Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallbladders removed at cholecystectomy are a potentially useful source of human receptor for the gastrointestinal peptide hormone cholecystokinin (CCK). Seven healthy gallbladders (removed incidentally at time of resection of hepatic metastases) and 50 diseased gallbladders were studied. Cholecystokinin radioligand binding to an enriched plasma membrane preparation from these tissues was shown to be rapid, reversible, temperature-dependent, saturable, specific, and high-affinity. Computer analysis of equilibrium binding data using the Ligand program best fit a single class of binding sites with Kd = 1.0 +/- 0.1 nM (mean +/- SEM). This was similar in health and disease, with no apparent differences related to age, gender, or body habitus. The structural specificity for binding to this site correlated well with relative potencies for CCK-gastrin peptides to stimulate gallbladder contraction. To biochemically characterize this receptor, we used a battery of reagents, including "long" (125I-Bolton Hunter-CCK-33) and "short" 125I-D-Try-Gly-[(Nle28,31)CCK-26-33] probes that were cross-linkable through their amino terminus and a monofunctional probe with a photolabile group at its carboxyl terminus 125I-D-Tyr-Gly[(Nle28,31,pNO2-Phe33)CCK-26-33]. All probes specifically labeled a human gallbladder muscularis protein of Mr = 85,000-95,000, which was also independent of diagnosis. Labeling of this band was inhibited in a concentration-dependent manner by CCK-8 and by L-364,718. Thus, the CCK receptor present on the very common surgically removed human gallbladder is functionally and biochemically intact and is useful for further characterization.
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PMID:Functional and biochemical characterization of the human gallbladder muscularis cholecystokinin receptor. 292 56

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.
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PMID:Aggressive resection of metastatic disease in selected patients with malignant gastrinoma. 293 50

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.
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PMID:Pancreatic islet cell carcinoma with gastrin and vasoactive intestinal polypeptide production. 299 97

A case of a 58-year-old woman with an unusual variant of malignant islet-cell tumor showing oncocytic features is described. Using the light microscopy technique, the tumor appeared comprised of solid nests of uniform cells with abundant, eosinophilic cytoplasm and round nuclei with granular chromatin. Ultrastructurally, the cells contained numerous abnormal mitochondria, dilated rough endoplasmic reticulum, and scattered dense-core neurosecretory granules, often associated with cytoplasmic filaments. Tumor cells were focally immunoreactive for insulin, glucagon, and somatostatin and diffusely immunoreactive for alpha 1-antitrypsin as assayed by the avidin--biotin technique. The tumor was immunonegative for human chorionic gonadotropin, gastrin, adrenocorticotropic hormone, and serotonin. The patient exhibited some of the clinical features associated with glucagonoma syndrome, including diabetes mellitus and chronic diarrhea. The tumor behaved in a malignant fashion, with widespread lymphatic involvement and bony metastases at the time of presentation. This report of an oncocytic islet-cell carcinoma supports the concept of oncocytic differentiation in islet-cell tumors in a fashion analagous to oncocytic carcinoids.
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PMID:Functioning oncocytic islet-cell carcinoma. Report of a case with electron-microscopic and immunohistochemical confirmation. 300 44

A patient with metastatic islet cell carcinoma demonstrated multiple clinical syndromes simultaneously with secretion of ACTH, gastrin, glucagon, and serotonin. Hepatic arterial embolization resulted in an initial decrease in all secretory products, which was sustained for glucagon and serotonin. Recrudescence of the Cushings and Zollinger-Ellison syndrome was managed by surgical extirpation of the primary tumor and regional metastases as well as bilateral adrenalectomy. Electron microscopy and immunocytochemistry of the primary tumor and the metastatic lesions revealed the presence of multiple types of granules within single cells and, different patterns of secretory profiles in different tumor sites.
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PMID:Metastatic islet cell tumor with ACTH, gastrin, and glucagon secretion. Clinical and pathologic studies with multiple therapies. 303 1

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.
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PMID:Diagnosis and treatment of Zollinger-Ellison syndrome. 304 57

Neoplastic proliferations of neuroendocrine cells (NE) may occur throughout the entire GI tract but affect particularly appendix and ileum ("midgut carcinoids"), rectum ("hindgut carcinoids"), as well as stomach and the duodenum ("foregut carcinoids"). Only more exceptionally, they arise in the esophagus, jejunum and colon. The NE tumors encompass a heterogeneous gross and microscopic structural spectrum, ranging from inconspicuous microproliferations ("mucous membrane nevi") to bulky tumor masses. Their growth patterns are usually characteristic and easily recognized. In doubtful cases their NE differentiation becomes established by a characteristic silver affinity, by the ultrastructurally observed presence of characteristic "endocrine" secretion granules, and by immunohistochemically detectable occurrence of "pan-NE markers" (neuron-specific enolase, chromogranins, and synaptophysin), biogenic amines (mainly serotonin), and neurohormonal peptides. Foregut carcinoids usually contain serotonin, gastrin, and somatostatin, midgut carcinoids often only serotonin and tachykinins, whereas the hindgut carcinoids as a rule are multihormonal with a wide spectrum of hormonal peptides, including even insulin. Most GI NE tumors are found in the appendix (50%) and the ileum (30%). Practically all (98%) of the appendiceal NE tumors are benign. They have recently been proposed as arising from apparently Schwann-cell-related NE cells in the submucosa, whereas the ileal--and probably also all the other non-appendiceal NE tumors--are derived from the totipotential cells in epithelial crypts of the mucosa. Among the ileal NE neoplasms a large number can metastasize and result in a fatal outcome. The ability to metastasize is related to the size and to the multiplicity of the primary tumors at the time of initial diagnosis and, to some extent, to their histopathologic growth pattern. Now, some relationship between the prognosis and the cytochemically assessed nuclear DNA content of the NE tumor cells has also been established; not less than about 1/4 to 1/3 seem to be aneuploid. Almost 90% of the rectal carcinoids are benign. Exceptionally, a highly malignant NE neoplasms can arise from the colon/rectum--as well as from the esophagus--composed of NE cells of small and intermediate size. The NE tumors of the stomach are often composed of ECL (enterochromaffin-cell-like) cells; such ECL cell carcinoids are related to atrophic gastritis with pernicious anemia; experimentally, they can be induced by hypergastrinemia in rats. Duodenal carcinoids often contain psammoma bodies and can be associated with neurofibromatosis.
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PMID:Neuroendocrine tumors of the gastrointestinal tract. 329 Aug 66

