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Background: Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence.Methods: Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case-control study evaluated women's personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear.Results: A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p < 0.005). Orthodontic treatment was not associated with attending dental appointment or gynecological check-ups. However, women with an orthodontic treatment in childhood were significantly more often vaccinated against human papillomavirus than women without orthodontic treatment (p < 0.03).Conclusion: Data suggest that women with orthodontic treatment in childhood are more conscious about prevention strategies in adulthood; therefore, compliant behavior might be established in childhood. [ABSTRACT FROM AUTHOR]

Purpose: In this case-control study, the impact on quality of life and sexual function in women with cervical dysplasia and conization will be evaluated, in order to address coping with such a premalignant lesion and to improve strategies for salutogenesis.Methods: This multicenter case-control study evaluates women at special dysplasia outpatient clinic (T1) as well as 3 (T2) and 6 (T3) months after the diagnosis of a dysplasia. The women were subgrouped upon dysplasia only (S2) or dysplasia with conization (S1). Sexual function as well as cervix-related and general quality of life was assessed using validated instruments (FSFI-d, EORTC-QLQ-CX24, SF-36).Results: Women with dysplasia had a lower sexual functioning than controls (FSFI: S1: 23.8 ± 9.7 (p < 0.003); S2: 25.3 ± 7.5 (p < 0.03); K: 29.1 ± 4.5) as well as a lower physical component score (SF-36: S1: 51.3 ± 8.6 (p < 0.02); S2: 51.7 ± 7.8 (p < 0.05); K: 54.2 ± 6.6) and had a significantly reduced body image (EORTC-QLQ-CX24: S1: 75.7 (p < 0.001); S2: 76.5 (p < 0.001), K:89.2). Sexual functioning was not affected by conization in the observational period over 6 months; however, sexual worry was impacted. Over temporal progression women who underwent conization worried more. Regression analysis revealed a cervical dysplasia to impact sexual function.Conclusion: Data suggest that women with the diagnosis of a cervical dysplasia are impaired in their sexual function as well as general and cervix-related quality of life, mostly independent of conization or further observation. To improve salutogenesis in the long run, the communication on dysplasia and its treatment strategy at the beginning, as well as part of aftercare, or psychosomatic intervention, might be treatment options for women at risk. [ABSTRACT FROM AUTHOR]

