Humanoid facial expressions as a tool to study human behaviour.

Besides action vitality forms, facial expressions represent another fundamental social cue which enables to infer the affective state of others. In the present study, we proposed the iCub robot as an interactive and controllable agent to investigate whether and how different facial expressions, associated to different action vitality forms, could modulate the motor behaviour of participants. To this purpose, we carried out a kinematic experiment in which 18 healthy participants observed video-clips of the iCub robot performing a rude or gentle request with a happy or angry facial expression. After this request, they were asked to grasp an object and pass it towards the iCub robot. Results showed that the iCub facial expressions significantly modulated participants motor response. Particularly, the observation of a happy facial expression, associated to a rude action, decreased specific kinematic parameters such as velocity, acceleration and maximum height of movement. In contrast, the observation of an angry facial expression, associated to a gentle action, increased the same kinematic parameters. Moreover, a behavioural study corroborated these findings, showing that the perception of the same action vitality form was modified when associated to a positive or negative facial expression.

Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

Sacubitril/valsartan and arrhythmic burden in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis.

The aim of this study was to assess whether angiotensin receptor/neprilysin inhibitor (ARNI) decreases ventricular arrhythmic burden compared to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonist (ACE-I/ARB) treatment in chronic heart failure with reduced ejection fraction (HFrEF) patients. Further, we assessed if ARNI influenced the percentage of biventricular pacing. A systematic review of studies (both RCTs and observational studies) including HFrEF patients and those receiving ARNI after ACE-I/ARB treatment was conducted using Medline and Embase up to February 2023. Initial search found 617 articles. After duplicate removal and text check, 1 RCT and 3 non-RCTs with a total of 8837 patients were included in the final analysis. ARNI was associated with a significative reduction of ventricular arrhythmias both in RCT (RR 0.78 (95% CI 0.63-0.96); p = 0.02) and observational studies (RR 0.62; 95% CI 0.53-0.72; p < 0.001). Furthermore, in non-RCTs, ARNI also reduced sustained (RR 0.36 (95% CI 0.2-0.63); p < 0.001), non-sustained VT (RR 0.67 (95% CI 0.57-0.80; p = 0.007), ICD shock (RR 0.24 (95% CI 0.12-0.48; p < 0.001), and increased biventricular pacing (2.96% (95% CI 2.25-3.67), p < 0.001). In patients with chronic HFrEF, switching from ACE-I/ARB to ARNI treatment was associated with a consistent reduction of ventricular arrhythmic burden. This association could be related to a direct pharmacological effect of ARNI on cardiac remodeling.Trial registration: CRD42021257977.

Post-COVID-19 Lung Transplantation Italian Pivotal Protocol: Some Ethical Considerations.

SARS­CoV­2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS­CoV­2 and subsequently recovered, it has been shown that some patients with post-COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post-COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post-COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS­CoV­2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease. The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

The influence of vitality forms on action perception and motor response.

During the interaction with others, action, speech, and touches can communicate positive, neutral, or negative attitudes. Offering an apple can be gentle or rude, a caress can be kind or rushed. These subtle aspects of social communication have been named vitality forms by Daniel Stern. Although they characterize all human interactions, to date it is not clear whether vitality forms expressed by an agent may affect the action perception and the motor response of the receiver. To this purpose, we carried out a psychophysics study aiming to investigate how perceiving different vitality forms can influence cognitive and motor tasks performed by participants. In particular, participants were stimulated with requests made through a physical contact or vocally and conveying rude or gentle vitality forms, and then they were asked to estimate the end of a passing action observed in a monitor (action estimation task) or to perform an action in front of it (action execution task) with the intention to pass an object to the other person presented in the video. Results of the action estimation task indicated that the perception of a gentle request increased the duration of a rude action subsequently observed, while the perception of a rude request decreased the duration of the same action performed gently. Additionally, during the action execution task, accordingly with the perceived vitality form, participants modulated their motor response.

How attitudes generated by humanoid robots shape human brain activity.

