Search

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma.

Introduction: Several studies have investigated whether patients with prior breast cancer (BC) are at an increased risk for endometrial cancer (EC)/uterine serous cancer (USC). We aimed to study this relationship and analyze the effect of prior BC on the incidence and prognosis of USC patients. Methods: With permission of the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, clinicopathological information of women diagnosed with BC and following USC were analyzed. The recorded data included age at diagnosis, stage of disease, cause of death, interval time between BC and USC diagnosis, and overall survival. Results: The SEER database included 10,021 patients with USC during the years 1975–2015. 698 (6.96%) of these patients had been previously diagnosed with BC. The incidence of USC in patients with BC history was 57 times higher than in women without BC history (p value p value 0.94). The mean survival of USC patients with previous BC history was 8 years (96 months, 95% CI: 85.7–106.2), shorter than in USC patients with no BC history, presenting a mean survival of 10.6 years (127 months, 95% CI: 124.0–130.8) (p value = 0.002). Conclusion: Our results highlight the relationship between BC and USC, suggesting an increased risk for USC among BC patients. This clinical association should be introduced to BC patients, and physicians should be alert to any EC presenting symptom in BC survivors.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

OBJECTIVES We assessed the relation between clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) and absence of residual disease, in women diagnosed with cervical cancer (CC) and adenocarcinoma in situ (AIS). MATERIALS METHODS Data were collected from 92 women diagnosed with CC and AIS who were positive to HR-HPV and had a repeat cervical HPV test 3-12 weeks after LLETZ (in which CC/AIS were diagnosed) and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV after LLETZ. RESULTS The HR-HPV results after the LLETZ operation were negative in 40 women and positive in 52 women. The HR-HPV-negative group included a significantly higher incidence of AIS: 14 (35%) vs 5 (9.6%, p < .006).In the negative HR-HPV post-LLETZ group, 36 (90%) had normal histology and only 2 (5%) had cancer in the final histological specimen. Among 34 women who underwent radical hysterectomy/trachelectomy after LLETZ, a normal final histology was observed in 75% and 9% of those who were HR-HPV negative and HR-HPV positive, respectively (p < .0005). The positive predictive value for absence of residual cancer, with clearance of HR-HPV after LLETZ, was 95%. CONCLUSIONS Clearance of HR-HPV from the cervix a short time after LLETZ has a high association with the absence of residual cancer in the final outcome, either in the pathology or the follow-up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Gestational trophoblastic disease comprises a spectrum of pregnancy-related disorders, consists of premalignant disorders of complete and partial hydatidiform mole, and malignant disorders such as invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumor/epithelioid trophoblastic tumor. These malignant forms are termed Gestational Trophoblastic Neoplasia (GTN). Until the early 1960's, hysterectomy was the treatment of choice for women with malignant trophoblastic diseases. The five-year survival rate was 40% for local disease, and around 20% in women with metastases. Chemotherapy, treatment according to the various risk factors and the use of β-hCG values as a marker for monitoring the disease, resulted in a cure rate exceeding 98%, while preserving patient's fertility. Due to its` extremely low incidence with relatively complex treatment protocols, in the presence of high potential for side effects, in most countries there are tertiary centers that coordinate the treatment and follow-up of these diseases. In this review, we will summarize strategies for the primary management of gestational trophoblastic disease, the evaluation and management of malignant gestational trophoblastic neoplasia (GTN) and surveillance after treatment.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

Integrative oncology (IO) is increasingly becoming part of palliative cancer care. This study examined the correlation between an IO treatment program and rates of survival among patients with advanced gynecological cancer. Patients were referred by their oncology healthcare professionals to an integrative physician (IP) for consultation and IO treatments. Those undergoing at least 4 treatments during the 6 weeks following the consultation were considered adherence to the integrative care program (AIC), versus non-adherent (non-AIC). Survival was monitored for a period of 3 years, comparing the AIC vs. non-AIC groups, as well as controls who did not attend the IP consultation. A total of 189 patients were included: 71 in the AIC group, 44 non-AIC, and 74 controls. Overall 3-year survival was greater in the AIC group (vs. non-AIC, p = 0.012; vs. controls, p = 0.003), with no difference found between non-AIC and controls (p = 0.954). Multimodal IO programs (≥ 3 modalities) were correlated in the AIC group with greater overall 3-year survival (p = 0.027). Greater rates of survival were also found in the AIC group at 12 (p = 0.004) and 18 months (p = 0.001). When compared with the AIC group, a multivariate analysis found higher crude and adjusted hazard ratios for 3-year mortality in the non-AIC group (HR 95% CI 2.18 (1.2–3.9), p = 0.010) and controls (2.23 (1.35–3.7), p = 0.002). Adherence to an IO treatment program was associated with higher survival rates among patients with advanced gynecological cancer. Larger prospective trials are needed to explore whether the IO setting enhances patients’ resilience, coping, and adherence to oncology treatment.

Background: Cervical cancer is a common gynecologic malignancy in reproductive-age patients. Radical trachelectomy (RT) is a vital treatment for those with early stage cervical cancer who wish to p...

