Geburtshilfe Und Frauenheilkunde最新文献

Congenital Imprinting Disorders (ImpDis) are caused by abnormal expression of parentally imprinted genes. They are characterized by disturbances of imprinting marks which are a specific type of epigenetic signatures and occur either sporadic or familial. So far, twelve ImpDis have been identified, eight of them manifest prenatally or in the neonate period. With exception of abdominal wall defects, ImpDis are rarely associated with major malformations, but predominant early manifestations are disturbed pre- and/or postnatal growth, muscular hypotonia, neonatal feeding difficulties and metabolic/hormonal dysfunction. With few exceptions prenatal clinical features of ImpDis are unspecific and manifest only in the late second or third trimester. In some ImpDis, behavioural, developmental, and neurological symptoms might emerge, and in single ImpDis there is a higher risk of cancer in childhood. Prenatal diagnosis plays a crucial role in appropriate pregnancy management and initial care of the newborn, which in turn has positive impact on the life-long outcome of the patient. Furthermore, the diagnosis of ImpDis is relevant for the prevention of pregnancy risks such as preeclampsia and possible reproductive problems in future pregnancies and other family members. Genetic analysis is not straightforward, and imprinting disturbances may escape both DNA sequencing analysis and (molecular-)cytogenetic diagnostics. After introducing the topic with a case report, this review focuses on the recognition of ImpDis including maternal and family history, exogeneous and genetic risk factors, fetal imaging, and genetic findings as well as interdisciplinary care and treatment approaches in the management and decision making of affected families and pregnancies.

With around 70000 new cases every year, breast cancer (BC) continues to be the most prevalent form of cancer. Hormone receptor-positive, HER2-negative (HR+/HER2-) BC is the most common type and accounts for around 70% of cases of early BC (eBC). The development of new drugs in recent years has significantly improved the survival of patients with eBC. Alongside established endocrine therapy (ET) options such as tamoxifen, aromatase inhibitors (AI), and GnRH analogs, additional treatment options such as CDK 4/6 inhibitors (abemaciclib and ribociclib) and the PARP inhibitor (olaparib) are now also available. To facilitate their use in clinical practice, this article provides a summary of the current information on the use of these drugs in clinical practice. Abemaciclib was approved for the adjuvant treatment of HR+/HER2- eBC in cases with positive lymph node involvement in 2022. The MonarchE trial showed that the addition of abemaciclib to ET improved invasive disease-free survival (iDFS) after 5 years by around 7.6% in patients with a high risk of recurrence. Ribociclib, another CDK4/6 inhibitor, was recently approved based on the results of the NATALEE trial. When combined with non-steroidal AIs, ribociclib showed a significant iDFS benefit of 4.9% after 4 years in node-positive and node-negative patients with a high risk of recurrence. The PARP inhibitor olaparib may be used to treat patients with BRCA germline mutation and HR+/HER2- eBC and a high risk of recurrence (CPS-EG score ≥ 3). The OlympiA approval study showed an iDFS benefit of 7.3% after four years and a benefit of 3.4% for overall survival. In summary, targeted therapies are expanding the range of adjuvant treatment options for patients with HR+/HER2- eBC and a higher risk of recurrence. Treating physicians are increasingly facing the challenge of choosing the optimal therapy for their patients. To do so, it is essential to carefully weigh up potential side effects against the expected benefit of treatment on a case-by-case basis.

Background: As part of the COGNITION diagnostic registry program, residual tumor material after neoadjuvant therapy (NAT) of patients with early breast cancer (eBC), who are still at high-risk for relapse after NAT, is analyzed by next generation sequencing to identify biomarkers and actionable alterations. This strategy aims to stratify patients for subsequent genomics-guided therapies to reduce the significant risk of metastatic dissemination and hence to improve disease-free survival.

Patients and methods: COGNITION-GUIDE is a multicenter umbrella phase-II-trial to translate molecular biomarker profiles generated in the COGNITION platform into six molecular-guided post-neoadjuvant therapeutic options in addition to standard-of-care treatment. Patients can be allocated toimmune checkpoint inhibition (PD-L1-antibody),PI3K inhibition,AKT inhibition,PARP inhibition,anti-Trop-2 antibody-drug-conjugate,HER2 inhibition or, in case of missing biomarkers, to observation for 12 months.The primary endpoint is invasive disease-free survival (IDFS) four years after surgery. Secondary endpoints include IDFS in each study arm separately, distant disease-free survival, overall survival and safety. 240 patients will be enrolled within four years.

Conclusions: The COGNITION-GUIDE trial, which was activated in June 2023 and will recruit in different centers in Germany, empowers a risk-adapted, biomarker-guided therapy escalation algorithm in eBC patients who are still at high risk of metastasis.

Background: This study provides an indirect treatment comparison of ribociclib combined with non-steroidal aromatase inhibitors and ovarian function suppression (ribociclib + NSAI + OFS) vs. a frequently used treatment option in German clinical routine (tamoxifen ± OFS) in premenopausal patients with HR-positive (HR+), HER2-negative (HER2-) early breast cancer (BC).

Material and methods: Data on premenopausal women treated with ribociclib and tamoxifen were derived from the NATALEE clinical trial (NCT03701334) and the retrospective German data collection CLEAR-B, respectively. NATALEE trial eligibility criteria were applied to the CLEAR-B dataset. Standardized mortality ratio weights were used for propensity score (PS) adjustment to balance study populations. All hazard ratios (HR) were calculated based on a 4-year-observation period for both treatment arms. Effectiveness endpoints comprised invasive and distant disease-free survival (iDFS, dDFS), recurrence-free survival (RFS), and overall survival (OS). Safety-related endpoints were treatment termination (TT) and toxicity-related TT (TTtox). For safety comparisons, the ribociclib arm was divided into groups that discontinued ribociclib + NSAI + OFS or ribociclib only.

Results: Significant beneficial effects favoring ribociclib + NSAI + OFS (n = 1115) over tamoxifen ± OFS (n = 822) were observed for all effectiveness outcomes (iDFS [HR = 0.5 (95% CI 0.35; 0.71); p < 0.01]; dDFS [HR = 0.52 (95% CI 0.35; 0.77); p = 0.01], RFS [HR = 0.42 (95% CI 0.29; 0.62); p < 0.01], OS [HR = 0.34 (95% CI 0.18; 0.63); p = 0.01]) during the 4-year-observation period. The effect of early treatment discontinuation showed no significant differences between ribociclib + NSAI + OFS and tamoxifen ± OFS (TT-a: HR = 1.2 [95% CI: 0.71; 2.01], p = 0.48; TTtox-a: HR = 0.54 [95% CI 0.22; 1.30], p = 0.23).

Conclusion: In this retrospective analysis, ribociclib + NSAI + OFS demonstrated advantages across all effectiveness endpoints, including OS, in premenopausal women with HR+, HER2- early BC, without increasing overall treatment discontinuation rates compared to tamoxifen ± OFS.

Purpose This is an official, recently updated guideline published and coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) together with the Austrian Society of Gynecology and Obstetrics ( Österreichische Gesellschaft für Gynäkologie und Geburtshilfe , OEGGG) and the Swiss Society of Gynecology and Obstetrics ( Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe , SGGG) as part of the guidelines program. Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management, and treatment requires a multidisciplinary approach. Methods This S2k guideline was first published in 2015. The update published here is again the result of a structured consensus of a representative interdisciplinary group of mandate holders and experts who carried out a selective search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus on recommendations and statements after a structured consensus process. Recommendations Recommendations were made about the epidemiology, classification, staging of uterine sarcomas, symptoms, general diagnostic workup, general pathology and genetic predisposition for uterine sarcomas, leiomyosarcomas, endometrial stromal sarcomas (low-grade and high-grade), undifferentiated uterine sarcomas, adenosarcomas, and rhabdomyosarcoma of the uterus in children and adolescents. The guideline also discusses the follow-up of uterine sarcomas, the management of morcellated uterine sarcomas, and the information provided to patients.

Iodine deficiency with the resultant maternal hypothyroxinemia and the effects of endocrine disruptors can, individually or together, have a negative effect on embryonic and fetal brain development. This is the conclusion of a recent review by the authors which examined and critically discussed a total of 279 publications from the past 30 years on the effects of mild to moderate iodine deficiency, reduced maternal thyroxine levels, and the influence of endocrine disruptors on child brain development during pregnancy. Adequate iodine intake is important for all women of childbearing age to prevent negative psychological and social consequences for their children. An additional threat to the thyroid hormone system is the ubiquitous exposure to endocrine disruptors, which can increase the impact of maternal iodine deficiency on the neurocognitive development of their offspring. Ensuring an adequate iodine intake is therefore not only crucial for healthy fetal and neonatal development in general, but could also prevent the potential effects of endocrine disruptors. Due to the current deficient iodine status of women of childbearing age and of children and adolescents in Germany and most European countries, urgent measures are needed to improve the iodine intake of the population. Therefore, in the opinion of the AKJ, young women of childbearing age should be instructed to take iodine supplements continuously for at least 3 months before conception and during pregnancy. In addition, detailed strategies for detecting and reducing exposure to endocrine disruptors in accordance with the "precautionary principle" should be urgently developed.

Objective: Inguinal sentinel lymph node dissection has been shown to be safe in early vulvar cancer in several studies and is considered or even recommended in many guidelines. The prognosis of inguinal recurrence is often poor and associated with significant mortality. To ensure an acceptably low false-negative rate and recurrence, vulvar sentinel lymph node dissection should only be performed using high-quality standards. This retrospective study aims to investigate the incidence of isolated groin recurrence in daily practice in six large cancer centers in Germany.

Methods: We identified all patients with early vulvar cancer in 2009-2015 who underwent inguinal sentinel lymphonodectomy and presented with node-negative final histologic results. Patient details regarding disease stage, sentinel procedure, and follow-up were examined using local cancer databases and patient registries.

