Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Inhibition of Tumor Microenvironment Cytokine Signaling Sensitizes Ovarian Cancer Cells to Antiestrogen Therapy.

Antiestrogen therapy (AET) is an alternative to cytotoxic chemotherapy for recurrent ovarian cancer, yet the often short duration of response suggests mechanisms of resistance. We previously demonstrated that tumor microenvironment interleukin-6/leukemia inhibitory factor (IL6/LIF) cytokines induce tumor cell JAK-STAT signaling to promote cancer growth. Crosstalk between estrogen signaling and cytokine signaling has been reported. Therefore, we sought to characterize the impact of IL6/LIF signaling on estrogen signaling in epithelial ovarian cancer and investigate the efficacy of combination therapy. We first assessed patient tumors for cytokine expression and compared it with response to AET to determine clinical relevance. In vitro, we determined the effect of IL6/LIF on estrogen receptor expression and signaling. Cell viability assays were used to determine the efficacy and potential synergy of cytokine blockade and AET. We then extended studies to animal models, incorporating patient-derived stromal cells. Our results demonstrated shorter progression-free interval on AET in patients with stromal IL6/LIF expression. In vitro, IL6/LIF increased tumor cell estrogen receptor expression and signaling, and combination cytokine blockade and AET resulted in synergistic inhibition of tumor cell growth. The anticancer effect was verified in a mouse model. In conclusion, due to crosstalk between IL6/LIF cytokine signaling and estrogen signaling, dual blockade is a potential new treatment approach for ovarian cancer.

The "Sweet Spot" of Targeting Tumor Metabolism in Ovarian Cancers.

The objective of this review is to explore the metabolomic environment of epithelial ovarian cancer that contributes to chemoresistance and to use this knowledge to identify possible targets for therapeutic intervention. The Warburg effect describes increased glucose uptake and lactate production in cancer cells. In ovarian cancer, we require a better understanding of how cancer cells reprogram their glycogen metabolism to overcome their nutrient deficient environment and become chemoresistant. Glucose metabolism in ovarian cancer cells has been proposed to be influenced by altered fatty acid metabolism, oxidative phosphorylation, and acidification of the tumor microenvironment. We investigate several markers of altered metabolism in ovarian cancer including hypoxia-induced factor 1, VEGF, leptin, insulin-like growth factors, and glucose transporters. We also discuss the signaling pathways involved with these biomarkers including PI3K/AKT/mTOR, JAK/STAT and OXPHOS. This review outlines potential metabolic targets to overcome chemoresistance in ovarian cancer. Continued research of the metabolic changes in ovarian cancer is needed to identify and target these alterations to improve treatment approaches.

The importance of considering a wide range of differential diagnoses forpatients presenting with complaints of urinary incontinence: Acase report.

Urinary incontinence (UI) is common in women and is often associated with decreased quality of life. It is important to consider a range of wide differential diagnoses when evaluating a patient presenting with presumed with UI. This case describes a patient referred to urogynecology for urinary incontinence caused by a common, benign and usually asymptomatic gynecologic condition: nabothian cysts. However, based on presentation and imaging, there was concern about a more serious condition: adenoma malignum. This case emphasizes the importance of considering a wide range of differential diagnoses and describes several important differential diagnoses associated with urinary incontinence.

Granulomatous Peritonitis secondary to Chlamydia Trachomatis: A case report.

BACKGROUND: This case provides a rare case of Chlamydia Trachomatis presenting with ascites and granulomatous peritonitis. CASE: A 23-year old gravida 0 presented as a new patient to her gynecologist with complaints of irregular menses. A pelvic ultrasound showed ascites and the ovaries appeared heterogenous with irregular borders. A CA125 was 432. The patient was taken to the operating room by gynecologic oncology for a diagnostic laparoscopy. Biopsies were taken and final pathology resulted as "diffuse granulomatous inflammation." Post-operatively, the etiology remained unknown. The patient was brought back to the office for more testing. She tested positive for Chlamydia and was diagnosed with pelvic inflammatory disease. CONCLUSION: When encountering granulomatous pathology, Chlamydia Trachomatis is a rare etiology however it should be included on the differential diagnosis.