Language：English   Publishing type：Research paper (scientific journal)  

Tissue factor pathway inhibitor-2 (TFPI2) is a Kunitz-type serine protease inhibitor and an ovarian clear cell carcinoma (CCC) biomarker. TFPI2 is expressed in several cancers and exerts tumor-suppressive effects; however, the role of TFPI2 in the CCC cell phenotype remains unclear. Therefore, in this study, we investigated the function of TFPI2 by establishing a gene knockout (KO) in ES-2 CCC cells and observed the change in phenotypes in vitro and in vivo. TFPI2 KO inhibited ES-2 cell proliferation, increased extracellular matrix protein adhesion, enhanced focal adhesion formation and activated integrin β1 cell surface clustering in vitro, and markedly increased ES-2 tumor growth and dissemination in the peritoneal cavity of a mouse xenograft model. These findings suggest a novel function of TFPI2 expression in suppressing the formation of focal adhesions in CCC cells, potentially by activating integrin β1. This function plays a role in the peritoneal growth characteristics of CCC cells.

DOI： 10.1016/j.bbrc.2024.150890

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Cervical cancer screening rates are low in Japan. Therefore, when a woman is pregnant, this is a good opportunity to visit an obstetrics and gynecology clinic to have cervical cytology. This study aimed to clarify the association between cervical cancer screening and the management of pregnant women's health. METHODS: We prospectively examined the relationships between cervical cytological results during prenatal checkups and the following factors: participant's background, cytological sampling instruments, and awareness of cytological results. RESULTS: Of the 2725 participants, 71 showed abnormal results defined as atypical squamous cells of undetermined significance or higher grade (ASC-US+). ASC-US+ detection rates were higher in smokers, younger participants, those with a low education, those without cancer screening in the past 2 years, and those who received cytology using a spatula or brush. A multivariable logistic regression analysis identified smoking (adjusted odds ratio: 2.99 [95% confidence interval: 1.41-6.33]) and a spatula/brush (adjusted odds ratio: 2.46 [95% confidence interval: 1.09-5.53]) as independent variables associated with detecting ASC-US+. Among the participants, 39.4% (28/71) self-reported "no abnormalities," despite obtaining an ASC-US+ result. CONCLUSIONS: Pre-pregnancy smoking and cytological sampling tools may contribute to detecting ASC-US+. Patients with detected abnormalities need accurate information and reliable follow-up.

DOI： 10.1177/03000605241285548

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1186/s12885-024-12827-0

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Other Link： https://link.springer.com/article/10.1186/s12885-024-12827-0/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The purpose of this study was to examine the trend in human papillomavirus (HPV) vaccination rates in Japan before and after a policy change in 2022, involving resumption of active recommendation and start of catch-up vaccination. METHODS: From 2021 to 2023, a web-based questionnaire survey was administered to newly enrolled female college students in Yokohama, Japan. The questionnaire included items such as age, HPV vaccination status, HPV vaccine awareness, and awareness of catch-up vaccination. We compared knowledge about the HPV vaccine and cervical cancer in 2021 and 2023, before and after resumption of the national vaccination program. RESULTS: The HPV vaccination rates were 5.4% in 2021, 7.5% in 2022, and 35.3% in 2023, with a significant upward trend (p < 0.001). A similar upward trend was observed for HPV vaccine awareness (p < 0.001). Comparing 2022 and 2023 after the start of catch-up vaccination, there was no significant difference in awareness of catch-up vaccination (p = 0.669), but there was a significant increase in awareness of free vaccination tickets (p < 0.001). After resumption of the national vaccination program with adoption of the catch-up vaccination program, there was no difference in knowledge of cervical cancer, but there was a difference in knowledge of the HPV vaccine. CONCLUSIONS: Although the HPV vaccination rate has increased after the policy change, it has not recovered to the level before the suspension of active recommendation. It is important for healthcare providers and school educators to actively communicate the safety and effectiveness of the HPV vaccine.

DOI： 10.1111/jog.16049

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INTRODUCTION: Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS). MATERIALS AND METHODS: Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation. RESULTS: After 24 months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24 months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24 months, TBS remained stable. CONCLUSION: Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.

DOI： 10.1007/s00774-024-01542-2

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Introduction: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery. Case Presentation: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation.We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel. Conclusion: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy.

DOI： 10.1159/000540524

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Publishing type：Research paper (scientific journal)   Publisher：BMJ  

Objective

The association between sarcopenia and prognosis in patients with platinum-resistant recurrent ovarian cancer remains unclear. This study investigated whether sarcopenia is a prognostic factor in patients with platinum-resistant recurrent ovarian cancer.

Methods

A total of 52 patients diagnosed with platinum-resistant recurrent ovarian cancer who had undergone non-platinum chemotherapy at our institution formed our study population. Body composition and clinicopathological data of these patients were collected retrospectively. Abdominal computed tomography (CT) scans obtained at the time of platinum-resistant recurrent ovarian cancer diagnosis were used to measure the cross-sectional area of skeletal muscles at L3 level. These values were corrected for height to calculate the skeletal muscle index, and accordingly sarcopenia was defined. Overall survival was defined as the primary outcome of the study. The impact of sarcopenia on overall survival was assessed using Cox proportional hazards regression models with inverse probability weighting of treatment based on propensity scores and log-rank tests.

Results

The median patient age was 63 years (IQR: 53–71). The most common International Federation of Gynecology and Obstetrics (FIGO) 2018 stage was stage III (50%) and the most common histology was serous or adenocarcinoma (67.3%). The optimal cut-off value of skeletal muscle index was 35.6 cm²/m², which was calculated using the data of 21 patients with sarcopenia and 31 without sarcopenia. Sarcopenia was significantly associated with shorter overall survival (HR 1.93; 95% CI 1.06–3.49; p=0.03). Subgroup analysis based on patient attributes and prognostic factors suggested a consistent prognostic impact of sarcopenia. Sarcopenia was identified as a significant risk factor, particularly in patients who had higher CA125 levels (HR, 2.47; 95% CI, 1.07 to 5.69; p=0.034) and a higher neutrophil-to-lymphocyte ratio (HR, 2.92; 95% CI, 1.02 to 8.31; p=0.045).

Conclusion

Sarcopenia significantly shortened the overall survival of patients with platinum-resistant recurrent ovarian cancer.

DOI： 10.1136/ijgc-2024-005323

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OBJECTIVE: This study aimed to clarify the maternal and neonatal outcomes based on the presence or absence of a Couvelaire uterus with placental abruption. METHODS: This single-center retrospective study was conducted at a tertiary perinatal center in Japan, including patients diagnosed with acute placental abruption who delivered live births via cesarean section between 2016 and 2023. Patients were divided into two groups based on the presence or absence of a Couvelaire uterus during surgery: the Couvelaire and normal uterus groups. Maternal and neonatal outcomes were assessed. RESULTS: This study included 76 patients: 24 in the Couvelaire group and 52 in the normal uterus group. No patients underwent hysterectomies. The Couvelaire group had significantly higher intraoperative blood loss (median 1152 vs 948 g, P = 0.010), blood transfusion rates (58% vs 31%, P = 0.022), fibrinogen administration rates (38% vs 13%, P = 0.038), intensive care unit/high care unit admission rates (29% vs 7.7%, P = 0.013), and disseminated intravascular coagulation complication rates (25% vs 7.7%, P = 0.038). There were no differences in birth weight, gestational age (median 2387 vs 2065 g, P = 0.082), Apgar score <4 at 5 min (4.2% vs 3.9%, P = 0.95), umbilical artery blood pH <7.1 (25% vs 22%, P = 0.82), and neonatal death (4.2% vs 1.9%, P = 0.57). CONCLUSION: A Couvelaire uterus indicated adverse maternal outcomes but not neonatal ones. Its presence necessitates preparation for blood transfusions and/or intensive patient follow-up.

