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ObjectiveOur study aimed to explore the effect of body mass index (BMI) change on cancer recurrence risk during the routine surveillance of endometrial cancer patients.MethodsData on patients with endometrial adenocarcinoma that had a staging procedure and continued follow-up was retrospectively collected. We compared patients’ BMI at time of surgery and during the last clinic follow-up. Univariate and multivariate analyses were performed to examine the effect of predictors on BMI change and the risk of recurrence.ResultsA total of 211 patients were included in the final analysis. The majority of patients had stage I disease (n=176, 89%) and endometrioid histology (n=178, 86%). Median follow-up time was 53.4 (standard deviation (SD) 40) months. The mean BMI was 30.4 kg/m2 (interquartile range (IQR) 25–34) at surgery compared with 30.9 kg/m2 (IQR 26–36) at last follow-up (p2at surgery compared with 33.5 (IQR 27–36) kg/m2at last follow-up (p=0.016). On multivariate analysis, age and BMI change were the only predictors that were significantly associated with the risk of recurrence (overall response (OR 1.07 (0.99–1.14), p=0.05, OR 1.37 (1.12–1.67), p=0.002, respectively).ConclusionPatients with endometroid endometrial cancer that had an increase in BMI during follow-up were at an increased risk for cancer recurrence compared with patients that did not change or had a decrease in BMI.

This study aimed to compare the rates of positive specimen margins and postconization recurrent dysplasia between loop electrosurgical excision procedures (LEEPs) performed under general anesthesia (GA) and LEEP under local anesthesia (LA).This retrospective cohort study included all consecutive women who underwent LEEP between 2011 and 2019. Collected data included demographics, LEEP indication, cone dimensions, and margin involvement as well as recurrence rate. Women who had undergone previous conization, cold-knife conization, or those who were lost to follow-up during the first 2 years after the procedure were excluded.Overall, 71 women who underwent LEEP under GA and 75 women under LA were included. Demographic characteristics were similar between the groups, as were the rates of preceding abnormal cytology and high-grade dysplasia before conization. Although cone depth and volume were higher for LEEP specimens done under GA compared with LA, the rate of positive specimen margins was comparable both for the endocervical margin (16/71 [22.5%] vs 16/75 [21.3%], respectively; p = .861) and the ectocervical margin (14/71 [19.7%] vs 11/75 [14.7%], respectively; p = .418). During the first 2 years after conization, the rates of high-grade dysplasia (cervical intraepithelial neoplasia ≥ 2) in repeat biopsy and the need for repeat conization were also not significantly different between the GA and LA groups (4.2% vs 1.3%, p = .356; 7.0% vs 9.3%, p = .614, respectively).Anesthesia mode does not seem to affect the rate of positive LEEP margins and the need for repeat conization. Our study findings suggest that LA should be preferred instead of GA in LEEP.

With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment.Prevention Relevance:Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.

Supplementary Table 2 breast cancer treatment costs

Supplementary Table 3 BRCA carriers followup costs

Supplementary Table 1 ovarian cancer treatment costs

Supplementary Figure 1 Tornado diagram

To examine the effect of the BNT162b, mRNA, SARS-CoV-2 virus vaccine on sperm quality.This was a prospective cohort study conducted on sperm donors at the sperm bank of a tertiary, university affiliated medical center. All sperm donors donated sperm repeatedly and the average sperm parameters of all available samples were compared before and after receiving the SARS-CoV-2 vaccine. Each donor served as his own control. For all participants, at-least one sperm sample was received 72 days after completing the second vaccine. Main outcome measures included total sperm count, total motile count and percent of motile sperm.A total of 898 sperm samples from 33 sperm donors that were vaccinated with the Pfizer BNT162b, mRNA, SARS-CoV-2 virus vaccine were analyzed, 425 samples were received before the vaccine, while 473 samples were received after vaccination. Total sperm count and total motile count increased after the second vaccine compared to samples before vaccination. Percent of motile sperm did not change after vaccine.The Pfizer BNT162b, SARS-CoV-2 vaccine has no deleterious effect on sperm quality. Patients and physicians should be counseled accordingly.

