The Value of DICER1 Mutation Analysis in "Subtle" Diagnostically Challenging Embryonal Rhabdomyosarcomas of the Uterine Cervix.

Embryonal rhabdomyosarcoma of the uterine cervix is a rare neoplasm which is almost invariably associated with pathogenic somatic or germline DICER1 mutations; patients with germline mutations have DICER1 syndrome. We report 2 subtle cervical embryonal rhabdomyosarcoma, one occurring in a 21-yr-old woman with a known history of DICER1 syndrome and the other in a 19-yr-old woman with no history of DICER1 syndrome or DICER1-associated neoplasms. Both neoplasms focally involved otherwise benign endocervical polyps and were characterized histologically by subtle areas of increased stromal cellularity, nuclear atypia and mitotic activity; there was focal nuclear staining of these areas with the skeletal muscle markers myogenin and myoD1. In both cases, demonstration of a somatic DICER1 RNase IIIb mutation in the tumor was instrumental in establishing the diagnosis. We believe these neoplasms represent the earliest discernible phase of cervical embryonal rhabdomyosarcoma. Pathologists should have a high index of suspicion when atypical stromal elements are present in endocervical polyps and immunohistochemistry together with DICER1 sequencing will assist in diagnosis.

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry.

BACKGROUND: In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. OBJECTIVE: To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. METHODS: A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. RESULTS: Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years. CONCLUSIONS: Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

A randomized controlled trial of WATAAP to promote physical activity in colorectal and endometrial cancer survivors.

OBJECTIVE: The objective of this study was to ascertain whether wearable technology coupled with action planning was effective in increasing physical activity (PA) in colorectal and endometrial cancer survivors at cardiovascular risk. METHODS: Sixty-eight survivors who had cardiovascular risk factors and were insufficiently active were randomized to intervention and control arms. Intervention participants were given a wearable tracker for 12 weeks, two group sessions, and a support phone call. Participants in the control arm received print materials describing PA guidelines. Assessments at baseline and 12 weeks measured triaxial and uniaxial estimates of moderate-vigorous physical activity (MVPA), sedentary behaviour, blood pressure, and body mass index (BMI). RESULTS: The intervention group significantly increased MVPA by 45 min/wk compared with a reduction of 21 min/wk in the control group. Group by time interactions were significant for minutes of MVPA (F1,126  = 5.14, P = 0.025). For those with diastolic hypertension, there was a significant group by time interaction (F1,66  = 4.89, P = 0.031) with a net reduction of 9.89 mm Hg in the intervention group. CONCLUSIONS: Significant improvements in MVPA were observed following the intervention. The results display promise for the use of pragmatic, low-intensity interventions using wearable technology.

Health-related quality of life and pelvic floor dysfunction in advanced-stage ovarian cancer survivors: associations with objective activity behaviors and physiological characteristics.

PURPOSE: Little is known about the relationship between health-related quality of life (HRQoL), pelvic floor dysfunction (PFD), and modifiable lifestyle and physiological factors for ovarian cancer survivors (OCS). The primary aim of the study was to compare post-treatment advanced-stage OCS with age-matched controls on measures of HRQoL and PFD. The secondary aim was to examine associations between HRQoL, PFD, objective activity behaviors, physical function, and body composition in OCS. METHODS: Twenty advanced-stage OCS and 20 controls completed questionnaires assessing HRQoL (SF-36) and PFD (Australian Pelvic Floor Questionnaire), and underwent objective assessments of activity behavior (7-day accelerometry), physical function (400-m walk, repeated chair rise, 6-m usual-pace walk, one-repetition maximum chest press, and single-leg extension), and body composition (dual-energy x-ray absorptiometry). RESULTS: Compared to controls, OCS had worse physical HRQoL (- 4.3 median difference, p = 0.013), but equivalent self-reported PFD, indicated by combined bladder, bowel, and pelvic organ prolapse symptoms (0.89 mean difference, p = 0.277). In OCS, physical HRQoL was significantly negatively associated with PFD (r = 0.468, p = 0.043). Decreased physical HRQoL and increased PFD were significantly associated with less moderate-to-vigorous physical activity in ≥ 10-min bouts (ρ = 0.627, p = 0.003; ρ = - 0.457, p = 0.049), more sedentary time (r = - 0.449, p = 0.047; r = 0.479, p = 0.038), and slower 400-m walk time (ρ = - 0.565, p = 0.022; ρ = 0.504, p = 0.028). CONCLUSIONS: Post-treatment advanced-stage OCS have decreased physical HRQoL, which is associated with modifiable factors such as worse PFD, less moderate-to-vigorous physical activity, more sedentary time, and decreased objective physical function. This highlights the need for ongoing supportive care and multidisciplinary interventions after first-line ovarian cancer treatment.

