Diagnosis and Treatment of Gastrinomas in Multiple Endocrine Neoplasia Type 1 (MEN-1) (original) (raw)
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Gastroenterology, 2005
The identification of precursor lesions has a great impact on the understanding of tumorigenesis. Precursor lesions of endocrine tumors are known to occur in the setting of the MEN1 syndrome. The aim of this study was to test the hypothesis that MEN1-associated duodenal gastrinomas originate from diffuse preneoplastic gastrin cell changes. Precursor lesions may precede the development of duodenal gastrinomas because, in contrast to sporadic gastrinomas, these tumors are usually multiple. Methods: The distribution of endocrine cells in the nontumorous duodenal tissue was analyzed qualitatively and quantitatively for 25 patients operated on for a duodenal gastrinoma. MEN1 status was assessed clinically and by polymerase chain reaction-based mutational analysis. Results: Fourteen of 25 patients with gastrinoma had proliferative, hyperplastic lesions consisting of gastrin cells in the nontumorous duodenal mucosa, similar to the gastric enterochromaffin-like cell lesions observed in chronic atrophic gastritis. All patients with Zollinger-Ellison syndrome with proven MEN1 had such proliferative gastrin cell lesions, and all patients with Zollinger-Ellison syndrome without precursor lesions were MEN1 negative. Conclusions: Duodenal gastrinomas in MEN1, but not sporadic duodenal gastrinomas, are associated with proliferative gastrin cell changes within the nontumorous mucosa. It is likely that these lesions precede the development of MEN1-associated duodenal gastrinomas.
Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas
British Journal of Surgery, 2007
Background: Gastrinomas are functional endocrine duodenopancreatic tumours and are responsible for Zollinger-Ellison syndrome (ZES). Clinical presentation, localization techniques and operative management were reviewed. Methods: An electronic search of the Medline database was undertaken for articles published in English between January 1987 and May 2007. This timeframe was chosen because of the fundamental changes in operative strategy, antisecretory therapy and localization techniques during this period. Results and conclusion: Most gastrinomas are located in the 'gastrinoma triangle', comprising the head of the pancreas, and the first and second parts of the duodenum. Some 20 per cent of gastrinomas occur in association with multiple endocrine neoplasia type 1 (MEN1) and 50-60 per cent of tumours are malignant at the time of diagnosis. Biochemical evidence justifies operation of which duodenotomy is an essential part. Only complete tumour resection allows 5-and 10-year survival rates of 90 per cent. Pylorus-preserving pancreaticoduodenectomy may be the procedure of choice for MEN1-ZES.
Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients
World Journal of Gastroenterology, 2011
Author contributions: Imamura M (chief surgeon), Komoto I, Ota S, Doi R, Awane M and Inoue N performed surgery for gastrinomas and duodenopancreatic neuroendocrine tumors in MEN 1 patients; Hiratsuka T performed pathological research on the resected pancreatoduodenal neuroendocrine tumors; Kosugi S performed genetic analysis of the patients with MEN 1.
Gastrinoma and Insulinoma in a Patient With Multiple Endocrine Neoplasia
The Endocrinologist, 2005
We report an unusual case of multiple endocrine neoplasia (MEN-1) presenting with hyperinsulinemia, hypergastrinemia, and hyperparathyroidism. The patient was referred to our department for further investigation of symptomatic hypoglycemic episodes and repeated nephrolithiasis. Laboratory studies revealed hypoglycemia, hyperinsulinemia, mild hypercalcemia, and hyperparathyroidism. Pituitary magnetic resonance imaging (MRI) and measurements of hypophyseal hormones were in the normal range. Two pancreatic masses, demonstrated on MRI, were removed surgically by means of enucleation and distal pancreatectomy. No hypoglycemic episodes occurred after surgery. After a symptomfree interval of 4 months, the patient had diarrhea and dyspeptic symptoms. Detailed investigation revealed a gastrinoma, which could be detected by octreotide scintigraphy. The gastrinoma was located between the duodenum and pancreatic head as a solitary lesion. Because of the close proximity of the lesion to the remaining pancreatic tissue and the failure of exact localization, we decided against surgery for the gastrinoma. The patient responded well to lansoprazole. The parathyroid glands were removed and half of one gland was implanted into the forearm. The implant functioned properly. The patient was discharged under medical treatment.
Endokrynologia Polska
This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially Guidelines Grażyna Rydzewska et al. Guidelines in the World Health Organization (WHO) and North American Neuroendocrine Tumor Society (NANETS) recommendations [12, 13] (Tab. 1). 1.1.1. Pathogenesis Type 1 and type 2 tumours develop from enterochromaffin-like (ECL) cells in the gastric mucosa in response to chronic oversecretion of gastrin. Secondary hypergastrinaemia-caused by achlorhydria in the course of chronic atrophic gastritis (CAG)-is responsible for the development of GNEN type 1. Primary hypergastrinaemia-in Zollinger-Ellison syndrome (ZES), sporadic or associated with multiple endocrine neoplasia 1 (MEN-1)-is responsible for GNEN type 2. Gastrin and its derivatives stimulate the proliferation, migration, and differentiation of ECL cells, which in turn leads to their hyperplasia and dysplasia. Hypergastrinaemia, without the interaction of the transforming factor/factors, does not cause the development of GNEN [4]. Menin dysfunction may constitute a transforming factor in patients with MEN-1. The literature also mentions other factors including the following: BCL2 apoptosis inhibiting protein, p53 protein, fibroblast growth factor (FGF), transforming growth factor (TGF), Regla protein dysfunction (inhibiting the proliferation of ECL cells) [14]. 1.1.2. Type 1 Gastric neuroendocrine neoplasms type 1 (70-80% GNEN) occur in patients with atrophic gastritis. They
Surgery for Gastrinoma and Insulinoma in Multiple Endocrine Neoplasia Type 1
Journal of the National Comprehensive Cancer Network, 2006
The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases...
Annals of Surgery, 2006
Objective: The aim of this study was to evaluate the results of pancreatic resection in pancreatic endocrine neoplasias (PENs) in patients affected by multiple endocrine neoplasia type 1 (MEN1) syndrome. Background: Since these tumors often show an indolent course, the role of diagnostic procedures and type of surgical approach are controversial. Experience with new diagnostic approaches and more aggressive surgery is still limited. Methods: Sixteen MEN1 patients were referred to our Surgical Unit (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003) and were operated on for the indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13 patients, 2 of whom experienced a recurrence after previous surgery. Preoperative tumor localization was carried out using ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1 patient also underwent an intraoperative secretin provocative test. Results: Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal pancreatectomy was performed. There was no postoperative mortality; 37% complications included pancreatic (27%) and biliary (6%) fistulas, abdominal collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most sensitive preoperative imaging techniques. At follow-up, 10 of 13 hypergastrinemic patients (77%) are currently eugastrinemic with negative secretin provocative test, while 3 are showing a recurrence of the disease. All patients affected by insulinoma were cured. Conclusions: MEN1 tumors should be considered surgically curable diseases. IGM may be of value in the assessment of surgical cure. Our experience suggests that PD is superior to less radical surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas and pancreatic neoplasias. (Ann Surg 2006;244: 61-70)
Gastric neuroendocrine tumors: Biology and management
Annals of Gastroenterology
Neoplasms may originate from any of the endocrine cells of the gastric wall, most commonly the enterochromaffinlike (ECL) cells of the oxyntic mucosa. In recent years, the increasing number of screening gastroscopies and biopsies, and the widespread application of sophisticated immunohistochemical stains for neuroendocrine markers, have resulted in the frequent detection of ECL tumors. The latter are regarded as a separate clinicopathological entity seen in the setting of hypergastrinemic states, and their pathogenesis follows the sequence hyperplasia dysplasia neoplasia. According to the most recent WHO classification, gastric neuroendocrine tumors (NETs) are generally divided into well-differentiated NETs (class 1a), welldifferentiated neuroendocrine carcinomas (NECs) (class 1b) and poorly differentiated NECs (class 2). Well-differentiated tumors (NETs and NECs), for which the historic term carcinoid is still in use, include three subgroups: Type I (70-80%), associated with chronic atrophic gastritis, which are benign (class 1a) ECL cell tumors in the vast majority of cases; Type II (<10%), associated with gastrinoma in patients with multiple endocrine neoplasia type1 (MEN1), which are usually benign; and Type III or sporadic (25-25%), which tend to behave aggressively (usually class 1b). Resent advances in the diagnosis and management of these tumors include the measurement of serum chromogranin-A levels, which reflect tumor mass, the use of synthetic somatostatin analogues for imaging and therapeutic purposes, and the introduction of aggressive multimodality protocols for the management of metastatic disease. Little progress has been made in the treatment of the rare, highly malignant, poorly differentiated neuroendocrine carcinomas, which are rapidly fatal, showing only short-lived responses to chemotherapy. Research is currently focusing on the study of the molecular pathways of gastric endocrine cell tumorigenesis, including the role of various growth factors and gene regulation mechanisms.