Preoperative Sonographic Prediction of Limited Axillary Disease in Patients with Primary Breast Cancer Meeting the Z0011 Criteria: an Alternative to Sentinel Node Biopsy?

PURPOSE: To assess the accuracy of preoperative sonographic staging for prediction of limited axillary disease (LAD, one or two metastatic lymph nodes) and to identify factors associated with high prediction-pathology concordance in patients with early-stage breast cancer meeting the Z0011 criteria. MATERIALS AND METHODS: Patients treated between January 2015 and January 2020 were included in this retrospective, multicentric analysis of prospectively acquired service databases. The accuracy of LAD prediction was assessed separately for patients with one and two suspicious lymph nodes on preoperative sonography. Test validity outcomes for LAD prediction were calculated for both groups, and a multivariate model was used to identify factors associated with high accuracy of LAD prediction. RESULTS: Of 2059 enrolled patients, 1513 underwent sentinel node biopsy, 436 primary and 110 secondary axillary dissection. For LAD prediction in patients with one suspicious lymph node on preoperative ultrasound, sensitivity was 92% (95% CI 87-95%), negative predictive value (NPV) was 92% (95% CI 87-95%), and the false-negative rate (FNR) was 8% (95% CI 5-13%). For patients with two preoperatively suspicious nodes, the sensitivity, NPV, and FNR were 89% (95% CI 84-93%), 73% (62-83%), and 11% (95% CI 7-16%), respectively. On multivariate analysis, the number of suspicious lymph nodes was associated inversely with correct LAD prediction ([OR 0.01 (95% CI 0.01-0.93), p ≤ 0.01]. CONCLUSIONS: Sonographic axillary staging in patients with one metastatic lymph node predicted by preoperative ultrasound showed high accuracy and a false-negative rate comparable to sentinel node biopsy for prediction of limited axillary disease.

Students' attitudes toward digital learning during the COVID-19 pandemic: a survey conducted following an online course in gynecology and obstetrics.

PURPOSE: The purpose of this survey was to assess medical students' opinions about online learning programs and their preferences for specific teaching formats during COVID 19 pandemic. METHODS: Between May and July 2020, medical students who took an online gynecology and obstetrics course were asked to fill in a questionnaire anonymously. The questionnaire solicited their opinions about the course, the teaching formats used (online lectures, video tutorials featuring real patient scenarios, and online practical skills training), and digital learning in general. RESULTS: Of 103 students, 98 (95%) submitted questionnaires that were included in the analysis. 84 (86%) students had no problem with the online course and 70 (72%) desired more online teaching in the future. 37 (38%) respondents preferred online to traditional lectures. 72 (74%) students missed learning with real patients. All digital teaching formats received good and excellent ratings from > 80% of the students. CONCLUSION: The survey results show medical students' broad acceptance of the online course during COVID 19 pandemic and indicates that digital learning options can partially replace conventional face-to-face teaching. For content taught by lecture, online teaching might be an alternative or complement to traditional education. However, bedside-teaching remains a key pillar of medical education.

Incidence of and risk factors for vaginal cuff dehiscence following total laparoscopic hysterectomy: a monocentric hospital analysis.

PURPOSE: Vaginal cuff dehiscence (VCD) is one of the major surgical complications following hysterectomy with data on incidence rates varying largely and studies assessing risk factors being sparse with contradictive results. The aim of this study was to assess the incidence rate of and risk factors for VCD in a homogenous cohort of women treated for benign uterine pathologies via total laparoscopic hysterectomy (TLH) with standardized follow-up. METHODS: All patients undergoing TLH at the Department of Gynecology and Obstetrics, Saarland University Hospital between November 2010 and February 2019 were retrospectively identified from a prospectively maintained service database. RESULTS: VCD occurred in 18 (2.9%) of 617 patients included. In univariate and multivariate analyses, a lower level of surgeon laparoscopic expertise (odds ratio 3.19, 95% confidence interval (CI) 1.0-9.38; p = 0.03) and lower weight of removed uterus (odds ratio 0.99, 95% CI 0.98-0.99; p = 0.02) were associated positively with the risk of VCD. CONCLUSION: In this homogenous cohort undergoing TLH, laparoscopic expertise and uterine weight influenced the risk of postoperative VCD. These findings might help to further reduce the rate of this complication.

