Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial.

BACKGROUND: The randomised findings of the UKW3 trial were that preoperative chemotherapy was associated with a more advantageous stage distribution and reduction in therapy burden versus immediate nephrectomy without compromising outcome in localised Wilms' tumour (WT). We analysed outcome in all WT registered in UKW3. PATIENTS AND METHODS: Seven hundred and eighteen WT cases (7% anaplastic) were registered in UKW3. We assigned a treatment stage and conducted survival analysis. RESULTS: Five-year event-free survival (EFS) and overall survival (OS) were 77.2% [95% confidence interval (CI) 73.9-80.2] and 87.5% (95% CI 84.8-89.7) after median follow-up of 9.5 years and 10.0 years, respectively. Five-year OS in localised non-anaplastic cases was 92.9% (95% CI 90.2-94.9). Anaplasia was associated with adverse outcome compared with non-anaplastic cases: 5-year EFS of 42.0% (95% CI 28.3-55.1) versus 79.8% (95% CI 76.5-82.7) and 5-year OS of 60% (95% CI 45.1-72.0) versus 89.6% (95% CI 87.0-91.7), respectively. Outcomes were similar for non-anaplastic stage I or II but significantly poorer in stage III cases than stage I. Five-year OS after relapse was 54.1% (95% CI 44.5-62.8). Forty-seven percent of non-anaplastic WT received anthracycline; 27% were treated with radiotherapy first line. CONCLUSION: These outcomes provide a baseline for future comparisons of WT treatment approach, burden and patient outcome.

Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome.

Relapsed ependymoma in children poses difficult dilemmas in management. Clinico-pathological and treatment data of 108 children with relapsed ependymoma in the United Kingdom (UK) treated between 1985 and 2002 were reviewed to identify prognostic factors affecting survival. The primary site was the most common site of relapse (84%). Overall 25% had metastatic relapse. Surgery at relapse was attempted in only 55%. Radiotherapy was delivered at relapse in 66% infants and 50% of older children were re-irradiated. Overall 5-year survival was 24% and 27% for children less than 3 years of age at initial diagnosis and older children, respectively. Multivariate analysis showed that, for infants, surgery (p=0.01) and radiotherapy (p=0.001) at relapse were independent predictors of survival. For older children regardless of the previous radiotherapy, repeat irradiation was associated with better outcome (p=0.05). Relapse was associated with poor outcome in both age groups. A survival advantage conferred by both radiotherapy and surgery at relapse is independently significant.

Complex patterns of chromosome 9 alterations including the p16INK4a locus in Wilms tumours.

BACKGROUND: Previous data implicating genetic and epigenetic events on chromosome 9, including the CDKN2A/2B locus, as molecular predictors of Wilms tumour relapse, have been conflicting. AIMS: To clarify this using genome-wide and focused molecular genetic analysis. METHODS: Microarray-based comparative genomic hybridisation (aCGH) using genome-wide coverage was applied to 76 favourable histology Wilms tumours. Additional investigation of the 9p21 locus was carried out using loss of heterozygosity (LOH) and fluorescence in situ hybridisation (FISH), as well as immunohistochemistry for CDKN2A/p16(INK4a) on a paediatric renal tumour tissue microarray. RESULTS: Approximately half of the tumours were found to show chromosome 9 copy number changes. Those cases which harboured alterations comprised at least four distinct patterns: gain of the entire chromosome, loss of 9p, gain of 9q34, or a more complex combination of gains/losses. None of these tumour groups showed any statistically significant correlation with clinicopathological variables. Deletion mapping of 9p by LOH revealed several regions of overlap, including the CDKN2A/2B locus in 4/34 (11.8%) tumours, which was confirmed to represent hemizygous deletions by FISH. CDKN2A/p16(INK4a) protein expression was predominantly negative in Wilms tumours as assessed by immunohistochemistry on a tissue array, reflecting the expression pattern in normal kidney. However, 38/236 (16.1%) non-anaplastic Wilms tumours, 4/9 (44.4%) anaplastic Wilms tumours, 5/7 (71.4%) rhabdoid tumours of the kidney, and 4/10 (40%) clear cell sarcomas of the kidney showed nuclear CDKN2A/p16(INK4a )immunoreactivity. CONCLUSIONS: These data reveal the complex nature of genetic alterations on chromosome 9 in Wilms tumours, but do not provide evidence for their involvement in or association with treatment failure.

Total tracheal obliteration after intubation with a low-pressure cuffed tracheal tube.

A 22-yr-old male had a head injury after a road traffic accident. His trachea was intubated for 5 days with a high-volume, low-pressure cuffed tracheal tube. When the trachea was extubated he showed signs of progressive upper airway obstruction which were relieved by tracheotomy. Computed axial tomography demonstrated complete tracheal obliteration at the previous cuff site. The patient underwent resection anastomosis of the destroyed tracheal segment which, on histological examination, showed fibrous tissue and bone formation. It is believed that excessive cuff pressure was the cause of the damage, as monitoring cuff pressure has not yet become a routine practice in anaesthesia and intensive care.

Rapidly repeated intravenous boluses of salbutamol for acute severe asthma.

We describe the use of intravenous boluses of salbutamol given rapidly (over 1-2 min) in children (5 microg x kg-1) and young adults (250 microg) with acute severe asthma who were not improving with doses of nebulised salbutamol. Intravenous boluses were repeated within a short time until improvement was seen. Two of the seven patients required tracheal intubation and ventilation.