Surgery for Recurrent Epithelial Ovarian Cancer.

PURPOSE OF REVIEW: To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.

Proteomic signature for detection of high-grade ovarian cancer in germline BRCA mutation carriers.

No current screening methods for high-grade ovarian cancer (HGOC) guarantee effective early detection for high-risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk-reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy is a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We aimed to develop a proteomic assay based on proximal liquid biopsy, as a decision support tool for monitoring high-risk population. Ninety Israeli BRCA1 or BRCA2 mutation carriers were included in the training set (17 HGOC patients and 73 asymptomatic women), (BEDOCA trial; ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 98 BRCA mutation carriers was used for validation. Safety information was collected for all women who opted for uterine lavage in a clinic setting. We present a 7-protein diagnostic signature, with AUC >0.97 and a negative predictive value (NPV) of 100% for detecting HGOC. The AUC of the biomarker in the independent validation set was >0.94 and the NPV >99%. The sampling procedure was clinically acceptable, with favorable pain scores and safety. We conclude that the acquisition of Müllerian tract proximal liquid biopsies in women at high-risk for HGOC and the application of the BRCA-specific diagnostic assay demonstrates high sensitivity, specificity, technical feasibility and safety. Similar classifier for an average-risk population is warranted.

Frequency and prediction of deep uterine involvement in advanced high-grade epithelial ovarian cancer: is uterine preservation an option?

INTRODUCTION: Hysterectomy is traditionally part of the surgical treatment for advanced high-grade epithelial ovarian carcinomas, although the incidence of uterine involvement has not been fully investigated. Some young patients with advanced high-grade epithelial ovarian carcinomas want uterine preservation. We aimed to determine the frequency of non-serosal (deep) uterine involvement in patients with high-grade epithelial ovarian carcinomas and to establish predictive factors for such involvement. METHODS: A retrospective cohort study was performed of 366 consecutive patients with advanced high-grade epithelial ovarian carcinomas who had surgery between January 2012 and December 2019. Data collected included demographic and clinical details, and surgical and pathological reports to determine macroscopic and microscopic deep uterine involvement. The characteristics of the patients with and without deep uterine involvement were compared and univariate and multivariate Cox proportional hazard models were used to assess correlations and determine risk factors. RESULTS: A total of 311 patients were included in the final analysis. The mean age was 62±11.6 years, with 32 (10.3%) being younger than 45. Most (92.3%) had serous carcinoma. Uterine involvement, excluding superficial (serosa-only), was present microscopically in 194 patients (62.4%) but was detected macroscopically at surgery in only 166 patients. Deep involvement was missed at surgery in 28 patients (14.4%), including parametrial involvement (n=18), parametria plus cervix (n=2), cervical involvement (n=3), endometrium (n=3), and myometrium (n=2). Multivariate analysis identified factors associated with deep uterine involvement including residual disease at surgery (HR 2.43, 95% CI 1.13 to 4.48; p=0.004) and CA125 >1000 U (HR 1.8, 95% CI 1.09 to 2.94; p=0.02). CONCLUSIONS: The incidence of deep uterine involvement in high-grade epithelial ovarian carcinomas is high. It can be diagnosed in most but not all cases on gross examination at surgery and is associated with residual disease and CA125 >1000 U. Patients who desire uterine preservation should be advised on an individual basis, given these factors and the operative findings.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

OBJECTIVES: We evaluated primiparous women with clinically diagnosed third- and fourth-degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears. METHODS: Primiparous women delivering in our maternity ward with intrapartum diagnoses of third- or fourth-degree anal sphincter tears, repaired by the overlapping technique, were recruited to undergo 3-dimensional transperineal sonography of the pelvic floor anatomy, including the anterior and posterior compartments. Primiparas with uncomplicated vaginal deliveries were recruited as a comparison group. Patient files were examined, and maternal backgrounds and delivery and neonatal details were extracted for all patients. RESULTS: Ninety-four women with tears were recruited to the study group, and 464 women with normal vaginal deliveries constituted the comparison group. The groups differed significantly in the rates of levator ani defects: 38 of 94 women (40.4%) in the study group versus 75 of 464 (16.2%) in the comparison group (P < .001; odds ratio, 3.53; 95% confidence interval, 2.18­5.7). Neonatal head circumference differed significantly between the study and comparison groups: (mean ・} SD, 34.5 ・} 1.3 cm in the study group versus 33.9 ・} 1.3 cm in the comparison group; P= .005), as did birth weight (3322 ・} 430 g in the study group versus 3169 ・} 458 g in the comparison group; P= .007). The groups did not differ in maternal age, gestational age at delivery, length of second stage of labor, and rates of epidural anesthesia, episiotomy, and vacuum extraction. CONCLUSIONS: Third- and fourth-degree intrapartum sphincter tears are associated with levator ani avulsion. Knowledge of complex pelvic floor damage may allow for prompt referral to secondary preventive measures for pelvic floor disorders.

