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Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

OBJECTIVEOssification of pterygoalar and pterygospinous ligaments traversing the superior aspect of the infratemporal fossa results in formation of osseous bars that can obstruct percutaneous needle access to the trigeminal ganglion through the foramen ovale (FO), interfere with lateral mandibular nerve block, and impede transzygomatic surgical approaches. Presence of these ligaments has been studied on dry skulls, but description of their radiological anatomy is scarce, in particular on cross-sectional imaging. The aim of this study was to describe visualization of pterygoalar and pterygospinous bars on computed tomography (CT) and to review their prevalence and clinical significance.METHODSThe authors retrospectively reviewed 200 helical sinonasal CT scans by analyzing 0.75- to 1.0-mm axial images, maximum intensity projection (MIP) reconstructions, and volume rendered (VR) images, including views along the anticipated axis of the needle in percutaneous Hartel and submandibular approaches to the FO.RESULTSOssified pterygoalar and pterygospinous ligaments were readily identifiable on CT scans. An ossified pterygoalar ligament was demonstrated in 10 patients, including 1 individual with bilateral complete ossification (0.5%), 4 patients with unilateral complete ossification (2.0%), and 5 with incomplete unilateral ossification (2.5%). Nearly all patients with pterygoalar bars were male (90%, p < 0.01). An ossified pterygospinous ligament was seen in 35 patients, including 2 individuals with bilateral complete (1.0%), 8 with unilateral complete (4%), 8 with bilateral incomplete (4.0%), 12 with bilateral incomplete (6.0%) ossification, and 5 (2.5%) with mixed ossification (complete on one side and incomplete on the contralateral side). All pterygoalar bars interfered with a hypothetical needle access to the FO using the Hartel approach but not the submandibular approach. In contrast, 54% of complete and 24% of incomplete pterygospinous bars impeded the submandibular approach to the FO, without affecting the Hartel approach.CONCLUSIONSThis study provides the first detailed description of cross-sectional radiological and applied surgical anatomy of pterygoalar and pterygospinous bars. Our data are clinically useful during skull base imaging to predict potential obstacles to percutaneous cannulation of the FO and assist in the choice of approach, as these two variants differentially impede the Hartel and submandibular access routes. Our results can also be useful in planning surgical approaches to the skull base through the infratemporal fossa.

OBJECTIVES Only few studies compared the surgical morbidity and mortality of thoracoscopic segmentectomy versus lobectomy for non-small-cell lung cancer, in particular, by relating the segmental resections with the corresponding anatomical lobes. METHODS We enrolled a total of 7487 patients who underwent VATS lobectomy (7269) or segmentectomy (218) from January 2014 to July 2019. A propensity score matching approach was used to account for potential confounding factors between the 2 groups. After matching, 349 lobectomies and 208 segmentectomies were included in the analysis. We analysed the operative and postoperative outcomes of video-assisted anatomical segmentectomy compared with video-assisted lobectomy and, in details, the results of segmentectomy with its corresponding lobectomy in a large cohort of patients from the Italian VATS Group Registry. RESULTS The overall conversion rate to thoracotomy was not statistically different between the groups (27 patients 8% vs 7 patients 3%, P = 0.1). The lobectomy group had a greater number of resected lymph nodes (median 11 vs 8, P = 0.006). No significant differences were detected in 30-day mortality (1.4%, 5 patients vs 0.9%, 2 patients), overall complications (18%, 62 patients vs 14%, 29 patients) and prolonged air leakage (31 patients, 9% vs 12 patients, 6%) between lobectomy and segmentectomy, respectively. No statistical differences were found regarding the median duration of drainage (3.2 days, P = 1) and the overall median length of hospital stay (6.4 days, P = 0.1) between the 2 groups. In the context of segmentectomy versus corresponding lobectomy, the right upper lobectomy compared with right upper segmentectomy showed a higher number of resected lymph nodes (P = 0.027). No statistical differences were reported in terms of conversion rate and postoperative complication and mortality. CONCLUSIONS Segmentectomy could be considered a safe procedure without significant differences compared to thoracoscopic lobectomy in terms of postoperative morbidity and mortality.

Funder: NIHR Cambridge Biomedical Research Centre, Funder: Addenbrooke’s Charitable Trust, Funder: National Institute for Health Research (NIHR), Funder: Mark Foundation For Cancer Research, Funder: Cambridge Commonwealth, European and International Trust, Funder: Cancer Research UK, Funder: Cambridge Clinical Trials Unit, Funder: Cancer Research UK Cambridge Centre, Funder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, Funder: Cambridge Experimental Cancer Medicine Centre, PURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p

Cerebral metabolism is tightly regulated and fundamental for healthy neurological function. There is increasing evidence that alterations in this metabolism may be a precursor and early biomarker of later stage disease processes. Proton magnetic resonance spectroscopy (1H-MRS) is a powerful tool to non-invasively assess tissue metabolites and has many applications for studying the normal and diseased brain. However, the technique has limitations including low spatial and temporal resolution, difficulties in discriminating overlapping peaks, and challenges in assessing metabolic flux rather than steady-state concentrations. Hyperpolarized carbon-13 magnetic resonance imaging is an emerging clinical technique that may overcome some of these spatial and temporal limitations, providing novel insights into neurometabolism in both health and in pathological processes such as glioma, stroke and multiple sclerosis. This review will explore the growing body of pre-clinical data that demonstrates a potential role for the technique in assessing metabolism in the central nervous system. There are now a number of clinical studies being undertaken in this area and this review will present the emerging clinical data as well as the potential future applications of hyperpolarized 13C magnetic resonance imaging in the brain, in both clinical and pre-clinical studies.

PURPOSE: To assess the potential role of computed tomography (CT) texture analysis (CTTA) in identifying vulnerable patients with carotid artery atherosclerosis. METHODS: In this case-control pilot study, 12 patients with carotid atherosclerosis and a subsequent history of transient ischemic attack or stroke were age and sex matched with 12 control cases with asymptomatic carotid atherosclerosis (follow-up time 103.58 ± 9.2 months). CTTA was performed using a commercially available research software package (TexRAD) by an operator blinded to clinical data. CTTA comprised a filtration-histogram technique to extract features at different scales corresponding to spatial scale filter (fine = 2 mm, medium = 3 mm, coarse = 4 mm), followed by quantification using histogram-based statistical parameters: mean, kurtosis, skewness, entropy, standard deviation, and mean value of positive pixels. A single axial slice was selected to best represent the largest cross-section of the carotid bifurcation or the greatest degree of stenosis, in presence of an atherosclerotic plaque, on each side. RESULTS: CTTA revealed a statistically significant difference in skewness between symptomatic and asymptomatic patients at the medium (0.22 ± 0.35 vs - 0.18 ± 0.39, p < 0.001) and coarse (0.23 ± 0.22 vs 0.03 ± 0.29, p = 0.003) texture scales. At the fine-texture scale, skewness (0.20 ± 0.59 vs - 0.18 ± 0.58, p = 0.009) and standard deviation (366.11 ± 117.19 vs 300.37 ± 82.51, p = 0.03) were significant before correction. CONCLUSION: Our pilot study highlights the potential of CTTA to identify vulnerable patients in stroke and TIA. CT texture may have the potential to act as a novel risk stratification tool in patients with carotid atherosclerosis.