Do Groin Drains Reduce Postoperative Morbidity in Women Undergoing Inguinofemoral Lymphadenectomy for Vulvar Cancer?

OBJECTIVE: Sentinel lymph node biopsy has been widely adopted in the surgical management of women with early-stage vulvar cancer, but many patients require inguinofemoral lymphadenectomy (IFL). Following IFL, many surgeons drain the groin to prevent lymphocyst formation despite a lack of evidence to support this practice. Our objective was to investigate whether groin drains after IFL are associated with reduced postoperative morbidity in women undergoing surgery for vulvar cancer. METHODS: A retrospective cohort study of women diagnosed as having primary vulvar cancer who underwent vulvectomy/radical local excision and unilateral or bilateral IFL was conducted. Cases were ascertained from the weekly outcome reports of a statewide tertiary gynecologic oncology tumor board. Data including postoperative outcomes were abstracted from medical records. Patients were stratified into 1 of 2 groups according to whether a groin drain had been used. RESULTS: Seventy-one patients were included. Inguinal drains were used in 48 patients (67.6%) and 23 patients (32.4%) did not have their groin wound(s) drained. The most common postoperative complications recorded were wound infection (59.2%), groin lymphocyst (32.4%), and cellulitis (25.4%). The mean length of hospital admission was 11.5 days (2-40 days). Compared with patients in whom inguinal drains were placed, those in the "no drain" group had a significantly lower incidence of postoperative groin cellulitis (8.7% vs 25.4% P = 0.039). No significant differences were observed between patients in the "drain" and "no drain" groups in lymphocyst formation, wound infection, return to the operating room, duration of hospital stay, readmission post-discharge, and lower-limb lymphedema. CONCLUSIONS: In this study of patients undergoing inguinofemoral dissection for primary vulvar cancer, postoperative cellulitis occurred less frequently in patients without an inguinal drain. The incidence of other postoperative complications was no different whether or not a groin drain was used. Prospective studies may be warranted.

Activity Behaviors and Physiological Characteristics of Women With Advanced-Stage Ovarian Cancer: A Preliminary Cross-sectional Investigation.

