Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In this study, liver metastases from a patient with a pancreatic glucagonoma producing the syndrome have been investigated histologically, ultrastructurally, and immunocytochemically. A comparison has also been made between the metastases and the primary pancreatic tumor investigated in a parallel study. In the metastatic tissue, glucagon-, pancreatic polypeptide (PP)-, and somatostatin-containing cells were found together with a majority of cells without any immunoreactivity. Glucagon-positive cells were much more numerous than PP- and somatostatin-immunoreactive cells. As in the primary tumor, double immunogold staining of ultrathin sections demonstrated the co-existence of glucagon and PP immunoreactivities in most of the granulated cells, but PP immunolabeling was often faint, so that it probably could not be revealed by the PAP method in light microscopical sections. Such a finding, together with the histological and ultrastructural features, is consistent with an ontogenic and phylogenetic primitiveness of the metastatic cell population.
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PMID:A malignant tumor of the pancreas producing glucagonoma syndrome: immunocytochemistry and ultrastructure of liver metastases and comparison with the primary tumor. 254 78

The authors evaluated the presence of somatostatin (SRIF) in the plasma and in the tumor tissue of a total of 22 patients with medullary thyroid cancer (MTC) and studied the effect of exogenous SRIF administration on basal and pentagastrin (PG)-stimulated plasma calcitonin (CT) and carcinoembryonic antigen (CEA) levels. Mean plasma SRIF concentrations were significantly higher than those found in normal controls, with five of 15 patients having plasma SRIF levels above the mean + 2 SD of normal controls. High immunoreactive SRIF concentrations were found in the extract of three tumor tissues but not in one follicular thyroid cancer or in one toxic diffuse goiter. By immunoperoxidase staining seven of 11 (63.6%) primary MTC and five of 13 (38.5%) metastases expressed SRIF antigen in a low number of cells and with a weak degree of staining. As expected, CT was expressed in almost 100% of the cases with positivity in most of the cells and strong degree of staining. Patients with positive SRIF staining in the primary tumor had longer survival than SRIF negative patients. Infusion of synthetic SRIF (11 micrograms/minute/45 minutes) produced a significant reduction of plasma CT (but not CEA) levels in 12 of the 15 patients submitted to this test. Maximal percent decrease of plasma CT ranged from 10.8% to 72.7% of the basal value and was usually observed between 30 and 45 minutes from the beginning of the infusion. When infused together with the injection of PG, SRIF was able to significantly (P less than 0.05) inhibit the PG-induced CT release in five of six patients tested. These results demonstrate the following: SRIF is present in a few cells of many primary MTC and less frequently in their metastases; tentatively, the expression of SRIF antigen in the tumor seems to be associated with longer survival; increased SRIF concentrations are found in the plasma of some patients with metastatic involvement; and treatment with exogenous SRIF reduces the basal and PG-induced CT (but not CEA) release from the tumor.
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PMID:Somatostatin in medullary thyroid cancer. In vitro and in vivo studies. 256 68

Proliferation of endocrine cells was found to occur during early, i.e., first 12 weeks, exocrine pancreatic carcinogenesis after 6 weekly treatments of Syrian hamsters with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Cells containing insulin (Ins), glucagon (Glu), and somatostatin (Som) were noted in all stages of tumor development and were present in adenocarcinomas and in metastases to the liver. Some of the cancer cells were of amphicrine (hybrid) type, i.e., produced both mucin and endocrine substances. Measurement of these hormones revealed a significant decrease in plasma Ins during early stages of carcinogenesis with concomitant increase of Ins level in pancreatic juice at 12 weeks after 6 weekly BOP treatments. Plasma Glu and Som were not changed. The changes noted, particularly in relation to Ins, suggest that proliferation of endocrine cells in pancreatic carcinogenesis may be associated with alterations in hormone secretion.
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PMID:Alteration of pancreatic endocrine cell patterns and their secretion during pancreatic carcinogenesis in the hamster model. 257 21

