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Cancer predisposition syndromes are recognized in about 10% of pediatric malignancies with several genes specifically involved in a subset of pediatric tumors such as DICER1, in pleuropulmonary blastoma, cystic nephroma, and brain sarcomas. By contrast, the role of BRCA1/2 in pediatric cancer predisposition is still under investigation. We present two cases of young first-degree cousins, both carrying a germline BRCA2 variant and developing tumors characterized by somatic DICER1 mutations. Patient 1 presented with a cystic nephroma harboring a somatic DICER1 variant (p.Asp1810Tyr), while patient 2 had a primary intracranial DICER1-mutated sarcoma showing a distinct somatic DICER1 variant (p.Asp1709Glu) as well as biallelic inactivation of TP53 (p.Val173Leu, VAF 91%) and APC (p.Ile1307Lys, VAF 95%) and a pathogenic variant in KRAS (p.Gln61His). Both patients carried the same germline BRCA2 variant (p.Arg2842Cys) of unknown significance. The same variant was found in the mother of patient 2 and in the father of patient 1, who are siblings. A homologous recombination deficiency signature was not identified in any of the two tumors, possibly suggesting a reduction of BRCA2 activity. The association of BRCA2 and DICER1 variants in our cases hints at a potential cooperative role in cancer pathogenesis. Further studies are warranted to elucidate the interplay between BRCA1/2 and DICER1 variants and their implications for cancer predisposition and treatment in pediatric patients., (© 2024. The Author(s).)

Introduction: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome., Patients and Methods: The clinical notes of patients diagnosed with stage III and IV malignant germ cell tumors from January 2010 until December 2020 at our Institution were retrospectively reviewed. The prevalence of GTS, treatment strategies, survival, and outcome were analyzed., Results: Thirty-three patients with high-stage malignant germ cell tumors were diagnosed in our institution in the analyzed period. Nine patients (28%) had radiologic evidence of enlargement of persistent masses with normal markers after chemotherapy; these patients were classified as GTS patients. All nine patients underwent resection of metastatic lymph nodes, and six had surgery on visceral metastases. In six patients, radical excision of all metastatic sites was achieved; five patients are alive and in complete remission, while one died because of peri-operative complications. Out of the three patients who could not achieve radical excision of the metastases, two died of progressive disease, and one is alive with progressive disease., Conclusions: Patients affected by GTS have a risk of progression of chemotherapy-resistant disease and death. Radical surgical excision is essential to achieve disease control and long-term survival., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis., Methods: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared., Results: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086)., Conclusions: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules., Plain Language Summary: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma., (© 2023 American Cancer Society.)

Objective: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma., Material and Methods: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted., Results: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10 -3 mm 2 /s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival., Conclusion: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients., (© 2023. The Author(s).)

Background and Aims: Thoracic air leak syndrome (TALS) is a complication related to chronic pulmonary graft-versus-host disease (pGvHD) that affects approximately 0.83%-3.08% patients after allogenic hematopoietic stem cell transplant. Such complication is defined as the occurrence of any form of air leak in the thorax, including spontaneous pneumomediastinum or pneumopericardium, subcutaneous emphysema, interstitial emphysema and pneumothorax and has a negative impact on post-transplant survival. The aim of the present study is to describe a single-center experience in the surgical management of recurrent TALS in adolescents and young adults and its outcome., Methods: We retrospectively reviewed the clinical notes of patients with previous allogenic hematopoietic stem cell transplant who underwent surgical procedures for recurrent TALS from January 2016 until March 2021. We analyzed clinical data, number of episodes of thoracic air leak, surgical procedures and relative outcome., Results: In the examined period, four patients, aged 16-25 years, underwent surgical procedures for TALS, including thoracostomy tube placement, thoracoscopic pleurodesis and thoracotomy. All the patients had been diagnosed with pGvHD before the onset of TALS, with a mean time lapse of 276 days (range 42-513). These patients experienced on average 4.5 air leak episodes (range 3-6). All the patients experienced at least two episodes before surgery. One patient underwent emergency tube thoracostomy only, three patients underwent thoracoscopic pleurodesis and two patients underwent thoracotomy. After surgery, patients were free from air leak symptoms for a mean time of 176 days (range 25-477). Pulmonary function progressively deteriorated, and all the patients eventually died because of respiratory failure after a mean time of 483 days (range 127-1045) after the first episode of air leak., Conclusions: Surgery provides temporary relief to symptoms related to TALS but has limited effects on the underlying pathophysiologic process. The development of TALS in a sign of progressive pulmonary function worsening and is associated with high risk of respiratory failure and mortality., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Hip involvement predicts severe disease in juvenile idiopathic arthritis (JIA) and is accurately assessed by MRI. However, a child-specific hip MRI scoring system has not been validated., Objective: To test the intra- and interobserver agreement of several MRI markers for active and chronic hip changes in children and young adults with JIA and to examine the precision of measurements commonly used for the assessment of growth abnormalities., Materials and Methods: Hip MRIs from 60 consecutive children, adolescents and young adults with JIA were scored independently by two sets of radiologists. One set scored the same MRIs twice. Features of active and chronic changes, growth abnormalities and secondary post-inflammatory changes were scored. We used kappa statistics to analyze inter- and intraobserver agreement for categorical variables and a Bland-Altman approach to test the precision of continuous variables., Results: Among active changes, there was good intra- and interobserver agreement for grading overall inflammation (kappa 0.6-0.7). Synovial enhancement showed a good intraobserver agreement (kappa 0.7-0.8), while the interobserver agreement was moderate (kappa 0.4-0.5). Regarding acetabular erosions on a 0-3 scale, the intraobserver agreement was 0.6 for the right hip and 0.7 for the left hip, while the interobserver agreement was 0.6 for both hips. Measurements of joint space width, caput-collum-diaphyseal angle, femoral neck-head length, femoral width and trochanteric distance were imprecise., Conclusion: We identified a set of MRI markers for active and chronic changes in JIA and suggest that the more robust markers be included in future studies addressing clinical validity and long-term patient outcomes., (© 2022. The Author(s).)

