Telomerase activation through induction of its catalytic component telomerase reverse transcriptase (TERT) expression is essential for malignant transformation. TERT promoter mutations namely C228T ...and C250T that stimulate TERT transcription and telomerase activation have recently been identified in many human malignancies. We thus determined these mutations and their biological and clinical implications in thyroid carcinomas in the present study. The TERT promoter was sequenced in 10 thyroid cancer cell lines and 144 tumors from 20 patients with anaplastic thyroid carcinoma (ATC), 51 with papillary thyroid carcinoma (PTC), 36 with follicular thyroid carcinoma (FTC), and 37 with medullary thyroid carcinoma (MTC). We identified C228T or C250T mutation in 6/8 of ATC cell lines, as well as in tumor tissue from 10/20, 13/51, 8/36 and 0/37 patients with ATC, PTC, FTC and MTC, respectively. In PTC patients, these mutations were exclusively present in the group with age >45 years (P<0.0001), and highly correlated shorter telomeres (P<0.0001) and distant metastasis (P=0.028). The previous radioactivity exposure did not induce the mutation. The presence of C228T or C250T was an independent predictor associated with shorter disease-related survival (DRS) in the entire cohort (P<0.0001), as well as among patients >45 years (P=0.021). ATC patients carrying the mutation survived shorter than those without mutations, although not statistically significant (P=0.129). The TERT promoter mutation was associated with overall survival (P=0.038) and DRS (P=0.058) of FTC patients. Taken together, age- and shorter telomere-dependent TERT promoter mutations occur frequently in follicular cell-derived thyroid carcinoma (ATC, PTC and FTC) but not in parafollicular cell-originated MTC, and may serve as a marker for aggressive disease and poor outcome.
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Background
Transection injury to the recurrent laryngeal nerve (RLN) has been associated with permanent vocal fold palsy, and treatment has been limited to voice therapy or local treatment of vocal ...folds. Microsurgical repair has been reported to induce a better function. The calcium channel antagonist nimodipine improves functional recovery after experimental nerve injury and also after cranial nerve injury in patients. This study aims to present voice outcome in patients who underwent repair of the RLN and received nimodipine during regeneration.
Methods
From 2002–2016, 19 patients were admitted to our center with complete unilateral injury to the RLN and underwent microsurgical repair of the RLN. After nerve repair, patients received nimodipine for 2–3 months. Laryngoscopy was performed repeatedly up to 14 months postoperatively. The Voice Handicap Index (VHI) was administered, and patients’ maximum phonation time (MPT) was recorded during the follow-up.
Results
All patients recovered well after surgery, and nimodipine was well tolerated with no dropouts. None of the patients suffered from atrophy of the vocal fold, and some patients even showed a small ab/adduction of the vocal fold on the repaired side with laryngoscopy. During long-term follow-up (>3 years), VHI and MPT normalized, indicating a nearly complete recovery from unilateral RLN injury.
Conclusions
In this cohort study, we report the results of the first 19 consecutive cases at our center subjected to reconstruction of the RLN and adjuvant nimodipine treatment. The outcome of the current strategy is encouraging and should be considered after iatrogenic RLN transection injuries.
Introduction:
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.
Background and Aims:
Primary aldosteronism is a common cause of secondary hypertension. Primary aldosteronism is caused by an aldosterone-producing adenoma or bilateral hyperplasia that in some cases ...is asymmetrical with one adrenal dominating aldosterone secretion. Most patients with aldosterone-producing adenoma are biochemically cured by unilateral adrenalectomy, but patients with bilateral hyperplasia have a significant risk of residual or recurrent disease. Here, immunohistochemistry of CYP11B1 and B2 was used to investigate whether these markers could aid in the diagnostic workup of primary aldosteronism patients.
Materials and Methods:
A total of 39 patients with primary aldosteronism who underwent unilateral adrenalectomy for a presumed adenoma during 2013–2016 were included. Immunohistochemistry using monoclonal antibodies identifying the enzymes CYP11B1 and B2 was part of routine histopathological workup in 6 cases; in 33 cases, it was applied retrospectively. The hyperplasia diagnosis was suggested when there was no dominating nodule but immunoreactivity for CYP11B2 was seen in several nodules, which were also seen on routine sections. To distinguish between adenoma and hyperplasia, a ratio between the largest and second largest CYP11B2-positive nodules was calculated.
Results:
In all, 22 patients had an aldosterone-producing adenoma, while 13 patients were judged to have hyperplasia. In four cases, a final diagnosis could not be established, thus these were judged equivocal. Among the 33 cases investigated retrospectively, the primary histopathological diagnosis was altered from hyperplasia to aldosterone-producing adenoma in 9 cases (27%) after immunohistochemistry, and the immunohistochemically rectified adenoma group displayed improved clinical cure rates compared to the routine H&E-diagnosed cohort. Moreover, the B2 ratio was significantly higher in adenoma than in hyperplasia and equivocal cases.
Conclusion:
Immunohistochemistry detecting CYP11B1 and B2 expression is of great help in establishing a final histopathological diagnosis in patients with primary aldosteronism. This procedure should be part of the histopathological routine in all operated primary aldosteronism patients.
Background
In patients with small intestinal neuroendocrine tumour (SI‐NET), liver resection or radiofrequency ablation (RFA) of liver metastases is performed for palliation of carcinoid syndrome, ...and in an effort to improve survival. Data are generally reported from case series, and no randomized trials have studied these treatments. The aim was to compare outcome after liver resection and/or RFA with that of non‐surgical treatment in patients with liver metastases from SI‐NET.
Methods
The study included patients with liver metastases from SI‐NET who underwent liver RFA/resection or were treated non‐surgically. A propensity score match was performed to reduce bias between groups, using baseline variables such as the Charlson co‐morbidity index, age, symptoms, carcinoid heart disease, extent of metastases and proliferation index.
Results
Some 103 patients who had RFA and/or liver resection were compared with 273 controls. Propensity score matching resulted in two matched groups, each of 72 patients, with no significant differences in baseline variables. The matched resection/RFA and control groups showed no difference in overall survival (both 74 per cent at 5 years; P = 0·869) or disease‐specific survival (74 versus 78 per cent respectively at 5 years; P = 1·000). However, urinary 5‐hydroxyindoleacetic acid levels were lower (median 77 versus 120 µmol per 24 h; P = 0·005) and the proportion of patients with progressive disease within the liver was smaller (2 of 18 versus 8 of 18; P < 0·001) in the resection/RFA group after 5 years.
Conclusion
These data do not support the use of liver resection and/or RFA in an effort to prolong survival in patients with liver metastases from SI‐NET.
Did not increase survival
Objectives:
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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