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Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of EGFR in treatment-naïve patients with advanced non–small cell lung cancer (NSCLC). CT scans from 109 treatment-naïve patients with NSCLC (21 EGFR-mutant and 88 EGFR-wild type) underwent radiomics analysis to develop a machine learning model able to recognize EGFR-mutant from EGFR-WT patients via CT scans. A “test–retest” approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinical features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, whereas the accuracy values in the datasets from TCIA and the external institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR-mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms.Significance:These findings demonstrate that data normalization and “test–retest” methods might improve the performance of machine learning models on radiomics images and increase their reliability when used on external validation datasets.

Supplementary Figure 1

Despite the widespread use of antibiotics, deep neck infections are still a relevant clinical problem and can cause severe and potentially life-threatening complications. Imaging plays a pivotal role into the clinical management of deep neck infections, allowing identification of the source of infections, definition of the precise extension of the disease and early diagnosis of local or distant complications. The complex anatomy of deep neck spaces may hide the actual extent of disease: the knowledge of neck anatomy enables radiologists to rapidly evaluate expected routes of spread of infections and to effectively communicate crucial information to surgeons. Computed Tomography is the most used imaging modality for assessing primary site of infection, extent of disease and local complications. Magnetic resonance imaging may be used as a second level imaging modality for individuating intracranial or spinal complications. The present work aims to review the imaging of deep neck spaces infections, focusing on relevant anatomy and clinical scenarios, underlining practical teaching points for each of them. Familiarity with deep neck spaces anatomy and knowledge of most common routes of spread of infections allow the radiologist to make a prompt diagnosis and to look for early signs of potential complications.

Simple Summary The aim of the study is to identify radiomic features capable of predicting the response to immunotherapy. Delta-radiomics can foresees the comparison between subsequent CT scans and therefore allows to predict the changes that occurred during the treatment. In this study, the individual lesions of patients with advanced non-small cell lung cancer treated with immunotherapy were analyzed. The study aims to discover the features that predict the response to immune checkpoint inhibitors. Abstract Delta-radiomics is a branch of radiomics in which features are confronted after time or after introducing an external factor (such as treatment with chemotherapy or radiotherapy) to extrapolate prognostic data or to monitor a certain condition. Immune checkpoint inhibitors (ICIs) are currently revolutionizing the treatment of non-small cell lung cancer (NSCLC); however, there are still many issues in defining the response to therapy. Contrast-enhanced CT scans of 33 NSCLC patients treated with ICIs were analyzed; altogether, 43 lung lesions were considered. The radiomic features of the lung lesions were extracted from CT scans at baseline and at first reassessment, and their variation (delta, Δ) was calculated by means of the absolute difference and relative reduction. This variation was related to the final response of each lesion to evaluate the predictive ability of the variation itself. Twenty-seven delta features have been identified that are able to discriminate radiologic response to ICIs with statistically significant accuracy. Furthermore, the variation of nine features significantly correlates with pseudo-progression.

The eighth edition of the TNM classification officially introduced “depth of invasion” (DOI) as a criterion for determining the T stage in tongue squamous cell carcinoma. The DOI is a well-known independent risk factor for nodal metastases. In fact, several experts strongly suggest elective neck dissection for tongue cancer with a DOI > 4 mm due to the high risk of early and occult nodal metastases. Imaging plays a pivotal role in preoperative assessments of the DOI and, hence, in planning the surgical approach. Intraoral ultrasound (IOUS) has been proposed for early-stage SCC of the oral tongue as an alternative to magnetic resonance imaging (MRI) for local staging. The aim of this work is to investigate the accuracy of IOUS in the assessment of the DOI in early oral SCC (CIS, pT1, and pT2). A total of 41 patients with tongue SCCs (CIS-T2) underwent a preoperative high-frequency IOUS. An IOUS was performed using a small-size, high-frequency hockey-stick linear probe. The ultrasonographic DOI (usDOI) was retrospectively compared to the pathological DOI (pDOI) as the standard reference. In patients who underwent a preoperative MRI, their usDOI, magnetic resonance DOI (mriDOI), and pDOI were compared. Specificity and sensitivity for the IOUS to predict a pDOI > 4 mm and to differentiate invasive and noninvasive tumors were also evaluated. A high correlation was found between the pDOI and usDOI, pDOI and mriDOI, and usDOI and mriDOI (Spearman’s ρ = 0.84, p < 0.0001, Spearman’s ρ = 0.79, p < 0.0001, and Spearman’s ρ = 0.91, p < 0.0001, respectively). A Bland–Altman plot showed a high agreement between the usDOI and pDOI, even though a mean systematic error was found between the usDOI and pDOI (0.7 mm), mriDOI and pDOI (1.6 mm), and usDOI and mriDOI (−0.7 mm). The IOUS was accurate at determining the T stage (p < 0.0001). The sensitivity and specificity for the IOUS to predict a pDOI ≥4 mm were 92.31% and 82.14%, respectively, with an AUC of 0.87 (p < 0.0001). The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) for the IOUS to predict an invasive cancer were 100%, 94.7%, 60%, and 100%, respectively. The AUC was 0.8 (95% CI 0.646–0.908, p < 0.0001). The IOUS was accurate in a preoperative assessment of a pDOI and T stage, and can be proposed as an alternative to MRI in the preoperative staging of tongue SCC.