Purpose: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT)., Methods and Materials: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices., Results: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia., Conclusion: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

Background: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics., Purpose: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors., Study Type: Consensus process using a Delphi method., Population: Not applicable., Field Strength/sequence: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T., Assessment: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions., Statistical Tests: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale., Results: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors., Data Conclusion: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts., Level of Evidence: 3 Technical Efficacy Stage: 3., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Neuroblastoma is the most common solid extracranial tumor in children. Patients affected by neuroblastoma are stratified into low, intermediate, and high risk in terms of event-free and overall survival. Some high-risk patients have an additional risk of acute hemorrhagic complications during induction chemotherapy. Aim: To find easily and rapidly assessed parameters that help clinicians identify those patients affected by high-risk neuroblastoma who have an additional risk of hemorrhagic complications. Methods: The clinical notes of patients diagnosed with high-risk neuroblastoma from January 2013 until February 2021 were retrospectively reviewed. Clinical, demographic and laboratory data, biological characteristics of the tumor, and information about treatment and hospital stay were identified. Results: In the examined period, 44 patients were diagnosed with high-risk neuroblastoma. Four of these patients had hemorrhagic complications within 2-7 days after the initiation of induction chemotherapy; two patients had hemothorax, one patient had hemoperitoneum and one patient had hemothorax and hemoperitoneum. The patient with isolated hemoperitoneum was treated with blood components transfusions, clotting factors and colloids infusions; the three patients with hemothorax underwent thoracostomy tube placement and respiratory support. At initial presentation, patients who suffered from hemorrhagic complications had a higher degree of hypertension (stage 2, p = 0.0003), higher levels of LDH (median 3,745 U/L, p = 0.009) and lower levels of hemoglobin (mean 7.6 gr/dl, p = 0.0007) compared to other high-risk patients. Conclusions: A subgroup of "additional" high-risk patients can be identified within the high-risk neuroblastoma patients based on mean arterial pressure, LDH levels and hemoglobin levels at presentation. Further studies to define cut-off values and optimal management strategies for these patients are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Voglino, Persano, Crocoli, Castellano, Serra, Giordano, Natali, Di Paolo, Martucci, Stracuzzi and Inserra.)

Background: MYCN amplification represents a powerful prognostic factor in neuroblastoma (NB) and may occasionally account for intratumoral heterogeneity. Radiomics is an emerging field of advanced image analysis that aims to extract a large number of quantitative features from standard radiological images, providing valuable clinical information., Procedure: In this retrospective study, we aimed to create a radiogenomics model by correlating computed tomography (CT) radiomics analysis with MYCN status. NB lesions were segmented on pretherapy CT scans and radiomics features subsequently extracted using a dedicated library. Dimensionality reduction/features selection approaches were then used for features procession and logistic regression models have been developed for the considered outcome., Results: Seventy-eight patients were included in this study, as training dataset, of which 24 presented MYCN amplification. In total, 232 radiomics features were extracted. Eight features were selected through Boruta algorithm and two features were lastly chosen through Pearson correlation analysis: mean of voxel intensity histogram (p = .0082) and zone size non-uniformity (p = .038). Five-times repeated three-fold cross-validation logistic regression models yielded an area under the curve (AUC) value of 0.879 on the training set. The model was then applied to an independent validation cohort of 21 patients, of which five presented MYCN amplification. The validation of the model yielded a 0.813 AUC value, with 0.85 accuracy on previously unseen data., Conclusions: CT-based radiomics is able to predict MYCN amplification status in NB, paving the way to the in-depth analysis of imaging based biomarkers that could enhance outcomes prediction., (© 2021 Wiley Periodicals LLC.)

