The Long chain Diol Index: A marine palaeotemperature proxy based on eustigmatophyte lipids that records the warmest seasons.

Long chain 1,13- and 1,15-diols are lipids which are omnipresent in marine environments, and the Long chain Diol Index (LDI), based on their distributions, has previously been introduced as a proxy for sea surface temperature. The main biological sources for long chain 1,13- and 1,15-diols have remained unknown, but our combined lipid and 23S ribosomal RNA (23S rRNA) analyses on suspended particulate matter from the Mediterranean Sea demonstrate that these lipids are produced by a marine eustigmatophyte group that originated before the currently known eustigmatophytes diversified. The 18S rRNA data confirm the existence of early-branching marine eustigmatophytes, which occur at a global scale. Differences between LDI records and other paleotemperature proxies are generally attributed to differences between the seasons in which the proxy-related organisms occur. Our results, combined with available LDI data from surface sediments, indicate that the LDI primarily registers temperatures from the warmest month when mixed-layer depths, salinity, and nutrient concentrations are low. The LDI may not be applicable in areas where Proboscia diatoms contribute 1,13-diols, but this can be recognized by enhanced contributions of C28 1,12 diol. Freshwater input may also affect the correlation between temperature and the LDI, but relative C32 1,15-diol abundances help to identify and correct for these effects. When taking those factors into account, the calibration error of the LDI is 2.4 °C. As a well-defined proxy for temperatures of the warmest seasons, the LDI can unlock important and previously inaccessible paleoclimate information and will thereby substantially improve our understanding of past climate conditions.

Efficacy of Lapatinib in Patients with HER2-Negative Metastatic Breast Cancer and HER2-Positive Circulating Tumor Cells-The DETECT III Clinical Trial.

BACKGROUND: The phenotypes of tumor cells change during disease progression, but invasive rebiopsies of metastatic lesions are not always feasible. Here we aimed to determine whether initially HER2-negative metastatic breast cancer (MBC) patients with HER2-positive circulating tumor cells (CTCs) benefit from a HER2-targeted therapy. METHODS: The open-label, interventional randomized phase III clinical trial (EudraCT Number 2010-024238-46, CliniclTrials.gov Identifier: NCT01619111) recruited from March 2012 until September 2019 with a follow-up duration of 19.5 months. It was a multicenter clinical trial with 94 participating German study centers. A total of 2137 patients with HER2-negative MBC were screened for HER2-positive CTCs with a final modified intention-to-treat population of 101 patients. Eligible patients were randomized to standard therapy with or without lapatinib. Primary study endpoints included CTC clearance (no CTCs at the end of treatment) and secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: In both treatment arms CTC clearance at first follow-up visit-although not being significantly different for both arms at any time point-was significantly associated with improved OS (42.4 vs 14.1 months; P = 0.002). Patients treated additionally with lapatinib had a significantly improved OS over patients receiving standard treatment (20.5 vs 9.1 months, P = 0.009). CONCLUSIONS: DETECT III is the first clinical study indicating that phenotyping of CTCs might have clinical utility for stratification of MBC cancer patients to HER2-targeting therapies. The OS benefit could be related to lapatinib, but further studies are required to prove this clinical observation. ClinicalTrials.gov Registration Number: NCT01619111.

Out of pocket health-care services in Germany during pregnancy under consideration of migration and acculturation.

PURPOSE: More than a quarter of the German population has a migration background (MB). As various studies in the healthcare sector have already shown, ethnic background and migration status can have an influence on individual patient care. The aim of our study was to evaluate whether there are differences in utilization of out of pocket health-care services and the consultation situation in the context of prenatal care, taking into account migration status, acculturation and socio-demographic aspects. METHODS: In the period from 01.03.21-01.03.22, a total of 511 women in childbed at the University Women's Hospital Ulm were interviewed in a retrospective survey using a standardized questionnaire translated into 9 languages and asked about their prenatal care. Due to the COVID pandemic, the study had to be terminated after one year. RESULTS: Women with MB-particularly 1st generation migrant women-used significantly fewer out of pocket prenatal care services (p < 0.001) and felt less informed and counselled regarding costs and benefits of possible prenatal care examinations (p < 0.001) compared to women without MB. Consistent with these results, there were associations between the assimilation index (AI) of patients with MB and both utilization and perception of individual healthcare services. CONCLUSION: Our study indicates that even today there are still differences in the treatment and perception of various health services in the context of prenatal care between women with and those without MB.

