The role of surgeon specialty in management and survival of malignant ovarian germ cell tumors: A population-based study.

OBJECTIVES: The aim of this study is to describe management and survival in adult patients with malignant ovarian germ cell tumors (MOGCT) undergoing surgery by general gynecologists (GG) versus gynecologic oncologists (GO). METHODS: This is a population-based retrospective cohort study, including patients (age ≥ 18 years old) with MOGCT identified in the provincial cancer registry of Ontario, (1996-2020). Baseline characteristics, surgical and chemotherapy treatment were compared between those with surgery by GG or GO. Cox proportional hazards (CPH) model was used to determine if surgeon specialty was associated with overall survival (OS). RESULTS: Overall, 363 patients were included. One-hundred and sixty (44%) underwent surgery by GO and 203 (56%) by GG. There were higher rates of stage II-IV in the GO group (27.5% vs 3.9%, p < 0.001, and higher proportion of chemotherapy (64.4% vs 37.4%, p < 0.0001). Five-year OS was 90% and 93% in the GO vs GG groups, respectively (p = 0.39). CPH model showed factors associated with increased risk of death were older age at diagnosis (HR 1.09, 95% CI 1.07-1.12) and chemotherapy (HR 3.12, 95% CI 1.44-6.75). Surgeon specialty was not independently associated with all-cause death (HR 1.04, 95% 0.51-2.15, p = 0.91). CONCLUSIONS: In this group of MOGCT, 5-year OS was not significantly different between patients having surgery by GO compared to GG. Nevertheless, survival rates were lower than expected in the GG group despite their low-risk features. Further exploration is warranted regarding the reasons for this and whether patients with suspected MOGCT may benefit from early assessment by GO for optimal management.

Fertility Preservation in Cervical Cancer-Treatment Strategies and Indications.

Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2-4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17-73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients.

Use of Rectus Flaps in Reconstructive Surgery for Gynecologic Cancer.

The aim of this study was to explore the outcomes of pelvic reconstruction with a rectus abdominis myocutaneous (RAM) or rectus abdominis myoperitoneal (RAMP) flap following radical surgery for gynecologic malignancy. This is a retrospective case series of all pelvic reconstructions with RAM or RAMP flap performed in a gynecologic oncology service between 1998 and 2023. Reconstructions with other flaps were excluded. A total of 28 patients were included. Most patients had vulvar cancer (n = 15, 53.6%) and the majority had disease recurrence (n = 20, 71.4%). Exenteration was the most common procedure, being carried out in 20 (71.4%) patients. Pelvic reconstruction was carried out with a RAM flap in 24 (85.7%) cases and a RAMP flap in 4 (14.3%) cases. Flap-specific complications included cellulitis (14.3%), partial breakdown (17.9%), and necrosis (17.9%). Donor site complications included surgical site infection and necrosis occurring in seven (25.0%) and three (10.7%) patients, respectively. Neovaginal reconstruction was performed in 14 patients. Out of those, two (14.3%) had neovaginal stenosis and three (21.4%) had rectovaginal fistula. In total, 50% of patients were disease-free at the time of the last follow up. In conclusion, pelvic reconstruction with RAM/RAMP flaps, at the time of radical surgery for gynecologic cancer, is an uncommon procedure. In our case series, we had a significant complication rate with the most common being infection and necrosis. The development of a team approach, with input from services including Gynecologic Oncology and Plastic Surgery should be developed to decrease post-operative complications and improve patient outcomes.

Sentinel lymph node mapping in endometrial cancer: Current evidence and practice.

Surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment is the standard of care for patients with clinical early-stage endometrial cancer. Traditionally, complete pelvic and para-aortic lymphadenectomy (LND) was performed to assess for nodal metastases; however, numerous prospective studies have demonstrated that sentinel lymph node biopsy has similar diagnostic accuracy, and is an acceptable alternative to complete LND. This has led to a paradigm shift in endometrial cancer staging.

Antenatal Corticosteroids for Small for Gestational Age in Late Preterm Newborns.

BACKGROUND: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear. OBJECTIVES: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates. METHODS: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34-36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012-December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea. RESULTS: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41-4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23-3.78, P = 0.007). CONCLUSIONS: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

Mismatch-repair deficiency, microsatellite instability, and lynch syndrome in ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes. METHODS: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing. RESULTS: A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%). CONCLUSION: MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid. PRECIS: The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.