A retrospective study of 224 patients with medullary thyroid carcinoma (MTC) diagnosed between 1963 and 1988 was performed to 1) establish the diagnosis of MTC in early childhood, 2) establish the role of prophylactic regional lymphadenectomy in patients with MTC, 3) study the effect of chemotherapy on MTC patients with metastatic disease, 4) study the effect of somatostatin analog 201-995 (Sandoz Pharmaceuticals) on the frequency of diarrhea in MTC, and 5) locate the common region(s) of gene deletion on chromosome 1 and examine the loss of heterozygosity on chromosome 10 in tumors. Our data indicated that a progressive rise of serum calcitonin in early childhood (rather than the expected fall with age seen in normal subjects) is diagnostic of MTC. No differences in clinical course of prognosis were observed between patients with MTC localized to the thyroid who had prophylactic neck node dissection and those who did not. Conventional chemotherapy had no significant benefit in the treatment of patients with metastatic disease. The somatostatin analog was found to be an effective drug in the treatment of diarrhea associated with MTC. Allelic losses were frequently found in MTCs and pheochromocytomas, and the loss of DNA sequences in these tumors appeared to involve the distal third of the short arm of chromosome 1, with a common breakpoint at 1p32.
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PMID:Diagnosis, management, and pathogenetic studies in medullary thyroid carcinoma syndrome. 257 46

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of subcutaneous administration of sandostatine (SMS 201.995) in 18 cases of thyroid medullary cancer]. 263 43

The increased knowledge of the pathobiology of gastrointestinal carcinoid (neuroendocrine) tumours and the improved therapeutic possibilities have brought a demand for more precise diagnosis. Although the carcinoid tumours can often be tentatively recognized in routinely processed microscopic slides, their more accurate identification requires additional diagnostic procedures. General neuroendocrine markers such as the argyrophil reaction of Grimelius and immunohistochemistry with application of antibodies against chromogranin A and of neuron-specific enolase are discriminatory staining methods which are used to reveal the neuroendocrine origin of almost all highly differentiated carcinoid tumours of the gastrointestinal tract. Mid-gut carcinoids, which predominate among these tumours almost unexceptionally contain serotonin. This biogenic amine can be demonstrated by the argentaffin reaction of Masson, serotonin immunoreactively or by formalin-induced fluorescence. The characteristic staining pattern of mid-gut carcinoids is almost invariably preserved in the metastatic deposits and consequently the staining methods for identifying serotonin can also be used on metastases to reveal a primary mid-gut carcinoid. The enterochromaffin-like (ECL) cell carcinoids of the body and fundic area of the stomach often seen in association with pernicious anaemia are argyrophil with the Sevier-Munger silver stain. Other neuroendocrine tumours, viz. antral, duodenal and rectal carcinoids should be studied by a battery of relevant peptide hormone antisera for adequate diagnosis. During the last decade new peptide hormones have been found in circulation in patients with carcinoid tumours, but serotonin and urinary 5-HIAA are still the most important markers for carcinoids of the mid-gut origin. Other clinically useful tumour markers are chromogranin A + B, pancreatic polypeptide, human chorionic gonadotropin alpha and beta subunits. For localizing procedures, angiography is the most reliable investigative method for primary tumours in the gut, whereas CT-scan and ultrasound investigations are good for detection of liver metastases. During the last five years, the therapy for malignant carcinoid tumours has been considerably improved. Chemotherapy has only revealed objective response rates in about 10-30% of the patients giving median survivals from start of therapy of about 10 months. Recently treatment with alpha interferons and the new somatostatin analogue octreotide have given objective responses in 50-75% of patients with malignant mid-gut carcinoid tumours. These patients have now a median survival from start of therapy of 70 months when treated with alpha interferons. In the future new therapies will come into use such as monoclonal antibodies and perhaps also agents blocking different growth factors.
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PMID:Gastrointestinal carcinoid tumours. Histogenetic, histochemical, immunohistochemical, clinical and therapeutic aspects. 266 60

The axillary lymph-node-status is the most important prognostic factor in breast cancer patients without distant metastases. The proportion of node positive axillae depends on the number of histologically documented nodes (at least 6 according to TNM recommendations). The prognostic significance of solitary micro-metastases and of metastases detected only by serial sectioning or by immunocytochemistry is not yet established. An important prerequisite for successful conserving breast-cancer treatment is patient selection. Selection leads to a high proportion of patients with favourable prognosis: primary tumors less than 3 cm in diameter, at least 2/3 without axillary lymph-node-metastases, at least 1/3 less than 50 years old. That means attribution of prognostically less favourable patients to mastectomy. Tumor diameter and grading are established prognostic parameters of the primary. The significance of grading is independent of the system used and also independent of the reproducibility by different investigators. Measurement of tumor cell ploidy, proliferation and of epidermal growth factor-receptor content may add to the safety of prognosis prediction. Steroid hormone receptor content, eventually also Somatostatin-receptor and Aromatase activity in the tumor tissue can influence the therapeutic decisions.
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PMID:[Pathologic-anatomic parameters for the prognosis of invasive breast cancer following amputation or saving the breast]. 266 53