ObjectiveOur study’s primary aim was to compare the incidence of endometrial carcinoma in patients with a presurgical diagnosis of endometrial intraepithelial neoplasia confined to the endometrium (EIN-E) versus endometrial intraepithelial neoplasia confined to a polyp (EIN-P). Our secondary aim was to examine the difference in pathological features, prognostic risk groups and sentinel lymph node involvement between the two groups.MethodsWe conducted a retrospective cohort study between January 2014 and December 2020 in a tertiary university-affiliated medical center. The study considered the characteristics of women who underwent hysterectomy with sentinel lymph node dissection for endometrial intraepithelial neoplasia (EIN). We compared EIN-E diagnosed by endometrial sampling via dilatation curettage or hysteroscopic curettage vs EIN-P. A multivariate logistic regression analysis was used to assess risk factors for endometrial cancer.ResultsEighty-eight women were included in the study, of those, 50 were women with EIN-P (EIN-P group) and 38 were women with EIN following an endometrial biopsy (EIN-E group).The median age was 57.5 years (range; 52–68) in the EIN-P group as compared with 63 years (range; 53–71) in the EIN-E group (p=0.47). Eighty-nine percent of the women in the EIN-E group presented with abnormal uterine bleeding whereas 46% of the women in the EIN-P group were asymptomatic (p=0.001). Pathology results following hysterectomy revealed concurrent endometrial carcinoma in 26% of women in the EIN-P group compared with 47% of women in the EIN-E group (p=0.038). Multivariate analysis showed that endometrial cancer was significantly less common in the EIN-P group (overall response (OR)=0.3 95% confidence interval (CI)=0.1–0.9, p=0.03). Eighty-four percent of cancers were grade one in the EIN-P group compared with 50% in the EIN-E group (p=0.048).ConclusionsConcurrent endometrial cancer is less frequent with EIN-P than with EIN-E. The high incidence of endometrial carcinoma in both groups supports the current advice to perform hysterectomy for post-menopausal women. Our data does not support performing sentinel lymph node dissection for EIN-P that was completely resected. The benefit of sentinel lymph node dissection for women with pre-operative EIN-E is yet to be determined.

Guidelines for the treatment of tubo-ovarian cancer patients beyond third line are lacking. We aimed to evaluate the effect of response in each line on patient's outcome as well as identify variables that predict response for additional line of chemotherapy. A cohort study was performed including all patients with advanced high-grade ovarian cancer. Survival analysis was performed using Kaplan-Meier curves and log-rank tests. Odds ratios and hazard ratios were calculated using multilevel, mixed-effects logistic regression and Cox regression, adjusting for repeated measures within individual patients. Two-hundred thirty-eight patients were included and underwent up to 10 lines of chemotherapy. The median progression-free survival was 15.6 and overall survival (OS) was 55.6 months. Response rates dropped with each additional line and by line 5, most patients (61%) became refractory and only 16% had any type of response (complete 4% or partial 12%). By line 2, whether a patient had partial disease (PR), stable disease (SD) or progressive disease (PD) did not have an effect on the OS. From line 2, whether a patient had PR, SD or PD did not have an effect on chemotherapy-free interval. Number of previous lines and time from previous line were the only variables that significantly correlated with both outcome of patients and response to the next line. In conclusion, time interval from the previous line of chemotherapy is the major clinical factor that predicts beneficial effect of another line of treatment in patients with ovarian cancer.

Background Conventional first-line combination therapy for ovarian cancer comprises 6 cycles of adjuvant or neoadjuvant carboplatin (AUC5-6) with paclitaxel (175 mg/m2) every 3 weeks (PC-3W). Weekly scheduling of paclitaxel may maximize its antiangiogenic effect and reduce adverse effects. We compared the efficacy and safety of PC-3W with a modified protocol of weekly paclitaxel 80 mg/m2 and weekly carboplatin AUC2 administered on days 1, 8, and 15 in a 28-day cycle (i.e., with 1 week off-treatment [PC-W]). Materials and Methods Medical records of consecutive patients treated between 2000 and 2018 were reviewed; 707 patients were analyzed for demographic and clinical characteristics, effectiveness and toxicity. Results PC-3W was administered to 402 patients (median age, 60.5 years) and PC-W to 305 patients (median age, 62.5 years). Most patients (91.4%) were diagnosed at stage III–IV. Notwithstanding a higher proportion of residual disease and older patients in the PC-W group, median progression-free survival was 21.4 months and 13.2 months for PC-W and PC-3W, respectively; median overall survival was 75.2 and 54.0 months for PC-W and PC-3W, respectively. Cox proportional hazards model indicated improved survival for patients treated with PC-W (hazard ratio, 0.54). Similar results were observed for older patients diagnosed at ≥75 years. PC-W demonstrated a better safety profile, with lower incidence of neuropathy, neutropenia, and alopecia. Conclusion PC-W is as active and better tolerated than the standard PC-3W regimen. PC-W may serve as an alternative option for elderly or frail patients. Implications for Practice Weekly scheduling of paclitaxel 80 mg/m2 and carboplatin AUC2, administered on days 1, 8, and 15 in a 28-day cycle (PC-W) for first-line therapy for advanced ovarian cancer, is as active and better tolerated than the standard regimen of carboplatin and paclitaxel (175 mg/m2) every 3 weeks (PC-3W). It is possible that the weekly holiday on day 21 in the PC-W regimen may ensure better completion rates (which may result in treatment delays for toxicity in PC-3W). The results of this retrospective analysis highlight the weekly regimen as a valid treatment option, especially for elderly patients and those with significant comorbidities.