Lung fibrosis has specific computed tomography (CT) findings and represents a common finding in advanced COVID-19 pneumonia whose reversibility has been poorly investigated. The aim of this study was to quantify the extension of collagen deposition and aeration in postmortem cryobiopsies of critically ill COVID-19 patients and to describe the correlations with qualitative and quantitative analyses of lung CT. Postmortem transbronchial cryobiopsy samples were obtained, formalin fixed, paraffin embedded and stained with Sirius red to quantify collagen deposition, defining fibrotic samples as those with collagen deposition above 10%. Lung CT images were analyzed qualitatively with a radiographic score and quantitatively with computer-based analysis at the lobe level. Thirty samples from 10 patients with COVID-19 pneumonia deceased during invasive mechanical ventilation were included in this study. The median [interquartile range] percent collagen extension was 6.8% (4.6–16.2%). In fibrotic compared to nonfibrotic samples, the qualitative score was higher (260 (250–290) vs. 190 (120–270), p = 0.036) while the gas fraction was lower (0.46 (0.32–0.47) vs. 0.59 (0.37–0.68), p = 0.047). A radiographic score above 230 had 100% sensitivity (95% confidence interval, CI: 66.4% to 100%) and 66.7% specificity (95% CI: 41.0% to 92.3%) to detect fibrotic samples, while a gas fraction below 0.57 had 100% sensitivity (95% CI: 66.4% to 100%) and 57.1% specificity (95% CI: 26.3% to 88.0%). In COVID-19 pneumonia, qualitative and quantitative analyses of lung CT images have high sensitivity but moderate to low specificity to detect histopathological fibrosis. Pseudofibrotic CT findings do not always correspond to increased collagen deposition.

Well-differentiated, low-grade neuroendocrine tumors (NETs) are the most frequent tumor types of the small bowel. Despite their generally indolent growth patterns and grade, these tumors tend to metastasize; indeed, at presentation, approximately 50% show nodal metastases and 30% of patients have distant metastases, even though they potentially show long survival. Little is available in the literature concerning the optimal nodal yield in small-bowel resections, and the clinical significance of nodal metastases and lymph node ratio (LNR) at this site is still debated. The aim of this review, through a systematic literature search, is to explore and analyze data regarding nodal status, adequacy of lymphadenectomy, and LNR on the prognosis of small bowel NETs using defined end points (progression-free survival, recurrence-free survival, and overall survival). Some surgical series have demonstrated that extended regional mesenteric lymphadenectomy, together with primary tumor resection, is associated with improved patient survival, and LNR is proving a prognostically important parameter. The new feature of mesenteric tumor deposits (MTDs; neoplastic deposits found in the mesenteric perivisceral adipose tissue that are not LN associated) seems to be a better prognostic predictor in small-bowel NETs compared to nodal metastases, and this feature is explored and critiqued in this review. In particular, increasing number of tumor deposits is correlated with increased risk of disease-specific death, and MTDs seem to correlate with peritoneal carcinomatosis.

Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23–59) and 69% (95%CI: 55–81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65–94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32–86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.