Maternal and neonatal outcomes following induction of labor for fetal growth restriction: Extra-amniotic balloon versus prostaglandins.

OBJECTIVE: To compare perinatal outcomes in pregnancies with fetal growth restriction (FGR) undergoing induction of labor by extra-amniotic balloon (EAB) versus prostaglandin E2 (PGE2 ). METHODS: A retrospective cohort study of women with singleton pregnancies and FGR, undergoing induction at term via EAB, PGE2 , or both, at a single medical center (2014-2017). Primary outcome was rate of cesarean deliveries (CDs). Secondary outcomes included composite maternal and neonatal outcomes. RESULTS: Overall, 266 women met the inclusion criteria. Among them, 131 (49.2%) underwent induction by PGE2 , 116 (43.6%) by EAB, and 19 (7.14%) by both methods. No differences were noted in baseline characteristics. Rate of CD (17.24% vs. 6.11% vs. 10.53%, P = 0.022) and maternal composite outcome (18.97% vs. 6.11% vs. 10.53%, P < 0.01) were higher among women who underwent induction by EAB compared with PGE2 or both. No difference was noted between groups in neonatal outcomes. In a multivariable logistic regression, rates of cesarean delivery and composite maternal outcome were no longer higher in the EAB group (adjusted odds ratio [aOR] 1.68, 95% confidence interval [CI] 0.68-4.16, P = 0.260; and aOR 1.94, 95% CI 0.84-4.45, P = 0.120, respectively). CONCLUSION: EAB and PGE2 have comparable maternal and neonatal outcomes when used for induction of labor due to FGR.

On the growth dynamics of the cyanobacterium Anabaena sp. PCC 7938 in Martian regolith.

The sustainability of crewed infrastructures on Mars will depend on their abilities to produce consumables on site. These abilities may be supported by diazotrophic, rock-leaching cyanobacteria: from resources naturally available on Mars, they could feed downstream biological processes and lead to the production of oxygen, food, fuels, structural materials, pharmaceuticals and more. The relevance of such a system will be dictated largely by the efficiency of regolith utilization by cyanobacteria. We therefore describe the growth dynamics of Anabaena sp. PCC 7938 as a function of MGS-1 concentration (a simulant of a widespread type of Martian regolith), of perchlorate concentration, and of their combination. To help devise improvement strategies and predict dynamics in regolith of differing composition, we identify the limiting element in MGS-1 - phosphorus - and its concentration-dependent effect on growth. Finally, we show that, while maintaining cyanobacteria and regolith in a single compartment can make the design of cultivation processes challenging, preventing direct physical contact between cells and grains may reduce growth. Overall, we hope for the knowledge gained here to support both the design of cultivation hardware and the modeling of cyanobacterium growth within.

Immune Checkpoint Inhibitors for the Treatment of Gestational Trophoblastic Neoplasia: Rationale, Effectiveness, and Future Fertility.

OPINION STATEMENT: Most individuals with gestational trophoblastic neoplasia (GTN) are cured with chemotherapy; however, about 5% of them will develop chemotherapy-resistant disease and will die of disease progression. Most GTN tissues express programmed death ligand-1 (PDL-1), making immune checkpoint inhibitors (ICIs) targeting this pathway an attractive treatment option for individuals with GTN. There is increasing evidence to support the use of ICIs for individuals with recurrent or resistant GTN, but available data are derived from case reports and small single arm trials. As promising as it seems, not all individuals with GTN respond to ICIs, and there is lack of evidence toward which factors mediate the effect of ICIs on GTN. In addition, treatment-related adverse events and impact on future fertility are not negligible and should be considered before initiating this treatment. Therefore, additional research is needed to evaluate treatment outcome of ICIs in GTN compared to standard treatment, and to identify molecular and clinical predictors for treatment response, before this treatment is incorporated into the standard of care.

Tumor-reactive antibodies evolve from non-binding and autoreactive precursors.

The tumor microenvironment hosts antibody-secreting cells (ASCs) associated with a favorable prognosis in several types of cancer. Patient-derived antibodies have diagnostic and therapeutic potential; yet, it remains unclear how antibodies gain autoreactivity and target tumors. Here, we found that somatic hypermutations (SHMs) promote antibody antitumor reactivity against surface autoantigens in high-grade serous ovarian carcinoma (HGSOC). Patient-derived tumor cells were frequently coated with IgGs. Intratumoral ASCs in HGSOC were both mutated and clonally expanded and produced tumor-reactive antibodies that targeted MMP14, which is abundantly expressed on the tumor cell surface. The reversion of monoclonal antibodies to their germline configuration revealed two types of classes: one dependent on SHMs for tumor binding and a second with germline-encoded autoreactivity. Thus, tumor-reactive autoantibodies are either naturally occurring or evolve through an antigen-driven selection process. These findings highlight the origin and potential applicability of autoantibodies directed at surface antigens for tumor targeting in cancer patients.

Sentinel Lymph Node Mapping in High-Grade Endometrial Cancer.

Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). While the assessment of pelvic and para-aortic lymph nodes is part of the surgical staging of EC, there is a long-standing debate over the therapeutic value of full lymphadenectomy in this setting. Although lymphadenectomy offers critical information on lymphatic spread and prognosis, most patients will not derive oncologic benefit from this procedure as the majority of patients do not have lymph node involvement. SLN mapping offers prognostic information while simultaneously avoiding the morbidity associated with an extensive and often unnecessary lymphadenectomy. A key factor in the decision making when planning for EC surgery is the histologic subtype. Since the risk of lymphatic spread is less than 5% in low-grade EC, these patients might not benefit from lymph node assessment. Nonetheless, in high-grade EC, the risk for lymph node metastases is much higher (20-30%); therefore, it is crucial to determine the spread of disease both for determining prognosis and for tailoring the appropriate adjuvant treatment. Studies on the accuracy of SLN mapping in high-grade EC have shown a detection rate of over 90%. The available evidence supports adopting the SLN approach as an accurate method for surgical staging. However, there is a paucity of prospective data on the long-term oncologic outcome for patients undergoing SLN mapping in high-grade EC, and more trials are warranted to answer this question.

Short and thick corpus callosum - the thin border between a minor anatomical variant to very poor outcome.

The corpus callosum (CC) is the largest commissure connecting the cerebral hemispheres. Its components are recognized sonographically at 18-20 GW and from that point forward, its growth can be assessed using nomograms for CC length and thickness according to gestational week. Prenatal diagnosis of agenesis of the CC has been reported comprehensively. On the contrary, information regarding findings as short or thick CC is very rare. Is short CC an expression of callosal dysgenesis or could it be a variant of the normal development when all its parts exist? We discuss this issue through this case report.

Fetal extraction maneuvers during cesarean delivery in the second stage of labor.

OBJECTIVE: To compare maternal and neonatal outcomes following cesarean delivery during second stage of labor, according to the fetal extraction method. METHODS: A retrospective cohort study of all women who underwent term cesarean delivery during the second stage of labor at a university-affiliated tertiary medical center (2012-2016). The cohort was divided according to three extraction methods: standard vertex extraction, the push method in which the head extraction is accompanied by pushing through the vagina, and the reverse breech extraction method. Primary outcomes were intraoperative maternal complications, and secondary outcomes were neonatal adverse events. RESULTS: Three hundred and fifty women were included, of whom 206 (59%) underwent standard vertex fetal extraction, 116 (33%) the push method extraction, and 28 (8%) reverse breech extraction. Operation time was significantly shorter in the standard vertex extraction method compared to push and reverse breech extraction methods (33.5 vs. 40.5 and 39.0 min, respectively, p = .013). Uterine laceration and incision extension frequencies were lower in the vertex extraction method as well (24.76 vs. 45.69-46.40% in others, p < .001). Delivery related neonatal injury was significantly more frequent in the reverse breech extraction method (39.29 vs. 12-15% in others, p < .001). In a multivariate analysis reverse breech extraction was associated with higher rates of uterine laceration and incision extension (OR = 2.739 95% confidence interval 1.44-6.56, p = .0237) and delivery related neonatal injury (OR = 2.837, 95% CI: 1.081-7.448, p = .0342). CONCLUSION: Standard vertex extraction method during second stage of labor cesarean delivery is safer both to the mother and neonate when compared to alternative extraction methods. ABBREVIATIONS: NRFHR: non-reassuring fetal heart rate; NICU: neonatal intensive care unit.

Postpartum voiding dysfunction following vaginal versus caesarean delivery.

