Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.

Cervical intraepithelial neoplasia--biopsy methods as AIDS for diagnosis and therapy.

Between 1977 and 1995, a total of 1610 patients were admitted to hospital with Pap III, IIID, IVa or IVb. The results of 1182 conisations with cervical abrasion and 428 ectocervical surface scrapings with cervical abrasion were evaluated. The percentage of findings of (CIN II was 35.2% for all cases and 23.3% for conisation alone. No atypical findings or CIN I was seen in 13.9% of all conisation cases. The introduction of a second biopsy method (ectocervical surface scraping (ESS) in 1985 resulted in the reduction of cases with a positive histological finding for conisations of (CIN I from 17.7% (1977-1984, n = 468) to 11.3% (1985-1995, n = 714). Evaluation of combined PA and punch biopsy from the ectocervix assisted by colposcopy was performed in 130 cases. Histological correspondence between the methods was seen in 44.6% of the cases. In 22.3% of the patients the highest CIN degree was seen in the biopsy material obtained under colposcopic observation, while in 33.1% of the cases the highest degree of dysplasia was seen in the material obtained by ectocervical surface scraping. Conisation as the sole diagnostic tool can be replaced by combined and simplified biopsy techniques without prejudice to safety. If only PA is performed, the possibility cannot be ruled out that in individual cases an early-stage invasive cervical carcinoma may be overlooked. Conisation performed without evidence of atypical epithelial structures or only CIN I findings must be regarded as over-treatment. For all CIN III cases, however, conisation remains the most important form of therapy.

Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer.

We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer.

[Breast asymmetry--differential diagnosis and surgical correction]. / Brustasymmetrie--Differentialdiagnose und operative Korrektur.

The problems of asymmetry of the female breast have been exemplified on four cases. Changes in a single breast due to anatomical defects or as a result of an accident, as well as changes due to a large fibroadenoma have been presented. Surgical correction was made after an individual evaluation of each case and included reduction mammoplasty, breast augmentation, lifting and nipple transplantation or reconstruction.

[Ductal carcinoma of the male breast]. / Das Karzinom der männlichen Brust.

Ductal carcinoma in the breast of a 64-year-old male is reported. Diagnosis, therapy, prognosis and follow-up are discussed. Current standard therapy is ablatio mammae, with axillary lymph node dissection. A decision in respect of chemotherapy depends on the results of staging. A follow-up control of the patients for early detection and therapy of metastasis is recommended. Our data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women.