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Biomedical subjects

N Breslow

Publications and source records attributed to N Breslow.

At least 19 recordsLinked to original sources

Surgical complications after nephrectomy for Wilms' tumor.

We reviewed the charts of 1,910 children enrolled in the Third National Wilms' Tumor Study who underwent primary nephrectomy. Four hundred and ninety-five surgical complications occurred in 379 children (19.8 percent). Patients with inoperable tumors, bilateral renal tumors, peroperative therapy and those who refused treatment were excluded from this review. The most common complication was intestinal obstruction, which occurred in 132 patients (6.9 percent). This was followed by extensive intraoperative hemorrhage (112 patients), defined as blood loss exceeding 50 milliliters per kilogram of body weight. Intraoperative injuries to other visceral organs (including intestine, liver and spleen) occurred in 21 children and extensive vascular injuries were reported in 27 patients. There were nine deaths attributed to surgical complications (0.5 percent), only one of which was intraoperative. Survival of patients with complications was similar to patients without complications when stratified by histologic study and stage. Factors associated with the development of surgical complications included advanced local tumor stage at diagnosis, intravascular tumor extension and resection of other visceral organs at the time of nephrectomy. Complete removal of the tumor is important, but not at the expense of radical removal of adjacent structures, because of gross appearances at operation. They are often not invaded by the tumor, but rather are compressed, distorted or adherent without tumor infiltration. Identification of these groups will aid the surgeon in choosing the appropriate management for these patients at high risk. When initial exploration and precise surgical staging indicate that only a formidable operation will achieve total excision, shrinkage of the tumor with selective use of chemotherapy or radiotherapy, or both, may facilitate removal and decrease surgical morbidity. Preoperative therapy may also be the preferred approach for children with extensive intravascular tumor.

Actuarial Analysis

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

Epidemiological basis for clinical diagnosis of childhood malaria in endemic zone in West Africa.

It is difficult to distinguish childhood malaria from other common febrile disorders by parasite count alone, because of the wide variation in tolerance of parasitaemia among individuals. We postulated that the proportion of febrile episodes among young children that can be attributed to parasitaemia varies according to simple clinical criteria. We studied 1114 children aged 2-9 years, who attended a dispensary in the Republic of Niger, with a case-control approach; each of 557 febrile children was matched with a non-febrile control by sex, age, ethnic group, and day of presentation. Febrile episodes were classified according to three clinical criteria: the presence of a likely non-malarial cause; the duration (less than 3 or more than 3 days before presentation); and the intensity (below 39 degrees C or 39 degrees C and above). There was no evidence for an association between febrile episodes and parasite count during the dry, low-transmission, season. During the rainy, high-transmission, season, by contrast, there was a highly significant relation (p less than 0.0001) between the likelihood of fever and the parasite count; each clinical criterion strengthened the association. There was no association between parasitaemia and low intensity fevers, with an obvious cause, that started 3 or more days before presentation, even in the rainy season; however, the relative risk of a fever that met all three criteria developing in those with vs those without parasitaemia was 27.5. The proportion of febrile cases attributable to detectable parasitaemia (population attributable risk) ranged from 0 to 0.92. Our results suggest that simple clinical criteria may be valuable in the selection of febrile patients for antimalarial treatment. In this geographic area, high fever of short duration and with no other obvious cause that occurs during the rainy season is most likely to be malaria.

Animals

Late effects of treatment for Wilms' tumor. A report from the National Wilms' Tumor Study Group.

The National Wilms' Tumor Study (NWTS) was initiated in 1969. One of its objectives was to modulate treatments according to risk factors to minimize the number and severity of treatment-related short-term and long-term iatrogenic complications. The NWTS has therefore incorporated a Long Term Follow-up Study (LTFS) within its framework to monitor late effects. The LTFS is confined to relapse-free survivors alive 5 years or longer after initial surgery, and data are collected using specifically designed forms. A total of 787 patients registered on NWTS-1 or NWTS-2 (1969 to 1979) were eligible, of whom 680 (86%) were available for analysis regarding musculoskeletal, cardiovascular, and neuropsychologic status, and the presence of benign and malignant tumors. Patients with early-stage disease who were treated with radiation had scoliosis reported, along with other musculoskeletal abnormalities (32 versus 2), nearly seven times as often as did the members of the cohort population who did not undergo radiation (35 of 57 versus 5 of 53, respectively). The difference in cardiovascular problems recorded in survivors who did and did not receive Adriamycin (Adria Laboratories, Columbus, OH) (2.4 versus 1.1 per 100-person years at risk) had borderline statistical significance (P = 0.06). No excess in neuropsychologic events was reported for those given the neurotoxin vincristine. When considering patients with disease of all stages, all 5 second malignant tumors occurred in the 623 patients who underwent radiation (RT patients); benign tumors were also more frequent in RT patients than in those patients who did not undergo radiation (41 of 486 or 8% versus 4 of 194 or 2%). Continuing study of this unique body of patients is needed, especially for those given Adriamycin, because of the known long interval needed for latent cardiomyopathy to become clinically manifest in some patients.

Cardiovascular Diseases

Further studies in the variability of pock counts.

The problem of estimating viral activity from pock counts that exhibit a substantial degree of overdispersion is revisited from the viewpoint of quasilikelihood with unknown parameters in the variance function. Score statistics are developed for tests and interval estimates of both mean and variance parameters. These yield somewhat different conclusions than do methods based exclusively on point estimates and standard errors, especially for the variance parameters. A Monte Carlo study confirms that, in the absence of strong prior information about the shape of the error distribution, inferences on variances are highly unstable in small to moderate samples.

Animals

Surgical evaluation of lymph node metastases in Wilms' tumor.

Because lymph node (LN) involvement continues to be an adverse prognostic factor in the later National Wilms' Tumor Study (NWTS) trials, the NWTS-3 Surgical Committee undertook a project to determine the accuracy of the present method of sampling. The committee concludes that: (1) there is a relatively low potential error rate (less than 10%) that would comprise adequate care when a policy of LN sampling is followed; (2) this does not encourage routine radical LN dissections in Wilms' tumor patients because of the well-known morbidities associated with that procedure; and (3) LN sampling in all Wilms' tumor patients should be performed with a high index of suspicion present in the mind of the operating surgeon.

Biopsy

Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study.

The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I-IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR +/- cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.

Adolescent

Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study.

The characteristics of 367 stage I-IV National Wilms' Tumor Study (NWTS) children who relapsed after initial treatment for unilateral disease in the second and third NWTS trials (NWTS-2 and -3) were analyzed to identify features predictive of survival. Although modifications in initial therapy resulted in a lower rate of first relapse in these two studies compared with NWTS-1, all previously identified prognostic factors after relapse remained statistically significant predictors of survival. Tumor histology, length of initial remission, initial therapy with two v three drugs, and site of relapse each were independently predictive of postrelapse survival. The 3-year postrelapse survival for all 367 patients was 30% +/- 3%; however, subgroups classified by these prognostic factors were identified that had 3-year postrelapse survival rates of greater than 40%. These subgroups included patients who had tumors of favorable histology (FH) that recurred (1) only in the lungs, (2) in the abdomen when radiotherapy (RT) was not initially given, or (3) that were originally stage I, (4) that were originally treated with only two drugs, or (5) that recurred 12 months or more after diagnosis. These results were achieved with the use of standard treatments, ie, surgery, RT, and chemotherapy using dactinomycin (AMD), vincristine (VCR), and Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH). It is suggested that patients in these groups might be managed with aggressive use of conventional therapies until newer chemotherapeutic agents and drug combinations are shown to be more effective. Patients with adverse prognostic features at relapse have a poor survival expectancy with standard measures. Salvage attempts for these patients are better based on experimental approaches.

Adolescent

Age distribution of Wilms' tumor: report from the National Wilms' Tumor Study.

Median ages at diagnosis were 36.5 and 42.5 mo for 1523 males and 1678 females with unilateral Wilms' tumor registered between October 1969 and December 1985; they were 23.5 mo and 30.5 mo for 100 males and 141 females with bilateral disease. The median age for multicentric, unilateral cases was intermediate between the bilateral and unicentric medians. Patients with hemihypertrophy in addition to their Wilms' tumor had a typical age distribution, whereas those with aniridia or characteristic genitourinary anomalies were substantially younger. Patients with perilobar nephroblastomatosis had a median age of 35.5 mo and those with intralobar nephroblastomatosis, a median age of 18.5 mo. Most of the bilateral disease occurred in the presence of one or both of these precursor lesions. These findings suggest heterogeneity in the pathogenesis of Wilms' tumor, having implications for genetic counselling, and call into question certain aspects of Knudson and Strong's two-stage mutational model for the origin of Wilms' tumor.

Adult

Intracaval and atrial involvement with nephroblastoma: review of National Wilms Tumor Study-3.

