Chromogenic in situ hybridization to detect HER-2/neu gene amplification in histological and ThinPrep-processed breast cancer fine-needle aspirates: a sensitive and practical method in the trastuzumab era

The increasing evidence of trastuzumab efficacy in breast cancer (BC) patients means that an accurate and reproducible evaluation of HER-2 statusis of paramount importance in histological and in cytological samples. Currently, the two main methods used to analyze HER-2 amplification or overexpression are fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Although the two methods are strongly correlated for histological tissue, the evaluation of tumor morphology through FISH may be difficult and fluorescence fades quickly. These limitations can be overcome by chromogenic in situ hybridization (CISH), which can visualize the amplification product along with morphological features. In view of this, in the present study, we analyzed the usefulness of CISH on formalin-fixed, paraffin-embedded (FFPE) BC specimens and investigated whether CISH can be a valid technique in the determination of HER-2 status for fine-needle aspirates (FNAs) processed by liquid-based cytology. The results we obtained in a retrospective series of 111 FFPE BC specimens demonstrated good concordance between CISH and IHC and between CISH and FISH. The former concordance was comparable with that observed between FISH and IHC. When CISH was applied to a prospective series of 53 FNAs, from surgically removed BC, our data showed evidence of a higher concordance of results between liquid-based cytology and the companion FFPE tissues using CISH rather than HercepTesttrade mark. Therefore, CISH analysis, which is avaluable and reproducible alternative to FISH for selecting breast cancer patients for trastuzumab therapy, can lower false-positive immunocytochemistry findings in ThinPrep-processed FNAs.     

Correlation of cytotechnologists' parameters with their performance in rapid prescreening of papanicolaou smears

BACKGROUND: Efficient quality control is essential to ensure high sensitivity of Papanicolaou (Pap) smears. For this purpose, rescreening of 10% random negative smears is increasingly felt to be ineffective. Rapid rescreening (RR) of all negative Pap smears is more practical and has received widespread acceptance, especially in Europe, although its sensitivity is difficult to monitor and its retrospective nature may influence the vigilance of the screeners. The method of rapid prescreening (RPS) overcomes these drawbacks because rapid review of Pap smears precedes full screening. METHODS: All routine conventional Pap smears (n = 8364) over 2 months underwent RPS by 12 cytotechnologists, followed by full screening. Data were analyzed to determine correlation between the RPS sensitivity of individual cytotechnologists and both their sensitivity in full screening and their years of experience as cytotechnologists. RESULTS: There was a striking variability in sensitivity (15.4%-72.7%) among the 12 screeners with an atypical squamous cells of undetermined significance (ASCUS) threshold. There was no correlation between RPS sensitivity of individual cytotechnologists with either their sensitivity in full screening or their years of experience as cytotechnologists. CONCLUSIONS: The skills required of a cytotechnologist for achieving a high sensitivity in RPS are apparently different from those of full screening and are independent of the sensitivity of the screeners at full screening or of the years of experience as cytotechnologists.     

Epidemiologic profile of sexually transmitted diseases (STD) through a specialized consultation of STD

INTRODUCTION: A confidential, free and specialised consultation of sexually transmitted diseases (STD) was initiated since 1993 in the department of Dermatology of hospital Charles Nicolle. We present the epidemiological and clinical features of this consultation. PATIENTS AND METHODS: It is a retrospective study including patients consulting during a period of 7 years (1993-1999). 546 patients were included. The mean age of our patients was 29 years and the sex-ratio 9. The diagnosis of urethritis was done for 242 patients. This diagnosis was clinic in the most cases. Urethral swabs was done for 71 patients. Neisseria gonorrhoeae was isolated in 56 cases and Chlamydia trachomatis in 15 cases. 41 patients were directed to our consultation for a positive syphilis serology. Condyloma were diagnosed in 23 cases and scabies in 12 cases. HIV serology was positive in 10 cases. In 3 cases, the diagnosis of HIV infection was done in this consultation. DISCUSSION: The epidemiologic profile showed a frequency of young men, bachelors and having multiple sexual partners. Clinically, urethritis was the principal STD observed.     

