Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed this study in order to evaluate the diagnostic accuracy of whole-body fluorodeoxyglucose positron emission tomography (FDG PET) imaging and somatostatin receptor scintigraphy (SRS) for localizing primary carcinoid tumours and evaluating the extent of the disease. A secondary aim was to correlate those findings with the histological characteristics of the lesions. FDG PET was performed in 17 patients and SRS in 16. All patients had pathologically proven carcinoids. All lesions were verified by histopathological analysis or by follow-up. Ki-67 and p53 expression were assessed as an indicator of the tumours' aggressiveness. FDG PET correctly identified 4/7 primary tumours and 8/11 metastatic spreads, as compared to six and 10 respectively, for SRS. Most tumours were typical carcinoids with low Ki-67 expression. No correlation was found between the histological features and the tracer's uptake. We conclude that SRS remains the modality of choice for evaluating patients with carcinoid tumours, regardless of their proliferative activity. FDG PET should be reserved to patients with negative results on SRS.
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PMID:Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. 1212 77

Somatostatin and its long-acting analogues have been introduced for the treatment of endocrine tumours of the gastrointestinal tract as they have been shown to effectively control symptoms resulting from excessive hormone release in patients with carcinoid, Verner-Morrison and glucagonoma syndromes. This beneficial effect is due to the presence of somatostatin receptors in high densities on the majority of endocrine tumours. The symptomatic effect is less pronounced in insulinomas, since 30 - 50% of these tumours lack or express only a few somatostatin receptors. With respect to symptomatic control, somatostatin receptor subtypes 2 and 5 are the most important and the currently available long-acting analogues octreotide and lanreotide bind preferentially to these receptor subtypes. Long-term studies have shown that somatostatin analogues are safe and that the most important adverse advent is the development of gallstones. The antiproliferative potency of somatostatin and its analogues in vitro and in experimental tumour models prompted a number of studies in patients with metastatic endocrine tumours that are generally unresponsive to conventional chemotherapeutic protocols. Stabilisation of tumour growth lasting for months to a few years was the most favourable result, occurring in 30 - 70% of patients. However, definite proof of antiproliferative potency in man is still pending since placebo-controlled studies are not available. Radioligand therapy based on 111Indium, 90Yttrium and 177Lutetium coupled to somatostatin analogues via bifunctional chelators is currently under investigation with promising data concerning long-lasting control of symptoms and tumour growth from Phase I trials.
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PMID:Somatostatin analogues in the treatment of endocrine tumors of the gastrointestinal tract. 1247 80

Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin receptor (sst) scintigraphy with PET, a novel carbohydrated (18)F-labelled sst ligand was developed and preclinically evaluated. Synthesis of N(alpha)-(1-deoxy- D-fructosyl)- N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate ([(18)F]FP-Gluc-TOCA) was completed in approximately 3 h (20%-30% yield). [(19)F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC(50): 437+/-84 n M) and hsst5 (IC(50): 123+/-8.8 n M) and very high affinity to hsst2 (IC(50): 2.8+/-0.4 n M). As a result of carbohydration, lipophilicity of [(18)F]FP-Gluc-TOCA was found to be low (lg P(OW)=-1.70+/-0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%+/-1.09%ID/g) and showed low uptake in liver (0.72%+/-0.14%ID/g) and intestine (1.88%+/-0.52%ID/g) and high tumour uptake (13.54%+/-1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, respectively. A similar biodistribution pattern was observed in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 microg Tyr(3)-octreotide, demonstrating sst-specific uptake. In a first [(18)F]FP-Gluc-TOCA-PET study of a patient with a metastatic carcinoid in the liver the tracer showed superior pharmacokinetics, e.g. rapid urinary excretion and low uptake in liver, kidney and spleen. Multiple liver lesions (SUVs ranging from 21.4 to 38.0) and previously unknown focal uptake in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an (18)F-labelled sst binding peptide; it indicates that [(18)F]FP-Gluc-TOCA offers excellent imaging characteristics and allows sst imaging with high tumour to non-tumour contrast.
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PMID:PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide. 1248 18