OBJECTIVES: Ovarian cancer (OC) survivors experience many disease and treatment adverse effects. However, the impact of OC and its treatment on objective activity behaviors and physiological status have not been examined. The purpose of this study was to compare objectively measured activity behaviors and physiological characteristics of advanced-stage OC survivors to age-matched controls. METHODS: Twenty stage III-IV OC survivors and 20 controls completed assessments of activity behaviors (7-day accelerometry), physical function (400-meter walk as indicator of cardiorespiratory fitness, repeated chair rise, 6-meter walking tests), muscle strength (1-repetition maximum and handgrip), body composition (dual-energy x-ray absorptiometry), and musculoskeletal morphology (peripheral quantitative computed tomography). RESULTS: Compared with controls, OC survivors spent more time/day in prolonged sedentary bouts (P = 0.039, r = 0.32), had lower cardiorespiratory fitness (P = 0.041, r = 0.33) and upper body strength (P = 0.023, r = 0.37), had higher areal bone mineral content (P = 0.047, r = 0.33) and volumetric trabecular density (P = 0.048, r = 0.31), but were not different in other measures of body composition nor in muscle morphology (P > 0.050). Only 20% (n = 4) of OC survivors accrued 150 minutes/week or greater moderate and vigorous physical activity (MVPA) time in 10-minute bouts or greater. Moderate and vigorous physical activity time/day in 10-minute bouts or greater was strongly associated with cardiorespiratory fitness (P = 0.001, ρ = -0.702) and lower extremity function (P = 0.019, ρ = -0.519) and moderately associated with muscle cross-sectional area (P = 0.035, ρ = 0.473). CONCLUSIONS: Posttreatment OC survivors spent more time in prolonged sedentary bouts and had lower cardiorespiratory fitness and upper body strength compared with controls. Moderate and vigorous physical activity was associated with physical function and muscle cross-sectional area. Future studies should test the efficacy of exercise interventions to increase MVPA, reduce sedentary behavior, and increase cardiorespiratory fitness and muscle strength in OC survivors.

Advanced Training of Gynecologic Surgeons and Incidence of Intraoperative Complications after Total Laparoscopic Hysterectomy: A Retrospective Study of More Than 2000 Cases at a Single Institution.

STUDY OBJECTIVE: To investigate whether surgeon factors including level of training undertaken in laparoscopic surgery, time in specialist practice, and case volume were associated with surgical morbidity for total laparoscopic hysterectomy (TLH). DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: A tertiary care setting in Western Australia. PATIENTS: Two thousand thirteen patients who underwent TLH for benign or malignant indications. INTERVENTIONS: Women undergoing TLH were allocated to 1 of 3 groups of surgeons: general gynecologists, gynecologic endoscopists, and subspecialists. MEASUREMENTS AND MAIN RESULTS: All patients undergoing elective TLH at St John of God Subiaco Hospital, Subiaco, Perth, Western Australia, between January 1, 2011, and December 31, 2016, were included for analysis. Variables recorded included cystotomy, ureteric injury, enterotomy/colostomy, bowel serosa injury, vascular injury, conversion to laparotomy, return to the operating room, hemorrhage, blood transfusion, operating time, length of stay, and postoperative complications to 42 days. The primary outcome was any major intraoperative complication. The incidence of any major intraoperative complication was 1.8% (36/2013 cases). Forty-five patients (2.2%) had a postoperative complication, and 74 (3.7%) patients were readmitted to the hospital after discharge. The incidence of any major intraoperative complication was significantly higher among general gynecologists compared with subspecialists (3.3% vs 1.1%, p = .002). No association was found between time in specialist practice and the incidence of major intraoperative complications (p = .629). A significant association for major intraoperative complications was observed for surgeons who had performed <100 laparoscopic hysterectomies during the study period (p = .032). CONCLUSION: In this study, despite a higher level of surgical acuity and the performance of additional and more complex procedures, surgical morbidity was lower in patients undergoing TLH by gynecologic surgeons with a higher level of subspecialist training.

Outcomes in women undergoing robotic-assisted laparoscopic hysterectomy compared to conventional laparoscopic hysterectomy at a tertiary hospital in Western Australia.

