Feasibility of targeted therapies in the adjuvant setting of early breast cancer in men: real-world data from a population-based registry.

BACKGROUND: Following the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials. PATIENTS AND METHODS: We conducted a data inquiry and analysis with the Cancer Registry of Baden-Württemberg of men with breast cancer diagnosed between January 1, 2015 and December 31, 2021. Men with eBC were identified and the number of patients at clinical high-risk according to the inclusion criteria of monarchE, NATALEE and OlympiA was assessed. RESULTS: Of 397 men with eBC, 354 (89.1%) had a HR + /Her2- and 4 (1.0%) a triple-negative subtype. 84 patients (21.2%) met the clinical high-risk criteria according to the monarchE, 189 (47.6%) those according to the NATALEE and 50 (12.6%) those according to the OlympiA trial. CONCLUSION: In a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

Proposal for a descriptive and differentiated presentation of the longitudinal impact of the new organized cancer screening guideline and HPV vaccination in Germany.

INTRODUCTION: Since 01/01/2020, the cervical cancer screening in Germany has been carried out due to the organized early cancer diagnosis guideline (oKFE-RL). In 2007, HPV vaccination was initiated in Germany. The main goal of both initiatives is to further reduce the incidence of invasive cervical cancer. To assess the effect of the new screening strategy in a timely manner, monitoring of short-term changes need to be considered. Ideally, the effects of both prevention methods would be presented together in one model. MATERIALS AND METHODS: Because no change in the incidence of invasive cervical cancer is initially expected, the incidence of CIN 3 is used as a surrogate parameter to assess the effects of the prevention efforts. Based on expected additional effects of vaccination and co-testing, a model-based estimation of the expected CIN 3 incidence during the evaluation of the screening program is performed using the CIN 3 incidence in the Saarland population. MODELING RESULTS: The oKFE-RL provides for two groups: Primary cytodiagnosis continues until 35 years of age. Here, in the next few years, CIN 3 incidence will be reduced not by the oKFE-RL but by the increasing proportion of vaccinated women. In the group over 35 years, co-testing was introduced with a stringent algorithm. Due to the higher sensitivity of the HPV test, significantly more CIN 3 are detected in the first round of 3 years and thus, the CIN 3 incidence initially increases. As these CIN 3 are absent in the second round, significantly fewer CIN 3 cases will be detected then. These effects suggest a global decrease in CIN 3 incidence of 25.8% after 6 years. CONCLUSION: Observation of the age distribution curve of CIN 3 allows both effects of prevention to be assessed in a timely manner and separately. In the future, data from epidemiologic cancer registries should be incorporated into the model to replace modeling with real data.

Efficacy and safety of two post-operative drains: results of a prospectively randomized clinical study in breast cancer patients after breast conserving surgery.

OBJECTIVE: To compare the efficacy and safety of two post-operative drains in breast cancer patients after breast conserving surgery. METHODS: This was a prospectively randomized comparative study of two drains investigated in breast cancer patients after breast conserving therapy. The Redon drain ends in a tip with 28 double perforations while the Quadrain drain features 4 flexible flaps of about 0.15 m length. The drains cost 0.28 € and 3.54 €, respectively. Primary target parameter was the duration of the drains staying in the surgical site. Secondary target parameters were pain post-surgery, seroma volume, final cosmetic result and surgical site infections. RESULTS: A total of 88 patients were randomized, 47 and 41 received the Redon drain and the Quadrain drain, respectively. The mean duration of the drains staying in the surgical site was not different between the Redon and the Quadrain drain, 42.6 h (± 25.8 h) and 50.1 h (± 28.5 h), respectively (p = 0.1959). The post-operative pain score, seroma size, cosmetic result and surgical site infections were not different for both systems. CONCLUSION: The Redon drain and the new Quadrain drain were not significantly different with respect to duration in the surgical site, post-operative pain, seroma volume and cosmetic result.

Safety and perioperative morbidity of laparoscopic sacropexy: a systematic analysis and a comparison with laparoscopic hysterectomy.

