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Background: Recurrent or persistent clear cell carcinoma (CCC) of the ovary is particularly chemotherapy resistant. The purpose of this study was to review our extensive institutional experiences with recurrent or persistent CCC with the aim of finding a more effective chemotherapy regimen. Methods: The medical records of 67 patients treated for CCC of the ovary were retrospectively reviewed to select patients subsequently treated for recurrence or persistence of the disease. Results: The review identified 20 patients treated for recurrent or persistent CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were administered. Gemcitabine monotherapy showed the best response rate [1 partial response (20%) and 2 stable diseases out of 5 patients so treated]. A partial response was observed with a combination of docetaxel plus irinotecan in 1 of 11 patients (9%). Stable disease was observed in 1 of 9 cases on a paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet. The median overall survival time was 8 months (range, 2-52). One group of patients who received gemcitabine therapy showed significantly better survival ( n = 5, median 18 months) compared with a group who did not ( n = 15, median 7 months) ( P = 0.0108, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that gemcitabine administration was a significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727-115.2255, P = 0.02). Conclusion: Although most chemotherapeutic regimens for recurrent or persistent CCC have little or no effect, gemcitabine showed modest activity and is the most effective agent we have tested to date. [ABSTRACT FROM AUTHOR]

A primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare lesion. To date, only 49 cases have been reported. The presence of mural nodules in a PRMC may indicate a worse prognosis. We report the case of a 40-year-old Japanese woman with a PRMC with mural nodules. Microscopic examination revealed that the stromal cells of the nodules were spindle-shaped and varied in size. The nodules were immunoreactive for vimentin but negative for cytokeratin and EMA, and the nuclei of the stromal cells were pleomorphic and strongly Ki-67 immunoreactive. The nodules were diagnosed as true sarcoma. To the best of our knowledge, this is 11th published case report of a PRMC with mural nodules. [ABSTRACT FROM AUTHOR]

We investigated the prognostic significance of multiple pelvic node metastases in cervical cancer patients who were treated with radical hysterectomy plus adjuvant chemoradiotherapy.We retrospectively reviewed the medical records of 311 patients with International Federation of Gynecology and Obstetrics stage IB1-IIB cervical cancer who had been treated with radical hysterectomy plus adjuvant radiotherapy (RT) between January 1998 and December 2008. Of these, 119 received adjuvant RT and 192 received adjuvant concurrent chemoradiotherapy (CCRT) postoperatively. Multivariate analysis for progression-free survival (PFS) was performed using the Cox proportional hazards regression model to investigate the prognostic significance of pelvic node metastases in the 2 treatment groups. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test.Multivariate analysis demonstrated pelvic node metastasis to be an independent prognostic factor for shorter PFS in both treatment groups. When the node-positive patients were analyzed according to the number of positive pelvic nodes, we found that the patients with multiple pelvic node metastases (≥3) displayed significantly shorter PFS than those with 1 or 2 pelvic node metastases in the RT group. In contrast, in the CCRT group, the PFS of the patients with multiple pelvic node metastases (≥3) was similar to that observed of the patients with 1 or 2 pelvic node metastases.The presence of multiple pelvic node metastases was not an independent predictor of shorter PFS in the CCRT group. [ABSTRACT FROM AUTHOR]

The median eminence (ME) anatomically consists of external (eME) and internal (iME) layers. The hypothalamic neurosecretory cells terminate their axons in the eME and secrete their neurohormones regulating anterior pituitary hormone secretion involved in stress responses into the portal vein located in the eME. Magnocellular neurosecretory cells (MNCs) which produce arginine vasopressin (AVP) and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON) terminate their axons in the posterior pituitary gland (PP) through the iME. Here, we provide the first evidence that oestrogen modulates the dynamic changes in AVP levels in the eME axon terminals in female rats, using AVP-eGFP and AVP-DREADDs transgenic rats. Strong AVP-eGFP fluorescence in the eME was observed at all oestrus cycle stages in adult female rats but not in male transgenic rats. AVP-eGFP fluorescence in the eME was depleted after bilateral ovariectomy but re-appeared with high-dose 17β-oestradiol. AVP-eGFP fluorescence in the MNCs and PP did not change significantly in most treatments. Peripheral clozapine-N-oxide administration induced AVP-DREADDs neurone activation, causing a significant increase in plasma corticosterone levels in the transgenic rats. These results suggest that stress-induced activation of the hypothalamic-pituitary-adrenal axis may be caused by oestrogen-dependent upregulation of AVP in the eME of female rats. [ABSTRACT FROM AUTHOR]