BACKGROUND: Robotic-assisted laparoscopic hysterectomy (RALH) is associated with improved outcomes compared to open surgery in patients with endometrial cancer but data are conflicting when comparing RALH to conventional total laparoscopic hysterectomy (TLH). In October 2014, a RALH program was established in Perth, Western Australia. AIM: To compare outcomes in patients undergoing RALH with a matched cohort undergoing TLH. MATERIALS AND METHODS: A retrospective matched cohort study compared outcomes in 45 patients who underwent RALH with 45 controls who were patients treated with TLH. RESULTS: Mean operating time was longer in the RALH group compared to controls (75.42 min vs 53.18 min, mean difference 22.24 min, P < 0.001, 95% Cl, 11.07-33.42). No differences were observed in mean pain scores (RALH 1.47 vs TLH 1.84 P = 0.31), mean parenteral and oral opioid use (RALH 14.3 mg and 42.4 mg vs TLH 17.5 mg and 52.57 mg, P = 0.42 and 0.42, respectively), and mean length of stay (RALH 1.51 vs TLH 1.67 days, P = 0.49). Two patients in the RALH group and one patient in the TLH group sustained iatrogenic bladder injuries (P = 0.62). CONCLUSION: The establishment of the RALH program at our institution appeared to be associated with equivalent morbidity, post-operative pain, opioid use and length of stay compared to conventional laparoscopy. A surgical learning curve for RALH was observed. Well-designed prospective studies are needed to further evaluate short- and long-term patient function, morbidity, quality of life and oncologic outcomes.

Risk of persistent and recurrent cervical neoplasia following incidentally detected adenocarcinoma in situ.

BACKGROUND: Adenocarcinoma in situ of the uterine cervix is a precursor to cervical adenocarcinoma and may coexist with both adenocarcinoma and high-grade squamous dysplasia (cervical intraepithelial neoplasia 2 and 3). Up to 60% of adenocarcinoma in situ lesions are detected incidentally following excisional biopsies performed for the treatment of cervical intraepithelial neoplasia 2/3. To date there are no data regarding risk factors for persisting or progressive cervical neoplasia in these patients. OBJECTIVE: We sought to investigate patient outcomes following incidentally detected cervical adenocarcinoma in situ after loop electrosurgical excision procedure or cold knife cone biopsy performed for the treatment of high-grade cervical intraepithelial neoplasia. STUDY DESIGN: We conducted a retrospective, population-based cohort study of Western Australian patients with an incidental diagnosis of adenocarcinoma in situ from 2001 through 2012. Primary outcomes were persistent or recurrent cervical intraepithelial neoplasia 2/3 and or adenocarcinoma in situ, and invasive adenocarcinoma during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 298 patients, with 228 (76.5%) treated initially by loop electrosurgical excision procedure and 70 (23.5%) treated by cold knife cone biopsy. The mean age was 31.2 (range 18-68) years and the median length of follow-up was 2.4 (range 0.3-12.2) years. Overall, 11 (3.7%) patients had cervical intraepithelial neoplasia 2/3, 23 (7.7%) had adenocarcinoma in situ, and 3 (1.0%) had adenocarcinoma diagnosed during the follow-up and surveillance periods. Age >30 years, pure adenocarcinoma in situ lesions, and larger lesions (>8 mm) were associated with a greater risk of disease persistence or recurrence. CONCLUSION: Following the incidental detection of adenocarcinoma in situ, age >30 years, pure adenocarcinoma in situ lesions, and lesions >8 mm were significantly associated with disease persistence/recurrence. In younger women, incidentally detected adenocarcinoma in situ that coexists with cervical intraepithelial neoplasia 2/3 and is <8 mm extent with clear margins may not require reexcision.

Factors influencing participation in health behaviors in endometrial cancer survivors.

BACKGROUND: The study purpose was to investigate endometrial cancer survivors' health perceptions following cessation of active cancer treatment and to explore factors influencing participation in health-promoting behaviors. METHODS: Face-to-face interviews were conducted with participants who had completed active treatment of cancer within the previous 3 years. Participants were 22 endometrial cancer survivors (mean age = 62.55 years, SD = 7.08) at risk of cardiovascular disease who were recruited from 2 oncologists in Perth, Western Australia. Interview transcripts were analyzed using thematic analysis. RESULTS: Five main themes emerged: physical activity knowledge and advice; authority of oncologists; accountability and external motivation; monitoring and barriers to healthy eating; and physical activity. Participants recalled that specific recommendations for physical activity or body weight were rarely made by the oncologists, but felt they would have followed such lifestyle advice if it had been given. The overarching theme was the need for accountability and monitoring to successfully change health behaviors. CONCLUSIONS: Interventions aimed at promoting health behaviors in endometrial cancer survivors should include referral and advice from oncologists, provision of monitoring, and promotion of planning and self-control. Implications for endometrial cancer survivors at risk of cardiovascular disease: these women are likely to benefit most from interventions aimed at promoting planning, self-regulation and problem solving and regular follow-up.

Value of Specialist Pathology Review in a Single Statewide Gynecologic Cancer Service.

OBJECTIVE: A case review by specialist diagnostic pathologists as part of a Gynecologic Oncology Multi-disciplinary Tumor group has the potential to influence the management of patients with cancer. The primary aim of this study was to determine the frequency of diagnostic discrepancies between the initial (nonspecialist) and final pathological diagnoses in cases referred to the Gynecologic Oncology Tumor Conference (TC) in Western Australia and the impact of such revised diagnosis on clinical management. A secondary aim was to assess the evolving workload encountered by the TC during a 5-year interval. METHODS: The records of the weekly TC for the 2 calendar years 2008 and 2013 were examined, and histological and cytological specimens that had been initially assessed by "outside" (nonspecialist) pathology departments, and subsequently reviewed by specialist pathologists, were assessed. The initial and final diagnoses were compared, and where the pathological findings were amended upon review, it was determined whether the change affected clinical management. Diagnostic discrepancies that resulted in a change in patient management were classified as major, whereas discrepancies that did not affect patient management were classified as minor. RESULTS: A total of 481 outside cases were included among 2387 cases presented for histological review at the TC during the 2 years. For outside cases alone, the incidence of major diagnostic discrepancies was 3.4% in 2008, 5.5% in 2013 (no significant difference, P = 0.3787), and 4.6% for the 2 years combined. A recommendation for surgery was the most common change in clinical management as a result of major discrepancy. The minor discrepancy rate was 4.4% of outside cases for both years combined. Pathological discrepancies (major and minor) of the uterine corpus and cervix were most frequent, followed by those of the vulva and ovary. There was a 48.4% increase in total case discussions at the TC during the interval period with a significant rise in nonmalignant cases, 29.8% of the total cases in 2008 compared with 36.8% in 2013 (P = 0.0004). CONCLUSIONS: Nonspecialist pathology departments maintained a high level of reporting accuracy during the interval period, with the major discrepancy rate not changing significantly between 2008 and 2013. Specimens from the uterine corpus and cervix in particular may prove diagnostically challenging on occasion. A pathology review of outside cases by a tertiary-based laboratory in conjunction with a TC can identify a small but clinically significant number of cases that lead to a change in clinical management. It is uncertain whether this affects patient outcomes.

Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.

OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test. RESULTS: Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed independent prognostic significance for PFS but not for OS.

Risk of persistent or recurrent neoplasia in conservatively treated women with cervical adenocarcinoma in situ with negative histological margins.

INTRODUCTION: Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins. MATERIAL AND METHODS: A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as <12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 360 women, with 175 (48.6%) initially treated by CKC and 185 (51.4%) treated by LEEP. The median patient age at time of excisional treatment was 30.0 years (range 18-64 years) and the median follow-up time was 3.9 years (range six months to 12.2 years). During the follow-up and surveillance periods, seven (1.9%) women were diagnosed with CIN 2/3, 10 (2.8%) with AIS, and one (0.3%) with cervical adenocarcinoma, despite their initial excision specimens having negative histological margins. CONCLUSION: In this study, there was a low but significant risk of persistent or recurrent cervical neoplasia in women who had initial conservative management of AIS with negative histopathological margins.

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

Prevalence of sexual dysfunction after risk-reducing salpingo-oophorectomy.

OBJECTIVES: To determine the prevalence of sexual dysfunction in women after risk-reducing salpingo-oophorectomy (RRSO) and to assess factors which may influence sexual wellbeing following this procedure. METHODS: This work is a cross-sectional study of women who underwent RRSO at a tertiary gynecologic oncology unit between January 2009 and October 2014. Data collection involved a comprehensive questionnaire including validated measures of sexual function, sexual distress, relationship satisfaction, body image, impact of event, menopause specific quality of life, and general quality of life. Participants were invited to undergo blood testing for serum testosterone and free androgen index (FAI). RESULTS: 119 of the 206 eligible women participated (58%), with a mean age of 52years. The prevalence of female sexual dysfunction (FSD) was 74% and the prevalence of hypoactive sexual desire disorder (HSDD) was 73%. Common sexual issues experienced included; lubrication difficulty (44%), reduced sexual satisfaction (41%), dyspareunia (28%) and orgasm difficulty (25%). Relationship satisfaction, the use of topical vaginal estrogen and lower generalized body pain were significantly associated with a decreased likelihood of sexual dysfunction. Serum testosterone, FAI, the use of systemic hormone replacement therapy (HRT), prior history of breast cancer, menopausal status at the time of surgery and hysterectomy did not correlate with sexual dysfunction. CONCLUSION: The prevalence of FSD and HSDD after RRSO was 74% and 73% respectively. Relationship satisfaction, low bodily pain and use of topical vaginal estrogen were associated with a lower likelihood of sexual dysfunction. There was no correlation between serum testosterone or FAI, and sexual dysfunction.

Discussing Sexuality With Women Considering Risk-Reducing Salpingo-oophorectomy: An International Survey of Current Practice in Gynecologic Oncology.

OBJECTIVE: To determine how frequently gynecologic oncologists discuss sexuality with women considering risk-reducing salpingo-oophorectomy. Secondary objectives were to assess the availability of resources, and the barriers to discussing sexuality. METHODS: Members of the Australian Society of Gynaecologic Oncologists, International Gynecologic Cancer Society, and Society of Gynecologic Oncology were invited to complete an online survey. Questions addressed frequency of, and barriers to, discussing sexuality, and availability of resources related to sexual issues. RESULTS: Three hundred eighty-eight physicians in 43 countries responded from 4,006 email invitations (9.7%). Ninety-one percent reported discussing sexuality preoperatively, and 61% discuss it with every patient. Factors associated with higher rates of discussion were female sex (P = 0.020), higher level of training (P = 0.003), time in practice (P = 0.003), and consulting more risk-reducing salpingo-oophorectomy patients per month (P = 0.006). Commonly discussed issues were vasomotor menopausal symptoms (91%) and vaginal dryness (85%). Eighty-eight percent of respondents believed that sexuality should be discussed preoperatively, and most felt that it is their responsibility (82%). Fear of causing distress was the most common barrier to discussing sexuality (49%). Twenty-four percent felt that they did not have adequate training to discuss sexual function. CONCLUSIONS: Although most respondents believed that discussing sexuality should occur preoperatively, only 61% discuss this with every patient. Resources specifically relating to sexuality are limited. The most common barrier to discussing sexuality was fear of causing distress. Nearly one quarter of gynecologic oncologists felt inadequately trained to discuss sexual function.

Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial.

STUDY OBJECTIVE: To determine if the use of a 5-mm umbilical incision and laparoscope would result in a higher likelihood of earlier discharge from hospital after total laparoscopic hysterectomy (TLH) compared with a 10-mm umbilical incision and laparoscope. Secondary objectives of the study were to determine if the use of a 5-mm laparoscope would lead to a reduction in postoperative pain scores and a shorter operating time without an increase in complication rates. DESIGN: Prospective, randomized, double-blinded, clinical trial (Canadian Task Force classification I). SETTING: A tertiary care setting. PATIENTS: Seventy-eight patients scheduled for TLH were prospectively recruited. INTERVENTIONS: Women undergoing TLH were assigned to either a 5-mm umbilical port and laparoscope (5LH) or a 10-mm umbilical port and laparoscope (10LH). All patients underwent a standardized operative technique and anesthetic protocol. Patients and research assistants responsible for postoperative pain assessment were blinded to group. Analysis was by intention-to-treat. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was length of hospital stay. Secondary outcome measures were operating time, pain scores on postoperative days 1 and 7, and complication rates. There was no difference in length of hospital stay between the 2 arms. Compared with the 10LH group, the 5LH group had shorter operative times (32.6 vs 40 minutes; p = .01) and less postoperative pain on day 1 (2.5 vs 3.3; p = .03 for "pain with movement") and on day 7 (.92 vs 1.8; p = .002). Complication rates were similar between the 2 groups. CONCLUSION: TLH with a 5-mm laparoscope resulted in shorter operative times and less pain on postoperative days 1 and 7, compared with a 10-mm laparoscope, with similar length of stay and complications.

Ovarian sex cord-stromal tumors in patients with probable or confirmed germline DICER1 mutations.

The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Recent studies have demonstrated somatic mutations in DICER1 in approximately 60% of ovarian Sertoli-Leydig cell tumors. Furthermore, patients with germline mutations in DICER1 are predisposed to developing a range of rare neoplasms including ovarian sex cord-stromal tumors most of which have been classified as Sertoli-Leydig cell tumor. However, the histologic features of these tumors have not been reported in detail. We describe the morphologic and immunophenotypic findings of 4 sex cord-stromal tumors arising in patients with proven or likely germline DICER1 mutations including 3 individuals from 1 family. Three tumors showed similar appearances characterized by marked architectural and cytologic heterogeneity including sertoliform, juvenile granulosa cell tumor-like, and unclassifiable elements. The remaining case mainly showed heterologous mucinous epithelial and neuroendocrine differentiation with only a minor intermediate-grade Sertoli cell component. This tumor and one of the 3 former cases arose in related patients with identical germline DICER1 mutations indicating that additional factors influence tumor morphology. All tumors were positive for steroidogenic factor-1 and FOXL2 on immunohistochemical analysis, whereas there was more variable expression of inhibin, calretinin, CD56, CD99, and hormone receptors. The present small series suggests that some ovarian Sertoli-Leydig cell tumor associated with germline DICER1 mutations may show distinctive histologic features in particular admixed Sertoli cell and juvenile granulosa cell tumor-like features. Larger studies are required to establish whether heterologous elements are also a more common feature of these tumors.

The positive impact of structured teaching in the operating room.

BACKGROUND: A survey of obstetric and gynaecology trainees in Australia found the trainee's opinion of the consultants' teaching ability for laparoscopic procedures and procedures dealing with complications as 'poor' in 21.2% and 23.4% of responses, respectively (Aust NZ J Obstet Gynaecol 2009; 49: 84). Surgical caseload per trainee is falling for a variety of reasons. Strategies need to be adopted to enhance the surgical learning experience of trainees in the operating room. AIMS: We describe the use of a structured encounter template to facilitate the teaching of surgery in the operating room and report the response of the trainees to this intervention. METHODS: Trainees attached to a gynaecologic surgery unit all underwent surgical training using a set format based on the surgical encounter template, including briefing, goal setting and intra-operative teaching aims as well as debriefing. Data on the trainees' experience and perception of their learning experience were then collected and analysed as quantitative and qualitative data sets. RESULTS: The trainees reported satisfaction with the use of a structured encounter template to facilitate the surgical teaching in the operating room. Some trainees had not received such clarity of feedback or the opportunity to complete a procedure independently prior to using the structured encounter template. CONCLUSIONS: A structured surgical encounter template based on andragogy principles to focus consultant teaching in the operating room is highly acceptable to obstetric and gynaecology trainees in Australia. Allowing the trainee the opportunity to set objectives and receive feedback empowers the trainee and enhances their educational experience.