Introduction: Systemic sclerosis (SSc) is a systemic immune-mediated disease, featuring fibrosis of the skin and organs, and has the greatest mortality among rheumatic diseases. The nervous system involvement has recently been demonstrated, although actual lung involvement is considered the leading cause of death in SSc and, therefore, should be diagnosed early. Pulmonary function tests are not sensitive enough to be used for screening purposes, thus they should be flanked by other clinical examinations, however, this would lead to a risk of overtesting, with considerable costs for the health system and an unnecessary burden for the patients. To this extent, Machine Learning (ML) algorithms could represent a useful add-on to the current clinical practice for diagnostic purposes and could help retrieve the most useful exams to be carried out for diagnostic purposes. Method: Here, we retrospectively collected high resolution computed tomography, pulmonary function tests, esophageal pH impedance tests, esophageal manometry and reflux disease questionnaires of 38 patients with SSc, applying, with R, different supervised ML algorithms, including lasso, ridge, elastic net, classification and regression trees (CART) and random forest to estimate the most important predictors for pulmonary involvement from such data. Results: In terms of performance, the random forest algorithm outperformed the other classifiers, with an estimated root-mean-square error (RMSE) of 0.810. However, this algorithm was seen to be computationally intensive, leaving room for the usefulness of other classifiers when a shorter response time is needed. Conclusions: Despite the notably small sample size, that could have prevented obtaining fully reliable data, the powerful tools available for ML can be useful for predicting early lung involvement in SSc patients. The use of predictors coming from spirometry and pH impedentiometry together might perform optimally for predicting early lung involvement in SSc.

Simple Summary Identifying reliable prognostic biomarkers of progression in the early phases of treatment is crucial in patients undergoing immune checkpoints inhibitors (ICI) administration for advanced non-small cell lung cancer (NSCLC). With this aim, in this study we combined the prognostic power of the degree of systemic inflammation (depicted by peripheral inflammation indexes), the quantification of the metabolically active tumor burden (estimated using 18F-fluorodeoxyglucose positron emission tomography/computed tomography) as well as their combination in NSCLC patients receiving immune checkpoints inhibitors. This combined approach could be used to improve the risk stratification and the subsequent clinical management in NSCLC patients treated with immune checkpoints inhibitors. Abstract An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the prognostic power of peripheral-blood systemic inflammation indexes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this clinical setting. In 45 patients showing radiological progression (defined as RECIST 1.1 progressive disease) during Nivolumab administration, the following lab and imaging parameters were collected: neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), systemic inflammation index (SII), maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and SII independently predicted OS. Their combination in the immune metabolic prognostic index (IMPI) allowed the identification of patients who might benefit from immunotherapy continuation, despite radiological progression. The combination of FDG PET/CT volumetric data with SII also approximates the immune-metabolic response with respect to baseline, providing additional independent prognostic insights. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden, and their combination might disclose the radiological progression in NSCLC patients receiving Nivolumab.

Objective The first-line therapeutic approach for oral cavity squamous cell carcinoma (OCSCC) is complete surgical resection. Preoperative assessment of depth of invasion (cDOI) is crucial to plan the surgery. Magnetic resonance (MR) and intraoral ultrasonography (IOUS) have been shown to be useful tools for assessment of DOI. The present analysis investigates the accuracy of MR and IOUS in evaluating DOI in OCSCC compared to histological evaluation (pDOI). Materials and methods Forty-nine previously untreated patients with cT1-T3 OCSCC were reviewed. Nine patients were staged with MR alone, 10 with IOUS alone, and 30 with both MR and IOUS. Results Mean difference between cDOIMR and pDOI values of 0.2 mm (95% CI − 1.0–1.3 mm) and between cDOIIOUS and pDOI of 0.3 mm (95% CI − 1.0–1.6 mm). Spearman R between cDOIMR and pDOI was R = 0.83 and between cDOIIOUS and pDOI was R = 0.76. Both radiological techniques showed high performance for the correct identification, with the optimum cut-off of 5 mm, of patients with a pDOI ≥ 4 mm and amenable to a neck dissection, with an AUC of 0.92 and 0.82 for MR and IOUS, respectively. Conclusion Both examinations were valid approaches for preoperative determination of DOI in OCSCC, although with different cost-effectiveness profiles and indications.

Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of EGFR in treatment-naïve patients with advanced non–small cell lung cancer (NSCLC). CT scans from 109 treatment-naïve patients with NSCLC (21 EGFR-mutant and 88 EGFR-wild type) underwent radiomics analysis to develop a machine learning model able to recognize EGFR-mutant from EGFR-WT patients via CT scans. A “test–retest” approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinical features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, whereas the accuracy values in the datasets from TCIA and the external institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR-mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. Significance: These findings demonstrate that data normalization and “test–retest” methods might improve the performance of machine learning models on radiomics images and increase their reliability when used on external validation datasets.

Background: Data on the pathologic features in COVID-19 are scarce; the few available studies show diffuse alveolar damage (DAD) however no data on the chronologic evolution of COVID-19 lung lesions are available. The primary aim of the study was to describe the chronology of lung pathological changes in COVID-19 by using a post mortem transbronchial lung cryobiopsy approach (TBLC). Our secondary aim was to correlate the histologic findings with computed tomography (CT) patterns. Methods: SARS-Cov2 positive patients, with available CT scans, who died while intubated and mechanically ventilated, were enrolled. TBLC procedure was performed 30 minutes after death, and all lung lobes sampled. Histopathologic analysis was performed on all available tissue. Findings: Eight patients met criteria. Two patients (illness duration

Because of the peculiar mechanism of action of immune checkpoint inhibitors (ICIs), evaluation of the radiologic response to them in solid tumors presents many challenges. We aimed to compare evaluation of the first response to nivolumab by means of CT-based criteria with respect to 18F-FDG PET response criteria in non–small cell lung cancer (NSCLC) patients. Methods: Seventy-two patients with advanced NSCLC were recruited in a single-institution ancillary trial within the expanded-access program (NCT02475382) for nivolumab. Patients underwent CT and 18F-FDG PET at baseline and after 4 cycles (the first evaluation). In cases of progressive disease, an additional evaluation was performed after 2 further cycles to confirm progression. We evaluated the treatment response on CT using RECIST 1.1 and the immune-related response criteria (irRC) and on 18F-FDG PET using PERCIST and immunotherapy-modified PERCIST. The concordance between CT- and PET-based criteria and the capability of each method to predict overall survival were evaluated. Results: Forty-eight of 72 patients were evaluable for a first response assessment with both PET- and CT-based criteria. We observed low concordance between CT- and PET-based criteria (κ-value of 0.346 and 0.355 between PERCIST and imPERCIST and RECIST, respectively. κ-value of 0.128 and 0.198 between PERCIST and imPERCIST and irRC, respectively). Regarding overall survival, irRC could more reliably distinguish responders from nonresponders. However, thanks to the prognostic value of partial metabolic response assessed by both PERCIST and immunotherapy-modified PERCIST, PET-based response maintained prognostic significance in patients classified as having progressive disease on the basis of irRC. Conclusion: Even though the present study did not support the routine use of 18F-FDG PET in the general population of NSCLC patients treated with ICIs, the findings suggest that metabolic response assessment has added prognostic value, potentially improving therapeutic decision making.

Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

This paper is intended to demonstrate the importance of collaboration between the Radiologist and the Medical Examiner, especially in cases of firearms injuries; Computer Tomography (CT) is the method normally used, thanks to its high anatomical definition and potential for three-dimensional reconstruction and multiplanar visualisation. The case considered here concerns a shooting victim. Upon his arrival at the emergency ward two injuries were observed, one in the lower back region and a second one in the left front mid axillary line; CT-scans were taken. The entrance wound was identified as the lower back wound, which was surrounded by a margin of abrasion of eccentric shape, with "burr" at the bottom and on the left: this suggested that the path of the projectile was from left to right and from below upwards. The exit wound, however, was located on the left side of the front of the torso: this could be compatible with deviation of the bullet's path within the victim's body caused by having hit bones. Only analysis of CT images and three-dimensional reconstruction could permit to define the correct path of the bullet and to exclude the possibility of deviation within this path; the atypical nature of the entrance wound was therefore the consequence of a bullet which had been deformed previously. The case described demonstrates how, in presence of non-typical entrance wounds, external examination of the victim can lead to misleading conclusions, so that, even in apparently simple cases, it is essential to work with a multidisciplinary team.

Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens. To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy. Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%. By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm2, and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not

In the last decades, in addition to conventional imaging techniques and magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has been shown to be relevant in the detection and management of breast cancer recurrence in doubtful cases in selected groups of patients. While there are no conclusive data indicating that imaging tests, including FDG PET/CT, produce a survival benefit in asymptomatic patients, FDG PET/CT can be useful for identifying the site of relapse when traditional imaging methods are equivocal or conflicting and for identifying or confirming isolated loco-regional relapse or isolated metastatic lesions. The present narrative review deals with the potential role of FDG PET in these clinical settings by comparing its accuracy and impact with conventional imaging modalities such as CT, ultrasound, bone scan, 18F-sodium fluoride PET/CT (18F-NaF PET/CT) as well as MRI. Patient-focused perspectives in terms of patients' satisfaction and acceptability are also discussed.

Octreotide and lanreotide, the first-generation somatostatin analogs, successfully control hormone hyperproduction, and related syndromes, in patients with acromegaly and neuroendocrine tumors. However, their anti-tumor effect, rather evident in large number of pituitary adenomas in acromegalic patients, has been hypothesized for a long time in patients with neuroendocrine tumors as well, although a significant tumor shrinkage has rarely been observed. However, the recent publication of the CLARINET study has strengthened the evidence, already emerged with the PROMID trial, that the long-term treatment with the first-generation long-acting somatostatin analogs may exert an anti-tumor activity on G1 and G2 enteropancreatic neuroendocrine tumors, as well. After the publication, majority of international guidelines have updated their algorithms in line with these results and this class of drugs obtained the indication as anti-tumor agents in the majority of patients with neuroendocrine tumors.

Because of the peculiar mechanism of action of immune checkpoint inhibitors (ICIs), evaluation of the radiologic response to them in solid tumors presents many challenges. We aimed to compare evaluation of the first response to nivolumab by means of CT-based criteria with respect to

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

The mobile cecum syndrome includes a spectrum of conditions. The cecal volvulus represents the acute form, with typical feature of a bowel obstruction that needs immediate operative treatment. On the other hand, a chronic form of mobile cecum syndrome which is the most common form reported a history of intermittent crampy abdominal pain, distension, and constipation. In this study, five patients came to our attention during the last ten years, presenting different symptoms due to a mobile cecum. All patients were investigated by several diagnostic techniques according to the specific clinical setting. All patients were found to have the cecum and ascending colon unattached to the posterior peritoneum. Surgery was the treatment of choice. In our experience, the best diagnostic technique was computed tomography scan, especially if performed in the Trendelenburg position. We also propose virtual colonoscopy as a good option for diagnosis (in patients with chronic syndrome) and follow-up after surgery. In conclusion, laparoscopic approach guaranteed a good result, with no symptoms of recurrence, in both acute and elective treatments. The diagnosis of mobile cecum needs a high index of suspicion and a targeted radiological investigation. Surgery, especially laparoscopic cecopexy and appendectomy, is the recommended treatment.

Neuroendocrine neoplasms (NENs) represent a clinically and pathologically heterogeneous group of tumours showing peculiar phenotypic characteristics and a common origin from cells of the diffuse neuroendocrine system [1–4]. NENs are commonly considered to be rare if compared to corresponding non-neuroendocrine neoplasms. Their frequency, however, has increased considerably in recent decades, as reported by epidemiological studies, such as the Surveillance, Epidemiology and End Results (SEER) registers in the USA, showing an increase of 1–5 new cases per 100,000/year [5]. In view of the more favourable prognosis of gastroenteropancreatic (GEP)-NEN than non-neuroendocrine neoplasms, the prevalence of GEP-NEN is 35 cases/100,000, shortly after colon adenocarcinoma and before all other gastroenteric adenocarcinomas [1].

