An Atypical Case of Meckel's Diverticulum Assessed by SPECT/CT Imaging.

ABSTRACT: A 17-year-old adolescent boy presented with multiple episodes of hematochezia. After a negative 99mTcO4 scan, upper endoscopy, colonoscopy, and CT angiography, the patient underwent a second 99mTcO4 scan with ranitidine. The anterior images demonstrated a faint, delayed focus of uptake in the midabdomen without correlate on lateral projections. SPECT/CT was performed for localization with the focus of activity seen in an anterior loop of distal small bowel adjacent to the umbilicus. The patient subsequently underwent diagnostic laparoscopy and resection of the diverticulum with postoperative resolution of the symptoms.

Value of chest CT over skeletal surveys in detection of rib fractures in pediatric patients.

Recent literature has raised concerns about the sensitivity and accuracy of radiographs at diagnosing rib fractures. Studies have shown that chest computed tomography (CT) has far greater sensitivity at detecting rib fractures than radiographs. The purpose of this study was to evaluate the sensitivity of skeletal survey (SS) radiographs at diagnosis of rib fractures compared to CT in the pediatric population. This retrospective review included 57 patients who had undergone both a SS and a CT chest or CT chest/abdomen/pelvis within 30 days of each other for the indication of either non-accidental (NAT) or accidental trauma between 2009 and 2017. Images and reports were analyzed by a pediatric radiology fellow for presence/absence of fracture, evidence of healing and location of rib fracture, including rib level, location within the rib (anterior, lateral, and posterior), and side (right versus left). 225 rib fractures were identified in 25 patients on CT. 38 of those fractures were missed on the preceding SS, yielding a miss rate of 17%. Acute fractures were more likely to be missed than chronic or healing fractures (p ≤ 0.01). Location within the rib did not impact rib detection on radiographs. Left-sided rib fractures were not more common in NAT patients, compared to accidental trauma. SS miss approximately 17% of all rib fractures and CT is more sensitive modality in the detection of rib fractures, particularly acute rib fractures, regardless of location. Low-dose Chest CT could be a helpful modality in the work-up of NAT trauma.

Quantifying lung and diaphragm morphology using radiographs in normative pediatric subjects, and predicting CT-derived lung volume.

OBJECTIVE: To quantify the effect of age on two-dimensional (2D) radiographic lung and diaphragm morphology and determine if 2D radiographic lung measurements can be used to estimate computer tomography (CT)-derived lung volume in normative pediatric subjects. MATERIALS AND METHODS: Digitally reconstructed radiographs (DRRs) were created using retrospective chest CT scans from 77 pediatric male and female subjects aged birth to 19 years. 2D lung and diaphragm measurements were made on the DRRs using custom MATLAB code, and Spearman correlations and exponential regression equations were used to relate 2D measurements with age. In addition, 3D lung volumes were segmented using CT scans, and power regression equations were fitted to predict each lung's CT-derived volume from 2D lung measurements. The coefficient of determination (R2 ) and standard error of the estimate (SEE) were used to assess the precision of the predictive equations with p < .05 indicating statistical significance. RESULTS: All 2D radiographic lung and diaphragm measurements showed statistically significant positive correlations with age (p < .01), including lung major axis (Spearman rho ≥ 0.90). Precise estimations of CT-derived lung volumes can be made using 2D lung measurements (R2 ≥ 0.95), including lung major axis (R2 ≥ 0.97). INTERPRETATIONS: The reported pediatric age-specific reference data on 2D lung and diaphragm morphology and growth rates could be clinically used to identify lung and diaphragm pathologies during chest X-ray evaluations. The simple, precise, and clinically adaptable radiographic method for estimating CT-derived lung volumes may be used when pulmonary function tests are not readily available or difficult to perform.

Morphology and growth of the pediatric lumbar vertebrae.

