Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)
- Emily Bergsland, MD
Emily Bergsland, MD
- Professor of Medicine
- University of California San Francisco
Patients with Zollinger-Ellison syndrome (ZES) have gastrin-secreting tumors and the associated clinical consequences. This disorder can occur sporadically, or as a manifestation of multiple endocrine neoplasia type 1 (MEN 1). Medical therapy is the current standard of care for most patients with ZES as part of the MEN 1 syndrome. By contrast, many patients with sporadic ZES are candidates for surgical therapy. (See "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "Multiple endocrine neoplasia type 1: Treatment" and 'Surgery' below.)
Prior to the development of effective acid suppression therapy, the major morbidity and mortality of ZES were related to complications of fulminant peptic ulcer disease; total gastrectomy was the only effective measure to protect patients from these problems .
The development of H2 antagonists and the more powerful proton pump inhibitors has resulted in a significant decrease in morbidity and mortality from ulcer disease and has obviated the need for gastrectomy . Of 212 patients with ZES studied prospectively for a mean of 13.8 years, a ZES-related cause of death could be identified in only half of the 31 percent who died. All of the ZES-related deaths were due to tumor spread; none were due to hypersecretory complications .
This topic review will discuss the two current goals of therapy in ZES :
●Control of the complications resulting from autonomous release of gastrinTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Meko JB, Norton JA. Management of patients with Zollinger-Ellison syndrome. Annu Rev Med 1995; 46:395.
- Quatrini M, Castoldi L, Rossi G, et al. A follow-up study of patients with Zollinger-Ellison syndrome in the period 1966-2002: effects of surgical and medical treatments on long-term survival. J Clin Gastroenterol 2005; 39:376.
- Yu F, Venzon DJ, Serrano J, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol 1999; 17:615.
- Jensen RT, Fraker DL. Zollinger-Ellison syndrome. Advances in treatment of gastric hypersecretion and the gastrinoma. JAMA 1994; 271:1429.
- Metz DC, Pisegna JR, Fishbeyn VA, et al. Control of gastric acid hypersecretion in the management of patients with Zollinger-Ellison syndrome. World J Surg 1993; 17:468.
- Maton PN, Vinayek R, Frucht H, et al. Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. Gastroenterology 1989; 97:827.
- Hirschowitz BI, Simmons J, Mohnen J. Clinical outcome using lansoprazole in acid hypersecretors with and without Zollinger-Ellison syndrome: a 13-year prospective study. Clin Gastroenterol Hepatol 2005; 3:39.
- Metz DC, Comer GM, Soffer E, et al. Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions. Aliment Pharmacol Ther 2006; 23:437.
- Metz DC, Pisegna JR, Fishbeyn VA, et al. Currently used doses of omeprazole in Zollinger-Ellison syndrome are too high. Gastroenterology 1992; 103:1498.
- Norton JA, Fraker DL, Alexander HR, et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244:410.
- Norton JA, Fraker DL, Alexander HR, Jensen RT. Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison syndrome. Ann Surg 2012; 256:509.
- Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341:635.
- Bartsch DK, Waldmann J, Fendrich V, et al. Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma. Br J Surg 2012; 99:1234.
- Norton JA. Surgical treatment and prognosis of gastrinoma. Best Pract Res Clin Gastroenterol 2005; 19:799.
- Norton JA, Doppman JL, Jensen RT. Curative resection in Zollinger-Ellison syndrome. Results of a 10-year prospective study. Ann Surg 1992; 215:8.
- Jensen RT. Should the 1996 citation for Zollinger-Ellison syndrome read: "Acid-reducing surgery in, aggressive resection out"? Am J Gastroenterol 1996; 91:1067.
- Pisegna JR, Norton JA, Slimak GG, et al. Effects of curative gastrinoma resection on gastric secretory function and antisecretory drug requirement in the Zollinger-Ellison syndrome. Gastroenterology 1992; 102:767.
- Ojeaburu JV, Ito T, Crafa P, et al. Mechanism of acid hypersecretion post curative gastrinoma resection. Dig Dis Sci 2011; 56:139.
- McArthur KE, Richardson CT, Barnett CC, et al. Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study. Am J Gastroenterol 1996; 91:1104.
- Fraker DL, Norton JA, Alexander HR, et al. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann Surg 1994; 220:320.
- Jaskowiak NT, Fraker DL, Alexander HR, et al. Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome? Surgery 1996; 120:1055.
- Contessa JN, Griffith KA, Wolff E, et al. Radiotherapy for pancreatic neuroendocrine tumors. Int J Radiat Oncol Biol Phys 2009; 75:1196.
- Strosberg J, Hoffe S, Gardner N, et al. Effective treatment of locally advanced endocrine tumors of the pancreas with chemoradiotherapy. Neuroendocrinology 2007; 85:216.
- Tennvall J, Ljungberg O, Ahrén B, et al. Radiotherapy for unresectable endocrine pancreatic carcinomas. Eur J Surg Oncol 1992; 18:73.
- Torrisi JR, Treat J, Zeman R, Dritschilo A. Radiotherapy in the management of pancreatic islet cell tumors. Cancer 1987; 60:1226.
- Gery B, Roussel A, Valla A. Usefulness of radiotherapy in the treatment of advanced gastrinomas. Radiother Oncol 1993; 27:259.
- Gibril F, Doppman JL, Reynolds JC, et al. Bone metastases in patients with gastrinomas: a prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their detection, frequency, location, and effect of their detection on management. J Clin Oncol 1998; 16:1040.
- Saijo F, Naito H, Funayama Y, et al. Octreotide in control of multiple liver metastases from gastrinoma. J Gastroenterol 2003; 38:905.
- 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.
- Burgess JR, Greenaway TM, Parameswaran V, Shepherd JJ. Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis. Cancer 1999; 86:2154.
- Gaztambide S, Vazquez JA. Short- and long-term effect of a long-acting somatostatin analogue, lanreotide (SR-L) on metastatic gastrinoma. J Endocrinol Invest 1999; 22:144.
- Tomassetti P, Migliori M, Gullo L. Slow-release lanreotide treatment in endocrine gastrointestinal tumors. Am J Gastroenterol 1998; 93:1468.
- Deol ZK, Frezza E, DeJong S, Pickleman J. Solitary hepatic gastrinoma treated with laparoscopic radiofrequency ablation. JSLS 2003; 7:285.
- 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.
- Grozinsky-Glasberg S, Barak D, Fraenkel M, et al. Peptide receptor radioligand therapy is an effective treatment for the long-term stabilization of malignant gastrinomas. Cancer 2011; 117:1377.
- Weber HC, Venzon DJ, Lin JT, et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology 1995; 108:1637.
- Berger AC, Gibril F, Venzon DJ, et al. Prognostic value of initial fasting serum gastrin levels in patients with Zollinger-Ellison syndrome. J Clin Oncol 2001; 19:3051.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- MEDICAL MANAGEMENT
- Proton pump inhibitors
- Reoperation for recurrence
- RADIATION THERAPY FOR NONSURGICAL CANDIDATES
- THERAPY OF METASTATIC DISEASE
- Somatostatin analogs
- Liver-directed therapy
- - Resection
- - Hepatic artery embolization
- - RFA and cryoablation
- - Liver transplantation
- Chemotherapy and novel treatment approaches
- POSTTREATMENT SURVEILLANCE
- SUMMARY AND RECOMMENDATIONS