Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers.

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority.

Prevalence of aneurysmal and solitary bone cysts in young patients.

Aneurysmal and solitary bone cysts develop most commonly during skeletal growth. The objective of our epidemiologic study was to evaluate the prevalence, recurrence rate, and probability of recurrence-free survival for aneurysmal and solitary bone cysts in young patients. We did a population-based analysis of 141 histologically confirmed cases. Seventy-three patients with aneurysmal bone cysts and 68 patients with solitary bone cysts were registered. The annual prevalence was 0.32 per 100,000 individuals (range, 0-1.238) for aneurysmal cysts, with a 1.8:1 male to female ratio and a median age of the patients of 11.1 years (range, 1-19.7 years). For solitary bone cysts, the calculated annual prevalence was 0.30 (range, 0-0.963) with a median age of the patients of 1.1 years (range, 0.5-19.9) and a 1.96:1 male to female ratio. Recurrent lesions occurred frequently in young males. Secondary aneurysmal bone cysts were observed only in females. During skeletal growth, aneurysmal and juvenile bone cysts more often occur in males with a peak prevalence at approximately 11 years of age. A greater prevalence of aneurysmal bone cysts in young individuals is associated with skeletal growth and immaturity. Young age and male gender are associated with an increased risk of local recurrence.

Doppler echocardiographic assessment of valvular regurgitation severity by measurement of the vena contracta: an in vitro validation study.

BACKGROUND: Noninvasive quantitation of valvular regurgitation remains a difficult problem. Measurements of the vena contracta (VC) by color Doppler echocardiography have been proposed but limited data are available on the actual accuracy of this method. METHODS: To evaluate how closely the color Doppler VC reflects the true fluid dynamic VC and the anatomic regurgitant orifice and whether this measurement is affected by flow changes, various models of valvular regurgitation were studied in an in vitro flow circuit. The VC diameter was measured with color Doppler using two different ultrasound systems (Agilent Sonos 5500; Agilent Technologies Inc, Palo Alto, Calif and Vingmed CFM 800; GE Healthcare, Chalfront St Giles, UK). Optical planimetry of the anatomic regurgitant orifice was performed, the true VC diameter was determined by laser particle flow visualization. RESULTS: Because of flow contraction, the true VC diameter was consistently smaller than the anatomic regurgitant orifice diameter. Anatomic orifice and true VC only marginally changed with flow rate. The diameter of the color Doppler VC, however, not only overestimated the anatomic orifice diameter by 45% to 60% and the true VC diameter by 130% to 160%, but was also highly affected by the flow rate and the ultrasound system. Despite these limitations a color Doppler VC diameter of 0.77 cm or more (Agilent) and 0.89 cm or more (Vingmed) detected severe regurgitation with a sensitivity of 93% and 84% and a specificity of 96% and 79%, respectively. CONCLUSIONS: Color Doppler estimates of the VC markedly overestimate regurgitant orifice and true VC. In contrast to the true VC, Doppler measurements are significantly affected by flow rate and by the ultrasound system used. Nevertheless, they allow semiquantitative assessment of valvular regurgitation separating severe from nonsevere regurgitation with acceptable accuracy.