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Purpose: The FUSION-X-US-II prototype was developed to combine 3D-automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device without decompressing the breast. We evaluated the technical function, feasibility of the examination workflow, image quality, breast tissue coverage and patient comfort of the ABUS device of the new prototype., Methods: In this prospective feasibility study, the FUSION-X-US-II prototype was used to perform ABUS in 30 healthy volunteers without history of breast cancer. The ABUS images of the prototype were interpreted by a physician with specialization in breast diagnostics. Any detected lesions were measured and classified using BI-RADS ® scores. Image quality was rated subjectively by the physician and coverage of the breast was measured. Patient comfort was evaluated by a questionnaire after the examination., Results: One hundred and six scans were performed (61 × CC, 23 × ML, 22 × MLO) in 60 breasts. Image acquisition and processing by the prototype was fast and accurate. Breast coverage by ABUS was approximately 90.8%. Sixteen breast lesions (all benign, classified as BIRADS ® 2) were identified. The examination was tolerated by all patients., Conclusion: The FUSION-X-US-II prototype allows a rapid ABUS scan with mostly high patient comfort. Technical developments resulted in an improvement of quality and coverage compared to previous prototype versions. The results are encouraging for a test of the prototype in a clinical setting in combination with tomosynthesis., (© 2021. The Author(s).)

Purpose: Maternal mental disorders develop frequently during the perinatal period, and can have detrimental effects on the developing bond between a mother and her child. While depression has already been widely associated with bonding disorders, the link between anxiety disorders and maternal-fetal attachment has received only limited attention. This study aimed to explore the link between maternal-fetal attachment in the third trimester and postpartum anxiety, as previous research has suggested a potentially protective association. Additionally, we hypothesized a mediating influence of postpartum bonding and partnership satisfaction as additional measurements of attachment capacity., Methods: Self-report questionnaires assessing maternal-fetal attachment, postpartum bonding, anxiety, depression, and partnership quality were completed at three time points: third trimester (T1, N = 324), first week postpartum (T2, N = 249), and 4 months postpartum (T3, N = 166). Conditional process analyses were used to test for mediation., Results: A statistically significant negative correlation of maternal-fetal attachment was found with maternal anxiety postpartum. Overall, the analyses supported the mediation hypothesis. There was a significant, indirect effect of maternal-fetal attachment during pregnancy on state anxiety in the first week postpartum, mediated through postpartum bonding quality and partnership satisfaction. All three variables together accounted for 18.25% (state anxiety) or 30.35% (trait anxiety) of the variance in postpartum anxiety., Conclusions: Our results showed that a close maternal-fetal attachment buffers postpartum symptoms of anxiety, partially mediated through postpartum bonding and partnership satisfaction. Therefore, strengthening the maternal-fetal attachment and the partnership during pregnancy has the potential to reduce maternal postpartum symptoms of anxiety.

Purpose: The Breast Cancer Treatment Outcome Scale (BCTOS) is a questionnaire to evaluate the aesthetic and functional outcome after breast conserving surgery (BCS). The original BCTOS with its 22 items on three subscales was refined to a shorter, improved, and easier to administer patient-reported outcome measure, the BCTOS-12. The BCTOS-12 consists of 12 items on two distinct subscales, the Functional Status and the Aesthetic Status. The aim of this study was to validate the BCTOS-12 in a prospective cohort., Methods: For this study, 239 breast cancer patients were included preoperatively, and 204 patients completed the BCTOS-12 and EORTC QLQ C30 BR23 shortly after their BCS, corresponding to a follow-up rate of 85%. The item-factor structure was examined by confirmatory factor analysis. The reliability was calculated by McDonald's Omega for estimating internal consistency. The convergent validity was assessed by Spearman's rank correlation coefficients between the related scales of the questionnaires., Results: The BCTOS-12 showed a robust item-factor structure and a good internal consistency with McDonald's Omega of 0.89 for the Aesthetic Status and 0.90 for the Functional Status. A high convergent and divergent validity was indicated by correlations between the subscales of the EORTC QLQ C30 BR23 and the BCTOS-12., Conclusion: Overall, the results demonstrate a successful psychometric validation of the BCTOS-12. The BCTOS-12 is a refined, improved, and now validated, instrument. It can be used in clinical studies and routine management for the evaluation of the aesthetic and functional outcome after BCS.

Purpose: The aim of this study is to analyze the correct staging of primary endometrial cancer (EC) using clinical examination and 3 Tesla (T) magnetic resonance imaging (MRI) results compared to histopathology., Methods: In this prospective, non-randomized, single-center study, 26 women with biopsy-proven EC were evaluated. All women underwent clinical examination including transvaginal ultrasound (CE/US) and 3T MRI (T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences) prior to surgery. Spearman's correlation coefficient was employed to analyze the correlation between both staging methods and histopathology and generalized estimation equation analysis to compare their staging results. Main outcome measures are determinations of local tumor extent for EC on CE/US and 3T MRI compared to histopathology (gold standard)., Results: Sixteen women had an early-stage pT1a tumor, 10 a locally advanced ≥ pT1b tumor. The early stage was correctly diagnosed at CE/US in 100%, by MRI in 81%. Spearman's correlation coefficient was r = 1.0 (p < 0.001) for correlation of CE/US and histopathology, r = 0.93 (p < 0.001) for correlation of MRI and pathology. A locally advanced tumor stage was exactly diagnosed by MRI in 70% and at CE/US in 50%., Conclusions: CE/US is sufficient for staging T1a endometrial cancer, while MRI provides higher sensitivity in detecting locally advanced tumors. Based on our results, combining CE/US and 3T MRI in patients with at least suspected deep myometrial invasion offers a more reliable workflow for individual treatment planning.

