Apparent regional differences in the spectrum of BARD1 pathogenic variants in Spanish population and importance of copy number variants.

Only up to 25% of the cases in which there is a familial aggregation of breast and/or ovarian cancer are explained by germline mutations in the well-known BRCA1 and BRCA2 high-risk genes. Recently, the BRCA1-associated ring domain (BARD1), that partners BRCA1 in DNA repair, has been confirmed as a moderate-risk breast cancer susceptibility gene. Taking advantage of next-generation sequencing techniques, and with the purpose of defining the whole spectrum of possible pathogenic variants (PVs) in this gene, here we have performed a comprehensive mutational analysis of BARD1 in a cohort of 1946 Spanish patients who fulfilled criteria to be tested for germline pathogenic mutations in BRCA1 and BRCA2. We identified 22 different rare germline variants, being 5 of them clearly pathogenic or likely pathogenic large deletions, which account for 0.26% of the patients tested. Our results show that the prevalence and spectrum of mutations in the BARD1 gene might vary between different regions of Spain and expose the relevance to test for copy number variations.

NOTES transvaginal cholecystectomy: preliminary clinical application.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is an emerging concept in the recent literature that could lead to potential benefits in clinical applications. Restricted to animal experiments, however, human procedures have not yet been published. Because of the technical and ethical challenges involved in perforation and closure of a healthy organ-as is also seen in operating via the transgastric route-and because of the lack of understanding of the physiopathology and infection risk with these approaches, they have not been applied in the clinical setting. Thus the present study, based on previous animal experiments, describes preliminary clinical application in four cases of transvaginal NOTES cholecystectomy, and discusses safety, feasibility, and potential benefits of the method. METHODS: Preliminary acute and survival animal experiments developed by the NOTES Research Group at our institution solved such technical problems for transvaginal NOTES as spatial orientation, insufflation, and instrumentation, making possible the introduction of NOTES as a clinical application. The trials were approved by ethics committee of our institution, and informed consent was obtained from all patients. Since 13 March 2007, four female patients with elective surgical indication for cholecystectomy have undergone transvaginal NOTES cholecystectomy. All intraoperative and postoperative parameters were documented. Vaginal access was achieved under direct vision with conventional instruments, and a 2-channel colonoscope was inserted into the abdominal cavity. After endoscopic insufflation to achieve pneumoperitoneum with CO(2), instruments were inserted through and alongside a colonoscope, allowing successful NOTES cholecystectomy in all patients, with vaginal extraction of the gallbladder. The vaginal wound was closed by direct vision using conventional instruments. RESULTS: The procedure was successful in all patients, with operative time of 45-115 min. Patients experienced low need for postoperative analgesia. Free oral intake was permitted 2 h after the procedure. There were no postoperative complications, and patients were discharged, according to the study protocol, 48 h after the procedure. CONCLUSIONS: Preliminary results showed the feasibility and safety of the transvaginal NOTES method in this small initial study population. The technique, developed in our institution, and not transgastric NOTES, may be the preferred approach to serve as the basis for clinical studies.

Biotransformation and genotoxic biomarkers in mullet species (Liza sp.) from a contaminated coastal lagoon (Ria de Aveiro, Portugal).

The aim of the present study was to assess liver ethoxyresorufin-O-deethylase (EROD) activity and erythrocytic nuclear abnormalities (ENA) frequency in three mullet species, as biotransformation and genotoxicity biomarkers, respectively, for monitoring aquatic ecosystems. Specimens of Liza aurata, Liza ramada and Liza saliens were caught bimonthly, between May 2000 and March 2001, at nine stations in the Ria de Aveiro (Portugal), a polluted coastal lagoon. The survey revealed two critical areas (Vagos and Carregal) where it was observed elevated EROD activity and ENA frequency, comparing to the reference sites. The results often reflect a contamination by a mixture of pollutants, from point and non-point sources. Nevertheless, the responses observed at Vagos are probably attributable to high polycyclic aromatic hydrocarbon (PAH) water levels measured at that station. All species were able to detect inter-site differences; however L. aurata seems to be the most appropriate bio-indicator due to its larger geographical distribution and abundance during the whole year. The adopted biomarkers, applied to mullet species, can be successfully employed for biomonitoring anthropogenic contamination in both Atlantic and Mediterranean European coastal waters.