[Tumor predisposition syndromes and nephroblastoma : Early diagnosis with imaging]. / Tumorprädispositionssyndrome und Nephroblastom : Frühe Diagnose mit Bildgebung.

CLINICAL/METHODICAL ISSUE: The Beckwith-Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys-Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of developing chronic kidney disease and bilateral and metachronous tumors as well as nephrogenic rests. STANDARD RADIOLOGICAL METHODS: Standard imaging diagnostics for WT include renal ultrasound and magnetic resonance imaging (MRI). In the current renal tumor studies Umbrella SIOP-RTSG 2016 and Randomet 2017, thoracic computed tomography (CT) is also recommended as standard. Positron emission tomography (PET)-CT and whole-body MRI, on the other hand, are not part of routine diagnostics. METHODOLOGICAL INNOVATIONS: In recent publications, renal ultrasound is recommended every 3 months until the age of 7 years in cases of clinical suspicion or molecularly proven TPS. PERFORMANCE: Patients with TPS and regular renal ultrasounds have smaller tumor volumes and lower tumor stages at WT diagnosis than patients without such a screening. This allows a reduction of therapy intensity and facilitates the performance of nephron sparing surgery, which is prognostically relevant especially in bilateral WT. ACHIEVEMENTS: Early diagnosis of WT in the context of TPS ensures the greatest possible preservation of healthy and functional renal tissue. Standardized screening by regular renal ultrasounds should therefore be firmly established in clinical practice. PRACTICAL RECOMMENDATIONS: The initial diagnosis of TPS is clinical and requires a skilled and attentive examiner in the presence of sometimes subtle clinical manifestations, especially in the case of BWSp. Clinical diagnosis should be followed by genetic testing, which should then be followed by sonographic screening.

Delayed Surgery for Perforated Appendicitis is Feasible in Children Without Compromising the Outcome in Selected Cases.

BACKGROUND AND AIM: The relationship between time to surgery and risk of postoperative complications and re-intervention has not been conclusively investigated in pediatric perforated appendicitis (PA). The aim of this study was to determine whether time to appendectomy (TTA) is a risk factor for postoperative complications and re-intervention in a cohort of children undergoing appendectomy for PA. METHODS: A total of 254 children (age: 8.7 ± 3.7 years) undergoing appendectomy for PA were retrospectively evaluated and stratified into Group I-III according to the Clavien-Dindo classification for postoperative complications (Group I n = 218, 86%; Group II n = 7, 3%; Group III n = 29, 11%). RESULTS: The TTA was comparable between all groups (group I: 8.8 ± 9.2 h; group II: 7.8 ± 5.3 h; group III: 9.5 ± 9.6 h; overall: 8.8 ± 9.1 h; p = 0.885). A C-reactive protein (CRP) value at admission of ≥128.6 mg/l indicated a higher risk for developing Grade II complications with no need for re-intervention (OR: 3.963; 95% CI: 1.810-8.678; p = 0.001) and Grade III complications with the need for re-intervention (OR: 3.346; 95% CI: 1.456-7.690; p = 0.004). This risk was independent of the TTA (OR: 1.007; 95% CI: 0.980-1.035; p = 0.613). CONCLUSIONS: Appendectomy can be delayed by an average time delay of about 9 h in children with PA without increasing the risk of postoperative complications and re-intervention, also in patients at high risk defined by the initial CRP level ≥ 128.6 mg/l. This data may support the correct risk-adjusted scheduling of surgical interventions in times of limited capacity.

[Imaging of renal tumors in children]. / Bildgebung renaler Tumoren im Kindesalter.

CLINICAL/METHODOLOGICAL ISSUE: Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. STANDARD RADIOLOGICAL METHODS: After sonography, magnetic resonance imaging (MRI) is the preferred imaging modality. The task of imaging includes differential diagnosis with the help of morphological and epidemiological criteria. Thorax computed tomography (CT) is introduced for initial staging. METHODOLOGICAL INNOVATIONS: Current studies of diffusion-weighted imaging (DWI)-MRI with analysis of the apparent diffusion coefficient (ADC) histogram indicate the potential to differentiate blastemal or anaplastic high-risk histology nephroblatoma subtypes. Imaging criteria for nephron-sparing surgery are defined and allow an individual therapy option in unilateral and especially in bilateral renal nephroblastoma. PERFORMANCE: In addition to nephroblastoma, the differential diagnosis includes congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney, clear cell sarcoma and renal cell carcinoma. The diagnosis of nephrogenic rests and nephroblastomatosis is challenging. ACHIEVEMENTS: Diagnostic standardization improves diagnosis and therapy of renal childhood tumors, and new prognostic markers may be introduced in the near future.