Somatostatin receptors expressed on tumor cells form the rationale for somatostatin analog treatment of patients with somatostatin receptor-positive neuroendocrine tumors. Nevertheless, although somatostatin analogs effectively control hormonal hypersecretion by GH-secreting pituitary adenomas, islet cell tumors, and carcinoid tumors, significant differences are observed among patients with respect to the efficacy of treatment. This may be related to a differential expression of somatostatin receptor subtypes among tumors. In addition, the property of somatostatin receptor subtypes to undergo agonist-induced internalization has important consequences for visualizing, as well as for therapy, of receptor-positive tumors using radioisotope- or chemotherapeutic-compound-coupled somatostatin analogs. This review covers the pathophysiological role of somatostatin receptor subtypes in determining the efficacy of treatment of patients with somatostatin receptor-positive tumors using somatostatin analogs, as well as the preclinical and clinical consequences of agonist-induced receptor internalization for somatostatin receptor-targeted radio- and chemotherapy. Herein, the development and potential role of novel somatostatin analogs is discussed.
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PMID:The pathophysiological consequences of somatostatin receptor internalization and resistance. 1258 7

Little is known of the natural history of thymic carcinoids in multiple endocrine neoplasia type 1 (MEN1). This is important because in 1993 they were identified as a frequent cause of death, yet only small retrospective studies and case reports exist. We report results of a prospective study of 85 patients with MEN1 evaluated for pancreatic endocrine tumors and followed over a mean of 8 yr with serial chest computed tomography, magnetic resonance imaging (MRI), chest x-ray, and, since 1994, octreoscans [somatostatin receptor scintigraphy (SRS)]. Seven patients (8%) developed thymic carcinoids. Patients with and without carcinoids did not differ in clinical, laboratory, or MEN1 tumor features, except for male gender and the presence of a gastric carcinoid. All thymic tumors were hormonally inactive. Four thymic carcinoids lacked 11q loss of heterozygosity, although it was found in three pancreatic endocrine tumors. Computed tomography and/or MRI were more sensitive than SRS or chest x-ray in detecting tumors initially or with recurrence. All patients underwent resection of the thymic carcinoid, and in all patients followed more than 1 yr, the tumor recurred. Bone metastases developed in two patients and were detected early only on MRI, not SRS. This study provides information on early thymic carcinoids and allows modifications of existing guidelines to be recommended for their diagnosis, surveillance, and treatment.
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PMID:Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. 1262 87

Carcinoid tumors are relatively rare neuroendocrine malignancies with an indolent clinical behavior. The majority of cases arise within the gastrointestinal tract, but they may also be encountered in other organs such as the bronchial system. While occurrence of carcinoid tumors has been reported in association with the multiple endocrine neoplasia (MEN) type I syndrome, no clear-cut risk factors have been established for the development of these malignancies. We report the case of a 50-year-old woman who was diagnosed with a pulmonary carcinoid in 2001 after having undergone allogeneic stem cell transplantation for chronic myeloid leukemia (CML) in 1997. This is the first case report of a carcinoid tumor following allogeneic bone marrow transplantation. At the moment, however, an association with CML as well as a causative role of transplantation and intake of immunosuppressants remains speculative. Apart from highlighting the occurrence of a carcinoid in this setting, our case again underscores the importance of nuclear medicine methods, i.e., somatostatin receptor scintigraphy, in staging and follow-up of patients with carcinoid tumors.
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PMID:Occurrence of a pulmonary carcinoid following allogeneic stem cell transplantation for chronic myelogenous leukemia: a case report. 1271 84

Since the development of synthetic somatostatin analogues, several therapeutic applications for somatostatin receptor agonist molecules have been defined. Established applications for somatostatin analogue treatment include pituitary tumours (growth hormone and thyrotropin-secreting adenomas), neuroendocrine tumours of the pancreas and gastrointestinal tract (so-called carcinoid tumours, vasoactive intestinal tumours) and gastroenterological conditions (pancreatitis, gastrointestinal bleedings, refractory diarrhoeas, pancreatic and intestinal fistulas, diarrhoea in AIDS). Further areas for development of somatostatin analogue therapy include obesity, polycystic ovary syndrome and diabetes mellitus, dysmetabolic conditions that are often interrelated. The challenge for the future will be to transform results from clinical trials conducted in heterogeneous clinical situations into novel options of somatostatin analogue use. Since obesity and diabetes mellitus both are disorders of marked heterogeneity, the subgroup of patients that will benefit most from somatostatin analogue treatment has yet to be defined. In addition, the development of more universal ligands covering all of the known somatostatin receptor molecules as well as receptor subtype specific agents is currently underway. The establishment of slow-release depot formulations of octreotide and lanreotide has already provided a more acceptable and consistent delivery mechanism. Use of biodegradable polymer microsphere formulations provides the basis for the development of novel applications, which include hyperinsulinaemia, obesity and polycystic ovary syndrome as components of the dysmetabolic syndrome. The most developed thus far is the use of octreotide in hyperinsulinaemic forms of obesity and in distinct stages of diabetic retinopathy.
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PMID:The therapeutic potential of somatostatin receptor ligands in the treatment of obesity and diabetes. 1294 94

