Hereditary Breast-Ovarian Cancer Team of the University Medical Centre Groningen (UMCG):a Report

Female carriers of a germline BRCA1 or BRCA2 mutation have a cumulative lifetime ovarian cancer risk of 39-54 % or 11-23%, respectively [1, 2]. Preventive health strategies for these women include gynaecological screening aiming at early cancer detection and prophylactic salpingo-ophorectomy aiming at cancer risk reduction. However, it is becoming increasingly clear that (bi) annual gynaecological screening by transvaginal ultrasonography and serum CA125 estimation in women at increased risk of ovarian cancer is ineffective in detecting presymptomatic ovarian cancer [4]. In a recent publication a positive predictive value of 17 % and a sensitivity of less than 50 % were found for screening for ovarian cancer in a high-risk population [3]. Preventive bilateral salpingo-oophorectomy (BSO) reduces ovaria

Implementing an Advanced Laparoscopic Procedure by Monitoring with a Visiting Surgeon

Study Objective: To investigate the feasibility of safely implementing a total laparoscopic hysterectomy (LH) in established gynecologists' practices with on-site coaching and monitoring of the learning curve by an experienced visiting surgeon. Design: Multicenter prospective feasibility and implementation study (Canadian Task Force classification II-2). Setting: Eleven general gynecologists in 8 hospitals (1 university hospital and 7 regional hospitals) participated. Patients: Laparoscopic hysterectomy was performed in 83 patients during the learning curve, and in 83 patients after the learning curve. Interventions: During the learning curve, an experienced visiting laparoscopist was available for coaching during each LH. A competence score was marked on an Objective Structured Assessment of Technical Skills (OSATS) form. Complications were recorded intraoperatively and postoperatively for 6 weeks after surgery in all patients. Measurements and Main Results: Nine of 11 gynecologists reached the competence score of at least 28 points during the study, from January 2005 to January 2007. A major complication occurred in 3 of 83 LH procedures (4%) performed during the learning curve, and in 5 of 83 LH procedures (6%) performed after the learning curve (p = .72). Conclusion: The concept of a visiting surgeon for on-site coaching and monitoring of established gynecologists during the learning curve of an advanced laparoscopic procedure using Objectively Structured Assessment of Technical Skills is feasible. According to the observed complication rate during and after the learning curve, on-site coaching is a useful tool when implementing a new laparoscopic technique in established gynecologists' practices. Journal of Minimally Invasive Gynecology (2010) 17, 771-778 (C) 2010 AAGL. All rights reserved

Feasibility of endometrial sampling by vaginal tampons in women with Lynch syndrome

Background: Endometrial sampling for the surveillance of women with Lynch syndrome is an invasive and painful procedure. The aim of this study was to evaluate the feasibility of a less invasive procedure of collecting vital cells by vaginal tampons. Methods: This was a prospective feasibility study of women scheduled to undergo annual gynecological surveillance, including endometrial sampling. We included consecutive asymptomatic women with Lynch syndrome or first-degree relatives and asked them to insert a vaginal tampon 2-4 h before attending their outpatient appointment. Feasibility was evaluated by the following metrics: Patient acceptance, pain intensity of each procedure (assessed by visual analog scale; range 0-10), and the presence of vital cells obtained by tampon-based or endometrial sampling methods. Two pathologists independently evaluated all samples. Results: In total, 25 of 32 approached women completed the tampon-based procedure, with 23 of these subsequently undergoing invasive endometrial sampling. The median visual analog scale scores for tampon use and invasive endometrial sampling were 0 (range, 0-10) and 5.5 (range, 1-10) (p < 0.001). None of the tampon samples analyzed by cytology showed endometrial cells, but they did contain vital squamous cells and granulocytes. By contrast, 18 (78%) of the invasive endometrial samples contained enough endometrial tissue for analysis. No endometrial abnormalities were found by endometrial sampling. Conclusions: Tampon-based endometrial surveillance was a well-accepted and non-painful procedure, and although tampons contained vital cells, they did not provide endometrial cells. However, this study was limited to asymptomatic women with Lynch syndrome (no endometrial pathology), indicating that research is needed to evaluate whether the tampon method has any utility for endometrial surveillance in women with Lynch syndrome

