Primary urethral carcinoma in females: an epidemiologic study on demographical factors, histological types, tumour stage and survival.

PURPOSE: To obtain insight into demographical factors, histology and survival rates of females diagnosed with primary urethral cancer and to determine favourable treatment. METHODS: Data from 91 females with primary urethral carcinoma, age varying from 15 to 85 years, registered between 1989 and 2008 at the National Cancer Registry of the Netherlands were used for this study. Demographical factors, incidence rate, morphology and tumour stage according to TNM classification were analysed. Kaplan-Meier survival curves were constructed and stratified by stage, histological type and treatment modality. RESULTS: The overall crude annual incidence was 0.7 per million women with a peak incidence in the age group of 80-84 years. Analysis of the morphology showed urothelial cell carcinoma (UCC) in 45 %, squamous cell carcinoma (SCC) in 19 %, adenocarcinoma (AC) in 29 %, and unknown or undifferentiated carcinoma accounted for 6 %. Almost half of patients (46 %) had advanced disease at time of diagnosis and was mainly treated with surgery and/or radiotherapy. The 5-year survival rates of stage 0-II, stage III and stage IV were 67, 53 and 17 %, respectively. The 5-year survival rates of SCC, UCC and AC were 64, 61 and 31 %, respectively. CONCLUSIONS: Female primary urethral carcinoma is a rare condition, and the majority of patients were aged above 65 years. Almost half of patients have advanced disease upon diagnosis. TNM stage and histological type of disease are the most determining factors for survival. Extended surgery with or without radiotherapy seems to be the most favourable treatment. Awareness and early diagnosis are important to improve survival.

Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat.

The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-beta), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI) showed that IFN-beta treatment reduced lesion volume on diffusion-weighted MRI by 70% (P < 0.01) at 1 day after stroke. IFN-beta attenuated the leakage of contrast agent through the blood-brain barrier (P < 0.005), indicating a better-preserved blood-brain barrier integrity. Both control and IFN-beta-treated animals showed a similar degree of relative hyperperfusion of the lesioned hemisphere, indicating that neuroprotection by IFN-beta was not mediated by improved cerebral perfusion as assessed 24 hours after stroke onset. IFN-beta treatment resulted in an 85% reduction (P < 0.0001) in infarct volume 3 weeks later, as determined from T2-weighted MRI and confirmed by histology. This effect was achieved even when treatment was started 6 hours after stroke onset. Quantitative immunohistochemistry at 24 hours after stroke onset showed that IFN-beta almost completely prevented the infiltration of neutrophils and monocytes into the brain. Gelatinase zymography showed that this effect was associated with a decrease in matrix metalloproteinase-9 expression. In conclusion, treatment with the antiinflammatory cytokine IFN-beta affords significant neuroprotection against ischemia/reperfusion injury, and within a relatively long treatment window. Because IFN-beta has been approved for clinical use, it may be rapidly tested in a clinical trial for its efficacy against human stroke.