14 research outputs found
Truth-telling and doctor-assisted death as perceived by Israeli physicians
Abstract Background Medicine has undergone substantial changes in the way medical dilemmas are being dealt with. Here we explore the attitude of Israeli physicians to two debatable dilemmas: disclosing the full truth to patients about a poor medical prognosis, and assisting terminally ill patients in ending their lives. Methods Attitudes towards medico-ethical dilemmas were examined through a nationwide online survey conducted among members of the Israeli Medical Association, yielding 2926 responses. Results Close to 60% of the respondents supported doctor-assisted death, while one third rejected it. Half of the respondents opposed disclosure of the full truth about a poor medical prognosis, and the others supported it. Support for truth-telling was higher among younger physicians, and support for doctor-assisted death was higher among females and among physicians practicing in hospitals. One quarter of respondents supported both truth-telling and assisted death, thereby exhibiting respect for patients’ autonomy. This approach characterizes younger doctors and is less frequent among general practitioners. Another quarter of the respondents rejected truth-telling, yet supported assisted death, thereby manifesting compassionate pragmatism. This was associated with medical education, being more frequent among doctors educated in Israel, than those educated abroad. All this suggests that both personal attributes and professional experience affect attitudes of physicians to ethical questions. Conclusions Examination of attitudes to two debatable medical dilemmas allowed portrayal of the multi-faceted medico-ethical scene in Israel. Moreover, this study, demonstrates that one can probe the ethical atmosphere of a given medical community, at various time points by using a few carefully selected questions
An intraoperative MRI system for margin assessment in breast conserving surgery: Initial results from a novel technique
© 2016 Wiley Periodicals, Inc. Background and Objectives: One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. Methods: Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. Results: Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P \u3c 0.00001]). Analysis for a determined cutoff of 11.7 ms revealed 91% sensitivity, 93% specificity, and 92% accuracy. ROC curve analysis yielded AUC of 0.97. Conclusions: This study demonstrates that the system is sensitive and specific in differentiating malignant and non-malignant tissues in freshly excised breast specimen. The system has the potential to be used for breast specimen margin assessment during BCS, with the goal of decreasing the need for re-operation. J. Surg. Oncol. 2016;114:22–26. © 2016 Wiley Periodicals, Inc
Tissue Specific DNA Methylation in Normal Human Breast Epithelium and in Breast Cancer
<div><p>Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.</p></div
Bidirectional “switch” in TRIM29 regulation from normal epithelium to the respective carcinomas.
<p>TCGA data analysis: (<b>A</b>) TRIM29 promoter methylation (average of 5 Illumina probes, <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091805#pone.0091805.s005" target="_blank">Table S4B</a></b>) in normal and in cancer tissues. Partial methylation was noted in breast and prostate normal tissues that increased in the respective cancers. In contrast, for the other tissue-types, methylation was high in the normal tissues and decreased in the respective carcinomas. (<b>B</b>) For breast and prostate cancers, increase in promoter methylation was associated with decrease in gene expression whereas the opposite was noted for the other tissues. BRCA = breast carcinoma, PRAD = prostate adenocarcinoma, LUSC = lung squamous cell carcinoma, BLCA = bladder carcinoma, PAAD = pancreatic adenocarcinoma, COAD = colon adenocarcinoma, READ = rectal adenocarcinoma UCEC = uterine-cervix carcinoma. Number of samples indicated at the bottom, <b>***</b>p<0.0001, NS – not significant, P-values between groups were calculated using Welch's corrected t-test.</p
Genome-wide methylation analysis of various normal human epithelial tissues.
<p>Pearson correlation coefficient was calculated (<b>A</b>) between the right and the left breast and (<b>B</b>) between breast epithelium and WBC of the same woman. (<b>C</b>) Principal Component Analysis (PCA) grouped 15 tissue samples by their global methylation resemblance into 5 clusters that corresponded with the origin of the tissues.</p
TRIM29 promoter methylation and gene expression varies in normal epithelial tissues.
<p>(<b>A&C</b>) Q-MSP at TRIM29 promoter in (<b>A</b>) various human normal tissues enriched for epithelium and (<b>C</b>) purified human normal epithelial cells. The same tissue samples studied by the Illumina methylation array were included in (A). Q-MSP amplicon overlapped with the sequence of Illumina probe #cg13625403 used for array analysis (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091805#pone.0091805.s005" target="_blank">Table S4</a></b>). (<b>B&D</b>) The same samples were used for gene expression analysis by qRT-PCR that showed inverse correlation with promoter methylation (RNA was not available for fallopian tube and urinary bladder). HMEC- human mammary epithelial cells, HPEpiC-prostate, OvEC-ovarian, HCEpiC- colon, HUtEpiC-uterine, HREC-renal. (<b>E</b>) Data from Illumina Infinium methylation450K array obtained from ENCODE showed similar pattern of TRIM29 promoter methylation in additional purified human normal epithelial cells. Methylation at 5 Illumina probes is shown: 1.cg20655548 2.cg12201660 3.cg17971587 4.cg13285004 5.cg13625403 (<b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091805#pone.0091805.s005" target="_blank">Table S4B</a></b>). Each row refers to one individual.</p