DOI： 10.1002/ijgo.15821

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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AIM: In 2017, the American College of Cardiology (ACC) re-defined hypertension (HT) as follows: elevated blood pressure (EBP), systolic blood pressure (SBP) 120-129 mmHg and diastolic blood pressure (DBP) <80 mmHg; stage 1 HT, SBP 130-139 mmHg or DBP 80-89 mmHg; and stage 2 HT: SBP ≥140 mmHg or DBP ≥90 mmHg. It is well known that women with stage 2 HT are at higher risk of preeclampsia and have poorer pregnancy and delivery outcomes. While there are few reports on the risk in women with EBP and stage 1 HT, and none from Japan. This study aimed to determine whether women in Japan with EBP and stage 1 HT are at risk of preeclampsia. METHODS: In this single-center retrospective study conducted in Japan, subjects were classified into stage 2 HT, stage 1 HT, EBP, and normal groups based on blood pressure measurements at the time of the first visit before 20 weeks of gestation. Women with a diagnosis of hypertension made before pregnancy were classified into the stage 2 HT group. We compared pregnancy and delivery outcomes, such as preeclampsia, between groups. RESULTS: A total of 5129 cases (normal, n = 4283; EBP, n = 427; stage 1 HT, n = 303; stage 2 HT, n = 116) were included. Preeclampsia incidence rates were 2.7%, 5.6%, 10.6%, and 21.6%, respectively. The adjusted OR (95% CI) for preeclampsia incidence were 2.90 (1.81-4.66), 5.90 (3.87-9.20), and 13.80 (7.97-24.0), respectively. CONCLUSIONS: Women with EBP and stage 1 HT are at high risk of preeclampsia, similar to those with stage 2 HT.

DOI： 10.1111/jog.15852

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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AIM: Cervical ripening is commonly performed before oxytocin administration during labor induction in pregnant women with an unfavorable cervix. In Japan, a controlled-release Dinoprostone vaginal insert (CR-DVI) was approved in 2020. Although many studies have compared the mechanical methods of ripening and prostaglandins, few have examined the impact of additional options for labor induction. This study aimed to assess the impact of CR-DVI as an additional option for labor induction in women with an unfavorable cervix. METHODS: In this single-center retrospective study conducted in Japan, 265 participants were divided into two groups: before (January 2018 to May 2020) and after (June 2020 to November 2022) CR-DVI introduction. Before CR-DVI was introduced, hygroscopic dilators were used for all cases instead. On the other hand, after the introduction of CR-DVI, the first choice for cervical ripening was CR-DVI. The CR-DVI was retained vaginally for up to 12 hours after insertion. However, if hyper-stimulation or non-reassuring fetal status was suspected, or if a new membrane rupture occurred, it was removed immediately according to the removal criteria. Oxytocin infusions were used during both periods if needed. We compared delivery and neonatal outcomes between the groups. RESULTS: The 265 participants were divided into two groups: before (n=116) and after (n=149) CR-DVI introduction. There were no significant differences in maternal characteristics except for the primiparous proportion. CR-DVI was used in 93% of cases after introduction. Hygroscopic dilators also continued to be used; however, their use decreased to about 34%. The vaginal delivery rate was significantly higher after the introduction of CR-DVI than before its introduction (50.9% vs. 66.4%; p=0.01). Multivariable analysis revealed a significantly higher rate of vaginal delivery after CR-DVI introduction. Of the 149 cases in which a CR-DVI was used, 111 (79.9%) were removed before 12 hours. There were no significant differences in neonatal outcomes. CONCLUSION: The rate of vaginal delivery was higher after CR-DVI introduction than before its introduction, and adverse pregnancy outcomes did not increase. Therefore, introducing CR-DVI as an option for labor induction may increase the probability of vaginal delivery. Safety can also be ensured by adhering to the removal criteria.

DOI： 10.7759/cureus.53180

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery. CASE PRESENTATION: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation. We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel. CONCLUSION: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy.

DOI： 10.1159/000540524

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Language：English   Publishing type：Research paper (scientific journal)  

Previous studies have shown that interpregnancy weight fluctuations impact perinatal outcomes. In order to examine this in Japanese women, we analyzed the data of 2,861 women in their first and second pregnancies who delivered singletons between 2000 and 2022. We compared the second pregnancy perinatal outcomes of women whose interpregnancy body mass index (BMI) change was -1 to 1 unit with those of women whose BMI change was < -1 or ≥ 1 unit. An interpregnancy BMI change ≥ 1 unit was associated with an increased risk of developing gestational diabetes mellitus (adjusted odds ratio [aOR], 1.51; 95% confidence interval [CI], 1.18-1.95) and delivering a large for gestational age neonate (aOR, 1.67; 95% CI, 1.15-2.42) but a decreased risk of preterm birth (aOR, 0.66; 95% CI, 0.46-0.95). An interpregnancy BMI change < -1 unit was associated with a decreased risk of developing gestational diabetes mellitus (aOR, 0.51; 95% CI, 0.31-0.85). In a subgroup analysis of three groups divided according to prepregnancy BMI, interpregnancy BMI changes ≥ 1 unit in women with a BMI of < 18.5 kg/m2 before their first pregnancy were associated with a remarkable risk reduction of developing preterm birth (aOR, 0.30; 95% CI, 0.11-0.81). Interpregnancy BMI changes < -1 unit in women with a BMI of ≥ 25 kg/m2 before their first pregnancy were associated with a remarkable risk reduction of developing gestational diabetes mellitus (aOR, 0.33; 95% CI, 0.12-0.88). Weight gain during interpregnancy period was related to an increased risk of gestational diabetes mellitus and delivery of a large-for-gestational-age neonate, whereas weight loss was related to a decreased risk of developing gestational diabetes mellitus. These results indicate the importance of interpregnancy weight control as part of preconception care; therefore, women considering additional pregnancies should be educated on the importance of maintaining a healthy weight.

DOI： 10.1371/journal.pone.0299794

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy  

DOI： 10.5180/jsgoe.39.2_56

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Language：English  

Vitamin K deficiency can cause coagulopathy; therefore, supplementation is recommended to prevent intracranial hemorrhage in newborns. Some reports have shown that maternal vitamin K deficiency is associated with intracranial hemorrhage in the fetus. However, no clear guidelines exist for the diagnosis and treatment of maternal vitamin K deficiency to prevent fetal intracranial hemorrhage. We report a case of intrauterine fetal death due to intracranial hemorrhage associated with maternal vitamin K deficiency resulting from hyperemesis gravidarum. In this case, maternal protein induced by vitamin K absence II (PIVKA-II) was high at the time of intrauterine fetal death. Therefore, measuring maternal PIVKA-II levels in high-risk cases may help determine the timing of therapeutic interventions for vitamin K deficiency during pregnancy.

DOI： 10.1016/j.crwh.2023.e00566

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Language：English   Publishing type：Research paper (scientific journal)  

In Japan, rubella antibodies are measured in all pregnant women in order to detect subclinical infection. The study aimed to assess the validity of measuring rubella antibodies to detect subclinical rubella among pregnant women in Japan. This single-center, retrospective study measured rubella hemagglutination inhibition (HI) titers and rubella-specific IgM antibody index values (IgM-values). IgM-values were measured by enzyme immunoassay, and IgM-values > 1.2 were considered positive. Of 14965 pregnant women who were included, 186 (1.2%) were IgM-positive. Only one patient was clinically diagnosed with rubella (HI titer, 1:2048; IgM-value, 10) and developed a fever and skin rash. She decided to terminate her pregnancy without a repeat blood test. Of the IgM-positive patients, 136 (73.1%) had rubella HI titers of < 1:256. The correlation coefficient of rubella HI titers and IgM-values was weakly positive (0.2527; p < 0.0001). This study showed that the single combination of rubella HI and rubella-specific IgM measurements alone did not detect subclinical rubella. Creating awareness among pregnant women by informing them that almost all rubella-specific IgM-positive individuals without symptoms are not acutely infected could decrease their anxiety and prevent unnecessary termination of pregnancies.

