Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome (original) (raw)
Related papers
Zollinger-Ellison syndrome: Revelation of the gastrinoma triangle
Zollinger-Ellison syndrome is a complex condition in which one or more tumors form in the patient’s pancreas or upper duodenum. These tumors, called gastrinomas, secrete excessive amounts of gastrin, and almost all develop ulcers. The vast majority of gastrinomas are present within the “gastrinoma triangle,” which is composed of the porta hepatis, duodenal sweep, and pancreatic head. As surgery remains the treatment of choice, localization of the primary lesion is often challenging but essential. We present a 50-year-old man with a tentative diagnosis of Zollinger-Ellison syndrome. His In-111 pentetreotide scan, fused onto a Tc-99m abdomen image, revealed an avid lesion adjacent to the duodenal loop. Operative resection was performed, and a primary pancreatic gastrinoma was diagnosed by immunohistochemical staining. The neuroendocrine tumors have somatostatin receptors upon them. Therefore, a penteteotide scan, using In-111 radiolabelled somatostatin analogues, is the current technique of choice. This dual-isotope display permits a visual perception of anatomic landmarks around the lesion.
Non-G cell gastrin-producing tumours of the pancreas
Virchows Archiv. B: Cell pathology, 1972
Three pancreatic gastrinomas, associated with the Zollinger-Ellison syndrome, were examined by staining, cytochemical and immunohistochemical, and ultrastructural techniques in order to compare the properties of their storage granules with those of normal gastrin-producing cells. In all three cases, despite their positive anti-gastrin fluorescence, there was only a partial correspondence of properties with those of the pyloric G cell or the pancreatic islet D cell. It is concluded that the available evidence supports the origin of pancreatic gastrinomas from the gastrin-secreting D cell of the normal islet. The relationship of the "small cell" of the normal islet to the D cell on the one hand, and to the gastrinoma cell on the other, has not been determined.
Annals of Surgery, 1986
In 1982, a prospective study was initiated of 52 consecutive patients ts with proven Zollinger-Ellison syndrome (ZES), involving surgical exploration with the goal of removing the gastrinoma after an extensive protocol to localize the tumor. Each patient underwent ultrasound, computed tomography (CT) with oral/ intravenous (IV) contrast, and selective arteriography. Eighteen patients had metastatic disease identified by imaging studies and confirmed by percutaneous biopsies, and two patients had multiple endocrine neoplasia type I (MEN-I) with negative imaging studies; therefore, these 20 patients did not undergo laparotomy. Each of the remaining 32 patients (3 with MEN-I and positive imaging studies) underwent laparotomy, and gastrinomas were removed in 20 patients. Preoperative ultrasound localized tumors in 20% of patients, CT in 40%, arteriography in 60%, and any of the modalities in 70% of patients. Infusion CT and arteriography were 100% specific. In 18 patients with either negative imaging (17) or false-positive imaging (1 ultrasound), gastrinomas were found and removed in six patients (33%). Twenty-four gastrinomas were found in 20 patients at laparotomy: eight in lymph nodes around the pancreatic head, four in the pancreatic head, one in the pancreatic body, three in the pancreatic tail, three in the pyloric channel, one in the duodenal wall, two in the jejunum at the ligament of Treitz, one in the ovary, and multiple liver metastases in one patient. If one excludes patients with MEN-I or liver metastatic disease, 12/28 (43%) of patients were biochemically "cured" immediately after operation. This result decreased to 7/23 (30%) with greater than 6 months follow-up. No patients with gastrinomas resected have developed recurrent gastrinoma on follow-up imaging studies (longest follow-up: 4 years). This study indicates that 95% of metastatic gastrinoma can be diagnosed before operation and that, by a combination of careful imaging studies and thorough exploration at surgery, 30% of patients with gastrinomas may be curable. I N 1954, ZOLLINGER AND ELLISON first described a syndrome associated with severe peptic ulcer diathesis and pancreatic tumors.' The syndrome would later bear their name, and their initial treatment, total
Sporadic Duodenal Gastrinoma causing Zollinger Ellison Syndrome – A Rare Case Report
International Journal of Contemporary Medical Research [IJCMR], 2019
Introduction: Gastrinoma is a rare gastrin secreting neuroendocrine tumor. Clinical manifestations are nonspecific gastrointestinal (GI) symptoms or as Zollinger Ellison Syndrome(ZES) which often delays the diagnosis in majority of patients. Hence a high clinical index of suspicion is warranted in patients who present with nonspecific GI symptoms to rule out gastrinoma. Case report: We report a case of 55 year old female who presented with long standing dyspepsia and chronic diarrhoea and was diagnosed with Sporadic Duodenal Gastrinoma on detailed evaluation. She was treated with surgical resection and pathologically diagnosed as well differentiated neuroendocrine tumor, Gastrinoma-grade I after IHC analysis. Patient was relieved of her symptoms and became eugastrinemic after surgery. Conclusion: Any patient with refractory dyspepsia associated with long standing non specific abdominal symptoms should be evaluated for Gastrinoma and treated accordingly to avoid misdiagnosis and complications in the long run.
