Zollinger-Ellison Syndrome Treatment & Management
- Author: Praveen K Roy, MD, AGAF; Chief Editor: Philip O Katz, MD, FACP, FACG more...
The goals of treatment in patients with Zollinger-Ellison syndrome (ZES) are medical control of gastric acid hypersecretion and surgical resection of the tumor. Inpatient care is aimed at first controlling the gastric acid hypersecretion. Once gastric acid hypersecretion is controlled, imaging studies should be obtained to localize the tumor and determine tumor extent.
If the patient is acutely ill, immediate control of gastric acid hypersecretion can be achieved with intravenous proton pump inhibitors. Previously, this was accomplished with histamine 2 (H2) receptor blockers. Intravenous pantoprazole was approved recently by the US Food and Drug Administration. Proton pump inhibitors are superior to H2 blockers for the control of gastric acid hypersecretion.
Patients who are candidates for surgical resection should be referred for resection of the tumor.
For patients with metastatic disease, chemotherapy, interferon, and octreotide may be helpful. The response to these agents in most studies has been low. Liver transplantation for hepatic metastasis also has been reported. For patients with a single confined liver metastatic lesion, surgical resection may be attempted.
Consider consultation with a gastroenterologist, surgeon, oncologist, and/or an endocrinologist.
All patients with sporadic Zollinger-Ellison syndrome (ZES) without hepatic metastases or medical contraindications to surgery are advised to undergo surgical resection of the tumor because this decreases the risk of developing liver metastases, which can decrease the survival of these patients.
The role and timing of surgical resection in patients with multiple endocrine neoplasia-type 1 (MEN 1) is less clear. An attempt at surgical resection has been recommended if the tumor is larger than 2.5 cm. Cure is rarely achieved by surgical resection in patients with MEN 1; however, it may reduce the risk of subsequent metastatic disease.
In a single-institution retrospective study with a median follow-up of 18 years from the time of the diagnosis of ZES, Mortellaro et al examined the long-term outcomes in 12 patients with MEN 1 and ZES from 1970 to the present. The pancreas (n = 10), duodenum (n = 4), lymph nodes (n = 3), and liver (n = 1) were the most commonly identified gastrinoma sites. A total of 15 celiotomies were performed, and surgeries included 4 each of distal pancreatectomies and acid-reducing procedures, 3 each of enucleation of pancreatic gastrinoma and duodenal resection, 1 pancreaticoduodenectomy, and 7 noted as other. There was 1 each of a patient with transient (3 y) biochemical postsurgical cure and liver metastasis of gastrinoma (but no deaths from metastatic gastrinoma).
Deaths included causes such as respiratory arrest (n = 1), possibly due to aspiration or pulmonary embolus, and nondisease related (n = 3). At the last follow-up, 7 patients were alive. The investigators observed patients with MEN 1 and ZES rarely achieve biochemical cures with surgery; however, extended surgical resection was not only not needed in resection of localized gastrinomas, but it was also associated with excellent long-term outcomes.
Because gastrinoma is a rare tumor, surgical resection should be attempted only at centers with personnel experienced in treating affected patients.
Outpatient postoperative care
After surgical resection of a gastrinoma, patients should be assessed for evidence of recurrence with serum fasting gastrin levels, a secretin test, and SRS. The first evaluation should be performed at 3-6 months postresection and then, optimally, yearly thereafter.
Proton pump inhibitors can be continued with the goal of maintaining the basal acid output (BAO) below 10 mEq/h before the next dose of the proton pump inhibitors.
Mortellaro VE, Hochwald SN, McGuigan JE, et al. Long-term results of a selective surgical approach to management of Zollinger-Ellison syndrome in patients with MEN-1. Am Surg. 2009 Aug. 75(8):730-3. [Medline].
Alexakis N, Neoptolemos JP. Pancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2008. 22(1):183-205. [Medline].
Anderson MA, Carpenter S, Thompson NW. Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas. Am J Gastroenterol. 2000 Sep. 95(9):2271-7. [Medline].
Azimuddin K, Chamberlain RS. The surgical management of pancreatic neuroendocrine tumors. Surg Clin North Am. 2001 Jun. 81(3):511-25. [Medline].
