71 research outputs found

    The Role of Epigenetic Alterations in Papillary Thyroid Carcinogenesis

    Get PDF
    Papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid malignancies. The molecular pathogenesis remains incompletely clarified although activation of the RET fusion oncogenes, and RAS and BRAF oncogenes, has been well characterized. Novel technologies using genome-wide approaches to study tumor genomes and epigenomes have provided great insights into tumor development. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression/function. It has been established beyond doubt that promoter cytosine methylation in CpG islands, and the subsequent gene silencing, is intimately involved in cancer development. These epigenetic events very likely contribute to significant variation in gene expression profiling, phenotypic features, and biologic characteristics seen in PTC. Hypermethylation of promoter regions has also been analyzed in PTC, and most studies have focused on individual genes or a small cohort of genes implicated in tumorigenesis

    Minimally Invasive Parathyroidectomy

    Get PDF
    Minimally invasive parathyroidectomy (MIP) is an operative approach for the treatment of primary hyperparathyroidism (pHPT). Currently, routine use of improved preoperative localization studies, cervical block anesthesia in the conscious patient, and intraoperative parathyroid hormone analyses aid in guiding surgical therapy. MIP requires less surgical dissection causing decreased trauma to tissues, can be performed safely in the ambulatory setting, and is at least as effective as standard cervical exploration. This paper reviews advances in preoperative localization, anesthetic techniques, and intraoperative management of patients undergoing MIP for the treatment of pHPT

    Validation of a stochastic digital packing algorithm for porosity prediction in fluvial gravel deposits

    Get PDF
    Porosity as one of the key properties of sediment mixtures is poorly understood. Most of the existing porosity predictors based upon grain size characteristics have been unable to produce satisfying results for fluvial sediment porosity, due to the lack of consideration of other porosity-controlling factors like grain shape and depositional condition. Considering this, a stochastic digital packing algorithm was applied in this work, which provides an innovative way to pack particles of arbitrary shapes and sizes based on digitization of both particles and packing space. The purpose was to test the applicability of this packing algorithm in predicting fluvial sediment porosity by comparing its predictions with outcomes obtained from laboratory measurements. Laboratory samples examined were two natural fluvial sediments from the Rhine River and Kall River (Germany), and commercial glass beads (spheres). All samples were artificially combined into seven grain size distributions: four unimodal distributions and three bimodal distributions. Our study demonstrates that apart from grain size, grain shape also has a clear impact on porosity. The stochastic digital packing algorithm successfully reproduced the measured variations in porosity for the three different particle sources. However, the packing algorithm systematically overpredicted the porosity measured in random dense packing conditions, mainly because the random motion of particles during settling introduced unwanted kinematic sorting and shape effects. The results suggest that the packing algorithm produces loose packing structures, and is useful for trend analysis of packing porosity

    American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

    Full text link
    Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods and Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98487/1/thy%2E2011%2E0317.pd

    Adrenocortical Carcinoma: Current Therapeutic State-of-the-Art

    Get PDF
    Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice
    corecore