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)

Gastrinomas from 25 patients were examined by immunohistochemistry (IHC) and in situ hybridization histochemistry (ISH). Most patients (84%) presented with the Zollinger-Ellison syndrome. Six had multiple endocrine neoplasia type I (MEN-I). Twelve patients (48%) had duodenal primaries and 11 of 12 of these had metastases to regional lymph nodes and/or liver in spite of the small sizes of the primary tumors (mean size of 0.9 cm). Five patients had pancreatic gastrinomas and eight patients had metastatic tumor in regional lymph nodes or liver at surgery but a primary was not found. IHC and ISH analyses showed that all cases were positive for gastrin protein and 24 of 25 (96%) expressed gastrin mRNA that was easily detected in formalin-fixed, paraffin-embedded tissue sections. Both benign and malignant tumors expressed alpha subunit of human chorionic gonadotropin protein (alpha-HCG). However, only malignant gastrinomas (29%) expressed adrenocorticotropic hormone protein or proopiomelanocortin (POMC) mRNA. ISH and Northern hybridization analysis revealed that chromogranin A mRNA was the most common member of the chromogranin/secretogranin (Cg/Sg) family which was expressed in both benign and malignant gastrinomas. These results indicate that duodenal gastrinomas are common in both sporadic and MEN-1-associated cases, and small duodenal primaries may be associated with extensive regional lymph node and liver metastases. Expression of ACTH/POMC protein and mRNA was consistently associated only with malignant gastrinomas while gastrin protein, gastrin mRNA and Cgs/Sgs mRNAs were readily detected in both benign and malignant gastrinomas.
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PMID:Analysis of gastrinomas by immunohistochemistry and in situ hybridization histochemistry. 128 76

Paraneoplastic syndromes are caused by factors produced by cancer cells that often act at a distance from both the primary site and its metastases. The most extensively characterized syndromes caused by cancer are those produced by polypeptide hormones, such as adrenocorticotropic hormone, and those produced by antibodies directed against tumor antigens that cross-react with neural tissue, such as in the Eaton-Lambert myasthenic syndrome. These syndromes develop in a minority of cancer patients, and are diagnoses of exclusion. Lung cancer, particularly small cell lung cancer, is the most common malignancy causing paraneoplastic syndromes. A large number of paraneoplastic syndromes have been described. This review focuses on the increased understanding of some of the well-documented syndromes that has occurred through recent advances principally in molecular biology and immunology.
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PMID:Paraneoplastic syndromes in thoracic malignancies. 206 93

The association of a bronchial or thymic carcinoid as a source for the ectopic production of adrenocorticotropic hormone (ACTH) has been reported since 1957, with approximately 72 cases in the literature. These patients are characterized by young age, long duration of Cushing's syndrome because of the inability to find the ectopic source, and a high incidence of hypophysectomy or adrenalectomy without curing the disease. A substantial number of patients, upon discovery of the thoracic ectopic source, are also found to have malignant carcinoid tumors with lymph node metastases. Fifteen patients have been explored for a presumed intrathoracic source of ACTH at our institution since 1983 and 14 carcinoids (13 bronchial, one thymic) have been resected. Seventy-one percent (10/14) of the patients appear cured with normal plasma ACTH levels 5 to 57 months after resection, despite a 50% incidence of positive lymph node disease. Management of these patients demands an aggressive evaluation to prevent unnecessary adrenalectomy or hypophysectomy and to allow earlier resections before these potentially curable malignancies metastasize. When the tumor is discovered, thorough exploration and complete lymph node mapping with resection must be performed.
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PMID:Management of the ectopic ACTH syndrome due to thoracic carcinoids. 216 61

A variety of imaging procedures were performed in 28 patients with ectopic adrenocorticotropic hormone (ACTH) syndrome in an attempt to localize the ACTH-producing tumor. Diagnosis was made on the basis of removal of an ACTH-producing tumor or biopsy of metastases in the 19 patients with a proved source and the absence of ACTH gradients in bilateral samples of the inferior petrosal sinuses in the nine patients in whom an ACTH-secreting tumor had not been localized. Eleven bronchial carcinoids, two thymic carcinoids, three pheochromocytomas, and three islet-cell tumors constituted the proved sources. The condition has been cured in eight patients, six are alive with residual tumor, and five have died. Of the nine patients with undetected sites of ACTH production, one has died of pneumocystis pneumonia and eight are being treated medically or with bilateral adrenalectomy. Computed tomography (CT) of the chest and abdomen was the most helpful study in the detection of these tumors. Selective arteriography (bronchial and visceral), systemic and portal venous sampling, and iodine-131 meta-iodobenzylguanidine scintigraphy failed to demonstrate tumors when findings at CT were negative. Bronchial carcinoids constituted most of the ACTH-secreting tumors in this study (58%) and in a review of four large series (47%). To assure early detection of these potentially malignant tumors, pulmonary CT should be performed every 6 months, even after hypercortisolism has been medically or surgically controlled.
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PMID:Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. 254 19

