Does an aptitude for surgery exist and can we predict it? an experimental study.

BACKGROUND: The selection and allocation of surgeons with a greater potential for high surgical performance are essential aspects of improving the quality, safety and effectiveness of surgical procedures. Objective of this trial was to determine the existence of basic skills and traits that would predict better performance in surgery, and those predictive factors that constitute a driving force in different stages of training. MATERIALS AND METHODS: The randomized crossover training trial took place from January 2021 to December 2021 and was conducted at an educational training center for minimally invasive surgery. A total of n=87 physicians (residents and experts) from surgical disciplines and n=239 fifth-year medical students were studied. The participants underwent extensive neuropsychological testing and surgical training, which was performed with conventional as well as robot-assisted laparoscopy by way of identical brief tasks conducted six times in a randomized crossover setting. Main Outcome was the latent factor structure of "psychomotor skills", "personality" and "motivation" based on structural equation modeling. RESULTS: The training performance of both students and physicians was significantly explained by the interaction of the three factors (explained variance: 8.2% for students, 23.8% for physicians). In students, motivation (explained variance 8.4%) and personality (explained variance 4.5%) revealed the highest contribution to surgical training performance (explained variance through psychomotor skills 1.1%). In physicians, psychomotor skills (explained variance 27.4%) made the greatest contribution to surgical training performance (explained variance through motivation 2.3%; explained variance through personality 10.5%). CONCLUSION: The study showed that surgical performance is sensitive to, and fragile in regard of non-surgery-related general individual traits. This aligns with the notion that early selection of surgeons with prospects of high surgical performance is possible, and perhaps even necessary in order to keep up with future demands on the medical system.

Correction: Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

[This corrects the article DOI: 10.1055/a-2238-3153.].

Peripartal management of dichorial twin pregnancy in a bicornuate bicollis uterus: a case report and review of the literature.

INTRODUCTION: The management of a pregnancy in a bicornuate uterus is particularly challenging. A bicornuate uterus is a rare occurrence and a twin pregnancy in a bicornuate uterus even more rare. These pregnancies call for intensive diagnostic investigation and interdisciplinary care. CASE PRESENTATION: We report on a 27-year-old European woman patient (gravida I, para 0) with a simultaneous pregnancy in each cavity of a bicornuate bicollis uterus after embryo transfer. The condition was confirmed by hysteroscopy and laparoscopy. Several unsuccessful in vitro fertilization (IVF) attempts had been performed earlier before embryo transfer in each cornus. After a physiological course of pregnancy with differential screening at 12 + 6 weeks and 22 + 0 weeks of gestation, the patient presented with therapy-resistant contractions at 27 + 2 weeks. This culminated in the uncomplicated spontaneous delivery of the leading fetus and delayed spontaneous delivery of the second fetus. DISCUSSION: Only 16 cases of twin pregnancy in a bicornuate unicollis uterus have been reported worldwide and only 6 in a bicornuate bicollis uterus. The principal risks in such pregnancies are preterm labor, intrauterine growth restriction, malpresentation and preeclampsia. These typical risk factors of a twin pregnancy are greatly potentiated in the above mentioned setting. CONCLUSION: A twin pregnancy in the presence of a uterine malformation is rare and difficult to manage. These rare cases must be collected and reported in order to work out algorithms of monitoring and therapy as well as issue appropriate recommendations for their management.

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy. Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed. Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients). Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.

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.

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.

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2023.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC).

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2023.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer. Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023. Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Chemotherapy-induced release of ADAM17 bearing EV as a potential resistance mechanism in ovarian cancer.

Ovarian cancer (OvCa) is the gynaecological disorder with the poorest prognosis due to the fast development of chemoresistance. We sought to connect chemoresistance and cancer cell-derived extracellular vesicles (EV). The mechanisms of how chemoresistance is sustained by EV remained elusive. One potentially contributing factor is A Disintegrin and Metalloprotease 17 (ADAM17)-itself being able to promote chemoresistance and inducing tumour cell proliferation and survival via the Epidermal Growth Factor Receptor (EGFR) pathway by shedding several of its ligands including Amphiregulin (AREG). We now demonstrate that upon chemotherapeutic treatment, proteolytically active ADAM17 is released in association with EV from OvCa cells. In terms of function, we show that patient-derived EV induce AREG shedding and restore chemoresistance in ADAM17-deficient cells. Confirming that ADAM17-containing EV transmit chemoresistance in OvCa, we propose that ADAM17 levels (also on EV) might serve as an indicator for tumour progression and the chemosensitivity status of a given patient.

Factors influencing surgical performance and learning progress in minimally invasive surgery - results of an interdisciplinary multicenter study.

BACKGROUND: Advancing surgical techniques require a high level of adaptation and learning skills on the part of surgeons. The authors need selection procedures and decision support systems for the recruitment of medical students and young surgeons. The authors aimed to investigate factors influencing the surgical performance and learning abilities of surgeons and medical students. MATERIALS AND METHODS: The training scores of persons attending 16 standardized training courses (at three training centers) of the German Working Group for Gynecological Endoscopy (AGE e.V.) from 2017 to 2020, individual characteristics, and the results of psychomotor tests of three-dimensional imagination and hand-eye coordination were correlated. Similar analyses were performed for medical students in their final clinical year from 2019 to 2020. The training concept was evaluated in a prospective, multicenter, interdisciplinary, multinational setting. RESULTS: In all, 180 of 206 physicians (response rate 87.4%) and 261 medical students (response rate 100%) completed the multistage training concept successfully. Of personal characteristics, the strongest correlation was noted for good surgical performance and learning success, and the absolute number of performed laparoscopic surgeries ( r =0.28-0.45, P <0.001/ r =0.1-0.28, P <0.05). A high score on the spatial visualization ability test was also correlated with good surgical performance ( r =0.18-0.27, P <0.01). Among medical students with no surgical experience, however, age was negatively correlated with surgical performance, that is the higher the age, the lower the surgical performance ( r =0.13/ r =0.22, P <0.05/ P <0.001). CONCLUSION: Individual factors (e.g. surgical experience, self-assessment, spatial visualization ability, eye-hand coordination, age) influence surgical performance and learning. Further research will be needed to create better decision support systems and selection procedures for prospective physicians. The possibilities of surgical training should be improved, promoted, and made accessible to a maximum number of surgical trainees because individual learning curves can be overcome even by less talented surgeons. Training options should be institutionalized for those attending medical school.

Sexually Transmitted Diseases-An Update and Overview of Current Research.

A rise in the rates of sexually transmitted diseases, both worldwide and in Germany, has been observed especially among persons between the ages of 15 and 24 years. Since many infections are devoid of symptoms or cause few symptoms, the diseases are detected late, may spread unchecked, and be transmitted unwittingly. In the event of persistent infection, the effects depend on the pathogen in question. Manifestations vary widely, ranging from pelvic inflammatory disease, most often caused by Chlamydia trachomatis (in Germany nearly 30% of PID) or Neisseria gonorrhoeae (in Germany <2% of PID), to the development of genital warts or cervical dysplasia in cases of infection with the HP virus. Causal treatment does exist in most cases and should always be administered to the sexual partner(s) as well. An infection during pregnancy calls for an individual treatment approach, depending on the pathogen and the week of pregnancy.

[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.

CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis.

Purpose: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers. Methods: Patients diagnosed with HR+/HER2- ABC who were treated in clinical routine with CDK4/6i between November 2016 and December 2020 at four certified German university breast cancer centers (Saarland University Medical Center, University Medical Center Charité Berlin, University Medical Center Bonn, and University Medical Center Hospital Schleswig-Holstein, Campus Kiel) were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on CDK4/6i therapy course [progression-free survival (PFS) following treatment initiation, toxicity, dose reduction, therapy discontinuation, prior and subsequent therapy line]. Results: Data from n = 448 patients were evaluated. The mean patient age was 63 (±12) years. Of these patients, n = 165 (36.8%) were primarily metastasized, and n = 283 (63.2%) had secondary metastatic disease. N = 319 patients (71.3%) received palbociclib, n = 114 patients (25.4%) received ribociclib, and n = 15 patients (3.3%) received abemaciclib, respectively. Dose reduction was performed in n = 132 cases (29.5%). N = 57 patients (12.7%) discontinued the treatment with CDK4/6i due to side effects. N = 196 patients (43.8%) experienced disease progression under CDK4/6i treatment. The median PFS was 17 months. Presence of hepatic metastases and prior therapy lines were associated with shorter PFS, whereas estrogen positivity and dose reduction due to toxicity were positively associated with PFS. Presence of bone and lung metastases, progesterone positivity, Ki67 index, grading, BRCA1/2 and PIK3CA mutation status, adjuvant endocrine resistance, and age did not significantly impact on PFS. Conclusion: Our RWD analysis on CDK4/6i treatment in Germany supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2- ABC. In comparison to data from the pivotal RCTs, median PFS was lower but within the expected range for RWD, which could result from inclusion of patients with more advanced diseases (i.e., higher therapy lines) to our dataset.

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.

Pediatric and adolescent gynecology- a current overview

In pediatric and adolescent gynecology we encounter a number of diseases that occur solely during a specific phase of physical development. The diseases need some experience in the field, as well as an accurate diagnosis and are therefore often diagnosed somewhat late. The separation and traction technique is a painless method of inspecting the child's genitals. It is also effective and easy to perform. In contrast to a routine investigation in adults, very specific diagnostic questions require the insertion of a speculum, vaginoscopy, taking swabs for analysis, ultrasound investigations, or blood sampling in children. A number of diseases that occur frequently in prepubertal girls will be discussed. The etiology, clinical characteristics, treatment and prognosis of the following diseases will be addressed in detail: vulvovaginitis, lichen sclerosus, labial adhesions, ovarian torsion, abnormal uterine bleeding, uterine fibroids, and hypertensive disorders of pregnancy.

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.

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.

Impact of Adenomyosis on Infertile Patients-Therapy Options and Reproductive Outcomes.

Adenomyosis is associated with a negative impact on reproductive outcomes. Although adenomyosis is detected more frequently in women of late reproductive age, its impact on pregnancy rates is important because, in today's world, family planning has shifted towards the late reproductive phase of life for many women. Although the diagnostic indications for imaging studies are well-known, we lack strict diagnostic criteria and classification systems concerning the extent of the disease. Selecting the optimal evidence-based treatment option for adenomyosis is difficult because of the paucity of evidence concerning the association between fertility and the degree and composition of adenomyosis. Furthermore, the treatment of infertility might interfere with the treatment of adenomyosis due to the presence of pain. The aim of this review is to analyze the association between adenomyosis and infertility, and describe treatment options to enhance reproductive outcomes. The following aspects will be addressed in detail: (a) prevalence and causes of adenomyosis, (b) diagnostic tools with imaging techniques, (c) clinical symptoms, (d) proposed pathomechanism of adenomyosis and infertility, and (e) different treatment approaches (pharmacological, surgical, others) and their impact on reproductive outcomes.