Objective: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. Patients and Methods: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50mg once daily sunitinib for 12days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. Results: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7–84.8%). The median OS was 33.7months and median PFS was 15.7months. Amongst those achieving a PR or CR, the median response duration was 8.7months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans, measured using DCE-MRI; all P&nbsp

Molecular imaging techniques have rapidly progressed over recent decades providing unprecedented in vivo characterization of metabolic pathways and molecular biomarkers. Many of these new techniques have been successfully applied in the field of neuro-oncological imaging to probe tumor biology. Targeting specific signaling or metabolic pathways could help to address several unmet clinical needs that hamper the management of patients with brain tumors. This review aims to provide an overview of the recent advances in brain tumor imaging using molecular targeting with positron emission tomography and magnetic resonance imaging, as well as the role in patient management and possible therapeutic implications.

Mood disorders (MD) are important and frequent psychiatric illness. The management of patients affected by these conditions represents an important factor of disability as well as a significant social and economic burden. The "in-vivo" studies can help researchers to understand the first developmental events of the pathology and to identify the molecular and non-molecular targets of therapies. However, they have strong limitations due to the fact that human brain circuitry can not be reproduced in animal models. In addition, these neural pathways are difficult to be selectively studied with the modern imaging (such as Magnetic Resonance and Positron Emitted Tomography/Computed Tomography) and non-imaging (such as electroencephalography, magnetoencephalography, transcranial magnetic stimulation and evoked potentials) methods. In comparison with other methods, the "in-vivo" imaging investigations have higher temporal and spatial resolution compared to the "in-vivo" non-imaging techniques. All these factors make difficult to fully understand the aetiology and pathophysiology of these disorders, and consequently hinder the analysis of the effects of pharmacological and non-pharmacological therapies, which have been demonstrated effective in clinical settings. In this review, we will focus our attention on the current state of the art of imaging in the assessment of treatment efficacy in MD. We will analyse briefly the actual classification of MD; then we will focus on the "in vivo" imaging methods used in research and clinical activity, the current knowledge about the neural models at the base of MD. Finally the last part of the review will focus on the analysis of the main markers of response to treatment.

Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.

A brain Magnetic resonance imaging (MRI) scan of a single individual consists of several slices across the 3D anatomical view. Therefore, manual segmentation of brain tumors from magnetic resonance (MR) images is a challenging and time-consuming task. In addition, an automated brain tumor classification from an MRI scan is non-invasive so that it avoids biopsy and make the diagnosis process safer. Since the beginning of this millennia and late nineties, the effort of the research community to come-up with automatic brain tumor segmentation and classification method has been tremendous. As a result, there are ample literature on the area focusing on segmentation using region growing, traditional machine learning and deep learning methods. Similarly, a number of tasks have been performed in the area of brain tumor classification into their respective histological type, and an impressive performance results have been obtained. Considering state of-the-art methods and their performance, the purpose of this paper is to provide a comprehensive survey of three, recently proposed, major brain tumor segmentation and classification model techniques, namely, region growing, shallow machine learning and deep learning. The established works included in this survey also covers technical aspects such as the strengths and weaknesses of different approaches, pre- and post-processing techniques, feature extraction, datasets, and models’ performance evaluation metrics., publishedVersion

Purpose This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region. Methods Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size. Results VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10−3 mm2/s vs. 0.98 ± 0.38 × 10−3 mm2/s, respectively; p = 0.18). Conclusion This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future. Key Points • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale. Electronic supplementary material The online version of this article (10.1007/s00330-019-6011-8) contains supplementary material, which is available to authorized users.

OBJECTIVES This study compares the uniportal with the 3-portal video-assisted thoracic surgery (VATS) by examining the data collected in the Italian VATS Group Database. The primary end point was early postoperative pain; secondary end points were intraoperative and postoperative complications, surgical time, number of dissected lymph nodes and length of stay. METHODS This was an observational, retrospective, cohort, multicentre study on data collected by 49 Italian thoracic units. Inclusion criteria were clinical stage I–II non-small-cell lung cancer, uniportal or 3-portal VATS lobectomy and R0 resection. Exclusion criteria were cT3 disease, previous thoracic malignancy, induction therapy, significant comorbidities and conversion to other techniques. The pain parameter was dichotomized: the numeric rating scale ≤3 described mild pain, whereas the numeric rating scale score >3 described moderate/severe pain. The propensity score-adjusted generalized estimating equation was used to compare the uniportal with 3-portal lobectomy. RESULTS Among 4338 patients enrolled from January 2014 to July 2017, 1980 met the inclusion criteria; 1808 patients underwent 3-portal lobectomy and 172 uniportal surgery. The adjusted generalized estimating equation regression model using the propensity score showed that over time pain decreased in both groups (P CONCLUSIONS Data from the Italian VATS Group Database showed that in clinical practice uniportal lobectomy seems to entail a higher risk of moderate/severe pain on second and third postoperative days.

Significance Carbon-13 MRI was used to assess exchange of hyperpolarized 13C label between injected [1-13C]pyruvate and the endogenous tumor lactate pool in breast cancer patients. Higher levels of 13C label exchange were observed in more-aggressive tumors, including all triple-negative cancers. The 13C label exchange correlated significantly with the expression of the transmembrane transporter mediating uptake of pyruvate into tumor cells and hypoxia inducible factor 1 (HIF1α), but no significant correlation with the expression of lactate dehydrogenase, the enzyme that catalyzes the exchange. The study has shown that 13C MRI can be used for metabolic imaging of breast cancer patients in the clinic, creating possibilities for noninvasive cancer monitoring in this patient group., Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

Sternal resection and anterior chest wall reconstruction techniques for malignant processes are not always standardized. We report an innovative method of sternal osteosynthesis in two patients, 65-year-old and 41-year-old women, with Ewing's sarcoma, and infiltrating thymoma, respectively. The first case manifested itself as a voluminous palpable mass while the second case was characterized for a paramediastinal mass widely extended to the anterior chest wall. Reconstruction with titanium mesh allowed the quick restoration of parietal stability, facilitating respiratory dynamic and recovery of patients.