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

Mucinous carcinoid tumor of the vermiform appendix, an uncommon variant of appendiceal carcinoid, may present clinically with ovarian metastases. We studied a tumor by immunohistochemistry and electron microscopy and reviewed eight similar cases from the literature. The primary and metastatic tumors in our case were composed of mucin-producing cells and small argyrophilic cells arranged in cords and acini. Tumor cells in both primary and metastatic sites exhibited identical patterns of immunoreactivity for epithelial antigens (epithelial membrane antigen, carcinoembryonic antigen) and neuroendocrine antigens (serotonin, vasoactive intestinal polypeptide, adrenocorticotropic hormone). Ultrastructurally, the cells contained either mucin vacuoles or dense-core neurosecretory granules; rare individual cells contained both types of inclusions. When bilateral solid mucinous ovarian tumors are discovered at laparotomy, diagnostic appendectomy is indicated if no obvious extraovarian primary tumor can be found.
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PMID:Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors. 300 29

A 75-year-old woman evaluated for "drop attacks" 3 years after anterior resection for colo-rectal cancer developed hyponatremia associated with a morning cortisol of 5.7 micrograms/dl, a plasma adrenocorticotropic hormone level of 319 pg/ml, and an inadequate response to cosyntropin. Computed tomography scan demonstrated bilateral adrenal masses. Fine needle aspiration biopsy of the adrenals revealed adenocarcinoma, histologically similar to her previous colon carcinoma. Addison's disease secondary to isolated colon cancer metastases to the adrenals is rare. Our report represents the first antemortem histologically confirmed diagnosis of this entity. A review of the available literature is presented.
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PMID:Adrenal insufficiency. A rare initial sign of metastatic colon carcinoma. 330 24

Seven female patients with a pancreatic islet cell tumor and Cushing's syndrome are described. Five patients initially had symptoms and signs of hypercortisolism, and two presented with an abdominal mass and had subsequent development of the syndrome. The tumors ranged in size from 2 to 12 cm in diameter, and all were argyrophilic with the Grimelius technique. Four cases had positive immunostaining for adrenocorticotropic hormone; other hormones were identified in four cases. Six of the patients were dead at the time of this report: five with metastatic tumor within 4 years of diagnosis and one 19 years after diagnosis with hepatic metastases of undetermined origin. One patient was alive with hepatic metastases 20 years after operation. Among the 42 known cases of pancreatic islet cell tumor and Cushing's syndrome, the 5-year survival was 16%.
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PMID:Pancreatic islet cell tumor associated with Cushing's syndrome. 609 31

Seven patients, four of whom subsequently proved to have bilateral and three, unilateral adrenal metastases, were evaluated regarding adrenal activity. Three of the patients had clinical signs and symptoms similar to those usually associated with manifest adrenal insufficiency. Massive tumor growth, with less than 20 per cent residual amounts of apparently normal adrenal tissue, was found in three of the four patients with bilateral metastases. The metastases in the fourth patient were smaller and could only be detected microscopically. Evaluation of the adrenal activity included the determination of cortisol levels in plasma at 8 am, 2 pm and 8 pm; single dose dexamethasone suppression test with adrenocorticotropic hormone stimulation, and analysis of 24 hour urinary excretion of epinephrine and norepinephrine. In all seven patients, the plasma cortisol levels, dexamethasone suppression--adrenocorticotropic hormone stimulation test results and urinary excretion of epinephrine and norepinephrine were similar to those found in comparable patients without adrenal metastases. Thus, the metastases did not seem to be of any clinically significant importance for the patients. It was concluded that, apparently, only minimal amounts of residual adrenal tissue are sufficient to maintain, for basic conditions, normal production of cortisol and of epinephrine and to even respond to stress.
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PMID:The clinical significance of metastases to the adrenal glands. 626 12

Thirty-nine patients with disseminated carcinoma but without metastases to the adrenal glands underwent a complete physical examination and laboratory work-up regarding signs and symptoms suggestive of adrenal insufficiency. Thereafter, they were categorized into two groups. In group A, 24 patients were in relatively good condition and had no symptoms suggestive of adrenal insufficiency. All 15 patients in group B had clinical signs and symptoms similar to those usually associated with adrenal insufficiency. The adrenal activity of each patient was evaluated through determination of cortisol in plasma at 8 am, 2 pm and 8 pm; dexamethasone suppression-adrenocorticotropic hormone stimulating test; analysis of 24 hour urinary excretion of cortisol, and analyses of 24 hour urinary excretion of epinephrine and norepinephrine. After completion of the evaluation of adrenal function, the patients included in group B were treated with cortisone acetate. Patients in group B, when compared with those of group A, generally had an increase in cortisol secretion as well as in epinephrine and norepinephrine excretion. Both groups responded to dexamethasone suppression and adrenocorticotropic hormone stimulation. Of the 13 patients treated with cortisone, only one patient objectively responded to the treatment, while two of the patients were clinically improved. All three of these patients had normal or increased adrenal activity. It was concluded that the symptoms frequently seen in patients with disseminated carcinoma and which are similar to those associated with adrenal insufficiency, do not indicate impaired cortisol secretion. Patients with these symptoms usually had an increase in adrenal activity, probably as a response to stress.
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PMID:Adrenal activity in patients with advanced carcinomas. 720 74


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