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J B Beckwith

Publications and source records attributed to J B Beckwith.

At least 55 records · Page 3Linked to original sources
PubMed1996

Focal versus diffuse anaplasia in Wilms tumor--new definitions with prognostic significance: a report from the National Wilms Tumor Study Group.

Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should therefore have critical prognostic relevance. The original definitions for focal anaplasia (FA) and diffuse anaplasia (DA) were based on quantitative rather than topographical criteria and lacked prognostic significance. A new definition was developed based on the distribution of anaplastic changes within the tumor: FA applies only to tumors with anaplasia confined to one or a few discrete loci within the primary tumor, with no anaplasia or marked nuclear atypia elsewhere. This revised definition was evaluated in 165 cases with anaplastic WT entered on the third and fourth National Wilms Tumor Study. Only three relapses and one death occurred among 39 cases with FA, regardless of tumor stage, a result comparable to that for nonanaplastic WT. Eight children with metastases at diagnosis and FA in the primary tumor were alive and free of relapse; 22 of 23 children with stage IV DA WT died of tumor. This new definition reinforces the importance of carefully documenting the exact site from which each tumor section is obtained.

Anaplasia↗
PubMed1996

Benign adenomatous kidney neoplasms in children with polycythemia: imaging findings.

PURPOSE: To correlate pathologic, computed tomographic (CT), and ultrasound (US) characteristics of nephrogenic adenofibromas and embryonal adenomas (uncommon pediatric renal tumors) in children. MATERIALS AND METHODS: Medical records and imaging and pathologic findings were reviewed in three children (aged 6 1/2, 7, and 11 years) with adenomatous renal tumors and polycythemia. Specimens were reviewed at the National Wilms Tumor Study Pathology Center (Loma Linda, Calif). RESULTS: All tumors were smaller than 3 cm in greatest dimension. They were hyperechoic on US scans and had high attenuation on unenhanced CT scans. Two patients underwent nephrectomy for initial diagnosis of Wilms tumor. The third underwent local excision. At pathologic examination, embryonal-appearing adenomatous epithelial cells were found to form tubules and papillae with abundant psammomatous calcifications. Two masses were classified as embryonal adenomas and one as nephrogenic adenofibroma. CONCLUSION: Increased attenuation on CT scans and increased echogenicity on US scans of renal adenomatous tumors are distinctive findings that may reflect the presence of tubulopapillary structures and psammomatous calcifications.

Adenofibroma↗
PubMed1995

Clonal expansion and attenuated apoptosis in Wilms' tumors are associated with p53 gene mutations.

The p53 gene product is required for activation of an apoptotic pathway triggered by oncogenes and cytotoxic agents. Wilms' tumor, a pediatric renal malignancy, provides a paradigm for evaluating genetic events involved in tumor progression. This malignancy is generally not associated with p53 mutations, and even in advanced disease states is quite responsive to current treatment regimens. The anaplastic histological variant of Wilms' tumor, however, is frequently associated with p53 gene mutations and shows poor prognosis. We analyzed seven Wilms' tumors for which we had paired samples from nonanaplastic and anaplastic regions. p53 mutations were detected in six of these tumors, five of which demonstrated mutations restricted to anaplastic regions. Nonanaplastic cells of the sixth sample were heterozygous for a p53 mutation, whereas the anaplastic area of this tumor showed reduction to homozygosity. These results indicate that progression to anaplasia is associated with clonal expansion of cells which have acquired a p53 mutation. We demonstrated that tumor cells with p53 mutations show attenuated apoptosis, suggesting that such lesions may provide a selective advantage in vivo by decreasing cell death.

Anaplasia↗
PubMed1995

Neonatal Wilms tumor.

Neonatal renal tumors are very rare. We have identified 15 cases of Wilm's tumors diagnosed in the first 30 days of life. The most common presentation was an abdominal mass on routine newborn examination, and three tumors were noted on an antenatal ultrasound. All of the infants underwent primary excision of the tumor. Five infants were not given postoperative chemotherapy after surgical excision. One of these children had a relapse and later died of progressive disease. The remaining children are alive at a median follow-up of 31 months. Eight of the tumors had evidence of nephrogenic rests. More frequent follow-up physical and imaging examinations are indicated in children not given adjuvant chemotherapy or whose tumors show nephrogenic rests.

Combined Modality Therapy↗
PubMed1995

Nuclear morphometric analysis of metastasis in Wilms' tumor after multimodal therapy: comparison with primary tumor.