Baffy G, Boyle JM. Association of Zollinger-Ellison syndrome with pancreatitis: report of five cases. Dig Dis Sci. 2000 Aug. 45(8):1531-4. [Medline].
Berger AC, Gibril F, Venzon DJ. Prognostic value of initial fasting serum gastrin levels in patients with Zollinger-Ellison syndrome. J Clin Oncol. 2001 Jun 15. 19(12):3051-7. [Medline].
Bloomfeld R, Bornstein J, Jowell P. A report of a gastrinoma localized preoperatively by endoscopic ultrasound only and a review of the approach to imaging in Zollinger- Ellison syndrome. Dig Dis. 1999. 17(5-6):316-8. [Medline].
Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. 2001 Jun. 81(3):527-42. [Medline].
Cadiot G, Jais P, Mignon M. Diagnosis of Zollinger-Ellison syndrome. From symptoms to biological evidence. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S147-52. [Medline].
Campana D, Piscitelli L, Mazzotta E. Zollinger-Ellison syndrome. Diagnosis and therapy. Minerva Med. 2005 Jun. 96(3):187-206. [Medline].
Chien RN, Chen TC, Chiu CT. Primary calcified gastrinoma of the liver. Dig Dis Sci. 2001 Feb. 46(2):370-5. [Medline].
Cisco RM, Norton JA. Surgery for gastrinoma. Adv Surg. 2007. 41:165-76. [Medline].
Corleto VD, Annibale B, Gibril F. Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?. Aliment Pharmacol Ther. 2001 Oct. 15(10):1555-61. [Medline].
Desir B, Poitras P. Oral pantoprazole for acid suppression in the treatment of patients with Zollinger-Ellison syndrome. Can J Gastroenterol. 2001 Dec. 15(12):795-8. [Medline].
Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):807-17. [Medline].
Ellison EC, Sparks J. Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors?. Am J Surg. 2003 Sep. 186(3):245-8. [Medline].
Fernandez JA, Robles R, Marin C. Role of liver transplantation in the management of metastatic neuroendocrine tumors. Transplant Proc. 2003 Aug. 35(5):1832-3. [Medline].
Gibril F, Chen YJ, Schrump DS. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2003 Mar. 88(3):1066-81. [Medline].
Gibril F, Jensen RT. Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors. Yale J Biol Med. 1997 Sep-Dec. 70(5-6):509-22. [Medline].
Gibril F, Lindeman RJ, Abou-Saif A. Retained gastric antrum syndrome: a forgotten, treatable cause of refractory peptic ulcer disease. Dig Dis Sci. 2001 Mar. 46(3):610-7. [Medline].
Gibril F, Reynolds JC, Lubensky IA. Ability of somatostatin receptor scintigraphy to identify patients with gastric carcinoids: a prospective study. J Nucl Med. 2000 Oct. 41(10):1646-56. [Medline].
Gibril F, Venzon DJ, Ojeaburu JV. Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form. J Clin Endocrinol Metab. 2001 Nov. 86(11):5282-93. [Medline].
Hung PD, Schubert ML, Mihas AA. Zollinger-Ellison Syndrome. Curr Treat Options Gastroenterol. 2003 Apr. 6(2):163-170. [Medline].
Imamura M, Komoto I, Ota S. Changing treatment strategy for gastrinoma in patients with Zollinger-Ellison syndrome. World J Surg. 2006 Jan. 30(1):1-11. [Medline].
Jensen RT, Gibril F. Somatostatin receptor scintigraphy in gastrinomas. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S179-85. [Medline].
Kohan E, Oh D, Wang H, et al. Duodenal bulb mucosa with hypertrophic gastric oxyntic heterotopia in patients with Zollinger Ellison syndrome. Diagn Ther Endosc. 2009. 2009:298381. [Medline]. [Full Text].
Lew EA, Pisegna JR, Starr JA. Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterology. 2000 Apr. 118(4):696-704. [Medline].
McIntyre TP, Stahlfeld KR, Sell HW Jr. Gastrinoma. Am J Surg. 2002 Jun. 183(6):666-7. [Medline].
Metz DC, Forsmark C, Lew EA. Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Am J Gastroenterol. 2001 Dec. 96(12):3274-80. [Medline].
