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)

Predictive tests for treatment with somatostatin analogues have been asked for by clinicians. We have shown previously that somatostatin receptor (sstr) scintigraphy may be used to predict therapeutic outcomes for carcinoid patients receiving somatostatin analogues. However, almost 20% of patients with pathological tracer uptake fail to respond to such treatment. To increase further the reliability and prognostic value of sstr identification, we investigated the presence of mRNA for the subtypes sstr1 and sstr2 by in situ hybridization on tumor specimen from 25 carcinoid patients (22 midgut, 2 foregut, and 1 hindgut), all receiving somatostatin analogue treatment (12 lanreotide, 8 octreotide, and 5 octastatin) and compared this to the therapeutic response evaluated as inhibition of hormone secretion. Expression of sstr2 mRNA could be detected in 15 patients, all responding to somatostatin analogue treatment and showing pathological tracer uptake in tumor lesions at sstr scintigraphy. In the remaining 10 patients, no sstr2 mRNA could be detected, and none of the patients responded to somatostatin analogue treatment. Three of these 10 patients failed to accumulate tracer activity at sstr scintigraphy, whereas 7 had a pathological uptake of [(111)In-DTPA-D-Phe(1)]-octreotide. We conclude that in this group of carcinoid patients, there was complete agreement between the presence of mRNA for sstr2 detected by in situ hybridization and therapeutic outcome. In patients with pathological tracer accumulation without expression of somatostatin sstr2 mRNA, other sstr may be present that can bind the somatostatin analogue but not inhibit hormone secretion.
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PMID:A comparison between the efficacy of somatostatin receptor scintigraphy and that of in situ hybridization for somatostatin receptor subtype 2 messenger RNA to predict therapeutic outcome in carcinoid patients. 865 98

Most carcinoid primary tumors are small and do not cause symptoms until complications (e.g. intestinal obstruction) or symptoms and signs of the carcinoid syndrome occur. Therefore in most cases an assessment of the primary tumor and its metastases must be performed. To determine the value of somatostatin receptor scintigraphy (SRS) for localizing carcinoid tumors, we compared the results of SRS with those obtained with computed tomography (CT) and ultrasonography (US) in 22 patients who had not undergone surgery for removal of the primary tumor. We could not find an advantage of SRS over CT and US for detecting the primary lesions. Tumors > 2 cm in diameter were regularly detected using all methods. SRS was not superior to CT or US for the detection of liver metastases. SRS showed the liver metastases in 16 of 18 patients, whereas CT and US detected liver metastases in all patients. For localization of extrahepatic abdominal and extraabdominal metastases (lymph nodes, bone), whole-body SRS showed an advantage over CT and US. We conclude that SRS is not superior to CT or US for localization of primary carcinoid tumors or liver metastases, although it did prove successful for visualizing extrahepatic and extraabdominal tumor spread. Additionally, SRS is useful for identifying receptor-positive metastases that may be treated by somatostatin analogs. Thus SRS should be performed in patients with a known carcinoid tumor, except those with an appendiceal carcinoid measuring < 1 cm in diameter.
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PMID:Value of somatostatin receptor scintigraphy for preoperative localization of carcinoids. 866 12