Neuroendocrine tumours of upper gastrointestinal tract fall into two main categories. First carcinoid tumours of the stomach and duodenum and secondly endocrine pancreatic tumours. The endocrine tumours of the gastric mucosa include two main types, so called ECL-oma of the corpus and fundic region and gastrin producing carcinoids or hyperplasia of the antrum and duodenum. The endocrine tumours of pancreas include entopically secreting insulinomas, glucagonomas, somatostatinomas, PP-omas, and ectopically secreting tumours, such as gastrinomas and tumours producing ACTH, GHRH, and calcitonin. The diagnosis of a neuroendocrine tumour of the upper gastrointestinal tract is based on the recognition of certain clinical syndromes and the determination of certain humoral products. A broad battery of radioimmunological assays for determination of different peptides is mandatory for the diagnosis and follow up of these patients. The diagnosis is also based on histological and immunocytochemical investigation of tissue specimens obtained at operation or by biopsy. Ultrasound investigation is the best non-invasive technique to detect metastases from neuroendocrine gut and pancreatic tumours, but angiography might unveil metastases down to a size of less than 5 mm. Surgery is still the primary treatment procedure but other treatments are needed because many patients have metastases already at the time of diagnosis. Chemotherapy with streptozocin combined with 5-fluorouracil or adriamycin and human leucocyte interferon has demonstrated objective response rate of about 70%. The new somatostatin analogue SMS 201-995 is an important adjunct in controlling clinical symptoms in patients with neuroendocrine gut and pancreatic tumours. A combination of different treatment procedures is needed for long-term management of these patients.
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PMID:Neuroendocrine tumours of the upper gastrointestinal tract and pancreas. 329 22

The Zollinger-Ellison syndrome, although uncommon, is not rare, and most patients with the disorder present with clinical manifestations similar to those of patients with common peptic ulcer. Early studies emphasized death due to complications of massive gastric acid hypersecretion. However, with the availability of potent antisecretory agents to control acid secretion, death is now more frequently associated with the metastatic potential of slowly growing but malignant gastrinomas. Therefore, physicians should maintain a high degree of suspicion of the Zollinger-Ellison syndrome in assessing patients with either chronic peptic ulcer or unexplained secretory diarrhea. An evaluation aimed at early diagnosis of the Zollinger-Ellison syndrome should be instituted in such patients and should begin with a determination of the fasting serum gastrin level. At least 50 percent of patients with gastrinoma will have nondiagnostic serum gastrin concentrations and will therefore require provocative testing to establish the correct diagnosis. After the presence of the syndrome is established, patients should be treated with a potent antisecretory agent in doses sufficient to reduce basal acid output to less than 10 mmol in the hour preceding administration of the next dose. Although some patients may be maintained satisfactorily in this manner for extended periods, an approach aimed at tumor localization and extirpation is recommended in most patients. Preoperative evaluation should begin with CT scanning with intravenous contrast material. Selective angiography, and occasionally, portal venous sampling for gastrin, should be performed if the location and extent of tumor remain in question. If metastatic disease is demonstrated, or if MEN-I is present, surgery aimed at tumor resection, although it is occasionally effective, will probably be unsuccessful. Because of the considerable morbidity and mortality associated with pancreatoduodenectomy, it should not be performed for unresectable tumor in the head of the pancreas. In other patients with the Zollinger-Ellison syndrome, exploratory surgery should be performed; this should include a careful search for, and resection of, all pancreatic and extrapancreatic gastrinomas. With this approach, it is likely that at least 20 percent of all patients with the Zollinger-Ellison syndrome can be cured.
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PMID:Zollinger-Ellison syndrome. Current concepts in diagnosis and management. 330 61

The usefulness of radio-metaiodobenzylguanidine (MIBG), a specific radiopharmaceutical agent for scintigraphic imaging and treatment of phaeochromocytoma and neuroblastoma, has been extended to the location of carcinoid tumors. Scintigraphic evaluation with I-123 MIBG in a patient with a histologically proven endocrine tumor (apudoma) of unknown origin with liver and bone metastases is reported. Elevated plasma hormone levels of gastrin, pancreatic polypeptide, and serotonin were found. Tumoral content of these hormones was immunocytochemically confirmed on liver biopsy. I-123 MIBG uptake could be seen in those areas of the liver with deficient lesions in the Tc-99m colloid image with a maximal uptake in a large mass at the level of the left liver lobe. No abnormal uptake could be observed at any other level, which was in contrast with autopsy findings of generalized metastatic disease.
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PMID:Iodine-123 MIBG imaging in a generalized pancreatic polypeptide-gastrin-serotonin secreting tumor. 339 Sep 81


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