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J B Beckwith

Publications and source records attributed to J B Beckwith.

At least 73 records · Page 4Linked to original sources
PubMed1993

Precursor lesions of Wilms tumor: clinical and biological implications.

Nephrogenic rests (NR) are persistent embryonal remnants in the kidney that are apparent precursors of Wilms tumor (WT). Nephroblastomatosis (Nbl) denotes multiple or diffuse NR. Two major categories of NR have been recognized to date, perilobar (PLNR) and intralobar (ILNR). A dynamic classification of NR according to their recognized developmental fates is presented. Dormancy, maturation, involution, hyperplastic overgrowth, and neoplastic induction are the common fates of NR. Hyperplastic NR are far more common than formerly recognized, and are frequently confused with WT, especially in cases of multicentric and bilateral tumors. Biopsy is of limited value in distinguishing hyperplastic NR from WT, and the use of surgery in cases of Nbl requires careful consideration, as its role can in many cases be reduced or supplanted due to the effectiveness of modern imaging techniques and chemotherapy. An understanding of the natural history of NR and Nbl is essential for rational patient care decisions, and is important for understanding the molecular biology of WT.

Humans↗
PubMed1993

Epidemiology of Wilms tumor.

Wilms tumor affects approximately one child per 10,000 worldwide before the age of 15 years. Incidence rates appear to be slightly elevated for U.S. and African Blacks in comparison to Whites, but are only half as great among Asians. Several case-control studies have suggested that paternal occupational or maternal hormonal exposures during pregnancy may increase the risk of Wilms tumor, but small numbers of subjects and inconsistencies in the patterns of exposures do not permit firm conclusions to be drawn. It is unlikely that such environmental exposures play a major role in the etiology of Wilms tumor. The median age-at-onset of Wilms tumor is 38 months in the U.S. National Wilms Tumor Study series, with cases in girls occurring on average 6 months later than in boys. Patients with bilateral tumors, aniridia, cryptorchism/hypospadias, Beck-with-Wiedemann syndrome, or intralobar nephrogenic rests tend to be diagnosed much younger than average (median 17-27 months). Those with familial disease or multicentric tumors have intermediate age-at-onset distributions, while those with perilobar nephrogenic rests are diagnosed at older ages. The epidemiologic features suggest that somatic mosaicism, rather than a germline mutation, may be responsible for some of the bilateral and multicentric cases.

Africa↗
PubMed1993

Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumor: a report from the National Wilms Tumor Study.

To evaluate the usefulness of regular radiographic screening to detect an asymptomatic intraabdominal tumor in patients with an increased risk of developing Wilms tumor, we reviewed the files of patients with hemihypertrophy, aniridia, or Beckwith-Wiedemann syndrome who were registered on the National Wilms Tumor Studies. Screening was employed infrequently in the management of children with hemihypertrophy, with only 25% (6/24) of those whose hemihypertrophy was identified more than 30 days prior to the diagnosis of Wilms tumor undergoing such examinations. Most patients with aniridia were evaluated regularly for the occurrence of Wilms tumor. There were more stage 1 tumors identified in patients whose tumor was detected only through radiographic evaluation. The role of routine radiographic screening needs to be carefully evaluated in a homogeneous group of patients such as those with aniridia using a prospective study design to determine if such screening improves the survival rate of children with this rapidly growing, but readily treatable form of childhood cancer.

Adolescent↗
PubMed1993

The use of nuclear morphometry to predict prognosis in pediatric urologic malignancies: a review.

Wilms tumor, the most common pediatric urologic malignancy, and genitourinary rhabdomyosarcoma, the most common soft tissue sarcoma of childhood, represent two of the most commonly diagnosed pediatric urologic malignancies. The introduction and use of multimodal therapy (surgery, radiation, and chemotherapy) by the National Wilms Tumor Study (NWTS) and the Intergroup Rhabdomyosarcoma Study (IRS) groups have greatly improved the survival among children with these malignancies. Present survival rates for Wilms tumor exceed 85% and for rhabdomyosarcoma survival rates are approaching 80% as well. For Wilms tumor, current treatment trends suggest less intense therapy for those children with favorable histology tumors who are considered at relatively low risk for tumor recurrence. Likewise, the significant morbidity associated with the present therapy regimens for rhabdomyosarcomas has prompted investigators to search for individualized management schemes for children with a high probability of responding. The need for accurate criteria to separate these high and low risk groups becomes imperative. In this review we present our work using nuclear morphometry, as a prognostic indicator, to retrospectively predict response to therapy for children with Wilms tumors and genitourinary rhabdomyosarcomas.

Adolescent↗
PubMed1993

Wilms' tumour and parental age: a report from the National Wilms' Tumour Study.

