Biomedical subjects

L N Sutton

Publications and source records attributed to L N Sutton.

At least 55 records · Page 3Linked to original sources

PubMed1996

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma).

PURPOSE: Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. METHODS AND MATERIALS: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. RESULTS: Actuarial survival at over 6 years is 70 +/- 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected velocities during the follow-up period, while the others grew normally. Three patients have received growth hormone, and none have required thyroid replacement. CONCLUSIONS: These data suggest that medulloblastoma patients can be cured with chemotherapy and reduced doses of craniospinal irradiation. The low doses of CSART given by us in conjunction with cis-platin-based chemotherapy produce minimal neurocognitive damage. Growth velocities in very young children so treated are, however, dramatically reduced. Better means of improving the therapeutic ratio are still needed.

Age Factors↗

PubMed1996

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors.

Primitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse-free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7-fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP-staining cells were associated with a 3.0-fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.

Adolescent↗

PubMed1996

Surgical management of medulloblastoma.

Recent technological aids and understanding of pathophysiology has made the surgery of medulloblastoma safer. The guiding principle for the neurosurgeon remains removal of bulky disease, but there is no justification for removal of small amounts of tumor from critical locations. Post-operative complications include hydrocephalus, hematoma, mutism, asceptic meningitis, gastroinstestinal hemorrhage, and cervical instability. Staging is best done preoperatively with MRI, and presence of dissemination remains the most important prognostic factor in this disease. Postoperative surveillance imaging is of questionable value.

Cerebellar Neoplasms↗

PubMed1996

Gangliogliomas involving the optic chiasm.

We report three patients with gangliogliomas involving the optic chiasm via distinct mechanisms. The ganglioglioma in one patient likely originated in the temporal lobe and spread medially to involve the chiasm, and diffuse spinal cord dissemination also occurred. Chiasmal involvement in this manner and dissemination at presentation are unusual for gangliogliomas. The tumor in a second patient was intrinsic to the hypothalmus and chiasm, while in the third patient, it involved both optic tracts, and a cyst compressed the chiasm laterally. Two patients developed severe bilateral visual loss, while the other had a stable bitemporal hemianopsia. Two patients received radiotherapy, but one continued to lose vision. Although gangliogliomas rarely involve chiasm, the mechanisms by which they produce chiasmal visual loss may be diverse, and the long-term visual prognosis is variable.

Adolescent↗

PubMed1996

Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons.

Medulloepithelioma is an uncommon childhood tumor of the central nervous system (CNS) whose histopathological appearance has been confused with medulloblastoma and other childhood primitive neuroectodermal tumors (PNETs), but which has a vastly different clinical course. The authors have reviewed the clinical features and treatment responses of eight children with these rare tumors, the largest series to date. In this series, the medulloepitheliomas were equally distributed between supratentorial and infratentorial primary sites. Four patients underwent gross- or near-total resections, one patient's tumor was partially resected, and one patient had biopsy only. Biopsy and ablative surgery were not attempted in two children with pontine tumors. Treatment included both radiation and chemotherapy (four patients), radiation alone (one patient), chemotherapy alone (one patient), and no post-operative treatment (two patients). Six patients died with a mean survival of 10 months and two are disease free with neurological impairment. Both long-term survivors underwent gross-total resections of their tumors. Postmortem examination revealed diffuse CNS tumor dissemination in four patients. Medulloepithelioma, often confused with less aggressive PNETs, can mimic intrinsic brainstem glioma, responds poorly to treatment, and is prone to CNS dissemination at the time of tumor progression.

Brain Neoplasms↗

PubMed1996

Postoperative surveillance imaging in children with cerebellar astrocytomas.

