Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carcinoids of the stomach, duodenum, and pancreas are represented by a variety of tumors with variable histologic and clinical features. Multicentric gastric carcinoids and concomitant nonantral argyrophilic hyperplasia are common in chronic atrophic gastritis, more rarely due to a multiple endocrine neoplasia (MEN)-related Zollinger-Ellison syndrome (ZES). These tumors are infrequently associated with metastases and may generally be dealt with by repeated endoscopic fulguration. Sporadic carcinoids tend to be larger, invasive, and more often metastatic, especially in the presence of atypical histology. Small tumors may be removed by endoscopy, but larger lesions need to be surgically excised. In association with metastases a histamine-related atypical carcinoid syndrome may evolve and require treatment with a somatostatin analog. Poorly differentiated neuroendocrine carcinomas of the stomach constitute markedly aggressive tumors that rarely are suitable for radical surgery. Gastrinomas are the most prevalent duodenal carcinoids and a common cause of ZES especially in MEN-I. Despite a marked tendency for regional lymph node dissemination, liver metastases occur late and duodenal gastrinomas are often excisable, thereby offering favorable odds for cure in ZES. Unusual somatostatin-rich carcinoids in the ampulla of Vater relate to von Recklinghausen's disease and may be the cause of obstructive jaundice; depending on their size, these tumors may be removed by local excision or pancreaticoduodenectomy. Gangliocytic paragangliomas are unusual, generally benign lesions of the duodenum. Rare pancreatic tumors with serotonin immunoreactivity may be classified as carcinoids and constitute an unusual cause of the carcinoid syndrome.
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PMID:Management of carcinoid tumors of the stomach, duodenum, and pancreas. 866 14

Long-acting somatostatin analogs, such as octreotide, comprise the therapeutic modality of choice for the symptomatic relief of flush and diarrhea in patients with carcinoid syndrome. The sequelae of gastric acid hypersecretion in patients with gastrin-producing duodenal carcinoids (gastrinoma) are perfectly controlled by proton pump inhibitors. Antiproliferative medical strategies to control the growth of metastatic carcinoid tumors include long-acting somatostatin analogs, interferon alpha, and the combination of the two. However, the success rate is less than 50%, and it is questionable whether true tumor regression can be expected. Controlled prospective studies are mandatory to address the question whether interferon or somatostatin analogs or the combination of the two should be used as first-line medical strategies and if hepatic artery embolization in patients with liver metastases should be performed before beginning medical therapy. Chemotherapy, including etoposide and cisplatin, has been shown to be effective only for purely differentiated neuroendocrine carcinomas and not for slowly growing carcinoids.
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PMID:Medical treatment of metastasizing carcinoid tumors. 866 18

We report a case of left ventricular (LV) myocardial uptake of a labeled somatostatin analog in a patient with a carcinoid tumor of the small bowel. The patient developed liver metastases and a carcinoid syndrome, including right carcinoid heart disease, without right-to-left shunt on contrast ultrasonography or left ventricular myocardial metastases. The basis for visualization of the LV myocardium is probable somatostatin receptor upregulation.
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PMID:Left ventricular myocardial uptake of a labeled somatostatin analog in carcinoid syndrome. 866 61

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.
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PMID:Somatostatin receptor imaging: predictive and prognostic considerations. 881 70

Octreotide therapy is expensive, but at present it and other somatostatin analogues appear to offer the best opportunity of controlling the symptoms of flushing and diarrhoea. It may also have other properties affecting general well-being. The question of whether it changes tumour growth remains unanswered and there is no convincing evidence that it alters survival. In all published studies the numbers of patients are small and there have been no control groups. However, since no other drug has yet proved effective against flushing, the somatostatin analogues, including octreotide, remain the treatment of choice for the symptomatic control of the carcinoid syndrome. Octreotide is of great therapeutic value pre-operatively and intra-operatively and it is essential that all operating theatres have this drug available for immediate use. Surgical debulking, if feasible, provides the best outcome potential in carcinoid disease. Present evidence suggests that the place of octreotide and other somatostatin analogues is in controlling the symptoms of the disease rather than its progress and in ensuring cardiovascular and respiratory stability during surgical procedures.
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PMID:Octreotide therapy in carcinoid disease. 882 81

Carcinoid tumours derived from the neural crest are usually associated with the symptoms of flushing and diarrhoea in the presence of liver metastases. Scintigraphs with 131I-metaiodobenzylguanidine (131I-MIBG) which is accumulated in the argentaffin granules of the cell, as well as with 111In-pentetreotide for the imaging of somatostatin receptors on the cell surface, are positive in a large proportion of carcinoid patients. To evaluate the complementary role of both radionuclide tests, we studied 20 consecutive carcinoid patients: 14 with the characteristic carcinoid syndrome and 6 with tumour symptoms, such as pain or obstruction. A positive test was found in 84% with either 131I-MIBG or 111In-pentetreotide; the combination yielded a sensitivity of 95%. A positive correlation was found with the presence of the carcinoid syndrome, but not with 5-HIAA excretion. A positive test may help in adjusting treatment: either to predict the response to octreotide or to select patients for 131I-labelled MIBG treatment. Application of a therapeutic dose of 111In-pentetreotide may be limited by the high normal uptake in the kidneys.
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PMID:Combined diagnostic imaging with 131I-metaiodobenzylguanidine and 111In-pentetreotide in carcinoid tumours. 894 76

