Background/Objectives: Numerous innovations have changed diagnosis and treatment of endometrial cancer in recent years, with molecular classification being a major factor. Limited data exist on how molecular classification changes in recurrence or metastasis and what effect this may have on therapy. This retrospective study aimed to compare the molecular classification and other histopathological parameters of the primary tumor with those of recurrence or metastasis and to discuss their implications. Methods: A total of 43 patients with primary endometrial cancer and histologically confirmed recurrence treated at the Tuebingen University Women’s Hospital between January 2003 and January 2017 were identified within a cohort of 964 cases. Immunohistochemistry for mismatch-repair status, estrogen receptor, p53 and L1CAM, as well as next-generation sequencing of the POLE genes were performed. Further histopathological and clinical data were collected and statistical analyses were performed. Results: No POLE-mutated patients were found. A higher proportion of high-grade tumors was observed in the recurrence (30% vs. 46%). All p53-mutated patients remained p53-mutated, while a changed molecular profile of the NSMP and MMRd subtypes was observed in nine patients (21%). L1CAM remained stable in 70% of the patients. A change in molecular profile was not associated with altered prognosis. Conclusions: Our study underlines the importance of additional histopathological analysis in case of recurrence or metastasis for individualized therapy planning. Further studies with larger case numbers are necessary to validate our findings.

The Mayer–Rokitansky–Küster–Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.

Ultrasound examination is an important imaging method used across the medical field (e.g. [1]). However, during medical education, practical training opportunities for ultrasound imaging are not yet widely available, while good potential exists for approaches that employ gamification (e.g. [3, 5]). SonoGame is a hands-on platform for medical students developed to train ultrasound skills using a game-based approach [6, 7]. It provides a step-by-step introduction to ultrasound imaging and aims at improving ultrasound skills. It consists of several mini games that challenge the player to examine, identify, and recreate 2D cross-sectional images of a 3D virtual volume underneath the table top that contains geometric objects (see Fig. 1). SonoGame focuses on learning how to orient in an ultrasound image and on developing the spatial visualization as well as hand-eye coordination skills that are needed for ultrasound imaging. In this contribution, we present and discuss a prospective, single-center study of the effects of SonoGame-based training on ultrasound skills. We recruited 56 medical students without previous practical ultrasound experience and randomly assigned them to either a control or to a SonoGame group. While the control group received no training, the SonoGame group repeatedly got to play the SonoGame over a period of four weeks (four sessions at 30 minutes each). For both groups, individual ultrasound skills as well as spatial cross-sectioning skills [2] were assessed before and after the four weeks. Results: Compared to the control group, the SonoGame group significantly improved in their ultrasound skills, particularly with complex anatomical structures (see Fig. 2), and, post-training, they reported feeling more familiar with and confident in their use of sonography. What is more, they considered SonoGame a valuable supportive tool for ultrasound skills training. For individual spatial cross-sectioning skills, both groups improved from first to second testing, though the extent of improvement did not differ between groups (see Fig. 3). We conclude that SonoGame-based training can usefully supplement conventional ultrasound education of medical students, as it promotes and supports the skill set required for ultrasound examinations.

Background: Endometriosis is known to be a common chronic disease that often affects the quality of life of patients. Especially for deep endometriosis (DE), the most challenging form of the disease, surgery remains an important component of treatment. However, long-term outcomes after surgery are poorly studied. Therefore, we aimed to evaluate the postoperative clinical course of women with DE who underwent surgery, particularly with regard to pain relief, fertility, and re-operations. Methods: Thus, women who underwent surgical treatment for DE between 2005 and 2015 were included in this retrospective questionnaire-based analysis. Results: A total of 87.0% of the patients who underwent surgery for pain reported a postoperative relief of their complaints. Moreover, 44.6% even stated that they were free of pain at the time of the questionnaire. Patients who underwent surgery for infertility and tried to become pregnant postoperatively gave birth to a child in 45.9% of cases. Approximately one-third of the patients had to undergo another surgery because of endometriosis-related symptoms. The main reasons for re-operation were pain and infertility. The median time to re-operation was 2.1 years. Conclusions: In this extraordinarily long follow-up with a remarkable response rate, we show that surgical treatment of DE leads to pain relief and improved fertility in most cases. However, the risk of recurrence and the need for re-operation remains remarkable.

Background: The aim of this study was to evaluate the impact of pathological tumor-free margin distance on survival in SCC patients treated with surgery alone. Methods: This retrospective study included 128 patients with node-negative disease that received no adjuvant treatment. Disease-free and overall survival were analyzed according to pathological tumor-free margin distance. Results: The patients were subclassified into three resection margin category groups: “1 to 3 mm” (n = 42), “>3 to 8 mm” (n = 47) or “>8 mm” (n = 39). Thirty-nine of the 128 patients (30.5%) developed recurrent disease. Median follow-up for disease-free survival (DFS) was 6.49 years (95% CI 5.16 years; 7.62 years), and median follow-up for overall survival (OS) was 6.29 years (95% CI 5.45 years; 7.33 years). The 5-year DFS rate was 0.70 (95% CI: 0.62–0.79), and the 5-year OS rate was 0.79 (95% CI: 0.71–0.87). Regarding the survival outcome, there were no independent significant differences in either disease-free survival (DFS) (p = 0.300) or overall survival (p = 1.000) among patients within the three tumor-free resection margin categories. Multivariate analyses did not show any statistically significant association between tumor-free resection margin distance and recurrent disease or death, either when analyzed as a categorical variable or when analyzed as a continuous variable. Conclusion: The present study did not show a significant impact of pathological tumor-free resection margin distance following surgery in patients with node-negative SCC of the vulva (that did not receive adjuvant treatment) on disease-free and overall survival.

Purpose Surgery and radiotherapy as part of breast cancer treatment can lead to lymphoedema of the upper extremities (breast cancer-related lymphoedema = BCRL) and reduce the quality of life (health-related quality of life = HRQoL). The aim of the present study was to investigate the influence of paddling in a dragon boat (PP) on HRQoL and BCRL in breast cancer survivors (BCS). Methods Between April and October 2017, a prospective case–control study evaluated the effects of PP compared to a control group. In the paddle group ( n = 28), weekly arm circumference measurements were taken at four defined anatomic areas of the arm before and after training; in the control group ( n = 70), the measurements were taken once a month. At the beginning and end of the study, questionnaires from both groups (SF 36, EORTC QLQ C30) were evaluated to understand the differences in HRQoL. Results The paddle group started with a higher HRQoL compared to the control group. Most interesting, whether the affected or unaffected arm, whether before or after training—the arm circumference decreased over time in the paddling group. A pre-existing lymphoedema was not negatively influenced by paddling. In the paddle group, the physical health was constant over the season, while the physical health of the control group decreased significantly over time. Conclusion PP in a dragon boat does not lead to the development or worsening of pre-existing lymphoedema due to breast cancer therapy, and seems to have a positive effect on the quality of life.

Cervical cancer represents the fourth leading cause of cancer among women and is associated with over 311,000 annual deaths worldwide. Timely diagnosis is crucial given the lengthy pre-cancerous phase, which is typified by cervical intraepithelial neoplastic lesions. However, current treatment methods are often tissue-destructive and can be accompanied by severe side effects. To address these concerns, our study introduces a novel, gentle approach for the tissue-preserving treatment of CIN lesions.We present findings of a controlled, prospective, single-armed phase IIb clinical trial performed at the Department for Women’s Health, Tübingen, Germany. From September 2017 to March 2022 we assessed 570 participants for study eligibility. Of the screened patients, 63 participants met with CIN1/2 lesions met the inclusion criteria and were treated with non-invasive physical plasma (NIPP). Assessment of treatment efficacy was based on a comprehensive analysis of histological and cytological findings, along with high-risk HPV infection load at 3 and 6 months post-treatment. Comparative analyses were performed retrospectively with data obtained from 287 untreated patients in the control group. Our findings indicate that patients treated with NIPP experienced an 86.2% rate of full remission, along with a 3.4% rate of partial remission of CIN lesions, which compares favorably to the control group’s rates of 40.4% and 4.5%, respectively. Additionally, we observed a twofold reduction in high-risk HPV infections following NIPP treatment. Minor side effects were observed, such as mild pain during treatment and short-term smear bleeding or increased vaginal discharge within 24 h after treatment. Given the experimental nature of NIPP treatment and the availability of established standard treatments, our study was designed as a non-randomized study.NIPP treatment offers a highly flexible and easy-to-apply method for treating pre-cancerous CIN1/2 lesions. This non-invasive approach is notable for its tissue-preserving nature, making it a promising alternative to current excisional and ablative treatments. CIN1/2 lesions were employed as preliminary in vivo models for the targeted treatment of CIN3 lesions.https://www.clinicaltrials.gov, identifier NCT03218436.

Zielsetzung Im Rahmen einer randomisiert kontrollierten Studie (RCT) wurden anatomische und funktionelle Ergebnisse sowie Komplikationen der nervenschonenden Kolposakropexie unter Verwendung von resorbierbarem (Vicryl) vs. nicht-resorbierbarem (Ethibond) Nahtmaterial erfasst und ausgewertet.

