Iodine contrast volume reduction in preoperative transcatheter aortic valve implantation computed tomography: Comparison with 64- and 256-multidetector row computed tomography.

INTRODUCTION: This study aimed to compare the vascular enhancement and radiation dose in preoperative transcatheter aortic valve implantation (TAVI) computed tomography (CT) with a reduced contrast medium (CM) using volume scans in 256-multidetector row CT (MDCT) with a standard CM using 64-MDCT. METHODS: This study included 78 patients with preoperative TAVI CT with either 64- or 256-MDCT. The CM was injected at 1.5 mL/kg in the 64-MDCT group and 1.0 mL/kg in the 256-MDCT group. We compared vascular enhancement of the aortic root and access routes, image quality (IQ) scores, and radiation dose in both groups. RESULTS: Despite the reduced CM (by 33 %) in the 256-MDCT group, the mean vascular enhancement of the right and left subclavian arteries was significantly higher than that in the 64-MDCT group [284 and 267 Hounsfield units (HU) vs. 376 and 359 HU; p < 0.05]; however, no significant differences in the mean vascular enhancement in the ascending aorta, abdominal aorta at the celiac level, and bilateral common femoral arteries were observed between the two groups (p > 0.05 for all). The median IQ scores at the aortic root were higher in the 256-MDCT group than in the 64-MDCT group (3 vs. 4; p < 0.05), and those at the femoral access routes were comparable (4 vs. 4; p = 0.33). The mean effective dose was significantly reduced by 30 % in the 256-MDCT group (23.6 vs. 16.3 mSv; p < 0.05). CONCLUSION: In preoperative TAVI CT, volume scans using 256-MDCT provide comparable or better vascular enhancement and IQ with a 30 % reduction in CM and radiation dose than those using 64-MDCT. IMPLICATIONS FOR PRACTICE: Volume scan using 256-MDCT for preoperative TAVI CT may reduce CM and radiation dose in TAVI patients with renal dysfunction.

Risk factors for surgical site infection following orthopaedic surgery for fracture by trauma: a nested case-control study.

BACKGROUND: Surgical site infection (SSI) is associated with higher medical expenses and lower patient quality of life. AIM: To identify specific modifiable risk factors for SSI after orthopaedic surgery for fractures caused by trauma. METHODS: This nested case-control study used a nationwide trauma registry, the Japan Trauma Data Bank (JTDB) database. Patient data from 280 hospitals between January 2004 and May 2019 were retrieved from the JTDB. Patients with SSI and identified patients without SSI as control subjects were included, using propensity score matching adjusted for unmodifiable factors. Risk factors associated with SSI after orthopaedic trauma surgery were assessed using multi-level mixed-effects logistic regression models. FINDINGS: In total, 15,910 patients were included in the analysis. Of these patients, 377 (2.4%) had SSI. After propensity score matching, 258 patients with SSI and 2580 matched patients without SSI were selected. In the multi-level mixed-effects logistic regression analysis, blood transfusion within 24 h (odds ratio (OR): 1.51; 95% confidence interval (CI): 1.06-2.13) was a significant risk factor for SSI following orthopaedic fracture surgery. The OR (95% CI) values for external fixation, transcatheter arterial embolization, and tourniquet for SSI following orthopaedic fracture surgery were 1.40 (0.96-2.03), 1.66 (0.81-3.38), and 2.99 (0.60-14.87), respectively. CONCLUSION: These findings highlight the necessity of exercising caution when implementing blood transfusion within 24 h as a risk factor associated with SSI following orthopaedic trauma surgery.

Pediatric focal calvarial lesions: an illustrated review.

Focal skull lesions in children can be diagnostically challenging with a wide variety of potential etiologies. Understanding the diverse pathologies and recognizing their associated clinical and imaging characteristics is crucial for accurate diagnosis and appropriate treatment planning. We review pertinent anatomy of the scalp and calvarium and review different pathologies that can present with focal skull lesions in pediatric patients. These include neoplastic, non-neoplastic tumor-like, congenital, post traumatic, and vascular-associated etiologies. We review the key clinical and imaging features associated with these pathologies and present teaching points to help make the correct diagnosis. It is important for radiologists to be aware of the common and rare etiologies of skull lesions as well as the clinical and imaging characteristics which can be used to develop an accurate differential to ensure a timely diagnosis and initiate appropriate management.

Co-occurrence of VHL and SDHA Pathogenic Variants: A Case Report.

