Blurry Boundaries: Do Epithelial Borderline Lesions of the Breast and Ductal Carcinoma In Situ Have Similar Rates of Subsequent Invasive Cancer?

Background

The histology of epithelial “borderline lesions” of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS.

Methods

Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma.

Results

A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.

Conclusions

When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite “borderline” histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.     

Summary of: Evaluation of the end user (dentist) experience of undertaking clinical audit in the post April 2001 general dental services (GDS) scheme

Introduction A mandatory scheme for clinical audit in the general dental services (GDS) was launched in April 2001. No evaluation of this mandatory scheme exists in the literature. This study provides an evaluation of this scheme. More recently a new dental contract was introduced in the general dental services (GDS) in April 2006. Responsibility for clinical audit activities was devolved to primary care trusts (PCTs) as part of their clinical governance remit.Methods All GDPs within Essex were contacted by letter and invited to participate in the research. A qualitative research method was selected for this evaluation, utilising audio-taped semi-structured research interviews with eight general dental practitioners (GDPs) who had taken part in the GDS clinical audit scheme and who fitted the sampling criteria and strategy. The evaluation focused on dentists' experiences of the scheme.Results The main findings from the analysis of the GDS scheme data suggest that there is clear evidence of change following audit activities occurring within practices and for the benefit of patients. However, often it is the dentist only that undertakes a clinical audit project rather than the dental team, there is a lack of dissemination of project findings beyond the individual participating practices, very little useful feedback provided to participants who have completed a project and very limited use of formal re-auditing of a particular topic.Conclusions This study provides evaluation of the GDS clinical audit scheme. Organisations who propose to undertake clinical audit activities in conjunction with dentistry in the future may benefit from incorporating and/or developing some findings from this evaluation into their project design and avoiding others.     

An evaluation of factors associated with sexual risk taking among Black men who have sex with men: a comparison of younger and older populations

In the United States, rates of human immunodeficiency virus (HIV) infection are highest among Black men who have sex with men (BMSM). Prior research indicates that younger BMSM in particular (i.e., BMSM 29 years of age and younger) are most at risk for HIV infection, and that HIV incidence in this subpopulation has risen in recent years. It remains unclear, however, why younger BMSM, relative to BMSM 30 years of age and older, are at increased risk for HIV infection. For the current study, we surveyed 450 BMSM located in the Atlanta, GA metropolitan and surrounding areas. We assessed BMSM’s depressive symptoms, substance use during sex, psycho-social risk factors (i.e., HIV risk perceptions, condom use self-efficacy, internalized homophobia, and perceived HIV stigmatization), and sexual risk taking (i.e., condomless anal intercourse [CAI]). We found that younger BMSM (YBMSM) and older BMSM (OBMSM) differed with respect to factors associated with CAI. In multivariable models, alcohol use before or during sex, lower educational attainment, and sexual orientation (i.e., bisexual sexual orientation) were significantly associated with increased CAI for YBMSM, while HIV risk perceptions and internalized homophobia were significantly, negatively associated with CAI among OBMSM. Rates of engaging in CAI were similar across the two age cohorts; however, factors related to CAI varied by these two groups. Findings emphasize the need to consider targeted interventions for different generational cohorts of BMSM.     

Regulation of the epithelial sodium channel by phosphatidylinositides: experiments, implications, and speculations

Recent studies suggest that the activity of epithelial sodium channels (ENaC) is increased by phosphatidylinositides, especially phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P₃). Stimulation of phospholipase C by either adenosine triphosphate (ATP)-activation of purinergic P2Y receptors or epidermal growth factor (EGF)-activation of EGF receptors reduces membrane PI(4,5)P₂, and consequently decreases ENaC activity. Since ATP and EGF may be trapped in cysts formed by the distal tubule, it is possible that ENaC inhibition induced by ATP and EGF facilitates cyst formation in polycystic kidney diseases (PKD). However, some results suggest that ENaC activity is increased in PKD. In contrast to P2Y and EGF receptors, stimulation of insulin-like growth factor-1 (IGF-1) receptor by aldosterone or insulin produces PI(3,4,5)P₃, and consequently increases ENaC activity. The acute effect of aldosterone on ENaC activity through PI(3,4,5)P₃ possibly accounts for the initial feedback for blood volume recovery after hypovolemic hypotension. PI(4,5)P₂ and PI(3,4,5)P₃, respectively, interacts with the N terminus of β-ENaC and the C terminus of γ-ENaC. However, whether ENaC selectively binds to PI(4,5)P₂ and PI(3,4,5)P₃ over other anionic phospholipids remains unclear.     

Evaluation of undergraduate students using Objective Structured Clinical Evaluation

This study proposed to develop an Objective Structured Clinical Evaluation (OSCE) for senior undergraduate nursing students. This evaluation process uses a simulated and standardized format to measure synthesis of knowledge and clinical skills. The benefit of OSCE is that it provides a formative evaluation for both students and the educational institute. The study included developing case studies, identifying or developing assessment tools, hiring and training standardized patients, obtaining a testing site, and analyzing data. A total of 49 students were assessed on three of six patient simulation stations and one of two nonpatient stationary stations. Both formative and summative evalu-     

Detection of hyponatremia in the PACU.

Fluid and electrolyte management is an important part of PACU nursing care. Any alteration in fluid and electrolytes, especially in the vulnerable elderly population, can be catastrophic. An assessment of hyponatremia following transurethral resection of the prostate requires that the PACU nurse be diligent in discovering the etiology of unexpected mental status changes.     

The XS106 cell: a Langerhans’ cell surrogate with a selective type 2 phenotype

Epidermal Langerhans’ cells (LC) play important roles in initiating and regulating cutaneous immune responses. However, LC comprise less than 3% of all epidermal cells and consequently are difficult to study ex vivo. In the current investigations, we have examined the utility of the XS106 cell line, a dendritic cell (DC) line derived from mouse epidermis, as a surrogate for LC. Membrane marker expression, type 1- and type 2-associated chemokine production, and migration patterns have been characterised following treatment of XS106 cells with a range of toll-like receptor (TLR) ligands. Comparisons have been made with mouse bone marrow-derived DC- and LC-derived ex vivo. Like BMDC, XS106 cells expressed generic DC markers, in addition to displaying higher levels of skin DC markers compared with BMDC. XS106 cells and LC-enriched epidermal fractions both displayed higher constitutive expression of type 2-associated chemokines than type 1 chemokines. Furthermore, although treatment with a range of TLR ligands induced cytokine secretion by XS106 cells, only type 2 TLR ligands increased membrane marker expression of major histocompatibility complex class II and co-stimulatory molecules. Moreover, type 1-associated TLR ligands failed to induce selective type 1 chemokine secretion by XS106 cells. XS106 cells also displayed functional similarity to LC, migrating in response to chemokines that are known to induce the migration of LC. On the basis of membrane marker expression and selective type 2 polarisation XS106 cells provide a useful surrogate for LC.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.