Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease

Background: The landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease-related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy. Methods: We performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited ( Results: In total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210-868), 1,087 (627-1,795), and 1,070 (475-1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively). Conclusion: Subtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach. (C) 2020 Elsevier Inc. All rights reserved

Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study

Purpose: The prognostic importance of RET and RAS mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. Experimental Design: A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes. Results: RET germ line mutations were detected in 40 patients (16.3%). Somatic RET and RAS mutations occurred in 135 (46.9%) and 57 (19.8%) patients, respectively. RETM918T was the most common somatic RET mutation (n = 75). RET somatic mutations were associated with male sex, larger tumor size, advanced American Joint Committee Cancer (AJCC) stage, vascular invasion, and high International Medullary Thyroid Carcinoma Grading System (IMTCGS) grade. When compared with other RET somatic mutations, RETM918T was associated with younger age, AJCC (eighth edition) IV, vascular invasion, extrathyroidal extension, and positive margins. RET somatic or germ line mutations were significantly associated with reduced distant metastasis-free survival on univariate analysis, but there were no significant independent associations on multivariable analysis, after adjusting for tumor grade and stage. There were no significant differences in outcomes between RET somatic and RET germ line mutations, or between RETM918T and other RET mutations. Other recurrent molecular alterations included TP53 (4.2%), ARID2 (2.9%), SETD2 (2.9%), KMT2A (2.9%), and KMT2C (2.9%). Among them, TP53 mutations were associated with decreased overall survival (OS) and disease-specific survival (DSS), independently of tumor grade and AJCC stage. Conclusions: RET somatic mutations were associated with high-grade, aggressive primary tumor characteristics, and decreased distant metastatic-free survival but this relationship was not significant after accounting for tumor grade and disease stage. RETM918T was associated with aggressive primary tumors but was not independently associated with clinical outcomes. TP53 mutation may represent an adverse molecular event associated with decreased OS and DSS in MTC, but its prognostic value needs to be confirmed in future studies

Elevated α-synuclein mRNA levels in individual UV-laser-microdissected dopaminergic substantia nigra neurons in idiopathic Parkinson's disease

The presynaptic protein α-synuclein is involved in several neurodegenerative diseases, including Parkinson's disease (PD). In rare familial forms of PD, causal mutations (PARK1) as well as multiplications (PARK4) of the α-synuclein gene have been identified. In sporadic, idiopathic PD, abnormal accumulation and deposition of α-synuclein might also cause degeneration of dopaminergic midbrain neurons, the clinically most relevant neuronal population in PD. Thus, cell-specific quantification of α-synuclein expression-levels in dopaminergic neurons from idiopathic PD patients in comparison to controls would provide essential information about contributions of α-synuclein to the etiology of PD. However, a number of previous studies addressing this question at the tissue-level yielded varying results regarding α-synuclein expression. To increase specificity, we developed a cell-specific approach for mRNA quantification that also took into account the important issue of variable RNA integrities of the individual human postmortem brain samples. We demonstrate that PCR –amplicon size can confound quantitative gene-expression analysis, in particular of partly degraded RNA. By combining optimized UV-laser microdissection- and quantitative RT–PCR-techniques with suitable PCR assays, we detected significantly elevated α-synuclein mRNA levels in individual, surviving neuromelanin- and tyrosine hydroxylase-positive substantia nigra dopaminergic neurons from idiopathic PD brains compared to controls. These results strengthen the pathophysiologic role of transcriptional dysregulation of the α-synuclein gene in sporadic PD

The Genomic and Evolutionary Landscapes of Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations

Потребительский экстремизм как правовое явление

Материалы XIII Междунар. науч. конф. студентов, магистрантов, аспирантов и молодых ученых, Гомель, 21–22 мая 2020 г

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Minimally Invasive Thyroid Surgery for Diagnostic Excision of Solitary Thyroid Nodules

Various techniques for minimally invasive thyroid surgery (MITS), including endoscopic and video-assisted procedures, have now been described. Based on our unit's experience with minimally invasive parathyroidectomy via a lateral incision, a similar technique for minimally invasive thyroid lobectomy has been developed and assessed. METHODS: The last 203 consecutive thyroid procedures using the MITS technique, performed between July 2002 and June 2006, comprised the study group. Inclusion criteria for initial surgery were: initial nodule < 3.0 cm; no preoperative evidence of malignancy; absence of clinical multinodular change. A 2.5- cm lateral incision, using a headlight illumination, provided optimal exposure. RESULTS: A total of 202 patients underwent 203 MITS procedures over the 4-year period, with one patient undergoing bilateral MITS. The procedures included 155 thyroid lobectomies and 48 nodule excisions; 31 of the patients underwent a minimally invasive parathyroidectomy (MIP) during which an ipsilateral thyroid nodule was removed. The mean tumour size was 17.3 mm, but the mean size of the thyroid lobe removed was 39.5 mm. Final diagnoses included benign multinodular goitre (26%), follicular adenoma (22%) and carcinoma (20%). The complication rate was low, with one permanent recurrent laryngeal nerve (RLN) palsy (anterior division only) (0.5%), four RLN neuropraxias which recovered (2%), and one haematoma not requiring re-operation (0.5%). The rate of complications was not significantly different from 819 conventional open hemithyroidectomies performed over the same period. CONCLUSION: MITS is a safe and feasible alternative to open thyroid surgery in appropriately selected cases. It offers a valuable option for diagnostic excision biopsy in patients with thyroid nodules demonstrating an “atypical” fine-needle biopsy whilst avoiding the need for a standard cervical “collar” incision