Circulating miR-200 family as predictive markers during systemic therapy of metastatic breast cancer.

PURPOSE: Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS). METHODS: Forty-seven patients with metastatic breast cancer from the University Women's Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated. RESULTS: Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS. CONCLUSION: Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy.

Cancer surveillance and distress among adult pathogenic TP53 germline variant carriers in Germany: A multicenter feasibility and acceptance survey.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome caused by pathogenic germline variants of TP53. Cancer surveillance has noted a significant survival advantage in individuals with LFS; however, little is known about the feasibility, acceptance, and psychosocial effects of such a program. METHODS: Pathogenic TP53 germline variant carriers completed a 7-part questionnaire evaluating sociodemographics, cancer history, surveillance participation, reasons for nonadherence, worries, and distress adapted from the Cancer Worry Scale. Counselees' common concerns and suggestions were assessed in MAXQDA Analytics Pro 12. RESULTS: Forty-nine participants (46 females and 3 males), aged 40.0 ± 12.6 years, formed the study population; 43 (88%) had a personal cancer history (including multiple cancers in 10 [20%]). Forty-three individuals participated (88%) in surveillance during the study or formerly. Willingness to undergo surveillance was influenced by satisfaction with genetic testing and counseling (P = .019 [Fisher-Yates test]) but not by sociodemographics, cancer history, or distress level. Almost one-third of the participants reported logistical difficulties in implementing surveillance because of the high frequency of medical visits, scheduling difficulties, and the travel distance to their surveillance providers. Self-reported distress and perceived emotional burden for family members and partners were moderate (median for self-reported distress, 3.3; median for perceived emotional burden, 3.0). For both, the interquartile range was moderate to very high (2.7-3.7 and 3.0-3.7, respectively). CONCLUSIONS: Individuals with LFS require efficient counseling as well as an accessible, well-organized, interdisciplinary, standardized surveillance program to increase adherence and psychological coping.

Joining to promote young talents: an experience report from the first German Summer School for Obstetrics and Gynaecology for medical students.

PURPOSE: The Commission for the Promotion of Young Talents of the German Society for Gynaecology and Obstetrics e.V. was founded in 2017, aiming to inspire medical students for a career in obstetrics and gynaecology by developing a concept for the first German Summer School in this field. Here, medical students shall be introduced to this multifaceted specialty and have their interest in it kindled. METHODS: This article reports about the experiences of the first gynaecological summer school which was held at the University Hospital Heidelberg for 2 days in August 2018. The programme included keynote presentations, discussion roundtables and skills-lab training. To assess students' related satisfaction, and to improve future projects, an evaluation survey with seven items and two open-comment questions was given to each participant after the event. RESULTS: Mostly female students [n (♀) = 37, 93%; n (♂) = 3, 7%] from 15 different medical universities from all over Germany participated. Available places were booked within 1 week. Participants were in their clinical part of their studies between the 5th and 16th semester. The average rating of the event was excellent with 1.1 points (1 = best-5 = worst), while the selection of topics scored lowest marks with an average rating of 1.7 points. CONCLUSION: Due to the great success, the high demand and the student's positive evaluation, annual summer schools in obstetrics and gynaecology are planned. Because most of the participating students have shown a high interest and have appropriate education in the domain, the information content of keynote presentations could be increased above basic level in future projects.

Adherence to gynecological screening impacted by experienced orthodontic treatment in childhood.

BACKGROUND: Dental and cervical controls are two established screening programs in Germany. Compliance to orthodontic treatment in childhood is essential for dental health and one of the first health interventions that requires adherent behavior; therefore, it may be associated with participation in further screening programs in adulthood. However, it is not yet known whether early orthodontic treatment influences long-term screening adherence. METHODS: Using a questionnaire administered during a visit to a special dysplasia outpatient service, this case-control study evaluated women's personal history of orthodontic care, long-term satisfaction, and dental and gynecological screening adherence. Oral health status and dental anxiety were assessed with validated instruments. Cases were categorized as cervical dysplasia only (S2) or cervical dysplasia with conization (S1) and compared to healthy controls with a normal PAP smear. RESULTS: A study population of 233 participants included 132 cases and 101 controls. The control group had had orthodontic treatment during childhood more often than our study population with abnormal PAP smears (68.3% controls versus 56.1% subjects; p < 0.005). Orthodontic treatment was not associated with attending dental appointment or gynecological check-ups. However, women with an orthodontic treatment in childhood were significantly more often vaccinated against human papillomavirus than women without orthodontic treatment (p < 0.03). CONCLUSION: Data suggest that women with orthodontic treatment in childhood are more conscious about prevention strategies in adulthood; therefore, compliant behavior might be established in childhood.