Predicting Postoperative Complications After Pediatric Perforated Appendicitis.

PURPOSE: Assessment of risk factors for postoperative complications following surgical treatment of pediatric perforated appendicitis (PA) is necessary to identify those patients in need of closer monitoring. In this study, we have investigated the impact of different risk factors on the occurrence of complications after an appendectomy in children with PA. MATERIAL AND METHODS: The study was a retrospective, single-centre analysis of all pediatric PA conducted over a 10-year period. Preoperative clinical and laboratory results, intraoperative findings, and postoperative complications were analyzed. Risk factors were defined and a risk score was determined for postoperative complications and reinterventions. RESULTS: Surgical treatment for appendicitis was performed in 840 pediatric patients during the observation period. 163 of the included patients were diagnosed with PA (mean age 8.9 ± 3.6 years). 19 (11.7%) patients developed postoperative complications, 17 (10.4%) of which required complication-related intervention. We identified five predictors of postoperative complications: the C-related protein value at admission, purulent peritonitis, open appendectomy (primary, secondary, or converted), placement of an abdominal drain, and administration of antibiotics not compliant to results from the subsequent antibiogram. The determined risk score was significantly higher in the complication group (p < .0001) and reintervention group (p < .001). CONCLUSIONS: Postoperative complications following pediatric PA can be predicted using specific preoperative, intraoperative, and postoperative risk factors. In the high-risk group, an active prevention, detection, and intervention of any occurring complication is necessary and we present a new specific pediatric risk score to define patients at risk for complications.

Long-term outcome in displaced lateral humeral condyle fractures following internal screw fixation in children.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome following open reduction and internal screw fixation of displaced lateral condyle fractures (LCFs) of the distal humerus and compare the outcome of primary and secondary LCFs. METHODS: The clinical outcome in 31 children (mean age 5.8±2.4 years) operated for primary or secondary LCFs was retrospectively analyzed by standardized clinical examination and compared using the Mayo score, Morger score, and Patients Satisfaction score. RESULTS: The scores did not differ significantly between the primary and secondary displacement groups (Mayo score: 99.3±3.3 vs. 100±0, p=0.852; Morger score: 3.8±0.5 vs. 3.9±0.3, p=0.852; Patients Satisfaction score: 3.7±0.6 vs. 3.9±0.3, p=0.546). Deficits in range of motion and joint axis deviation were minor (< 10°) and no elbow instabilities were observed. CONCLUSIONS: Surgical treatment of a secondary displaced LCF with open reduction and internal screw fixation leads to a favorable long-term outcome. The long-term outcome is similar between primary and secondary displaced LCFs.

[Lung diseases in children]. / Lungenerkrankungen im Kindesalter.

BACKGROUND: Lung diseases belong to the most common acute and chronic childhood diseases. With specific diagnostics and therapy the outcome of many congenital and acquired pulmonary diseases in children and adults can be substantially improved. OBJECTIVE: The aim of this review is the presentation and evaluation of important lung diseases in children taking recent developments into consideration. MATERIAL AND METHODS: This article presents a review of the literature on selected acute and chronic lung diseases in children and adolescents. RESULTS: Acute pneumonia remains one of the most frequent causes of mortality in children worldwide. Antibiotic treatment has reduced the morbidity and mortality in Western industrialized countries; however, the treatment of complications, such as pleural empyema and lung abscesses remains challenging. With a prevalence of 10 %, asthma has evolved into the most common chronic disease in children and adolescents in Germany. Using anti-inflammatory inhalation therapy, effective control of asthma symptoms can be achieved in most patients. Cystic fibrosis (CF) remains the most common fatal inherited disease among Caucasians. More than 90 % of the mortality and morbidity of CF are caused by an early onset and progressive chronic obstructive lung disease. Approval of the first causal mutation-specific pharmacotherapy for a subgroup of patients with CF represents a milestone in individualized therapy of lung diseases. The pathogenesis of other rare chronic lung diseases including interstitial lung diseases (ILD) is still mostly unknown. CONCLUSION: Continuous improvement in the diagnostics and therapy is crucial to further improve the management and outcome of acute and chronic lung diseases in children. Pediatric pulmonology, as an interdisciplinary subspecialty at the interface of pediatrics, pulmonology and infectious diseases, plays a key role in the translation of scientific progress into clinical practice.

Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma.

BACKGROUND: Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma. METHODS: Retrospective analysis of 121 consecutive patients with stage V nephroblastoma registered from January 1989 to May 2005. Registration, prospective data collection and treatment were carried out within the framework of 3 consecutive SIOP/GPOH-nephroblastoma-trials. RESULTS: 19 patients had metastasis and 29 syndromes at diagnosis. 13 patients had been pretreated for bilateral nephroblastomatosis. 1 patient was not treated and 17 patients had upfront surgery. Preoperative treatment duration ranged from 1-12 weeks (n=103). 1-3 preoperative treatment-cycles resulted in average tumor-volume-reduction of 45%. 1 patient underwent bilateral nephrectomy. 52% of the patients had 2 functioning kidneys after the end of treatment. 20 patients had died after mean follow-up of 8.6 years. 5y-Progression-Free (PFS) and Overall-Survival (OS) were excellent for patients having a localized disease without pretreatment for nephroblastomatosis (5yPFS/OS: 80±4%/93±3%). Metastasis at diagnosis (51±12%/56±12%; p=0.003) and pretreatment for nephroblastomatosis (37±14%/67±13%; p<0.001) were associated with significantly poorer outcome. Cox-regression analysis revealed an independent influence of pretreatment for nephroblastomatosis, metastasis and syndromes on PFS. The latter 2 as well as anaplasia and age (<2 years or >3 years) had an independent influence on OS. CONCLUSIONS: Pretreatment for nephroblastomatosis, metastasis and syndromes are independent risk factors. 1-3 preoperative treatment-cycles are sufficient to achieve save nephron-sparing-surgery in most patients.

Primary lung metastases in pediatric malignant non-Wilms renal tumors: data from SIOP 93-01/GPOH and SIOP 2001/GPOH.

Malignant non-Wilms renal tumors (NWRT) are a small but relevant subgroup of renal neoplasms in children. In this study we analyzed corresponding data from the trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the Society of Pediatric Oncology and Hematology.Data of 22 patients with NWRT and primary lung metastases were retrospectively reviewed. Analyses included epidemiology, tumor characteristics, chemotherapy, local treatment, and outcome.The following diagnoses were registered: Malignant Rhabdoid tumor of the kidney (MRTK, n=15), Renal-cell carcinoma (RCC, n=3), Clear-cell sarcoma of the kidney (CCSK, n=3), and primitive neuro ectodermal tumor (PNET, n=1). Median age of patients at diagnosis was 14 months. Overall survival was 36.36% (8/22). Of the 15 children with MRTK 3 survived, 3/3 patients with RCC, 1/3 patients with CCSK, and 1/1 patient with PNET survived. Lung metastases disappeared in 6 patients after initial chemotherapy, 6/8 patients undergoing local treatment of lung metastases (surgery, irradiation, or both) achieved complete remission. Only patients with complete clearance of lung lesions, either through neoadjuvant chemotherapy or subsequent local treatment, survived. Mean Follow up was 31 months (1-137).Survival of patients with stage IV NWRT is dismal. Complete removal of lung metastases seems mandatory for survival. An aggressive diagnostic and therapeutic approach seems justified in affected children.

Computed tomographic examination of South American sea lions (Otaria flavescens) with suspected Mycobacterium pinnipedii infection.

Ten South American sea lions (Otaria flavescens) were presented for clinical evaluation and diagnosis of tuberculosis following known exposure to Mycobacterium pinnipedii. CT was used to determine whether foci of calcification in mediastinal lymph nodes, typically associated with pinniped tuberculosis, could be detected and whether CT was a useful diagnostic modality, in conjunction with other tests, for the diagnosis of tuberculosis in this species. Blood was collected from the caudal gluteal vein of each animal for serological testing using commercially available serological tests (ElephantTB STAT-PAK and DPP Vet; Chembio Diagnostic Systems) and a multiantigen print immunoassay (MAPIA), carried out at Chembio to verify the in-house kits. In four of nine animals that underwent CT scanning, lesions consistent with pinniped tuberculosis were apparent and these were confirmed at subsequent postmortem examination. The five remaining animals did not show any abnormalities on CT, with three being negative on serological tests, which were considered to be normal and potentially used as reference images for healthy sea lions. One animal could not be CT scanned due to its large size and weight (510 kg).

