Update on imaging recommendations in paediatric uroradiology: the European Society of Paediatric Radiology workgroup session on voiding cystourethrography.

Voiding cystourethrography (VCUG) is a fluoroscopic technique that allows the assessment of the urinary tract, including the urethra, bladder, and-if vesicoureteral reflux (VUR) is present-the ureters and the pelvicalyceal systems. The technique also allows for the assessment of bladder filling and emptying, providing information on anatomical and functional aspects. VCUG is, together with contrast-enhanced voiding urosonography (VUS), still the gold standard test to diagnose VUR and it is one of the most performed fluoroscopic examinations in pediatric radiology departments. VCUG is also considered a follow-up examination after urinary tract surgery, and one of the most sensitive techniques for studying anatomy of the lower genitourinary tract in suspected anatomical malformations. The international reflux study in 1985 published the first reflux-protocol and graded VUR into five classes; over the following years, other papers have been published on this topic. In 2008, the European Society of Paediatric Radiology (ESPR) Uroradiology Task Force published the first proposed VCUG Guidelines with internal scientific society agreement. The purpose of our work is to create a detailed overview of VCUG indications, procedural recommendations, and to provide a structured final report, with the aim of updating the 2008 VCUG paper proposed by the European Society of Paediatric Radiology (ESPR). We have also compared VCUG with contrast-enhanced VUS as an emergent alternative. As a result of this work, the ESPR Urogenital Task Force strongly recommends the use of contrast-enhanced VUS as a non-radiating imaging technique whenever indicated and possible.

Crohn's Disease in a Patient With Bardet-Biedl Syndrome: Random Anomaly or Rare Phenotypic Trait?

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystem nonmotile ciliopathy. There are anecdotal reports of the co-occurrence of BBS and autoimmune diseases, including inflammatory bowel disease (IBD). We present the first case report of a child with BBS7 who developed Crohn disease, adding to the evidence on the association between BBS and IBD. A 13-year-old girl with BBS7 presented with abdominal pain and significant weight loss (-13%), but without other classical symptoms of IBD, such as diarrhea and blood loss. Fecal calprotectin was elevated, but on gastroscopy and colonoscopy, no macroscopic abnormalities were found. Ultrasound and MRI revealed an intestinal stenosis which was treated surgically. Histopathological examination confirmed the diagnosis Crohn disease. In conclusion, the reported co-occurrence of BSS and autoimmune diseases and the atypical presentation of IBD in this patient warrant a low threshold to perform diagnostic tests for IBD in patients with BBS and gastrointestinal symptoms.

Imaging of anorectal malformations: where are we now? Abdominal imaging task force of the European Society of Paediatric Radiology.

Anorectal and cloacal malformations are a broad mix of congenital abnormalities related to the distal rectum and anus. Confusion exists between all the forms in this large and heterogeneous group. The spectrum includes everything from anal stenosis, ventral anus, anal atresia (with and without fistula) and the full spectrum of cloacal malformations. Imaging in these conditions is done through the whole armamentarium of radiologic modalities, with very different imaging strategies seen across the centres where these conditions are managed. In 2017, the European Society of Paediatric Radiology (ESPR) abdominal imaging task force issued recommendations on the imaging algorithm and standards for imaging anorectal malformations. This was followed by further letters and clarifications together with an active multispecialty session on the different imaging modalities for anorectal malformations at the 2018 ESPR meeting in Berlin. Through this paper, the abdominal task force updates its guidelines and recommended imaging algorithm for anorectal malformations.

International Comparisons of Clinical Demographics and Outcomes in the International Society of Pediatric Oncology Wilms Tumor 2001 Trial and Study.

