Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.
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PMID:Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. 1515 56

Functional gastroenteropancreatic tumors express all 5 somatostatin receptor subtypes (sst) in different quantities. Octreotide and lanreotide treat patients with these tumors by binding preferentially to sst2 and, to a lesser extent, to sst3 and sst5 receptors, thereby controlling prominent symptoms caused by hormone hypersecretion (diarrhea and flushing). Although symptoms initially improve in most patients, a loss of response occurs in about 50% during continuous treatment. The functional activity at sst receptors of SOM230, a new multiligand somatostatin analog, has been described and compared with that of somatostatin (SRIF-14) and octreotide. These data show that SOM230 is a full agonist with nanomolar potency at sst(1,2,3) and sst5 receptors. The multiligand activity profile of SOM230, together with its nondesensitizing inhibitory effect on growth hormone and insulin-like growth factor-I secretion in rats, may underlie its successful use in clinical trials and its potential for use in refractory patients with carcinoid tumors.
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PMID:Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors. 1547 17

Carcinoid tumors derived from neuroendocrine cells can release serotonin and other vasoactive substances into the systemic circulation, resulting in carcinoid syndrome. Testicular carcinoid, a rare disease accounting for less than 1% of all testicular neoplasms, rarely manifests symptoms of carcinoid syndrome. We describe a case of carcinoid syndrome arising from a primary testicular carcinoid tumor. A 21-year-old male patient presented with facial flushing and diarrhea for 5 years. He had an enlarged left testis and a 1-cm, ill-defined, hard, non-tender mass in his right testis. His 24 h urinary excretion of 5-hydroxyindoleacetic acid was elevated (16.1 mg/day). Somatostatin receptor scintigraphy correlated with carcinoid tumor in both testes. Following bilateral orchiectomy, the patient's facial flushing and diarrhea disappeared.
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PMID:Primary carcinoid tumor of the bilateral testis associated with carcinoid syndrome. 1550 16

Carcinoid tumors were first described more than a century ago, but the treatment of patients with advanced disease remains a challenge to physicians. The etiology of carcinoid tumors, the biologic determinants of the growth of these malignancies, as well as the high frequency of multiple carcinoid and/or non-carcinoid tumors in patients with this disease also remain to be elucidated. A 5-decade analysis of 13,715 carcinoid tumors in the USA showed that distant metastases were demonstrated at the time of diagnosis in 12.9% of patients with this neoplasia. The overall 5-year survival rate for all patients with carcinoids regardless of the site, was reported to be 67.2%. The prognosis of patients with early stage disease is good and surgical resection is the standard form of treatment. The resection of local or regional metastases can result in cure for some cases. However, patients with metastatic dissemination have poor outcomes since chemotherapy is generally ineffective. Surgical resection of isolated hepatic metastases, surgical hepatic artery ligation or embolization produce responses in selected patients. Radiation therapy may ease the pain of bone metastases. The administration of long acting analogs of somatostatin can control the symptoms of diarrhea and flushing in patients with the malignant carcinoid syndrome. However, a complete regression of metastatic carcinoid tumors following the administration of somatostatin analog octreotide has been reported so far in only 3 cases. Other modalities of treatment, including liver transplantation and the administration of radiolabeled somatostatin analogs have likewise been applied in patients with advanced disease. It is expected that advances in proteomics research will contribute to our understanding of the mechanisms of diseases and aid in designing new drugs.
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PMID:A clinical overview of carcinoid tumors: perspectives for improvement in treatment using peptide analogs (review). 1564 13

A 53-year-old man with In-111 octreotide-positive metastatic hepatic carcinoid was referred for Y-90 lanreotide therapy. A diagnostic In-111 lanreotide scan, performed to assess suitability for therapy, showed less uptake in lesions compared with In-111 octreotide. After 3 therapy doses of Y-90 lanreotide, a repeat In-111 lanreotide scan showed intense uptake in old lesions, appearance of new lesions, and uptake in the spleen. This was associated with improvement in flushing and regression of liver size. Computed tomography scan showed stable disease. Increased expression of somatostatin receptors has been observed with In-111 octreotide but not with In-111 lanreotide. If this is a flare response, then pretreatment with "cold" lanreotide may be beneficial before Y-90 lanreotide therapy.
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PMID:Changes in the expression of somatostatin receptor imaging following Y-90 lanreotide therapy for carcinoid tumor: a flare response? 1576 78