Purpose The purpose is to analyse perioperative complications associated with the retropubic tension-free vaginal tape (TVT) procedure and their management. Methods This retrospective, monocentric cohort study included 960 women after retropubic TVT procedure performed by one surgeon from 2011 to 2016. Complications were identified up to 6 weeks after the procedure, divided into specific and general complications and classified based on the Clavien–Dindo (CD) Classification. A visit 6 weeks after the surgical procedure was attended by all patients. Results 77 complications, of which 74 occurred postoperatively and 3 intraoperatively, affecting 72 (7.5%) out of 960 women. Urinary retention and voiding problems were the most common complication. The mean age of women suffering complications was 3.4 years higher in comparison to the mean age of women without complications ( p = 0.036). The Body Mass Index (BMI) of the group of women with perioperative complications had an average BMI which was 0.5 kg/m 2 lower than the average BMI of the women without complications. 22 (12.8%) out of 172 women with recurrent stress incontinence had postoperative complications, of which 21 were related to the TVT. Conclusion The retropubic TVT is a surgical procedure associated with a low number of perioperative complications, even in the group of elderly and overweight women, as well as in cases of recurrent stress incontinence.

The purpose of the study was to analyze anatomical and functional outcomes after sacrocolpopexy (SCP) for vaginal vault prolapse pelvic organ prolapse quantification (POPQ) II–III by random use of absorbable (Vicryl) and non-absorbable sutures (Ethibond) for vaginal mesh fixation. This study was designed as a two-center randomized controlled study (RCT). The primary objective was to evaluate the anatomical outcome. Success was defined when the vaginal apex (point C; POPQ) did not descend more than 50% of the total vaginal length (tvl) during Valsalva. Patients completed a pelvic examination incorporating the POPQ and questionnaires (the German pelvic floor questionnaire and the PISQ-12 questionnaire) at baseline and 6 months postsurgery. Perioperative adverse events (AE) were recorded. Sample size calculations, based on a 10% non-inferiority limit required 100 participants per group, with power = 90%. In 190 out of 195 women (ETH group n = 96; VIC group n = 94) anatomical success was achieved. The relative risk of anatomical success failure in the VIC group versus the ETH group was 0.69, with a 95% confidence interval 0.12–4.02. The change in the symptom scores did not differ significantly between the ETH and the VIC group. In the ETH group, three suture penetrations into the vagina were observed, and none in the VIC group 6 months postoperatively. Anatomical success after SCP for vaginal vault prolapse POPQ II–III is not affected by suture type for vaginal monofilament mesh attachment. Moreover, we did not see any differences in functional outcomes between the two groups. Three suture penetrations into the vagina were observed in the ETH group, and none in the VIC group 6 months postoperatively.

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12 e1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy. (C) 2021 Elsevier Ltd. All rights reserved.

Purpose Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu ® without drainage is equal/ non-inferior to standard mastecomy with drainage. Methods The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu ® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. Results Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu ® group than in the drainage group, especially aspirations of clinically relevant seromas ( p = 0.014). The TissuGlu ® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu ® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu ® compared to standard drainage couldn’t be reached. Discussion The present evaluation shows no advantage of the tissue adhesive TissuGlu ® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.

Background Aim of this study is to examine pelvic floor symptoms, anatomical results and patients’ satisfaction after sacrospinous vaginal fixation for stage 4 pelvic organ prolapse. Methods All patients with stage 4 pelvic organ prolapse were treated with vaginal hysterectomy, native tissue cystocele and rectocele repair and bilateral sacrospinous vaginal fixation. Anatomical and functional outcomes according to the POPq classification system and the German version of the Australian pelvic floor questionnaire were assessed. Changes between baseline, first follow-up and second follow-up were assessed by the paired Wilcoxon rank test using R, version 3.5.1. Results 20 patients were included in the study. Scores in all four domains of the pelvic floor symptom questionnaire (bladder, bowel, prolapse, sexual function) were significantly improved at 6 and 12-months follow-up. One patient presented with a symptomatic stage 3 cystocele that needed a second surgical intervention and two patients needed surgery due to a de novo stress urinary incontinence. There were no perioperative adverse events and all patients reported full satisfaction after surgery. Conclusions The vaginal approach with hysterectomy, native tissue repair and bilateral sacrospinous vaginal fixation seems to be a safe and effective method for the treatment of advanced stage POP, offering excellent relief in all pelvic floor symptoms. Trial registration ClinicalTrials.gov ( NCT 02998216 ), December 20th, 2016. Prospectively registered.