Age distributions of parents at birth of patients registered in the National Wilms' Tumour Study were compared to those of the general population. An increasing incidence of sporadic Wilms' tumour with increasing paternal age was found, with a relative risk of 2.1 of tumour in children of fathers over 55 compared to children of fathers younger than 20. A similar effect for maternal age was found, with a relative risk of 1.4 in children of mothers over 40 compared to children of mothers younger than 20. The maternal age effect was much weaker among patients registered later in the study; in the later, more completely ascertained cohort, paternal age appears to be the major contributor to the parental age effect. Little difference in paternal age distribution was found between patients with bilateral and unilateral tumour and between male and female patients. In contrast, patients with reported associated congenital anomalies, patients with evidence of nephrogenic rests, and patients with early or late age-of-onset of tumour had parents who were, on average, substantially older than the remainder. These findings lend support to the idea that many Wilms' tumours result from new germline mutations. Further, the histologic composition of such tumours may be sufficiently distinct as to provide a valuable diagnostic indicator of the etiology of these tumours.

Adult↗
PubMed1993

Treatment outcomes in patients less than 2 years of age with small, stage I, favorable-histology Wilms' tumors: a report from the National Wilms' Tumor Study.

PURPOSE: Retrospective analyses were performed to determine the effect of tumor weight and therapy modifications on outcome in patients less than 2 years of age with stage I favorable-histology Wilms' tumors. PATIENTS AND METHODS: The 4-year relapse-free and overall survival percentages for patients randomized to different treatment regimens in National Wilms' Tumor Studies (NWTS)-1, -2, and -3 were calculated and compared. RESULTS: The 4-year relapse-free survival percentages of patients whose specimen weight was less than 550 g were found to be 89.1% on NWTS-1, 96.0% on NWTS-2, and 93.2% on NWTS-3. There was no evidence that the relapse-free survival of these patients had improved over time (P value for trend = .99). The 4-year relapse-free survival percentage for similar age and stage patients whose specimen weight was 550 g or greater was significantly poorer than that of patients with smaller tumors (P = .02). CONCLUSION: Changes in the NWTS treatment regimens over a period of more than 20 years have not improved on the excellent prognosis of patients who are less than 2 years of age at diagnosis and who have a stage I, favorable-histology Wilms' tumor with specimen weight less than 550 g. These data could be used as the basis for a future trial in which a subgroup of such patients is treated with nephrectomy only.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The use of nuclear morphometry to predict response to therapy in Wilms' tumor.

Using nuclear morphometric analysis, a retrospective study was made of 27 patients with Wilms' tumor. The blinded group consisted of 17 patients with Stage I and II favorable-histology Wilms' tumors who did not respond to therapy and ten patients with Stage III and IV favorable-histology Wilms' tumors who did respond. In this complex group of patients, multivariate analysis (with several morphologic descriptors) was used to predict which patients responded to therapy. No single-shape descriptor predicted the response to therapy (P greater than 0.5). However, three shape descriptors: maximum ellipticity (ME), standard error of bending energy (SEBE), and the range of chain code-maximum peak (RCCM), with the multivariate formula of (1131 x SEBE) + (-7 x ME) + (50 x RCCM) + 7.18, separated the two groups (P less than 0.004). This result was statistically significant. Using this multivariate equation and a cutoff value of 0.6 units, this test yielded a sensitivity of 94% and a specificity of 70%. This result, in a complex group of patients, suggests that nuclear morphometry may be useful in the initial assessment of patients with Wilms' tumor and warrants further analysis.

Cell Nucleus↗
PubMed1992

Renal transplacental carcinogenicity of 3,3-dimethyl-1-phenyltriazene in rats: relationship of renal mesenchymal tumor to congenital mesoblastic nephroma and intralobar nephrogenic rests.

Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.

Animals↗
PubMed1992

Nephrogenic adenofibroma. A novel kidney tumor of young people.

Nephrogenic adenofibroma is a novel kidney tumor of young people (mean age of presentation, 13 years), who present with polycythemia, hypertension, or hematuria, which resolve following nephrectomy. The typical nephrectomy specimen contains a solitary, nonencapsulated, vaguely circumscribed, irregularly shaped or spherical, firm mass with either tan, gray-white, or pale yellow coloration. Cysts are sometimes present within the tumor. The histologic appearance is distinctive and characterized by a marked proliferation of spindled mesenchymal cells resembling the classical type of congenital mesoblastic nephroma, encasing discrete nodules of embryonal epithelium similar to the hyperplastic nephrogenic rests (nephroblastomatosis) usually associated with Wilms' tumor. The mesenchymal component consists of a fascicular proliferation of tightly interlaced, uniform, benign-appearing spindled cells that immunostatin for vimentin and fibronectin, but not desmin or actin. The epithelial component consists of discrete islands of blastemal cells that are partially or fully differentiated toward tubular, tubulopapillary, or papillary structures. Psammoma bodies are plentiful. Embryonal epithelium immunostains for cytokeratin but not epithelial membrane antigen. The overall histologic appearance of the mesenchymal and epithelial components is benign, and preliminary clinical data suggest that the tumor has a benevolent course. Two cases, however, contained small, well-circumscribed papillary lesions near the renal pelvis that resembled low-grade collecting duct carcinoma. The clinical implications of the latter finding are unclear.