DOI： 10.7883/yoken.JJID.2023.222

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/rheumatology/kead608

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Biologically compatible vascular grafts are urgently required. The scaffoldless multi-layered vascular wall is considered to offer theoretical advantages, such as facilitating cells to form cell-cell and cell-matrix junctions and natural extracellular matrix networks. Simple methods are desired for fabricating physiological scaffoldless tissue-engineered vascular grafts. Here, we showed that periodic hydrostatic pressurization under hypoxia (HP/HYP) facilitated the fabrication of multi-layered tunica media entirely from human vascular smooth muscle cells. Compared with normoxic atmospheric pressure, HP/HYP increased expression of N-myc downstream-regulated 1 (NDRG1) and the collagen-cross-linking enzyme lysyl oxidase in human umbilical artery smooth muscle cells. HP/HYP increased N-cadherin-mediated cell-cell adhesion via NDRG1, cell-matrix interaction (i.e., clustering of integrin α5β1 and fibronectin), and collagen fibrils. We then fabricated vascular grafts using HP/HYP during repeated cell seeding and obtained 10-layered smooth muscle grafts with tensile rupture strength of 0.218-0.396 MPa within 5 weeks. Implanted grafts into the rat aorta were endothelialized after 1 week and patent after 5 months, at which time most implanted cells had been replaced by recipient-derived cells. These results suggest that HP/HYP enables fabrication of scaffoldless human vascular mimetics that have a spatial arrangement of cells and matrices, providing potential clinical applications for cardiovascular diseases. STATEMENT OF SIGNIFICANCE: Tissue-engineered vascular grafts (TEVGs) are theoretically more biocompatible than prosthetic materials in terms of mechanical properties and recipient cell-mediated tissue reconstruction. Although some promising results have been shown, TEVG fabrication processes are complex, and the ideal method is still desired. We focused on the environment in which the vessels develop in utero and found that mechanical loading combined with hypoxia facilitated formation of cell-cell and cell-matrix junctions and natural extracellular matrix networks in vitro, which resulted in the fabrication of multi-layered tunica media entirely from human umbilical artery smooth muscle cells. These scaffoldless TEVGs, produced using a simple process, were implantable and have potential clinical applications for cardiovascular diseases.

DOI： 10.1016/j.actbio.2023.09.041

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)日本臨床化学会  

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OBJECTIVE: To examine the prevalence trends of minimally invasive hysterectomy for benign indications in Japan and investigate regional disparities. STUDY DESIGN: A retrospective cohort and ecological study using "The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data". SETTING: Nationwide Japan. PATIENTS: Individuals who underwent hysterectomy for benign indications from 2014 to 2020. INTERVENTIONS: Trend analysis of minimally invasive surgery (MIS) rates through laparoscopic hysterectomies (LH) and robotic-assisted laparoscopic hysterectomies (RA-LH) at the national and prefecture levels. Examination of regional factors contributing to the disparity in MIS implementation rates by second medical service area (SMSA). RESULTS: The number of LH has increased from 16,016 in 2014 to 27,755 in 2020. The nationwide MIS hysterectomy rate increased from 29% in 2014 to 55% in 2020 (p less than 0.001). More than 50% of hysterectomies have been performed as MIS since 2019. There was an increasing trend in MIS rates in all age groups. All prefectures except one showed a significant upward trend (p less than 0.05) in the MIS rates, but MIS rates varied widely (23-84%). In a multivariable model, the MIS was more likely to be performed in the SMSAs in western Japan (p = 0.011), in the SMSAs where the number of laparoscopy-qualified gynecologists is 5-10 (p = 0.013), and 11 or higher (p less than 0.001). CONCLUSIONS: This study reveals a shift towards minimally invasive surgery (MIS) in total hysterectomy procedures in Japan. However, significant disparities in the prevalence of MIS hysterectomy exist, potentially influenced by the number of laparoscopy-qualified gynecologists.

DOI： 10.1016/j.ejogrb.2023.08.388

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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PURPOSE: In Japan, Japan's Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the "suspension of recommendation" ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination.  METHODS: In February of 2022, we conducted an internet survey targeted women who were born in 1997-2004 but who had not yet been HPV vaccinated. RESULTS: We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p < 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p < 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p < 0.05). CONCLUSION: Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the "vaccinated generation" and the "vaccine-suspended generation".

DOI： 10.1007/s10147-023-02411-0

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BACKGROUND: Antibody-drug conjugates (ADCs) are attractive targeted agents in anticancer treatment with their unique mechanism of action and reduced toxicity. Little is known about the spectrum of adverse events associated with ADCs, despite tens of clinical trials. METHODS: A systematic review of randomized controlled trials evaluating ADCs efficacy in anticancer treatment was conducted. PubMed, EMBASE, and ClinicalTrial.gov were searched for relevant studies. Meta-analyses assessed the odds ratios (ORs) of 12 treatment-related symptoms and toxicities in ADC-treated patients compared to those receiving other anticancer agents without ADCs. All-grade and high-grade (grade 3 or higher) toxicities were examined. RESULTS: 20 studies involving 10,075 patients were included. Compared with control groups, ADCs were associated with a higher risk for all-grade fatigue (OR, 1.25; 95% CI, 1.08-1.45), anorexia (OR, 1.36 [1.09-1.69]), nausea (OR, 1.46 [1.09-1.97]) and sensory neuropathy (OR, 2.18 [1.27-3.76]) as treatment-related symptoms. Patients treated with ADCs had a significantly lower risk of all-grade febrile neutropenia (OR, 0.46 [0.22-0.96]). Conversely, they had a higher risk of thrombocytopenia (OR, 2.07 [1.00-4.31]), increased alanine aminotransferase (OR, 2.51 [1.84-3.40]), and increased aspartate aminotransferase (OR, 2.83 [2.04-3.93]). Subgroup analysis showed a similar toxicity profile when comparing the solid tumors vs hematologic malignancy groups and the ADC vs ADC plus chemotherapy groups, except for some neurologic and hematologic adverse events. CONCLUSIONS: This comprehensive profile of adverse events associated with ADC-based treatment shows an increase in various types of all-grade treatment-related symptoms and adverse events although no increase in high-grade adverse events was seen.

DOI： 10.1093/jncics/pkad069

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

特発性血小板減少性紫斑病合併妊娠は、妊娠中及び分娩時の出血管理目的に治療を要することがある。今回内科的治療により効果が乏しく、妊娠中に脾臓摘出術を行った症例を経験したので報告する。症例は27歳、1妊0産、既往歴はない。妊娠初期検査において血小板数1万/μL未満と減少を認め、特発性血小板減少性紫斑病の診断に至った。免疫グロブリン大量療法には反応するも、プレドニゾロンでは血小板数を維持できず、妊娠17週に腹腔鏡下脾臓摘出術を施行した。脾臓摘出後も血小板数は上昇せず、シクロスポリンを追加し、免疫グロブリン大量療法を複数回投与することで分娩までの血小板数を維持した。妊娠37週0日に帝王切開により分娩した。出産後も治療を継続した。児も血小板減少を認め免疫グロブリン投与を要した。特発性血小板減少性紫斑病合併妊娠において安全性や有用性の確立された治療法は少ない。脾臓摘出術も考慮される治療選択肢の一つに挙がるが、その施行時期や適応については慎重に決めるべきである。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The relationship between familial Mediterranean fever (FMF) and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association. METHODS: Electronic databases-the PubMed, Web of Science, Cochrane, and Embase-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomised clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. Odds ratios (OR) and 95% confidence intervals (CI) summarised the results using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827. RESULTS: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1,242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%). CONCLUSIONS: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted.

