Correspondence

Surgery to Cure the Zollinger–Ellison Syndrome

N Engl J Med 1999; 341:2096-2097December 30, 1999

Article

To the Editor:

Norton et al. (Aug. 26 issue)1 report 10-year surgical-cure rates of 34 percent in 123 patients with sporadic gastrinomas and 0 percent in 28 patients with multiple endocrine neoplasia type 1. The authors' objective was limited to the elimination of discoverable gastrinoma, as determined by measurements of serum gastrin, secretin tests, and imaging studies. A preferable objective would have been to eliminate reliably the aggressive peptic ulcer disease and diarrhea that characterize the Zollinger–Ellison syndrome by suppressing acid secretion with the use of proton-pump–inhibitor therapy.2

Norton et al. provide little information on morbidity or the functional outcome after surgery — for example, the number of patients who still required drug treatment. At 10 years, the rates of cure, or disease-free survival, were much lower than the rates of disease-specific survival (95 percent in the patients with sporadic gastrinomas and 85 percent in those with multiple endocrine neoplasia type 1). This good outcome despite the failure to achieve a cure with surgery can just as readily be achieved by treatment with a proton-pump inhibitor alone.2

We need a clearer understanding of the true therapeutic benefit of surgery in patients with the Zollinger–Ellison syndrome and of when to avoid surgery. Many patients cannot be cured surgically, and among those who are, only 40 percent no longer require drug treatment postoperatively.2

Basil I. Hirschowitz, M.D.
University of Alabama at Birmingham, Birmingham, AL 35294-0007

2 References

1. 1

   Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999;341:635-644
   Full Text | Web of Science | Medline

2. 2

   Hirschowitz BI. Clinical course of nonsurgically treated Zollinger-Ellison syndrome. Front Gastrointest Res 1995;23:360-371
   

Author/Editor Response

The authors reply:

To the Editor: We thank Dr. Hirschowitz for his comments. There are two distinct clinical problems with the Zollinger–Ellison syndrome. First, the hypersecretion of gastric acid causes severe peptic ulcer disease and diarrhea, as Dr. Hirschowitz points out. These symptoms can be effectively controlled with antisecretory drugs in all patients except those few who cannot or will not take oral medications.1 However, these drugs have no effect on the second problem, which is tumor growth.

In our study of 212 patients with the Zollinger–Ellison syndrome,2 31 percent of the patients died over a mean follow-up period of 14 years (range, 0.1 to 31 years); half the deaths were related to tumor growth, and none to hypersecretion of gastric acid. At present, there is no established antitumor treatment except effective surgery. In our study, the morbidity and mortality associated with surgery remained less than 12 and 1 percent, respectively, as we reported previously.3 In our study comparing the outcome of medical treatment alone with that of surgical resection, surgery did not prolong survival (P=0.085)4; however, surgery decreased the probability of subsequent metastasis (P<0.003), which is the main prognostic factor for tumor-related death.2

Surgery also has important effects on the requirement for antisecretory drugs. We are still determining the exact proportion of patients cured who will be able to stop drug therapy; in our preliminary analysis, it is 40 to 50 percent.5 With curative resection, there is a 75 percent decrease in basal acid output and a 44 percent decrease in maximal acid output in response to pentagastrin, and among patients continuing to require antisecretory-drug treatment, the majority require a low dose of an antisecretory agent, usually a histamine H₂-receptor antagonist. For the reasons reviewed above and because surgery can cure a substantial proportion of these patients, as demonstrated by our study, we recommend surgery in patients with the sporadic form of the Zollinger–Ellison syndrome.

Jeffrey A. Norton, M.D.
University of California, San Francisco, San Francisco, CA 94121-1598

Fathia Gibril, M.D.
Robert T. Jensen, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-1804

5 References

1. 1

   Metz DC, Jensen RT. Advances in gastric antisecretory therapy in Zollinger-Ellison syndrome. Front Gastrointest Res 1995;23:240-257
   

2. 2

   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;17:615-630
   Web of Science | Medline

3. 3

   Norton JA, Doppman JL, Jensen RT. Curative resection in Zollinger-Ellison syndrome: results of a 10-year prospective study. Ann Surg 1992;215:8-18
   CrossRef | Web of Science | Medline

4. 4

   Fraker DL, Norton JA, Alexander HR, Venzon DJ, Jensen RT. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann Surg 1994;220:320-330
   CrossRef | Web of Science | Medline

5. 5

   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;102:767-778
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Michelle L. Li, Jeffrey A. Norton. (2001) Gastrinoma. Current Treatment Options in Oncology 2:4, 337-346
   CrossRef