PURPOSE: The high prevalence of Pelvic Organ Prolapse (POP) along with the demographic trend of the ageing population raises the value of sacropexy in the treatment of POP. Thus, efforts to decrease risks associated with this procedure have the potential for public health impact. We examined the perioperative morbidity of laparoscopic sacropexy regarding the surgical access and compared it with the morbidity of one of the most common gynecological procedure, the laparoscopic hysterectomy. Our aim was to prove the safety of laparoscopic sacropexy. METHODS: A retrospective evaluation of 80 consecutive laparoscopic sacropexies performed from Sept. 2012 until Oct. 2014 and 126 laparoscopic hysterectomies for a benign indication were undertaken. We assessed the anatomical outcome and the intra- and postoperative complications using the classification system according to Clavien-Dindo (CD). RESULTS: Apical success rate after sacropexy was 100% and global success rate was 95% (POP-Q stage ≤1). The decline in hemoglobin was low in both groups and showed no statistically significant differences. Both operative time (P < 0.001) and the duration of hospitalization (P < 0.001) were longer in case of a sacropexy. Although overall intraoperative complications seemed more frequent during a sacropexy, differences were not statistically significant. Both early and late postoperative complications showed a higher rate of mild complications (CD-I/II) and a lower rate of severe complications (CD-IIIa/IIIb) after a sacropexy. The differences were not statistically significant. CONCLUSION: The laparoscopic sacropexy represents a safe procedure with good anatomical outcome. Despite higher technical severity, it doesn't seem to bare higher risks for perioperative morbidity than the laparoscopic hysterectomy does.

Conversion of intraperitoneal cytology during laparoscopic surgery of uterine cancer.

INTRODUCTION: The laparoscopic surgery of uterine cancer is an oncological safe treatment option in early stage cancer. However, there are no data about whether laparoscopy can lead to intraperitoneal tumor cell dissemination. We aimed in our study to detect a possible cytological conversion during laparoscopic procedures. METHODS: In this prospective study, we included all patients receiving laparoscopic treatment at the early stage endometrial and cervical cancer in the Department of Obstetrics and Gynecology at the University of the Saarland and obtained peritoneal wash for cytological examination at the beginning and at the end of laparoscopic surgery. All patients received stage-adjusted operative and adjuvant therapy. RESULTS: We enrolled 43 patients [endometrial cancer (n = 24) and cervical cancer (n = 19)]. At the beginning of the operation, one patient with endometrial cancer and one patient with cervical cancer showed a positive cytology. One tumor cell conversion from negative to positive cytology during surgery was detected in a patient suffering from endometrial cancer stage FIGO Ia. The median duration of surgery was 191.8 ± 79.3 min. The average time of follow-up was 16.5 ± 10.3 month. At the end of data evaluation at December 2014, two patients (8.6 %) are suffering from recurrent disease, two patients died, none of these patients had a positive cytology. All patients with positive cytology are free of cancer. CONCLUSION: During laparoscopic surgery of early stage endometrial and cervical cancer, only one conversion of cytology was detected, which proves that laparoscopy does not appear to increase the intraoperative tumor cell dissemination or rate of positive cytological results.

The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

Vaginal operative delivery in Germany: a national survey about experience and self-reported competency.

BACKGROUND: To determine German obstetricians' self-perceived experience with vacuum and forceps deliveries. PATIENTS AND METHODS: Using a web-based survey, German obstetricians were invited to participate in a survey. This survey was approved by the German society of obstetrics and gynecology. RESULTS: Surveys of 635 obstetricians were received. All obstetricians reported performing significantly less forceps than vacuum deliveries. Almost all obstetricians want to perform more delivery, which indicates the willingness to learn both. More obstetricians felt confident to perform vacuum than forceps. In a similar obstetrical indication, most of the obstetricians would prefer to perform a vacuum assisted delivery. The majority of the obstetricians wished to receive more training in vaginal operative deliveries. CONCLUSION: Most of the German obstetricians prefer to use vacuum-assisted vaginal deliveries and feel less confident to perform forceps deliveries. Standardized training to improve the quality of care is recommended.

Osteopathy for Endometriosis and Chronic Pelvic Pain - a Pilot Study.

Introduction: Pelvic pain is a common problem in gynaecological practice. It is often unclear whether definite causality exists between reported symptoms and objective clinical findings of the female genital tract, and medical or operative treatments do not always achieve long-term resolution of symptoms. Methods: This pilot study investigated 28 patients (age 20-65, median 36.5 years) from a gynaecology practice whose only clinical finding was painful pelvic floor muscle tightness. Following standardised gynaecological and physiotherapist examination, all patients received osteopathic treatment. Pain had been present for a median of 3 years (range 1 month to 20 years). 14 patients had previously confirmed endometriosis. Treatment success was evaluated on consultation with patients in person or in writing. Results: 22 of the 28 participants completed the treatment according to plan. Overall, 17 reported symptom improvement, while 10 of the 14 patients with endometriosis did. Conclusion: Osteopathy is well received by women with painful pelvic floor muscle tightness and appears to be an effective treatment option.

Expectations for Endoscopic Training During Gynaecological Specialty Training - Results of a Germany-wide Survey.

Question: Endoscopy is an integral part of surgical gynaecology and is playing an increasingly important role in ensuring adequate gynaecological training in the context of specialty training in general. At present, little is known about the expectations and notions of young junior doctors with respect to endoscopic training. For this reason, junior doctors throughout Germany were surveyed on this topic and asked to share their opinions. Methods: Using an anonymized standardized survey, the following information was elicited: importance of endoscopic training, willingness to take courses, expectations for instructors and the hospital, ideas about the number of required operations, both as a surgical assistant and as a surgeon, as well as satisfaction with the current status of training. The questionnaires were sent via the Young Forum (Junges Forum) of the German Society of Gynaecology and Obstetrics (DGGG) and the newsletter of the Working Group for Gynaecological Endoscopy (AGE). Results: The evaluation of the study was based on 109 completed questionnaires. The resident junior doctors were 31 years old on average and were in their third to fourth year of their specialty training on average. The majority of the participants (87 %) considered the learning of endoscopic techniques to be very important and advocated regular participation in endoscopy training courses. Among the participants, 48 % were prepared to invest up to €1500 of their own funds to attend courses up to twice a year during the entire specialty training period. The expectations of the instructors and institutions focused on technical expertise, the willingness and time for teaching and on the number and range of surgical procedures, followed by being granted leave for the courses and having costs covered for the courses. Thirty-eight per cent stated that their expectations had been completely or mostly met and 62 % said they had been met in part or inadequately. Eighty-three per cent of the respondents reported that they would change specialty training institutions in order to achieve their own goals in the context of specialty training. Conclusions: This study presents data for the first time on the satisfaction of young junior doctors and their expectations for endoscopic specialty training. The residents exhibited a high level of interest in endoscopy and a high level of willingness to actively shape the specialty training, including course participation. However, there appears to be a great deal of room for improvement for endoscopic specialty training, independent of the current training institution, training year or sex of the junior doctors.

Diagnostic Methods of Ectopic Pregnancy and Early Pregnancy Loss: a Review of the Literature.

This review article presents recent evidence on early pregnancy loss and ectopic pregnancy. In the light of recent evidence, the ß-hCG discriminatory zone may be extended in clinically stable cases without evidence of bleeding. A possible cut-off is 4300 mIU/ml, which corresponds to when a sonographer should detect an intrauterine pregnancy. Embryonic demise can be confirmed when a transvaginal ultrasound finding shows no heartbeat in an embryo of more than 7 mm CRL, no embryo in a gestational sac having a mean sac diameter of more than 25 mm, or no appearance of an embryo within 7-10 days after the primary examination. These are considered definitive signs of embryonic demise. Suggestive signs of embryonic demise require closer monitoring of the pregnancy.

Influence of the Preoperative Decision-Making Process on the Postoperative Outcome after Hysterectomy for Benign Uterine Pathologies.

Introduction: The aim of this study was to assess whether the preoperative decision-making process might influence treatment success in premenopausal women undergoing hysterectomy for benign uterine pathologies Materials and Methods: All premenopausal women treated with hysterectomy for benign uterine pathologies between April 2011 and June 2013 at a tertiary university center were enrolled in this prospective observational cohort study. Five parameters of the preoperative decision-making process were assessed upon their correlation with postoperative quality of life, sexual function and patients' satisfaction. These outcome measures were assessed for the pre- and postoperative (six months after surgery) status using two validated questionnaires (EQ-5D and "female sexual function index" (FSFI). Patients' satisfaction with the postoperative outcome was assessed with a self-developed questionnaire. Results: 255 of 402 (63 %) patients completed the study. A correlation between the co-variables "interval between first counseling and decision to surgery", "subjectively perceived quality of the preoperative counseling" and "certainty in the decision for the intervention" and postoperative outcomes were found. The co-variables "person mainly responsible for election of hysterectomy mode" and "discussion of decision for surgery with others" showed no influence on postoperative patients-reported outcomes. Conclusion: We found a correlation between certain parameters of the preoperative decision-making process and postoperative patient-reported sexual function, quality of life and patients' satisfaction in premenopausal women undergoing hysterectomy for benign uterine pathologies. An optimization of these factors could contribute to an improvement in treatment outcomes.