Objective To evaluate the accuracy of ascites cytology in the diagnosis of epithelial ovarian cancer among postmenopausal women. Methods Ascites samples of women older than 51 years sent for cytology evaluation at our institution between 2010 and 2015 were retrospectively compared to final histology. The sensitivity, specificity, negative, and positive predictive values were calculated. Immunohistochemistry stain results were collected to determine diagnostic profiles. Results A total of 551 patients, 51 years and over had both cytology and diagnostic histology samples. Of those, 161 patients had pathology confirmed ovarian tumors, 155 of which were malignant. Of the 155 cases of ovarian cancer, 125 patients had malignant cells on cytology examination (true positive); in 30 cases, ascites was negative for malignancy (false negative). In six cases both ascites and final pathology were negative for malignancy (true negative). There were no cases of positive cytology and negative final pathology (ie, no false-positive cases). The sensitivity, specificity, positive, and negative predictive value for cytology diagnosis of ovarian cancer were 80.6%, 100%, 100%, and 16.7%, respectively. Immunohistochemistry was done on cell blocks in 79 cases of ovarian cancer, 75 (94.9%) had profiles diagnostic for ovarian origin. Conclusions Ascites cytology for postmenopausal women older than 51 years with immunohistochemistry is highly accurate in diagnosis of ovarian cancer. Neoadjuvant chemotherapy can be safely prescribed based on paracentesis evaluations. : Video Summary:http://links.lww.com/MENO/A570.

Introduction The objective was to assess whether an early response to neoadjuvant chemotherapy in women with advanced ovarian cancer may predict short- and long-term clinical outcome. Material and methods This is a retrospective study of all women with stage III-IV tubo-ovarian cancer treated with neoadjuvant chemotherapy at a single center in Montreal between 2003 and 2014. Logistic regression models were used to evaluate the association between cancer antigen 125 (CA-125) levels during neoadjuvant chemotherapy and debulking success. Cox proportional hazard models were used to estimate hazard ratios and their respective 95% CI for death and recurrence. Harrell's concordance indices were calculated to evaluate which variables best predicted the chemotherapy-free interval and overall survival in our population. Results In all, 105 women were included. Following the first, second, and third cycles of neoadjuvant chemotherapy, CA-125 levels had a median reduction of 43.2%, 85.4%, and 92.9%, respectively, compared with CA-125 levels at diagnosis. As early as the second cycle, CA-125 was associated with overall survival (hazard ratio 1.03, 95% CI 1.01-1.05, per 50 U/mL increment). By the third cycle, CA-125 did not only predict overall survival (hazard ratio 1.04, 95% CI 1.01-1.08), but it predicted overall survival better than the success of debulking surgery (Harrell's concordance index 0.646 vs 0.616). Both absolute CA-125 levels and relative reduction in CA-125 levels after 2 and 3 cycles predicted the chance to achieve complete debulking (P Conclusions Reduction of CA-125 levels during neoadjuvant chemotherapy provides an early predictive tool that strongly correlates with successful cytoreductive surgery and long-term clinical outcome in women with advanced high-grade serous and endometrioid ovarian cancer.

Lower uterine segment scarring after cesarean section can decrease intraoperative bleeding during subsequent surgery. We examined whether first elective cesarean section is associated with greater average blood loss compared to repeated surgery.Decrease in maternal hemoglobin and hematocrit after surgery was retrospectively compared between three study groups, women in their first, second and third or more cesarean section. Surgery length and need for blood transfusion were also compared.Out of 9401 cases reviewed between January 2010 November 2020, 3917 had a first cesarean section, 3159 s cesarean section and 2325 had a third or more cesarean section. Hemoglobin and hematocrit drops were highest after first cesarean section (1.1 vs 1.0 vs 1.0 mg/dL, P 0.001 and 3.3 vs 3.0, vs 2.9%, P 0.001, respectively). Surgery length was significantly longer and more patients after third cesarean section required blood transfusions (2.5% vs 1.4% vs. 0.8%, P 0.001). First cesarean section, younger age and BMI35 were associated with increased hemoglobin drop in univariate and multivariate analysis.Although repeated cesarean section is associated with longer surgery and higher need for blood transfusion, average hemoglobin drop after first cesarean section is higher. Scarring of the lower uterine segment can explain this paradoxical finding.

