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Abstract After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.

Background Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes fetal growth restriction defined as birthweight 32 weeks). To assess if the performance of the prediction models is generalisable for various definitions of FGR, and assess the association between various birthweight centiles calculated using customised and population-based standards and perinatal morbidity and mortality. To estimate the net benefit (clinical utility) of the developed prediction models using decision curve analysis (DCA). To assess the costs and outcomes and the potential impact of resource use of the prediction models. Methods We followed existing recommendations for prediction model development and validation and reported in line with guidelines for prognostic research and IPD meta-analysis. Our meta-analysis utilised IPD within the IPPIC Network database. IPPIC is a living data repository of cleaned and harmonised data of pregnant women from large birth or population-based cohorts, study cohort data, registries or unpublished data from hospital records. The primary outcomes were (1) FGR defined as birthweight

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, −18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of −22.3 g (Allen cohort), −33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (−154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045

Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5—HIF-1α—COX2 axis could promote endometrial cancer progression.

Tokophobia is regarded as the intensive fear of childbirth that some pregnant women have. However, little is known about the psychopathological details of tokophobia (fear of childbirth). Between 2020 and 2021, a total of 10 pregnant women (nine nulliparae and one multipara) with a strong fear of childbirth were referred by obstetricians. Semi-structured psychopathological interviews were conducted, and two cases were judged to have obsession, three an overvalued idea, and one secondary delusion. Three were characterised by both obsession and overvalued idea and one by both obsession and secondary delusion. In total, six cases had features of an overvalued idea. All of the participants except one had a lifetime history of a specific phobia. In addition, their history included social phobia in two cases, panic disorder in one case, obsessive–compulsive disorder (other than tokophobia) in two cases, depressive disorder in two cases, bipolar disorder in two cases, and PTSD in six cases. To conclude, this study showed that tokophobia was not a phobic disorder but a kind of overvalued idea that requires specific assessment and treatment.

Abstract We report on a patient with a distal 16.4-Mb duplication at 2q36.3-qter, who presented with severe intellectual disability, microcephaly, brachycephaly, prominent forehead, hypertelorism, prominent eyes, thin upper lip, and progenia. Copy number analysis using whole exome data detected a distal 2q duplication. This is the first report describing a distal 2q duplication at the molecular level.

Intrauterine balloon prolapse sometimes occurs, and the intrauterine balloon must be reinserted. Furthermore, intrauterine balloon tamponade (IBT) failure can necessitate additional invasive procedures. We report a case of cervical cerclage with IBT for placenta previa with a cervical dilation. In our case, emergency cesarean section was performed at 35 + 4 weeks of gestation because of persistent hemorrhage. During the operation, we performed IBT to prevent further postpartum hemorrhage. However, immediately after the operation, uterine cervical dilatation was 6 cm, which resulted in cervical dilation and prolapse of the intrauterine balloon. Therefore, we performed cervical cerclage using absorbable sutures with IBT and blood transfusion. We speculated that the intrauterine balloon might have induced cervical canal ripening during the operation. Our case suggested that cervical cerclage with IBT is a useful method to prevent intrauterine balloon prolapse in cases with cervical dilation.

Abstract Background The aim of the present study was to clarify fetal heart rate (FHR) evolution patterns in infants with cerebral palsy (CP) according to different types of umbilical cord complications. Methods This case–control study included children born: with a birth weight ≥2000 g, at gestational age ≥33 weeks, with disability due to CP, and between 2009 and 2014. Obstetric characteristics and FHR patterns were compared among patients with CP associated with (126 cases) and without (594 controls) umbilical cord complications. Results There were 32 umbilical cord prolapse cases and 94 cases with coexistent antenatal umbilical cord complications. Compared with the control group, the persistent non-reassuring pattern was more frequent in cases with coexistent antenatal umbilical cord complications (p = 0.012). A reassuring FHR pattern was observed on admission, but resulted in prolonged deceleration, especially during the first stage of labor, and was significantly identified in 69% of cases with umbilical cord prolapse and 35% of cases with antenatal cord complications, compared to 17% of control cases (p

Abstract Background This study aimed to clarify predictors of depressive symptoms and anxiety symptoms after cancer diagnosis among Japanese cancer survivors (CSs). Methods As part of a Japanese cancer survivorship research project commissioned by the Ministry of Health, Labour and Welfare (MHLW) of Japan, we conducted a web-based nationwide survey of CSs in 2018. We analyzed the risk factors for depressive and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale Japanese version (HADS). Results Of 1,234 Japanese CSs, mean score of HADS-depression and HADS-anxiety were 4.08 and 4.78, respectively. At the time of the study, the number of CSs with symptoms of depression and anxiety were 111 (9.0%) and 269 (21.8%), respectively. After multivariable analysis, CSs ≥ 60 years old (reference: ≤ 39 years old, odds ratios (OR): 0.39, 95%CI: 0.17–0.90) and those ≥ 10 years from cancer diagnosis (reference: 0–4 years, OR: 0.55, 95%CI: 0.32–0.96) had lower odds for depressive symptoms. And CSs ≥ 60 years old (reference: ≤ 39 years old, OR: 0.27, 95%CI: 0.15–0.49) and those ≥ 10 years from cancer diagnosis (reference: 0–4 years, OR: 0.62, 95%CI: 0.42–0.90) also had lower odds for anxiety symptoms. CSs who received chemotherapy (OR: 1.56, 95%CI: 1.10–2.20) had higher odds for anxiety symptoms. Conclusions Based on manifestation of symptoms, CSs who were younger, closer to the time of cancer diagnosis, had advanced-staged cancer, or received chemotherapy may be at higher risk for depressive or anxiety symptoms. Those CSs who have higher risk for depression and anxiety symptoms, should be followed-up more carefully for better cancer survivorship, by medical professionals, companies, and society.