Results: A total of 414 patients with available follow-up data were found, with a mean follow-up time of 38.4 months. The mean tumor size, measured in the dermal plane before surgery, was 40.0 mm, with a median tumor size of 36 mm. Isolated groin recurrence was found in 13 of 414 cases, leading to an isolated groin recurrence rate of 3.1%. The mean time to isolated groin recurrence was 17.7 months. There was no statistically significant association of any of the different quality requirements (tumor size < 4 cm, unifocal tumor, histologic ultra-staging, and preoperative exclusion of suspicious groins) with isolated groin recurrence.

Conclusion: Sentinel lymphadenectomy in vulvar cancer is a safe procedure in daily practice. The requirements of the cancer guidelines (unifocal tumor, ≤ 4 cm, histologic ultrastaging, and exclusion of suspicious groins preoperatively) should be followed to ensure a low isolated groin recurrence rate. However, in this study, we could not find any difference between the patients who fulfilled the guideline requirements and those who did not.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) has a lasting impact on quality of life with a high prevalence and the lack of preventive and causal treatment options. In addition, they are often dose-limiting for curative and palliative oncological therapy. The aim of this study was to systematically investigate the occurrence of paclitaxel-induced peripheral microcirculatory dysfunction and its potential impact on peripheral neuropathy using an experimental in vivo approach.

Methods: 77 female 8-week-old mice were randomly assigned into three groups. Each group was exposed to the following intraperitoneal interventions in a blinded fashion: The therapy group was treated with six cycles of paclitaxel. In the control group, mice received six cycles of saline solution. In the vehicle group, animals received six cycles of cremophor. Various microscopic, neurological and biochemical analyses were performed to assess the effects on peripheral nerve function, microcirculation and inflammation.

Results: Von Frey's neurological test showed a progressive peripheral neuropathy with a significant change in the sensitivity in the sense of hypesthesia of the hind paws in mice treated with paclitaxel. Beside signs of systemic inflammation, intravital microscopic analysis showed a significant reduction in functional capillary density, increased venular leukocyte adherence and endothelial permeability in the paclitaxel-treated mice compared to the control groups. In addition, serological tests and histopathological examinations underlined the paclitaxel-induced inflammation and nerve damage as well as the disturbance of the microcirculation.

Conclusion: The presented findings suggest that paclitaxel-induced microcirculatory disturbances may contribute to the development and severity of CIPN, highlighting the importance of considering microvascular and inflammatory mechanisms in the pathogenesis and management of chemotherapy-induced neuropathy.

Thrombocytopenia is a common hematologic disorder characterized by reduced platelet count in peripheral blood. Acquired and chronic thrombocytopenia is very important in obstetrics. A decreased platelet count of 15-20% is normal in uncomplicated pregnancies; platelet count decreases continuously from 1st trimester on, however usually remains within the normal ranges of between 150 and 450 G/L. The occurrence of mild thrombocytopenia (100-149 G/L) in pregnancy is usually due to gestational thrombocytopenia and does not require further evaluation. But a differential diagnostic examination should be carried out if the platelet count drops to < 100 G/L. Other forms of thrombocytopenia may also occur or become activated in pregnancy and they require special attention. This recommendation presents the diagnostic workup, differential diagnoses, and possible consequences of different thrombocytopenia conditions in pregnancy. The recommendations are based on current international recommendations (George 2023, Bussel 2023) and a search of the literature using the search terms "thrombocytopenia" and "pregnancy".

Organized cancer screening programs (oKFE) aim to detect and treat various cancers in their early stages. The German oKFE Directive has set out the requirements for evaluating the efficacy, quality, and safety of such programs. The first evaluation report on the cervical cancer screening program in Germany was published in May 2024 and covers the years 2021 and 2022. Women with statutory health insurance who are above the age of 20 and live in Germany are entitled to be screened for cervical cancer. Between the ages of 20 and 34 years, women are offered an annual cytology-based examination. From the age of 35 years and above, screening consists of a cytology examination and an HPV test (co-testing). The current evaluable data consists of pseudonymized data obtained from statutory health insurance companies and service providers as defined by the specifications of the IQTIG. The evaluation shows that around three million women between 20 and 34 years of age undergo cervical cancer screening every year, which corresponds to a response rate of 45%. As regards the co-testing carried out in women aged 35 years and above, around 2.3 million women with statutory health insurance had cytological examinations and co-testing in 2021 and 1.3 million women were similarly examined in 2022. The participation rate for this cohort cannot yet be determined as the three-year interval for persons eligible for this type of screening cannot be depicted using only two years of data. 97% of cytology smears were unremarkable. Fewer than 0.1% of smears resulted in cytological findings indicating precancerous cervical lesions or cervical malignancies. The average positive rate for HPV tests carried out as part of co-testing was 8.56%. The high-risk human papilloma viruses 16/18 were identified in 30% of cases with positive HPV tests, and the presence of these high-risk viruses increased in parallel with an increase in the severity of cytological findings. More than 30% of insured women aged between 20 and 34 years have been fully vaccinated against HPV. The limitations of this evaluation are the short observation period, some data gaps, and the not yet implemented combination of screening data with data from the cancer registries of the German federal states. It is not yet possible to make valid statements about the acceptance of the screening program and the long-term impact of this program.