Biomedical subjects

B L Webber

Publications and source records attributed to B L Webber.

At least 19 recordsLinked to original sources

PubMed1992

Renal tumors in childhood.

A great variety of tumors and tumor-like lesions affect the kidneys in childhood. We have discussed the practical aspects of the examination of tumors because the pathologist's role is becoming more critical to the staging and management of these patients. The use of newer techniques shows promise in renal tumors, and flow cytometry with DNA ploidy analysis may prove useful in more precisely identifying high-risk patients. Invaluable data continue to be generated from the large cooperative groups, particularly the National Wilms' Tumor Study, which helps refine our understanding of the renal tumors and their proper management. Close collaboration between the oncologist, the radiologist, the surgeon, the pathologist, and the radiation oncologist is the mainstay in providing the best possible outcome for these patients.

Adolescent↗

PubMed1992

Rhabdomyosarcoma. A new classification scheme related to prognosis.

We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.

Adolescent↗

PubMed1991

Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma.

Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.

Adolescent↗

PubMed1990

Development and characterization of pediatric osteosarcoma xenografts.

Of 33 surgical specimens of osteosarcoma obtained from 24 patients, eight were established as transplantable tumor lines in immune-deprived CBA/CaJ inbred mice. Each line retained the histological characteristics of the corresponding primary tumor and produced human lactate dehydrogenase isozymes. Volume doubling times, which ranged from a mean of 12.3 +/- 5.6 to 39.3 +/- 9.8 days, were stable for individual lines over multiple passages. Flow cytometric analysis indicated similar cellular DNA content values in the primary human tumors and established xenograft lines; the presence of two separate stem lines, as in the original tumors, was observed in the laboratory models. Comparison of two methods of immune deprivation indicated that thymectomy, whole-body irradiation, and bone marrow reconstitution was associated with a higher rate of successful engraftment than was thymectomy, 1-beta-D-arabinofuranosylcytosine treatment, and whole-body irradiation. Bone marrow-reconstituted mice also showed less variability in tumor volume doubling time. We conclude that osteosarcoma can be heterotransplanted into bone marrow-reconstituted mice with a relatively high success rate and that the xenografts retain features characteristic of the tumors of origin. The availability of these models should prove useful in the development of new therapeutic regimens and in understanding the biology of osteosarcoma.

Animals↗

PubMed1990

Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma.

Transcripts for the muscle regulatory gene MyoD1 are expressed during normal skeletal muscle myogenesis and in rhabdomyosarcomas but not in other tissues or in soft-tissue sarcomas. Here we report the distribution of MyoD1 protein, determined by reactivity with anti-MyoD1 polyclonal sera in normal tissues, rhabdomyosarcoma cell lines, and in a variety of pediatric solid tumors. The distribution of MyoD1 protein was highly restricted in normal tissues and was detected only in fetal skeletal muscle and more faintly in adult skeletal muscle. All six human rhabdomyosarcoma cell lines analyzed expressed MyoD1 mRNA transcripts as well as immunoreactive protein. The immunohistochemical expression of MyoD1 protein was then examined in 49 surgical specimens from a variety of pediatric solid tumors. Each of 16 rhabdomyosarcoma specimens was positive for MyoD1, including four that did not express the intermediate filament protein desmin. Two of five specimens originally designated sarcoma type indeterminate (STI) and two of three specimens originally designated extraosseous Ewing's sarcoma (EOE) were positive for MyoD1, suggesting commitment to myogenic differentiation. Three of eight Wilms' tumors, which also expressed desmin and had clearly evident myogenic elements, also were positive for MyoD1. Tumors that failed to express MyoD1 protein included neuroblastoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma, embryonal sarcoma of the liver, malignant fibrous histiocytoma, malignant rhabdoid tumor, and Ewing's sarcoma of the bone. These results indicate that expression of MyoD1 protein is highly restricted in normal human tissues and that expression of this gene product in malignant tissue may be diagnostic for rhabdomyosarcoma. Furthermore MyoD1 staining may be a valuable adjunct in the classification of pediatric soft-tissue sarcomas.