DOI： 10.1093/rheumatology/kead417

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Introduction: Several healthy euploid births have been reported following the transfer of mosaic embryos, including both euploid and aneuploid blastomeres. This has been attributed to a reduced number of aneuploid cells, as previously reported in mice, but remains poorly explored in humans. We hypothesized that mitochondrial function, one of the most critical factors for embryonic development, can influence human post-implantation embryonic development, including a decrease of aneuploid cells in mosaic embryos.

Methods: To clarify the role of mitochondrial function, we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development (n = 27 embryos). Karyotyping, whole mitochondrial DNA (mtDNA) sequencing, and mtDNA copy number assays were performed on all pre- and post-culture samples.

Results: The ratio of euploid embryos was significantly enhanced during in vitro culture, whereas the ratio of mosaic embryos was significantly reduced. Furthermore, post-culture euploid and culturable embryos had significantly few mtDNA mutations, although mtDNA copy numbers did not differ.

Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation, and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy. Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer.

DOI： 10.3389/fcell.2023.1215626

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cancer incidence is expected to increase with population aging, making the availability of places for treating patients with terminal cancer a pressing issue. However, little is known about the actual state of home end-of-life care (HEC) in Japan. OBJECTIVE: The objective of this study was to examine the real-world state of HEC for older adults with cancer. METHODS: The Yokohama Original Medical Database was used to identify the cohort. Data of target patients was extracted based on three criteria: age ≥65 years, malignant neoplasm diagnosis, and having a specific billing code of HEC. Multivariable linear and logistic regression models were used to evaluate the association between age groups and HEC services or outcome indexes. RESULTS: Overall, 1323 people (554 and 769 aged < 80 and ≥ 80 years, respectively; men, 59.2%) had planned to receive HEC. The < 80 years group had more frequent emergent home visits than the ≥ 80-year group (P < 0.001), but the number of monthly home visits was similar between the two groups (P = 0.267). The rate of emergent admission was 5.9% in the ≥ 80-year group, which was higher than that in the < 80-year group (3.1%; P = 0.018). Conversely, the rates of central venous nutrition and opioid use were higher in the < 80-year group than those in the ≥ 80-year group. CONCLUSIONS: This study reported patterns of use of HEC among older adults with cancer in the terminal stage. Our findings may provide the basis for providing HEC for older adults with cancer.

DOI： 10.1002/agm2.12246

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: To verify the effectiveness of intervention in early pregnancy for women with early-onset gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: This study included women with a singleton pregnancy who were diagnosed with early-onset GDM by 20 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) threshold. We retrospectively evaluated the pregnancy outcomes in pregnant women with early-onset GDM. In the treatment from early pregnancy group (n=286), patients were diagnosed with early-onset GDM at the Yokohama City University Medical Center (YCU-MC) in 2015-2017 and were treated for GDM from early pregnancy. Concerning the treatment from mid-pregnancy group (n=248), participants were diagnosed with early-onset GDM at five sites, including the YCU-MC in 2018-2019, and were followed up without treatment until the second 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Treatment for GDM was given only if the GDM pattern was still present in the second OGTT. RESULTS: There were no significant differences in maternal backgrounds, including GDM risk factors and gestational weight gain, between the groups. Among the treatment from mid-pregnancy group, the false-positive early GDM was 124/248 (50%). Regarding pregnancy outcome, the rate of large for gestational age (LGA) was 8.8% in the treatment from early pregnancy group and 10% in the treatment from mid-pregnancy group, with no significant difference, whereas small for gestational age (SGA) was significantly higher in the treatment from early pregnancy group (9.4%) than in the treatment from mid-pregnancy group (4.8%) (p=0.046). There were no significant differences in maternal adverse events and neonatal outcomes between the groups. In a subanalysis limited to body mass index >25 kg/m2, LGA was significantly lower in the treatment from early pregnancy group than in the treatment from mid-pregnancy group. CONCLUSIONS: The strategy for diagnosing GDM by IADPSG thresholds in early pregnancy and providing treatment to all patients from early pregnancy did not improve the pregnancy outcomes, but rather increased the SGA rate.

DOI： 10.1136/bmjdrc-2022-003230

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Language：English  

In a cervico-isthmic pregnancy, the risk of placenta accreta increases with advancing gestational age. Previous reports have detailed cases that required hysterectomy at delivery or artificial abortion at an early gestational age. However, to the best of our knowledge, there have been no previous reports on the management of a cervico-isthmic pregnancy with fetal death during the second trimester. A 33-year-old primigravid woman was diagnosed with a cervico-isthmic pregnancy and fetal death at 15 weeks of gestation. Placenta accreta was suspected; hence, we chose expectant management and to observe the patient for placental tissue regression. After 5 weeks of expectant management, the ultrasonographic findings suggested remission of placenta accreta. Therefore, we performed a cesarean delivery and terminated the pregnancy. All uterine contents were removed, and the uterus was preserved. In cervico-isthmic pregnancy cases with fetal death, as in the current case, the possibility of fertility preservation could be increased by observing for placental tissue regression through expectant management.

DOI： 10.1016/j.crwh.2023.e00501

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.nut.2022.111966

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Pregnant women presumably gather information about the coronavirus disease 2019 (COVID-19) from various sources. However, it is difficult for pregnant women who are not medical professionals to source the appropriate information because of the infodemic related to the COVID-19 pandemic. Therefore, the objective of our study was to investigate how pregnant women gathered information about COVID-19 and COVID-19 vaccination. To address this issue, we conducted an online questionnaire survey between 5 October and 22 November 2021, which was approved by the Ethics Committee of Nihon University School of Medicine. We received 4962 responses after excluding 1179 insufficient answers. Our study found that age, occupation, and infection-risk anxiety influenced the selection of media for obtaining information. Pregnant women who were older, medical professionals, public servants, or educators tended to rely on specialized medical websites, whereas housewives tended to use mass media, social media, and sources with uncertain scientific evidence. Additionally, the number of weeks of gestation and the method of conception (natural or assisted reproductive conception) affected the selection of media. The accessibility of COVID-19 information for pregnant women was determined by their social background and pregnancy status. We need to continue making efforts to ensure that appropriate information is readily available to pregnant women and their families.

DOI： 10.3390/vaccines11040805

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Language：English   Publishing type：Research paper (scientific journal)  

Cancer tissues generally have molecular oxygen and serum component deficiencies because of poor vascularization. Recently, we revealed that ICAM1 is strongly activated via lipophagy in ovarian clear cell carcinoma (CCC) cells in response to starvation of long-chain fatty acids and oxygen and confers resistance to apoptosis caused by these harsh conditions. CD69 is a glycoprotein that is synthesized in immune cells and is associated with their activation via cellular signaling pathways. However, the expression and function of CD69 in non-hematological cells is unclear. Here, we report that CD69 is induced in CCC cells as in ICAM1. Mass spectrometry analysis of phosphorylated peptides followed by pathway analysis revealed that CD69 augments CCC cell binding to fibronectin (FN) in association with the phosphorylation of multiple cellular signaling molecules including the focal adhesion pathway. Furthermore, CD69 synthesized in CCC cells could facilitate cell survival because the CD69-FN axis can induce epithelial-mesenchymal transition. Experiments with surgically removed tumor samples revealed that CD69 is predominantly expressed in CCC tumor cells compared with other histological subtypes of epithelial ovarian cancer. Overall, our data suggest that cancer cell-derived CD69 can contribute to CCC progression through FN.

