Quality Improvement Campaign Improved Utilization of Rapid Sequence MRI for Diagnosis of Pediatric Appendicitis.

INTRODUCTION: Appendicitis is the most common indication for emergency general surgery in the pediatric population. Computed tomography (CT) or magnetic resonance imaging (MRI) may be used for diagnosis when ultrasound findings are equivocal. However, CT involves unnecessary radiation exposure if MRI is available. After introducing a rapid sequence MRI (rsMRI) appendicitis protocol at our institution, CT was still preferentially used. We therefore implemented a quality improvement (QI) campaign to reduce the rate of CTs and increase the rate of rsMRI. Here, we assess the effectiveness of the QI campaign while evaluating potential barriers to using rsMRI. METHODS: We conducted a mixed methods study, first performing stakeholder interviews which informed the design of a QI campaign initiated in May 2021 and a midway feedback survey in December 2021. A retrospective cohort study was then performed of children evaluated for appendicitis at our institution between January 1, 2016, and April 30, 2022. CT and rsMRI rates were compared before and after QI campaign implementation. RESULTS: There was a significant decrease in rate of CTs and increase in rate of rsMRIs performed following the initiation of the QI campaign (p < 0.0001). The rate of CT scans decreased by a factor of 0.4 while the rate of rsMRI increased by a factor of 9.5. CONCLUSION: A successful QI campaign was initiated at our institution, resulting in decreased utilization of CT and increased use of rsMRI for the evaluation of suspected appendicitis. These results highlight the potential impact of QI projects. LEVEL OF EVIDENCE: III.

Rate of Anti-NMDA Receptor Encephalitis in Ovarian Teratomas.

BACKGROUND: The rate of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) in ovarian teratomas is unknown. We aim to identify the prevalence of NMDARE as well as volumetric and histopathologic characteristics of ovarian teratomas in patients with versus without. METHODS: We performed a retrospective cohort study to identify patients with confirmed ovarian teratomas and the characteristics of teratomas in NMDARE compared with non-NMDARE patients. Patients aged between 0 and 21 years with confirmed histopathological diagnosis of ovarian teratoma after resection were included. The rate of NMDARE in ovarian teratomas was identified. Moreover, volumes of ovarian teratomas and the frequency of neuronal glial elements on histopathology in NMDARE versus non-NMDARE patients were assessed. RESULTS: Five out of one-hundred-and-sixty-three (3.07%) patients with histopathology confirmed ovarian teratomas were diagnosed with NMDARE. Age was not different between the NMDARE (mean: 13.8 years, standard deviation: 3.9) and non-NMDARE groups (median: 14, interquartile range [IQR]: 5). Teratoma volumes from NMDARE patients were smaller than those of non-NMDARE patients (median 28.3 cm3 with IQR of 431.2 and median 182.8 with IQR of 635.0, respectively). Both age and NMDARE diagnosis were statistically significant variables in the analysis of variance on a multiple linear regression model. Age (p = 0.013) had a positive correlation with teratoma size, whereas presence of NMDARE had a negative correlation (p = 0.008). CONCLUSION: The rate of NMDARE in ovarian teratomas is low and NMDARE patients have smaller teratomas than non-NMDARE. Further studies are needed to understand the timing of anti-NMDA receptor antibodies in teratomas and the development of NMDARE.

Routine Neuroimaging of the Preterm Brain.

Neuroimaging of the preterm infant is a common assessment performed in the NICU. Timely and focused studies can be used for diagnostic, therapeutic, and prognostic information. However, significant variability exists among neonatal units as to which modalities are used and when imaging studies are obtained. Appropriate timing and selection of neuroimaging studies can help identify neonates with brain injury who may require therapeutic intervention or who may be at risk for neurodevelopmental impairment. This clinical report reviews the different modalities of imaging broadly available to the clinician. Evidence-based indications for each modality, optimal timing of examinations, and prognostic value are discussed.

Compensatory Ovarian Hypertrophy after Unilateral Oophorectomy: Evaluation of Ovarian Volumes in Pediatric and Adolescent Populations.