Significance of image-defined risk factors for surgical complications in patients with abdominal neuroblastoma.

INTRODUCTION: Neuroblastoma (NB) is one of the most common malignant tumors in infancy. The commonly used International Neuroblastoma Staging System is not suitable for determining the surgical risks. To address this, we aimed to evaluate the correlation between so-called image-defined risk factors (IDRFs) and the surgical risks in abdominal neuroblastoma. MATERIAL AND METHODS: We evaluated 60 cases who underwent surgical intervention and examined the pre-surgical radiological imaging to look for IDRFs and surgical complications in children with abdominal neuroblastoma. RESULTS: The MRI- and CT-scans showed a total of 122 IDRFs in 39 cases. Complete resection was carried out in 50%, partial excision in 32%, and biopsy in 18% of cases. Total resection was possible in 100% of cases with no IDRF. Where IDRFs were present, total resection was only possible in 26% of cases (p<0.0001). We found a highly significant, negative correlation between the number of IDRFs and the possibility of performing complete resection of NB (p<0.0001). 7 (11.6%) complications were detected, all in patients who showed at least one IDRF previously. CONCLUSION: Our findings indicate that IDRFs are useful indicators for predicting surgical risk and surgical outcome and thus should be taken into account when planning surgery.

Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group.

INTRODUCTION: Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤ 6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced. PATIENTS AND METHODS: We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially. RESULTS: 3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11). CONCLUSION: Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group.

Neuroblastoma imaging.

Neuroblastoma is an embryonic tumor of the sympathetic nervous system which represents one of the most common malignancies in early childhood. Its clinical and biological behavior show a remarkable heterogeneity, ranging from spontaneous regression to inexorable progression with a fatal outcome. This review summarizes the clinical risk stratification and treatment options. An extensive overview of the role of imaging during the course of the disease and typical imaging findings in all imaging modalities are demonstrated.

[Shape analysis of retroperitoneal tumors in childhood in magnetic resonance imaging]. / Formanalyse in der Magnetresonanztomografie - Landmarken und Objektdifferenzierung bei retroperitonealen Tumoren im Kindesalter.

2D-shape analysis of biological objects is described first in 2007 with MRI-data (magnetic resonance imaging) of renal tumours of infancy. For shape analysis the evaluation of landmarks is necessary (n >2). In this study 24 landmarks are selected. Every object is described by these landmarks. The shape is the standardised and centred object. The procedure is applied on transversal as well as on frontal images. The results for frontal and transversal images are compared. Tumours of different origin, topography and size can be analysed. The differentiation of relevant landmarks is important for statistical and medical reason. In this study, evaluation of landmarks and their possibility for tumour differentiation is demonstrated.

Multiple hemangiomas and hemangiomatosis--risk factors and outcome over an eight year period.

INTRODUCTION: Hemangiomas are the most common tumors of infancy. Multiple cutaneous hemangiomas may be associated with the presence of hemangiomas in inner organs. However, there is little data on the risk factors for organ involvement and the outcome of a large sample of patients. PATIENTS AND METHODS: patients with 3 or more cutaneous hemangiomas were evaluated with regard to patient characteristics, distribution of hemangiomas, results of radiological abdominal/cerebral imaging, clinical course, and therapeutic approach. We analyzed the risk factors for organ involvement and complications/outcome. RESULTS: The average gestational week at birth was 32.8; radiological imaging showed liver hemangiomas in 13.5% and mesenteric lesions in 1 (1.9%) but no cerebral lesions. Preterm infants (p=0.02) and patients with high numbers of cutaneous hemangiomas (p=0.02) were at higher risk of organ involvement. A life-threatening event occurred in 1 patient (1.9%). None of the patients died. CONCLUSIONS: Organ manifestation is relatively common in patients with multiple hemangiomas, complications are rare, but potentially life-threatening. We recommend abdominal imaging for patients with 3 or more hemangiomas, especially in preterm infants.

Surgical complications in abdominal tumor surgery in children. Experiences at a single oncological center.

