Landmarking the brain for geometric morphometric analysis: An error study

Neuroanatomic phenotypes are often assessed using volumetric analysis. Although powerful and versatile, this approach is limited in that it is unable to quantify changes in shape, to describe how regions are interrelated, or to determine whether changes in size are global or local. Statistical shape analysis using coordinate data from biologically relevant landmarks is the preferred method for testing these aspects of phenotype. To date, approximately fifty landmarks have been used to study brain shape. Of the studies that have used landmark-based statistical shape analysis of the brain, most have not published protocols for landmark identification or the results of reliability studies on these landmarks. The primary aims of this study were two-fold: (1) to collaboratively develop detailed data collection protocols for a set of brain landmarks, and (2) to complete an intra- and inter-observer validation study of the set of landmarks. Detailed protocols were developed for 29 cortical and subcortical landmarks using a sample of 10 boys aged 12 years old. Average intra-observer error for the final set of landmarks was 1.9 mm with a range of 0.72 mm-5.6 mm. Average inter-observer error was 1.1 mm with a range of 0.40 mm-3.4 mm. This study successfully establishes landmark protocols with a minimal level of error that can be used by other researchers in the assessment of neuroanatomic phenotypes. © 2014 Chollet et al

MicroRNA-mediated drug resistance in breast cancer

Chemoresistance is one of the major hurdles to overcome for the successful treatment of breast cancer. At present, there are several mechanisms proposed to explain drug resistance to chemotherapeutic agents, including decreased intracellular drug concentrations, mediated by drug transporters and metabolic enzymes; impaired cellular responses that affect cell cycle arrest, apoptosis, and DNA repair; the induction of signaling pathways that promote the progression of cancer cell populations; perturbations in DNA methylation and histone modifications; and alterations in the availability of drug targets. Both genetic and epigenetic theories have been put forward to explain the mechanisms of drug resistance. Recently, a small non-coding class of RNAs, known as microRNAs, has been identified as master regulators of key genes implicated in mechanisms of chemoresistance. This article reviews the role of microRNAs in regulating chemoresistance and highlights potential therapeutic targets for reversing miRNA-mediated drug resistance. In the future, microRNA-based treatments, in combination with traditional chemotherapy, may be a new strategy for the clinical management of drug-resistant breast cancers

The role of laparoscopic adrenalectomy for adrenal tumours of 6 cm or greater

<b>Background</b><br /> Laparoscopic adrenalectomy (LA) has been shown to reduce hospital stay and morbidity when compared to open adrenalectomy (OA). It is uncertain if the laparoscopic resection of large (≥6 cm) potentially malignant adrenal tumours is appropriate due to concern over incomplete resection and local recurrence. The aim of the present study was to compare the outcomes of LA for tumours ≥6 cm with those &lt; 6 cm.<p></p> <b>Methods</b><br /> Details of all patients referred with adrenal tumours between January 1999 and January 2006 had been recorded prospectively on a database. LA was performed using a lateral transabdominal approach. Contraindications to LA were local invasion requiring en bloc resection of adjacent organs or the requirement of additional open procedures. <p></p> <b>Results</b><br /> 103 patients were referred for adrenal resection. Three with metastatic adrenal carcinoma and two with severe cardiorespiratory disease were deemed unsuitable for operation. One hundred and eleven adrenalectomies were performed: 101 LAs and 10 OAs. Thirty-nine LA were for tumours ≥6 cm while nine OA were for tumours ≥6 cm. There were no significant differences between the median total anaesthetic time, postoperative complications or postoperative stay for patients undergoing LA for tumours ≥6 cm versus tumours &lt;6 cm. Of the six conversions, five were performed for adrenal tumours ≥6 cm [local invasion (n = 3), adhesions (n = 1), primary renal carcinoma (n = 1)]. All tumours in the LA group were resected with clear margins and at a median follow up of 50 months (range 38–74 months). There has been no evidence of local recurrence. <p></p> <b>Conclusions</b><br /> In the absence of local invasion, the outcomes of laparoscopic adrenalectomy for patients with tumours ≥6 cm were comparable to those with tumours &lt;6 cm. This has helped confirm a policy of initial laparoscopic resection for all noninvasive adrenal tumours can be applied safely. <p></p