Purpose: Breast-conserving therapy (BCT) is the standard procedure for most patients with primary breast cancer (BC). By contrast, axillary management is still under transition to find the right balance between avoiding of morbidity, maintaining oncological safety, and performing a staging procedure. The rising rate of primary systemic therapy creates further challenges for surgical management., Methods: Patients with primary, non-metastatic BC treated between 01.01.2003 and 31.12.2016 under guideline-adherent conditions were included in this study. For this prospectively followed cohort, breast and axillary surgery patterns are presented in a time-trend analysis as annual rate data (%) for several subgroups., Results: Overall, 6700 patients were included in the analysis. While BCT rates remained high (mean 2003-2016: 70.4%), the proportion of axillary lymph node dissection has declined considerably from 80.1% in 2003 to 16.0% in 2016, while the proportion for sentinel lymph node biopsy (SLND) has increased correspondingly from 10.3 to 76.4%. Among patients with cT1-2, cN0 breast cancer receiving BCT with positive SLND, the rate of axillary completion has decreased from 100% in 2008 to 24.4% in 2016., Conclusions: In the past decade, SLNB has been established as the standard procedure for axillary staging of clinically node-negative patients. Surgical morbidity has been further reduced by the rapid implementation of new evidence from the ACOSOG Z0011 trial into clinical routine. The results reflect the transition towards more individually tailored, less invasive treatment for selected patient subgroups, especially in regards to axillary lymph node management.

Purpose: To investigate the real-life epidemiology of mental disorders during pregnancy and their impact on birth outcome in an unselected low-risk population in Germany., Methods: Claims data of the Techniker Krankenkasse (TK) were analyzed as part of a retrospective observational study over a one-year period from 01/2008 to 12/2008 including 38,174 pregnant women. ICD-10 codes were clustered into four diagnostic groups: depression, anxiety disorders, somatoform/dissociative disorders and acute stress reactions. The relationship between mental disorders, birth mode and infant weight was tested using chi-squared tests and multivariate logistic regression. Main outcome measures included the prevalence of mental disorders during pregnancy, performed cesarean sections and infants born underweight., Results: N = 16,639 cases with at least one diagnosis from the four mental disorder diagnostic groups were identified: 9.3% cases of depression, 16.9% cases with an anxiety disorder, 24.2% cases with a somatoform/dissociative disorder, and 11.7% cases of acute stress reactions. Women diagnosed with a mental disorder were more likely to deliver their child by cesarean section ([depression: OR =1.26 (95% CI 1.14-1.39); anxiety: OR 1.11 (95% CI 1.02-1.19); somatoform disorders: OR 1.12 (95% CI 1.05-1.20); acute stress reactions: OR 1.17 (95% CI 1.07-1.28)]. Furthermore, infants of women diagnosed with an ICD-10 code for depression during pregnancy were more likely to be underweight and/or delivered preterm [OR =1.34 (95% CI 1.06-1.69)]., Conclusions: We observed substantially high prevalence rates of mental disorders during pregnancy which urgently warrant more awareness for validated screening and adequate treatment options.

Purpose: To compare dynamic magnetic resonance imaging (dMRI) and introital ultrasound results with regard to urethral length measurements and the evaluation of bladder neck changes., Methods: Retrospective analyses of urethral length measurements and detection of bladder neck changes (rotated/vertical bladder neck descent, urethral funneling) were conducted in women-scheduled for surgical treatment with alloplastic material-who had undergone introital ultrasound and dMRI presurgery and 3 months postsurgery. Measurement differences between both imaging modalities were evaluated by assessing the confidence interval for the difference in means between the datasets using bootstrap analysis., Results: Based on data from 40 patients (320 image series), the urethra could be clearly measured on every pre- and postsurgical dMRI dataset but not on preoperative ultrasound images in nine women during Valsalva maneuver due to a large cystocele. The estimation of the mean difference distribution based on 500,000 bootstrap resamples indicated that the urethral length was measured shorter by dMRI pre- and postsurgery at rest and postsurgery during Valsalva maneuver (median 1.6-3.1 mm) but longer by dMRI (median 0.2 mm) during Valsalva maneuver presurgery. Rotated/vertical bladder neck descent and urethral funneling diagnoses showed concordance of 67-74% in the direct comparison of patients; the estimation of the concordance indicated poorer outcomes with 50-72%., Conclusions: Metric information on urethral length from dMRI is comparable to that from introital ultrasound. dMRI is more advantageous in cases with an extended organ prolapse. At present, dMRI does not give the same diagnosis on bladder neck changes as introital ultrasound does.

