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)

The somatostatin analogue octreotide is effective in the treatment of neuroendocrine and other tumours. 111-In-labelled DTPA-octreotide scintigraphy is successful in localizing primary neuroendocrine tumours and metastases and other tumours containing somatostatin receptors. An antiproliferative effect of octreotide was also demonstrated for colorectal carcinoma. Since only about 40% of colorectal carcinomas express somatostatin receptors, we tried to establish whether 111-In-labelled DTPA-octreotide scintigraphy is able to reveal the receptor status of liver metastases in patients with colorectal liver metastases. This would be useful in selecting patients for adjuvant therapy studies with octreotide. We performed 111-In-labelled DTPA-octreotide scintigraphy in ten patients with nonresectable liver metasoffes of colorectal origin and curatively resected primary. In nine of ten patients the liver metastases were somatostatin receptor negative, in one patient somatostatin receptor positive. In the patient with somatostatin receptor-positive liver metastases after resection of a rectal carcinoma, the histological examination of the biopsies from the liver metastases showed a solid tumour of neuroendocrinal differentiation. In the repeated histological examination of the specimen of the rectal primary, a small solid tumour with neuroendocrinal differentiation was found between formations of adenocarcinoma (adenoendocrine carcinoma). In our study 111-In-labelled DTPA-octreotide scintigraphy did not indicate the receptor status of liver metastases from colorectal carcinoma and was not useful in the planning of therapeutic regimens. For the diagnosis of the receptor status of colorectal liver metastases autoradiographic investigation on tissue biopsies are still necessary. In patients with adenoendocrine carcinomas 111-In-labelled DTPA-octreotide scintigraphy may help to histologically differentiate the metastases.
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PMID:[111-indium DTPA octreotide scintigraphy in colorectal liver metastases]. 949 5

Small-cell lung cancer (SCLC) cells may express somatostatin receptors [14]. Receptor-positive tissue can be visualised in vivo by scintigraphy with radiolabelled somatostatin analogues. In a prospective study we examined 18 patients with histologically proven SCLC for the diagnostic value of somatostatin receptor scintigraphy using indium-111 pentetreotide. Planar whole body scanning was performed 4 and 24 hours after administration. Additional SPECT imaging of the thorax and the abdomen was done at 24 hours. The results were compared with conventional staging procedures: ultrasound, x-ray, computed tomography and bone scintigraphy. In all 18 patients the primary tumour was correctly identified. Out of 13 patients with mediastinal lymphoma formation 10 patients showed positive SRS. In 2 more patients SRS showed mediastinal uptake while CT scanning was negative. The detection of distant metastases in patients with extensive disease was true positive in 8 cases (OSS, HEP, BRA), false negative in 4 cases (PLE, ADR, HEP), corresponding to a sensitivity of 67%. In 2 patients cerebral metastases were no longer detectable by SRS after previous local irradiation. Even though the method is limited in respect of revealing distant metastases in the upper abdominal area due to physiological uptake in liver, spleen and kidneys, differentiation between limited disease (LD) and extensive disease (ED) was possible in all cases. We conclude that [111In]pentetreotide scintigraphy is a suitable method for the detection of SCLC primary tumours and a substantial tool for differentiation between LD and ED if combined with ultrasonography of the upper abdomen.
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PMID:[Diagnostic value of somatostatin receptor scintigraphy with indium-111 pentetreotide in small-cell bronchial carcinoma]. 955 59

This paper employs classical concepts of diminishing marginal utility to demonstrate that risk-aversion can increase the perceived value of diagnostic procedures and thus raise optimum diagnostic expenditures. The theory is applied to a model in the spirit of Phelps and Mushlin's initial technology assessments. The specific evaluation is the cost-effectiveness of somatostatin receptor scintigraphy used to detect distant metastases of carcinoid liver tumours in a patient otherwise eligible for surgical resection of the liver. Data for the model are taken from published sources and financial databases, when available, and otherwise from a senior clinician's experience (LKK). The quantitative results indicate that receptor scintigraphy may have two beneficial impacts to risk-neutral individuals. First, it may reduce the combined costs of therapy and treatment because the diagnostic procedure costs less than the expected savings generated by avoiding inappropriate surgeries. Second, it may improve the patient's expected health-status-adjusted life years (HSALY) because the information allows physicians to better match treatment to the cancer's stage. Finally the paper demonstrates that risk aversion, as embodied in classical diminishing marginal utility applied to health status, can increase the value of the diagnostic tests and can lead the patient to choose a less beneficial treatment. An illustrative risk-averse utility function changed the optimum treatment from surgery to chemotherapy and increased scintigraphy's benefit by 500%.
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PMID:Reduced uncertainty as a diagnostic benefit: an initial assessment of somatostatic receptor scintigraphy's value in detecting distant metastases of carcinoid liver tumours. 956 71

