Grey-scale analysis improves the ultrasonographic evaluation of thyroid nodules

Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03-0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4-74.5%), specificity of 72.0% (67.8-75.9%), positive likelihood ratio (LR) of 2.023 (1.434-2.852), and negative LR of 0.602 (0.398-0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59-7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69-105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7-90.1%), specificity of 46.8% (42.3-51.4%), positive LR of 1.442 (1.164-1.786), and negative LR of 0.498 (0.259-0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure

Ultrasound-guided laser ablation for local control of neck recurrences of medullary thyroid cancer. A feasibility study.

Surgery is the standard treatment for cervical metastases of medullary thyroid cancer (MTC) diagnosed after initial surgical treatment. Repeated neck dissections, however, carry an elevated risk of complications, have an adverse impact on the quality of life, and sometimes do not achieve cure of the disease Clinical case: In a patient who had undergone two cervical neck dissections complicated by accessory nerve injury, an US-guided laser ablation (LA) of a lymph node metastasis of MTC was performed. LA was performed with two treatments during a five month period. The procedure was carried out with one optical fiber and an energy delivery of 3300 and 360 Joules. Treatments were well tolerated and resulted in complete structural and biochemical cure during a 12 month follow-up. No major complication was registered.LA is a promising tool for the management of relapsing cervical metastases that are localized in non- critical areas and are characterized by low progression rate. Advantages of LA are the outpatient setting, the absence of general anesthesia, the tolerability and the safety of the procedure. Thus, LA may be considered as an alternative approach to surgery or active surveillance for the management of local recurrences of MTC in selected patients

Thyroid autoantibodies and breast cancer

Dear Editor We read with interest the recent article by Shi and colleagues (2014) reporting a meta-analysis on the relationship between thyroid hormones, thyroid autoantibodies and breast cancer (BC). In the paper, the authors analyzed eight different studies, including 4,189 participants, and concluded that serum levels of free-triiodothyronine, thyroperoxidase and thyroglobulin autoantibodies are higher in patients affected by BC, compared with the control group. These findings are in agreement with the meta-analysis reported by Hardefeldt and colleagues, showing an increased risk of BC in patients with autoimmune thyroid disease, and with a recent article by our group in which the prevalence of BC in 3,921 female patients affected by both benign and malignant thyroid diseases was evaluated (Hardefeldt et al., 2012; Prinzi et al., 2014). In the latter, we showed that the prevalence of BC in patients affected by thyroid disease, as a whole, was significantly higher, compared to the general population (OR 3.3). Moreover, the age-matched analysis showed that the risk of BC was higher in younger patients (0–44 yr, OR 15.2), to decline with the increasing age. In the same study, when patients were dichotomized based on the presence or the absence of thyroglobulin and/or thyroperoxidase autoantibodies, both groups showed a higher risk of BC, compared to the general female population. When the two groups were compared to each other, however, the risk of BC was significantly lower in autoantibody positive patients. Thus, as clearly stated in our article, among patients affected by thyroid diseases, the presence of thyroid autoantibodies may have a protective role against BC (Prinzi et al., 2014). As a consequence, the sentence reported by Shi and colleagues in the Discussion section of their article stating that their findings are in disagreement with our data is not correct and should be, if at all possible, amended

Management of patient with gaves' orbitopathy [Gestione del paziente con orbitopatia di graves]

Management of patient with Gaves' Orbitopathy Graves'orbitopathy (GO) is the most common and important extrathyroidal manifestation of Flajani-Basedow-Graves' disease, with autoimmune etiology. In most cases they are mild forms, in 3-5% they are severe and progressive. For therapeutic purposes, it is classified according to the severity (mild, moderate-severe or sight threatening), to the activity (active if clinical activity score is ≥3), and to the impact on quality of life. The choice of medical or surgical therapy depends on the activity of the disease. Therapy for mild GO consists of abolition of risk factors, local treatments, oral administration of selenium. Therapy for moderate-severe and active GO consists of administration of intravenous, oral, topic and local (retrobulbar, peribulbar and subconjunctival) glucocorticoids (GC). The therapy of choice, after careful selection of patients, is pulse therapy with intravenous GC, with 79% of response. Orbital radiotherapy is effective in 60% of cases; diabetes mellitus and hypertension are absolute contraindications. Contemporary administration of oral GC and orbital radiotherapy are more effective than single therapies. Marginal and not validated therapies are cyclosporine, somatostatin analogues, TNF-α inhibitors and rituximab. The treatment for dysthyroid optic neuropathy (DON) consists of combination of steroids, orbital radiotherapy and, if necessary, orbital decompression surgery. The surgical therapies are orbital decompression and rehabilitative surgery. © Società Editrice Universo (SEU)

Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein.