["Who cares about us?" Results of a cross-sectional study on the psychosocial health of obstetricians and midwives after traumatic birth experiences]. / "Wer kümmert sich um uns?" Ergebnisse einer Querschnittsuntersuchung zur psychosozialen Gesundheit von Geburtshelfer*innen und Hebammen nach traumatischen Geburtserlebnissen.

BACKGROUND: Traumatic births not only cause emotional stress for expectant parents but can also affect the psychosocial health of midwives and obstetricians due to their professional demands. AIM: To evaluate the impact of traumatic birth experiences on the psychosocial health of obstetric healthcare professionals. METHODS: A cross-sectional study using validated measurement tools (Impact of Event Scale Revised IES-R, Copenhagen Burnout Inventory CBI) and assessing post-traumatic growth (PGI-SF) through an online survey of midwives and obstetricians in German-speaking areas. RESULTS: The study included 700 participants with peripartum and/or personal traumas. Of the 528 participants who completed the IES-R, 33 (6.3%) with post-traumatic stress disorder (PTSD) received less support from colleagues (p = 0.007) and were more likely to experience workplace consequences (p < 0.001) than participants without PTSD. A moderate to high level of burnout was found in 66.2% of the 542 participants who completed the CBI. Personal growth through experiencing trauma was reported by 75.9% of the 528 participants who completed the PGI-SF. CONCLUSION: The psychosocial health of midwives and obstetricians is at risk due to traumatic birth experiences. Screening tests and the provision of collegial and professional debriefings to strengthen resilience are essential preventive interventions.

Effect of histological breast cancer subtypes invasive lobular versus non-special type on survival in early intermediate-to-high-risk breast carcinoma: results from the SUCCESS trials.

BACKGROUND: Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival. METHODS: From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan-Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models. RESULTS: In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77-1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85-1.50, p = 0.414) for OS, 1.21 (95% CI 0.89-1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73-1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients. CONCLUSIONS: Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.

Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value.

BACKGROUND: Circulating tumour cells (CTCs) are mainly enriched based on the epithelial cell adhesion molecule (EpCAM). Although it was shown that an EpCAM low-expressing CTC fraction is not captured by such approaches, knowledge about its prognostic and predictive relevance and its relation to EpCAM-positive CTCs is lacking. METHODS: We developed an immunomagnetic assay to enrich CTCs from metastatic breast cancer patients EpCAM independently using antibodies against Trop-2 and CD-49f and characterised their EpCAM expression. DNA of single EpCAM high expressing and low expressing CTCs was analyzed regarding chromosomal aberrations and predictive mutations. Additionally, we compared CTC-enrichment on the CellSearch system using this antibody mix and the EpCAM based enrichment. RESULTS: Both antibodies acted synergistically in capturing CTCs. Patients with EpCAM high-expressing CTCs had a worse overall and progression-free survival. EpCAM high- and low-expressing CTCs presented similar chromosomal aberrations and mutations indicating a close evolutionary relationship. A sequential enrichment of CTCs from the EpCAM-depleted fraction yielded a population of CTCs not captured EpCAM dependently but harbouring predictive information. CONCLUSIONS: Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumour surrogate material-although they may be prognostically less relevant than EpCAM high-expressing CTCs-and have particular benefit if no CTCs are detected using EpCAM-dependent technologies.

Testing for terrestrial and freshwater microalgae productivity under elevated CO2 conditions and nutrient limitation.

BACKGROUND: Microalgae CO2 fixation results in the production of biomass rich in high-valuable products, such as fatty acids and carotenoids. Enhanced productivity of valuable compounds can be achieved through the microalgae's ability to capture CO2 efficiently from sources of high CO2 contents, but it depends on the species. Culture collections of microalgae offer a wide variety of defined strains. However, an inadequate understanding of which groups of microalgae and from which habitats they originate offer high productivity under increased CO2 concentrations hampers exploiting microalgae as a sustainable source in the bioeconomy. RESULTS: A large variety of 81 defined algal strains, including new green algal isolates from various terrestrial environments, were studied for their growth under atmospheres with CO2 levels of 5-25% in air. They were from a pool of 200 strains that had been pre-selected for phylogenetic diversity and high productivity under ambient CO2. Green algae from terrestrial environments exhibited enhanced growth up to 25% CO2. In contrast, in unicellular red algae and stramenopile algae, which originated through the endosymbiotic uptake of a red algal cell, growth at CO2 concentrations above 5% was suppressed. While terrestrial stramenopile algae generally tolerated such CO2 concentrations, their counterparts from marine phytoplankton did not. The tests of four new strains in liquid culture revealed enhanced biomass and chlorophyll production under elevated CO2 levels. The 15% CO2 aeration increased their total carotenoid and fatty acid contents, which were further stimulated when combined with the starvation of macronutrients, i.e., less with phosphate and more with nitrogen-depleted culture media. CONCLUSION: Green algae originating from terrestrial environments, Chlorophyceae and Trebouxiophyceae, exhibit enhanced productivity of carotenoids and fatty acids under elevated CO2 concentrations. This ability supports the economic and sustainable production of valuable compounds from these microalgae using inexpensive sources of high CO2 concentrations, such as industrial exhaust fumes.

