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Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as a subgroup of T cells that possess strong proliferative capacity and that can expand and differentiate following interactions with dendritic cells (DCs). In this study, we explored the pattern of expression of a recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) and its ligand, poliovirus receptor-related ligand 2 (PVRL2), in the human tumor microenvironment. Using spatial and single-cell RNA transcriptomics data across diverse cancer indications, we found that among the T-cell checkpoints, PVRIG is uniquely expressed on TSCM and PVRL2 is expressed on DCs in immune aggregate niches in tumors. PVRIG blockade could therefore enhance TSCM-DC interactions and efficiently drive T-cell infiltration to tumors. Consistent with these data, following PVRIG blockade in patients with poorly infiltrated tumors, we observed immune modulation including increased tumor T-cell infiltration, T-cell receptor (TCR) clonality, and intratumoral T-cell expansion, all of which were associated with clinical benefit. These data suggest PVRIG blockade as a promising strategy to induce potent antitumor T-cell responses, providing a novel approach to overcome resistance to immunotherapy in immune-excluded tumors., (©2024 American Association for Cancer Research.)

Objective: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy., Methods: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021., Results: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy., Conclusions: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the surgical and oncological outcomes of elderly patients with intermediate to high-risk endometrial cancer undergoing staging with sentinel lymph node (SLN) sampling and pelvic lymphadenectomy., Methods: We conducted a retrospective study of elderly (>65-year-old) patients diagnosed with endometrial cancer between December 2007 and August 2017. These patients had been treated at a single center in Montreal, Canada. We compared the surgical and oncological outcomes of three cohorts undergoing surgical staging in non-overlapping eras: 1) lymphadenectomy, 2) lymphadenectomy and SLN sampling, 3) SLN sampling alone. Using life tables, Kaplan-Meier survival curves and log-rank tests, we analyzed 2-year progression-free survival, overall survival, and disease-specific survival., Results: Our study included 278 patients with a median age of 73 years (range; 65-91): 84 (30.2%) underwent lymphadenectomy, 120 (43.2%) underwent SLN sampling with lymphadenectomy, and 74 (26.6%) had SLN sampling alone. The SLN sampling alone group had shorter operative times with a median duration of 199 minutes (range, 75-393) compared with 231 (range, 125-403) and 229 (range, 151-440) minutes in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts; respectively (p<0.001). The SLN sampling alone group also had lower estimated blood loss with a median loss of 20 mL (range, 5-150) vs 25 mL (range, 5-800) and 40 mL (range, 5-400) in the SLN sampling with lymphadenectomy and lymphadenectomy cohorts, respectively (p=0.002). The 2 year overall survival and progression-free survival were not significantly different between the three groups (p=0.45, p=0.51, respectively). On multivariable analysis after adjusting for age, American Society of Anesthesiologists (ASA) score, stage, grade, and lymphovascular space invasion, adding SLN sampling was associated with better overall survival, (HR 0.2, CI [0.1 to 0.6], p=0.006) and progression-free survival (HR 0.5, CI [0.1 to 1.0], p=0.05)., Conclusion: Sentinel lymph node-based surgical staging is feasible and associated with better surgical outcomes and comparable oncological outcomes in elderly patients with intermediate and high - risk endometrial cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

DNA repair by homologous recombination (HR) is critical for the maintenance of genome stability. Germline and somatic mutations in HR genes have been associated with an increased risk of developing breast (BC) and ovarian cancers (OvC). However, the extent of factors and pathways that are functionally linked to HR with clinical relevance for BC and OvC remains unclear. To gain a broader understanding of this pathway, we used multi-omics datasets coupled with machine learning to identify genes that are associated with HR and to predict their sub-function. Specifically, we integrated our phylogenetic-based co-evolution approach (CladePP) with 23 distinct genetic and proteomic screens that monitored, directly or indirectly, DNA repair by HR. This omics data integration analysis yielded a new database (HRbase) that contains a list of 464 predictions, including 76 gold standard HR genes. Interestingly, the spliceosome machinery emerged as one major pathway with significant cross-platform interactions with the HR pathway. We functionally validated 6 spliceosome factors, including the RNA helicase SNRNP200 and its co-factor SNW1. Importantly, their RNA expression correlated with BC/OvC patient outcome. Altogether, we identified novel clinically relevant DNA repair factors and delineated their specific sub-function by machine learning. Our results, supported by evolutionary and multi-omics analyses, suggest that the spliceosome machinery plays an important role during the repair of DNA double-strand breaks (DSBs)., (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer.)

Purpose: To evaluate the association between a single abnormal value on a 3-h 100 g oral glucose tolerance test (OGTT) results and future type-2 diabetes mellitus (Type-2 DM)., Methods: Retrospective cohort study of women between 18 and 45 years of age who underwent a 3-h OGTT during pregnancy and delivered in a tertiary medical center between 2007 and 2014. The women  were followed for a median period of 64 months postpartum. According to OGTT values, women were divided into three groups: normoglycemic (normal OGTT), single abnormal OGTT value (SAV) and gestational diabetes mellitus (two or more abnormal OGTT values, GDM). General pre-pregnancy characteristics, cardiovascular risk factors and future diagnosis of Type-2 DM, as the primary outcome, were recorded., Results: During the study period, 5295 women underwent an OGTT and were followed for a median period of 64 months (interquartile range of 32). The cohort was divided as following: 3639 (68.73%) were normoglycemic, 854 (16.13%) had a SAV in the OGTT and 802 (15.15%) were diagnosed with GDM. Compared with normoglycemic controls, women with SAV and GDM tended to be older (32.20, 33.10 and 31.35 years for SAV, GDM and controls, respectively, p < 0.001); with higher rates of pre-pregnancy obesity (18.62%, 20.77% and 13.22% for SAV, GDM and controls, respectively, p < 0.001), pre-pregnancy hyperlipidemia (13.35%, 15.30% and 10.52% for SAV, GDM and controls, respectively, p = 0.021) and pre-pregnancy chronic hypertension (5.50%, 4.43% and 3.18% for SAV, GDM and controls, respectively, p = 0.01). Post-pregnancy Type-2 DM was diagnosed at a higher rate among women with SAV or GDM (2.69% for SAV, 7.39% for GDM and 0.66% for normoglycemic controls, p < 0.001). Using a cox proportional hazard regression, SAV and GDM were significantly and independently associated with a higher rate of future overt type-2 diabetes (adjusted aOR 3.59 for SAV and 11.38 for GDM, p < 0.001). In a sub-analysis of the OGTT values, overall, abnormal fasting glucose had the highest correlation with developing future Type-2 DM (8.95% compared with 6.02% for OGTT&#95;60, 6.03% for OGTT&#95;120 and 7.35% for OGTT&#95;180, p < 0.001). A predictive model, combining multiple risk factors, as pre-pregnancy obesity and hypertension with SAV complicating the index pregnancy showed a risk as high as 3.40% for developing future Type-2 DM., Conclusion: SAV is independently associated with a significant higher rate of future Type-2 DM, as early as 5 years following the index pregnancy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This is a retrospective analysis of mothers with abnormal 1-hour, 50-grams glucose challenge test (GCT) who did not take a 3-hour, 100-gram oral glucose tolerance test (OGTT). This study group of women was compared to three control groups, based on an OGTT diagnostic test- normal OGTT, single pathological value and gestational diabetes mellitus. Overall- 4,185 women were included and sub-divided accordingly into four groups: Group A-340 (8.12%)- no OGTT; Group B-2,585 (61.77%)- Norm OGTT (All values normal); Group C- 564 (13.48%)- SinOGTT (single pathological value) and Group D- 696 (16.63%)- Gestational Diabetes Mellitus (GDM, ≥ 2 pathological values). Groups A, C and D had higher rates of intrapartum Caesarean Delivery (10.29%, 11.52% and 10.19% vs. 8.43%, p  < .0001). Group A had highest rates of neonatal adverse outcomes, as neonatal intensive care unit (NICU) admission (12.4% vs. 8.4%, 11.0% and 10.0%, p  = .039), small for gestational age (SGA) neonates (7.0% vs. 5.3%, 3.7% and 6.0%, p  = .0092) and neonatal hypoglycaemia (3.5% vs. 1.3%, 3.2% and 2.9%, p  = .007). A multivariable regression revealed that having an abnormal GCT without an OGTT was an independent risk factor for neonatal intensive care unit admission, neonatal hypoglycaemia and intrapartum caesarean delivery. We concluded that women with pathological GCT who did not complete OGTT have higher rates of obstetric adverse outcomes. They should be closely monitored during delivery and should not be overlooked.IMPACT STATEMENT What is already known on this subject? Adverse outcomes of gestational diabetes mellitus are well established. But, the group of women who fail to complete a confirmatory OGTT following a pathological GCT is not well described. What the results of this study add? Our results point out that women who fail to complete an OGTT, suffer from higher rates of obstetric complications, presumably attributed to disrupted glucose values, but also to poor prenatal care. What the implications are of these findings for clinical practice and/or further research? These women should not be overlooked. They should be closely monitored during labour and delivery.

Background: Poly ADP-ribose glycohydrolase (PARG) is responsible for the catabolism of PARP-synthesized PAR to free ADP-ribose. Inhibition of PARG leads to DNA repair interruption and consequently induces cell death. This study aims to evaluate the effect of a PARG inhibitor (PARGi) on epithelial ovarian cancer (OC) cell lines, alone and in combination with a PARP inhibitor (PARPi) and/or Cisplatin., Methods: PARG mRNA levels were studied in three different OC datasets: TCGA, Hendrix, and Meyniel. PARG protein levels were assessed in 100 OC specimens from our bio-bank. The therapeutic efficacy of PARGi was assessed using cell migration and clonogenic formation assays. Flow cytometry was used to evaluate the cell apoptosis rate and the changes in the cell cycle., Results: PARG protein was highly expressed in 34% of the OC tumors and low expression was found in another 9%. Similarly, Hendrix, Meyneil and TCGA databases showed a significant up-regulation in PARG mRNA expression in OC samples as compared to normal tissue (P=0.001, P=0.005, P=0.005, respectively). The use of PARGi leads to decreased cell migration. PARGi in combination with PARPi or Cisplatin induced decreased survival of cells as compared to each drug alone. In the presence of PARPi and Cisplatin, PARG knockdown cell lines showed significant G2/M cell cycle arrest and cell death induction., Conclusions: PARG inhibition appears as a complementary strategy to PARP inhibition in the treatment of ovarian cancer, especially in the presence of homologous recombination defects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Matanes, López-Ozuna, Octeau, Baloch, Racovitan, Dhillon, Kessous, Raban, Kogan, Salvador, Lau, Gotlieb and Yasmeen.)

Objective: Although its use in endometrial cancer staging is relatively new, sentinel lymph node (SLN) sampling has been shown to be highly accurate and is associated with few complications. However, some studies report lower rates of detection with SLN sampling among patients with obesity. The aim of the current study is to evaluate the feasibility of SLN sampling in endometrial cancer for patients with obesity, and to determine whether omitting lymph node dissection (LND) in surgical staging using SLN sampling impacts oncologic outcomes., Methods: we conducted a retrospective study of patients with obesity (BMI ≥35 kg/m 2) , diagnosed with endometrial carcinoma between 2007 and 2017, that compared surgical and oncologic outcomes of 2 cohorts: patients who underwent LND and patients who underwent SLN without lymphadenectomy. The primary outcome was operative time. Secondary outcomes included intraoperative bleeding; lymph node assessment information; intraoperative and postoperative adverse events; and oncologic outcomes including progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS). PFS was defined as the time from surgery to the recurrence or death from any cause. OS was defined as time from diagnosis to death or the last date the patient was known to be alive, and DSS was defined as the time from the surgery to death from the disease., Results: Out of 223 patients with a median BMI of 40.6 kg/m 2 , 140 underwent LND and 83 underwent SLN alone. The median operative time for patients in the SLN group was shorter than that of patients in the LND group (190.5 [range 108-393] vs. 238 [131-440] min; P < 0.001), and the SLN group had lower median estimated blood loss than the LND group (30 [range 0-300] vs. 40 [range 0-800] mL; P = 0.03). At the 24-month follow-up cut-off, 98% of patients were alive and 95.5% were disease free, with no significant differences in OS, DSS, and PFS between the 2 groups (P = 0.7, P = 0.8, and P = 0.4, respectively)., Conclusions: In patients with obesity, omitting LND from surgical staging with SLN sampling was associated with shorter operative times and less bleeding and did not affect survival at 2 years., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.)

Background: We aimed to assess the association of pre-operatively evaluated ultrasonographic endometrial thickness with outcomes of patients with endometrial cancer., Methods: An Israel Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer who underwent surgery between 2002 and 2014 in one of eleven academic centers. Patients were categorized by endometrial thickness into two groups: ≤20 mm and >20 mm. Clinical and pathological features were compared using Student T-test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations., Results: 1113 patients in whom endometrial thickness data was recorded were the subject of this study and included 2 groups: ≤20 mm (n = 930), >20 mm (n = 183). The median follow-up was 52 months (range 12-120 months). Patients with endometrial thickness >20 mm had significantly lower recurrence-free survival (log rank, p < .0001), disease-specific survival (log rank, p = .01), and overall survival (log rank, p < .0001). On multivariate Cox proportional hazards analysis, endometrial thickness >20 mm remained independently associated with an increased hazard of recurrence and death (HR = 1.77, 95% CI 1.07-2.96, p = .03 for recurrence; and HR = 1.68; 95% CI 1.07-2.65; p = .03 for overall survival)., Conclusion: In patients with endometrial cancer, endometrial thickness>20 mm as measured preoperatively by ultrasound, is independently associated with decreased recurrence-free and overall survival. This finding suggests that thick endometrium may be considered as one of the risk factors for poor prognosis., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis., Material and Methods: In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling., Results: A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001)., Conclusions: Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Background: This retrospective study compared perioperative measures, costs, quality of life and survival after open vs. robotic surgery, among obese women diagnosed with low-grade endometrial cancer., Methods: Obese women (body mass index (BMI) ≥ 30) who underwent open or robotic surgery for endometrial cancer, in one of two tertiary medical centers in the center of Israel, 2013-2016, postoperative grade 1-2, were included. Costs per patient, including 30-days post-surgery were calculated. Quality of life was evaluated by Physical and Mental Components of the SF-36 and a recovery from surgery questionnaire. Overall survival outcomes were obtained from patients' files. Surgical outcomes, including operating and anesthesia times, length of hospital stay, and intraoperative and postoperative complications according to the Clavien-Dindo classification scale were reviewed., Results: In all, 138 women with BMI ≥30 underwent open (n = 61) or robotic surgery (n = 77) during the study period. The groups had similar BMI, comorbidities, demographics and tumor characteristics. Robotic surgery was associated with shorter hospital stays (mean 1.7 vs. 4.8 days; P < .0001) and fewer postoperative complications (Clavien-Dindo > 2, 5.2% vs. 19.7%; P = .0008), but longer operating theater time (3.8 vs. 2.8 h; P < .001). Costs are equivalent when at least 350 robotic surgeries are performed annually, not including the initial system costs. Quality of life measures were better after robotic surgery. SF-36 showed better measures for robotic surgery (Physical 56 vs. 39 and Mental 73 vs. 56; P < .01). After robotic surgery, patients tended to recover quicker when compared to open surgery, as they returned to normal activities earlier, with less need for family and governmental assistance (mean recovery time, 23 vs. 70 days; P < 0.006 and mean change in preoperative total functioning score, - 1.5 vs. -3.9: P < 0.05, respectively). Overall, 5-year survival was 89.8% for the open surgery group vs. 94% for the robotic surgery group (log rank, P = 0.330)., Conclusions: Obese women with low-grade endometrial cancer had better quality of life after robotic vs. open surgery. They also had shorter hospital stays and fewer postoperative complications. Centers with high volumes of robotic surgery can achieve similar costs when comparing both methods. These results were achieved without jeopardizing survival. Our results further emphasize the need for the Israeli healthcare system to include specific reimbursement for robotic procedures in the population we studied.

Objectives: Primary, to explore correlation between the extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer and the number of nodes with metastasis. Secondary, evaluate survival measures in relation to the number of excised nodes., Methods: A retrospective multi-center study of prospectively collected information of 2014 women with endometrial cancer, 1032 of whom underwent lymph node staging. Spearman's rank correlation was used to assess the correlation between the number of pelvic nodes excised and the number of metastatic nodes. Women's data were dichotomized by the median number of excised pelvic nodes. Kaplan-Meier and log rank tests were used to examine the effect of the number of pelvic nodes excised on survival., Results: There was no significant correlation between the number of pelvic nodes harvested and the number of metastatic lymph nodes (r = 0.301; p = 0.28). The median number of excised pelvic nodes was 9 (range 1-77). There was no difference between women with up to 9 and women with more than 9 lymph nodes excised in the 5-year recurrence-free survival (82.4% vs. 83.9%; p = 0.90), disease-specific survival (83.6% vs. 86.7%; p = 0.37), or overall survival (75.8% vs. 82.8%; p = 0.11)., Conclusions: The extent of pelvic lymphadenectomy in the surgical staging of endometrial cancer is not associated with a higher yield of metastatic nodes or with longer survival. Current focus should be on sentinel node procedures that offer women the benefit of accurate staging without the complications associated with extensive lymphadenectomy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity., Objectives: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT)., Methods: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS)., Results: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001)., Conclusions: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.

Objective: To assess whether statin use by endometrial cancer patients was associated with a survival advantage., Methods: A retrospective chart review study, by the Israeli Gynecologic Oncology Group, of consecutive endometrial cancer patients who underwent surgery in one of 11 medical centers between 2002 and 2014. Clinical and pathological reports, and measures of survival were compared between statin users and nonusers. Kaplan-Meier and Cox proportional hazard models were used to assess the effect of using statins on survival measures., Results: Over a mean follow-up period of 6.2 years (range, 1-12 years) for 2017 endometrial cancer patients with complete data, 663 (32.8%) used statins prior to diagnosis and 1354 (67.1%) did not. No statistically significant differences between the groups were observed for most demographic and clinical characteristics. There was no difference between statin users and nonusers in 5-year recurrence-free survival (82% vs 83%; P=0.508), disease-specific survival (86% vs 84%; P=0.549), or overall survival (77% vs 75%; P=0.901)., Conclusions: In this large cohort of patients with endometrial cancer, no significant associations were found between use of statins and endometrial cancer survival., (© 2019 International Federation of Gynecology and Obstetrics.)

Objectives: To evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) upon diagnosis, and its impact on surgical outcome, among patients with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy (NACT)., Methods: A retrospective cohort study included all women with stage IIIC and IV ovarian carcinoma receiving NACT in Rabin Medical Center, Petah-Tikva, Israel; January 1, 2005, to June 30, 2017. Demographics and treatment outcome were compared between patients with NLR at diagnosis ≥6.0 and those with NLR <6.0. Primary outcome was optimal debulking (<1 cm largest residual disease). Overall survival was compared between groups using Kaplan-Meier survival analysis., Results: Of 111 patients, 33 (29.7%) had NLR ≥6.0 at diagnosis, and 78 (70.3%) had NLR <6.0. No difference was found in rates of optimal debulking between the group with NLR ≥6.0 and that with NLR <6.0 (78.9% vs 84.7%, respectively, P=0.555). Using Kaplan-Meier survival analysis, NLR ≥6.0 was associated with significantly worse overall survival (P<0.05). In a multivariate Cox proportional hazard model, elevated NLR was not statistically associated with poor overall survival (P=0.080)., Conclusions: In advanced stage ovarian carcinoma, NLR ≥6.0 at diagnosis did not predict surgical outcome, however it was a predictive factor for poor overall survival., (© 2019 International Federation of Gynecology and Obstetrics.)

Objective: To compare survival measures of women with early-stage endometrial cancer who underwent either hysteroscopy or a non-hysteroscopic procedure as a diagnostic procedure., Study Design: An Israel Gynecologic Oncology Group multicenter study of 1324 patients with stage I endometrial cancer who underwent surgery between 2002 and 2014. Patients were divided into two groups: hysteroscopy and non-hysteroscopy (curettage or office endometrial biopsy). Clinical, pathological, and survival measures were compared between the groups., Results: There were 355 patients in the hysteroscopy group and 969 patients in the non-hysteroscopy group. The median follow-up was 52 months (range 12-120 months). There were no differences between the groups in the 5-year recurrence-free survival (90.2% vs. 88.2%; p = 0.53), disease-specific survival (93.4% vs. 91.7%; p = 0.5), and overall survival (86.2% vs. 80.6%; p = 0.22)., Conclusion: Our findings affirm that hysteroscopy does not compromise the survival of patients with early-stage endometrial cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Little is known on the impact of neoadjuvant chemotherapy (NACT) treatment modifications on surgical outcome and progression-free survival (PFS) in patients with ovarian carcinoma. We aimed to report the changes we made during NACT and to evaluate its impact on patient outcome., Methods: A retrospective cohort study of all women with advanced stage ovarian carcinoma treated with NACT followed by interval cytoreduction in one university-affiliated medical center (January 2005 to June 2017). We excluded those who were treated with NACT without any surgical intervention. NACT modifications included delay in treatment, change in chemotherapy, and dose reduction. Demographics, tumor characteristics, surgical outcome, and PFS were compared between patients exposed to NACT treatment modifications and those who received standard treatment., Results: Seventy-nine patients met inclusion criteria of whom, 59 patients received standard, nonmodified treatment and 20 patients modified NACT. There were no intergroup differences with respect to age at diagnosis (59.5±11.6 vs. 64.70±8.09, P=0.09) and stage of disease (P=0.13). Radiologic complete response rates (25.0% vs. 32.2%, P=0.545) and optimal cytoreduction rates (75.0% vs. 86.4%, P=0.23) were similar in both treatment groups. Mean PFS (in months) was comparable between patients receiving standard treatment and those who required NACT modifications (18.5 vs. 12.2, P=0.125)., Conclusions: NACT treatment modifications did not affect surgical outcome and PFS. We conclude that when clinically indicated, dose alteration and scheduling can be implemented without apparent detriment to outcome.

Objectives: To report the preoperative ultrasound (US) signs of isolated fallopian tube torsion in surgically verified cases and to estimate whether preoperative US detection of this condition can be improved., Methods: The charts of 27 women with a surgical diagnosis of isolated fallopian tube torsion at a tertiary medical center from 2005 to 2016 were retrospectively reviewed. Data were collected from the electronic database of the US unit and compared with the surgical findings., Results: Isolated fallopian tube torsion was correctly diagnosed by US before surgery in 8 of the 27 women (29.6%). In the remainder, the US signs were attributed to torsion of the ovary or the entire adnexa (n = 13), or no torsion was suspected (n = 6). Fallopian tube edema was listed as a US finding in 7 patients, of whom 5 had a correct diagnosis of isolated fallopian tube torsion. The presence of a paraovarian cyst concomitant with normal-appearing ovaries was assumed by US in 5 of the 8 cases that were accurately diagnosed as isolated fallopian tube torsion. The most misinterpreted US finding was an ovarian cyst (suspected in 10 patients and verified at surgery in 2). Absence of blood flow was described in 12 women, of whom 5 had an accurate diagnosis of isolated fallopian tube torsion. Six of the patients with a correct US diagnosis were adults (37.5% of total adults), and 2 were adolescents (18.2% of total adolescents)., Conclusions: The US diagnosis of isolated fallopian tube torsion is challenging. A high index of suspicion is necessary to improve its detection, especially when there are possible US signs of torsion in the presence of a normal-appearing ovary., (© 2018 by the American Institute of Ultrasound in Medicine.)

Objectives: Data on the outcome of stage IIA1 cervical cancer is limited, as these tumors comprise a small percentage of early tumors. NCCN guidelines suggest consideration of surgical management for small tumors with vaginal involvement. Our objective was to evaluate the risk of adjuvant radiotherapy in stage IIA1 cervical cancer and its associated features, in order to improve selection of patients for surgical management., Methods: A retrospective cohort study comparing surgically treated cervical cancer patients with stage IB1 and stage IIA1 disease. Women treated between 2000 and 2015 in ten Israeli medical centers were included. Patient and disease features were compared between stages. The relative risk (Fisher's exact test) of receiving post-operative radiation was calculated and compared for each risk factor. A general linear model (GLM) was used for multivariable analysis., Results: 199 patients were included, of whom 21 had stage IIA1 disease. Most features were comparable for stage IB1 and stage IIA1 disease, although patients with vaginal involvement were more likely to have close surgical margins (23.8% vs 8.5%, p = 0.03). Patients with stage IIA1 disease were more likely to receive radiation after surgery (76% vs. 46%, RR = 1.65 (1.24-2.2), p = 0.011). Vaginal involvement as well as depth of stromal invasion, LVSI and lymph node metastases were independent predictors of radiation on multivariable general linear modeling., Conclusions: Cervical cancer patients with vaginal involvement are highly more likely to require postoperative radiation. We recommend careful evaluation of these patients before surgical management is offered., (Copyright © 2018. Published by Elsevier Inc.)

Background: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking., Objective: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer., Study Design: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared., Results: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37)., Conclusion: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ascites is a common finding in patients with ovarian cancer. Paracentesis is a relatively simple, safe, and effective procedure for draining fluid from the peritoneum, but valid quality-of-life tools are needed to determine its subjective value for alleviating symptoms and improving patient quality of life. The objective of this study was to prospectively evaluate the performance of a novel Ascites Symptom Mini-Scale (ASmS) and compare it with a previously available questionnaire., Methods: Patients with ovarian cancer-related ascites presenting for paracentesis were asked to complete the newly devised ASmS before the procedure and 1 and 24 hours after. Patients also completed a pain assessment scale and a previously validated ascites questionnaire at the same time points., Results: The cohort included 28 patients of median age 68 years (range, 51-86 years), 13 (46.4%) with primary ovarian cancer and 15 with recurrent disease. A median of 3300 mL of ascites was drained. The median score on the ASmS decreased significantly from 21.5 before paracentesis to 11.0 at 1 hour after paracentesis (P < 0.001) and remained low at 24 hours. No demographic factor predicted greater benefit from the procedure. Patients with both mild and severe symptoms reported significant relief., Conclusions: The ASmS is a robust quality-of-life tool for the specific assessment of symptoms of ovarian cancer-related malignant ascites. It can be used in the clinical trial setting assessing interventions aimed at treating ascites and in the clinic to identify those patients with mild symptoms, who may benefit from paracentesis.

Objective: Many patients undergo hysterectomy for the treatment of cervical dysplasia. Factors that correlate with residual high-grade squamous intraepithelial lesions (HGSIL) at hysterectomy are not clear. We set out to determine preoperative features that may predict residual disease for patients treated for cervical dysplasia., Materials and Methods: A retrospective database was reviewed for women who underwent simple hysterectomy for HGSIL between 1990 and 2013. Clinical data included age, history of dysplasia, initial treatment, follow-up colposcopy, indications for surgery, time elapsed between initial treatments, and pathology findings after hysterectomy. Significant residual disease was defined as HGSIL or cervical carcinoma. Statistical analyses were performed with the SPSS, independent Student t test, and Pearson χ test. Significance was set at p < .05., Results: Eighty-three women met the study criteria. The indication for hysterectomy was residual histological finding at conization pathology in 30 women and patients' request in 53 women. Residual disease was found in 42 hysterectomy specimens: in 16 of 30 with residual histological finding and in 26 of the 53 patients' request. Reason for the hysterectomy was not statistically significant for residual disease (p = .708). Median age of patients with residual disease was 46.5 years versus 44.1 years for those without residua (p = .02). Postmenopausal patients had a higher rate of residual disease, 12 (32.4%) of the 28 premenopausal patients and 25 (67.6%) of the 54 postmenopausal patients (p = .04). Conization margin status was not associated with residual disease (p = .878)., Conclusions: Older women and those in menopause are at significantly higher risk of residual disease at hysterectomy.

Objective: To investigate the association between subclinical hypothyroidism and preterm contractions., Methods: Prospective observational study among women at 23 + 0/7 and 34 + 6/7 weeks of gestation, with no known thyroid function abnormality, and preterm uterine contractions (PTC). All patients underwent laboratory evaluation of Thyroid Stimulating Hormone (TSH) and Free Thyroxin (FT4). Patients with and without PTC were compared., Results: No association was found between PTC and subclinical hypothyroidism. Rate of spontaneous preterm delivery (PTD) was comparable between women with abnormal and normal thyroid function tests. Excluding indicated PTD, patients in the study group had a higher rate of spontaneous PTD (24.7% versus 9.6%, p = 0.03). Patients with past PTD and preterm contractions had higher rates of hypothyroxinemia compared with patients without past PTD (54.6% versus 19.0% and 31.2%, p = 0.001), and patients with past PTD (regardless of the presence or absence of PTC) had higher rate of subclinical hypothyroidism compared with patients with PTC and without PTD (59.1% and 66.7% versus 31.6%, p = 0.017)., Conclusions: No association was found between PTC and subclinical hypothyroidism in the entire cohort, except for patients with preterm contractions and a history of past PTD. This specific group of patients might benefit from thyroid function evaluation.

Objective: We aimed to evaluate the performance of a non-invasive EMG electrical uterine monitor (EUM) versus tocodynamometry (TOCO) by comparing both to internal uterine pressure catheter (IUPC)., Study Design: Prospective observational trial. Uterine activity was recorded continuously and simultaneously, in women during active term labor, with TOCO, EUM and IUPC. Uterine activity tracings were analyzed by three blinded physicians., Results: Overall, 385 tracings from 43 women were analyzed. A similar rate of interpretable tracings between physicians was demonstrated for EUM (87%; 95% CI 80.9-92.7%) and IUPC (94.8%; 95% CI 83.4-96.3%), with a significantly lower rate for TOCO (67.5%; 95% CI 59.4-76.8%, p < 0.001). There is a significant difference in the contraction frequency for EUM versus IUPC (0.77 ± 2.3) compared to TOCO versus IUPC (-3.34 ± 4.97). There is a high variability between the timing of TOCO contractions as compared to IUPC (4.74 ± 10.03 seconds), while a gap of 8.46 ± 4.24 seconds was detected for EUM. The sensitivity, positive predictive value and false positive rate for individual contraction identification by TOCO and EUM are 54.0%, 84.4%, 15.6% and 94.2%, 87.6%, 12.4%, respectively., Conclusion: EUM is efficient as IUPC for uterine activity assessment and both techniques are superior in comparison to external tocodynamometry. Our results support the use of non-invasive EMG technology to monitor uterine activity.

Objective: Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis., Methods: A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease-free interval (DFI) and overall survival (OS) were recorded., Results: Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0 months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3 months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS., Conclusion: The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of prostaglandin E2 (PGE2) on electrical uterine activity using a novel uterine muscle electromyography device in patients undergoing induction of labor., Study Design: Electrical uterine myography (EUM) was prospectively measured using a noninvasive nine channels recorder in 31 women undergoing induction of labor with vaginal PGE2 tablets. Women were monitored before and up to 12 hours after vaginal PGE2 application. EUM index was defined as mean electrical activity of the uterine muscle over a period of 10 minutes measured in units of microjoule (µJ, µWs)., Results: The EUM index was not increased significantly during the first 2 hours following PGE2 application (overall increase of 5.3 ± 60.1%, p = 0.7). Peak EUM activity was observed during 2 to 8 hours following PGE2 application, which represented a statistically significant increase compared with the EUM index before PGE2 application (3.3 ± 0.5 µJ vs. 2.5 ± 0.95 µJ, p = 0.01), and with the EUM index 0 to 2 hours following PGE2 application (3.3 ± 0.5 µJ vs. 2.3 ± 0.9 µJ, p = 0.004)., Conclusion: The data suggests that in women undergoing labor induction with PGE2, uterine activity peaks 2 to 8 hours following PGE2 application. This information may provide more insight into the mechanism of PGE2 action., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: We aimed to determine the association between young maternal age at delivery with adverse pregnancy outcome in a single, tertiary, university-affiliated medical center., Methods: A retrospective, cohort, matched control study using the first percentile distribution of maternal age at delivery (21 years old, n = 461) as the study group, and four control groups by maternal age matched by parity in a 2:1 ratio (22-25, 26-30, 31-35 and 36-40 years; n = 922 each)., Results: Women aged ≤21 years were found to have lower rates of chronic hypertension [compared with women aged 36-40 years old (0.0% versus 1.3%, p < 0.05)], lower rates of gestational diabetes mellitus (GDM) (1.3% versus 3.7%, p = 0.007), higher rates of perineal lacerations [compared with women aged 31-35 and 36-40 years old, 41% versus 31.8% and 31.1%, respectively, p < 0.01)], higher rates of postpartum hemorrhage (4.6% versus 1.5%, p < 0.0001) and higher rates of low 5-min Apgar score (2.2% versus 0.8%, p = 0.004). No significant differences were found in terms gestational age at delivery, birth weight, fetal sex, intrapartum or antepartum mortality., Conclusion: Young maternal age at delivery is associated with increased risk of short-term complications after delivery.

Objective: The purpose of this study was to investigate the effect of atosiban (Tractocile; Ferring, Limhamn, Sweden), an oxytocin receptor antagonist, on uterine electrical activity in women with preterm labor and to determine whether this information can assist in the prediction of preterm delivery., Study Design: Uterine electrical activity was recorded prospectively in 21 women with preterm labor before and during treatment with Tractocile and, for purpose of comparison, in 4 pregnant women without uterine contractions to set the baseline of uterine electrical activity in a quiescent uterus. Uterine activity was recorded with a noninvasive, 9-channel recorder with an electromyography amplifier and a 3-dimensional position sensor with an automatic data analyzer. Uterine electrical activity was quantified by an electrical uterine monitor (EUM) and measured in microwatts per second (μW/s)., Results: The overall pre-Tractocile EUM index was 3.43 ± 0.58 μW/s, which was significantly higher than baseline uterine activity in women without preterm contractions (2.3 ± 0.11 μW/s; P = .001). During the administration of Tractocile, the EUM index gradually decreased in a relatively constant rate from 3.43 ± 0.58 μW/s to 2.56 ± 0.88 μW/s after 330 minutes of continuous therapy (P < .001). The peak effect of Tractocile was observed 4 hours after the initiation of treatment and was followed by a relative plateau. Women with a latency of <7 days from treatment to delivery were characterized by a distinct EUM-pattern in response to Tractocile, compared with women with a latency of ≥7 days (P < .001). A similar EUM-pattern after the administration of Tractocile was also observed for women who delivered at <37 weeks of gestation compared with the women who delivered at term., Conclusion: Tractocile reduces uterine electrical activity in women with preterm labor. This information can provide more insight into the effects of tocolytic agents and to aid in the risk stratification of preterm delivery in women with preterm contractions., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Introduction: The NBM-200 is a novel device allowing noninvasive hemoglobin measurement. The system is based on occlusion spectroscopy technology in the red/near-infrared range. At the core of this technology is the production of a new bio-physical signal, resulting from temporarily occluding the blood flow in the measurement site. The measurement is performed using an annular, multi-wavelength probe with pneumatically operated cuffs, with which an over-systolic pressure is produced at the finger base., Methods: OrSense NBM200 was tested during the years 2011-2012 in a population of pregnant women. Upon receipt of informed consent, two noninvasive Hemoglobin measurements were performed on the right and left thumbs of each subject. Reference hemoglobin values were obtained from venous blood samples drawn at the same time of the noninvasive measurement. Blood Hemoglobin was evaluated on an LH-750 Beckman Coulter counter, acting as the reference "gold standard.", Results: A total of 126 data pairs were obtained in the trial from 63 women. The mean error (bias) of the NBM200 readings compared to the reference was 0.1 g/dL and the accuracy, defined as the standard deviation of error, was 0.86 g/dL. A Bland-Altman comparison of the NBM200 versus the Coulter device shows that the 95% limits of agreement is -1.59 to 1.79 g/dL., Conclusion: Our study demonstrates a good correlation between reference blood hemoglobin and noninvasive hemoglobin measurements. The NBM-200 can accurately assess hemoglobin levels, in a noninvasive fashion, during pregnancy.

Objective: To determine whether introducing a pre-prepared birth plan upon labor admission has an impact on obstetrical outcome., Methods: A retrospective study of all women who prepared an ante-partum birth plan, from 2007-2010. Outcome was compared with a control group consisting of women without a birth plan matched by age, parity and gestational week in a 3:1 ratio., Results: 154 women were compared to a matched control group of 462 women. Women preparing a birth plan, were less likely to undergo an intra partum cesarean section (11.7% vs. 20.3%, p = 0.016). First and second degree perineal tears occurred more frequently in women preparing a birth plan (72.1% vs. 25.5%, p < 0.001). The utilization of birth plan was also associated with a higher rate of epidural administration (81.2% vs. 68.8%, p = 0.004) and a lower rate of intravenous analgesics use (1.3% vs. 10.2%, p < 0.001)., Conclusion: Women presenting with a birth plan, compared to an age-, parity- and gestational week- matched control group are less likely to undergo a cesarean section, more likely to have first and second degree perineal tears and more likely to use an epidural. The paucity of data and the mis-concepts of medical staff suggest that larger prospective studies are needed.