The aims of the study were to evaluate the prevalence and prognosis of human papillomavirus (HPV)-negative cervical cancer (CC) and to compare these to data for HPV-positive CC.This retrospective cohort study compared between HPV-negative CC and HPV-positive CC patients. Primary end points were disease-free survival and overall survival. Secondary end points were demographic and clinical variables including histological diagnosis, stage, and treatment.Of 233 women with CC, 18 (8%) tested HPV-negative. During a median follow-up of 45 months, 33 (14%) recurrences and 41 (18%) deaths were observed. Eleven of the 18 women (61%) who tested HPV-negative and 41 of the 215 (19%) who tested HPV-positive had only adenocarcinoma (p.001). In a multivariate logistic regression analysis, advanced age (p = .003) and primary treatment with chemotherapy and/or radiotherapy (p.001) remained statistically significant for recurrence or mortality (disease-free survival). The factors associated with lower survival were advanced age (p = .008), higher stage at diagnosis (p.001), and HPV negativity (p = .062). Median overall survival for HPV-positive CC was not reached, compared with 24 months for HPV-negative CC. Kaplan-Meier curves showed lower rates of disease-free survival (p = .008) and overall survival (p = .011), for women with HPV-negative compared with HPV-positive CC.The relatively poor prognosis of HPV-negative CC is important in light of its relatively high prevalence, which could increase proportionally to HPV-positive CC due to increased HPV screening and vaccination. Further studies are needed to confirm whether HPV status is truly an independent prognostic factor in CC.

Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs.To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries.We compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017 to December 2018) and after (January 2019 to March 2020) the implementation of the ERAS protocol. Eighty women were included in each group.The clinical and demographic characteristics were similar among the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89 ± 2.56 to 4.09 ± 1.65 days, P = 0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%), P = 0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%), P0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications.Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding, and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications or with re-admissions.

Introduction/Background* About 40% of CC are in women under age 40 years, for whom fertility-sparing treatment might be very important and should always be considered. More than half the patients who undergo radical surgery (trachelectomy or hysterectomy) have no remnant tumor in the final pathology specimen. HPV clearance is a test of cure after conisation, but it is not a test of cure in CC. Our objective was to assess correlation of clearance of high-risk human papillomavirus (HR-HPV) after large loop excision of the transformation zone (LLETZ) with absence of residual disease, in women diagnosed with cervical cancer (CC) and Adenocarcinoma in Situ (AIS). Methodology Data was collected from 92 women diagnosed with CC and AIS who were positive to High –Risk HPV (HR-HPV), and had a repeat cervical HPV test 3-12 weeks post-LLETZ, and before final surgical treatment. We compared characteristics of women with negative and positive HR-HPV post-LLETZ. Result(s)* The pathological results of women who were HR-HPV negative (n=40) compared to HR-HPV positive (n=52) at the post-LLETZ follow-up visit included a significantly higher incidence of AIS: 14 (35%) vs 5(9.6%) (p Conclusion* Clearance of HR-HPV from the cervix a short time after LLETZ has a high correlation with the absence of residual cancer in the final outcome, either in the pathology or the follow up. Testing for HR-HPV a short time after LLETZ might serve as a parameter for risk assessment.

Introduction/Background* To evaluate the prevalence and prognosis of human papillomavirus (HPV)-negative cervical cancer (CC), and compare these to data for HPV-positive CC. Methodology This retrospective cohort study compared between HPV-negative CC and HPV-positive CC patients. Primary endpoints were recurrence-free survival, disease-free survival, and overall survival. Secondary endpoints were demographic and clinical variables including histological diagnosis, stage, and treatment. Result(s)* Of 233 women with CC, 18 (8%) were HPV negative. During a median follow up of 45 months, 33 (14%) recurrences and 41 (18%) deaths were observed. Eleven (61%) of the 18 women who were HPV negative and 41 (19%) of the 215 who were HPV positive had only adenocarcinoma (P Conclusion* The relatively poor prognosis of HPV-negative CC is important in light of its relatively high prevalence, which could increase proportionally to HPV-positive CC due to increased HPV screening and vaccination. Further studies are needed to confirm if HPV status is truly an independent prognostic factor in CC.

Introduction/Background* Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower health care costs. Our objective was to evaluate the implementation of the ERAS protocol, and its effect on recovery during the hospitalization period after gynecological laparotomy surgeries. Methodology In this retrospective cohort study we compared demographic and clinical data of consecutive patients at a single institute who underwent open gynecological surgeries before (August 2017- December 2018) and after (January 2019- March 2020) the implementation of the ERAS protocol. Eighty women were included in each group. Result(s)* The clinical and demographic characteristics were similar between the women operated before and after implementation of the ERAS protocol. Following implementation of the protocol, decreases were observed in post-surgical hospitalization (from 4.89±2.56 to 4.09±1.65 days; p=0.01), in patients reporting nausea symptoms (from 18 (22.5%) to 7 (8.8%); p=0.017), and in the use of postoperative opioids (from 77 (96.3%) to 47 (58.8%); p Conclusion* Implementation of the ERAS protocol is feasible and was found to result in less postoperative opioid use, a faster return to normal feeding and a shorter postoperative hospital stay. Implementation of the protocol implementation was not associated with an increased rate of complications nor with re-admissions.