PURPOSE: International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes. METHODS: All patients with unilateral Wilms tumor (WT), age > 6 months, treated with preoperative chemotherapy as per protocol, and registered between 2001 and 2011 were eligible. Countries were grouped to give comparable case numbers and geographical representation. Cox univariable and multivariable (MVA) statistics were applied, with the German collaborative group (Gesellschaft für Pädiatrische Onkologie und Hämatologie-Austria, Germany, and Switzerland) as reference for hazard ratios for event-free survival (EFS) and overall survival (OS). RESULTS: A total of 3,176 eligible patients were registered from 24 countries assigned into six groups. Age and histologic risk group distribution were similar across all groupings. The distribution of WT stage varied by country grouping, with 14.9% (range, 11.1%-18.2%) metastatic at diagnosis. Median follow-up was 78.9 months. For localized WT, 5-year EFS varied from 80% (Brazilian group) to 91% (French group; P < .0001), retaining significance only for Brazil in MVA (P = .001). Five-year OS varied from 89% (Brazilian group) to 98% (French group; P < .0001). In MVA, only superior OS in France was significant (P = .001). Five-year EFS/OS for stage IV did not vary significantly. High-risk histology and tumor volume at surgery were significantly associated with increased risk of death in MVA for metastatic disease. CONCLUSION: International benchmarking of survival rates from WT within a large trial/study database has demonstrated statistically significant differences. Clinical interpretation should take account of variation in tumor stage but also treatment factors.

[A girl with a tumor at the base of the tongue]. / Een meisje met een zwelling op de tongbasis.

An 8-year-old girl with a lingual thyroid was evaluated because of a tumor at the base of the tongue. Ultrasound showed a hypoechogenic homogeneous parenchymatous structure at the base of the tongue consistent with thyroid tissue. Suboptimal levothyroxine treatment resulted in longstanding TSH stimulation causing a lingual goiter.

Surveillance of Fontan-associated liver disease: current standards and a proposal from the European Society of Paediatric Radiology Abdominal Task Force.

Since Francis Fontan first introduced the eponymous technique, the Fontan procedure, this type of surgical palliation has allowed thousands of children affected by specific heart malformations to reach adulthood. Nevertheless, abdominal, thoracic, lymphatic and neurologic complications are the price that is paid by these patients. Our review focuses on Fontan-associated liver disease; the purpose is to summarize the current understanding of its physiopathology, the aim of follow-up and the specific radiologic follow-up performed in Europe. Finally, we as members of the Abdominal Task Force of the European Society of Paediatric Radiology propose a consensus-based imaging follow-up algorithm.

Radiologic follow-up in Fontan-associated liver disease in Europe: European Society of Paediatric Radiology survey demonstrates the need for a consensus protocol.

Fontan surgery is a life-saving procedure for newborns with complex cardiac malformations, but it originates complications in different organs. The liver is also affected, with development of fibrosis and sometimes cirrhosis and hepatocellular carcinoma. There is no general agreement on how to follow-up these children for the development of liver disease. To understand the current practice on liver follow-up, we invited members of the European Society of Paediatric Radiology (ESPR) to fill out an online questionnaire. The survey comprised seven questions about when and how liver follow-up is performed on Fontan patients. While we found some agreement on the use of US as screening tool, and of MRI for nodule characterization, the discrepancies on timing and the lack of a shared protocol make it currently impossible to compare data among centers.

Accuracy of controlled attenuation parameter compared with ultrasound for detecting hepatic steatosis in children with severe obesity.