The standard follow-up care for children with cerebellar astrocytomas includes regular surveillance imaging of the brain with computerized tomography or magnetic resonance. The purpose of surveillance imaging is to detect asymptomatic tumor recurrence at an early stage and permit safer reoperation. The authors evaluated the effectiveness of an intensive surveillance program for cerebellar astrocytoma and tested different models of surveillance frequency and duration to arrive at a specific recommended program. Review of the records of 93 children with typical cerebellar astrocytomas who received follow-up care between 1975 and 1993 was performed. Immediate postoperative and surveillance images were classified as showing definite equivocal, or no tumor based on the radiology report at the time the image was obtained. Various surveillance models were then tested for their predictive value for detecting tumor recurrence. Seventeen (18%) of the 93 children had tumor recurrence or progression. Eleven of these tumors were asymptomatic and detected only by surveillance image. Tumor recurred in only one patient with a total resection, whereas tumor progression occurred in five of 21 patients with equivocal postoperative images and in 11 of 14 patients with residual tumor. A model in which patients with possible or definite residual tumor after surgery undergo surveillance at 12, 18, 30, 42, and 66 months, and later have one additional image, yielded optimum predictive value for recurrence and/or progression with the fewest images. Patients with tumor recurrence were satisfactorily treated, and only one patient died. Children with totally resected cerebellar astrocytomas do not appear to benefit from routine surveillance, because the likelihood of recurrence is small. Surveillance is of benefit in those who may have subtotal resection based on the immediate postoperative imaging.

Astrocytoma↗

PubMed1995

Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up.

BACKGROUND: Gliomas of the hypothalamus and optic pathways (H/OPG) comprise 5% of pediatric intracranial tumors, present most frequently in patients younger than age 5 years, and may have a more aggressive course in younger children. This study examined clinical characteristics and consequences of treatment of young children diagnosed with H/OPG: METHODS: The authors reviewed the course, treatment, and outcomes of 46 children diagnosed with H/OPG younger than age 5 years; the median follow-up was 72 months. The median age at diagnosis was 27 months. RESULTS: Fifteen (33%) of 46 patients had neurofibromatosis-1 (NF-1). Forty children (87%) had tumor progression in the follow-up period, and tumor growth was less common in children with NF-1. Initial therapy was limited to surgical resection in three and radiation in five children. To postpone radiation until after the age of 5 years, initial therapy was limited to chemotherapy in 32 patients. Radiation was not required in 9 of these patients and was postponed for 40 months (mean) in 17. Of the 46 children, 5 died of tumor progression, 4 became blind, and 20 of 34 evaluable patients had endocrine abnormalities. Endocrinopathy did not correlate with therapy. Ten of 17 children evaluated by questionnaire required special education. There was a trend for educational problems to occur in children who were irradiated before the age of 5 years. CONCLUSIONS: Gliomas of the hypothalamus and optic pathways and their treatment cause long term morbidity in young children. Chemotherapy postpones radiation effectively, and this delay may reduce neurologic morbidity; however, 60% of children eventually relapse. By contrast, patients with NF-1 have indolent disease.

Child Behavior Disorders↗

PubMed1995

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

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.

Adolescent↗

PubMed1995

Growing skull fractures and their craniofacial equivalents.

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.

Brain↗

PubMed1995

Tissue lactate in pediatric head trauma: a clinical study using 1H NMR spectroscopy.

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 patients. On the basis of MRI scans, the regions of interest were classified as normal (6 hemispheres), or showing diffuse axonal injury (3 hemispheres), contusion (4 hemispheres), or cerebral infarction (8 hemispheres). In comparison with normal brain there was no significant elevation in tissue lactate in the diffuse axonal injury patients, but a significant increase in the regions of contusion and infarction. It is concluded that treatment strategies using buffering agents are most likely to benefit these two groups of patients.

Acidosis↗

PubMed1995

Deep hypothermia diminishes the ischemic induction of heat-shock protein-72 mRNA in piglet brain.

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 degrees 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 degrees 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 degrees C (n = 9) or 15 degrees C (n = 9) before circulatory arrest for 1 hour. In an additional group of animals (n = 5), the temperature was lowered to 29 degrees C before arrest for 45 minutes. All animals were reperfused at 37 degrees C for 2 hours, and the regional expression of HSP72 mRNA was assessed using in situ hybridization. RESULTS: After ischemia at 15 degrees 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% (mean +/- SEM). Ischemia at 23 degrees C triggered expression of HSP72 mRNA in a significantly larger portion of the cortex (68 +/- 8%, P < .001). Ischemia at 29 degrees C failed to induce substantial expression of HSP72 mRNA in the cerebral cortex. CONCLUSIONS: These results suggest that, relative to ischemia at 23 degrees C, deep hypothermia (15 degrees C) diminishes ischemic alterations leading to induction of HSP72 mRNA. The lack of cortical expression of HSP72 mRNA following ischemia at 29 degrees C may be secondary to inadequate recovery of energy metabolism.

