Lymph node staging in grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

OBJECTIVE: The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. METHODS: Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. RESULTS: 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). CONCLUSION: Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Low anterior resection syndrome and its impact on quality of life of ovarian carcinoma patients: A prospective longitudinal study.

OBJECTIVES: Bowel dysfunction is frequently reported in patients with ovarian carcinoma (OC). Our aim was to evaluate the incidence of low anterior resection syndrome (LARS) like symptoms in patients with primary OC and its impact on quality of life (QoL). METHODS: A prospective longitudinal observational cohort study was performed, including patients with newly diagnosed OC treated by primary or interval surgery with residual tumor <1 cm, from 2018 until 2021. Patients with a stoma or recurrence of disease were excluded. Intestinal dysfunction was assessed using the validated LARS score questionnaire pre- and postoperatively. There are 3 subgroups based on the results: no, minor, or major LARS. The impact on QoL was evaluated by an additional question to demonstrate the severity of patient's life impairment. RESULTS: The questionnaire was answered by 78 patients pre- and post-operatively. LARS like symptoms were reported preoperatively in 34.6% (24.4% minor/10.2% major) and significantly increased postoperatively to 47.4% (28.2% minor/19.2% major; p = 0.011). Moderate to severe impairment of QoL correlated with LARS scores pre- (80%) and post-operatively (90%). Patients with two bowel anastomoses (mean score 18.6 pre- and 24.9 post-operatively, p = 0.041) showed a significant increase of the questionnaire score. CONCLUSIONS: Major LARS like symptoms appear in 10% of OC patients preoperatively and significantly increase to almost two-fold postoperatively. Multiple bowel anastomoses had a significant risk for higher postoperative LARS score. QoL impairment correlates linearly with LARS positive scoring, independent on the timing of the complaints.

Incidence and Prognostic Impact of Deleterious Germline Mutations in Primary Advanced Ovarian Carcinoma Patients.

Data on deleterious variants in genes other than BRCA1/2 remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk® germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleterious BRCA1/2 mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showed BRCA1/2 mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A, p < 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C, p = 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25-0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27-0.61 and HR 0.49; 95% CI 0.37-0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other than BRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients.

Impact of substage and histologic type in stage I ovarian carcinoma survival: a multicenter retrospective observational study.

OBJECTIVE: This international study aimed to investigate the impact of substage, histological type and other prognostic factors on long-term survival for stage I ovarian carcinoma. METHODS: Our study was a retrospective multicenter cohort study that included patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I (IA-IC3) ovarian carcinoma treated at four European referral centers in Germany and Italy. Using Kaplan-Meier survival curves we compared overall and disease-free survival between the different stage I groups. RESULTS: A total of 1115 patients were included. Of these, 48.4% (n=540) were in stage IA, 6.6% (n=73) stage IB, and 45% (n=502) stage IC, of the latter substage IC1, 54% (n=271), substage IC2, 31.5% (n=158), and substage IC3, 14.5% (n=73). Five-year overall and disease-free survival rates for the entire cohort were 94% and 86%, respectively, with no difference between stage IA and IB. However, there was a significantly better overall and disease-free survival for stage IA as compared with stage IC (p=0.007 and p<0.001, respectively). Multivariate analysis revealed incomplete/fertility-sparing staging (HR 1.95; 95% CI 1.27 to 2.99, and HR 3.54; 95% CI 1.83 to 6.86, respectively), and stage IC (HR 2.47; 95% CI 1.63 to 3.75) as independent risk factors for inferior disease-free survival, while low-grade endometrioid (HR 0.42; 95% CI 0.25 to 0.72) and low-grade mucinous (HR 0.17; 95% CI 0.06 to 0.44) histology had superior disease-free survival. Considering overall survival, stage IC (HR 2.41; 95% CI 1.45 to 4.01) and older age (HR 2.41; 95% CI 1.46 to 3.95) were independent risk factors. CONCLUSION: Although stage I ovarian carcinoma exhibited excellent outcomes, the prognosis of patients with stage IA differs significantly compared with stage IC. Sub-optimal staging as an indicator for quality of care, and tumor biology defined by histology (low-grade endometrioid/mucinous) independently impact disease-free survival.

Fertility treatments and the risk of pediatric obstructive sleep apnea in the offspring-Results from a population-based cohort study.