OBJECTIVES: To determine the diagnostic accuracy of controlled attenuation parameter (CAP) on FibroScan® in detecting and grading steatosis in a screening setting and perform a head-to-head comparison with conventional B-mode ultrasound. METHODS: Sixty children with severe obesity (median BMI z-score 3.37; median age 13.7 years) were evaluated. All underwent CAP and US using a standardized scoring system. Magnetic resonance spectroscopy proton density fat fraction (MRS-PDFF) was used as a reference standard. RESULTS: Steatosis was present in 36/60 (60%) children. The areas under the ROC (AUROC) of CAP for the detection of grade ≥ S1, ≥ S2, and ≥ S3 steatosis were 0.80 (95% CI: 0.67-0.89), 0.77 (95% CI: 0.65-0.87), and 0.79 (95% CI: 0.66-0.88), respectively. The AUROC of US for the detection of grade ≥ S1 steatosis was 0.68 (95% CI: 0.55-0.80) and not significantly different from that of CAP (p = 0.09). For detecting ≥ S1 steatosis, using the optimal cutoffs, CAP (277 dB/m) and US (US steatosis score ≥ 2) had a sensitivity of 75% and 61% and a specificity of 75% and 71%, respectively. When using echogenicity of liver parenchyma as only the scoring item, US had a sensitivity of 70% and specificity of 46% to detect ≥ S1 steatosis. The difference in specificity of CAP and US when using only echogenicity of liver parenchyma of 29% was significant (p = 0.04). CONCLUSION: The overall performance of CAP is not significantly better than that of US in detecting steatosis in children with obesity, provided that the standardized scoring of US features is applied. When US is based on liver echogenicity only, CAP outperforms US in screening for any steatosis (≥ S1). KEY POINTS: • The areas under the ROC curves of CAP and ultrasound (US) for detecting grade ≥ S1 steatosis were 0.80 and 0.68, respectively, and were not significantly different (p = 0.09). • For detecting grade ≥ S1 steatosis in severely obese children, CAP had a sensitivity of 75% and a specificity of 75% at its optimal cutoff value of 277 dB/m. • For detecting grade ≥ S1 steatosis in clinical practice, both CAP and US can be used, provided that the standardized scoring of US images is used.

Outcome of patients with stage IV high-risk Wilms tumour treated according to the SIOP2001 protocol: A report of the SIOP Renal Tumour Study Group.

INTRODUCTION: High-risk (HR) metastatic (stage IV) Wilms tumours (WTs) have a particular poor outcome. METHODS: Here, we report the results of HR (diffuse anaplastic [DA] or blastemal type [BT]) stage IV WT treated patients according to the HR arm in the SIOP2001 prospective study. RESULTS: From January 2002 to August 2014, 3559 patients with WT were included in the SIOP2001 trial. Among the 525 patients (15%) with metastatic WT, 74 (14%) had stage IV HR-WT. The median age at diagnosis was 5.5 years (range: 1.4-18.3). Thirty-four patients (47%) had BT-WT and 40 (53%) had DA-WT. Five-year event-free survival rates were 44 ± 17% and 28 ± 15% for BT-WT and DA-WT, respectively (p = 0.09). Five-year overall survival rates were 53 ± 17% and 29 ± 16% for BT-WT and DA-WT, respectively (p = 0.03). Metastatic complete response after preoperative treatment was significantly associated with outcome in univariate and multivariate analyses (hazards ratio = 0.3; p = 0.01). Postoperative radiotherapy of metastatic sites might also be beneficial. Forty-three of 74 patients experienced a relapse or progression predominantly in the lungs (80%). The median time to relapse/progression after diagnosis was 7.3 months (range: 1.6-33.3) and 4.9 months (range: 0.7-28.4) for BT-WT and DA-WT, respectively (p = 0.67). This is the first prospective evidence of inferior survival of stage IV BT-WT as compared with historical intermediate-risk WT. Survival of patients with stage IV DA-WT has not improved compared to the previous SIOP93-01 study. CONCLUSION: These results call for new treatment approaches for patients with HR stage IV WT.

Emergency imaging in paediatric oncology: a pictorial review.