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

An observed case of carcinoid tumor of the large-bowel in a 68-year-old woman leads to an analysis of the clinical-diagnostic and therapeutic aspects of this rare gastrointestinal tumour. Carcinoid tumour represents 0.8-1.5% of malignant digestive tumours, in 6% of cases it is localized in large-bowel and in 2-3% in cecal-bowel. In our experience there is no specific symptoms and diagnosis was based on postoperative histopathologic analysis. Right hemicolectomy with lymphadenectomy performed and the operative specimen included a 7 cm diameter tumour, which had narrowed the lumen by 80% and infiltrated ileocecal valve. Carcinoid tumour presents considerable problems of diagnosis because symptoms are aspecific. Diagnosis is possible only in patients with high urinary levels of 5-HIAA, in presence of carcinoid syndrome and by endoscopic biopsy when tumour infiltrated gastrointestinal mucosa. False negative cases are frequent in small carcinoids ( < 2 cm) because the tumour tissues are covered by integral mucosa. C.T., ultrasonography and angiography play a primary role in the diagnosis of this tumour but octreotide scintigraphy is very important for tumour and metastases localization in consequence of its ability to demonstrate somatostatin receptor positive tumours. Radical surgery is the only treatment in very little carcinoids to prevent metastases risk. Determinant risk factors are: primary size, localization, serosal penetration. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended. Other prognostic factors include histologic differentiation, the presence of macroscopic residual disease after initial surgery and level of 5-HIAA in urine. We think that neither adjuvant chemotherapy, or radiotherapy may play a significant role in this neoplasm. Many authors report considerable unsuccessful with this treatment and it is used mainly for palliation. At present, the medical treatment of inoperable gastrointestinal carcinoid consist in association with interferon alpha and octreotide. During this treatment the size of the tumour is stable: reduction of symptoms and 5-HIAA urinary levels are noted.
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PMID:[A carcinoid with cecal localization. Apropos a case]. 867 47

Through the development of somatostatin scintigraphy with the labeled somatostatin analog Indium111-Octreotide, it has recently become possible to accurately diagnose primary tumors of the APUD system as well as their metastases, since these tumors usually have somatostatin receptors. Experience with this method is already available for endocrine and exocrine tumors of the gastrointestinal tract, neuroendocrine and breast tumors, small cell bronchial carcinomas and certain lymphomas. In the present study, this new diagnostic technique was used for the first time in various head and neck tumors (carcinoid of the larynx, Merkel cell tumor, glomus tumor of the carotid and glomus jugulare tumor). Concurrently, some of these tumors shown by this diagnostic method to be somatostatin receptor positive were treated using the somatostatin analog Octreotide, a therapeutic approach new for the ENT-specialty. Our initial results prove that the detection of the ENT tumors which we studied by means of receptor scintigraphy is reliable. The preliminary results of this Octreotide therapy show a growth inhibitory effect, especially for those tumors of the head and neck which are inoperable or are difficult to approach surgically.
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PMID:Somatostatin receptor scintigraphy and therapy of neuroendocrine (APUD) tumors of the head and neck. 872 46

Due to the increased costs of medical care, a cost-benefit analysis is needed when trying for the 'ultimate' biochemical diagnosis of gastro-enteropancreatic (GEP) tumours. The glycoprotein chromogranin family has proved useful in screening for neuroendocrine tumours. In patients with midgut carcinoid tumours, chromogranin A is more sensitive than urinary 5-hydroxyindoleacetic acid but by combining these two biochemical markers most GEP tumours can be diagnosed. Chromogranin A is also a prognostic marker for survival in patients with midgut carcinoid tumours. Pancreastatin constitutes a part of the chromogranin A molecule and is a less sensitive general screening marker for neuroendocrine gut and pancreatic tumours, but levels, in combination with chromogranin A, might give some insight into tumour biology. Specific markers such as gastrin, glucagon, vasoactive intestinal peptide, insulin, neuropeptide K and substance P should be used to further characterise hormone production in neuroendocrine tumours. However, in some patients, confirmation of diagnosis requires provocation tests, such as the secretin or meal provocation tests. Staging information can be obtained by new investigations such as intra-operative or endoscopic ultrasound, octreoscan, and positron emission tomography. We combine the biochemical characterisation of neuroendocrine tumours with studies of growth factors/receptors, adhesion molecules, proliferation markers, somatostatin receptor content, induction of the enzymes p68 kinase and 2'5'-A-synthetase, and apoptosis, to establish a sound rationale for therapeutic decisions, enabling every patient to receive individualised treatment.
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PMID:The ultimate biochemical diagnosis of gastro-enteropancreatic tumours. 881 68