OBJECTIVE: While the impact of fertility treatments on the perinatal outcome is well established, the long-term effects on offspring are yet to be determined. The current study aimed to investigate the risk of long-term obstructive sleep apnea (OSA) among children born following in vitro fertilization (IVF) and ovulation induction (OI) as compared with spontaneously conceived pregnancies. STUDY DESIGN: A retrospective population-based cohort study was performed. Exposure was defined as delivery following pregnancies conceived by IVF or OI. Incidence of OSA related hospitalizations of the offspring, up to the age of 18 years, was evaluated. A Kaplan-Meier survival curve and multivariable Cox regression models were used to assess the association. RESULTS: During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% were conceived following IVF (n = 2603), and 0.7% following OI (n = 1721). Offspring hospitalization rates, involving OSA (n = 1607), were higher among children conceived following IVF and OI pregnancies as compared with the rate in children conceived spontaneously (1.4% vs 1.2% vs 0.7%, respectively; P < .001). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of OSA related hospitalizations following IVF and OI (log-rank P < .001). Using multiple Cox regression models, controlled for gestational age, maternal age, maternal smoking, maternal obesity, birthweight, offspring gender and obesity, IVF as well as OI exhibited a significant and independent association with pediatric OSA in all models with adjusted hazard ratios of 2.25, (95% confidence interval [CI] = 1.6-3.1) and 1.63 (95% CI = 1.1-2.5), respectively. CONCLUSION: Both IVF and OI treatments appear to be independently associated with OSA in the offspring.

Impact of Body Mass Index on female fertility and ART outcomes.

As the global mean Body Mass Index (BMI) is on the rise, the importance of understanding exactly how female fertility is impacted by once outlier BMI values, becomes ever more important. Studies have implicated abnormal BMI on the female reproductive system by contributing to anovulation, irregular menses, adverse oocyte quality, endometrial alterations, and hormonal imbalances. These well ultimately result in female infertility, which could complicate natural conception efforts and request considering assisted reproductive technology (ART) in such couples. With an increase in the demand for ART, it is crucial to understand what factors can be altered by the female BMI in order to maximize the opportunity for successful pregnancy. The current manuscript aimed to review the information about the effect of BMI on the female fertility and ART outcomes. The complex nature of the female reproductive system leaves space for multiple factors to adversely affect its processes. Imbalances in the hypothalamus-pituitary-ovarian axis can impede efforts for couples to conceive. Leptin and estrogen are two hormones that have been implicated in regulating BMI as well as reproductive physiology. Lifestyle modifications prior to, and during ART have shown promise in enhancing fecundity. The intricacies in female reproductive system leaves much to the unknown, and often with conflicting results. Further research is required to fully elucidate what aspects of female fertility are influenced by BMI, and how the healthcare provider can facilitate successful outcomes. The current review will enable a better consultation and treatment.

Advanced maternal age during pregnancy and the risk for malignant morbidity in the childhood.

In the past several decades, rates of delayed childbearing have increased, and as a result, maternal age has advanced. Our objective was to evaluate whether advanced maternal age is independently associated with an increased risk of childhood cancers in the offspring. A retrospective cohort study of women who delivered between the years 1991 and 2014 was conducted. Elderly parturients (≥ 35 years) were divided into two sub-categories: 35-39 and 40-50 years. The comparison group consisted of parturients aged 20-34 years. All hospitalizations of offspring up to the age of 18 years involving malignant morbidity were compared between the groups. A Kaplan-Meier survival curve was used to compare cumulative malignant morbidity incidence of the offspring. A Weibull regression model was used to control for confounders. During the study period, 201,738 deliveries met the inclusion criteria. Of them, 16.3% (n = 32,804) occurred in mothers aged 35 years or more (35-39 years old n = 26,145, 79.7%; 40-50 years old n = 6659, 20.3%). In the Weibull regression model, advanced maternal age exhibited no association with general malignant morbidity in the offspring up to 18 years of age (mothers aged 35-39: adjusted HR 1.06, 95% CI 0.76-1.48, p = 0.727; mothers aged 40-50: adjusted HR 0.73, 95% CI 0.36-1.46, p = 0.373). For leukemia, the regression model exhibited an independent association in maternal ages of 35-39 (adjusted HR 2.23, 95% CI 1.34-3.69, p = 0.002). CONCLUSION: Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. The specific nature of the association between maternal age and leukemia of the offspring necessitates further investigation. What is Known: • Advanced maternal age is associated with a marked elevation in the risk of different pregnancy complications and adverse pregnancy outcomes. What is New: • Advanced maternal age does not appear to raise the risk for future malignancy in the offspring up to the age 18 years. • Leukemia of the offspring may be associated with advanced maternal age although the specific nature of the association necessitates further investigation.