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Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.

Background: Thymic epithelial tumors (TETs) are rare neoplasms, originating from epithelial thymic cells. The oncogenic potential of these rare neoplasms is still largely undefined, and a deeper molecular characterization could result in a relevant advance in their management, greatly improving diagnosis, prognosis and treatment choice. Deregulation of N6-methyladenosine (m6A) RNA modification, catalyzed by the METTL3/METTL14 methyltransferase complex, is emerging as a relevant event in cell differentiation and carcinogenesis. Various studies have reported that altered expression of METTL3 is associated with an aggressive malignant phenotype and favors migration and invasiveness, but its role in Thymic Tumors remains unknown. Results: In this study, we characterized that METTL3 contributes to Thymic Epithelial Tumor phenotype. We evidenced that METTL3 is overexpressed in tumor tissue compared to normal counterpart. Silencing of METTL3 expression in thymic carcinoma cells results in reduced cell proliferation and overall translation rate. Of note, METTL3 is responsible for the induction of c-MYC expression in TET cells. Specifically, high expression of c-MYC protein is enabled by lncRNA MALAT1, which is methylated and delocalized by METTL3. Interestingly, blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death. Conclusion: This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET.

In recent years, in our university hospital, the number of odontogenic and non-odontogenic abscesses has been rapidly increasing. We included 70 patients from January 4th 2018 to February 19th 2020 affected by the odontogenic ones. Deep neck infection can spread to the chest and is associated with high morbidity and mortality. The purpose of this mini-review is to demonstrate that, in case of complications, a multidisciplinary approach is needed to treat these infections, so that all practitioners should work together to achieve the patient’s rapid recovery.

Long non-coding RNAs are emerging as new molecular players involved in many biological processes, such as proliferation, apoptosis, cell cycle, migration, and differentiation. Their aberrant expression has been reported in variety of diseases. The aim of this study is the identification and functional characterization of clinically relevant lncRNAs responsible for the inhibition of miR-145-5p, a key tumor suppressor in thymic epithelial tumors (TETs). Starting from gene expression analysis by microarray in a cohort of fresh frozen thymic tumors and normal tissues, we identified LINC00174 as upregulated in TET. Interestingly, LINC00174 expression is positively correlated with a 5-genes signature in TETs. Survival analyses, performed on the TCGA dataset, showed that LINC00174 and its associated 5-genes signature are prognostic in TETs. Specifically, we show that LINC00174 favors the expression of SYBU, FEM1B, and SCD5 genes by sponging miR-145-5p, a well-known tumor suppressor microRNA downregulated in a variety of tumors, included TETs. Functionally, LINC00174 impacts on cell migration and lipid metabolism. Specifically, SCD5, one of the LINC00174-associated genes, is implicated in the control of lipid metabolism and promotes thymic cancer cells migration. Our study highlights that LINC00174 and its associated gene signature are relevant prognostic indicators in TETs. Of note, we here show that a key controller of lipid metabolism, SCD5, augments the migration ability of TET cells, creating a link between lipids and motility, and highlighting these pathways as relevant targets for the development of novel therapeutic approaches for TET.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed

OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P =

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country

OBJECTIVES: Lung transplantation (LTx) is the only effective treatment for end-stage lung disease. In rapidly deteriorating patients awaiting transplant, supportive strategies for lung function allow only a short period of support and lung transplantation remains the definitive therapy. An urgent transplant programme may reduce the waiting time, allowing lung transplantation in these patients.METHODS: Since November 2010 a nation-wide urgent lung transplant programme has been established in Italy and patients on the waiting list dependent on mechanical ventilation and/or extracorporeal lung support (ECLS) can be transplanted on an emergency basis with the first available graft in the country. Results of the first 14 months of this programme are analysed here.RESULTS: From November 2010 to December 2011, 28 patients (14 males, mean age 33.6 ± 14.4 years) were considered for urgent LTx. Rapidly deteriorating lung function was supported with mechanical ventilation alone in 4 patients (14.3%), ECLS in 13 patients (46.4%) and mechanical ventilation plus ECLS in the remaining 11 patients (39.3%). Three patients (10.7%) were excluded because of worsening conditions, 3 patients (10.7%) while on the urgent listed and 22 patients (78.6%) underwent transplantation after 9.8 ± 6.2 days of being on the urgent list. The 30-day mortality rate after LTx was 18%, and the 1-year survival rate was 71.4%.CONCLUSIONS: The urgent lung transplant programme allowed transplantation in a significant percentage of prioritized patients with acceptable 30-day and 1-year mortality rates. An accurate selection of recipients may further improve the clinical impact of this programme, reducing the ethical concerns about transplantation in high-risk patients.

