gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1130Research ArticleНАЦИОНАЛЬНАЯ ШКОЛА ГАСТРОЭНТЕРОЛОГОВ, ГЕПАТОЛОГОВNATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTSСиндром Золлингера–Эллисона: современные аспекты диагностики и леченияZollinger–Ellison syndrome: modern aspects of diagnostics and treatmentМаевИ. В.MayevI. V.

Маев Игорь Вениаминович — член-корреспондент РАМН, доктор медицинских наук, профессор, заведующий кафедрой пропедевтики внутренних болезней и гастроэнтерологии

Maev Igor V — corresponding member of the Russian Academy of Science, MD, PhD, professor head of the Chair of internal diseases propedeutics and gastroenterology

proped@mail.ruАндреевД. Н.AndreevD. N.

Андреев Дмитрий Николаевич — аспирант кафедры пропедевтики внутренних болезней и гастроэнтерологии

Москва, ул. Делегатская, д. 20, стр.1

Andreev Dmitry N — assistant lecturer, Chair of internal diseases propedeutics and gastroenterology 

Moscow, street Delegatskaya, д. 20, bld. 1

dna-mit8@mail.ruКучерявыйЮ. А.KucheryavyyYu. A.

Кучерявый Юрий Александрович — кандидат медицинских наук, доцент кафедры пропедевтики внутренних болезней и гастроэнтерологии

ДичеваД. Т.DichevaD. T.

Дичева Диана Тодоровна — кандидат медицинских наук, доцент кафедры пропедевтики внутренних болезней и гастроэнтерологии 

di.di4eva@yandex.ruГБОУ  ВПО  «Московский   государственный  медико-стоматологический  университет  им.  А. И.  Евдокимова»  Минздрава  РоссииРоссияState educational government-financed institution of higher professional education «Yevdokimov Moscow State University of Medicine and Dentistry» Ministry of Healthcare of the Russian FederationRussian Federation2014190420242445769Copyright © Маев И.В., Андреев Д.Н., Кучерявый Ю.А., Дичева Д.Т., 20142014Маев И.В., Андреев Д.Н., Кучерявый Ю.А., Дичева Д.Т.Mayev I.V., Andreev D.N., Kucheryavyy Y.A., Dicheva D.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/1130Цель обзора

Цель обзора. Отразить современные представления о клинике, диагностике и лечении синдрома Золлингера–Эллисона (СЗЭ).

Основные положения

Основные положения. СЗЭ относится к редким заболеваниям, сопряженным с состоянием внутрижелудочной гиперацидности. Явление гиперацидности в рамках СЗЭ обусловлено гипергастринемией, ассоциированной с эктопической продукцией гастрина гастрин-продуцирующей опухолью — гастриномой. Заболевание нередко развивается у пациентов с синдромом множественной эндокринной неоплазии 1-го типа. Клиническая картина СЗЭ представляет прямое отражение гиперсекреции соляной кислоты с формированием эрозивноязвенных поражений пищевода, желудка и двенадцатиперстной кишки, резистентных к терапии стандартными дозами ингибиторов протонной помпы (ИПП). Одними из базисных методов диагностики СЗЭ являются определение уровня сывороточного гастрина и изучение состояния внутрижелудочного кислотообразования. Консервативная терапия включает назначение высоких доз ИПП, а также аналогов октреотида.

Заключение

Заключение. Несмотря на то, что СЗЭ не относится к широко распространенным заболеваниям, знание о клиническом течении этой патологии важно для ее своевременного распознавания. Необходимо включение СЗЭ в круг дифференциальной диагностики у пациентов с часто рецидивирующими и резистентными к терапии стандартными дозами ИПП эрозивно-язвенными поражениями верхних отделов желудочно-кишечного тракта.

The aim of review

The aim of review. To reflect modern concepts on clinic, diagnostics and treatment of Zollinger–Ellison syndrome (ZES).

Key points

Key points. ZES is rare disease related to intragastric hyperacidity. Phenomenon of hyperacidity in ZES patients is caused by hypergastrinemia associated with ectopic gastrin production. Disease frequently develops in patients with multiple endocrine neoplasia syndrome of the 1-st type. Clinical presentation of ZES directly reflects hypersecretion of hydrochloric acid with development of erosive — ulcerative lesions of esophagus, stomach and duodenum, resistant to standard dozes of proton pump inhibitors (PPI). One of basic methods of ZES diagnostics is assessment of serum gastrin level and intragastric acid production. Conservative treatment includes prescription of high PPI dozes, and octreotide analogues.