BACKGROUND CONTEXT: The majority of existing literature describing pediatric lumbar vertebral morphology are limited to characterization of the vertebral bodies, pedicles, and spinal canal and no study has described the rates of growth for any lumbar vertebral structure. While it is known that growth of the lumbar vertebrae results in changes in vertebral shape, the dimension ratios used to quantify these shape changes do not represent the 3D morphology of the vertebral structures. Additionally, many of the previous evaluations of growth and shape are purely descriptive and do not investigate sexual dimorphism or variations across vertebral levels. PURPOSE: This study aims to establish a database of pediatric lumbar vertebra dimension, growth, and shape data for subjects between and ages of 1 and 19 years. STUDY DESIGN: A retrospective study of computed tomography (CT) data. METHODS: Retrospective, abdominal, CT scans of 102 skeletally normal pediatric subjects (54 males, 48 females) between the ages of 1 and 19 years were digitally reconstructed and manually segmented. Thirty surface landmark points (LMPs), 30 vertebral measurements, the centroid size, centroid location, and the local orientation were collected for each lumbar vertebra along with the centroid size of the LMPs comprising each subject's full lumbar spine and their intervertebral disc (IVD) heights. Nonparametric statistics were used to compare dimension values across vertebral levels and between sexes. Linear models with age as the independent variable were used to characterize dimension growth for each sex and vertebral level. Age-dependent quadratic equations were fit to LMP distributions resulting from a generalized Procrustes analysis (GPA) of the vertebrae and fixed effects models were used to investigate differences in model coefficients across levels and between sexes. RESULTS: Intervertebral level dimension differences were observed across all vertebral structures in both sexes while pedicle widths and IVDs heights were the only measurements found to be sexually dimorphic. Dimension growth rates generally varied across vertebral levels and the growth rates of males were typically larger than those of females. Differences between male and female vertebral shapes were also found for all lumbar vertebral structures. CONCLUSIONS: To the authors' knowledge, this is the first study to report growth rates for the majority of pediatric lumbar vertebral structures and the first to describe the 3D age-dependent shapes of the pediatric lumbar spine and vertebrae. In addition to providing a quantitative database, the dimension, growth, and shape data reported here would have applications in medical device design, surgical planning, surgical training, and biomechanical modeling.

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group.

PURPOSE: The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF. PATIENTS AND METHODS: Patients were eligible at first relapse or first designation of refractory disease. Oral T and intravenous (IV) irinotecan were administered on days 1 to 5 of 21-day cycles. DIN was administered IV (days 2-5), and GM-CSF was administered subcutaneously (days 6-12). The primary end point was objective response, analyzed on an intent-to-treat basis per the International Neuroblastoma Response Criteria. RESULTS: Seventeen eligible patients were randomly assigned to I/T/DIN/GM-CSF (February 2013 to March 2015); 36 additional patients were nonrandomly assigned to I/T/DIN/GM-CSF (August 2016 to May 2017). Objective (complete or partial) responses were observed in nine (52.9%) of 17 randomly assigned patients (95% CI, 29.2% to 76.7%) and 13 (36.1%) of 36 expansion patients (95% CI, 20.4% to 51.8%). Objective responses were seen in 22 (41.5%) of 53 patients overall (95% CI, 28.2% to 54.8%); stable disease was also observed in 22 of 53. One-year progression-free and overall survival for all patients receiving I/T/DIN/GM-CSF were 67.9% ± 6.4% (95% CI, 55.4% to 80.5%) and 84.9% ± 4.9% (95% CI, 75.3% to 94.6%), respectively. Two patients did not receive protocol therapy and were evaluable for response but not toxicity. Common grade ≥ 3 toxicities were fever/infection (18 [35.3%] of 51), neutropenia (17 [33.3%] of 51), pain (15 [29.4%] of 51), and diarrhea (10 [19.6%] of 51). One patient met protocol-defined criteria for unacceptable toxicity (grade 4 hypoxia). Higher DIN trough levels were associated with response. CONCLUSION: I/T/DIN/GM-CSF has significant antitumor activity in patients with relapsed/refractory neuroblastoma. Study of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers.