• In total, 147 cases (72 articles) reporting the clinical course of uterine tumours resembling ovarian sex cord tumours (UTROSCTs) were examined. These tumours are extremely rare. • No significant difference in 10-year disease-free survival was found between patients who underwent hysterectomy and patients who underwent mass resection. • Mass resection is an acceptable treatment option in patients aged < 40 years who wish to preserve their childbearing potential. • It is recommended that women who wish to achieve pregnancy should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years based on the low risk of recurrence or metastasis. Uterine tumours resembling ovarian sex cord tumours (UTROSCTs) are extremely rare. To date, most patients with UTROSCTs have undergone hysterectomy and had a benign clinical course. Fertility-preserving surgery should be considered because some patients with UTROSCTs are aged < 40 years. This paper reviews the treatment and prognosis for patients with UTROSCTs, with a focus on fertility. PubMed, MEDLINE and Scopus were searched systematically for case reports and case series of UTROSCTs published in English from inception to December 2022, and initial treatment and recurrence rates were compared. The following data were extracted: age; symptoms; initial therapy; metastasis at diagnosis; disease-free survival (DFS); and recurrence. In total, 147 patients (72 studies) reporting the clinical course of UTROSCTs were analysed. The median age at diagnosis was 50 years, and 28 (19.0 %) patients were aged < 40 years. Most patients (n = 125, 85.0 %) underwent hysterectomy as the initial surgery, with a recurrence rate of 17.6 % (n = 22). The recurrence rate was 30 % (n = 6) in patients who underwent mass resection (n = 20). Among the 15 patients who underwent mass resection aged < 40 years, seven went on to achieve pregnancy (46.7 %) and six had successful deliveries (40.0 %). No significant differences in 5- and 10-year DFS were found between the hysterectomy and mass resection groups (p = 0.123 and 0.0612, respectively). Bilateral salpingo-oophorectomy in addition to hysterectomy was not significantly associated with 10-year DFS (p = 0.548). While total hysterectomy is the recommended treatment for UTROSCTs based on recurrence rates, mass resection is an acceptable treatment option for patients who wish to retain their childbearing potential. It is recommended that these women should plan for pregnancy and delivery as soon as possible after mass resection, and should undergo hysterectomy within 5 years. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Syphilis infections discovered late in pregnancy, as in this case, may not be treated long enough for delivery. The Japanese guidelines should be revised because they do not describe the mode of delivery for pregnant women infected with syphilis. [ABSTRACT FROM AUTHOR]

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of newly diagnosed gynecological cancers has not been extensively investigated in Japan. This study determined the impact of COVID-19 on the incidence of gynecological cancer. Methods: Using the Japanese Society of Obstetricians and Gynecologic Oncology registry database, the distribution of the number of patients based on clinical staging or tumor-node-metastasis classifications before and during the COVID-19 pandemic was analyzed to compare the trends. The clinical staging classification of cervical cancer in Japan was based on the International Federation of Gynecology and Obstetrics (FIGO) 2008 from 2018 to 2020 and on the FIGO 2018 from 2021. Since FIGO-2018 classified N1 cases as stage IIIC, we focused on T classification without referencing the clinical staging (FIGO staging) of patients with cervical cancer in 2021. Results: The number of patients with endometrial cancer and malignant ovarian tumors of all clinical stages increased uniformly yearly, while that of those with stage III cervical cancer rapidly increased in 2021 owing to the adoption of the revised classification. On comparing cases of cervical cancer in 2020 and 2021, we found that T1 cases decreased and T2 and T3 cases increased in 2021 compared to those in 2020 (p = 0.006). Cervical intraepithelial neoplasia/adenocarcinoma in situ incidence decreased in 2020 compared to that in 2019 but increased again in 2021. The number of patients with cervical cancer decreased in most prefectures in 2020. Conclusion: The incidence of locally advanced cervical cancer increased during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The article "Occupational exposure of pregnant women to refined oil and infant wheezing: Japan environment and children's study findings" examines the relationship between prenatal exposure to refined oil (RO) and infant wheezing. The study, based on data from the Japan Environment and Children's Study (JECS), found that exposure to kerosene, petroleum, gasoline, and benzene during pregnancy was associated with infant wheezing, with stronger associations for more frequent exposure and exposure during the early second trimester. The findings suggest that pregnant women should be cautious about occupational exposure to RO to protect their children's health. Another study investigated the association between RO exposure during pregnancy and the diagnosis of infant asthma. The results showed that exposure to RO, particularly during the early second trimester, increased the risk of infant asthma. The study also found that pregnant women with monthly or weekly RO exposure were more likely to continue smoking after pregnancy, had lower income, and lived in wooden houses with kerosene or charcoal heaters. However, the study acknowledges limitations such as potential inaccuracies in self-reported exposure and asthma diagnosis, and further research is needed to understand the mechanisms behind the association between RO exposure and asthma development in children. Another article discusses the use of a specific medication in the treatment of Rett syndrome, a rare neurological disorder. The study evaluated the effectiveness and safety of the medication in a group of patients with Rett syndrome and found that it had a positive impact on certain symptoms of the disorder. However [Extracted from the article]