Early referral to palliative care services in patients with advanced cancer is widely accepted. In addition, the use of futile intervention at the end of life is a pivotal aspect of assessing quality of care at that time.To evaluate the use of palliative care and aggressive treatments during the last month of life in women with gynecological malignancies.The study was designed in two steps. The first step included a retrospective analysis of a gynecologic oncology cohort that underwent end-of-life (EOL) care. In the second part, a questionnaire regarding EOL care was completed by family members. Since our palliative care service became more active after 2014, we compared data from the years 2013-2014 to the years 2015-2019.We identified 89 patients who died from gynecological malignancy during study period; 21% received chemotherapy and 40% underwent invasive procedures during their last month of life. A palliative care consultation was documented for 49% of patients more than one week before their death. No statistical difference was achieved between the two time periods regarding the use of chemotherapy or invasive procedures in the last month of life. Nonetheless, after the incorporation of palliative medicine more women had palliative care consultations and had EOL discussions. Most of the patients' relatives were satisfied with EOL care.Many aggressive interventions were given during the last month of life. EOL discussions were documented in the medical charts of most patients and the rates increased with time.

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.

OBJECTIVE: To evaluate the consequences of COVID-19 pandemic restrictions on the postpartum course. METHODS: A retrospective cross-sectional study compared women who gave birth between March and April 2020 (first wave), between July to September 2020 (second wave), and a matched historical cohort throughout 2017-2019 (groups A, B, and C, respectively). Primary outcomes were postpartum length of stay (LOS), presentations to the emergency department (ED), and readmissions 30 days or longer after discharge. Following Bonferroni correction, p

The COVID-19 outbreak caused persons to be reluctant to seek medical care due to fear of contracting the infection.To evaluate the effect of the COVID-19 pandemic on admission rates to the delivery room and the feto-maternal unit, and to assess the effect on the nature of presenting obstetrical complaints to the emergency department.A retrospective cohort study in one medical center. The population was women20 weeks pregnant who presented to the obstetrical emergency department with self-complaints during 29 days at the peak of the pandemic outbreak, and a matched group during the exact period in the previous year. We compared between the groups: clinical, obstetrical, and demographic data, including age, area of residence, gravidity, parity, previous cesarean deliveries, high-risk pregnancy follow-up, the last 30 days admissions to the obstetrical emergency department, gestational age, chief complaints, cervical dilatation, cervical effacement, admissions to the delivery room or feto-maternal unit, time from admissions to the delivery room to birth, if applicable, and acute obstetrical complications diagnosed at the emergency department.During the pandemic outbreak, 398 women met study inclusion criteria, compared to 544 women in the matched period of the previous year. During the COVID-19 period, women visited the obstetrical emergency department at a more advanced mean gestational age (37.6 ± 3.7 vs. 36.7 ± 4.6,The pandemic outbreak of COVID-19 caused a behavioral change among women who presented to the obstetrical emergency department. This was characterized by delayed arrival to the obstetrical emergency department and the delivery room, which led to a significant increase in urgent and acute interventions. The change in behavior did not affect the rates of maternal and neonatal morbidity.

To study the possible association between uterine cancer and the BRCA1/2 associated cancer syndrome and discuss the implications of such an association on the clinical managment of patients with BRCA1/2 mutations.A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Study protocol was prospectively registered at PROSPERO International prospective register of systematic reviews (registration number CRD42020193496). Considered for inclusion were studies providing the diagnosis rate of uterine cancer in patients with BRCA1/2 mutations by comparing observed and expected rate according to a known disease incidence. The results were measured by standardized incidence ratio (SIR). The primary outcome was defined as any uterine cancer diagnosis and subgroup analyses were conducted for uterine serous papillary cancer (USPC) specifically and for BRCA1 and BRCA2 mutations separately.4591 records were identified through database search; eight studies were finally included, comprising 13,098 patients with BRCA1/2 mutations. BRCA1/2 mutated patients were found to have a significantly higher risk for uterine cancer compared to the general population (SIR = 2.22, 95% CI 1.76-2.8, p 0.001). A higher incidence of USPC was also found in patients with BRCA1/2 mutations (SIR = 17.97, 95% CI 9.89-32.66, p 0.001), as well as in a separate analysis for BRCA1 (SIR = 2.81, 95% CI 2.09-3.79, p 0.001) and BRCA2 (SIR = 1.75, 95% CI 1.09-2.80, p 0.001) mutations.Patients who carry a BRCA1/2 mutation are at a significantly higher risk of developing uterine cancer, specifically USPC, supporting that USPC may be a component of the BRCA1/2 syndrome. The decision to perform concurrent hysterectomy at the time of the risk reduction bilateral salpingo -oophorectomy surgery should be considered individually.

