Patients with Zollinger-Ellison syndrome who also have multiple endocrine neoplasia type 1 usually follow an indolent clinical course that rarely results in disease-related death, unlike those who have the sporadic form of the syndrome, Dr. Maneesh H. Singh and his colleagues reported in the November issue of Clinical Gastroenterology and Hepatology.
This finding, from a retrospective study of 49 patients treated at a single tertiary care center since 1994, argues against surgery for the estimated 25%-50% of Zollinger-Ellison syndrome (ZES) patients who have multiple endocrine neoplasia type 1 (MEN-1). "Given these results, we support a conservative approach to disease management ... focusing on symptom control with pharmacologic agents," the investigators wrote (Clin. Gastroenterol. Hepatol. 2012 Aug. 20 [doi:10.1016/j.cgh.2012.08.014]).
Early and aggressive surgery is recommended for sporadic ZES because it improves survival and can be curative. But surgery’s role in those with MEN-1 has been contentious because it doesn’t appear to improve survival in these patients. Only the most radical surgery, which carries a 40% complication rate, appears to be curative in those with MEN-1,reported Dr. Singh and his colleagues at the Hospital of the University of Pennsylvania, Philadelphia.
Because ZES is such a rare disorder, this follow-up study of 34 ZES patients who underwent surgery and 15 who did not "represents one of the largest long-term studies of surgical outcomes from a tertiary care hospital" conducted to date, they wrote.
The study subjects’ mean age at diagnosis was 47 years. The mean duration of follow-up from the time of diagnosis was 7 years, ranging from 0 to 5 years for 19 patients, from 5 to 10 years for 10, from 10 to 20 years for 15, and for more than 20 years for 5.
Of the 15 patients who did not undergo surgery, 5 declined after a discussion of the risks and benefits of the procedure, 2 because they had no lesions greater than 2 cm in diameter in imaging studies, 3 because of extensive liver involvement that was deemed unresectable, and 5 because they had unrelated comorbidities that made them poor surgical candidates.
A total of 33 subjects had sporadic ZES, while the other 16 had associated MEN-1. In the latter group, there was no significant difference between the median survival for the nine who underwent surgery (22.4 years) and for the seven who did not (25.5 years).
Standard gastrinoma resection with duodenotomy did not achieve a cure in any of the ZES patients with accompanying MEN-1.
In contrast, surgery improved both disease-related and all-cause mortality in the sporadic form of the disorder, and surgery was deemed curative in 6 (32%) of the patients with sporadic ZES.
None of the patients with MEN-1died of progressive ZES, compared with 28 (85%) of the patients with sporadic ZES. Thus, the form of the disease associated with MEN-1 appears to have a much more benign course than the sporadic form, Dr. Singh and his associates reported.
ZES associated with MEN-1 also tends to have an earlier symptom onset than does sporadic ZES, but because it is more indolent, the mean age at death was nearly identical between the two groups.
In this study, ZES patients with MEN-1had rates of liver involvement at diagnosis and rates of later liver metastases that were similar to those of patients with sporadic ZES. But again, this did not reduce their survival as it did with sporadic ZES.
This finding suggests that there may be a fundamental difference in the basic tumor biology between the two forms of the disease. It supports the theory that sporadic ZES is "a rapidly progressive, malignant form of gastrinoma that defies prediction and advocates for swift surgical intervention," the researchers wrote.
They reported no industry support for this study and no other financial conflicts.
