Livingstonmelgaard3066
Frozen section examination of adenocarcinomas with poorly cohesive growth, including signet-ring cell carcinoma, is challenging. Due to their diffuse morphology, the tumor cells may be indistinct and difficult to distinguish from inflammatory or stromal cells. Ruboxistaurin supplier Misdiagnosis may result in significant adverse clinical outcome. We performed a detailed retrospective analysis of such cases to identify features that are helpful to avoid misdiagnosis at the time of frozen section. We reviewed the original frozen section slides from 50 patients with poorly cohesive carcinoma (PCC) including 32 with positive and 18 with negative frozen section slides. Tumor cells and inflammatory cells were evaluated for 17 distinct cytologic and nine architectural or stromal features. Features with 100% specificity and positive predictive value (PPV) for carcinoma included the presence of cells with a single distinct cytoplasmic mucin vacuole, focal gland formation, and perineural invasion. Features with high specificity, sensitivity, PPV, and negative predictive value (NPV) (all > 75%) included irregular nuclear contours, large nuclear size with many nuclei > 4× the size of a small lymphocyte, and disruption/obliteration of normal structures. Other features with high specificity and PPV (both ≥ 85%) but relatively low sensitivity and NPV-included crescent-shaped/indented nuclei, prominent nucleoli, anisonucleosis (> 41 difference in nuclear size), multinucleation, and the presence of mitotic figures. We characterized useful histologic features of poorly cohesive carcinoma that may serve to distinguish carcinoma cells from benign inflammatory or stroma cells. Knowledge of the relatively specific features in particular may help surgical pathologists avoid false-negative interpretation resulting in significant clinical morbidity.PURPOSE To compare automated breast volumetric scanning (ABVS) with hand-held bilateral whole breast ultrasound (HHUS) prospectively in regards to patient workflow, woman preference, efficacy in lesion detection, and characterization. MATERIALS AND METHODS Supplemental screening was performed with both ABVS and HHUS to 345 women with dense breasts and negative mammograms. Acquisition and evaluation times were recorded. Lesions were classified according to BIRADS US criteria and compared one to one. Women were recalled for a secondary HHUS examination if ABVS showed any additional lesions. Findings were compared based on biopsy results and/or 36-48 months of follow-up. RESULTS Findings could be compared for 340 women. There were two carcinomas which were detected by both methods, with no interval cancers in the follow-up period. Recall rate was 46/340 (13.05%) for ABVS and 4/340 (1.18%) for HHUS. ABVS recalls decreased with experience. HHUS had more true negative (BIRADS 1-2) results, while ABVS had more false positive ones (p less then 0.001). Positive predictive value was 4.17% for ABVS and 50% for HHUS. ABVS overdiagnosed shadowings (p less then 0.01), distortions (p less then 0.034), and irregular nodules (p less then 0.001) in comparison to HHUS. At ABVS, 10.6% of women experienced severe pain. 59.7% stated that they would choose HHUS if they had the chance. CONCLUSION ABVS is as good as HHUS in lesion detection. However, the recall rate is higher and positive predictive value is lower with ABVS, which could result in more follow-ups, and more anxiety for the women. More than 50% women stated they would prefer HHUS if they were given the chance.OBJECTIVE(S) Growing evidence supports that isothiocyanates exert a wide range of bioactivities amongst of which is their capacity to interact with the epigenetic machinery in various cancers including melanoma. Our aim was to characterise the effect of sulforaphane and iberin on histone acetylation and methylation as a potential anti-melanoma strategy. METHODS We have utilised an in vitro model of malignant melanoma [consisting of human (A375, Hs294T, VMM1) and murine (B16F-10) melanoma cell lines as well as a non-melanoma (A431) and a non-tumorigenic immortalised keratinocyte (HaCaT) cell line] exposed to sulforaphane or iberin. Cell viability was evaluated by the Alamar blue assay whilst total histone deacetylases and acetyltransferases activities were determined by the Epigenase HDAC Activity/Inhibition and EpiQuik HAT Activity/Inhibition assay kits, respectively. The expression levels of specific histone deacetylases and acetyltransferases together with those of lysine acetylation and methylation marks were obtained by western immunoblotting. RESULTS Overall, both sulforaphane and iberin were able to (1) reduce cell viability, (2) decrease total histone deacetylase activity and (3) modulate the expression levels of various histone deacetylases as well as acetyl and methyl transferases thus modulating the acetylation and methylation status of specific lysine residues on histones 3 and 4 in malignant melanoma cells. CONCLUSIONS Our findings highlight novel insights as to how sulforaphane and iberin differentially regulate the epigenetic response in ways compatible with their anticancer action in malignant melanoma.PURPOSE Neurophysiologic intraoperative monitoring (NIOM) abnormalities during scoliosis surgery led to a diagnosis of Friedreich's ataxia in this illustrative case. This prompted the retrospective examination of NIOM for pediatric scoliosis surgery in polyneuropathy patients. METHODS Among patients who underwent scoliosis surgery in 2010-2017, there were six polyneuropathy patients identified. Their clinical history and baseline NIOM data were reviewed. RESULTS Scoliosis accompanied Charcot-Marie-Tooth disease, Friedreich's ataxia, and ataxia telangiectasia. Some patients with no recorded somatosensory evoked potentials (SEPs) exhibited motor evoked potentials (MEPs); no patients with absent MEPs had SEPs present. NIOM modifications included SEP stimulation rate; type of SEP electrodes used; train parameters for MEP acquisition; and sweep speed. CONCLUSIONS This sample of NIOM data for previously monitored scoliosis cases in children with polyneuropathy allowed investigation of patterns of findings and troubleshooting attempts to optimize monitoring.