Prevalence of pre-malignant and malignant lesions in prophylactic mastectomy specimens of BRCA1 mutation carriers: comparison with a control group.

PURPOSE: BRCA1 mutation carriers are at high risk for breast cancer (BC). The risk management strategy may include radiological investigations for early detection or prophylactic mastectomy (PM). For a mutation carrier, PM may be more significant than surveillance alone when pre-malignant and malignant changes occur increasingly in mastectomy specimens, given normal findings on radiological investigations. In the present study we retrospectively investigated the differences between histological findings in PM specimens of BRCA1 carriers and those of a control group. METHODS: Twenty-four healthy and 28 affected carriers in the presence of normal preoperative radiological findings were included in the study. To compare the frequency of pre-malignant and malignant lesions in PM specimens, a control group matched for age and disease status was included. T-tests for independent samples and Wilcoxon's signed-rank test were used for comparison of groups. RESULTS: The entire study group differed significantly from the control group (42.3 vs. 5.8%; P < 0.001) in terms of the occurrence of pre-malignant and malignant lesions. Both, the sub-group comparison of healthy mutation carriers as well as diseased carriers with their controls, showed a significant difference in terms of the occurrence of pre-malignant and malignant changes (45.8 vs. 0%; P = 0.002; 39.3 vs. 10.7%; P = 0.03). In PM specimens of mutation carriers, carcinomas were identified in 5.8% (3/52) and pre-malignant changes in 36.5% (19/52). CONCLUSIONS: BRCA1 mutation carriers should be informed of the fact that pre-malignant and even malignant changes are frequently found in PM specimens despite normal radiological findings.

Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients.

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.

Biocatalytic approaches for the quantitative production of single stereoisomers from racemates.

Strategies for the chemoenzymatic transformation of a racemate into a single stereoisomeric product in quantitative yield have been developed. A range of industrially relevant alpha-hydroxycarboxylic acids was deracemized in a stepwise fashion via lipase-catalysed enantioselective O-acylation, followed by mandelate racemase-catalysed racemization of the remaining non-reacted substrate enantiomer. Alternatively, aliphatic alpha-hydroxycarboxylic acids were enzymatically isomerized using whole resting cells of Lactobacillus spp. Enantioselective hydrolysis of rac-sec-alkyl sulphate esters was accomplished using novel alkyl sulphatases of microbial origin. The stereochemical path of catalysis could be controlled by choice of the biocatalyst. Whereas Rhodococcus ruber DSM 44541 and Sulfolobus acidocaldarius DSM 639 act through inversion of configuration, stereo-complementary retaining sulphatase activity was detected in the marine planctomycete Rhodopirellula baltica DSM 10527.

Delinquents and nondelinquents in depressed areas: Some guidelines for community preventive action.

Attention is directed to the reasons why all children from unwholesome homes do not become delinquent and why there are children from "good" families who do become delinquent. With these findings as a basis, foci of communitywide preventive programs that would take into realistic account the needs of special groups of delinquents and non-delinquents are suggested.

Using molecular and ecological data to diagnose endangered populations of the puritan tiger beetle Cicindela puritana.

Populations of the puritan tiger beetle Cicindela puritana in the eastern United States were found to be highly threatened at the Connecticut River, whereas several large populations on the western shore and newly discovered populations on the eastern shore of the Chesapeake Bay appeared to be less endangered. We assessed if the disjunct C. puritana subgroups are genetically distinct and therefore should be treated as separate units for conservation purposes. A total of 13 individuals from the Connecticut River and 27 individuals from the Chesapeake Bay were each analysed by sequencing of up to 837 base pairs of mitochondrial DNA per individual. Five different haplotypes could be distinguished. In a phylogenetic analysis of these DNA sequences that included four related Cicindela species as out-groups, haplotypes from the Chesapeake Bay represent a distinct clade. The conservation status of these populations was evaluated using a phylogenetic approach based on cladistic analysis and the framework of the phylogenetic species concept. According to this analysis, beetles from the Connecticut River and the Chesapeake Bay have to be considered as independent units. Populations from the eastern and western shore of Chesapeake Bay are not split in more than one unit using the same criteria, although they exhibited some degree of genetic subdivision. The results from the mtDNA analysis were corroborated by ecological parameters in that the Chesapeake Bay populations can be distinguished from all congeners by their different habitat association.