Multimodality detection of tumour rupture in children with Wilms tumour.

BACKGROUND AND AIMS: Tumour rupture (TR) signifies stage III disease and requires treatment intensification, which includes radiotherapy. We studied the associations between radiological, surgical and pathology TR in children with Wilms tumour (WT) in a United Kingdom multicentre clinical study. PATIENTS AND METHODS: The IMPORT (Improving Population Outcomes for Renal Tumours of Childhood) study registered 712 patients between 2012 and 2021. Children with TR on central radiology review (CRR) at diagnosis and/or indication of preoperative TR on surgical forms were included. Correlation between radiology/surgery/pathology findings was made. RESULTS: Total 141 patients had TR identified (69 on CRR, 43 on surgical form and 29 on both), and 124/141 had images available for CRR, and 98/124 had features suggestive of TR on diagnostic CRR (63 magnetic resonance imaging/35 computed tomography). TR was limited to the renal fossa in 47/98 (48%) and intraperitoneal in 51/98 (52%). Three of 98(3%) had upfront surgery, and 87/95 (92%) had TR confirmed on post-chemotherapy preoperative scans. Among 80/98 (82%) cases with TR on CRR and available surgical forms, TR was not confirmed on surgery or pathology in 38/80, giving a false-positive rate of 48%. Preoperative TR was indicated on 72 surgical forms, with images available for CRR in 55. Twenty-six of 55 (47%) were false-negative for TR on CRR and of those 10/26 (38%) had TR confirmed on pathology. CONCLUSIONS: Radiology alone should not be used to define TR, as it does not accurately correlate with surgical or pathology findings, and therefore cannot be relied upon for definitive staging and treatment. A multidisciplinary team should take the decision regarding the final abdominal stage and treatment using a multimodality approach considering clinical, radiological, surgical and pathological findings.

Intraoperative ultrasound-guided paediatric urological surgery: a pictorial review.

Intraoperative ultrasound is described widely in multiple pathological scenarios in adult practice and in image-guided interventions in children. We aim to describe the technique and range of potential uses of intraoperative ultrasound in paediatric urological surgery, from outlining the process of case selection, preparation, and logistics to demonstrating the ranging benefits of real-time, high spatial resolution ultrasound during resection. At our centre, we use intraoperative ultrasound to assist in a variety of operations. These include guiding excision margins in nephron-sparing surgery, assessing for vascular infiltration in renal tumours, and identifying salvageable testicular tissue in orchidectomy. By exhibiting these scenarios, we hope to display the unique value that intraoperative ultrasound can have to the paediatric surgeon and inspire additional uses further afield.

Diagnostic magnetic resonance imaging characteristics of congenital mesoblastic nephroma: a retrospective multi-center International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) radiology panel study.

BACKGROUND: Congenital mesoblastic nephroma is the most common solid renal tumor in neonates. Therefore, patients <3 months of age are advised to undergo upfront nephrectomy, whereas invasive procedures at diagnosis in patients ≥3 months of age are discouraged by the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG). Nevertheless, discriminating congenital mesoblastic nephroma, especially from the more common Wilms tumor, solely based on imaging remains difficult. Recently, magnetic resonance imaging (MRI) has become the preferred modality. Studies focusing on MRI characteristics of congenital mesoblastic nephroma are limited. OBJECTIVE: This study aims to identify diagnostic MRI characteristics of congenital mesoblastic nephroma in the largest series of patients to date. MATERIALS AND METHODS: In this retrospective multicenter study, five SIOP-RTSG national review radiologists identified 52 diagnostic MRIs of histologically proven congenital mesoblastic nephromas. MRI was performed following SIOP-RTSG protocols, while radiologists assessed their national cases using a validated case report form. RESULTS: Patients (24/52 classic, 11/52 cellular, and 15/52 mixed type congenital mesoblastic nephroma, 2/52 unknown) had a median age of 1 month (range 1 day-3 months). Classic type congenital mesoblastic nephroma appeared homogeneous with a lack of hemorrhage, necrosis and/or cysts, showing a concentric ring sign in 14 (58.3%) patients. Cellular and mixed type congenital mesoblastic nephroma appeared more heterogeneous and were larger (311.6 and 174.2 cm3, respectively, versus 41.0 cm3 for the classic type (P<0.001)). All cases were predominantly T2-weighted isointense and T1-weighted hypointense, and mean overall apparent diffusion coefficient values ranged from 1.05-1.10×10-3 mm2/s. CONCLUSION: This retrospective international collaborative study showed classic type congenital mesoblastic nephroma predominantly presented as a homogeneous T2-weighted isointense mass with a typical concentric ring sign, whereas the cellular type appeared more heterogeneous. Future studies may use identified MRI characteristic of congenital mesoblastic nephroma for validation and for exploring the discriminative non-invasive value of MRI, especially from Wilms tumor.

Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions.

BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.

Surgical management, staging, and outcomes of Wilms tumours with intravascular extension: Results of the IMPORT study.

PURPOSE: To review surgical management, tumour stage and clinical outcomes in children with intravascular extension of Wilms tumour (WT) registered in a national clinical study (2012-19). METHODS: WTs with presence/suspicion of tumour thrombus in the renal vein (RV) or beyond on radiology, surgery or pathology case report forms were identified. Only cases where thrombus was confirmed by surgeon and/or reference pathologist were included. Surgical management, disease stage, overall (OS) and event free survival (EFS) were investigated. RESULTS: 69/583 (11.8%) patients met the inclusion criteria. Forty-six (67%) had abdominal stage III due to thrombus-related reasons: 11 had macroscopically incomplete resection, including 8 cases where cavotomy was not performed; 20 had piecemeal complete resection of thrombus; 15 had microscopically positive resection margins at the RV. 66% of tumour thrombi contained viable tumour. There were eight relapses and five deaths. EFS, but not OS, was significantly associated with completeness of surgical resection (P<0.05). OS and EFS were also significantly associated with histological risk group (P<0.05) but not with viability of tumour thrombus (P=0.19; P=0.59). CONCLUSIONS: WTs with intravascular extension have a high risk of local stage III due to thrombus-related reasons. Controlled complete removal of the thrombus should be the aim of surgery. LEVEL OF EVIDENCE: Level II.

MRI Characteristics of Pediatric Renal Tumors: A SIOP-RTSG Radiology Panel Delphi Study.

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.

18F-FDG PET/MRI for Staging and Interim Response Assessment in Pediatric and Adolescent Hodgkin Lymphoma: A Prospective Study with 18F-FDG PET/CT as the Reference Standard.

Treatment regimens for pediatric Hodgkin lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of 18F-FDG PET/MRI with a 18F-FDG PET/CT reference standard for staging and response assessment. Methods: Twenty-four patients (mean age, 15.4 y; range, 8-19.5 y) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both 18F-FDG PET/CT and 18F-FDG PET/MRI at initial staging (n = 24) and at response assessment (n = 21). The diagnostic accuracy of 18F-FDG PET/MRI for both nodal and extranodal disease was compared with that of 18F-FDG PET/CT, which was considered the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors, and 18F-FDG PET/MRI and 18F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann Arbor staging and Deauville grading was also assessed. Results: For nodal and extranodal sites combined, corrected staging 18F-FDG PET/MRI sensitivity was 100% (95% CI, 96.7%-100%) and specificity was 99.5% (95% CI, 98.3%-99.9%). Corrected response-assessment 18F-FDG PET/MRI sensitivity was 83.3% (95% CI, 36.5%-99.1%) and specificity was 100% (95% CI, 99.2%-100%). Modified Ann Arbor staging agreement between 18F-FDG PET/CT and 18F-FDG PET/MRI was perfect (κ = 1.0, P = 0.000). Deauville grading agreement between 18F-FDG PET/MRI and 18F-FDG PET/CT was excellent (κ = 0.835, P = 0.000). Conclusion:18F-FDG PET/MRI is a promising alternative to 18F-FDG PET/CT for staging and response assessment in children with HL.

Quantitative assessment of terminal ileum motility on MR enterography in Crohn disease: a feasibility study in children.