During interpersonal interactions, people perform actions with different forms of vitality, communicating their positive or negative attitude toward others. For example, a handshake can be "soft" or "vigorous", a caress can be 'kind' or 'rushed'. While previous studies have shown that the dorso-central insula is a key area for the processing of human vitality forms, there is no information on the perception of vitality forms generated by a humanoid robot. In this study, two fMRI experiments were conducted in order to investigate whether and how the observation of actions generated by a humanoid robot (iCub) with low and fast velocities (Study 1) or replicating gentle and rude human forms (Study 2) may convey vitality forms eliciting the activation of the dorso-central insula. These studies showed that the observation of robotic actions, generated with low and high velocities, resulted in activation of the parieto-frontal circuit typically involved in the recognition and the execution of human actions but not of the insula (Study 1). Most interestingly, the observation of robotic actions, generated by replicating gentle and rude human vitality forms, produced a BOLD signal increase in the dorso-central insula (Study 2). In conclusion, these data highlight the selective role of dorso-central insula in the processing of vitality forms opening future perspectives on the perception and understanding of actions performed by humanoid robots.

A transition clinic model for inflammatory bowel disease between two tertiary care centers: outcomes and predictive factors.

OBJECTIVE: Few models of transition have been proposed for inflammatory bowel disease (IBD). The aim of the present study is to evaluate the feasibility of a transition model and the predictive factors for success/failure. PATIENTS AND METHODS: Patients with low activity or remission IBD were enrolled. Proposed model: three meetings every four-six weeks: the first one in the pediatric center (Bambino Gesù Children's Hospital); the second one, in the adult center (Foundation Polyclinic University A. Gemelli), with pediatric gastroenterologists; the last one, in the adult center, with adult gastroenterologists only. Questionnaires included anxiety and depression clinical scale, self-efficacy, quality of life, visual-analogic scale (VAS). Transition was considered successful if the three steps were completed. RESULTS: Twenty patients were enrolled (range 18-25 years; M/F: 12/8; Ulcerative Colitis/Crohn's Disease 10/10); eight accepted the transition program, four delayed the process and eight refused. Patients who completed transition generated higher scores on the resilience scale, better scores on well-being perception, and had lower anxiety scores. Patients who failed transition were mostly women. The perceived utility of the transition program was scored 7.3 on a VAS scale. CONCLUSIONS: The proposed transition program seems to be feasible. Psychological scores may help in selecting patients and predicting outcomes.

The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes.

INTRODUCTION: The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited. METHODS: We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated. RESULTS: The analysis included 66 stage I-III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval [CI]: 0.16-0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17-0.81, p: 0.013) for multivariate analysis. CONCLUSIONS: Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I-III SCLCs and warrants further investigation.

Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical-pathological features and intratumor heterogeneity over time.

Background: Tumor immune microenvironment (TME) plays a key role in malignant pleural mesothelioma (MPM) pathogenesis and treatment outcome, supporting a role of immune checkpoint inhibitors as anticancer approach. This study retrospectively investigated TME and programmed death ligand 1 (PD-L1) expression in naïve MPM cases and their change under chemotherapy. Patients and methods: Diagnostic biopsies of MPM patients were collected from four Italian and one Slovenian cancer centers. Pathological assessment of necrosis, inflammation, grading, and mitosis was carried out. Ki-67, PD-L1 expression, and tumor infiltrating lymphocytes were detected by immunohistochemistry. When available, the same paired sample after chemotherapy was analyzed. Pathological features and clinical characteristics were correlated to overall survival. Results: TME and PD-L1 expression were assessed in 93 and 65 chemonaive MPM samples, respectively. Twenty-eight samples have not sufficient tumor tissue for PD-L1 expression. Sarcomatoid/biphasic samples were characterized by higher CD8+ T lymphocytes and PD-L1 expression on tumor cells, while epithelioid showed higher peritumoral CD4+ T and CD20+ B lymphocytes. Higher CD8+ T lymphocytes, CD68+ macrophages, and PD-L1 expression were associated with pathological features of aggressiveness (necrosis, grading, Ki-67). MPM cases characterized by higher CD8+ T-infiltrate showed lower response to chemotherapy and worse survival at univariate analysis. Patients stratification according to a combined score including CD8+ T lymphocytes, necrosis, mitosis, and proliferation index showed median overall survival of 11.3 months compared with 16.4 months in cases with high versus low combined score (P < 0.003). Subgroup exploratory analysis of 15 paired samples before and after chemotherapy showed a significant increase in cytotoxic T lymphocytes in MPM samples and PD-L1 expression in immune cells. Conclusions: TME enriched with cytotoxic T lymphocytes is associated with higher levels of macrophages and PD-L1 expression on tumor cells and with aggressive histopathological features, lower response to chemotherapy and shorter survival. The role of chemotherapy as a tumor immunogenicity inducer should be confirmed in a larger validation set.

Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy.

PURPOSE: The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events. METHODS: The cohort was composed by 199,569 individuals aged ≥ 65 years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008-2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14 days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs. CONCLUSIONS: Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment.

PURPOSE: The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. MATERIAL AND METHODS: Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25Gy in five fractions over 5 consecutive days. RESULTS: We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3-54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5-24.1] compared to 19.4 months for patients not submitted to surgery. CONCLUSION: Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival.

Overexpression of Hypoxia-Inducible Factor-1α in Primary Graft Dysfunction Developing in an Orthotopic Lung Transplantation Rat Model.

BACKGROUND: Primary graft dysfunction (PGD) is the major cause of early morbidity and mortality after transplantation. A high rate of PGD is a frequent complication in orthotopic lung transplantation (OLT) models, which are currently used to investigate acute and chronic rejection pathways. Hypoxia-inducible factor (HIF)-1α is a heterodimeric αß transcription factor that mediates tissue response to hypoxia. In other solid organ transplantations, a significant correlation between HIF-1α expression and PGD was detected. To our knowledge no data are available on HIF-1α expression in PGD developing in lung transplantation. The aims of this study were to investigate HIF-1α expression (using immunohistochemistry) and correlate it to the main histological parameters related to ischemia-reperfusion (IR) injury, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) -positive apoptotic cells). METHODS: OLT was performed in 32 inbred rat strains and 11 of them died in the early postoperative period (from day 0-3) for IR injury. The histological and molecular evaluations were done in all lung tissues. Unimplanted donor rat lungs were used as controls. HIF-1α expression was correlated with all morphological parameters. RESULTS: Lung samples of animals with IR injury showed high scores of HIF-1α expression, edema, blood extravasation, granulocyte margination, apoptotic index, and necrosis in 91% of cases. Tissue overexpression of HIF-1α was detected in all lung samples with high scores of histological parameters and with high apoptotic indexes. CONCLUSION: Our data demonstrate that HIF-1α was overexpressed in more severe rat lung IR injury. The use of HIF-1α inhibitors could provide a translatable route into manipulating this complex system in vivo.

Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETA R) and the angiotensin II receptor type 1 (AT1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ETA R and anti-AT1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient.

The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.

Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.

Dynamic esophageal stents.

Esophageal stenting represents a new strategy in the treatment of resistant or recurrent stenosis that obviates the need for multiple dilations. Our custom dynamic stent (DS) improves esophageal motility unlike the widespread self-expandable plastic or metallic esophageal stents. The DS allows food and secretions to pass in the space between the esophageal wall and the stent wall. This contrasts with the other types of stent, in which food passes into the stent that presses into the esophageal wall. Until the stent patent is complete, we use slices of silicon drains overlapped with each other to fashion the stent to the desired length and diameter (7-, 9-, or 12.7-mm external diameter). It is built coaxially on a nasogastric tube that guarantees the correct position. The two ends are tailored to allow an easy introduction and food passage between stent and esophageal wall. The stent is inserted after stricture dilations (Savary-Gilliard dilators) under fluoroscopic guidance. All patients who underwent stenting were treated with dexamethasone (2 mg/kg/day) for 3 days and proton pump inhibitors (omeprazole or lansoprazole, 1-2 mg/kg/day). From 1992 to 2012, 387 patients (mean age 38.6 months; range 3-125 months) with post-surgical esophageal stricture because of esophageal atresia correction were enrolled in this study. Twenty-six of 387 patients (6.7%) underwent custom DS placement for recurrent stricture instead of a program of serial dilations. The stent was left in place for at least 40 days and was effective in 21 (80.7%) of 26 patients. There were two stent-related major complications (subclavian-esophageal fistula). Our custom stent represents an effective and safe option in the treatment of severe and recurrent post-surgical esophageal strictures. Surgery with stricture resection, and reanastomosis or jeunoplasty represents the rescue strategy.