PREsurgery thoughts - thoughts on prehabilitation in oncologic gynecologic surgery, a qualitative template analysis in older adults and their healthcare professionals

Purpose This study aimed to reveal information that can be used for composing a prehabilitation program tailored to elderly gynecological oncological patients and is applicable to healthcare professionals. We investigated possible content and indications for prehabilitation, and what potential barriers might exist. Materials and methods Because of the primary exploratory study aim, inductive thematic template analysis on semi-structured interviews with gynecologic oncological patients aged >= 60 years and healthcare professionals were used. Results 16 patients and 20 healthcare professionals were interviewed. Three themes important for prehabilitation were found: (1) "Motivation," (2) "Practical issues and facilitators," and (3) "Patient-related factors." A short time interval between diagnosis and surgery was reported as a potential barrier for prehabilitation. Given components for a tailor-made prehabilitation program are: (1) The first contact with a nurse who screens the patients, gives tailor-made advice on prehabilitation and keeps patients motivated and supports them mentally; (2) If patients are referred to a more extensive/supervised program, this should preferably be arranged close to a patients' home. Conclusion Based on our findings, an outline of a patient-tailored prehabilitation program was developed. The main important themes for prehabilitation were "Motivation," "Practical issues and facilitators," and "Patient-related factors.

Risk assessment for postoperative outcomes in a mixed hospitalized gynecological population by the Dutch safety management system (Veiligheidsmanagementsysteem, VMS) screening tool 'frail elderly'

PURPOSE: Frailty is associated with a higher risk for negative postoperative outcomes. This study aimed to determine the association between the screening tool of the Dutch safety management system, Veiligheidsmanagementsysteem (VMS) ‘frail elderly’ and postoperative complications in a gynecological population. METHODS: This cohort study included women aged 70 years or older, who were scheduled for any kind of gynecological surgery. VMS screening data (including risk for delirium, falling, malnutrition, and functional impairment) were extracted from the electronic patient records. VMS score could range between 0 and 4 patients with a VMS score of one or more were considered frail. Data on possible confounding factors and complications within 30 days after surgery, classified with the Clavien–Dindo classification, were collected. Regression analysis was performed. RESULTS: 157 women were included with a median age of 74 years (inter quartile range 71–79). Most patients underwent prolapse surgery (52%) or hysterectomy (31%). Forty-one patients (26%) experienced any postoperative complication. Sixty-two patients (39%) were considered frail preoperatively by the VMS screening tool. Frailty measured with the VMS screening tool was not independently associated with postoperative complications in multivariable analysis (Odds ratio 1.18; 95% CI 0.49–2.82). However, a recent fall in the last 6 months (n = 208) was associated with postoperative complications (Odds ratio 3.90; 95% CI 1.57–9.66). CONCLUSION: An independent association between frailty, determined by the VMS screening tool ‘Frail elderly’, and postoperative complications in gynecological surgery patients could not be confirmed. A recent fall in the last 6 months seems associated with postoperative complications

Surgical volume and conversion rate in laparoscopic hysterectomy:Does volume matter? A multicenter retrospective cohort study

Background A multicenter, retrospective, cohort study was conducted in the Netherlands. The aim was to evaluate whether surgical volume of laparoscopic hysterectomies (LHs) performed by proven skilled gynecologists had an impact on the conversion rate from laparoscopy to laparotomy. Methods In 14 hospitals, all LHs performed by 19 proven skilled gynecologists between 2007 and 2010 were included in the analysis. Surgical volume, conversion rate and type of conversion (reactive or strategic) were retrospectively assessed. To estimate the impact of surgical volume on the conversion rate, logistic regressions were performed. These regressions were adjusted for patient's age, Body Mass Index (BMI), ASA classification, previous abdominal surgery and the indication (malignant versus benign) for the LH. Results During the study period, 19 proven skilled gynecologists performed a total of 1051 LHs. Forty percent of the gynecologists performed over 20 LHs per year (median 17.3, range 5.4-49.5). Conversion to laparotomy occurred in 5.0% of all LHs (53 of 1051); 38 (3.6%) were strategic and 15 (1.4%) were reactive conversions. Performing over 20 LHs per year was significantly associated with a lower overall conversion rate (ORadjusted 0.43, 95% CI 0.24-0.77), a lower strategic conversion rate (ORadjusted 0.32, 95% CI 0.16-0.65), but not with a lower reactive conversion rate (ORadjusted 0.96, 95% CI 0.33-2.79). Conclusion A higher annual surgical volume of LHs by proven skilled gynecologists is inversely related to the conversion rate to laparotomy, and results in a lower strategic conversion rate