We reviewed the records of 77 children enrolled in the National Wilms Tumor Study-3 who had involvement of the inferior vena cava with tumor thrombus. None of these patients received preoperative chemotherapy or radiotherapy. Ultrasonography and inferior venacavography were more helpful than computerized tomography in the preoperative diagnosis. The median followup for the group was 2.7 years. The 3-year survival rates for patients with intracaval involvement were determined by stage (88, 89 and 62 per cent for stages II, III and IV, respectively). The most important prognostic factor was histological type. The level of vena caval involvement had no effect on survival; all 16 patients with atrial involvement survived 3 or more years. We continue to recommend appropriate surgical excision of the tumor and thrombus when it is technically feasible.

Adolescent

Chemotherapy-related toxicity in infants treated according to the Second National Wilms' Tumor Study.

Babies under 12 months of age have been included in the National Wilms' Tumor Study (NWTS) series of clinical trials. Undue chemotherapy-related toxicity was encountered early during the course of the second NWTS. The prescribed doses of actinomycin D (AMD), vincristine (VCR), and Adriamycin ([ADR] doxorubicin; Adria Laboratories, Columbus, OH) were therefore halved. The frequency of severe hematologic toxic episodes was reduced (30 of 64 or 47% for babies receiving full doses [FD], and six of 48 or 13% for those given reduced doses [RD]). Similar reductions in pulmonary and hepatic effects were noted, and treatment-related deaths were reduced from 6% to 0 for the FD and RD samples, respectively. These frequencies among RD babies were similar to those encountered in 530 older children administered FD. Reduction of dose did not compromise therapeutic effectiveness.

Antineoplastic Combined Chemotherapy Protocols

Nonparametric estimation of relative mortality functions.

The standardized mortality ratio (SMR), which is the ratio of the number of deaths from a particular disease observed in a study cohort to the number expected from national vital statistics, has a long history of use in epidemiology. Separate SMRs computed according to discrete intervals of time since initial exposure, time on study, age or calendar year are used to examine effects of these variables on relative mortality. Applying some recent ideas of Andersen et al. (Biometrics 1985; 41: 921-932), we discuss refinements of this procedure that yield a nonparametric estimate of the SMR as a function of one time-varying factor while at the same time adjusting for the effects of other factors in a regression equation. The method is utilized to study relative lung cancer mortality as a function of years since initial employment in cohorts of 8014 Montana smelter workers and 679 Welsh nickel refinery workers. Suggestions are made for approximating the relative mortality function using only data for cases and matched controls sampled from the full cohort.

Epidemiologic Methods

Bilateral Wilms tumor.

Despite institutional variation in the treatment of synchronous bilateral Wilms tumor, a 76 per cent over-all 3-year survival rate has been achieved. We reviewed 145 patients with stage V disease (synchronous bilateral Wilms tumor) registered with National Wilms Tumor Studies 2 and 3. The majority of the patients (94, or 65 per cent) underwent initial surgical resection followed by chemotherapy with or without radiation, with a 3-year survival rate of 82 per cent. However, survival of 45 patients who underwent initial biopsy, postoperative chemotherapy and second-look surgery was 57 per cent at 3 years, a result not significantly different statistically from the 82 per cent figure. Only 38 per cent of the patients had all tumor resected at 1 or more operations. Therefore, emphasis is being placed on chemotherapy as the predominant treatment modality for this disease. Unfavorable histology was found in 10 per cent of the patients and 6 patients (4 per cent) had discordant histology, that is unfavorable histology on 1 side with contralateral favorable histology. Better prognostic factors were patient age less than 3 years at diagnosis, lower stage of the most advanced lesions, favorable histology and negative nodal involvement. Currently, routine bilateral biopsy of tumors is recommended, followed by chemotherapy according to the stage of the most advanced lesion. Impressive shrinkage of tumor can be expected with the hope that surgery will allow renal preservation (excisional biopsy or partial nephrectomy) rather than nephrectomy.

Adolescent

Comparisons among heterosexual, bisexual, and homosexual male sadomasochists.

Between 1982 and 1984 a questionnaire designed to elicit demographic and behavioral information concerning individuals who participate in sadomasochism (S&M) was distributed nationally. Data from 136 heterosexual, 45 bisexual, and 91 homosexual male sadomasochists (N = 272) were analyzed. Similarities and differences among these three groups in response to 15 of the 40 questions asked concerning age and manner of first S&M interest, openness with others concerning those interests, self image and adjustment, sexual behavior, and sex role orientation are reported and compared to findings previously reported by Spengler (1977), Lee (1979), Kamel (1980), Weinberg & Falk (1980) and Weinberg, Williams, & Moser (1984). Issues concerning the categorization of the respondents into appropriate S&M sex role types are also discussed.

Gender Identity