Noninvasive high-frequency percussive ventilation in the prone position after lung transplantation.

Noninvasive positive-pressure ventilation (NIV), which represents a consolidated treatment of both acute and chronic respiratory failure, is increasingly being used to maintain spontaneous ventilation in lung transplant patients with impending pulmonary complications. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) has proven to be useful in preventing endotracheal mechanical ventilation, airway injury, and infections. Lung recipients with closure of the small airways in the dependent regions may also benefit from the prone position, which is helpful to promote recruitment of nonaerated alveoli and faster healing of consolidated atelectatic areas. In patients with localized or diffuse lung infiltrates, high-frequency percussive ventilation (HFPV), by either an invasive airway or a facial mask, has been adopted as an alternative ventilatory mode to enhance airway opening, limit potential respirator-associated lung injury, and improve mucus clearance. In nonintubated lung recipients at risk for volubarotrauma with conventional mechanical ventilation, it allows oxygen diffusion into the distal airways at lower mean airway pressures while avoiding repetitive cyclical opening and closing of the terminal airways. We summarize the clinical course of 3 patients with post-lung transplantation respiratory complications who were noninvasively ventilated with HFPV in the prone position. Major advantages of this treatment included gradual improvement of spontaneous clearance of bronchial secretions, significant attenuation of graft infiltrates and consolidations, a reduction in the number of bronchoscopies required, a decrease in spontaneous respiratory rate and work of breathing, and a significant improvement in gas exchange. The patients found HFPV with either standard facial mask or total mask interface to be comfortable or only mildly uncomfortable, and after the sessions they felt more restored. HFPV by facial mask in the prone position may be an interesting and attractive alternative to standard NIV, one that is more useful when implemented before full-blown respiratory failure is established.

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

BACKGROUND: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT. MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features. RESULTS: Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E). CONCLUSIONS: All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.

Synovial sarcoma: CT imaging of a rare primary malignant tumour of the thorax.

PURPOSE: This paper presents computed tomography (CT) features of three patients with primary synovial sarcoma of the lung (PSSL) who came to our attention and underwent surgery; reviews of the literature on this rare thoracic tumour are also presented. MATERIALS AND METHODS: The patients, all men, with a mean age of 58 years, underwent clinical and radiological re-evaluation after receiving a histological diagnosis. None of the patients had multifocal disease or other concomitant neoplasms. All patients had undergone both chest X-rays and computed tomography, and two had also been studied with positron emission tomography (PET)-CT. Two patients underwent surgical removal of the tumour, whereas the third initially underwent surgery (following an incorrect diagnosis) and then thoracoscopic biopsy of the pleural lesions that subsequently arose. RESULTS: In each case, chest X-rays showed changes, with the presence of pulmonary masses noted in all patients. In one patient, pleural effusion was also visible. CT scans showed parenchymal masses that were largely of a colliquative nature (in two out of three patients). Ipsilateral pleural effusion was present in two patients, associated in one with solid nodules within the pleura. Mediastinal lymphadenopathy, which was not radiologically significant, was present in only one patient. The two patients who also underwent PET-CT examination showed pathological tracer uptake confined to the lesion site without other thoracoabdominal or musculoskeletal localisations. CT-guided biopsy, performed in one patient only, was positive for mesenchymal tumour. In the two patients who underwent surgery, a definitive diagnosis of monophasic synovial sarcoma of the lung was made. The diagnosis of monophasic synovial sarcoma in the third patient was confirmed using thoracoscopic biopsy DISCUSSION: Both in the cases described and in those identified in the literature review, standard chest X-rays mainly showed a parenchymal mass of pleural origin with either irregular or well-defined margins. CT characteristics are more definite, with evidence of a mass with regular and sharply defined margins, occasionally polycyclic, with inhomogeneous density due to the presence of colliquative areas within the tumour. CONCLUSIONS: Although PSSL is a rare tumour, a pulmonary mass of inhomogeneous density, associated with pleural effusion but without lymphadenopathy, detected in an asymptomatic or poorly symptomatic patient, should lead to PSSL being considered in the differential diagnosis, provided that metastases from the more common synovial sarcomas of the musculoskeletal system have been excluded.