Conclusion

Conclusion. ZES is not a common disease, anyhow knowledge of its clinical course is important for duly recognition. ZES should be considered at differential diagnostics in patients with frequently relapsing upper gastro-intestinal erosive-ulcerative lesions and in patients resistant to standard dozes of PPI.

синдром Золлингера–Эллисонагастриноманейроэндокринная опухольгипергастринемиягастрингиперацидностьZollinger–Ellison syndromegastrinomaneuroendocrine tumorhypergastrinemiagastrinhyperacidityReferencesГастроэнтерология: Национальное руководство / Под. ред. В.Т. Ивашкина, Т.Л. Лапиной. М.: ГЭОТАРМедиа; 2008. 706 с.Гастроэнтерология: Национальное руководство / Под. ред. В.Т. Ивашкина, Т.Л. Лапиной. М.: ГЭОТАРМедиа; 2008. 706 с.Гуревич Л.Е. Диагностика нейроэндокринных опухолей желудочно-кишечного тракта. Практическая онкология 2005; 4:193-201.Гуревич Л.Е. Диагностика нейроэндокринных опухолей желудочно-кишечного тракта. Практическая онкология 2005; 4:193-201.Калинин А.В. Нейроэндокринные опухоли поджелудочной железы и желудочно-кишечного тракта. Клин перспективы гастроэнтерол гепатол 2010; 4:3-11.Калинин А.В. Нейроэндокринные опухоли поджелудочной железы и желудочно-кишечного тракта. Клин перспективы гастроэнтерол гепатол 2010; 4:3-11.Маев И.В., Кучерявый Ю.А., Андреев Д.Н., Дичева Д.Т. Нейроэндокринные опухоли поджелудочной железы: молекулярные механизмы онкогенеза и таргетной терапии. Мол мед 2013; 5:20-27.Маев И.В., Кучерявый Ю.А., Андреев Д.Н., Дичева Д.Т. Нейроэндокринные опухоли поджелудочной железы: молекулярные механизмы онкогенеза и таргетной терапии. Мол мед 2013; 5:20-27.Маев И.В., Кучерявый Ю.А. Болезни поджелудочной железы: В 2 т. М.: Медицина, изд-во «Шико»; 2008. 976 с.Маев И.В., Кучерявый Ю.А. Болезни поджелудочной железы: В 2 т. М.: Медицина, изд-во «Шико»; 2008. 976 с.Эндокринология: Национальное руководство. Краткое издание / Под ред. И.И. Дедова, Г.А. Мельниченко. М.: ГЭОТАР-Медиа; 2011. 752 с.Эндокринология: Национальное руководство. Краткое издание / Под ред. И.И. Дедова, Г.А. Мельниченко. М.: ГЭОТАР-Медиа; 2011. 752 с.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; 95:2271-7.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; 95:2271-7.Ardill J.E., Erikkson B. The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocr Relat Cancer 2003; 10(4):459-62.Ardill J.E., Erikkson B. The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocr Relat Cancer 2003; 10(4):459-62.Arnold R., Trautmann M.E., Creutzfeldt W., et al. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut 1996; 38:430-8.Arnold R., Trautmann M.E., Creutzfeldt W., et al. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut 1996; 38:430-8.Arnold R. Diagnosis and differential diagnosis of hypergastrinemia. Wien Klin Wochenschr 2007; 119:564-9.Arnold R. Diagnosis and differential diagnosis of hypergastrinemia. Wien Klin Wochenschr 2007; 119:564-9.Assalia A., Gagner M. Laparoscopic pancreatic surgery for islet cell tumors of the pancreas. World J Surg 2004; 28:1239-47.Assalia A., Gagner M. Laparoscopic pancreatic surgery for islet cell tumors of the pancreas. World J Surg 2004; 28:1239-47.Banasch M., Schmitz F. Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. Wien Klin Wochenschr 2007; 119:573-8.Banasch M., Schmitz F. Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. Wien Klin Wochenschr 2007; 119:573-8.Benya R.V., Metz D.C., Venzon D.J., et al. ZollingerEllison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia-type I. Am J Med 1994; 97(5):436-44.Benya R.V., Metz D.C., Venzon D.J., et al. ZollingerEllison syndrome can be the initial endocrine manifestation in patients with multiple endocrine neoplasia-type I. Am J Med 1994; 97(5):436-44.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(6):331-64.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(6):331-64.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 2229 cases from the literature. Medicine (Baltimore) 2006; 85:295-330.