STUDY OBJECTIVE: Limited data exist on the morphologic and physiologic effect on the remaining ovary after unilateral oophorectomy, especially in the pediatric population. Our aim is to evaluate ovarian volumes following unilateral oophorectomy to determine whether compensatory ovarian hypertrophy occurs in the remaining contralateral ovary. DESIGN: This was a retrospective chart review of ovarian volume measured on ultrasounds that were completed after unilateral oophorectomy. Postoperative ovarian volumes were compared to established radiologic standards. SETTING: Large tertiary care academic children's hospital in Atlanta, GA. PARTICIPANTS: Female patients less than 21 years old who underwent unilateral oophorectomy. MAIN OUTCOME MEASURES: Ovarian volumes measured on postoperative ultrasounds. RESULTS: A total of 93 patients met inclusion criteria for this study. Serial ultrasounds were performed in slightly more than half of the patients (n = 48, 51.6%), totaling 193 postoperative ovarian volumes. The average age of oophorectomy was 10.8 years. Prior to surgery, the majority of patients presented with abdominal pain (n = 51, 54.8%) or pelvic mass (n = 51, 54.8%), and most (n = 77, 82.8%) had benign final pathology. Ovarian volumes were compared to 4 published radiologic ultrasound standards. More than 62.2% of ovarian volumes from girls who had previously had unilateral oophorectomy were larger than age-matched standard ovarian volumes. CONCLUSION: Ovarian enlargement occurs in the contralateral ovary following unilateral oophorectomy in the pediatric and adolescent population. This supports the concept of compensatory ovarian hypertrophy. This knowledge provides valuable information for interpretation of radiologic images in young female individuals who have undergone oophorectomy, and can assist with counseling on the risk of adnexal complications due to ovarian hypertrophy after unilateral oophorectomy.

Incidence and importance of portal venous gas in children with hypertrophic pyloric stenosis.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) is a common cause of gastric outlet obstruction in young infants. Infants with HPS present with projectile vomiting, sometimes have electrolyte abnormalities and typically undergo pyloromyotomy to alleviate the obstruction. Abdominal US is the gold standard imaging study for diagnosis. Case reports of incidental hepatic portal venous gas have been reported in infants with HPS; however, no large studies have been conducted to determine the incidence or possible clinical implications of this finding. OBJECTIVE: To assess the incidence of portal venous gas in infants with HPS and to determine whether the presence of this gas in infants with HPS indicates a more unstable patient, increased length of stay or worse outcome. MATERIALS AND METHODS: We conducted a retrospective review of sonographic reports containing "pyloric stenosis," excluding negative descriptor, at a tertiary-care children's hospital from November 2010 to September 2017. Data collected included pyloric thickness/length, liver evaluation, portal venous gas, any additional imaging, demographics, symptomatology days, electrolyte abnormality, and length of hospital stay. RESULTS: In a 7-year period, 545 US exams were positive for HPS. Of these, 334 exams included enough hepatic parenchyma to evaluate for portal venous gas. Infants in 6 of the 334 exams demonstrated portal venous gas (1.8%). Clinical presentation (length of symptoms and electrolyte abnormalities), demographics (male predominance and age at presentation) and imaging characteristics (pyloric thickness and length) were similar for the HPS groups with and without portal venous gas. There was no significant difference in outcome or length of hospital stay. CONCLUSION: Visualization of portal venous gas in infants with HPS is not rare and appears benign, without need for further imaging. Portal venous gas in infants with HPS does not portend a more severe patient presentation or outcome.

Prospective Cohort Study of Next-Generation Sequencing as a Diagnostic Modality for Unexplained Encephalitis in Children.

BACKGROUND: Encephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens. METHODS: Hospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database. RESULTS: Twenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis. CONCLUSION: We describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.

ACR Appropriateness Criteria® Scoliosis-Child.

Scoliosis is frequently encountered in childhood, with prevalence of 2%. The majority is idiopathic, without vertebral segmentation anomaly, dysraphism, neuromuscular abnormality, skeletal dysplasia, tumor, or infection. As a complement to clinical assessment, radiography is the primary imaging modality used to classify scoliosis and subsequently monitor its progression and response to treatment. MRI is utilized selectively to assess for neural axis abnormalities in those at higher risk, including those with congenital scoliosis, early onset idiopathic scoliosis, and adolescent idiopathic scoliosis with certain risk factors. CT, although not routinely employed in the initial evaluation of scoliosis, may have a select role in characterizing the bone anomalies of congenital scoliosis and in perioperative planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Congenital Limb Overgrowth Syndromes Associated with Vascular Anomalies.

Congenital limb length discrepancy disorders are frequently associated with a variety of vascular anomalies and have unique genetic and phenotypic features. Many of these syndromes have been linked to sporadic somatic mosaicism involving mutations of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, which has an important role in tissue growth and angiogenesis. Radiologists who are aware of congenital limb length discrepancies can make specific diagnoses based on imaging findings. Although genetic confirmation is necessary for a definitive diagnosis, the radiologist serves as a central figure in the identification and treatment of these disorders. The clinical presentations, diagnostic and imaging workups, and treatment options available for patients with Klippel-Trenaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular anomalies, epidermal nevi, and scoliosis/spinal deformities) syndrome, fibroadipose vascular anomaly, phosphatase and tensin homolog mutation spectrum, Parkes-Weber syndrome, and Proteus syndrome are reviewed. ©RSNA, 2019.

