Basket study of oral progesterone antagonist onapristone extended release in progesterone receptor-positive recurrent granulosa cell, low-grade serous ovarian cancer, or endometrioid endometrial cancer.

OBJECTIVE: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC). METHODS: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety. RESULTS: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%). CONCLUSIONS: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed.

Barriers to cervical cancer prevention in a safety net clinic: gaps in HPV vaccine provider recommendation and series completion among Ob/Gyn patients.

Objective: The primary objective of this study was to evaluate patients' knowledge regarding HPV vaccination and vaccine uptake in a diverse patient population. The secondary objective was to evaluate factors influencing the decision to vaccinate, potential barriers to vaccination, and to assess whether HPV vaccines were offered to or discussed with eligible patients in a safety net Obstetrics and Gynecology (Ob/Gyn) clinic. Methods: A 28-item survey was developed using Likert scale survey questions to assess patient agreement with statements regarding HPV and the vaccine. The surveys were administered to patients in the Ob/Gyn outpatient clinics from May 2021 through September 2022. Additionally, pharmacy data were reviewed and chart review was performed as a quality improvement initiative to assess the impact of expanded HPV vaccine eligibility to patients with private insurance on vaccine uptake. Descriptive statistics were performed. Results: 304 patients completed surveys from May 2021 through September 2022. The median age of respondents was 32 (range 18-80). 16 (5%) were Non-Hispanic White, 124 (41%) were Hispanic White, 58 (19%) were Non-Hispanic Black, 6 (2%) were Hispanic Black, 29 (9.5%) were Haitian, 44 (14%) were Hispanic Other, 7 (2%) were Non-Hispanic Other, 20 (6.6%) did not respond. 45 (14%) patients were uninsured. Many patients (62%) reported that a physician had never discussed HPV vaccination with them. Seventy nine percent of patients reported they had never received the HPV vaccine, and 69% of patients reported that lack of a medical provider recommendation was a major barrier. Among patients to whom HPV vaccination had been recommended, 57% reported that the vaccine was not available the same day in clinic. Conclusion: Our study demonstrated that many patients never had a provider discuss HPV vaccination with them and never received the HPV vaccine. Additionally, amongst those who did initiate HPV vaccination, completion of the series remains a key barrier. Ensuring that providers discuss HPV vaccination and that patients receive HPV vaccines, along with expanding access to and convenience of HPV vaccination are critical aspects of preventing cervical cancer.

Cholecystectomy at the time of open cytoreductive surgery for ovarian cancer.

Introduction: We sought to demonstrate a method of performing open cholecystectomy at the time of cytoreductive surgery for ovarian cancer. Case/Methods: In this surgical film, we present the case of a 78-year-old woman with metastatic high-grade serous ovarian cancer who underwent primary cytoreductive surgery at Memorial Sloan Kettering Cancer Center (New York, NY). The surgery was recorded via video, and important steps of performing a cholecystectomy were highlighted. The indications for cytoreductive surgery and cholecystectomy were discussed. Right upper quadrant anatomy was reviewed, including key anatomic variants that can lead to inadvertent injury during dissection. The critical view of safety was emphasized, highlighting the requirement of clear visualization of the structures of the hepatocystic triangle (Strasberg et al., 1995, Strasberg and Brunt, 2010, Manatakis, 2023). Key considerations in identifying, isolating, and ligating the cystic artery and duct were reviewed. Perioperative outcomes were summarized. Conclusion: Performance of cholecystectomy at the time of cytoreductive surgery for advanced ovarian cancer is safe and feasible (Son, 2023). Anatomic variants to the biliary system are common, and it is important to be vigilant of the location and course of key structures to avoid inadvertent injury.

An overview of the current debate between using minimally invasive surgery versus laparotomy for interval cytoreductive surgery in epithelial ovarian cancer.

