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F H Gilles

Publications and source records attributed to F H Gilles.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization.

PURPOSE: Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. METHODS: MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. RESULTS: Taurine (Tau) was significantly elevated in medulloblastomas (P < .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentration, in pineal germinomas. Creatine (Cr) was significantly reduced in pilocytic astrocytomas, distinguishing them from All Other (P < .000001). The MR spectra of choroid plexus papillomas exhibited low Cr (P < .01) concentrations; however, myoinositol was elevated (P < .01) and total choline (tCho) (P < .0001) was reduced relative to All Other. Choroid plexus carcinomas had low Cr (P < .01 versus All Other) and the lowest Cr/tCho ratio (P < .0001 versus All Other) among all tumors studied. Guanidinoacetate was reduced in low-grade astrocytomas and anaplastic astrocytomas (P < .00001) versus All Other, whereas ependymoma and anaplastic ependymomas exhibited particularly low N-acetylaspartate (P < .00001 versus All Other). CONCLUSION: Quantitative proton MR spectroscopy reveals features of pediatric brain tumors that are likely to improve preoperative diagnoses.

Adolescent↗
PubMed2004

Abducens length and vulnerability?

BACKGROUND: Several sources have attributed the vulnerability of the abducens nerve to its long intracranial course. However, other anatomic factors likely contribute to the apparent vulnerability of the abducens nerve to mass lesions and trauma. METHODS: The authors performed a two-part anatomic study of the abducens nerve. In the first part of the study, they compared the length of the abducens with another cranial nerve, the trochlear, at the autopsy of 26 pediatric patients. In the second part of the study, the authors used an endoscopic exposure of these two cranial nerves in a preserved human cadaver head. RESULTS: The abducens nerve was consistently approximately one-third the length of the trochlear nerve at all ages that they studied. The endoscopic views revealed the structural and vascular relationships of the abducens nerve in situ. CONCLUSIONS: The authors conclude from these findings and the literature that abducens nerve vulnerability results from factors other than its intracranial length.

Abducens Nerve↗
PubMed2001

Choroid plexus tumors in children: significance of stromal invasion.

OBJECTIVE: A group of choroid plexus tumors fit the cellular criteria for choroid plexus papilloma (CPP) except for invasion into the adjacent parenchyma, with associated loss of the normal villus architecture at the site of invasion. These tumors retain a benign cellular appearance. In the existing literature, it is unclear whether these tumors are classified as choroid plexus carcinomas or as CPPs. In our experience, although evidence of invasion is present, these tumors tend to exhibit benign behavior. We suggest that stromal invasion of this type remains consistent with a benign clinical course, although surgical results may demonstrate higher morbidity rates, given the invasive nature of the tumors. The failure to classify these tumors as CPPs may explain some of the variability in outcomes reported for various studies. METHODS: To study this question, clinical and histological data for children diagnosed with CPPs (either with or without stromal invasion) between 1985 and 1995 were examined. Only cases with pre- and postoperative magnetic resonance imaging data were included in the series. RESULTS: A total of 12 patients with CPPs were identified, with 4 tumors being notable for stromal invasion. After gross total tumor removal, none of the eight children with CPPs received adjuvant therapy at our institution; all are alive without evidence of tumor recurrence after surgical excision (mean, 108 mo). Of the four patients with stromal invasion, three underwent gross total resection. The one patient who underwent subtotal resection received chemotherapy at another facility. All four of these patients are alive, after a mean of 100 months of follow-up monitoring. CONCLUSION: It is recommended that CPPs with a benign cellular appearance but with evidence of local parenchymal invasion and loss of the normal villus architecture at the site of invasion be classified as CPPs. Patients with these tumors respond to surgical therapy alone, without the need for adjuvant treatment.

Child↗
PubMed2000

Limitations of the World Health Organization classification of childhood supratentorial astrocytic tumors. Children Brain Tumor Consortium.

BACKGROUND: In the context of many implied but not rigorously stated histologic feature combinations, the World Health Organization (WHO) classification of astrocytic tumors specifies only the presence or absence of endothelial proliferation, necrosis, and mitosis to distinguish astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. METHODS: The authors examined the effects of these and other reliably recognized histologic features on survival in the Childhood Brain Tumor Consortium (CBTC) sample of 340 children with supratentorial astrocytic tumors. RESULTS: Overall, the WHO criteria distinguished only two prognostically distinct classes of astrocytomas. When the specific combinations of the three features were unambiguously designated, three diagnostic categories resulted. These revised diagnostic categories are consistent with WHO guidelines and have significantly different survival distributions. However, neither the original WHO diagnoses nor the revised categories adequately separated these tumors prognostically, because histologic features other than those specified by WHO were significantly associated with improved or worsened survival. CONCLUSIONS: Classifications based on small numbers of specified histologic features may not be feasible because they inadequately separate childhood astrocytic tumors into prognostically homogeneous groups. Preferable classification techniques are those that simultaneously account for all reliably recognized histologic features.

Adolescent↗
PubMed2000

Autoregulation of the interleukin-1 system and cytokine-cytokine interactions in primary human astrocytoma cells.

Cytokines are proposed to play important roles in brain tumor biology. Previous studies reported on interleukin-1beta (IL-1beta) production and IL-1 receptor type I (IL-1RI, signaling receptor) expression in human astrocytomas, and on IL-1beta action in astrocytoma cell lines. However, all studies that have tested the direct action of cytokines have used exclusively astrocytoma cell lines, which do not recapitulate the in situ astrocytoma. Here, we demonstrate that astrocytoma cells obtained shortly after tumor neurosurgical resection respond to the direct application of human IL-1beta with a significant upregulation of IL-1alpha, IL-1beta, IL-1RI, and tumor necrosis factor-alpha (TNF-alpha) mRNAs. IL-1 receptor antagonist (IL-1Ra, an endogenous inhibitor that blocks IL-1alpha and IL-1beta actions) mRNA was not upregulated. Application of heat-inactivated IL-1beta had no effect on any cytokine component examined, demonstrating specificity of action. On the other hand, IL-1beta application did not modulate any cytokine component in acutely resected and dissociated primitive neuroectodermal tumor cells. The data have implications for a positive autoregulatory IL-1beta feedback system and synergistic IL-1beta <=> TNF-alpha interactions, which can be involved in the growth of pilocytic astrocytomas. The results together with our previous studies also support the notion that IL-1Ra or a compound with similar cytokine inhibitory activity could be useful for brain immunotherapy of astrocytomas.

Astrocytoma↗
PubMed1998

Interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor type I, IL-1 receptor antagonist, and TGF-beta 1 mRNAs in pediatric astrocytomas, ependymomas, and primitive neuroectodermal tumors.

Interleukin-1 alpha (IL-1 alpha), IL-1 beta, interleukin-1 receptor type I (IL-1RI, signaling receptor), and IL-1 receptor antagonist (IL-1Ra, endogenous inhibitor) are pivotal components of the IL-1 system. IL-1 and other cytokines induced by IL-1, such as TGF-beta 1, may participate in the growth of various tumor cells. In children, primary nervous system tumors represent the most common solid malignancy. We investigated the levels of IL-1 alpha, IL-1 beta, IL-1RI, IL-1Ra, and TGF-beta 1 mRNAs in pediatric astrocytomas (n = 19), ependymomas (n = 13), and primitive neuroectodermal tumors (n = 22) using sensitive and specific RNase protection assays. The data show a significant distinct cytokine mRNA profile among brain tumor types. Pilocytic, nonpilocytic, and anaplastic astrocytomas have significant increased levels of IL-1 beta, IL-1RI, and TGF-beta 1 mRNAs, but low levels of IL-1Ra mRNA; this may have implications for an IL-1 beta feedback system and IL-1 beta<-->TGF-beta 1 interactions in astrocytomas. Ependymomas show increased levels of IL-1 alpha and IL-1 beta mRNAs associated with low levels of IL-1Ra mRNA; primitive neuroectodermal tumors do not exhibit increased levels of any cytokine component examined. The data also suggest that a dysregulation of the balance between stimulatory and inhibitory cytokines may be involved in the growth and development of brain tumors via autocrine/paracrine mechanisms.

Adolescent↗
PubMed1998

Myelopathy resulting from invasive aspergillosis.

