Background
A gastrinoma is a gastrin-secreting tumor usually found in the pancreas or duodenum. [1, 2] Duodenal wall tumors are frequently small and multiple. Sporadic tumors occurring in the pancreas tend to be solitary and have a greater malignant potential as compared to duodenal gastrinomas. [3]
More than 80% of gastrinomas arise within the triangle defined as the confluence of the cystic and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially.
Rarely, primary tumors also occur in a variety of ectopic sites, including the body of the stomach, jejunum, peripancreatic lymph nodes, [1] splenic hilum, omentum, liver, gallbladder, common bile duct, and the ovary.
Over 50% of gastrinomas are malignant and can metastasize to the regional lymph nodes and the liver. One fourth of gastrinomas are related to multiple endocrine neoplasia (MEN) type I and are associated with hyperparathyroidism and pituitary adenomas. These MEN I associated tumors have been observed to occur at an earlier age than sporadic tumors and often follow a more benign course.
The triad of nonbeta islet cell tumors of the pancreas (gastrinomas), hypergastrinemia, and severe ulcer disease was described by Zollinger and Ellison in 1955, hence the eponym Zollinger-Ellison syndrome (ZES).
Pathophysiology
Enormous secretion of gastrin from the tumor cells leads to hyperplasia of the fundic parietal cells and increased basal acid secretion. This results in severe ulcer disease. Ulceration may extend into the small intestine. The acidic content of the small intestine causes the release of secretin, which is responsible for the diarrhea, in part, caused by the outpouring of water and bicarbonate from the pancreas and small intestine.
A small study by Kohan et al describes duodenal bulb mucosa with hypertrophic heterotopia in patients with Zollinger-Ellison syndrome (ZES). [4] The investigators evaluated the incidence of duodenal gastric oxyntic hypertrophic heterotopia in 7 patients with ZES over an average period of 5 years. The patients underwent endoscopic examinations with methylene blue staining and biopsy of the gastric and duodenal mucosa every 3-6 months.
Of the 7 patients with ZES and an intact stomach and duodenum, 2 had no evidence of duodenal mucosal hypertrophic heterotopia, but 5 did, in whom bowel mucosal biopsies revealed patchy replacement of the surface epithelium by gastric-type epithelium with hypertrophic oxyntic glands in the lamina propria. [4] In addition, patients with gastric oxyntic hypertrophic heterotopia had higher levels of average serum gastrin and basal acid output levels than those without gastric oxyntic hypertrophic heterotopia, a finding that Kohan et al suggest that not only could the hypertrophic and heterotopic gastric mucosa result from increased gastrin levels but that an increased incidence of postbulbar ulcers may result in affected patients. [4]
Epidemiology
United States data
Gastric carcinoids or neuroendocrine tumors are reported to account for an estimated 0.6-2% of detected gastric polyps. [5] In the United States, the incidence of these tumors has greatly increased over the past several decades. [5]
International data
The true incidence of Zollinger-Ellison syndrome (ZES) is not known. ZES constitutes 0.1% or more of the cases of peptic ulcer disease. Although rare, gastrinomas are the most common pancreatic islet cell tumors.
In a 2013 German epidemiologic review of 2 time periods (1976-1988 and 1998-2006) comprising more than 10.8 million people, there was an approximately 5-fold increase in the cases of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) between 1976 and 2006, accompanied by a change in the anatomic distribution. [6]
Sex- and age-related demographics
Gastrinomas are more common in males than in females, with ratios from 1.5:1 to 2:1.
Although gastrinomas can occur at any age, the initial clinical manifestation usually appears in people aged 30-50 years.
Prognosis
Patients with hepatic metastases may have a remaining life span of less than 1 year; the 5-year survival rate is 20-30%.
In patients with localized disease or metastasis to local lymph nodes without liver metastasis, the 5-year survival rate may be 90%.
Surgical resection of localized disease leads to a complete cure without any recurrence in 20-25% of patients with gastrinomas.
Morbidity/mortality
With the advent of anti-ulcer medications, the number of deaths secondary to ulcer complications has decreased significantly. The primary determinants of survival for patients with gastrinomas are the size of the primary tumor and the occurrence of tumor metastasis.
