Laparoscopic surgery for endometrial cancer is oncologically safe and improves hospital stay duration: a retrospective single-center study over a 16-year period.

OBJECTIVE: To investigate changes in surgical procedures and patient outcomes of patients diagnosed with endometrial cancer (EC) at a German university hospital between 1998 and 2014. METHODS: A monocentric, retrospective review was conducted to identify patients diagnosed and treated with EC during the aforementioned period at the Department of Gynecology and Obstetrics at the University Hospital Kiel, Germany. RESULTS: 303 patients were identified. Patient demographics, risk factors, histological subtypes and stages of EC remained consistent over time. The most common surgical procedure was total abdominal hysterectomy (TAH) (81.9%). In 2011, the institution carried out its first total laparoscopic hysterectomy (TLH) for EC, resulting in a significant increase in laparoscopic surgical procedures (2011-2014: N = 70; TAH 44.2%; TLH 51.4%). Although the total number of lymph node stagings remained consistent over time, there was a significant increase in the performance of simultaneous pelvic and para-aortic lymphonodectomy (LNE) compared to pelvic LNE alone (2.6 in 2001-2005 vs. 18.0% in 2011-2014, p ≤ 0.001). The duration of hospital stays significantly decreased over time, with a mean of 20.9 days in the first and 8.5 days in the last period. When comparing surgical procedures, TLHs resulted in significantly shorter postoperative stays with an average of 6.58 vs. 13.92 days for TAH. The surgical procedure performed did not affect 5-year overall survival rates in this study (84.9% for TAH and 85.3% for TLH, p = 0.85). CONCLUSIONS: Our retrospective single-center study demonstrates that laparoscopic surgery for endometrial cancer is oncologically safe and shortens hospital stays.

The Feasibility of Practical Training in Minimally Invasive Surgery at Medical School-A Prospective Study on the Pelvitrainer.

Background and Objectives: The acquisition of practical skills at medical school is an important part of the multidimensional education program of future physicians. However, medical schools throughout the world have been slow in incorporating practical skills in their curriculum. Therefore, the aims of the present prospective study were (a) to demonstrate the feasibility of such surgical training, (b) to objectify its benefit in medical education, and (c) to investigate the impact of such training on subsequent career choices. Material and Methods: We introduced a two-day laparoscopy course on the pelvitrainer as part of the curriculum of the gynecological internship of fifth year medical students from 2019 to 2020. The results of the students' training were matched to those of surgeons who completed the same curriculum in a professional postgraduate laparoscopy course from 2017 to 2020 in a comparative study design. Additionally, we performed a questionnaire-based evaluation of the impact of the course on medical education and subsequent career choices directly before and after completing the course. Results: A total of 261 medical students and 206 physicians completed the training program. At baseline, the students performed significantly more poorly than physicians in a median of three of four exercises (p < 0.001). However, this evened out in the final runs, during which students performed more poorly than physicians only in one exercise and even better than physicians in one. The general integration of surgical training in medical school curricula was rated very low (12.4% on the VAS, IQR 3-16%) despite the high demand for such training. In the survey, the course was deemed very beneficial for medical education (median VAS 80.7%, IQR 73-98%), but did not appear to influence the students' subsequent career preferences. Conclusions: The acquisition of practical surgical skills during medical school is significantly under-represented in many medical faculties. The benefits of such training, as demonstrated in our study, would improve the education of future physicians.

Fluorescence in situ hybridization test for detection of endometrial carcinoma cells by non-invasive vaginal swab.

Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array-based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH-probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut-off value has been defined. A first validation of this EC-FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut-off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non-invasive EC-FISH Test to predict EC in women with suspected EC.

Intrahepatic cholestasis of pregnancy: an evaluation of obstetric management in German maternity units.

