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E L Sobel

Publications and source records attributed to E L Sobel.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1995

The applicability of Collins' Law to childhood brain tumors and its usefulness as a predictor of survival.

In 1955, Collins made the observation that tumor recurrence in children with Wilms' tumor was correlated with the child's age plus 9 months. This concept of a period of risk for recurrence was later applied to a variety of tumors in children and became known as Collins' Law (CL). The law has been a successful predictor of survival for some children with neural tumors within the central nervous system and a poor predictor for others. We tested Collins' concept of a period of risk for recurrence and extended it to survival for 14 childhood neural tumors described in the Childhood Brain Tumor Consortium (CBTC) database. The CBTC data describe clinical, surgical, and histological details (over a 49-year period in 10 institutions) from 3921 patients under the age of 21 years at the time of their first surgical procedure for a brain tumor. CL was considered to be a good predictor of survival if fewer than 10% of patients who die survive beyond the expiration of the period of risk for that child. We found that CL applied to tumors such as anaplastic astrocytoma, glioblastoma, pineoblastoma, medulloblastoma or "primitive neuroectodermal tumor," teratoma, and germinoma, as well as ependymoma, papilloma, and tumors that could not be classified; it had no predictive value in craniopharyngioma, oligodendroglioma, or plain, fibrillary, pilocytic, or protoplasmic astrocytoma. We had sufficient follow-up data to determine adherence to CL when the child's age at diagnosis was less than 8 years; it is likely that CL applies to older children with these tumors, but we did not have the data to show this unequivocally.

Adolescent↗
PubMed1995

Age-related changes in diagnoses, histological features, and survival in children with brain tumors: 1930-1979. The Childhood Brain Tumor Consortium.

In the Childhood Brain Tumor Consortium database, the proportions of older children (> or = 11 yr) with pilocytic astrocytomas, fibrillary astrocytomas, and ependymomas significantly increased (P < 0.05) over the 50 years (1930-1979) of the study. The increased proportions of pilocytic astrocytomas occurred whether the tumors were located in the supratentorial or infratentorial compartments. The increases in fibrillary astrocytomas and ependymomas were found only within the supratentorial tumor location. Some histological features found in pilocytic astrocytomas (e.g., Rosenthal fibers, granular bodies, and very low cell density) were more likely to be found in older children. Other histological features were also more likely to be found in older children (e.g., parenchymal calcification, intertwined fascicles, intermediate and large-size nuclei, pleomorphic, elongated, or irregular nuclei, prominent nucleoli, multinucleated cells, thick hyaline blood vessels, hemosiderin, and parenchymal and perivascular lymphocytes). The probability of 5-year survival for young children with supratentorial ependymomas remained at approximately 0.4 in contrast to that for young children with infratentorial ependymomas, for whom it improved, but without significant linear trend. The probability of 5-year survival for both younger and older children with primitive neuroectodermal tumors (medulloblastomas) improved, but without significant linear trend. The changes in the proportions of childhood brain tumors and histological features occurred without similar changes in the proportions of older and younger children in the cities involved between 1930 and 1979. These changes were so distinctive as to raise the possibility of significant shifts in environmental exposures in younger and older children over the 50 years of this study.

Adolescent↗
PubMed1994

Histologic feature reliability in childhood neural tumors. Childhood Brain Tumor Consortium.

We studied intraobserver reproducibility in recognizing the presence or absence of 57 histologic feature or patterns in a random subset of tumors (822) from the Childhood Brain Tumor Consortium database. The study protocol maximized consistency of the observer. We found that only six histologic features had high (> or = 0.75) reliability estimates while a large number had intermediate estimates of 0.50-0.74. Supratentorial or infratentorial tumor location sometimes altered reliability. Reliability estimates were unacceptable for certain histologic features often used as diagnostic criteria, descriptors of tumor characteristics, or markers of anaplasia. We hypothesize that low reliability reflects, in part, the need for more specific operational definitions, particularly those with subjective boundaries (e.g. granular bodies) may also contribute to low reliability. We also show that the kappa statistic, a commonly used measure of reliability, is inappropriate for very common or uncommon histologic features (e.g. features at the extremes of prevalence in the study cases) and we offer a simple empiric method for determining when an alternative measure, the Jaccard statistic, is appropriate.

