A spatial proteomic study of platinum refractory HGSOC implicates dual AKT and WNT activity linked to an immunosuppressive tumor microenvironment.

OBJECTIVE: Advanced-stage high-grade serous ovarian cancer (HGSOC) remains a deadly gynecologic malignancy with high rates of disease recurrence and limited, effective therapeutic options for patients. There is a significant need to better stratify HGSOC patients into platinum refractory (PRF) vs. sensitive (PS) cohorts at baseline to improve therapeutic responses and survival outcomes for PRF HGSOC. METHODS: We performed NanoString for GeoMx Digital Spatial Profile (G-DSP) multiplex protein analysis on PRF and PS tissue microarrays (TMAs) to study the bidirectional communication of cancer cells with immune cells in the tumor microenvironment (TME) of HGSOC. We demonstrate robust stratification of PRF and PS tumors at baseline using multiplex spatial proteomic biomarkers with implications for tailoring subsequent therapy. RESULTS: PS patients had elevated apoptotic and anti-tumor immune profiles, while PRF patients had dual AKT1 and WNT signaling with immunosuppressive profiles. We found that dual activity of AKT1 and WNT signaling supported the exclusion of immune cells, specifically tumor infiltrating lymphocytes (TILs), from the TME in PRF tumors, and this was not observed in PS tumors. The exclusion of immune cells from the TME of PRF tumors corresponded to abnormal endothelial cell structure in tumors with dual AKT1 and WNT signaling activity. CONCLUSIONS: We believe our findings provide improved understanding of tumor-immune crosstalk in HGSOC TME highlighting the importance of the relationship between AKT and WNT pathways, immune cell function, and platinum response in HGSOC.

Impact of steroid use and glycemic control on postoperative complications in diabetic gynecologic oncology patients undergoing laparotomy.

Objective: We aimed to assess the impact of preoperative steroid administration and perioperative glycemic control on postoperative complications in diabetic gynecologic oncology patients undergoing laparotomy. Methods: This retrospective cohort study included gynecologic oncology patients with Type I and Type II diabetes (DM) undergoing laparotomy for any gynecologic indication at a single academic center from 10/2017 to 09/2020. The primary outcome was the rate of postoperative complications. Preoperative steroid administration and 24-hour postoperative average serum blood glucose (BG) ≥ 180 mg/dL were the studied exposures. Data was analyzed with SPSS Statistics v.28. Results: 225 patients met inclusion criteria; 47.6 % had postoperative complications. Patient demographics were similar between patients with and without postoperative complications. Patients with complications had higher BMIs (36.8 vs. 34.0; p = 0.03), bowel surgery (33.0 % vs. 17.1 %; p = 0.008), operative time ≥ 240 min (14.2 % vs. 5.1 %; p = 0.02) and average BG ≥ 180 (63.6 % vs. 40.2 %; p < 0.01). On multivariate analysis, bowel surgery (OR 2.4 (1.2-4.8); p = 0.01) and average BG ≥ 180 (OR 2.8 (1.6-4.9); p < 0.01) remained significant predictors of postoperative complications. There were no differences in complication rates (42.3 % vs. 42.6 %; p = 1.0) between patients who received preoperative steroids and those who did not. When stratified by average postoperative BG < 180 mg/dL vs. BG ≥ 180 mg/dL, there was no difference in Clavien-Dindo classification, 30-day readmission rate (28.2 % vs. 22.1 %; p = 0.49) or 30-day mortality rate (2.9 % vs. 0.0 %; p = 0.53). Conclusion: The administration of preoperative steroids did not increase complication rates. Perioperative hyperglycemia was associated with an increased risk of postoperative complications. Optimizing perioperative glycemic control is imperative to decrease postoperative complications.

Misoprostol and estradiol to enhance visualization of the transformation zone during cervical cancer screening: An integrative review.

The purpose of this integrative literature review was to appraise studies conducted worldwide using misoprostol and estradiol in converting Type 3 transformation zone (TZ) of the cervix into Types 1 or 2 and to assess which regimen could be more feasible in low-and-middle-income countries (LMICs). We reviewed the English language literature for peer-reviewed studies that evaluated strategies to convert Type 3 TZs to Types 1 or 2 for cervical cancer screening. Web of Science and PubMed searches were performed up to July 2020. Search terms included: "cervical colposcopy," "inadequate colposcopy", "cervical cancer screening", "transformation zone," "estrogen", "estradiol", and "misoprostol." Inclusion criteria were articles published in the English language, original research, and peer reviewed articles. A total of 127 articles were abstracted, 24 articles were reviewed, and 9 articles met all inclusion criteria. We found that intravaginal misoprostol, intravaginal estradiol, and oral estradiol can successfully convert Type 3 TZ to Types 1 or 2. A single dose of vaginal misoprostol had a similar maximum response rate (20-80%) to a multi-dose regimen over several days or weeks of both intravaginal estradiol (64-83%) and oral estradiol (50-70%). Misoprostol administration was associated with more side effects such as abdominal cramping and vaginal bleeding compared to estradiol, although these were generally mild. In conclusion, Oral estradiol, intravaginal estradiol, and intravaginal misoprostol can be used to convert Type 3 TZ to Types 1 or 2. Intravaginal misoprostol is well tolerated and more feasible in LMICs due to availability and shorter treatment schedule compared to oral or intravaginal estradiol.

Pathology findings among women with alterations in uterine bleeding patterns in cameroon.

PURPOSE: Endometrial cancer is on the rise in high-income countries but it has not been adequately studied in low-and-middle income countries especially in sub-Saharan Africa (SSA), likely due to scarce pathology facilities. The purpose of this study was to characterize and quantify the prevalence of endometrial hyperplasia or cancer in a cohort of women with abnormal uterine bleeding (AUB) who underwent endometrial biopsy in Cameroon. METHODS: We designed a cross-sectional study using medical records to characterize women who underwent endometrial biopsy in the Cameroon Baptist Convention Health Services (CBCHS) from 2008 to 2019. Pathologic diagnoses were classified as either endometrial hyperplasia, endometrial cancer, or no endometrial hyperplasia/cancer. We reported the overall prevalence of endometrial hyperplasia or cancer. Bivariate analyses compared patient characteristics between women with endometrial cancer, endometrial hyperplasia, and neither. RESULTS: The average age was 46.2 years and women had an average of 5.1 parity. We found that, 61 [(36.7% of 166 women; 95% CI (27.6-47.0%)] had endometrial hyperplasia or cancer. There were no cases of hyperplasia with atypia and 13 women had endometrial cancer. The remainder were comprised of benign or infectious pathologic findings. In bivariate analysis, mean ages were statistically different among the three groups (hyperplasia, cancer, and no hyperplasia/cancer), p < 0.001, and women with cancer had the highest age. Parity was statistically significantly different among the three groups (p = 0.002) and women with endometrial cancer had higher parity. CONCLUSION: We found that just over 1 in 3 women with AUB who underwent endometrial biopsy at a health system in SSA were found to have pathologic findings of endometrial hyperplasia or cancer, with no cases of hyperplasia with atypia. Women with endometrial cancer had higher mean age and parity.