A large number of endocrine tumors express somatostatin receptors, and the use of radiolabeled somatostatin analogs has been recently introduced for their localization. Using in vivo scintigraphy with 111In-pentetreotide, primary tumor localizations were demonstrated in 3/3 carcinoids (2 intestinal carcinoids and 1 lung ACTH-secreting carcinoid; in 2 patients liver metastases larger than 1 cm were visualized), in 1/1 GH-secreting pituitary macroadenoma, and in 1/1 thyroid localization of MTC. Bone and/or lymph node metastases were imaged in 2/4 patients previously treated for MTC, with persistently high CT and CEA levels; in the other 2 patients the other scintigraphic techniques were also negative. Octreotide scintigraphy was negative in 2/2 insulinomas and in 2/2 ACT-producing pituitary adenomas. In 2 patients with carcinoid syndrome and 1 patient with Cushing syndrome due to ectopic ACTH, octreotide therapy induced a significant decrease in tumoral markers. Our preliminary data are in agreement with the results of larger series reported in literature: octreotide scintigraphy is a useful noninvasive tool to detect endocrine tumors expressing somatostatin receptors, particularly for carcinoids. It is of great use in the differential diagnosis of Cushing syndrome due to ectopic ACTH. Moreover, 111In-pentetreotide scintigraphy may be useful in selecting patients who may benefit from octreotide therapy to control hormonal hypersecretion effects.
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PMID:111In-octreotide scintigraphy in endocrine tumors. Preliminary data. 900 67

Neuroendocrine tumours can form in any part of the gastrointestinal tract. The most common types are the ECL cell tumours of the oxyntic mucosa of the stomach, G cell tumours of the duodenum, argentaffin, EC cell tumours of the small intestine and L cell tumours of the large bowel. The only well-defined clinical syndromes associated with hormone hypersecretion are ZES, resulting from duodenal gastrinomas, and carcinoid syndrome, caused by malignant argentaffin tumours. Genetic predisposition has been demonstrated for some tumour types, e.g. duodenal gastrinoma in MEN 1 and duodenal somatostatin cell tumours in MEN 2. Other factors predisposing to the genesis of these lesions include circulating hormone levels and the maintenance of chronic inflammatory states. As with most neuroendocrine tumours, malignant potential is difficult to assess on the basis of histology alone and prognostic evaluation depends more on size and evidence of local invasion and/or distant metastases.
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PMID:Gastrointestinal endocrine tumours. Pathology. 911 12

With the introduction of longer-acting somatostatin analogues symptomatic relief is easy to achieve in patients with functionally active endocrine tumours and will be further facilitated by still longer-acting formulations. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome can be prevented by all proton-pump inhibitors currently on the market. Despite the various antiproliferative strategies that have been offered to patients with metastatic disease, available data are controversial and, more importantly, are supported by few prospective and controlled studies. Most experts agree that surgery with curative extirpation of the primary in the absence of metastases and tumour debulking in metastatic disease should be intended wherever possible. Controversy concerns residual disease. According to our view, any further antiproliferative strategy should consider the growth characteristics and biology of a given tumour (Figure 4). In the case of rapid progression, chemotherapy should be offered if tumours originate from the pancreas or reveal an undifferentiated histology. In contrast, chemotherapy should not be offered to patients with well-differentiated non-functional or functional tumours (carcinoid syndrome) arising from the intestine. The same applies for patients with tumours with no or only slow growth within an given observation period of 3-12 months. These patients should be treated only symptomatically. Patients with tumours of slow progression might favourably respond to long-acting somatostatin analogues. We start with octreotide and offer patients not responding to octreotide monotherapy additional IFN alpha. If further tumour progression takes place, hepatic artery embolization is the next step (Figure 5) followed by chemotherapy, the latter in patients with tumours of pancreatic origin only. This strategy recognizes the severity of side-effects of the different therapeutic modalities and starts with octreotide because of its very few side-effects. Other groups start with chemoembolization followed by octreotide, alpha-interferon or its combinations (Ahlman et al, 1996). Ongoing studies will, it is hoped, answer the question of the ideal sequence of therapeutic strategies. Every available patient with metastasised gastrointestinal endocrine tumours should be included in one of the ongoing European multicentre trials.
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PMID:Gastrointestinal endocrine tumours: medical management. 911 20

The use of long-acting and potent somatostatin analogues is a major advance in the management of carcinoid tumours. In addition to providing effective symptom relief in malignant carcinoid syndrome, octreotide can also be used for diagnostic purposes. Despite its expense, octreotide is the current agent of choice for the treatment of this condition while analogues with different receptor specificities and pharmacokinetics hold promise for the future. Gastric carcinoids have aroused interest because of their experimental association with chronic hypergastrinaemia, a condition now commonplace because of the widespread use of H2-blockers and proton-pump inhibitors. This subject is reviewed. The slow evolution of many tumours demands prolonged follow-up and the active use of a variety of palliative interventions. These include measures such as hepatic and cardiac surgery, which might be deemed inappropriate for patients with other types of metastatic malignancy. Interferons may have a role when first-line treatments have failed. Chemotherapy is, generally, of limited value.
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PMID:Carcinoid tumours. 949 64


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