Imaging of Wilms tumor: an update.

Wilms tumor is the most common pediatric renal tumor, accounting for approximately 7% of all childhood cancers. Imaging plays an important role in the detection, staging, post-therapy evaluation and surveillance of Wilms tumor. Wilms tumor can be detected during surveillance of a known cancer predisposition or after a child presents with symptoms. In this manuscript we describe an evidence-based approach to the initial evaluation of Wilms tumor using current guidelines from the Children's Oncology Group (COG). We illustrate the COG staging system for pediatric renal tumors and highlight key imaging findings that are critical for surgical management. We also discuss the controversies regarding detection and significance of <5-mm pulmonary nodules at initial staging. And finally, we present some thoughts regarding surveillance of Wilms tumor, where overall survival has now approached 90%.

Imaging surveillance for children with predisposition to renal tumors.

Effective surveillance is necessary for early detection of tumors in children with cancer predisposition syndromes. Instituting a surveillance regimen in children comes with practical challenges that include determining imaging modality and timing, and considering cost efficiency, accessibility, and the significant consequences of false-positive and false-negative results. To address these challenges, the American Association for Cancer Research has recently published consensus recommendations that focus on surveillance of cancer predisposition syndromes in children. This review condenses the imaging surveillance recommendations for syndromes that carry a predisposition to renal tumors in childhood, and includes summaries of the predisposition syndromes and discussion of considerations of available imaging modalities.

Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective.

Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.

Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial.

BACKGROUND: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. METHODS: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis. Patients of any age were eligible at first designation of relapse or progression, or first designation of refractory disease, provided organ function requirements were met. Patients previously treated for refractory or relapsed disease were ineligible. Computer-based randomisation with sequence generation defined by permuted block randomisation (block size two) was used to randomly assign patients (1:1) to irinotecan and temozolomide plus either temsirolimus or dinutuximab, stratified by disease category, previous exposure to anti-GD2 antibody therapy, and tumour MYCN amplification status. Patients in both groups received oral temozolomide (100 mg/m2 per dose) and intravenous irinotecan (50 mg/m2 per dose) on days 1-5 of 21-day cycles. Patients in the temsirolimus group also received intravenous temsirolimus (35 mg/m2 per dose) on days 1 and 8, whereas those in the dinutuximab group received intravenous dinutuximab (17·5 mg/m2 per day or 25 mg/m2 per day) on days 2-5 plus granulocyte macrophage colony-stimulating factor (250 µg/m2 per dose) subcutaneously on days 6-12. Patients were given up to a maximum of 17 cycles of treatment. The primary endpoint was the proportion of patients achieving an objective (complete or partial) response by central review after six cycles of treatment, analysed by intention to treat. Patients, families, and those administering treatment were aware of group assignment. This study is registered with ClinicalTrials.gov, number NCT01767194, and follow-up of the initial cohort is ongoing. FINDINGS: Between Feb 22, 2013, and March 23, 2015, 36 patients from 27 COG member institutions were enrolled on this groupwide study. One patient was ineligible (alanine aminotransferase concentration was above the required range). Of the remaining 35 patients, 18 were randomly assigned to irinotecan-temozolomide-temsirolimus and 17 to irinotecan-temozolomide-dinutuximab. Median follow-up was 1·26 years (IQR 0·68-1·61) among all eligible participants. Of the 18 patients assigned to irinotecan-temozolomide-temsirolimus, one patient (6%; 95% CI 0·0-16·1) achieved a partial response. Of the 17 patients assigned to irinotecan-temozolomide-dinutuximab, nine (53%; 95% CI 29·2-76·7) had objective responses, including four partial responses and five complete responses. The most common grade 3 or worse adverse events in the temsirolimus group were neutropenia (eight [44%] of 18 patients), anaemia (six [33%]), thrombocytopenia (five [28%]), increased alanine aminotransferase (five [28%]), and hypokalaemia (four [22%]). One of the 17 patients assigned to the dinutuximab group refused treatment after randomisation; the most common grade 3 or worse adverse events in the remaining 16 patients evaluable for safety were pain (seven [44%] of 16), hypokalaemia (six [38%]), neutropenia (four [25%]), thrombocytopenia (four [25%]), anaemia (four [25%]), fever and infection (four [25%]), and hypoxia (four [25%]); one patient had grade 4 hypoxia related to therapy that met protocol-defined criteria for unacceptable toxicity. No deaths attributed to protocol therapy occurred. INTERPRETATION: Irinotecan-temozolomide-dinutuximab met protocol-defined criteria for selection as the combination meriting further study whereas irinotecan-temozolomide-temsirolimus did not. Irinotecan-temozolomide-dinutuximab shows notable anti-tumour activity in patients with relapsed or refractory neuroblastoma. Further evaluation of biomarkers in a larger cohort of patients might identify those most likely to respond to this chemoimmunotherapeutic regimen. FUNDING: National Cancer Institute.