The standard of care for treatment of advanced-stage epithelial ovarian cancer is primarily surgery followed by platinum-based chemotherapy, with the operative goal to achieve complete gross resection. Cytoreductive surgeries for epithelial ovarian cancer historically were performed via open laparotomy; however, as minimally invasive techniques became more widely accepted within gynecologic oncology, interest in employing this approach in the setting of cytoreductive surgery for epithelial ovarian cancer has grown. The purpose of this review was to examine the current debate between the use of minimally invasive surgery versus laparotomy as an approach to interval cytoreductive surgery in advanced epithelial ovarian cancer. While numerous retrospective and feasibility studies have found comparable outcomes with respect to complete gross residual disease, progression-free survival, and overall survival between minimally invasive and laparotomy approaches to interval cytoreductive surgery for epithelial ovarian cancer, methodological challenges limit the utility of these data. Given potential risks of underestimating disease burden and failing to achieve complete resection using a minimally invasive approach, further rigorous studies are needed to evaluate the safety and efficacy of minimally invasive surgery in this setting and to better define the subset of patients who would receive the greatest benefit from a minimally invasive approach.

Guillain-Barre Syndrome With Concomitant Severe Preeclampsia: A Case Report.

With an estimated 100,000 new cases yearly worldwide, Guillain-Barre syndrome (GBS) is the most common cause of flaccid paralysis. GBS is exceedingly rare in pregnancy and carries high maternal and fetal risk. We report a case of a 38-year-old essential primigravida who presented at 38 weeks six days gestational age with ascending paraplegia progressing to dysarthria, dysphagia, and facial weakness. A clinical diagnosis of GBS was made in an outside institution, supported by elevated protein on lumbar puncture. During the antepartum period, a diagnosis of gestational hypertension progressed to preeclampsia with severe features when a sudden rise in liver function tests occurred. The patient underwent an uneventful planned cesarean delivery but could not be extubated due to respiratory failure. After a 20-day critical care admission, she was extubated and had an improvement in neurologic status to near her baseline.

Factors contributing to delays in initiation of front-line cervical cancer therapy: disparities in a diverse south Florida population.

OBJECTIVE: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation. METHODS: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis. RESULTS: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center. CONCLUSION: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time.

Leveraging teachable moments in cancer prevention by improving HPV vaccination in health professional students (HPS): A systematic review.

Introduction: Vaccination against HPV is safe and effective in cancer prevention, yet vaccination uptake remains low. Strong recommendation of HPV vaccination by healthcare providers increases immunization rates, but gaps in knowledge persist surrounding HPV and HPV vaccination amongst health professional students (HPS). It is critical to educate HPS in all professions to maximize vaccination opportunities and increase vaccine uptake. The objective of this study is to evaluate evidence on HPV knowledge, vaccine uptake, and educational interventions in HPS to identify specific deficits to improve education. Methods: A systematic literature search for articles on HPV vaccine uptake, knowledge, and educational interventions in HPS was performed in PubMed, Embase, Web of Science, CINAHL, and Scopus from January 1, 2006 - July 21, 2021. Included studies assessed HPS for HPV vaccine uptake, knowledge, counseling comfort, or educational interventions to increase HPV vaccine knowledge. Studies were screened for inclusion by 2 independent reviewers and evaluated for risk of bias. PRISMA guidelines for reporting were followed. Results: Twenty-one unique articles met inclusion criteria and were included in the analysis. Of the studies included, 20 included knowledge, 11 included vaccine uptake, 8 included interventions, and 12 included counseling comfort. The students in the studies included medical (n=14), dental (n=7), dental hygiene (n=6), nursing (n=3), physician assistant (n=2), public health (n=1), and pharmacy (n=1). Across studies, HPV vaccine series initiation ranged from 34.6-70.3%, with 28.3-58.3% up to date on vaccination. Most students knew that HPV causes cervical cancer (99%), but fewer knew that HPV causes head and neck cancer (40-47%) and oropharyngeal cancer (45%). Educational interventions included team-based approaches and lectures, and improved outcomes including vaccine knowledge, vaccination schedule, and cancer knowledge. Medical students with lower knowledge of HPV were more hesitant to recommend vaccination at baseline but were more likely to recommend vaccination after an education session. Discussion: Across HPS, inadequacies persist in HPV vaccine uptake, knowledge, and counseling comfort. It is critical to target vaccine uptake in this population and improve existing educational efforts to reduce preventable cancers. Institutions must prioritize HPV vaccine education to impact HPV related death.

Retreatment of chemotherapy-resistant metastatic choriocarcinoma with immunotherapy.

Introduction: Recurrent metastatic choriocarcinoma is a rare disease with historically limited guidance in the literature regarding standardized treatment protocols. In this case report, we review the course of a patient with recurrent metastatic choriocarcinoma re-treated with single agent pembrolizumab.Our patient was initially diagnosed with metastatic choriocarcinoma (FIGO Stage IV, WHO Score 13) after presenting for evaluation of amenorrhea. She received standard treatment with etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO), with a complete response. However, she recurred one year later. Molecular profiling of a chest wall tumor demonstrated strong expression of programmed cell death ligand 1 (PD-L1), and she was started on treatment with single agent pembrolizumab achieving a complete response. Unfortunately, she recurred again 6 months following completion of treatment. She was re-treated with pembrolizumab for 2 years with complete response after 25 cycles and is currently without evidence of disease. She has been followed on surveillance, with no evidence of disease for more than 24 months following treatment. Conclusion: This case represents the first to our knowledge to discuss re-treatment with pembrolizumab for relapsed choriocarcinoma after achieving a complete response.

"Because the resources aren't there, then we fail. We fail as a society": A Qualitative Analysis of Human Trafficking Provider Perceptions of Child Welfare Involvement among Trafficked Mothers.

BACKGROUND: Little is understood about child welfare involvement (CWI) in cases where the birth mother has experienced human trafficking. OBJECTIVES: The aim of this study was to explore provider perceptions of the impact of CWI for the trafficked mother. METHODS: Participants were selected among providers caring for trafficked birth mothers. Semi-structured interviews were conducted with providers and qualitative content analysis was conducted. RESULTS: Interviewees reported reasons for CWI, positive and negative impacts of CWI and provided recommendations for systems improvement. CONCLUSION FOR PRACTICE: Recommendations from this exploratory study include mechanisms to support trafficked mothers, train hospital social workers, and systems change. During the prenatal period, strategies to support the trafficked mother may include addressing gaps in social determinants of health, ensuring appropriate medical and mental health care, early screening and referral to substance use treatment services, enhancing community support, and working to develop safety plans for survivors and their families. Enhanced engagement of social workers and all providers to improve understanding of the unique complexity of trafficked mothers is needed. Education should include an understanding that judgement of a caretaker's ability to parent should be current and holistic and not reflexive based on history in the electronic medical record. An exploration of the child welfare system itself should also be undertaken to identify and modify discriminatory laws and policies. Finally, efforts to address social determinants of health in the community and enhance the trauma-informed nature of child welfare referrals could improve the lives of trafficked mothers.

Evaluation of BMI as a Risk Factor for Complications following Gender-affirming Penile Inversion Vaginoplasty.

BACKGROUND: Gender affirmation surgery (GAS) has a positive impact on the health of transgender patients; however, some centers employ body mass index (BMI) as a strict selection criterion for surgical candidacy. Several single-center studies have found no clear correlation between BMI and complication rates. We conducted a retrospective multicenter study at 2 university-based centers to test the null hypothesis: obesity is not a significant determinant of the risk of acute surgical complications in patients undergoing penile inversion vaginoplasty (PIV). METHODS: This is a retrospective chart review of all adult patients at the University of Michigan and the University of Miami undergoing gender-affirming PIV with minimum follow-up time of 3 months between 1999 and 2017. A logistic regression model of analysis is used to examine the predictive factors for surgical complications and delayed revision urethroplasty in our patient sample. RESULTS: One hundred and one patients met inclusion criteria for this study. The mean BMI at the time of procedure was 26.9kg/m2 (range 17.8-48.2). Seventeen patients (16.8%) had major complications and 36 patients (35.6%) had minor complications. On logistic regression analysis, none of the recorded covariates were significant predictors of delayed revision urethroplasty or major, minor, or any complications. CONCLUSIONS: We found that obese patients can safely undergo GAS and that BMI alone should not preclude appropriately selected patients from undergoing GAS. We acknowledge that selection based on overall health and other medical comorbidities is certainly warranted for gender-affirming PIV and all other surgical procedures.