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 2229 cases from the literature. Medicine (Baltimore) 2006; 85:295-330.Bou-Saif A., Lei J., McDonald T.J., et al. A new cause of Zollinger-Ellison syndrome: non-small cell lung cancer. Gastroenterology 2001; 120:1271-8.Bou-Saif A., Lei J., McDonald T.J., et al. A new cause of Zollinger-Ellison syndrome: non-small cell lung cancer. Gastroenterology 2001; 120:1271-8.Capurso G., Festa S., Valente R., et al. Molecular pathology and genetics of pancreatic endocrine tumours. J Mol Endocrinol 2012; 49(1):37-50.Capurso G., Festa S., Valente R., et al. Molecular pathology and genetics of pancreatic endocrine tumours. J Mol Endocrinol 2012; 49(1):37-50.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; 15:1555-61.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; 15:1555-61.Corleto V.D., Delle Fave G., Jensen R.T. Molecular insights into gastrointestinal neuroendocrine tumors: Importance and recent advances. Dig Liver Dis 2002; 34:668-80.Corleto V.D., Delle Fave G., Jensen R.T. Molecular insights into gastrointestinal neuroendocrine tumors: Importance and recent advances. Dig Liver Dis 2002; 34:668-80.Debray M.P., Geoffroy O., Laissy J.P., et al. Imaging appearances of metastases fromneuroendocrine tumours of the pancreas. Br J Radiol 2001; 74:1065-70.Debray M.P., Geoffroy O., Laissy J.P., et al. Imaging appearances of metastases fromneuroendocrine tumours of the pancreas. Br J Radiol 2001; 74:1065-70.Duerr E.M., Chung D.C. Molecular genetics of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab 2007; 21:1-14.Duerr E.M., Chung D.C. Molecular genetics of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab 2007; 21:1-14.Ellison E.C., Johnson J.A. The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr Probl Surg 2009; 46:13106.Ellison E.C., Johnson J.A. The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr Probl Surg 2009; 46:13106.Ellison E.H., Wilson S.D. The Zollinger-Ellison syndrome: Re-appraisal and evaluation of 260 registered cases. Ann Surg 1964; 160:512-30.Ellison E.H., Wilson S.D. The Zollinger-Ellison syndrome: Re-appraisal and evaluation of 260 registered cases. Ann Surg 1964; 160:512-30.Elvin A., Skogseid B., Hellman P. Radiofrequency ablation of neuroendocrine liver metastases. Abdom Imaging 2005; 30:427-34.Elvin A., Skogseid B., Hellman P. Radiofrequency ablation of neuroendocrine liver metastases. Abdom Imaging 2005; 30:427-34.Faiss S., Pape U.F., Bohmig M., et al. 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; 21:2689-96.Faiss S., Pape U.F., Bohmig M., et al. 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; 21:2689-96.Frank M., Klose K.J., Wied M., et al. Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 1999; 94(5):1381-1387.Frank M., Klose K.J., Wied M., et al. Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 1999; 94(5):1381-1387.Gabriel M., Decristoforo C., Kendler D., et al. 68Ga-DOTA-Tyr3-Octreotide PET in Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and CT. J Nucl Med 2007; 48:508-18.Gabriel M., Decristoforo C., Kendler D., et al. 68Ga-DOTA-Tyr3-Octreotide PET in Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and CT. J Nucl Med 2007; 48:508-18.Gibril F., Jensen R.T. Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumors. Dig Liver Dis 2004; 36:106-20.Gibril F., Jensen R.T. Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumors. Dig Liver Dis 2004; 36:106-20.Gibril F., Jensen R.T. Zollinger-Ellison syndrome revisited: Diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr Gastroenterol Rep 2004; 6:454-63.Gibril F., Jensen R.T. Zollinger-Ellison syndrome revisited: Diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr Gastroenterol Rep 2004; 6:454-63.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.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.Gibril F., Schumann M., Pace A., et al. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore) 2004; 83(1):43-83.Gibril F., Schumann M., Pace A., et al. Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore) 2004; 83(1):43-83.Gurevich L., Kazantseva I., Isakov V., et al. The analysis of immunophenotype of gastrin-producing tumors of pancreas and gastrointestinal tract. Cancer 2003; 98(9):1967-76.Gurevich L., Kazantseva I., Isakov V., et al. The analysis of immunophenotype of gastrin-producing tumors of pancreas and gastrointestinal tract. Cancer 2003; 98(9):1967-76.Hoffmann K.M., Furukawa M., Jensen R.T. Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005; 19:675-97.Hoffmann K.M., Furukawa M., Jensen R.T. Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment. Best Pract Res Clin Gastroenterol 2005; 19:675-97.Imam H., Gobl A., Eriksson B., Oberg K. Interferonalpha induces bcl-2 proto-oncogene in patients with neuroendocrine gut tumor responding to its antitumor action. Anticancer Res 1997; 17:4659-66.Imam H., Gobl A., Eriksson B., Oberg K. Interferonalpha induces bcl-2 proto-oncogene in patients with neuroendocrine gut tumor responding to its antitumor action. Anticancer Res 1997; 17:4659-66.Ito T., Cadiot G., Jensen R.T. Diagnosis of ZollingerEllison syndrome: increasingly difficult. World J Gastroenterol 2012; 18(39):5495-503.Ito T., Cadiot G., Jensen R.T. Diagnosis of ZollingerEllison syndrome: increasingly difficult. World J Gastroenterol 2012; 18(39):5495-503.Ito T., Igarashi H., Uehara H., et al. Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother 2013; 14(3):307-21.Ito T., Igarashi H., Uehara H., et al. Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother 2013; 14(3):307-21.Jensen R.T., Berna M.J., Bingham M.D., Norton J.A. Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management and controversies. Cancer 2008; 113(suppl):1087-43.Jensen R.T., Berna M.J., Bingham M.D., Norton J.A. Inherited pancreatic endocrine tumor syndromes: Advances in molecular pathogenesis, diagnosis, management and controversies. Cancer 2008; 113(suppl):1087-43.Jensen R.T., Niederle B., Mitry E., et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology 2006; 84:173-82.Jensen R.T., Niederle B., Mitry E., et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology 2006; 84:173-82.Jensen R.T., Norton J.A. Endocrine tumors of the pancreas and gastrointestinal tract. In: Feldman M., Friedman L.S., Brandt L.J., eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia, Pa: Saunders Elsevier 2010: chap 32.Jensen R.T., Norton J.A. Endocrine tumors of the pancreas and gastrointestinal tract. In: Feldman M., Friedman L.S., Brandt L.J., eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia, Pa: Saunders Elsevier 2010: chap 32.Jensen R.T. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med 1998; 243:477-88.Jensen R.T. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med 1998; 243:477-88.Jensen R.T. Zollinger-Ellison syndrome. In: Doherty G.M., Skogseid B., eds. Surgical Endocrinology: Clinical Syndromes. Philadelphia: Lippincott Williams & Wilkins 2001:291-344.Jensen R.T. Zollinger-Ellison syndrome. In: Doherty G.M., Skogseid B., eds. Surgical Endocrinology: Clinical Syndromes. Philadelphia: Lippincott Williams & Wilkins 2001:291-344.Kann P.H. The value of endoscopic ultrasound in localizing gastrinoma. Wien Klin Wochenschr 2007; 119(19-20):585-7.Kann P.H. The value of endoscopic ultrasound in localizing gastrinoma. Wien Klin Wochenschr 2007; 119(19-20):585-7.Kulke M.H., Lenz H.J., Meropol N.J., et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008; 26:3403-10.Kulke M.H., Lenz H.J., Meropol N.J., et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008; 26:3403-10.Kwekkeboom D.J., de Herder W.W., Kam B.L., et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26(13):2124-30.Kwekkeboom D.J., de Herder W.W., Kam B.L., et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26(13):2124-30.Lehy T., Cadiot G., Mignon M., et al. Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome. Gut 1992; 33:1275-9.Lehy T., Cadiot G., Mignon M., et al. Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in patients with the Zollinger-Ellison syndrome. Gut 1992; 33:1275-9.Leimer M., Kurtaran A., Smith-Jones P., et al. Response to treatment with yttrium 90-DOTA-lanreotide of a patient with metastatic gastrinoma. J Nucl Med 1998; 39:2090-4.Leimer M., Kurtaran A., Smith-Jones P., et al. Response to treatment with yttrium 90-DOTA-lanreotide of a patient with metastatic gastrinoma. J Nucl Med 1998; 39:2090-4.Long S.H., Berna M.J., Thill M., et al. Secretin receptor and secretin-receptor-variant expression in gastrinomas: Correlation with clinical and tumoral features and secretin and calcium provocative test results. J Clin Endocrinol Metab 2007; 92:4394-402.Long S.H., Berna M.J., Thill M., et al. Secretin receptor and secretin-receptor-variant expression in gastrinomas: Correlation with clinical and tumoral features and secretin and calcium provocative test results. J Clin Endocrinol Metab 2007; 92:4394-402.Lorenz K., Dralle H. Surgical treatment of sporadic gastrinoma. Wien Klin. Wochenschr 2007; 119:597-601.Lorenz K., Dralle H. Surgical treatment of sporadic gastrinoma. Wien Klin. Wochenschr 2007; 119:597-601.Maton P.N., Miller D.L., Doppman J.L., et al. Role of selective angiography in the management of patients with Zollinger-Ellison syndrome. Gastroenterology 1987; 92:913-8.Maton P.N., Miller D.L., Doppman J.L., et al. Role of selective angiography in the management of patients with Zollinger-Ellison syndrome. Gastroenterology 1987; 92:913-8.Mazzaglia P.J., Berber E., Milas M., et al. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: A 10-year experience evaluating predictors of survival. Surgery 2007; 142:10-9.Mazzaglia P.J., Berber E., Milas M., et al. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: A 10-year experience evaluating predictors of survival. Surgery 2007; 142:10-9.McLean A.M., Fairclough P.D. Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. Best Pract Res Clin Endocrinol Metab 2005; 19:177-93.McLean A.M., Fairclough P.D. Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. Best Pract Res Clin Endocrinol Metab 2005; 19:177-93.Metz D.C., Jensen R.T. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. GastroenterologyMetz D.C., Jensen R.T. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology; 135(5):1469-92.; 135(5):1469-92.Metz D.C., Strader D.B., Orbuch M., et al. Use of omeprazole in Zollinger-Ellison: A prospective nine-year study of efficacy and safety. Aliment Pharmacol Ther 1993; 7:597-610.Metz D.C., Strader D.B., Orbuch M., et al. Use of omeprazole in Zollinger-Ellison: A prospective nine-year study of efficacy and safety. Aliment Pharmacol Ther 1993; 7:597-610.Miller L.S., Vinayek R., Frucht H., et al. Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology 1990; 98:341-6.Miller L.S., Vinayek R., Frucht H., et al. Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology 1990; 98:341-6.Moertel C.G., Lefkopoulo M., Lipsitz S., et al. Streptozotocin-doxorubicin, streptozotocin-flourouracil or chlorozotocin in the treatment of advanced islet cell carcinoma. N Engl J Med 1992; 326:519-23.Moertel C.G., Lefkopoulo M., Lipsitz S., et al. Streptozotocin-doxorubicin, streptozotocin-flourouracil or chlorozotocin in the treatment of advanced islet cell carcinoma. N Engl J Med 1992; 326:519-23.Murugesan S.V., Varro A., Pritchard D.M. Review article: Strategies to determine whether hypergastrinaemia is due to Zollinger-Ellison syndrome rather than a more common benign cause. Aliment Pharmacol Ther 2009; 29(10):1055-68.Murugesan S.V., Varro A., Pritchard D.M. Review article: Strategies to determine whether hypergastrinaemia is due to Zollinger-Ellison syndrome rather than a more common benign cause. Aliment Pharmacol Ther 2009; 29(10):1055-68.Nieto J.M., Pisegna J.R. The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome. Expert Opin Pharmacother 2006; 7(2):169-75.Nieto J.M., Pisegna J.R. The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome. Expert Opin Pharmacother 2006; 7(2):169-75.Noda S., Norton J.A., Jensen R.T., Gay W.A. Jr. Surgical resection of intracardiac gastrinoma. Ann Thorac Surg 1999; 67:532-3.Noda S., Norton J.A., Jensen R.T., Gay W.A. Jr. Surgical resection of intracardiac gastrinoma. Ann Thorac Surg 1999; 67:532-3.Norton J.A., Alexander H.R., Fraker D.L., et al. Comparison of surgical results in patients with advanced ad limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg 2001; 234(4):495-505.Norton J.A., Alexander H.R., Fraker D.L., et al. Comparison of surgical results in patients with advanced ad limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg 2001; 234(4):495-505.