Neuroblastoma Presenting as Non-MIBG-Avid Widespread Soft Tissue Metastases Without Bone Involvement Revealed by FDG PET/CT Imaging.

Soft tissue metastases from neuroblastoma very rarely occur without concurrent osseous metastases. We report 1 case of non-MIBG-avid, high-risk neuroblastoma in a pediatric patient who had widespread soft tissue metastases without concurrent osseous lesion on FDG PET/CT imaging.

Age- and gender-related changes in pediatric thoracic vertebral morphology.

BACKGROUND CONTEXT: Although it is well known that the growth of thoracic spine changes significantly with age, gender, and vertebral level in the skeletally normal pediatric population, there have been very few studies attempting to comprehensively quantify such variations. Biomechanical and computational models of the growing thoracic spine have provided insight into safety and efficacy of surgical and noninvasive treatments for spinal deformity. However, many of these models only consider growth of the vertebral body and pedicles and assume a consistent growth rate for these structures across thoracic levels. PURPOSE: To enhance the understanding of age-, gender-, and level-related growth dynamics of the pediatric thoracic spine by comprehensively quantifying the thoracic vertebral morphology for subjects between 1 and 19 years. STUDY DESIGN: A retrospective computed tomography (CT) image analysis study. METHODS: Retrospectively obtained chest CT scans from 100 skeletally normal pediatric subjects (45 males and 55 females between the ages 1 and 19 years) were digitally reconstructed using medical imaging software. Surface point clouds of thoracic vertebrae were extracted and 26 vertebral geometry parameters were measured using 25 semiautomatically identified surface landmarks and anatomical slices from each thoracic vertebra (T1-T12). Data were assessed for normality, symmetry, and age-, gender-, and level-related differences in geometric measures and growth. Linear regression was performed to estimate of the rates of variation with age for each measurement. RESULTS: Asymmetries (bilateral, superior-inferior, and anteroposterior) were observed in vertebral body heights, end plate widths and depths, and interfacet widths. Within genders, significant interlevel differences were observed for all geometric measures, and significant differences in the rates of growth were found across thoracic levels for most parameters. Significant differences were observed between genders for pedicle, spinous process, and facet measurements. Growth rates of the pedicles and vertebral bodies were also found to vary significantly between genders. CONCLUSIONS: The rates of growth for most thoracic vertebral structures varied between genders and across vertebral levels. These growth rates followed trends similar to those of their associated vertebral dimensions and this indicates that, across levels and between genders, larger vertebral structures grow at faster rates, whereas smaller structures grow at a slower rate. Such level- and gender-specific information could be used to inform clinical decisions about spinal deformity treatment and adapted for use in biomechanical and computational modeling of thoracic growth and growth modulation.