Purpose: Annual cervical cancer screening is recommended in Germany as a part of the statutory preventive care. Abnormal results can provoke psychological distress and anxiety, compromising women's adherence. Little is known about how a cervical dysplasia impacts adherence follow-up visits and prevention habits over time. To optimize care strategies, this study aims to identify women at risk for nonadherence to follow-up visits after a screening event., Methods: Between November 2015 and May 2017, participants with an abnormal Pap smear at the Heidelberg and Leipzig University Hospitals received a four-part questionnaire (sociodemographic data, PHQ-D, self-designed fear and prevention habit questions) at the first consultation (T1) and subsequently after 3 (T2) and 6 (T3) months; healthy controls completed the questionnaire at T1., Results: 132 women with an abnormal Pap smear [with conization: S1 (n = 68, 51.5%), without intervention: S2 (n = 64, 48.5%)] and healthy controls (K, n = 101) generally adhered to gynecological checkups, except S1 6 months after the first diagnosis (S1/T3 - 0.47, signed rank p < 0.0005). Knowledge of primary prevention information, i.e., HPV vaccination, was significantly higher among K (K 58%, S1 29%, S2 44%, Chi-squared p = 0.01) as was vaccine uptake (K 39% versus S1/S2 7% and 17%, respectively, Chi-squared p = 0.0004). Fear of upcoming Pap smears rose significantly over time (S1/T1-S1/T2-S1/T3, Wilcoxon signed-rank test p < 0.001) and was higher among those with conization at T2 (Chi-square test, p = 0.01) and partially accompanied by panic disorders at T1 (Chi-square test p = 0.035). Realization of general preventive habits rose significantly among women without an operative procedure (S2) over the study., Conclusion: This study advances the understanding of non-participation in follow-up visits after a dysplasia diagnosis, identifying post-conization women as a special risk group for decreased adherence.

Purpose: It was the aim to evaluate the personal preference of mode of delivery and to analyze differences between medical professionals and non-medical professionals. Interest in participating in a risk stratification system was evaluated. We hypothesized that gaining information about risk stratification provided in the survey could potentially change participants' decision regarding the preferred mode of delivery; therefore, subjects were asked twice (before and after providing information)., Methods: Five cohorts [four professionals (MP) including participants of the German Urogynecology Congress 2017, employees of two major university hospitals in Germany, and members of the German Society of Gynecology and Obstetrics, and one non-professional group (NP) including pregnant women] were invited online to participate in this survey., Results: Vaginal delivery was the preferred mode of delivery in both groups (MP 90.4% vs. NP 88.8%; p = 0.429). MP are more likely to opt for CS due to concerns regarding pelvic floor disorders (MP 56.6% vs. NP 9.1%; p < 0.001). Likewise, parity and prior experienced CS (pCS) had a significant impact on the decision towards vaginal delivery (parity MP OR 7.5 95% CI 4.6-12.3, NP OR 9.3 95% CI 1.9-44.2; (pCS) MP OR 0.12 95% CI 0.07-0.19, NP OR 0.05 95% CI 0.01-0.25). There is great interest in participating in risk stratification systems in the majority of participants (68.9%)., Conclusions: MP and NP prefer vaginal birth for themselves or their partners. Within the group that opted for CS, MP were significantly more often concerned about pelvic floor disorders. Future prevention aspects might include education about pelvic floor disorders.

Introduction: Female sexual dysfunction is known to have a huge impact on quality of life and is highly prevalent during the peripartum period. Several influencing variables were found to be associated with impaired sexual function postpartum, among them breastfeeding and partnership quality. However, little is known about the predictive value of these variables. Therefore, this longitudinal cohort study aimed to examine prospectively the influence of the two variables on sexual function 4-month postpartum., Materials and Methods: Questionnaires were administered to 330 women prenatally (TI, third trimester) and postpartum (TII, 1 week; TIII, 4 months). Medical data were collected from the respondents' hospital records. The Female Sexual Function Index (FSFI) was used to determine overall sexual function, desire, arousal, lubrication, orgasm, satisfaction, and pain perinatally., Results: At all timepoints, mean FSFI scores were below the critical FSFI-score of 26.55. Partnership quality, breastfeeding, high maternal education, and maternal depressive symptoms correlated significantly with FSFI scores postpartum. Further analyses confirmed antenatal partnership quality and breastfeeding behavior as strong predictors of sexual function 4-month postpartum, explaining 24.3% of variance. Women who stopped breastfeeding or never breastfed at all showed the highest FSFI scores., Conclusion: Our findings indicate that exclusively breastfeeding women and those who report low partnership quality have an increased likelihood of sexual functioning problems 4-month postpartum. Health-care providers need to be encouraged to counsel on postpartum sexuality and influencing factors during prenatal classes to de-pathologize those changes and to foster a positive approach to peripartum sexuality.

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.