Integrative oncology (IO) is increasingly becoming part of palliative cancer care. This study examined the correlation between an IO treatment program and rates of survival among patients with advanced gynecological cancer.Patients were referred by their oncology healthcare professionals to an integrative physician (IP) for consultation and IO treatments. Those undergoing at least 4 treatments during the 6 weeks following the consultation were considered adherence to the integrative care program (AIC), versus non-adherent (non-AIC). Survival was monitored for a period of 3 years, comparing the AIC vs. non-AIC groups, as well as controls who did not attend the IP consultation.A total of 189 patients were included: 71 in the AIC group, 44 non-AIC, and 74 controls. Overall 3-year survival was greater in the AIC group (vs. non-AIC, p = 0.012; vs. controls, p = 0.003), with no difference found between non-AIC and controls (p = 0.954). Multimodal IO programs (≥ 3 modalities) were correlated in the AIC group with greater overall 3-year survival (p = 0.027). Greater rates of survival were also found in the AIC group at 12 (p = 0.004) and 18 months (p = 0.001). When compared with the AIC group, a multivariate analysis found higher crude and adjusted hazard ratios for 3-year mortality in the non-AIC group (HR 95% CI 2.18 (1.2-3.9), p = 0.010) and controls (2.23 (1.35-3.7), p = 0.002).Adherence to an IO treatment program was associated with higher survival rates among patients with advanced gynecological cancer. Larger prospective trials are needed to explore whether the IO setting enhances patients' resilience, coping, and adherence to oncology treatment.

Treatment for ovarian cancer has been challenging for many years. It is composed of debulking surgery and chemotherapy. During the first line of treatment most patients are sensitive to primary platinum-based chemotherapy, however, unfortunately, most of them will suffer from recurrence in 36 months. About 20-25% of ovarian cancer patients exhibit a germ line mutation in the pathway of double strand DNA repair including BRCA. Poly ADP ribose polymerase inhibitors (PARP Inhibitors) may inhibit enzymes responsible for single strand DNA repair, thus leaving the BRCA mutated cell without a repair mechanism for DNA damage leading to synthetic lethality. Recently, phase 3 studies have shown that ovarian cancer patients with recurrent, platinum sensitive disease who were treated with PARP inhibitors have shown statistically significant improvement in progression free survival. A recent pivotal trial has shown the addition of PARP inhibitor, as a maintenance treatment after first line chemotherapy to ovarian cancer patients with BRCA mutation, had significantly increased the progression-free survival. The side effect profile of PARP inhibitors was tolerable and manageable, although they should be well familiar to care givers. Following these studies, the FDA and the European authorities granted an accelerated approval for the use of PARP inhibitors as maintenance treatment after first line treatment, for BRCA carriers, and at the recurrence for platinum sensitive patients. Subsequently, it was added to the benchmark medications for recurrent platinum sensitive BRCA carriers (germ line or somatic) by the Ministry of Health in Israel. The future seams to provide new combination treatments of PARP inhibitors with immunological agents and vascular endothelial growth factors inhibitors aiming to improve the poor prognosis of ovarian cancer patients.

IntroductionShort-term survival rates of patients with BRCA-mutated ovarian cancer have been previously shown to be longer than those of non-carriers. We aimed to study the long-term survival rates of these patients and investigate whether the 5-year advantage decreases over time.MethodsA systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes (PRISMA) statement. The study protocol can be assessed at PROSPERO International prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42019137455). We considered for inclusion studies providing Kaplan–Meier survival curves up to and including 10 years, comparing patients with ovarian cancer with and without BRCA mutations. Our main outcome was the conditional probability of surviving an additional 5 years.ResultsA total of 13 references comprising 4565 patients was analyzed, of which 1131 BRCA1/2-mutated carriers and 3434 non-carriers were included. The expected higher 5-year survival rate in BRCA-mutated patients was observed (risk difference (RD)=14.9%, p=0.0002, risk ratio (RR)=1.36, p=0.001). Ten-year survival rates were comparatively less improved in BRCA-mutated patients (RD=8.6%, p=0.042, RR=1.25, p=0.12). After already surviving 5 years, no advantage in probability of further surviving 5 additional years was observed for the BRCA-mutated group (RD=2.9%, p=0.71, RR=0.97, p=0.78).ConclusionOur results provide insight into long-term survival rates and prognosis in patients with BRCA-mutated ovarian cancer which suggest that, despite the improved 5-year prognosis, the conditional probability of surviving an additional 5 years does not show the same advantage. The relatively low long-term advantage highlights the significance of epithelial ovarian cancer recurrence prevention. In the era of poly adenosine ribose inhibitors, future studies should explore the adequate follow-up and the benefit of a longer maintenance treatment phase, aiming to prolong the long-term survival of BRCA-mutated patients.

The aim was to collect cases of cesarean scar pregnancy (CSP) and describe the evolution of diagnosis, treatment modalities, and outcome. A retrospective cohort study was conducted of patients who had been diagnosed with CSP. Treatment decision was made according to the type of CSP, levels of beta human chorionic gonadotropin (hCG), and estimated vascularity. Forty cases with CSP were recorded. Overall success of the primary treatment was recorded among 30 of 40 cases (75%) and significantly correlated with degree of vascularity, type of CSP, and beta hCG levels. The treatment methods included serial methotrexate in 20 cases; 15 of them (75%) were successful. In this specific group, we found type 2 scar and high vascularity to be significantly associated with treatment failure. In conclusion, cases with type 2 CSP, high vascularity, and high beta hCG levels should be considered high risk, and extra caution should be taken in choosing treatment modality and follow-up.

