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.

Patient reported opioid usage following vulvar surgery in gynecologic oncology.

Background: There remains a paucity of data for vulvar surgery outcomes in gynecologic oncology in the era of Enhanced Recovery After Surgery (ERAS) ®. As such, the primary objective is to assess the impact of patient and procedural factors on patient reported postoperative opioid usage following vulvar surgery. Secondary objective is to create a tailored opioid prescribing algorithm for this population. Methods: A retrospective cohort study was performed of patients who underwent vulvar surgery for a gynecologic malignancy between 3/2019-7/2022. Covariates of interest included a history of risk factors for opioid usage, age, anatomic location of the vulvar resection, radicality of surgery, groin dissection, use of postoperative non-steroidal anti-inflammatory drugs (NSAIDs), and complications. Logistic regression models evaluated the effects that sociodemographic characteristics and procedural factors have on opioid usage. Linear regression models were created to determine prescribing guidelines. Results: A total of 100 patients were included. Following surgery, 35 patients (35 %) were not sent home with an opioid prescription, 39 patients (39 %) reported using at least one opioid pill from their prescription, and 26 patients (26 %) reported not using any opioid pills from their prescription. In the regression models, patient age (p < 0.006) had a significant impact on opioid use, while all other factors did not. Contraindications to NSAIDs did not have a statistically significant impact (p = 0.1) but was deemed clinically meaningful and included in the final model. Proposed opioid prescribing guidelines were created. Conclusion: In conclusion, most patients after vulvar surgery require little to no opioids. Identifiable preoperative factors can aid providers to manage postoperative pain while minimizing unnecessary opioid prescriptions.

Germline genetic testing reveals pathogenic variants in uterine serous carcinoma patients.

An increase in the risk of developing uterine serous carcinoma (USC) has been observed among BRCA1 and BRCA2 germline pathogenic variant carriers in the published literature. However, routine germline genetic testing is not currently incorporated into USC management guidelines. The primary objective of this study is to define the incidence of germline pathogenic variants identified through genetic counseling referrals for USC patients at our institution. A retrospective cohort study was performed of patients diagnosed with USC at a single institution over a seven-year interval. A total of 91 patients with uterine serous carcinoma were identified. Almost half of the patients were referred to genetic counseling, and just over half of referred patients (24/43, 56%) ultimately underwent germline genetic testing. Pathogenic variants were noted in 12.5% (3/24) of the patients who were tested. Pathogenic mutations were found in BRCA1, BRCA2, and MSH6. Variants of unknown significance (VUS) were seen in 16.6% (4/24) of patients. Based on our findings, we recommend integration of germline testing into the standard management of patients with USC.

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.

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.

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.

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.