A microplate-based bioassay for toxicity testing using the large benthic algal species Closterium ehrenbergii.

Pollution of water bodies by metals has long been studied but still remains a threat to healthy ecosystems. While most ecotoxicological studies on algae are performed with planktonic standard species such as Raphidocelis subcapitata, benthic algae may depict the majority of the algal flora in rivers and streams. These species encounter different exposure scenarios to pollutants as they are sedentary and not carried away by the current. This particular way of life leads to an integration of toxic effects over time. Therefore, in this study, the effects of six metals on the large unicellular benthic species Closterium ehrenbergii were examined. A miniaturized bioassay with low cell densities of 10-15 cells/mL using microplates was developed. Through chemical analysis, metal complexing properties in the culture medium were demonstrated, that could lead to an underestimation of metal toxicity. Thus, the medium was modified by excluding EDTA and TRIS. The toxicity of the six metals ranked by EC50 values in descending order, was as follows: Cu (5.5 µg/L) > Ag (9.2 µg/L) > Cd (18 µg/L) > Ni (260 µg/L) > Cr (990 µg/L) > Zn (1200 µg/L). In addition, toxic effects on the cell morphology were visualized. Based on a literature review, C. ehrenbergii was shown to be partly more sensitive than R. subcapitata which suggests that it can be a useful addition to ecotoxicological risk assessment.

Post-traumatic stress syndromes following childbirth influenced by birth mode-is an emergency cesarean section worst?

PURPOSE: The experience of birth is an emotional challenge for women. Traumatic birth experiences can cause psychological stress symptoms up to post-traumatic stress disorders (PTSD), with impact on women's wellbeing. Primarily unplanned interventions can trigger birth-mode-related traumatization. The aim of the study was to evaluate whether an emergency cesarean section (ECS) is the most traumatizing. METHODS: A retrospective case-control study was undertaken. Therefore, data were collected by standardized questionnaires (Impact of Event Scale-Revised and City Birth Trauma Scale) that were sent to women with singleton pregnancies > 34 weeks of gestation who either give birth by ECS (case group, n = 139), unplanned cesarean section (UCS), operative vaginal birth (OVB), or natural birth (NB) (three control groups, n = 139 each). The investigation period was 5 years. RESULTS: Overall, 126 of 556 (22%) sent questionnaires were returned and could be analyzed (32 ECS, 38 UCS, 36 OVB, and 20 NB). In comparison to other birth modes, women with ECS were associated with a higher degree of traumatization as revealed by statistically significant differences regarding the DSM-5 criteria intrusion and stressor. In addition, women who underwent ECS declared more frequently a demand for professional debriefing compared to other birth modes. DISCUSSION: ECS is associated with more post-traumatic stress symptoms compared to other birth modes. Therefore, early interventions are recommended to reduce long-term psychological stress reactions. In addition, outpatient follow-ups by midwives or emotional support programs should be implemented as an integral component of postpartum debriefings.

The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C.

BACKGROUND: Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy. METHODS: Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models. RESULTS: AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology. CONCLUSION: For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.

The femur too short? 1373 fetuses with short femur during second-trimester screening.