Thoracoscopic lobectomy (VATS-L) for non-small-cell lung cancer (NSCLC) is a well-established option for early stage NSCLC, but the evidences are limited for octogenarians.The objectives of this multi-institutional study were to evaluate the post-operative outcomes of VATS-L in octogenarians and to estimate the post-operative quality of life (QoL) using a validated questionnaire (EuroQoL5D).Data from patients underwent VATS-L between 2014 and 2019 were analysed and divided into two groups: Group A (younger patients) and Group B (octogenarians). To define predictors for complications, univariate and multivariable logistic regression analysis were performed.7023 patients underwent VATS-L and 329 (4.6%) were octogenarians. 30-day and 90-day post-operative mortality were similar (0.95% vs 0.91%, p = 0.84 and 1.3% vs 1.2%, p = 0.58), whereas the percentage of patients who suffered from any complication (25.5% vs 31.9%, p = 0.012) and the complication rate (31.6% vs 45.2%, p=0.01) were higher for octogenarians. At discharge, the values of EuroQoL5D were worse in group B, but after one month these levels became similar. Age80 years had a significant influence on morbidity on both univariate and multivariable analyses (p = 0.025).VATS-L for NSCLC can be performed in selected octogenarians without increased risk of post-operative death, acceptable not-life-threatening complications and a moderate impact on QoL.

Surgery in COVID‐19 disease complicated by APF represents the last life‐saving treatment option. The choice of the therapeutic period to indicate this approach is fundamental. In fact, the clinical stability of patient is necessary in order to allow single‐lung ventilation and to minimize postoperative sequelae.

Background Carotid artery atherosclerosis is an important cause of ischaemic stroke. In oncology, textural analysis (“radiomics”) of computed tomography (CT) images can predict the metastatic potential and prognosis of several types of malignant tumours. We investigated whether this quantitative approach could be applied in carotid artery disease. Purpose (1) To evaluate the feasibility of computed tomography angiography (CTA) texture analysis in differentiating symptomatic from asymptomatic patients. (2) To investigate whether CTA carotid texture analysis can identify culprit lesions in patients with stroke and transient ischaemic attack (TIA). Methods Carotid CTAs of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CTA imaging. Asymptomatic (ASX) patients had no prior stroke/TIA. Both TexRAD, a research texture analysis software, and PyRadiomics, a Python package for radiomics studies, were used to extract 99 first-order and higher-order texture features from regions-of-interest (ROI) drawn around the outer wall of the carotid artery. Single-slice analysis compared the carotid bifurcations of symptomatic and asymptomatic patients, and of culprit (CC) and non-culprit (NC) arteries in symptomatic patients. Multi-slice analysis was conducted using a 3D volume defined by ROIs drawn on 14 consecutive CT slices of 3mm thickness, covering 3cm of carotid artery. The Mann-Whitney U test was used for inter-subject comparisons (ASX vs CC; ASX vs NC) and the Wilcoxon signed-rank test was used for intra-subject comparisons (CC vs NC). A p value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. Single-slice analysis revealed greater homogeneity in asymptomatic carotids versus symptomatic culprit carotids (Uniformity: ASX 0.11 (0.05); CC 0.08 (0.05), p Conclusion Textural analysis of carotid CTAs reveal significant differences between symptomatic and asymptomatic patients and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could be used to identify patients at high risk of further stroke for aggressive medical therapy and surveillance. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Background Convolutional neural networks (CNNs), part of deep learning, are used widely for computer vision tasks and in some medical domains, such as mammography interpretation. The application of deep learning to carotid artery imaging is scarce. We investigated the ability of deep learning to correctly classify contrast CT images of the carotid arteries without the need for prior feature selection. Purpose (1) To assess the ability of deep learning to differentiate symptomatic patients (had prior stroke or transient ischaemic attack [TIA]) from asymptomatic patients (no prior stroke/TIA) using contrast CT scans alone. (2) To investigate whether deep learning can further discriminate between culprit and non-culprit carotid arteries in symptomatic patients. (3) To assess the interpretability of the deep learning models. Methods Carotid contrast CT scans of consented research subjects were included in the study. Symptomatic patients had confirmed carotid artery-related ischaemic stroke or TIA in the 7 days before CT imaging, and asymptomatic patients had no prior cerebrovascular events. The dataset comprised 1148 axial symptomatic slices (covering a 3cm area of each carotid artery in 41 patients; 41 culprit and 41 non-culprit carotids) and 700 asymptomatic slices (from the bilateral carotid arteries of 25 patients). The dataset was split such that 75% was used for training and 25% for testing. A 30x30 bounding box was used to create patches of the carotid arteries from these axial slices for use as input to the CNN, a modified VGG16 architecture initialised with ImageNet weights to leverage transfer learning (the application of a model trained in one domain to a different domain) implemented in Python. Data augmentation was applied to the training set and the model was trained for 100 epochs using a cyclic learning rate, the RMSProp optimizer and binary cross-entropy loss. Class activation heatmaps were generated using the GradCAM method to highlight the areas of the image that were most important to the model for making its classification decision. Results The deep learning model was 92% accurate in correctly identifying carotid arteries from symptomatic patients versus those from asymptomatic patients. Discriminating between culprit versus non-culprit carotid arteries in symptomatic patients alone was 71% accurate. The class activation heatmaps demonstrated how the model learnt to localise the carotid artery within the image patch, and to ignore the arterial lumen when making its classification decision. Conclusions Deep learning can be used to differentiate between symptomatic and asymptomatic carotid CT scans from stroke/TIA subjects without the need for prior feature engineering. The model learns to identify relevant features in the image that predict the patients' symptom state. If further validated, this approach could be used to identify high-risk patients for intensive medical therapy. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): EPVL is undertaking a PhD funded by the Cambridge School of Clinical Medicine and the Medical Research Council's Doctoral Training Partnership

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of both upper and lower motor neuron located in the spinal cord and brainstem. Diagnosis of ALS is predominantly clinical, nevertheless, electromyography and Magnetic Resonance Imaging (MRI) may provide support. Several advanced MRI techniques have been proven useful for ALS diagnosis and, indeed, the combination of different MRI techniques demonstrated an improvement in sensitivity and specificity as far as 90%. This review focus on the imaging techniques currently used in the diagnosis and management of ALS with brief considerations on future applications.

