Advertisement

Endocrine

, Volume 60, Issue 1, pp 15–27 | Cite as

The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma?

  • Valentina Guarnotta
  • Chiara MartiniEmail author
  • Maria Vittoria Davì
  • Genoveffa Pizza
  • Annamaria Colao
  • Antongiulio Faggiano
  • on behalf of NIKE group
Review
  • 393 Downloads

Abstract

Purpose

Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy.

Methods

We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines.

Results

The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents.

Conclusions

The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.

Keywords

Somatostatin Somatostatin analogues Neuroendocrine tumours Gastrinoma 

Notes

Acknowledgements

This review is part of the ‘NIKE’ project (Neuroendocrine tumors Innovation Knowledge and Education) led by Prof Annamaria Colao, which aims at increasing the knowledge on NETs. We would like to acknowledge all the Collaborators of this project: Albertelli M., Amoroso V., Arvat E., Badalamenti G., Bajetta E., Baldelli R., Bianchi A., Botti G., Buzzoni R., Campana D., Carnaghi C., Cingarlini S., Circelli L., Corcione F., De Rosa G., degli Uberti E., Delle Fave G., Del Basso De Caro M.L., Di Sarno A., Falconi M., Fanciulli G., Ferolla P., Ferone D., Fiore F., Gallo M., Gaudenzi G., Giordano C., Giuffrida D., Grossrubatscher E., Guadagno E., Izzo F., Lania A., Lastoria S., Leo S., Lo Calzo F., Logoluso F., Malandrino P., Marchetti M., Marotta V., Mazzaferro V., Messina E., Milione M., Modica R., Montesarchio V., Muto P., Nappi O., Nazzari E., Panzuto F., Pia A., Piovesan A., Pontecorvi A., Pusceddu S., Razzore P., Riccardi F., Rindi G., Rota F., Scarpa A., Sciammarella C., Spada F., Tafuto S., Versari A., Vitale G., Volante M., Zatelli M.C.

Compliance with ethical standards

Conflict of interests

A.C and A.F report support to research from Novartis, Ipsen and Italfarmaco. The remaining authors declare that they have no competing interests.