Twenty-one cases of cutaneous neuroendocrine (Merkel cell) carcinoma (CNEC) were examined by the ABC-immunoperoxidase method with a panel of antibodies to 5 intermediate filaments, 6 neuroendocrine-associated antigens, 6 peptide hormones, as well as melanoma-associated cytoplasmic antigen (HMB-45) and leukocyte common antigen. All tumors showed strong cytokeratin staining in characteristic dense, inclusion-like, cytoplasmic globules and in a reticular peripheral cytoplasmic pattern. Cytoplasmic coexpression of inclusions of neurofilament antigen was observed in 9/21 cases. Staining for one or more neuroendocrine markers in formalin-fixed tissue (bombesin, 7/20; chromogranin, 11/21; synaptophysin, 6/21) was weak and focal but present in 17/21 cases. In 3 cases, sections of unfixed, snap-frozen tumor were compared with formalin-fixed tissue, and these showed strong, diffuse staining for multiple neuroendocrine antigens. Immunostaining for peptide hormones was not observed, with the exception of weak, focal staining for insulin (1 case), calcitonin (1 case) and somatostatin (2 cases). In 13 cases DNA indices and S-phase fractions (SPF) were determined by flow cytometry on nuclear suspensions from paraffin blocks. DNA histograms in 12 of 13 cases had normal range DNA content (diploid) and elevated S-phase fractions (mean 15%, range 8 to 22%). Mean SPF was not significantly different in the group of patients who developed recurrent and/or metastatic disease (15.6%, N = 10) compared with patients without recurrence (15.8%, N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cutaneous neuroendocrine (Merkel cell) carcinoma: an immunophenotypic, clinicopathologic, and flow cytometric study. 266 40

The treatment of patients with Zollinger-Ellison syndrome (ZES) has undergone dramatic evolution during the past decade. Although initially regarded as an incurable tumor, resection of gastrinoma for potential cure has been reported in 30% to 40% of selected patients in recent series. Conversely, although definitive control of acid hypersecretion is achieved by total gastrectomy, histamine (H2)-receptor antagonists and the newly introduced agents omeprazole and somatostatin analogues allow effective medical therapy of gastric acid overproduction. Confirmation of the diagnosis is best achieved with the I.V. secretin stimulation test, and tumor localization techniques are mandatory to identify candidates for operative tumor resection. Intraoperative sonography and careful exploration are required for tumor removal; successful tumor resection is associated with prolonged survival. The majority of patients (60%) are still found to have malignant disease at the time of diagnosis, but 10-year overall survival commonly exceeds 40%. The presence of multiple endocrine neoplasia type I (MEN-I) is seen in 10% to 25% of patients; correction of hypercalcemia alone may have therapeutic benefit in some ZES patients, and while gastrinoma resection is rarely possible, MEN-I patients demonstrate prolonged survival. The choice of medical rather than surgical therapy for acid hypersecretion depends on the suitability of each patient for careful and repeated endoscopic and chemical studies, versus the likelihood of a successful postoperative outcome. Socioeconomic, geographic, and related medical factors in each case may dictate the form of long-term antisecretory therapy. Exploration for possible tumor resection is indicated for virtually all patients who have no documented metastatic disease.
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PMID:Current diagnosis and management of Zollinger-Ellison syndrome. 268 66

During the last 5-year period aggressive surgical debulking was performed in 19 of 21 consecutive patients with the midgut carcinoid syndrome. Two patients were excluded due to severe cardiac disease. Fourteen of the patients had hepatic metastases. Carcinoid symptoms can occur also in patients without proven liver disease with sole lymph node metastases or retroperitoneal tumours. In 4 patients all metastatic tumour tissue could be removed resulting in biochemical cure and no symptoms. In patients with multifocal hepatic metastases surgical debulking was followed by transarterial embolisations of the hepatic arteries. All patients had good symptomatic relief of the combined surgical and radiological treatment. Five patients had currently stable disease anatomically and biochemically, 2 slowly progressive disease and one patient has a more rapid progression. Three patients have just undergone debulking and are waiting for further treatment. During the observation period 4 patients have died. Of these deaths one was related to the surgical procedures. After the introduction of somatostatin analogues major surgery can be performed safely in these patients with little risk of carcinoid crises. The role of additional drug therapy in these rare patients must be evaluated critically in randomized multicenter trials using a common surgical primary treatment.
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PMID:Surgical treatment of patients with the carcinoid syndrome. 274 79


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