PURPOSE: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse fetal and neonatal outcome. Evidence for improvement by obstetric management is sparse. Common international guidelines recommend induction of labor before term, however, they differ in recommendations of monitoring the disease and time point of active management. So far, an official guideline for treatment and management of ICP in Germany does not exist. This study aims to compile common practice and policy in obstetric management of ICP in German maternity units. The objective is to gather obstetricians' opinion on management of ICP, and to estimate the need for standardization of current practice in Germany on the background of existing evidence. METHODS: A questionnaire focusing on indications for interventions was developed including fourteen multiple-choice questions comprising the areas of diagnostic criteria, laboratory testing, fetal monitoring, treatment, and delivery timing. The survey was sent to 699 maternity clinics and was distributed to participants of the annual congress hosted by the German society of perinatal medicine (DGPM). Collected data were summarized and evaluated in relation to available evidence and existing guidelines. Descriptive statistics and Fisher's exact test were used. RESULTS: 334 completed questionnaires returned corresponding to a response rate of 48.1%. Coinciding with existing international guidelines, 48.8% of the participants acknowledge bile acid concentrations above 10 µmol/L to be indicative of ICP. 85.0% of obstetricians recommend antenatal testing with cardiotocography, exceeding common standards of maternity policy guidelines; 50.3% execute active management in ICP-affected pregnancies as they generally recommend a delivery between 37 + 0 and 38 + 6 weeks of gestation. Although recent studies evinced a risk of stillbirth in ICP-affected pregnancies not until a bile acid concentration of > 100 µmol/L, 22.2% of the respondents recommend delivery before 37 + 0 weeks of gestation due to raised bile acids of 40-99 µmol/L. CONCLUSIONS: Opinions on the management of ICP in German maternity units differ widely and partly deviate by large from international standards. Reasons for this may be the lack of a national guideline and the low awareness due to the rarity of the disease on the one hand and the very slow dynamics in evidence generation and thus the uncertainty about the actual risks and optimal management on the other. The present data highlight the need for further research and clinical guidelines to standardize and optimize treatment based on the best available evidence.

Assessing the Phenotype of a Homologous Recombination Deficiency Using High Resolution Array-Based Comparative Genome Hybridization in Ovarian Cancer.

Ovarian cancer (OC) cells with homologous recombination deficiency (HRD) accumulate genomic scars (LST, TAI, and LOH) over a value of 42 in sum. PARP inhibitors can treat OC with HRD. The detection of HRD can be done directly by imaging these genomic scars, or indirectly by detecting mutations in the genes involved in HR. We show that HRD detection is also possible using high-resolution aCGH. A total of 30 OCs were analyzed retrospectively with high-resolution arrays as a test set and 19 OCs prospectively as a validation set. Mutation analysis was performed by HBOC TruRisk V2 panel to detect HR-relevant mutations. CNVs were clustered with respect to the involved HR genes versus the OC cases. In prospective validation, the HRD status determined by aCGH was compared with external HRD assessments. Two BRCA mutation carriers did not have HRD. OC could approximately differentiate into two groups with characteristic CNV patterns with different survival rates. Mutation frequencies have a linear regression on the HRD score. Mutations in individual HR-relevant genes do not always indicate HRD. This may depend on the mutation frequency in tumor cells. The aCGH shows the genomic scars of an HRD inexpensively and directly.

Molecular Determinants of Uterine Receptivity: Comparison of Successful Implantation, Recurrent Miscarriage, and Recurrent Implantation Failure.

Embryo implantation is one of the most remarkable phenomena in human reproduction and is not yet fully understood. Proper endometrial function as well as a dynamic interaction between the endometrium itself and the blastocyst-the so-called embryo-maternal dialog-are necessary for successful implantation. Several physiological and molecular processes are involved in the success of implantation. This review describes estrogen, progesterone and their receptors, as well as the role of the cytokines interleukin (IL)-6, IL-8, leukemia inhibitory factor (LIF), IL-11, IL-1, and the glycoprotein glycodelin in successful implantation, in cases of recurrent implantation failure (RIF) and in cases of recurrent pregnancy loss (RPL). Are there differences at the molecular level underlying RIF or RPL? Since implantation has already taken place in the case of RPL, it is conceivable that different molecular biological baseline situations underlie the respective problems.

[The Importance of Feedback in Proctoring in Robotic Surgery - a Cornerstone of the Concept of Success?] / Der Stellenwert des Feedbacks beim Proctoring in der robotergestützten Chirurgie ­ ein Grundstein des Erfolgskonzeptes?

Robot-assisted surgical methods are a development and supplement to conventional laparoscopy. Thus, appropriate training of surgeons in this specialty is indispensable. Especially for the initial phase, simulation programs - similar to those used in aviation - are ideally suited to introduce surgeons to the technically challenging surgical procedure. Later on, but still at the beginning of the learning curve, proctoring has proven its worth in order to allow the surgeon to be trained on site, to train him individually and to introduce him to more complex cases. An essential component of successful training concepts is the feedback: after some time and in written form, the surgeon to be trained receives a summary or a guideline, which describes the existing situation as well as suggestions for improvement and future potential. The implementation of such feedback allows the surgeon, in addition to the number of cases completed, to put his self-assessment into perspective and adjust development goals. Thus, feedback is the crucial interface between the beginning of a learning curve and advanced surgical skills, including the possibility of realistic self-assessment.

Challenges in the Diagnosis and Individualized Treatment of Cervical Cancer.

Cervical cancer is still the fourth most common cancer in women throughout the world; an estimated 604,000 new cases were observed in 2020. Better knowledge of its pathogenesis, gained in recent years, has introduced new preventive and diagnostic approaches. Knowledge of its pathogenesis has made it possible to provide individualized surgical and drug treatment. In industrialized countries, cervical cancer has become a less frequent tumor entity due to the accessibility of the human papilloma virus vaccination, systematic preventive programs/early detection programs, health care infrastructure and the availability of effective therapy options. Nevertheless, globally, neither mortality nor morbidity has been significantly reduced over the past 10 years, and therapy approaches differ widely. The aim of this review is to address recent advances in the prevention, diagnostic investigation and treatment of cervical cancer globally, focusing on advances in Germany, with a view toward providing an updated overview for clinicians. The following aspects are addressed in detail: (a) the prevalence and causes of cervical cancer, (b) diagnostic tools using imaging techniques, cytology and pathology, (c) pathomechanisms and clinical symptoms of cervical cancer and (d) different treatment approaches (pharmacological, surgical and others) and their impact on outcomes.

Expanding Robotic-Assisted Surgery in Gynecology Using the Potential of an Advanced Robotic System.

Minimally invasive surgery (MIS) in gynecology was introduced to achieve the same surgical objectives as traditional open surgery while minimizing trauma to surrounding tissues, reducing pain, accelerating recovery, and improving overall patient outcomes. Minimally invasive approaches, such as laparoscopic and robotic-assisted surgeries, have become the standard for many gynecological procedures. In this review, we aim to summarize the advantages and main limitations to a broader adoption of robotic-assisted surgery compared to laparoscopic surgeries in gynecology. We present a new surgical system, the Dexter Robotic System™ (Distalmotion, Switzerland), that facilitates the transition from laparoscopy expertise to robotic-assisted surgery.

Lymphadenectomy in endometrial cancer - achieving more with less?

The lymph node status of patients with endometrial cancer is known to be a crucial determinant for the prognosis of the disease. It also provides the indication for further adjuvant treatment. The staging of endometrial cancer by surgery has been a controversial issue for more than 30 years. The significant complication rate after lymphadenectomy and the development of minimally invasive surgery have led to the use of sentinel lymph node (SLN) mapping. In the present review, we present the development of surgical staging procedures in patients with endometrial cancer and summarize the recently expanding body of published literature on the subject. SLN mapping is a safe and accurate technique, especially when indocyanine green is used as a tracer. SLN mapping appears to reduce complication rates as well as costs without affecting the oncologic outcome. Large prospective studies are needed to establish the effects of SLN mapping on the outcome of disease, especially in high-risk patients with endometrial cancer. Furthermore, the need for additional systematic lymphadenectomy prior to adjuvant radio-chemotherapy in patients diagnosed with isolated lymph node metastasis during SLN biopsy must be investigated further. This might pave the way for a new surgical approach in patients with endometrial cancer.

Establishment and evaluation of a training course in advanced laparoscopic surgery based on human body donors embalmed by ethanol-glycerol-lysoformin fixation.

BACKGROUND: Education of clinical anatomy and training of surgical skills are essential prerequisites for any surgical intervention in patients. Here, we evaluated a structured training program for advanced gynecologic laparoscopy based on human body donors and its impact on clinical practice. METHODS: The three-step training course included: (1) anatomical and surgical lectures, (2) demonstration and hands-on study of pre-dissected anatomical specimens, and (3) surgical training of a broad spectrum of gynecological laparoscopic procedures on human body donors embalmed by ethanol-glycerin-lysoformin. Two standardized questionnaires (after the course and 6 months later) evaluated the effectiveness of each of the training modules and the benefits to surgical practice. RESULTS: Eighty participants took part in 6 training courses using a total number of 24 body donors (3 trainees/body donor). Based on a 91.3% (73/80) response rate, participants rated high or very high the tissue and organ properties of the body donors (n = 72, 98.6%), the technical feasibility to perform laparoscopic surgery (n = 70, 95.9%), and the overall learning success (n = 72, 98.6%). Based on a 67.5% (54/80) response rate at 6 months, participants rated the benefit of the course to their daily routine as very high (mean 80.94 ± 24.61%, n = 53), and this correlated strongly with the use of body donors (r = 0.74) and the ability to train laparoscopic dissections (r = 0.77). CONCLUSIONS: This study demonstrates the technical feasibility and didactic effectiveness of laparoscopic training courses in a professional and true-to-life setting by using ethanol-glycerol-lysoformin embalmed body donors. This cost-efficient fixation method offers the option to integrate advanced surgical training courses into structured postgraduate educational curricula to meet both the technical demands of minimal invasive surgery and the ethical concerns regarding patients´ safety.

Impact of nicotine and maternal BMI on fetal birth weight.

BACKGROUND: According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. As the individual factors (body mass index - BMI (kg/m2) - and cigarette consumption) have been extensively investigated in pregnancy, we aimed to establish how maternal BMI and nicotine interact with regard to perinatal outcomes and birth weight. METHODS: Data from 110.047 singleton pregnancies, achieved from the German Perinatal Survey in Schleswig-Holstein and registered between 2010 and 2017 were analyzed in August 2018 concerning maternal BMI and smoking. The BMI was taken from the maternity log. Information concerning the smoking status were self-reported and further subdivided into the following four categories: a) non-smokers; b) 1-7 cigarettes/day; c) 8-14 cigarettes/ day; and d) ≥ 15 cigarettes/ day. Furthermore, we classified women by their BMI into underweight, normal weight, overweight and obese. Comparisons between non-smokers and the respective smoking group, and their relationship with maternal BMI were performed by the t-test (birth weight). A P-value ≤0.05 was considered to indicate statistical significance. RESULTS: A number of 97.092 women (88.2%) were non-smokers and 12.955 (11.8%) were smokers. Furthermore 10.3% of women of normal weight smoked during pregnancy, but both high and low BMI were associated with a high prevalence of smoking. The proportion of smokers was highest (18.1%) among underweight women (BMI ≤ 18.5 kg/m2). A large number of smokers (15.5%) were registered in the obesity group (BMI ≥ 30 kg/m2). Mean birth weight (≥ 37 + 0 gestational age) increased with increasing maternal BMI, and was reduced by smoking for every BMI category. The differences between smokers and non-smokers were always highly significant (p < 0.001). Mean birth weight varied between 2995 g in underweight frequent smokers and 3607 g in obese non-smokers. CONCLUSION: Both maternal BMI and smoking during pregnancy influences the birth weight and therefore pregnancy outcome. Smoking during pregnancy was significantly associated with low birth weight. Pregnant women should be advised to cease or at least reduce smoking in order to improve the birth weight of the newborn and to minimize child morbidities.

Recurrent implantation failure - an overview of current research.

BACKGROUND: Recurrent implantation failure (RIF) can be defined as a failure to achieve a clinical pregnancy after transfer of at least four embryos of good quality in a minimum of three fresh or frozen cycles in women under the age of 40. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. SUMMARY: Anatomical conditions of the uterus, thrombophilia, genetic abnormalities, or immunological factors are only a few examples which could be responsible for RIF. The recommendations for women with RIF vary depending on the source of their problem. There is not just one treatment option, but many depending on the etiology and the severity of the problem. KEY MESSAGE: However, it would help to establish a set of standardized examinations and tests to use, in order to do a preliminary evaluation on each patient, which would then hopefully direct the approach of treatment for each individual couple.

Involvement of medical students in a surgery congress: impact on learning motivation, decision-making for a career in surgery, and educational curriculum.

During the preclinical period of medical school, the clinical relevance of theoretical knowledge is given little attention. Medical students of the second year were invited to participate in an interdisciplinary congress for robot-assisted and digital surgery. The students had to evaluate the impact of the congress on their learning motivation, decision-making for a career in surgery, and relevance for their educational curriculum. Participation in the congress increased their learning motivation for preclinical subjects, and significantly increased their interest in a surgical career. Most students considered active involvement in medical congresses a valuable supplement to the medical curriculum. Congress participation during the preclinical period was ranked positively by medical students. Greater learning motivation and enthusiasm for the pilot teaching project as well as for surgical disciplines were registered. Thus, early involvement of medical students in scientific congresses should be an integral part of their educational curriculum.

Evaluation of Laparoscopy Virtual Reality Training on the Improvement of Trainees' Surgical Skills.

Background and objectives: The primary objective was to evaluate the benefit of training with virtual reality simulation. The secondary objective was to describe the short-term skill acquisition obtained by simulation training and to determine the factors affecting its magnitude. Materials and Methods: We prospectively performed a three-stage evaluation: face, constructive, and predictive to evaluate the training with a laparoscopic simulator with haptic feedback. The participants (n = 63) were divided according to their level of experience into three groups: 16% residents; 46% specialists and 38% were consultants. Results: Face evaluation demonstrates the acceptance of the design and realism of the tasks; it showed a median score of eight (IQR 3) on a Likert scale and 54% of participants (n = 34) gave the tissue feedback a moderate rating. Constructive evaluation demonstrates the improvement of the participants in the training session and the ability of the designed task to distinguish the experienced from the inexperienced surgeon based on the performance score, at task I (transfer of pegs) and II (laparoscopic salpingectomy). There was an improvement in both tasks with a significant increase in score and reduction in time. The study showed that those with a high score at the pre-test recorded a high score post-test, showing a significant pair-wise comparison (Z) and correlation (p) showing a significant statistical significance (p < 0.001). The predictive evaluation demonstrates the beneficiary effect of training four weeks afterward on the practice of surgeons addressed with five questions. It showed an improvement regarding implementation into daily routine, performance of procedure, suturing, shortening of the operative time, and complication management. Conclusions: Virtual reality simulation established high ratings for both realism and training capacity, including clinical relevance, critical relevance, and maintaining training enthusiasm.

Dasatinib prevents skeletal metastasis of osteotropic MDA-MB-231 cells in a xenograft mouse model.

PURPOSE: Bone metastasis in breast cancer has been linked to activity of c-Src kinase, one of the extensively explored tyrosine kinases in cell biology. The impact of TNF-related apoptosis inducing ligand (TRAIL) and TRAIL receptors has just recently been integrated into this conception. METHODS: An osteotropic clone of MDA-MB-231 cells simulated a model for bone metastasis of triple-negative breast cancer (TNBC). The effects of Dasatinib, a clinically established inhibitor of Src kinases family and Abl were evaluated in vitro and in vivo. In vivo effects of Dasatinib treatment on the occurrence of skeletal metastases were tested in a xenograft mouse model after intra-cardiac injection of osteotropic MDA-MB-231-cells. Ex vivo analyses of the bone sections confirmed intraosseous growth of metastases and allowed determination of osteoclastic activity. RESULTS: Treatment of osteotropic MDA-MB-231 cells with Dasatinib inhibited proliferation rates in vitro. A shift in TRAIL-receptor expression towards an induction of oncogenic TRAIL-R2 was observed. In vivo, 15 of 30 mice received an intra-peritoneal treatment with Dasatinib. These mice showed significantly less skeletal metastases in bioluminescence scans. Moreover, a pronounced increase in bone volume was observed in the treatment group, as detected by µ-Computed Tomography. Dasatinib treatment also led to a greater increase in bone density in tibiae without metastatic affection, which was accompanied by reduced recruitment of osteoclasts. CONCLUSION: Our observations support the concept of utilizing Dasatinib in targeting early-stage bone metastatic TNBC and sustaining bone health.

Impact of Acoustic and Interactive Disruptive Factors during Robot-Assisted Surgery-A Virtual Surgical Training Model.

The use of virtual reality trainers for teaching minimally invasive surgical techniques has been established for a long time in conventional laparoscopy as well as robotic surgery. The aim of the present study was to evaluate the impact of reproducible disruptive factors on the surgeon's work. In a cross-sectional investigation, surgeons were tested with regard to the impact of different disruptive factors when doing exercises on a robotic-surgery simulator (Mimic Flex VRTM). Additionally, we collected data about the participants' professional experience, gender, age, expertise in playing an instrument, and expertise in playing video games. The data were collected during DRUS 2019 (Symposium of the German Society for Robot-assisted Urology). Forty-two surgeons attending DRUS 2019 were asked to participate in a virtual robotic stress training unit. The surgeons worked in various specialties (visceral surgery, gynecology, and urology) and had different levels of expertise. The time taken to complete the exercise (TTCE), the final score (FSC), and blood loss (BL) were measured. In the basic exercise with an interactive disruption, TTCE was significantly longer (p < 0.01) and FSC significantly lower (p < 0.05). No significant difference in TTCE, FSC, or BL was noted in the advanced exercise with acoustic disruption. Performance during disruption was not dependent on the level of surgical experience, gender, age, expertise in playing an instrument, or playing video games. A positive correlation was registered between self-estimation and surgical experience. Interactive disruptions have a greater impact on the performance of a surgeon than acoustic ones. Disruption affects the performance of experienced as well as inexperienced surgeons. Disruption in daily surgery should be evaluated and minimized in the interest of the patient's safety.

[Ethical decision-making in the face of increasing economization of hospitals : A study on ethical mistrust in decisions taken on the length of hospital stay among students and doctors]. / Ethische Entscheidungen in zunehmend ökonomisierten Krankenhäusern : Eine Untersuchung zum ethischen Misstrauen in Verweildauerentscheidungen bei Studierenden und ÄrztInnen unterschiedlicher Positionen.

Are medical values receding in importance because of economization of the German health system? Within the frame of a vignette study, a case is presented based on prolongation of the hospitalization of an elderly and not entirely recovered patient. All respondents of the questionnaire predicted the relevance of decision criteria, such as medical accuracy, empathy towards the patient, and identification with the hospital. Participants (N = 1,239) believe that decision-makers view medical accuracy as the most important criterion, followed by empathy. The more the respondent had universalistic values, the more likely the person was to favor an extended hospitalization. The more security-oriented and less pro-social the respondent, the more likely the person was to support an early discharge. It can be concluded that in the course of their training doctors acquire their grounded deontological-ethical decision-making autonomy, which may in some cases contradict existing regulations.

[Does Apolipoprotein B Level in Early Pregnancy Predict Excessive Gestational Weight Gain and Adverse Pregnancy Outcome?] / Exzessive Gewichtszunahme in der Schwangerschaft und die prognostische Bedeutung des Apolipoprotein B.

INTRODUCTION: Excessive maternal gestational weight gain (GWG) is a risk factor for maternal and fetal complications. The lipid profile changes physiologically during pregnancy. Weight gain can affect lipid metabolism. The hypothesis of the study was that apoB levels early in pregnancy are associated with excessive GWG and predictive for adverse outcomes. METHODS: Out of 547 patients there were 95 women with inadequate GWG, 171 with adequate GWG, and 281 with excessive GWG. Out of 581 patients there were 14 patients with pregnancy-induced hypertonus/pre-eclampsia, 67 with small-for-gestational-age (SGA) infants, and 7 with fetal growth restriction (FGR). ApoB levels were measured by ELISA. RESULTS: There was no significant difference in apoB levels between the different GWG groups. We found significantly higher levels of apoB in overweight and obese patients compared to those with normal BMI. Smoking was correlated with higher apoB levels. There were no differences either between women with PIH/PE and normotensive women or between SGA/IUGR and pregnancies without. Women with pre-existing hypertension showed significantly higher apoB levels than the control group. CONCLUSIONS: ApoB cannot be used as a marker for identifying the risk of excessive GWG or adverse pregnancy outcomes early in pregnancy. However, it may be involved in the pathophysiology of adverse pregnancy outcomes in high-risk patients.

Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients.

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.