Gastrointestinal (GI) carcinoids are ill-understood, enigmatic malignancies, which, although slow growing compared with adenocarcinomas, can behave aggressively. Carcinoids are classified based on organ site and cell of origin and occur most frequently in the GI (67%) where they are most common in small intestine (25%), appendix (12%), and rectum (14%). Local manifestations--mass, bleeding, obstruction, or perforation--reflect invasion or tumor-induced fibrosis and often result in incidental detection at emergency surgery. Symptoms are protean (flushing, sweating, diarrhea, bronchospasm), usually misdiagnosed, and reflect secretion of diverse amines and peptides. Biochemical diagnosis is established by elevation of plasma chromogranin A (CgA), serotonin, or urinary 5-hydroxyindoleacetic acid (5-HIAA), while topographic localization is by Octreoscan, computerized axial tomography (CAT) scan, or endoscopy/ultrasound. Histological identification is confirmed by CgA and synaptophysin immunohistochemistry. Primary therapy is surgical excision to avert local manifestations and decrease hormone secretion. Hepatic metastases may be amenable to cytoreduction, radiofrequency ablation, embolization alone, or with cytotoxics. Hepatic transplantation may rarely be beneficial. Chemotherapy and radiotherapy have minimal efficacy and substantially decrease quality of life. Intravenously administered receptor-targeted radiolabeled somatostatin analogs are of use in disseminated disease. Local endoscopic excision for gastric (type I and II) and rectal carcinoids may be adequate. Somatostatin analogues provide the most effective symptomatic therapy, although interferon has some utility. Overall 5-year survival for carcinoids of the appendix is 98%, gastric (types I/II) is 81%, rectum is 87%, small intestinal is 60%, colonic carcinoids is 62%, and gastric type III/IV is 33%.
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PMID:Current status of gastrointestinal carcinoids. 1588 61

(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.
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PMID:Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). 1625 95

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.
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PMID:Carcinoid syndrome: diagnosis and medical management. 1644 70

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 microg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.
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PMID:Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects. 1703 95

Patients with carcinoid tumours frequently present with metastatic disease. There are only a few therapeutic options for these patients, and the main goal of palliative treatment is to reduce symptoms and thus to improve quality of life. Current therapy includes surgical resection, hepatic artery embolisation, chemotherapy and somatostatin analogue treatment; however, all these options have limitations. It seems probable that therapeutic modalities based on radiopharmaceuticals may provide better therapy, not only in relation to symptom reduction but may also improve patient survival. In this case report we present a 46-year-old woman with a symptomatic carcinoid, who at the time of diagnosis had liver and abdominal lymph node metastases, the primary tumour being located in the terminal ileum. (111)In-pentetreotide scanning was negative, whereas (123)I-MIBG scanning showed high avidity in the tumour tissue. After right hemicolectomy, two courses of (131)I-MIBG treatment were given (12.95 GBq and 12 GBq, respectively). After the second dose of (131)I-MIBG temporary pancytopenia was present. Octreotide therapy was given empirically only for a short time and was stopped because of drug intolerance. The patient underwent tricuspid and pulmonary valve replacement because of her carcinoid heart disease, followed by two courses of embolisation of liver metastases. While (131)I-MIBG therapy reduced the patient's symptoms of flushing and diarrhoea, there has not yet been any effect on tumour response or 5-HIAA production. This case illustrates the multimodality and multidisciplinary approach to such patients.
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PMID:Multimodality palliative treatment of (111)In-pentetreotide negative/(123)I-MIBG positive metastatic carcinoid - a case report. 1877 5


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