Medical cannabis and its effect on oncological outcomes in patients with ovarian cancer treated with PARP inhibitors.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) play a pivotal role in ovarian cancer management. With medical cannabis emerging as a novel component of supportive care, this study investigated the impact of medical cannabis use on oncological outcomes in patients with ovarian cancer undergoing PARPi therapy. METHODS: The study included patients from a single institution database treated for ovarian cancer between January 2014 and January 2020 who received PARPi maintenance therapy in a first-line or recurrent disease setting after a confirmed response to platinum-based treatment. The study categorized patients as cannabis users and cannabis-naïve. Univariate and multivariate Cox regression analysis and the Kaplan-Meier method were used to assess the effects of medical cannabis use on the duration of PARPi therapy, progression-free survival, and overall survival. RESULTS: Among the eligible patients (n=93), most were cannabis-naïve (69%, n=64) while the rest used medical cannabis (31%, n=29). Medical cannabis use rates were comparable for patients receiving PARPi therapy post-primary treatment or for recurrence (42%, n=9, vs 27%, n=20; p=0.1). Both groups exhibited similar median duration for PARPi therapy (12.1 vs 9.5 months; p=0.89) and progression-free survival (20 vs 21 months; p=0.83). Kaplan-Meier analysis detected no differences in progression-free survival associated with cannabis use. Although cannabis users had an extended overall survival compared with the cannabis-naïve group (129.3 vs 99 months; p=0.03), cannabis use was insignificant for overall survival on multivariate analysis (p=0.10). Multivariate analysis showed stage IV at diagnosis (p=0.02) to be the sole factor associated with progression-free survival (p=0.02). CONCLUSION: Medical cannabis usage in patients receiving PARPi treatment showed no association with duration of PARPi therapy, progression-free survival, or overall survival.

Routine Automated Assessment Using Surgical Intelligence Reveals Substantial Time Spent Outside the Patient's body in Minimally Invasive Gynecological Surgeries.

OBJECTIVE: To demonstrate the use of surgical intelligence to routinely and automatically assess the proportion of time spent outside of the patient's body (out-of-body-OOB) in laparoscopic gynecological procedures, as a potential basis for clinical and efficiency-related insights. DESIGN: A retrospective analysis of videos of laparoscopic gynecological procedures. SETTING: Two operating rooms at the Gynecology Department of a tertiary medical center. PARTICIPANTS: All patients who underwent laparoscopic gynecological procedures between January 1, 2021 and December 31, 2022 in those two rooms. INTERVENTIONS: A surgical intelligence platform installed in the two rooms routinely captured and analyzed surgical video, using AI to identify and document procedure duration and the amount and percentage of time that the laparoscope was withdrawn from the patient's body per procedure. RESULTS: A total of 634 surgical videos were included in the final dataset. The cumulative time for all procedures was 639 hours, of which 48 hours (7.5%) were OOB segments. Average OOB percentage was 8.7% (SD = 8.7%) for all the procedures and differed significantly between procedure types (p < .001), with unilateral and bilateral salpingo-oophorectomies showing the highest percentages at 15.6% (SD = 13.3%) and 13.3% (SD = 11.3%), respectively. Hysterectomy and myomectomy, which do not require the endoscope to be removed for specimen extraction, showed a lower percentage (mean = 4.2%, SD = 5.2%) than the other procedures (mean = 11.1%, SD = 9.3%; p < .001). Percentages were lower when the operating team included a senior surgeon (mean = 8.4%, standard deviation = 9.2%) than when it did not (mean = 10.1%, standard deviation = 6.9%; p < .001). CONCLUSION: Surgical intelligence revealed a substantial percentage of OOB segments in laparoscopic gynecological procedures, alongside associations with surgeon seniority and procedure type. Further research is needed to evaluate how laparoscope removal affects postoperative outcomes and operational efficiency in surgery.

Revaccination of children with acute lymphoblastic leukemia following completion of chemotherapy.

BACKGROUND: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy. METHODS: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination. RESULTS: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster. CONCLUSIONS: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated.

Prognostic significance of delayed complete metabolic response on PET/CT after primary chemoradiation treatment of cervical cancer.