Exploratory laparotomy is considered the gold standard treatment for women with suspected uterine rupture. We aimed to investigate the feasibility and safety of laparoscopy as an alternative for laparotomy for the management of hemodynamically stable women with suspected postpartum uterine rupture.We conducted a case series study including all women who were diagnosed with postpartum uterine rupture following vaginal delivery in a university-affiliated tertiary hospital, between November 2012 and July 2021. Until 2016, all women with suspected post-partum uterine rupture underwent laparotomy. Following 2016, a new tailored protocol based on laparoscopy for the management of postpartum uterine rupture in hemodynamically stable women was implemented. A comparison was made between women who underwent emergent laparoscopy to laparotomy.During the study period 17 women were diagnosed with postpartum uterine rupture. From January 2012 to January 2016, four cases of uterine rupture were diagnosed, all of whom underwent laparotomy. Since 2016, thirteen cases of uterine rupture were diagnosed, of whom seven women (54%) underwent laparoscopy and 6 (46%) laparotomy. The median time interval from delivery to surgery was 70.5 min IQR (40-179) in the laparotomy group and 202 min IQR (70-485) in the laparoscopy group. The median operative time for laparoscopic surgery was 80 min (IQR 60-114) and 78 min (IQR 58-114) for the laparotomy group. Four women who underwent laparotomy (40%) and one who underwent laparoscopy (14.2%) were admitted to the intensive care unit following surgery. Blood products transfusion was required in six women who had laparotomy (60%) and one who had laparoscopy (14.2%). Median hospitalization period was 5 d IQR (4-5) in the laparotomy group as compared to 3 d IQR (3-4) in the laparoscopy group. There were no conversions to laparotomy in the laparoscopy group.In hemodynamic stable women laparoscopic surgery for suspected postpartum uterine rupture is feasible and safe.

Highlights • Patients suffering from both breast and endometrial cancer seem to have unique characteristics. • The sequence of occurrence of malignancies appears to have significance. • In patients that endometrial cancer was diagnosed as a second tumor, it tended to present in a more aggressive form. • In this group, a longer time interval between diagnoses might offer diagnostic and prophylactic opportunities. • No correlation was found to tamoxifen usage among patients., Objective To examine whether patients with both breast cancer (BC) and endometrial cancer (EC) have different features of disease, and whether the sequence of appearance of these tumors is correlated with a more aggressive course. Methods A retrospective, multi-center observational cohort study of patients treated in two tertiary medical centers between 2014 and 2020. Files of patients who had a co-diagnosis of BC and EC were reviewed and clinical, epidemiological, pathological and genetic characteristics were collected. Results 67 patients with a co-diagnosis of both malignances were divided into two groups according to primary tumor diagnosis: BC first group (43/67, 64%) and EC first group (24/67, 36%). The time interval between diagnosis of malignancies was significantly longer in the BC first group (mean 144.5 months vs. 67 months, p

Background Diagnosis of cervical dysplasia and subsequent conization of the uterine cervix might affect women’s’ sexual health. Aim To assess the effect of cervical conization on women’s sexual function and psychological wellbeing. Methods Patients undergoing conization of the cervix were assessed before, and 6 months after conization. Assessment of sexual distress and function was done using the female sexual distress scale-revised (FSDS-r) and the female sexual function inventory (FSFI), respectively. Risk for anxiety and depression, was assessed using the Hospital Anxiety and Depression Scale (HADS). Main Outcome Measures FSDS-r, FSFI and HADS scores before and after conization Results From October 2018 to March 2021, 55 patients undergoing cervical conization were recruited. No significant differences were found in FSDS-r scores before and after conization. An equal number of patients indicated having sexual distress (29 patients, 53%, before and after conization, P=1.0). No significant changes were noticed on any FSDS domains or the total FSDS score before and after conization, (26.8 vs. 26.0, p=0.461). The percent of patients that indicated an overall sexual dysfunction, increased from 49 percent before conization, to 59 percent after conization, P=0.388. A high percent of patients indicated signs of anxiety on the HADS questionnaire, both before and after conization (49% and 47%, respectively). The median anxiety and depression scores did not change after conization, p=1.0. Clinical implications A high percent of patients undergoing conization suffer from sexual distress, sexual dysfunction and general anxiety, both before and after conization. The conization procedure itself did not seem to effect questionnaire scores. Strengths and limitations This was a prospective cohort, with comprehensive assessment of female sexual and psychological wellbeing after conization. Not all subjects reported sexual intercourse prior to questionnaire completion. Conclusion Gynecologists should be aware of the psychological and sexual effect of the diagnosis and treatment of cervical pre-cancerous lesions, patients should be counselled accordingly.