References

  1. 1.
    R.M. Zollinger, E.H. Ellison, Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann. Surg. 142, 709–728 (1955)PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    J.E. McGuigan, M.M. Wolfe, Secretin injection test in the diagnosis of gastrinoma. Gastroenterology 79, 1324–1331 (1980)PubMedGoogle Scholar
  3. 3.
    E.C. Ellison, J.A. Johnson, The Zollinger-Ellison syndrome: a comprehensive review of historical, scientific, and clinical considerations. Curr. Probl. Surg. 46, 13–106 (2009)PubMedCrossRefGoogle Scholar
  4. 4.
    G.A. Kaltsas, G.M. Besser, A.B. Grossman, The diagnosis and medical management of advanced neuroendocrine tumors. Endocr. Rev. 25, 458–511 (2004)PubMedCrossRefGoogle Scholar
  5. 5.
    M.J. Berna, K.M. Hoffmann, J. Serrano, F. Gibril, R.T. Jensen, 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 85, 295–330 (2006)PubMedCrossRefGoogle Scholar
  6. 6.
    J.A. Norton, Neuroendocrine tumors of the pancreas and duodenum. Curr. Probl. Surg. 31, 77–156 (1994)PubMedCrossRefGoogle Scholar
  7. 7.
    T. Ito, H. Igarashi, R.T. Jensen, Zollinger-Ellison syndrome: recent advances and controversies. Curr. Opin. Gastroenterol. 29, 650–661 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    R.V. Thakker, P.J. Newey, G.V. Walls, J. Bilezikian, H. Dralle, P.R. Ebeling, S. Melmed, A. Sakurai, F. Tonelli, M.L. Brandi, Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metabol. 97, 2990–3011 (2012)CrossRefGoogle Scholar
  9. 9.
    F. Gibril, R.T. Jensen, Zollinger-Ellison syndrome revisited: diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Curr. Gastroenterol. Rep. 6, 454–463 (2004)PubMedCrossRefGoogle Scholar
  10. 10.
    M.V. Davì, L. Boninsegna, L. Dalle Carbonare, M. Toaiari, P. Capelli, A. Scarpa, G. Francia, M. Falconi, Presentation and outcome of pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1 syndrome. Neuroendocrinology 94, 58–65 (2011)PubMedCrossRefGoogle Scholar
  11. 11.
    J.A. Norton, D.J. Venzon, M.J. Berna, H.R. Alexander, D.L. Fraker, S.K. Libutti, S.J. Marx, F. Gibril, R.T. Jensen, Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPT. Ann. Surg. 247, 501–510 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    C. Donow, M. Pipeleers-Marichal, S. Schroder, B. Stamm, P.U. Heitz, G. Klöppel, Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer 68, 1329–1334 (1991)PubMedCrossRefGoogle Scholar
  13. 13.
    S. Wilkinson, B.T. Teh, K.R. Davey, J.P. McArdle, M. Young, J.J. Shepherd, Cause of death in multiple endocrine neoplasia type 1. Arch. Surg. 128, 683–690 (1993)PubMedCrossRefGoogle Scholar
  14. 14.
    K.M. Hoffmann, M. Furukawa, R.T. Jensen, Duodenal neuroendocrine tumors: classification, functional syndromes, diagnosis and medical treatment.Best Pract. Res. Clin. Gastroenterol. 19, 675–697 (2005)PubMedCrossRefGoogle Scholar
  15. 15.
    T. Ito, H. Igarashi, H. Uehara, M.J. Berna, R.T. Jensen, Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors. Medicine 92, 135–181 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    M.J. Berna, K.M. Hoffmann, S.H. Long, J. Serrano, F. Gibril, R.T. Jensen, 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 85, 331–364 (2006)PubMedCrossRefGoogle Scholar
  17. 17.
    P. Poitras, M.H. Gingras, J.F. Rehfeld, The Zollinger-Ellison syndrome: dangers and consequences of interrupting antisecretory treatment. Clin. Gastroenterol. Hepatol. 10, 199–202 (2012)PubMedCrossRefGoogle Scholar
  18. 18.
    M. Falconi, B. Eriksson, G. Kaltsas, D.K. Bartsch, J. Capdevila, M. Caplin, B. Kos-Kudla, D. Kwekkeboom, G. Rindi, G. Klöppel, N. Reed, R. Kianmanesh, R.T. Jensen, ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 103, 153–171 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    S.A. Deppen, E. Liu, J.D. Blume, J. Clanton, C. Shi, L.B. Jones-Jackson, V. Lakhani, R.P. Baum, J. Berlin, G.T. Smith, M. Graham, M.P. Sandler, D. Delbeke, R.C. Walker, Safety and efficacy of 68Ga-DOTATATE PET/CT for diagnosis, staging and treatment management of neuroendocrine tumors. J. Nucl. Med. 57, 708–714 (2016)PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    D.M. McCarthy, Report on the United States experience with cimetidine in Zollinger-Ellison syndrome and other hypersecretory states. Gastroenterology 74, 453–458 (1978)PubMedGoogle Scholar
