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Obesity is a risk factor for endometrial hyperplasia (EH), endometrial intraepithelial neoplasia (EIN), and early type 1 endometrial cancer (EC) in 70%–90% of patients and is often a significant contributor to overall morbidity and mortality due to comorbidities. In 2011, bariatric surgery (BS) with lifestyle modification was identified as an intervention for reduction in overall mortality as well as risk for gynecologic cancers (Tsui et al., 2021). Our aim was to assess awareness of obesity as a risk factor and understanding of BS in an underinsured obese patient population with EC or EH. This IRB-approved survey was distributed to patients with type I EC or EH within the past 5 years and a BMI >30. Questions addressed demographics, health habits, cancer and obesity awareness, as well as benefits and concerns about undergoing BS. Information was provided about dietary requirements after BS, and then interest in BS was surveyed. 61.2% of surveyed patients were interested in bariatric surgery for weight loss after receiving education about the procedure. Interest in bariatric surgery was correlated with higher BMI, higher ideal and comfortable weight loss in pounds and higher estimated weight loss that could be obtained with bariatric surgery. Additionally, patients who were interested in BS had better understanding of the risks of obesity with cancer overall. Obese patients with history of EC/EIN/EH are aware of hazards associated with excess weight and understand the relationship between EC/EIN/EH diagnosis and obesity, and overall are very interested in BS as a modality to improve their health. • Low resource endometrial cancer and precancer patients understand that excess weight increases their risk for cancer. • More than half of endometrial cancer or precancer patients are interested in bariatric surgery after education about diet. • Endometrial cancer patients not interested in weight loss surgery are concerned about cost, recovery and complications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aims of this study were to implement a patient-administered checklist designed to identify endometrial cancer patients at elevated risk for Lynch syndrome; measure subsequent genetic counseling and testing; and identify differences between those who attended genetic counseling and those who did not. Methods: We developed a 4-item yes/no checklist of personal and family history risk factors for Lynch syndrome-associated endometrial cancer and recommended referral for genetic counseling for patients meeting any of the criteria. Retrospective chart review was performed to determine subsequent genetic counseling and testing outcomes over a 15month period. Results: 6/387 (1.6%) of endometrial cancer patients tested positive for a Lynch syndrome mutation. 4/24 (17%) of endometrial cancer patients who met referral criteria and attended genetic counseling tested positive. 38/70 (55%) of patients who met referral criteria were not seen for genetic counseling. Patients who were diagnosed with endometrial cancer at younger ages, who had primary surgery at our institution, or who met more than one referral criteria were more likely to be seen for genetic counseling. Conclusions: Endometrial cancer patients who met referral criteria and attended genetic counseling comprised a population enriched for Lynch syndrome. This approach allowed Lynch syndrome evaluation resources to be targeted to a population of patients that is high risk and interested in the information. The referral rate of at-risk patients needs to be improved, and allocating resources towards this goal could increase the identification of Lynch syndrome while avoiding some of the pitfalls of universal screening. [Copyright &y& Elsevier]