Surgical Methods for the Treatment of Uterine Fibroids - Risk of Uterine Sarcoma and Problems of Morcellation: Position Paper of the DGGG.

The appropriate surgical technique to treat patients with uterine fibroids is still a matter of debate as is the potential risk of incorrect treatment if histological examination detects a uterine sarcoma instead of uterine fibroids. The published epidemiology for uterine sarcoma is set against the incidence of accidental findings during surgery for uterine fibroids. International comments on this topic are discussed and are incorporated into the assessment by the German Society for Gynecology and Obstetrics (DGGG). The ICD-O-3 version of 2003 was used for the anatomical and topographical coding of uterine sarcomas, and the "Operations- und Prozedurenschlüssel" (OPS) 2014, the German standard for process codes and interventions, was used to determine surgical extirpation methods. Categorical qualifiers were defined to analyze the data provided by the Robert Koch Institute (RKI), the German Federal Bureau of Statistics (DESTATIS; Hospital and Causes of Death Statistics), the population-based Cancer Register of Bavaria. A systematic search was done of the MEDLINE database and the Cochrane collaboration, covering the period from 1966 until November 2014. The incidence of uterine sarcoma and uterine fibroids in uterine surgery was compared to the literature and with the different registries. The incidence of uterine sarcoma in 2010, standardized for age, was 1.53 for Bavaria, or 1.30 for every 100 000 women, respectively, averaged for the years 2002-2011, and 1.30 for every 100 000 women in Germany. The mean incidence collated from various surveys was 2.02 for every 100 000 women (0.35-7.02; standard deviation 2.01). The numbers of inpatient surgical procedures such as myoma enucleation, morcellation, hysterectomy or cervical stump removal to treat the indication "uterine myoma" have steadily declined in Germany across all age groups (an absolute decrease of 17 % in 2012 compared to 2007). There has been a shift in the preferred method of surgical access from an abdominal/vaginal approach to endoscopic or endoscopically assisted procedures to treat uterine fibroids, with the use of morcellation increasing by almost 11 000 coded procedures in 2012. Based on international statements (AAGL, ACOG, ESGE, FDA, SGO) on the risk of uterine sarcoma as an coincidental finding during uterine fibroid surgery and the associated risk of a deterioration of prognosis (in the case of morcellation procedures), this overview presents the opinion of the DGGG in the form of four Statements, five Recommendation and four Demands.

Electrochemotherapy in Breast Cancer: A Review of References.

Electrochemotherapy is a new method for the local treatment of cutaneous and subcutaneous metastases. If surgery and/or radiotherapy are no longer possible, this innovative technology can be used effectively for local tumour control. The minor side effects of the therapy and the low intraoperative duration of treatment make it possible to admit patients to hospital for just a short time. Thus, the repeated use of electrochemotherapy has allowed for an increase in the rate of complete remissions. In fact, in 2013, this form of treatment, which consists of a low-dose cytostatic and electroporation, was also included in the mammary guidelines of the Working Group for Gynaecological Oncology (AGO) and the German Cancer Society (DKG). The favourable cost-benefit ratio makes this method of treatment very interesting in clinical practice and, as a result, it is already being used successfully in many German hospitals.

Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work.

Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options.

Use of Laparoscopy in the Treatment of Endometrial and Cervical Cancer - Results of a 2012 Germany-wide Survey.