Congenital and acquired airway anomalies represent a relatively common albeit diagnostic and therapeutic challenge, even for the most skilled operators in dedicated centers. Airway malformations encompass a wide spectrum of pathologies involving the larynx, trachea and bronchi, esophagus, mediastinal vessels. These developmental lesions are often isolated but the association of two or more anomalies is not infrequent. From the traditional chest X-ray to the newest applications of Optical Coherence Tomography, non- or mini-invasive diagnostic techniques represent useful tools to integrate invasive procedures. Comprehensive knowledge of the characteristics of each diagnostic test is mandatory for its useful application. The aim of our paper is to analyze the clinical indications for Imaging the Airway disease in pediatric population, and describe the diagnostic techniques. Only by a close interaction between all the operators involved in diagnosis and treatment of pediatric airway, as it happens in Multidisciplinary Airway Team, the non- or mini-invasive imaging is effective.

To compare regional vascular distribution and biological determinants of visible calcium load, as assessed by computed tomography, as well as of molecular calcium deposition as assessed by (18)F-NaF positron emission tomography. Eighty oncologic patients undergoing (18)F-NaF PET/CT scan were included in the study. Cardiovascular-risk stratification was performed according to a simplified version of the Framingham model [including age, diabetes, smoking, systolic blood pressure and body mass index (BMI)]. Arterial (18)F-NaF uptake was measured by drawing regions of interest comprising the arteries on each slice of the transaxial PET/CT and normalized to blood (18)F-NaF activity to obtain the arterial target-to-background ratio (TBR). The degree of arterial calcification (AC) was measured using a software program providing Agatston-like scores. Differences in mean values and regression analysis were tested. Predictors of AC and TBR were evaluated by univariate and multivariate analysis. p value of 0.05 was considered statistically significant. No correlation was documented between regional calcium load and regional TBR in any of the studied arterial segments. Visible calcium deposition was found to be dependent upon age while it was not influenced by all the remaining determinants of cardiovascular risk. By contrast, (18)F-NaF uptake was significantly correlated with all descriptors of cardiovascular risk, with the exception of BMI. Vascular (18)F-NaF uptake displays a different regional distribution, as well as different biological predictors, when compared to macroscopic AC. The tight dependency of tracer retention upon ongoing biological determinants of vascular damage suggests that this tool might provide an unexplored window on plaque pathophysiology.

SummaryThe “blood vulnerability”, resulting from the complex balance between serum molecules and inflammatory cell atherosclerotic activities, is a major determinant in the evaluation of the “global patient cardiovascular vulnerability”. In the present study, we focused on the role of the soluble receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL, a potential marker of coronary calcification and vulnerability) in the release of neutrophilic proteases. Then, the association between these mediators and the degree of coronary calcification (assessed by coronary calcium score [CCS]) was investigated in 20 subjects (aged ≥65 years) asymptomatic for cardiovascular disease. Results showed that RANKL dose-dependently induced matrix metalloprotease (MMP)-8 and MMP-9 release from human primary neutrophils cultured in Teflon dishes (suspension condition, mimicking cells circulating in the blood stream). Conversely, when adherent to polystyrene, neutrophils became unresponsive to RANKL. RANKL did not influence the release of other neutrophilic products in suspension and adherence cultures as well as neutrophil migration. RANKL-induced release of MMPs was dependent on the activation of defined intracellular signalling pathways (PI3K/Akt and ERK1/2). In asymptomatic subjects, serum levels of RANKL, MMP-8 and MMP-9 positively correlated with CCS, reflecting a potential relationship between circulating RANKL and coronary calcification. In conclusion, RANKL increased the release of neutrophilic products potentially related to the “blood” vulnerability via defined intracellular pathways. Serum levels of RANKL might represent a potential biomarker of coronary calcification and related cardiovascular risk.

Conflicting results have been reported about the clinical value of fluorodeoxyglucose (FDG) imaging in predicting the risk of rupture of abdominal aortic aneurysm (AAA). The present study tests the hypothesis that FDG uptake is low in asymptomatic noninflammatory AAA due to the low cell density in aneurysmal walls.Positron emission tomography (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-μm slices for incubation with 2-3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-μm slices. Autoradiographic images were coregistered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B.No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas.The loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication.