Evidence for a Novel Endometrioid Carcinogenic Sequence in the Fallopian Tube With Unique Beta-Catenin Expression

Epithelial proliferations in the fallopian tube have been characterized by some as stem cell outgrowths (SCOUTs) and divided into type I and type II. Type II SCOUTs exhibit diffuse cellular beta-catenin nuclear staining (β-catenin+), implying a CTNNB1 mutation. SCOUTs are more common in perimenopausal and postmenopausal women and are associated with ovarian cancer but have not been linked directly to malignancy. We analyzed type II SCOUTs in various gynecologic conditions, and searched for endometrioid atypical hyperplasias (tubal endometrioid intraepithelial neoplasia) or adenocarcinomas in the tube. β-catenin+ SCOUT frequency in cases of neoplasia was 66.7% per case and 30.7% per nonfimbrial cross-section for uterine endometrioid carcinomas versus 25% and 13.3% for controls, respectively (P=0.02 and 0.09). Multiple (3 or more) β-catenin+ SCOUTs in a single section were uncommon; 6 of 9 were associated with a carcinoma or proliferative lesion in the endometrium. Tubal endometrioid intraepithelial neoplasia/atypical hyperplasia displayed complex growth, including focal cribriform growth patterns and squamous morules. Two cases of type II SCOUTs associated with tubal endometrioid intraepithelial neoplasia/atypical hyperplasia and/or adenocarcinomas in the fallopian tube were identified, both of which coexisted with a separate endometrioid adenocarcinoma, one with bilateral ovarian endometrioid adenocarcinomas. Both benign and neoplastic tubal lesions were β-catenin+. This report is the first to link components of a unique β-catenin+ endometrioid carcinogenic sequence in the fallopian tube. It further emphasizes the multifocal nature of endometrioid neoplasia in the female genital tract and poses questions regarding the frequency and biologic underpinnings of β-catenin+ proliferations in the oviduct

The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer:Tumor-First or Germline-First?

Objective: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.Methods: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated.Results: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986).Conclusions: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.</p

Loss of skeletal muscle density during neoadjuvant chemotherapy in older women with advanced stage ovarian cancer is associated with postoperative complications

Objective: To assess the association between loss of lumbar skeletal muscle mass and density during neoadjuvant chemotherapy (NACT) and postoperative complications after interval cytoreductive surgery (CRS) in older patients with ovarian cancer. Materials and methods: This multicenter, retrospective cohort study included patients aged 70 years and older with primary advanced stage ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV), treated with NACT and interval CRS. Skeletal muscle mass and density were retrospectively assessed using Skeletal Muscle Index (SMI) and Muscle Attenuation (MA) on routinely made Computed Tomography scans before and after NACT. Loss of skeletal muscle mass or density was defined as >2% decrease per 100 days in SMI or MA during NACT. Results: In total, 111 patients were included. Loss of skeletal muscle density during NACT was associated with developing any postoperative complication ≤30 days after interval CRS both in univariable (Odds Ratio (OR) 3.69; 95% Confidence Interval (CI) 1.57–8.68) and in multivariable analysis adjusted for functional impairment and WHO performance status (OR 3.62; 95%CI 1.27–10.25). Loss of skeletal muscle density was also associated with infectious complications (OR 3.67; 95%CI 1.42–9.52) and unintended discontinuation of adjuvant chemotherapy (OR 5.07; 95%CI 1.41–18.19). Unlike loss of skeletal muscle density, loss of skeletal muscle mass showed no association with postoperative outcomes. Conclusion: In older patients with ovarian cancer, loss of skeletal muscle density during NACT is associated with worse postoperative outcomes. These results could add to perioperative risk assessment, guiding the decision to undergo surgery or the need for perioperative interventions