Objective: This study aimed to clarify the effectiveness of cervical cerclage in preventing recurrent preterm births. Materials and methods: A retrospective study was conducted using the perinatal registration database of the Japan Society of Obstetrics and Gynecology for the Perinatal Center from 2014 to 2016. The efficacies of history-indicated, ultrasound-indicated, and physical examination-indicated cerclage as preventive treatments for women with a history of preterm birth were evaluated by comparing cerclage and non-cerclage cases. Fisher's exact test was performed to evaluate any significant differences in patient backgrounds. Prior to the evaluation, propensity score matching was performed for history-indicated and ultrasound-indicated cerclage patients. Results: For this study, 6060 multiparous women with a history of preterm birth were reviewed. After excluding 17 patients with unknown indications for cervical cerclage, 6043 patients were included in the study. History-indicated and ultrasound-indicated cerclage did not reduce the risk of preterm birth in subsequent pregnancies for any of the pregnancy periods (p = 0.413, p = 1.000). In contrast, physical examination-indicated cerclage significantly reduced the risk of subsequent preterm births for all pregnancy periods (p

Background: A negative response towards a current pregnancy consists of two elements: unwantedness of and unhappiness about the current pregnancy. Little is clear about whether pregnant women can be categorized in terms of unwantedness and unhappiness as well as what the correlates are of these categories. Methods: An internet survey of 696 women in their first trimester of pregnancy examined the participants’ intention of and emotional reaction towards pregnancy, borderline personality traits, adult attachment style, depression, fear of childbirth, obsessive-compulsive symptoms, fetal bonding disorder, avoidance of taking part in child care, and consideration about termination of pregnancy (TOP). About one third of the participants were followed up with in their second trimester. Results: Two-step cluster analysis using the participants’ intention of and emotional reaction towards pregnancy revealed three groups of pregnant women: those who wanted and were happy about the pregnancy (Cluster 1), those who were unhappy about the pregnancy (Cluster 2), and those who did not intend to be pregnant but were happy about pregnancy (Cluster 3). Cluster 2 women, but not Cluster 3 women, were likely to be single, with borderline personality traits as well as unstable adult attachment styles, accompanied by depression, fear of childbirth, obsessive-compulsive symptoms, and fetal bonding disorder. They were more likely to avoid caring for the baby after childbirth and consider TOP. Conclusion: Expectant women who were unhappy about their pregnancy were at risk of psychological adjustment and need specific perinatal mental health assessment and care.

Abstract Purpose To identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next‐generation sequencing. Methods We investigated α‐ and β‐diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure. Results The endometrial microbiotas had higher α‐diversities than did the vaginal microbiotas (P

Objective: Incarcerated gravid uterus is a condition in which uterine myoma and intraperitoneal adhesion lead to persistent uterine retroversion. Accurate diagnosis before cesarean section is crucial so that the procedure can be planned with regard to the spatial relationship between the uterine incision and other organs. This study investigated the effects of well-planned management on the outcome of cesarean sections. Materials and methods: Four patients with incarcerated gravid uterus who received well-planned management and preoperative magnetic resonance imaging were compared with three unexpected patients who were operated without preoperative diagnosis. Results: In the preoperatively diagnosed group, compared with the non-preoperatively diagnosed group, the frequency of cervical canal damage tended to be lower (0% vs. 100%), blood loss tended to be less (1171 ± 290 mL vs. 2000 ± 300 mL), and surgery duration tended to be shorter (82 ± 17 min vs. 147 ± 84 min). None of the preoperatively diagnosed cases required allogeneic blood transfusion, and no organ damage was observed. Conclusion: The early detection of a suspected incarcerated uterus, and a thorough understanding of diagnostic methods and the use of preoperative magnetic resonance imaging and ultrasonography facilitate the safe performance of a cesarean section.

Abstract Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.

Abstract Background In Japan, 55.5% of breast cancer survivors (BCSs) are of working age, so various perspectives regarding return to work (RTW) after cancer diagnosis need to be considered. Therefore, this study aimed to clarify the risk factors for resignation and taking sick leave (SL) among BCSs in continued employment at the time of diagnosis. Methods A web-based retrospective cross-sectional survey was conducted on BCSs using data from a 2018 Japanese national research project (Endo-Han) commissioned by the Ministry of Health, Labour and Welfare of Japan. The subjects were women aged 18–69 years who had been diagnosed with breast cancer for the first time at least 1 year previously. The risk factors for resignation and taking SL after breast cancer diagnosis, including age at diagnosis, education level, cancer stage, surgery, chemotherapy, radiotherapy, employment status, and occupational type, were then analyzed using a logistic regression model. Results In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of the multivariable analysis indicated that lower education level (odds ratio [OR]: 3.802; 95% confidence interval [CI]: 1.233–11.729), taking SL (OR: 2.514; 95%CI: 1.202–5.261), and younger age at diagnosis (OR: 0.470; 95%CI: 0.221–0.998) were predictors of resignation. Of 229 patients who continued working, SL was taken by 72 (31.4%). In addition, undergoing surgery was found to be a predictor of taking SL (OR: 8.311; 95%CI: 1.007–68.621). Conclusions In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of this study indicated that younger age, lower education level, and taking SL were predictors of resignation after breast cancer diagnosis.

Intense fear of childbirth by expectant women is called tokophobia. Because there are no qualitative studies targeting women with an intense fear of childbirth in Japan, it is unknown whether there is any link between the type of fear of objects/situations among tokophobic women and their psychological/demographic background. Furthermore, there is no available summary of the lived experience of Japanese women with tokophobia. This study aims to identify the intensity patterns of various types of fear among the participants and summarize the lived experience of having intense fear of childbirth. A qualitative descriptive study was conducted using a semi-structured interview. Pregnant women with an intense fear of childbirth participated in individual interviews facilitated by a psychiatrist and a midwife. Audio recordings of the interviews were transcribed and analyzed using a content analysis approach. The number of participants was ten. The types of feared objects varied individually and these were categorized as being related to either prospective or retrospective fear. The participants’ experiences were grouped into three categories: difficulty in daily life, preoccupied negative expectation towards childbirth, and psychological adaptation to the upcoming childbirth. The results imply that women with tokophobia continuously suffer from fear in their daily life; hence, a special approach is needed to detect and reduce their fear.

Little is known about the causality of antenatal depression (AND). We focused on the causal relationships between AND, fear of childbirth (FOC), and obsessive-compulsive symptoms (OCS) during the COVID-19 pandemic in Japan. We also examined whether the perceived threat of COVID-19 is associated with AND. Participants were recruited for an Internet survey conducted in December 2020. A total of 245 pregnant women completed the online survey at 12 to 15 weeks’ gestational age (Time 1) and approximately 10 weeks later (Time 2). AND was estimated using the first two diagnostic items of Major Depressive Episode. The estimated prevalence of AND was 4.5% and 2.9% at Time 1 and Time 2, respectively. At both time points, no association was found between AND and the perception of COVID-19 threat. Structural equation modeling showed that AND predicted OCS (β = 0.16, p < 0.001), which, in turn, predicted FOC (β = 0.09, p = 0.042); FOC, in turn, predicted AND (β = 0.23, p < 0.001). AND, OCS, and FOC were predicted by borderline personality traits. Insecure adult attachment influenced AND and FOC via the perceived negative impact of the current pregnancy. Perinatal care providers should assess the personality and perception of pregnancy to prevent depression and pay attention to symptoms such as FOC and OCS in addition to those of depression.

Abstract Objective This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. Methods The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. Results A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06–2.81) and during the night shift (OR 2.29, 95% CI 1.30–4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97–2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70–2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47–3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76–4.84). Conclusion Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.