OBJECTIVES: The outlook for children with Wilms' tumor has improved with the use of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children with tumors with favorable histologic findings continue to recur unpredictably. We previously reported that nuclear morphometry (the distribution of nuclear roundness factor [NRF], lowest values for ellipticity, and age) when combined in a multivariate analysis accurately predicted response to therapy for patients with histologically favorable Wilms' tumors. METHODS: To investigate further the nuclear shape changes associated with disease recurrence, we analyzed histologic sections taken from primary tumors and postmultimodal therapy metastatic lesions for 7 children who had a recurrence with initially histologically favorable primary tumors. RESULTS: Mean NRF was significantly lower (P = 0.0001) in the metastatic lesion (35 +/- 5) group when compared with the primary tumor group (50 +/- 5). The percent coefficient of variation for NRF was also significantly lower (P = 0.006) in the metastatic lesion when compared with the primary tumor. Nuclear area was increased (P = 0.02), although the nuclear perimeter was unchanged (P = 0.1). CONCLUSIONS: (1) Nuclei in metastatic lesions from Wilms' tumors with favorable histologic findings after multimodal therapy are more round and exhibit less variable distribution, suggesting clonal homogeneity within the metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in the primary tumors yet have an unchanged perimeter, which may be due to internal nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA) ploidy. Although the results of this study are promising, we are currently extending this hypothesis to a larger group of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Measurement of attitudes of trainee professionals to people with disabilities.

The importance of measuring attitudes of trainee professionals to people with disabilities was addressed. A questionnaire which included the Scale of Attitudes toward Disabled Persons (SADP) and the Intellectual Disability Misconceptions Scale (IDMS) was completed by first and final year tertiary students enrolled in a 3-year course on intellectual disability. The attitude measures did not discriminate between the two groups of students, psychometric properties were poor and the factor structure of the SADP did not replicate previous findings. As expected, there was some convergence between the two attitude measures, and relationships to subject variables were consistent with previous research. Recommendations for subsequent research were discussed.

Adolescent↗
PubMed1995

Histopathology of childhood renal tumors.

The different subtypes of childhood renal tumors are well defined both clinically and pathologically. Classification and estimation of prognosis are feasible even after chemotherapy. A small group of tumors remains in which an estimate of prognosis is difficult. This is especially true for Wilms tumors with persistent blastema after chemotherapy. It is to be hoped that studies of the molecular genetics of these tumors will yield new data that will help refine therapeutic strategies.

Anaplasia↗
PubMed1994

The relationship between microsubstaging variables, age at diagnosis, and tumor weight of children with stage I/favorable histology Wilms' tumor. A report from the National Wilms' Tumor study.

BACKGROUND: The purpose of this study was to determine the relationship between histologic microsubstaging variables, patient age, and tumor specimen weight in patients with Stage I/favorable histology Wilms' tumors. METHODS: The authors reviewed all randomized patients from the Fourth National Wilms' Tumor Study, who had Stage I/favorable histology Wilms' tumors evaluated for one or more of the microsubstaging variables: (1) the presence of an inflammatory pseudocapsule, (2) renal sinus invasion, (3) tumor in the intrarenal vessels, and (4) tumor capsule invasion. The authors determined the correlation between microsubstaging variables and age at diagnosis or tumor specimen weight. RESULTS: Patients who were younger than 2 years of age at diagnosis were significantly more likely to have all negative microsubstaging variables. Patients who had tumors weighing less than 550 g were more likely to have all negative microsubstaging variables. However, neither renal sinus invasion nor tumor in the intrarenal vessels was more frequent in tumors weighing more than 550 g. CONCLUSIONS: An age at diagnosis of younger than 2 years and a tumor specimen weight of less than 550 g are highly correlated with the absence of adverse microsubstaging variables. The clinical variables of age at diagnosis and tumor specimen weight, compared with the assessment of microsubstaging variables, have the practical advantage of being more objectively determined and not requiring a central pathologic review for confirmation.

Adolescent↗
PubMed1994

Increased birth weights of National Wilms' Tumor Study patients suggest a growth factor excess.

An analysis of over 1800 patients with Wilms' tumor revealed significantly higher birth weights than newborns in the general United States population. The highest birth weights were found not only in patients diagnosed with the Beckwith-Wiedemann syndrome (mean, 3.78 kg), as had been expected, but also in those with hemihypertrophy (3.80 kg) or perilobar nephrogenic rests (3.56 kg) in addition to their Wilms' tumor. The birth weights of Wilms' tumor patients with intralobar nephrogenic rests (3.43 on average kg) and of those without associated anomalies (3.45 kg) were slightly but still significantly higher on average than national birthweights (overall mean, 3.35 kg) adjusted for gender, race, and year of birth in each subgroup. Birth weights of children with aniridia and Wilms' tumor (2.99 kg) were lower than the national mean. Among more than 3000 patients with Wilms' tumor, heights and weights at diagnosis were significantly higher for the subgroups of patients with Beckwith-Wiedemann syndrome or hemihypertrophy, and height was lower for those with aniridia or characteristic genitourinary anomalies, when compared to other patients with Wilms' tumor. These data suggest prenatal effects of growth factors on the development of Wilms' tumors, or vice versa, and provide further epidemiological support for heterogeneity in the pathogenesis of Wilms' tumors associated with perilobar nephrogenic rests versus intralobar nephrogenic rests.

