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- Aarum, S, et al.
(author)
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Operation for primary hyperparathyroidism: the new versus the old order. A randomised controlled trial of preoperative localisation
- 2007
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In: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1457-4969. ; 96:1, s. 26-30
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Journal article (peer-reviewed)abstract
- In patients with primary hyperparathyroidism (PHPT), parathyroid imaging is nowadays routinely used for the purpose to perform a focused unilateral minimally invasive operation. The outcome of this new strategy has, however, not been established in randomised trials. Material and Methods: Patients were randomised to either preoperative localisation with sestamibi scintigraphy and ultrasonography (group I) or no preoperative localisation (group II). In group I, a minimally invasive parathyroidectomy was performed in patients in whom both localisation studies were consistent with a single pathological gland, whereas a conventional bilateral neck exploration was performed in cases with negative localisation findings. In group II all patients underwent conventional bilateral neck exploration. Primary outcome measure was normocalcaemia at 6 months postoperatively. Results: In the preoperative localisation group (group I) 23/50 (46%) of the patients could be operated on with the focused operation whereas 26/50 (52%) were operated on by bilateral neck exploration. All patients in the no localisation group (group II; n=50) were operated on with the intended bilateral neck operation. Normocalcaemia was obtained in 96% and 94% in group I and II, respectively. Total (localisation and operative) costs were 21% higher in group I. Conclusions: Routine preoperative localisation, with the intention to perform minimally invasive parathyroidectomy, is not cost effective if concordant results of scintigraphy and ultrasonography are a prerequisite for the focused operation. Less than half of the patients were successfully managed with this strategy, at a higher cost and without obtaining a more favourable clinical outcome.
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- Hydman, J, et al.
(author)
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Diagnosis and prognosis of iatrogenic injury of the recurrent laryngeal nerve
- 2009
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In: The Annals of otology, rhinology, and laryngology. - : SAGE Publications. - 0003-4894 .- 1943-572X. ; 118:7, s. 506-511
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Journal article (peer-reviewed)abstract
- Following perioperative injury to a macroscopically intact recurrent laryngeal nerve (RLN), there are two possible intraneural injury types: 1) axonal injury, including disruption of axons, and 2) conduction block, only affecting the Schwann cells and the nodes of Ranvier. In this study, it was hypothesized that the functional outcome after RLN injury may depend on the type of nerve injury. Methods: Fifteen patients with acute postoperative unilateral RLN paralysis were prospectively studied. Electrophysiological examination (laryngeal electromyography) was used to differentiate between the two types of nerve injury. Vocal fold motions were monitored by repeated laryngoscopy during the study period (up to 6 months). Three of the patients with axonal injury were treated with the regeneration-promoting agent nimodipine. Results: The patients with conduction block all recovered normal vocal fold motion, whereas patients with axonal injury within the nerve had a significantly worse outcome. The 3 patients who were treated with nimodipine all recovered normal or near-normal vocal fold mobility despite the more severe axonal injury. Conclusions: In contrast to previous reports, our results show that laryngeal electromyography is a reliable tool for diagnosing the type of injury within the injured RLN, making it possible to predict the functional outcome in these patients. On the basis of the results, a future randomized study on nimodipine treatment for RLN axonal injury is suggested.
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- Palmhag, D, et al.
(author)
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A single parathyroid hormone measurement two hours after a thyroidectomy reliably predicts permanent hypoparathyroidism
- 2021
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In: Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society. - : SAGE Publications. - 1799-7267. ; 110:3, s. 322-328
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Journal article (peer-reviewed)abstract
- Hypoparathyroidism is the most common complication following thyroidectomy, and various algorithms for early detection have been suggested. The aim of this study was to evaluate the predictive value of measuring the parathyroid hormone level 2 h after thyroidectomy and whether determination of the perioperative decline in parathyroid hormone added diagnostic value. Methods: Patients subjected to thyroidectomy for benign thyroid disorders were analyzed in (1) a retrospective register-based study (366 consecutive patients treated during 2015–2016) and (2) a prospective observational study (39 patients treated during 2018). Optimal cut-off values for postoperative parathyroid hormone and perioperative decline (%) in parathyroid hormone were determined by receiver operating characteristics and area under the curve. Sensitivity, specificity, positive and negative predictive values were calculated using cross tabulation. Results: The prevalence of hypoparathyroidism the first day after thyroidectomy was higher among patients treated for hyperthyroidism (30% vs 20%; P = 0.03). The optimal cut-off level for postoperative parathyroid hormone was 1.1 pmol/L (area under the curve = 0.887, 95% confidence interval: 0.839–0.934; positive predictive value: 88%, negative predictive value: 93%) for the entire cohort. When the groups were analyzed separately, the optimal cut-off was 1.05 for the non-hyperfunctioning group and 1.55 pmol/L for the group with hyperthyroidism. Twelve months after thyroidectomy, 3% were defined as having permanent hypoparathyroidism. Measurement of parathyroid hormone decline added diagnostic value for one patient with preoperative parathyroid-hormone-elevation associated with vitamin D deficiency. Conclusions: For patients with vitamin D sufficiency, the diagnostic accuracy of a single measurement of parathyroid hormone 2 h after thyroidectomy is an excellent indicator for predicting transient hypoparathyroidism.
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- Teh, Bin T, et al.
(author)
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Thymic carcinoids in multiple endocrine neoplasia type 1
- 1998
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In: Annals of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 228:1, s. 99-105
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Journal article (peer-reviewed)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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- Weber, G, et al.
(author)
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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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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 3:10, s. 1775-1781
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Journal article (peer-reviewed)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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- Berglund, Erik, et al.
(author)
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Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells.
- 2014
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In: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 25:4, s. 415-22
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Journal article (peer-reviewed)abstract
- Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract. In most GISTs, the underlying mechanism is a gain-of-function mutation in the KIT or the PDGFRA gene. Imatinib is a tyrosine kinase inhibitor that specifically blocks the intracellular ATP-binding sites of these receptors. A correlation exists between plasma levels of imatinib and progression-free survival, but it is not known whether the plasma concentration correlates with the intracellular drug concentration. We determined intracellular imatinib levels in two GIST cell lines: the imatinib-sensitive GIST882 and the imatinib-resistant GIST48. After exposing the GIST cells to imatinib, the intracellular concentrations were evaluated using LC-MS (TOF). The concentration of imatinib in clinical samples from three patients was also determined to assess the validity and reliability of the method in the clinical setting. Determination of imatinib uptake fits within detection levels and values are highly reproducible. The GIST48 cells showed significantly lower imatinib uptake compared with GIST882 in therapeutic doses, indicating a possible difference in uptake mechanisms. Furthermore, imatinib accumulated in the tumor tissues and showed intratumoral regional differences. These data show, for the first time, a feasible and reproducible technique to measure intracellular imatinib levels in experimental and clinical settings. The difference in the intracellular imatinib concentration between the cell lines and clinical samples indicates that drug transporters may contribute toward resistance mechanisms in GIST cells. This highlights the importance of further clinical studies to quantify drug transporter expression and measure intracellular imatinib levels in GIST patients.
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