Adjuvant 5-flurouracil, alpha-interferon and interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial.

BACKGROUND: The purpose of this trial was to compare adjuvant 5-flurouracil, alpha-interferon and interleukin-2 to observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma (RCC) in terms of disease free survival, overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients 8weeks post nephrectomy for RCC, without macroscopic residual disease, with stage T3b-c,T4 or any pT and pN1 or pN2 or positive microscopic margins or microscopic vascular invasion, and no metastases were randomised to receive adjuvant treatment or observation. QoL was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQC-30). Treatment delivery and toxicity were monitored. The trial was designed to detect an increase in 3year disease free survival (DFS) from 50% on observation to 65% on treatment (hazard ratio (HR)=0.63) with 90% power and two-sided alpha=0.05. RESULTS: From 1998 to 2007, 309 patients were randomised (155 to observation; 154 to treatment). 35% did not complete the treatment, primarily due to toxicity (92% of patients experienced ⩾grade 2, 41% ⩾grade 3). Statistically significant differences between the arms in QoL parameters at 2months disappeared by 6months although there was suggestion of a persistent deficit in fatigue and physical function. Median follow-up was 7years (maximum 12.1years). 182 patients relapsed or died. DFS at 3years was 50% with observation and 61% with treatment (HR 0.84, 95% confidence interval (CI) 0.63-1.12, p=0.233). 124 patients died. Overall survival (OS) at 5years was 63% with observation and 70% with treatment (HR 0.87, 95% CI 0.61-1.23, p=0.428). CONCLUSIONS: The treatment is associated with significant toxicity. There is no statistically significant benefit for the regimen in terms of disease free or overall survival.

Collateral benefits and hidden hazards of soil arsenic during abatement assessment of residential lead hazards.

Abatement of soil-lead hazards may also reduce human exposure to other soil toxins, thereby achieving significant collateral benefits that are not accounted for today. This proposition was tested with the specific case of soil-arsenic, where 1726 residential soil samples were collected and analyzed for lead and arsenic. The study found that these two toxins coexisted in most samples, but their concentrations were weakly correlated, reflecting the differing sources for each toxin. Collateral benefits of 9% would be achieved during abatement of the lead-contaminated soils having elevated arsenic concentrations. However, a hidden hazard of 16% was observed by overlooking elevated arsenic concentrations in soils having lead concentrations not requiring abatement. This study recommends that soil samples collected under HUD programs should be collected from areas of lead and arsenic deposition and tested for arsenic as well as lead, and that soil abatement decisions consider soil-arsenic as well as soil-lead guidelines.

Chemical behavior of residential lead in urban yards in the United States.

Long after federal regulations banned the use of lead-based paints and leaded gasoline, residential lead remains a persistent challenge. Soil lead is a significant contributor to this hazard and an improved understanding of physicochemical properties is likely to be useful for in situ abatement techniques such as phytoremediation and chemical stabilization. A laboratory characterization of high-lead soils collected from across the United States shows that the lead contaminants were concentrating in the silt and clay fractions, in the form of discrete particles of lead, as observed by scanning electron microscopy coupled with energy dispersive X-ray analysis. Soil lead varied widely in its solubility behavior as assessed by sequential and chelate extractions. Because site-specific factors (e.g., soil pH, texture, etc.) are believed to govern the solubility of the lead, understanding the variability in these characteristics at each site is necessary to optimize in situ remediation or abatement of these soils.

Hormone replacement therapy after surgery for stage 1 or 2 cutaneous melanoma.

A total of 206 women were followed for a minimum of 5 years after primary melanoma surgery to establish if hormone replacement therapy (HRT) adversely affected prognosis. In all, 123 had no HRT and 22 have died of melanoma; 83 had HRT for varying periods and one has died of melanoma. After controlling for known prognostic factors, we conclude that HRT after melanoma does not adversely affect prognosis.

Enhancing the power of record linkage involving low quality personal identifiers: use of the best link principle and cause of death prior likelihoods.

The Heartstart Scotland study collects details of all resuscitation attempts carried out by the Scottish Ambulance Service. The linkage between records for Heartstart study subjects who died before admission to a hospital and the national file of death records maintained by the Registrar General for Scotland is described. The conditions under which the Heartstart data is collected make it inevitable that the personal identifying information on which linkage must rely tends to be relatively incomplete and of low accuracy. The linkage process was able to use the best-link principle to take maximum advantage of the fact that, because the Heartstart subjects involved had died, there was an extremely high a priori probability that they would be represented on the national deaths file. In addition, although no cause of death information was recorded on the Heartstart records, a priori expectations of the distribution of causes of death among linked death records were used. Despite these enhancements, however, clerical resolution of a proportion of the potential links generated by the automatic algorithm significantly improved the accuracy of the linkage.