Purpose To evaluate if an individual's locus of control (LOC) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients. Methods Multi-site analysis of women with newly diagnosed stages II–IV ovarian, primary peritoneal or fallopian tube cancer. Patients completed the following surveys: Locus of Control Scale (LOC), Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy—Spiritual (FACIT-Sp), Edmonton Symptom Assessment score (ESAS), Hospital Anxiety Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site of care, race, and partnership status as potential confounders. Results This study enrolled 104 patients from three separate treatment facilities. After adjusting for site, race and partnership status, higher levels of external LOC predicted decreased QOL (FACT-O) (p < 0.05). Higher levels of external LOC also correlated with increased death anxiety and general anxiety (p ≤ 0.05). Additionally, higher levels of external LOC predicted decreased hope (HHI) (p ≤ 0.01). Discussion Ovarian cancer patients with a high external LOC may be at risk for decreased QOL at the time of their cancer diagnosis. They may also experience higher levels of anxiety and decreased feelings of hope. Identification of these women and interventions designed to increase a woman's sense of control over her situation may improve QOL and overall mental well-being. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether women with low-grade serous ovarian cancer (LGSOC) have personal and family histories of breast and ovarian cancer that are less suggestive of Hereditary Breast and Ovarian Cancer (HBOC), as compared to women with high-grade serous ovarian cancer (HGSOC). Methods: A single institution, case-control retrospective review of medical records was conducted. Personal demographics, personal cancer history, and family history of breast and ovarian cancer of women with LGSOC were collected and compared to controls with HGSOC, which is known to be associated with HBOC. Results: 195 cases of LGSOC and 386 controls with HGSOC were included in the analysis. Women with LGSOC were significantly less likely to have a first- or second-degree relative with breast or ovarian cancer (p =0.0016). Additionally, when the personal and family histories were quantified using the AMyriad BRC mutation prevalence tables, women with LGSOC had lower scores indicative of a less suggestive family history for HBOC (p =0.027). Conclusions: In this study, women with LGSOC had family histories that were less suggestive of HBOC compared to women with HGSOC, especially when the degree of relatedness of affected relatives was taken into account. By beginning to determine if LGSOC is part of the tumor spectrum seen in HBOC, this study is an important step towards refining hereditary cancer risk assessment for women with ovarian cancer. [ABSTRACT FROM AUTHOR]

Our pilot clinical study of EphA2 inhibitor (dasatinib) plus paclitaxel and carboplatin showed interesting clinical activity in endometrial cancer with manageable toxicity. However, the underlying mechanisms of dasatinib resistance in uterine cancer are unknown. Here, we investigated potential mechanisms underlying resistance to EphA2 inhibitors in uterine cancer and examined the anti-tumor activity of EphA2 inhibitors alone and in combination with a MEK inhibitor. We evaluated the antitumor activity of EphA2 inhibitors plus a MEK inhibitor using in vitro and in vivo orthotopic models of uterine cancer. EphA2 inhibitor induced MAPK in dasatinib-resistant uterine cancer cells (HEC-1A and Ishikawa) and BRAF/CRAF heterodimerization in HEC-1A cells. EphA2 inhibitor and trametinib significantly increased apoptosis in cancer cells resistant to EphA2 inhibitors compared with controls (p < 0.01). An in vivo study with the orthotopic HEC-1A model showed significantly greater antitumor response to combination treatment compared with dasatinib alone (p < 0.01). Combination treatment increased EphrinA1 and BIM along with decreased pMAPK, Jagged 1, and c-MYC expression in dasatinib-resistant cells. In addition, Spearman analysis using the TCGA data revealed that upregulation of EphA2 was significantly correlated with JAG1, MYC , NOTCH1 , NOTCH3 and HES1 expression (p < 0.001, r = 0.25–0.43). Specifically, MAP3K15 and the NOTCH family genes were significantly related to poor clinical outcome in patients with uterine cancer. These findings indicate that the MAPK pathway is activated in dasatinib-resistant uterine cancer cells and that EphrinA1-mediated MEK inhibition overcomes dasatinib resistance. Dual targeting of both EphA2 and MEK, combined with chemotherapy, should be considered for future clinical development. • Our pilot clinical study of dasatinib showed clinical activity in endometrial cancer. • The underlying mechanisms of dasatinib resistance in uterine cancer are unknown. • MAPK pathway is activated in dasatinib-resistant uterine cancer cells. • MEK inhibition overcomes dasatinib resistance in uterine cancer. • Dual targeting of EphA2 and MEK should be considered for future clinical development. [ABSTRACT FROM AUTHOR]

To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53–81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline. • Use of propranolol during primary chemotherapy and surgical treatment of ovarian cancer is feasible • Combination chemotherapy and propranolol may improve overall quality of life [ABSTRACT FROM AUTHOR]