Background: The use of mobile health has increased worldwide, but along with its increased utilization comes the risk of the digital divide, inequity in access to information and communications technologies, exerting greater influence on health inequity caused by socioeconomic determinants of health. There is a growing need to investigate whether the digitization of existing health interventions has a risk of worsening the health gap. Methods: We investigated the attitudes of mothers and pregnant women toward digitization of the Maternal and Child Health Handbook (MCHH), a popular personal health record (PHR) used by almost every pregnant woman or mother in Japan, using a cross-sectional survey. We determined sociodemographic factors associated with favorable opinions toward digitization using a multivariate regression model. We then grouped the participants using partitioning around medoids clustering, a machine-learning approach, to interpret their varying attitudes toward digitization in light of their sociodemographic characteristics as well as their affinity toward the paper MCHH. Findings: Higher income and educational level, older age, and less reliance on the MCHH were significantly associated with favorable opinion toward digitization. Clustering analysis identified four latent clusters. The cluster with the highest socioeconomic status (SES) was the most favorable toward digitization, while two clusters with the lowest SES, one of which relied heavily on the paper MCHH, were less favorable of digitization compared to the high SES cluster. The final cluster was comprised of mothers with the experience of raising multiple children and did not rely heavily on the MCHH. Interpretation: Our study identified a socioeconomic divide in opinions toward digitization of an existing health intervention. A hasty digitization may result in an unbalanced uptake of the digitized health intervention among different social classes.

Cesarean section for placenta previa accreta spectrum carries a significant risk of massive hemorrhage. Hence, it is necessary to understand the various hemostatic procedures, damage control surgery and resuscitation for massive hemorrhage, and systemic management against hypovolemic shock and coagulopathy. In cases of placenta previa with previous cesarean section, the operation should be performed in a tertiary medical facility with well-trained staff and blood availability for transfusion. Preoperative placement of an intra-arterial balloon occlusion catheter in the common iliac artery or aorta is useful for preventing massive hemorrhage.

Background: Stigma towards COVID-19 may negatively impact people who suffer from it and those supporting and treating them. Objective: To develop and validate a scale to assess 11-item COVID-19–related stigma. Methods: A total of 696 pregnant women at a gestational age of 12 to 15 weeks were surveyed using an online survey with a newly developed scale for COVID-19 stigma and other variables. The internal consistency of the scale was calculated using omega indices. We also examined the measurement invariance of the scale. Results: Exploratory factor analyses (EFAs) of the scale items were conducted using a halved sample (n = 350). Confirmatory factor analyses (CFAs) among the other halved sample (n = 346) compared the single-, two-, three-, and four-factor structure models derived from the EFAs. The best model included the following three-factor structure (χ2/df = 2.718, CFI = 0.960, RMSEA = 0.071): Omnidirectional Avoidance, Attributional Avoidance, and Hostility. Its internal consistency was excellent (all omega indices > 0.70). The three-factor structure model showed configuration, measurement, and structural invariances between primiparas and multiparas, and between younger (less than 32 years) and older women (32 years or older). Fear of childbirth, mother–fetal bonding, obsessive compulsive symptoms, depression, adult attachment self-model, and borderline personality traits were not significantly correlated with the Omnidirectional Avoidance subscale but correlated with the Attributional Avoidance and Hostility subscales (p < 0.001). Conclusion: The findings suggested that our scale for COVID-19 stigma was robust in its factor structure, as well as in construct validity.

When cesarean hysterectomy is scheduled in cases of placenta previa accreta/increta/percreta, it is necessary that the departments of obstetrics, anesthesiology, blood transfusion, urology, and radiology hold a preoperative conference to assure full preparation for the surgery. A ureteral stent inserted just before cesarean section serves as a marker. A uterine incision should be made at a site free of placental contact. The presence/absence of bladder invasion by villi, adhesions, and the degree of vascularization greatly influence the amount of bleeding, and bleeding control is a key point. For prevention of massive hemorrhage, methods of blood flow blockage, such as balloon occlusion catheterization of the aorta or common iliac artery, should be considered. Stored autologous blood and Cell Saver should be prepared. When hysterectomy is performed with the placenta left in situ, handling of the elongated cardinal ligament, ureteric injury, and bladder injury are important issues because the lower uterine segment is enlarged with the placenta. If blood flow is not blocked, separation of the bladder at the area of placenta percreta should be performed as the last step, to reduce bleeding (Pelosi's method). At this time, after handling of the cardinal ligament, bladder separation can be performed more safely if the posterior vaginal wall is incised and exposed first. In cases of placenta accreta or partial placenta accreta/increta/percreta, a diagnosis of morbidly adherent placenta may not be obtained until separation of the placenta is performed. If bleeding from the placental separation surface cannot be controlled, total hysterectomy should be performed without hesitation.

Cancer cells rely on mitochondrial respiration to satisfy their metabolic demands. Here the authors show that the mitochondrial supercomplex assembly factor COX7RP is abundantly expressed in breast and endometrial cancer cells and promotes tumor growth and hypoxia tolerance partially by altering levels of the tricarboxylic acid cycle intermediates.

Placental abruption is a condition that should be carefully considered in perinatal management because it is associated with serious events in both the mother and neonate, such as intrauterine fetal death, cerebral palsy, obstetric critical bleeding, and uncontrollable bleeding. The concomitant presence of disseminated intravascular coagulation (DIC) more easily causes critical bleeding that may necessitate hysterectomy or multi-organ failure resulting in maternal death. Therefore, early management should be provided to prevent progression to serious conditions by performing both hemostatic procedures and DIC treatment. To take measures to improve the outcomes in both the mother and neonate, health guidance for pregnant women, early diagnosis, early treatment, development of the emergency care system, and provision of a system for transport to higher-level medical institutions should be implemented.

