Methylated APC and GSTP1 genes in serum DNA correlate with the presence of circulating blood tumor cells and are associated with a more aggressive and advanced breast cancer disease

<p>Abstract</p> <p>Background</p> <p>Tumor-related methylated DNA and circulating tumor cells (CTC) in the peripheral blood might be of prognostic importance in breast cancer. Thus, the aim of our study was to examine free methylated DNA and CTC in the blood from breast cancer patients and to correlate it with clinicopathological features known to influence prognosis.</p> <p>Materials and methods</p> <p>We prospectively obtained serum samples from 85 patients with breast cancer and 22 healthy volunteers. Sera were analysed by methylation specific PCR (MethyLight PCR) for five genes: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A), estrogen receptor 1 (ESR1), CDKN2A (p16) and glutathione s-transferase pi 1 (GSTP1). Beta actin (ACTB) served as control. In parallel matched peripheral blood of 63 patients was used to assay for circulating tumor cells in the peripheral blood by a modified immunomagnetic AdnaTest BreastCancerSelect with PCR detection for EPCAM, MUC1, MGB1 and SPDEF.</p> <p>Results</p> <p>We found a hypermethylation in the APC gene in 29% (25/85), in RASSF1A in 26% (22/85), in GSTP1 in 18% (14/76) and in ESR1 in 38% (32/85) of all breast cancer patients. No hypermethylation of CDKN2A was found (0/25). Blood samples of patients were defined CTC positive by detecting the EPCAM 13% (8/63), MUC1 16% (10/63), MGB 9% (5/55), SPDEF 12% (7/58) and in 27% detecting one or more genes (15/55). A significant difference was seen in methylated APC DNA between cancer patients and healthy volunteers. Moreover, methylated APC, RASSF1 and CTC were significantly different in metastatic versus non-metastatic disease. In addition, the presence of methylated APC, RASSF1A and CTC correlated significantly with AJCC-staging (p = 0.001, p = 0.031 and 0.002, respectively). High incidences of methylations were found for the genes RASSF1 and ESR1 in healthy individuals (both 23% 5/22). Methylated GSTP1 was predominantly found in the serum of patients with large primaries (p = 0.023) and was highly significantly correlated with positive Her2/<it>neu </it>status (p = 0.003). Elevated serum CA15.3 was strongly correlated with methylated APC and CTC detection (both p = 0.000). Methylated ESR1 failed to exhibit significant correlations with any of the above mentioned parameters. The presence of CTC in peripheral blood was significantly associated with methylated APC (p = 0.012) and methylated GSTP1 (p = 0.001).</p> <p>Conclusion</p> <p>The detection of methylated APC and GSTP1 DNA in serum correlated with the presence of CTC in the blood of breast cancer patients. Both methylated DNA and CTC correlated with a more aggressive tumor biology and advanced disease.</p

Obesity and Gastroesophageal Reflux: Quantifying the Association Between Body Mass Index, Esophageal Acid Exposure, and Lower Esophageal Sphincter Status in a Large Series of Patients with Reflux Symptoms

Obesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms. Data of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance. Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R 2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p &lt; 0.0001). Compared to patients with normal weight, obese patients are more than twice as likely to have a mechanically defective LES [OR = 2.12(1.63–2.75)]. An increase in body mass index is associated with an increase in esophageal acid exposure, whether BMI was examined as a continuous or as a categorical variable; 13% of the variation in esophageal acid exposure may be attributable to variation in BMI

Height loss in elderly women is preceded by osteoporosis and is associated with digestive problems and urinary incontinence

This study explores risk factors for height loss and consequences in terms of health and wellbeing, in older women. Osteoporosis, low body-mass index, being born in Europe and using medications for both sleep and anxiety were risk factors for height loss. Height loss was associated with digestive problems; excessive height loss was also associated with urinary stress-incontinence and a decline in self-rated health

Tracheal tube and laryngeal mask cuff pressure during anaesthesia - mandatory monitoring is in need

<p>Abstract</p> <p>Background</p> <p>To prevent endothelium and nerve lesions, tracheal tube and laryngeal mask cuff pressure is to be maintained at a low level and yet be high enough to secure air sealing.</p> <p>Method</p> <p>In a prospective quality-control study, 201 patients undergoing surgery during anaesthesia (without the use of nitrous oxide) were included for determination of the cuff pressure of the tracheal tubes and laryngeal masks.</p> <p>Results</p> <p>In the 119 patients provided with a tracheal tube, the median cuff pressure was 30 (range 8 - 100) cm H₂O and the pressure exceeded 30 cm H₂O (upper recommended level) for 54 patients. In the 82 patients provided with a laryngeal mask, the cuff pressure was 95 (10 - 121) cm H₂O and above 60 cm H₂O (upper recommended level) for 56 patients and in 34 of these patients, the pressure exceeded the upper cuff gauge limit (120 cm H₂O). There was no association between cuff pressure and age, body mass index, type of surgery, or time from induction of anaesthesia to the time the cuff pressure was measured.</p> <p>Conclusion</p> <p>For maintenance of epithelia flow and nerve function and at the same time secure air sealing, this evaluation indicates that the cuff pressure needs to be checked as part of the procedures involved in induction of anaesthesia and eventually checked during surgery.</p