  21. 21.
    D.C. Metz, D.B. Strader, M. Orbuch, P.D. Koviack, K.M. Feigenbaum, R.T. Jensen, Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety. Aliment. Pharmacol. Ther. 7, 597–610 (1993)PubMedCrossRefGoogle Scholar
  22. 22.
    P.S. Fox, J.W. Hofmann, J.J. Decosse, S.D. Wilson, The influence of total gastrectomy on survival in malignant Zollinger-Ellison tumors. Ann. Surg. 180, 558–566 (1974)PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    R.M. Zollinger, E.C. Ellison, P.J. Fabri, J. Johnson, J. Sparks, L.C. Carey, Primary peptic ulcerations of the jejunum associated with islet cell tumors. Twenty-five-year appraisal. Ann. Surg. 192, 422–430 (1980)PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    D.L. Fraker, J.A. Norton, Z.A. Saeed, P.N. Maton, J.D. Gardner, R.T. Jensen, A prospective study of perioperative and postoperative control of acid hypersecretion in patients with Zollinger-Ellison syndrome undergoing gastrinoma resection. Surgery 104, 1054–1063 (1988)PubMedGoogle Scholar
  25. 25.
    C.J. Auernhammer, B. Göke, Medical treatment of gastrinomas. Wien. Klin. Wochenschr. 119, 609–615 (2007)PubMedCrossRefGoogle Scholar
  26. 26.
    C.M. Wilcox, T. Seay, J.T. Arcury, J. Mohnen, B.I. Hirschowitz, Zollinger-Ellison syndrome: presentation, response to therapy, and outcome. Dig. Liver Dis. 43, 439–443 (2011)PubMedCrossRefGoogle Scholar
  27. 27.
    T. Ito, H. Igarashi, H. Uehara, R.T. Jensen, Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin. Pharmacother. 14, 307–321 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    M.F. Brennan, R.T. Jensen, R.A. Wesley, J.L. Doppman, D.M. McCarthy, The role of surgery in patients with Zollinger-Ellison syndrome managed medically. Ann. Surg. 196, 239–245 (1982)PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    E.C. Ellison, B.S. Sparks, Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors? Am. J. Surg. 186, 245–248 (2003)PubMedCrossRefGoogle Scholar
  30. 30.
    J.A. Norton, R.T. Jensen, Role of Surgery in Zollinger-Ellison Syndrome. J. Am. Coll. Surg. 205, 834–837 (2007)CrossRefGoogle Scholar
  31. 31.
    J.A. Norton, H.R. Alexander, D.L. Fraker, D.J. Venzon, F. Gibril, R.T. Jensen, 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. 239, 617–625 (2004)PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    G.W. Krampitz, J.A. Norton, Current management of the Zollinger-Ellison syndrome. Adv. Surg. 47, 59–79 (2013)PubMedCrossRefGoogle Scholar
  33. 33.
    J.A. Norton, D.L. Fraker, H.R. Alexander, D.J. Venzon, J.L. Doppman, J. Serrano, S.U. Goebel, P.L. Peghini, P.K. Roy, F. Gibril, R.T. Jensen, Surgery to cure the Zollinger-Ellison syndrome. N. Eng. J. Med. 341, 635–644 (1999)CrossRefGoogle Scholar
  34. 34.
    J.A. Norton, R.T. Jensen, Resolved and unsolved controversies in the surgical management of patients with Zollinger-Ellison syndrome. Ann. Surg. 240, 757–773 (2004)PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    N.W. Thompson, A.I. Vinik, F.E. Eckhauser, Microgastrinoma of the duodenum a cause of failed operations for the Zollinger-Ellison syndrome. Ann. Surg. 209, 396–404 (1989)PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    F. Maire, A. Sauvanet, A. Couvelard, V. Rebours, M.P. Vullierme, R. Lebtahi, O. Hentic, J. Belghiti, P. Hammel, P. Lévy, P. Ruszniewski, Recurrence after surgical resection of gastrinoma: who, when, where and why? Eur. J. Gastroenterol. Hepatol. 24, 368–374 (2012)PubMedGoogle Scholar
  37. 37.
    J.A. Norton, D.L. Fraker, H.R. Alexander, F. Gibril, D.J. Liewehr, D.J. Venzon, R.T. Jensen, Surgery increases survival in patients with gastrinoma. Ann. Surg. 244, 410–419 (2006)PubMedPubMedCentralGoogle Scholar
  38. 38.
    J.A. Norton, D.L. Fraker, H.R. Alexander, R.T. Jensen, Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison syndrome. Ann. Surg. 25, 509–517 (2012)CrossRefGoogle Scholar
  39. 39.
    C.L. Lopez, M. Falconi, J. Waldmann, L. Boninsegna, V. Fendrich, P.K. Goretzki, P. Langer, P.H. Kann, S. Partelli, D.K. Bartsch, Partial pancreaticoduodenectomy can provide cure for duodenal gastrinoma associated with multiple endocrine neoplasia type 1. Ann. Surg. 257, 308–314 (2013)PubMedCrossRefGoogle Scholar
  40. 40.