Objective: The aim of this study was to evaluate the outcomes of neoadjuvant chemotherapy (NAC) with bevacizumab (Bev) at our institute. Materials and methods: Eleven patients with stage IIIC or IV peritoneal/ovarian cancer who underwent interval debulking surgery (IDS) after NAC with Bev between December 2014 and December 2016 were enrolled retrospectively (TCB group). As a control group, we enrolled 13 patients evaluated between December 2012 and December 2014 who underwent IDS and received NAC without Bev (TC group). Both the TCB and TC groups received combination chemotherapy consisting of paclitaxel (175 mg/m2) or docetaxel (70 mg/m2) and carboplatin (area under the curve 6 mg/mL/min) administered intravenously every 3 weeks (cycles 3–6). Results: All patients in both groups underwent IDS. There were 7 (63.6%) and 8 (61.5%) cases with stage IIIC disease and 4 (36.3%) and 5 (30.7%) with stage IV disease in the TCB and TC groups, respectively. The complete resection rate was 81.8% in the TCB group and 69.2% in the TC group. The rate of achieving either complete or optimal resection was 100% in the TCB group and 69.2% in the TC group (p = 0.043). Hematoxicity (grade 3 or higher) was observed in 9 patients (81.8%) in the TCB group and 12 (92.3%) patients in the TC group. One patient (9%) in the TCB group experienced abdominal incisional hernia due to a fascial defect. Conclusion: IDS after NAC with Bev is safe, with a similar efficacy as that after NAC without Bev. Keywords: Ovarian cancer, Neoadjuvant chemotherapy, Interval debulking surgery, Bevacizumab

Induction and augmentation of labor is one of the most common obstetrical interventions. However, this intervention is not free of risks and could cause adverse events, such as hyperactive uterine contraction, uterine rupture, and amniotic-fluid embolism. Our previous study using a new animal model showed that labor induced with high-dose oxytocin (OXT) in pregnant mice resulted in massive cell death in selective brain regions, specifically in male offspring. The affected brain regions included the prefrontal cortex (PFC), but a detailed study in the PFC subregions has not been performed. In this study, we induced labor in mice using high-dose OXT and investigated neonatal brain damage in detail in the PFC using light and electron microscopy. We found that TUNEL-positive or pyknotic nuclei and Iba-1-positive microglial cells were detected more abundantly in infralimbic (IL) and prelimbic (PL) cortex of the ventromedial PFC (vmPFC) in male pups delivered by OXT-induced labor than in the control male pups. These Iba-1-positive microglial cells were engulfing dying cells. Additionally, we also noticed that in the forceps minor (FMI) of the corpus callosum (CC), the number of TUNEL-positive or pyknotic nuclei and Iba-1-positive microglial cells were largely increased and Iba-1-positive microglial cells phagocytosed massive dying cells in male pups delivered by high-dose OXT-induced labor. In conclusion, IL and PL of the vmPFC and FMI of the CC, were susceptible to brain damage in male neonates after high-dose OXT-induced labor.

Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 Wistar rats were exposed to unilateral GMH through intracranial injection into the striatum close to the germinal matrix with 0.1, 0.2, or 0.3 U of collagenase VII. During 10 days following GMH induction, motor functions and body weight were assessed and brain tissue collected at P16. Animals were tested for anxiety, motor coordination and motor asymmetry on P22–26 and P36–40. Using immunohistochemical staining and neuropathological scoring we found that a collagenase dose of 0.3 U induced GMH. Neuropathological assessment revealed that the brain injury in the collagenase group was characterized by dilation of the ipsilateral ventricle combined with mild to severe cellular necrosis as well as mild to moderate atrophy at the levels of striatum and subcortical white matter, and to a lesser extent, hippocampus and cortex. Within 0.5 h post-collagenase injection there was clear bleeding at the site of injury, with progressive increase in iron and infiltration of neutrophils in the first 24 h, together with focal microglia activation. By P16, blood was no longer observed, although significant gray and white matter brain infarction persisted. Astrogliosis was also detected at this time-point. Animals exposed to GMH performed worse than controls in the negative geotaxis test and also opened their eyes with latency compared to control animals. At P40, GMH rats spent more time in the center of open field box and moved at higher speed compared to the controls, and continued to show ipsilateral injury in striatum and subcortical white matter. We have established a P5 rat model of collagenase-induced GMH for the study of preterm brain injury. Our results show that P5 rat pups exposed to GMH develop moderate brain injury affecting both gray and white matter associated with delayed eye opening and abnormal motor functions. These animals develop hyperactivity and show reduced anxiety in the juvenile stage.

Objective Contrast-enhanced ultrasonography (CEU) has been used in critical trauma situations to visualize extravasation; however, its use is limited in the field of obstetrics. Cases of ruptured uterine artery pseudoaneurysm (UAP) were analyzed to clarify the efficacy to CEU during uterine balloon tamponade. Methods Cases of ruptured UAP diagnosed at a teaching university hospital from January 2015 to December 2017 were retrospectively analyzed. UAP was diagnosed using color Doppler ultrasonography. Extravasation was identified using computed tomography and double checked using CEU with an intravenously administered contrast agent (Sonazoid; Daiichi Sankyo Company, Ltd., Tokyo, Japan) and an ultrasound instrument (HI VISION Preirus; Hitachi Aloka Medical, Ltd., Tokyo, Japan). A balloon was then inserted into the uterine cavity and inflated at the point of bleeding until extravasation ceased. Results Three patients exhibited ruptured UAP during the study period. Bleeding points were successfully identified using CEU in all cases, and hemostasis was achieved using uterine balloon tamponade. Obliteration of UAP was confirmed using magnetic resonance imaging, and no patients developed recurrent UAP or any complications. Conclusion CEU can be used at the bedside to promptly diagnose ruptured UAP. Moreover, it precisely facilitates balloon compression at the point of bleeding.

Gene structure alterations, such as chromosomal rearrangements that develop fusion genes, often contribute to tumorigenesis. It has been shown that the fusion genes identified in public RNA-sequencing datasets are mainly derived from intrachromosomal rearrangements. In this study, we explored fusion transcripts in clinical ovarian cancer specimens based on our RNA-sequencing data. We successfully identified an in-frame fusion transcript SPON1-TRIM29 in chromosome 11 from a recurrent tumor specimen of high-grade serous carcinoma (HGSC), which was not detected in the corresponding primary carcinoma, and validated the expression of the identical fusion transcript in another tumor from a distinct HGSC patient. Ovarian cancer A2780 cells stably expressing SPON1-TRIM29 exhibited an increase in cell growth, whereas a decrease in apoptosis was observed, even in the presence of anticancer drugs. The siRNA-mediated silencing of SPON1-TRIM29 fusion transcript substantially impaired the enhanced growth of A2780 cells expressing the chimeric gene treated with anticancer drugs. Moreover, a subcutaneous xenograft model using athymic mice indicated that SPON1-TRIM29-expressing A2780 cells rapidly generated tumors in vivo compared to control cells, whose growth was significantly repressed by the fusion-specific siRNA administration. Overall, the SPON1-TRIM29 fusion gene could be involved in carcinogenesis and chemotherapy resistance in ovarian cancer, and offers potential use as a diagnostic and therapeutic target for the disease with the fusion transcript.

