Borderline breast core needle histology: predictive values for malignancy in lesions of uncertain malignant potential (B3)

Breast core needle biopsy (CNB) is an accurate test but may result in borderline histology (lesions of uncertain malignant potential or B3). This is an evaluation of the largest series (to date) of B3 histology, which focusses on estimating positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a 10-year period in a single institution (N=372) from a series of 4035 consecutive needle biopsies. We describe the imaging findings, and report excision histology outcomes (N=279) and category-specific PPV for B3 lesions using two approaches including estimates based on subjects who had either excision or follow-up (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in 181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37 invasive carcinoma). Positive predictive value for malignancy (based on excision histology) was 35.1% (95% CI: 29.5–40.7) and PPV (based on excision or review) was 29.9% (95% CI: 24.9–34.8). Lesion-specific PPV (estimates in parentheses for excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%. Approximately one-third of CNB results classified as B3 are malignant on excision, and the likelihood of malignancy varies substantially between specific lesion groups. Whereas cases may be selectively managed without surgery, the majority warrant excision biopsy based on our estimates. Research is needed to improve differentiation between malignant and benign diseases in B3 lesions using diagnostic or predictive methods

Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined

Higher Sensitivity of Human Auditory Nerve Fibers to Positive Electrical Currents

Most contemporary cochlear implants (CIs) stimulate the auditory nerve with trains of amplitude-modulated, symmetric biphasic pulses. Although both polarities of a pulse can depolarize the nerve fibers and generate action potentials, it remains unknown which of the two (positive or negative) phases has the stronger effect. Understanding the effects of pulse polarity will help to optimize the stimulation protocols and to deliver the most relevant information to the implant listeners. Animal experiments have shown that cathodic (negative) current flows are more effective than anodic (positive) ones in eliciting neural responses, and this finding has motivated the development of novel speech-processing algorithms. In this study, we show electrophysiologically and psychophysically that the human auditory system exhibits the opposite pattern, being more sensitive to anodic stimulation. We measured electrically evoked compound action potentials in CI listeners for phase-separated pulses, allowing us to tease out the responses to each of the two opposite-polarity phases. At an equal stimulus level, the anodic phase yielded the larger response. Furthermore, a measure of psychophysical masking patterns revealed that this polarity difference was still present at higher levels of the auditory system and was therefore not solely due to antidromic propagation of the neural response. This finding may relate to a particular orientation of the nerve fibers relative to the electrode or to a substantial degeneration and demyelination of the peripheral processes. Potential applications to improve CI speech-processing strategies are discussed

Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41379/1/10162_2002_Article_3018.pd

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered