Clinical impact of primary tumour 123ImIBG response to induction chemotherapy in children with high-risk neuroblastoma.

BACKGROUND: More than 50% children with high-risk neuroblastoma (HR-NBL) experience disease progression, which we hypothesise is due to non-response of primary tumour to treatment. Current imaging techniques are unable to characterise response in primary tumour (necrotic versus viable tissue) at diagnosis or follow-up. OBJECTIVES: Compare clinico-histological characteristics between primary 123ImIBG-avid tumours that became entirely 123ImIBG-non-avid (responders) after induction chemotherapy (IC) versus primary 123ImIBG-avid tumour that remained 123ImIBG-avid (non-responders). METHODS: Retrospective review of clinico-radiological data of children diagnosed with 123ImIBG-avid HR-NBL at our centre (2005-2016). Patients received Rapid COJEC IC and two additional courses of TVD if metastatic response was inadequate. Primary tumour 123ImIBG response was assessed qualitatively as positive, negative or intermediate at diagnosis and after IC. Post-surgical histopathology slices were marked considering percentage of viable tissue. RESULTS: Sixteen of 61 patients showed complete primary tumour 123ImIBG response, 20 partial response, while 25 no response. There was no statistically significant difference between clinical demographics of complete responders and group of non- or partial responders. Mean percentage of viable tumour cells was higher in non-responders than in complete responders (44.6% vs 20.6%; p = 0.05). Five-year EFS was significantly higher in complete responders than non-responders (43 ± 15% vs 7 ± 6%; p < 0.005). CONCLUSIONS: 123ImIBG response in primary HR-NBL correlates with amount of necrotic tissue, skeletal metastatic 123ImIBG response and outcome. An entirely 123ImIBG non-avid tumour can still harbour viable tumour cells. Therefore, our findings do not support utility of primary tumour 123ImIBG response in decision making regarding residual tumour surgery. Combining both, primary and metastatic 123ImIBG response will improve interpretability of clinical trial results.

Ligamentum arteriosum calcification on paediatric postmortem computed tomography.

BACKGROUND: Ligamentum arteriosum calcification may be a normal finding in some children, although the frequency has not been well described. OBJECTIVE: To estimate the frequency of ligamentum arteriosum calcification in children at postmortem imaging. MATERIALS AND METHODS: We conducted a single-centre retrospective review of paediatric postmortem CT and chest radiographic imaging over a 6-year period (January 2012 to December 2018). Two independent reviewers assessed the presence of calcification on imaging. We calculated descriptive statistical analysis of ligamentum arteriosum calcification frequency and association with age and gender. RESULTS: During the study period, 220 children underwent whole-body postmortem CT and 182 underwent radiographic imaging. The frequency was higher on postmortem CT than plain radiographs (67/220, 30.5% vs. 3/182, 1.6%) and was highest in children ages 1-7 years (53.6-66.7%), with gradual reduction in frequency in older children, and none in children older than 12 years. There was no gender predilection. CONCLUSION: In the postmortem setting, ligamentum arteriosum calcification is a common finding in children <8 years of age. It can be better identified on postmortem CT than chest radiographs. Radiologists new to reporting postmortem paediatric CT studies should recognise this as a common normal finding to avoid unnecessary further investigations at autopsy.

An unusual cause of stridor.

A 12-month-old infant was referred with a 6-week history of recurrent admissions with worsening stridor. On each previous admission, the stridor responded well, but transiently, to oral dexamethasone. At this presentation, he required high-dependency unit care with high flow oxygen due to marked increased work of breathing.He was born at term, previously well, and up to date with immunisations. There was no significant family history. There were no smokers and two cats at home.He was afebrile with moderate subcostal recession and tracheal tug. On auscultation, breath sounds were normal with transmitted sounds of inspiratory and expiratory stridor. The rest of his examination was normal.He commenced dexamethasone 0.15 µg/kg three times a day, which was weaned as his clinical status improved.Blood tests showed total white cell count 9 x 10ˆ9/L, CRP <1 mg/L, lactate dehydrogenase level and blood film normal. Chest radiograph showed left lung hyperexpansion and apparent right-sided bronchial narrowing (figure 1). Flexible nasendoscopy was unremarkable. Microlaryngoscopy and bronchoscopy showed external airway compression at the level of the carina (figure 2). CT thorax demonstrated a non-enhancing mediastinal mass extrinsic to the airway, approximately 3cmx2.5cmx1.5cm, compressing the carina and main-stem bronchi (figure 3).

Technique, pitfalls, quality, radiation dose and findings of dynamic 4-dimensional computed tomography for airway imaging in infants and children.