OBJECTIVES: Investigate the relationship between quantified terminal ileal (TI) motility and histopathological activity grading, Crohn Disease MRI Index (CDMI) and faecal calprotectin. METHODS: Retrospective review of children with Crohn disease or unclassified inflammatory bowel disease, who underwent MR enterography. Dynamic imaging for 25 patients (median age 12, range 5 to 16) was analysed with a validated motility algorithm. The TI motility score was derived. The primary reference standard was TI Endoscopic biopsy Assessment of Inflammatory Activity (eAIS) within 40 days of the MR enterography. Secondary reference standards: (1) the Crohn Disease MRI Index (CDMI) and (2) faecal calprotectin levels. RESULTS: MR enterography median motility score was 0.17 a.u. (IQR 0.12 to 0.25; range 0.05 to 0.55), and median CDMI was 3 (IQR 0 to 5.5). Forty-three percent of patients had active disease (eAIS > 0) with a median eAIS score of 0 (IQR 0 to 2; range 0 to 5). The correlation between eAIS and motility was r = - 0.58 (p = 0.004, N = 23). Between CDMI and motility, r = - 0.42 (p = 0.037, N = 25). Motility score was lower in active disease (median 0.12 vs 0.21, p = 0.020) while CDMI was higher (median 5 vs 1, p = 0.04). In a subset of 12 patients with faecal calprotectin within 3 months of MR enterography, correlation with motility was r = - 0.27 (p = 0.4). CONCLUSIONS: Quantified terminal ileum motility decreases with increasing histopathological abnormality in children with Crohn disease, reproducing findings in adults. TI motility showed a negative correlation with an MRI activity score but not with faecal calprotectin levels. KEY POINTS: • It is feasible to perform MRI quantified bowel motility assessment in children using free-breathing techniques. • Bowel motility in children with Crohn disease decreases as the extent of intestinal inflammation increases. • Quantified intestinal motility may be a candidate biomarker for treatment efficacy in children with Crohn disease.

Colonic Basidiobolomycosis-An Unusual Presentation of Eosinophilic Intestinal Inflammation.

Basidiobolomycosis is a rare fungal disease caused by Basidiobolus ranarum. Involvement of the gastrointestinal tract is unusual and poses both a diagnostic and therapeutic challenge, as clinical signs are non-specific and predisposing risk factors are lacking. It can mimick inflammatory bowel disease, primary immunodeficiency, or a malignancy and should be considered in patients who do not respond to standard therapy. We present the case of a 22 months old boy with confirmed colonic Basidiobolomycosis, who presented with severe eosinophilic inflammation of the gastrointestinal tract. Panfungal PCR performed on DNA extracted directly from a tissue sample confirmed the presence of Basidiobolus. He made a full recovery with a combination of surgery and prolonged targeted antifungal medication.

The role of imaging in the initial investigation of paediatric renal tumours.

Imaging has a key role in the assessment of paediatric renal tumours, especially when the initial treatment approach is to proceed to standard chemotherapy without histological confirmation. In Europe, according to the International Society of Paediatric Oncology guidelines, core needle biopsy is not routinely done unless the child is older than 10 years. Between age 6 months and 9 years, the child is treated with a standard regimen of preoperative chemotherapy unless there are concerns about non-Wilms' tumour pathology. Atypical imaging findings could therefore stratify a child into a different treatment protocol, and can prompt the need for pretreatment histology. This review details the latest protocols and techniques used in the assessment of paediatric renal tumours. Important imaging findings are discussed, especially the features that might prompt the need for a pretreatment biopsy. Local radiology practices vary, but both MRI and CT are widely used as routine imaging tests for the assessment of paediatric renal tumours in Europe. Advances in imaging technology and MRI sequences are facilitating the development of new techniques, which might increase the utility of imaging in terms of predicting tumour histology and clinical behaviour. Several of these new imaging techniques are outlined here.

Enhancing the role of paediatric ultrasound with microbubbles: a review of intravenous applications.

Contrast-enhanced ultrasound (CEUS) represents a complementary technique to greyscale and colour Doppler ultrasonography which allows for real-time visualization and characterization of tissue perfusion. Its inherent advantages in the child makes ultrasonography an ideal imaging modality; repeatability and good tolerance along with the avoidance of CT, a source of ionizing radiation, renders ultrasonography imaging desirable. Although currently paediatric CEUS is principally used in an "off-label" manner, ultrasonography contrast agents have received regulatory approval for assessment of paediatric focal liver lesions (FLL) in the USA. The safety of ultrasound contrast-agents is well documented in adults, as safe as or even surpassing the safety profile of CT and MR contrast agents. Except for the established intracavitary use of CEUS in voiding urosonography, i.v. paediatric applications have been introduced with promising results in the abdominal trauma initial diagnosis and follow-up, characterization and differential diagnosis of FLL and characterization of lung, pleura, renal and splenic pathology. CEUS has also been used to detect complications after paediatric transplantation, evaluate inflammatory bowel disease activity and assess tumour response to antiangiogenic therapy. The purpose of this review was to present these novel i.v. paediatric applications of CEUS and discuss their value.

Detecting inflammation in the unprepared pediatric colon - how reliable is magnetic resonance enterography?

BACKGROUND: Pediatric inflammatory bowel disease frequently affects the colon. MR enterography is used to assess the small bowel but it also depicts the colon. OBJECTIVE: To compare the accuracy of MR enterography and direct visualization at endoscopy in assessing the colon in pediatric inflammatory bowel disease. MATERIALS AND METHODS: We included children with inflammatory bowel disease who had undergone both MR enterography and endoscopy, and we restrospectively assessed the imaging and endoscopic findings. We scored the colonic appearance at MR using a total colon score. We then compared scores for the whole colon and for its individual segments with endoscopy and histology. RESULTS: We included 15 children. An elevated MR colonic segmental score predicted the presence of active inflammation on biopsy with a specificity of 90% (95% confidence interval [CI] 79.5-96.2%) and sensitivity of 60% (CI 40.6-77.3%); this compares reasonably with the predictive values for findings at colonoscopy - specificity 85% (CI 73.4-92.9%) and sensitivity 53.3% (CI 34.3%-71.6%). Accuracy did not change significantly with increasing bowel distension. CONCLUSION: MR-derived scores had comparable accuracy to those derived during visualization at colonoscopy for detecting biopsy-proven inflammation in our patient group. MR enterography might prove useful in guiding biopsy or monitoring treatment response. Collapse of a colonic segment did not impair assessment of inflammation.

Fusion and subtraction post-processing in body MRI.

Interpreting complex paediatric body MRI studies requires the integration of information from multiple sequences. Image processing software, some freely available, allows the radiologist to use simple and rapid post-processing techniques that may aid diagnosis. We demonstrate the use of fusion and subtraction post-processing techniques with examples from four areas of application: enterography, oncological imaging, musculoskeletal imaging and MR fistulography.

Multi-detector thoracic CT findings in cerebro-costo-mandibular syndrome: rib gaps and failure of costo-vertebral separation.

Cerebro-costo-mandibular syndrome (CCMS) describes a triad of mandibular hypoplasia, brain dysfunction and posterior rib defects ("rib gaps"). We present the CT imaging for a 2-year-old girl with CCMS that highlights the rib gap defects and shows absent transverse processes with abnormal fusion of the ribs directly to the vertebral bodies. We argue that this is likely to relate to abnormal lateral sclerotome development in embryology, with the failure of normal costo-vertebral junctions compounding impaired thoracic function. The case also highlights the use of CT for specific indications in skeletal dysplasia.

Renal lymphangiomatosis, interrupted IVC with persistent primitive hepatic venous plexus and multiple anomalous venous channels: parts of an overlap syndrome?

A 5-year-old girl with cutis marmorata telangiectasia congenita (CMTC) and congenital glaucoma, who had previously presented with seizures, transient hemiplegia, upper gastrointestinal bleeding and hemihypertrophy, developed a large pleural effusion. Subsequent imaging revealed renal lymphangiomatosis, multiple anomalous intra-abdominal venous channels, an interrupted inferior vena cava with a persistent primitive hepatic venous plexus (PPHVP) and meningeal angiomas. To the best of our knowledge, the CT findings of PPHVP and the combination of the demonstrated abnormalities have not been previously reported. They may represent an overlap syndrome of CMTC, Sturge-Weber syndrome and Klippel-Trenaunay syndrome. The complexity and degree of overlap highlights the importance of an accurate clinical and anatomical description and good communication among clinicians.