Clinical Data on Immunotherapy in Breast Cancer.

BACKGROUND: Breast cancer has traditionally been considered to have a low immunogenic potential compared to other tumor entities. SUMMARY: The most extensively studied immunotherapeutic agents for breast cancer to date are immune checkpoint inhibitors, with the results of the IMpassion130 trial leading to the approval of atezolizumab plus nab-paclitaxel for first-line treatment of programmed cell death ligand 1-positive, metastatic, triple-negative breast cancer, and studies in earlier stages have yielded promising results. Other immunotherapeutic options being assessed in phases 2 and 3 trials include vaccine-based therapies and treatment with anti-human epidermal growth factor receptor 2 (H-directed immune-linked antibodies) and substances evaluated in early clinical trials as cellular therapies (adoptive cell therapy and chimeric antigen receptor T cells). KEY MESSAGES: Immunotherapy is an emerging modality for the treatment of breast cancer, as evidenced by the plethora of preclinical and clinical concepts and ongoing trials. Early studies established the role of immunotherapeutic agents in the metastatic setting. Ongoing studies will expand our knowledge about the timing of administration, best partners for combination therapy, and predictive biomarkers to guide immunotherapy for breast cancer.

Use of a microsurgical vascular clip system (Yasargil clip) in laparoscopic fibroid enucleation

This video demonstrates the use of a microsurgical temporary vascular clip system to facilitate laparoscopic enucleation of uterine fibroids. Throughout the course of the last three decades, the laparoscopic route has been established as the approach of choice in the surgical treatment of uterine fibroids. Laparoscopic fibroid enucleation is characterized by a low morbidity rate and a high patient satisfaction level. Especially when treating a large fibroid or multiple fibroids, the well-vascularized myometrium can constitute a technical challenge in endoscopic fibroid enucleation. Diffuse bleeding may lead to significant intraoperative hemorrhage. The extensive use of bipolar or monopolar diathermy, in order to achieve hemostasis, might lead to post-operative uterine wall necrosis with a potential risk of uterine rupture during subsequent pregnancies. To address this clinical challenge, we developed a technique with temporary interruption of the uterine blood supply by applying a microsurgical vascular clip (Yasargil vascular clip system, Aesculap, Tuttlingen, Germany) to the uterine artery and the utero-ovarian vessel arcade to minimize bleeding during endoscopic fibroid enucleation.

Correlation between total sperm count and sperm motility and pregnancy rate in couples undergoing intrauterine insemination.

The frequency and significance of sterility is increasing due to different socio-demographic factors in the industrialized countries. At the same time, the patients' demand for more natural and less invasive fertility treatments is increasing. The most common method used in subfertility is intrauterine insemination (IUI). Retrospectively, the data from the patients were analyzed, in which at least one insemination and a maximum of eight inseminations were performed in the last five years (observation period 01.01.2014-31.12.2018) at the Women's University Hospital Homburg. The primary endpoint was the onset of a clinical pregnancy. Clinical pregnancy was correlated with the partner's total sperm count (sperm density in millions), sperm concentration and motility during insemination. These three parameters were evaluated according the World Health Organization (WHO) 2010 guidelines. The results of the spermiograms were correlated with clinical pregnancy outcome. The data were examined for 138 women with sterility, in which a total of 345 inseminations were performed (median 2.5 per woman, range 8 inseminations). There was no correlation found between spermiogram parameters and pregnancy probability in any of the inseminations. After 5 inseminations no further pregnancy occurred. The present study showed no correlation between the conception probability of intrauterine insemination (IUI) and the total sperm count/concentration/motility. After the sixth IUI, we no longer found conceptions in our patient collective. Therefore, data from this study indicate that intrauterine inseminations can be performed at all severity levels of oligoasthenozoospermia. However, the treatment should be limited to five attempts.

