Surgical nodal assessment for endometrial hyperplasia - A meta-analysis and systematic review.

OBJECTIVE: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. METHODS: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). RESULTS: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. CONCLUSIONS: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy.

Sentinel lymph node sampling versus full lymphadenectomy in endometrial cancer: a SEER database analysis.

OBJECTIVE: To assess the long term outcomes and prognosis of sentinel lymph node sampling compared with full lymph node dissection in endometrial cancer patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for information on women diagnosed with endometrial cancer from 2010 to 2019. We conducted a comparison including overall survival between patients who had undergone sentinel lymph node sampling only and patients who had undergone formal lymph node dissection. Propensity score matching was performed according to the patient's age, type of endometrial cancer, grade and stage of disease, and adjuvant therapy. Subgroup analyses were performed according to type and grade of endometrial cancer. RESULTS: 41411 endometrial cancer patients were identified through the database. After matching, 6019 patients each were included in the sentinel lymph node and lymph node dissection groups. Median (interquartile range (IQR)) follow-up time was 16 (7-31) months in both groups. One year survival rates were longer in the sentinel lymph node group compared with the lymph node dissection group (hazard ratio (HR) 1.61 (95% confidence interval (CI) 1.17 to 2.21); p=0.004). Subgroups analysis according to grade of disease showed that 1 year survival rates were longer in the sentinel lymph node group in patients with endometrioid-type grade 1-2 endometrial cancer (HR 1.70 (95% CI 1.31 to 2.56); p=0.01), while no difference in survival was found between the sentinel lymph node and lymph node dissection groups in the subgroup of patients with high grade endometrial cancer (HR 1.40 (95%CI 0.94 to 2.24); p=0.17). In patients with low grade endometrial cancer included in the sentinel lymph node group, only 7% had lymph nodes positive for malignancy compared with 17% in the high grade group. CONCLUSION: Survival rates were not compromised in endometrial cancer patients undergoing sentinel lymph node sampling versus full lymph node dissection for all grades of disease.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer-Implications for counseling-A SEER analysis.

OBJECTIVE: To assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging. STUDY DESIGN: With permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years. RESULTS: A total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56-1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo-oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83-1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment. CONCLUSION: Ovarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

A randomized-controlled trial assessing the effect of intraoperative acupuncture on anesthesia-related parameters during gynecological oncology surgery.

CONTEXT AND OBJECTIVES: The present study examined the impact of intraoperative acupuncture on anesthesia-related parameters in patients undergoing gynecological oncology surgery. METHODS: Participants underwent preoperative integrative oncology (IO) touch/relaxation treatments, followed by intraoperative acupuncture (Group A); preoperative IO treatments without acupuncture (Group B); or standard care only (Group C). Mean arterial pressure (MAP), heart rate (HR), MAP variability (mean of MAP standard deviation), bispectral index (BIS), and calculated blood pressure Average Real Variability (ARV) were measured intraoperatively. RESULTS: A total of 91 patients participated: Group A, 41; Group B, 24; Group C, 26. Among patients undergoing open laparotomy, Group A showed lower and more stable MAP and HR compared to Group B, (MAP, p = 0.026; HR, p = 0.029) and Group C (MAP, p = 0.025). Mean BIS, from incision to suture closing, was lower in Group A (vs. controls, p = 0.024). In patients undergoing laparoscopic surgery, MAP was elevated within Group A (p = 0.026) throughout surgery, with MAP variability significantly higher in Group A (P = 0.023) and Group B (P = 0.013) 10 min post-incision (vs. pre-incision). All groups showed similar intraoperative and post-anesthesia use of analgesic medication. CONCLUSION: Intraoperative acupuncture was shown to reduce and stabilize MAP and HR, and reduce BIS in gynecology oncology patients undergoing laparotomy, with no impact on perioperative analgesic medication use. In the laparoscopic setting, intraoperative acupuncture was associated with elevated MAP. Further research is needed to explore the hemodynamic and BIS-associated benefits and risks of intraoperative acupuncture, and the impact on the use of analgesic drugs in response to these changes.

[GESTATIONAL TROPHOBLASTIC DISEASE: THE NEED FOR CENTRALIZATION OF TREATMENT CENTERS IN ISRAEL].

INTRODUCTION: 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 ß-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.

Five-year survival decreases over time in patients with BRCA-mutated ovarian cancer: a systemic review and meta-analysis.

INTRODUCTION: Short-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. METHODS: A 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. RESULTS: A 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). CONCLUSION: Our 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.

Enhanced Recovery after Surgery is Feasible and Beneficial and Should Be the Standard in Major Gynecological Surgeries.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are evidence-based protocols designed to standardize medical care, improve outcomes, and lower healthcare costs. OBJECTIVES: To evaluate the implementation of the ERAS protocol and the effect on recovery during the hospitalization period after gynecological laparotomy surgeries. METHODS: 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. RESULTS: 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%), P < 0.001). No significant changes were identified between the two periods regarding vomiting, 30-day re-hospitalization, and postoperative minor and major complications. CONCLUSIONS: 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.

Should the risk for uterine cancer influence decision making for prophylactic hysterectomy in BRCA1/2 mutated patients- a systematic review and meta-analysis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[PARP INHIBITORS FOR ADJUVANT TREATMENT FOR OVARIAN CANCER].

INTRODUCTION: 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.

Low-Risk Human Papillomavirus Types in Cervical Intraepithelial Neoplasia 2-3 and in Invasive Cervical Cancer Patients.

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.

Pain relief by continuous intraperitoneal nebulization of ropivacaine during gynecologic laparoscopic surgery--a randomized study and review of the literature.

STUDY OBJECTIVE: To evaluate the efficacy of intraperitoneal nebulization of ropivacaine on pain relief during and after gynecologic laparoscopic procedures including a review of the literature. DESIGN: Double-blinded, randomized, controlled, clinical trial (Canadian Task Force classification I). SETTING: University hospital ambulatory gynecoendoscopic department. PATIENTS: Forty patients (20 patients in each arm) undergoing elective gynecologic same-day outpatient laparoscopic surgery including unilateral/bilateral salpingo-oophorectomy or unilateral/bilateral ovarian cystectomy. INTERVENTIONS: The study group received 10 mL of 1% ropivacaine and the control group received 10 mL of sterile water by intraperitoneal nebulization. During surgery, vital signs were recorded and summarized. Postoperatively patients were followed up for 24 hours including visual analog scale scores and analgesic use. MEASUREMENTS AND MAIN RESULTS: No significant differences existed between the groups during surgery and at the recovery department in terms of arterial blood pressure (p=.42) or heart rate (p=.60). Regarding postoperative analgesia, no difference existed between the groups in terms of morphine consumption (p=.52) or other analgesics (p=.53). No significant difference existed between the groups in postoperative visual analog scale scores including visceral, abdominal wall, and shoulder pain during rest and during cough at the different time frames (30, 60, and 120 minutes and 6 and 24 hours after surgery). CONCLUSION: Our study is the first to examine the effects of intraperitoneal nebulization of ropivacaine throughout laparoscopic gynecologic procedures on patients undergoing general anesthesia. Nebulization of 100 mg of ropivacaine under our specific regimen of anesthesia does not improve patients' outcome in terms of intraoperative and postoperative pain along with consumption of analgesics. Further research with other regimens is required.