PurposeTo evaluate the use of an intrauterine manipulator on the oncologic outcome of women who had minimally invasive surgery for endometrial cancer. MethodsRetrospective analysis of consecutive patients who were operated with or without the use of an intrauterine manipulator. Univariate and multivariate analysis were used to adjust for possible confounders. Results699 patients were included, of whom 220 (32.8%) were operated with an intrauterine manipulator. The median follow-up was 44 months (range, 29-67). Disease-free survival was similar between groups. 19 (8.8%) patients had positive cytology in the manipulator group vs. 21 (4.4%) in the comparison group (p=0.02). Total recurrence rate was similar between the groups (12.3% vs. 11.9%; p = 0.8). Vaginal vault recurrence was the most common site of recurrence with higher incidence in the manipulator group (4.5% vs. 1.3%; p=0.007). Sub-group analysis of patients who did not receive adjuvant treatment showed higher recurrence rate (8.3% vs. 3%; p=0.023) and worse disease-free survival (p=0.01) for the manipulator group. After controlling for other variables, the use of a manipulator did not affect the risk of recurrence for the whole cohort (HR, 1.28; 95% CI, 0.7-2.1, p=0.3) and for the sub-group of patients who did not receive adjuvant treatment (HR, 2.47; 95% CI, 0.8-7, p=0.08).ConclusionThe use of a manipulator during surgery for endometrial cancer increases the risk of positive cytology as well as vaginal vault recurrences, but it does not reduce the disease-free and overall survival of patients.

Background Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs’). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Results IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusions IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

Objectives: Although non-inferior overall survival and reduced surgical morbidity with neoadjuvant therapy (NAC) compared to primary debulking surgery, upfront debulking surgery remains the treatment of choice for newly diagnosed advanced stage ovarian cancer (OC) in the US. This can be partially attributed to the association of aggressive surgical treatment with long term survival (LTS) demonstrated in high grade serous OC (HGSOC). On the contrary, NAC has been shown to lower the odds for LTS. We aimed to identify clinico-pathologic factors associated with LTS in advanced epithelial OC (EOC) treated with NAC. Methods: This is a retrospective case-control study. Women with FIGO stage III-IV high grade epithelial cancer of the ovary, fallopian tube or peritoneum diagnosed and treated with NAC prior to 2013 were extracted from consecutive patient records of the Tel-Aviv Sourasky Medical Center. Women surviving longer than 7 years from diagnosis (defined as long-term survivors, LTS) were compared to women surviving 6-24 months from diagnosis (defined as short-term survivors, STS). Patients with low grade or low malignant potential tumors were excluded. Results: We identified 190 women with stage III/IV epithelial OC. Seventy-eight patients (41%) survived longer than 5 years from diagnosis and 47 (24%) survived longer than 7 years from diagnosis, significantly higher proportions compared to previous reports. Thirty-nine patients (20%) survived 6-24 months, similar to previous reports. Clinicopathologic and treatment characteristics of both groups are displayed in Table 1. CA125 pre-treatment or after 4 courses of chemotherapy and the number of adjuvant and total chemotherapy courses administered were similar between the groups. LTS were significantly younger than STS at diagnosis, with a mean age of 60.05 years vs 65.95 years, respectively (p=0.008). The majority of LTS received 3 courses of NAC or less compared to STS (59.6% vs 33.4%), implying a smaller disease burden or better response to NAC. LTS had a significantly longer disease-free interval (80.49 months vs 3.65 months, p Download : Download high-res image (404KB) Download : Download full-size image Conclusions: Our analysis, to the best of our knowledge, is the first to demonstrate that NAC does not compromise the odds of long-term survivorship in women with advanced EOC, further strengthening NAC as an equivalent alternative to primary debulking surgery. In addition, we identified basic clinicpathologic and treatment-related factors associated with long term survival of epithelial OC patients treated with NAC. Further investigation is needed to determine which factors should be integrated into treatment-related decisions.

