Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND: Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. METHODS: The authors have investigated the use of 111-In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. RESULTS: The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111-In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111-In-pentetreotide was a 4-mm duodenal tumor. CONCLUSIONS: Scintigraphy with 111-In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases.
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PMID:Localization of Neuroendocrine Tumors Using Somatostatin Receptor Imaging With Indium-111-Pentetreotide (OctreoScan). 1076 2

The preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.
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PMID:Anesthetic implications for surgical patients with endocrine tumors. 1081 14

We report a very rare case of ovarian gastrinoma in the context of multiple endocrine neoplasia type I, including primary hyperparathyroidism and Zollinger-Ellison syndrome. Somatostatin receptor scintigraphy revealed the ovarian involvement at an early stage. Oophorectomy led to the final diagnosis and complete healing.
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PMID:Ovarian gastrinoma in multiple endocrine neoplasia type I: a case report. 1117 12

Most gastroenteropancreatic neuroendocrine tumors contain high-affinity binding sites for somatostatin, and somatostatin-receptor scintigraphy has been introduced for the in-vivo evaluation of such tumors. We report two patients with gastroenteropancreatic neuroendocrine tumors, in whom it was quite difficult to localize the tumors by conventional techniques, and in whom we found that (111)In-DTPA-pentetreotide scintigraphy was useful for accurate information on tumor localization. In the first patient, who had gastrinoma, multiple tumors were shown in the gastrinoma triangle, but we could not clarify whether there were any tumors in the pancreatic body. The selective arterial secretin injection (SASI) test diagnosed that the gastroduodenal artery was the feeder of the gastrinomas, and (111)In-DTPA-pentetreotide scintigraphy with single-photon emission computed tomography indicated the absence of tumors in the pancreatic body. In the second patient, who had insulinoma, multiple liver tumors and a large mass in the hilum of the spleen were shown. (111)In-DTPA-pentetreotide scintigraphy was useful in determining that there was no secretion of insulin from the tumor in the hilum of the spleen. In conclusion, X-ray computed tomography is superior for detection of neuroendocrine tumors, because not all neuroendocrine tumors have somatostatin receptors; however, somatostatin receptor scanning, as well as the SASI test, may be useful for the surveillance of patients with known primary tumors, for monitoring patients with disseminated disease, and for following the treatment of these patients.
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PMID:Role of (111)In-DTPA-pentetreotide scintigraphy in accurate diagnosis of neuroendocrine gastroenteropancreatic tumors. 1170 59

Therapeutic strategy of neuroendocrine tumours is complex, due to their heterogeneity and to the fact that although generally slow growing, a significant proportion demonstrates aggressive tumour growth. Symptomatic carcinoid syndrome and various pancreatic endocrine tumours with symptomatic syndromes are well controlled with somatostatin analogues. Surgery remains the mainstay of treatment if the tumour can be resected. Metastatic pancreatic neuroendocrine tumour are treated when resection is not feasible with combination chemotherapy using adriamycin and streptozotocin, which remains a standard of care. In well differentiated tumour of the gut or the lung there is no clear standard of chemotherapy and treatment vary according to the tumour course. In indolent cases, somatostatin analogues are the best treatment, in case of aggressive tumours chemoembolisation should be preferred when the disease is located or predominant in the liver. Poorly differentiated tumours are treated by combination chemotherapy with etoposide and cisplatin, and surgery has no indication. Gastrinoma and other pancreatic tumours arising in the context of multiple endocrine neoplasia type I disease need a specific therapeutic strategy.
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PMID:[Treatment strategy of neuroendocrine tumors]. 1192 20

An 18-year-old male presented in 1979 with a gastrinoma of unknown primary origin. Massive upper-digestive haemorrhage led to total gastrectomy, at which histology evidenced liver metastases, confirmed 9 months later at reoperation for an intestinal occlusion. Postoperative morphological evidence of liver metastases was repeatedly negative using abdominal ultrasound and computerized tomography (CT) scans and magnetic resonance imaging (MRI), but a recent somatostatin-receptor-specific scintigraphy (Octreoscan) was positive only in the liver area. Twenty-two years after diagnosis, the primary tumour has not been identified, the patient leads a normal life, and his circulating gastrin levels, although still elevated at 317-550 pg/ml (normal < 127 pg/ml), have fallen over recent years from > 1000 pg/ml. We discuss the relevance of the described prognostic factors.
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PMID:Twenty-two years' survival of metastatic gastrinoma evidenced recently by somatostatin-receptor-specific scintigraphy. 1195 3

In preclinical studies in rats we evaluated biodistribution and therapeutic effects of different somatostatin analogs, [(111)In-DTPA]octreotide, [(90)Y-DOTA,Tyr(3)]octreotide and [(177)Lu-DOTA,Tyr(3)]octreotate, currently also being applied in clinical radionuclide therapy studies. [Tyr(3)]octreotide and [Tyr(3)]octreotate, chelated with DTPA or DOTA, both showed high affinity binding to somatostatin receptor subtype 2 (sst(2)) in vitro. The radiolabelled compounds all showed high tumor uptake in sst(2)-positive tumors in vivo in rats, the highest uptake being reached with [(177)Lu-DOTA,Tyr(3)]octreotate. In preclinical therapy studies in vivo in rats, excellent, dose dependent, tumor size responses were found, responses appeared to be dependent on tumor size at therapy start. These preclinical data showed the great promise of radionuclide therapy with radiolabelled somatostatin analogues. They emphasised the concept that especially the combination of somatostatin analogs radiolabeled with different radionuclides, like (90)Y and (177)Lu, is most promising to reach a wider tumor size region of high curability. Furthermore, different phase I clinical studies, using [(111)In-DTPA]octreotide, [(90)Y-DOTA,Tyr(3)]octreotide or [(177)Lu-DOTA, Tyr(3)]octreotate are described. Fifty patients with somatostatin receptor-positive tumors were treated with multiple doses of [(111)In-DTPA(0)]octreotide. Forty patients were evaluable after cumulative doses of at least 20 GBq up to 160 GBq. Therapeutic effects were seen in 21 patients: partial remission in 1 patient, minor remissions in 6 patients, and stabilization of previously progressive tumors in 14 patients. The toxicity was generally mild bone marrow toxicity, but 3 of the 6 patients who received more than 100 GBq developed a myelodysplastic syndrome or leukemia. Radionuclide therapy with [(90)Y-DOTA,Tyr(3)]octreotide started in 3 different phase I trials. Overall, antimitotic effects have been observed: about 20% partial response and 60% stable disease (N = 92) along with complete symptomatic cure of several malignant insulinoma and gastrinoma patients. Maximum cumulative [(90)Y-DOTA,Tyr(3)]octreotide dose was about 26 GBq, without reaching the maximum tolerable dose. New is the use of [(177)Lu-DOTA,Tyr(3)]octreotate, which shows the highest tumor uptake of all tested octreotide analogs so far, with excellent tumor-to-kidney ratios. Radionuclide therapy with this analog in a phase 1 trial started recently in our center in 63 patients (238 administrations), Interim analysis of 18 patients with neuroendocrine tumors was performed very recently. According to the WHO, toxicity criteria no dose limiting toxicity was observed. Minor CT-assessed tumor shrinkage (25% - 50% reduction) was noticed in 6% of 18 patients and partial remission (50% - 100% reduction, SWOG criteria) in 39%. Eleven percent of patients had tumor progression and in 44% no changes were seen. These data show that radionuclide therapy with radiolabelled somatostatin analogs, like [DOTA, Tyr(3)]octreotide and [DOTA, Tyr(3)octreotate is a most promising new treatment modality for patients who have sst(2)-positive tumors.
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PMID:Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. 1196 8

Gastrinoma treatment has evolved considerably in the last 20 years. In particular, the advent of effective acid-reducing pharmacologic agents has changed the primary morbidity of this disease entity from one of acid hypersecretion to one of tumor growth and spread. Thus, while symptoms can be temporized using histamine receptor antagonists, proton pump inhibitors, or somatostatin analogs, cure can be effected only by surgical means. Recent advances in operative techniques and pre- and intra-operative imaging studies, including routine duodenotomy, somatostatin-receptor scintigraphy, and intraoperative ultrasound, have allowed for identification and subsequent resection of more than 95% of gastrinoma tumors. Most experts agree that all sporadic cases of localized gastrinoma should be excised. In addition, debulking of metastatic tumor may improve symptoms and survival when cure cannot be ascertained. There is, however, some controversy as to the surgical approach for gastrinoma found in the setting of multiple endocrine neoplasia, type 1. Because of the usual multiplicity and particular indolence of these tumors, two primary strategies have emerged: aggressive approaches have been advocated in an effort to eradicate all present and potential tumor; and less aggressive, or nonoperative, approaches have been suggested because it is unclear whether intervention offers survival or disease-free benefit in this population. We advocate surgical intervention for patients with gastrinoma and multiple endocrine neoplasia, type 1 when tumors exceed 2.5 cm in size. This tumor size has been associated with a higher likelihood of hepatic metastases, which ultimately affects survival. The role of adjuvant therapies for gastrinoma remains limited.
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PMID:Gastrinoma. 1205 14

Glucose is a major metabolic fuel in mammals and is transported into organs and cells by a facilitated diffusion which involves binding of glucose to glucose transporters (GLUTs). Among several GLUTs so far indentified, GLUT-2 is specifically localized immunocytochemV cally in beta-islet cells. Using immunocytochemical staining, normal pancreases and 27 cases of islet cell tumors, including insulinomas, gastrinomas, glucagonomas, pancreatic polypeptide-omas (PPomas), and a nonfunctioning islet cells tumor, were systematically stained for four different pancreatic hormones, gastrin, and GLUT-2. GLUT-2 staining in beta-islet cells was more diffuse than that of insulin immunostaining, and corresponded with the positive staining in the lateral segments of beta-cell plasma membrane, that faced adjacent beta-cells. Glucagon, somatostatin (SRIF) and PP cells stained weakly for GLUT-2, weaker than that of beta-cells. Some nonbeta cells, especially extra-islet PP cells were not stained for GLUT-2. Among islet cell tumors, insulinomas stained less strongly for GLUT-2 than normal beta-cells from the adjacent normal pancreas. Gastrinomas, glucagonomas, and PPomas stained weaker than insulinomas. Even nonfunctioning islet cell tumors were weakly stained for GLUT-2. The positive staining for GLUT-2 observed for islets cells and all islet tumors is consistent with the notion that all pancreatic islet cells and islet cell tumors utilize glucose as a major fuel, requiring transporter-facilitated diffusion of glucose into the cells of normal organ and their tumors.
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PMID:Immunocytochemical Localization of Glucose Transporter-2 (GLUT-2) in Pancreatic Islets and Islet Cell Tumors. 1211 1

Zollinger-Ellison syndrome (ZES) is caused by a gastrin-producing tumor called a gastrinoma, which results in gastric acid hypersecretion. Gastrin stimulates the parietal cell to secrete acid directly and indirectly by releasing histamine from enterochromaffin-like (ECL) cells, and induces hyperplasia of parietal and ECL cells. ZES should be suspected in patients with severe erosive or ulcerative esophagitis, multiple peptic ulcers, peptic ulcers in unusual locations, refractory peptic ulcers, complicated peptic ulcers, peptic ulcers associated with diarrhea, and a family history of multiple endocrine neoplasia type 1 (MEN-1) or any of the endocrinopathies associated with MEN-1. The initial diagnostic test for ZES should be a fasting serum gastrin level when antisecretory medications are discontinued. If the gastrin level is elevated, gastric acidity should be assessed through pH or gastric analysis. It should be noted that hypochlorhydria causes feedback stimulation of antral gastrin secretion. In suspected cases of ZES with mild hypergastrinemia, the secretin stimulation test may be useful. Initial treatment for ZES should be oral high-dose proton pump inhibitors. If parenteral therapy is needed, intermittent bolus injection of pantoprazole is recommended. Total gastrectomy and antisecretory surgery is rarely required. Somatostatin receptor scintigraphy (SRS) is the initial localization study of choice. Endoscopic ultrasound (EUS) may have a similar sensitivity for identifying primary tumors. A combination of SRS and EUS detects greater than 90% of gastrinomas. In patients without metastasis and without MEN-1, surgical cure is possible in 30%. It has been suggested that patients with gastrinomas larger than 2.5 cm, irrespective of whether they have MEN-1, should undergo surgical resection in an effort to decrease the risk for metastasis.
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PMID:Zollinger-Ellison Syndrome. 1262 75


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