Between 1987 and 1996 a total of 25 patients with proved Zollinger-Ellison syndrome (ZES) have been treated in our department. If preoperative imaging studies did not show diffuse metastatic disease, patients were scheduled for operation with a standardized surgical approach including thorough exploration and intraoperative ultrasonography (IOUS) of the pancreas and a longitudinal duodenotomy, with separate palpation of the anterior and posterior walls. Postoperatively, patients were followed up by physical examination, fasting gastrin levels, and the secretin stimulation test. Altogether 10 patients had duodenal wall gastrinoma, 14 patients pancreatic gastrinoma, and the tumor was not found in 1 patient. Only 15 tumors (60%) (2 duodenal wall and 13 pancreatic gastrinomas) could be visualized preoperatively. Intraoperatively, 24 of 25 primary gastrinomas were localized. The mean size of duodenal wall gastrinomas (9.6 mm) was significantly smaller than that of pancreatic gastrinomas (28.7 mm) (p < 0.05). At the time of surgical exploration, five duodenal and seven pancreatic gastrinomas had metastasized. The incidence of lymph node metastases was similar for both tumor sites, whereas patients with pancreatic gastrinomas more frequently had liver metastases. The presence of liver metastases was the most important determinant for survival. Four patients (40%) with duodenal and seven with pancreatic (50%) gastrinomas (mean follow-up 5.2 years) were biochemically cured by operation. Of the remaining patients, eight are still alive with recurrent disease. Our results suggest that preoperative localization of gastrinomas often fails despite all modern imaging methods. Therefore a standardized surgical exploration of the pancreas including IOUS and a duodenal exploration should be performed to achieve optimal results. Preoperative diagnostic imaging tests should include computed tomography, ultrasonography, and somatostatin receptor scintigraphy to exclude diffuse metastases. In contrast to liver metastases, lymph node metastases do not have a significant influence on survival.
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PMID:Localization, malignant potential, and surgical management of gastrinomas. 960 77

An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was relatively stable in human serum (t1/2 3.8 d for 90Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2 12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90Y radiotherapy of somatostatin receptor-positive tumours and their metastases.
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PMID:Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours. 962 Jun 21

We have shown previously that expression of mRNA for somatostatin receptor subtype 2 (sst2) detected by in situ hybridization correlates to therapeutic outcome in patients with carcinoid tumors treated with somatostatin analogues. However, in situ hybridization is laborious and not practical in clinical routine work. We have, therefore, developed polyclonal antibodies directed against sst2 that may be used for immunohistochemistry on tissue specimens. The staining is specific and is highly correlated to expression of mRNA for sst2 (P < 0.01) as well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There is also a good correlation to the therapeutic response in carcinoid patients treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid tumors included in this investigation, 25 stained positive with the antibodies. Twenty-two of these were investigated by somatostatin receptor scintigraphy and showed tracer uptake in metastases. An additional two patients that did not stain with the antibodies showed pathological uptake of the tracer in metastases, which might indicate binding to somatostatin receptor subtype 5. None of the 10 patients without positive immunostaining responded to somatostatin analogue treatment, whereas patients with a positive stain had a biochemical response or remained stable during treatment. Thus, these antibodies may be used to determine the presence of sst2 in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice.
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PMID:Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies. 962 77

The somatostatin analogue [111In-DTPA-d-Phe1]-octreotide (111In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111In-octreotide. Planar images of the head in four views with a 128x128 matrix and single-photon emission tomographic images (64x64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and therefore can be visualized by [111In-DTPA-d-Phe1]-octreotide scintigraphy. This technique can be valuable in the differentiation between meningiomas and pituitary adenomas, based on qualitative tracer uptake. [111In-DTPA-d-Phe1]-octreotide scintigraphy allows differentiation between meningiomas and neurinomas or neurofibromas and therefore provides complementary information to computed tomography or magnetic resonance imaging. Furthermore, this technique allows differentiation between scar tissue and recurrent meningiomas postoperatively and can help in non-invasive tumour differentiation of multiple intracranial lesions, which can be of value in defining the most adequate therapeutic strategy.
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PMID:Somatostatin receptor imaging in intracranial tumours. 966 88

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.
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PMID:Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings. 1004 54

Gastrinomas secrete gastrin and cause symptoms related to gastric acid hypersecretion that can be controlled by antisecretory medications. Primary tumors are located within the pancreas or duodenum and 60% metastasize. Liver metastases are associated with decreased survival. Localization studies especially somatostatin receptor scintigraphy are indicated to image the extent of disease. Surgery is indicated to potentially cure the patient, or control the malignant tumoral process and prolong survival.
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PMID:Gastrinoma: advances in localization and treatment. 973 37

Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging (SRI). However, there may be differences in sensitivity depending on the site of the primary tumour and/or its metastases. We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic (GEP) tract. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients were examined for staging purposes, 80 were in follow-up. Images were acquired 24 and 48 h after the injection of 150-220 MBq of indium-111 pentetreotide. Whole-body and SPET images were obtained in all patients. Patients were also studied with computed tomography (CT), ultrasound (US), and other procedures. Tumours were classified according to their site of origin: pancreas n = 39, ileum n = 32, stomach n = 16, appendix n = 9, duodenum n = 5, jejunum n = 5, rectum n = 3, biliary tract n = 2, colon n = 2, caecum n = 1, liver metastases from unknown primary = 15, widespread metastases from unknown primary = 2. Sensitivity for primary tumour localisation was as follows: SRI = 62%; CT = 43%; US = 36%; other procedures = 45%. Sensitivity for liver metastases: SRI = 90%; CT = 78%; US = 88%; other procedures = 71%. Sensitivity for the detection of extrahepatic soft tissue lesions was: SRI = 90%; CT = 66%; US = 47%; other procedures = 61%. Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites: SRI 4/17; CT 0/13; US 0/12; other procedures 1/10. In 28% of the patients SRI revealed previously unknown lesions, and in 21% it determined a modification of the scheduled therapy. Our study confirms the important role of SRI in the management of GEP tumours. However, we feel that a critical investigation should address its role in locating primary tumours, in particular in patients with metastases from unknown primary sites.
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PMID:Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours. 981 79


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