Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.     

Predicting abdominal adipose tissue in overweight Latino youth.

OBJECTIVES: 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. STUDY DESIGN: Cross-sectional. PARTICIPANTS: 196 overweight 8-13-year-old Latino youth. Two-thirds (n = 131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n = 65) was used as a cross-validation group. METHODS AND PROCEDURES: Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). RESULTS: The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p < 0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p < 0.001). Regression analyses showed approximately 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. CONCLUSIONS: Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level.     

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.     

Anaesthetic agents in paediatric day case surgery: do they affect outcome?

Both the numbers of children undergoing day case surgery and the type of procedures performed in this way are increasing. This expansion will only be beneficial if anaesthesia and surgery are provided with minimal post-operative morbidity e.g. postoperative delirium or nausea and vomiting. The choice of anaesthetic technique is considered critical to optimizing the service provided to patients and for this reason much research has addressed this question. This review considers the effect of anaesthetic technique on postoperative outcome in paediatric day case surgery. The outcome measures reviewed by this article are induction of anaesthesia, effects on the cardiovascular system, recovery from anaesthesia and postoperative nausea and vomiting. In each section both quantitative and qualitative outcome measures are discussed. Comparisons are made between sevoflurane and halothane, sevoflurane and propofol, propofol and halothane, desflurane and halothane and the presence or absence of nitrous oxide.     

Flexible real-time control of MagStim 200(2) units for use in transcranial magnetic stimulation studies

A method for two-way serial communication with MagStim 200(2) BiStim units using LabVIEW is described. A suite of LabVIEW 'virtual instruments' which give simple and reliable control of pulse parameters and delivery is described and made freely available online. The advantages of serial control include the ability to quickly and reliably change pulse parameters during an experiment, to randomly intersperse pulses with different parameters without manually resetting the unit, to deliver pulses with a reliable temporal relationship to other external events, and to control pulse parameters interactively. An application that uses the method for adaptive control of pulse intensity is reported.     

Pentafecta: a new concept for reporting outcomes of robot-assisted laparoscopic radical prostatectomy

Background

Widespread use of prostate-specific antigen screening has resulted in younger and healthier men being diagnosed with prostate cancer. Their demands and expectations of surgical intervention are much higher and cannot be adequately addressed with the classic trifecta outcome measures.

Objective

A new and more comprehensive method for reporting outcomes after radical prostatectomy, the pentafecta, is proposed.

Design, setting, and participants

From January 2008 through September 2009, details of 1111 consecutive patients who underwent robot-assisted radical prostatectomy performed by a single surgeon were retrospectively analyzed. Of 626 potent men, 332 who underwent bilateral nerve sparing and who had 1 yr of follow-up were included in the study group.

Measurements

In addition to the traditional trifecta outcomes, two perioperative variables were included in the pentafecta: no postoperative complications and negative surgical margins. Patients who attained the trifecta and concurrently the two additional outcomes were considered as having achieved the pentafecta. A logistic regression model was created to evaluate independent factors for achieving the pentafecta.

Results and limitations

Continence, potency, biochemical recurrence–free survival, and trifecta rates at 12 mo were 96.4%, 89.8%, 96.4%, and 83.1%, respectively. With regard to the perioperative outcomes, 93.4% had no postoperative complication and 90.7% had negative surgical margins. The pentafecta rate at 12 mo was 70.8%. On multivariable analysis, patient age (p = 0.001) was confirmed as the only factor independently associated with the pentafecta.

Conclusions

A more comprehensive approach for reporting prostate surgery outcomes, the pentafecta, is being proposed. We believe that pentafecta outcomes more accurately represent patients’ expectations after minimally invasive surgery for prostate cancer. This approach may be beneficial and may be used when counseling patients with clinically localized disease.