Adenofibroma↗
PubMed1991

Prognostic factors in nonmetastatic, favorable histology Wilms' tumor. Results of the Third National Wilms' Tumor Study.

A comprehensive statistical analysis of relapses to lung and abdomen and of deaths due to tumor that occurred among 1466 patients with nonmetastatic, favorable histology (FH) Wilms' tumor entered on the Third National Wilms' Tumor Study (NWTS-3) was undertaken. In addition to lymph node involvement, age at diagnosis and tumor size as measured by the weight of the excised specimen were the most important determinants of outcome. The effects of tumor size were most apparent for patients with localized (Stage I) disease; age effects were found for patients with regional (Stage II or III) disease. The presence of microscopic tumor in the margin of surgical resection was an independent predictor of abdominal recurrence and death in the latter group. Although the report of the surgeon of diffuse soilage of the peritoneal cavity from tumor spilled or cut across in the course of nephrectomy was highly correlated with outcome, it was not possible to establish an independent prognostic role for such a finding after adjustment for the aforementioned factors. Patients with intralobar nephrogenic rests (ILNR) had a favorable survival outlook even after accounting for their generally younger ages and lower stages.

Abdominal Neoplasms↗
PubMed1991

Prognostic implications of hepatic adhesion, invasion, and metastases at diagnosis of Wilms' tumor. The National Wilms' Tumor Study Group.

In the Third National Wilms' Tumor Study, (NWTS-3), 190 patients with Favorable Histology (FH) Wilms' tumor (WT) were identified as having tumor adherent to, directly invading, or metastatic to the liver at diagnosis. Analyses of the 3-year relapse-free survival and survival of these patients show that adhesion to the liver surface, direct invasion of the liver, and liver metastases have no additional detrimental effect on prognosis stage-for-stage. The authors conclude that hepatic involvement, when present at the time of diagnosis, should not be regarded as different from other patterns of the disease. Treatment policies should follow those appropriate for stage.

Adhesiveness↗
PubMed1991

The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study.

Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage.

Anaplasia↗
PubMed1991

Complete remission in refractory anaplastic adult Wilms' tumor treated with cisplatin and etoposide.

A 61-year-old woman underwent a left radical nephrectomy for Stage II anaplastic Wilm's tumor. She received no adjuvant therapy. One year later computerized tomography (CT) of the abdomen revealed a mass in the left renal fossa and retroperitoneal adenopathy. A CT-guided needle biopsy was nondiagnostic. The patient had progressive disease after treatment with dactinomycin, doxorubicin, and vincristine, but achieved a complete response after treatment with cisplatin and etoposide. The therapy of Wilms' tumor in adults is discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Hepatocellular carcinoma as second malignant neoplasms in successfully treated Wilms' tumor patients. A National Wilms' Tumor Study report.

Although rare, second malignant neoplasms (SMN) after treatment for Wilms' tumor are deadly. A recent National Wilms' Tumor Study (NWTS) report identified 15 patients with second malignancies discovered over 14,381 person-years of observation. This report described four patients with secondary hepatocellular carcinoma in greater detail. These patients were strikingly similar in that all had right-sided tumors and each one had received right upper-quadrant irradiation. All patients died shortly after diagnosis of the SMN.

Adult↗
PubMed1991

Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study.

The long-term survival of patients with synchronous bilateral Wilms tumor is not well defined. Retrospective review of 185 patients registered with the National Wilms Tumor Study from January 1974 to July 1986 with stage V tumors suggests that the long-term outcome remains good. Over-all survival is 83%, 73% and 70% at 2, 5 and 10 years, respectively. Unfavorable histology, age at diagnosis and the most advanced stage of the individual tumors remain the most important prognostic variables. No significant difference in survival was noted between patients undergoing initial surgical resection of the tumor and those managed with initial tumor biopsy followed by chemotherapy with or without radiotherapy and subsequent surgical resection. Survival does not appear to be compromised by attempting to conserve native renal function with renal-sparing operations.

Age Factors↗