Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole.

BACKGROUND: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. METHODS: Between 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. RESULTS: Among 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. CONCLUSION: Patient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Generation of a Specific Fluorescence In Situ Hybridization Test for the Detection of Ovarian Carcinoma Cells.

Examinations of ovarian cancer cells require the ability to identify tumor cells. Array-based comparative genome hybridization (aCGH) on 30 ovarian carcinomas (OC) identified three genomic loci (8q24.23; 17p12; 18q22.3) over- or under-represented in OC. A fluorescence in situ hybridization (FISH) probe of these three loci is intended to identify tumor cells by their signal pattern deviating from a diploid pattern. Human DNA from these three loci is isolated from bacterial artificial chromosomes (BAC), amplified and labeled with fluorescent dyes. After a standard FISH procedure, 71 OC suspensions from primary tumors, three OC cell lines, three lymphocyte suspensions, and one mesenchymal cell line LP-3 are analyzed with a fluorescence microscope. On average, 15% of the lymphocytes deviate from the expected diploid signal pattern, giving a cut-off of 36%. If this value is exceeded, tumor cells are detected. The mesenchymal cell line LP-3 shows only 21% as a negative control. The OC cell lines as positive controls exceed this value at 38%, 67%, and 54%. Of the 71 OC primary cultures, four cases fell below this cut-off as false negatives. In the two-sample t-test, the percentages of conspicuous signal patterns differ significantly.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, 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. Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024. Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

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.].

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.

Encouraging medical students to become surgeons? Impact of psychological and surgical factors on career choice at medical school.

Aim: Training decisions are viewed as a problem by the majority of medical students.In the present study we compared sociodemographic and psychological characteristics of students who are interested in surgical training to those who preferred a non-surgical specialty. Furthermore, we examined whether students who wish to be trained as surgeons performed better than their non-surgical counterparts in a course designed to acquire skills in minimally invasive surgery. Method: From October 2020 to January 2021 we performed a cross-sectional survey among 116 medical students prior to their year of practical training at Christian-Albrechts University in Kiel. Based on their intended field of specialization, the students were divided into a non-surgical and a surgical group. Sociodemographic and psychological characteristics such as self-efficacy expectations, resilience and stress perception were evaluated and compared between groups. Simultaneously, we compared their surgical performance in two laparoscopic exercises and their self-assessment as surgeons. Statistical differences between the training groups were determined by the Mann-Whitney U test or Pearson's Chi square test. Results: Ninety-two students participated in the study, of whom 64.1% intended to train in a non-surgical specialty and 35.9% in a surgical specialty. Students who wished to be trained as surgeons had higher general self-efficacy expectations (p<0.001) and greater resilience (p=0.009). However, on comparison they had a lower stress level (p=0.047). The inter-group comparison of training results and self-assessment as surgeons revealed no unequivocal differences in surgical performance. Conclusion: Interest in surgical specialties is correlated, among other factors, with the strength of psychological skills such as general self-efficacy expectations, resilience and stress perception. Early attention to these psychological resources in academic training might assist medical students in future career choices.

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 nonsurgery-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.

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.

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.