European Network of Trainees in Obstetrics and Gynaecology-ENTOG Exchange 2017: an experience report from Slovenia outlining the different trainee situations around Europe.

PURPOSE: The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is a non-profit, independent organisation that represents young trainees in obstetrics and gynaecology around Europe. At present, ENTOG has 32 member countries. The organisation was founded in 1997 and shall assure the exchange of experiences between young physicians all over Europe. The aim is to improve the quality of traineeship in all participating countries and consequently enhance the standards for women's healthcare. METHODS: This article reports about the experiences of trainees during the ENTOG Exchange 2017 in Slovenia and gives an overview of the trainee situations in different ENTOG member countries. RESULTS: The ENTOG exchange in Slovenia was a unique opportunity to get insights to the Slovenian medical system. Reflecting about their training situations, the participants found considerable differences in the training of young gynaecologists throughout Europe. CONCLUSIONS: Working on the ENTOG goal of raising the quality of training is still highly relevant. The ENTOG exchange is an excellent way to build a network among trainees and stimulate their commitment to improve women's healthcare in their home countries and beyond.

"Blame it on the Comorbidities": A 5-Year Follow-Up of 53 Chronic Dialysis-Dependent Patients Who Underwent Cardiac Surgery.

Objectives This study evaluates midterm survival rates and risk factors for mortality of chronic dialysis-dependent patients undergoing cardiac surgery. Methods Fifty-three dialysis-dependent patients (34 males, aged 67 ± 12 years) with end-stage renal disease operated within March 2007 and May 2012 were analyzed retrospectively. Survival rates were calculated using Kaplan-Meier methods. Predictors of midterm survival were identified with multivariate Cox-regression analysis. Results Twenty-three patients received isolated coronary artery bypass graft surgery, 17 received isolated valve replacement, and 13 received combined procedures. Thirty-day mortality was 24.5% (n = 13). Follow-up was complete for 94.3% (n = 50). Survival rates at 1, 3, and 5 years were: 82, 50, and 17%, respectively. Neither age, gender, poor ejection fraction, emergency, ECC/X-clamp (cross-clamp) time, nor use of left internal thoracic artery or right internal thoracic artery had any influence on midterm survival. Causes of death within midterm follow-up period were related to cardiac events in 16% and neurological events in 16%. In the majority (47%), cause of death was associated with peripheral arterial disease (PAD).The only comorbidity, which could be identified as a significant risk factor, was PAD (p = 0.035). Five patients underwent successful renal transplantation within the follow-up period. Conclusion Although 30-day mortality in this high-risk patient population was increased, midterm survival rates were comparable to the results described in the literature. Cause of death within midterm follow-up period was mostly noncardiac related. Given the limited number of patients, predictors for enhanced 30-day mortality, such as preoperative myocardial infarction, prolonged extracorporeal circulation, operation time, and diabetes mellitus, did not have an influence on midterm survival.

Cardiac surgery in dialysis-dependent patients: impact of gender on early outcome in single-center experience with 204 consecutive cases.