Postoperative non-traumatic compartment syndrome (PNCS) in gynecologic surgery.

PURPOSE: The postoperative non-traumatic compartment syndrome (PNCS) is a rare, but serious postoperative complication. Etiology, risk factors and clinical manifestation of PNCS are not well characterized since data in gynecologic and obstetric patients are limited. METHODS: We performed a retrospective monocentric study of patients who underwent surgery for gynecologic or obstetrics conditions and identified five cases of PNCS, which were analyzed and compared to a control cohort in regard of incidence, clinical presentation, risk factors and clinical outcome. RESULTS: Five cases of PNCS were identified among 19.432 patients treated between 2008 and 2019 with an incidence rate of 0.026%. The clinical examination was shown to be unreliable, lacking sensitivity in most clinical signs. Young age, obesity and long operation time were risk factors for the development of a PNCS. Fasciotomy for the treatment of a PNCS should not be delayed, since permanent function loss may occur early. CONCLUSION: A low threshold of clinical suspicion might be prudent to identify PNCS following gynecologic surgery. In the presence of the described risk factors, any suspicion of a PNCS should be evaluated further and if necessary treated with fasciotomy urgently.

Patient satisfaction with personal patient care (PPC) in the inpatient treatment of endometriosis.

PURPOSE: The aim of this retrospective cohort study was to validate patient's satisfaction and surgical complication rate in patients treated at a certified endometriosis centre with personal patient care (PPC). METHODS: The implementation of PPC at a gynaecologic treatment centre was retrospectively evaluated by analysing perioperative complications using the Clavien Dindo (CD) classification and patient satisfaction utilizing the Picker Patient Experience Questionnaire (PPE-15) for a total of 219 symptomatic endometriosis patients treated surgically at a certified endometriosis centre (Agaplesion Diakonie Hospital, Kassel, Germany) between November 2018 and April 2019. Data from our sample on complication rates and satisfaction were compared with those from reference samples published by Radosa et al. and Jenkinson et al. RESULTS: An overall complication rate of 10.96% (24 out of 219 patients) was observed. Four endometriosis patients (1.83%) had major complications with complications grade III according to the CD classification system. 155 patients out of 219 chose to answer the PPE-15 (return rate 70.78%). 92 patients (59.35%) reported about problems during their treatment in our hospital in their PPE-15. "Doctors sometimes talked as if I was not here" was the best rated item (1.2%) in our cohort. "Staff gave conflicting information" was the most mentioned item (33.55%) by patients during their hospital stay in relation to patient dissatisfaction. CONCLUSION: Incorporation of PPC in the surgical inpatient treatment of endometriosis patients resulted in a low postoperative complication rate and a high patient satisfaction in our study cohort. Furthermore, nursing staff of endometriosis patients also needs particular attention.

Evaluating the use of Clavien-Dindo classification and Picker Patient Experience Questionnaire as quality indicators in gynecologic endoscopy.

PURPOSE: Over the last few decades, laparoscopy has become a standard procedure within gynecological surgery. Validated quality indicators for the determination of the objective (perioperative complications) and subjective (patient satisfaction) quality of treatment as a surrogate parameter for the success of the treatment have so far found no regular application in the clinical routine. The purpose of this study was to evaluate the use of the Clavien-Dindo (CD) classification for postoperative complications and the Picker Patient Experience Questionnaire (PPE-15) as tools in the evaluation of endoscopic therapies in clinical routine. METHODS: Retrospectively, perioperative complications using the CD classification and patient satisfaction utilizing the PPE-15 were reviewed for a total of 212 consecutive patients at a gynecologic endoscopic referral center (Agaplesion Diakonie Kliniken, Kassel, Germany) in September 2018. RESULTS: An overall complication rate of 13.21% (28 out of 138 patients) was observed. Five patients (2.36%) had complications grade III and above according to the CD classification system. 138 patients out of 212 chose to answer the PPE-15 (return rate 65.01%). 112 patients (81.16%) reported about problems during their treatment in our hospital in their PPE-15. "Purpose of medicines not explained" was the most mentioned item (28.99%) by patients during their hospital stay. CONCLUSION: CD classification and PPE-15 may be helpful instruments to evaluate the quality of care in gynecology. The application of both instruments for the assessment of treatment quality in clinical routine should be further investigated in prospective studies.