Child↗

PubMed1988

Artificial intelligence: a computerized decision aid for trauma.

A computerized decision support system has been developed to advise ATLS-trained surgeons on the initial definitive management of patients with penetrating injuries of the abdomen immediately following resuscitation and stabilization. The program was developed as an "expert system," using the techniques of artificial intelligence. It is able to suggest: the need for further examination; additional tests; diagnoses; and treatments. In this study, the advice offered by the expert system was compared to that of physicians-in-training. Five actual patient care situations were presented to the system and to 13 medical students and surgical residents: four MS-III, three PGY-I, three PGY-III, and three PGY-V. The suggestions of each of the 13 trainees, the advice of the expert system, and the actual management were blinded. Five surgeons versed in trauma and otherwise not involved in the project judged whether each of the 15 purported management plans was acceptable and ranked them in order of preference. Only the actual care and the advice from the system were judged acceptable for all five problems. The rankings of the expert system were better than those of any individual trainee. The differences were statistically significant for two of the three chief residents, five of nine residents overall, and all four students. This preliminary validation of a prototype expert system is encouraging for the prospect of a computerized decision support system that can help surgeons make initial definitive management plans for patients with major trauma.

Abdominal Injuries↗

PubMed1987

Hepatic undifferentiated (embryonal) sarcoma and rhabdomyosarcoma in children. Results of therapy.

From July 1972 through September 1984, 8 of 44 children diagnosed as having primary malignant hepatic tumors, who were treated at St. Jude Children's Research Hospital, had undifferentiated (embryonal) sarcoma (five patients) or rhabdomyosarcoma (three patients). The natural history and response to multimodal therapy of these rare tumors are described. The pathologic material was reviewed and evidence for the differentiating potential of undifferentiated (embryonal) sarcoma is presented. At diagnosis, disease was restricted to the right lobe of the liver in three patients, was bilobar in four patients, and extended from the left lobe into the diaphragm in one patient. Lung metastases were present in two patients at diagnosis. All three patients with rhabdomyosarcoma had intrahepatic lesions without involvement of the biliary tree. Survival ranged from 6 to 73 months from diagnosis (median, 19.5 months); two patients are surviving disease-free for 55+ and 73+ months, and one patient recently underwent resection of a recurrent pulmonary nodule 22 months from initial diagnosis. Three patients died of progressive intrahepatic and extrahepatic abdominal tumors, and two patients, who died of progressive pulmonary tumor, also had bone or brain metastasis but no recurrence of intra-abdominal tumor. Six patients had objective evidence of response to chemotherapy. The authors suggest an aggressive multimodal approach to the treatment of these rare tumors in children.

Adolescent↗

PubMed1987

A specific chromosomal abnormality in rhabdomyosarcoma.

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal. Cytogenetic hallmarks of gene amplification (double minute chromosomes and homogeneously staining regions) were apparent in three cases. Other frequent abnormalities included rearrangements of chromosomes lp and trisomy of chromosome 8. The absence of the t(2;13) in more than 100 cases of other pediatric solid tumors investigated in our laboratory indicates its specificity for rhabdomyosarcoma. These cytogenetic findings suggest directions for further investigation of the molecular events underlying the genesis of this tumor.

Adolescent↗

PubMed1986

Therapy for childhood soft-tissue sarcomas other than rhabdomyosarcoma: a review of 62 cases treated at a single institution.

The rarity and diverse characteristics of the nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) in children have hindered study of their clinical presentations and response to therapy. Here we describe the findings of a retrospective analysis of 62 cases of NRSTS seen in a single institution from 1962 through 1983. The most common histopathologic diagnosis was synovial sarcoma, occurring in 18 patients, followed by malignant schwannoma in 12. The median age at diagnosis was 11 years (range, 2 months to 20 years). Anatomic sites of primary tumors were the trunk (28), extremity (24), and head and neck (10). Of the 31 patients whose tumors were completely resected, 26 (84%) survive with no evidence of disease. Postoperative chemotherapy, administered to nearly one half of this group, did not produce any demonstrable gains in survival. Only one of the 26 patients with local or metastatic gross tumor after resection survives. We conclude that an aggressive surgical approach is imperative in patients with NRSTS and that the contribution of other treatment modalities needs to be defined in a collaborative group trial.