Background and purpose Hepatitis C virus (HCV) co-infection’s role on cognitive impairment of human immunodeficiency virus (HIV) positive patients is still debated and functional neuroimaging evaluation on this matter is lacking. To provide further insight about HCV’s neuro-effects on HIV associated neurocognitive disorder (HAND), we performed a pilot resting state (RS) functional connectivity magnetic resonance imaging (fcMRI) study to find eventual functional connectivity alteration that could reflect HCV related cognitive performance degradation. Methods Eighteen patients (8 HIV, 10 HIV + HCV), either impaired or not impaired, were assessed with RS fcMRI. A statistic model including cognitive testing results was elaborated during data processing to evaluate brain networks alteration related to actual cognitive status in patients. Results Statistically significant different patterns of connectivity were found: HCV co-infection modified 17 ROIs’ connectivity with 45 supra-threshold connections (p-FDR min 0.0022, max 0.0497). ROIs most involved were right pallidum, brainstem, vermian lobules 1–2 and right cerebellar lobule 10. Graph theory analysis did not demonstrate significant difference between networks, but HCV related modifications at ROI’s local level were found, with particular involvement of ROIs of frontal lobe, basal ganglia and cerebellum. Increased fronto-striatal dysfunctions have been already reported as consequences of HCV infection and could reflect an additive effect. Cerebellar alterations are associated with HIV and HAND, but not with HCV infection, suggesting a synergic effect of HCV. Conclusion Our study demonstrates RS fcMRI can help to understand the interactions between HIV and HCV co-infection, and our preliminary results suggest synergic effects of HCV in HIV-related brain functional modification.

Sophisticated volume measurements of brain structures on magnetic resonance imaging (MRI) may improve specificity in determining long-term progression of multiple sclerosis (MS), but these techniques are laborious. The optic chiasm (OC) is a white matter (WM) structure clearly visible on a routine MRI and is related to the optic nerves (ONs), which are known to atrophy in MS. We hypothesized that OC morphometric measurements would show OC atrophy in MS compared to normal patients. If so, this could help establish a novel simplified brain MRI measure of WM atrophy in MS patients. We retrospectively evaluated standard brain MRIs of 97 patients with known MS and 98 normal individuals. We electronically measured eight OC morphometrics on axial T2WIs and midsagittal T1WIs: OC width and anteroposterior (AP) diameter, diameters of each ON and optic tract (OT), and angles between the ONs or OTs. Mean OC width, AP diameter, and height in MS patients were 11.83 ± 1.25 mm (95% CI 11.58–12.09), 2.99 ± 0.65 mm (95% CI 2.85–3.12), and 2.09 ± 0.37 mm (95% CI 2–2.19), respectively. In normal individuals, they were 12.1 ± 1.4 mm (95% CI 11.78–12.34), 3.43 ± 0.63 mm (95% CI 3.3–3.58), and 2.15 ± 0.37 mm (95% CI 2.07–2.23), respectively. There were statistically significant differences between MS patients and controls for AP diameter (P = 0.000), but not for width (P = 0.204) or height (P = 0.183). The ONs were significantly smaller in MS (P < 0.0017), but not the OTs. Thus, the OC is significantly atrophied in an unstratified cohort of MS patients. Future studies may establish an MRI OC morphometric index to evaluate demyelinating disease in the brain. Clin. Anat. 32:1072–1081, 2019. © 2019 Wiley Periodicals, Inc.

OBJECTIVESInherent technical aspects of pulmonary lobectomy by video-assisted thoracoscopic surgery (VATS) may limit surgeons’ ability to deal with factors predisposing to complications. We analysed complication rates after VATS lobectomy in a prospectively maintained nationwide registry.METHODSThe registry was queried for all consecutive VATS lobectomy procedures from 49 Italian Thoracic Units. Baseline condition, tumour features, surgical techniques, devices, postoperative care, complications, conversions and the reasons thereof were detailed. Univariable and multivariable regressions were used to assess factors potentially linked to complications.RESULTSFour thousand one hundred and ninety-one VATS lobectomies in 4156 patients (2480 men, 1676 women) were analysed. The median age-adjusted Charlson index of the patients was 4 (interquartile range 3–6). Grade 1 and 2 and Grade 3–5 complications were observed in 20.1% and in 5.8%, respectively. Ninety-day mortality was 0.55%. The overall conversion rate was 9.2% and significantly higher in low-volume centres (CONCLUSIONSVATS lobectomy is a safe procedure even in medically compromised patients. An improved classification system for conversions is proposed and prevention strategies are suggested to reduce conversion rates and possibly complications in less-experienced centres.

Surgery is the gold standard treatment of lung cancer. The minimally invasive technique does not only concern access to the chest but also the limits of parenchymal resection. The study debates on the safety and oncological adequacy of sublobar resections in bronchogenic carcinoma patients. A systematic analysis of the data in the literature was carried out, comparing the outcomes of patients with resectable non-small lung cancer (NSCLC) who underwent lobectomy or sublobar resection. These last interventions include both segmentectomies and wedge resections taking into consideration the following parameters: complications, relapse rate and overall survival. The complication rate is higher in patients underwent lobectomy compared to sublobar resection, especially in presence of high comorbidity index or octogenarian patients (overall values respectively between 0 and 48% and 0 and 46.6%). Contrarily, the relapse rate (6.2% to 32% vs. 3.6% to 53.4%) and overall survival (50.2% to 93.8% vs. 38.6% to 100%) are more favorable in patients undergoing lobectomy. Sublobar resections are particularly indicated in elderly patients and in patients with high comorbidity index or reduced respiratory functional reserve. However, pulmonary lobectomy still remains the safest and oncologically correct method in patients with good performance status or higher risk of recurrence.