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 (ZES)? Ann Surg 2004; 239:617-26.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 (ZES)? Ann Surg 2004; 239:617-26.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; 102:958-66.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; 102:958-66.Norton J.A., Fraker D.L., Alexander H.R., et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244:410-9.Norton J.A., Fraker D.L., Alexander H.R., et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244:410-9.Norton J.A., Fraker D.L., Alexander H.R., et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341:635-44.Norton J.A., Fraker D.L., Alexander H.R., et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341:635-44.Norton J.A., Jensen R.T. Role of surgery in ZollingerEllison syndrome. J Am Coll Surg 2007; 205:34–7.Norton J.A., Jensen R.T. Role of surgery in ZollingerEllison syndrome. J Am Coll Surg 2007; 205:34–7.Norton J.A., Venzon D.J., Berna M.J., et al. Prospective study of surgery for primary hyperaparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1), and Zollinger-Ellison syndrome (ZES): Long-term outcome of a more virulent form of HPT. Ann Surgery 2008; 247(3):501-10.Norton J.A., Venzon D.J., Berna M.J., et al. Prospective study of surgery for primary hyperaparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1), and Zollinger-Ellison syndrome (ZES): Long-term outcome of a more virulent form of HPT. Ann Surgery 2008; 247(3):501-10.O’Toole D., Hentic O., Corcos O., Ruszniewski P. Chemotherapy for gastro-enteropancreatic endocrine tumours. Neuroendocrinology 2004; 80(suppl 1):79-84.O’Toole D., Hentic O., Corcos O., Ruszniewski P. Chemotherapy for gastro-enteropancreatic endocrine tumours. Neuroendocrinology 2004; 80(suppl 1):79-84.Oberg K., Kvols L., Caplin M., et al. Consensus report on the use of somatostatin analogues for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004; 15:966-73.Oberg K., Kvols L., Caplin M., et al. Consensus report on the use of somatostatin analogues for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004; 15:966-73.Oberg K. Advances in chemotherapy and biotherapy of endocrine tumors. Curr Opin Oncol 1998; 10:58-65.Oberg K. Advances in chemotherapy and biotherapy of endocrine tumors. Curr Opin Oncol 1998; 10:58-65.Oberstein P.E., Remotti H., Saif M.W., et al. Pancreatic neuroendocrine tumors: entering a new era. JOP 2012; 13(2):169-73.Oberstein P.E., Remotti H., Saif M.W., et al. Pancreatic neuroendocrine tumors: entering a new era. JOP 2012; 13(2):169-73.Osefo N., Ito T., Jensen R.T. Gastric acid hypersecretory states: recent insights and advances. Curr Gastroenterol Rep 2009; 11(6):433-41.Osefo N., Ito T., Jensen R.T. Gastric acid hypersecretory states: recent insights and advances. Curr Gastroenterol Rep 2009; 11(6):433-41.Paganelli G., Zoboli S., Cremonesi M., et al. Receptormediated radiotherapy with 90Y-DOTAD-Phe1-Tyr3octreotide. Eur J Nucl Med 2001; 28:426-34.Paganelli G., Zoboli S., Cremonesi M., et al. Receptormediated radiotherapy with 90Y-DOTAD-Phe1-Tyr3octreotide. Eur J Nucl Med 2001; 28:426-34.Panzuto F., Di Francesco V., Iannicelli E., et al. Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol 2006; 17:461-6.Panzuto F., Di Francesco V., Iannicelli E., et al. Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol 2006; 17:461-6.Peghini P.L., Annibale B., Azzoni C., et al. Effect of chronic hypergastrinemia on human enterochromaffin-like cells: Insights from patients with sporadic gastrinomas. Gastroenterology 2002; 123:68-85.Peghini P.L., Annibale B., Azzoni C., et al. Effect of chronic hypergastrinemia on human enterochromaffin-like cells: Insights from patients with sporadic gastrinomas. Gastroenterology 2002; 123:68-85.Peng L., Schwarz R.E. Pancreatic neuroendocrine tumors: signal pathways and targeted therapies. Curr Mol Med 2013; 13(3):333-9.Peng L., Schwarz R.E. Pancreatic neuroendocrine tumors: signal pathways and targeted therapies. Curr Mol Med 2013; 13(3):333-9.Plockinger U., Wiedenmann B. Management of metastatic endocrine tumours. Best Pract Res Clin Gastroenterol 2005; 19:553-76.Plockinger U., Wiedenmann B. Management of metastatic endocrine tumours. Best Pract Res Clin Gastroenterol 2005; 19:553-76.Pritchard D.M. Zollinger-Ellison syndrome: still a diagnostic challenge in the 21st century? GastroenterologyPritchard D.M. Zollinger-Ellison syndrome: still a diagnostic challenge in the 21st century? Gastroenterology; 140(5):1380-3.; 140(5):1380-3.Rehfeld J.F., Friis-Hansen L., Goetze J.P., et al. The biology of cholecystokinin and gastrin peptides. Curr Top Med Chem 2007; 7(12):1154-65.Rehfeld J.F., Friis-Hansen L., Goetze J.P., et al. The biology of cholecystokinin and gastrin peptides. Curr Top Med Chem 2007; 7(12):1154-65.Rindi G., Bordi C. Endocrine tumours of the gastrointestinal tract: aetiology, molecular pathogenesis and genetics. Best Pract Res Clin Gastroenterol 2005;Rindi G., Bordi C. Endocrine tumours of the gastrointestinal tract: aetiology, molecular pathogenesis and genetics. Best Pract Res Clin Gastroenterol 2005;(4):519-34.(4):519-34.Roy P.K., 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 a review of 984 cases in the literature. Medicine (Baltimore) 2001; 80(3):189-222.Roy P.K., 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 a review of 984 cases in the literature. Medicine (Baltimore) 2001; 80(3):189-222.Roy P.K., Venzon D.J., Shojamanesh H., et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore) 2000; 79(6):379-411.Roy P.K., Venzon D.J., Shojamanesh H., et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore) 2000; 79(6):379-411.Ruszniewski P., Laucournet H., Elouaer-Blanc L., et al. Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for sustained efficacy. Pancreas 1988; 3:145-52.Ruszniewski P., Laucournet H., Elouaer-Blanc L., et al. Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for sustained efficacy. Pancreas 1988; 3:145-52.Sahani D.V., Bonaffini P.A., Fernández-Del Castillo C., et al. Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management. Radiology 2013; 266(1):38-61.Sahani D.V., Bonaffini P.A., Fernández-Del Castillo C., et al. Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management. Radiology 2013; 266(1):38-61.Shepherd J.J. The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg 1991; 126(8):935-52.Shepherd J.J. The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg 1991; 126(8):935-52.Shojamanesh H., Gibril F., Louie A., et al. Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma. Cancer 2002; 94:331-43.Shojamanesh H., Gibril F., Louie A., et al. Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma. Cancer 2002; 94:331-43.Soga J., Yakuwa Y. The gastrinoma/Zollinger-Ellison syndrome: statistical evaluation of a Japanese series of 359 cases. J Hepatobiliary Pancreat Surg 1998; 5:77-85.Soga J., Yakuwa Y. The gastrinoma/Zollinger-Ellison syndrome: statistical evaluation of a Japanese series of 359 cases. J Hepatobiliary Pancreat Surg 1998; 5:77-85.Stabile B.E., Morrow D.J., Passaro JrE. The gastrinoma triangle: operative implications. Am J Surg 1984; 147:2531.Stabile B.E., Morrow D.J., Passaro JrE. The gastrinoma triangle: operative implications. Am J Surg 1984; 147:2531.Strosberg J.R., Kvols L.K. A review of the current clinical trials for gastroenteropancreatic neuroendocrine tumours. Expert Opin Investig Drugs 2007; 16:219-24.Strosberg J.R., Kvols L.K. A review of the current clinical trials for gastroenteropancreatic neuroendocrine tumours. Expert Opin Investig Drugs 2007; 16:219-24.Sundin A., Garske U., Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007; 21:69-85.Sundin A., Garske U., Orlefors H. Nuclear imaging of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 2007; 21:69-85.Sutliff V.E., Doppman J.L., Gibril F., et al. Growth of newly diagnosed, untreated metastatic gastrinomas and predictors of growth patterns. J Clin Oncol 1997; 15:2420-31.Sutliff V.E., Doppman J.L., Gibril F., et al. Growth of newly diagnosed, untreated metastatic gastrinomas and predictors of growth patterns. J Clin Oncol 1997; 15:2420-31.Tan E.H., Tan C.H. Imaging of gastroenteropancreatic neuroendocrine tumors. World J Clin Oncol 2011;Tan E.H., Tan C.H. Imaging of gastroenteropancreatic neuroendocrine tumors. World J Clin Oncol 2011;(1):28-43.(1):28-43.Termanini B., Gibril F., Stewart C.A., et al. A prospective study of the effectiveness of low-dose omeprazole as initial therapy in Zollinger-Ellison syndrome. Aliment Pharmacol Ther 1996; 10:61-71.Termanini B., Gibril F., Stewart C.A., et al. A prospective study of the effectiveness of low-dose omeprazole as initial therapy in Zollinger-Ellison syndrome. Aliment Pharmacol Ther 1996; 10:61-71.Tomassetti P., Campana D., Piscitelli L., et al. Treatment of Zollinger-Ellison syndrome. World J Gastroenterol 2005; 11(35):5423-32.Tomassetti P., Campana D., Piscitelli L., et al. Treatment of Zollinger-Ellison syndrome. World J Gastroenterol 2005; 11(35):5423-32.Touzios J.G., Kiely J.M., Pitt S.C., et al. Neuroendocrine hepatic metastases: Does aggressive management improve survival? Ann Surg 2005; 241:776-83.Touzios J.G., Kiely J.M., Pitt S.C., et al. Neuroendocrine hepatic metastases: Does aggressive management improve survival? Ann Surg 2005; 241:776-83.Triponez F., Goudet P., Dosseh D., et al. Is surgery beneficial for MEN1 patients with small ≤2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 2006; 30:654-62.Triponez F., Goudet P., Dosseh D., et al. Is surgery beneficial for MEN1 patients with small ≤2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 2006; 30:654-62.Van Eijck C.H., Lamberts S.W., Lemaire L.C., et al. The use of somatostatin receptor scintigraphy in the differential diagnosis of pancreatic duct cancers and islet cell tumors. Ann Surg 1996; 224:119-24.Van Eijck C.H., Lamberts S.W., Lemaire L.C., et al. The use of somatostatin receptor scintigraphy in the differential diagnosis of pancreatic duct cancers and islet cell tumors. Ann Surg 1996; 224:119-24.Weber H.C., Venzon D.J., Jensen R.T., Metz D.C. Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter pylori and proton pump inhibitor therapy. Gastroenterology 1997; 112:84-91.Weber H.C., Venzon D.J., Jensen R.T., Metz D.C. Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter pylori and proton pump inhibitor therapy. Gastroenterology 1997; 112:84-91.Weber H.C., Venzon D.J., Lin J.T., et al. Determinants of metastatic rate and survival in patients with ZollingerEllison syndrome: A prospective long-term study. Gastroenterology 1995; 108:1637-49.Weber H.C., Venzon D.J., Lin J.T., et al. Determinants of metastatic rate and survival in patients with ZollingerEllison syndrome: A prospective long-term study. Gastroenterology 1995; 108:1637-49.Welage L.S., Berardi R.R. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc 2000; 40:52-62.Welage L.S., Berardi R.R. Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases. J Am Pharm Assoc 2000; 40:52-62.Wiedmann M.W., Mössner J. Safety and efficacy of sunitinib in patients with unresectable pancreatic neuroendocrine tumors. Clin Med Insights Oncol 2012; 6:381-93.Wiedmann M.W., Mössner J. Safety and efficacy of sunitinib in patients with unresectable pancreatic neuroendocrine tumors. Clin Med Insights Oncol 2012; 6:381-93.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; 17:615-30.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; 17:615-30.Zollinger R.M., Ellison E.H. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 1955; 142(4):709-23.Zollinger R.M., Ellison E.H. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 1955; 142(4):709-23.

The authors declare that there are no conflicts of interest present.