Abdominal myomectomy for a huge myomas, especially uterine cervical myoma, is difficult because of risks, such as intraoperative bleeding or injury to adjacent organs. Therefore, understanding of the positional relationships among a huge myoma, especially cervical or intraligamental myoma, and the vascular plexuses in the right and left cardinal ligaments is important for prevention of massive bleeding during myomectomy. While sufficiently performing preoperative assessment with pelvic examination, ultrasonography, magnetic resonance imaging (MRI), etc., surgeons should always keep in mind how they can reduce the blood loss volume, while safely and surely performing resections. For a cervical myoma of the uterus and giant uterine leiomyoma that leave no intrapelvic space and prevent palpation and identification of the uterine arteries and the internal iliac arteries, surgery can be performed safely by preoperatively placing balloon catheters in the internal iliac arteries. Hemostaic strategies for myomectomy and tips of subsequent pregnancy following myomectomy are also described.

Cesarean section in breech or transverse presentation involves more complicated procedures than cesarean section in cephalic presentation because the former requires additional manipulations for guiding the presenting part of the fetus, liberation of the arms, and the after-coming head delivery; therefore, those cesarean sections are likely to be more invasive. Making a rather wide uterine incision to prevent uterine injury during delivery of the fetus facilitates smooth delivery of the fetus. Furthermore, in cases of breech or transverse presentation, it is important to initially identify the presenting part of the fetus and guide it to the incision opening in the lower uterine segment, because delivering the presenting part of the fetus first is a basic rule of delivery of the fetus. Smooth delivery of the fetus by means of breech extraction can prevent excessive stress or injury to the fetus. Therefore, it is important to acquire the knowledge and skills necessary to perform these techniques, including the internal version. Smooth delivery of the fetus is also less invasive for the mother because an extension of the uterine excision or injury to arteries and veins in the uterus and parametrium can be avoided. Incarcerated uterus occurring in cases of pregnancy with intrapelvic adhesion, endometriosis, cervical myoma, or extended cervix may result in excessive uterine and cervical injury when a transverse incision of the lower uterine segment is performed without caution. These conditions may result in difficulty in fetal delivery. Therefore, it is important to identify risks in advance and to choose the incision line with great care. Countermeasures for difficult delivery of the fetus need to be mastered by all practitioners of obstetrics. If the transverse incision fails to reach the uterine cavity, an inverted T-shaped or J-shaped incision should be made. Risks of complications such as injury to the cervical canal, the vagina, the bladder or ureter, and massive hemorrhage must be kept in mind.

According to the increase in the rate of cesarean section and the increase of high-aged pregnancy, we seem to more often encounter cases with placenta previa and placenta previa accrete spectrum. There are concerns about these cases, such as difficulty in controlling bleeding from the separation surface of placenta previa, the need for hysterectomy as a life-saving procedure, systemic management and hemostasis during massive hemorrhage, and treatment of disseminated intravascular coagulation (DIC). These cases are most frequently associated with cesarean hysterectomy.

Cervicovaginal atresia with a functional uterus is rare. There are no established surgical methods to treat this condition, and only a few reports have been published on surgical techniques. Furthermore, postoperative complications, such as restenosis, often require reoperation. A 19-year-old woman was pointed out cervical hypoplasia and referred to our hospital for further examination and treatment. A pelvic examination revealed that the vagina had a slight recession with a blind end. Transrectal ultrasound and pelvic magnetic resonance imaging revealed congenital vaginal agenesis and cervical hypoplasia. Elective surgery was performed after reshaping the vagina. A radical surgery was performed 10 months later after sufficient self-dilation by using Frank's technique in an outpatient setting. At first, we approached by laparoscopically to correct autologous peritoneum and to bladder detach, then the cervical canal was identified. Next, a skin biopsy punch was used several times to hollow out the cervical tissue to shape and expand the cervical canal. A catheter was then placed in the uterus and autologous peritoneum was wrapped around it and fixed to the cervical canal. The catheter was removed 6 weeks postoperatively, and the patient continued dilating her vagina until she was able to have sexual intercourse, and then stopped the self-dilation. Eight months postoperatively, the patient did not report any menstrual irregularities. It is important to make corrections to prevent restenosis of the vagina and cervical canal and prevent the symptoms from recurring. Make use of autologous peritoneum as graft onto the cervical canal is effective method for the treatment of cervicovaginal atresia.

LEFTY2 (endometrial bleeding associated factor; EBAF or LEFTYA), a cytokine released shortly before menstrual bleeding, is a negative regulator of cell proliferation and tumour growth. LEFTY2 down-regulates Na+/H+ exchanger activity with subsequent inhibition of glycolytic flux and lactate production in endometrial cancer cells. Glucose can be utilized not only for glycolysis but also for glycogen formation. Both glycolysis and glycogen formation require cellular glucose uptake which could be accomplished by the Na+ coupled glucose transporter-1 (SGLT1; SLC5A1). The present study therefore explored whether LEFTY2 modifies endometrial SGLT1 expression and activity as well as glycogen formation. Ishikawa and HEC1a cells were exposed to LEFTY2, SGLT1 and glycogen synthase (GYS1) transcript levels determined by qRT-PCR. SGLT1, GYS1 and phospho-GYS1 protein abundance was quantified by western blotting, cellular glucose uptake from 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake, and cellular glycogen content utilizing an enzymatic assay and subsequent colorimetry. As a result, a 48-hour treatment with LEFTY2 significantly increased SGLT1 and GYS1 transcript levels as well as SGLT1 and GYS1 protein abundance in both Ishikawa and HEC1a cells. 2-NBDG uptake and cellular glycogen content were upregulated significantly in Ishikawa (type 1) but not in type 2 endometrial HEC1a cells, although there was a tendency of increased 2-NBDG uptake. Further, none of the effects were seen in human benign endometrial cells (HESCs). Interestingly, in both Ishikawa and HEC1a cells, a co-treatment with TGF-β reduced SGLT1, GYS and phospho-GYS protein levels, and thus reduced glycogen levels and again HEC1a cells had no significant change. In conclusion, LEFTY2 up-regulates expression and activity of the Na+ coupled glucose transporter SGLT1 and glycogen synthase GYS1 in a cell line specific manner. We further show the treatment with LEFTY2 fosters cellular glucose uptake and glycogen formation and TGF-β can negate this effect in endometrial cancer cells.