Von Hippel Lindau(VHL)syndrome presents with cerebellar and spinal hemangioblastomas, renal cell cancer, neuroendocrine pancreatic tumor, and pheochromocytoma and it is caused by germline mutations in the VHL gene. Pathogenic germline variants in the succinate dehydrogenase A (SDHA) gene are associated with paraganglioma and pheochromocytoma. Here we report co-occurrence of germline pathogenic variants in both VHL and SDHA genes in a patient who presented with pancreatic neuroendocrine tumor. As these genes converge on the pseudo-hypoxia signaling pathway, further studies are warranted to determine the significance of co-occurrence of these variants in relation to tumor penetrance, disease severity, treatment response and clinical outcomes in this selected group of patients.

Na+/K+ ATPase α1 and ß3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts.

STUDY QUESTION: Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo? SUMMARY ANSWER: Na+/K+ ATPase α1, ß1 and ß3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion. WHAT IS KNOWN ALREADY: In mouse embryos, Na+/K+ ATPase α1 and ß1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation). STUDY DESIGN, SIZE, DURATION: A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining. MAIN RESULTS AND THE ROLE OF CHANCE: RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, ß1 and ß3 isoforms in human blastocysts. Isoforms α1 and ß3 were localized to the basolateral membrane of TE cells, and ß1 was localized between TE cells. A high level of ß3 mRNA expression correlated with easier hatching (P = 0.0261). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis. WIDER IMPLICATIONS OF THE FINDINGS: Of the various Na+/K+ ATPase isoforms, expression levels of the α1, ß1 and ß3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and ß3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The ß1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.

Radiation dose reduction method combining the ECG-Edit function and high helical pitch in retrospectively-gated CT angiography.

INTRODUCTION: The purpose of this study was to demonstrate that dose reduction does not compromise image quality when combining high helical pitch (HP) and the ECG-Edit function during low HP retrospectively gated computed tomography angiography (CTA). METHODS: This study made use of a pulsating cardiac phantom (ALPHA 1 VTPC). The heart rate (HR) of the cardiac phantom was changed in five intervals, every 5 beats per minute (bpm), from 40 to 60 bpm. Evaluation of a range of HR was important because data loss might occur when combining a low HR and high HP. We performed retrospectively gated CTA scans five times using a low HP (0.16) and high HP (0.24), for each of the five HR intervals, using a 64-detector row CT scanner. The CT volume dose index (CTDIvol) was recorded from the CT console of each scan. For the images with data loss, data were repaired using the ECG-Edit function. We compared the CTDIvol, estimated cardiac phantom volume, and the visualization of the coronary ladder phantom between HP 0.16, with or without repaired HP 0.24, using the ECG-Edit function. RESULTS: Data loss occurred with a HR of 40 bpm and 45 bpm when using HP 0.24. The CTDIvol was reduced by approximately 33% with HP 0.24 when compared with HP 0.16. There were no significant differences in the mean cardiac motion phantom volume and visualization scores between HP 0.16 and with and without repaired HP 0.24 using the ECG-Edit function (p < 0.05). CONCLUSION: The ECG-Edit function is potential useful for repairing the lost data in patients with a low HR, and when combined with a high HP, it is possible to reduce the radiation dose by approximately 33%. IMPLICATIONS FOR PRACTICE: The ECG-Edit function and high HP may be a viable option in pediatric CTA studies.

Deep learning with convolutional neural network for estimation of the characterisation of coronary plaques: Validation using IB-IVUS.

INTRODUCTION: Deep learning approaches have shown high diagnostic performance in image classifications, such as differentiation of malignant tumors and calcified coronary plaque. However, it is unknown whether deep learning is useful for characterizing coronary plaques without the presence of calcification using coronary computed tomography angiography (CCTA). The purpose of this study was to compare the diagnostic performance of deep learning with a convolutional neural network (CNN) with that of radiologists in the estimation of coronary plaques. METHODS: We retrospectively enrolled 178 patients (191 coronary plaques) who had undergone CCTA and integrated backscatter intravascular ultrasonography (IB-IVUS) studies. IB-IVUS diagnosed 81 fibrous and 110 fatty or fibro-fatty plaques. We manually captured vascular short-axis images of the coronary plaques as Portable Network Graphics (PNG) images (150 × 150 pixels). The display window level and width were 100 and 700 Hounsfield units (HU), respectively. The deep-learning system (CNN; GoogleNet Inception v3) was trained on 153 plaques; its performance was tested on 38 plaques. The area under the curve (AUC) obtained by receiver operating characteristic analysis of the deep learning system and by two board-certified radiologists was compared. RESULTS: With the CNN, the AUC and the 95% confidence interval were 0.83 and 0.69-0.96, respectively; for radiologist 1 they were 0.61 and 0.42-0.80; for radiologist 2 they were 0.68 and 0.51-0.86, respectively. The AUC for CNN was significantly higher than for radiologists 1 (p = 0.04); for radiologist 2 it was not significantly different (p = 0.22). CONCLUSION: DL-CNN performed comparably to radiologists for discrimination between fatty and fibro-fatty plaque on CCTA images. IMPLICATIONS FOR PRACTICE: The diagnostic performance of the CNN and of two radiologists in the assessment of 191 ROIs on CT images of coronary plaques whose type corresponded with their IB-IVUS characterization was comparable.

Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study.

BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.

Machine learning to identify lymph node metastasis from thyroid cancer in patients undergoing contrast-enhanced CT studies.

INTRODUCTION: We compared the diagnostic performance of morphological methods such as the major axis, the minor axis, the volume and sphericity and of machine learning with texture analysis in the identification of lymph node metastasis in patients with thyroid cancer who had undergone contrast-enhanced CT studies. METHODS: We sampled 772 lymph nodes with histology defined tissue types (84 metastatic and 688 benign lymph nodes) that were visualised on CT images of 117 patients. A support vector machine (SVM), free programming software (Python), and the scikit-learn machine learning library were used to discriminate metastatic-from benign lymph nodes. We assessed 96 texture and 4 morphological features (major axis, minor axis, volume, sphericity) that were reported useful for the differentiation between metastatic and benign lymph nodes on CT images. The area under the curve (AUC) obtained by receiver operating characteristic analysis of univariate logistic regression and SVM classifiers were calculated for the training and testing datasets. RESULTS: The AUC for all classifiers in training and testing datasets was 0.96 and 0.86, at the SVM for machine learning. When we applied conventional methods to the training and testing datasets, the AUCs were 0.63 and 0.48 for the major axis, 0.70 and 0.44 for the minor axis, 0.66 and 0.43 for the volume, and 0.69 and 0.54 for sphericity, respectively. The SVM using texture features yielded significantly higher AUCs than univariate logistic regression models using morphological features (p = 0.001). CONCLUSION: For the identification of metastatic lymph nodes from thyroid cancer on contrast-enhanced CT images, machine learning combined with texture analysis was superior to conventional diagnostic methods with the morphological parameters. IMPLICATIONS FOR PRACTICE: Our findings suggest that in patients with thyroid cancer and suspected lymph node metastasis who undergo contrast-enhanced CT studies, machine learning using texture analysis is high diagnostic value for the identification of metastatic lymph nodes.

The combined application of the contrast-to-noise index and 80 kVp for cardiac CTA scanning before atrial fibrillation ablation reduces radiation dose exposure.

INTRODUCTION: To compare the radiation dose, diagnostic accuracy, and the resultant ablation procedures using 80 and 120-kVp cardiac computed tomography angiography (CCTA) protocols with the same contrast-to-noise ratio in patients scheduled for atrial fibrillation (AF) ablation. METHODS: This retrospective study was performed following institutional review board approval. We divided 140 consecutive patients who had undergone CCTA using a 64-MDCT scanner into two equal groups. Standard deviation (SD) of the CT number was set at 25 Hounsfield units (HU) for the 120-kVp protocol. To facilitate a reduction in radiation dose it was set at 40 HU for the 80 kVp protocol. We compared the two protocols with respect to the radiation dose, the diagnostic accuracy for detecting left atrial appendage (LAA) thrombi, matching for surface registration, and the resultant ablation procedures. RESULTS: At 120 kVp, the dose length product (DLP) was 2.2 times that at 80 kVp (1269.0 vs 559.0 mGy cm, p < 0.01). The diagnostic accuracy for thrombus detection was 100% using both protocols. There was no difference between the two protocols with respect to matching for surface registration. The protocols did not differ with respect to the subsequent time required for the ablation procedures and the ablation fluoroscopy time, and the radiation dose (p = 0.54, 0.33, and 0.32, respectively). CONCLUSION: For the same CNR, the DLP at 80 kVp (559.0 mGy cm) was 56% of that delivered at 120 kVp (1269.0 mGy cm). There was no reduction in diagnostic accuracy. IMPLICATIONS FOR PRACTICE: Maintaining CNR allows for a reduction in the radiation dose without reducing the image quality.

Adjuvant management of locally advanced oral squamous cell carcinoma - real-world challenges and opportunities.