This retrospective review of 33 children's dynamic 4-dimensional (4-D) computed tomography (CT) images of the airways, performed using volume scanning on a 320-detector array without anaesthesia (free-breathing) and 1.4-s continuous scanning, was undertaken to report technique, pitfalls, quality, radiation doses and findings. Tracheobronchomalacia (airway diameter collapse >28%) was recorded. Age-matched routine chest CT scans and bronchograms acted as benchmarks for comparing effective dose. Pitfalls included failure to administer intravenous contrast, pull back endotracheal tubes and/or remove nasogastric tubes. Twenty-two studies (67%) were diagnostic. Motion artefact was present in 16 (48%). Mean effective dose: dynamic 4-D CT 1.0 mSv; routine CT chest, 1.0 mSv, and bronchograms, 1.4 mSv. Dynamic 4-D CT showed tracheobronchomalacia in 20 patients (61%) and cardiovascular abnormalities in 12 (36%). Fourteen children (70%) with tracheobronchomalacia were managed successfully by optimising conservative management, 5 (25%) underwent surgical interventions and 1 (5%) died from the presenting disorder.

Paediatric magnetic resonance enteroclysis under general anaesthesia - initial experience.

MR enterography is the accepted imaging reference standard for small bowel assessment in inflammatory bowel disease. There is an increasing cohort of children with inflammatory bowel disease presenting at an early age (<5 years) with severe disease. Younger children present a technical challenge for enterography because of the need for sedation/general anaesthesia to allow image optimisation and the need for oral contrast to allow adequate luminal assessment. Through our experiences, MR enteroclysis under general anaesthesia has proven to be a successful imaging technique for the work-up of these patients. In this paper, we present our institutional practice for performing MR enteroclysis under general anaesthesia.

Artificial intelligence for interpretation of segments of whole body MRI in CNO: pilot study comparing radiologists versus machine learning algorithm.

BACKGROUND: To initiate the development of a machine learning algorithm capable of comparing segments of pre and post pamidronate whole body MRI scans to assess treatment response and to compare the results of this algorithm with the analysis of a panel of paediatric radiologists. METHODS: Whole body MRI of patients under the age of 16 diagnosed with CNO and treated with pamidronate at a tertiary referral paediatric hospital in United Kingdom between 2005 and 2017 were reviewed. Pre and post pamidronate images of the commonest sites of involvement (distal femur and proximal tibia) were manually selected (n = 45). A machine learning algorithm was developed and tested to assess treatment effectiveness by comparing pre and post pamidronate scans. The results of this algorithm were compared with the results of a panel of radiologists (ground truth). RESULTS: When tested initially the machine algorithm predicted 4/7 (57.1%) examples correctly in the multi class model, and 5/7 (71.4%) correctly in the binary group. However when compared to the ground truth, the machine model was able to classify only 33.3% of the samples correctly but had a sensitivity of 100% in detecting improvement or worsening of disease. CONCLUSION: The machine learning could detect new lesions or resolution of a lesion with good sensitivity but failed to classify stable disease accurately. However, further validation on larger datasets are required to improve the specificity and accuracy of the machine model.

Reciprocal Regulation of Substance P and IL-12/IL-23 and the Associated Cytokines, IFNγ/IL-17: A Perspective on the Relevance of This Interaction to Multiple Sclerosis.

UNLABELLED: The neuropeptide substance P (SP) exhibits cytokine-like properties and exerts different effects in autoimmune inflammation. Various immune cells express SP and its neurokinin-1 receptor (NK1R) isoforms. A role for SP has been demonstrated in a number of autoimmune conditions, including multiple sclerosis (MS). In this work, we studied the role of SP and NK1R in human immune cells with a focus on their relationship with IL-12/IL-23 family cytokines and the associated IFN-γ/IL-17. AIMS: (1) To determine the role of SP mediated effects on induction of various inflammatory cytokines in peripheral blood mononuclear cells (PBMC); (2) to investigate the expression of SP and its receptor in T cells and the effects of stimulation with IL-12 and IL-23. Quantitative real-time PCR, flow cytometry, ELISA, promoter studies on PBMC and primary T cells from healthy volunteers, and Jurkat cell line. Treatment with SP significantly increased the expression of IL-12/IL-23 subunit p40, IL-23 p19 and IL-12 p35 mRNA in human PBMC. Expression of NK1R and SP in T cells was upregulated by IL-23 but a trend was observed with IL-12. The IL-23 effect likely involves IL-17 production that additionally mediates IL-23 effects. Mutual interactions exist with SP enhancing the cytokines IL-23 and IL-12, and SP and NK1R expression being differentially but potentially synergistically regulated by these cytokines. These findings suggest a proinflammatory role for SP in autoimmune inflammation. We propose a model whereby immunocyte derived SP stimulates Th1 and Th17 autoreactive cells migrating to the central nervous system (CNS), enhances their crossing the blood brain barrier and perpetuates inflammation in the CNS by being released from damaged nerves and activating both resident glia and infiltrating immune cells. SP may be a therapeutic target in MS.