Animals↗

PubMed1995

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

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).

Bone Nails↗

PubMed1995

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

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.

Adolescent↗

PubMed1995

Lipomyelomeningocele.

Lipomyelomeningocele is one of the more common forms of occult spinal dysraphism seen in clinical practice. It is now universally accepted that prophylactic surgery is indicated in most cases, but areas of controversy remain. These include the diagnosis and management of retethering, the value of intraoperative physiological monitoring, and indications for surgery in stable adults and when the conus is in the normal position.

Follow-Up Studies↗

PubMed1995

Proton MR spectroscopy of pediatric cerebellar tumors.

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.

Adolescent↗

PubMed1994

Surveillance scanning of children with medulloblastoma.

BACKGROUND: The standard follow-up care for children with medulloblastoma includes regular clinical evaluations and surveillance scanning of the central nervous system with computed tomography or magnetic resonance imaging. The evaluations and scanning assess the response of the tumor to treatment, detect any recurrence of disease, and monitor any complications of treatment. We compared the effectiveness of a periodic history taking and physical examination with that of surveillance scanning in detecting recurrent tumors. METHODS: We reviewed the medical records, including 794 scanning reports or scans, of 86 children with posterior fossa medulloblastoma who were followed regularly between 1980 and 1991. Recurrent tumors were classified as symptomatic if neuroimaging studies had been prompted by clinical symptoms or signs and as radiographic if the tumor had been detected by imaging in an asymptomatic patient. RESULTS: Twenty-three of the 86 children (27 percent) had a recurrence of tumor. Four recurrences (17 percent) were detected on scanning only, and 19 (83 percent) were associated with symptoms arising a median of four months after the previous scan. The median and range of survival after a recurrence of the tumor were 5 months and < 1 to 38 months, respectively, for a symptomatic recurrence and 20 months and 10 to 32 months, respectively, for a radiographic recurrence (P = 0.03). No patient survived after a recurrence. The longer survival of patients with recurrent tumors detected by scanning most likely reflects the small number of patients and lead-time and length biases associated with screening. CONCLUSIONS: Among children with medulloblastoma, surveillance scanning is of little clinical value. Scanning detected a minority of recurrences, and no patient who had a recurrence survived.

Adolescent↗

PubMed1994

Abnormalities of chromosome 22 in pediatric meningiomas.

Cytogenetic studies of eight meningiomas in young children or adolescents were performed. Two tumors exhibited normal karyotypes. Two tumors from patients with bilateral acoustic neurofibromatosis demonstrated monosomy 22 as the only abnormality. Four patients had more complicated karyotypes in which one or both of the chromosomes 22 were missing or structurally altered. The most common secondary changes in these four tumors involved monosomy or structural abnormalities of chromosome 6. These findings confirm that the primary cytogenetic changes in meningioma are similar in children and adults. Molecular analyses of pediatric meningiomas with deletions or translocations of chromosome 22 will be useful for identifying the role of chromosome 22 tumor suppressor genes in this disease.

Adolescent↗

PubMed1994

Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: age-dependent effects of whole brain radiation.

Twenty-four children, aged 1.5-20 yr at diagnosis, with noncortical brain tumors, primarily medulloblastoma, have been followed for 3-4 yr for intellectual status. All the children received craniospinal irradiation, and 19 of 24 received chemotherapy as well. For the group as a whole. Full Scale IQ fell from 104 at baseline to 91 at final follow-up. Children younger than 7 yr at diagnosis showed a significant decrease in IQ as early as year 1, and all changes from baseline to years 3 and 4 were significant. In contrast, children older than 7 yr at diagnosis did not show a significant IQ change from baseline to year 3 or 4. The Spearman correlation coefficient between IQ change and age at diagnosis from baseline to year 4 was 0.57 (P = 0.003). This study supports the hypothesis that children treated with whole brain radiation at a younger age have more severe cognitive impairment than those treated at a later age. Limitations in sample size and duration of observations do not permit us to identify whether a true plateau occurs 2-4 yr after irradiation versus a continued progressive decline in intellectual performance. Moreover, we cannot at this time distinguish between a true dementing process versus failure to acquire new cognitive skills at a rate comparable to age-matched peers.

Adolescent↗