Patients with locally advanced oral squamous cell cancer (LAOSCC) are treated with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) following surgical ablation. This depends on the pathological risk factors and aims to reduce the risk of local recurrence and improve survival. Delivery of these aggressive treatments is, however, challenging particularly following major surgery. To inform the adaptations necessary to deliver gold-standard therapy, we aimed to describe real-world delivery of multimodality treatment in LAOSCC, in a UK population with high levels of disease incidence and low socioeconomic status. Patients with LAOSCC (T1-4 N1-3/T3-4 N0) who were treated between October 2014 and October 2016 and had a minimum follow up of 24 months were included. They were identified using the Somerset Cancer Register and data were collected through retrospective case note review. Approval was obtained from the audit departments at the relevant NHS institutions, and data were analysed using IBM SPSS Statistics for Windows version 24 (IBM Corp). The analysis included 129 patients with 82% having an initial performance status (PS) of 0-1. The most frequent change in PS was a one point drop (46%). Twenty of the 93 eligible patients (22%) underwent adjuvant CRT. A total of 37 (40%) began adjuvant CRT/RT within 42 days, and 79 (85%) within 56 days. A delay in initiating adjuvant therapy was associated with higher rates of complications and a longer postoperative hospital stay. Concordance between imaging and pathological nodal staging was poor (cK 0.223). PS frequently declines after complex surgical procedures and long postoperative recovery periods, leading to difficulties providing adjuvant treatments within the national guidance of 42 days. Frequent deviation from planned adjuvant therapies highlights the need for improved treatment strategies.

Recent progress in space weather research for cosmic radiation dosimetry.

The radiation environment in space is a complex mixture of particles of solar and galactic origin with a broad range of energies. In astronaut dose estimation, three sources must be considered: galactic cosmic radiation, trapped particles, and solar energetic particles (SEPs). The astronaut dose due to SEP exposure during a space mission is more difficult to estimate than the other components because the occurrence of a large solar particle event cannot be predicted by the current space weather research. Thus, several models have been proposed to estimate the worst-case scenario and/or the probability of the integral SEP fluence during a particular space mission, considering the confidence level, solar activity, and duration of the mission. In addition, recent investigations of the cosmogenic nuclide concentrations in tree rings and ice cores have revealed that the sun can cause solar particle events much larger than the largest event recorded in the modern solar observations. If such an extreme event occurs during a mission to deep space, astronauts may suffer from radiation doses in excess of the threshold value for some tissue reactions (0.5 Gy) and their career limit (0.6-1.2 Sv). This article reviews the recent progress made in space weather research that is useful for cosmic radiation dosimetry.

Study of charged particle activation analysis (II): Determination of boron concentration in human blood samples.

Boron Neutron Capture Therapy (BNCT) is a radiotherapy for the treatment of intractable cancer. In BNCT precise determination of 10B concentration in whole blood sample before neutron irradiation of the patient, as well as accurate neutron dosimetry, is crucial for control of the neutron irradiation time. For this purpose ICP-AES and neutron induced prompt γ-ray analysis are generally used. In Ibaraki Neutron Medical Research Center (iNMRC), an intense proton beam will be accelerated up to 8 MeV, which can also be used for Charged Particle Activation Analysis (CPAA). Thus, in this study, we apply the CPAA utilizing the proton beam to non-destructive and accurate determination of 10B concentration in whole blood sample. A CPAA experiment is performed by utilizing an 8 MeV proton beam from the tandem accelerator of Nuclear Science Research Institute in Japan Atomic Energy Agency. The 478 keV γ-ray of 7Be produced by the 10B(p, α)7Be reaction is used to quantify the 10B in human blood. The 478 keV γ-ray intensity is normalized by the intensities of the 847 keV and 1238 keV γ-rays of 56Co originating from Fe in blood. The normalization methods were found to be linear in the range of 3.27 µg 10B/g to 322 µg 10B/g with correlation coefficients of better than 0.9999.

Regional pancreatoduodenectomy versus standard pancreatoduodenectomy with portal vein resection for pancreatic ductal adenocarcinoma with portal vein invasion.