International Surgery Journal, 2021
Neuroendocrine tumors of the gastrointestinal tract are rare. Existence of primary nodal gastrinoma is rare and mired with controversies as to whether it is a primary nodal disease or a metastasis to a lymphnode from primary in the pancreas or gastrointestinal tract. They usually occur in the nests of embryonic tissue and lymph nodes in the region of gastrinoma triangle. Rarely the nodes may be located outside the Passaro triangle. Here we report one such case of gastrinoma with only discernable nodal disease located outside the confines of the conventional gastrinoma triangle and discuss the relevant available literature.
World Journal of Surgery, 1993
Studies have shown that the duodenum is a more common site (30-40%) of primary gastrinomas than previously reported. These tumors are often occult to conventional exploration, and their detection requires duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Furthermore, tumors as smaU as 1 to 2 mm may be associated with iymph node metastases. Seven patients with duodenal gastrinomas treated during a 2-year period are reported. Four had sporadic ZoUinger-Ellison syndrome (ZES), and three had multiple endocrine neoplasia type I (MEN-I) syndrome. Ail seven patients had malignant duodenal gastrinomas as proved by metastatic lymph nodes and in one case a large liver metastasis as well. Local excision of the tumor, iymph node excisions, and in one case liver Iobectomy resulted in eugastrinemia in the 4 with sporadic ZES. Two of the three with MEN-I were also eugastrinemic after similar procedures, with the addition of distal pancreatectomy. Duodenotomy is considered an essential procedure in sporadic ZES patients when no pancreatic tumor is found and in ail MEN-I/ZES patients, regardless of the pancreatic findings. Regional lymph node excisions are essential when a duodenal tumor has been found. At one time it was assumed that most patients with Zollinger-Ellison syndrome (ZES) had malignant pancreatic tumors with metastases that precluded a curative surgical resection. Therefore nearly ail patients were treated by total gastrectomy with the exception of a few with primary extrapancreatic tumors [1, 2]. Once drugs became available that adequately controlled gastric acid hypersecretion, more emphasis was placed on identifying ZES patients who were potentially curable by tumor resection. Currently, it is estimated that up to 40% of patients with sporadic ZES have tumors that can be successfully resected [3]. These patients have primary tumors arising in the pancreas or duodenum with or without regional lymph node spread but no liver metastases. However, during the past decade, as many as 40% of patients proved biochemically to have ZES who have undergone exploration have had negative findings [4]. As a result, these patients were subsequently treated with drug therapy or had palliative surgical procedures such as selective vagotomy or even total gastrectomy. Furthermore, in most centers, multiple endocrine neoplasia type I (MEN-I)/ZES patients have been treated by drugs without
World Journal of Surgery, 2004
Enterochromaffin-like (ECL) tumors are documented in patients with hypergastrinemia secondary to chronic atrophic gastritis or with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1 (ZES-MEN-1). In patients with ECL tumors and atrophic gastritis, normogastrinemia after antrectomy has resulted in resolution, regression, or stabilization of ECL tumors. The natural history of ECL tumors associated with ZES-MEN-1 following normalization of gastrin levels after gastrinoma resection has not been previously reported. The purpose of this study was to determine the course of ECL tumors in patients with ZES-MEN-1 following normalization of serum gastrin levels after gastrinoma resection. Two patients with ZES-MEN-1 had biopsy-proven ECL tumors on endoscopic evaluation. They then underwent surgical exploration that included distal pancreatectomy, enucleation of pancreatic head tumors, duodenotomy with excision of submucosal tumors, and peripancreatic lymphadenectomy. Gastric ECL tumors larger than 1.0 cm were locally excised. Patients underwent long-term follow-up with biochemical and endoscopic surveillance. Normogastrinemia was achieved and sustained following gastrinoma resection in two patients with ZES-MEN-1. Periodic endoscopic surveillance over a 6-year period showed complete resolution of the ECL tumors. The development of ECL tumors associated with ZES-MEN-1 is multifactorial. Studies identified a genetic influence on tumor growth with loss of heterozygosity at the MEN-1 gene locus in ECL tumors. The resolution of ECL tumors in ZES-MEN-1 patients who are normogastrinemic indicates that an elevated gastrin level is a primary initiator for development of these tumors. Therefore both genetic defects and hypergastrinemia are causative agents. Normalization of serum gastrin levels is critical for the prevention of aggressive forms of ECL tumors.
Gastrinomas: Medical or Surgical Treatment
Endocrinology and metabolism clinics of North America, 2018
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.
The Zollinger–Ellison Syndrome and Mismeasurement of Gastrin
Gastroenterology, 2011
Zollinger-Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of gastrin in plasma. METHODS: We examined the accuracy of commercial kits to measure gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or falsehigh concentrations of gastrin. RESULTS: Failure to diagnose gastrinomas has serious consequences. Four kits found false-low concentrations of gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only gastrin-17. Three kits found false-high concentrations of gastrin, because the reagents had increased reactions to sulfated gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of gastrin. CONCLUSIONS: Seven of 12 tested commercial kits inaccurately measure plasma concentrations of gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of gastrinoma based on lack of specificity of assays for gastrin results in ineffective or inappropriate therapy for patients with ZES.