Background: Pediatric patients with relapsed or refractory sarcomas have poor outcome and need novel therapies that provide disease control while maintaining an acceptable quality of life. The safety of vincristine, irinotecan, and pazopanib (VIPaz) association has not yet been published in this population. Methods: A chart review was conducted in children and adolescents with relapsed or refractory bone and soft tissue sarcomas who received VIPaz in our institution. Results: One hundred sixty-six patients with a diagnosis of soft or bone sarcoma were admitted to our hospital in the period between March 2015 and August 2018, 30 were relapsed or resistant. Seventeen out of 30 resistant or relapsed patients (median age, 14 years) received 114 VIPaz cycles (median six cycles per patient, range 1-17). Sixteen courses (15%) resulted in gastrointestinal toxicity with Grade two diarrhea; 35 courses (30%) resulted in Grade ≥3 neutropenia. One patient presented Grade two hypothyroidism after nine courses, and another one had Grade two hyperbilirubinemia after 12 courses. Two and five patients required a 25% dose reduction of irinotecan (because of diarrhea) and pazopanib (because of neutropenia four and hyperbilirubinemia 1), respectively. No patient experienced heart failure, hypertension, nor posterior reversible encephalopathy syndrome. Pneumothorax was not reported in any case even in lung metastatic patients. After two and four VIPaz cycles, we observed one complete response (CR), five partial responses (PRs), seven stable diseases (SDs), and four progressive diseases (PDs). With a median follow-up of 15 months (range 3-32), five out of 17 (29%) patients were alive, and four patients were in continuous CR after 12 VIPaz cycles. Conclusions: The VIPaz regimen might be a safe option in children and adolescents with relapsed or refractory sarcomas otherwise unable to be enrolled in other clinical trials; on the other hand, the efficacy of pazopanib observed cannot be sustained from the current study., (Copyright © 2020 Russo, Di Paolo, Crocoli, Mastronuzzi, Serra, Di Paolo, Di Giannatale, Miele and Milano.)

Purpose: To investigate associations between imaging features of tumors and age, gender and body mass index (BMI) in patients with renal cell carcinoma., Method: This IRB-approved, HIPAA-compliant study included 1348 patients with histopathologically confirmed renal cell carcinoma of the clear cell subtype (ccRCC, n = 904) or non-clear cell subtype (n = 444), who underwent pre-treatment CT imaging less than 180 days before nephrectomy between 1999 and 2011. Two radiologists independently, retrospectively analyzed all imaging studies and identified features (necrosis, renal vein invasion, contact with renal sinus fat, multicystic appearance and nodular enhancement), which were then correlated with patient age, gender and BMI at time of surgery., Results: Inter-reader agreement on imaging features ranged from substantial to excellent (kappa: 0.688 to 0.982). In the ccRCC group, multicystic tumor appearance was significantly associated with lower patient age (p < 0.05) and lower BMI (p < 0.05); the presence of renal vein invasion was significantly associated with lower BMI in males (p < 0.05); and both tumor contact with the renal sinus and nodular enhancement were significantly associated with greater patient age (p < 0.05). In the non-clear cell RCC group, necrosis was associated with lower BMI for females (p < 0.05)., Conclusions: This study demonstrated significant associations between imaging features of RCC and patient age and BMI, hinting an influence of these factors on tumor biology and genomic make-up. These findings could aid future studies in selecting patients while investigating genomic, molecular and metabolic variables in RCC and might potentially impact on future stratification and therapy of patients., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: We determined the diagnostic performance of 18 F-FDG (fluorodeoxyglucose) positron emission tomography/computerized tomography for detecting nodal metastases in patients with muscle invasive urothelial bladder cancer before radical cystectomy., Materials and Methods: Preoperative 18 F-FDG positron emission tomography/computerized tomography scans (208) were retrospectively reviewed. Scans were routinely performed in 185 patients with muscle invasive urothelial bladder cancer between August 2012 and February 2017, all of whom underwent radical cystectomy and pelvic lymph node dissection. Analyses were stratified by clinical node involvement and chemotherapy status. The diagnostic performance of 18 F-FDG positron emission tomography/computerized tomography was assessed according to sensitivity, specificity, positive predictive value and negative predictive value., Results: Lymph node metastases at time of pelvic lymph node dissection were present in 21.8% of those without suspicious nodes on computerized tomography (clinically node negative) and 52.6% of those with suspicious nodes on computerized tomography (clinically node positive). Median metastatic focus size was 5 mm. In clinically node negative cases 18 F-FDG positron emission tomography/computerized tomography rarely detected nodal metastases (sensitivity 7% to 23%). In clinically node positive cases negative 18 F-FDG positron emission tomography/computerized tomography was useful in ruling out lymph node metastases (sensitivity 92% to 100%). This study was limited by its mixed population and focus on pelvic nodal metastases only., Conclusions: 18 F-FDG positron emission tomography/computerized tomography appears to be most useful for better characterization of enlarged nodes identified by computerized tomography. Routine preoperative 18 F-FDG positron emission tomography/computerized tomography has limited utility in clinically node negative cases.

The purpose of this recommendation of the Oncology Task Force of the European Society of Paediatric Radiology (ESPR) is to indicate reasonable applications of whole-body MRI in children with cancer and to address useful protocols to optimize workflow and diagnostic performance. Whole-body MRI as a radiation-free modality has been increasingly performed over the last two decades, and newer applications, as in screening of children with germ-line mutation cancer-related gene defects, are now widely accepted. We aim to provide a comprehensive outline of the diagnostic value for use in daily practice. Based on the results of our task force session in 2018 and the revision in 2019 during the ESPR meeting, we summarized our group's experiences in whole-body MRI. The lack of large evidence by clinical studies is challenging when focusing on a balanced view regarding the impact of whole-body MRI in pediatric oncology. Therefore, the final version of this recommendation was supported by the members of Oncology Task Force.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and rarely occur in pediatric patients. 85% of pediatric GISTs and 15% of adult GISTs lack of KIT or PDGFRA mutations. 40% of these "wild-type" GISTs present loss of function mutations in genes encoding for the subunits of the succinate dehydrogenase (SDH) complex. Germline mutations in SDH complex genes have been described in patients with the Carney-Stratakis syndrome (CSS), a rare inherited condition that predisposes to GIST and paraganglioma. We report two pediatric patients with multifocal GIST, harboring respectively a novel and a previously reported loss-of-function germline variant, in SDHC and SDHB genes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier Inc.)

Radiologists are sometimes requested to determine a person's age based on skeletal radiographs. Critical reviews demonstrate that this cannot be done with sufficient accuracy with existing methods.

Background: Approximately 20-50% of children with juvenile idiopathic arthritis (JIA) have hip involvement within 6 years of diagnosis. Scoring systems for hip-related radiographic changes are lacking., Objective: To examine precision of potential radiographic variables and to suggest a scoring system., Materials and Methods: We reviewed a set of 75 pelvic radiographs from 75 children with JIA hip involvement across two European centres. We assessed findings of (1) destructive change and (2) growth abnormality, according to a pre-defined scoring system. All radiographs were scored independently by two sets of radiologists. One set scored the radiographs a second time. We used kappa statistics to rate inter- and intra-observer variability., Results: Assessment of erosions of the femoral head, femoral neck and the acetabulum showed moderate to good agreement for the same reader (kappa of 0.5-0.8). The inter-reader agreement was, however, low (kappa of 0.1-0.3). There was moderate to high agreement for the assessment of femoral head flattening (kappa of 0.6-0.7 for the same reader, 0.3-0.7 between readers). Joint space narrowing showed moderate to high agreement both within and between observers (kappa of 0.4-0.8). Femoral neck length and width measurements, the centrum-collum-diaphysis angle, and trochanteric-femoral head lengths were relatively precise, with 95% limits of agreement within 10-15% of the observer average., Conclusion: Several radiographic variables of destructive and growth abnormalities in children with hip JIA have reasonable reproducibility. We suggest that future studies on clinical validity focus on assessing only reproducible radiographic variables.

Hip involvement is common and estimated to occur in approximately 35-63% of children with juvenile idiopathic arthritis (JIA). It is more prevalent in the aggressive systemic subtypes, with irreversible changes occurring as early as within 5 years of diagnosis. Whilst clinical parameters and joint examination can be useful for assessing disease severity, subclinical disease is known to exist and delayed treatment may herald a lifetime of disability and pain. Early recognition of JIA changes is therefore crucial in determining treatment options. Validated scoring systems in the radiologic assessment of the hip for clinical drug trials may inform treatment outcomes, although robust tools for analysis are still lacking. This review article details the modalities utilised for imaging the hip in children with JIA with particular efforts focused upon reliability and validity in their assessment of joint disease. We conclude with a short literature review on the potential future techniques being developed for hip joint imaging in JIA.

Background: Rhabdomyosarcoma (RMS), one of the most common soft tissue sarcomas of childhood, is very rare in the neonatal period (0.4-2% of cases). In order to gain a deeper understanding of this disease at such age, patient and tumor features, as well as treatment modality and outcome need to be reported., Case Presentation: We describe two cases with congenital RMS treated at Bambino Gesù Children's Hospital between 2000 and 2016. They represent only 2.24% of all RMS patients diagnosed during that period in our Institution; this data is in agreement with the incidence reported in the literature. They reflect the two different clinical forms in which the disease may manifest itself. One patient, with the alveolar subtype (positive for specific PAX3-FOXO1 fusion transcript) and disseminated disease, had a fatal outcome with central nervous system (CNS) progression despite conventional and high dose chemotherapy. The other child, with the localized embryonal subtype, was treated successfully with conservative surgery and conventional chemotherapy, including prolonged maintenance therapy. He is disease free at 7 years of follow-up., Conclusions: RMS can also be diagnosed during the neonatal period. Given the young age, disease management is often challenging, and especially for the alveolar subtype, the outcome is dismal despite intensified multimodality therapy. In fact, it characteristically manifests with multiple subcutaneous nodules and progression most commonly occurs in the CNS (Rodriguez-Galindo et al., Cancer 92(6):1613-20, 2001). In this context, CNS prophylaxis could play a role in preventing leptomeningeal dissemination, and molecular studies can allow a deeper tumor characterization, treatment stratification and identification of new potential therapeutic targets.