Antioxidant supplements and risk of breast cancer recurrence and breast cancer-related mortality among postmenopausal women

Despite widespread use, only a few clinical or epidemiological studies have examined the relationship between antioxidant supplements and risk of breast cancer recurrence or breast cancer-related mortality. We used proportional hazards and logistic regression modeling to estimate rate ratios and odds ratios (ORs) for recurrence and mortality among 385 postmenopausal women diagnosed with breast cancer between 1986 and 1988 enrolled into a case-control study on diet and cancer. Women were recontacted with a single questionnaire to ascertain the use of nutritional supplements during 12-14 yr of follow-up time. In multivariable models, antioxidant supplement users compared with nonusers were less likely to have a breast cancer recurrence or breast cancer-related death (OR = 0.54, 95% CI = 0.27-1.04). Vitamin E supplements showed a modest protective effect when used for more than 3 yr (OR = 0.33, 95% CI = 0.10-1.07). Premorbid dietary intake of vitamins C or E from diet, supplements, or both showed no relationship with risk. Risks of recurrence and disease-related mortality were reduced among women using vitamin C and vitamin E supplements for more than 3 yr. Recall bias among proxy respondents for women who died during follow-up may have contributed to these findings. This study provides limited support for the hypothesis that antioxidant supplements may reduce the risk of breast cancer recurrence or breast cancer-related mortality.     

Soy consumption and colorectal cancer

We explored the postulated association between soy foods and colorectal cancer incidence by analyzing 13 epidemiological studies: 3 ecological, 1 cohort, and 9 case control. Seven case-control studies evaluated the association between soy intake and colon or colorectal cancer (2,008 cases). Point estimates generally suggest an inverse association between higher soy consumption and colon cancer onset, although nearly all of the confidence intervals overlap 1.0. Two of the nine case-control studies focused on adenomas as the outcome (675 total cases), and results for these studies also showed inverse associations. Of the six case-control studies that evaluated the association between soy consumption and rectal cancer (732 cases), the point estimates generally suggest an inverse association with unfermented soy consumption and rectal cancer onset but not fermented soy products. These studies have many limitations, particularly with regard to dietary measurement issues, such as incomplete assessment of soy intake, inadequate quantification, and inappropriate time period for cancer prevention as well as inadequate adjustment for confounders. Most of these issues would contribute to underestimations of any association. In spite of the methodological issues, the available evidence is compelling enough to warrant further study utilizing stronger methodology.     

Humanized docking system for assembly of targeting drug delivery complexes.

Targeted drug delivery requires 'loading' drugs onto targeting proteins. Traditional technologies for loading drugs rely on chemical conjugation of drugs or drug carriers to targeting proteins. An alternative approach might rely on assembly of targeting complexes using a docking system that includes two components: a 'docking' tag fused to a targeting protein, and a 'payload' module containing an adapter protein for non-covalent binding to the docking tag. We describe here a fully humanized adapter/docking tag system based on non-covalent interaction between two fragments of human pancreatic RNase I. A 15 amino acid long N-terminal fragment of RNase I designed to serve as a docking tag, was fused to the N-terminus of human vascular endothelial growth factor that served as a targeting protein. An 18-125 and an 18-127 amino acid long fragments of RNase I were engineered, expressed and refolded into active conformations to serve as adapter proteins. Interactions between the targeting and adapter proteins were characterized using enzymatic analysis and surface plasmon resonance. Targeting DNA delivery complexes were assembled, characterized by dynamic light scattering, and found to be very effective in receptor-mediated DNA delivery.     

Administration of vancomycin during cardiopulmonary bypass

Vancomycin was given during cardiopulmonary bypass to 12 anaesthetised patients undergoing open heart surgery. Injection of vancomycin 1 g within 60 s via the venous inlet of the oxygenator resulted in a moderate and transient decrease of mean arterial pressure. This minimal reaction may be attributed to dilution of vancomycin by the extracorporeal circuit volume, to the bypassing of the lungs which are a major site of storage of vasoactive substances, or to the maintenance of adequate perfusion flow during cardiopulmonary bypass. The results suggest that the haemodynamic adverse reactions to vancomycin, given as antibiotic prophylaxis, may be decreased by its administration after initiation of cardiopulmonary bypass.