Prognostic impact of residual disease in simultaneous additional excision specimens after one-step breast conserving therapy with negative final margin status in primary breast cancer

Purpose

The purpose of this study was the evaluation of risk factors for local recurrence after breast conserving surgery (BCS) with special focus on the impact of residual disease in specimens of simultaneous additional excisions (AE) from the tumor cavity on patients' outcome in patients with negative final margin status after one-step BCS.

Is rural radiation oncology practice quality as good as the big smoke? Results of the Australian radiotherapy single machine unit trial

Radiotherapy utilization rates in rural Australia are suboptimal, with one solution being the building of single machine units (SMUs). One concern raised with such an approach is the quality of care delivered in SMUs. The Australian and Victorian governments have established two SMUs in the state of Victoria, with each SMU operated as a satellite service of a major ‘hub’ site. We report on the planned evaluation of practice quality. Radiation oncologist (RO) clinical practice was externally audited using the Royal Australian and New Zealand College of Radiologists Peer Review Audit instrument. This tool splits RO clinical practice into documentation/quality assurance (QA) criteria and decision‐making criteria. Over the four sites, 130 patients were randomly selected for audit. At hub sites, 79.6% of all criteria audited were adequate, compared with 84.4% of criteria audited at SMUs (P = 0.0002). This difference was largely because of better adherence to documentation/QA criteria at the SMU sites. RO decision‐making and protocol adherence were routinely very high and consistent with other clinical practice audits. There were no significant differences between hubs and SMUs for adherence to decision‐making criteria; however, the few potential deficiencies in patient care identified occurred only at the hub sites. In at least one of these cases, potential suboptimal management was as a direct result of inadequate documentation. This audit found that SMUs provide as high a standard of radiotherapeutic care as larger hub departments. The findings also emphasize the need for all departments to target clinical documentation.     

Dashboard (in the) Knee

We present the case of a 19-year-old individual presenting to an orthopaedic outpatient clinic several months following a dashboard knee injury during a road traffic accident with intermittent mechanical symptoms. Despite unremarkable examination findings and normal magnetic resonance imaging, the patient was identified subsequently as having an intra-articular plastic foreign body consistent with a piece of dashboard on arthroscopic knee assessment, the retrieval of which resulted in a complete resolution of symptoms.     

Effective reprocessing of reusable dispensers for surface disinfection tissues – the devil is in the details

Background: It has recently been reported that reusable dispensers for surface disinfection tissues may be contaminated, especially with adapted Achromobacter species 3, when products based on surface-active ingredients are used. Fresh solution may quickly become recontaminated if dispensers are not processed adequately. Methods: We evaluated the abilities of six manual and three automatic processes for processing contaminated dispensers to prevent recolonisation of a freshly-prepared disinfectant solution (Mikrobac forte 0.5%). Dispensers were left at room temperature for 28 days. Samples of the disinfectant solution were taken every 7 days and assessed quantitatively for bacterial contamination. Results: All automatic procedures prevented recolonisation of the disinfectant solution when a temperature of 60–70°C was ensured for at least 5 min, with or without the addition of chemical cleaning agents. Manual procedures prevented recontamination of the disinfectant solution when rinsing with hot water or a thorough cleaning step was performed before treating all surfaces with an alcohol-based disinfectant or an oxygen-releaser. Other cleaning and disinfection procedures, including the use of an alcohol-based disinfectant, did not prevent recolonisation.Conclusions: These results indicate that not all processes are effective for processing reusable dispensers for surface-disinfectant tissues, and that a high temperature during the cleaning step or use of a biofilm-active cleaning agent are essential.     

Mitogen‐activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere‐associated protein E inhibition

Inhibition of centromere‐associated protein‐E (CENP‐E) has demonstrated preclinical anti‐tumor activity in a number of tumor types including neuroblastoma. A potent small molecule inhibitor of the kinesin motor activity of CENP‐E has recently been developed (GSK923295). To identify an effective drug combination strategy for GSK923295 in neuroblastoma, we performed a screen of siRNAs targeting a prioritized set of genes that function in therapeutically tractable signaling pathways. We found that siRNAs targeted to extracellular signal‐related kinase 1 (ERK1) significantly sensitized neuroblastoma cells to GSK923295‐induced growth inhibition (p = 0.01). Inhibition of ERK1 activity using pharmacologic inhibitors of mitogen‐activated ERK kinase (MEK1/2) showed significant synergistic growth inhibitory activity when combined with GSK923295 in neuroblastoma, lung, pancreatic and colon carcinoma cell lines. Synergistic growth inhibitory activity of combined MEK/ERK and CENP‐E inhibition was a result of increased mitotic arrest and apoptosis. There was a significant correlation between ERK1/2 phosphorylation status in neuroblastoma cell lines and GSK923295 growth inhibitory activity (r = 0.823, p = 0.0006). Consistent with this result we found that lung cancer cell lines harboring RAS mutations, which leads to oncogenic activation of MEK/ERK signaling, were significantly more resistant than cell lines with wild‐type RAS to GSK923295‐induced growth inhibition (p = 0.047). Here we have identified (MEK/ERK) activity as a potential biomarker of relative GSK923295 sensitivity and have shown the synergistic effect of combinatorial MEK/ERK pathway and CENP‐E inhibition across different cancer cell types including neuroblastoma.