Aim: To develop a nomogram from clinical and computed tomography (CT) data for pre-treatment identification of indolent renal cortical tumours., Patients and Methods: A total of 1201 consecutive patients underwent dedicated contrast-enhanced CT prior to nephrectomy for a renal cortical tumour between January 2000 and July 2011. Two radiologists evaluated all tumours on CT for size, necrosis, calcification, contour, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, nodular enhancement, and the degree of nephrographic phase enhancement. CT and clinical predictors (gender, body mass index [BMI], age) were incorporated into the nomogram. We employed multivariable logistic regression analysis to predict tumour type and internally validated the final model using the data from reader 1. External validation was performed by using all data from reader 2. We applied Wilcoxon rank sum test and Fisher's exact test to investigate for differences in tumour size, BMI, age, and differences in CT imaging features between patients with aggressive and those with indolent tumours., Results: 63.6% (764/1201) of patients had clear-cell or other aggressive non-clear-cell RCC (i.e. papillary RCC type 2, unclassified RCC) and 36.4% (437/1201) had indolent renal cortical tumours (i.e. papillary RCC type 1, chromophobe RCC, angiomyolipoma, or oncocytoma). On CT, indolent tumours were significantly smaller (p < 0.001) than aggressive tumours and significantly associated with well-defined tumour contours (p < 0.001). Aggressive RCC were significantly associated with necrosis, calcification, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, and nodular enhancement (all, p < 0.001). The nomogram's concordance index (C-index) was 0.823 after internal and 0.829 after external validation., Concluding Statement: We present a nomogram based on 1201 patients combining CT features with clinical data for the prediction of indolent renal cortical tumours. When externally validated, this nomogram resulted in a C-index of 0.829., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Tumor characteristics affect surgical complexity and outcomes of partial nephrectomy (PN)., Objective: To develop an Arterial Based Complexity (ABC) scoring system to predict morbidity of PN., Design, Setting, and Participants: Four readers independently scored contrast-enhanced computed tomography images of 179 patients who underwent PN., Intervention: Renal cortical masses were categorized by the order of vessels needed to be transected/dissected during PN. Scores of 1, 2, 3S, or 3H were assigned to tumors requiring transection of interlobular and arcuate arteries, interlobar arteries, segmental arteries, or in close proximity of the renal hilum, respectively during PN., Outcome Measurements and Statistical Analysis: Interobserver variability was assessed with kappa values and percentage of exact matches between each pairwise combination of readers. Linear regression was used to evaluate the association between reference scores and ischemia time, estimated blood loss, and estimated glomerular filtration rates at 6 wk and 6 mo after surgery adjusted for baseline estimated glomerular filtration rate. Fisher's exact test was used to test for differences in risk of urinary fistula formation by reference category assignment., Results and Limitations: Pairwise comparisons of readers' score assignments were significantly correlated (all p<0.0001); average kappa = 0.545 across all reader pairs. The average proportion of exact matches was 69%. Linear regression between the complexity score system and surgical outcomes showed significant associations between reference category assignments and ischemia time (p<0.0001) and estimated blood loss (p=0.049). Fisher's exact test showed a significant difference in risk of urinary fistula formation with higher reference category assignments (p=0.028). Limitations include use of a single institutional cohort to evaluate our system., Conclusions: The ABC scoring system for PN is intuitive, easy to use, and demonstrated good correlation with perioperative morbidity., Patient Summary: The ABC scoring system is a novel anatomy-reproducible tool developed to help patients and doctors understand the complexity of renal masses and predict the outcomes of kidney surgery., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess interobserver variability of R.E.N.A.L., preoperative aspects and dimensions used for an anatomical classification system (PADUA), and centrality index (C-Index) systems among observers with varying degrees of clinical experience and each system's subscale correlation with surgical outcome metrics., Methods: Computed tomography images of 90 patients who underwent open, laparoscopic, or robot-assisted laparoscopic partial nephrectomy were scored by one radiology fellow, two urology fellows, one radiology resident, and one secondary school student. Agreement among readers was determined calculating intraclass correlation coefficients. Associations between radiology fellow scores (reference standard as reader with greatest clinical experience), ischemia time, and percent change in postoperative estimated glomerular filtration rate (eGFR) were evaluated using Spearman's correlation., Results: Agreement using C-Index method (ICC = 0.773) was higher than with PADUA (ICC = 0.677) or R.E.N.A.L (ICC = 0.660). Agreement between reference and secondary school student was lower than with other physicians, although the differences were not statistically significant. The reference's scores were significantly (p < 0.05) associated with ischemia time on all three scoring systems and with percent change in eGFR at 6 weeks using C-Index (p = 0.016). Tumor size, nearness to sinus, and location relative to polar lines (R.E.N.A.L.) and tumor size, renal sinus involvement, and collecting system involvement (PADUA) correlated with ischemia time (all p ≤ 0.001). No R.E.N.A.L. or PADUA subscales significantly correlated with percent change in postoperative eGFR., Conclusions: Clinical experience reduces interobserver variability of existing nephrometry systems though not significantly and less so when using directly measureable anatomic variables. Consistently, only measures of tumor size and distance to intrarenal structures were useful in predicting clinically relevant outcomes.