Purpose: Reduction of maternal morbidity and mortality is a major worldwide objective anchored in the millennium goals of the United Nations. To improve fetal and maternal care, a constant attempt to discover groundbreaking technologies is ongoing. One approach is the enhancement of non-invasive fetal ECG devices. Most importantly, acceptance of new technologies by pregnant women is a prerequisite for successful implementation., Methods: This questionnaire-based study conducted at the University Hospital Heidelberg, Germany between May and June 2017 evaluates pregnant women's attitudes towards a new device for fetal ECG monitoring and its potential home usage. The study population was questioned after exposure to the Parides/Atlantis prototype (Nemo Healthcare, Veldhoven, The Netherlands), whereas the maternal and gestational age-matched control group was left to envision telemedical topics., Results: The prototype and its potential usage in a clinical and telemedical setting was highly accepted, and its comfort and appearance satisfied participants. Its use caused significantly improved telemedical understanding as envision increased (p = 0.0015). Implementation and integration of telemedical devices into antenatal care was significantly preferred by the study group (p = 0.0011), though participants desire more specific features for their personal use. Optional home-based self-monitoring to reduce scheduled doctoral visits (p = 0.0004) as well as self-assessment prior to self-initiated, unscheduled consultation (p < 0.0001) could be affected positively by such a device. Furthermore, it could reduce face-to-face interaction with the care provider (p = 0.0163)., Conclusions: The positive feedback on remote self-monitoring might open options for a more "patient as partners" oriented prenatal care in the future. Safety and reliability remain a major issue. More comprehensive studies with new technologies are needed to diligently ensure quality of care. Finally, results for new technologies must be communicated to pregnant women for their acceptance and usage of new devices.

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.

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.

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.

Purpose: To evaluate the occurrence of urogynecological symptoms in obese women treated in a university outpatient clinic for obesity, setting a focus on younger women., Methods: In this explorative, prospective, cross-sectional, single-center, multidisciplinary clinical trial, all consecutively recruited women received the Prolapse Quality of Life questionnaire (P-QOL) for data acquisition. The total study population (TSP) and a subgroup (SG) aged 18-49 years were evaluated descriptively regarding symptom demonstration., Results: Of the TSP (n = 166, mean age 40.2, standard deviation (SD) 12.98, mean body mass index (BMI) 45 kg/m 2 , SD 8.44) 105 (63%) and of the SG (n = 125, mean age 34.6, SD 9.29, mean BMI 44.9 kg/m 2 , SD 8.26) 72 (58%) women suffered from urinary incontinence (UI) being most impaired by stress urinary incontinence (SUI; TSP: 25%; SG: 27%) and least by urge urinary incontinence (UUI; TSP: 15%; SG: 11%). A significant correlation in the TSP between UI and age was detectable (p < 0.001, r φ  = 0.37), but not between UI and BMI (p = 0.296, r φ  = 0.08). The highest QOL impairment is detected for the domain general health perceptions [GHP; TSP & SG score >50 (score scale 0-100)]. Women with UI are significantly more affected than women with pelvic organ prolapse (GHP UI: TSP p = 0.04, SG p = 0.037; GHP POP: TSP p = 0.081, SG p = 0.659)., Conclusions: A remarkable number of young obese women mentioned urogynecological symptoms and quality-of-life impairment. The P-QOL questionnaire proved to be an easily applicable tool to scan for concerned obese women. Its use in non-urogynecological departments, as performed, enables an early introduction of symptomatic women to urogynecologists, possibly preventing future growing urogynecological health issues.

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.

Background: Some women of families at high risk of breast cancer (BC) choose prophylactic mastectomy (PM) in spite of ambiguous evidence for survival benefits. The aim of this study was to investigate counselees' characteristics, decisions on PM, and frequencies of different procedures to better understand how to tailor interventions., Patients and Methods: Eight hundred and forty-nine counselees who attended interdisciplinary consultation for genetic risk adjustment at the University Hospital Heidelberg between July 2009 and July 2011 received a tripartite questionnaire addressing sociodemographic characteristics, psychological parameters, behavioural questions, and medical data., Results: Six hundred and twelve of the 849 counselees (72%) returned the questionnaire. Four hundred were classified as high risk of genetic BC (19.5% BRCA mutation carriers; 4% unclassified variant (UV); and 76.5% calculated as high risk by pedigree). Two hundred and thirteen out of 400 (53%) were diagnosed with BC. Fourteen out of 54 (27%) BRCA mutation carriers with BC chose contralateral PM (CPM) compared to 24/126 (14%) without a mutation but with a personal BC history (p = 0.2175). Of those without BC, 12/27 (44%) mutation carriers opted for bilateral PM (BPM) compared to none without a mutation (p < 0.0001). Women who received any PM (CPM and BPM) reported a higher emotional burden from partners (p = 0.003) and family (p = 0.008), more worries regarding children and family (p = 0.003) and were associated with positive mutation status and higher heterozygous and lifetime risk (all p < 0.001)., Conclusion: Although evidence on survival benefit is unclear in several clinical situations, a relevant number of counselees opt for PM. Counselees may decide based on other reasons than survival benefit.