    J.A. Norton, T.D. Fang, R.T. Jensen, Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J. Natl. Compr. Cancer Netw. 4, 148–153 (2006)CrossRefGoogle Scholar
  41. 41.
    D.C. Metz, R.T. Jensen, Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135, 1469–1492 (2008)PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    C.M. Wilcox, B.I. Hirschowitz, Treatment strategies for Zollinger-Ellison syndrome. Expert Opin. Pharmacother. 10, 1145–1157 (2009)PubMedCrossRefGoogle Scholar
  43. 43.
    J.M. Nieto, J.R. Pisegna, The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome. Expert. Opin. Pharmacother. 7, 169–175 (2006)PubMedCrossRefGoogle Scholar
  44. 44.
    J.A. Ziemniak, M. Madura, A.J. Adamonis, E.J. Olinger, M. Dreyer, J.J. Schentag, Failure of cimetidine in Zollinger-Ellison syndrome. Dig. Dis. Sci. 28, 976–980 (1983)PubMedCrossRefGoogle Scholar
  45. 45.
    R.T. Jensen, M.J. Collen, S.J. Pandol, H.D. Allende, J.P. Raufman, B.M. Bissonnette, W.C. Duncan, P.L. Durgin, J.C. Gillin, J.D. Gardner, Cimetidine-induced impotence and breast changes in patients with gastric hypersecretory states. N. Eng. J. Med. 308, 883–887 (1983)CrossRefGoogle Scholar
  46. 46.
    M.J. Collen, J.M. Howard, K.E. McArthur, J.P. Raufman, M.J. Cornelius, C.A. Ciarleglio, J.D. Gardner, R.T. Jensen, Comparison of ranitidine and cimetidine in the treatment of gastric hypersecretion. Ann. Intern. Med. 100, 52–58 (1984)PubMedCrossRefGoogle Scholar
  47. 47.
    J.M. Howard, A.N. Chremos, M.J. Collen, K.E. McArthur, J.A. Cherner, P.N. Maton, C.A. Ciarleglio, M.J. Cornelius, J.D. Gardner, R.T. Jensen, Famotidine, a new, potent, long-acting histamine H2-receptor antagonist: comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison syndrome. Gastroenterology 88, 1026–1033 (1985)PubMedCrossRefGoogle Scholar
  48. 48.
    B.I. Hirschowitz, J. Simmons, J. Mohnen, Clinical outcome using lansoprazole in acid hypersecretors with and without Zollinger-Ellison syndrome: a 13-year prospective study. Clin. Gastroenterol. Hepatol. 3, 39–48 (2005)PubMedCrossRefGoogle Scholar
  49. 49.
    V.D. Corleto, B. Annibale, F. Gibril, S. Angeletti, J. Serrano, D.J. Venzon, G. Delle Fave, R.T. Jensen, Does the widespread use of proton pump inhibitors mask, complicate and /or delay the diagnosis of Zollinger-Ellison syndrome? Aliment. Pharmacol. Ther. 15, 1555–1561 (2001)PubMedCrossRefGoogle Scholar
  50. 50.
    P. Shah, M.H. Singh, Y.X. Yang, D.C. Metz, Hypochlorhydria and achlorhydria are associated with false-positive secretin stimulation testing for Zollinger-Ellison syndrome. Pancreas 42, 932–936 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    T. Ito, R.T. Jensen, 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. 12, 448–457 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    J.M. Ruscin, R.L. Page II, R.J. Valuck, Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann. Pharmacother. 36, 812–816 (2002)PubMedCrossRefGoogle Scholar
  53. 53.
    R.J. Valuck, J.M. Ruscin, A case–control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J. Clin. Epidemiol. 57, 422–428 (2004)PubMedCrossRefGoogle Scholar
  54. 54.
    W.P. den Elzen, Y. Groeneveld, W. de Ruijter, J.H. Souverijn, S. le Cessie, W.J. Assendelft, J. Gussekloo, Long-term use of proton pump inhibitors and vitamin B12 status in elderly individuals. Aliment. Pharmacol. Ther. 27, 491–497 (2008)CrossRefGoogle Scholar
  55. 55.
    J.R. Lam, J.L. Schneider, W. Zhao, D.A. Corley, Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 310, 2435–2442 (2013)PubMedCrossRefGoogle Scholar
  56. 56.
    B. Termanini, F. Gibril, V.E. Sutliff, F. Yu, D.J. Venzon, R.T. Jensen, Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am. J. Med. 104, 422–430 (1998)PubMedCrossRefGoogle Scholar
  57. 57.
    V.R. Sharma, M.A. Brannon, E.A. Carloss, Effect of omeprazole on oral iron replacement in patients with iron deficiency anemia. South. Med. J. 97, 887–889 (2004)PubMedCrossRefGoogle Scholar
  58. 58.
    C. Hutchinson, C.A. Geissler, J.J. Powell, A. Bomford, Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut 56, 1291–1295 (2007)PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    C.A. Stewart, B. Termanini, V.E. Sutliff, J. Serrano, F. Yu, F. Gibril, R.T. Jensen, Assessment of the risk of iron malabsorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment. Pharmacol. Ther. 12, 83–98 (1998)PubMedCrossRefGoogle Scholar
