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PURPOSE: To assess the diagnostic value of strain ratio elastography (SRE), a semiquantitative elastosonographic method based on the displacement of the tissue from an external source (manual compression with the transducer), as compared and in combination with conventional ultrasound for the differentiation of breast lesions. METHODS: One hundred and eighty-two patients with breast lesions consecutively underwent B-mode, color Doppler US, and strain US-elastography. Each lesion was classified according to the BI-RADS lexicon by evaluating the size, the B-mode, and color Doppler features and then evaluated by SRE. Histology proven by biopsy was used as the gold standard and the patients with malignant lesions subsequently underwent operations. The diagnostic performance of each method was assessed with 2 × 2 contingency tables and ROC curve analysis. To maximize the SRE sensitivity and specificity, the SRE cut-off value was calculated using the Youden test. RESULTS: Histological examination revealed 66 benign and 116 malignant breast lesions. The conventional ultrasound showed sensitivity and specificity for the differentiation of benign and malignant lesions of 86.2% and 75.8%, respectively. Similar results were found for strain US-elastography with a cut-off of 2.49, with sensitivity and specificity of 89.7% and 72.7%, respectively. The association of conventional ultrasound with the SRE value increased the sensitivity (98.3%) but decreased the specificity compared with conventional US alone (63.6%). CONCLUSION: Strain US-elastography can be associated with BI-RADS US examination. According to our preliminary results, it helped increase the sensitivity although it decreased the specificity. However, further multicenter studies on a larger population are warranted.

Background: Treatment of breast cancer (BC) includes locoregional and systemic therapies depending on tumor and patient’s characteristics. Inositol hexaphosphate (IP6) is known as a strong antioxidant agent, able to improve local (i.e., breast region) side effects, functional status and quality-of-life. We investigated some potential beneficial effects, including hematological and local, of the combined therapy with oral myo-inositol administration and topical IP6 application in patients undergoing surgery for BC and eligible to adjuvant chemotherapy. Methods: We considered BC patients randomly assigned to the Inositol Group (oral myo-inositol + IP6 local application for the entire neoadjuvant treatment period) and to the Control Group (standard of care). The EORTC QLQ-BR23 and QLQ-C30 questionnaires were administered to both groups and blood parameters were assessed as per clinical routine practice at baseline (before starting adjuvant chemotherapy), T1 (after the first two doses of epirubicin-cyclophosphamide regimen), T2 (at the end of epirubicin-cyclophosphamide regimen), T3 (after the first six doses of paclitaxel regimen), and T4 (at the end of the paclitaxel treatment). Results: A total of 36 BC patients were considered, 18 in the Inositol Group and 18 in the Control Group. The Inositol Group showed a lower decrease in red blood cells, hemoglobin levels and white blood cells with respect to controls (p ≤ 0.02), as well as amelioration in scores related to breast and arm local symptoms (p ≤ 0.02), body image (p = 0.04) and quality-of-life related symptoms (p ≤ 0.04). Conclusions: In our cohort of BC patients, a combined treatment with oral myo-inositol + IP6 local application was able to improve local symptoms and quality-of-life related symptoms which represent clinically relevant aspects associated with patient’s prognosis.

Multiple primary malignant neoplasms are multiple tumors with different pathogenetic origin. They may be synchronous or metachronous. The management of these conditions represents an interesting clinical scenario. A crucial aspect is the decision regarding which tumor to treat initially, and how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. We describe a case report of a female patient affected by primary synchronous tumors of the breast and pectoral skin, which raised a series of diagnostic, etiological and therapeutic issues persuading us to carry out a critical review of the literature.

PURPOSE Herein we describe the in vitro and in vivo activity of FK228 (Romidepsin), an inhibitor of class I HDACs, in counteracting and radiosensitizing embryonal (ERMS, fusion-negative) and alveolar (ARMS, fusion-positive) rhabdomyosarcoma (RMS). METHODS RH30 (ARMS, fusion-positive) and RD (ERMS, fusion-negative) cell lines and human multipotent mesenchymal stromal cells (HMSC) were used. Flow cytometry analysis, RT-qPCR, western blotting and enzymatic assays were performed. Irradiation was delivered by using an x-6 MV photon linear accelerator. FK228 (1.2 mg/kg) in vivo activity, combined or not with radiation therapy (2 Gy), was assessed in murine xenografts. RESULTS Compared to HMSC, RMS expressed low levels of class I HDACs. In vitro, FK228, as single agents, reversibly downregulated class I HDACs expression and activity and induced oxidative stress, DNA damage and a concomitant growth arrest associated with PARP-1-mediated transient non-apoptotic cell death. Surviving cells upregulated the expression of cyclin A, B, D1, p27, Myc and activated PI3K/Akt/mTOR and MAPK signaling, known to be differently involved in cancer chemoresistance. Interestingly, while no radiosensitizing effects were detected, in vitro or in vivo, on RD cells, FK228 markedly radiosensitized RH30 cells by impairing antioxidant and DSBs repair pathways in vitro. Further, FK228 when combined with RT in vivo significantly reduced tumor mass in mouse RH30 xenografts. CONCLUSION FK228 did not show antitumor activity as a single agent whilst its combination with RT resulted in radiosensitization of fusion-positive RMS cells, thus representing a possible strategy for the treatment of the most aggressive RMS subtype.