Objectives: In understanding early disturbances in the mother-child relationship, maternal-fetal attachment has become an important concept. To date no study has investigated the reliability and validity of the German version of the Maternal Fetal Attachment Scale (MFAS). The present study aimed to close this gap.Methods: Questionnaires were completed in a sample of 324 women [third trimester (T1), first week postpartum (T2), and 4 months postpartum (T3)]. In addition to the MFAS (T1), the following measures were assessed: the questionnaire of partnership (T1), the postpartum bonding questionnaire (T2), the Edinburgh Postnatal Depression Scale (T1-T3), the State Trait Anxiety Inventory (T1-T3), and the pregnancy related anxiety questionnaire (T1-T3). Factor structure was analyzed using a principal component analysis (PCA) with varimax rotation. Internal and convergent validities were calculated.Results: In contrast to the original version with five subscales, PCA yielded a three-factor solution, consisting of the three independent dimensions "anticipation", "empathy", and "caring", explaining 34.9% of the variance together. Good internal reliabilities were found for the total MFAS scale. Maternal-fetal attachment showed a significant negative correlation with postpartum bonding impairment. While no correlations were found with depression, general anxiety and pregnancy-related anxiety during pregnancy, maternal-fetal attachment was significantly related to aspects of partnership quality. In the postpartum period, maternal attachment showed a strong negative correlation with maternal anxiety.Conclusions: Our results suggest that the German version of the MFAS is a reliable and valid questionnaire to measure the emotional relationship of the mother to the unborn child during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are pro-inflammatory cytokines which have been shown to be involved in the pathophysiology of implantation disorders. Both cytokines in combination are able to sensitize primarily resistant human endometrial stromal cells (ESCs) to Fas-induced apoptosis. Since CCL (CC-chemokine ligand) 5 and CCL2 are important regulators of the endometrial immune cell population, we examined the impact of TNF-α and IFN-γ on these two chemokines under non-apoptotic and apoptotic conditions.Methods: ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with TNF-α, IFN-γ, an activating anti-Fas antibody and a caspase-inhibitor. CCL5 and CCL2 were measured using ELISA and real-time RT-PCR. Apoptosis was determined by flow cytometry, and cellular viability and membrane integrity were measured by fluorescent assays.Results: The secretion of CCL5 and CCL2 was stimulated in undifferentiated and decidualized ESCs by the combination of TNF-α and IFN-γ under non-apoptotic as well as apoptotic (with Fas-stimulation in parallel) conditions. TNF-α or IFN-γ alone did not have this effect. The stimulatory influence of TNF-α plus IFN-γ on CCL5 and CCL2 in ESCs was also seen on the transcriptional level. Inhibition of cell death by a caspase-inhibitor had no influence on the secretion of CCL5 and CCL2 in ESCs under apoptotic stimulation.Conclusion: TNF-α and IFN-γ modulate the secretion of chemokines in ESCs independently of Fas-induced apoptosis. These results suggest a constant response pattern on pro-inflammatory cytokines within the population of human ESCs. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the leading cause of death from cancer in women and the most common cancer in the world [1]. To date, many patients with estrogen-receptor-positive (ER+) breast cancer are overtreated with chemotherapy when the rationale for adjuvant chemotherapy is based on clinicopathologic parameters. Different studies were able to demonstrate that a 21-gene expression assay (Oncotype DX® Genomic Health, Redwood City, CA) can predict the benefit from adjuvant chemotherapy in ER+ breast cancers [2, 3] and provide additional prognostic information independent of clinicopathological features [4].Results: Data from all patients with ER+ Her2neu- breast cancer undergoing Oncotype DX® testing between 2011 and 2014 at a tertiary referral center in Germany were analyzed. Oncotype DX® was performed in 69 cases, in 2 cases data were missing and in 3 cases Oncotype DX® could not be performed by the company. The results showed a low risk in 39 cases, an intermediate risk in 22 cases and a high risk in 3 cases. Based on Oncotype results, treatment recommendations were changed in 39 of 64 patients (61%). Before Oncotype DX® testing, chemotherapy was recommended in 67 patients, afterwards only in 25 patients. Data from 44 of 67 patients were matched to controls for stage, tumor grade, menopausal and hormone receptor status. Within a mean observation time of 19.7 months, cancer recurrence was observed in two patients.Conclusions: Oncotype DX® testing can be recommended for risk-tailored chemotherapy. Results should be validated in larger prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: Breast ultrasound could be a valuable tool complementary to mammography in breast cancer screening. Automated 3D breast ultrasound (ABUS) addresses challenges of hand-held ultrasound and could allow double reading analysis of ultrasound images. This trial assesses the inter-rater reliability and double reading analysis of an ABUS system.Methods: To assess the reproducibility and diagnostic validity of the ABUS system, SomoV™, a blinded double reading analysis, was performed in 1019 patients (2038 breasts) by two examiners (examiner A/B) and compared to single reading results, as well as to the reference standard regarding its diagnostic validity. Cohen's kappa coefficients were calculated to measure the inter-rater reliability and agreement of the different diagnostic modalities. Patient comfort and time consumption for image acquisition and reading were analyzed descriptively as secondary objectives.Results: Analysis of inter-rater reliability yielded agreement in 81.6% (κ = 0.37; p < 0.0001) showing fair agreement. Single reading analysis of SomoV™ exams (examiner A/examiner B) compared to reference standard showed good specificity (examiner A: 88.3%/examiner B: 84.5%), fair inter-rater agreement (examiner A: κ = 0.31/examiner B: κ = 0.31), and adequate sensitivity (examiner A: 53.1%/examiner B: 64.2%). Double reading analysis yielded good sensitivity and specificity (73.7 and 77.7%). Mammography (n = 1911) alone detected 160 of 176 carcinomas (sensitivity 90.1%). Adding SomoV™ to mammography would have detected 12 additional carcinomas, resulting in a higher sensitivity of 97.7%.Conclusion: SomoV™ is a promising technique with good sensitivity, high patient comfort, and fair inter-examiner reliability. It allows double reading analysis that, in combination with mammography, could increase detection rates in breast cancer screening. [ABSTRACT FROM AUTHOR]