Sarcoidosis is a chronic multisystem disease that usually has a good prognosis but in some cases, especially when cardiac involvement occurs, the outcome is fatal. Cardiac sarcoidosis is insidious to diagnose because it is usually asymptomatic and when clinically apparent, it may have a wide variety of manifestations. The aim of this study was to investigate the possible cardiac involvement in cutaneous sarcoidosis patients. Diagnosis of cutaneous sarcoidosis was confirmed by skin biopsy, laboratory tests and radiological findings in 13 Caucasian patients. To evaluate cardiac damage, electrocardiography, echocardiography, and contrast-enhanced cardiac magnetic resonance were performed. Magnetic resonance identified cardiac sarcoidosis only in one of the cutaneous sarcoidosis patients. We suggest investigating cardiac involvement in patients with cutaneous sarcoidosis, albeit asymptomatic, since cardiac lesions are frequently associated with a poorer prognosis.

Positron Tomography/Computer Tomography (PET/CT) imaging of 18F-Fluorodeoxyglucose (18F-FDG) uptake is frequently used to recognize malignant nature of abnormal findings at anatomical investigations. However, several benign structures can mimic cancer glucose avidity. This case report pertains to a large mediastinal mass, incidentally detected on a coronary Computer Tomography (CT) study and showing heterogeneous signal hyperintensity in T1- weighted sequences at a subsequent Magnetic Resonance Imaging (MRI). CT-guided biopsy failed to provide adequate specimen; 18F-FDG PET/CT documented an extremely high glucose analogue consumption (maximum Standardized Uptake Value: 29). In order to exclude every alternative possibility before attempting a potentially hazardous surgery, we hypothesized the possible presence of a hibernoma. To test this hypothesis, we verified the influence of sympathetic innervation on lesion uptake, by repeating 18F-FDG imaging under beta-blockade: this scan documented the complete disappearance of the anomalous tracer uptake. A 6-months follow-up scan documented stable lesion volume and persistently absent 18F-FDG uptake under the beta-blockers, thus presumably excluding the malignant nature of the increased tracer uptake.

Purpose: To evaluate the correlation of absolute attenuation values of unenhanced computed tomography (CT) with signal intensity (SI) quantitative analysis on chemical shift (CS) magnetic resonance (MR) imaging in differentiating adrenal adenomas from metastases. Material and Methods: Forty-one adrenal masses (27 adenomas, 14 metastases) were studied with CS MR imaging and unenhanced CT. MR included T1-weighted breathhold gradient-echo in-phase (IP) and opposed-phase (OP) sequences. The SI index (SI-i) [(SIIP−SIOP/SIIP)]×100% and chemical-shift ratio (CS-r) relative to the spleen [(SIlesion/SIspleen)OP/(SIlesion/SIspleen)IP] were calculated for each lesion. CT absolute attenuation values were also determined. Results: The mean attenuation value of metastases was significantly greater than that of adenomas ( Conclusion: Since CS MR imaging and CT both depict the presence of lipids within adrenal lesions, absolute attenuation values are highly correlated with MR quantitative analysis. SI-i is the most reliable tool for differentiating adrenal adenomas from metastases, showing better accuracy than lesion-to-spleen CS-r, in particular for adenomas with indeterminate absolute attenuation values.

BACKGROUND: The present study aimed to evaluate the added value of contrast-enhanced computed tomography (ceCT) in comparison to standard, non-enhanced CT in the context of a combined positron emission tomography (PET)/CT examination by means of a tumor-, site-, and clinical question-based approach. METHODS: Analysis was performed in 202 patients undergoing PET/CT consisting of a multiphase CT protocol followed by a whole-body PET. The Cochran Q test was performed, followed by a multiple comparisons correction (McNemar test and Bonferroni adjustment), to compare standard and contrast-enhanced PET (cePET/CT). Histopathology or clinical-radiologic follow-up greater than 1 year was used as a reference. RESULTS: cePET/CT showed significantly different results with respect to standard PET/CT in head and neck and gastrointestinal cancer (P = 0.02 and 0.0002, respectively), in the evaluation of lesions located in the abdomen (P = 0.009), and in the context of disease restaging (P = 0.003). In all these clinical scenarios, adding ceCT resulted in a distinct benefit, by yielding a higher percentage of change in patient management. CONCLUSION: These data strongly underline the importance of strictly selecting patients for the combined exam. In particular, patient selection should not be driven solely by mere tumor classification, but should also account for the clinical question and the anatomical location of the neoplastic disease, which can significantly impact patient management.