Ectopic ACTH hypersecretion is a rare cause of Cushing's syndrome. Bronchial carcinoids are the most common neoplasms causing the occult ectopic ACTH syndrome (EAS). Localization of these tumors is often difficult. The diagnostic utility of somatostatin receptor scintigraphy (SRS) in EAS has been studied in a limited number of patients with conflicting results. Herein we report our experience with 12 consecutive cases. Histological confirmation was obtained in nine patients, the majority being bronchial carcinoids. Among the seven patients with histologically confirmed bronchial carcinoids, SRS was performed in six patients. In three patients SRS correctly localized a bronchial carcinoid tumor at presentation. In the remaining three it became positive after 8, 22, and 27 months during follow-up. In two patients SRS was positive without any finding in the corresponding conventional imaging study. In two patients positive computed tomography/magnetic resonance imaging preceded SRS localization. There was no false positive SRS. Among three patients with highly suspected EAS, SRS was positive in one. Both patients with EAS due to medullary thyroid carcinoma had focal positive uptake. In summary, in this study a substantial number of patients had positive tumor localization by SRS. Therefore, SRS is a useful tool in the evaluation of patients with EAS.
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PMID:A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotropin Cushing's syndrome. 1455 51

Carcinoid tumors belong to the family of neuroendocrine tumors, which are usually slow growing with distinct biological and clinical characteristics. The incidence of these tumors is approximately 2.5 in 100,000 people per year. The former classification system of foregut, midgut and hindgut tumors is still used in clinical routine, although there is a new World Health Organization classification. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. Proliferation capacity measured by Ki67 is used to guide forthcoming medical treatment. Localization procedures include computerized tomography, ultrasound, magnetic resonance imaging, somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemoembolization. Biological treatment includes cytotoxic agents, such as somatostatin analogs and interferon-alpha, which should be applied in slow-growing neoplasms. Combination regimens including cisplatin, etoposide, streptozotocin and 5-fluorouracil should be reserved for treatment of highly proliferating tumors. Future therapy of carcinoid tumors will be based on the specific tumor biology and treatment will be customized for each individual patient. New therapies, such as antiangiogenic agents and new, long-acting somatostatin analogs, together with further development of tumor-targeted treatments, will come into clinical use in the near future.
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PMID:Diagnosis and treatment of carcinoid tumors. 1468 8

Five somatostatin receptor (sst) subtype genes, sst(1), sst(2), sst(3), sst(4) and sst(5), have been cloned and characterised. The five sst subtypes all bind natural somatostatin-14 and somatostatin-28 with high affinity. Endocrine pancreatic and endocrine digestive tract tumours also express multiple sst subtypes, but sst(2) predominance is generally found. However, there is considerable variation in sst subtype expression between the different tumour types and among tumours of the same type. The predominant expression of sst(2) receptors on pancreatic endocrine or carcinoid tumours is essential for the control of hormonal hypersecretion by the octapeptide somatostatin analogues such as octreotide and lanreotide. Somatostatin and its octapeptide analogues are also able to inhibit proliferation of normal and tumour cells. The high density of sst(2) or sst(5) on pancreatic endocrine or carcinoid tumours further allows the use of radiolabelled somatostatin analogues for in vivo visualisation. The predominant expression of sst(2) receptors in these tumours and the efficiency of sst(2) receptors to undergo agonist-induced internalisation is also essential for the application of radiolabelled octapeptide somatostatin analogues. Currently, [(111)In-DTPA(0)]octreotide, [(90)Y-DOTA(0),Tyr(3)]octreotide, [(177)Lu-DOTA(0)Tyr(3)]octreotate, [(111)In-DOTA(0)]lanreotide and [(90)Y-DOTA(0)]lanreotide can be used for this purpose.
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PMID:Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. 1471 57


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