Adolescent↗

PubMed1985

Childhood multifocal osteosarcoma. Clinicopathologic and radiologic correlates.

The authors reviewed the clinical charts and pathologic and radiographic materials of nine pediatric patients (mean age, 11.0 years) presenting with multiple skeletal foci of osteosarcoma. Four patients presented with pulmonary metastases, and five had osseous disease only. All had densely sclerotic, predominantly osteoblastic tumors, usually in metaphyseal locations. Evidence of aggressive tumor cell behavior--such as vascular, articular, epiphyseal, or soft-tissue invasion--was usually present in surgical specimens. Despite intensive chemotherapy, all patients died from 6 to 37 months after diagnosis (median survival, 12 months). Comparison of clinical and pathologic features for patients presenting with or without pulmonary metastases failed to disclose any notable differences between the two groups, indicating a common pathogenesis and evolution for their multifocal disease. The authors conclude that this variant of osteosarcoma is a highly aggressive form of the disease that may be accompanied by pulmonary metastases.

Adolescent↗

PubMed1984

Disseminated varicella at autopsy in children with cancer.

The autopsies of seven patients with disseminated varicella were reviewed. Six patients had acute lymphoblastic leukemia (ALL) and the seventh had Hodgkin's disease. All the patients were on chemotherapy at the time of commencement of their varicella rash, and at autopsy only the patient with Hodgkin's disease had residual tumor. The typical anatomic lesion of varicella was one of focal necrosis (often hemorrhagic) with eosinophilic intranuclear (Cowdry type-A) inclusions. In fatal disseminated varicella the complications most commonly encountered at autopsy were interstitial pneumonitis, hepatitis, necrotizing splenitis and lymphadenitis, esophagitis, enteritis, colitis, and pancreatitis. The most significant of these complications appears to be the interstitial pneumonitis, as the major cause of death is respiratory failure.

Acute Disease↗

PubMed1983

Hydrocele formation in patients with Hodgkin's disease.

Hydroceles developed in 12 (7.7%) of 155 consecutive male patients who had Hodgkin's disease treated between 1962 and 1981. Except for one patient who had a hydrocele at diagnosis, all developed this complication during remission, 8 months to 7.5 years after inverted-Y or abdominopelvic 60Co irradiation (3000-3800 rad). Hydroceles were bilateral in five patients and on the right side in seven. No tumor was found in the hydrocele sacs of the ten patients who underwent hydrocelectomy. Lymphatic obstruction was evidenced by lymphatic dilation in the hernia sac in six patients. The authors believe postirradiation fibrosis of the lymphatic pathway was the main cause of hydrocele formation.

Adolescent↗

PubMed1982

Histopathological features of rapidly progressing breast carcinoma in Tunisia: a study of 94 cases.

The histological features of 94 cases of carcinoma of the breast seen in Tunisia were recorded and subsequently correlated with the clinical classification of the patients in terms of poussée évolutive (PEV) categories. Histological features analyzed in the breast tissues and skin included tumor type, nuclear grade, number of mitoses, involvement of the dermis, cutaneous inflammatory infiltrate and edema. Twenty-eight percent of the cases in which the skin was examined showed tumor emboli in the lymphatics of the dermis. The frequency of cutaneous permeation correlated with the PEV categories. The percentage of cases with nuclear grade 3 was higher for the group with rapid progression of the disease (PEV 1,2,3) than for the cases belonging to the PEV-0 category (90% versus 64.2%). The present study demonstrates that a large proportion of breast carcinoma patients in Tunisia suffer from "inflammatory carcinoma of the breast".

Breast Neoplasms↗

PubMed1982

Growth and characterization of childhood rhabdomyosarcomas as xenografts.