Third- or Fourth-Degree Intrapartum Anal Sphincter Tears Are Associated With Levator Ani Avulsion in Primiparas.

OBJECTIVES: We evaluated primiparous women with clinically diagnosed third- and fourth-degree and anal sphincter tears, to evaluate the rate of levator ani muscle injury compared to primiparous women without sphincter tears. METHODS: Primiparous women delivering in our maternity ward with intrapartum diagnoses of third- or fourth-degree anal sphincter tears, repaired by the overlapping technique, were recruited to undergo 3-dimensional transperineal sonography of the pelvic floor anatomy, including the anterior and posterior compartments. Primiparas with uncomplicated vaginal deliveries were recruited as a comparison group. Patient files were examined, and maternal backgrounds and delivery and neonatal details were extracted for all patients. RESULTS: Ninety-four women with tears were recruited to the study group, and 464 women with normal vaginal deliveries constituted the comparison group. The groups differed significantly in the rates of levator ani defects: 38 of 94 women (40.4%) in the study group versus 75 of 464 (16.2%) in the comparison group (P < .001; odds ratio, 3.53; 95% confidence interval, 2.18-5.7). Neonatal head circumference differed significantly between the study and comparison groups: (mean ± SD, 34.5 ± 1.3 cm in the study group versus 33.9 ± 1.3 cm in the comparison group; P= .005), as did birth weight (3322 ± 430 g in the study group versus 3169 ± 458 g in the comparison group; P = .007). The groups did not differ in maternal age, gestational age at delivery, length of second stage of labor, and rates of epidural anesthesia, episiotomy, and vacuum extraction. CONCLUSIONS: Third- and fourth-degree intrapartum sphincter tears are associated with levator ani avulsion. Knowledge of complex pelvic floor damage may allow for prompt referral to secondary preventive measures for pelvic floor disorders.

Single-dose methotrexate-based protocol for the treatment of caesarean scar pregnancy and successive pregnancy outcomes.

The incidence of caesarean scar pregnancy (CSP) increases in recent years. Yet, the best mode of treatment and its effects on successive pregnancies is not well established. The aim of this study was to investigate the success rate of single-dose methotrexate (MTX) in the management of CSP, and the outcomes of subsequent pregnancies in a retrospective cohort study. All women who were treated for CSPs between the years 2011 and 2019 were included. Treatment included systemic MTX and ultrasound-guided needle aspiration (UGNA) in cases with active foetal heartbeat. Overall, 34 women were diagnosed with CSP, of whom 31 were treated with systemic MTX. Twelve patients (38.7%) needed additional curettage or hysteroscopy. The only identified risk factor for failure of MTX-based treatment was time interval between the previous caesarean delivery and CSP (22 vs 34 months, p = 0.04). Twelve women had a subsequent pregnancy. Five pregnancies ended in term delivery, three in preterm delivery, three in abortion and one woman had a recurrent CSP. The study conclusion is that a single dose MTX with UGNA in cases of active heartbeat is an effective mode of treatment in cases of CSP with good sequential pregnancy outcomes. Longer time interval from the previous caesarean delivery was identified as a risk factor for failure of conservative management.

Fetal brain biometry in isolated mega cisterna magna: MRI and US study.