INTRODUCTION We compared oncologic and clinical outcomes in patients with advanced ovarian cancer who received dose-dense weekly paclitaxel with 3-weekly carboplatin with those who received standard 3-weekly chemotherapy. MATERIAL AND METHODS Comparison of all consecutive patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer who received a dose-dense protocol between 2010 and 2016 with an immediate historical cohort of consecutive patients who received standard chemotherapy. Patients who received less than three cycles of treatment were excluded. RESULTS In all, 246 patients were included in the study, of whom 128 received the dose-dense protocol and 118 were treated with the standard Q3-week protocol. Patients in the dose-dense group had significantly better progression-free survival than those receiving the standard protocol (median progression-free survival 22 vs 15 months; log rank = 0.026). The overall survival of patients in the dose-dense group was also better than that of the patients in the standard protocol group; however, this difference was not statistically significant (median overall survival 66 vs 54 months; log rank = 0.185). The dose-dense protocol remained significantly associated with favorable survival outcome in multivariable analysis adjusted for stage, histologic type, cytoreductive results and neoadjuvant chemotherapy. The use of the dose-dense protocol was associated with higher rates of gastrointestinal, dermatologic, neurologic and hematologic side effects. CONCLUSION Despite the limitations associated with the comparison to a historical cohort, a dose-dense chemotherapy protocol resulted in a significantly improved progression-free survival and the overall survival tended to be better, but this difference did not reach statistical significance compared with the standard chemotherapy protocol, and may be considered as a treatment alternative, albeit with some increased side effects.

Study Objective To assess the effect of carbon dioxide (CO2) pneumoperitoneum and steep Trendelenburg position on patients’ cardiac function and hemodynamics during minimally invasive staging surgery for endometrial cancer. Design Single-center prospective longitudinal study. Setting University-affiliated tertiary hospital. Patients Patients with endometrial cancer undergoing minimally invasive surgery. Interventions After consent, the patients’ hemodynamic parameters were assessed by the Non-Invasive Cardiac System (NI Medical, Petah Tikva, Israel) at 5 time points: before general anesthesia, after induction of general anesthesia, after CO2 insufflation of the peritoneum, after steep Trendelenburg position, and at the end of surgery. Measurements and Main Results Twenty-three women were recruited. The median age of the patients was 68 years (interquartile range [IQR] 62–75), with a median body mass index of 34.9 kg/m2 (IQR 31.2–39.5) and an American Society of Anesthesiologists score ≥2. The initial median mean arterial pressure was 108 mmHg (IQR 101–113), and the baseline median cardiac output was 7.2 L/min (IQR 5.6–8.7). The median mean arterial pressure significantly decreased by 18% after insufflation (p = .001), again after Trendelenburg position (p = .003), and did not fully recover at the end of surgery in comparison with the preanesthesia baseline (p = .001). The median stroke volume significantly decreased by 17% after insufflation compared with the baseline (p = .01) and then gradually recovered to the baseline levels by the end of surgery. The median cardiac power significantly decreased by 35% after insufflation (0.009), remained low during Trendelenburg position (p = .009), and recovered by the end of surgery to 18% below the baseline levels (p = .035). Conclusion Significant hemodynamic changes occur during minimally invasive staging surgery for endometrial cancer. CO2 insufflation is accompanied by the most dramatic hemodynamic deterioration during surgery, and this does not get affected much with Trendelenburg. Knowledge of the hemodynamic values of women classified as high risk when using a noninvasive technique during surgery is obtainable and may assist both surgeon and anesthesiologist to ensure a safer procedure.

With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment. Prevention Relevance: Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.

Objective To propose a treatment algorithm, after the LACC trial, of laparoscopic sentinel lymph node biopsy with frozen section, followed by immediate open radical hysterectomy in node-negative cases, for early stage cervical cancer. Methods We retrospectively collected all cases of cervical cancer that were surgically treated in 2019-2020. In all cases, surgery began with laparoscopic sentinel lymph node biopsy ± ovarian transposition. Node-negative cases continued with open radical hysterectomy. In node-positive cases, surgery was discontinued, sparing the patient a laparotomy incision. Results Nine patients with cervical cancer were referred for surgery. Laparoscopic bilateral lymph node identification was achieved in all. In two cases, sentinel lymph nodes were positive for metastatic cancer and surgery was discontinued. For the other seven, node-negative patients, open radical hysterectomy was completed. Four patients had laparoscopic ovarian transposition. There were no cases where nodes were negative on frozen section but positive on final pathology. Conclusion Laparoscopic sentinel lymph node biopsy before open radical hysterectomy may spare a considerable number of laparotomies on the one hand and bi-modal treatment with surgery and radiation on the other, for node-positive patients. The oncological safety of this approach is yet to be determined.

