Performance of a six-methylation-marker assay on self-collected cervical samples - A feasibility study.

OBJECTIVES: In high-income countries, a high proportion of cervical cancers is diagnosed in screening non-attendees. One approach to improve screening coverage is to offer self-sampling for human papillomavirus (HPV) testing. However, especially young women are often HPV positive without having a precancerous lesion in need of treatment. To improve the rather low specificity of HPV testing additional markers such as DNA-methylation can be used. The aim of this feasibility study was to examine the performance of the methylation marker assay GynTect®, comprising six methylation markers, on dry self-collected cervico-vaginal samples compared to physician-taken samples. METHODS: We recruited 89 patients from our colposcopy clinic of whom 87 qualified for the study. The women took a self-sample with the Evalyn-Brush. Afterwards the planned colposcopy was performed and smears for cytology and reference HPV testing were taken as well as a biopsy in cases of abnormalities. Physician-taken and self-collected samples were tested for HPV DNA and were analyzed with GynTect®. RESULTS: We obtained 95.5 % valid results for the self-collected samples which was very close to the physician-taken samples. Only about half of the self-collected samples were GynTect® positive in comparison to the physician-taken samples. GynTect® scores were significantly lower for self-collected than for physician-taken samples (p = 0.001, paired t-test). The overall concordance for GynTect® results was moderate (kappa 0.394; p < 0.001). For HPV testing we obtained a good concordance (kappa 0.586; p < 0.001). The GynTect® results for the self-collected samples showed a sensitivity for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+) of 26.1 % (95 %-CI: 0.13-0.46) and a specificity of 95.6 % (95 %-CI: 0.85-0.99), in comparison to a sensitivity of 45.5 % (95 %-CI: 0.27-0.65) and a specificity of 78.3 % (95 %-CI: 0.64-0.88) for the physician-taken samples. CONCLUSIONS: GynTect® methylation marker testing has a satisfactory amount of valid results on self-collected samples. However, the results of the self-collected samples differed clearly in comparison to the reference samples. To justify an application in screening, a larger study with more cases of high-grade cervical dysplasia and HPV positive patients will be needed.

Quality of Life after Bilateral and Contralateral Prophylactic Mastectomy with Implant Reconstruction.

BACKGROUND: Prophylactic mastectomy is an effective approach to breast cancer risk reduction in patients at high risk. Further studies using standardized measures for quality of life are needed to better understand the effect of prophylactic mastectomy on individual patients and, thereby, allow for better patient counseling and selection. METHODS: In this prospective study patients undergoing bilateral mastectomy were asked to complete the BREAST-Q questionnaire before and 1 year after surgery. All patients underwent bilateral mastectomy with implant-based breast reconstruction. Patient- and surgery-related information was collected in a database. RESULTS: In total, 48 patients underwent bilateral skin-sparing mastectomy. Of these, 29 (60.4%) suffered from breast cancer. A 2-stage reconstruction with intermediate expander implantation was conducted in 19 (39.6%) patients. All patients completed the BREAST-Q questionnaire. The domain "psychosocial well-being" was significantly improved from a mean score of 74.98 preoperatively to a postoperative score of 81.56 (p = 0.021). In contrast, the domain "physical well-being" dropped -8.38 points on average to a postoperative score of 74.96 (p < 0.001). Interestingly, patients with the lowest preoperative score in the domain "satisfaction with breast" showed the greatest increase after surgery (50.31 vs. 67.25, p < 0.001). On the contrary, patients with the highest preoperative values experienced the strongest decrease in satisfaction (91.60 vs. 75.27, p = 0.012). CONCLUSION: Implant-based prophylactic mastectomy leads to good quality-of-life results in patients at high risk for breast cancer. Especially, patients with a low preoperative satisfaction with their breasts have a significantly higher chance of experiencing substantial improvements in their quality of life.

Foetal Morbidity Depending on the Day and Time of Delivery.

Introduction It is known that perinatal mortality is increased with births at night and at the weekend. The aim of the study was to investigate whether there is also an association between the time of delivery (weekday, night, weekend) and perinatal morbidity. Material and Methods All births at Hannover Medical College between 2000 and 2014 were included in a retrospective data analysis. Multiple births, primary sections, severe foetal malformations and intrauterine deaths were not included. A 5-minute Apgar score ≤ 5 and cord arterial pH < 7.10 were defined as perinatal morbidity. Besides the time of delivery, different variables that are regarded as risk factors for increased perinatal morbidity were studied. Univariate logistical regression analysis was performed, followed by multivariate analysis. Results 18 394 deliveries were included in the study. Pathological prepartum Doppler, medical induction of labour and delivery at night and/or at the weekend significantly increased the probability of an Apgar score ≤ 5 after 5 minutes. The probability that a child will have cord arterial pH < 7.1 post partum is significantly increased with a BMI > 25 before pregnancy, primiparity, medical induction of labour, peripartum administration of oxytocic agents, when the delivery took place at night and weekend combined, but also when the delivery took place at night or at the weekend/on a public holiday. Multivariate regression analysis showed that a time of delivery at night and/or at the weekend or on a public holiday is not a prognostic factor for a 5-minute Apgar score ≤ 5 (p = 0.2377) but is a prognostic factor for cord arterial pH < 7.1 (p = 0.0252). Conclusion The time of delivery at night or at the weekend/on a public holiday increases the risk for cord arterial pH < 7.1 by ~ 30% compared with delivery on a weekday. However, the time of delivery at night or at the weekend/on a public holiday does not increase the risk for the baby of having a 5-minute Apgar score ≤ 5.

Implications of maternal conditions and pregnancy course on offspring's medical problems in adult life.

In the last decade, numerous epidemiological, clinical and experimental data show that periconceptional, perinatal and postnatal environment determines the offspring's risk for later-life chronic disease. For this phenomenon, the term "fetal" or "perinatal programming" is used. In exposed offspring already in childhood and early adulthood, metabolic and cardiovascular changes can be observed, leading to obesity, diabetes and hypertension. Nowadays, the mode of conception (e.g., in vitro fertilization), maternal metabolic conditions (e.g., undernutrition, overnutrition, diabetes) and complications during pregnancy (e.g., preeclampsia, intrauterine growth restriction) are suspected to be negative predictors for offspring's long-term health. Mechanisms responsible for these effects still remain mainly unclear, but include epigenetic, transcriptional, endoplasmic reticulum stress, and reactive oxygen species. This review presents a piece of the puzzle with regards to periconceptional and early perinatal conditions determining later-life risk for chronic adult disease.