DOI： 10.1111/cas.15774

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

DOI： 10.1007/s10995-023-03597-5

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy  

DOI： 10.5180/jsgoe.39.1_31

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

症例は47歳、2妊2産で、月経周期に一致した臍部の疼痛を主訴とした。腹部MRI検査では臍部の病変は筋膜に達し、生検で子宮内膜症と診断した。産婦人科で筋膜切除を含めた臍切除を行った後、鏡視下に骨盤内の子宮内膜症病変の有無を確認し、閉腹後に形成外科が臍形成を行う方針とした。産婦人科医が20mm大の弾性硬、境界明瞭な臍部腫瘤を電気メスにて切除し、12mmのバルーントロッカーを用いて臍切除部より気腹したが、気腹維持が困難であったためラップディスクミニを使用した。腹腔内観察で右卵巣の1/3が骨盤壁と強固に癒着しているのを認め、子宮内膜症病変と判断して右付属器切除を施行した。臍部の筋膜を縫合閉創した後に形成外科医が一期的に臍形成術を施行した。臍部腫瘤および右付属器の病理組織診断は子宮内膜症であった。術後3日目に退院し、14日目よりジエノゲスト内服を開始した。術後12ヵ月経過して臍部疼痛の再燃は認めていない。

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy  

DOI： 10.5180/jsgoe.39.1_41

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Language：Japanese   Publisher：横浜市立大学医学会  

背景:近年,遺伝性乳がん卵巣がん症候群(HBOC)を含めた各種遺伝学的検査の保険診療が拡充している中で,2020年4月から当院に遺伝子診療科が新設された.これまで各診療科で対応していたBRCA遺伝学的検査に対し,2021年4月から検査前から遺伝カウセリングを行う体制とした.遺伝子診療科開設前後のBRCA遺伝学的検査実施体制についてまとめ,問題点や今後の課題について考察した.対象と方法:2018年8月～2022年2月に当院でBRCA遺伝学的検査実施検討症例について,診療録をもとに後方視的に検討した.結果:BRCA遺伝学的検査実施症例は173例,BRCA変異陽性は18例(10.4%),陰性153例(88.4%),variant of uncertain significance(VUS) 2例(1.2%)であった.遺伝子診療科開設後は全例自施設で検査後カウンセリングが実施できていたが,サーベイランスに結びついている症例は5例,家系員の検査実施は2例のみであった.また多遺伝子パネル検査を推奨する症例25例(80.6%)にも,適切な遺伝カウンセリングが実施できていた.結語:検査前遺伝カウンセリングは重要であるが,HBOCと診断された家系員の検査の受検率の向上や,他の遺伝性腫瘍が疑われる患者への介入,遺伝カウンセリングの継続のタイミングなど,今後も検討が必要である.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01499&link_issn=&doc_id=20230111330001&doc_link_id=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F2600&url=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F2600&type=%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Elucidation of spatial interactions between cancer and host cells is important for the development of new therapies against disseminated cancers. The aim of this study is to establish easy and useful method for elucidating spatial interactions. In this study, we developed a practical spatial analysis method using a gel-based embedding system and applied it to a murine model of cancer dissemination. After euthanization, every abdominal organ enclosed in the peritoneum was extracted en bloc. We injected agarose gel into the peritoneal cavities to preserve the spatial locations of the organs, including their metastatic niches, and then produced specimens when the gel had solidified. Preservation of the original spatial localization was confirmed by correlating magnetic resonance imaging results with the sectioned specimens. We examined the effects of spatial localization on cancer hypoxia using immunohistochemical hypoxia markers. Finally, we identified the mRNA expression of the specimens and demonstrated the applicability of spatial genetic analysis. In conclusion, we established a practical method for the in vivo investigation of spatial location-specific biological mechanisms in disseminated cancers. Our method can elucidate dissemination mechanisms, find therapeutic targets, and evaluate cancer therapeutic effects.

DOI： 10.1038/s41598-022-24827-w

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Other Link： https://www.nature.com/articles/s41598-022-24827-w

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

Placental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases.

Methods

We used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups–blood transfusion and non-transfusion–to compare the maternal characteristics and pregnancy outcomes.

Results

In patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group.

Conclusions

In PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.

DOI： 10.1186/s12884-022-05187-9

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Other Link： https://link.springer.com/article/10.1186/s12884-022-05187-9/fulltext.html

Language：English  

Lobular endocervical glandular hyperplasia (LEGH) is characterized by clinically profuse and watery vaginal discharge. In pregnancy with LEGH, with watery fluid leakage persisting throughout pregnancy, it is often difficult to visually diagnose PROM. Adding to this difficulty, auxiliary diagnostic tests might also show positive results, complicating treatment and management.

DOI： 10.1002/ccr3.6630

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ccr3.6550

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Other Link： https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638085/

Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

Nuchal translucency(NT)肥厚は胎児染色体異常や先天異常と関連し,出生前遺伝学的検査の一つとなっているが,通常の妊婦健診で指摘されることもあり,その情報提供に難渋する症例も少なくない。そこで当院の出生前診断外来を受診した妊婦のうち胎児NT肥厚が認められた児の転機をまとめ,その対応のあり方を考察した。単胎154例のうちNT値は2.5～16mmであった。染色体異常・形態異常のない症例は61.7%,染色体異常は26%,形態異常は7.1%であった。NT3mm未満(43例)では1例を除き,生児を得ていた。またNT肥厚6.5mm以上(26例)では1例であるが染色体異常も形態異常も認めず生児を得ていた。NT肥厚症例に対しては,正しい情報に基づいた出生前遺伝カウンセリングが行われる必要があり,その遺伝カウンセリングは慎重に対応する必要がある。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Gonadotropin-releasing hormone agonists are used to treat premenopausal uterine leiomyomas; however, leiomyoma volume reduction is not always achieved. The reduction rate after this treatment varies for each leiomyoma, even in the same patient. Therefore, an effective method for predicting uterine leiomyoma volume reduction is required to reduce the adverse hypoestrogenic effects and drug-related economic burden related to gonadotropin-releasing hormone agonists. OBJECTIVE: We aimed to determine the predictive utility of MED12 mutations for evaluating the effect of gonadotropin-releasing hormone agonist treatment with respect to reducing uterine leiomyoma volume and to predict the MED12 mutation status based on the findings of magnetic resonance imaging performed before treatment. STUDY DESIGN: MED12 exon 2 mutation and erythropoietin expression in uterine leiomyomas were evaluated in relation to volume reduction, as measured using magnetic resonance imaging. We developed a system for classifying leiomyomas according to T2-weighted magnetic resonance imaging signals to non-invasively predict the presence or absence of MED12 mutations in leiomyomas. Leiomyoma samples (>5 cm) were obtained from 168 patients during surgery (hysterectomy or myomectomy) between 2005 and 2021 at Yokohama City University Hospital. To analyze the rate of leiomyoma volume reduction, 41 patients had been preoperatively administered the gonadotropin-releasing hormone agonist (leuprorelin acetate 3.75 mg, monthly subcutaneous injection) for 3 months; magnetic resonance imaging was performed before and after treatment without contrast material. RESULTS: Compared to leiomyomas expressing wild-type MED12 exon 2, those with MED12 exon 2 mutations were less likely to have reduced volume following treatment with the gonadotropin-releasing hormone agonist (P<.001, Mann-Whitney U test) and displayed lower signal intensity on T2-weighted images. The newly proposed magnetic resonance imaging-based classification system showed that MED12 exon 2 mutations were more frequent in the low-signal group than in the high-signal group, with nearly equal proportions of mutated and wild-type MED12 exon 2 leiomyomas noted in the intermediate group. The low-signal group had significantly lower erythropoietin expression levels than the high-signal group (P<.001, Kruskal-Wallis test with Dunn's post hoc analysis). CONCLUSIONS: MED12 mutation status can be a candidate marker for predicting the effect of gonadotropin-releasing hormone agonists on uterine leiomyoma reduction. Magnetic resonance imaging findings can be used to determine MED12 mutation status as a noninvasive strategy to select patients who will most likely benefit from gonadotropin-releasing hormone agonist treatment.