Introduction: Endoscopy has begun to play an increasingly important role in the surgical therapy of uterine cancers. To date, there is no data on the use of laparoscopy to treat endometrial cancer (EC) and cervical cancer (CC). Method: A Germany-wide, anonymised survey was done of all gynaecological clinics/endoscopy clinics, using a standardised questionnaire. Results: A total of 128 clinics responded: 16 university clinics (12.5 %), 30 hospitals offering maximum care (23.4 %), 66 general hospitals (51.5 %), 5 outpatient clinics (3,9 %), 4 physicians in private practice affiliated to hospitals (3.1 %) and 7 hospitals (5.4 %) which did not indicate status. Laparoscopy was used in the treatment of 82 % of all EC and 54 % of CC. Surgery for EC was done completely laparoscopically in 58 % of cases and with laparoscopic assistance using a vaginal approach in 32 % of cases. If lymphadenectomy (LNE) was additionally performed, this was done abdominally in 42 % of cases and laparoscopically in 53 %. Cervical cancer was treated by laparoscopic radical hysterectomy (HE) in 44 % of cases and by radical HE using a vaginal approach in 14 %. 4 % of hospitals reported the use of other endoscopic methods (e.g. DaVinci). While the majority of hospitals (43.3 %) treated more than 75 % of EC patients using laparoscopy, in many clinics (38.3 %) less than 25 % of CC patients were treated using endoscopy. Discussion: Laparoscopy is used more often in EC surgery as compared to surgery for CC. However, there are still major differences between hospitals with regard to case numbers, the number of uterine cancers treated using endoscopic surgery, and the type of endoscopic surgery.

Pathophysiology of Bone Remodelling and Current Therapeutic Approaches.

Different metabolic bone parameters such as RANK (receptor activator of nuclear factor-κB), RANK ligand (receptor activator of nuclear factor-κB ligand) and OPG (osteoprotegerin) control physiological bone remodelling. The pathophysiology of these factors in bone diseases and osseous metastases is becoming clearer. In metastatic breast cancer, osteolytic bone metastases are the result of increased osteoclastic activity caused either by increased RANK ligand or decreased OPG expression of metastatic osseous tumour cells. These findings may lead to new therapeutic options for the treatment of breast cancer patients. The aim of this work is to provide an overview of physiological bone remodelling and of the interaction between tumour cells and bone environment. Current therapy approaches and the mechanisms of action of drugs are described.

Endometrial Cancer: Comparison of Patients with Synchronous Primary Carcinoma of the Endometrium and Ovary vs. Endometrial Carcinoma with Ovarian Metastases.

Purpose: The aim of our study was to investigate the rate of secondary carcinomas in patients with endometrial carcinoma (EC). In particular, we wanted to describe the subset of patients with endometrial and simultaneous ovarian carcinoma (OC), including outcomes. The study also compared patients with EC and ovarian metastasis with patients with EC and simultaneous OC. Patients and Methods: Data from 251 patients with primary endometrial carcinoma who underwent surgery in the years 2005-2009 at the Department of Obstetrics and Gynaecology, University of Tübingen, were analysed retrospectively. Results: A total of 28 patients (11.1 %) had a secondary carcinoma: 18 patients (7.1 %) had OC; 9 (3.5 %) patients had a history of breast cancer, and one patient (0.4 %) respectively had simultaneous carcinoma of the vulva or bladder. 14 patients (5.5 %) had advanced stage EC with ovarian metastasis or, in one case, metastasis to the ovarian tube. Patients with ovarian metastasis had a mean age of 71.2 ± 9.2 years at primary diagnosis, making them significantly older compared to patients with EC and simultaneous OC (55.3 ± 11.8 years, p < 0.001). Moreover, patients with ovarian metastasis significantly more often had EC with a higher tumour grade (grade 1: 0, grade 2: 21.4 %, grade 3: 78.6 %) compared to patients with simultaneous EC and OC (grade 1: 11.1 %, grade 2: 77.8 %, grade 3: 11.1 %; p < 0.001). Conclusion: Almost one in 10 patients with EC had a secondary carcinoma. The most common secondary carcinoma was OC followed by breast cancer. This should be taken into account in the diagnosis and therapy of patients with EC. Patients with simultaneous EC and OC were significantly younger than patients with EC and ovarian metastasis. In addition, their tumour had better prognostic features: thus, the tumour grade of the EC was significantly lower. Overall, the prognosis for patients with synchronous EC and OC is better than that for patients with EC and ovarian metastasis.