Multiphase acquisitions in pediatric abdominal-pelvic CT are a common practice and contribute to unnecessary radiation dose.

BACKGROUND: Many patients at our pediatric hospital have had a contrast-enhanced CT of the abdomen and pelvis performed by an outside imaging facility before admission. We have noticed that many of these exams are multiphase, which may contribute to unnecessary radiation dose. OBJECTIVE: To determine the frequency of multiphase acquisitions and radiation dose indices in contrast-enhanced CTs of the abdomen and pelvis performed by outside imaging facilities in patients who were subsequently transferred to our pediatric hospital for care, and compare these metrics to contrast-enhanced CTs of the abdomen and pelvis performed internally. MATERIALS AND METHODS: A retrospective analysis was performed of contrast-enhanced CTs of the abdomen and pelvis from outside imaging facilities uploaded to our picture archiving and communication system (PACS) between January 1, 2012, and December 31, 2015. CT images and dose pages were reviewed to determine the number of phases and dose indices (CT dose index-volume [CTDIvol], dose-length product, size-specific dose estimate). Exams for abdominal or pelvic mass, trauma or urinary leak indications were excluded. Data were compared to internally acquired contrast-enhanced CTs of the abdomen and pelvis by querying the American College of Radiology (ACR) Dose Index Registry. This review was institutional review board and HIPAA compliant. RESULTS: There were 754 contrast-enhanced CTs of the abdomen and pelvis from 104 outside imaging facilities. Fifty-three percent (399/754) had 2 phases, and 2% (14/754) had 3 or more phases. Of the 939 contrast-enhanced CTs of the abdomen and pelvis performed internally, 12% (115) were multiphase exams. Of 88% (664) contrast-enhanced CTs of the abdomen and pelvis from outside imaging facilities with dose data, CTDIvol was 2.7 times higher than our institution contrast-enhanced CTs of the abdomen and pelvis (939) for all age categories as defined by the ACR Dose Index Registry (mean: 9.4 vs. 3.5 mGy, P<0.0001). The majority (74%) of multiphase exams were performed by 9 of 104 outside imaging facilities. CONCLUSION: Multiphase acquisitions in routine contrast-enhanced CT of the abdomen and pelvis exams at outside imaging facilities are more frequent than those at a dedicated pediatric institution and contribute to unnecessary radiation dose. A contrast-enhanced CT of the abdomen and pelvis exam from an outside imaging facility with two passes may have as much as four times to six times the dose as the same exam performed with a single pass at a pediatric imaging center. We advocate for imaging facilities with high multiphase rates to eliminate multiple phases from routine contrast-enhanced CT of the abdomen and pelvis exams in children.

ACR Appropriateness Criteria® Headache-Child.

Headaches in children are not uncommon and have various causes. Proper neuroimaging of these children is very specific to the headache type. Care must be taken to choose and perform the most appropriate initial imaging examination in order to maximize the ability to properly determine the cause with minimum risk to the child. This evidence-based report discusses the different headache types in children and provides appropriate guidelines for imaging these children. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Pediatric Dental Clinic-Associated Outbreak of Mycobacterium abscessus Infection.

BACKGROUND: Mycobacterium abscessus is an uncommon cause of invasive odontogenic infection. METHODS: M abscessus-associated odontogenic infections occurred in a group of children after they each underwent a pulpotomy. A probable case-child was defined as a child with facial or neck swelling and biopsy-confirmed granulomatous inflammation after a pulpotomy between October 1, 2013, and September 30, 2015. M abscessus was isolated by culture in confirmed case-children. Clinical presentation, management, and outcomes were determined by medical record abstraction. RESULTS: Among 24 children, 14 (58%) were confirmed case-children. Their median age was 7.3 years (interquartile range, 5.8-8.2 years), and the median time from pulpotomy to symptom onset was 74 days (range, 14-262 days). Clinical diagnoses included cervical lymphadenitis (24 [100%] of 24), mandibular or maxillary osteomyelitis (11 [48%] of 23), and pulmonary nodules (7 [37%] of 19). Each child had ≥1 hospitalization and a median of 2 surgeries (range, 1-6). Of the 24 children, 12 (50%) had surgery alone and 11 (46%) received intravenous (IV) antibiotics. Nineteen of the 24 (79%) children experienced complications, including vascular access malfunction (7 [64%] of 11), high-frequency hearing loss (5 [56%] of 9), permanent tooth loss (11 [48%] of 23), facial nerve palsy (7 [29%] of 24), urticarial rash (3 [25%] of 12), elevated liver enzyme levels (1 [20%] of 5), acute kidney injury (2 [18%] of 11), incision dehiscence/fibrosis (3 [13%] of 24), and neutropenia (1 [9%] of 11). CONCLUSIONS: M abscessus infection was associated with significant medical morbidity and treatment complications. Unique manifestations included extranodal mandibular or maxillary osteomyelitis and pulmonary nodules. Challenges in the identification of case-children resulted from an extended incubation period and various clinical manifestations. Clinicians should consider the association between M abscessus infection and pulpotomy in children who present with subacute cervical lymphadenitis. The use of treated/sterile water during pulpotomy might prevent further outbreaks.

