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

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

Incidence and Risk Factors for Occult Level 3 Lymph Node Metastases in Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) frequently disseminates into cervical lymph nodes. Lateral node involvement is described in up to 50 % patients undergoing prophylactic lateral neck dissection. This study aimed to assess this finding and identify which factors predict for occult lateral node disease. Patients with fine needle aspiration-confirmed PTC (Bethesda V or VI), without evidence of cervical lymph node metastases, underwent a total thyroidectomy with prophylactic ipsilateral central and level 3 dissection. Level 3 nodes were removed by compartmental dissection or by sampling the sentinel nodes overlying the jugular vein, according to surgeon preference. Data were collected prospectively from January 2011 to August 2014. Statistical analysis was performed by SPSS software. A total of 137 patients underwent total thyroidectomy with prophylactic ipsilateral central and level 3 dissection for PTC. The incidence of occult level 3 disease was 30 % (41/137 patients). A total of 48 % of patients (66/137) harbored occult central neck disease. A total of 80.5 % of patients with pN1b disease had macrometastases (aeyen2 mm), and 15 % exhibited skip metastases with central compartment sparing. In patients with pN1b disease, a median of 6 level 3 nodes were retrieved, with an average involved nodal ratio of 0.29. Multivariate regression demonstrated risk factors for occult lateral neck metastasis include tumor size (odds ratio 1.1), upper pole tumors (odds ratio 6.6), and vascular invasion (odds ratio 3.2) (p <0.05). PTC is associated with a significant incidence of occult central and lateral nodal metastases. In patients undergoing prophylactic central neck dissection, inclusion of level 3 dissection should be considered in patients with large upper lobe cancers

Dysregulation of microRNAs in adrenocortical tumors.

International audienceMicroRNAs (miRNAs) are short non-coding RNAs that are involved in the epigenetic regulation of cellular processes. Different malignancies are often associated with the deregulation of specific sets of miRNAs. The prognosis of adrenocortical cancers (ACCs) is very poor as compared to adrenocortical adenomas (ACAs), and even within ACCs there are cases with better disease specific survival. An improved understanding of the pathobiology of this disease will therefore be useful in facilitating better management of ACCs as well as distinguishing high risk versus low risk subgroups. One third of coding genes are regulated by miRNAs and therefore changes in miRNA expression may be associated with cancer development and progression. In this review we summarize the current understanding of miRNAs in adrenocortical tumors, and highlight their potential in differentiating between ACCs and ACAs, risk stratification and prognosis

Translational applications of microRNAs in cancer, and therapeutic implications

The search for targeted novel therapies for cancer is ongoing. MicroRNAs (miRNAs) display a number of characteristics making them an attractive and realisable option. In this review, we explore these applications, ranging from diagnostics, prognostics, disease surveillance, to being a primary therapy or a tool to sensitise patients to treatment modalities such as chemotherapy and radiotherapy. We take a particular perspective towards miRNAs and their impact on rare cancers. Advancement in the delivery of miRNAs, from viral vectors and liposomal delivery to nanoparticle based, has led to a number of pre-clinical and clinical applications for microRNA cancer therapeutics. This is promising, especially in the setting of rare cancers

Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer

Micro-RNAs are dysregulated in medullary thyroid carcinoma (MTC) and preliminary studies have shown that miRNAs may enact a therapeutic effect through changes in autophagic flux. Our aim was to study the in vitro effect of miR-9-3p on MTC cell viability, autophagy and to investigate the mRNA autophagy gene profile of sporadic versus hereditary MTC. The therapeutic role of miR-9-3p was investigated in vitro using human MTC cell lines (TT and MZ-CRC-1 cells), cell viability assays, and functional mechanism studies with a focus on cell cycle, apoptosis, and autophagy. Post-miR-9-3p transfection mRNA profiling of cell lines was performed using a customized, quantitative RT-PCR gene array card. This card was also run on clinical tumor samples (sporadic: n = 6; hereditary: n = 6) and correlated with clinical data. Mir-9-3p transfection resulted in reduced in vitro cell viability; an effect mediated through autophagy inhibition. This was accompanied by evidence of G2 arrest in the TT cell line and increased apoptosis in both cell lines. Atg5 was validated as a predicted miR-9-3p mRNA target in TT cells. Post-miR-9-3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP-1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin-1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin-1 expression may be a useful prognostic biomarker of aggressive disease