Mapping the robotic hysterectomy learning curve and re-establishing surgical training metrics.

OBJECTIVE: Common robotic training curricula in the US entail completion of an online module followed by lab training with standardized exercises, such as manipulating needles with robotic needle drivers. Assessments are generally limited to elapsed time and subjective proficiency. We sought to test the feasibility of a simulation-based robotic hysterectomy curriculum to collect objective measurements of trainee progress, map the trainee learning curve and provide a system for trainee-specific evaluation. METHODS: An observational cohort study of a single institutions' residency members participating in a procedural hysterectomy simulation performed every 4 months. Each simulation episode had one-on-one teaching. The robotic platform was used to measure all movements within cartesian coordinates, the number of clutches, instrument collisions, time to complete the simulated hysterectomy, and unintended injuries during the procedure. RESULTS: Voluntary participation was high. Objective metrics were successfully recorded at each session and improved nearly universally. More senior residents demonstrated superior capabilities compared to junior residents as expected. The majority of residents (29/31) were able to complete an entire simulated hysterectomy in the allotted 30-minute training session period by the end of the year. CONCLUSIONS: This program establishes learning curves based on objective data points using a risk-free simulation platform. The curves can then be used to evaluate trainee skill level and tailor teaching to specific objective competencies. The pilot curriculum can be tailored to the unique needs of each surgical discipline's residency training.

The Society of Gynecologic Oncology wellness curriculum pilot: A groundbreaking initiative for fellowship training.

OBJECTIVES: Trainee well-being is a core component of ACGME program requirements and the SGO has recognized the high incidence of burnout among gynecologic oncologists and its negative impact. To foster a culture of wellness throughout the SGO community we sought to engage current fellows along with fellowship directors in a structured didactic program designed to teach wellness. We evaluated the feasibility of and preliminary responses to a pilot curriculum designed to teach skills that promote wellness and prevent burnout. METHODS: The SGO Wellness Taskforce developed a curriculum with topics based on established evidence as well as specialty specific stressors such as end of life discussions. Faculty leaders from 15 pilot-sites attended a full-day training course and then taught four modules over four months. Interactive modules engaged fellows through reflective writing, guided discussion, and multimedia presentations. Fellows completed the Perceived Stress Scale pre- and post-implementation and provided feedback regarding attitudes toward wellness and the individual modules. Faculty curriculum leaders completed surveys regarding their attitudes toward the curriculum as well as their trainees' reactions. RESULTS: Among 73 participating gynecologic oncology fellows, 95% (69/73) and 52/73 (71%) completed the pre-and post-surveys, respectively. Only 34/73 (49%) respondents reported that there was wellness programming at their institution prior to the initiation of the SGO curriculum. At institutions where such programming was available, 35% (12/34) reported not utilizing them. Fifty-five (80%) fellows had PSS scores greater than 12 compared to 39 (75%) post-intervention. After the curriculum, the percentage of fellows comfortable discussing wellness topics increased from 63 to 74%. Prior to the curriculum, 75% felt they could identify symptoms of burnout or psychosocial distress. This increased to 90% post-intervention. The modules were well received by fellows, and the time spent addressing wellness was widely appreciated. CONCLUSIONS: A structured curriculum to promote wellness among gynecologic oncology fellows is feasible and was associated with observed decreased reported stress among fellows at participating programs. This curriculum addresses ACGME requirements regarding trainee well-being, and showed potential for more programmatic, nationwide implementation. Fellowship culture change was not directly measured, but may have been one of the most significant positive outcomes of the wellness program. Further longitudinal studies will be necessary to understand the natural course of fellow burnout and the impact of structured wellness programming.

The Reliability of Intraoperative Assessment on Predicting Tumor Size, Myometrial Invasion, and Cervical Involvement in Patients With a Preoperative Diagnosis of Complex Atypical Hyperplasia or (Clinical Stage I) Endometrial Cancer: A Prospective Cohort Study.

OBJECTIVES: The objective of this study is to assess the reliability of intraoperative uterine assessment compared with the final pathologic evaluation in patients with endometrial cancer (EC) and whether assessment improves with experience. METHODS: After Institutional Review Board approval, a prospective cohort study of women surgically managed with biopsy-proven complex atypical hyperplasia (CAH) or EC between March 2015 and December 2016 was performed. Demographics, preoperative biopsy results, procedure, intraoperative and final pathologic evaluation of lesion size, myometrial invasion, and lower uterine segment/cervical involvement were abstracted. The agreement between the intraoperative and final pathologic evaluation of tumor involvement of the uterus was determined using the kappa statistic and the intraclass correlation coefficient. RESULTS: A total of 264 patients with a preoperative diagnosis of CAH or EC were included-71 (26.9%) with CAH and 193 (73.1%) with EC. The mean age was 62.6±11.5, and mean body mass index was 37.2±10.1. The majority of women were white (67%). A total of 227 (85.9%) patients underwent a laparoscopic or robotic hysterectomy, whereas 36 (13.6%) underwent an abdominal hysterectomy. 233 (88.3%) patients had EC and 21 (7.9%) patients had CAH on final pathology. There was a fair agreement between the intraoperative estimation of myometrial invasion (κ=0.37). A moderate agreement exists between the intraoperative estimation of lower uterine segment/cervical involvement (κ=0.57). There was a strong agreement between intraoperative tumor size assessment and the final path (intraclass correlation coefficient=0.74). The intraoperative correlation of tumor size was similar for the first half of the cohort (κ=0.50) and the second half (κ=0.46) chronologically. CONCLUSIONS: Despite only a fair correlation in the myometrial invasion, intraoperative assessment of cervical involvement and especially tumor size is more readily identified and overall accurate. Therefore, intraoperative evaluation is an additional tool to use when making the decision to proceed with surgical staging.

Differences in referral patterns based on race for women at high-risk for ovarian cancer in the southeast: Results from a Gynecologic Cancer Risk Assessment Clinic.

OBJECTIVE: To compare referral patterns, genetic testing and pathogenic variant rates in Black women (BW) and White women (WW) in a large academic Gynecologic Cancer Risk Assessment Clinic (GCRAC). METHODS: Cross sectional study of an IRB-approved prospective, cohort study from a GCRAC. Data evaluated included: age, race, referral provider specialty and indication, genetic testing frequency, as well as frequency and types of pathogenic variants. RESULTS: 588 WW and 57 BW were evaluated from 1/2010-12/2015. Although approximately one-third of BW and WW were referred for family history alone, referral indications varied. BW were more likely referred for a known pathogenic variant (20.0% vs. 6.2%) although less likely referred for a personal history of ovarian cancer (24.0% vs. 46.8%; p = 0.0023). While gynecologic oncologists referred most patients (BW 43.6% vs. WW 63.0%), BW were more likely to be referred by surgical oncologist (23.0% vs. 12.8%) or genetic counselor (12.8% vs. 5.9%) than WW (p = 0.0234). Referral from non-OBGYN primary care providers was <3% in both groups. Genetic testing rates were similar in both races (82.4% vs. 85.5%). Rates of BRCA1 mutations (12.7% vs. 11.5%) were similar; however, BW had more BRCA2 mutations (21.3% vs. 9.5%; p = 0.0194). CONCLUSIONS: Since BW are more likely to be referred by surgical oncology or genetics counselor, breast clinics might be an entry point to ensure genetic counseling and testing. Continued efforts to increase awareness regarding the importance of patient referral at the primary care level may help identify the subset of women not currently undergoing counseling and testing.

The impact of physician burnout on clinical and academic productivity of gynecologic oncologists: A decision analysis.

OBJECTIVE: Physician burnout is associated with mental illness, alcohol abuse, and job dissatisfaction. Our objective was to estimate the impact of burnout on productivity of gynecologic oncologists during the first half of their career. METHODS: A decision model evaluated the impact of burnout on total relative value (RVU) production during the first 15years of practice for gynecologic oncologists entering the workforce from 2011 to 2015. The SGO practice survey provided physician demographics and mean annual RVUs. Published data were used to estimate probability of burnout for male and female gynecologic oncologists, and the impact of depression, alcohol abuse, and early retirement. Academic productivity was defined as annual PubMed publications since finishing fellowship. RESULTS: Without burnout, RVU production for the cohort of 250 gynecologic oncologists was 26.2 million (M) RVUs over 15years. With burnout, RVU production decreased by 1.6 M (5.9% decrease). Disproportionate rates of burnout among females resulted in 1.1 M lost RVUs for females vs. 488 K for males. Academic production without burnout was estimated at 9277 publications for the cohort. Burnout resulted in 1383 estimated fewer publications over 15years (14.9%). CONCLUSIONS: The impact of burnout on clinical and academic productivity is substantial across all specialties. As health care systems struggle with human resource shortages, this study highlights the need for effective burnout prevention and wellness programs for gynecologic oncologists. Unless significant resources are designated to wellness programs, burnout will increasingly affect the care of our patients and the advancement of our field.

Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.

Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent. A dose dependent response in mRNA and protein expression was seen with entinostat. Combination treatment showed higher MHC II protein expression than with single agent treatment. In patient derived xenografts, CIITA, CD74, and MHC II mRNA transcripts were significantly increased after combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice was increased with both agents relative to control. Combination treatment significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic treatment increases expression of MHC II on ovarian cancer cells and impedes tumor growth. This approach warrants further study in ovarian cancer patients.

Comparative primate obstetrics: Observations of 15 diurnal births in wild gelada monkeys (Theropithecus gelada) and their implications for understanding human and nonhuman primate birth evolution.

OBJECTIVES: The birth process has been studied extensively in many human societies, yet little is known about this essential life history event in other primates. Here, we provide the most detailed account of behaviors surrounding birth for any wild nonhuman primate to date. MATERIALS AND METHODS: Over a recent ∼10-year period, we directly observed 15 diurnal births (13 live births and 2 stillbirths) among geladas (Theropithecus gelada) at Guassa, Ethiopia. During each birth, we recorded the occurrence (or absence) of 16 periparturitional events, chosen for their potential to provide comparative evolutionary insights into the factors that shaped birth behaviors in humans and other primates. RESULTS: We found that several events (e.g., adopting standing crouched positions, delivering infants headfirst) occurred during all births, while other events (e.g., aiding the infant from the birth canal, licking infants following delivery, placentophagy) occurred during, or immediately after, most births. Moreover, multiparas (n = 9) were more likely than primiparas (n = 6) to (a) give birth later in the day, (b) isolate themselves from nearby conspecifics while giving birth, (c) aid the infant from the birth canal, and (d) consume the placenta. DISCUSSION: Our results suggest that prior maternal experience may contribute to greater competence or efficiency during the birth process. Moreover, face presentations (in which infants are born with their neck extended and their face appearing first, facing the mother) appear to be the norm for geladas. Lastly, malpresentations (in which infants are born in the occiput anterior position more typical of human infants) may be associated with increased mortality in this species. We compare the birth process in geladas to those in other primates (including humans) and discuss several key implications of our study for advancing understanding of obstetrics and the mechanism of labor in humans and nonhuman primates.

Ovarian cancer and the immune system - The role of targeted therapies.

The majority of patients with epithelial ovarian cancer are diagnosed with advanced disease. While many of these patients will respond initially to chemotherapy, the majority will relapse and die of their disease. Targeted therapies that block or activate specific intracellular signaling pathways have been disappointing. In the past 15years, the role of the immune system in ovarian cancer has been investigated. Patients with a more robust immune response, as documented by the presence of lymphocytes infiltrating within their tumor, have increased survival and better response to chemotherapy. In addition, a strong immunosuppressive environment often accompanies ovarian cancer. Recent research has identified potential therapies that leverage the immune system to identify and destroy tumor cells that previously evaded immunosurveillance mechanisms. In this review, we discuss the role of the immune system in ovarian cancer and focus on specific pathways and molecules that show a potential for targeted therapy. We also review the ongoing clinical trials using targeted immunotherapy in ovarian cancer. The role of targeted immunotherapy in patients with ovarian cancer represents a field of growing research and clinical importance.

HPV vaccines: Translating immunogenicity into efficacy.

Currently available human papillomavirus (HPV) vaccines are very successful at preventing persistent HPV infection and premalignant cervical lesions. In part due to the unique aspects of HPV immunogenicity and high levels of efficacy no immune correlate has been identified for HPV vaccination. Serum neutralizing antibodies are used to measure vaccine response, but their role as a correlate has not been verified, and this theory fails to explain the prevention of HPV related non-mucosal lesions. Identifying a true correlate would aid in future work in this area but will be difficult in the setting of a highly efficacious vaccine.

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma.

OBJECTIVES: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. RESULTS: Thirty-one angiogenic-related genes were significantly associated with survival (q≤0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p=0.01, HR=0.8), CD44 (q=0.003; TCGA p=0.05, HR=0.9), EPHB2 (q=0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q=0.02; TCGA p=0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q=0.03; GSE26712 p=0.01, HR=3.1); PF4 (q=0.02; GSE26712 p=0.01, HR=3.0); NRP1 (q=0.02; GSE26712 p<0.04, HR>1.4); COL4A3 (q=0.04; GSE26712 p=0.03, HR=1.3); and ANGPTL3 (q=0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. CONCLUSIONS: Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases.

Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging.

STUDY OBJECTIVE: To retrospectively evaluate perioperative pain and analgesic and antiemetic use in patients who underwent surgical staging for endometrial cancer using traditional versus robotic-assisted laparoscopy. DESIGN: We identified women in a single institution who underwent minimally hysterectomy for endometrial cancer from 2008 to 2012. Patient characteristics and perioperative outcomes, including analgesic and antiemetic use and pain scores, were analyzed. After univariate analysis, a multivariate linear regression model was generated to determine factors associated with narcotic use in the post anesthesia care unit (PACU) (Canadian Task Force Classification II-3). SETTING: A single academic institution in the United States from 2008 to 2012. PATIENTS: Women undergoing total laparoscopic hysterectomy or robotic-assisted laparoscopic hysterectomy for endometrial cancer. INTERVENTIONS: Laparoscopic or robotic-assisted laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: Three hundred thirty-five women were included (213 laparoscopy and 122 robotic-assisted laparoscopy). There was no difference in pain scores at 0 to 6 and 6 to 12 hours after surgery; at 12 to 24 hours, robotic-assisted surgery was associated with higher median pain scores (5/10 vs 4/10, p = .012). Robotic-assisted surgery was associated with a longer anesthesia time (289 vs 255 minutes, p < .001), similar antiemetic use (p = .40), and lower narcotic use in the postanesthesia care unit (PACU) (1.3 mg vs 2.5 mg morphine equivalents, p = .003). There was no difference in narcotic use on the postoperative floor (p = .46). In multivariate analysis controlling for age, menopausal status, anesthesia duration, and local anesthetic use, hysterectomy type was not a significant predictor of PACU narcotic use (p = .86). CONCLUSIONS: In a retrospective analysis, a robotic-assisted approach to endometrial cancer was not associated with reduced PACU narcotic or antiemetic use compared with the traditional laparoscopic approach. Twenty-four-hour narcotic and antiemetic use was also not different between the 2 approaches.

Fitness impacts of tapeworm parasitism on wild gelada monkeys at Guassa, Ethiopia.

Parasitism is expected to impact host morbidity or mortality, although the fitness costs of parasitism have rarely been quantified for wildlife hosts. Tapeworms in the genus Taenia exploit a variety of vertebrates, including livestock, humans, and geladas (Theropithecus gelada), monkeys endemic to the alpine grasslands of Ethiopia. Despite Taenia's adverse societal and economic impacts, we know little about the prevalence of disease associated with Taenia infection in wildlife or the impacts of this disease on host health, mortality and reproduction. We monitored geladas at Guassa, Ethiopia over a continuous 6½ year period for external evidence (cysts or coenuri) of Taenia-associated disease (coenurosis) and evaluated the impact of coenurosis on host survival and reproduction. We also identified (through genetic and histological analyses) the tapeworms causing coenurosis in wild geladas at Guassa as Taenia serialis. Nearly 1/3 of adult geladas at Guassa possessed ≥1 coenurus at some point in the study. Coenurosis adversely impacted gelada survival and reproduction at Guassa and this impact spanned two generations: adults with coenuri suffered higher mortality than members of their sex without coenuri and offspring of females with coenuri also suffered higher mortality. Coenurosis also negatively affected adult reproduction, lengthening interbirth intervals and reducing the likelihood that males successfully assumed reproductive control over units of females. Our study provides the first empirical evidence that coenurosis increases mortality and reduces fertility in wild nonhuman primate hosts. Our research highlights the value of longitudinal monitoring of individually recognized animals in natural populations for advancing knowledge of parasite-host evolutionary dynamics and offering clues to the etiology and control of infectious disease.

Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report.

•Uterine morcellation is common in minimally invasive hysterectomy but should be performed with caution due to risk of unsuspected malignancy.•Intraoperative techniques should be considered to minimize dissemination of endometrial tissue during morcellation.•Strategies to ensure accurate pathologic evaluation of morcellated specimens and to improve preoperative risk stratification before morcellation procedures are necessary.