In this prospective study, we evaluated postpartum voiding dysfunction stratified by mode of delivery - vaginal delivery versus elective caesarean delivery (CD). We recruited nulliparous women carrying singleton gestation at term admitted to delivery room or elective CD. Pre-labour voiding function was assessed by recording the post-voiding residual volume (PVRV) using a bladder scan. PVRV evaluation was repeated at least 12 hours following delivery and before discharge. PVRVs were considered abnormal if ≥150 mL. PVRVs were compared between vaginal and CD. Overall, 54 women were included. Of them, 34 (63%) delivered vaginally and 20 (37%) had an elective CD. Postpartum mean PVRVs were significantly higher compared to pre-labour PVRVs (215 vs. 133 mL, p<.001). Abnormal postpartum PVRV was significantly higher in vaginal delivery compared to CD (73.5% vs. 45%, p<.05). In conclusion, delivery adversely affects voiding function. Vaginal delivery is associated with more severe voiding dysfunction compared to elective CD.Impact StatementWhat is already known on this subject? Delivery is associated with voiding dysfunction. While most studies on postpartum voiding dysfunction were related to vaginal delivery, little is known on the effect of mode of delivery (vaginal versus caesarean delivery (CD)) on voiding dysfunction.What the results of this study add? In this study, we found that postpartum post-voiding residual volume is significantly higher than the pre-labour PVRV in women delivered vaginally. In addition, postpartum PVRV was significantly higher in women delivered vaginally compared to elective CD.What the implications are of these findings for clinical practice and/or further research? This study implicates that women with vaginal delivery are more prone to voiding dysfunction compared to elective CD. However, larger observational studies are warranted to confirm these results and evaluate whether this difference still exists beyond the post-partum period.

High incidence of gynecologic sarcomas in Israel-A comparison to European and American reports: Gynecologic Sarcoma in Israel.

OBJECTIVE: Gynecologic Sarcomas are rare, aggressive tumors. The aim of this study was to explore the incidence and outcomes of gynecologic sarcomas in a large national data registry and to compare them with reports from other countries. STUDY DESIGN: Records of gynecologic sarcomas diagnosed in Israel (1980-2014) were extracted from the National Cancer Registry and classified according to International Classification of Diseases for Oncology-3 and characterized according to anatomical site, morphology and demographics. Age-standardized incidence rates and 1, 3, 5 and 10-year relative survival rates were calculated for 3 time periods (1980-1994, 1995-2001 and 2005-2014) according to patient age, stage and years of diagnosis. RESULTS: During 1980-2014, 1271 new gynecologic sarcomas were diagnosed in Israel, with incidence slightly increasing in 1980-2004, to an age-standardized incidence rate of 13 per million women. The most common histologic diagnosis was leiomyosarcoma (48%) and the most common anatomical site was the uterus (89%). The age-standardized incidence rate for uterine sarcoma is higher in Israel (10.55 per million) than in England (7.4 per million) and Germany (5.8 per million) respectively. The 5-year overall survival was significantly poorer in patients >70-years, as compared to younger patients (p<0.001) and in those with leiomyosarcoma compared to endometrial stromal sarcoma (p<0.001). The survival rate of patients with leiomyosarcoma in Israel are comparable to survival rates reported by other studies, although substantially lower regarding endometrial stromal sarcoma. CONCLUSIONS: Uterine leiomyosarcoma was the most common gynecologic sarcoma found in the Israeli, European and American registries. Older patients and those with leiomyosarcoma have the worst prognoses. Histological and anatomical variations in Israel are comparable with global statistics, but the incidence in Israel seems higher than in Europe.

The association between maternal cytomegalovirus urinary excretion and congenital infection rate.

BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study.

OBJECTIVE: To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. STUDY DESIGN: Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. RESULTS: Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). CONCLUSION: The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

Breast cancer incidence in BRCA mutation carriers with ovarian cancer: A longitudal observational study.

OBJECTIVES: We evaluated the incidence of breast cancer and overall survival in a multi-center cohort of ovarian cancer patients carrying BRCA1/2 mutations in order to assess risks and formulate optimal preventive interventions and/or surveillance. METHODS: Medical records of 502 BRCA1/2 mutation carriers diagnosed with ovarian cancer between 2000 and 2018 at 7 medical centers in Israel and one in New York were retrospectively analyzed for breast cancer diagnosis. Data included demographics, type of BRCA mutations, surveillance methods, timing of breast cancer diagnosis, and family history of cancer. RESULTS: The median age at diagnosis of ovarian cancer was 55.8 years (range, 23.9-90.1). A third (31.5%) had a family history of breast cancer and 17.1% of ovarian cancer. Most patients (67.3%) were Ashkenazi Jews, 72.9% were BRCA1 carriers. Breast cancer preceded ovarian cancer in 17.5% and was diagnosed after ovarian cancer in 6.2%; an additional 2.2% had a synchronous presentation. Median time to breast cancer diagnosis after ovarian cancer was 46.0 months (range, 11-168). Of those diagnosed with both breast cancer and ovarian cancer (n = 31), 83.9% and 16.1% harbored BRCA1 and BRCA2 mutations, respectively. No deaths from breast cancer were recorded. Overall survival did not differ statistically between patients with an ovarian cancer diagnosis only and those diagnosed with breast cancer after ovarian cancer. CONCLUSION: The low incidence of breast cancer after ovarian cancer in women carrying BRCA1/2 mutations suggests that routine breast surveillance, rather than risk-reducing surgical interventions, may be sufficient in ovarian cancer survivors.

