Occult residual ovarian tissue at the time of minimally invasive risk reducing surgery in women with BRCA mutations.

OBJECTIVE: To describe extension of ovarian tissue beyond visible and National Comprehensive Cancer Network recommended margins among patients with BRCA mutations undergoing minimally invasive risk-reducing salpingo-oophorectomy. METHODS: A prospective study of patients with BRCA mutations who underwent minimally invasive risk-reducing bilateral salpingo-oophorectomy was conducted. Patient enrollment occurred between October 2021 and 2023. Tissue specimens were analyzed according to the Sectioning and Extensively Examining the Fimbriated End protocol. RESULTS: Twenty women with BRCA mutations were prospectively enrolled. All patients underwent minimally invasive surgery with 70% undergoing concurrent hysterectomy (n = 14). Approximately half of these procedures were performed with robotic assistance (n = 9, 45%). One patient was admitted overnight (5%); the other nineteen were discharged on the day of surgery (95%). One patient experienced a major complication and required readmission (5%). Extension of ovarian tissue beyond the visible ovary was noted on pathologic examination of six specimens (30%). In one patient this was observed on the left (17%), in three on the right (50%), and in two bilateral extension (33%) was noted. The distance ovarian stroma extended microscopically beyond the visible ovary was between 2 and 14 mm, with a median of 5 mm. Among patients with microscopic extension of ovarian tissue, the majority (n = 5, 83%) had a BRCA2 mutation. CONCLUSION: In women with BRCA mutations undergoing risk-reducing minimally invasive surgery, approximately one third had microscopic extension of ovarian stroma beyond the visible ovary. Current guidelines which recommend resection of at least 20 mm of tissue beyond the visible ovary are likely adequate in this population.

Characterization of pre-operative anemia in patients undergoing surgery by a gynecologic oncologist and association with post-operative complications.

OBJECTIVE: Anemia is prevalent in patients with gynecologic cancers and is associated with increased peri-operative morbidity. We aimed to characterize risk factors for pre-operative anemia and describe outcomes among patients undergoing surgery by a gynecologic oncologist to identify potential areas for impactful intervention. METHODS: We analyzed major surgical cases performed by a gynecologic oncologist in the National Surgical Quality Improvement Program (NSQIP) database from 2014 to 2019. Anemia was defined as hematocrit <36%. Demographic characteristics and peri-operative variables for patients with and without anemia were compared using bivariable tests. Odds of peri-operative complications in patients stratified by pre-operative anemia were calculated using logistic regression models. RESULTS: Among 60 017 patients undergoing surgery by a gynecologic oncologist, 23.1% had pre-operative anemia. Women with ovarian cancer had the highest rate of pre-operative anemia at 39.7%. Patients with advanced-stage cancer had a higher risk of anemia than early-stage disease (42.0% vs 16.3%, p≤0.001). In a logistic regression model adjusting for potential demographic, cancer-related, and surgical confounders, patients with pre-operative anemia had increased odds of infectious complications (odds ratio (OR) 1.16, 95% CI 1.07 to 1.26), thromboembolic complications (OR 1.39, 95% CI 1.15 to 1.68), and blood transfusion (OR 5.78, 95% CI 5.34 to 6.26). CONCLUSIONS: There is a high rate of anemia in patients undergoing surgery by a gynecologic oncologist, particularly those with ovarian cancer and/or advanced malignancy. Pre-operative anemia is associated with increased odds of peri-operative complications. Interventions designed to screen for and treat anemia in this population have the potential for significant impact on surgical outcomes.

Effect of pre-operative warm-up on trainee intraoperative performance during robot-assisted hysterectomy: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The objective was to study the effect of immediate pre-operative warm-up using virtual reality simulation on intraoperative robot-assisted laparoscopic hysterectomy (RALH) performance by gynecology trainees (residents and fellows). METHODS: We randomized the first, non-emergent RALH of the day that involved trainees warming up or not warming up. For cases assigned to warm-up, trainees performed a set of exercises on the da Vinci Skills Simulator immediately before the procedure. The supervising attending surgeon, who was not informed whether or not the trainee was assigned to warm-up, assessed the trainee's performance using the Objective Structured Assessment for Technical Skill (OSATS) and the Global Evaluative Assessment of Robotic Skills (GEARS) immediately after each surgery. RESULTS: We randomized 66 cases and analyzed 58 cases (30 warm-up, 28 no warm-up), which involved 21 trainees. Attending surgeons rated trainees similarly irrespective of warm-up randomization with mean (SD) OSATS composite scores of 22.6 (4.3; warm-up) vs 21.8 (3.4; no warm-up) and mean GEARS composite scores of 19.2 (3.8; warm-up) vs 18.8 (3.1; no warm-up). The difference in composite scores between warm-up and no warm-up was 0.34 (95% CI: -1.44, 2.13), and 0.34 (95% CI: -1.22, 1.90) for OSATS and GEARS respectively. Also, we did not observe any significant differences in each of the component/subscale scores within OSATS and GEARS between cases assigned to warm-up and no warm-up. CONCLUSION: Performing a brief virtual reality-based warm-up before RALH did not significantly improve the intraoperative performance of the trainees.

Uterine Leiomyosarcoma Associated With Leiomyoma With Bizarre Nuclei: Histology and Genomic Analysis of 2 Cases.

Leiomyoma with bizarre nuclei (LM-BN) is a rare variant of leiomyoma with overall benign clinical course. It has histologic features showing focal or diffuse nuclear atypia surrounded by usual type leiomyoma. Uterine leiomyosarcomas (LMS) are a group of rare and aggressive malignancies with limited treatment options available. The potential association between LM-BN with LMS is largely unknown. In this study, we report 2 cases of uterine smooth muscle tumor with typical histologic and molecular evidence of LM-BN, which are associated with its progression to the malignant counterpart of LMS. We summarize the detailed histologic, morphologic, and genomic characteristics of these 2 sets of cases. Our findings suggest that LMS progressing from preexisting LM-BN can be one of the tumor pathogenesis pathways in uterine leiomyosarcomas.

Discrepancies between author- and industry-reported disclosures of financial relationships at an annual gynecologic oncology research meeting.

OBJECTIVE: Trillions of dollars pass to physicians from industry-related businesses annually, leading to many opportunities for financial conflicts of interest. The Open Payments Database (OPD) was created to ensure transparency. We describe the industry relationships as reported in the OPD for presenters at the 2019 Society of Gynecologic Oncology (SGO) Annual Meeting and evaluate concordance between author disclosures of their financial interests and information provided by the OPD. METHODS: This is an observational, cross-sectional study. Disclosure data were collected from authors with oral and featured abstract presentations in the 2019 SGO annual conference. These disclosures were compared to data available for each author in the 2018 OPD, which included the amount and nature of industry payments. RESULTS: We examined the disclosures of 301 authors who met inclusion criteria. Of 161 authors who had disclosure statements on their presentations,147 reported "no disclosures," and 14 disclosed industry relationships. The remaining 140 did not list any disclosure information. Sixty percent (184/301) of authors had industry relationships in the 2018 OPD, including 173 of 287 (60.3%) of authors who either reported no disclosures or did not have disclosure data available in their presentations. These transactions totaled over 43 million USD from 122 different companies, with most payments (46%) categorized as "Research or Associated Research." Accurate disclosure reporting was associated with receiving higher payments or research payments, and being a presenting author. CONCLUSIONS: Most authors at the SGO annual conference did not correctly disclose their industry relationships when compared with their entries in the OPD.

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

Treatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation.

OBJECTIVE: Plasma energy ablation vaporizes tissues similar to carbon dioxide laser ablation, but is not hindered by the unique hazards and regulation of laser technology. We aimed to evaluate the complication rate and effectiveness of plasma versus laser ablation in the treatment of vulvovaginal high-grade squamous intra-epithelial lesions (HSIL). METHODS: We performed a retrospective cohort study of women treated with plasma or carbon dioxide laser ablation for histologically proven HSIL of the vulva or vagina from January 2014 to October 2019 at a single institution. Demographic factors, surgical characteristics, and complications were compared by ablation type using Fisher's exact tests. Recurrence-free survival was evaluated by ablation type using Kaplan-Meier curves, weighted log-rank tests, and Cox proportional hazards ratio estimates. RESULTS: Forty-two women were included; 50% underwent plasma and 50% underwent carbon dioxide laser ablation. Demographic factors were similar between the groups. 50% (n=21) were immunosuppressed, 45.2% (n=19) had prior vulvovaginal HSIL treatment, and 35.7% (n=15) were current smokers. Most women (n=25, 59.5%) were treated for vulvar HSIL, 38.1% (n=16) for vaginal HSIL. Complication rates did not differ by treatment: 9.5% (n=2) for laser ablation versus 4.8% (n=1) for plasma ablation (p=1.0). Over a median follow-up time of 29.3 months (IQR 11.0-45.0 months), recurrence rates were similar: 28.6% in the laser ablation group versus 33.3% in the plasma ablation group (weighted log rank p=0.43; 24-month HR 0.54, 95% CI 0.15 to 2.01). CONCLUSION: Plasma energy ablation of vulvovaginal HSIL has similar complication rates and recurrence risk to carbon dioxide laser ablation. This technique could be considered as an alternative treatment modality for vulvovaginal HSIL and warrants further investigation.

The addition of metformin to progestin therapy in the fertility-sparing treatment of women with atypical hyperplasia/endometrial intraepithelial neoplasia or endometrial cancer: Little impact on response and low live-birth rates.

OBJECTIVE: Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment. METHODS: A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999-2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models. RESULTS: Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m2, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group. CONCLUSIONS: Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART.

Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study.

OBJECTIVE: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.

Association between surgical approach and survival following resection of abdominopelvic malignancies.

BACKGROUND AND OBJECTIVES: Recent studies demonstrating decreased survival following minimally invasive surgery (MIS) for cervical cancer have generated concern regarding oncologic efficacy of MIS. Our objective was to evaluate the association between surgical approach and 5-year survival following resection of abdominopelvic malignancies. METHODS: Patients with stage I or II adenocarcinoma of the prostate, colon, rectum, and stage IA2 or IB1 cervical cancer from 2010-2015 were identified from the National Cancer Data Base. The association between surgical approach and 5-year survival was assessed using propensity-score-matched cohorts. Distributions were compared using logistic regression. Hazard ratio for death was estimated using Cox proportional-hazard models. RESULTS: The rate of deaths at 5 years was 3.4% following radical prostatectomy, 22.9% following colectomy, 18.6% following proctectomy, and 6.8% following radical hysterectomy. Open surgery was associated with worse survival following radical prostatectomy (HR, 1.18; 95% CI, 1.05-1.33; P = .005), colectomy (HR, 1.45; 95% CI, 1.39-1.51; P < .001), and proctectomy (HR, 1.28; 95% CI, 1.10-1.50; P = .002); however, open surgery was associated with improved survival following radical hysterectomy (HR, 0.61; 95% CI, 0.44-0.82; P = .003). CONCLUSIONS: These results suggest that MIS is an acceptable approach in selected patients with prostate, colon, and rectal cancers, while concerns regarding MIS resection of cervical cancer appear warranted.

Minimally Invasive Surgery Rate as a Quality Metric for Endometrial Cancer.

STUDY OBJECTIVE: To determine the frequency with which Commission on Cancer-accredited hospitals met a metric of ≥80% minimally invasively performed hysterectomies for endometrial cancer and to compare the clinical outcomes of hospitals meeting this metric with those that did not. DESIGN: Retrospective cohort study. SETTING: Hospitals caring for ≥20 endometrial cancer patients per year recorded in the National Cancer Database in 2015 were included. PATIENTS: Women who had undergone hysterectomy for endometrial cancer and had an epithelial histology, a Charlson comorbidity score of 0, and stage I to III disease. INTERVENTION: Patient characteristics, patterns of care, and outcomes were compared between hospitals performing ≥80% minimally invasive hysterectomies and hospitals not meeting this metric. MEASUREMENTS AND MAIN RESULTS: The hospitals (n = 510) treated 20 670 women with endometrial cancer. In 283 (55%) hospitals ≥80% of hysterectomies were minimally invasively performed (high-minimally invasive surgery [MIS] hospitals, overall MIS rate 89%). In the 227 hospitals that did not meet this metric, 61% of hysterectomies for endometrial cancer were performed using a minimally invasive approach. In high-MIS hospitals, patients were more likely to be white (87% vs 82%, p<.001), privately insured (53% vs 49%, p <.001), and have stage I disease (84% vs 82%, p = .002) and an endometrioid histology (79% vs 76%, p <.001). Surgery was more often performed robotically (80% vs 71%), and conversion to laparotomy was less likely (1.5% vs 3.2%, adjusted odds ratio [aOR], 0.47; 95% confidence interval [CI], 0.39-0.57) (both p <.001). Patients treated at high-MIS hospitals were more likely to have undergone lymph node assessment at the time of surgery (76% vs 69%; aOR, 1.43; 95% CI, 1.35-1.53) and been discharged on the same or next day (74% vs 57%; aOR, 2.27; 95% CI, 2.13-2.42) and were less likely to have an unplanned 30-day readmission (1.8% vs 2.9%; aOR, 0.64; 95% CI, 0.53-0.77). CONCLUSION: An MIS rate of ≥80% for endometrial cancer is feasible on a national scale and is associated with other hospital-level measurements of high-quality care.

Risk of empty lymph node packets in sentinel lymph node mapping for endometrial cancer using indocyanine green.

OBJECTIVE: To determine whether the rate of sentinel lymph node (SLN) dissections that do not yield a lymph node on pathological analysis ('empty packet dissection') changes with increasing surgeon experience in the setting of patients undergoing minimally invasive hysterectomy and SLN mapping using indocyanine green dye for endometrial cancer. METHODS: All patients undergoing SLN mapping using indocyanine green dye at the time of minimally invasive hysterectomy for endometrial cancer or complex atypical hyperplasia were identified between January 2013 and September 2017 at our institution. All surgeons had prior experience performing SLN mapping for endometrial cancer using other methods. The rate of empty packet dissections and SLN counts were evaluated using a logistic regression model analysis. RESULTS: In total, 236 patients undergoing SLN mapping for either endometrial cancer (85%) or complex atypical hyperplasia (15%) were identified from a prospectively maintained database. When examining all six surgeons together, the percentage of empty packet dissections decreased with increasing number of procedures performed. Each additional procedure was associated with a 3.6% reduction in the odds of an empty packet SLN dissection. After adjusting for individual surgeons, each additional procedure was associated with a 4.9% reduction in the odds of an empty packet. The expected odds of an empty packet after 10 additional procedures decreased by 40.1% (95% CI 12.4% to 58.6%). The addition of two covariates (age and body mass index) did not contribute significantly to the model (likelihood ratio test: X2=2.75, p=0.25). The rate of empty packets appeared to stabilize after approximately 30 procedures. The number of SLNs removed did not change with increasing surgeon experience. CONCLUSION: The rate of empty packet SLN dissections using indocyanine green dye decreases with increasing number of procedures. This stabilizes after 30 procedures, suggesting completion of a learning curve.

A prospective trial of acute normovolemic hemodilution in patients undergoing primary cytoreductive surgery for advanced ovarian cancer.

OBJECTIVES: Our objective was to determine the safety and efficacy of acute normovolemic hemodilution (ANH) to reduce the requirement for allogenic red blood cell (RBC) transfusions in patients undergoing primary cytoreduction for advanced ovarian cancer. METHODS: Patients undergoing primary cytoreduction for advanced ovarian cancer were enrolled in a prospective trial assessing ANH at time of surgery. Intraoperative blood withdrawal was performed to a target hemoglobin of 8.0 g/dL. A standardized transfusion protocol first using autologous then allogenic blood was applied intraoperatively and throughout hospitalization according to institutional guidelines. The primary endpoint was to determine the overall rate of allogenic RBC transfusions in the intra- and postoperative periods. A predetermined allogenic RBC transfusion rate <35% was deemed a meaningful reduction from a 50% transfusion rate in historical controls. RESULTS: Forty-one patients consented to participate. Median blood withdrawn during ANH was 1650 mL (range, 700-3000). Cytoreductive outcomes were as follows: 0 mm, 30 (73%); 1-10 mm, 8 (20%); and >10 mm, 3 (7%) residual disease. Estimated blood loss was 1000 mL (range, 150-2700). Fourteen patients (34%) received allogenic RBC transfusions intra- or postoperatively, meeting the primary endpoint. No patients were transfused outside protocol guidelines. The rate of ≥grade 3 complications (20%) and anastomotic leaks (7%) were similar to historical controls and met predefined safety thresholds. CONCLUSIONS: For patients with advanced ovarian cancer undergoing primary cytoreductive surgery, ANH appears to reduce allogenic RBC transfusion rates versus historical controls without increasing perioperative complications. Further evaluation of the technique is warranted.

Minimally invasive hysterectomy surgery rates for endometrial cancer performed at National Comprehensive Cancer Network (NCCN) Centers.

OBJECTIVES: Minimally invasive surgery (MIS) is a quality measure for endometrial cancer (EC) established by the Society of Gynecologic Oncology and the American College of Surgeons. Our study objective was to assess the proportion of EC cases performed by MIS at National Comprehensive Cancer Network (NCCN) centers and evaluate perioperative outcomes. METHODS: A retrospective cohort study of women who underwent surgical treatment for EC from 2013 to 2014 was conducted at four NCCN centers. Multivariable mixed logistic regression models analyzed factors associated with failure to perform MIS and perioperative complications. RESULTS: In total 1621 patients were evaluated; 86.5% underwent MIS (robotic-assisted 72.5%, laparoscopic 20.9%, vaginal 6.6%). On multivariable analysis, factors associated with failure to undergo MIS were uterine size >12cm (Odds Ratio [OR]: 0.17, 95% CI 0.03-0.9), stage III (OR: 0.16, 95% CI 0.05-0.49) and IV disease (OR: 0.07, 95% CI 0.02-0.22). For stage I/II disease, complications occurred in 5.1% of MIS and 21.7% of laparotomy cases (p<0.01). Laparotomy was associated with increases in any complication (OR: 6.0, 95% CI 3.3-10.8), gastrointestinal (OR: 7.2, 95% CI 2.6-19.5), wound (OR: 3.7, 95% CI 1.5-9.2), respiratory (OR 37.5, 95% CI 3.9-358.0), VTE (OR 10.5, 95% CI 1.3-82.8) and 30-day readmission (OR: 2.6, 95% CI 1.4-4.9) compared to MIS. CONCLUSIONS: At NCCN-designated centers, the MIS hysterectomy rate in EC is higher than the published national average, with low perioperative complications. Previously identified disparities of age, race, and BMI were not observed. A proposed MIS hysterectomy benchmark of >80% in EC care is feasible when performed at high volume centers.

Narcotics reduction, quality and safety in gynecologic oncology surgery in the first year of enhanced recovery after surgery protocol implementation.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs are mechanisms for achieving value-based improvements in surgery. This report provides a detailed analysis of the impact of an ERAS program on patient outcomes as well as quality and safety measures during implementation on a gynecologic oncology service at a major academic medical center. METHODS: A retrospective review of gynecologic oncology patients undergoing elective laparotomy during the implementation phase of an ERAS program (January 2016 through December 2016) was performed. Patient demographics, surgical variables, postoperative outcomes, and adherence to core safety measures, including antimicrobial and venous thromboembolism (VTE) prophylaxis, were compared to a historical patient cohort (January 2015 through December 2015). Statistical analyses were performed using t-tests, Wilcoxon rank sum tests, and Chi squared tests. RESULTS: The inaugural 109 ERAS program participants were compared to a historical patient cohort (n=158). There was no difference in BMI, race, malignancy, or complexity of procedure between cohorts. ERAS patients required less narcotics (70.7 vs 127.4, p=0.007, oral morphine equivalents) and PCA use (32.1% vs. 50.6%, p=0.002). Despite this substantial reduction in narcotics, ERAS patients did not report more pain and in fact reported significantly less pain by postoperative day 3. There were no differences in length of stay (5days), complication rates (13.8% vs. 20.3%, p=0.17) or 30-day readmission rates (9.5 vs 11.9%, p=0.54) between ERAS and historical patients, respectively. Compliance with antimicrobial prophylaxis was 97.2%. However, 33.9% of ERAS patients received substandard preoperative VTE prophylaxis. CONCLUSIONS: ERAS program implementation resulted in reductions in narcotic requirements and PCA use without changes in length of stay or readmission rates. Compliance should be diligently audited during the implementation phase of ERAS programs, with special attention to adherence to pre-existing core safety measures.

Loss of ARID1A expression in endometrial samplings is associated with the risk of endometrial carcinoma.

OBJECTIVES: Inactivating somatic mutations of ARID1A, a chromatin remodeling gene, are common in endometrioid endometrial carcinoma (EEC) but rare in complex atypical hyperplasia (CAH). Our objectives were to determine the clinical significance of ARID1A loss during tumor progression from CAH to EEC and to assess its role as a predictive cancer biomarker. METHODS: In cohort A, ARID1A immunoreactivity was evaluated in endometrial sampling (biopsy/curettage) specimens showing CAH to determine whether ARID1A expression correlates with the presence of EEC at subsequent hysterectomy. In cohort B, ARID1A immunoreactivity was evaluated in the hysterectomy specimens with concurrent CAH and EEC to assess for the concordance of ARID1A expression in both components. RESULTS: In cohort A, loss of ARID1A immunoreactivity was identified in the endometrial sampling specimen of 31% of patients undergoing hysterectomy for a preoperative diagnosis of CAH. EEC was identified in the hysterectomy specimen of 94% of patients with loss of ARID1A in the endometrial sampling specimen while only 15% of patients with retained ARID1A expression (P < 0.0001). No association was observed between ARID1A expression and demographic characteristics. In cohort B, 14 (31%) of 45 patients with concurrent CAH/EEC in their hysterectomy specimens had complete loss of ARID1A expression in the EEC components. Among these 14 patients, 50% also had loss of ARID1A immunoreactivity in the CAH component. CONCLUSIONS: ARID1A immunostaining may correlate with malignant transformation and the presence of concurrent EEC in patients with CAH identified at pre-hysterectomy endometrial sampling. Further investigation to determine the potential utility of ARID1A expression as a tissue biomarker is warranted.

Where Are We Going with Sentinel Lymph Node Mapping in Gynecologic Cancers?

PURPOSE OF REVIEW: Sentinel lymph node (SLN) mapping is a standard of care for lymphatic assessment of many early-stage gynecologic malignancies. We review the current data, emphasizing the utility of SLN mapping in the management of gynecologic cancers. RECENT FINDINGS: Endometrial cancer: recent studies have focused on confirming the safety and efficacy of SLN mapping for high-risk patients. Cervical cancer: the LACC Trial demonstrated reduced survival with minimally invasive surgery, calling into question the validity of prior studies evaluating SLN mapping with a minimally invasive approach. Vulvar cancer: the ongoing GROINS-V-II trial is investigating whether patients with SLN metastasis < 2 mm in diameter can safely undergo adjuvant radiation ± chemotherapy without completion inguinal lymphadenectomy. NCCN guidelines have incorporated SLN mapping as a lymphatic assessment strategy for endometrial, cervical, and vulvar malignancies. SLN mapping appears to reduce morbidity while still maintaining an appropriate detection rate of lymphatic metastasis. Additional clinical trials will further our knowledge of these procedures.

Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations.

The emphasis in contemporary medical oncology has been "precision" or "personalized" medicine, terms that imply a strategy to improve efficacy through targeted therapies. Similar attempts at precision are occurring in surgical oncology. Sentinel lymph node (SLN) mapping has recently been introduced into the surgical staging of endometrial cancer with the goal to reduce morbidity associated with comprehensive lymphadenectomy, yet obtain prognostic information from lymph node status. The Society of Gynecologic Oncology's (SGO) Clinical Practice Committee and SLN Working Group reviewed the current literature for preparation of this document. Literature-based recommendations for the inclusion of SLN assessment in the treatment of patients with endometrial cancer are presented. This article examines.

Primary cytoreductive surgery and adjuvant hormonal monotherapy in women with advanced low-grade serous ovarian carcinoma: Reducing overtreatment without compromising survival?

OBJECTIVES: Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). METHODS: A retrospective study was performed at two academic cancer centers. Patients with Stage II-IV LGSC underwent either primary or interval CRS followed by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all cases. Two-year progression-free (PFS) and overall survival (OS) were calculated. RESULTS: Twenty-seven patients were studied; primary CRS followed by HT were administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction to no gross residual was achieved in 85.2%. Ninety six percent of tumors expressed estrogen receptors, while only 32% expressed progesterone receptors. Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1% and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients (22.2%) have developed a tumor recurrence and two patients have died of disease. Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and 96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively. CONCLUSIONS: Our series describes the initial experience with cytoreductive surgery and hormonal monotherapy for women with Stage II-IV primary ovarian LGSC. While surgery remains the mainstay of treatment, chemotherapy may not be necessary in patients with advanced-stage disease who receive adjuvant hormonal therapy. A cooperative group, Phase III trial is planned to define the optimal therapy for women with this ovarian carcinoma subtype.

Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: In the staging of endometrial cancer, controversy remains regarding the role of sentinel lymph node mapping compared with other nodal assessment strategies. OBJECTIVE: We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of sentinel lymph node mapping in the management of endometrial cancer. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Registry of Controlled trials for studies published in English before March 25, 2016 (PROSPERO CRD42016036503). STUDY ELIGIBILITY CRITERIA: Studies were included if they contained 10 or more women with endometrial cancer and reported on the detection rate, sensitivity, and/or impact on treatment or survival of sentinel lymph node mapping. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. The detection rate, sensitivity, and factors associated with successful mapping (study size, body mass index, tumor histology and grade, injection site, dye type) were synthesized through random-effects meta-analyses and meta-regression. RESULTS: We identified 55 eligible studies, which included 4915 women. The overall detection rate of sentinel lymph node mapping was 81% (95% confidence interval, 77-84) with a 50% (95% confidence interval, 44-56) bilateral pelvic node detection rate and 17% (95% confidence interval, 11-23) paraaortic detection rate. There was no difference in detection rates by patient body mass index or tumor histology and grade. Use of indocyanine green increased the bilateral detection rate compared with blue dye. Additionally, cervical injection increased the bilateral sentinel lymph node detection rate but decreased the paraaortic detection rate compared with alternative injection techniques. Intraoperative sentinel lymph node frozen section increased the overall and bilateral detection rates. The sensitivity of sentinel node mapping to detect metastases was 96% (95% confidence interval, 91-98); ultrastaging did not improve sensitivity. Compared with women staged with complete lymphadenectomy, women staged with sentinel lymph node mapping were more likely to receive adjuvant treatment. CONCLUSION: Sentinel lymph node mapping is feasible and accurately predicts nodal status in women with endometrial cancer. The current data favors the use of cervical injection techniques with indocyanine green. Sentinel lymph mapping may be considered an alternative standard of care in the staging of women with endometrial cancer.