BACKGROUND: Pancreatoduodenectomy (PD) with portal vein resection (PVR) is a standard operation for pancreatic ductal adenocarcinoma (PDAC) with portal vein (PV) invasion, but positive margin rates remain high. It was hypothesized that regional pancreatoduodenectomy (RPD), in which soft tissue around the PV is resected en bloc, could enhance oncological clearance and survival. METHODS: This retrospective study included consecutive patients who underwent PD with PVR between January 2005 and December 2016 in a single high-volume centre. In standard PD (SPD) with PVR, the PV was skeletonized and the surrounding soft tissue dissected. In RPD, the retropancreatic segment of the PV was resected en bloc with its surrounding soft tissue. The extent of lymphadenectomy was similar between the procedures. RESULTS: A total of 268 patients were included (177 SPD, 91 RPD). Tumours were more often resectable in patients undergoing SPD (60·5 per cent versus 38 per cent in those having RPD; P = 0·014), and consequently they received neoadjuvant therapy less often (7·9 versus 25 per cent respectively; P < 0·001). R0 resection was achieved in 73 patients (80 per cent) in the RPD group, compared with 117 (66·1 per cent) of those in the SPD group (P = 0·016), although perioperative outcomes were comparable between the groups. Median recurrence-free (RFS) and overall (OS) survival were 17 and 32 months respectively in patients who had RPD, compared with 11 and 21 months in those who had SPD (RFS: P = 0·003; OS: P = 0·004). CONCLUSION: RPD is as safe and feasible as SPD, and may increase the survival of patients with PDAC with PV invasion.

ANTECEDENTES: La duodenopancreatectomía (pancreaticoduodenectomy, PD) con resección de la vena porta (portal vein resection, PVR) es una operación estándar para el adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) con invasión de la vena porta (portal vein, PV); sin embargo, las tasas de margen positivo siguen siendo altas. Nuestra hipótesis fue que la duodenopancreatectomía regional (regional pancreaticoduodenectomy, RPD) en la que el tejido blando alrededor de la PV se reseca en bloque podría mejorar el resultado oncológico y la supervivencia. MÉTODOS: Este estudio retrospectivo incluyó pacientes consecutivos que se sometieron a PD con PVR entre enero de 2005 y diciembre de 2016 en un solo centro de alto volumen. En la PD estándar (SPD) con PVR, la PV se esqueletizó disecando el tejido blando circundante. En la RPD, el segmento retropancreático de la PV se resecó en bloque con el tejido blando circundante. La extensión de la linfadenectomía fue similar en ambos procedimientos. RESULTADOS: Se incluyeron un total de 268 pacientes (177 sometidos a SPD y 91 a RPD). Los pacientes sometidos a SPD presentaron con mayor frecuencia tumores resecables (35 (38%) versus 107 (61%), P = 0,014)) y recibieron con mayor frecuencia terapia neoadyuvante (23 (25%) versus 14 (8%), P < 0,001)) que los pacientes sometidos a RPD. La resección R0 se logró en 73 (80%) pacientes pertenecientes al grupo RPD, en comparación con 117 (66%) pacientes sometidos a SPD (P = 0.011), aunque los resultados perioperatorios fueron comparables entre los grupos. La mediana de supervivencia libre de recidiva (recurrence-free survival, RFS) y de supervivencia global (overall survival, OS) fueron 17 meses y 31 meses, respectivamente, en pacientes sometidos a RPD, en comparación con 11 meses y 21 meses en pacientes sometidos a SPD, (P = 0,003 para RFS y P = 0,004 para la OS). CONCLUSIÓN: La RPD es tan segura y factible como la SPD y puede aumentar la supervivencia de pacientes con PDAC con invasión de la PV.

Neurocristopathies: Enigmatic Appearances of Neural Crest Cell-derived Abnormalities.

The neural crest is an important transient structure that develops during embryogenesis in vertebrates. Neural crest cells are multipotent progenitor cells that migrate and develop into a diverse range of cells and tissues throughout the body. Although neural crest cells originate from the ectoderm, they can differentiate into mesodermal-type or endodermal-type cells and tissues. Some of these tissues include the peripheral, autonomic, and enteric nervous systems; chromaffin cells of the adrenal medulla; smooth muscles of the intracranial blood vessels; melanocytes of the skin; cartilage and bones of the face; and parafollicular cells of the thyroid gland. Neurocristopathies are a group of diseases caused by the abnormal generation, migration, or differentiation of neural crest cells. They often involve multiple organ systems in a single person, are often familial, and can be associated with the development of neoplasms. As understanding of the neural crest has advanced, many seemingly disparate diseases, such Treacher Collins syndrome, 22q11.2 deletion syndrome, Hirschsprung disease, neuroblastoma, neurocutaneous melanocytosis, and neurofibromatosis, have come to be recognized as neurocristopathies. Neurocristopathies can be divided into three main categories: dysgenetic malformations, neoplasms, and combined dysgenetic and neoplastic syndromes. In this article, neural crest development, as well as several associated dysgenetic, neoplastic, and combined neurocristopathies, are reviewed. Neurocristopathies often have clinical manifestations in multiple organ systems, and radiologists are positioned to have significant roles in the initial diagnosis of these disorders, evaluation of subclinical associated lesions, creation of treatment plans, and patient follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study.

BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.