Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival

BACKGROUND: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables. The aim of our study was to compare the DNA ploidy status measured using FCM-DNA and ICM-DNA in gastric cancer and to evaluate its association with clinicopathological variables. METHODS: Cell nuclei were isolated from 221 formalin-fixed, paraffin-embedded gastric cancer samples. DNA ploidy was assessed using FCM-DNA and ICM-DNA. RESULTS: A total of 178 (80.5%) gastric cancer samples were classified as DNA aneuploid using FCM-DNA, compared with 172 (77.8%) gastric cancer samples when using ICM-DNA. Results obtained from both methods were concordant in 183 (82.8%) cases (kappa = 0.48). Patients with ICM-DNA diploid gastric cancer survived significantly longer than those with ICM-DNA aneuploid gastric cancer (log rank 10.1, P = 0.001). For FCM-DNA data, this difference did not reach statistical significance. The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status. CONCLUSION: ICM-DNA ploidy status is an independent predictor of survival in gastric cancer patients and may therefore be a more clinically relevant read out of gross genomic damage than FCM-DNA. British Journal of Cancer (2009) 101, 1011-1018. doi:10.1038/sj.bjc.6605266 www.bjcancer.com (C) 2009 Cancer Research U

Sedation in palliative care – a critical analysis of 7 years experience

BACKGROUND: The administration of sedatives in terminally ill patients becomes an increasingly feasible medical option in end-of-life care. However, sedation for intractable distress has raised considerable medical and ethical concerns. In our study we provide a critical analysis of seven years experience with the application of sedation in the final phase of life in our palliative care unit. METHODS: Medical records of 548 patients, who died in the Palliative Care Unit of GK Havelhoehe between 1995–2002, were retrospectively analysed with regard to sedation in the last 48 hrs of life. The parameters of investigation included indication, choice and kind of sedation, prevalence of intolerable symptoms, patients' requests for sedation, state of consciousness and communication abilities during sedation. Critical evaluation included a comparison of the period between 1995–1999 and 2000–2002. RESULTS: 14.6% (n = 80) of the patients in palliative care had sedation given by the intravenous route in the last 48 hrs of their life according to internal guidelines. The annual frequency to apply sedation increased continuously from 7% in 1995 to 19% in 2002. Main indications shifted from refractory control of physical symptoms (dyspnoea, gastrointestinal, pain, bleeding and agitated delirium) to more psychological distress (panic-stricken fear, severe depression, refractory insomnia and other forms of affective decompensation). Patients' and relatives' requests for sedation in the final phase were significantly more frequent during the period 2000–2002. CONCLUSION: Sedation in the terminal or final phase of life plays an increasing role in the management of intractable physical and psychological distress. Ethical concerns are raised by patients' requests and needs on the one hand, and the physicians' self-understanding on the other hand. Hence, ethically acceptable criteria and guidelines for the decision making are needed with special regard to the nature of refractory and intolerable symptoms, patients' informed consent and personal needs, the goals and aims of medical sedation in end-of-life care

‘There is a Time to be Born and a Time to Die’ (Ecclesiastes 3:2a): Jewish Perspectives on Euthanasia

Reviewing the publications of prominent American rabbis who have (extensively) published on Jewish biomedical ethics, this article highlights Orthodox, Conservative and Reform opinions on a most pressing contemporary bioethical issue: euthanasia. Reviewing their opinions against the background of the halachic character of Jewish (biomedical) ethics, this article shows how from one traditional Jewish textual source diverse, even contradictory, opinions emerge through different interpretations. In this way, in the Jewish debate on euthanasia the specific methodology of Jewish (bio)ethical reasoning comes forward as well as a diversity of opinion within Judaism and its branches

Cervical lymph node metastasis in adenoid cystic carcinoma of the larynx: a collective international review

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended

DNA ploidy measurement in oral leukoplakia: Different results between flow and image cytometry

SummaryThe estimated prevalence of oral leukoplakia is worldwide approximately 2%, with an annual malignant transformation rate of approximately 1%. The aim of the present study was to evaluate the possible contribution of ploidy measurement to the prediction of the clinical course, in a well defined cohort of patients with oral leukoplakia. Ploidy was measured by both flow cytometry (FCM-DNA) and image cytometry (ICM-DNA) and we focussed on the comparison of the two different techniques to determine ploidy. A total of 41 patients have been included, with a mean age of 59years (range 36–78years). With FCM-DNA, three lesions were aneuploid, with ICM-DNA, 19 lesions were aneuploid. DNA ploidy was compared with clinicopathological and patients parameters. There were no statistically significant differences between DNA ploidy and any patient factor with both FCM-DNA and ICM-DNA. Using FCM-DNA, DNA aneuploid lesions showed statistically significant more dysplasia (p=0.04) than diploid lesions. Furthermore, DNA aneuploid lesions were more frequently encountered at high-risk locations (p=0.03) as being determined with FCM-DNA. These relations were not found when DNA ploidy was determined with ICM-DNA

Prognostic value of DNA ploidy status in patients with oral leukoplakia

Oral leukoplakia is a potentially malignant disorder that will develop into oral cancer at an estimated rate of 1-2% per year. Aim of the present study is to assess the possible predictive value of DNA ploidy for malignant progression of oral leukoplakia. A cohort of 62 leukoplakia patients was studied and their biopsy was examined with standard histopathology and DNA image cytometry. Cox regression analysis was performed to establish the relationship between progression-free survival and the DNA ploidy status. During the follow-up time (median of 69 months) 13 patients developed an oral squamous cell carcinoma (OSCC). DNA aneuploidy was observed in 27 (44%) patients and was significantly associated with a shorter progression-free survival [Hazard ratio of 3.7, 95% confidence intervals (CI) of 1.1 and 13.0 and a p-value of 0.04]. Sensitivity and specificity scores were 54% and 60%, respectively. Aneuploidy was not correlated with dysplasia grading (chi-square analysis). DNA aneuploidy in oral leukoplakia is associated with an increased risk of progression to OSCC. However, for the individual leukoplakia patient, DNA ploidy status as single biomarker has limited value to predict progression to cancer

Comparative evaluation of genetic assays to identify oral pre-cancerous fields

Background: Oral squamous cell carcinomas often develop in a pre-cancerous field, defined as mucosal epithelium with cancer-related genetic alterations, and which may appear as a clinically visible lesion. The test characteristics of three genetic assays that were developed to detect pre-cancerous fields were investigated and compared to histology. Methods: In total, 10 pre-cancerous fields that were not visible at clinical inspection and gave rise to malignant transformation based on an identical TP53 mutation in tumor and mucosal epithelium in the surgical margin, as well as 10 normal oral mucosa specimens were analyzed for numerical chromosomal changes with multiplex ligation-dependent probe amplification (MLPA), for loss of heterozygosity (LOH), with microsatellite PCR and for DNA index alterations with DNA image analysis. Results: No alterations were detected in normal tissue by either of the assays. Both MLPA and LOH assays detected all pre-cancerous fields. DNA cytometry identified aneuploidy in four of 10 pre-cancerous fields, while the corresponding tumors that developed in these fields were shown to be aneuploid. Conclusions: Both the MLPA and LOH assay seem suitable for screening pre-cancerous fields in subjects at high risk for oral cancer even in the absence of clinically abnormal appearing oral mucosa. Measurements of DNA index might be valuable to determine the time to progression