DOI： 10.1016/j.ajog.2022.09.024

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Language：English   Publishing type：Research paper (scientific journal)  

In 2013, the Ministry of Health, Labor, and Welfare (MHLW) in Japan announced a suspension of the governmental recommendation for routine HPV vaccinations. In 2020, MHLW started individual notifications of HPV vaccine to the targeted girls. In April 2022, the governmental recommendation was restarted, and catch-up vaccinations started. We evaluated the benefits and limitations of the MHLW's new vaccination strategies by estimating the lifetime risk for cervical cancer for each birth FY under different scenarios to suggest a measure for the vaccine suspension generation. It was revealed that catch-up immunization coverage among the unvaccinated must reach as high as 90% in FY2022, when the program begins, in order to reduce the risk of the females already over the targeted ages to the same level or lower than that of women born in FY1994-1999 who had high HPV vaccination rates. For women whose vaccination coverage waned because of their birth FYs, strong recommendations for cervical cancer screening should be implemented.

DOI： 10.3390/vaccines10091455

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Language：Japanese   Publisher：神奈川産科婦人科学会  

維持透析中女性の妊娠出産は羊水量の異常や妊娠高血圧症候群の合併などが多く、ハイリスク妊娠である。今回、内科と連携して妊娠中にドライウエイトを慎重に管理しながら頻回透析管理を行ったことにより、正期産に経腟分娩できた症例を経験した。症例は31歳、2妊0産。小児期から巣状分節性糸球体硬化症と診断され、慢性腎不全に対して29歳で週3回の血液維持透析を導入された。妊娠前に高血圧は指摘されていなかった。タイミング妊娠が成立し、妊娠4週で当科を受診した。妊娠高血圧症候群予防のため、妊娠28週まで低用量アスピリン療法を行った。また、妊娠7週からは透析頻度を週5回に増やし、妊娠23週からは入院管理とし、週6回の頻回透析を行った。羊水過多及び血圧上昇傾向に対して妊娠29週よりドライウエイトの増量を中止としたところ、血圧及び羊水量は正常に復した。妊娠37週0日にオキシトシンによる分娩誘発により正常経腟分娩に至った。児は2,740g、Apgar scoreは1分値8点、5分値9点で母児ともに経過良好であった。透析患者の妊娠症例では、内科と連携して厳重に管理し頻回に透析を行うことで、早産リスクを低減できる可能性があり、産科管理のみならず慎重で専門的な内科的管理が必要であるため、維持透析導入妊婦は、他科との連携を綿密にとることのできる医療施設での分娩が望ましい。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

卵巣腫瘍における術中迅速病理組織検査(以下迅速診断)は、良悪性や組織型を術中に鑑別することで適切な術式選択を可能とし、不要な二期的手術や拡大手術を防ぐために重要である。2014年7月から2019年6月までに当院で迅速診断を施行した卵巣腫瘍118例を対象とし、最終病理診断との乖離、手術術式に与えた影響、合併症、予後等について診療録をもとに後方視的に検討した。最終病理診断は良性31例、境界悪性25例、悪性62例であった。迅速診断と最終病理診断との乖離は18例で認められ、迅速診断の正診率は84.7%であった。2016年7月に卵巣腫瘍・卵管癌・腹膜癌取扱い規約が改訂され良悪性の診断基準が一部変更されたが、規約改定前後での乖離はそれぞれ3例、15例であった。正診率はそれぞれ94.1%、77.6%と有意な差を認めた(p=0.019)。迅速診断の正診率低下には、規約改訂による境界悪性の微小浸潤の定義の変更が関与している可能性が示唆された。間質浸潤の所見をもとに迅速診断で悪性と過大評価した境界悪性の2例では、骨盤及び傍大動脈リンパ節の系統的郭清による術後合併症として乳び漏、下肢浮腫をそれぞれ1例ずつ認めた。迅速診断で間質浸潤の有無を評価するには限界があり、最終病理診断との乖離が生じる可能性を考える必要がある。その場合には術前と術中の臨床的所見も含めた総合的な視野で、合併症のリスクを伴う拡大手術を避けるため、二期的手術も念頭においた術式選択を考慮すべきである。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

To investigate the relationships between communicative and critical health literacy (CCHL) and anxiety and depressive symptoms (ADs) in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was conducted and 5466 pregnant women responded in Japan in September 2020. A Kessler 6 scale (K6) score ≥ 10, an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13, and four CCHL groups were analyzed using a logistic regression model and trend test. The proportions of pregnant women with a K6 score ≥ 10 and EPDS score ≥ 13 were 13.5 and 15.4%, respectively. In comparisons with the low CCHL group, the adjusted odds ratio (95% CI) for anxiety symptoms was 0.770 (0.604-0.982) in the high CCHL group, while those for depressive symptoms were 0.777 (0.639-0.946), 0.665 (0.537-0.824), and 0.666 (0.529-0.838) in the lower, higher, and high CCHL groups (all p < 0.05), respectively, after adjustments for potential confounding factors, such as age, weeks of gestation, complications, history, number of children, marital status, education, employment, and income. Higher CCHL was associated with significantly lower adjusted odds ratios for anxiety (p for trend = 0.019) and depressive symptoms (p for trend < 0.001). These results suggest a relationship between CCHL and ADs in pregnant women during the COVID-19 pandemic.

DOI： 10.1038/s41598-022-18405-3

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

To investigate whether false-positive early gestational diabetes mellitus (GDM) women can be managed similarly as normal glucose tolerance (NGT) women.

Methods

This retrospective study was conducted at a tertiary care center in Japan. Pregnancy and neonatal outcomes of 67 singleton pregnancies with false-positive early GDM and 1774 singleton pregnancies with NGT who delivered after 22 weeks of gestation were compared. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (patients having one or more of the following: fasting plasma glucose ≥ 92 mg/dL and a 75 g oral glucose tolerance test (OGTT) value ≥ 180 mg/dL at 1 h, or ≥ 153 mg/dL at 2 h). Pregnant women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria on the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation.

Results

Maternal age, pre-pregnancy body mass index, and gestational weight gain were significantly higher in the false-positive GDM group than in the NGT group. No significant differences were found in pregnancy outcomes, including gestational age, birth weight, large for gestational age rate, and cesarean delivery rate. Except for a higher neonatal hypoglycemia rate in the false-positive early GDM group, no significant differences were found in neonatal outcomes.

Conclusions

There were no clinically significant differences between early GDM false-positive women exhibiting GDM patterns only during early pregnancy and NGT women. False-positive early GDM women can be managed similarly as NGT women, suggesting that World Health Organization diagnostic guidelines, applying the IADPSG criteria during early pregnancy, need revision.