OBJECTIVE: To characterize the biometric parameters in ultrasound and brain MRI of fetuses with isolated mega cisterna magna (MCM). METHODS: Cross-sectional historical cohort study conducted at a single tertiary medical center between 2011 and 2018. All fetuses underwent US and brain MRI scans. Matching analysis was performed according to gender and gestational age. RESULTS: The study included a total of 103 fetuses; 44 fetuses with isolated MCM in the study group, and a control group of 59 fetuses with normal CNS. The study group had larger biparietal diameter (BPD) (86 vs. 79.8 mm, p = .001) and head circumference (HC) (318 vs. 292 mm, p < .001) on ultrasound. On MRI, study group had larger occipitofrontal diameter (OFD) (99 vs. 92 mm, p < .001) and BPD (77 vs. 72 mm, p < .001). Male fetuses' prevalence was higher in the study group (77.3% vs. 47.5%). After matching 20 fetuses from each group, the study group had larger HC (310.1 versus 300.7 mm, p = .029) and OFD (113.4 versus 108.3 mm, p = .009) on ultrasound, and larger OFD (97.4 versus 94.6, p = .013) on brain MRI. CONCLUSIONS: Isolated MCM may be related to other large fetal CNS biometric measurements in both ultrasound and MRI and might be influenced by fetal gender.

Neonatal and maternal outcome of small-for-gestational-age neonates delivered by vacuum-assisted delivery.

OBJECTIVE: To evaluate the association between neonatal weight centile and neonatal and maternal morbidity following vacuum-assisted delivery (VAD) among term nulliparous women. METHODS: A retrospective cohort study of all nulliparous women who delivered at term by VAD between 2011 and 2019. Deliveries were allocated into two groups and compared: (1) delivery of an small-for-gestational-age (SGA) neonate, and (2) delivery of an appropriate-for-gestational-age (AGA) neonate. RESULTS: Overall, 3116 women were included in the study; 2878 (92.4%) were AGA and 163 (5.2%) were SGA and comprised the study groups. Neonatal and maternal adverse outcomes did not vary between groups. Rates of composite neonatal adverse outcome for SGA and AGA neonates were 26 (16.0%) versus 462 (16.1%), respectively (P = 0.972). Duration of the second stage of labor and rate of prolonged second stage were significantly lower among the SGA group compared with the AGA group (P < 0.001 for both comparisons). Maternal rates of anal sphincter injury and postpartum hemorrhage did not differ between groups. CONCLUSION: Neonatal outcomes among SGA neonates delivered by VAD at term did not differ from those of AGA neonates. Maternal outcome did not differ. These data provide reassurance for practitioners to perform VAD in SGA neonates at term.

A double-blind randomized trial comparing lidocaine spray and placebo spray anesthesia prior to cervical laminaria insertion.

OBJECTIVE: To compare pain during laminaria insertion after lidocaine spray versus placebo spray anesthesia in women about to undergo a surgical abortion procedure. STUDY DESIGN: A double blind, randomized, placebo-controlled trial of women at 12-24 weeks gestation one day prior to surgical uterine evacuation procedure. Participants received lidocaine 10% or placebo (saline 0.9%) spray to the endocervix and ectocervix two minutes before laminaria insertion. The primary outcome was participants' pain score immediately after initial laminaria insertion, measured using a 10 cm visual analog scale (VAS). Secondary outcomes included scores at speculum removal and 15 min after speculum insertion. RESULTS: From 7/2016 through 8/2018, we enrolled 68 and 66 women to the lidocaine and placebo groups, respectively. Baseline characteristics were similar in both groups. The primary outcome did not differ between lidocaine and placebo groups (median VAS 2.0 vs. 2.0 respectively, p = 0.69). Reported VAS after speculum removal and 15 min from speculum insertion were similar in the lidocaine and placebo groups (median 2.0, p = 0.99; median 1.0 vs. 1.5 respectively, p = 0.32). In multivariate analyses, lidocaine use was associated with decreased VAS score at 15 min from speculum insertion [95%CI -0.96 (-1.74 to -0.18), p = 0.016]. Reported VAS ≥7 at 1st laminaria insertion did not differ between lidocaine and placebo groups (5.88% vs. 10.61% respectively, p = 0.362). CONCLUSION: In women scheduled for laminaria insertion prior to surgical uterine evacuation at 12-24 weeks gestation, topical application of lidocaine spray to the cervix before insertion did not result in lower reported pain as compared with placebo. IMPLICATIONS: Our results imply that physicians should not use topical application of lidocaine spray to the cervix before laminaria insertion to reduce women's pain. Continued efforts must be made to find means to relieve pain by using simple, effective analgesia or adjusting the technique, and not using a tenaculum whenever possible.