OBJECTIVE To compare the outcome of patients with uterine papillary serous cancer (UPSC) carrying a BRCA mutation with that of patients with UPSC who are BRCA wild-type. METHODS The present retrospective, multicenter cohort study included women with UPSC who were diagnosed between January 1, 1993, and December 31, 2014, and were tested for the BRCA mutation at three Israeli medical centers. Data were collected from the medical records, and patient and tumor characteristics and disease outcomes were compared between BRCA mutation carriers and noncarriers. The primary outcome was overall survival. RESULTS In total, 14 BRCA mutation carriers and 50 noncarriers were included. Both groups had similar treatment modalities (P=0.530). A non-significant trend toward BRCA mutation carriers being diagnosed more frequently at an advanced stage compared with noncarriers was observed (P=0.090). Median overall survival (25 vs 37 months; P=0.442), progression-free survival (37 vs 29 months; P=0.536), and disease-specific survival (60 vs 39 months; P=0.316) were similar between the carrier and noncarrier groups. CONCLUSIONS Although not significant, BRCA mutation carriers tended to have more advanced disease at diagnosis. However, the survival was similar irrespective of the BRCA status in this small group. Further research is needed to confirm these findings in a larger cohort.

Introduction Cervical punch biopsies are a common ambulatory procedure, performed routinely by gynaecologists. The aim of the present study was to assess the efficacy of forced coughing as a pain-reducing technique during cervical punch biopsy compared to a control group. Materials and methods The study was a prospective randomised-control trial. The study group comprised 90 women who underwent cervical punch biopsies during investigation of abnormal Pap test results. The women were randomly assigned to 'cough' and control groups. Pain was measured on a 10 cm visual analogue scale (VAS) during different stages of the procedure. Results VAS pain score during biopsies was significantly lower in the 'cough' group. The median pain level in the 'cough' group was 1.5, compared to 4.0 in the control group. Eighty percent of the women in the 'cough' group reported a pain level of 2.0 or less compared to 40% of the women in the 'control' group (P = 0.0002). In the second biopsy, 69% of the women reported VAS ≤ 2.0 in the cough group compared to 28% of the patients in the control group. Forced coughing was shown both to reduce anxiety regarding the prospect of future cervical procedures and to decrease patients' desires for future pain management. This was true for 32% of the women in the 'control' group compared to 12% of the women in the 'cough' group (P = 0.05). Conclusion Forced coughing provides significant pain relief during cervical punch biopsy and reduces the patients' fears and desires for pain medications in future procedures.

Objectives In cervical cancer, a number of pathological parameters have been explored for their utility in tailoring a less aggressive approach for patients with low-risk early stage disease. We examined whether, in patients with cervical cancer stage IA1 to IB1, diagnosed by loop excision of the transformation zone (LLETZ), positive for high-risk human papillomavirus (hrHPV), clearance of hrHPV after LLETZ correlates with absence of residual disease at the final pathology after definitive or further surgery. Materials and methods Data were collected from patients diagnosed with early stage invasive cervical cancer and positive hrHPV DNA, who had a repeat cervical HPV test 3 to 12 weeks after LLETZ and before final surgical treatment. We compared characteristics of patients with post-LLETZ negative and positive hrHPV. Results Of 28 patients, 13 were post-LLETZ negative hrHPV; of these, 11 did not have residual cancer in the final pathological specimen; two patients had cervical intraepithelial neoplasia 3. Of the 15 women who had post-LLETZ positive hrHPV, 10 had residual cancer in the final pathological specimen and 3 had cervical intraepithelial neoplasia or adenocarcinoma in situ; only 2 were negative for cancer. The post-LLETZ hrHPV test shows a sensitivity of 86.7% and specificity of 84.6%. Conclusions Clearance of hrHPV from the cervix after LLETZ was found to correlate with the absence of residual cancer in the final surgical specimen. Testing for hrHPV post-LLETZ might serve as a new parameter for risk assessment and tailoring of a less radical operation in women with early stage cervical cancer.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare uterine neoplasms. These tumors are usually benign, displaying a nodular or polypoid growth pattern; common occurrence is observed at the 4th to 6th decade of life. This entity is divided according to clinical behavior and pathological typical findings including different immunohistochemical staining. Traditionally type I tumors show a predominant endometrial stromal pattern with less than 50% ovarian sex cord component. This type has been shown to behave more aggressively with a decreased disease free survival period. Type II tumors, the classical UTROSCT, are less invasive but have the tendency to recur. We report a case of a 57-year-old patient presenting with postmenopausal bleeding. Hysteroscopic polypectomy showed the diagnosis of UTROSCT. This case presents a less morbid minimally invasive treatment plan and exemplifies that in patients where low malignant potential exists and their will is taken into consideration such management is both crucial and correct.

Introduction/Background 95–99% of patients with invasive cervical cancer are positive to human papilloma virus (HPV). The objective of the current study was to evaluate the incidence of Low Risk (LR-HPV) types among women with Cervical Intra-epithelial Neoplasia 2–3 (CIN 2–3) and cervical cancer (CC). Methodology We conducted a nested cohort study of patients diagnosed from May 2008 until October 2017 with CIN 2–3 or cervical cancer. Results During the study period we collected clinical data on 608 women of whom 402 were with CIN 2-3 and 206 with diagnosis of cervical cancer (CC). The most common presenting symptom among CIN 2–3 patients was post-coital bleeding (33.3%) compared to post-menopausal bleeding (36.2%) among CC patients. Of patients with CIN 2-3, 90.3% were found positive to at least one type of HR-HPV, compared to 89.3% of CC patients. 4.5% of patients with CIN 2-3 and 3.9% of those with CIN2-3 were positive to only one LR-HPV, or to some of a few LR-HPV types. Among 5.2% with CIN 2-3 and 6.3% of those with CC no HPV types were detected. Conclusion The prevalence of the LR-HPV is low but it could not be ignored due to the expected decrease in CC caused by HPV types that are included in the bi-, quadri-, and nano-valent vaccine. The CIN 2-3 and CC patients with LR-HPV types and with negative HPV are challenging the sensitivity of HPV screening that is based on HPV screening of a limited number of HR-HPV types. Disclosure Nothing to disclose.

OBJECTIVES A total of 95% to 99% of patients with invasive cervical cancer (CC) are infected with human papillomavirus (HPV). The aim of the study was to evaluate the incidence of low-risk HPV (LR-HPV) types among women with cervical intraepithelial neoplasia (CIN 2-3) and CC. MATERIALS AND METHODS We conducted a nested cohort study of patients diagnosed with CIN 2-3 or CC. Inclusion criteria were diagnosis of CIN 2-3 or CC and HPV-DNA testing from the cervix. RESULTS During the study period, we collected clinical data on 608 women of whom 402 were with CIN 2-3 and 206 with diagnosis of CC. When examining 14 high-risk HPV (HR-HPV) types, patients with CIN 2-3, 90.3% were found positive to at least one type of HR-HPV, 89.8% from CC patients were found positive to at least one type of HR-HPV. A total of 4.5% of patients with CIN 2-3 and 3.9% of those with CC were positive to only one LR-HPV or to some of a few LR-HPV types. Among 5.2% with CIN 2-3 and 6.3% of those with CC, no HPV types were detected. CONCLUSIONS The prevalence of the LR-HPV in high-grade squamous intraepithelial lesion cervical lesions is low but is expected to increase in the future because of the expected decrease in CC caused by HPV types that are included in the bi-, quadri-, and nanovalent vaccine. The CIN 2-3 and CC patients with LR-HPV types and with negative HPV, challenge HPV screening sensitivity, which is based on a limited number of HR-HPV types.

Introduction Patients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high-detail TVS, and positron emission tomography with 18 F-labeled fluoro-2-deoxyglucose and computed tomography (18 F-FDG PET/CT) may contribute to triage efficiency of cervical cancer patients. Material and methods This is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010-2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities-a thorough physical examination, a high-detail TVS, and positron emission tomography (PET) with 18 F-FDG and computed tomography (18 F-FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation. Results Seventy-three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone. Conclusions The combination of high-detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18 F-FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.

Background: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. Material and Methods: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. Results: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28–0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03–3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). Conclusions: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Background Ultrasonography is frequently used to diagnose acute appendicitis in women of reproductive age, but its diagnostic value in pregnant patients remains unclear. This study sought to compare the diagnostic performance of ultrasound in pregnant and young nonpregnant women with suspected acute appendicitis. Methods The database of a single tertiary medical center was reviewed for all women of reproductive age who underwent appendectomy either during pregnancy (2000–2014) or in the nonpregnant state (2004–2007) following ultrasound evaluation. The performance of ultrasound in terms of predicting the final pathologic diagnosis was compared between the pregnant and non pregnant groups using receiver operating characteristic curve analysis. Results Of 586 young women treated for appendicitis during the study periods (92 pregnant, 494 non-pregnant), 200 underwent preoperative ultrasound [67 pregnant, and 133 nonpregnant young women]. The pregnant and nonpregnant groups were comparable in age and presenting symptoms. There was no significant difference in the predictive performance of ultrasound between the two groups (AUC 0.76 and 0.73 respectively, p = 0.78) or within the pregnant group, by trimester [first (n = 23), AUC 0.73; second (n = 32), AUC 0.67; third (n = 12), AUC 0.86; p = 0.4]. Ultrasound had a positive predictive value of 0.94 in the pregnant group and 0.91 in the nonpregnant group; corresponding negative predictive values were 0.40 and 0.43. Conclusions There appears to be no difference in the ability of ultrasound to predict the diagnosis of acute appendicitis between pregnant women and nonpregnant women of reproductive age. Therefore, similar preoperative imaging algorithms may be used in both patient populations.