Around the world, cervical cancer is one of the most common neoplastic diseases among women, and the prognosis of patients in an advanced stage remains poor. To reduce the mortality rate of cervical cancer, early diagnosis and treatment are essential. DNA methylation is an important aspect of gene regulation, and aberrant DNA methylation contributes to carcinogenesis and cancer progression in various cancers. Although 5-methylcytosine (5mC) has been analyzed intensively, the function of 5-hydroxymethylcytosine (5hmC) has not been clarified. The purpose of our study was to identify the molecular biomarkers for early diagnosis of cervical tumors due to epigenetic alterations. To assess the clinical relevance of DNA methylation, we used immunohistochemistry (IHC) to characterize the level of 5hmC in 102 archived human cervical intraepithelial neoplasia (CIN) samples and cervical cancer specimens. The level of 5hmC was significantly decreased between CIN2 and CIN3. The progression of cervical tumors is caused by a reduction of TP53 and RB1 because of HPV infection. We observed that Tp53 and Rb1 were knocked down in mouse embryonic fibroblasts (MEF), a model of normal cells. The level of 5hmC was reduced in Tp53-knockdown cells, and the expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) were induced. In contrast, there was no significant change in Rb1-knockdown cells. Mechanistically, we focused on apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) 3B (A3B) as a cause of 5hmC reduction after TP53 knockdown. In the human cell line HHUA with a wild-type TP53 gene, A3B was induced in TP53-knockdown cells, and A3B knockdown recovered 5hmC levels in TP53-knockdown cells. These data indicate that TP53 suppression leads to 5hmC reduction in part through A3B induction. Moreover, IHC showed that expression levels of A3B in CIN3 were significantly higher than those in both normal epithelium and in CIN2. In conclusion, 5hmC levels are decreased between CIN2 and CIN3 through the TP53-A3B pathway. Since A3B could impair genome stability, 5hmC loss might increase the chances of accumulating mutations and of progressing from CIN3 to cervical cancer. Thus, these epigenetic changes could predict whether CINs are progressing to cancer or disappearing.

Objective. This study aimed to clarify the effects of cesarean delivery on neonatal respiratory morbidity when women had preterm premature rupture of membranes. Methods. This retrospective study included women with preterm premature rupture of membranes who delivered from 23 weeks to 33 weeks of gestation between January 2009 and December 2014. Neonatal outcomes were compared between infants delivered by cesarean section and those delivered vaginally. The primary outcome was respiratory distress syndrome (RDS). Neonatal intubation and mechanical ventilation periods were secondary outcomes. Propensity score matching was used to compare outcomes between cesarean and vaginal delivery cases. Results. There were 101 cesarean deliveries and 89 vaginal deliveries. A comparison of the presence or absence of neonatal complications based on the delivery type indicated a higher occurrence of RDS with cesarean deliveries (P=0.025). The intubation and mechanical ventilation periods were not significantly longer in neonates delivered via cesarean section. Conclusions. Cesarean delivery is a risk factor for neonatal RDS in women with preterm premature rupture of membranes. Trials identifying long-term neonatal prognoses are needed to further develop optimal management strategies in such cases.

Background: Recurrent pregnancy loss (RPL) is associated with the loss of endometrial mesenchymal stem-like progenitor cells (eMSC). DPP4 inhibitors may increase homing and engraftment of bone marrow-derived cells to sites of tissue injury. Here, we evaluated the effect of the DPP4 inhibitor sitagliptin on eMSC in women with RPL, determined the impact on endometrial decidualization, and assessed the feasibility of a full-scale clinical trial. Methods: A double-blind, randomised, placebo-controlled feasibility trial on women aged 18 to 42 years with a history of 3 or more miscarriages, regular menstrual cycles, and no contraindications to sitagliptin. Thirty-eight subjects were randomised to either 100 mg sitagliptin daily for 3 consecutive cycles or identical placebo capsules. Computer generated, permuted block randomisation was used to allocate treatment packs. Colony forming unit (CFU) assays were used to quantify eMSC in midluteal endometrial biopsies. The primary outcome measure was CFU counts. Secondary outcome measures were endometrial thickness, study acceptability, and first pregnancy outcome within 12 months following the study. Tissue samples were subjected to explorative investigations. Findings: CFU counts following sitagliptin were higher compared to placebo only when adjusted for baseline CFU counts and age (RR: 1.52, 95% CI: 1.32–1.75, P

Abstract Background The mortality rate of ovarian cancer is the highest among all gynecological malignancies in Japan. Ovarian tumors are classified as benign, borderline malignant, or malignant. Anticipating the histological subtype with imaging only is often difficult because of several histological subtypes of epithelial ovarian tumors (such as serous, mucinous, endometrioid, clear cell, and Brenner tumors). In addition, the majority of mucinous tumors in the ovary are metastatic. Furthermore, mucinous tumors belong to one of the two different subclasses (i.e., intestinal and seromucinous types). Ovarian seromucinous cystic tumors of borderline malignancy are infrequent and only rarely coexist with other malignant tumors. Case presentation We have reported a 53-year-old Japanese woman with anaplastic carcinoma in an ovarian seromucinous cystic tumor of borderline malignancy. Her MRI and CT analysis revealed an ovarian tumor with a mural nodule, ascites, and peritoneal dissemination. Enhanced MRI revealed that the mural nodule was enhanced. Enhanced CT analysis revealed that the lymph nodes were not swollen. Intriguingly, the mural nodule crossed the cyst wall into the cavity and onto the surface. Her laboratory data revealed high serum CA 125 level. Cumulatively, these results suggested ovarian malignancy. The patient underwent hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of the disseminated lesions. Lymph node biopsy was omitted because of the suggestion of enhanced CT image findings and palpation during surgery. Her postoperative specimen examination determined FIGO at least stage IIIB, and accordingly, adjuvant chemotherapy was prescribed. After 3 years of the operation, the patient is presently alive without clinical tumor recurrences. Conclusion Imaging studies with pathognomonic findings contributed to ovarian cancer diagnosis in this case. To the best of our knowledge, this is the first study in English literature to report detailed classification of mucinous borderline malignancy, seromucinous cystic, and anaplastic carcinoma in an ovarian seromucinous cystic tumor of borderline malignancy.

Abstract Background The natural killer cell line, NK-92MI, is cytotoxic against various types of cancer. The aim of this study was to develop chimeric antigen receptor-modified (CAR) NK-92MI cells targeting carcinoembryonic antigen-expressing (CEA) tumours and increase killing efficacy by pharmacologically modifying CEA-expression. Result We generated anti-CEA-CAR NK-92MI cells by retroviral vector transduction. This genetically-modified cell line recognised and lysed high CEA-expressing tumour cell lines (LS174T) at 47.54 ± 12.60% and moderate CEA-expressing tumour cell lines (WiDr) at 31.14 ± 16.92% at a 5:1 effector: target (E/T) ratio. The cell line did not lyse low CEA-expressing tumour cells (HCT116) as they did their parental cells (NK-92MI cells). The histone deacetylase-inhibitor (HDAC) sodium butyrate (NaB) and the methylation-inhibitor 5-azacytidine (5-AZA), as epigenetic modifiers, induced CEA-expression in HCT116 and WiDr cells. Although the IC50 of 5 fluorouracil (5-FU) increased, both cell lines showed collateral sensitivity to anti-CEA-CAR NK-92MI cells. The cytolytic function of anti-CEA-CAR NK-92MI cells was increased from 22.99 ± 2.04% of lysis background to 69.20 ± 11.92% after NaB treatment, and 69.70 ± 9.93% after 5-AZA treatment, at a 10:1 E/T ratio in HCT116 cells. The WiDr cells showed similar trend, from 22.99 ± 4.01% of lysis background to 70.69 ± 10.19% after NaB treatment, and 59.44 ± 10.92% after 5-AZA treatment, at a 10:1 E/T ratio. Conclusions This data indicates that the effector-ability of anti-CEA-CAR NK-92MI increased in a CEA-dependent manner. The combination of epigenetic-modifiers like HDAC-inhibitors, methylation-inhibitors, and adoptive-transfer of ex vivo-expanded allogeneic-NK cells may be clinically applicable to patients with in 5-FU resistant condition.