Aims: Jarisch–Herxheimer reactions (JHR) is a transient adverse event that occurs during initial antimicrobial treatment for syphilis patients, and is known to develop uterine contractions and fetal distress in pregnant women complicated with syphilis. The aim of this study is to identify risk factors for JHR in patients with syphilis, and to clarify whether pregnancy status is a risk factor for JHR, and to describe the characteristics of pregnant women who develop JHR. Methods: This was a retrospective chart review in a singleton university hospital in Japan. We collected data of syphilis patients who were diagnosed and treated at department of obstetrics and gynecology, dermatology between January 2010 and May 2022. There were no validated diagnostic criteria for JHR, we defined JHR as one or more of the following in addition to raised body temperature (≧38.0°C) within 24 h of initial antibiotic treatment: headache, chills, myalgias, tachycardia (≧110 bpm), new rash. Results: There were 30 syphilis patients. Of whom nine (30%) were pregnant women and all their neonates were not diagnosed with congenital syphilis. Five patients (17%) developed JHR at the time of initial treatment (JHR group, n = 5). There was no difference between JHR group and non‐JHR group (n = 25) in pregnancy status. Secondary syphilis was an only significant risk factor for JHR. Two pregnant women with JHR were both treated for secondary syphilis in the third trimester of pregnancy. Conclusion: Pregnancy status was not a risk factor for JHR in syphilis patients. Further research is needed. [ABSTRACT FROM AUTHOR]

Introduction: In laparoscopic surgery, the cooperation of the first assistant surgeon is essential for the creation and maintenance of an appropriate and safe surgical field. The aim of this study is a validation of the impact of our educational system for first assistant laparoscopic surgeon residency in a single university‐affiliated teaching hospital. Methods: Five residents were recruited for this study. We created a slide‐set as an educational tool using Microsoft's PowerPoint that was in line with our surgical procedure to master the assistant skills of laparoscopic gynecologic surgery. Immediately after surgery, the attending doctor and residents reviewed videos of the first assistant's operative procedures. This study evaluated the effect of our educational checklist against the transition of evaluation scores before and after training in two groups of residents, those with minimal experience (Group 1) or with high experience (Group 2). Results: Before receiving our training tool, there was an expected significant difference in the review scores of the two experience groups (29.1 ± 3.1 vs 48.7 ± 3.9, P =.01). After our modified training, the inexperienced residents of Group 1 received review scores comparable to or higher than those of the experienced residents of Group 2 (81.9 ± 5.9 vs 70.4 ± 7.5, P =.23). As they assisted with more surgeries, the concordance between the resident's self‐assessment and the attending doctor's assessment scores significantly increased (P <.001). Conclusions: Our educational system for first assistant surgeons is effective for new residents, as it proved capable of imparting them with many of the same skill sets as much more experienced attending doctors. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether vascularization index (VI), flow index (FI), and vascularization flow index (VFI) correlate with the pathological structure of the placenta and whether there were any differences in VI, FI, VFI, and placental pathological structure between the normal and preeclampsia (PE) groups. Methods: Fifty‐five pregnant women (normal group, n = 27; PE group, n = 28) underwent VI, FI, and VFI at four locations in the placenta during the second and third trimesters. Two hematoxylin and eosin (HE)‐stained specimens of the postpartum placenta were prepared. We randomly selected two of these locations and used ImageJ, an open‐source image package, to quantify intervillous blood vessels (IBV), intervillous spaces (IS), and intervillous blood vessels + intervillous spaces (IBV + IS) per unit placenta and analyzed their correlation with VI, FI, and VFI. Results: There was no positive correlation between VI, FI, VFI, IBV, IS, and IBV + IS. There were no significant differences in VI, FI, and VFI between the normal and PE groups; however, there were significant differences in IBV, IS, and IBV + IS in the PE group compared to those in the normal group. Conclusions: Placental hemodynamics measured by VI, FI, and VFI were not positively correlated with placental morphology in the third trimester. There were no differences in the VI, FI, and VFI in the third trimester between the normal and PE groups, suggesting that these may reflect placental circulatory insufficiency. [ABSTRACT FROM AUTHOR]