Rationale and Objectives: To compare prostate volume measurements from 3-Tesla endorectal coil magnetic resonance imaging (ERC MRI) obtained with the prolate ellipsoid volume formula (EVF) and volumetry to pathology-based volume measurements., Methods: The institutional review board waived informed consent for this retrospective, health insurance portability and accountability act (HIPAA) compliant study, which included 195 patients who underwent 3-T ERC MRI between January 2008 and October 2011 and had pathologic prostate measurements available. Two readers in consensus measured the prostate length, height, and width on each MRI. They estimated prostate volumes using the prolate EVF (length × height × width × [π/6]) and also by performing three-dimensional volumetry. Pathologic specimen mass and dimensions were used to calculate prostate volume. Agreement was measured with Lin's concordance correlation coefficient (CCC). Volume differences were assessed using the Wilcoxon signed-rank test. Correct prostate-specific antigen (PSA) density classification rates were compared between EVF-based and volumetry-based PSA density levels using the exact McNemar test, with pathology-based PSA density as the reference standard., Results: Concordance was high between EVF and volumetry measurements (CCC, 0.950 [95% confidence interval, 0.935-0.962]) and between both kinds of MRI measurements and pathology (both CCC > 0.80). Based on a cut-off of ≤0.15 ng/mL/cm(3), use of EVF-based volume produced correct classification of 46 of 48 PSA density levels >15 ng/mL/cm(3) and 113 of 147 PSA density levels ≤15 ng/mL/cm(3); use of volumetry-based volume produced correct classification of 47 of 48 PSA density levels >15 ng/mL/cm(3) and 121 of 147 PSA density levels ≤15 ng/mL/cm(3). Rates of underclassification (P > .95) and overclassification (P = .10) did not differ significantly between EVF and volumetry., Conclusions: EVF appears to be suitable for measuring prostate volume from ERC-MRI., (Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate if computed tomographic (CT) features of intradiverticular bladder cancer can predict clinical outcome., Methods: Retrospective study of 34 patients with intradiverticular bladder cancer. Two radiologists independently evaluated all CT exams., Results: CT tumor length and width were significantly associated with survival for both readers [hazard ratios (HRs) 1.31-1.62, P<.001-.043]. No other tumor features were significantly associated with survival. The interreader agreement for the assessment of CT features was fair to substantial (k=0.34-0.78, concordance correlation coefficient=0.56-0.66). There was no association between transurethral resection pathology stage and survival (HR 2.10, P=.21)., Conclusions: In patients with intradiverticular bladder cancer, the tumor length and width measured on the pretreatment CT predicted survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Purpose: Multiple sclerosis (MS) has been associated with chronic cerebrospinal venous insufficiency. We aim to evaluate the correlation between extracranial veins stenosis evaluated with MR venography (MRV) and clinical/MR parameters of MS., Methods: In 29 consecutive MS patients we performed a standard brain MRI protocol, completed by the evaluation of extra-cerebral venous system using a phase-contrast and a Volumetric Interpolated Breath Hold Examination (VIBE) sequence before and after gadolinium. The T2-proton density images were used to calculate the lesion volume. The jugular veins were evaluated qualitatively (in terms of presence and severity of stenoses) and quantitatively (degree of stenosis). The phase-contrast images were analyzed to calculate the average and peak velocity in the internal jugular veins., Results: Postcontrast VIBE successfully showed the jugular veins in all the subjects. T2-lesion-volume was 8.2 [4.6] cm³. A stenosis of the internal jugular veins > of 50% was observed in 10/29(33%) patients. No significant correlation was observed between T2-lesion-volume and degree-of-stenosis (r = .362, P = .302). No different flow parameters were found in the subgroups of patients with and without stenosis (P = .54)., Conclusions: In MS the presence/severity of jugular vein stenosis identified with 3T-MRV is not related to MR-visible tissue damage. Moreover no abnormal flow parameters were found in stenosed veins.

