Leslie N. Sutton

Bio: Leslie N. Sutton is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Fetal surgery & Primitive neuroectodermal tumor. The author has an hindex of 69, co-authored 261 publications receiving 16734 citations. Previous affiliations of Leslie N. Sutton include Children's National Medical Center & University of Arkansas for Medical Sciences.

A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

Abstract: The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatalsurgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Conclusions Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.)

Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age.

Abstract: Head injury in the youngest age group is distinct from that occurring in older children or adults because of differences in mechanisms, injury thresholds, and the frequency with which the question of child abuse is encountered. To analyze some of these characteristics in very young children, the authors prospectively studied 100 consecutively admitted head-injured patients 24 months of age or younger who were drawn from three institutions. Mechanism of injury, injury type, and associated injuries were recorded. All patients underwent ophthalmologic examination to document the presence of retinal hemorrhages. An algorithm incorporating injury type, best history, and associated findings was used to classify each injury as inflicted or accidental. The results confirmed that most head injuries in children younger than 2 years of age occurred from falls, and while different fall heights were associated with different injury types, most household falls were neurologically benign. Using strict criteria, 24% of injuries were presumed inflicted, and an additional 32% were suspicious for abuse, neglect, or social or family problems. Intradural hemorrhage was much more likely to occur from motor vehicle accidents and inflicted injury than from any other mechanism, with the latter being the most common cause of mortality. Retinal hemorrhages were seen in serious accidental head injury but were most commonly encountered in inflicted injury. The presence of more serious injuries associated with particular mechanisms may be related to a predominance of rotational rather than translational forces acting on the head.

Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy

Abstract: ✓ It has previously been reported in a single-institution trial that progression-free survival of children with medulloblastoma treated with radiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cisplatin, and vincristine chemotherapy during and after radiotherapy was better than the outcome in children treated with radiotherapy alone. To better characterize long-term outcome and duration of disease control, this treatment approach was used for 10 years and expanded to three institutions. Sixty-three children with posterior fossa medulloblastomas were treated with craniospinal local-boost radiotherapy and adjuvant chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligible for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic disease, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factor...

Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele.

Abstract: ContextHindbrain herniation occurs in a large percentage of children with myelomeningocele and is the leading cause of death in this population. The effect of early fetal closure of myelomeningocele on hindbrain herniation is unknown.ObjectiveTo determine whether early fetal closure of myelomeningocele affects hindbrain herniation.DesignCase series of patients undergoing fetal myelomeningocele closure with serial measurements of hindbrain herniation and a mean follow-up of 182 days.SettingTertiary care medical center.ParticipantsTen patients undergoing fetal myelomeningocele closure at 22 to 25 weeks' gestation between March 1998 and February 1999.Main Outcome MeasuresNeed for shunt placement; degree of hindbrain herniation (grades 0-3) found on magnetic resonance imaging (MRI) performed prior to surgery and 3 and 6 weeks after fetal surgery, as well as shortly after birth; gestational age at delivery.ResultsAll initial fetal MRI scans performed at 19 to 24 weeks' gestation showed significant (grade 3) cerebellar herniation and absence of spinal fluid spaces around the cerebellum. Six fetuses were delivered electively at 36 weeks' gestation after lung maturity was established. The other 4 were delivered prematurely, at 25, 30, 30, and 31 weeks of gestation, and the 25-week gestation neonate died. All 9 surviving neonates showed improvement in the hindbrain hernia at the 3-week postoperative fetal scan (grade 2, n = 4; grade 1, n = 5). On the postnatal scan, all patients showed grade 1 hindbrain herniation. Only 1 patient required placement of a ventriculoperitoneal shunt.ConclusionIn this series of patients, fetal myelomeningocele closure resulted in improvement in hindbrain herniation as demonstrated by serial MRI scans.

A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results.

Abstract: As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties. After CRT, children with brain tumors also demonstrated a fall in a wide range of achievement scores and an increased need, over time, for special help in school. The 2-year results of this study suggest that children with brain tumors treated with CRT are cognitively impaired and that these deficits worsen over time. The younger the child is at the time of treatment, the greater is the likelihood and severity of damage. These children, although not retarded, have a multitude of neurocognitive deficits which detrimentally affects school performance. New treatment strategies are needed for children with malignant brain tumors.

Cancerous stem cells can arise from pediatric brain tumors

Abstract: Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2, musashi-1, bmi-1, maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.

The new WHO classification of brain tumours.

Abstract: The new edition of the World Health Organization (WHO) book on 'Histological Typing of Tumours of the Central Nervous System' reflects the progress in brain tumour classification which has been achieved since publication of the first edition in 1979. Several new tumour entities have been added, including the pleomorphic xanthoastrocytoma, central neurocytoma, the infantile desmoplastic astrocytoma/ganglioglioma, and the dysembryoplastic neuroepithelial tumour. The list of histological variants has also been expanded. In line with recent morphological and molecular data on glioma progression, the glioblastoma is now grouped together with astrocytic tumours. The classification of childhood tumours has been largely retained, the diagnosis primitive neuroectodermal tumour (PNET) only being recommended as a generic term for cerebellar medulloblastomas and neoplasms that are histologically indistinguishable from medulloblastoma but located in the CNS at sites other than the cerebellum. The WHO grading scheme was revised and adapted to new entities but its use, as before, remains optional.

Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC)

Abstract: The health-care facility environment is rarely implicated in disease transmission, except among patients who are immunocompromised. Nonetheless, inadvertent exposures to environmental pathogens (e.g., Aspergillus spp. and Legionella spp.) or airborne pathogens (e.g., Mycobacterium tuberculosis and varicella-zoster virus) can result in adverse patient outcomes and cause illness among health-care workers. Environmental infection-control strategies and engineering controls can effectively prevent these infections. The incidence of health-care--associated infections and pseudo-outbreaks can be minimized by 1) appropriate use of cleaners and disinfectants; 2) appropriate maintenance of medical equipment (e.g., automated endoscope reprocessors or hydrotherapy equipment); 3) adherence to water-quality standards for hemodialysis, and to ventilation standards for specialized care environments (e.g., airborne infection isolation rooms, protective environments, or operating rooms); and 4) prompt management of water intrusion into the facility. Routine environmental sampling is not usually advised, except for water quality determinations in hemodialysis settings and other situations where sampling is directed by epidemiologic principles, and results can be applied directly to infection-control decisions. This report reviews previous guidelines and strategies for preventing environment-associated infections in health-care facilities and offers recommendations. These include 1) evidence-based recommendations supported by studies; 2) requirements of federal agencies (e.g., Food and Drug Administration, U.S. Environmental Protection Agency, U.S. Department of Labor, Occupational Safety and Health Administration, and U.S. Department of Justice); 3) guidelines and standards from building and equipment professional organizations (e.g., American Institute of Architects, Association for the Advancement of Medical Instrumentation, and American Society of Heating, Refrigeration, and Air-Conditioning Engineers); 4) recommendations derived from scientific theory or rationale; and 5) experienced opinions based upon infection-control and engineering practices. The report also suggests a series of performance measurements as a means to evaluate infection-control efforts.