Introduction Carotid atherosclerosis is the main cause of ischaemic stroke. Texture analysis is a radiomic approach used to quantify image heterogeneity which can predict tumour aggression in oncology. We investigated whether this method could be applied to carotid artery disease to differentiate symptomatic from asymptomatic patients and culprit from non-culprit plaques, and then whether machine learning (ML) could correctly classify plaques based on these features. Methods CT angiography (CTA) images from symptomatic patients with carotid artery-related cerebrovascular accidents (CVAs) and from asymptomatic (ASX) patients were studied. Regions-of-interest (ROIs) were drawn on 14 consecutive carotid artery CTA slices with 3mm slice thickness. PyRadiomics was used for isotropic image (1x1x1) resampling and normalisation prior to texture feature extraction from 6 different classes (Table 1). Asymptomatic carotids were compared to culprit carotids (CC), and non-culprit (NC) carotids using the Mann Whitney U test or Wilcoxon signed-rank tests as appropriate, with a p-value Results The dataset comprised 82 carotid arteries from 41 symptomatic patients (41 culprit; 41 non-culprit) and 50 carotid arteries from 25 asymptomatic patients. CC and NC carotids showed significant differences in both first- and second-order features (IH Median: CC 618 (61); NC 646 (97), p Conclusions Textural analysis combined with machine learning on carotid CT scans reveals highly significant differences between symptomatic and asymptomatic patients, and between culprit and non-culprit carotid arteries within symptomatic patients. This approach could help identify patients at high-risk of stroke for aggressive medical therapy and surveillance. Conflict of Interest None

Notwithstanding advances in medical and surgical management of flail chest, its morbidity and mortality rates are still high. Aim of this study is to compare three approaches for parietal thoracic stabilization by analyzing both early and long-term patient outcomes.A retrospective study from January 2006 to January 2018 involving sixty-five surgical flail chest (25 plates,11 struts and 29 wires fixations) was conducted. A mean Abbreviated Injury Scale (AIS) was 2.38±0.82 and a mean Injury Severity Score (ISS) was 32.02±8.21.Struts and plates stabilizations compared with wires fixation showed an immediate restoring of the partial pressure of oxygen (90.56 mmHg vs 91.90 mmHg vs 89.23 mmHg, p = 0.021), the carbon-dioxide levels (36.00 mmHg vs 35.03 mmHg vs 38.98 mmHg, p = 0.000) and the oxygen-blood saturation (97.71% vs 98.21% vs 92.12%, p = 0.000) in the early postoperative period. Furthermore, struts and plates ensured a better recovery of daily activities up to the 3rdmonth (QoL=1.0: p0.001 in lateral flail chest and p0.02 in anterior and antero-lateral flail chest). At the 12thmonth no difference in QoL was found between the different approaches.Plate and strut fixation revealed a lower rate of postoperative morbidity and mortality. Wires stabilization was characterized for a reduction of operative time.

Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors.From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status.Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and 12 resected nodes were independent predictors of nodal upstaging.The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Malignant melanoma is the third most common type of tumor that causes brain metastases. Patients with cerebral involvement have a dismal prognosis and their treatment is an unmet medical need. Brain involvement is a multistep process involving several signaling pathways such as Janus kinase/signal Transducer and Activator of Transcription (JAK/STAT), Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Vascular Endothelial Growth Factor and Phosphatase and Tensin Homolog (PTEN). Recently therapy that targets the MAPK signaling (BRAF/MEK inhibitors) and immunotherapy (anti-CTLA4 and anti-PD1 agents) have changed the therapeutic approaches to stage IV melanoma. In contrast, there are no solid data about patients with brain metastases, who are usually excluded from clinical trials. Retrospective data showed that BRAF-inhibitors, alone or in combination with MEK-inhibitors have interesting clinical activity in this setting. Prospective data about the combinations of BRAF/MEK inhibitors have been recently published, showing an improved overall response rate. Short intracranial disease control is still a challenge. Several attempts have been made in order to improve it with combinations between local and systemic therapies. Immunotherapy approaches seem to retain promising activity in the treatment of melanoma brain metastasis as showed by the results of clinical trials investigating the combination of anti-CTL4 (Ipilimumab) and anti-PD1(Nivolumab). Studies about the combination or the sequential approach of target therapy and immunotherapy are ongoing, with immature results. Several clinical trials are ongoing trying to explore new approaches in order to overcome tumor resistance. At this moment the correct therapeutic choices for melanoma with intracranial involvement is still a challenge and new strategies are needed.

Background: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) is considered a useful noninvasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18 F-FDG-PET/CT for malignant pulmonary nodules. Methods: A computerized research, including published articles from 2012 and 2017, was carried out. 18 F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. Results: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794– 0.843), 0.624 (95% CI: 0.582–0.665), 2.190 (95% CI: 1.950–2.440), 0.290 (95% CI: 0.250–0.330), 0.802 (95% CI: 0.783–0.819), 0.652 (95% CI: 0.618–0.684) and 0.649 (95% CI: 0.625–0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. Conclusions: The results suggest 18 F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.

Background. Although positron emission tomography/computed tomography, often integrated with 2-deoxy-2-[fluorine-18] fluorine-D-glucose (18F-FDG-PET/CT), is fundamental in the assessment of lung cancer, the relationship between metabolic avidity of different histotypes and maximum standardized uptake value (SUVmax) has not yet been thoroughly investigated. The aim of the study is to establish a reliable correlation between Suvmax and histology in non-small cell lung cancer (NSCLC), in order to facilitate patient management. Methods. We retrospectively assessed the data about lung cancer patients entered in the Italian Registry of VATS Group from January 2014 to October 2019, after establishing the eligibility criteria of the study. In total, 8139 patients undergoing VATS lobectomy were enrolled: 3260 females and 4879 males. The relationship between SUVmax and tumor size was also analyzed. Results. The mean values of SUVmax in the most frequent types of lung cancer were as follows: (a) 4.88 ± 3.82 for preinvasive adenocarcinoma; (b) 5.49 ± 4.10 for minimally invasive adenocarcinoma; (c) 5.87 ± 4.18 for invasive adenocarcinoma; and (d) 8.85 ± 6.70 for squamous cell carcinoma. Processing these data, we displayed a statistically difference (p < 0.000001) of FDG avidity between adenocarcinoma and squamous cell carcinoma. Moreover, by classifying patients into five groups based on tumor diameter and after evaluating the SUVmax value for each group, we noted a statistical correlation (p < 0.000001) between size and FDG uptake, also confirmed by the post hoc analysis. Conclusions. There is a correlation between SUVmax, histopathology outcomes and tumor size in NSCLC. Further clinical trials should be performed in order to confirm our data.