Objective To compare short-term fertility rates after medical and surgical management of early miscarriage. Design Observational cohort study. Setting Academic tertiary-care medical center. Patient(s) A total of 203 patients were enrolled between June 2017 and May 2018, comprising 106 surgical evacuations and 97 medical evacuations. Intervention(s) Either surgical or medical evacuation of the uterine cavity. Main Outcome Measure(s) Conception rates 6 months after miscarriage. Result(s) Conception rates 6 months after miscarriage among women who had attempted to become pregnant were similar between the medically and surgically evacuated groups (68.0% vs. 65.1%). There were no significant differences in background characteristics between the groups, apart from younger age and earlier gestational age among the medically treated group. There was no difference in the proportion of women using assisted reproductive technologies between the medically and surgically managed groups (15.5% vs. 12.6%, respectively). The median time-to-conception was 4 ± 2 months in both groups. Cumulative pregnancy rate 12 months after pregnancy loss, live birth rate, and repeat miscarriage rate also were similar between groups. Conclusion(s) Modality of uterine evacuation after early miscarriage does not affect short-term fertility outcomes.

Objective To evaluate the impact of surgical wait times on outcome of patients with grade 3 endometrial cancer. Methods All consecutive patients surgically treated for grade 3 endometrial cancer between 2007 and 2015 were included. Patients were divided into two groups based on the time interval between endometrial biopsy and surgery: wait time from biopsy to surgery ≤12 weeks (84 days) vs more than 12 weeks. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. Results A total of 136 patients with grade 3 endometrial cancer were followed for a median of 5.6 years. Fifty-one women (37.5%) waited more than 12 weeks for surgery. Prolonged surgical wait times were not associated with advanced stage at surgery, positive lymph nodes, increased lymphovascular space invasion, and tumor size (P = .8, P = 1.0, P = .2, P = .9, respectively). In multivariable analysis adjusted for clinical and pathological factors, wait times did not significantly affect disease-specific survival (adjusted hazard ratio [HR]: 1.2, 95% confidence interval [CI], 0.6-2.5, P = .6), overall survival (HR: 1.1, 95% CI, 0.6-2.1, P = .7), or progression-free survival (HR: 0.9, 95% CI, 0.5-1.7, P = .8). Conclusion Prolonged surgical wait time for poorly differentiated endometrial cancer seemed to have a limited impact on clinical outcomes compared to biological factors.

Objective This study sought to evaluate the incidence, risk factors, and estimated cost associated with venous thromboembolism (VTE) following robotic surgery for endometrial cancer. Methods The study included all consecutive patients with newly diagnosed endometrial cancer who underwent robotic surgery, excluding patients with a previous history of VTE (3%), those taking long-term warfarin (3%), and patients with conversions to laparotomy (3%). The incidence of postoperative symptomatic VTE within 90 days was analyzed. Direct and indirect medical costs were estimated using a linked billing database for standardized, inflation-adjusted costs. Results A total of 558 cases were identified. Median BMI was 29 kg/m2 (range, 17–85 kg/m2), median operative time was 227 minutes (range, 75–419 minutes), and median blood loss was 30 mL (range, 3–400 mL). All patients received thromboprophylaxis with intraoperative subcutaneous heparin and sequential pneumatic compression devices. Extended postoperative prophylaxis for 28 days was administered to 88 (17.2%) patients with high-risk factors. A total of eight patients (1.6%) developed symptomatic VTE, and all eight were in the group that did not receive extended prophylaxis. The number needed to treat to prevent one VTE was 52.8, with an absolute risk reduction 1.89% (95% CI 0.59% to 3.19%). The average cost for treatment of a VTE was $7653 (range, $4396–$12 211), equivalent to the cost of treating 21 patients with extended prophylaxis ($356 per patient). Conclusion The incidence of VTE in patients with endometrial cancer who underwent robotic-assisted surgery was low (1.6%), and none of the VTEs occurred in the cohort of high-risk patients who received extended thromboprophylaxis.