Association of term isolated microcephaly with mode of delivery and perinatal outcome - a retrospective case-control analysis.

BACKGROUND: We aimed to evaluate the association of isolated fetal microcephaly measured by ultrasound prior to delivery at term with mode of delivery and perinatal outcome. METHODS: A single-center retrospective study was conducted in 2012-2016. Fetal microcephaly was defined as head circumference > 2 standard deviations of the mean for gestational age and sex. We compared the obstetric, delivery, and outcome parameters of women in whom ultrasound performed up to 10 days prior to term delivery showed isolated fetal microcephaly (study group) or normal head circumference (reference group). Exclusion criteria were intrauterine fetal death, birthweight below the 10th percentile, and antepartum cesarean delivery for any indication. RESULTS: Of 3677 women included in the study, 26 (0.7%) had a late ultrasound finding of isolated fetal microcephaly. Baseline characteristics were similar in the two groups except for estimated fetal weight based on abdominal circumference and biparietal diameter, which was lower in the microcephaly group (3209.8 ± 557.6 vs. 2685.8 ± 420.8 g, p < .001). There was no significant between-group difference in rate of vaginal operative deliveries (11.7% vs 14.8%, respectively, p = 0.372). The study group had no intrapartum cesarean deliveries compared to 6.3% of the reference group (NS). Compared to controls, neonates in the study group were smaller (3323.2 ± 432.2 vs. 2957.0 ± 330.4 g, p < .001), with lower birthweight percentile (60.5 ± 26.5 vs. 33.6 ± 21.5%, p < .001) and were more often males (48.2 vs. 90.0%, p < .001). No significant differences were noted in perinatal outcomes between the groups, including admission to neonatal intensive care unit, intraventricular hemorrhage, 5-min Apgar score < 7, asphyxia, seizures, and sepsis. CONCLUSIONS: Isolated microcephaly in term fetuses is not advantageous for a vaginal delivery, nor does it does not pose a greater than normal risk of adverse perinatal outcome.

Neoadjuvant Chemotherapy for Elderly Patients with Advanced Stage Ovarian Carcinoma.

BACKGROUND: The treatment of elderly patients with advanced stage ovarian carcinoma is challenging due to a high morbidity. OBJECTIVES: To evaluate the clinical course and outcome of elderly patients with advanced stage ovarian carcinoma receiving neoadjuvant chemotherapy (NACT). METHODS: A retrospective study of all patients with stage IIIC and IV ovarian carcinoma receiving NACT in one medical center (between 2005 and 2017). The study group criteria age was above 70 years. The control group criteria was younger than 70 years old at diagnosis. Demographics and treatment outcomes were compared between groups. Primary outcomes were progression-free survival (PFS) and overall survival (OS). RESULTS: Overall, 105 patients met the inclusion criteria, 71 patients (67.6%) were younger than 70 years and 34 patients (32.4%) older. Rates of interval cytoreduction were significantly higher in younger patients (76.1% vs. 50.0%, P = 0.01). Of those who underwent interval cytoreduction, no difference was found in rates of optimal debulking between groups (83.35% vs. 100%, P = 0.10). Using a Kaplan-Meier survival analysis, no significant differences were observed between groups in PFS or OS, P > 0.05. Among the elderly group alone, patients who underwent interval cytoreduction had significantly longer PFS than those without surgical intervention (0.4 ± 1.7 vs. 19.3 ± 19.4 months, P = 0.001). CONCLUSIONS: Elderly patients with ovarian carcinoma who received NACT undergo less interval cytoreduction than younger patients, with no difference in PFS and OS. However, among the elderly, interval cytoreduction is associated with significantly higher PFS.