PURPOSE: A short fetal femur in prenatal diagnosis might be an indicator for intrauterine growth retardation (IUGR), a genetically determined small child (SGA) with or without associated fetal malformations and/or an adverse fetal outcome. METHODS: 1373 singleton pregnancies with a femoral length < 5th percentile detected between 1999 and 2015 during second-trimester screening in a tertiary prenatal diagnostic center were subjected to a descriptive retrospective analysis with regard to fetal characteristics as well as pregnancy outcome. RESULTS: 685 (49.9%) fetuses presented an isolated short femur, while 688 (50.1%) showed additional abnormalities. 293 (42.6%) of those were SGA babies without any malformation, while 395 (57.4%) had one or more severe anomaly of the following organ systems: 157 (11.5%) cardiovascular, 101 (7.4%) musculoskeletal, 82 (6.0%) urogenital, 72 (5.2%) cerebrocephalic, 50 (3.6%) gastrointestinal, and 5 (0.4%) thoracic. 75 (5.5%) of the fetuses showed chromosomal aberrations of which Trisomy 13, 18 and 21 were found in 2, 13 and 27 of the cases, respectively. Fetuses with associated malformations had a significantly lower live birth rate than those without (64.2% vs. 98.1%, p < 0.001); in addition, a higher rate of preterm births 36.6% vs. 11.3%, p < 0.001) and SGA babies (51.4% vs. 30.4%, p < 0.001) were observed in the first collective. CONCLUSION: Diagnosis of a short fetal femur should lead to an extended organ screening; in the case of associated abnormalities, additional genetic testing has to be offered, as well as intensified pregnancy monitoring in pregnancies at risk for IUGR and/or preterm birth.

Trend natural family planning - an online survey to assess attitudes towards NFP among German-speaking women.

PURPOSE: To study trends regarding the use of contraceptive methods and digital health modalities and to identify target groups of natural family planning (NFP). MATERIAL AND METHODS: Using an online questionnaire specifically developed for this study in German (utilizing the online tool at 'www.surveymonkey.com'), we analysed the attitude towards NFP -methods and -apps, the need for contraceptive effectiveness in general, the perceived contraceptive effectiveness of NFP methods, and differences between NFP users and non-NFP users among 779 sexually active German-speaking women of fertile age (18-50 years) from November 2019 to October 2020. RESULTS AND CONCLUSIONS: Participants used NFP more frequently than they did five years ago. Women aged 30 years and older, with higher levels of education, who are living with a partner and have children, seem to be the target group for NFP methods. Concerning the wish for contraceptive effectiveness we found significant (p < .001) differences between NFP and non-NFP users. Furthermore, an increasing number of women wants to use NFP-methods and -apps for contraception; thus, non-hormonal contraceptive options should be offered. The majority of current NFP users stated that the handling and effectiveness of NFP have been improved by digitalisation.

BRCA1 mislocalization leads to aberrant DNA damage response in heterozygous ABRAXAS1 mutation carrier cells.

Whilst heterozygous germline mutations in the ABRAXAS1 gene have been associated with a hereditary predisposition to breast cancer, their effect on promoting tumourigenesis at the cellular level has not been explored. Here, we demonstrate in patient-derived cells that the Finnish ABRAXAS1 founder mutation (c.1082G > A, Arg361Gln), even in the heterozygous state leads to decreased BRCA1 protein levels as well as reduced nuclear localization and foci formation of BRCA1 and CtIP. This causes disturbances in basal BRCA1-A complex localization, which is reflected by a restraint in error-prone DNA double-strand break repair pathway usage, attenuated DNA damage response and deregulated G2-M checkpoint control. The current study clearly demonstrates how the Finnish ABRAXAS1 founder mutation acts in a dominant-negative manner on BRCA1 to promote genome destabilization in heterozygous carrier cells.

Ki67 as Proliferative Marker in Patients with Early Breast Cancer and Its Association with Clinicopathological Factors.

INTRODUCTION: Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. MATERIAL AND METHODS: Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (n = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. RESULTS: 595 (64.9%) patients had a Ki67 <20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1-90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2-) disease (n = 717), 20% for HR+/HER2+ (n = 76), 30% for HR-/HER2+ (n = 45), and 60% for HR-/HER2- (n = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (<20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%). CONCLUSION: This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

Fishing for (in)continence: long-term follow-up of women with OASIS-still a taboo.

PURPOSE: Obstetric anal sphincter injuries (OASIS) increase the risk for pelvic floor dysfunctions. The goal of this study was to examine the long-term outcomes after OASIS on pelvic floor functions and quality of life. MATERIAL AND METHODS: Between 2005 and 2013, 424 women had an OASIS at the Women University Hospital Ulm. Out of these 71 women completed the German pelvic floor questionnaire, which includes questions regarding prolapse symptoms as well as bladder, bowel and sexual function. In addition, 64 women were physically examined, including a speculum examination to evaluate the degree of prolapse, a cough test to evaluate urinary stress incontinence (SI) and an evaluation of both pelvic floor sphincter (modified Oxford score) and anal sphincter contraction. RESULTS: A high rate of pelvic floor disorders after OASIS was found, as 74.6% of women reported SI, 64.8% flatus incontinence and 18.3% stool incontinence, respectively. However, only few women stated a substantial negative impact on quality of life. The clinical examination showed that a positive cough test, a weak anal sphincter tone and a diagnosed prolapse correlated with the results of the self-reported questionnaire. CONCLUSION: On one hand, OASIS has an influence on pelvic floor function going along with lots of complaints, while on the other hand, it still seems to be a taboo topic, as none of the participants spoke about the complaints after OASIS with a doctor. Therefore, the gynecologist should actively address these issues and offer therapy options for the women with persisting problems.

