Vitiligo and autoimmune thyroid disorders

Vitiligo represents the most common cause of acquired skin, hair and oral depigmentation, affecting 0.5-1% of the population worldwide. It is clinically characterized by the appearance of disfiguring circumscribed skin macules following melanocyte destruction by autoreactive cytotoxic T lymphocytes. Patients affected by vitiligo usually show a poorer quality of life and are more likely to suffer from depressive symptoms, particularly evident in dark-skinned individuals. Although vitiligo is a non-fatal disease, exposure of affected skin to UV light increases the chance of skin irritation and predisposes to skin cancer. In addition, vitiligo has been associated to other rare systemic disorders due to presence of melanocytes in other body districts, such as in the eyes, auditory, nervous and cardiac tissues, where melanocytes are thought to have roles different from that played in the skin. Several pathogenetic models have been proposed to explain vitiligo onset and progression, but clinical and experimental findings point mainly to the autoimmune hypothesis as the most qualified one. In this context, it is of relevance the strong association of vitiligo with other autoimmune diseases, in particular with autoimmune thyroid disorders, such as Hashimoto thyroiditis and Graves’ disease. In this review, after a brief overview of vitiligo and its pathogenesis, we will describe the clinical association between vitiligo and autoimmune thyroid disorders and discuss the possible underlying molecular mechanism(s)

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

Left main bronchus resection and reconstruction. A single institution experience

<p>Abstract</p> <p>Background</p> <p>Left main bronchus resection and reconstruction (LMBRR) is a complex surgical procedure indicated for management of inflammatory, benign and low grade malignant lesions. Its application provides maximal parenchymal sparing.</p> <p>Methods</p> <p>Out of 98 bronchoplastic procedures performed at the Authors' Institution in the 1995-2011 period, 4 were LMBRR. Indications were bronchial carcinoid in 2 cases, inflammatory pseudotumor in 1 case, TBC stricture in 1 case. All patients underwent preoperatively a rigid bronchoscopy to restore the airway lumen patency. At surgery a negative resection margin was confirmed by frozen section in the neoplastic patients. In all patients an end-to-end bronchial anastomosis was constructed according to Grillo.</p> <p>Results</p> <p>There were neither mortality nor major complications. Airway lumen was optimal in 3 patients, good in 1.</p> <p>Conclusion</p> <p>LMBRR is a valuable option for the thoracic surgeon. It maximizes the parenchyma-sparing philosophy, broadening the spectrum of potential candidates for cure. It remains a technically demanding procedure, to be carried out by an experienced surgical team. Correct surgical planning affords excellent results, both in the short and long term.</p

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

Long-term metabolic effects of laparoscopic sleeve gastrectomy

Objective Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the longterm follow-up. Methods One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG < 100 mg/dl, A1c < 6.0%), partial remission (FPG 100–125 mg/dl, A1c < 6.5%), or relapse. Results Before surgery, body weight and BMI were 123 ± 21 kg and 44.6 ± 6.8 kg/m2 respectively; at a mean follow-up of 7 years (range 4–10), body weight was 104.9 ± 18 kg and BMI 37 ± 6 kg/m2 . Minimum weight was reached after 2 years. T2DM remission was observed in 66, 57, and 52% at short ( 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively. Conclusions LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-u

Long-term metabolic effects of laparoscopic sleeve gastrectomy

Objective Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the longterm follow-up. Methods One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG < 100 mg/dl, A1c < 6.0%), partial remission (FPG 100–125 mg/dl, A1c < 6.5%), or relapse. Results Before surgery, body weight and BMI were 123 ± 21 kg and 44.6 ± 6.8 kg/m2 respectively; at a mean follow-up of 7 years (range 4–10), body weight was 104.9 ± 18 kg and BMI 37 ± 6 kg/m2 . Minimum weight was reached after 2 years. T2DM remission was observed in 66, 57, and 52% at short ( 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively. Conclusions LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-u

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)

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