OBJECTIVE: To investigate the prognostic significance of near-complete metabolic response on initial follow-up PET/CT after primary chemoradiation treatment of cervical cancer. METHODS: Survival data were retrospectively compared between patients who had complete metabolic response on first follow-up PET/CT, 3 months after chemoradiation (group 1) with those who had near-complete metabolic response on first PET/CT and later showed complete metabolic response at subsequent PET/CT, 6 months or more after treatment (group 2). RESULTS: Of the 108 patients included in the final analysis, 74 (68.5%) showed complete metabolic response on initial PET/CT, 3 months after treatment, and 34 patients (31.5%) showed complete metabolic response on subsequent PET/CT, 6 months after treatment. Tumor characteristics were comparable between groups. Group 1 had higher percent of stage 1 (12% vs 0%) and lower percent of stage 4 disease (3% vs 14%) than those of group 2. Group 2 patients had significantly fewer cases of recurrences and deaths than group 1 patients (6% vs 26%, p=0.018; 0% vs 20%, p=0.003, respectively), with comparable 3-year survival rates (group 1, 90% vs group 2, 100%, p=0.31). Twelve patients had progressive disease on first follow-up PET/CT; these patients had significantly worse overall survival compared with all other patients (log-rank test, p<0.001). Younger age and delayed complete metabolic response were associated with lower chance of recurrence and death on univariate analysis. On multivariate analysis, delayed complete metabolic response remained significantly associated with no recurrence HR=0.14 (95% CI 0.25 to 0.84), p=0.031. CONCLUSIONS: Survival outcome of patients with cervical cancer who show residual 18F-fluorodeoxyglucose uptake on initial PET/CT after treatment, but reach complete metabolic response on follow-up PET/CT, is not inferior compared with survival of patients who show complete metabolic response on initial PET/CT 3 months after treatment. Watchful waiting with follow-up PET/CT seems a safe option for these patients.

Effect of BMI change on recurrence risk in patients with endometrial cancer.

OBJECTIVE: Our study aimed to explore the effect of body mass index (BMI) change on cancer recurrence risk during the routine surveillance of endometrial cancer patients. METHODS: Data 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. RESULTS: A 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 (p<0.001). The BMI increase was most pronounced in patients with endometroid histology that recurred, 31.6 (IQR 24-35) kg/m2 at surgery compared with 33.5 (IQR 27-36) kg/m2 at 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). CONCLUSION: Patients 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.

Primary Resectoscopic Treatment of First-Trimester Miscarriage.

OBJECTIVES: To determine the feasibility and safety of resectoscopic treatment for uterine evacuation of first-trimester miscarriage. METHODS: A single-centre prospective study performed between April 2021 and October 2021 at a university-affiliated tertiary medical centre. Patients diagnosed with early miscarriage of up to 12 weeks from the last menstrual period were eligible for participation. Recruited patients underwent hysteroscopic uterine evacuation under general anaesthesia by a Versapoint 2 bipolar resectoscope 24Fr (Johnson and Johnson, Germany). RESULTS: A total of 15 patients were recruited for the study. The procedural characteristics as well as intra- and postoperative adverse events were recorded. The mean duration of the procedure was 14.3 ± 3.7 minutes. The achievement of complete evacuation was recorded in all cases, and no adverse events occurred during any procedure. Post-procedure follow-up 6 weeks after treatment was conducted by office hysteroscopy in 10 women and by ultrasonography in 4 women. One woman had conceived prior to her scheduled follow-up visit. In total, 2 (13.3%) cases of retained products of conception were diagnosed during office hysteroscopy and they were removed by the "see-and-treat" technique without anaesthesia. The diagnosis was confirmed pathologically. No intrauterine adhesions were detected and none of the women required a second hysteroscopy under anaesthesia due to retained products of conception. CONCLUSIONS: Hysteroscopic evacuation of first-trimester miscarriage by a standard resectoscope is a safe and feasible technique.

Impact of COVID-19 Pandemic on Human Papillomavirus Vaccine Uptake in Israel.

OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.

The Effect of Cervical Conization on Women's' Sexual Function and Psychological Health, A Prospective Observational Study.

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. Michaan N, Loboda N, Ochshorn I, et al., The Effect of Cervical Conization on Women's' Sexual Function and Psychological Health, A Prospective Observational Study. J Sex Med 2022;19:257-262.

Incidence of endometrial carcinoma in patients with endometrial intraepithelial neoplasia versus atypical endometrial polyp.

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. METHODS: We 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. RESULTS: Eighty-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). CONCLUSIONS: Concurrent 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.