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial.

BACKGROUND: When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients. METHODS: A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety. RESULTS: No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively. CONCLUSION: Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting. TRIAL REGISTRATION: Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.

Influence of the New FIGO Classification for Cervical Cancer on Patient Survival: A Retrospective Analysis of 265 Histologically Confirmed Cases with FIGO Stages IA to IIB.

OBJECTIVE: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. METHODS: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. RESULTS: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. CONCLUSION: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.

Feasibility of a large multi-center translational research project for newly diagnosed breast and ovarian cancer patients with affiliated biobank: the BRandO biology and outcome (BiO)-project.

INTRODUCTION: Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected. METHODS: The target population includes the German "Alb-Allgäu-Bodensee Region" which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets. RESULTS: Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients. CONCLUSIONS: The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.

Quality of life during and after adjuvant anthracycline-taxane-based chemotherapy with or without Gemcitabine in high-risk early breast cancer: results of the SUCCESS A trial.

PURPOSE: In high-risk early breast cancer, adjuvant taxane-Gemcitabine combinations result in a recurrence-free survival similar to single-agent taxanes. However, haematologic toxicities and need for dose reductions are more frequent in combinations. Which option ultimately provides a better quality of life (QoL) is unknown. We compared the QoL curves before, during, and up to one year after three cycles of Fluorouracil-epirubicin-cyclophosphamide followed by three cycles of Docetaxel-Gemcitabine or Docetaxel. METHODS: Overall, 3691 women with recent R0-resection of a primary epithelial breast cancer participated in the nationwide SUCCESS A clinical trial. The centres sent QoL questionnaires of the European Organisation for Research and Treatment of Cancer before and up to 15 months after randomisation to Docetaxel-Gemcitabine versus Docetaxel. Multilevel analysis by chemotherapy arm estimated the QoL time curves, questionnaire return, and dropout. RESULTS: The combination caused one-point higher global QoL (95% confidence ±1; p = 0.05) and 1.1 lower odds of adherence to the outcome (95% confidence 1.0-1.1; p = 0.23) than the monotherapy. In both groups, a 10-point decrease during therapy preceded a 16-point increase after chemotherapy (p < 0.001). The secondary QoL outcomes showed transient superiority of the combination at the end of chemotherapy. Discontinuation from chemotherapy and its reasons were equal in both groups. CONCLUSIONS: While patients perceive a one-point QoL difference as meaningless, a six-point increase is clinically relevant for them. That is, both regimens cause the same relevant long-term QoL improvement. With the similar recurrence-free survival, the lower toxicity, and the shorter chemotherapy duration in mind, taxanes without Gemcitabine are the preference. This challenges previous recommendations supporting combinations.

Emergency peripartal hysterectomy - a single-center analysis of the last 13 years at a tertiary perinatal care unit.

Background Peripartal hysterectomy (PH) is a challenging surgical procedure with elevated maternal morbidity. Methods From 2004 to 2016, 41 emergency PHs were performed at the tertiary care center of the Department of Gynecology and Obstetrics at University Hospital Ulm. In our retrospective analysis, the incidence of PH in our hospital was 12.8 per 10,000 deliveries with a maternal mortality of 2.4%. PH followed in 80.5% after cesarean section (c-section). Underlying causes/indications for PH were abnormal placentation (53.7%; n=22), uterine atony (26.8%; n=11), uterine lacerations (14.6%; n=6) and in rare cases uterine infection (4.9%; n=2). The median number of transfused products was 11 packed red blood cells (range 0-55 products), 10 fresh frozen plasma units (range 1-43) and two platelet concentrates (0-16). Results Loss of blood as estimated by surgeons was significantly correlated with actual transfused blood volume (P<0.001). Clinically relevant intra- and/or postoperative complications occurred in 53.7% of patients (n=22). Abnormal placentation was the leading cause for PH with an increased incidence during the last 10 years presumptively representing the elevated rate of c-sections. Conclusion PH goes along with increased rates of blood product transfusions independently of indication for surgery and has a high morbidity with a major complication rate of more than 50%. Prepartal assessment of risk factors like abnormal invasive placenta are crucial for reducing maternal morbidity.