J. Med. 1998; 104: 422–430.

183. Ojeaburu J.V., Ito T., Crafa P. et al. Mechanism of acid hypersecretion post-curative gastrinoma resection. Dig. Dis. Sci. 2011; 56: 139–154.

184. Pisegna J.R., Norton J.A., Slimak G.G. et al. Effects of curative resection on gastric secretory function and antisecretory drug requirement in the Zollinger-Ellison syndrome. Gastroenterology 1992; 102: 767–778.

185. Maton P.N., Frucht H., Vinayek R. et al. Medical management of patients with Zollinger–Ellison syndrome who have had previous gastric surgery: a prospective study. Gastroenterology 1988; 94: 294–299.

186. Vezzosi D., Bennet A., Rochaix P. et al. Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies. Eur. J. Endocrinol. 2005; 152: 757–767.

187. Kulke M.H., Bergsland E.K., Yao J.C. Glycemic control in patients with insulinoma treated with everolimus. N. Engl. J. Med. 2009; 360: 195–197.

188. Bourcier M.E., Sherrod A., DiGuardo M. et al. Successful control of intractable hypoglycemia using rapamycin in an 86-yearold man with a pancreatic insulin-secreting islet cell tumor and metastases. J. Clin. Endocrinol. Metab. 2009; 94: 3157–3162.

189. Ong G.S., Henley D.E., Hurley D. et al. Therapies for the medical management of persistent hypoglycaemia in two cases of inoperable malignant insulinoma. Eur. J. Endocrinol. 2010; 162: 1001–1008.

190. Oberg K., Kvols L., Caplin M. et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann. Oncol. 2004; 15: 966–973.

191. Fazio N., de Braud F., Delle Fave G. et al. Interferon-a and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination? Ann. Oncol. 2007; 18: 13–19.

192. Petrossians P., Thonnard A.S., Beckers A. Medical treatment in Cushing’s syndrome: dopamine agonists and cabergoline. Neuroendocrinology 2010; 92 (suppl 1): 116–119.

193. Castinetti F., Conte Devolx B., Brue T. Medical treatment of Cushing’s syndrome: glucocorticoid receptor antagonists and mifepristone. Neuroendocrinology 2010; 92 (suppl 1): 125–130.

194. Pivonello R., Ferone D., Lamberts S.W. et al. Cabergoline plus lanreotide for ectopic Cushing’s syndrome. N. Engl. J. Med. 2005; 352: 2457–2458.

195. Feelders R.A., Hofland L.J., de Herder W.W. Medical treatment of Cushing’s syndrome: adrenal-blocking drugs and ketaconazole. Neuroendocrinology 2010; 92 (suppl 1): 111– 115.

196. Pavel M., Baudin E., Couvelard A. et al. ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2012; 95, 157–176.

197. Arnold R., Rinke A., Klose K.J. et al. Octreotide versus octreotide plus interferon in endocrine gastroenteropancreatic tumors: a randomized trial. Clin. Gastroenterol. Hepatol. 2005; 3: 761–771.

198. Faiss S., Pape U.F., Bohmig M. et al. International Lanreotide and Interferon Alfa Study Group: prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors – the International Lanreotide and Interferon Alfa Study Group. J. Clin. Oncol. 2003; 21: 2689–2696.

199. Butturini G., Bettini R., Missiaglia E. et al. Predictive factors of efficacy of the somatostatin analogue octreotide as firstline therapy for advanced pancreatic endocrine carcinoma. Endocr. Relat. Cancer 2006; 13: 1213–1221.

200. Delaunoit T., Ducreux M., Boige V. et al. The doxorubicinstreptozotocin combination for the treatment of advanced well-differentiated pancreatic endocrine carcinoma; a judicious option? Eur. J. Cancer 2004; 40: 515–520.

201. Fjallskog M.L., Janson E.T., Falkmer U.G. et al. Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors. Neuroendocrinology 2008; 88: 53–58.