Report of the survey on current opinions and practice of German Society for Gynecologic Endoscopy (AGE) members regarding the laparoscopic treatment of ovarian malignancies.

PURPOSE: The purpose of this survey was to assess the opinions of members of the German Society of Gynecologic Endoscopy (AGE) regarding the laparoscopic treatment of ovarian malignancies and current practice at their institutions. METHODS: Between February and October 2015, the AGE sent an anonymous online survey via mail to its members. The questionnaire solicited participants' opinions about the laparoscopic treatment of ovarian cancers according to T stage and borderline tumors, and information about current practice at their institutions. Participants were also asked their opinions on currently available data on this issue. RESULTS: Of 228 AGE members who completed the survey, 132 (58%) were fellows or attending physicians and 156 (68%) worked at university hospitals or tertiary referral centers. Most [212 (93%)] respondents stated that < 10% of all ovarian cancer cases were currently treated laparoscopically at their institutions. Most participants indicated that T1 (a, b, c) tumors [145 (64%)] and ovarian borderline tumors [206 (90%)], but not T2 [48 (21%)] or T3/4 [9 (4%) ovarian tumors] should or could be treated laparoscopically. One hundred seventy-two (75%) participants considered currently available data on this topic to be insufficient and 152 (66%) stated that they would take part in a clinical trial assessing a laparoscopic approach to T1/2 ovarian cancer. CONCLUSION: According to this survey, to the opinion of the majority of AGE members, laparoscopy might be a considerable option for the treatment of early ovarian malignancies and borderline tumors and should be evaluated further in future studies.

Postoperative Quality of Life and Sexual Function in Premenopausal Women Undergoing Laparoscopic Myomectomy for Symptomatic Fibroids: A Prospective Observational Cohort Study.

INTRODUCTION: Uterine leiomyomas are the most common benign gynecologic tumors. To date laparoscopy myomectomy is the gold standard for treatment of symptomatic fibroids in reproductive-aged women. Detailed counseling about the effects of this procedure on postoperative sexuality and quality of life is important in these patients. However, available data on these subjects are limited and contradictory. The aim of this study was to assess sexual function and quality of life in premenopausal women undergoing laparoscopic myomectomy for symptomatic uterine fibroids. MATERIAL AND METHODS: All premenopausal women who underwent laparoscopic myomectomy for symptomatic fibroids between April 2012 and August 2014 at a tertiary university center were enrolled in this prospective observational cohort study. Sexual function and quality of life were assessed for the pre- and postoperative (six months post-operatively) state using two validated questionnaires, the Female Sexual Function Index (FSFI) and the European Quality of Life Five-Dimension Scale (EQ-5D). RESULTS: Ninety-five of the 115 (83%) eligible patients completed the study. Overall a significant improvement in quality of life and sexual function was observed in the study cohort: Median FSFI (28 (18.7-35.2)) and EQ-5D scores (1 (0.61-1) after laparoscopic myomectomy were significantly higher than preoperative scores (21.2 (5.2-33.5); 0.9 (0.2-1); p ≤ 0.01). The number, position and localization of the largest fibroids were not correlated with pre- or postoperative sexual function or quality of life. CONCLUSION: Laparoscopic myomectomy might have positive short-term effects on postoperative quality of life and sexual function in premenopausal women suffering from symptomatic fibroids.

