Epithelial-derived high-grade serous ovarian cancer (HGSOC) is the deadliest gynecologic malignancy. Roughly 80% of patients are diagnosed with late-stage disease, which is defined by wide-spread cancer dissemination throughout the pelvic and peritoneal cavities.HGSOC dissemination is dependent on tumor cells acquiring the ability to resist anoikis (apoptosis triggered by cell detachment). Epithelial cell detachment from the underlying basement membrane or extracellular matrix leads to cellular stress, including nutrientdeprivation. In this report, we examined the contribution of fatty acid oxidation (FAO) in supporting anoikis resistance. We examined expression Carnitine Palmitoyltransferase 1A (CPT1A) in a panel of HGSOC cell lines cultured in adherent and suspension conditions. With CPT1A knockdown cells, we evaluated anoikis by caspase 3/7 activity, cleaved caspase 3 immunofluorescence, flow cytometry, and colony formation. We assessed CPT1A-dependent mitochondrial activity and tested the effect of exogenous oleic acid on anoikis and mitochondrial activity. In a patient-derived xenograft model, we administered etomoxir, an FAO inhibitor, and/or platinum-based chemotherapy. CPT1A is overexpressed in HGSOC, correlates with poor overall survival, and is upregulated in HGSOC cells cultured in suspension. CPT1A knockdown promoted anoikis and reduced viability of cells cultured in suspension. HGSOC cells in suspension culture are dependent on CPT1A for mitochondrial activity. In a patient-derived xenograft model of HGSOC, etomoxir, significantly inhibited tumor progression.Implications: Targeting FAO in HGSOC to promote anoikis and attenuate dissemination is a potential approach to promote a more durable anti-tumor response and improve patient outcomes.

Objectives: This was a study of the scope of practice and autonomy of emergency medicine (EM) physician assistants (PAs) practicing in rural versus urban emergency departments (EDs).Methods: Using the American Academy of Physician Assistants (AAPA) Masterfile, a random sample of 200 U.S. EM PAs were surveyed, with oversampling of an additional 200 rural PAs. Location was classified by zip code-based rural-urban commuting area codes, and responses were compared about conditions managed, procedures performed, and physician supervision between rural versus urban groups.Results: A total of 237 responses were received from PAs in 44 U.S. states, of which (201) were valid responses (105 rural, 96 urban) from PAs currently practicing in EDs (59.3% exclusion-adjusted response rate). Compared to urban PAs, rural PAs more frequently managed cardiac arrest (67% vs. 44%), stroke (86% vs. 72%), multisystem trauma (83% vs. 70%), active labor (44% vs. 23%), and critically ill children (82% vs. 65%) in the past year. They were more likely to have performed intubation (65% vs. 44%), needle thoracostomy (21% vs. 8%), and tube thoracostomy (46% vs. 26%). Rural PAs more often reported never having a physician present in the ED (38% vs. 0%) and less often reported always having a physician present (50% vs. 98%). Rural PAs were also less likely to report that a physician evaluates more than 75% of their patients (8% vs. 18%) and more likely that a physician never evaluates all of their patients (19% vs. 7%).Conclusions: Rural PAs reported a broader scope of practice, more autonomy, and less access to physician supervision than urban PAs.ACADEMIC EMERGENCY MEDICINE 2014;21:520-525

High-grade serous ovarian cancers (HGSOCs) arise from exfoliation of transformed cells from the fallopian tube, indicating that survival in suspension, and potentially escape from anoikis, is required for dissemination. We report here the results of a multi-omic study to identify drivers of anoikis escape, including transcriptomic analysis, global non-targeted metabolomics, and a genome-wide CRISPR/ Cas9 knockout (GeCKO) screen of HGSOC cells cultured in adherent and suspension settings. Our combined approach identified known pathways, including NOTCH signaling, as well as novel regulators of anoikis escape. Newly identified genes include effectors of fatty acid metabolism, ACADVL and ECHDC2, and an autophagy regulator, ULK1. Knockdown of these genes significantly inhibited suspension growth of HGSOC cells, and the metabolic profile confirmed the role of fatty acid metabolism in survival in suspension. Integration of our datasets identified an anoikis-escape gene signature that predicts overall survival in many carcinomas.