Data supporting a survival advantage of endometrial cancer diagnosed before the onset of postmenopausal bleeding are lacking. This study sought to compare overall survival and disease recurrence between women who were asymptomatic at diagnosis and women who were symptomatic at diagnosis. A systemic search was conducted in databases using the terms: "asymptomatic," "ultrasound," "screening," and "endometrial cancer." Only original research studies that compared characteristics of tumour advancement and survival measures were included. The six articles included in the meta-analysis comprised 2961 patients. Data were collected on study design and period, number and characteristics of participants, and outcomes in terms of tumour histology and survival measures. Higher rates of stage I tumours were shown among asymptomatic patients (relative risk 1.19). The proportion of high-grade histology did not differ between the two groups (relative risk 0.92). The crude pooled estimate for overall survival did not yield statistical significance, nor did recurrence-free survival (which was reported by three studies). In conclusion, endometrial cancer diagnosed in asymptomatic women is not associated with higher survival than in symptomatic women. Invasive procedures in asymptomatic women with incidental ultrasonographic findings should be carefully weighed because no survival advantage is expected.

ObjectivesUterine papillary serous carcinoma (UPSC) is a highly aggressive subtype of endometrial carcinoma. Histopathologically, it resembles the pattern of serous papillary carcinoma of the ovary. Cancer antigen 125 (CA-125) is the most widely used biomarker in epithelial ovarian carcinoma. Its use in UPSC evaluation has yet to be determined. The purpose of this study was to investigate the significance of preoperative serum CA-125 as a prognostic factor in patients with UPSC.MethodsThe study cohort included all women with UPSC operated in our institution between January 2002 and June 2016. All patients underwent complete surgical staging. Preoperative CA-125 was reviewed and correlated with clinical and pathological parameters.ResultsSixty-one women met the study criteria. Median preoperative CA-125 was found to be significantly associated with disease stage. Patients with disease stages I to IV had median preoperative CA-125 levels of 12.15, 19.6, 22.6, and 177.5 U/mL (P < 0.0001) respectively. Levels of CA-125 were significantly associated with positive cytology (P < 0.0001), omental disease (P < 0.0001), pelvic or para-aortic lymph node metastasis (P < 0.0001), and adnexal involvement (P < 0.0001). The optimal cutoff that provided the best sensitivity and specificity for omental and parametrial involvement as well as positive cytology was 57.5 U/mL. For adnexal and lymph node involvement, the optimal cutoff value was 41.8 U/mL.ConclusionsIn patients with UPSC, preoperative CA-125 level correlates with known prognostic parameters of endometrial carcinoma and is associated with extrauterine involvement. These data should stimulate the need for further evaluation of the role of CA-125 in predicting recurrence and survival in UPSC.

BACKGROUND The loop electrosurgical excision procedure (LEEP) is one of the treatments for cervical intraepithelial neoplasia 1 (CIN1). One of the risks of LEEP is preterm birth. We evaluated final pathological diagnoses following LEEP as treatment for CIN1 lesions, for procedures in which cone height was determined by patients' age. METHODS A retrospective study of 329 women diagnosed with CIN1 on a cervical biopsy and treated by LEEP. In patients under age 35 years, a thin LEEP COIN was performed, and in women over 35 years, a regular LEEP was performed. RESULTS The final pathological diagnosis was CIN2 and CIN3 in 14.6% of the women. The average excision height was 0.64 cm in women aged under 35 years, 0.82 cm in women aged 36-45 years, and 0.96 cm in women older than 46 (P

Invasive cervical cancer is caused by human papillomavirus (HPV).To describe the prevalence and genotype distribution of HPV types in women at risk for cervical neoplasia.Our study summarized HPV types detected in 6654 samples that were sent to the serology laboratory from cervical clinics in northern Israel between 2006-2014. The HPV test was performed during investigation of atypical squamous cells of undetermined significance (ASCUS) results on Pap tests or due to complaints suggestive of cervical neoplasia. HPV types were classified as high risk (HPV-HR) and low risk (HPV-LR).Of the samples, 46.4% (3085/6654) were HPV-HR positive. Of women with cervical intraepithelial neoplasia 2-3 (CIN 2-3) or cancer, 292/318 (91.8%) and 137/145 (94.5%), respectively, were HPV-HR positive. HPV 16 and HPV 18 were detected in 11.8% of the total samples and in 48.2% and 64.9% of the women with CIN 2-3 and with cancer, respectively. HPV was negative in 8/145 (5.5%) and 26/318 (8.2%) of women with cervical cancer and CIN 2-3, respectively.This study shows the prevalence of HPV types in women at risk for cervical neoplasia. The sensitivity of all HPV types for CIN 2-3 and cervical cancer was 91.8% and 94.5%, respectively; and of HPV-HR types, 89% and 92.4%, respectively. Triage of HPV-HR types should be considered in women with ASCUS because HPV-HR types were discovered in only 36.7%. The distribution of HPV types in our population is similar to that reported for other developed countries.