DOI： 10.1186/s12902-022-01124-1

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Other Link： https://link.springer.com/article/10.1186/s12902-022-01124-1/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: To investigate whether false-positive early gestational diabetes mellitus (GDM) women can be managed similarly as normal glucose tolerance (NGT) women. METHODS: This retrospective study was conducted at a tertiary care center in Japan. Pregnancy and neonatal outcomes of 67 singleton pregnancies with false-positive early GDM and 1774 singleton pregnancies with NGT who delivered after 22 weeks of gestation were compared. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (patients having one or more of the following: fasting plasma glucose ≥ 92 mg/dL and a 75 g oral glucose tolerance test (OGTT) value ≥ 180 mg/dL at 1 h, or ≥ 153 mg/dL at 2 h). Pregnant women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria on the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation. RESULTS: Maternal age, pre-pregnancy body mass index, and gestational weight gain were significantly higher in the false-positive GDM group than in the NGT group. No significant differences were found in pregnancy outcomes, including gestational age, birth weight, large for gestational age rate, and cesarean delivery rate. Except for a higher neonatal hypoglycemia rate in the false-positive early GDM group, no significant differences were found in neonatal outcomes. CONCLUSIONS: There were no clinically significant differences between early GDM false-positive women exhibiting GDM patterns only during early pregnancy and NGT women. False-positive early GDM women can be managed similarly as NGT women, suggesting that World Health Organization diagnostic guidelines, applying the IADPSG criteria during early pregnancy, need revision.

DOI： 10.1186/s12902-022-01124-1

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/s1470-2045(22)00259-5

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: In Japan, in June 2013, The Ministry of Health, Labor and Welfare (MHLW) decided to temporarily suspend its official recommendation for the participation of girls in the national immunization program. The HPV vaccination rate in Japan soon declined to below 1%. In October 2020, the MHLW notified that the municipalities could and should begin to individually notify girls and their parents targeted for routine vaccination. We have examined how that type of individual notification has affected the number of vaccinations. METHODS: From 12 municipalities (with a combined total population of approximately 4.06 million), we collected vaccination data for all girls who attended grades 6 through 10 from April 2019 to March 2021. We analyzed the number of initial-round vaccinations that occurred by month and the timing and the subjects of the individual notifications. RESULTS: The annual vaccination rate for tenth-grade students in 2020 in the six municipalities that had implemented individual notification was 9.46% (342/3618), which was significantly higher than the rate of 3.22% (54/1676) in the three municipalities that had not implemented individual notification (p < 0.001). On the other hand, the annual vaccination rate for the sixth to ninth-grade students in 2020 in the six municipalities that had implemented individual notification was not significantly (p = 0.56) higher than the rate in the three municipalities that did not: 1.43% (197/13,785) versus 1.33% (83/6260), respectively. CONCLUSION: This study clearly demonstrates the importance of providing information for routine vaccination directly to the targets and their parents.

DOI： 10.1007/s10147-022-02213-w

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：English   Publishing type：Research paper (scientific journal)  

To investigate the vaccination status and adverse reactions to the COVID-19 vaccine among pregnant women in Japan, we conducted an online questionnaire survey from October 5 to November 22, 2021. The number of participants in the online survey was 6576. Of the participants, 4840 (73.6%) were vaccinated twice, and 557 (8.5%) were vaccinated once. A total of 1179 (17.9%) responders had never been vaccinated against COVID-19. The most frequent adverse reaction was local pain at the injection site. The incidence of local adverse reactions was almost identical after the first and the second vaccinations, while systemic reactions, such as fever and fatigue/malaise, and adverse reactions outside the vaccination site such as headache and arthralgia, were more frequent after the second vaccination than after the first vaccination. Regarding the obstetrical complications, uterine tension and/or contraction was observed in 1.65% of the pregnant women after the first vaccination and in 2.98% after the second vaccination, and uterine pain appeared in 1.06% of the pregnant women after the second vaccination. However, serious symptoms, such as hemorrhage, decreased fetal movement, edema, increased blood pressure, and amniorrhexis, were seen in less than 1% of vaccinated women after both the first and second vaccinations. This study clarified the characteristics of vaccination, adverse reactions, and obstetrical symptoms in pregnant women in Japan who had the COVID-19 vaccine up to the second dose. As a booster vaccination is currently underway, further study is needed to improve the management of pregnant women during the current pandemic.

DOI： 10.1111/jog.15285

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Language：English   Publishing type：Research paper (scientific journal)  

Japanese girls aged 12-16 years are offered free human papillomavirus (HPV) vaccination and cervical cancer screening is conducted with cytology and not HPV testing from the age of 20 years. So far, no study has analyzed the effect of HPV vaccination against cervical precancers considering HPV infection status and sexual activity. We aimed to analyze the vaccine effectiveness (VE) against HPV infection and cytological abnormalities, adjusted for sexual activity. This study comprised women aged 20-26 years who underwent cervical screening in Niigata. We obtained HPV vaccination status from municipal records and a questionnaire along with information concerning sexual activity. Of 5194 women registered for this study, final analyses included 3167 women in the vaccinated group (2821 vaccinated women prior to sexual debut) and 1386 women in the unvaccinated group. HPV 16/18 (0.2% vs 3.5%), 31/45/52 (3.4% vs 6.6%), and 31/33/45/52/58 (5.0% vs 9.3%) positive rates were significantly lower in the vaccinated group (P < 0.001). No women vaccinated before sexual debut had HPV 16/18-related cytological abnormalities. VE for HPV 16/18 infection and high-grade cytological abnormalities in women vaccinated prior to sexual debut were 95.8% (95% CI 81.9-99.0%; P < 0.001) and 78.3% (95% CI 11.3-94.7%; P = 0.033), respectively, in multivariate analyses adjusted for age and number of sexual partners. However, analyses of all vaccinated women did not show significant effectiveness against cytological abnormalities. Our results showed the effectiveness of HPV vaccine against high-grade cervical cytological abnormalities and the importance of the vaccination before sexual debut.

DOI： 10.1111/cas.15471

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: To investigate how an extremely prolonged second stage of labor of 12 h or more affects maternal and neonatal outcomes. MATERIAL AND METHODS: This retrospective cohort study included nulliparous, pregnant women with 37 + 0 to 41 + 6 weeks of gestation whom vaginal delivery was attempted at the Yokohama City University Medical Center between 2014 and 2018. RESULTS: In 446 cases of the prolonged second stage of labor, there were 296 women (66%) in the 2- to 6-h second stage of labor group, 112 women (25%) in the 6- to 12-h group, and 38 women (8.5%) in the 12-h or longer group. The longer the second stage of labor, the more significant was the increase in the rates of augmentation of the delivery, emergency cesarean delivery, and operative vaginal delivery. Even in the 12 h or longer group, 82% were able to have vaginal delivery. The 6- to 12-h group had a significant increase in third- or fourth-degree perineal lacerations compared to the 2- to 6-h group (aOR 8.12 [95% CI 1.55-42.6]). Clinical chorioamnionitis was significantly increased in the 12 h or longer group (aOR 4.88 [95% CI 1.62-14.8]). In terms of neonatal outcomes, comparison between the three groups showed no significant difference. CONCLUSION: With an extremely prolonged second stage of labor, maternal complications involved a significant increase in severe perineal lacerations and chorioamnionitis; however, there was no increase in adverse outcomes for neonates. It was not possible to conclusively determine if the duration of the second stage is acceptable.