Background The purpose of this study was to assess if there is a correlation between the carotid computed tomography (CT) Hounsfield unit (HU)-based plaque attenuation values measured using dual-energy CT (DECT) scanner and brain leukoaraiosis (LA). Methods Fifty consecutive patients (34 males, 16 females; mean age, 69 years; age range, 46-84 years) who underwent carotid CT and brain magnetic resonance imaging were included in the study. CT examinations were performed with a DECT scanner, and LA lesion volume quantification was performed using a semiautomated segmentation technique. Results We found an inverse statistically significant correlation between the HU-based carotid artery plaque attenuation and the LA lesion volume. Because of the presence of calcified plaques, a second model was calculated at low kiloelectron volt levels from 66 to 100 and 100 kV by taking into consideration the fatty and mixed plaques, and this further led to the associations between HU-based attenuation and LA volume in brain and vascular territories. Conclusions The results of our study suggest that the associations between HU attenuation of the carotid artery plaques (with the exclusion of calcified plaques) and the volume of LA are emphasized at low keV energy levels.

Background BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes. Patients and methods The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients’ clinical characteristics. Kaplan–Meier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. Results A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P = 0.017), to melanoma thickness according to Clark levels, (level V versus III, P = 0.004; level V versus IV, P = 0.04), to lymph node metastases rather than cutaneous (P = 0.04) or visceral (P = 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P = 0.04; PFS P = 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P = 0.014 and P = 0.003, respectively). Conclusion These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition., Highlights • In melanoma the response to anti-BRAF targeted therapies is heterogeneous and influenced by several features. • The role of the BRAF VAF as provider of sensitivity to target therapies is debated. • We found that high BRAF VAFs are associated with patient age, melanoma thickness, non-brisk TILs and lymph node metastases. • We proved the independent prognostic value of high BRAF VAFs in melanoma patients treated with targeted therapies. • The quantitative evaluation of BRAF mutations allows stratifying melanoma patients to the BRAF/MEK targeted treatment.

Purpose: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses. Experimental Design: Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter oct4. Their stemness potential was confirmed in vivo by limiting dilution assays. We explored the sensitivity of eGFP+ mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, in vitro. First, we treated MCs in vitro with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells. CIK cell activity against chemoresistant mCSCs was confirmed in vivo in two distinct immunodeficient murine models. Results: We visualized eGFP+ mCSCs (14% ± 2.1%) in 11 MCs. The tumorigenic precursor rate in vivo was higher within eGFP+ MCs (1/42) compared with the eGFP− counterpart (1/4,870). In vitro mCSCs were relatively resistant to CHT and BRAFi, but killed by CIK cells (n = 11, 8/11 autologous), with specific lysis ranging from 95% [effector:tumor ratio (E:T), 40:1] to 20% (E:T 1:3). In vivo infusion of autologous CIK cells into mice bearing xenografts from three distinct melanomas demonstrated significant tumor responses involving CHT-spared eGFP+ mCSCs (P = 0.001). Sequential CHT–immunotherapy treatment retained antitumor activity (n = 12, P = 0.001) reducing mCSC rates (P = 0.01). Conclusions: These findings are the first demonstration that immunotherapy with CIK cells is active against autologous mCSCs surviving CHT or BRAFi. An experimental platform for mCSC study and rationale for CIK cells in melanoma clinical study is provided. Clin Cancer Res; 23(9); 2277–88. ©2016 AACR.

Background: To investigate current role of three-dimensional video-assisted thoracoscopic surgery (VATS) and its differences from conventional flat video-assisted procedures for lymph node dissections in both pulmonary and esophageal cancers. Methods: A PubMed Embase, Google Scholar, OpenDOAR research was carried out according to a prepended Boolean function in order to speculate some difference in mean harvested lymph nodes, blood loss and postoperative chylothorax according to the techniques. Results: Electing six articles, for a total of 1,262 patients (609 3D-VATS and 653 2D-VATS patients), significant differences favouring a 3D approach were found in mean node count [mean difference: 1.56; standard error (SE): 0.23; 95% confidence interval (95% CI): 1.11–2.01, difference freedom (DF) =1,260; t=6.85; P 2 =0.009; 95% CI: −1.61–1.69, DF=1; P=0.926). Conclusions: The management of the hilar and mediastinal lymphatic areas seems to be ameliorated by the adoption of three-dimensional video-assisted strategies potentially significantly influencing patients’ outcome.

Aim To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. Material and methods Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. Results Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets ( p >0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p =0.001; mixed versus 140 kVp, p =0.001; 80 kVp versus mixed, p =0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets ( p Conclusions The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

BRAF signaling is involved in melanoma growth in more than half of metastatic patients. In the last few years, new drugs that block this pathway have significantly improved the outcomes of patients with metastatic melanoma. Ninety percent of BRAF mutations involve exon 15, and the most frequent, V600E, results from the amino acid change from valine (V) to glutamic acid (E). BRAF inhibitor treatments have shown a notable overall response rate and improvements in progression-free and overall survival. Rare BRAF mutations of codon 599 have been also described in a few patients with papillary thyroid cancer and melanoma. Nowadays, no evidence is available in the literature, describing the role of target therapies as treatment in patients with this specific codon mutation. We describe the case of a young woman with metastatic melanoma with a particular BRAF mutation, T599I, who has benefited from treatment with a BRAF inhibitor, vemurafenib.

Purpose: To determine the preliminary feasibility, safety, and clinical efficacy of magnetic resonance (MR)-guided focused ultrasound for the treatment of painful osteoid osteoma. Materials and Methods: This prospective institutional review board-approved study involved six consecutive patients (five males and one female; mean age, 21 years) with a diagnosis of osteoid osteoma based on clinical and imaging findings. All patients underwent MR-guided focused ultrasound ablation after providing informed consent. Lesions located in the vertebral body were excluded. The number of sonications and the energy deposition were recorded. Treatment success was determined at 1, 3, and±months after treatment. A visual analog scale (VAS) score for pain was used to assess changes in symptoms. MR imaging features of osteoid osteoma (edema, hyperemia, and nidus vascularization) were considered at baseline and at imaging follow-up. Results: Treatment was performed with a mean of 4 sonications±1.8 (standard deviation), with a mean energy deposition of 866 J±211. No treatment-or anesthesia-related complications occurred. The pre-and posttreatment mean VAS scores significantly differed (7.9±1.4 and 0.0±0.0, respectively). At imaging, the edema and hyperemia associated with osteoid osteoma gradually disappeared in all lesions. However, nidus vascularization still persisted after treatment in four of six patients. Conclusion: This limited series demonstrated that MR-guided focused ultrasound treatment of osteoid osteoma can be performed safely with a high rate of success and without apparent treatment-related morbidity. © RSNA, 2013.

Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and elongation of the large- and medium-sized arteries with predisposition to stenoses and aneurysms. ATS is caused by mutations in the SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10) and is described typically in pediatric patients. We report on a 51-year-old woman, originally ascertained because of unexplained widespread chronic pain and positive family history of aortic malformation. The main findings included aged appearance, congenital joint hypermobility, joint instability complications, chronic fatigue syndrome, progressive painful joint stiffness, abdominal hernias, pelvic prolapses, multiple cardiac valve prolapses, varicose veins, easy bruising, and gingival recession. Vascular imaging revealed kinking and anomalous origin of the aortic arch branches, marked tortuosity of the aorta, pulmonary and most middle arteries, and a small aneurysm of the splenic artery. SLC2A10 analysis disclosed homozygosity for the novel c.1411+1G>A splice mutation, leading to a 41 amino acids GLUT10 internal deletion. Expression study by immunofluorescence using healthy control cells showed lack of membrane internalization of GLUT10 in patient's skin fibroblasts. This report describes the first splice-site SLC2A10 mutation and increases to 19 the repertoire of known mutations in this gene. Comparison with the few previously published adult patients with ATS contributes to the natural history of this condition, which is probably under diagnosed within the expanding family of inherited connective tissue disorders. © 2012 Wiley Periodicals, Inc.

Purpose: To determine whether wide-volume perfusion computed tomography (CT) performed with a new generation scanner can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on the whole tumor mass in patients with locally advanced lung adenocarcinoma and to determine if changes in CT numbers correlate with the response to therapy as assessed by conventional response evaluation criteria in solid tumors (RECIST) Materials and Methods: Forty-five patients with unresectable lung adenocarcinoma underwent perfusion CT before and 40 and 90 days after chemotherapy and antiangiogenetic treatment. RECIST measurements and calculations of blood flow, blood volume, time to peak, and permeability were performed by two independent blinded radiologists. Pearson correlation coefficient was used to assess the correlation between baseline CT numbers. Baseline and follow-up perfusion parameters of the neoplastic lesions were tested overall for statistically significant differences by using the repeatedmeasures analysis of variance and then were also compared on the basis of the therapy response assessed according to the RECIST criteria. Results: Pearson correlation coefficient showed a significant correlation between baseline values of blood flow and blood volume ( ρ = 0.48; P = 001), time to peak and permeability ( ρ = 0.31; P = 04), time to peak and blood flow ( ρ = - 0.66; P < 001), and time to peak and blood volume ( ρ = - 0.39; P = 007). Blood flow, blood volume, and permeability values were higher in responding patients than in the other patients, with a significant difference at second follow-up for blood flow ( P = 0001), blood volume ( P = 02), and permeability ( P = 0001); time to peak was higher in nonresponding patients ( P = 012). Conclusion: Perfusion CT imaging may allow evaluation of lung cancer angiogenesis demonstrating alterations in vascularity following treatment. © RSNA, 2011.

Purpose: This study was done to assess the diagnostic potential of dual-source computed tomography (DSCT) in the functional evaluation of lung cancer patients undergoing surgical resection. The CT data were compared with pulmonary perfusion scintigraphy and pulmonary function tests (PFTs). Materials and methods: All patients were evaluated with DSCT, scintigraphy and PFTs. The DSCT scan protocol was as follows: two tubes (80 and 140 kV; Care Dose protocol); 70 cc of contrast material (5 cc/s); 5- to 6-s scan time; 0.6 mm collimation. After the automatic calculation of lung perfusion with DSCT and quantification of air volumes and emphysema with dedicated software applications, the perfusional CT studies were compared with scintigraphy using a visual score for perfusion defects; CT air volumes and emphysema were compared with PFTs. Results: The values of accuracy, sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of DSCT compared with perfusion scintigraphy as the reference standard were: 0.88, 0.84, 0.90, 0.93 and 0.88, respectively. The McNemar test did not identify significant differences either between the two imaging techniques (p=0.07) or between CT and PFTs (p=0.09). Conclusions: DSCT is a robust and promising technique that provides important and accurate information on lung function. © 2011 Springer-Verlag Italia.

Purpose: The authors performed a preliminary study with blood-pool contrast-enhanced magnetic resonance angiography (MRA) in evaluating the degree of carotid artery stenosis and plaque morphology, comparing the diagnostic performance of first-pass (FP) and steady-state (SS) acquisitions with 64-slice computed tomography angiography (CTA) and using digital subtraction angiography (DSA) as the reference standard. Materials and methods: Twenty patients with ≥50% carotid artery stenosis at Doppler sonography underwent blood-pool contrast-enhanced MRA, CTA and DSA. Two independent radiologists evaluated MRA and CTA examinations to assess the degree of stenosis and characterise plaque morphology. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for FP, SS and CTA. The McNemar and Wilcoxon tests were used to determine significant differences (p0.05). Conclusions: Blood-pool contrast-enhanced MRA with SS sequences allow improved diagnostic evaluation of the degree of carotid stenosis and plaque morphology compared with FP and is substantially equal to CTA and DSA. © 2010 Springer-Verlag Italia Riassunto.

Solitary pulmonary nodules are common radiologic findings and their detection has increased due to the introduction and improvement of diagnostics. Since a nodule can be an expression of early lung cancers, a proper classification and management are required because its treatment might lead to decreased morbidity and mortality. In this regard, prominent guidelines are available although they are characterized sometimes by discordant and misleading evidences. Furthermore, the same results of studies in the literature appear conflicting. Aim of this work is to evaluate the role of imaging through an extensive literature review but focusing on 18-fluorine fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) in order to assess the limits and future perspectives of solitary pulmonary nodule characterization in early detection of lung cancer. Key messages Detection of solitary pulmonary nodules has increased. Management of solitary pulmonary nodules is still debated. Future perspectives of early solitary pulmonary nodule characterization.

The challenge of surgeons in our era is a less-invasive procedure. Over the last 20 years, video assisted thoracic surgery (VATS) become the treatment of choice in multiple chest related illnesses. Usually, VATS requires general anaesthesia with the selective intubation. However, in severe patients, with a high comorbidity index or elevated risk for anaesthesia, general anaesthesia may not be possible. An alternative is to perform the VATS in patients under local anaesthesia, awake, and non-intubated. We conducted an attempt of systematic literature review and meta-analysis of non-intubated VATS (AVATS) focusing attention on mortality rate, the complications and the hospital length of stay. AVATS is a feasible and safe technique that is increasingly aware of the possibility of applying for surgery even patients with high indexes of comorbidity, reduced cardiovascular function and general conditions contraindicating general anaesthesia. Nevertheless, further investigations are required to confirm these findings.

