Older age is an adverse prognostic factor in stage I, favorable histology Wilms' tumor treated with vincristine monochemotherapy: a study by the United Kingdom Children's Cancer Study Group, Wilm's Tumor Working Group.

PURPOSE: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms' tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. PATIENTS AND METHODS: During two consecutive trials of the United Kingdom Children's Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms' tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. RESULTS: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P =.001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P =.01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P =.66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). CONCLUSION: Treatment for stage I FH Wilms' tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms' tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.     

Augmentation laser for proliferative diabetic retinopathy that fails to respond to initial panretinal photocoagulation.

PURPOSE: A study was performed to determine if diabetic subjects who fail to respond to initial panretinal photocoagulation with regression of retinopathy risk factors do better with supplemental panretinal photocoagulation. METHODS: Thirty-five patients with 3 or more retinopathy risk factors who failed to respond to panretinal photocoagulation with regression to less than 3 retinopathy risk factors by 3 weeks after initial panretinal photocoagulation were prospectively randomized to augmentation laser panretinal photocoagulation (MORE) or to no additional treatment (NOMORE). RESULTS: Six months after initial treatment, the MORE group (n = 16) had regressed a mean of -0.94 retinopathy risk factors (with 95% confidence interval [CI] -1.60 to -0.26), compared with -0.21 retinopathy risk factors (95% CI -0.69 to 0.27) in the NOMORE (n = 19) group (P = 0.055). However, by 1 year, there was no statistically significant difference in the amount of regression of retinopathy risk factors with a mean decrease of -1.12 (95% CI -2.0 to -0.24) versus -1.05 retinopathy risk factors (95% CI -1.80 to -0.28) in the 2 groups, respectively. Similarly, for visual acuity, there was no difference in outcome. For all study patients, the persistence of three or more retinopathy risk factors was associated with a poorer visual result than if there was regression to less than three retinopathy risk factors. CONCLUSION: This study shows that although augmentation panretinal photocoagulation achieved faster regression of retinopathy risk factors, by 1 year, there was no difference in either mean regression of retinopathy risk factors or visual acuity between eyes treated or not treated with augmentation panretinal photocoagulation. In addition, the study shows that the persistence of 3 or more retinopathy risk factors 1 year after treatment was associated with a poorer visual result. Because sample size limited the power of the study to find small differences between groups, and because in proliferative diabetic retinopathy small differences could be important clinically, the authors do not recommend changes in current clinical practice.     

Enhancement of benzo[a]pyrene-induced sister chromatid exchanges in lymphocytes from cigarette smokers occupationally exposed to asbestos

The frequencies of base-line and benzo[a]pyrene [(BP) CAS 50-38-8]-induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BP was observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of SCE by in vitro exposure to BP (P = .01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line SCE frequency in both asbestos-exposed and nonexposed workers (P = .001), and an interaction between smoking and asbestos in the production of base-line SCE was suggested (P = .07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of SCE by BP or with an elevation of base-line SCE. Increased age was associated with an increase in SCE inducibility by BP (P = .01), and a history of smoking was marginally associated with SCE inducibility by BP (P = .07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon-induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.     

von Willebrand factor as a marker of endothelial cell activation following BMT.

Endothelial cell activation may play a role in thrombotic complications of BMT such as hepatic veno-occlusive disease (VOD), right atrial line thrombosis and microangiopathic haemolysis. To assess this, von Willebrand factor antigen (vWF:ag) was measured in 72 patients (25 allografts, 46 autografts and one syngeneic) during the first 6 weeks post-transplant. There was a significant rise in vWF:ag in both allografts and autografts but a greater increase was seen in the allografts. The changes in vWF:ag did not correlate with changes in C reactive protein showing that this was not merely an acute phase response. vWF multimers were normal in a subgroup of uncomplicated transplants showing that there was no large scale endothelial cell disruption. Patients with VOD did not have changes in vWF:ag that were consistently different from uncomplicated controls. Three of four patients who developed line thrombosis had higher levels of vWF:ag compared with control groups; multimeric structure of the vWF was again normal. These results show that there is endothelial cell activation post-BMT and that this is greater in allografts compared with autografts, thus suggesting a possible mechanism for the higher incidence of VOD in this group. There were no useful predictive markers of VOD or thrombosis in individual patients.     

The ensemble-averaged impedance cardiogram: An evaluation of scoring methods and interrater reliability

The interrater reliability and concurrent validity of two methods of scoring the ensemble-averaged impedance cardiogram were evaluated. Impedance cardiographic and electrocardiographic signals were recorded from 40 undergraduate men and women during a baseline rest period and a vocal mental arithmetic task period. Recordings were scored by four raters using a conventional method, involving ensemble averaging after careful editing of beat-to-beat waveforms, and a streamlined method, involving ensemble averaging without beat-to-beat editing. Intraclass correlations for interrater reliability exceeded .92, whereas intraclass correlations for concurrent validity exceeded .97, indicating excellent agreement between raters and scoring methods for all cardiac measures. The streamlined method was significantly faster than the conventional method. The results indicate that variations in beat-to-beat editing do not constitute a serious source of error in the ensemble-averaged impedance cardiogram and support the interrater reliability and concurrent validity of the two scoring methods.