Introduction: Seroma formation represents one of the most frequent postoperative complications of axillary dissection in breast cancer (BC) patients. We aimed to retrospectively explore the effectiveness of the intraoperative use of a synthetic cyanoacrylate glue (specifically Glubran®2) vs. the intraoperative use of a fibrin sealant (specifically Tisseel) in reducing seroma formation compared to the use of nonsealant in BC patients who underwent breast surgery and axillary dissection. Materials and Methods: We conducted a retrospective, monocentric observational study on BC patients who underwent axillary dissection associated with breast surgery. The axillary dissection was completed with the application of a closed suction drain and was preceded by the application of either Glubran®2 glue or Tisseel sealant or nonsealant. We analyzed the quantity of serum drained in the first 3 postoperative days, length of hospitalization, days of permanence of axillary drain, seroma development, and presence of postoperative infection signs. Results: Forty-one BC patients were considered. Based on the device used during the surgical treatment, the patients were divided into three groups: group A (17 patients), to whom suction axillary drain was applied; group B (7 patients), to whom Tisseel and axillary suction drain were applied; and group C (17 patients), to whom Glubran®2 and axillary suction drain were applied. Among the three groups, we did not find significant differences in terms of amount of serum drained in the first 3 postoperative days, length of hospitalization, and incidence of seroma. Group C maintained the axillary drain in a significantly lower number of days compared to the other two groups (p = 0.02); it also had a lower incidence of postoperative infections (6%) compared to group A (23%) and group B (57%) (p = 0.02). Conclusions: We did not find any evidence that the use of surgical glues may reduce the formation of seroma following axillary dissection in BC patients. Nevertheless, the use of cyanoacrylate glue in association with closed suction axillary drain seems to contribute to the reduction in days of axillary drain permanence and of postoperative infections, which are known factors delaying the schedule of any adjuvant oncological therapies.

Background:Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells. Methods:Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique. Results:Our results show a decrease in the expression of GPx1 and TrxR1 (-45.7 and -43.2% respectively, p&nbsp

International audience; Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

// Ilaria Benevento 1, * , Nadia Bulzonetti 1, * , Francesca De Felice 1 , Daniela Musio 1 , Massimo Vergine 2 and Vincenzo Tombolini 1 1 Department of Radiotherapy, Policlinico Umberto I, Sapienza University of Rome, Rome 155, Italy 2 Department of Surgical Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome 155, Italy * These authors contributed equally to this work Correspondence to: Ilaria Benevento, email: ilaria.benevento@uniroma1.it Keywords: adjuvant therapy; chemoradiotherapy; radiotherapy; gastric cancer Received: May 29, 2018 Accepted: August 27, 2018 Published: September 21, 2018 ABSTRACT Background and Purpose: Complete surgical resection remains the only curative treatment option in locally advanced gastric cancer (GC). Several studies were conducted to prevent local recurrence and to increase the chance of cure. The aim of this study was to summarize our experience in locally advanced GC patients treated with adjuvant chemoradiotherapy (CRT) and to evaluate overall survival (OS), disease-free survival (DFS), toxicity rate and compliance to treatment. Materials and Methods: Locally advanced GC stage IB-III were included. Adjuvant CRT consisted of 45–50.4 Gy (1.8 Gy/day, 5 days/week) with concomitant Macdonald regimen (Mcd) or Epirubicin, Cisplatin and 5-Fluorouracil (ECF) scheme. Univariate and multivariate analysis of several prognostic factors for OS was conducted. Results: Fourty-nine GC patients were treated: 24 received Mcd and 25 received ECF. Median follow up was 48 months. Acute grade 3–4 toxicity was observed in 6 patients. The 2-year and 5-year OS rates were 65.3% and 41.5%, respectively. The 2-year and 5-year DFS were 59.2% and 41.2%, respectively. No prognostic factors were significantly associated with OS. Conclusions: Adjuvant CRT is a feasible strategy in locally advanced GC. It has an acceptable toxicity rate and it is able to increase both DFS and OS.

Background The mediastinal ectopic thyroid is very rare, accounting for less than 1% of all cases of ectopic thyroid tissue. The differential diagnoses with other diseases such as lymphomas, thymic tumors and dermoid cysts is mandatory, in fact each one, needs different management and treatment. Case presentation Here, we discuss a rare case of mediastinal ectopic thyroid presenting with a paratracheal mass laying on the right bronchus without symptoms. A 63-year-old male presented with an abnormal well-defined mass along the right paratracheal side, detected by chest x-ray. The CT scan confirmed the presence of a 6 × 8 cm heterogeneously enhanced mass, located behind the superior vena cava and left brachiocephalic artery, reaching azygos vein and right bronchus, without a mass effect. Taking into account the clinical importance of a mediastinal mass, we removed it surgically, through a double surgical approach consisting in a classical transverse cervicotomy for the left thyroid lobe, followed then by a longitudinal sternal splitting to remove the mediastinal mass and complete the thyroidectomy. Conclusions In case of mediastinal masses, the surgical excision is recommended, presenting the double advantage to clarify the diagnosis and to treat the pathology. As demonstrated in this case, a mediastinal ectopic thyroid should be taken into account in the differential diagnosis, considering its clinical importance.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with striking vascular proliferations. CD is categorized as being either localized or disseminated and further subdivided into hyaline-vascular, plasma cell, or mixed histopathological patterns. Here we report a case of CD in a 15-year-old girl who presented with a solitary asymptomatic hyaline-vascular mass in the right supraclavicular space. In addition, we discuss the pathogenesis, clinical features and reported comorbidities of unicentric and multicentric CD and evaluate effective treatment strategies based on the results of lymph node biopsy and careful staging. Surgical excision is curative for the localized variants of CD, either hyaline-vascular or plasma cell type. If complete resection is not possible, partial resection or radiotherapy may be useful to control possible systemic manifestations. Multicentric CD, regardless of the histological subtype, is a more aggressive clinical entity, commonly with a chronic or rapidly fatal course. Patients with multicentric CD do not benefit from surgical treatment and should be candidates for systemic therapy (steroids, combination chemotherapy, novel therapies), although this is still in a fairly experimental phase.