Purpose: To investigate associations between computed tomographic (CT) features of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2, KDM5C, or BAP1 genes., Materials and Methods: The institutional review board approved this retrospective, hypothesis-generating study of 233 patients with clear cell RCC and waived the informed consent requirement. The study was HIPAA compliant. Three radiologists independently reviewed pretreatment CT images of all clear cell RCCs without knowledge of their genomic profile. One radiologist measured largest diameter and enhancement parameters of each clear cell RCC. Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and BAP1 genes were tested by using the Fisher exact test. Associations between mutations and size and enhancement were assessed by using the independent t test. Interreader agreement was calculated by using the Fleiss κ., Results: Mutation frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233); PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well-defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1 were significantly associated with evidence of renal vein invasion (P = .022 and .046, respectively). The genotype of solid clear cell RCC differed significantly from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC. Interreader agreement for CT feature assessments ranged from substantial to excellent (κ = 0.791-0.912)., Conclusion: This preliminary radiogenomics analysis of clear cell RCC revealed associations between CT features and underlying mutations that warrant further investigation and validation., (©RSNA, 2013)

Objective: Although renal collecting system invasion is not considered in the current TNM staging system, this finding may be relevant in terms of treatment planning and prognosis. The objective of this study was to investigate the frequency of collecting system invasion in renal cell carcinoma (RCC) and to assess the diagnostic performance of excretory phase CT for the assessment of collecting system invasion., Materials and Methods: We conducted a retrospective study of 261 patients (171 men and 90 women; average age, 61 years; age range, 32-86 years) who underwent CT before nephrectomy for RCC between November 2008 and July 2011 at a single institution. On excretory phase contrast-enhanced CT images, two radiologists independently determined whether RCC components caused a filling defect within the collecting system and whether the RCC was in contact to the collecting system wall or separated from it. Histopathology served as the standard of reference. Interreader agreement and diagnostic performance tests for the detection of collecting system invasion were calculated., Results: Histopathology identified collecting system invasion exclusively in clear cell RCC that showed a filling defect within the collecting system on excretory phase CT images (5.4%, 14/261). Tumors separated from or in contact with the collecting system on imaging (both readers; 94.6%, 247/261) did not show collecting system invasion on histopathology (sensitivity, 100%; specificity, 100%). Interreader agreement was excellent (κ, 0.965; 95% CI, 0.93-0.99)., Conclusion: CT provides reliable assessment of collecting system invasion in patients with RCC, with excellent sensitivity and specificity.

Objective: The amount of cerebral white matter lesions (WMLs) and the severity of carotid artery disease are correlated in this study. The association between the severity of WMLs and the volume of the different components of carotid artery plaque is also evaluated., Materials and Methods: Fifty consecutive patients (39 men, 11 women; mean [SD] age, 71 ± 9 years) with carotid artery stenosis who underwent carotid endarterectomy were included in this study. On admission, patients underwent head and neck CT angiography (CTA) and brain MRI. The CTA-based plaque volume and the percentages of the three main plaque components (fatty, mixed, and calcified) were calculated according to the attenuation values. Leukoaraiosis lesion volume on FLAIR images was determined using a semiautomated segmentation technique. Pearson correlation was conducted between the leukoaraiosis lesion volume on FLAIR images and the volumes of the different plaque components., Results: Pearson correlation analysis was performed to determine WML volume versus total carotid plaque volume (ρ = 0.2531; p = 0.0262), fatty plaque volume (ρ = 0.387; p = 0.0005), mixed plaque volume (ρ = 0.1709; p = 0.15), and calcified plaque volume (ρ = 0.0146; p = 0.899). The WML volume was also compared against fatty plaque percentage (ρ = 0.343; p = 0.0018), mixed plaque percentage (ρ = 0.181; p = 0.124), and calcified plaque percentage (ρ = -0.209; p = 0.068)., Conclusion: The cerebral WML volume and the total volume of the plaque are correlated. The amount of fat within the plaque is an additional risk factor, whereas the calcified component seems to be protective.

Purpose: To assess diagnostic performance and interreader agreement of tumor-to-sinus distance measurements and visual assessment of renal sinus fat invasion at T2-weighted magnetic resonance (MR) imaging as predictors of muscular venous branch invasion (MVBI) in patients with renal cell carcinoma (RCC)., Materials and Methods: The institutional review board approved this retrospective study and waived the informed consent requirement. The study was HIPAA compliant. A total of 186 consecutive patients underwent preoperative 1.5-T MR imaging; 188 RCCs were identified. Blinded to histopathologic information, two readers independently measured the tumor-to-sinus distance and assessed renal sinus fat invasion on transverse and coronal T2-weighted MR images. Interreader agreement (intraclass correlation coefficient, Cohen κ) and performance characteristics of imaging tests were calculated. Histopathologic findings served as the standard of reference., Results: Histopathologic findings indicated MVBI in 35% (66 of 188) of tumors. At imaging, all tumors with MVBI had a tumor-to-sinus distance of 0 mm. All tumors with renal sinus fat invasion at imaging had MVBI. Sensitivity and specificity for the detection of renal sinus fat invasion were 100% (95% confidence interval [CI]: 92%, 100%) and 94% (95% CI: 89%, 98%). In the absence of renal sinus fat invasion at imaging, a tumor-to-sinus distance of 0 mm was associated with MVBI in 21% (18 of 86) of cases. Interreader agreement for quantitative (intraclass correlation coefficient = 0.92; 95% CI: 0.89, 0.94) and qualitative (κ = 0.89; 95% CI: 0.81, 0.96) assessments was excellent., Conclusion: Tumor-to-sinus distance measurements and the assessment of renal sinus fat invasion at T2-weighted MR imaging can be used reliably to rule out MVBI in patients with RCC., (© RSNA, 2013.)