Despite the decline in mortality rates over the last 20 years, cancer remains one of the leading causes of death in children worldwide. Early recognition and treatment for acute oncological emergencies are vital in preventing mortality and poor outcomes, such as irreversible end-organ damage and a compromised quality of life.Imaging plays a pivotal and adjunctive role to clinical examination, and a high level of interpretative acumen by the radiologist can make the difference between life and death. In contrast to adults, the most accessible cross-sectional imaging tool in children typically involves ultrasound. The excellent soft tissue differentiation allows for careful delineation of malignant masses and along with colour Doppler imaging, thromboses and large haematomas can be easily identified. Neurological imaging, particularly in older children is an exception. Here, computed tomography (CT) is required for acute intracranial pathologies, with magnetic resonance imaging (MRI) providing more definitive results later.This review is divided into a 'body systems' format covering a range of pathologies including neurological complications (brainstem herniation, hydrocephalus, spinal cord compression), thoracic complications (airway obstruction, superior vena cava syndrome, cardiac tamponade), intra-abdominal complications (bowel obstruction and perforation, hydronephrosis, abdominal compartment syndrome) and haematological-related emergencies (thrombosis, infection, massive haemorrhage). Within each subsection, we highlight pertinent clinical and imaging considerations.The overall objective of this pictorial review is to illustrate how primary childhood malignancies may present with life-threatening complications, and emphasise the need for imminent patient management.

Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands.

BACKGROUND: Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood. METHODS: For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries. Standardized incidence ratios were calculated using cancer incidence rates from the general Dutch population. Excess relative risks (ERRs) per 100 mGy organ dose were calculated with Poisson regression. All statistical tests were two-sided. RESULTS: Standardized incidence ratios were elevated for all cancer sites. Mean cumulative bone marrow doses were 9.5 mGy at the end of follow-up, and leukemia risk (excluding myelodysplastic syndrome) was not associated with cumulative bone marrow dose (44 cases). Cumulative brain dose was on average 38.5 mGy and was statistically significantly associated with risk for malignant and nonmalignant brain tumors combined (ERR/100 mGy: 0.86, 95% confidence interval = 0.20 to 2.22, P = .002, 84 cases). Excluding tuberous sclerosis complex patients did not substantially change the risk. CONCLUSIONS: We found evidence that CT-related radiation exposure increases brain tumor risk. No association was observed for leukemia. Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.

The impact of reconstruction techniques on observer performance for the detection and characterization of small pulmonary nodules in chest CT of children under 13 years.

OBJECTIVE: To compare three different reconstruction techniques of CT data for the detection of pulmonary nodules in children under 13 years. Secondly to assess the prevalence of perifissural nodular opacities. MATERIALS AND METHODS: The study consisted of chest CTs of 31 children (median age 6.9 years, range 2.1-12.7), of whom 17 had known extra-thoracic malignancies. Four observers assessed three techniques for the presence of nodules: axial 5 mm maximum intensity projections (MIPs) used in conjunction with 1 mm slices (mode A), 1 mm slices alone (mode B) and 3 mm slices (mode C). All modes were available in 3D. Per mode sensitivities were determined above a certain threshold of reader agreement. Confidence level and reader agreement for identification of an opacity as nodule served as surrogate for quality of nodule characterization. RESULTS: 103 nodules (median size 2.0 mm) were detected. Mode A yielded the highest interreader agreement (κ 0.336) and a superior sensitivity (71%, p = 0.003) compared to mode B and C (κ 0.218, sensitivity 57% and κ 0.247, sensitivity 56%, respectively). Mode B provided the highest confidence level and interreader agreement with respect to nodule identification (mean 4.3/5, κw 0.508). Double reading improved and evened interreader agreement for all modes (κ 0.450), mode A maintained the highest sensitivity (89.1%, p = 0.05-0.08). A median of 1 intrapulmonary lymph node/patient was seen in children with and without malignancy. CONCLUSION: MIP improves the detection of pulmonary nodules in chest CTs of children, but overall interreader agreement is only fair. Double reading represents a powerful tool to increase diagnostic reliability in chest CTs of children with a malignancy. Nodule characterization is best with 1 mm slices. Intrapulmonary lymph nodes occur in children with and without malignancy.

Position paper: Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol.

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours - the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in children between 2 and 4 years of age, is specifically addressed in the UMBRELLA protocol.

Position paper: Rationale for the treatment of Wilms tumour in the UMBRELLA SIOP-RTSG 2016 protocol.

The Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new protocol for the diagnosis and treatment of childhood renal tumours, the UMBRELLA SIOP-RTSG 2016 (the UMBRELLA protocol), to continue international collaboration in the treatment of childhood renal tumours. This protocol will support integrated biomarker and imaging research, focussing on assessing the independent prognostic value of genomic changes within the tumour and the volume of the blastemal component that survives preoperative chemotherapy. Treatment guidelines for Wilms tumours in the UMBRELLA protocol include recommendations for localized, metastatic, and bilateral disease, for all age groups, and for relapsed disease. These recommendations have been established by a multidisciplinary panel of leading experts on renal tumours within the SIOP-RTSG. The UMBRELLA protocol should promote international collaboration and research and serve as the SIOP-RTSG best available treatment standard.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

OBJECTIVE: The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. METHODS: We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. RESULTS: TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) (P = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower (P < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. CONCLUSION: Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia.

Trends and patterns of computed tomography scan use among children in The Netherlands: 1990-2012.

OBJECTIVE: To evaluate trends and patterns in CT usage among children (aged 0-17 years) in The Netherlands during the period 1990-2012. METHODS: Lists of electronically archived paediatric CT scans were requested from the Radiology Information Systems (RIS) of Dutch hospitals which reported >10 paediatric CT scans annually in a survey conducted in 2010. Data included patient identification, birth date, gender, scan date and body part scanned. For non-participating hospitals and for years prior to electronic archiving in some participating hospitals, data were imputed by calendar year and hospital type (academic, general with <500 beds, general with ≥ 500 beds). RESULTS: Based on 236,066 CT scans among 146,368 patients performed between 1990 and 2012, estimated annual numbers of paediatric CT scans in The Netherlands increased from 7,731 in 1990 to 26,023 in 2012. More than 70 % of all scans were of the head and neck. During the last decade, substantial increases of more than 5 % per year were observed in general hospitals with fewer than 500 beds and among children aged 10 years or older. CONCLUSION: The estimated number of paediatric CT scans has more than tripled in The Netherlands during the last two decades. KEY POINTS: • Paediatric CT in The Netherlands has tripled during the last two decades. • The number of paediatric CTs increased through 2012 in general hospitals. • Paediatric CTs continued to increase among children aged 10 years or older.

Chronic Complications After Femoral Central Venous Catheter-related Thrombosis in Critically Ill Children.

Prescription of thromboprophylaxis is not a common practice in pediatric intensive care units. Most thrombi are catheter-related and asymptomatic, without causing acute complications. However, chronic complications of these (a)symptomatic catheter-related thrombi, that is, postthrombotic syndrome (PTS) and residual thrombosis have not been studied. To investigate these complications, critically ill children of 1 tertiary center with percutaneous inserted femoral central venous catheters (FCVCs) were prospectively followed. Symptomatic FCVC-thrombosis occurred in 10 of the 134 children (7.5%; 95% confidence interval [CI], 2.4-9.5). Only FCVC-infection appeared to be independently associated (P=0.001) with FCVC-thrombosis. At follow-up 2 of the 5 survivors diagnosed with symptomatic thrombosis developed mild PTS; one of them had an occluded vein on ultrasonography. A survivor without PTS had a partial occluded vein at follow-up. Asymptomatic FCVC-thrombosis occurred in 3 of the 42 children (7.1%; 95% CI, 0.0-16.7) screened by ultrasonography within 72 hours after catheter removal. At follow-up, mild PTS was present in 6 of the 33 (18.2%; 95% CI, 6.1-30.3) screened children. Partial and total vein occlusion was present in 1 (3%) and 4 (12%) children, respectively. In conclusion, children on pediatric intensive care units are at risk for (a)symptomatic FCVC-thrombosis, especially children with FCVC-infection. Chronic complications of FCVC-thrombosis are common. Therefore, thromboprophylaxis guidelines are warranted in pediatric intensive care units to minimize morbidity as a result of FCVC-thrombosis.