International audienceAurora-C, a member of the Aurora kinase family, is implicated in the regulation of mitosis. In contrast to Aurora-A and Aurora-B its cellular localization and functions are poorly characterized. TACC1 protein belongs to the transforming acidic coiled-coil family shown to interact with the Aurora kinases. In the present study we analyzed the interaction between Aurora-C and TACC1 by means of immunofluorescence (IF), co-immunoprecipitation (IP) and in vitro phosphorylation experiments. We demonstrated that Aurora-C and TACC1 proteins co-localize to the midbody of HeLa cells during cytokinesis. Immunoprecipitated TACC1 from HeLa cell extracts was associated with Aurora-C. In addition, the interaction of the two proteins was tested by analyzing the phosphorylation of TACC1 in vitro. The results demonstrated that TACC1 is phosphorylated by Aurora-C on a serine at position 228. In conclusion, the study demonstrated that TACC1 localizes at the midbody during cytokinesis and interacts with and is a substrate of Aurora-C, which warrant further investigation in order to elucidate the functional significance of this interaction

Emerging molecular markers for the prognosis of differentiated thyroid cancer patients

Epithelial thyroid cancers are represented by the differentiated papillary and follicular thyroid carcinomas which, following dedifferentiation, are thought to give rise to the highly aggressive and incurable anaplastic thyroid carcinomas. Although derived from the same cell type, the different thyroid tumors show specific histological features, biological behavior and degree of differentiation as a consequence of different genetic alterations. Over the last few years, our knowledge regarding the molecular alterations underlying thyroid cell malignant transformation and cancer progression has considerably increased; however, the prognosis of differentiated thyroid cancer patients still relies on high-risk clinic-pathological variables. In particular, the actual staging systems provides only a rough prediction for cancer mortality and risk of recurrences, including in each risk group patients with highly different tumor-specific progression, disease-free interval and survival time. In order to improve DTC patient's risk stratification, both the European and the American Thyroid Associations proposed practical guidelines to integrate the actual staging systems with additional clinical features such as the tumor histological variant, the results of post-ablative whole body scan and the serum thyroglobulin levels. Despite that, patients within the same risk group still show a very heterogeneous behavior in terms of disease-free interval. As a consequence, the identification of new prognostic molecular biomarkers able to testify tumor aggressiveness is highly required. Here we'll review recently characterized new molecular markers potentially able to ameliorate the prognosis in DTC patients. © 2014 Surgical Associates Ltd

Preclinical testing of selective Aurora kinase inhibitors on a medullary thyroid carcinoma-derived cell line

Purpose: Deregulated expression of the Aurora kinases (Aurora-A, -B and -C) is thought to be involved in cell malignant transformation and genomic instability in several cancer types. Over the last decade, a number of small molecule inhibitors of Aurora kinases have been developed, which have proved to efficiently restrain malignant cell growth and tumorigenicity. Regarding medullary thyroid carcinoma (MTC), we previously showed the efficacy of a pan-Aurora kinase inhibitor (MK-0457) in impairing growth and survival of the MTC-derived cell line TT. In the present study, we sought to establish if one of the Aurora kinases might represent a preferential inhibitor target for MTC. Methods: The effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on TT cell proliferation, apoptosis, cell cycle and ploidy. Results: The two inhibitors reduced TT cell proliferation in a time- and dose-dependent manner, with IC50 19.0±2.4 nM for MLN8237 and 401.6±44.1 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited phosphorylation of histone H3(Ser10) by Aurora-B, while did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3(Ser10) phosphorylation. Cytofluorimetry experiments showed that both inhibitors induced accumulation of cells in G2/M phase and increased the subG0/G1 fraction and polyploidy. Finally, both inhibitors triggered apoptosis. Conclusions: We demonstrated that inhibition of either Aurora-A or Aurora-B has anti-proliferative effects on TT cells, and thus it would be worthwhile to further investigate the therapeutical potential of Aurora kinase inhibitors in MTC treatment

Stat3-positive tumor cells contribute to vessels neoformation in primary central nervous system lymphoma

With the aim of elucidating the relationship between Stat3 expression and tumor vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3 expression by Real-time PCR and by immunohistochemistry in biopsy sections from PCNSL patients. Correlations of the expression levels with the presence of aberrant vessels were analyzed by confocal laser microscopy analysis, using FVIII as endothelial cell marker, CD133 and nestin as cancer stem cell (CSC) marker, CD20 as tumor cell marker, and Stat3. In addition, we investigated Stat3 mutations in lymphoma cells to clarify the role of the constitutive expression of Stat3 and of its phosphorylated forms. Results showed that in PCNSL, putative endothelial cells lining the vessels are heterogeneous, expressing FVIII/ pStat3/CD133 (presumably originally they are vascular progenitor cells), as well as FVIII/CD20/CD133 (presumably originally they are tumor cells). Finally, we detected a fraction of the FVIII+ endothelial cell that co-expressed Stat3 bearing a tetraploid karyotype, while no amplification signal for the Stat3 gene was detected