Summary: Skin necrosis is a rare complication after thoracomyoplasty and usually needs conservative treatment. We described positive findings with surgical approach. A 54-year-old man showed bronchopleural fistula after undergoing right pneumonectomy for lung cancer, treated with thoracomyoplasty. On the 20th postoperative day, a skin wound lesion was noted, whose deterioration required a skin flap transposition. Patient was discharged from hospital on the 7th postoperative day and did not show relapse at the 7th year follow-up. Surgery can be the most viable alternative to medical treatments in the management of a chest wall cutaneous complication even in high-risk patients.

Background: The VATS Group and the National Register for VATS Lobectomy were set up in 2013. Both quality and quantity of collected data within the database are two fundamental tools for scientific and statistical purposes, similar to other important databases, such as the European Society of Thoracic Surgeons (ESTS) Database, the Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) and the Danish Lung Cancer Registry (DLCR). Methods: Four thousand seven hundred and four VATS lobectomy patients have recruited to date. Several parameters were recorded, such as preoperative clinical condition, surgical treatment as far as technical details, postoperative course and follow-up. Results: The Eastern Cooperative Oncology Group (ECOG) performance status was 0.27. Uni-portal approach was used in 332 patients, three-portal approach in 3,825 and bi-portal approach in 547. Lymphadenectomy was performed in 4,704 patients: a sampling nodal dissection in 1,180 patients and a radical nodal dissection in 3,524 cases. Conversion rate was in 9.99% of cases. Adenocarcinoma is the most common histologic type (53.34%), followed by squamous carcinoma (15.53%). Conclusions: The structure of the Italian Registry of VATS Lobectomy makes it a valid source to draw on for statistical studies for scientific purposes.

Purpose. The aim of this study was to validate a 64-row multidetector computed tomography (64-MDCT) acquisition protocol with biphasic administration of contrast medium for comprehensive assessment of the coronary and systemic arterial tree in a single examination. Materials and methods. The scanning protocol comprised two acquisitions: an electrocardiograph (ECG)-gated scan at the level of the heart, followed by a total-body, low-dose scan of the systemic arterial circulation. Twenty patients were evaluated using two different strategies for contrast administration. In ten patients, the delay between the two acquisitions was set at 40 s, whereas in the remaining patients, it varied between 45 s and 65 s. For both strategies, the degree of systemic arterial opacification and the attenuation gradient between arterial and venous structures were quantitatively assessed at six extracoronary locations. Two observers evaluated in consensus the presence or absence of atherosclerosis and the degree of stenosis of arterial segments. Results. Three hundred coronary segments were analysed. Arterial-wall changes were depicted in 155 (51%) segments, and in 35 (23%), the degree of stenosis was >50%. Of the 640 extracoronary arterial segments, 250 (39%) presented atherosclerotic wall alterations, in 50 (20%), the degree of stenosis was >50% and five were affected by aneurysmal dilatation. The magnitude of arterial opacification values and attenuation gradients between arterial and venous structures were significantly higher in patients scanned with the 40-s fixed-delay strategy. Conclusions. Whole-body CT angiography with biphasic administration of contrast agent and fixed scan delay has been shown to be a feasible and reproducible technique. Comprehensive data on the global atherosclerotic burden potentially offer important therapeutic options for subclinical, high-risk segments. © 2008 Springer-Verlag.

Background: Malignant pleural mesothelioma (MPM) is a rare neoplasm with indolent course and worse prognosis. Notwithstanding improvements in histologic and cytologic characterization, a generalized lack of consensus about diagnostic criteria still claims debate, though several new immunohistochemical markers have been introduced. Aim of this study is to evaluate current role and accuracy of glucose transporter-1 (GLUT-1) assay in the evaluation of malignant mesothelial proliferations. Methods: A PubMed Embase, Google Scholar research was carried out by identifying eight eligible articles fulfilling inclusion criteria. Quality assessment was conducted according to QUADAS-2 test. Data were extracted to evaluate true positive (TP), false positive (FP), true negative (TN) and false negative (FN) rates. Results: Enrolling 728 patients (297 MPM vs. 431 reactive pleural diseases), TP, FP, TN and FN cases were 215, 33, 398 and 82, respectively. A proportion of 74.25% of MPM patients showed immunoreactivity for GLUT-1. The pooled sensitivity (Se), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy (DA) and disease prevalence (DP) were 0.74 [95% confidence interval (CI): 0.57–0.85], 0.91 (95% CI: 0.79–0.96), 0.87 (95% CI: 0.82–0.90), 0.83 (95% CI: 0.80–0.85), 0.84 (95% CI: 0.81–0.97) and 0.41 (95% CI: 0.37–0.44). Conclusions: In conclusions, GLUT-1 immunohistochemistry for MPM is characterized both by high Se and Spe rates. However, according to DP rates, its properties should be considered in the setting of a panel of markers rather than alone.

Combined PET/MR is a relatively new technique and so far there has been a very limited report of the potential simultaneous PET/MR and PET/CT application in the evaluation of neuroendocrine tumours. The present study aimed to compare "Ga-DOTATATE PET/CT and PET/MR imaging in patients with known neuroendocrine tumours (NET) and assess the confidence in anatomic lesion detection and localization. We analysed the data of 37 NET patients who underwent both 68Ga-DOTATATE PET/CT and PET/MR using the same injected activity. Visual findings by two observers of the two modalities were recorded. SUV max of both primary tumour and liver lesions for both modalities and PET/MR derived apparent diffusion coefficient (ADC) values were measured. To study the value of additional MRI sequences, the differences in performance between PET with T1+T2w, PET with DWI reads, and PET with post contrast was assessed. No significant differences between the two modalities were seen regarding the number of patients affected by primary or metastatic disease. However, counting the number of lesions per patient, both observers were able to recognize more liver lesions in MRI T1 and T2. The interclass correlation coefficient (ICC) demonstrated a strong correlation between SUV max derived from PET/CT and PET/MR in both primary lesions (ICC = 0.92; p = 0.001) and liver (ICC = 0.882; p = 0.001). In the evaluation of lesion per patient, PET+ contrast and DWI detected more metastasis than the evaluation of PET +T1 and T2 alone. There was no significant correlation between ADC values and PET/MR SUV max of the tumour (respectively: p = 0.43, p 0.88 and p = 0.295). PET/MRI has comparable accuracy in localization and staging to PET/CT, and has a potential to become a valid alternative to PET/CT in staging and follow up of NET patients, with advantages in the characterization of liver lesions. In our study DWI and contrast helped to detect more lesions.