Eleven surgical specimens of childhood rhabdomyosarcoma (RMS), two bone marrow samples, and cells from ascitic fluid from 1 patient were implanted sc into immune-deprived inbred CBA/CaJ mice. From these, seven lines of RMS were obtained as xenografts, each retaining the histologic characteristics of the tumor of origin and human lactate dehydrogenase isozymes; these represented 6 of the 11 surgical specimens, whereas one line originated from the transplanted cells from ascitic fluid. It was concluded that children RMS has a fairly high frequency of heterotransplantability in this system and that such a laboratory model may prove useful in the development of new therapeutic regimens in this disease.

Adolescent↗

PubMed1981

Early distant metastases from epithelioid sarcoma of the hand.

The authors describe a patient with epithelioid sarcoma in whom the presenting lesion was cervical lymph node metastasis. This proved to be a difficult diagnostic problem, until the occult primary tumor was discovered in the ipsilateral hand. A cerebral metastasis became evident early in the course of the disease. The authors believe this to be the first case reported in whom the presenting lesion was a nonregional metastasis. The rapid clinical progression of this patient's malignancy is of interest and illustrates the need for early intervention in patients with an epithelioid sarcoma, since the clinical course is not always indolent.

Adolescent↗

PubMed1981

Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma.

One hundred ninety-one cases of unilateral noninvasive breast carcinoma were studied with regard to the development of subsequent cancers in the contralateral breast. The majority of patients were treated by mastectomy and have been followed for an average of nine years. Their overall survival did not differ significantly from that of age-specific population survival figures for U. S. women. Among all cases, 13 or 6.8% subsequently developed contralateral carcinoma; 3.1% of these contralateral tumors were invasive. The authors found only one histological type, namely lobular carcinoma in-situ for which the development of subsequent contralateral carcinomas was statistically significant. Seven of the 68 women with this type developed second breast cancers (10.3%; 4.4% of these were invasive). These data suggest that the occurrence of clinically apparent subsequent cancers developing in the opposite breast following the diagnosis of in-situ carcinoma is relatively small.

Adult↗

PubMed1981

Prospective evaluation of aspiration needle, cutting needle, transbronchial, and open lung biopsy in patients with pulmonary infiltrates.

Twenty consecutive patients with pulmonary infiltrates undiagnosed by routine, noninvasive methods were entered into a prospective study designed to evaluate the diagnostic yield of four methods of lung biopsy. Percutaneous aspiration needle, cutting needle, transbronchial, and open (anterior thoracotomy) biopsy were performed synchronously on all patients. Specimens were evaluated by microbiological, virological, and pathological methods. The diagnostic yields of the four methods were as follows: aspiration needle, 29%; cutting needle, 53%; transbronchial, 59%; and open lung biopsy, 94%. Open lung biopsy was significantly better in yielding a diagnosis than aspiration needle (p less than 0.001), cutting needle (p less than 0.001), and transbronchial biopsy (p less than 0.04).

Adolescent↗

PubMed1979

Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis.

In this restrospective study we review the clinical features of patients with the sicca syndrome in the presence and absence of rheumatoid arthritis. All patients were followed at the National Institutes of Health for at least five years after the diagnosis of sicca syndrome was established. Twenty-two patients had sicca syndrome alone, and 21 patients had definite rheumatoid arthritis and the sicca syndrome. Rheumatoid arthritis tended to precede the developement of sicca syndrome. The mean age at diagnosis of sicca syndrome is the same in both groups. No significant differences in serum innumoglobulins, the third component of complement (C3), rheumatoid factor titer and salivary histopathology were found. However, the clinical features were quite distinct. Patients with sicca syndrome alone had a significantly greater frequency of recurrent parotitis, Raynaud's phenomenon, purpura, lymphadenopathy, myositis and renal involvement. The clinical characteristics of these two groups coupled with the known serologic and genetic differences suggest that sicca syndrome alone is a distinct pathologic entity.

Arthritis, Rheumatoid↗