Rare presentation of four primary pediatric cardiac tumors.

Pediatric cardiac tumors are extremely rare and usually benign. We selected four unique cases of pediatric cardiac tumors from a 15-year period at our institution. The four chosen cases represent unique, rare primary tumors of the heart. Our selection includes a case of Rosai Dorfman disease without systemic involvement, which is, to our knowledge, the second case of isolated cardiac Rosai Dorfman disease in a child. We present a case of subtotal replacement of myocardium by granulocytic sarcoma with minimal bone marrow involvement, representing the first reported case in a child manifested as hypertrophic cardiomyopathy, as well as a case of a primary synovial sarcoma arising from the atrioventricular (AV) node, representing the fourth reported pediatric case of a cardiac synovial sarcoma, and it is the first to arise from the AV node. Finally, we present a primary congenital infantile fibrosarcoma of the heart, which is, to our knowledge, the first confirmed cardiac congenital infantile fibrosarcoma. These four cases represent the need for continued inclusion of rare cardiac conditions in a clinician's differential diagnosis. Furthermore, they present the need for more in-depth molecular and genomic analysis of pediatric cardiac tumors in order to identify their etiopathogenesis.

Fetal and Postnatal Magnetic Resonance Imaging of Unilateral Cystic Renal Dysplasia in a Neonate with Tuberous Sclerosis.

Tuberous sclerosis (TS) is an autosomal dominant condition associated with mutations in the TSC1 and/or TSC2 genes. Clinical manifestations are multisystemic, and they often include lesions in the brain, skin, heart, kidneys, and bones. TSC2 gene mutations can be seen concomitantly with autosomal dominant polycystic kidney disease gene mutations. We present a case of a fetus with prenatal diagnosis of TS that had unique asymmetrical distribution of renal cystic disease. We describe the extensive work up with both fetal and neonatal magnetic resonance imaging with correlating images of the unilateral polycystic renal disease in addition to typical TS brain findings.

Benefits of brain magnetic resonance imaging over computed tomography in children requiring emergency evaluation of ventriculoperitoneal shunt malfunction: reducing lifetime attributable risk of cancer.

OBJECTIVES: The rapid growth of computed tomography (CT) has resulted in increased concerns of ionizing radiation exposure and its subsequent risk of cancer development. We evaluated the impact of a new protocol using rapid sequence magnetic resonance imaging (rsMRI) instead of CT in children presenting with possible ventriculoperitoneal shunt (VPS) malfunction to promote patient safety. METHODS: This is a retrospective case series of pediatric patients who received a neuroimaging study for emergency evaluation of possible VPS malfunction at New York University's Tisch Hospital Emergency Department between January 2010 and July 2011. Radiology Charge Master was queried to identify the patient database. The trend in the use of rsMRI and CT was calculated for 3 patient age groups and compared across 3 chronological intervals. The effective dose of ionizing radiation per CT scan was calculated using the CT dose index and dose-length product for each patient. RESULTS: Total of 365 patients with the mean age of 8.87 years received either rsMRI or CT study during the study period. One hundred forty-four of these patients required the imaging studies because of VPS malfunction. Overall, 62% of all VPS malfunction cases used rsMRI instead of CT. The ratio of the number of patients receiving rsMRI divided by CT studies has progressively increased from 1.4:1 to 2.1:1 over 3 chronologic periods. CONCLUSIONS: Children with VPS are subject to multiple neuroimaging studies throughout their lifetime. Rapid sequence MRI is an effective alternative to CT while providing no ionizing radiation exposure or risk of developing radiation-induced cancer.

Intracranial Mycobacterium abscessus infection in a healthy toddler.

We present the first case of pediatric intracranial Mycobacterium abscessus infection in a 16-month-old female with neurofibromatosis type 1. We describe a successful treatment regimen including excisional biopsy combined with high-dose steroids and 16 weeks of triple antimicrobial therapy that resulted in clinical cure and an excellent neurologic outcome.

Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?

BACKGROUND: Diagnosis of adolescent polycystic ovary syndrome (PCOS) remains a challenge despite several existing criteria, and may be difficult to distinguish from pubertal changes. Different parameters to study ovarian function using ultrasonography have been proposed, but there is still no consensus about their diagnostic value. OBJECTIVE: To evaluate the role of ultrasonography in the diagnosis of adolescent PCOS by reviewing available studies that assessed the ovarian volume (OV) and other ovarian morphological features such as location and number of follicles, stromal area, and volume. METHODS: MEDLINE/PubMed database were searched to identify studies that assessed ovarian characteristics of adolescent PCOS patients by ultrasound. Studies on adults were also reviewed if study population included adolescents and stromal characteristics were assessed by three-dimensional (3D) sonogram. RESULTS: Five studies, including 262 PCOS adolescents (10-19 years of age) and two-dimensional (2D) ultrasound analysis, were identified. Mean OV was 9.29 cm³ for PCOS patients and 4.77 cm³ for controls. The morphology of ovarian follicles, when reported, showed multiple (>10) peripheral follicles in 83% of cases. Two studies, including 157 PCOS adolescents and young women (15-35 years of age) and 2D and 3D ultrasound analysis, were identified. Patients with PCOS patients had a MOV 13.1 cm³, multiple follicles (>15), and a statistically significant greater S/A ratio compared to controls. Stromal volume indices were positively correlated with hyperandrogenemia in PCOS patients. CONCLUSION: Pelvic ultrasound is an increasingly important aid in the diagnosis of PCOS in adolescents. Besides ovarian volume, ovarian morphology must be assessed with 2D ultrasound to look for peripherally located multiple follicles. Further studies are warranted to evaluate the utility of 3D ultrasonographic assessment in adolescents with PCOS.

Evaluation of the pro-inflammatory cytokine tumor necrosis factor-α in adolescents with polycystic ovary syndrome.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) often suffer from comorbidities associated with chronic inflammation characterized by elevations in pro-inflammatory cytokines. There is limited data on markers of chronic inflammation, in particular Tumor Necrosis Factor-alpha (TNF-α), in adolescents with PCOS. OBJECTIVES: To compare serum levels of TNF-α in overweight or obese adolescents with PCOS and obese controls. In the PCOS group, to correlate serum TNF-α levels with body mass index (BMI) z-score, severity of hyperandrogenism, degree of insulin resistance, and ovarian ultrasonographic characteristics. METHODS: We performed a cross-sectional retrospective analysis of clinical and biochemical findings in 23 overweight or obese adolescent females with PCOS (mean BMI z-score 2, mean age 15.2 yrs) and 12 obese age- and sex-matched controls (mean BMI z-score 2, mean age 14.1 y). All subjects were post-menarchal. Serum TNF-α levels were compared between groups. In the PCOS group, cytokine levels were correlated with BMI z-score, androgen levels, fasting insulin and glucose levels as well as ovarian ultrasonographic features. RESULTS: Both groups were comparable in age, BMI z-score, fasting glucose, and fasting insulin. Mean free testosterone was 9.76 ± 5.13 pg/mL in the PCOS group versus 5 ± 2.02 pg/mL in the control group (P = .0092). Serum TNF-α was 7.4 ± 4 pg/mL in the PCOS group versus 4.8 ± 3.16 pg/mL in the control group (P = .0468). There was no significant correlation between serum TNF-α and BMI z-score, free testosterone, fasting insulin, or fasting glucose. No correlation existed between serum TNF-α and ovarian follicle number, distribution, or volume. CONCLUSIONS: Serum TNF-α is elevated in overweight/obese adolescents with PCOS. Chronic inflammation in adolescents with PCOS render them at a potential increased risk for the development of atherosclerosis, type 2 diabetes, cancer, infertility, and other comorbidities. Every effort should be made to identify adolescents with PCOS early and initiate aggressive therapy to prevent future complications.

Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas.

BACKGROUND: Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS: Key eligibility criteria included age ≥ 2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m(2)/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS: Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS: Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib.

This report describes a 6-year-old boy with disseminated low-grade astrocytoma and ventriculo-peritoneal shunt, who developed recurrent ascites while receiving sorafenib on a clinical trial. Laboratory analysis of the peritoneal fluid showed no elevation of protein content and no evidence of underlying infection or tumor dissemination. This report highlights ascites as a previously unrecognized adverse reaction to sorafenib in a patient with a ventriculo-peritoneal shunt. We conclude that such patients should be closely monitored for this complication when treated with sorafenib.