Purpose To evaluate the effectiveness of vaginal Er:YAG laser as treatment in patients with mild or moderate stress urinary incontinence. Methods The study was a prospective, non-randomised, single center study of 33 women treated with two Er:YAG laser applications on an interval of four weeks. Follow-up evaluations were performed 4 and 8 weeks and 6 months after the first vaginal Er:YAG laser application (4 weeks and 5 months after the second vaginal Er:YAG laser application, respectively). The subjective outcomes were assessed using the International Consultation of Incontinence Modular Questionnaire Short Form (ICIQ-SF) and medical history. Patients rated their quality of life on a scale from 0 to 10. Results The average quality of life (QoL) showed a significant improvement 5 months after both Er:YAG laser applications. The mean QoL score was 6.0 (SD 2.4) and improved to a mean of 7.6 (SD 1.8) (p = 0.004). The mean ICIQ-SF score changed significantly from 12.3 (SD 3.2, median 13, range 8-18) before treatment to 6.8 (SD 4.0, median 7, range 0-15) 6 months after treatment (p <0.001). 24 patients out of 32 (75%) would again choose to have this therapy performed and 25 patients of 32 (78%) would recommend the vaginal Er:YAG laser therapy to a friend. The rate of side effects was low and none of the patients needed a medical treatment. Conclusions This study confirms that vaginal Er:YAG therapy can improve clinical and quality of life outcomes in patients with SUI.

Abstract Introduction As early breast cancer might relapse even after complete removal of breast and lymphnodes, the disease must persist in secondary sites. The detection of disseminated tumor cells (DTC) in the bone marrow (BM) has been described as a surrogate of residual disease. Various trials showed an impaired prognosis of DTC positive early breast cancer (EBC) patients. The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is a large international pooled analysis that aimed to assess the prognostic impact of DTC detection in patients with EBC. Methods A pre-specified protocol was followed, and centers known to practice BM sampling for DTC detection were contacted for individual patient data. Patients with EBC, with available follow-up data and BM sampling before any anti-cancer treatment were eligible. BM aspirates were collected at the time of primary surgery. DTC were identified by antibody (A45-B/B3, AE1/AE3, 2E11 and E29) staining against cytokeratin. The DTC status was compared to other prognostic factors using the chi-squared test. Univariate log-rank test and multivariate cox regression were used to compare survival of DTC positive versus DTC negative patients. Results Individual data from 10,320 patients (11 centers from Europe and USA) were included with a median follow-up of 91 months. Of all patients, 2,823 (27.4 %) were DTC positive. DTC detection was associated with higher tumor grade, higher T stage, nodal positivity, ER and PR negativity, and HER2 positivity (all p<0.001). In univariate analyses, overall, breast cancer specific, disease-free and distant disease-free survival (OS, BCSS, DFS, DDFS) were significantly shorter in DTC positive patients with p-values of <0.001. Multivariate analyses showed the DTC status to be an independent prognostic marker for OS, BCSS, DFS and DDFS with hazard ratios (HR) and 95%-confidence intervals (CI) of 1.23 (95%-CI: 1.06-1.42, p=0.007), 1.38 (95%-CI: 1.11-1.72, p=0.004), 1.29 (95%-CI: 1.10-1.50, p=0.001) and 1.32 (95%-CI: 1.10-1.58, p=0.003), respectively. Conclusions Detection of DTC in the bone marrow is an independent prognostic marker in patients with non-metastatic breast cancer. Further studies should investigate the impact of DTC on metastatic cancer progression and their role for clinical decision making. Citation Format: Hartkopf AD, Brucker SY, Taran F-A, Harbeck N, von Au A, Naume B, Pierga J-Y, Hoffmann O, Beckmann MW, Rydén L, Fehm T, Aft R, Montserrat S, Walter V, Rack B, Schuetz F, Borgen E, Ta M-H, Bittner A-K, Fasching P, Fernö M, Krawczyk N, Weilbaecher K, Margelí M, Hahn M, Jueckstock J, Domschke C, Bidard F-C, Kasimir-Bauer S, Schoenfisch B, Kurt AG, Wallwiener M, Gebauer G, Wallwiener D, Janni W, Pantel K. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-07.

To characterize and understand the demographics (age and body mass index, BMI) of a cohort of women who delivered at a single institution over an 11-year period. The purpose of this analysis is to look for effects over time of demographic characteristics on mode of delivery.

In the Original article publication, the name of the co-author Antje Ganz was not included. The Correct order of authors is as given above.

Abstract Purpose: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. Materials and methods: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). Results: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. Conclusion: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA.