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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.

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.

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.

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.

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.

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.

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.

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 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.

PurposeEpithelial-mesenchymal transition (EMT) is a critical process for cancer metastasis and recurrence. Metformin, an effective oral antidiabetic drug, has been associated with decreased cancer risk and mortality. In this pilot study, we started to evaluate the effect of metformin on EMT in vivo and in vitro in endometrial cancer (EC).MethodsEndometrial cancer cell lines and freshly isolated EC tumor specimens were used to assess EMT after metformin treatment. Cell lines were subjected to wound healing and AlamarBlue assays to determine cell migration and cell proliferation; messenger RNA levels were measured by real-time reverse transcriptase (RT) quantitative polymerase chain reaction (PCR), and protein levels were measured by Western blots to detect EMT marker expression.ResultsProtein expression and messenger RNA of E-cadherin was found to be increased (P = 0.02 and 0.04, respectively) in 30 EC tumor specimens of diabetic patients treated with metformin compared with 20 EC tumor specimens of diabetic patients treated with other antidiabetic agents. In vitro, metformin reduced cell migration at 5 mM for 48 hours, as determined by the wound healing assay in EC cell lines (Ishikawa, 45% reduction; HEC50, 40% reduction), whereas more than 90% of the cells remained viable on the AlamarBlue assay. Metformin reduced EMT in the cell lines and regulated the expression of the EMT-related epithelial markers, E-cadherin and Pan-keratin; the mesenchymal markers, N-cadherin, fibronectin, and vimentin; and the EMT drivers, Twist-1, snail-1, and ZEB-1.ConclusionsTumors of patients on metformin have increased E-cadherin expression, and metformin decreases EMT in EC cell lines in vitro, suggesting clinical biological relevance of metformin in women with EC.

Objectives Israel is traditionally considered to have the lowest prevalence of cervical cancer compared with that in other countries of the Western world. The aim of the present study was to establish the human papillomavirus (HPV) genotypes distribution among Israeli Jewish women with premalignant and cervical cancer. Methods Fifty-two specimens with invasive cervical cancer and 50 specimens with high-grade cervical intraepithelial neoplasia (CIN2/3) were identified. Human papillomavirus genotyping in paraffin-embedded specimens was performed by deparaffinization of the tissue sections and DNA extraction, followed by HPV genotype detection using a validated polymerase chain reaction (PCR)–based HPV GenoArray test kit, to simultaneously identify 21 HPV genotypes. Results Forty-eight (48/52; 92.3%) cervical cancer samples demonstrated PCR-amplifiable DNA (non-HPV DNA). Forty (83.3%) of 48 samples were high-risk (HR) HPV positive. Six (12.5%) of 48 patients showed multiple HR HPV infections. Human papillomavirus types 16 and 18 dominated covering 28 (58.3%) and 14 (29.16%) of 48 samples. Human papillomavirus types 16 and 18 coinfected all 6 cases of multiple HR HPV infections. In CIN2/3 samples, 37 (78.7%) of 47 samples demonstrated PCR-amplifiable DNA (non-HPV DNA), and 20 (54.0%) of these 37 samples were infected by HPV. Human papillomavirus type 16 was found in 19 (95.0%) of 20 cases. Human papillomavirus type 18 was found in 3 (15.0%) of 20 cases; hence, HPV16 and HPV18 contributed to 100% of the cases. Conclusions Human papillomavirus types 16 and 18 were responsible for the vast majority of invasive cervical cancer and CIN2/3 specimens (81.2% and 100%, respectively). Therefore, it is essential to include the HPV vaccine in the vaccine schedule of the Israeli population.

Pseudomyxoma peritonei is a rare, chronic relapsing disease in which tumor cells in the abdomen produce excessive mucin with a significant mortality rate. We describe a young unmarried nulligrava who underwent fertility preservation by in vitro fertilisation and embryo cryopreservation prior to radical surgery and adjuvant chemotherapy. Pregnancy was achieved, although complicated by obstructive uropathy. She delivered a healthy infant at 32 weeks' gestation. The few descriptions of fertility and pregnancy outcome in pseudomyxoma peritonei that appear in the literature are reviewed.

To evaluate the significance of persistent lower abdominal pain in women with previous cesarean delivery.Various maternal outcomes were compared between women who underwent repeated cesareans owing to persistent lower abdominal pain (study group) and women who underwent repeated cesareans without persistent abdominal pain (control group).The incidence of uterine rupture was significantly higher in the study group than in the control group (8/81 [9.9%] vs 0/119 [0.0%]; P0.001). While all women with persistent lower abdominal pain and uterine rupture had an additional sign or symptom, only 6/73 (8.2%) women with persistent abdominal pain without uterine rupture had any additional symptoms (P0.001). There was no difference in incidence of uterine scar dehiscence between the groups. However, the hospitalization period was significantly longer in the study group (4 vs 3.7days; P0.05). Trial of labor was a contributing factor to uterine rupture.Isolated persistent lower abdominal pain in women with previous cesarean is a poor indicator of uterine rupture. However, the positive predictive value for uterine rupture is 57% when an additional sign or symptom is present. Dehiscence of the uterine scar is relatively common and it is not associated with persistent abdominal pain.

A growing number of Eritrean and Sudanese refugees seek medical assistance in the labor and delivery ward of our facility. Providing treatment to this unique population is challenging since communication is limited and pregnancy follow-up is usually absent.To compare the perinatal outcome of refugees and Israeli parturients.The medical and financial records of all refugees delivered between May 2010 and April 2011 were reviewed. Perinatal outcome was compared to that of native Israeli controls.During this period 254 refugees were delivered (2.3% of deliveries). Refugees were significantly younger and leaner. They had significantly more premature deliveries under 37 weeks (23 vs. 10, P = 0.029) and under 34 weeks gestation (9 vs. 2, P = 0.036) with more admissions to the neonatal intensive care unit (15 vs. 5, P = 0.038). Overall cesarean section rate was similar but refugees required significantly more urgent surgeries (97% vs. 53%, P = 0.0001). Refugees had significantly more cases of meconium and episiotomies but fewer cases of epidural analgesia. There were 2 intrauterine fetal deaths among refugees, compared to 13 of 11,239 deliveries during this time period (P = 0.036), as well as 7 pregnancy terminations following sexual assault during their escape. Sixty-eight percent of refugees had medical fees outstanding with a total debt of 2,656,000 shekels (US$ 767,250).The phenomenon of African refugees giving birth in our center is of unprecedented magnitude and bears significant medical and ethical implications. Refugees proved susceptible to adverse perinatal outcomes compared to their Israeli counterparts. Setting a pregnancy follow-up plan could, in the long run, prevent adverse outcomes and reduce costs involved in treating this population.