All you need to know about gastrinoma today | Gastrinoma and Zollinger-Ellison syndrome: A thorough update.

Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 µg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.

A germline c.1546dupC MEN1 mutation in an MEN1 family: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors. PATIENT CONCERNS: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma. DIAGNOSES: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM_130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1. INTERVENTION: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism. OUTCOMES: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age. LESSONS: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors.

[Neuroendocrine tumors of the gastrointestinal tract]. / Neuroendokrine Tumoren des Gastrointestinaltraktes.

Neuroendocrine tumors (NET) of the gastrointestinal tract are rare and constitute 0.5-1% of all human malignancies. Based on their endocrine secretion, they are functional active or inactive. They are further classified into fore-, mid-, or hindgut tumors. The recently published WHO-classification grouped the tumors according to their tumor size, angioinvasion and Ki-67 index. NET are mainly diagnosed in an advanced tumor stadium because of the paucity of symptoms or when symptoms occur due to endocrine hypersecretion. NET are diagnosed serologically by their hormone secretion and by measuring Chromogranin A levels. They are further detected by CT, MRI or endoscopy including endoscopic ultrasound. Many NET have somatostatin receptors on their surface and can be diagnosed by somatostatin receptor scintigrafy with high sensitivity and specificity. Only by surgery NET can be cured. Because many tumors are diagnosed late, medical options are of utmost importance. Symptom control can be established by somatostatin analogues and interferon-ot. Diazoxid can further inhibit insulin secretion, proton pump inhibitors are the therapy of choice for acid hypersecretion in Zollinger-Ellison syndrome. Advanced neuroendocrine cancers can be treated with chemotherapy. Recently, radio receptor therapy with 90Y-DOTA Octreotid and 177Lu-DOTA Octreotate was established in advanced neuroendocrine cancers and is further evaluated in studies. Net of the gastrointestinal tract should be treated in a multidisciplinary approach with gastroenterologists, surgeons and experts in nuclear medicine. An overview about epidemiology, clinical features, diagnostic methods and therapy of NET of the gastrointestinal tract will is provided in this article.

Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma.

The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control). We compared results of the calcium injection test with those of the secretin test and the selective arterial secretagogue injection (SASI) test. The SASI test with secretin was performed in 24 of 26 patients with hypergastrinemia, including 22 of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The secretin test was negative in 3 of 21 patients with ZES (14%). Either the secretin test or the SASI test was positive in 22 of 23 patients (96%). The calcium injection test was administered to 12 patients in the HG group and 4 controls. The HG group showed significantly higher serum gastrin levels than those of the control group in the calcium injection test. Eight of 10 ZES patients (80%) had a positive calcium injection test. We could diagnose gastrinomas in 100% of ZES patients by either the calcium injection test or the secretin test. We have thus confirmed the efficacy of the intravenous calcium injection test in the diagnosis of gastrinoma. The calcium injection test could become an adjunct in the diagnosis of gastrinoma, which often goes undetected with routine testing.

Long-term follow up of patients with Zollinger-Ellison syndrome (ZES).

We have followed 14 patients with the Zollinger-Ellison syndrome for a median period of 9 years. All patients have suffered from peptic ulcer disease and six of the 14 have had complications such as bleeding or perforated ulcer. Almost half the patients have had diarrhoea as a dominant symptom and 4 patients suffered from multiple endocrine neoplasia. Before 1978, the year when the H2-receptor antagonists were introduced, the majority of the patients were operated with total gastrectomy. After that year there has been no need for gastrectomies, but all but two patients have undergone an explorative laparotomy. We have been able to localize the gastrinoma in 9 of 12 operated patients; in 7 cases it was localized within the gastrinoma triangle. Three of the patients are considered to have been cured after surgery. Eight patients have needed adjuvant acid-reducing medical therapy. Five of these have been failures to high doses of H2-receptor antagonists and have been successfully treated with omeprazole. Five patients have died during the follow-up period and death in two of these cases was related to tumor progression.