INTRODUCTION: Surgical complications after tumor operations are frequent in children, with rates of up to 30% cited in the literature. Various approaches to reduce these complication rates have been attempted, with preoperative chemotherapy holding pride of place. One approach to minimize surgical complications is better preoperative preparation. In a retrospective analysis, we evaluated the complications associated with tumor surgery. MATERIAL AND METHODS: We retrospectively analyzed patient data from 1991 to 2007. The distribution of the various tumors, the type of surgery, and complications were evaluated. For neuroblastomas a differentiated analysis of complications was performed, which included staging and radiologically defined surgical risk factors (SRFs). Patients were divided into two groups: A and B. Intensified surgical planning with 3D visualization was used in patients of group B. RESULTS: A total of 145 operations for abdominal tumors were performed in 123 patients. The three most common diseases were neuroblastoma (36%), nephroblastoma (26%), and ovarian tumor (19%). In 68% of patients complete resection and in 19% of cases partial resection of the tumor was carried out; open biopsy was performed in 13%. A total of 15 (10.3%) complications developed: the incidence of complications for group A was 11.8% and 7.7% for group B (p=0.5). For nephroblastoma these figures were 27.9% and 21.2% (p=1.0). In the group of patients with neuroblastoma, six complications developed in patients from group A (21.4%) and one in a group B patient (4.2%) (p=0.107). 54% of neuroblastomas were completely and 33% partially resected; these figures and the distribution of SRFs were similar in the two groups. A significant increase in the risk of complications could be seen with an increase in SRFs (p=0.0267) and with disease stages 2 and 3 (p=0.016). Tumor reduction surgery was also associated with an increase in complications (p=0.086). CONCLUSIONS: In summary, tumor surgery is associated with considerable risks in children. Therefore it is very important to look for new approaches that could potentially minimize these risks. As the causes of surgical complications are multifactorial, we are of the opinion that intensified surgical planning can contribute to reducing risks. Particularly neuroblastoma surgery could profit from an increased use of 3D visualization and improved preoperative planning.

Clinical application of MRI in children for the assessment of pulmonary diseases.

The standard examination technique for the chest in children is an X-ray examination - it is fast, cheap and provides a good overview of anatomy and pathology. In cases with an unclear pathology or if more details are needed (i. e. pre-therapeutically), computed tomography is most often performed with the well known drawbacks of limited soft tissue contrast and radiation. Radiation should be avoided in children, especially if follow-up examinations are needed. Recent magnetic resonance (MR) techniques allow for fast and reliable assessment of pulmonary diseases in children. Due to the inherent soft tissue contrast, diagnosis can be frequently performed without contrast media application. This review provides an exemplary MR examination protocol for routine application in pediatric patients. The diagnostic value of MRI is shown in patients with infectious diseases, patients with immunodeficiency, anatomic abnormalities, acquired chronic diseases, and pulmonary tumors. Since MRI is especially suitable for functional imaging, an MR protocol is provided for the examination of thoracic deformities. This review summarizes the use of thoracic MRI in the clinical pediatric setting with special focus on the clinical indications as a radiation-free method.

DTI of commissural fibers in patients with Chiari II-malformation.

Chiari II-malformation is a complex congenital deformity of the brain which is frequently associated with hydrocephalus. Abnormalities of the corpus callosum are known to occur in the majority of patients. The objective of the present study was to study the microstructure of the corpus callosum (CC) and the anterior commissure (AC) to differentiate between different mechanisms of damage to these structures. We investigated 6 patients with Chiari II-malformation and 6 well-matched healthy volunteers employing T1-weighted 3D imaging and diffusion tensor imaging (DTI) to determine the fractional anisotropy (FA) and cross-sectional area of the CC and AC, as well as with neuropsychological testing. Four patients showed hydrocephalus, two patients had callosal dysplasia and four had a hypoplastic CC. The callosal FA in the patients was significantly reduced which was less pronounced for the genu alone. The area of CC was also reduced in Chiari II-patients. There was a strong correlation between the size and FA of the CC in the patients. In contrast, the thickness of the AC was significantly increased and was associated with higher FA in the patients. In psychological tests all patients showed reduced verbal memory; all but one patient showed reduced IQ as well as impaired visuo-spatial performance, indicating deficits in tasks requiring parieto-occipital integration. The existence of callosal dysplasia in two patients, the diminished FA reduction in the genu and the correlation of the cross-sectional area and FA in the patients point to a developmental white matter damage beside that exerted by hydrocephalus alone.