Objective: Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed. Methods: From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method. Results: Overall, median OS, CSS, and RFS were 29 (95 % CI 18–39), 48 (95 % CI 19–78), and 22 (95 % CI 17–27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21–7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00–1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95–6.63, p < 0.0001) with tumor size ≥5

Background: Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p. Then, we examine the functional role of miR-145-5p in TETs and its epigenetic transcriptional regulation. Methods: mRNAs expression profiling of a cohort of fresh frozen TETs and normal tissues was performed by microarray analysis. MiR-145-5p role in TETs was evaluated in vitro, modulating its expression in a Thymic Carcinoma (TC1889) cell line. Epigenetic transcriptional regulation of miR-145-5p was examined by treating the TC1889 cell line with the HDAC inhibitor Valproic Acid (VPA). Results: Starting from the identification of a 69-gene signature of miR-145-5p putative target mRNAs, whose expression was inversely correlated to that of miR-145-5p, we followed the expression of some of them in vitro upon overexpression of miR-145-5p; we observed that this resulted in the down-regulation of the target genes, impacting on TETs cancerous phenotype. We also found that VPA treatment of TC1889 cells led to miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p target genes and exhibited antitumor effects, as indicated by the induction of cell cycle arrest and by the reduction of cell viability, colony forming ability and migration capability. The importance of miR-145-5p up-regulation mediated by VPA is evidenced by the fact that hampering miR-145-5p activity by a LNA inhibitor reduced the impact of VPA treatment on cell viability and colony forming ability of TET

Background: To assess the long-term patency of the biologic prosthetic conduit used for reconstruction of the superior vena cava (SVC) by magnetic resonance imaging (MRI). Methods: Patients undergoing oncologic resection and reconstruction of the SVC by a bovine pericardial prosthesis (January 2003 to April 2010) have been studied after 1 year (if surviving) by MRI for the assessment of the conduit long-term patency. Results were compared with those of a control group of patients with normal SVC. Blood flow and area of lumen section at 3 different levels (proximal, middle, distal) were analyzed. Results: Sixteen consecutive patients surviving after 1 year from surgery out of 17 (9 lung cancer, 8 mediastinal malignancy) undergoing SVC reconstruction were included. One patient died postoperatively and was not included. Sixteen patients with similar demographic characteristics were studied in the control group. Mean blood flow was 18.4 ± 3.5 mL/sec (range 14.3 to 25.7) in patients with reconstructed SVC and 20.8 ± 4.1 mL/sec (range 15.3 to 27.7) in the control group. Mean area of the conduit lumen section was 2.2 ± 0.6 cm2 (range 1.6 to 3.6) at proximal level, 2.9 ± 1.3 cm2 at middle level (range 1.3 to 5.7), and 2.1 ± 0.9 cm2 (range 0.5 to 4) at distal level in the reconstructed group, and 2.6 ± 0.7 cm2 (range 1.8 to 4.2), 2.7 ± 0.7 cm 2 (range 1.9 to 4.3), and 2.4 ± 0.3 cm2 (range 1.8 to 3.1), respectively, at proximal, middle, and distal levels in the control group. Differences between the 2 groups were not significant (p > 0.05). Conclusions: The MRI assessment in terms of blood flow and area of lumen section at 3 different levels confirms that bovine pericardial conduit used for SVC replacement shows an optimal patency over the long term. © 2013 by The Society of Thoracic Surgeons.