202. Kouvaraki M.A., Ajani J.A., 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: 4762–4771.

203. Moertel C.G., Lef kopoulo M., Lipsitz S. et al. Streptozocindoxorubicin, streptozocin-f luorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N. Engl. J. Med. 1992; 326: 519–523.

204. Walter T., Bruneton D., Cassier P.A. et al. Evaluation of the combination 5-f luorouracil, dacarbazine, and epirubicin in patients with advanced well-differentiated neuroendocrine tumors. Clin. Colorectal. Cancer 2010; 9: 248–254.

205. Strosberg J.R., Fine R.L., Choi J. et al. Firstline chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011; 117: 268–275.

206. Auernhammer C.J., Goke B. Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum/ileum and pancreatic origin. Gut 2011; 60: 1009–1021.

207. Vogl T.J., Naguib N.N., Zangos S. et al. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur. J. Radiol. 2009; 72: 517–528.

208. Nazario J., Gupta S. Transarterial liver-directed therapies of neuroendocrine hepatic metastases. Semin. Oncol. 2010; 37: 118–126.

209. Kwekkeboom D.J., de Herder W.W., van Eijck C.H. et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin. Nucl. Med. 2010; 40: 78–88.

210. Kwekkeboom D.J., de Herder W.W., Kam B.L. et al. Treatment with the radiolabeled somatostatin analog [177LuDOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. J. Clin. Oncol. 2008; 26: 2124–2130.

211. Bushnell D.L. Jr, O’Dorisio T.M., O’Dorisio M.S. et al. 90Yedotreotide for metastatic carcinoid refractory to octreotide. J. Clin. Oncol. 2010; 28: 1652–1659.

212. Yao J.C., Shah M.H., Ito T. et al. Everolimus for advanced pancreatic neuroendocrine tumors. N. Engl. J. Med. 2011; 364: 514–523.

213. Plockinger U., Wiedenmann B. Management of metastatic endocrine tumours. Best Pract. Res. Clin. Gastroenterol. 2005; 19: 553–576.

214. Khasraw M., Gill A., Harrington T. et al. Management of advanced neuroendocrine tumors with hepatic metastasis. J. Clin. Gastroenterol. 2009; 43: 838–847.

215. Shah T., Caplin M. Biotherapy for metastatic endocrine tumours. Best. Pract. Res. Clin. Gastroenterol. 2005; 19: 617–636.

216. Teunissen J.J., Kwekkeboom D.J., de Jong M. et al. Peptide receptor radionuclide therapy. Best. Pract. Res. Clin. Gastroenterol. 2005; 19: 595–616.

217. Toumpanakis C., Meyer T., Caplin M.E. Cytotoxic treatment including embolization/ chemoembolization for neuroendocrine tumours. Best Pract. Res. Clin. Endocrinol. Metab. 2007; 21: 131–144.

218. Eriksson J., Stalberg P., Nilsson A. et al. Surgery and radiofrequency ablation for treatment of liver metastases from midgut and foregut carcinoids and endocrine pancreatic tumors. Wld J. Surg. 2008; 32: 930–938.

219. King J., Quinn R., Glenn D.M. et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 2008; 113: 921–929.

220. Oberg K.E., Reubi J.C., Kwekkeboom D.J. et al. Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology 2010; 139: 742–753, 753.e1.

221. Kwekkeboom D.J., Krenning E.P., 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: 220–226.

222. Arnold R., Chen Y.J., Costa F. et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: follow-up and documentation. Neuroendocrinology 2009; 90: 227–233.

223. Poitras P., Gingras M.H., Rehfeld J.F. The Zollinger-Ellison syndrome: dangers and consequences of interrupting antisecretory treatment. Clin. Gastroenterol. Hepatol. 2012; 10: 199–202.

224. Raymond E., Dahan L., Raoul J.L. et al. Sunitinib Malate for the treatment of pancreatic neuroendocrine tumors. N. Engl. J. Med. 2011; 364: 501–513.

225. Jensen R.T., Delle Fave G. Promising advances in the treatment of malignant pancreatic endocrine tumors. N. Engl. J. Med. 2011; 364: 564–565.