Ovarian cancer is commonly diagnosed at an advanced stage, with disease involving the upper abdomen. The finding of enlarged cardiophrenic lymph nodes (CPLNs) on pre-operative imaging often indicates the presence of malignant spread to the mediastinum. Surgical resection of CPLN through a transdiaphragmatic approach can help to achieve cytoreduction to no gross residual. A retrospective chart review was conducted on all patients who underwent transdiaphragmatic cardiophrenic lymph node resection from 8/1/11 through 2/1/15. All relevant pre-, intra-, and post-operative characteristics and findings were recorded. A brief description of the surgical technique is included for reference. Eleven patients were identified who had undergone transdiaphragmatic resection of cardiophrenic lymph nodes. Malignancy was identified in 18/21 (86%) of total lymph nodes submitted. The median number of post-operative days was 7. The overall post-operative morbidity associated with CPLN resection was low, with the most common finding being a small pleural effusion present on chest x-ray between POD# 3–5 (55%). Transdiaphragmatic CPLN resection is a feasible procedure with relatively minor short-term post-operative morbidities that can be used to achieve cytoreduction to no gross residual disease.

Background Patients with ovarian cancer who are enrolled on phase 1 trials typically have platinum‐resistant and heavily pretreated disease, with a poor prognosis. In the current study, the authors assessed prognostic factors and survival in women with recurrent ovarian cancer who were treated on phase 1 clinical trials. Methods The authors performed a retrospective analysis of patients treated from 2008 through 2018 at the University of Colorado Cancer Center. Patient characteristics and treatment and toxicity‐related survival data were assessed. Descriptive statistics and Cox proportional hazards models were used to identify risk factors associated with survival time. Results A total of 132 patients were treated on phase 1 clinical trials. Patients had a median age of 59 years (range, 33‐88 years) with a median of 5.5 previous chemotherapy lines (range, 1‐13 lines). Of the 132 patients, 53 (40%) were treated on multiple phase 1 trials with a median of 1 (range, 0‐5) prior phase 1 trial. The overall response rate was 14.7%. The median overall survival was 11.3 months (95% CI, 9.1‐13.4 months). Two patients died on trial due to progression of disease whereas no patients died of treatment‐related toxicity. Independent risk factors found to be predictive of shorter survival were an elevated cancer antigen 125 (CA 125) level (hazard ratio [HR], 2.8; 95% CI, 1.6‐5.2) and albumin <3.5 g/dL (HR, 2.5; 95% CI, 1.65‐3.79). A body mass index >25 kg/m2 was predictive of longer survival (HR, 0.65; 95% CI, 0.44‐0.96). Conclusions In the current single‐institution series, patients with heavily pretreated ovarian cancer who were treated on phase 1 clinical trials experienced a median overall survival of 11.3 months. When available, phase 1 clinical trials represent a reasonable treatment option for patients with heavily pretreated ovarian cancer with a preserved performance status.

Objectives To compare the incidence and potential risk factors of trocar site hernia formation in women undergoing robotically assisted versus standard laparoscopic staging (RBT vs. LSC, respectively) for endometrial cancer. Methods We retrospectively identified all patients who underwent MIS staging for endometrial cancer at our institution from 01/09–12/12. Data collection involved the review of all operative notes, postoperative follow-up visit notes, and postoperative imaging reports. Appropriate statistical tests were used. Results We identified 760 eligible patients (LSC, 193; RBT, 567). The overall median age was 61 years (range, 33–90). The median BMI was 28.5 kg/m2 for LSC (range, 16.6–67.6) and 29.5 kg/m2 for RBT (range, 17.9–66) patients (p=0.8). A trocar site hernia developed in 16 patients (2.1%)—5 (2.6%) of 193 LSC and 11 (1.9%) of 567 RBT patients (p=0.6). Median time to hernia diagnosis was 13 (range, 5–20.5) and 18 months (range, 3–49), respectively (p=0.5). All hernias in the LSC cohort developed at the camera trocar site. In the RBT cohort, 10 developed at the camera trocar site and 1 at a lateral trocar site. Only BMI was associated with the development of hernias. A hernia was diagnosed in 7 (6.9%) of 101 patients with a BMI ≥40 kg/m2 compared with 9 (1.4%) of 659 with a BMI <40 kg/m2 (p=0.001). Conclusion MIS for endometrial cancer is associated with a low rate of trocar site hernia formation, with similar rates associated with RBT and standard LSC. Higher BMI is associated with the development of postoperative trocar site hernias.

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Highlights In a cohort of patients with borderline ovarian tumor (BOT), rate of uterine involvement was 6.0%. In patients with BOT grossly confined to ovaries, rate of uterine involvement was 0%. Hysterectomy may be able to be safely excluded from non-fertility-sparing BOT surgery.