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

Neuroendocrine gut and pancreatic tumours have provided a diagnostic and therapeutic challenge over the years. These rather slowly growing neoplasms have been assigned a good prognosis but when liver metastases are present the prognosis is not better than that of most other malignant tumours. Despite the development of improved diagnostic procedures many patients are still referred at a stage of the disease too late for surgical cure, at which time medical treatment is warranted. The diagnosis is based on histopathological diagnosis including silver stainings (Grimelius, Masson) and immunohistochemistry for chromogranin A and synaptophysin. Analysis of chromogranin A in the plasma is an important adjunct in the screening for various types of neuroendocrine gut and pancreatic tumours. About 80%-100% of patients with verified neuroendocrine gastrointestinal tumours have elevated circulating levels of this glycoprotein. Depending on clinical symptoms the chromogranin A analysis is supplemented by other peptide hormone analyses as well as urinary 5-HIAA for patients with midgut carcinoid tumours. In the past the localization procedures were based on CT, MRI and ultrasound investigations but in recent years somatostatin receptor scintigraphy (octreoscan) and endoscopic ultrasonography have significantly improved the diagnostic potential. Almost 80% of neuroendocrine gastrointestinal tumours present somatostatin receptor subtype 2 binding 111Indium-labelled octreotide which can be used for staging of the disease, and which also indicates whether or not somatostatin analogues can be used in the treatment of these tumours. Surgery is still a cornerstone in the treatment of neuroendocrine gastrointestinal tumours, even if the patients are beyond cure. Debulking procedures and bypassing operations are important for improving clinical condition and facilitating impending medical treatment, and during the past decade a more aggressive surgical approach has emerged. The medical treatment is based on chemotherapy, and the use of somatostatin analogues and alpha-interferons. Chemotherapy, in particular the combination of streptozotocin with 5-FU or doxorubicin, is still first-line treatment for most endocrine pancreatic tumours, while somatostatin analogues and alpha-interferons are considered first-line for classical midgut carcinoids. Chemotherapy and biotherapy can be combined in many patients, and changes from one medical treatment to another during the course of the disease is mandatory for control of the disease. It is important to realise that most patients with malignant tumours are not cured by medical treatment but that the disease can be controlled for extended periods of time. In the future it will be possible to individualize treatments on the basis of new information about such features of tumour biology as proliferation capacity, expression of adhesion molecules, and growth factors and their receptors.
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PMID:Neuroendocrine gastrointestinal tumours. 883 99

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.
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PMID:Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue. 892 46

Carcinoid tumours offer a diagnostic and therapeutic challenge. Although new biochemical markers and improved methods for tumour detection, including PET and somatostatin receptor scintigraphy, have been developed during the last two decades many patients are still diagnosed at late stages of the disease. This is supported by the fact that the age of diagnosis is about the same today as it was 10 years ago. It is our opinion that plasma chromogranin A levels should be be determined in all patients which are investigated because of symptoms that might be connected to a neuroendocrine tumour. In cases with flushing or diarrhoea, U-5-HIAA should also be determined and these two tumour markers are enough to diagnose most patients with midgut carcinoid tumours. In patients with foregut or hindgut tumours other specific hormones should be included. For the localization procedure conventional radiological techniques including CT, MRI and ultrasound investigations should be supplemented with somatostatin receptor scintigraphy. Endoscopic ultrasound investigations might in the future be relevant for diagnosis of duodenal carcinoids, whereas gastric and rectal carcinoids are diagnosed by endoscopy. A combination of more aggressive surgery combined with medical treatment such as somatostatin analogues and alpha-interferon has significantly increased the survival rates in patients with classical midgut carcinoid tumours. Metastatic foregut and hindgut tumours are still a therapeutic challenge and it is important in the future to classify all carcinoid tumours based on specific tumour biology patterns. Such a tumour biology based treatment is a prerequisite for a more individually based therapy in the future.
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PMID:Carcinoid tumours. 911 14


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