Purpose: The present study aims to analyze a cohort of advanced breast cancer patients in Germany to assess their interest in complementary and alternative medicine (CAM) and patient's use of most frequent CAM methods., Patients and Methods: Based on the PREGNANT real-time breast cancer registry which is a multicenter study in Germany, questionnaires of 580 patients with advanced breast cancer were evaluated. The implemented questionnaire for CAM asked for general interest in CAM and for patient's use of different CAM methods at present and in the past. The interest and application of CAM were analyzed for association with patients' characteristics such as tumor, patient, and therapy characteristics., Results: In total, 436 out of 580 (75%) patients claimed to be interested in CAM. Further, interest in CAM is significantly correlated with younger age and absence of metastasis at the time of diagnosis. Multivariate analysis confirmed the patient's age and distant disease status at the time of diagnosis as related to interest in CAM. A total of 56.4% of patients applied any CAM method in the past. Moreover, with increasing lines of therapies, the more frequent use of CAM was observed. Hereby, praying, vitamin supplements, and other food supplements were most frequently applied., Conclusion: Our data demonstrate high overall interest and frequent use of CAM in advanced breast cancer patients supporting a strong demand of breast cancer patients for complementary counseling and treatments additional to the established cancer therapies. It is indispensable to implement counseling and evidence-based complementary treatments into clinical routine of cancer centers and to adapt postgraduate medical education, respectively.

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.

Purpose: Advances in genetics and increased public awareness increased the demand for interdisciplinary genetic outpatient consultation (IOGC). Communicating cancer risk is complex, and ideally information transfer should be individualized. Although psychological experiences with genetic testing have been studied in detail, studies on long-term experiences with IOGC and information transfer are lacking. We assessed patients' understanding and satisfaction with IOGC in families at risk of hereditary breast and ovarian cancer (HBOC) with the aim of informing best clinical practice, improving compliance and informed decision-making., Methods: Female counselees referred for IOGC between July 1, 2009 and July 1, 2011 were eligible. Data were collected using a 47-item postal questionnaire to assess sociodemographic, psychological, behavioral parameters. Overall satisfaction and personal usefulness of IOGC were assessed with a five-point, and risk perception with a visual analog scale. Data were analyzed using Spearman rank, Wilcoxon U or Chi-squared test., Results: 612 (72 %) of 849 women participated reported being highly satisfied (75 %, n = 430) and declared personal usefulness (73 %, n = 421) on average 3.5 years after IOGC. Women deemed "high risk" assessed their risk of developing BC as significantly higher than non-high-risk counselees (3.2 versus 3.0, p = 0.00484). Risk perception was lower in BRCA1/2 mutation carriers than in women with unclassified variants or no mutation (2.8 versus 3.5 and 3.1, respectively)., Conclusion: Women with an HBOC background have additional needs to achieve long-term satisfaction after IOGC. Prospective studies are required to optimize care for the increasing number of people who seek genetic consultation, particularly as the complexity of genetics knowledge increases.

Objectives: Today´s written part of the medical state examination requires students to retrieve a comprehensive amount of knowledge in a limited period of time. Therefore, the main study objectives were to implement and to evaluate a two-day exam preparation course for the German Medical State Examination in obstetrics and gynecology. The project evaluation focused on acceptability, satisfaction and the gain of knowledge for the participants of such a face-to-face course., Study Design: The two-day intensive training for senior medical students offered a review of the entire exam-relevant content in the field of obstetrics and gynecology in combination with interactive discussions along selected exam questions. Skill gains were assessed using pre- and post-course multiple choice tests. In addition, a qualitative questionnaire assessed attitudes and satisfaction of course participants., Results: A total of 101 fifth year senior medical students from Heidelberg University Medical School participated in the two pilot courses (summer 2014 and winter 2015). Pre- and post-course tests showed a significant skill-gain from 14.9 to 18.0 points [of a maximum of 20; pre-post difference 95 % CI (2.21; 3.98), t test: p < 0.001]. Furthermore, the qualitative results showed high satisfaction with the course, with an average Likert scale grading of 5.63 (2014) and 5.44 (2015) on a scale from 1 ("extraordinary bad") to 6 ("extraordinary good")., Conclusions: This study shows that a two-day intensive course in obstetrics and gynecology is feasible, effective and highly appreciated by senior medical students preparing for the Second German Medical State Examination. It further suggests surplus value for academic clinical departments to recruit future residents. Methods and tools presented in this paper are intended to inspire and guide clinical colleagues in implementing the format at their respective universities.

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.

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.

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.

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.

Purpose: To compare patient-reported quality-of-life and sexual function outcomes in women after laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) for benign uterine disease., Methods: Out of a cohort of 1,952 patients from a previous implementation study of LSH and TLH, 1,886 patients who had not undergone intraoperative conversion to laparotomy or were ineligible for other reasons were invited by mail to participate in this prospective, questionnaire-based follow-up study., Results: Of the 915/1,952 (48.5 %) survey respondents included in the analysis, 788 (86.1 %) and 127 (13.9 %) had undergone LSH or TLH, respectively. Women undergoing LSH reported significantly lower pain levels (p = 0.037) and faster partial (p = 0.015) and complete (p < 0.001) resumption of normal daily activities compared to those undergoing TLH. As regards sexual function, women undergoing LSH resumed sexual activity significantly sooner (p = 0.018), rated sexual desire as higher (p = 0.023), and reported more frequently that their sexual life had improved postoperatively (p = 0.008) than did women undergoing TLH., Conclusions: Women undergoing LSH for benign uterine disease may have better outcomes regarding certain quality-of-life and sexual function parameters than women undergoing TLH for benign uterine disease.