Recurrent Dysplasia After a Loop Electrosurgical Excision Procedure: Local Versus General Anesthesia.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

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.

Cardiac Function and Hemodynamic Changes during Minimally Invasive Hysterectomy with Pneumoperitoneum and Steep Trendelenburg Position for Patients with Endometrial Cancer Who Are Obese.

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.

Impact of rotavirus vaccine on admissions due to acute gastroenteritis and rotavirus gastroenteritis in Israel.

AIM: We examined the impact of insertion of the Rotavirus vaccine (RVV) into the Israeli National Immunisation Programme (NIP) on hospitalisations due to both acute gastroenteritis (AGE) and Rotavirus gastroenteritis (RVGE) in children. METHODS: We retrospectively analysed the medical records of children aged <5 years admitted with a diagnosis of AGE between 2008 and 2016 in two children's hospitals in central Israel. Clinical, laboratory, microbiological data and RV immunisation status were retrieved. Data were compared before and after the introduction of the RVV into the NIP. RESULTS: A total of 2042 children were admitted with AGE. Hospitalisations due to AGE and RVGE decreased from 3310 to 1950 and from 1027 to 585 per 100 000 admissions, respectively, after the RVV (relative risk reduction (RRR) of 41% and 43%, respectively). RV remained the most common pathogen in both study periods. There was no significant difference in the clinical course between immunised and non-immunised children admitted with RVGE. CONCLUSION: The introduction of the RVV to the NIP significantly reduced the admissions due to both AGE and RVGE in children <5 years. However, RV is still the most common agent for admissions due to AGE in this age group.

Comprehensive geriatric assessment is correlated to overall survival among gynaecologic oncology patients.

OBJECTIVE: To investigate the correlation of comprehensive geriatric assessment to overall survival among older gynaecologic oncology patients. METHODS: Between 2011 and 2017, patients >70 years had geriatric assessment before treatment. Geriatric assessment included the following tests: Old American resource and services, instrumental activities of daily living, modified Barthels index, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, risk of falling and medication use. Overall survival was calculated for patients' groups below and above median tests scores. Univariate as well as multivariate analysis was done to evaluate the association between each variable and survival. RESULTS: About 120 patients had geriatric assessment. Mean patients' age was 76.4 ± 5. A total of 78 Patients had ovarian cancer, 16 uterine cancer, 17 cervical cancer and 9 had other gynaecologic malignancies. No correlation was found between age, BMI (body mass index) and cancer type to overall survival. Patients with scores below cut-off values of modified Barthels index, instrumental activities of daily living, mini-nutritional assessment and mini-nutritional assessment had significantly shorter overall survival (P = 0.004, 0.031, 0.046 and 0.004, respectively). This remained significant in both univariate and multivariate analysis. CONCLUSIONS: Gynaecologic oncology patients with lower geriatric assessment scores have significantly lower overall survival, irrespective of cancer type. Geriatric assessment tests allow objective assessment of older patients with worst prognosis before treatment planning.

Prognostic Value of Pathologic Chemotherapy Response Score in Patients With Ovarian Cancer After Neoadjuvant Chemotherapy.

OBJECTIVES: The aim of the study was to investigate the correlation of chemotherapy response score (CRS) after neoadjuvant chemotherapy (NACT) to treatment outcomes in ovarian cancer (OC). METHODS: Chemotherapy response score was retrospectively determined on pathology slides of all patients with epithelial OC that had interval debulking surgery (IDS) between 2009-2014. Chemotherapy response score 1 was given when tumor was present and infiltrated by inflammatory cells, CRS 2 when both tumor and regressive chemotherapy changes were present, and CRS 3 when scant tumor was seen within extensive chemotherapy-induced changes. Patients' characteristics including survival data were collected and compared between CRS groups. RESULTS: Pathology slides of 132 patients were reviewed. Forty-nine patients had CRS 1, 65 had CRS 2, and 18 had CRS 3. Age, stage, and grade were not different across CRS groups. A higher percent of CRS 1 and 2 patients required more than 3 cycles of NACT, whereas CRS 3 patients had higher rates of no residual disease at completion of IDS. Chemotherapy response score 3 group showed the most significant CA125 decrease after NACT (97% decrease, P = 0.016). Kaplan-Meir survival curves showed a significantly longer progression-free survival but not overall survival for patients with CRS 3 (median progression-free survival = 7.5, 12, and 17 months for CRS 1, 2, and 3, respectively, P = 0.012), and this remained statistically significant in both univariate and multivariate analysis. Interobserver reproducibility for CRS was good (weighed κ = 0.762). CONCLUSIONS: Patients with CRS 3 have longest progression-free survival and highest CA125 drop after NACT. These parameters have important prognostic value and can be used for clinical decision-making.