Laparoscopic myomectomy: a 6-year follow-up single-center cohort analysis of fertility and obstetric outcome measures.

PURPOSE: To evaluate fertility, pregnancy and delivery outcomes after laparoscopic myomectomy (LM) during long-term follow-up. METHODS: In this single-center retrospective observational study, data were analyzed from 59 women aged 23-42 years with the desire to have children and who underwent LM for symptomatic uterine leiomyoma between January 2001 and December 2006 and subsequently delivered at our hospital. RESULTS: During a mean follow-up period of 73.55 months, the post-LM conception rate was 68 %. The proportion of miscarriages (n = 16) among all pregnancies (n = 55) was lower after (24 %) than before (43 %) LM. Thirty-nine (46 %) deliveries were primary cesarean sections (CSs). CS was performed due to patients' preference, placental complications, and uterine rupture (UR). Labor was successful in 62 % of all vaginal delivery trials. UR and placental complications occurred in 10 and 13 % of all pregnancies, respectively. CONCLUSIONS: LM reduced the abortion rate and increased the CS rate in our cohort. UR risk may have been affected by suturing technique, the size and location of myomas removed.

Preoperative multimodal strategies for risk assessment of adnexal masses: analysis of 1362 cases in a gynecologic cancer center.

OBJECTIVE: Assessment of adnexal masses focuses on the accurate discrimination between benign and malignant lesions. In our tertiary referral center, we evaluated the discriminative power of expert sonography, serum CA-125 measurement, risk malignancy index (RMI) by Jacobs, and 2 preoperative triage strategies (combination of CA-125 measurement and RMI assessment with expert sonography). METHODS: From 2002 to 2008, a total of 1362 surgical explorations with indication of an adnexal mass from our department were included in this study. Preoperative workup in all patients comprised a gynecologic examination, expert sonography, and serum CA-125 measurement. We calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV), and Cohen κ (prevalence-adjusted measurement) to evaluate the discriminative power of each diagnostic test. RESULTS: Discriminative power of the evaluated tests differed depending on patients' menopausal state. In the premenopause, expert sonography reached the highest discriminative power with a κ value of 0.53, a PPV of 0.45, and an NPV of 0.99. In the postmemopause, the combinations of expert sonography with CA-125 serum measurement or RMI assessment achieved the highest discriminative power: The combination of CA-125 and expert sonography reached a PPV of 0.89 and an NPV of 0.97; κ yielded 0.84. The RMI combined with expert sonography as a triage strategy showed comparable results with a PPV of 0.89, an NPV of 0.96, and a κ value of 0.82. CONCLUSIONS: Preoperative assessment of an adnexal mass may be guided by the patient's menopausal state. In premenopausal patients, expert sonography is helpful for preoperative differentiation between benign and malignant lesions; in postmenopausal patients, the use of triage strategies of either CA-125 serum measurement or RMI combined with expert sonography can be recommended.

M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

Differential effects of the muscarinic M1 receptor agonist RS-86 and the acetylcholine-esterase inhibitor donepezil on REM sleep regulation in healthy volunteers.

Broad evidence from preclinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the generation of rapid eye movement (REM) sleep. However, a potential role of different acetylcholine receptor (AChR) subtypes for the regulation of three main aspects of REM sleep, (1) REM onset, (2) REM maintenance, and (3) generation of REMs, are not clear. In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M1 muscarinic AChR (mAChR) agonist RS-86 and the ACh-esterase inhibitor donepezil to further specify the AChR subtype function on REM sleep regulation in n = 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p = 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p = 0.000 compared to placebo; p = 0.003 compared to RS-86) and the number of REMs (p = 0.000 compared to placebo; p = 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M1, but presumably M2 mAChR activity. These findings are of interest for the understanding of sleep regulation and of neuropsychiatric disorders, such as Alzheimer's dementia and depressive disorders, whose etiopathology may involve alterations in cholinergic neurotransmission.