Aspergillus, a ubiquitous mold, may cause invasive and fatal disease in immunosuppressed patients. Myelopathy is an uncommon presentation of invasive aspergillosis. This report describes three children admitted to the hospital between 1988 and 1995 who developed myelopathy as the first evidence of invasive aspergillosis. All had advanced leukemia and were profoundly immunosuppressed because of chemotherapy and broad-spectrum antibiotics. Weakness and pain presented first; then, sensation to pain and temperature was lost 2 to 6 days later, followed by complete myelopathy. Multiple brain lesions were seen on magnetic resonance imaging in one patient. Despite antifungal therapy, aspergillosis proved fatal within 1 month of onset of myelopathy in all patients. Physicians caring for immunocompromised children should be aware of myelopathy as a presentation of invasive aspergillosis.

Adolescent↗
PubMed1998

Clusters of histologic characteristics in children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Five quantitative histologic factors, differing linear combinations of 26 reliably recognized histologic features, account for much of the histologic variance in 1068 children with infratentorial neuroglial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the Spongy, Proliferative, Ring, Fibrillary, and Nuclear factors in cluster analyses and identified 11 clusters of children's tumors. Each had statistically significant differences in histology and relative histologic homogeneity. Three clusters had ependymoma-like histologic features; 4 had astrocytoma-like features; and 4 had primitive neuroectodermal-like (PNET or medulloblastoma) features. Each cluster had a unique high/low mean factor score pattern. Multiple operative and other clinical features characterized the three groups of clusters. We used Kaplan-Meier survival models to test for differences in survival among clusters and proportional hazards survival models to adjust for associated covariates. Among the 'ependymoma' clusters the 5 year survival probability ranged from 0.25 to 0.54. Among the 4 'astrocytoma' clusters, 5 year survival probability ranged from 0.59 to 0.94. The 5 year survival probability for the 'medulloblastoma' clusters ranged from 0.20 to 0.44. Within the three groups, clusters had differing covariates associated with survival. The tumor clusters identified in this study ensure relatively homogeneous histologic subsets. The five factor scores of a child's tumor provide the basis for finding the cluster nearest to that tumor. We propose that this tumor clustering strategy be employed for selection of children and for analyses of therapeutic clinical trials.

Astrocytoma↗
PubMed1998

Groups of histopathologic abnormalities in brains of very low birthweight infants.

The neuropathologic changes in brains of very premature infants are well recognized but relatively few studies have attempted to identify if specific neuropathologic features cluster together. These data could assist in determining pathogenetic mechanisms of immature brain injury. The goal of this study is to identify which, if any, combinations of histologic features occur together. We identified the presence or absence of 19 histologic features in the brains of 67 infants from a multicenter study of 1,665 prematurely born infants whose birthweight was 500-1,500 grams. We used clustering algorithms and factor analysis to group pathologic features that occurred together. Our results indicate that certain histopathologic features do cluster. For example, telencephalic white matter astrocytosis occurs in 2 groups: 1) associated with amphophilic globules, and, 2) in an uncorrelated group, associated with focal macrophage deposits and coagulative necroses. Parenchymal hemorrhage was not found to be associated with any telencephalic leukoencephalopathy, regardless of whether characterized by rarefaction, astrocytosis, focal coagulative necroses, or foci of macrophages in the white matter. Intraventricular hemorrhage and germinal matrix hemorrhage were not seen together more often than by chance expectation. Intraventricular hemorrhage was only marginally associated with parenchymal hemorrhage. Our data indicate that specific histopathologic features tend to preferentially cluster with each other in groups. This clustering may represent the manifestation of a common mechanism for each. These data should be valuable indicators for future research attempting to establish pathogenesis.

Algorithms↗
PubMed1998

Prognostic limitations of the Daumas-Duport grading scheme in childhood supratentorial astroglial tumors.

The Daumas-Duport grading scheme (DDGS) is a commonly used method for determining the grade of a tumor. It scores 4 histologic features and is used as a prognostic tool in adult astroglial tumors. This system of assigning children to prognostically homogeneous groups has not been evaluated. The Childhood Brain Tumor Consortium (CBTC) database includes 327 children with a CBTC assigned World Health Organization (WHO) diagnosis of supratentorial astroglial tumor and histologic features necessary for Daumas-Duport grading. We compared survival estimates for tumors within and between DDGS grades using a slightly broadened definition of endothelial prominence. The DDGS yielded only 3 histologic groups in children and only 2 prognostically differing groups. Subgroups within DDGS grades had significantly different survival distributions. The summing of 4 disparate histologic features in the DDGS is inadequate for the assessment of childhood supratentorial astroglial tumors. A classification system more fully summarizing the complete histologic content of tumors is most likely to provide diagnoses useful for clinical purposes.

Adolescent↗
PubMed1997

Frequency of neuropathological abnormalities in very low birth weight infants.

The occurrences of histologic changes in the central nervous system of very low birth weight infants (500 to 1500 grams) according to gestational age and postnatal age are incompletely reported. In order to better understand the abnormalities present in this patient population, the brains of 67 very low birth weight infants who died after having had at least one cranial ultrasound scan were studied. More than half the infants were born at gestational ages of 24 to 26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who had to agree on the presence and/or absence of each histologic characteristic. Among infants who died within 24 h of birth, fully one quarter had parenchymal hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20% had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury to the nervous system was common. Compared with infants who died before the sixth day, those who survived at least 6 days were twice as likely to have moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than those who died before the 7th postnatal day. Parenchymal hemorrhage and moderate/severe ventriculomegaly decreased in frequency with increasing gestational age. On the other hand, the older the gestational age, the higher the likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage foci, and zones of coagulative necrosis upon neuropathologic examination. Our data indicate that several central nervous system abnormalities appear to increase with both older gestational age and older postnatal age for infants born weighing less than 1500 grams. We were unable, however, to determine the relative contribution of gestational age and postnatal age to the specific neuropathologic findings in this study.

Aging↗
PubMed1997

Pediatric intracranial hemangioendotheliomas: case report.

OBJECTIVE AND IMPORTANCE: Intracranial hemangioendotheliomas are rare lesions, especially in the pediatric age group. Recognizing hemangioendotheliomas as a differential in intracranial tumors of vascular origin is important; complete excision results in a cure, and medical therapy for those lesions that are not resectable produces long-term survival. CLINICAL PRESENTATION: We report two patients, a 7-year-old female patient with a lesion in the right gasserian ganglion and a 3-month-old male patient with a cervicomedullary junction tumor. INTERVENTION: The 7-year-old underwent a gross total removal with no recurrence. The 3-month-old underwent a partial resection followed by treatment with interferon alpha-2a, with a decrease in the size of the residual tumor. Both patients have been followed for more than 4 years without a recurrence or progression of the tumor. CONCLUSION: Hemangioendotheliomas are fairly indolent tumors and may be treated with complete surgical resection, resulting in a cure. In cases in which complete tumor removal is not possible, adjunctive therapy with interferon alpha-2a may control residual tumor growth.

Brain Neoplasms↗
PubMed1996

Usefulness of [18F]fluorodeoxyglucose positron emission tomography in pediatric epilepsy surgery.

We sought to analyze our experience with pediatric epilepsy surgery patients to determine the place of [18F]fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET) in the preoperative evaluation of such children relative to chronic invasive intracranial monitoring. Fifty-six children who received an interictal FDG-PET as part of a phase 1 epilepsy surgery evaluation were compared with 44 children who did not have this study in a retrospective analysis of 100 patients accrued over a 4-year period. There was no significant difference between the two groups of children in terms of age or follow-up or was there a significant difference between the FDG-PET group and the no-FDG-PET group in regard to the numbers of children who had surgery, the type of procedure done, whether chronic invasive intracranial monitoring was performed, or outcome. The hypometabolic area demonstrated on interictal FDG-PET was concordant with that of the epileptogenic zone as mapped out with ictal recordings from subdural electrodes in 2 of 13 patients in whom a complete data set was available for comparison. In the other 11 children there was either poor agreement between interictal FDG-PET and ictal electrocorticographic data or the interictal FDG-PET was normal in the face of an epileptogenic focus which was successfully mapped by invasive electrophysiologic techniques and excised. We conclude that one cannot exclude a child with intractable partial seizures from surgical consideration because the interictal FDG-PET is normal; nor is there sufficient correlation between the interictal hypometabolic area on FDG-PET and the epileptogenic zone in terms of anatomic location and size to justify forgoing chronic invasive intracranial monitoring in children with intractable partial seizures being evaluated for epilepsy surgery unless there is absolute concordance between all neuroimaging, clinical, and video-electroencephalographic data.

Adolescent↗
PubMed1996

Survival of children with infratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

OBJECTIVE: The goal of this study is the improvement of the prognostic information associated with conventional diagnoses. Our previous factor analysis of 26 reliably identified histological features in infratentorial childhood neuroglial tumors yielded five interpretable, uncorrelated, quantitative histological factors that we named spongy, fibrillary, proliferative, nuclear, and ring. Five quantitative scores, one for each of the five factors, provide an objective method for quantifying the histological heterogeneity of a tumor. The scores, alone or in conjunction with conventional diagnoses, identify groups of histologically homogeneous tumors. METHODS: Multivariate Cox proportional hazards models were developed to assess the contribution of each factor to survival prognosis, after allowing patient-specific demographic and clinical data in the models as covariates. Hazard ratios, estimated for each statistically significant factor and covariate in the multivariate model, provide the basis for the determination of the prognosis. The hazard ratio is the ratio of the hazard function for subjects with an attribute, e.g., an age of 10 years, to the hazard function for subjects who have some chosen baseline attribute, e.g., an age of 1 year. The important criterion of this ratio is beta, a statistic estimated from the survival data in the Childhood Brain Tumor Consortium database of infratentorial neuroglial tumors. Kaplan-Meier survival curves were used to investigate differences in the survival of factor-determined subgroups of patients with various diagnoses. RESULTS: An increased likelihood of survival is associated with older age, more tumor removal, more recent decade of surgical intervention, and high spongy and fibrillary factor scores. A decreased likelihood of survival is associated with high nuclear, proliferative, and ring factor scores. Gender, location within the infratentorial compartment, and subsequent treatment did not add prognostic information. For certain subgroups of astrocytoma and for ependymoma and medulloblastoma, factors are important in predicting survival with greater accuracy. CONCLUSION: Factor scores provide clinically useful quantitative estimates of survival probability that are more specific and accurate than the general estimates based on the conventional diagnosis alone.

Adolescent↗
PubMed1995

Misclassification of a prognostic dichotomous variable: sample size and parameter estimate adjustment.

Under general conditions, Lagakos showed that for an explanatory variable observed with error, the asymptotic relative efficiency (ARE) when using the observed rather than the true values in linear models, logistic models and proportional hazards models for survival is the square of the correlation between the true and observed variables. The result is useful for sample size adjustment when this correlation is estimable. Often, one cannot observe correct values of the explanatory variable under any circumstances. We show, however, that under the models considered by Lagakos for a dichotomous explanatory variable, the ARE equals the kappa statistic in a read-reread protocol. Consequently, one need not know 'truth' in this situation to estimate the ARE and to adjust sample size to maintain desired power; divide the estimated sample size obtained with the assumption of no measurement error by the consistent estimate of the kappa statistic (which is unlikely to be zero or negative). We then develop heuristically an adjusted estimate of the beta parameter in a proportional hazards survival model. The work was motivated by analyses of the Childhood Brain Tumour Consortium database. Examples from this database illustrate the method.

Brain Neoplasms↗
PubMed1995

Medulloblastoma and Collins' law: a critical review of the concept of a period of risk for tumor recurrence and patient survival.

Collins' law (CL) states that the period of risk for recurrence for a tumor is the age of the patient plus 9 months. Originally a clinical observation in Wilms' tumor, CL has been applied to other tumors such as medulloblastoma (MB). Although CL does not apply to all childhood tumors, it seems to be a valid observation for childhood MB, despite several reports of violations or exceptions to CL in the literature. We sought to test CL in a large population of children with MB from the Childhood Brain Tumor Consortium (CBTC). We analyzed data from 602 children with MB, of whom 421 died and 181 were censored but alive at the last follow-up. We found 16 additional CL exceptions to supplement the 22 already present in the literature. This is both the greatest number of exceptions and the largest MB study population for CL reported to date. We provide clinical data on our 16 uncensored exceptions to CL and critically review those 22 cases cited previously in the literature. All of the CBTC exceptions were under 6 years of age at the time of initial diagnosis and were followed for an average of 7.5 years. All 16 CBTC exceptions died. Children older than 8 years of age could not be followed for a sufficient period of time to be able to state whether CL applies; as age at initial diagnosis increases, the period of observation required to determine CL validity becomes impractically long. Exceptions to CL are rare and amounted to 3.8% of 405 uncensored CBTC patients who died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