Purpose: Some reproductive factors are well-known general risk factors for breast cancer (BC). On the other hand, BC subtypes also have a high prognostic value. Correlations, however, that link these risk factors to the development of a particular one of the different BC subtypes are still poorly understood. The primary objective of our study was to assess the influence of different reproductive factors (duration of breastfeeding, parity, and age at first childbirth) on pathological BC subtypes. Secondarily, we correlated body mass index (BMI), age at primary diagnosis, and smoking behavior with tumor subclasses.Patients and Methods: We performed a retrospective chart review of 1082 patients with BC who had been treated for postmenopausal BC at the Heidelberg University Hospital during the period 2009-2014. For statistical analysis, different types of correlation analysis as well as a logistic regression model were used.Results: Relating to the primary objective, we found that patients with luminal-like BC had significantly fewer children than patients with triple-negative or HER2-positive subtype tumors (P = 0.027). Concerning the duration of breastfeeding, patients with a luminal A-like tumor had a significantly lower mean nursing period than patients with other subtypes (P = 0.012). Furthermore, patients who did breastfeed presented with a significantly lower number of hormone receptor-positive tumors (estrogen receptor-positive, P = 0.04; progesterone receptor-positive, P = 0.017) but the highest rate of HER2-overexpressing malignancies (P = 0.011). Moreover, late first childbirth was associated with the occurrence of luminal tumors (OR 0.952; P = 0.041). Regarding our secondary aim, higher BMI (P = 0.031) and higher age at primary diagnosis (P = 0.038) were both found to be significantly associated with luminal-like BC.Conclusion: The results suggest a correlation of the occurrence of luminal-like BC subtypes with low parity and short or no duration of breastfeeding. Prospective investigations are needed for further confirmation and to evaluate the molecular basis of our findings. [ABSTRACT FROM AUTHOR]

Purpose: This study aims at developing and evaluating a prototype of a lesion candidate detection algorithm for a 3D-US computer-aided diagnosis (CAD) system.Methods: Additionally, to routine imaging, automated breast volume scans (ABVS) were performed on 63 patients. All ABVS exams were analyzed and annotated before the evaluation with different algorithm blob detectors characterized by different blob-radiuses, voxel-sizes and the quantiles of blob filter responses to find lesion candidates. Lesions found in candidates were compared to the prior annotations.Results: All histologically proven lesions were detected with at least one algorithm. The algorithm with optimal sensitivity detected all cancers (sensitivity = 100 %) with a very low positive predictive value due to a high false-positive rate.Conclusions: ABVS is a new technology which can be analyzed by a CAD software. Using different algorithms, lesions can be detected with a very high and accurate sensitivity. Further research for feature extraction and lesion classification is needed aiming at reducing the false-positive hits. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to identify differences between breast cancer patients with and without migrant background in Germany, especially differences concerning patient characteristics, tumor biology, diagnostics, therapy, and oncological outcome.Patients and Methods: In 99 breast cancer patients (composed of 50 native, randomly selected Germans and 49 consecutively selected immigrants of Anatolian origin) who were operated due to breast cancer at the Heidelberg University Hospital between the years 2009-2012, relevant information was retrospectively reviewed.Results: Patients with migrant background were significantly younger at the time of receiving the diagnosis of breast cancer than native German patients with an average age difference of nine years (p < 0.001). Moreover, immigrants needed a second operation for re-excision more frequently than native Germans (45 vs. 20 %, p = 0.01). The medication used for hormone therapy was significantly different between the two cohorts (p = 0.049). Although statistically not significant, a tendency towards difference was observed in six characteristics examined: Premenopausal status, estrogen receptor-positive tumors, multifocal or bilateral tumors, BRCA-1 mutations, and an accompanying carcinoma in situ were more common in patients with migrant background. On the other hand, correspondence was found between both patient groups relating to tumor staging, grading and metastasis as well as surgical, drug, and radiologic therapies employed. Oncologic outcome data were not different either.Conclusion: A difference in age between breast cancer patients of diverse ethnic groups has already been described previously. The difference in the frequency of surgical re-excision might be explained by several factors like a young age at first diagnosis, premenopausal status, multifocal tumors and an accompanying carcinoma in situ which were more common in the migrant patients of this study and are known to increase the risk of re-excision. The medication used for hormonal therapy was also different between migrants and native Germans, which might be interpreted by the difference in patients' age and menopausal status. Of note, however, in the present study, the overall breast cancer outcome did not show any substantial disparity between the different ethnic patient groups investigated. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with non-platinum-sensitive recurrent ovarian cancer is poor. There is a need for salvage therapies with anti-tumor activity and acceptable toxicity for maintaining quality of life. Pegylated liposomal doxorubicin (PLD, Caelyx(®)) is a promising drug fulfilling these demands. We present retrospective data of patients with advanced epithelial ovarian cancer (EOC) who were treated with pegylated liposomal doxorubicin at the University of Heidelberg between 2007 and 2009.Patients and Methods: Eligible patients for this retrospective study had advanced ovarian cancer and were treated in a palliative setting with PLD at the university hospital of Heidelberg, Germany. Primary objectives were toxicity and efficacy of PLD. 34 patients were included in this study between November 2007 and December 2009; one patient received PLD twice as palliative treatment.Results: The median age of the 34 patients enrolled in this study was 59.9 years (range 27-77 years). The median weight of the patients was 69 kg (range 47-109 kg), the median height 164 cm (range 140-176 cm). Pegylated liposomal doxorubicin was administered every 4 weeks with a dosage of 40 mg/m(2) body surface. PLD was administered for three cycles in median (range 1-9 cycles). Dose reduction was necessary in only four patients. In our study time to progression and overall survival was 8.74 and 14.23 months.Conclusions: In conclusion, this retrospective study showed the efficacy and low toxicity of pegylated liposomal doxorubicin in patients with advanced EOC. Further observations are needed to confirm these preliminary experiences on a larger number of patients. [ABSTRACT FROM AUTHOR]