Brain Neoplasms↗
PubMed1992

Temporal trends among childhood brain tumor biopsies. The Childhood Brain Tumor Consortium.

We sought temporal trends in the demographic, clinical, histologic feature, diagnostic class, and quality of life data over the interval 1930-1979 in the Childhood Brain Tumor Consortium database. The proportion of children younger than eight years old declined from 72% to 55% and the proportion of those older than ten more than doubled from 12% to 27%. The relative frequency of tumors in the supratentorial compartment increased significantly, while infratentorial tumors decreased. We found significant declines in supratentorial ependymomas and pilocytic astrocytomas. Similarly, some infratentorial tumors, especially ependymomas, decreased and brain stem tumors increased. Infratentorial medulloblastoma (primitive neuroectodermal tumor) increased significantly. Some individual histologic features which are markers of anaplasia increased in frequency in both supratentorial and infratentorial tumors. There was a significant increase in biopsies that contained nonneoplastic neural tissue in addition to tumor for both compartments and among supratentorial tumors there was a marked increase in the proportion of cases containing an indistinct neural tissue boundary. The probability of postoperative death declined, but the probability of survival five or ten years after surgery did not improve significantly for children who had tumors in either compartment. Among children who survived five years after the initial craniotomy, the proportion who had significant long term deficits increased. Most of this increase occurred in the last decade (1970-79). In this decade, the proportion of children for whom no deficits were reported five years following operation was 4% if they had a supratentorial tumor and 27% if they had an infratentorial tumor. The proportions of children alive five years following first surgery who had arachnoidal metastases increased significantly for infratentorial tumors.

Adolescent↗
PubMed1991

Employment and caregiver strain: an integrative model.

This study examines a multifactorial model of caregiving strain and its effects in a sample of 341 employed caregivers, using a LISREL framework to estimate path coefficients. Work disruptions associated with caregiving significantly affected caregiving strain and the perceived likelihood of job termination. Work interference was in turn affected by the care recipient's level of impairment and the perceived adequacy of the support received. Respondents with more flexible job responsibilities reported lower levels of work interference than did other respondents.

Adult↗
PubMed1987

Clinical implications of immunologic phenotyping in cutaneous T cell lymphoma.

The composition of cutaneous lesions from 158 patients with confirmed cutaneous T cell lymphoma, 91 patients with suspected cutaneous T cell lymphoma, and 145 patients with lymphoid disorders other than cutaneous T cell lymphoma was quantitated in situ with the use of commercially available murine monoclonal antibodies that identify the Pan T, T-helper/inducer (Th), T cytotoxic/suppressor (Ts), and Pan B lymphocyte subsets. On average, cutaneous infiltrates of confirmed cutaneous T cell lymphoma were found to contain significantly more Th and less Ts or Pan B cells compared to benign lymphoid disorders. Moreover, when analyzed in terms of the type of lesion examined by biopsy, the absolute amount of Th cells progressively expands with increasing magnitudes of infiltrate in the dermis while the amount of Ts and Pan B cells remains relatively constant among lesions. A useful diagnostic criterion (anti-Leu 1/4 greater than or equal to 70% and anti-Leu 3a/anti-Leu 2a ratio greater than or equal to 6) correctly discriminated between cutaneous T cell lymphoma and non-cutaneous T cell lymphoma in 87.5% of cases. A positive immunodiagnostic result also may be useful for the prediction of subsequent histopathologic confirmation of cutaneous T cell lymphoma in patients who have suspect lymphoid infiltrates, such as alopecia mucinosis or idiopathic generalized erythroderma, when first seen. With the use of multivariate analysis, stage and possibly the percentage of Th cells within the T cell component in cutaneous infiltrates were covariates with significant relationships to survival in patients with confirmed cutaneous T cell lymphoma. In addition, Ts cells in infiltrates did not correlate significantly with observed responses to topical treatment and subsequent course in pretumorous mycosis fungoides. These results indicate that Ts cells play little biologic role in modifying the natural history of cutaneous T cell lymphoma.

Antibodies, Monoclonal↗
PubMed1985

Diagnostic and prognostic significance of Sézary cells in peripheral blood smears from patients with cutaneous T cell lymphoma.