Metz DC, Soffer E, Forsmark CE. Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion. Am J Gastroenterol. 2003 Feb. 98(2):301-7. [Medline].
Metz DC, Starr JA. A retrospective study of the usefulness of acid secretory testing. Aliment Pharmacol Ther. 2000 Jan. 14(1):103-11. [Medline].
Mignon M, Cadiot G. Natural history of gastrinoma: lessons from the past. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S98-103. [Medline].
Mussig K, Wehrmann M, Horger M, et al. Lymph node gastrinoma in multiple endocrine neoplasia type 1 - a diagnostic challenge. Exp Clin Endocrinol Diabetes. 2008 Oct. 116(9):554-7. [Medline].
Ng T, Maziak DE, Shamji FM. Esophageal perforation: a rare complication of Zollinger-Ellison syndrome. Ann Thorac Surg. 2001 Aug. 72(2):592-3. [Medline].
Norton JA. Gastrinoma: advances in localization and treatment. Surg Oncol Clin N Am. 1998 Oct. 7(4):845-61. [Medline].
Norton JA. Surgery and prognosis of duodenal gastrinoma as a duodenal neuroendocrine tumor. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):699-704. [Medline].
Norton JA. Surgical treatment and prognosis of gastrinoma. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):799-805. [Medline].
Norton JA, Alexander HR, Fraker DL. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg. 2001 Oct. 234(4):495-505; discussion 505-6. [Medline].
Norton JA, Alexander HR, Fraker DL. Possible primary lymph node gastrinoma: occurrence, natural history, and predictive factors: a prospective study. Ann Surg. 2003 May. 237(5):650-7; discussion 657-9. [Medline].
Norton JA, Fraker DL, Alexander HR. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med. 1999 Aug 26. 341(9):635-44. [Medline].
Norton JA, Jensen RT. Current surgical management of Zollinger-Ellison syndrome (ZES) in patients without multiple endocrine neoplasia-type 1 (MEN1). Surg Oncol. 2003 Aug. 12(2):145-51. [Medline].
Norton JA, Kivlen M, Li M. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 2003 Aug. 138(8):859-66. [Medline].
Odelowo OO, Nidiry JJ, Zulu SH. Primary lymph node gastrinoma: a case report. J Natl Med Assoc. 2003 Feb. 95(2):168-71. [Medline].
Orloff SL, Debas HT. Advances in the management of patients with Zollinger-Ellison syndrome. Surg Clin North Am. 1995 Jun. 75(3):511-24. [Medline].
Ramdani A, Mignon M, Samoyeau R. Effect of pantoprazole versus other proton pump inhibitors on 24-hour intragastric pH and basal acid output in Zollinger-Ellison syndrome. Gastroenterol Clin Biol. 2002 Apr. 26(4):355-9. [Medline].
Roy PK, Venzon DJ, Feigenbaum KM. 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 May. 80(3):189-222. [Medline]. [Full Text].
Roy PK, Venzon DJ, Shojamanesh H. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore). 2000 Nov. 79(6):379-411. [Medline].
Saijo F, Naito H, Funayama Y. Octreotide in control of multiple liver metastases from gastrinoma. J Gastroenterol. 2003. 38(9):905-8. [Medline].
Strader DB, Doppman DL, Orbuch M. Functional localization of pancreatic endocrine tumors. Mignon M, Jensen RT, eds. Endocrine Tumors of the Pancreas: Recent Advances in Research and Management. Basel, Switzerland: S Karger AG; 1995. Vol 23: 282-97.
Tartaglia A, Bianchini S, Vezzadini P. Biochemical diagnosis of gastroenteropancreatic endocrine tumors. Minerva Med. 2003 Feb. 94(1):1-7. [Medline].
Termanini B, Gibril F, Reynolds JC. Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. Gastroenterology. 1997 Feb. 112(2):335-47. [Medline].
Zimmer T, Scherubl H, Faiss S. Endoscopic ultrasonography of neuroendocrine tumours. Digestion. 2000. 62 Suppl 1:45-50. [Medline].
Zogakis TG, Gibril F, Libutti SK. Management and outcome of patients with sporadic gastrinoma arising in the duodenum. Ann Surg. 2003 Jul. 238(1):42-8. [Medline].