Gastrinomas: Medical or Surgical Treatment

Abstract

This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor (gastrinoma). It concentrates on the status at present but also briefly reviews the changes over time in treatment approaches. Generally, surgical and medical therapy are complementary today; however, in some cases, such as patients with ZES and multiple endocrine neoplasia type 1, the treatment approach remains controversial.

Keywords: Acid secretion; Gastrinoma; Multiple endocrine neoplasia type 1; Neuroendocrine tumor; Proton pump inhibitors; Zollinger-Ellison syndrome.

Figure 1

Extent of disease effect on survival and acid hypersecretion in ZES patients. Panel A. Shown are results from 212 ZES patients prospectively followed.. Panel B. Results are from 205 ZES patients without previous gastric acid recuing surgery. Each point represents data from one patient. The dotted line is the upper limit of normal. The mean ± SEM is shown for each. Data from Refs , and .

Figure 2

Disease free survival post-surgery (enucleation, resection) in patients with ZES with or without MEN1. Data are from 123 patients with sporadic ZES and 28 patients with MEN1/ZES. Patents were treated by a fixed protocol involving enucleation of tumor, local tumor resection, and distal pancreatectomy where indicated, but without Whipple resections. Adapted from Norton JA, Fraker DL, Alexander HR et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999;341:635–644; with permission.

Figure 3

Effect of curative gastrinoma resection on basal acid hypersecretion(BAO) (Panel A) and effect of parathroidectomy (Panel B) on basal acid hypersecretion, fasting serum gastrin levels and responsiveness to antisecretory drugs in MEN1/ZES patients with hyperparathyroidism. Panel A. Shown are results from 20 patients surgically rendered disease-free. Mean preoperative BAO was 39 mEq/hr, and the mean serum fasting gastrin 1020 pg/ml (nl<100). By 3–6 mos. postoperatively BAO had decreased 75% and remained unchanged. Dotted lines show upper limit of normal in these studies. Adapted from Pisegna JR, Norton JA, Slimak G, et al. Effects of curative resection on gastric secretory function and antisecretory drug requirement in the Zollinger-Ellison syndrome. Gastroenterology 1992;102:767–778; with permission. Panel B. Shown are results from 10 consecutive MEN1/ZES patients with hyperparathyroidism with basal acid output, fasting serum gastrin levels(FSG), and sensitivity to antisecretory drugs (Histamine H2 receptor antagonists [], determined before and a different times post parathyroidectomy. All patients except patient 4 became normocalcemic post parathyroidectomy. Post parathyroidectomy 9/10 (90%) had a decrease in BAO, and 7/10 showed a decrease in FSG including to normal levels in 2 patients. Acid responsiveness was expressed as the percent of the BAO at a given time after taking the same dose of histamine H₂ receptor antagonist. In each of the three patients studied the given dose of histamine H₂ receptor antagonist caused greater acid suppression post parathyroidectomy. Adapted from Norton JA, Cornelius MJ, Doppman JL et al. Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome and multiple endocrine neoplasia Type I: A prospective study. Surgery 1987;102:958–966; with permission.

Figure 4

Results of performing a duodenotomy (Panel A) on disease-free status and results of surgical exploration for possible cure in ZES patients with or without positive pre-operative imaging studies (Panel B). Panel A. Effect of duodenotomy(DUODX) on disease free-status in 142 patients with ZES without MEN1. With DUODX, gastrinomas were found in 98%, duodenal gastrinomas in 62%, and the cure rate postoperatively was 65% compared with patients without DUODX (p<0.01) in whom gastrinomas were found in 76%, 18% had duodenal gastrinomas found and 44% were cured post resection. Modified and drawn from data in . Panel B. Surgical results from 117 patients with sporadic ZES with positive imaging are compared to results in 58 patients with sporadic ZES with negative preoperative imaging. Postoperatively 63% of the patients with negative imaging were disease free postoperatively, whereas it was seen in 54% with positive imaging and at a 20-yr follow-up, the negative imaging patients had a better survival (71% vs 58%), and better disease related survival (88% vs 73%, [p=0.15]). Adapted from Norton JA, Fraker DL, Alexander HR et al. Value of surgery in patients with negative imaging and sporadic zollinger-ellison syndrome. Ann Surg 2012;256:509–517; with permission.

Figure 5

Imaging results in a patient with a panNET obstructing the proximal portal vein. Panel A shows a coronal planar view and Panel B shows a transverse view of the CT scan. The label PET shows the location of a panNET obstructing the proximal portal vein and with the development of extensive collateral veins. This patient had the tumor and a portion if the portal vein resected with venous reconstruction. This patient is representative af a subgroup of gastrinomas and other PanNET that are thought by many to be unresectable because of the vascular involvement, however a recent study shows most are resectable. Adapted from Norton JA, Harris EJ, Chen Y et al. Pancreatic endocrine tumors with major vascular abutment, involvement, or encasement and indication for resection. Arch Surg 2011;146:724–732; with permission.

Figure 6

Survival of different groups of MEN1/ZES patients. Data are for 81 MEN1/ZES patients of which 17 were in group 1(all panNETs imaged preoperative <2.5 cm diameter-no surgery); and Group 3 (n=8) with diffuse liver metastases and no surgical resection. Group 2 consisted of 17 patients in Group 2A with a single panNET (2.5–6 cm in diameter) and Group 2B (n=31) with two or more lesions >2.5 cm, who underwent laparotomy. Group 1, 2A and 2B had similar 15-year survival rates of 89–100%, which was better than patients with diffuse liver metastases in Group 3 (52%). This study concluded that patients with small panNETs<2.5cm with MEN1/ZES can be followed without surgery (15-yr survival=100%) and that patients with larger lesions should have them resected if possible . Adapted from Norton JA, Alexander HR, Fraker DL et al. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg 2001;234:495–506; with permission.