Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder of children and young adults that is characterized by nonbacterial osteomyelitis. Patients typically present with multifocal bone pain secondary to sterile osseous inflammation, and the disease has a relapsing and remitting course. The cause of CRMO remains unclear, although the results of several studies have suggested a genetic component. The typical imaging findings of CRMO include lytic and sclerotic lesions in the metaphyses of long bones and the medial clavicles. Other common sites of disease are the vertebral bodies, pelvis, ribs, and mandible. CRMO is often bilateral and multifocal at presentation. Owing to the lack of a diagnostic test, CRMO remains a diagnosis of exclusion. Although generally a self-limiting disease, CRMO can have a prolonged course and result in significant morbidity. Radiologists can be the first to suggest this diagnosis given its characteristic radiographic appearance and distribution of disease. Radiologists should be familiar with the typical imaging findings of CRMO to prevent unnecessary multiple biopsies and long-term antibiotic treatment in children with CRMO.

Summary Background Gut bacteria might predispose to or protect from necrotising enterocolitis, a severe illness linked to prematurity. In this observational prospective study we aimed to assess whether one or more bacterial taxa in the gut differ between infants who subsequently develop necrotising enterocolitis (cases) and those who do not (controls). Methods We enrolled very low birthweight (1500 g and lower) infants in the primary cohort (St Louis Children’s Hospital) between July 7, 2009, and Sept 16, 2013, and in the secondary cohorts (Kosair Children’s Hospital and Children’s Hospital at Oklahoma University) between Sept 12, 2011 and May 25, 2013. We prospectively collected and then froze stool samples for all infants. Cases were defined as infants whose clinical courses were consistent with necrotising enterocolitis and whose radiographs fulfilled criteria for Bell’s stage 2 or 3 necrotising enterocolitis. Control infants (one to four per case; not fixed ratios) with similar gestational ages, birthweight, and birth dates were selected from the population after cases were identified. Using primers specific for bacterial 16S rRNA genes, we amplified and then pyrosequenced faecal DNA from stool samples. With use of Dirichlet multinomial analysis and mixed models to account for repeated measures, we identified host factors, including development of necrotising enterocolitis, associated with gut bacterial populations. Findings We studied 2492 stool samples from 122 infants in the primary cohort, of whom 28 developed necrotising enterocolitis; 94 infants were used as controls. The microbial community structure in case stools differed significantly from those in control stools. These differences emerged only after the first month of age. In mixed models, the time-by-necrotising-enterocolitis interaction was positively associated with Gammaproteobacteria (p=0·0010) and negatively associated with strictly anaerobic bacteria, especially Negativicutes (p=0·0019). We studied 1094 stool samples from 44 infants in the secondary cohorts. 18 infants developed necrotising enterocolitis (cases) and 26 were controls. After combining data from all cohorts (166 infants, 3586 stools, 46 cases of necrotising enterocolitis), there were increased proportions of Gammaproteobacteria (p=0·0011) and lower proportions of both Negativicutes (p=0·0013) and the combined Clostridia–Negativicutes class (p=0·0051) in infants who went on to develop necrotising enterocolitis compared with controls. These associations were strongest in both the primary cohort and the overall cohort for infants born at less than 27 weeks’ gestation. Interpretation A relative abundance of Gammaproteobacteria (ie, Gram-negative facultative bacilli) and relative paucity of strict anaerobic bacteria (especially Negativicutes) precede necrotising enterocolitis in very low birthweight infants. These data offer candidate targets for interventions to prevent necrotising enterocolitis, at least among infants born at less than 27 weeks’ gestation. Funding Nation...

A number of syndromes are associated with CVJ pathology, the most notable being Klippel-Feil and Down syndromes, achondroplasia, the mucopolysaccharidoses, and osteogenesis imperfecta. Skull-base softening associated with some of these syndromes results in acquired basilar invagination or basilar impression. In this article, we present a detailed review of essential anatomy and craniometry needed for radiographic assessment of the CVJ and illustrate various congenital anomalies of the occiput, atlas, and axis. The common syndromes affecting this region are also discussed and illustrated.

The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018. © 2018 American Cancer Society.

PURPOSE To characterize the epidemiology, histology, radiographic features and surgical approach of pediatric and adolescent renal cell carcinoma (pRCC). PATIENTS AND METHODS pRCC cases prospectively enrolled on the Children's Oncology Group study AREN03B2 underwent central pathology, radiology, surgery and oncology review. RESULTS As of June 2012, of 3250 patients enrolled on AREN03B2, 120 (3.7%) had unilateral RCC (median age 12.9 years, range 1.9-22.1; 52.5% female). Central review classified these as translocation morphology (56), papillary (20), renal medullary carcinoma (13), chromophobe (4), oncocytoma (1), conventional clear cell (1), and RCC not otherwise specified (25). Lymph node (LN) involvement (N+) was found in 35/73 (47.9%) cases for which LN were sampled, including 19/40 (47.5%) with primary tumors < 7cm. Using a size cut-off of 1cm, imaging detection of N+ had a sensitivity of 57.14% [(20/35); 95% CI: 39.35%, 73.68%] and specificity of 94.59% [(35/37); 95% CI: 81.81%, 99.34%]. Distant metastases were present in 23 (19.2%). Initial surgery was radical nephrectomy (RN) in 88 (73.3%), nephron-sparing surgery (NSS) in 18 (15.0%), and biopsy in 14 (11.7%). Patients undergoing NSS compared to RN were less likely to have LNs sampled (6/18 (33.3%) vs. 65/88 (73.9%), p-value = 0.002). CONCLUSIONS Translocation RCC is the most common form of pediatric and adolescent RCC. Nodal disease is common and seen with small primary tumors. Imaging has a high specificity but relatively low sensitivity for detection of such lymph node disease. Failure to sample LNs results in incomplete staging and potentially inadequate disease control for younger RCC patients.

Renal malignancies are among the most prevalent pediatric cancers. The most common is favorable histology Wilms tumor (FHWT), which has 5-year overall survival exceeding 90%. Other pediatric renal malignancies, including anaplastic Wilms tumor, clear cell sarcoma, malignant rhabdoid tumor, and renal cell carcinoma, have less favorable outcomes. Recent clinical trials have identified gain of chromosome 1q as a prognostic marker for FHWT. Upcoming studies will evaluate therapy adjustments based on this and other novel biomarkers. For high-risk renal tumors, new treatment regimens will incorporate biological therapies. A research blueprint, viewed from the perspective of the Children’s Oncology Group, is presented.

Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children's Oncology Group protocol AREN0532. MethodsFrom October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. ResultsA total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P , .01) and absence of LOH 1p or 16q (P , .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). ConclusionMost patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.