  60. 60.
    Y.X. Yang, J.D. Lewis, S. Epstein, D.C. Metz, Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 296, 2947–2953 (2006)PubMedCrossRefGoogle Scholar
  61. 61.
    C. Roux, K. Briot, L. Gossec, S. Kolta, T. Blenk, D. Felsenberg, D.M. Reid, R. Eastell, C.C. Glüer, Increase in vertebral fracture risk in postmenopausal women using omeprazole. Calcif. Tissue Int. 84, 13–19 (2009)PubMedCrossRefGoogle Scholar
  62. 62.
    L.E. Targownik, L.M. Lix, C.J. Metge, H.J. Prior, S. Leung, W.D. Leslie, Use of proton pump inhibitors and risk of osteoporosis-related fractures. Can. Med. Assoc. J. 179, 319–326 (2008)CrossRefGoogle Scholar
  63. 63.
    P.O. Lewis, J.M. Litchfield, J.L. Tharp, R.M. Garcia, M. Pourmorteza, C.M. Reddy, Risk and severity of hospital-acquired clostridium difficile infection in patients taking proton pump inhibitors. Pharmacotherapy 36, 986–993 (2016)PubMedCrossRefGoogle Scholar
  64. 64.
    C. Giuliano, S.M. Wilhelm, P.B. Kale-Pradhan, Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev. Clin. Pharmacol. 5, 337–344 (2012)PubMedCrossRefGoogle Scholar
  65. 65.
    P.L. Peghini, B. Annibale, C. Azzoni, M. Milione, V.D. Corleto, F. Gibril, D.J. Venzon, G. Delle Fave, C. Bordi, R.T. Jensen, Effect of chronic hypergastrinemia on human enterochromaffin-like cells: insights from patients with sporadic gastrinomas. Gastroenterology 123, 68–85 (2002)PubMedCrossRefGoogle Scholar
  66. 66.
    M.J. Berna, B. Annibale, M. Marignani, T.V. Luong, V. Corleto, A. Pace, T. Ito, D. Liewehr, D.J. Venzon, G. Delle Fave, C. Bordi, R.T. Jensen, A prospective study of gastric carcinoids and enterochromaffin-like cells changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors. J. Clin. Endocrinol. Metabol. 93, 1582–1591 (2008)CrossRefGoogle Scholar
  67. 67.
    P.N. Maton, E.E. Lack, M.J. Collen, M.J. Cornelius, E. David, J.D. Gardner, R.T. Jensen, The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric oxyntic endocrine cells. Gastroenterology 99, 943–950 (1990)PubMedCrossRefGoogle Scholar
  68. 68.
    J.C. Yao, M.H. Shah, T. Ito, C.L. Bohas, E.M. Wolin, E. Van Cutsem, T.J. Hobday, T. Okusaka, J. Capdevila, E.G. de Vries, P. Tomassetti, M.E. Pavel, S. Hoosen, T. Haas, J. Lincy, D. Lebwohl, K. Öberg, RAD001 in advanced neuroendocrine tumors, third trial (RADIANT-3) study group. Everolimus for advanced pancreatic neuroendocrine tumors. N. Eng. J. Med. 364, 514–523 (2011)CrossRefGoogle Scholar
  69. 69.
    E. Raymond, L. Dahan, J.L. Raoul, Y.J. Bang, I. Borbath, C. Lombard-Bohas, J. Valle, P. Metrakos, D. Smith, A. Vinik, J.S. Chen, D. Hörsch, P. Hammel, B. Wiedenmann, E. Van Cutsem, S. Patyna, D.R. Lu, C. Blanckmeister, R. Chao, P. Ruszniewski, Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N. Eng. J. Med. 364, 501–513 (2011)CrossRefGoogle Scholar
  70. 70.
    T. Von Schrenck, J.M. Howard, J.L. Doppman, J.A. Norton, P.N. Maton, F.P. Smith, R. Vinayek, H. Frucht, S.A. Wank, J.D. Gardner et al. Prospective study of chemotherapy in patients with metastatic gastrinoma. Gastroenterology 94, 1326–1334 (1988)CrossRefGoogle Scholar
  71. 71.
    J.R. Strosberg, R.L. Fine, J. Choi, A. Nasir, D. Coppola, D.T. Chen, J. Helm, L. Kvols, First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 117, 268–275 (2011)PubMedCrossRefGoogle Scholar
  72. 72.
    A.V. Schally, Oncological applications of somatostatin analogues. Cancer Res. 48, 6977–6785 (1988)PubMedGoogle Scholar
  73. 73.
    Pollak M.N., Schally A.V., Mechanisms of antineoplastic action of somatostatin analogs. Proc. Soc. Exp. Biol. Med. 217, 143–152 (1998)PubMedCrossRefGoogle Scholar
  74. 74.
    S. Pyronnet, C. Bousquet, S. Najib, R. Azar, H. Laklai, C. Susini, Antitumor effects of somatostatin. Mol. Cell Endocrinol. 286, 230–237 (2008)PubMedCrossRefGoogle Scholar
  75. 75.
    R. Arnold, M.E. Trautmann, W. Creutzfeldt, R. Benning, M. Benning, C. Neuhaus, R. Jurgensen, K. Stein, H. Schafer, C. Bruns, H.J. Dennler, Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut 38, 430–438 (1996)PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    M. Di Bartolomeo, E. Bajetta, R. Buzzoni, L. Mariani, C. Carnaghi, L. Somma, N. Zilembo, A. Di Leo, Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group. Cancer 77, 402–408 (1996)PubMedCrossRefGoogle Scholar
