Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study.

OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. PATIENTS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47·6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant. CONCLUSIONS: The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.

Cost-minimization analysis of CHOP, fludarabine and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma in the U.K.

The optimal therapy for patients with relapsed indolent B-cell non-Hodgkin's lymphoma is unclear. Combination chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or purine analogues including fludarabine are frequently used and the anti-CD20 monoclonal antibody rituximab has recently been licensed for use. However, no comparative studies of these therapies have been reported. Since relapsed indolent B-cell NHL is generally regarded as incurable with current therapies, the place of each of these therapies is likely to be determined by their relative efficacy, toxicity and cost. We undertook a literature review and a retrospective analysis of patients receiving combination chemotherapy for relapsed indolent B-cell NHL at our institution to determine the response rates and the duration of response when treated with CHOP or fludarabine. Reported response rates and median response duration for these regimens are similar, and similar to those reported in phase II studies of rituximab. A cost minimization analysis was therefore conducted. The per patient costs for the treatment of drug-related adverse events were pound 5049 for CHOP, pound 2953 for fludarabine and pound 109 for rituximab. When costs of a full course of each treatment were compared, the costs per patient for CHOP, fludarabine and rituximab were pound 7210 (pound 5975-8445), pound 10022 (pound 8917-11126) and pound 6080 (pound 5892-6267) respectively. In this preliminary analysis, rituximab appeared to have a similar efficacy rate to CHOP and fludarabine, but had significantly fewer adverse events and a lower total cost per patient. These data require confirmation in a prospective randomized study with formal assessment of cost-effectiveness.

Material and structural characterization of human saphenous vein.

Saphenous vein patch rupture after carotid endarterectomy is an infrequent but devastating complication. This study was undertaken to evaluate the material and structural properties of fresh human saphenous veins to understand the causes of this complication. Segments of saphenous veins were obtained from 22 patients from vein harvested during coronary artery bypass surgery. Ninety-three specimens, oriented in both circumferential (n = 45) and longitudinal (n = 48) directions, were prepared from the available vein segments for testing. Specimens were mounted on specially designed grips and then subjected to uniaxial tension testing. For each specimen the following material and structural parameters were determined: vessel diameter, tensile stiffness, failure and ultimate forces, and tensile modulus, failure stress, and strain. The physical properties of specimens evaluated in longitudinal orientations and thus limit the inherent strength of the vein. The physical properties of circumferentially tested vein specimens were negatively correlated to age, female gender, diabetes, and hypertension. The data obtained in this investigation suggest that age, hypertension, as well as diabetes and gender may adversely influence the circumferential tensile strength of human saphenous veins used as patch grafts.