Background: The PIP/Rofil Medical breast implant recall affected around 40,000 women worldwide. An impact on quality of life (QoL) has been suspected but not yet reported., Objective: To quantify QoL and anxiety in affected women with respect to implant indication and their removal., Patients and Methods: Women who attended consultation and opted for implant removal between December 2011 and 2012 were eligible for study. Quality of life and anxiety were measured using validated questionnaires pre- and postoperatively., Results: Fifty-five patients completed at least one questionnaire, of which 32 had received implants for breast cancer, 15 for aesthetic augmentation, and 8 for primary breast malformations. Removal of the implants improved QoL in every group, especially those who had malformations. The QoL of breast cancer patients was generally better compared to the patients with implant for other reasons., Conclusion: The recall of PIP/Rofil Medical breast implants had a measurable impact on QoL in affected women and no pathological worry was measurable among those women.

Purpose: The aim of this study was to evaluate the staging accuracy of magnetic resonance imaging (MRI) with an endorectal surface coil on patients with endometrial cancer compared to results obtained using the International Federation of Gynecology and Obstetrics (FIGO) classification and histopathology., Methods: In this prospective study, patients with biopsy-proven endometrial cancer were staged clinically using the FIGO classification before undergoing 1.5 T MRI with an endorectal surface coil (eMRI). The staging results from the FIGO classification and from eMRI were compared with the histopathological results after surgery. Furthermore, each patient was given a questionnaire designed by the authors to evaluate the patients' opinions on eMRI. The responses were examined using the methods of descriptive analysis., Results: A total of 33 consecutive patients were recruited and clinically staged before undergoing eMRI. Subsequently, 21 patients underwent primary surgery and 12 patients primary radiochemotherapy. The FIGO stages were identical to the histopathological results in 17 (81 %) cases, and those of eMRI were identical in 15 (71 %). In 13 (62 %) cases, FIGO and eMRI staged identically. In 12 (57 %) of the 21 cases, all three staging modalities diagnosed the same tumor stage. eMRI overstaged the tumor in four patients and understaged it in two. All T1a tumors were staged correctly by eMRI. Eighteen patients answered the questionnaire, of whom 11 (61 %) patients stated that their experience with eMRI was overall positive., Conclusions: It seems feasible in principle to employ eMRI for diagnosing patients with endometrial cancer stage T1a. Yet, the results of eMRI for our study population were not better than the results obtained using the FIGO classification or than those from using MRI without an endorectal surface coil. eMRI thus does not meet the expectations based on its use in other pelvic tumor entities.

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.

Background: The bone marrow (BM) of breast cancer patients harbors tumor-reactive memory T cells (TCs) with therapeutic potential. We recently described the immunologic effects of adoptive transfer of ex vivo restimulated tumor-reactive memory TCs from the BM of 12 metastasized breast cancer patients in a clinical phase-I study. In this trial, adoptive T cell transfer resulted in the occurrence of circulating tumor antigen-reactive type-1 TCs. We here describe the long-term clinical outcome and its correlation with tumor-specific cellular immune response in 16 metastasized breast cancer patients, including 12 included in the original study., Methods: Sixteen metastatic breast cancer patients with preexisting tumor-reactive BM memory TCs were included into the study. The study protocol involved one transfusion of TCs which were reactivated in vitro with autologous dendritic cells pulsed with lysates of MCF-7 breast cancer cells as source of tumor antigens. The presence of tumor-reactive memory TCs was analyzed by IFN-γ ELISpot assays., Results: Tumor-reactive memory TCs in the peripheral blood were induced de novo in 7/16 patients (44 %) after adoptive TC transfer. These patients were considered immunologic responders to the therapy. Positive adoptive immunotherapy (ADI) response was observed significantly more often in patients without bone metastases (p = 0.0051), in patients with high levels of tumor-reactive BM TCs prior to therapy (p = 0.036) and correlated significantly with the estimated numbers of transferred tumor-reactive TCs (p = 0.0021). After the treatment, we observed an overall median survival of 33.8 months in the total cohort with three patients alive at last follow-up and more than 7 years after ADI. Numbers of transferred tumor-reactive TCs correlated significantly with the overall survival of patients (p = 0.017). Patients with an immunologic response to ADI in the peripheral blood had a significantly longer median survival than nonresponders (median survival 58.6 vs. 13.6 months; p = 0.009)., Conclusion: In metastasized breast cancer patients, adoptive transfer of BM TCs can induce the presence of tumor antigen-reactive type-1 TCs in the peripheral blood. Patients with immunologic response after ADI show a significantly longer overall survival. Patients with bone metastases significantly less frequently respond to the treatment and, therefore, might not be optimal candidates for ADI. Although the present study does not yet prove the therapeutic effect of ADI, these findings shed light on the relation between immune response and cancer prognosis and suggest that transfer of reactivated BM TCs might bear therapeutic potential.