Beckwith-Wiedemann Syndrome↗
PubMed1994

Prediction of disease-free survival after therapy in Wilms' tumor using nuclear morphometric techniques.

The outlook for children with Wilms' tumor has markedly improved with the use of multimodal therapy, and survival currently exceed 85%. Current trends have been to use less intense therapy for children whose tumors have favorable histology (FH). By decreasing the amount of therapy given to patients whose conditions have an excellent chance of responding, the need for accurate criteria to separate high-risk and low-risk groups becomes imperative. Nuclear morphometric techniques have been developed and extensively tested in the author's laboratory. Preliminary studies of FH Wilms' tumors demonstrated the applicability of this technique. Herein, the authors present a retrospective study of 108 patients with FH tumors, with a mean follow-up period of 1,994 +/- 107 days (66 months) for those whose tumors did respond to therapy, and 686 +/- 61 days (23 months) for those whose tumors did not respond. The univariate predictors were age (P = .02), the skewness of nuclear roundness factor (SNRF) (P = .009), and the mean of the lower five values for nuclear ellipticity, measured by the feret diameter method (L5EFD) (P = .01). A multivariate analysis combining all three variables better separated the two groups (P = .00016). A probability function curve was constructed to predict poor prognosis. Kaplan-Meier actuarial survival analysis was used to predict disease-free survival as clinical progression, and separated the two groups (P = .0004, Wilcoxon-Gehan statistic). These results suggest that nuclear morphometry is useful in the initial assessment of patients with Wilms' tumor.

Adolescent↗
PubMed1994

The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy.

The existence of extrarenal rhabdoid tumor (ERRT) as a discrete pathologic entity has been controversial despite frequent reports of its occurrence. We performed immunohistochemistry, electron microscopy, or both on 42 cases with this diagnosis sent in consultation to us. Only 12 of the 42 neoplasms had the histological findings of "classic" malignant rhabdoid tumor of the kidney; the remainder displayed a variety of neural, epithelial, myoid, mesenchymal, or ependymal patterns. Electron microscopy also showed that most possessed neural, epithelial, or ependymal features. Immunohistochemistry generally revealed marked polyphenotypia, with immunoreactivity to a wide array of antibodies against neural, epithelial, glial, and myogenic markers. A specific tissue-based diagnostic category could not be assigned in only 11 of the 42 cases, seven of which lacked material for a comprehensive ultrastructural or immunohistochemical study. We conclude that tumors currently diagnosed as ERRT represent a heterogeneous group of neoplasms that may form unique subsets of known entities within the specific site where they arise or that may defy classification into a specific alternative category. Our findings lead us to believe that the term ERRT is not valid as representing a specific diagnostic entity and to prefer the term "poorly differentiated neoplasm with rhabdoid features" for undifferentiated tumors.

Abdominal Neoplasms↗
PubMed1994

Management and outcome of inoperable Wilms tumor. A report of National Wilms Tumor Study-3.

METHODS: The authors reviewed 131 children enrolled in National Wilms Tumor Study-3 (NWTS-3) who received preoperative treatment for tumors unable to be resected at surgery or judged inoperable by imaging evaluation. Preoperative biopsies were performed on 103 patients. Patients were assigned a pretreatment stage: stage II (11 patients), stage III (39 patients), stage IV (66 patients), and unknown (15 patients). The chemotherapy regimen included dactinomycin and vincristine (81 patients), dactinomycin, vincristine, and doxorubicin (30 patients), dactinomycin, vincristine, doxorubicin, and cyclophosphamide (10 patients), and other (8 patients). Preoperative radiation therapy was started concurrently with chemotherapy (27 patients) or because of lack of response (14 patients). Two patients were given preoperative irradiation without chemotherapy. RESULTS: Response to therapy was assessed after the first trial of chemotherapy. Partial responses were noted in 110 patients (85%), 3 had complete responses, 13 had no response or progression of disease, and 5 patients were not able to be evaluated. There were no significant differences in preoperative response to the different chemotherapy regimens. Median time interval from diagnosis to nephrectomy was 58.5 days. When compared with NWTS-3 patients not receiving preoperative treatment, survival was reduced for patients treated preoperatively (88% vs. 74%, respectively, 4-year survival), which was only partially explained by differences in stage distribution. Median duration of follow-up was 5.9 years. Lack of response to the preoperative treatment was associated with a poor prognosis. Eight children died before removal of the primary tumor. All eight had either progressive disease or no response to the preoperative treatment. CONCLUSIONS: The use of preoperative treatment can facilitate subsequent surgical resection in selected patients with inoperable Wilms tumors. Although these very large tumors--judged unable to be resected--have a somewhat worse prognosis, nephrectomy was completed in 93% of patients after preoperative treatment. However, preoperative treatment will lead to less accurate surgical and pathologic staging, and undertreatment should be avoided in these high-risk patients.

