Background: The population of women undergoing abdominal myomectomy for symptomatic large fibroid uterus is unique. We seek to characterize the timing, risk factors as well as the presenting symptoms which led patients to undergo repeat surgery in this patient population. Methods and findings: We followed 592 patients who underwent an abdominal myomectomy from March 1998 to June 2010 at St. Vincent’s Catholic Medical Center and presented later during the study period with a recurrence of symptoms attributable to a reemergence of fibroids and who chose to undergo repeat surgical management. Twelve percent of patients exhibited symptoms of fibroid uterus which led to reoperation within the study period. The mean age at repeat surgery was 44.1 ± 0.6 years old (n = 69) and the mean time between operations was 7.9 ± 0.3 years. Presentation was variable but included bleeding, pain and infertility. Patients presented for surgery with a significantly smaller sized uterus than at their initial surgery. Timing between surgeries correlated with age at initial surgery and uterine size but race, number of fibroids, aggregate weight of fibroids removed, operative time or blood loss at the initial surgery did not correlate. Data is suggestive that intraperitoneal triamcinolone may reduce reoperation rates but not timing of recurrence. Conclusion: These results may help in counseling patients, particularly younger women, on the risks of fibroid recurrence necessitating repeat surgery. Further research is necessary to assess if triamcinolone can alter fibroid reurrence in patients who undergo uterus sparing procedures.

The study aims to determine resident applicant metrics most predictive of academic and clinical performance as measured by the Council of Resident Education in Obstetrics and Gynecology (CREOG) examination scores and Accreditation Council for Graduate Medical Education (ACGME) clinical performance (Milestones) in the aftermath of United States Medical Licensing Examination Scores (USMLE) Step 1 becoming a pass/fail examination. In this retrospective study, electronic and paper documents for Wayne State University Obstetrics and Gynecology residents matriculated over a 5-year period ending July 2018 were collected. USMLE scores, clerkship grade, and wording on the letters of recommendation as well as Medical Student Performance Evaluation (MSPE) were extracted from the Electronic Residency Application Service (ERAS) and scored numerically. Semiannual Milestone evaluations and yearly CREOG scores were used as a marker of resident performance. Statistical analysis on residents (n = 75) was performed using R and SPSS and significance was set at P < .05. Mean USMLE score correlated with CREOG performance and, of all 3 Steps, Step 1 had the tightest association. MSPE and class percentile also correlated with CREOGs. Clerkship grade and recommendation letters had no correlation with resident performance. Of all metrics provided by ERAS, none taken alone, were as useful as Step 1 scores at predicting performance in residency. Regression modeling demonstrated that the combination of Step 2 scores with MSPE wording restored the predictive ability lost by Step 1. The change of USMLE Step 1 to pass/fail may alter resident selection strategies. Other objective markers are needed in order to evaluate an applicant’s future performance in residency.

Low-grade-serous ovarian carcinomas (LGSOC) are rare tumors characterized by a high recurrence rate and limited treatment options. Most LGSOC are estrogen receptor (ER)-positive and demonstrate alterations in the RAS/MAPK pathway. Avutometinib is a dual RAF/MEK clamp, whereas defactinib and VS-4718 are focal adhesion kinase (FAK) inhibitors. Fulvestrant is an ER antagonist/degrader. We assessed the preclinical efficacy of fulvestrant, avutometinib + VS-4718 (FAKi), and the triple combination in a chemotherapy/aromatase inhibitor-resistant LGSOC patient-derived tumor xenograft (PDX) model. Tissue obtained from a LGSOC patient wild-type for KRAS/NRAS/BRAF mutations in progression after chemotherapy/anastrozole was transplanted into female CB17/lcrHsd-Prkdc/SCID mice (PDX-OVA(K)250). The animals were treated with either saline/control, fulvestrant, avutometinib/FAKi, or the triple combination of avutometinib/FAKi/fulvestrant. Avutometinib and FAKi were given five-days on and two-days off through oral gavage. Fulvestrant was administered subcutaneously weekly. Mechanistic studies were performed ex vivo using Western blot assays. Animals treated with the triple combination demonstrated stronger tumor growth inhibition compared to all the other experimental groups including control/saline (p < 0.001), single-agent fulvestrant (p = 0.04 from day eight and onwards), and avutometinib/FAKi (p = 0.02 from day 18). Median survival for mice treated with saline/control was 29 days while mice in all other experimental groups were alive at day 60 (p < 0.0001). Treatment was well tolerated across all experimental treatments. By Western blot, exposure of OVA(K)250 to the triple combination demonstrated a decrease in phosphorylated MEK (p-MEK) and p-ERK levels. The addition of fulvestrant to avutometinib/FAKi is well tolerated in vivo and enhances the antitumor activity of avutometinib/FAKi in a LGSOC-PDX model with acquired resistance to chemotherapy/aromatase inhibitors. These results support the clinical evaluation of avutometinib/defactinib in combination with fulvestrant or an aromatase inhibitor in patients with recurrent LGSOC.

Carboplatin/paclitaxel (CP) chemotherapy is the cornerstone of therapy for advanced stage ovarian cancer (OC). However, despite initial sensitivity, this regimen cannot avoid the emergence of resistance. Ixabepilone ± bevacizumab (IB) is a combination recently added to NCCN guidelines for the treatment of platinum-resistant OC. It would be desirable to identify biomarkers able to differentiate patients who are resistant to CP and IB, and biomarkers that identify which patients may benefit from IB treatment. We analyzed whole-exome-sequencing (WES) data from 49 OC patients exposed to CP, including 28 platinum-sensitive vs. 21 platinum-resistant, and 31 additional platinum-resistant patients, including 16 responders (i.e., CR/PR) vs. 15 non-responders (SD/PD) to ixabepilone ± bevacizumab. Comprehensive genetic analyses were performed to identify alterations correlated with resistance to CP and IB. WES analysis of CP responders vs. non-responders revealed differences in HRD-signatures (p < 0.05), OS (p < 0.005) and gain/loss-of-function in multiple genes associated with tumor growth/progression including but not limited to ACVR2A, INHBA, MAP3K7, ATG5, SGK1, FYN, RSPO3, NOD1 and LRRK2. WES analysis of platinum-resistant IB-treated patients revealed additional nominally significant genes and deranged pathways including gains in the DROSHA and SDHA genes in responders vs. non-responders (p < 0.05). Patients harboring HRD-signatures showed significantly higher sensitivity to CP and prolonged survival compared to HRD-negative patients. Alterations in genes associated with tumor growth/progression correlated with resistance to CP regimen and may represent novel “druggable” candidate biomarkers for the targeted treatment of CP/IB-resistant patients. Further validation in independent cohorts and preclinical experiments in CP/IB-resistant models are warranted to establish the clinical utility of these findings.