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.

Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several preclinical and clinical observations suggest that Treg can be depleted by cyclophosphamide. Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50 mg cyclophosphamide p.o. daily. Cyclophosphamide treatment initially caused a significant reduction in circulating Treg by more than 40% (P = 0.002). However, Treg numbers completely recovered during the treatment due to increased proliferative activity and maintained their suppressive capacity. Treg depletion coincided with a strong increase in breast tumor-reactive T cells (P = 0.03) that remained at high levels during the whole period. Numbers of tumor-reactive T cells but not of Treg correlated with disease stabilization (P = 0.03) and overall survival (P = 0.027). We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients.

Breast cancer and associated diabetes mellitus have gained raising interest as an elevated risk of breast cancer prognosis resulting in increased mortality in diabetic patients. In this context, the long-acting insulin analog glargine and other antidiabetics have been discussed to promote tumorigenesis. In contrast, the biguanide class oral antidiabetic metformin has been shown capable of enhancing cell cycle arrest and inducing apoptosis as well as reducing growth factor signaling. Consequently, several studies are underway to evaluate a possible role of metformin in breast cancer treatment. Although mechanisms involved are not definitely clear yet, here, we discuss metformin's anticancer effects including the potential impact of the immune system.

A wide variety of cancer types has been associated with paraneoplastic autoimmune disorders and with the induction of autoimmunity against several autoantigens, among them self-antigens that are also expressed by tumor cells. This raises the question of autoimmune disorders as a result of immune reactions to the tumor. To date, however, requirements for the generation of autoimmune reactions in cancer patients remain largely unclear. In this study, we characterized conditions in altogether 131 patients, which determine autoimmune responses in primary breast cancer patients. We used ex vivo IFN-γ EliSpot assays against autologous tumor or skin lysates to evaluate tumor- and auto-reactive T-cells (TCs) in the bone marrow (BM) as well as ELISA, ECLIA, and turbidimetric immunoassays for the detection of auto-reactive antibodies in the peripheral blood and compared results to intratumoral cytokine concentrations and pathobiological features of the primary tumor tissue. We here demonstrate a significant correlation between anti-tumor BMTC responses and cellular autoimmune reactivity in primary breast cancer patients (P = 0.002). Humoral autoimmune reactions, however, were negatively correlated with anti-tumor TC immunity (P = 0.039). We observed auto-reactive BMTCs especially in patients with well-differentiated, hormone receptor-positive carcinomas (P = 0.009). Furthermore, elevated concentrations of intratumoral IFN-α significantly correlated with the induction of cellular autoimmune reactivity (P = 0.0002), while humoral autoimmune reactions correlated with increased levels of intratumoral IL-12 (P = 0.04). Altogether, these data indicate a significant role of the tumor microenvironment and particularly that of IFN-α and IL-12 in the induction of systemic autoimmune responses and imply that the primary tumor tissue represents an integral site of autoimmune regulation in cancer patients.

Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-gamma producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-gamma EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A(*0201)-restricted peptides from the tumor-associated antigens MUC1, Hpa(16-24) and Hpa(183-191) was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM.

Background: Breast cancer patients frequently harbour tumour-reactive memory T cells in their bone marrow (BM) but not in the blood. After reactivation ex-vivo these cells rejected autologous breast tumours in xenotransplanted mice demonstrating therapeutic potential upon reactivation and mobilization into the blood. We conducted a clinical pilot study on metastasized breast cancer patients to investigate if ex-vivo reactivation of tumour-reactive BM memory T cells and their adoptive transfer is feasible and increases the frequencies of tumour-reactive T cells in the blood., Methods: The study protocol involved one transfusion of T cells which were reactivated in vitro with autologous dendritic cells pulsed with lysate of MCF7 breast cancer cells as source of tumour antigens. Immunomonitoring included characterization of T cell activation in vitro and of tumour-specific T cells in the blood by interferon (IFN)-gamma ELISPOT assay, HLA-tetramers and antigen-induced interleukin (IL)-4 secretion., Results: Twelve patients with pre-existing tumour-reactive BM memory T cells were included into the study. In all cases, the treatment was feasible and well tolerated. Six patients (responders) showed by ELISPOT assay de-novo tumour antigen-specific, IFN-gamma-secreting T cells in the blood after 7 days. In contrast, non responders showed in the blood tumour antigen-induced IL-4 responses. All responders received more than 6.5 x 10(3) tumour-reactive T cells. In contrast, all non responders received lower numbers of tumour antigen-reactive T cells. This was associated with reduced activation of memory T cells in activation cultures, increased amounts of CD4(+) CD25(high) regulatory T cells in the BM and increased tumour antigen-dependent IL-10 secretion. The latter was prevented by preceding depletion of regulatory T cells suggesting that regulatory T cells in the BM can inhibit reactivation of tumour-specific T cells., Conclusion: Taken together, adoptive transfer of ex-vivo re-stimulated tumour-reactive memory T cells from BM of metastasized breast cancer patients can induce the presence of tumour antigen-reactive type-1 T cells in the peripheral blood.