[HORMONE REPLACEMENT THERAPY AFTER GYNECOLOGICAL MALIGNANCIES].

INTRODUCTION: Treatment of gynecological malignancies can cause an abrupt onset of menopausal symptoms along with associated long term morbidity. Hormone replacement therapy (HRT) is the most effective treatment to alleviate these symptoms but the safety of HRT among gynecologic oncology patients remains controversial. We conducted a review of the published literature on the risk of recurrent disease among gynecologic cancer patients using HRT. Our research revealed a shortage of prospective, randomized trials on this important subject. The current evidence, mainly cohort studies, did not find an increased risk of recurrence for endometrial cancer in women with early stage disease or increased risk for recurrent ovarian epithelial cancer among HRT users after oncological treatment. Vulvar cancer and most cases of cervical cancer are presumably hormone independent malignancies and the small number of published works did not find an increased risk of recurrence among HRT users. In summary, according to current literature, there is no clear contraindication to HRT among gynecological cancer patients. Treatment should be individualized and the lack of good evidence, along with the advantages and possible disadvantages of this treatment, should be discussed with patients.

Perinatal outcome and financial impact of Eritrean and Sudanese refugees delivered in a tertiary hospital in Tel Aviv, Israel.

BACKGROUND: 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. OBJECTIVES: To compare the perinatal outcome of refugees and Israeli parturients. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Impact of Intrauterine Manipulators on Outcome and Recurrence Patterns of Endometrial Cancer Patients Undergoing Minimally Invasive Surgery.

Objective: To evaluate the use of manipulators on the outcome of women who had minimally invasive surgery for endometrial cancer. Methods: Retrospective analysis of patients operated with or without an intrauterine manipulator. Results: Six hundred ninety-nine patients were included. The median follow-up was 44 months (range, 29-67). Nineteen (8.8%) patients had positive cytology in the manipulator group versus 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). Subgroup analysis of low-risk 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 (hazard ratio [HR], 1.28; confidence interval [95% CI], 0.7-2.1, p = 0.3) and for the low-risk subgroup of patients who did not receive adjuvant treatment (HR, 2.47; 95% CI, 0.8-7, p = 0.08). Conclusion: The use of a manipulator increases the risk of positive cytology as well as vaginal vault recurrences, but it does not reduce the overall survival of patients.

Human Papilloma Virus Typing as a Triage Tool for Women with Postcoital Bleeding: A Retrospective Cohort Study.

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1-6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies.

The direct effect of SARS-CoV-2 virus vaccination on human ovarian granulosa cells explains menstrual irregularities.

Following administration of the SARS-CoV-2 vaccine, many women worldwide reported short-term menstrual irregularities. Although menstrual bleeding, "the fifth vital sign", is experienced by more than 300 million people on any given day worldwide, these changes were only partially studied. Irregular periods are important well beyond fertility and the discomfort they impose; they are associated with the risk of cardiovascular morbidity, chronic diseases, and premature mortality. Pre-clinical examination of the vaccine polymeric envelope indicates its accumulation in the ovaries. The somatic endocrine cells of the ovarian follicle - the granulosa cells (GCs)-participate in the strict hypothalamic-pituitary-ovarian (HPO) feedback loop that governs the menstrual cycle via endocrine and paracrine regulators, as AMH and Inhibins. We aimed to unravel the direct effect of the COVID-19 vaccine on GCs and link their post-vaccine activity to changes in menstrual patterns. Human primary GCs exposed in-vitro to the Pfizer COVID-19 vaccine BNT162b2, demonstrated no change in their viability but altered mRNA transcripts, specifically of the regulatory key factors: InhibinB was upregulated, whereas AMH was downregulated. We further examined pre- and post-vaccination blood samples from individual women and found a 2-3 folds change in the post-vaccination FSH/InhibinB protein level ratio, compared to their pre-vaccination values. This altered expression of InhibinB could significantly impact the HPO axis in vaccinated women and may ultimately influence the endometrium cyclicity, manifested clinically by the commonly reported changes in menstrual bleeding patterns.