Child, Preschool↗
PubMed1994

Treatment of children with stages II to IV anaplastic Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: To evaluate the effect of the combination of vincristine, dactinomycin, and doxorubicin with (regimen J) or without (regimen DD-RT) cyclophosphamide on the relapse-free survival of children with stages II to IV Wilms' tumor and focal or diffuse anaplasia. PATIENTS AND METHODS: We reviewed the clinical courses of all randomized patients from National Wilms' Tumor Study (NWTS)-3 and NWTS-4 with stages II to IV anaplastic Wilms' tumor, and determined the 4-year relapse-free survival rate separately for those with focal or diffuse anaplasia. Anaplasia was evaluated using newly developed topographic definitions for focal and diffuse anaplasia. RESULTS: The 4-year relapse-free survival rate for five children with focal anaplasia who received regimen DD-RT was 80.0%, compared with 100.0% for eight children who received regimen J (P = .68). The 4-year relapse-free survival rate for 29 children with diffuse anaplasia treated with regimen DD-RT was 27.2%, compared with 54.8% for 30 children treated with regimen J (P = .02). CONCLUSION: We conclude that children with focal anaplasia have an excellent prognosis when treated with vincristine, doxorubicin, and dactinomycin. The addition of cyclophosphamide to the three-drug treatment regimen improved the 4-year relapse-free survival rate of children with stage II to IV diffuse anaplasia. This result suggests that further intensification of the treatment regimen for children with diffuse anaplasia may result in an additional improvement in prognosis.

Anaplasia↗
PubMed1994

Treatment of children with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group.

PURPOSE: To evaluate the effect of the sequential addition of doxorubicin (DOX) and cyclophosphamide (CTX) to the combination of vincristine (VCR) and dactinomycin (AMD) on the relapse-free survival of children with clear-cell sarcoma of the kidney (CCSK). PATIENTS AND METHODS: We determined the 6-year relapse-free survival rate for patients with CCSK treated on National Wilms' Tumor Study (NWTS)-1, NWTS-2, or NWTS-3 with the combination of VCR and AMD, with or without DOX, and for patients treated on NWTS-3 with the combination of VCR, AMD, and DOX with (regimen J) or without (regimen DD-RT) CTX. RESULTS: The 6-year relapse-free survival rate for the eight children with CCSK treated with VCR, AMD, and radiation therapy was 25.0%, compared with 63.5% for the 58 children treated with VCR, AMD, DOX, and radiation therapy (P = .09). The 6-year relapse-free survival rate for children with CCSK treated on regimen DD-RT was 64.6%, compared with 58.2% for those treated on regimen J (P = .79). CONCLUSION: We conclude that the addition of DOX to the combination of VCR plus AMD appeared to improve the 6-year relapse-free survival rate of children with CCSK. The addition of CTX in the dose and schedule used in NWTS-3 did not improve the 6-year relapse-free survival rate of children with CCSK. Because 30% of relapses occurred more than 2 years after diagnosis, prolonged follow-up evaluation of patients with CCSK is necessary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Congenital mesoblastic nephroma metastatic to the brain.

BACKGROUND: Congenital mesoblastic nephroma (CMN) is generally considered to be a benign neoplasm requiring only total excision. Rare local recurrences have usually been related to incomplete removal, and distant metastases to the lung have been reported three times. METHODS: The authors reported the first case of CMN metastatic to the brain, illustrating a comparison of the histopathology of the primary and secondary lesions. RESULTS: The gross appearance of the renal tumor was that of a benign CMN. On histopathologic examination, there was a single nodule of more cellular tissue with focal necrosis. This area was diagnosed as within the designation "cellular" mesoblastic nephroma. The appearance of the brain metastasis corresponded to that of the cellular nodule. CONCLUSIONS: This report expands the spectrum of metastatic potential of CMN. Though a rare event, this case underscores the need for close follow-up of infants with CMN.

Brain Neoplasms↗