  77. 77.
    T. Aparicio, M. Ducreux, E. Baudin, J.C. Sabourin, T. De Baere, E. Mitry, M. Schlumberger, P. Rougier, Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. Eur. J. Cancer 37, 1014–1019 (2001)PubMedCrossRefGoogle Scholar
  78. 78.
    S. Faiss, U.F. Pape, M. Böhmig, Y. Dörffel, U. Mansmann, W. Golder, E.O. Riecken, B. Wiedenmann, 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. 21, 2689–2696 (2003)PubMedCrossRefGoogle Scholar
  79. 79.
    A. Rinke, H.H. Müller, C. Schade-Brittinger, K.J. Klose, P. Barth, M. Wied, C. Mayer, B. Aminossadati, U.F. Pape, M. Bläker, J. Harder, C. Arnold, T. Gress, R. Arnold, Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study. J. Clin. Oncol. 27, 4656–4663 (2009)PubMedCrossRefGoogle Scholar
  80. 80.
    M.E. Caplin, M. Pavel, J.B. Ćwikła, A.T. Phan, M. Raderer, E. Sedláčková, G. Cadiot, E.M. Wolin, J. Capdevila, L. Wall, Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N. Eng. J. Med. 371, 224–233 (2014)CrossRefGoogle Scholar
  81. 81.
    D. Hoyer, H. Lubbert, C. Bruns, Molecular pharmacology of somatostatin receptors. Naunyn Schmiedeberg’s Arch. Pharmacol. 350, 441–453 (1994)CrossRefGoogle Scholar
  82. 82.
    M. Vanetti, M. Kouba, X. Wang, G. Vogt, V. Hollt, Cloning and expression of a novel mouse somatostatin receptor (SSTR2B). FEBS Lett. 311, 290–294 (1992)PubMedCrossRefGoogle Scholar
  83. 83.
    Y.C. Patel, M. Greenwood, G. Kent, R. Panetta, C.B. Srikant, Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochem. Biophys. Res. Commun. 192, 288–294 (1993)PubMedCrossRefGoogle Scholar
  84. 84.
    S.W. Lamberts, E.P. Krenning, J.C. Reubi, The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr. Rev. 12, 450–482 (1991)PubMedCrossRefGoogle Scholar
  85. 85.
    L.J. Hofland, H.A. Visser-Wisselaar, S.W. Lamberts, Somatostatin analogs: clinical application in relation to human somatostatin receptor subtypes. Biochem. Pharmacol. 50, 287–297 (1995)PubMedCrossRefGoogle Scholar
  86. 86.
    J.C. Reubi, J. Laissue, E. Krenning, S.W. Lamberts, Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J. Steroid Biochem. Mol. Biol. 43, 27–35 (1992)PubMedCrossRefGoogle Scholar
  87. 87.
    J.C. Reubi, B. Waser, J.C. Schaer, J.A. Laissue, Somatostatin receptor sst1–sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur. J. Nucl. Med. 28, 836–846 (2001)PubMedCrossRefGoogle Scholar
  88. 88.
    S. Vikic-Topic, K.P. Raisch, L.K. Kvols, S. Vuk-Pavlovic, Expression of somatostatin receptor subtypes in breast carcinoma, carcinoid tumor, and renal cell carcinoma. J. Clin. Endocrinol. Metabol. 80, 2974–2979 (1995)Google Scholar
  89. 89.
    L.J. Hofland, Q. Liu, P.M. van Koetsveld, J. Zuijderwijk, F. van der Ham, R.R. de Krijger, A. Schonbrunn, S.W. Lamberts, Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors. J. Clin. Endocrinol. Metab. 84, 775–780 (1999)PubMedCrossRefGoogle Scholar
  90. 90.
    J.C. Reubi, J. Laissue, B. Waser, U. Horisberger, J.C. Schaer, Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann. N. Y. Acad. Sci. 733, 122–137 (1994)PubMedCrossRefGoogle Scholar
  91. 91.
    H. Kulaksiz, R. Eissele, D. Rössler, S. Schulz, V. Hollt, Y. Cetin, R. Arnold, Identification of somatostatin receptor subtypes 1, 2A, 3, and 5 in neuroendocrine tumours with subtypespecific antibodies. Gut 50, 52–60 (2002)PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    S.W. Lamberts, A.J. van der Lely, W.W. de Herder, L.J. Hofland, Octreotide. N. Eng. J. Med. 334, 246–254 (1996)CrossRefGoogle Scholar
  93. 93.
    E.J. Mozell, A.L. Cramer, T.M. O’Dorisio, E.A. Woltering, Long-term efficacy of octreotide in the treatment of Zollinger-Ellison syndrome. Arch. Surg. 127, 1019–1024 (1992)PubMedCrossRefGoogle Scholar
  94. 94.
    E.P. Krenning, D.J. Kwekkeboom, W.H. Bakker, W.A. Breeman, P.P. Kooij, H.Y. Oei, M. van Hagen, P.T. Postema, M. de Long, J.C. Reubi et al. Somatostatin receptor scintigraphy with [1 l ‘In-DTPA-D-Phe’]- and [123I-Tyr3]- octreotide: the Rotterdam experience with more than 1000 patients. Eur. J. Nucl. Med. 20, 716–731 (1993)PubMedCrossRefGoogle Scholar
  95. 95.
