Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)
- Stephen E Goldfinger, MD
Stephen E Goldfinger, MD
- Professor of Medicine
- Harvard Medical School
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 "Clinical manifestations and diagnosis of Zollinger-Ellison syndrome (gastrinoma)" 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 gastrin
- 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 April 01, 2014).
- 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