Purpose: Automated three-dimensional (3D) breast ultrasound (US) systems are meant to overcome the shortcomings of hand-held ultrasound (HHUS). The aim of this study is to analyze and compare clinical performance of an automated 3D-US system by comparing it with HHUS, mammography and the clinical gold standard (defined as the combination of HHUS, mammography and-if indicated-histology). Methods: Nine hundred and eighty three patients (=1,966 breasts) were enrolled in this monocentric, explorative and prospective cohort study. All examinations were analyzed blinded to the patients´ history and to the results of the routine imaging. The agreement of automated 3D-US with HHUS, mammography and the gold standard was assessed with kappa statistics. Sensitivity, specificity and positive and negative predictive value were calculated to assess the test performance. Results: Blinded to the results of the gold standard the agreement between automated 3D-US and HHUS or mammography was fair, given by a Kappa coefficient of 0.31 (95 % CI [0.26;0.36], p < 0.0001) and 0.25 (95 % CI [0.2;0.3], p < 0.0001), respectively. Our results showed a high negative predictive value (NPV) of 98 %, a high specificity of 85 % and a sensitivity of 74 % based on the cases with US-guided biopsy. Including the cases where the lesion was seen in a second-look automated 3D-US the sensitivity improved to 84 % (NPV = 99 %, specificity = 85 %). Conclusion: The results of this study let us suggest, that automated 3D-US might be a helpful new tool in breast imaging, especially in screening. [ABSTRACT FROM AUTHOR]

Purpose: To compare women undergoing laparoscopic hysterectomy with adenomyosis and women with leiomyomas. Materials and methods: Retrospective and questionnaire-based study was conducted at the Department of Obstetrics and Gynecology, University Women's Clinic, Tuebingen, Germany. The study sample comprised a total of 454 women who underwent hysterectomy for adenomyosis or leiomyomas and responded to the questionnaire; 52 (11.4 %) women with a histologic diagnosis of adenomyosis and 452 (88.6 %) women with a histologic diagnosis of leiomyomas. Results: Both groups of patients had enlarged uteri, but women with adenomyosis had a lower mean uterine weight as compared to women with leiomyomas ( p < 0.001). Women with adenomyosis had significantly more pregnancies ( p = 0.003), were more likely to have more than one pregnancy ( p = 0.033) or more than one delivery ( p = 0.025) as compared to women with leiomyomas. In addition, women with adenomyosis had a significantly higher surgical procedure score ( p = 0.017), had more frequently a history of laparotomy ( p = 0.042) and a history of Cesarean section as compared to women with leiomyomas only ( p = 0.024). Significantly, more women with adenomyosis had pelvic pain or pressure as compared to women with leiomyomas ( p = 0.045). We observed no differences between the two groups of patients regarding pelvic pain during the menstrual period, irregular menstrual periods, heavy bleeding, painful sexual intercourse and urination problems. Furthermore, we observed no differences in the therapeutic impact of the surgical procedure between the two patient groups. Conclusions: Women with a histologic diagnosis of adenomyosis differ from women who have only leiomyomas at the time of hysterectomy. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic staging is rapidly evolving as an important surgical approach in the field of gynecology oncology. However, the specific learning curve associated with this approach remains poorly investigated. This study aimed to evaluate the learning curve for laparoscopic staging of uterine cancers. Methods: A series of 28 consecutive laparoscopic hysterectomies with or without pelvic and/or para-aortic lymph node sampling for the treatment of early and locally advanced endometrial or cervical cancer were performed between July 2008 and January 2011. The analyses of the learning curves of the institution were performed for 20 patients who had undergone pelvic lymphadenectomy and/or para-aortal lymph node sampling. The learning curve period has also been compared with the last 26 patients who received laparotomy staging ('open' group) due to the same diagnosis and by the same surgical team. To assess the short- and long-term outcomes, we used validated questionnaires to record the clinical and follow-up results, any complaints or subjective reports from the patients, and details of their quality of life. All data were collected prospectively in a database and reviewed retrospectively. The learning was evaluated using the cumulative sum (CUSUM) method. Results: The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 9 cases) and phase 2 (the subsequent cases) which presented the mastery phase, with the operative time of 397.7 ± 63.5 versus 300.6 ± 19.4 min ( p < 0.0001). The significance of the difference between the two phases and 'open' group changed in terms of number of lymph nodes retrieved, intra-operative blood loss and hospital stay. The conversion rate of phase 1 was higher than phase 2 [2 (22.2 %) respectively 1 (9 %)]. Conclusions: This series confirms previous study findings concerning the feasibility and the safety of laparoscopic staging and provides information for surgeons in single centers considering adopting an endoscopic strategy to monitor the different aspects of outcomes during the implementation process for internal benchmarking. The operative outcome of laparoscopic staging intervention improves with experience. The data reported in this article suggest that after a learning curve of 9 patients, a relevant improvement at least regarding the duration of the operation can be achieved for experienced surgeons who start performing laparoscopic staging of uterine cancers. However, due to the limited number of patients as well as number of para-aortic lymph node sampling procedures, further studies are required for firm conclusions to be drawn. [ABSTRACT FROM AUTHOR]