Background: In order to prepare for the introduction of a universal newborn hearing screening program on a larger scale, TEOAE and ABR were recorded on automated screening instruments from both ears of 501 newborns at the University Hospital Heidelberg over a period of 13 months. The parents of children in whom OAE and ABR could not be detected in both ears, were requested to allow a complete exploration of the auditory status of the children at the department of pediatric audiology., Subjects and Methods: Internally available data networks were used for the acquisition and evaluation of data and for the organization of tracking and follow-up. Of the children 35% exhibited risk factors for congenital hearing impairment., Results: The pass rate was 98.7% for the exclusion of binaural and 91.6% for monaural hearing disorders (TEOAE or ABR detectable). On the basis of the data it can be shown how pass rates can be optimized by selecting a suitable moment for the examination and by prescribing a minimum number of test repetitions (3 for TEOAE and 2 for AABR)., Conclusion: Quality control of screening programs should include these parameters and, in particular the number of repetitions of test measurements in all screening steps.

There is no consensus regarding the clinical significance of conventional two-dimensional ultrasound in the diagnosis of meniscal tears of the knee. Three-dimensional ultrasound spatially reconstructs a transparent image of subsequent ultrasound scans. In an experimental study of 96 menisci, radial and oblique tears were detected more often by three-dimensional ultrasound. In a clinical study of 60 menisci the two- and three-dimensional ultrasound reached a sensitivity of 92% and 100%, a specificity of 83% and 88%, a positive predictive value of 58% and 67%, and a negative predictive value of 98% and 100%, respectively. Altogether, there was no statistically significant difference between both methods. The high negative predictive value, however, shows that the three-dimensional ultrasound may be a clinically relevant examination for special questions in the diagnostics of meniscal tears.

On the assumption that the architecture of blood vessels of malignant tumors, formed by neoangiogenesis, shows characteristics that are different from those of blood vessels of benign tumors or physiological findings, we have tried in the present study to investigate the behavior of these different vessels under increased blood pressure. Using a special stand, the same sonographic section could be stably maintained during an examination time of approx. 4 minutes. Using a new computer program, the color pixels of the employed Angio color technique were quantified and recorded as a function of the measured blood pressure. To increase blood pressure, the patient had to press a hand grip, which practically always caused a systolic blood pressure elevation of more than 15-20 mmHg. Seventy patients with sonographically detected breast tumors were examined; 54 (14 benign and 40 malignant tumors) could be included in the evaluation. We found four typical types of curves: Curve type 1 is associated with an instantaneous increase in blood flow with increased blood pressure, followed by a drop in the blood pressure, with a slow decrease in blood flow as the blood pressure drops (with 29 malignant and 3 benign tumors). Curve type 2 shows a continuous increase in blood flow-though somewhat delayed with respect to the rise in blood pressure-which is also observed when the blood pressure drops (exclusively benign tumors). In curve type 3, maximum blood flow is reached after the blood pressure maximum, and then the blood flow decreases (1 benign and 3 malignant tumors). Curve type 4 features decreased blood flow in spite of increased blood pressure (3 benign and 5 malignant tumors). The described quantification method, in combination with the stand, permits for the first time analysis of a tumor under increased blood pressure as to its blood flow behavior over time in an examination using a challenge test. Here one can find two distinctive curve types (types 1 and 2) that correlate mostly with malignant (type 1) or benign (type 2) breast tumors. Should this tendency be substantiated by additional large-scale studies, it would seem that a new ultrasonic possibility for differential diagnosis has been found.

Sonography of the knee has gained in significance in the diagnosis of the meniscus; experimental and clinical studies have demonstrated that the normal and pathological anatomy of the meniscus can be visualized on a sonogram. The aim of this comparative investigation is to evaluate sonographic lesion diagnosis in comparison with arthroscopic findings, using a standardized examination method. Two hundred and six knee joints were first scanned sonographically using a 7.5 MHz sector transducer. The examining doctor had neither anamnestic nor clinical information in advance. On the following day, the joints were examined arthroscopically, without the findings of the day before being available to the examiner. When the findings were compared, the sensitivity of sonographic diagnosis of lesions was found to be 82.2% and its specificity 87.6%. The patients were of varying ages and had varying anamneses. The results show that sonography of the meniscus is a valuable diagnostic help when the knee-joint symptoms are not clear, given that the correct technical equipment and sufficient experience with this form of examination are at hand. The advantage of sonography is that, in contrast to arthroscopy, it is noninvasive and easily available.

After satisfactory experimental results with three-dimensional data acquisition and presentation of the kidney in vitro, we wanted to show how our technique could be used for medical application in vivo, such as ultrasonic 3D reconstruction of organs. The sector scans were taken by rotating the scan head 10 degrees in any direction around the length of the axis. The organ was scanned with 18 images and reconstructed. The digital images, using the organ contours, allowed 3D reconstruction of the original organ, relying on the computer memory. The first results in reconstructing uteri show how this scan head can be used in combination with the computer programs for medical application. For the first time, it has become possible to present computer-generated views of an organ cross-section that has been impossible to obtain by means of traditional ultrasound techniques. Recent experiments using this method show new ways of diagnosing tumors.