    E. de Kerviler, G. Cadiot, R. Lebtahi, M. Faraggi, D. Le Guludec, M. Mignon, Somatostatin receptor scintigraphy in forty-eight patients with Zollinger-Ellison syndrome. GRESZE: Group d’Etude du Syndrome de Zollinger-Ellison. Eur. J. Nucl. Med. 21, 1191–1197 (1994)PubMedCrossRefGoogle Scholar
  96. 96.
    R.T. Jensen, F. Gibril, Somatostatin receptor scintigraphy in gastrinomas. Ital. J. Gastroenterol. Hepatol. 31, S179–85 (1993)Google Scholar
  97. 97.
    F. Gibril, J.C. Reynolds, J.L. Doppmann, C.C. Chen, D.J. Venzon, B. Termanini, H.C. Weber, C.A. Steward, R.T. Jensen, Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study. Ann. Intern. Med. 125, 26–34 (1996)PubMedCrossRefGoogle Scholar
  98. 98.
    J.C. Reubi, J.C. Schär, B. Waser, S. Wenger, A. Heppeler, J.S. Schmitt, H.R. Mäcke, Affinity profiles for human somatostatin receptor subtypes SST1–SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur. J. Nucl. Med. 27, 273–282 (2000)PubMedCrossRefGoogle Scholar
  99. 99.
    A. Mojtahedi, S. Thamake, I. Tworowska, D. Ranganathan, E.S. Delpassand, The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am. J. Nucl. Med. Mol. Imaging 4, 426–434 (2014)PubMedPubMedCentralGoogle Scholar
  100. 100.
    N. Naswa, P. Sharma, R. Soundararajan, S. Karunanithi, A.H. Nazar, R. Kumar, A. Malhotra, C. Bal, Diagnostic performance of somatostatin receptor PET/CT using 68 Ga DOTANOC in gastrinoma patients with negative or equivocal CT findings. Abdom. Imaging 38, 552–560 (2013)PubMedCrossRefGoogle Scholar
  101. 101.
    J.C. Reubi, H.R. Mäcke, E.P. Krenning, Candidates for peptide receptor radiotherapy today and in the future. J. Nucl. Med. 46, 67S–75S (2005)PubMedGoogle Scholar
  102. 102.
    D.J. Kwekkeboom, J.J. Teunissen, W.H. Bakker, P.P. Kooij, W.W. de Herder, R.A. Feelders, C.H. van Eijck, J.P. Esser, B.L. Kam, E.P. Krenning, Radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate in patients with endocrine gastroenteropancreatic tumors. J. Clin. Oncol. 23, 2754–2762 (2005)PubMedCrossRefGoogle Scholar
  103. 103.
    S. Grozinski-Glasberg, D. Barak, M. Fraenkel, M.A. Walter, J. Müeller-Brand, J. Eckstein, L. Applebaum, I. Shimon, D.J. Gross, Peptide receptor radioligand therapy is an effective treatment for the long-term stabilization of malignant gastrinomas. Cancer 117, 1377–1385 (2011)CrossRefGoogle Scholar
  104. 104.
    G. Delle Fave, D.J. Kwekkeboom, E. Van Cutsem, G. Rindi, B. Kos-Kudla, U. Knigge, H. Sasano, P. Tomassetti, R. Salazar, P. Ruszniewski, ENETS consensus guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology 95, 74–87 (2012)PubMedCrossRefGoogle Scholar
  105. 105.
    R.T. Jensen, G. Cadiot, M.L. Brandi, W.W. de Herder, G. Kaltsas, P. Komminoth, J.Y. Scoazec, R. Salazar, A. Sauvanet, R. Kianmanesh, ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology 95, 98–119 (2012)PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    M. Pavel, E. Baudin, A. Couvelard, E. Krenning, K. Öberg, T. Steinmüller, M. Anlauf, B. Wiedenmann, B. Salazar, NETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 95, 157–176 (2012)PubMedCrossRefGoogle Scholar
  107. 107.
    G. Delle Fave, D. O’Toole, A. Sundin, B. Taal, P. Ferolla, J.K. Ramage, D. Ferone, T. Ito, W. Weber, Z. Zheng-Pei, W.W. De Herder, A. Pascher, P. Ruszniewski, ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms. Neuroendocrinology 103, 119–124 (2016)PubMedCrossRefGoogle Scholar
  108. 108.
    M. Pavel, D. O’Toole, F. Costa, J. Capdevila, D. Gross, R. Kianmanesh, E. Krenning, U. Knigge, R. Salazar, U.F. Pape, K. Öberg, ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 103, 172–185 (2016)PubMedCrossRefGoogle Scholar
  109. 109.
    M.H. Kulke, L.B. Anthony, D.L. Bushnell, W.W. de Herder, S.J. Goldsmith, D.S. Klimstra, S.J. Marx, J.L. Pasieka, R.F. Pommier, J.C. Yao, R.T. Jensen, NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 39, 735–752 (2010)PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    P.L. Kunz, D. Reidy-Lagunes, L.B. Anthony, E.M. Bertino, K. Brendtro, J.A. Chan, H. Chen, R.T. Jensen, M.K. Kim, D.S. Klimstra, M.H. Kulke, E.H. Liu, D.C. Metz, A.T. Phan, R.S. Sippel, J.R. Strosberg, J.C. Yao, Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 42, 557–577 (2013)PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    K. Öberg, U. Knigge, D. Kwekkeboom, A. Perren, Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 23, 124–130 (2012)Google Scholar