Bisphenol F diglycidyl ether (BFDGE) is widely used in the synthesis process of plastic products. While exposure to bisphenol A diglycidyl ether (BADGE), which has a similar structure to BFDGE and which is used for the same purpose, has been reported to cause health risks, there is still little information on BFDGE. Because it is estimated that the industrial workers are exposed to large amounts of BFDGE, the health risks associated with BFDGE exposure need to be clarified. We investigated the toxicity of cutaneous exposure to BFDGE using an in vitro evaluation system and a mouse exposure model. The tumorigenic potential of BFDGE was confirmed by the Bhas 42 cell transformation assay, which showed that BFDGE has both promoter and initiator activity, in vitro. A single dermal application of BFDGE was associated with minor contact hypersensitivity symptoms. In contrast, repeated dermal exposure to BFDGE for 2 weeks induced persistent acute inflammation with features similar to inflammation in human psoriasis. This is the first report evaluating the toxicity of BFDGE in animals, and we showed that BFDGE carries a health risk of inducing skin dermatitis similar to that in human psoriasis in an exposure period‐dependent manner. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to clarify the impact of coronavirus disease 2019 on gynecology practice in Japan, in particular, on surgeries for benign gynecological diseases. Methods: An online questionnaire was distributed to 966 facilities in Japan, including core facilities, facilities participating in perinatal and gynecologic oncology registries, and facilities certified for training by the Japanese Society of Obstetrics and Gynecology Endoscopy. The number of surgeries performed was compared between 2019 and 2020, when the novel coronavirus disease was prevalent. Results: Five hundred and eighty (58.2%) facilities responded. The total number of surgeries decreased from 129 648 in 2019 to 118 565 in 2020, by 8.5%, for all surgical procedures. However, there was a clear increase in the number of robotic surgeries performed in 2020 compared to that in 2019 for all populations. The number of total hysterectomies decreased markedly from 15 385 in 2019 to 12 531 in 2020, a fall of 10.1%. Conclusions: The number of surgeries for benign gynecological diseases decreased by 8.5% in 2020 compared to that in 2019. This value is among the lowest in the world. [ABSTRACT FROM AUTHOR]

Background: Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin'yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety.Methods: In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as < 11.0 g/dL Hemoglobin [Hb]) were randomly assigned (1:1) into the iron supplementation and NYT groups. Patients of the iron supplementation group and the NYT group received 100 mg/day iron supplementation with and without NYT (7.5 g/day) for at least 10 days before surgery. The primary endpoint was improvement in Hb levels before and after treatment, and Cancer Fatigue Scale (CFS) and Visual Analogue Scale for Anxiety (VAS-A) scores between groups. Statistical analyses were performed with Wilcoxon signed rank test, Wilcoxon rank sum test, and Fisher's exact test as appropriate.Results: Forty patients were enrolled of whom 30 patients were finally analyzed after allocating 15 to each group. There was no difference in the characteristics between both groups. Hb significantly increased in both groups (iron supplementation group, 9.9 ± 0.8 g/dL vs. 11.9 ± 1.6 g/dL; NYT group, 9.8 ± 1.0 g/dL vs. 12.0 ± 1.0 g/dL); the difference in the elevations in Hb between both groups was statistically insignificant (P = 0.72). Contrarily, CFS (17.9 ± 10.2 vs. 8.1 ± 5.2) and VAS-A (56 mm (50-70) vs. 23 mm (6-48)) scores were significantly decreased only in the NYT group and these changes were greater in the NYT group (∆CFS, P = 0.015; ∆VAS-A, P = 0.014). Liver dysfunction occurred in one patient of the NYT group.Conclusions: For treating preoperative anemia in women with gynecological conditions, NYT administration along with iron supplementation safely and efficiently improved the preoperative fatigue and anxiety in addition to the recovery from anemia.Trial Registration: jRCT1051190012 (28/April/2019, retrospectively registered). [ABSTRACT FROM AUTHOR]

We experienced a case of preeclampsia in which massive ascites became apparent in the postpartum period. The patient had isolated proteinuria without hypertension before delivery. The infant had fatal growth restriction and neonatal distress. Massive ascites and isolated proteinuria are important symptoms for predicting the aggravation of PE. [ABSTRACT FROM AUTHOR]

The impact of parent-childbearing age on child development at 36 months of age is controversial. We used data from a large cohort study with multiple imputation and mediation analyses of variables. A total of 72,606 parent–child pairs from the Japan Environment and Children's Study were included in the study. Parents' ages were categorized into five groups. We used five domains of the Japanese translation of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3). Scores below the cutoff value at 36 months were defined as developmental delays in each domain. We used three logistic analysis models. In Model 3, we analyzed maternal and paternal age using other variables and covariates. The outcome was a developmental delay in the five domains of J-ASQ-3. In Model 3, ORs for the developmental delay scores regarding parental age were significantly associated with all five domains of J-ASQ-3. The mediation analysis showed a significant mediation interaction effect for mothers but localized for fathers. Advanced paternal and maternal ages were associated with developmental delay in children. Awareness of the risks of childbearing at an advanced age is crucial. This manuscript used data from a large cohort study with multiple imputation and mediation analyses. With these analyses, we identified the pure effect of advanced parental age on their children's development at 36 months. • Both advanced paternal and maternal ages were associated with developmental delay in children. • The effects of advanced maternal age on child developmental delay are similar to the paternal one. • Awareness of the risk of childbearing at an advanced parental age is crucial. [ABSTRACT FROM AUTHOR]

Lifelong health is dependent on prenatal growth and development, influenced by the placental intrauterine environment. Charged with dual functions––exchange of oxygen and nutrients as well as a barrier against toxins––the placenta itself is susceptible to environmental exposure to heavy metals. To examine the use of placenta weight as a biomarker for heavy metal exposure using a large Japanese cohort of pregnant women. The placenta weight, as a biomarker of exposure to heavy metals (cadmium, lead, and mercury), was investigated using data from the Japan Environment and Children's Study (2011–2014). Selenium and manganese were included as factors directly affecting fetal growth or heavy metal toxicity. Maternal blood samples collected in the second or third trimester were used to measure heavy metal concentrations. The association between maternal blood metal concentrations and placenta weight was explored by applying Z scores and multivariable logistic regression analysis and classifying participants into quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. This study included a total of 73,005 singleton pregnant women who delivered via live births and met the inclusion criteria. The median heavy metal concentrations in the maternal whole blood were 0.662 ng/g cadmium, 5.85 ng/g lead, 3.61 ng/g mercury, 168 ng/g selenium, and 15.3 ng/g manganese. Regression analysis revealed a significant correlation between placenta weight Z scores and maternal blood metal concentrations: cadmium, 0.0660 (standard error = 0.0074, p < 0.001); selenium, −0.3137 (standard error = 0.0276, p < 0.001); and manganese, 0.1483 (standard error = 0.0110, p < 0.001). This study provides a robust examination of the association between heavy metal exposure and placenta weight. Cadmium and manganese showed a positive correlation with significant differences, whereas selenium showed a negative correlation. Essential elements notably affect placenta weight differently. No significant association was noted between lead or mercury and placenta weight. [ABSTRACT FROM AUTHOR]