Objective: To predict acidosis in fetus showing deceleration associated with non-reassuring fetal status during delivery, we examined the relationship between duration of the deceleration and umbilical arterial pH. Materials and methods: A total of 19,907 deliveries in eight facilities of the Juntendo Perinatal Care Group, 895 cases of vaginal deliveries with level 3 decelerations were selected for the subjects of this study. The cut-off point of time when the umbilical arterial pH fell below 7.20 in all cases of level 3 and for each deceleration type were examined. The explanatory variables were the pH and pO2 of umbilical arterial gas and the time from onset of the level 3 pattern to delivery. From receiver operating characteristic (ROC) analysis using these variables, the critical point indicating low Apgar score was set at an umbilical arterial pH

Background/Aims: Despite the benefits of laparoscopic surgery, which is being performed with increasing frequency, complications that do not occur during laparotomy are sometimes encountered. Such complications commonly occur during the initial trocar insertion, making this a procedural step of critical importance. Methods: In 2002, we experienced, upon initial trocar insertion, a serious major vascular injury (MVI) that led to hemorrhagic shock, and we thus modified the conventional closed entry method to an approach that we have found to be safe. We began developing the method by first measuring, in a patient undergoing laparoscopic cystectomy, the distance between the inner surface of the abdominal wall and the anterior spine when the abdominal wall was lifted manually for trocar insertion and when it was lifted by other methods, and we determined which method provided the greatest distance. We then devised a new approach, summarized as follows: The umbilical ring is elevated with Kocher forceps. The umbilicus is everted, and the base is incised longitudinally. This allows penetration of the abdominal wall at its thinnest point, and it shortens the distance to the abdominal cavity. A bladeless trocar (Step trocar) is used to allow insertion of the Veress needle. We began applying the new entry technique in July 2002, and by December 2014, we had applied it to 9676 patients undergoing laparoscopic gynecology surgery. Results: All entries were performed successfully, and no MVI occurred. The umbilical incision often resulted in an umbilical deformity, but in a questionnaire-based survey, patients generally reported satisfaction with the cosmetic outcome. Conclusion: A current new approach provides safe outcome with a minor cosmetic problem. Keywords: Closed laparoscopy, Laparoscopic myomectomy, Major vascular injury, Umbilical deformity

Abstract 2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells. Metformin restored liver COMT protein levels, and metformin-induced liver AMPK phosphorylation was abolished by COMT inhibition. The amelioration in glucose tolerance by 2-ME was associated with biphasic insulin secretion in an environment-dependent manner. 2-ME-induced insulin secretion was associated with the AMPK phosphorylation, PDX-1 phosphorylation, and MST-1 suppression in MIN-6 cells. Furthermore 2-ME displayed PPARγ agonist-like activity. These results suggest that COMT is an enzyme to maintain glucose homeostasis and 2-ME is a potential endogenous multi-target anti-diabetic candidate.

Objective: Surgery for uterine cervical fibroids is difficult because of restricted surgical access and risks such as intraoperative bleeding or injury to other organs. The internal iliac artery balloon occlusion catheter (IIABOC) provides effective hemostasis for placenta previa and atonic hemorrhage, and is increasingly used in surgery for uterine fibroids for controlling intraoperative hemorrhage. We investigated the efficacy and safety of the IIABOC for controlling intraoperative bleeding in total abdominal hysterectomies (TAH) and abdominal myomectomies (AM) for large cervical fibroids. Material and methods: From 2007 to 2014, the IIABOC was used in 22 cases (12 for TAH and 10 for AM) in which cervical fibroids fully occupied the pelvic cavity. Intraoperative blood loss, operating time, sample weight, use of blood transfusion, and injury to other organs were assessed. Result: Mean blood loss, operative time, and sample weight in the IIABOC cases were 510 mL, 178 min, and 2550 g for TAH; and 727.5 mL, 157.5 min, and 1850 g for AM. Blood loss divided by sample weight in IIABOC cases was significantly lower than that in non-IIABOC cases during the same time period, for both TAH and AM. Allogeneic blood transfusion was not necessary, and complications of injury to other organs did not occur in any of the 22 cases. Conclusions: For large cervical fibroids with limited operating space, surgery was performed under bleeding control by occlusion of the internal iliac artery with an IIABOC. This technique enables control of hemorrhage and safe operative management in gynecological surgery.

Objective: To analyze the efficacy of positron emission tomography/computed tomography (PET/CT) for the diagnosis of uterine sarcoma. Materials and methods: Thirty-four patients evaluated between January 2010 and March 2015 were retrospectively enrolled. All patients in whom uterine sarcoma was suspected based on contrast-enhanced magnetic resonance imaging (MRI) findings (heterogeneous, high signal intensity on T2-weighted images and/or high intensity on T1-weighted images) underwent PET/CT for further assessment. Patients were divided into 2 groups based on postoperative pathological findings: uterine sarcoma (n = 15) and leiomyoma (n = 19). The maximum standardized uptake value (SUVmax) of all lesions was measured using PET/CT; we calculated the optimal cutoff value for diagnosing sarcoma. Results: The median SUVmax for uterine sarcoma and leiomyoma was 12 and 4.1, respectively; these values were significantly different. An SUVmax of greater than 7.5 was able to exclude leiomyoma with 80.8% sensitivity and 100% specificity (area under the curve, 95.3%). A cutoff SUVmax of 7.5 yields 100% specificity, and a cutoff SUVmax of 4.4 yields a 100% negative predictive value (NPV). The combination of PET/CT and lactate dehydrogenase (LDH) levels had a sensitivity of 86.6%, specificity of 100%, positive predictive value of 100%, and an NPV of 90.4%. No relation between histopathology or International Federation of Gynecology and Obstetrics (FIGO) stage and 18-fluoro-2-deoxy-d-glucose uptake value on PET/CT was seen. The surgical outcome trended toward a correlation with the SUVmax, although this was not statistically significant. Conclusions: In patients with MRI findings consistent with either uterine sarcoma or leiomyoma, PET/CT can decrease the false-positive rate by setting an optimal cutoff SUVmax of 7.5. Using this cutoff can avoid unnecessary surgery.

Objective: Rupture of uterine artery pseudoaneurysm (UAP) is a life-threatening event after childbirth. Hysterectomy or uterine arterial embolization was often needed for hemostasis. However, such procedures may cause severe morbidities for these women. To estimate the efficacy of uterine balloon tamponade (UBT) for controlling ruptured UAP bleeding, a retrospective analysis in a single teaching hospital was performed. Materials and methods: We reviewed the medical record of Juntendo University Hospital in 2015. All the women diagnosed with UAP were recruited to this study and management for UAP was investigated. Results: Three women were treated with UBT for ruptured UAP. All cases achieved hemostasis. One case had recurrent UAP after 24 h of UBT, and was retreated with UBT for a longer duration. The UAP was obliterated after more than 2 days of UBT in all cases. Conclusion: UBT has potential as a therapeutic technique not only for treatment of a ruptured UAP but also for obliteration of a UAP.

Objective: To determine whether our newly developed short-term training program contributes to the acquisition of basic laparoscopic surgery skills. Design: Prospective study (Canadian Task Force Class II). Setting: University Hospital. Participants: Four obstetrics-gynecology residents who participated in our 2-month laparoscopic training course. Interventions: Virtual reality laparoscopic surgery simulator-based assessment of four basic tasks: (1) “camera manipulation”; (2) “eye-hand coordination”; (3) “two-handed maneuvers”; and (4) “cutting,” before and after the course. Measurements and main results: Mean times required to perform the tasks before and after training were compared. The mean times required to perform three of the four tasks (except camera manipulation) were significantly reduced after training. Total instrument path lengths were reduced, especially for instruments used by the dominant hand. Conclusion: Use of the virtual reality laparoscopic surgery simulator allowed us to objectively assess residents' acquisition of basic laparoscopic skills. We found that residents more readily acquired dominant-hand skills during their 2-month training. We conclude that our training system serves as an effective initial step towards the acquisition of the necessary laparoscopic surgery skills, even though residents do not actually perform surgeries during the training period.

Study objective: The purpose of this study was to elucidate the surgical and oncological outcomes after laparoscopic surgery for endometrial cancer at our hospital. Materials and methods: Surgical outcomes, complications rates, 2-year survival rates, and recurrence rates were evaluated in 44 patients who underwent total laparoscopic hysterectomy (TLH) and 57 patients who underwent total abdominal hysterectomy (TAH) for endometrial cancer at our hospital between August 2010 and November 2013. Results: There was no significant difference between the two groups with respect to age or body mass index. More than 80% of patients in both groups had stage I cancer. In the TLH group, the histological types were endometrioid adenocarcinoma in 42 of 44 patients, carcinosarcoma in one patient, and serous adenocarcinoma in one patient. Operative times were significantly longer in the TLH group, but patients in this group had less intraoperative blood loss, shorter hospital stays, and reduced levels of postoperative pain, compared to patients in the TAH group. There were four cases of postoperative infection and one case of vessel injury in the TLH group. No patient in this group required blood transfusion or conversion to open surgery. There were recurrences in two (4.7%) patients in the TLH group (i.e., carcinosarcoma and serous adenocarcinoma) and in five (8.6%) patients in the TAH group. Conclusion: Laparoscopic surgery is safe and feasible for patients with early-stage endometrial cancer. However, patients with carcinosarcoma and other histologic types of endometrioid adenocarcinoma require special attention because of the high risk of recurrence and poor prognosis.

Reduced-port surgery (RPS) is widely used for various abdominal surgeries. In this paper, we review RPS as it applies specifically to the field of obstetrics and gynecology with a view toward its usefulness and future prospects. Due to an advisory that was issued by the U.S. Food and Drug Administration in May 2014 sales of the Johnson & Johnson Morcellex devices were discontinued, as a result a great number of institutions are forced to seek alternative methods of morcellation. Thus, we also approach the question of specimen retrieval during myomectomy. When RPS, including single-port surgery, is performed by a competent surgeon for established indications, it is superior to conventional laparoscopic surgery in cosmetic outcome, and it can also reduce pain and shorten the hospital stay. Although ligature manipulations can be problematic, sealing devices are useful for performing total hysterectomy and adnexectomy without ligature. Furthermore, using a single-port technique when it is possible to extend the umbilical incision, manual tissue morcellation is facilitated.

Uterine compression suturing is a relatively easy and effective way of hemostasis during cesarean section and is becoming widely accepted. However, complications such as necrosis or synechiae have been reported. We firstly report a case of laparoscopic removal of vertical compression sutures and discuss its benefits and improvements to be made. This case report is of a 32-year-old woman with placenta previa who received uterine vertical compression sutures for controlling massive bleeding during cesarean section. Because she complained of unbearable pelvic pain, laparoscopic compression suture removal was performed. Her pain was relieved after the threads were removed, suggesting that the compression sutures were the cause of her pelvic pain due to uterine ischemia. Although the risks of reoperation during the early postpartum period still exist, compression suture thread removal should be considered in cases of suspected uterine ischemia.

Endometrial cancer is common among postmenopausal women and its incidence is increasing in developed countries. Considering that >80% of endometrial cancers are assumed to be estrogen-related, higher estrogen exposure will be relevant to tumorigenesis. Therefore, the roles of estrogen target genes will be important to understand the pathophysiological mechanisms. We previously revealed that estrogen-responsive RING finger protein Efp contributes to breast cancer progression through the protein degradation of cell cycle checkpoint 14-3-3σ. We and others also proposed that Efp has tumor-promoting activities in estrogen receptor (ER)-negative cancer cells. In addition, Efp plays a role in type I interferon production by activating antiviral signaling, which provokes nuclear factor-κB (NF-κB) signaling. In the present study, we investigate whether Efp plays a critical role in endometrial cancer biology. We show that siRNA-mediated Efp knockdown represses the proliferation and migration of endometrial cancer ER-positive Ishikawa and ER-negative HEC-1A cells. Efp knockdown increases 14-3-3σ protein levels and decreases the rates proliferative stage cells. Efp siRNA significantly inhibits the in vivo tumor growth of endometrial cancer cells in both subcutaneous and orthotopic xenograft models. Intriguingly, Efp knockdown represses NF-κB-dependent transactivation and transcription of target genes, such as IL6ST and IL18, in endometrial cancer cells. Overall, Efp would exert a tumor-promoting role through modulating NF-κB pathway and 14-3-3σ protein degradation in endometrial cancer regardless of its estrogen receptor status. Our results indicate that Efp could be a potential diagnostic and therapeutic target for endometrial cancer.