Blood smears stained with Wright-Giemsa were obtained from 124 patients with pathologically confirmed cutaneous T cell lymphoma (CTCL), 70 patients with various other cutaneous disorders, and ten healthy adult volunteers. These were examined in a blinded fashion for atypical lymphocytes with cerebriform nuclei (CLs), which were characterized further according to cell diameter. CLs, comprising up to 15% of lymphocytes in smears, were observed in 20% of the patients with benign dermatitis. CLs, comprising up to 89% of lymphocytes in smears, were found in 22%, 30%, 50%, and 96% of patients with patch, plaque, tumor, and erythrodermic CTCL, respectively. Large-diameter CLs (15 to 20 micron) were observed only in smears from patients with CTCL. Total CL counts above 15 per 100 lymphocytes and/or the presence of large CLs occurred in 33 of 49 (67%) patients with erythrodermic disease and in only two patients with other skin manifestations. Blood smears obtained at the time of cytogenetic studies indicated that a total CL count above 15% was the smear criterion that correlated best with the demonstration of a chromosomally abnormal malignant clone in the blood. The presence of large CLs per se, although also predictive of a malignant clone, was less useful. Multivariate survival analysis showed that the duration of disease before the blood smear and the proportion of large CLs within the total CL population were the covariates that correlated most significantly with survival. We speculate that the reduced survival of patients with increased proportions of large CLs in smears reflects the presence of polyploid malignant lymphocytes in the blood.

Actuarial Analysis↗
PubMed1984

Increased 2',5'-oligoadenylate synthetase activity in blood mononuclear leukocytes from patients with advanced cutaneous T-cell lymphoma.

The activity of the interferon-induced enzyme 2',5'-oligoadenylate synthetase (2',5' An synthetase) was found to be increased in the lysates of peripheral blood mononuclear leukocytes obtained from 10 of 25 (40%) patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome). A positive association was found between the level of mean total synthetase activity and extent of involvement (stage) of disease. However, the leukocytes from two patients with relatively high proportions of neoplastic T-cells in the blood (Sézary syndrome) had negligible enzyme activity. It is speculated that increased interferon production in vivo may account for the observed enzyme changes in normal blood leukocytes from these patients, and that the neoplastic T-cell population is the most likely source of the presumed interferon production. Possible mechanisms and biologic consequences of high levels of endogenous interferon in patients with cutaneous T-cell lymphoma are discussed.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Dehydroepiandrosterone (DHEA) and 3 beta-methylandrost-5-en-17-one: inhibitors of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papilloma formation in mice.

Long-term oral administration of the adrenal steroid, dehydroepiandrosterone (DHEA), has previously been shown to inhibit the development of spontaneous breast cancer and chemically induced lung and colon tumors in various mouse strains. In the two-stage skin papilloma system in the mouse, topical application of DHEA inhibits both 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate promotion of these tumors. The synthetic steroid, 3 beta-methylandrost-5-en-17-one, which, unlike DHEA, is not demonstrably estrogenic in the rat, also inhibits papilloma development.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Definitive classes of childhood supratentorial neuroglial tumors. The Childhood Brain Tumor Consortium.

Our objective in this study was to identify histologically homogenous classes of childhood supratentorial neuroglial tumors. Previously, we identified five quantitative histologic factors (differing linear combinations of 17 reliably recognized histologic features in neuroglial tumors). They account for much of the histologic variance in the 703 supratentorial tumors in the Childhood Brain Tumor Consortium (CBTC) database. In this study, we used the scores on the factors in cluster analyses and identified eight classes of neuroglial tumors. Each of these classes had significant differences in histology, allowing the separation of many of the conventional types of neuroglial tumors into two or more classes. For instance, fibrillary astrocytoma, pilocytic astrocytoma, subependymal giant cell astrocytoma, anaplastic astrocytoma, oligodendroglioma, and ependymoma were represented in two or more classes. Often these classes had statistically significant differences in survival distributions. For instance, the two classes of "anaplastic astrocytomas" have widely discrepant 5-year survival probabilities of 0.7 and 0.2. Use of the classes identified in this study ensures relatively homogeneous histologic subsets of tumors. We suggest that these classes will be useful for the selection of children for therapeutic clinical trials.

Astrocytoma↗
PubMedDate not supplied

Kynurenic acid and xanthurenic acid excretion after tryptophan loading in actinic reticuloid.

The metabolism of L-tryptophan (TRP) before and after an oral loading dose of 20 mg/kg body weight was studied in three patients with actinic reticuloid (AR) and four healthy male volunteers. The preload mean plasma TRP concentrations and mean 24-hour urinary excretions of TRP in the AR group were significantly lower than in the control group. After oral TRP administration, plasma TRP concentrations increased normally in AR, thereby excluding defective intestinal absorption. The mean preload and postload excretions of kynurenic acid (KA), xanthurenic acid (XA), 5-hydroxyindoleacetic acid (5HIAA), and 3-indoleacetic acid (3IAA) were not significantly different between the two groups. We conclude that KA, which has been shown to have phototoxic properties in vitro, is not altered primarily in AR, and that the reported abnormalities of TRP metabolism are most likely the consequence of the severe photosensitivity in this disorder.

Aged↗
PubMedDate not supplied

Quantitative histologic factors for grouping childhood supratentorial neuroglial tumors.

The histologic heterogeneity of childhood supratentorial neuroglial tumors, when quantified, identifies relatively homogeneous subgroups for prognostic purposes and for assignment in clinical trials. Our sample consisted of supratentorial tumors in the Childhood Brain Tumor Consortium. The data consist of reliably identified histologic features and demographic, clinical, operative, and survival information. Factor analysis was used to identify uncorrelated "factors," each represented by a different combination of histologic features in 703 tumors. The defining histologic features were used to label each factor. The heterogeneity of each tumor was summarized using the factor scores for each factor. We compared the survival estimates of subgroups of tumors within common diagnostic classes. We identified five uncorrelated quantitative factors that accounted for much of the histologic variation. Our factor labels were Jumbo, Fibrillary, Proliferative, Spongy, an Oligodendroglial. Two thirds of tumors had high scores on two or more factors, indicating a high degree of heterogeneity among these tumors. Eighty-four percent of supratentorial tumors were accounted for by 19 nonoverlapping relatively homogeneous histologic groups. The five quantitative factors complement standard qualitative taxonomies by summarizing more completely the histologic feature aspects of a tumor than by diagnosis alone and quantify the histologic heterogeneity of individual tumors. Histologically homogeneous groups of tumors are essential for clinical trials, biologic research, and prognostic models.

Adolescent↗
PubMedDate not supplied

Prognosis for children with supratentorial neuroglial tumors.

Factor analysis of reliably identified histologic features in supratentorial glial tumors yielded five interpretable "factors": Spongy, Fibrillary, Proliferative, Jumbo, and Oligodendroglial. Quantitative scores can be calculated for each factor in a tumor to summarize its heterogeneity. The objective was to investigate whether factor scores are useful for prognostic purposes. The sample consisted of 703 children with supratentorial neuroglial tumors with factor scores for each of the five factors. Data were based on the presence or absence of 26 reliably identified histologic features, plus clinical and survival information. Multivariate proportional hazards models assessed each factor's contribution to survival for children who survived 1 month after operation (n = 609). Patient-specific clinical data were allowed in the models. Increased likelihood of survival is associated with greater tumor removal, later decade of surgery, and high Spongy and high Oligodendroglial factor scores. Decreased likelihood of survival is associated with high Proliferative factor scores and radiation and/or chemotherapy treatment. Gender, age, location, and Jumbo and Fibrillary factor scores did not provide additional prognostic information. Three reliable histologic features, nondefining for any histologic factor, added prognostic information: Rosenthal fibers and glomeruli are associated with improved prognosis; pleomorphic nuclei are associated with worse prognosis. A high Oligodendroglial factor score is associated with a worse prognosis for some classes of astrocytoma but with a better prognosis for oligodendroglial tumors. A high Proliferative score is associated with a worse prognosis for anaplastic astrocytomas, ependymomas, and unclassifiable tumors. A high Spongy score is associated with a better prognosis for anaplastic astrocytomas but with a worse prognosis for pilocytic astrocytomas. For giant cell astrocytomas, gangliogliomas, and miscellaneous tumors, none of the factors is prognostic. Spongy, Oligodendroglial, and Proliferative factors provide important prognostic information for children with supratentorial neuroglial tumors.

Adolescent↗