Background: Our goal is to identify subgroups of women undergoing breast-conserving therapy (BCT) who are at increased risk for requiring a secondary surgical procedure, and to identify tumor and patient profiles that will allow surgeons to anticipate the need for taking larger margins when removing the tumor. Methods: One hundred female patients who had palpable, invasive carcinomas of the breast, and had undergone a primary BCT, were included in the study. Of these, all women ( n = 25) who had incomplete resections, or questionable margins of resection, had to undergo re-excisions. Results: Patients who had multifocal disease, accompanying ductal carcinoma in situ, involvement of regional lymph nodes, high-grade breast cancer (Grade 3 vs. 1/2), lympho-vascular invasion or negative hormone-receptor-status, were significantly more likely to have undergone incomplete removal of tumor tissue-these patients thus required a secondary surgery. Conclusion: The clinical and pathological predictors described above indicate that surgery in breast cancer patients meeting these criteria require larger safety margins to minimize the incidence rate of re-excision at a later date. [ABSTRACT FROM AUTHOR]

First trimester risk assessment for fetal aneuploidies is computed on the base of a general background risk, which is depending on the maternal age. Thereby, the adjusted risk tends to rise with increasing age. Obversely, more unsuspicious fetal parameters [measurement of the nuchal translucency (NT) and biochemical parameters, free beta human chorionic gonadotropine (fß-Hcg) and pregnancy associated plasma protein A (Papp-A)] have to be observed to result in an unsuspicious test at higher age. It was the aim of this study to investigate the potential value of a novel risk assessment algorithm explicitly disregarding the maternal age. This was an ultrasound cohort study of 1,463 singleton pregnancies at 11–14 weeks of gestation undergoing a first trimester screening for fetal aneuploidies by measuring the (NT), Papp-A and fß-hCG. In each case, the pregnancy outcome was obtained. Regarding either the detection of genetic affections or the combined detection of genetic or somatic anomalies, the test performance parameters (sensitivity, specificity, positive and negative predictive values) were calculated and compared with each other. For risk calculation the standard Fetal Medicine Foundation (FMF)-Software and an alternative software with a similar algorithm (JOY-Software) were utilized. Compared to this, the risk assessment had been modified by implementing a novel calculation algorithm (advanced first trimester screening algorithm, AFS) purposely disregarding the maternal age and again, the test performance parameters had been computed and were compared with the first ones. At the mere genetic analysis, all four test-strategies revealed to have identical sensitivity and negative predictive values. Compared to the standard FMF-Software, the JOY-Software showed a reduced false positive rate. In addition, in both softwares, the false positive rate is highly significant-reduced by implementing the AFS-algorithm. At combined genetic and somatic analysis, analogous results on different counts could be found. In the effort to create an algorithm characterising somatic and fetal conditions of the fetus most properly, the inclusion of maternal age is not a helpful value and excluding the age from risk calculation leads to a high significant reduction of the false positive rate. Further, a comparable marked increase of both, specificity and positive predictive values, can be achieved for the FMF- and JOY-Software on the background of the generally more favourable JOY test performance. [ABSTRACT FROM AUTHOR]

In the Original article publication, the name of the co-author Antje Ganz was not included. The Correct order of authors is as given above. [ABSTRACT FROM AUTHOR]