BACKGROUND: This study evaluates the impact of gender in dialysis-dependent patients undergoing cardiac surgery. METHODS: We retrospectively identified 204 dialysis-dependent patients (68.6% male, aged 66.6 ± 9.9 years) with end-stage renal disease undergoing cardiac surgery and compared them to a propensity-score-pair-matched control collective. RESULTS: A 30-day mortality was 13.2% (14/106) for coronary artery bypass grafting (CABG), 19.3% (6/31) for aortic valve replacement (AVR), and 23.8% (16/67) for combined procedures. Postoperative chest tube output was significantly higher in men (1,007 ± 946 mL) versus women (687 ± 598 mL, p = 0.014). Compared with a propensity-score-pair-matched control collective of 204 patients, we identified significant differences in terms of 30-day mortality: overall mortality revealed 17.6 versus 4.6% (p = 0.0001), 13.2 versus 3.4% (p = 0.014) for CABG, 19.3 versus 0% (p = 0.051) for AVR, and 23.8 versus 9.1% (p = 0.02) for combined procedures. CONCLUSION: Multivariate analysis identified preoperative myocardial infarction, prolonged extracorporeal circulation time, operation time, and surgical reexploration as independent predictors of 30-day mortality. There was a higher occurrence of bleeding complications in men that remained significant even after correction for body surface area.

The Influence of Different Genres of Music on the Performance of Medical Students on Standardized Laparoscopic Exercises.

PURPOSE: Whether and how music influences the performance of surgical procedures such as laparoscopy is unclear and can be feasibly determined using laparoscopic box training tools under standardized conditions. The aim of this prospective study is to evaluate the effect of different genres of music on the performance of laparoscopic novices. METHODS: Between May 2018 and December 2018, n = 82 students (38 male, 44 female) from Heidelberg University Medical School performed 3 different laparoscopic exercises (A, B, C) from the "Luebecker Toolbox" with 2 repetitions each under standardized conditions. Time was recorded for each exercise. The students were assigned either to one of four groups, each of which was exposed to a compilation of music from 1 genre (hip hop, classical, rock, or mixed radio music), or to a fifth, control group, without exposure to music. The music was played at a constant sound pressure level of 70 decibels . Each group was compared with the others using a t-test for independent samples. RESULTS: Exposure to music generally led to better performance compared with the control group. Compared with exposure to mixed radio music or to rock, significantly better performance could be demonstrated for exposure to classical music in Exercise B, with an average exposure time of 127 s needed (± 21.4; p < 0.05). No significant differences could be demonstrated for Exercise A, though for classical music, best performance was possible with 120 s (±17.3) of exposure. In Exercise C, hip hop triggered significantly better performance than rock or radio music (p < 0.05). CONCLUSIONS: At an sound pressure level of 70 decibels, exposure to classical music or hip hop appears to have beneficial effects on training performance for surgical novices under standardized conditions.

Breast cancer characteristics and surgery among women with Li-Fraumeni syndrome in Germany-A retrospective cohort study.

BACKGROUND: Women with Li-Fraumeni syndrome (LFS) have elevated breast cancer (BC) risk. Optimal BC treatment strategies in this population are yet unknown. METHODS: BC subtypes and treatment were retrospectively investigated between December 2016 and January 2019 in a multicentre study. BC risks were evaluated according to the type of surgery. RESULTS: Thirty-five women of our study population (35/44; 79.5%) had developed 36 breast lesions at first diagnosis at a mean age of 34 years. Those breast lesions comprised 32 invasive BCs (89%), three ductal carcinoma in situ alone (8%) and one malignant phyllodes tumour (3%). BCs were mainly high-grade (18/32), of no special type (NST; 31/32), HER2-enriched (11/32) or luminal-B-(like)-type (10/32). Affected women (n = 35) received breast-conserving surgery (BCS, n = 17) or a mastectomy (ME, n = 18) including seven women with simultaneous contralateral prophylactic mastectomy (CPM) at first diagnosis. Nineteen women suffered 20 breast or locoregional axillary lesions at second diagnosis with mean age of 36. Median time between first and second diagnosis was 57 months; median time to contra- and ipsilateral recurrence depended on surgical strategies (BCS: 46 vs. unilateral ME: 93 vs. bilateral ME > 140 months). Women with a primary treatment of solitaire therapeutic ME suffered from contralateral BC earlier compared to those with therapeutic ME and CPM (median: 93 vs. >140 months). CONCLUSION: Aggressive BC subtypes occur among women with LFS. Surgical treatment, i.e. ME and CPM, may prolong time to a second BC diagnosis. Conclusion on long-term survival benefit is pending. Individual competing tumour risks and long-term outcomes need to be taken into consideration.