According to the new and reproducible grading system of the MD Anderson Cancer Center (MDACC), low grade serous cancer (LGSC) differs greatly from the commonly known high grade serous cancer (HGSC). Pathology speaking, LGSC has less mitotic index; the grade of nuclear atypia is low to intermediate. Genetically speaking, these tumors tend to show mutation in the mitogen-activated protein kinase (MAPK) pathway, mainly in the KRAS and BRAF genes, resulting in uncontrolled proliferation; however, it seems that the presence of this mutation might be related to a better prognosis compared to their absence. The presenting symptoms and spread is similar to HGSC, such as the elevated Ca-125 and the advanced stage at the presentation. The rate of proliferation, on one hand affects the prognosis and therefore, although it tends to present in advanced stages such as HGSC, the prognosis is better. On the other hand, low proliferation might be the reason for the relative decrease in the sensitivity to the common chemotherapy given in HGSC. Treatment strategy, as well. is similar to HGSC consisting of debulking surgery followed by or after chemotherapy. Molecular and pathology studies confirm borderline tumor might be a precursor of some of LGSC, since it shares similar mutation pathways seen in LGSC. Those pathways are targets for newer chemotherapy agents, currently under phase II and III promising trials.

Tamoxifen acts as an estrogen antagonist within the breast tissue. In the uterus, tamoxifen is an agonist for some estrogen receptors and therefore can cause hyperplasia or neoplasia in the endometrium.To compare characteristics of patients with uterine sarcoma who were and were not previously treated with tamoxifen.The medical records of all women with uterine sarcoma who had been treated at the Carmel Medical Center in Haifa, Israel, during 2000-2013 were retrospectively reviewed. Disease characteristics, histological type of sarcoma, patient demographics, treatments and final outcomes were compared between patients who had and those who had not been exposed to tamoxifen.Of the 66 patients identified, 14 (21%) had been exposed to tamoxifen, one of them for 3 years and 13 for at least 5 years. Mean ages were 69 ± 8 and 66 ± 12 years for those exposed and those not exposed to the drug, respectively. Rates of uterine carcinosarcoma were 86% (12/14) and 44% (23/52), respectively (P0.006). Patients with carcinosarcoma were older than other sarcoma patients (73 ± 7 vs. 59 ± 11 P0.005).There were no statistically significant differences between the two groups in rates of diabetes mellitus, hypertension, dyslipidemia or heart disease. The mean time from diagnosis to death was 7.37 ± 0.42 years. The overall survival rates of carcinosarcoma patients were not statistically different from that of other sarcoma patients. Tamoxifen exposure was not associated with overall survival among all sarcoma patients, nor among the subgroup of carcinosarcoma patients.Tamoxifen treatment was associated with elevated incidence of carcinosarcoma among women with uterine sarcoma, but was not found to be associated with prognosis or with co-morbidities.

Background Human papilloma virus (HPV) is classified as a biologic carcinogen causing cervical cancer. Our aim was to identify all the HPV types responsible for cervical cancer and pre-cervical cancer in Israel. Methods This study included 226 women, diagnosed with cervical intraepithelial neoplasia (CIN) 2-3 and 115 women diagnosed with cervical cancer, and tested for all HPV typing during the period of January 2006 to May 2013. Results HPV was detected in 92.9% of women with CIN 2-3 and high-risk HPV (HR-HPV) was detected in 85.8% of them. In women with cervical cancer, HPV was positive in 96.5%, HR-HPV detected in 93%. In the CIN 2-3 group the most common HPV types were 16 (42%), 31 (8.8%) and 18 (4.9%) and in the cancer group HPV 16 (57.4%), 45 (9.6%), and 18 (7.8%). Multiple HPV types were seen in 12.8% of CIN 2-3 group but only in 0.9% of cancer group. The chief complaint led to cancer diagnosis was post menopause bleeding (27%), while abnormal Papanicolaou (Pap) test lead to CIN 2-3 diagnosis in 75.2% of the women. Only 22.6% of women diagnosed with cancer were diagnosed due to abnormal Pap test and 76.9% of them were diagnosed at stage I, as compared to women diagnosed with cancer because of bleeding or abnormal mass, of them 57.1 % were diagnosed at stage I (P Conclusions HR-HPV types were found in 93% of cancer group and 85.8% of CIN 2-3 group, and low-risk HPV (LR-HPV) was detected in 3.5% and 7.1% of women with cervical cancer and CIN 2-3 respectively. The most common HPV types in cervical cancer women were 16, 45 and 18. Women diagnosed with cancer because abnormal Pap test were in earlier stage compared to women diagnosed because of complains. Including LR-HPV types in screening HPV can increase the sensitivity of the test.

Most ovarian cancer patients are diagnosed in an advanced stage; and after the initial treatment experience disease recurrence, which eventually becomes palliative. Many questions arise in this setting including how to address patients in the palliative setting, how to discuss end-of-life issues, and how to manage symptoms. In this review, we discuss the timing and setting of end-of-life discussion in the context of end-stage ovarian cancer. We review the approach to relieving disease burden by improving and decreasing symptoms. These symptoms include recurrent ascites, bowel obstruction, pain, pulmonary effusion, and deep vein thrombosis.