Abstract: Objective: Obesity-associated hyperestrogenism and hyperinsulinemia contribute significantly to the pathogenesis of endometrial cancer. We recently demonstrated that metformin, a drug long used for treatment of type 2 diabetes, attenuates both insulin- and estrogen-mediated proliferative signaling in the obese rat endometrium. In this study, we sought to identify tissue biomarkers that may prove clinically useful to predict tissue response for both prevention and therapeutic studies. We identified CGRRF1 (cell growth regulator with ring finger domain 1) as a novel metformin-responsive gene and characterized its possible role in endometrial cancer prevention. Methods: CGRRF1 mRNA expression was evaluated by RT-qPCR in the endometrium of obese and lean rats, and also in normal and malignant human endometrium. CGRRF1 levels were genetically manipulated in endometrial cancer cells, and its effects on proliferation and apoptosis were evaluated by MTT and Western blot. Results: CGRRF1 is significantly induced by metformin treatment in the obese rat endometrium. In vitro studies demonstrate that overexpression of CGRRF1 inhibits endometrial cancer cell proliferation. Analysis of human endometrial tumors reveals that CGRRF1 expression is significantly lower in hyperplasia, Grade 1, Grade 2, Grade 3, MMMT, and UPSC endometrial tumors compared to normal human endometrium (p<0.05), suggesting that loss of CGRRF1 is associated with the presence of disease. Conclusion: CGRRF1 represents a novel, reproducible tissue marker of metformin response in the obese endometrium. Furthermore, our preliminary data suggests that up-regulation of CGRRF1 expression may prove clinically useful in the prevention or treatment of endometrial cancer. [Copyright &y& Elsevier]

Abstract: Objective: To compare outcomes of patients undergoing continent or incontinent urinary diversion after pelvic exenteration for gynecologic malignancies. Methods: Data on patients who underwent pelvic exenteration for gynecologic malignancies at The University of Texas MD Anderson Cancer Center between January 1993 and December 2010 were collected. A multivariate logistic regression model was used and statistical significance was P <0.05. Results: A total of 133 patients were included in this study. The mean age at exenteration was 47.6 (range, 30–73) years in the continent urinary diversion group and 57.2 (range, 27–86) years in the incontinent urinary diversion group (P <0.0001). Forty-six patients (34.6%) had continent urinary diversion, and 87 patients (65.4%) had incontinent urinary diversion. The rates of postoperative complications in patients with continent and incontinent urinary diversion, respectively, were as follows: pyelonephritis, 32.6% versus 37.9% (P =0.58); urinary stone formation, 34.8% versus 2.3% (P <0.001); renal insufficiency, 4.4% versus 14.9% (P =0.09); urostomy stricture, 13.0% versus 1.2% (P =0.007); ureteral (anastomotic) leak, 4.4% versus 6.9% (P =0.71); ureteral (anastomotic) stricture, 13.0% versus 23% (P =0.25); fistula formation, 21.7% versus 19.5% (P =0.82); and reoperation because of complications of urinary diversion, 6.5% versus 2.3% (P =0.34). Among patients with continent urinary diversion, the incidence of incontinence was 28.3%, and 15.2% had difficulty with self-catheterization. Conclusion: There were no differences in postoperative complications between patients with continent and incontinent conduits except that stone formation was more common in patients with continent conduits. [Copyright &y& Elsevier]

Abstract: Objectives: Previous studies report a survival advantage in ovarian cancer patients with Ashkenazi Jewish (AJ) breast cancer gene (BRCA) founder mutations. The purpose of this study was to determine if this association exists in patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations. We also sought to account for “survival bias” by minimizing lead time that may exist between diagnosis and genetic testing. Methods: Patients with stage III/IV ovarian cancer and a non-AJ BRCA mutation, seen between January 1996 and July 2007, were identified from eight institutions. Patients with sporadic ovarian cancer were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. Progression-free (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Fisher''s exact test and chi-square were also used for analysis. Results: Ninety-five advanced stage ovarian cancer patients with non-AJ BRCA mutations and 183 sporadic controls were analyzed. Compared to sporadic ovarian cancer patients, non-AJ BRCA patients had longer PFS (27.9 months vs. 17.9 months, HR 0.61 [95% CI 0.43–0.86]) and OS (101.7 months vs. 54.3 months, HR 0.43 [95% CI 0.27–0.68]). BRCA status was an independent predictor of PFS and OS. Conclusions: This multicenter study demonstrates a significant survival advantage in advanced stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. This improved survival was evident when accounting for the “survival bias” that coincides with genetic testing. [Copyright &y& Elsevier]