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- Grama, D, et al.
(författare)
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Pancreatic tumors in multiple endocrine neoplasia type 1 : clinical presentation and surgical treatment
- 1992
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Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 16:4, s. 611-618
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Tidskriftsartikel (refereegranskat)abstract
- Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.
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- Eriksson, B. K., et al.
(författare)
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Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors
- 1998
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Ingår i: Cancer. - 0008-543X .- 1097-0142. ; 83:11, s. 2293-2301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, interferon-alpha (IFN), and somatostatin analogs are established therapies for these patients, but all of them eventually fail. Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients. METHODS Between 1981 and 1995, a total of 55 liver embolizations with gel foam powder were performed on 41 patients with histopathologically verified neuroendocrine tumors; 29 had carcinoid tumors and 12 had endocrine pancreatic tumors (EPTs). All patients had received medical treatment, including chemotherapy (n = 18), IFN (n = 31), and octreotide (n = 19), and were experiencing treatment failure when liver embolization was performed at a median of 37 months after diagnosis of liver metastases. Medical treatment was continued after embolization. RESULTS An overall objective response was noted in 15 of 29 patients with carcinoid tumors (52%). The median duration of effect was 12 months in patients with midgut carcinoid tumors. An overall objective response was observed in 6 of 12 patients with EPTs (50%), with a median duration of effect of 10 months. Adverse events were observed, and, in agreement with earlier reports, the rate of serious complications was 10%. Survival analyses showed a median survival of 80 months and a 5-year survival rate of 60% from the performance of embolization on patients with midgut carcinoid tumors, whereas for patients with EPTs the median survival from embolization was only 20 months. CONCLUSIONS Liver embolizations performed relatively late in the clinical course in our series appeared to be as effective as "early" embolizations in other series of patients with carcinoid tumors. The results for those with EPTs were poorer, and earlier embolizations may result in better outcomes for these patients. Considering the morbidity associated with the procedure, it is imperative to select patients according to extent of liver involvement, severity of carcinoid heart disease, and somatostatin receptor status.
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- Fahlke, Claudia, 1964, et al.
(författare)
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Förord
- 2018
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Ingår i: Alkohol och samhället, tema alkohol och äldre.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Granberg, D, et al.
(författare)
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Lung and thymic carcinoids.
- 2000
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Ingår i: Surgical Endocrinology. - : Williams and Wilkins Publishers. ; , s. 413-
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Kerkhofs, Tm, et al.
(författare)
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Comparison of Two Mitotane Starting dose Regimens in Patients with Advanced Adrenocortical Carcinoma
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:12, s. 2281-
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Tidskriftsartikel (refereegranskat)abstract
- Context:Mitotane is the only approved drug for treatment of adrenocortical carcinoma(ACC). Its pharmacokinetic properties are not fully elucidated and different dosing regimens have never been compared head-to-head.Objective:To investigate the relationship between mitotane dose and plasma concentration comparing two dosing regimens.Design/Setting:Prospective open-label multicenter trial of a predefined duration of twelve weeks.Patients/Interventions:Forty mitotane-naïve patients with metastatic ACC were assigned to a predefined low- or high-dose regimen by the local investigator. Thirty-two could be evaluated in detail.Main Outcome Measure:Difference in median mitotane plasma levels between both treatment groups.Results:Despite a difference in mean cumulative dose (440±142g versus 272±121g), median maximum plasma levels were not significantly different between the two groups (high-dose 14.3mg/L (6.3-29.7,n=20) versus 11.3mg/L (5.5-20.0,n=12), p=0.235). Ten out of twenty patients on the high-dose regimen reached plasma concentrations ≥14mg/L after 46 days (18-81 days) compared to four of twelve patients on the low-dose regimen after 55 days (46-74 days,p=0.286). All patients who reached 14mg/L at 12 weeks displayed a level ≥4.1 mg/L on day 33 (100% sensitivity). There were no significant differences in frequency and severity of adverse events. Among patients not receiving concomitant chemotherapy mitotane exposure was higher in the high-dose group: 1013±494mg.d/L versus 555±168mg.d/L, p=0.080.Conclusions:The high-dose starting regimen did neither result in significantly different mitotane levels nor in a different rate of adverse events, but concomitant chemotherapy influenced these results. Thus, for mitotane monotherapy the high-dose approach is favorable, whereas for combination therapy a lower dose seems reasonable.
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- Tacon, Lyndal J., et al.
(författare)
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The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:11, s. 4591-4599
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. The Weiss score is the most widely accepted method for distinguishing an ACC from an adrenocortical adenoma (ACA); however, in borderline cases, accurate diagnosis remains problematic. We recently discovered that the glucocorticoid receptor (GR) gene NR3C1 is significantly up-regulated in ACCs compared with ACAs in global gene expression studies. OBJECTIVE: Our objective was to study GR expression in adrenocortical tumors (ACTs) and to assess its utility as an adjunct to the Weiss score. DESIGN: Microarray analysis, real-time quantitative RT-PCR (qPCR), immunohistochemistry, Western blot, and direct sequencing were performed. RESULTS: Analysis of 28 ACTs by microarray and 49 ACTs by qPCR found NR3C1 expression to be up-regulated in ACCs compared with ACAs (P < 0.001). Western blotting and RT-PCR confirmed the presence of the GRalpha isoform in ACCs, and no mutations were detected on direct sequencing. Immunohistochemistry for GR in an overlapping cohort of ACTs demonstrated strongly positive nuclear staining in 31 of 33 ACCs (94%), with negative staining in 40 of 41 ACAs (98%) (P < 0.001). This finding was validated in an external cohort of ACTs, such that 14 of 18 ACCs (78%) demonstrated positive nuclear staining whereas 32 of 33 ACAs (94%) were negative (P < 0.001). CONCLUSIONS: The immunohistochemical finding of nuclear GR staining identified ACCs with high diagnostic accuracy. We propose that GR immunohistochemistry may complement the Weiss score in the diagnosis of ACC in cases that display borderline histology. The possibility that GR is transcriptionally active in these tumors, and may therefore be a therapeutic target, requires further study.
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- Teh, Bin T, et al.
(författare)
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Thymic carcinoids in multiple endocrine neoplasia type 1
- 1998
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Ingår i: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 228:1, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved.
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| 37. |
- Weber, G, et al.
(författare)
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The phospholipase C b 3 gene located in the MEN 1 region shows loss of expression in endocrine tumors
- 1994
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 3:10, s. 1775-1781
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Tidskriftsartikel (refereegranskat)abstract
- Oncogenesis of tumours related to multiple endocrine neoplasia type 1 (MEN1) is associated with somatic deletions involving the MEN1 locus, suggesting inactivation of a tumour suppressor gene in this region. Identification of meiotic cross-overs in MEN1 families has placed the MEN1 locus centromeric of D11S807. An extended deletion mapping was performed in 27 primary parathyroid tumours, and identified D11S427 as the closest centromeric flanking marker. Through physical mapping using newly isolated cDNA clones, we estimated the distance between the flanking markers D11S807 and D11S427 to be less than 900 kb. One of these cDNA clones showed expression of a 4.4 kb message in multiple tissues, including those affected in MEN1, while in five endocrine tumours no transcript was detected. Sequence characterization showed that this gene encodes for the phospholipase C beta 3, a key enzyme in signal transduction.
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