The purpose of this article is to illustrate the imaging findings of lesions that present as cyst with a mural nodule tumor (CMNT). CMNT is a subtype pattern of intra-axial enhancement in central nervous system tumors, typical of a variety of brain neoplasms, including, as the most common, hemangioblastoma, pilocytic astrocytoma, ganglioglioma and pleomorphic xanthoastrocytoma and as less common tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma and cystic metastasis. A retrospective design was chosen given the rarity of CMNT. Relevant cases were obtained retrospectively to review the different lesions that can present with the appearance of CMNT.

Purpose: This study was performed to validate a high-resolution whole-body magnetic resonance angiography (MRA) protocol with parallel imaging and biphasic administration of a single bolus of contrast agent in the preliminary assessment of systemic atherosclerotic burden in patients referred for endovascular procedures., Materials and Methods: Forty patients referred for endovascular treatment of atherosclerotic disease of the carotid arteries (n=23), peripheral vessels (n=14) or aorta (n=3) on the basis of previous clinical and diagnostic examinations underwent high-resolution whole-body MRA at 1.5 T with 3D spoiled gradient recalled echo (GRE) sequences, featuring parallel imaging acquisition technique with x2 acceleration factor. Sixty-eight surface coil elements and a four-station imaging protocol were employed. Biphasic intravenous administration of a paramagnetic contrast agent [gadolinium benzyloxyproprionic-tetraacetic acid (Gd-BOPTA)] was performed with the following protocol: 10 ml at a speed of 1 ml/s followed by further 10 ml at a speed of 0.5 ml/s. For image analysis, the arterial system was divided into 42 segments for evaluation. The presence or absence of atherosclerotic lesions was evaluated by two observers in consensus; segments were classified as having clinically significant disease (>or=50% stenosis or an aneurysmal dilatation) or no significant disease (<50% stenosis). The presence of stenoocclusive disease, determined at all segments, was compared with findings on digital subtraction angiography (DSA), which were interpreted by a third independent reader. Sensitivity, specificity and concordance of whole-body MRA findings with DSA were calculated, and receiver operating characteristic (ROC) analysis was performed for all vascular territories., Results: A total of 1,680 arterial segments was evaluated; 138 (8.3%) were affected by atherosclerotic alterations. Carotid lesions were confirmed in 23 patients (34 segments), involvement of peripheral vessels in 14 (57 segments) and abdominal aneurysms in three. Sensitivity and specificity of whole-body MRA were, respectively, 95%-97% for head and neck vessels, 100%-100% for thoracoabdominal vessels, 98%-97% for thigh vessels and 84%-88% for calf vessels; concordance with the DSA findings was significant (p<0.05). Subclinical atherosclerotic lesions were evidenced in 25 patients, involving carotid arteries (12 segments), peripheral vessels (21 segments) and abdominal aorta (one segment). All these lesions were confirmed by a second modality, and ten of these patients required further care., Conclusions: High-resolution whole-body MRA with Gd-BOPTA may be considered a reliable modality for imaging systemic atherosclerosis in candidates for endovascular procedures. The subclinical detection of the total atherosclerotic burden has potential implications for secondary care in this population.

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.

Aim: Recently whole-body 3D MR angiography (MRA) with blood-pool contrast agent has become available. The purpose of this study was to introduce and evaluate this technique to demonstrate arterial steno-occlusive involvement in systemic atherosclerosis and to compare blood-pool enhanced MRA results with those of CT angiography (CTA) as reference modality., Methods: Twenty patients with clinically and US documented carotid occlusive disease underwent whole-body MRA on a 1.5 T scanner and CTA on a 64-MDCT unit. Ten milliliters of a blood-pool agent (MS-235 Gadofosveset Trisodium, VASOVIST, Schering, Berlin, Germany) were administered intravenously and four 3-D MRA stations were acquired successively through automatic table moving. Images were reviewed by two observers. Overall image quality of each arterial segment was assessed and rated for both MRA and CTA examinations; MRA sensitivity, MRA specificity interobserver and intermodality agreement were calculated., Results: Whole-body MRA with blood-pool contrast agent was well tolerated by all patients. It yielded a detailed display of the arterial system with a short examination time. In 14 out of 20 patients there was extensive involvement of the arterial bed by steno-occlusive atherosclerotic disease; for the identification and characterization of vessel damage in the various vascular districts MRA sensitivity was 92-100%, MRA specificity was 95-100%; in 2 cases MRA underestimated the degree of peripheral vessel stenosis. Interobserver agreement calculated with K value was 0.63, intermodality agreement with CTA was 93% (P<0.01)., Conclusion: The whole-body MRA technique is a valuable tool for comprehensive evaluation of arterial steno-occlusive involvement in systemic arterial atherosclerosis; there is a good agreement between blood-pool enhanced MRA results and CTA, used as modality of reference.