Objective: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC). Methods: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing. Results: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%, P = .03; distant: 50% vs. 17.5%, P = .004) and progression events (73.1% vs. 26.3%, P

Objective The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens. Study design RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naive patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival. Results In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively. Conclusion Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naive patients.

The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p &lt, 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population.

Objective Pilot study to assess the value of weekly paclitaxel plus carboplatin every 3weeks (dose dense regimen, DD) compared to the standard 3-weekly protocol in the adjuvant setting for endometrial cancer. Methods Retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer, undergoing DD protocol (from 2011 to 2015) to a non-overlapping historical cohort with similar characteristics who received treatment every three weeks (2008–2011). Results 122 patients with endometrial cancer were included in the study, of these, 61 patients received the dose dense protocol and 61 were treated with the standard 3-weekly protocol. After a median follow-up of 61.6months in the 3-weekly cohort, compared with 41.6months in the DD cohort, 40 progressions were recorded. 29 progressions were observed in women treated in the standard protocol, with a three years progression free survival (PFS) of 57.4%, compared to 11 progressions observed in patients in the DD schedule, with a three years PFS of 79.5% ( P =0.03). Patients who were treated with the DD protocol were less likely to have progression events compared to the standard cohort with a hazard ratio of 0.4 on multivariate analysis (CI 95%, 0.2–0.8, P =0.01), had significantly less distant metastases ( P =0.01), and had improved overall survival when diagnosed with advanced stage disease ( P =0.02). Complaints of musculoskeletal pain were more frequent in the standard cohort ( n =17, 27.9%) compared to the dose dense cohort ( n =4, 6.6%), P =0.005. Conclusion Preliminary data suggests that dose dense chemotherapy might be a reasonable and superior option for adjuvant treatment of endometrial cancer, compared to standard chemotherapy.

Background Phosphatase and Tensin homolog (PTEN) is a tumor suppressor gene. Loss of its function is the most frequent genetic alteration in endometrioid endometrial cancers (70–80%) and high grade tumors (90%). We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status. We also highlighted a direct pathway linking PTEN to DNA repair. Methods Using endometrial cancer cellular models with known PTEN status, we evaluated their homologous recombination (HR) functionality by RAD51 foci formation assay. The 50% Inhibitory concentration (IC50) of PI3K and PARP inhibitors in these cells was assessed, and western blotting was performed to determine the expression of proteins involved in the PI3K/mTOR pathway. Moreover, we explored the interaction between RAD51 and PI3K/mTOR by immunofluorescence. Next, the combination effect of PI3K and PARP inhibitors on cell proliferation was evaluated by a clonogenic assay. Results Cells with mutated PTEN showed over-activation of the PI3K/mTOR pathway. These cells were more sensitive to PARP inhibition compared to PTEN wild-type cells. In addition, PI3K inhibitor treatment reduced RAD51 foci formation in PTEN mutated cells, and sensitized these cells to PARP inhibitor. Conclusion Targeting both PARP and PI3K might lead to improved personalized therapeutic approaches in endometrial cancer patients with PTEN mutations. Understanding the complex interaction of PTEN mutations with DNA repair in endometrial cancer will help to better select patients that are likely to respond to some of the new and costly targeted therapies.

Objective To evaluate clinical outcome in patients selected to receive neoadjuvant chemotherapy (NACT) compared to primary debulking surgery (PDS). Methods Retrospective study including all consecutive patients diagnosed and treated for advanced (stages III-IV) ovarian cancers between the years 2003–2015. Results 263 women were included in the study, of these, 127 patients were selected to receive NACT and 136 were treated with PDS followed by adjuvant chemotherapy. PDS was associated with longer OS in stage IIIc disease (median OS: 60.2 vs. 48.8months; p -value 0.039) compared with NACT. Patients achieved higher rates of complete cytoreduction in the NACT group compared to the PDS group (65.9% vs. 40.2%; p =0.001). Patients attaining complete cytoreduction after PDS had the best survival, (median OS 106months) followed by those with complete cytoreduction after NACT (median OS 71months), followed by those with residual disease after PDS (median OS 55months). Patients with residual disease following interval debulking after NACT had the worst outcome (median OS 36months). Platinum sensitivity following first line and second line chemotherapy was similar whether patients received neoadjuvant chemotherapy or not. Conclusion PDS was associated with improved outcome. NACT appears to improve survival outcome in patients that would have had residual disease after PDS, and attain complete cytoreduction at the time of interval cytoreduction. This treatment option can be used in selected patients that are not candidates for complete cytoreduction at PDS.