  112. 112.
    B. Wormann, K. Kutz, R. Ottenjann, Treatment of relapsing bleeding peptic ulcers with the somatostatin analogue SMS 201 995 in a patient with Zollinger-Ellison syndrome. Hepatogastroenterology 32, 152–153 (1985)PubMedGoogle Scholar
  113. 113.
    P. Ruszniewski, H. Laucournet, L. Elouaer-Blanc, M. Mignon, S. Bonfils, Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for susteined efficacy. Pancreas 3, 145–152 (1988)PubMedCrossRefGoogle Scholar
  114. 114.
    P. Ruszniewski, F. Girard, R. Benamouzig, M. Mignon, S. Bonfils, Long-acting somatostatin treatment of paraneoplastic Cushing’s syndrome in a case of Zollinger-Ellison syndrome. Gut 29, 838–842 (1988)PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    R. Arnold, R. Benning, C. Neuhaus, M. Rolwage, M.E. Trautmann, Gastroenteropancreatic endocrine tumors: effect of sandostatin on tumor growth. Ger. Sandostatin Study Group Metabol. 41, 116–118 (1992)Google Scholar
  116. 116.
    R. Arnold, C. Neuhaus, R. Benning, W.B. Schwerk, M.E. Trautmann, K. Joseph, C. Bruns, Somatostatin analog sandostatin and inhibition of tumor frowth in patients with metastatic endocrine gastroenteropancreatic tumors. World J. Surg. 17, 511–519 (1993)PubMedCrossRefGoogle Scholar
  117. 117.
    S. Angeletti, V.D. Corleto, O. Schillaci, A. Moretti, F. Panzuto, B. Annobale, G. Delle Fave, Single dose of octreotide stabilize metastatic gastro-entero-pancreatic endocrine tumors. Ital. J. Gastroenterol. Hepatol. 31, 23–27 (1999)PubMedGoogle Scholar
  118. 118.
    S. Gaztambide, J.A. Vazquez, Short-and long term effect of a long-acting somatostatin analogue, lanreotide (SR-L) on metastatic gastrinoma. J. Endocrinol. Invest. 22, 144–146 (1999)PubMedCrossRefGoogle Scholar
  119. 119.
    A.N.M. Wymenga, B. Eriksson, P.I. Salmela, M.B. Jacobsen, E.J.D.G. Van Cutsem, R.H. Fiasse, M.J. Välimäki, J. Renstrup, E.G.E. de Vries, K.E. Öberg, Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. J. Clin. Oncol. 17, 1111–1117 (1999)PubMedCrossRefGoogle Scholar
  120. 120.
    P. Tomassetti, M. Migliori, R. Corinaldesi, L. Gullo, Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR. Aliment. Pharmacol. Ther. 14, 557–560 (2000)PubMedCrossRefGoogle Scholar
  121. 121.
    H. Shojamanesh, F. Gibril, A. Louie, J.V. Ojeaburu, S. Bashir, A. Abou-Saif, R.T. Jensen, Prospective study of the antitumor efficacy of long-term octreotide treatment in patients with progressive metastatic gastrinoma. Cancer 94, 331–343 (2002)PubMedCrossRefGoogle Scholar
  122. 122.
    F. Saijo, H. Naito, Y. Funayama, K. Fukushima, C. Shibata, A. Hashimoto, T. Kitayama, M. Nagao, S. Matsuno, I. Sasaki, Octreotide in control of liver metastases from gastrinoma. J. Gastroenterol. 38, 905–908 (2003)PubMedCrossRefGoogle Scholar
  123. 123.
    D. Granberg, H. Jacobsson, K.E. Öberg, J. Gustavsson, M. Lehtihet, Regression of a large malignant gastrinoma on treatment with Sandostin LAR: a case report. Digestion 77, 92–95 (2008)PubMedCrossRefGoogle Scholar
  124. 124.
    M. Yamaguchi, Y. Yamada, Y. Hosokawa, R. Iwamoto, S. Tamba, A. Ihara, K. Yamamoto, Y. Hoshida, Y. Matzuzawa, Long-term suppressive effect of Octreotide on progression of metastatic gastrinoma with multiple endocrine neoplasia type 1: seven-year follow up. Intern. Med. 49, 1557–1563 (2010)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Valentina Guarnotta
    • 1
  • Chiara Martini
    • 2
    Email author
  • Maria Vittoria Davì
    • 3
  • Genoveffa Pizza
    • 4
  • Annamaria Colao
    • 4
  • Antongiulio Faggiano
    • 5
  • on behalf of NIKE group
  1. 1.Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrine-Metabolic DiseasesUniversity of PalermoPalermoItaly
  2. 2.Clinica Medica 3^, Department of Medicine, DIMEDUniversity of PadovaPadovaItaly
  3. 3.Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Department of MedicineUniversity of VeronaVeronaItaly
  4. 4.Department of Clinical Medicine and Surgery“Federico II” University of NaplesNaplesItaly
  5. 5.Thyroid and Parathyroid Surgery UnitIstituto Nazionale per lo studio e la cura dei tumori “Fondazione G. Pascale” – IRCCSNaplesItaly

Personalised recommendations