Showing papers by "Leslie N. Sutton published in 1995"

Proton MR spectroscopy of pediatric cerebellar tumors.

Abstract: PURPOSE To investigate the role of proton MR spectroscopy in pediatric cerebellar tumor diagnosis. METHODS Single voxel pulse sequences with long echo time (135 or 270 milliseconds, voxel size 8 to 19 cm3), were used to obtain proton spectra of primary pediatric cerebellar tumors. Eleven primitive neuroectodermal tumors (patient age, 2 to 12 years; mean, 7 years), 11 low-grade astrocytomas (age, 2 to 16 years; mean, 9 years), 4 ependymomas (age, 1 to 6 years; mean, 4 years), 1 mixed glioma ependymo-astrocytoma (age, 11 years), 1 anaplastic ependymoma (age, 7 years), 1 ganglioglioma (age, 14 years), and 1 malignant teratoma (age, 6 days) were studied. Control cerebellum spectra were acquired from five patients without abnormality in cerebellum (age, 2 to 15 years; mean, 8 years). The signal intensities from choline-containing compounds (Cho), creatine/phosphocreatine (Cr), N-acetyl-aspartate (NAA), and lactate (Lac) were quantified. The mean and standard deviation of metabolite ratios were calculated. RESULTS The control spectra ratios (NAA:Cho = 1.49 +/- 0.36, Cr:Cho = 1.13 +/- 0.23) were distinct from the tumor spectra (NAA:Cho = 0.41 +/- 0.27 and Cr:Cho = 0.37 +/- 0.23). Most of primitive neuroectodermal tumors had low NAA:Cho (0.17 +/- 0.09) and Cr:Cho (0.32 +/- 0.19). Compared with primitive neuroectodermal tumors, low-grade astrocytomas and ependymomas had higher NAA:Cho ratio (0.63 +/- 0.19 and 0.39 +/- 0.12). The Cr:Cho ratio was higher for ependymomas (0.60 +/- 0.20) than for astrocytomas (0.27 +/- 0.12) and primitive neuroectodermal tumors. No NAA was found in the malignant teratoma. Lac:Cho ratio was 0.66 +/- 0.40, 0.58 +/- 0.30, and 0.08 +/- 0.12 for astrocytoma, ependymoma, and primitive neuroectodermal tumor, respectively. Lactate was elevated in the mixed glioma ependymo-astrocytoma, ganglioglioma, and teratoma. The NAA and lactate signals were sometimes obscured by lipids in the spectra. Discriminant analysis was carried out using NAA:Cho and Cr:Cho ratios to differentiate the three major tumor types. The sensitivity/specificity values for diagnosing astrocytoma, ependymoma, and primitive neuroectodermal tumor were found to be 0.91/0.84, 0.75/0.92, and 0.82/0.89, respectively, based on this study. CONCLUSION In many cases, proton MR spectroscopy can be used to help differentiate cerebellar primitive neuroectodermal tumor, low-grade astrocytoma, and ependymoma.

Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery.

Abstract: The feasibility of radical surgery for astrocytomas of the optic chiasm/hypothalamus has been reported by several groups. Such surgery carries significant risks, however, including permanent damage to the pituitary gland, optic apparatus, hypothalamic structures, and carotid arteries. The benefits of radical surgery, both in terms of efficacy and toxicity, should, therefore, be evaluated against standard therapy, as is usually done for new chemotherapeutic protocols. To this end, a retrospective review was performed of 33 patients treated at Children's Hospital of Philadelphia between 1976 and 1991 who met criteria that would have made them eligible for radical surgery in many centers today, but were treated with either no surgery or conservative surgery (< 50% resection) or biopsy followed by adjuvant therapy with local radiation therapy (29 patients) and/or chemotherapy with actinomycin-D and vincristine (18 patients). The review encompassed all children with a globular enhancing mass of at least 2 cm in the hypothalamic/chiasmatic region, no evidence of optic nerve involvement or involvement of the optic radiations by computerized tomography or magnetic resonance imaging, and follow up of at least 3 years. All but one patient had tissue confirmation of a low-grade or pilocytic astrocytoma. Thirteen of the patients were 2 years of age or younger at diagnosis. Five individuals died: three of tumor progression, one of acute shunt malfunction, and one of intercurrent infection. The remaining 28 were alive at last follow up, a mean of 10.9 years from diagnosis. Twenty-three surviving patients have functional vision in at least one eye, 12 require no endocrine replacement, and 16 are in or have completed schooling with regular academic requirements. If radical surgery is to become standard care for children with low-grade astrocytomas of the hypothalamic/chiasmatic region, long-term survival and functional outcome will have to equal or surpass those of historical controls who were treated conservatively.

Proximal fibular osteochondroma with associated peroneal nerve palsy: a review of six cases.

Abstract: Osteochondroma of the proximal fibula is relatively common, but reports of this lesion in conjunction with peroneal nerve palsy have been scarce. Six patients with peroneal nerve palsy and fibular exostosis are presented with the results of electrical studies, radiographic evaluation, physical examination, and operative treatment. A wide variation in presentation and outcome was observed. Preoperative and postoperative electromyography and nerve-conduction studies are useful in evaluation. A heightened awareness of this entity is required to avoid permanent damage in an otherwise treatable condition.

p53 gene mutations in pediatric brain tumors

Abstract: We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4-8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wild-type allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients.

Isochromosome 17q demonstrated by interphase fluorescence in situ hybridization in primitive neuroectodermal tumors of the central nervous system.

Abstract: We previously reported an i(17q) as a non-random finding in childhood primitive neuroectodermal tumors (PNETs) of the central nervous system. In the present study, we describe a two-color interphase fluorescence in situ hybridization (FISH) assay for detection of chromosome 17 abnormalities in tumors. Thirty-four PNETs were analyzed by FISH with a series of chromosome 17-specific probes which map to 17p13.3-17q25. The results from the FISH assay were then compared to the karyotypes prepared from the tumors. Ten of the 34 cases demonstrated an i(17q) by FISH and standard cytogenetics. Two PNETs were shown to have an i(17q) by FISH alone, and three additional tumors had deletions of 17p. Thus, a total of 15 of 34 (44%) of the PNETs in this series had a deletion of 17p. This study confirms and extends our previous reports that an i(17q) is the most common cytogenetic abnormality in PNETs. The interphase FISH assay which we employed will have clinical utility for diagnosis of children with malignant brain tumors, and it may be used for identification of tumors with 17p deletions for molecular studies aimed at identifying disease genes.

Exon scanning for mutations of the NF2 gene in pediatric ependymomas, rhabdoid tumors and meningiomas.

Abstract: Deletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 (NF2) locus. The purpose of our study was to determine the frequency of germ-line and somatic NF2 mutations in a selected group of brain tumors in children. Using single-strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ-line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF2 might be responsible for tumorigenesis.

Occipitocervical arthrodesis in children. A new technique and analysis of results.

Abstract: A new wiring technique for occipitocervical arthrodesis was used in sixteen consecutive children between 1985 and 1992. The twelve boys and four girls had an average age of nine years and six months (range, two years and five months to nineteen years and three months) at the operation. The arthrodesis was performed between the occiput and the second cervical vertebra in ten patients and between the occiput and the third cervical vertebra in six. The instability was related to congenital anomalies (six patients), decompression for cervical stenosis (four patients), Down syndrome (three patients), trauma (one patient), resection of a tumor (one patient), and neurofibromatosis (one patient). Six patients needed a laminectomy for decompression because of cervical stenosis or for removal of a tumor. All of the patients were managed with an autogenous bone graft from the iliac crest and postoperative immobilization with a halo device. Fusion was achieved in fifteen of the sixteen patients. Complications developed in seven patients. The use of wire fixation, combined with the inherent stability of the bone-graft construct, allowed for removal of the halo device relatively early (range, six to twelve weeks), before the fusion was fully mature. No graft was displaced. All of the patients were followed at least until there was radiographic evidence of fusion (fifteen patients) or until a reoperation was performed (one patient). The average duration of follow-up was thirty-seven months (range, twelve to 108 months).

Tissue Lactate in Pediatric Head Trauma: A Clinical Study Using 1H NMR Spectroscopy

Abstract: In order to define the metabolic abnormalities associated with different types of pediatric head injury, proton magnetic resonance spectroscopy was performed on 21 cerebral regions obtained from 17 pa

Deep Hypothermia Diminishes the Ischemic Induction of Heat-Shock Protein-72 mRNA in Piglet Brain

Abstract: Background and Purpose Expression of the 72-kD heat-shock protein (HSP72) has served as a useful indicator of ischemic stress after cerebral ischemia. Moderate hypothermia (30°C) has been reported to block the induction of HSP72 after a brief episode of forebrain ischemia. The objective of the present study was to examine the effects of deep hypothermia (15°C) on expression of HSP72 after a prolonged period of cerebral ischemia. Methods Piglets, 19 to 23 days old, were placed on cardiopulmonary bypass, and brain temperature was lowered to 23°C (n=9) or 15°C (n=9) before circulatory arrest for 1 hour. In an additional group of animals (n=5), the temperature was lowered to 29°C before arrest for 45 minutes. All animals were reperfused at 37°C for 2 hours, and the regional expression of HSP72 mRNA was assessed using in situ hybridization. Results After ischemia at 15°C, expression of HSP72 mRNA was limited to a few scattered regions of cerebral cortex; the percentage of cortex exhibiting HSP72 mRNA was 23±7%...

Growing skull fractures and their craniofacial equivalents.

Abstract: Growing skull fractures occur most commonly after head injury; however, their "craniofacial equivalents" may occur after neurosurgical or craniofacial operations in pediatric patients. Experience with five separate cases is reviewed, including one case that involved the anterior cranial base and presented with vertical dystopia and proptosis. Necessary contributing factors appear to include (1) cranial bone defect, (2) dural tear, and (3) expanding intracranial process (e.g., growth of the brain). Prompt recognition and the diagnosis of the problem are essential to prevent the development of progressive neurological complications. The pathophysiology and principles of surgical management of these complex problems are explored in detail.