DOI： 10.1111/jog.15212

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Providing adequate information to parents who have children eligible for human papillomavirus (HPV) vaccination is essential to overcoming vaccine hesitancy in Japan, where the government recommendation has been suspended. However, prior trials assessing the effect of brief educational tools have shown only limited effects on increasing the willingness of parents to vaccinate their daughters. OBJECTIVE: The aim of this trial is to assess the effect of a cervical cancer survivor's story on the willingness of parents to get HPV vaccination for their daughters. METHODS: In this double-blinded, randomized controlled trial (RCT) implemented online, we enrolled 2175 participants aged 30-59 years in March 2020 via a webpage and provided them with a questionnaire related to the following aspects: awareness regarding HPV infection and HPV vaccination, and willingness for HPV vaccination. Participants were randomly assigned (1:1) to see a short film on a cervical cancer survivor or nothing, stratified by sex (male vs female) and willingness for HPV vaccination prior to randomization (yes vs no). The primary endpoint was the rate of parents who agreed for HPV vaccination for their daughters. The secondary endpoint was the rate of parents who agreed for HPV vaccination for their daughters and the HPV vaccination rate at 3 months. The risk ratio (RR) was used to assess the interventional effect. RESULTS: Of 2175 participants, 1266 (58.2%) were men and 909 (41.8%) were women. A total of 191 (8.8%) participants were willing to consider HPV vaccination prior to randomization. Only 339 (15.6%) participants were aware of the benefits of HPV vaccination. In contrast, 562 (25.8%) participants were aware of the adverse events of HPV vaccination. Although only 476 (21.9%) of the respondents displayed a willingness to vaccinate their daughters for HPV, there were 7.5% more respondents in the intervention group with this willingness immediately after watching the short film (RR 1.41, 95% CI 1.20-1.66). In a subanalysis, the willingness in males to vaccinate daughters was significantly higher in the intervention group (RR 1.50, 95% CI 1.25-1.81); however, such a difference was not observed among females (RR 1.21, 95% CI 0.88-1.66). In the follow-up survey at 3 months, 1807 (83.1%) participants responded. Of these, 149 (8.2%) responded that they had had their daughters receive vaccination during the 3 months, even though we could not see the effect of the intervention: 77 (7.9%) in the intervention group and 72 (8.7%) in the control group. CONCLUSIONS: A cervical cancer survivor's story increases immediate willingness to consider HPV vaccination, but the effect does not last for 3 months. Furthermore, this narrative approach to parents does not increase vaccination rates in children eligible for HPV vaccination. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000039273; https://tinyurl.com/bdzjp4yf.

DOI： 10.2196/34715

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: This study was conducted to evaluate the status and role of cervical cytology affected by human papillomavirus infection and other infectious diseases screened during routine prenatal checkups. METHODS: We retrospectively examined medical records containing the screening results for infectious diseases and cervical cancer in women who delivered neonates in our hospital from 2014 to 2017. RESULTS: Among 3393 deliveries, 18.8% of women underwent a regular cervical cancer screening within 1 year of becoming pregnant, and 2641 women underwent a cervical cytology screening during this pregnancy. The cytological diagnostic results showed that 2562 women (97.0%) were negative for intraepithelial lesions or malignancy, whereas 79 (3.0%) had abnormal results. Of those with abnormal cytology results, 70 had abnormal cytology that was newly detected in this pregnancy, and 42 had grade ≥1 cervical intraepithelial neoplasia lesions. Spatulas were the most frequently used cytological sampling instruments, followed by cotton swabs. Cervical cytology revealed no major adverse reactions during these pregnancies. CONCLUSIONS: Our results confirm the importance of screening for infectious diseases during pregnancy. Only 20% of the women underwent a regular pre-pregnancy cervical cytology screening. Cervical cytology screening during pregnancy may currently be playing a crucial role in preventing cervical cancer in Japan.

DOI： 10.1177/03000605221097488

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Serum starvation and hypoxia (SSH) mimics a stress condition in tumours. We have shown that intercellular adhesion molecule-1 (ICAM-1) protein is synergistically expressed in ovarian clear cell carcinoma (CCC) cells under SSH in response to an insufficient supply of fatty acids (FAs). This ICAM-1 expression is responsible for resistance against the lethal condition, thereby promoting tumour growth. However, the underlying mechanisms that link SSH-driven ICAM1 gene expression to impaired FA supply and its clinical relevance are unclear. METHODS: The underlying mechanisms of how FA deficiency induces ICAM-1 expression in cooperation with hypoxia were analysed in vitro and in vivo. Clinical significance of CCC cell-derived ICAM-1 and the mechanism associated with the transcriptional synergism were also investigated. RESULTS: ICAM-1 expression was mediated through lipophagy-driven lipid droplet degradation, followed by impaired FA-lipid droplet flow. Lipophagy induced ICAM1 expression through stabilisation of NFκB binding to the promoter region via Sam68 and hTERT. Analyses of clinical specimens revealed that expression of ICAM-1 and LC3B, an autophagy marker associated with lipophagy, significantly correlated with poor prognoses of CCC. CONCLUSIONS: The lipophagy-ICAM-1 pathway induced under a tumour-like stress conditions contributes to CCC progression and is a potential therapeutic target for this aggressive cancer type.

DOI： 10.1038/s41416-022-01808-4

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Language：English   Publishing type：Research paper (scientific journal)  

This study aimed to identify the factors predicting rubella vaccination status based on self-reported data and the presence of sufficient rubella antibody titers in pregnant women in Japan. We used the results of the nationwide questionnaire survey conducted at obstetric facilities in the Pregnant Women Health Initiative Project (PWHI), with 23 participating hospitals recruiting pregnant women from June 2018-November 2019. We extracted age, the number of deliveries, educational level, household income, pre-pregnancy smoking, and knowledge of rubella from questionnaires and medical records. We analyzed the association of rubella vaccination status and antibodies with each of these factors. We found that the number of previous deliveries, educational level, annual household income, smoking before pregnancy, and knowledge of rubella were factors predicting self-reported rubella vaccination status, while age and the number of previous deliveries were identified as factors predicting the presence of sufficient rubella antibody titers (32 folds or higher). Women considering pregnancy should be immunized against rubella to prevent congenital rubella syndrome in the future. Furthermore, social policies are needed to strongly encourage vaccination, especially for all citizens who were not given the opportunity or missed the chance to be vaccinated against rubella.

DOI： 10.3390/vaccines10050638

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Language：English   Publishing type：Research paper (scientific journal)  

Background: In patients with secondary upper limb lymphedema, positive correlations have been observed between the dermal back flow (DBF) type and visualization of lymph nodes around the clavicle, between the former and the lymph flow pathway type, and between the latter and the visualization of lymph nodes around the clavicle when using single photon-emission computed tomography/computed tomography/lymphoscintigraphy (SPECT-CT LSG). Methods and Results: We analyzed the associations between the visualization of inguinal lymph nodes, the lymph flow pathway type, and the DBF type using SPECT-CT LSG in 81 patients with unilateral secondary lower limb lymphedema by statistical analysis using Fisher's exact test. We revealed that the lymph flow pathways in the lower limb can be classified into nine types because the type in the lower leg is not always equal to the type in the thigh. Associations were observed between the visualization of inguinal lymph nodes and types of DBF (p < 0.01), between the types of lymph flow pathway in the thighs and visualization of the inguinal lymph nodes (p = 0.02), and between the lymph flow pathway types in the thighs and lower legs (p < 0.01). Conclusion: Detriment to the superficial lymph flow pathways in the lower limb appears to usually start from the proximal side, and deep pathways are considered to become dominant from a compensatory perspective as lymphedema severity increases.

DOI： 10.1089/lrb.2021.0040

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Language：English   Publishing type：Research paper (scientific journal)  

In Japan, public funding for HPV vaccination began in 2010 for girls aged 13-16 years (birth cohort years 1994-1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long-term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25-26 years who underwent cervical cancer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993-1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vaccinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92-109 months). The HPV high-risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vaccine effectiveness was 100%. The cross-protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long-term 9-year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.

DOI： 10.1111/cas.15282

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Language：English   Publishing type：Research paper (scientific journal)  

The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s.

DOI： 10.3390/vaccines10020256

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

令和2年度神奈川県産科婦人科医会婦人科悪性腫瘍登録の集計結果を報告する。登録用紙を令和3年1月に発送し3月末日まで回収した。総施設数364に対して284施設(78.0%)から回答を得た。県下で治療された婦人科悪性腫瘍総数は4,256例でCIS、AIS、AEHと境界悪性腫瘍を除くと2,455例であった。子宮頸癌1,954例(扁平上皮癌1,731例、腺癌系223例)、子宮体癌1,258例、卵巣癌813例、卵管癌29例、腹膜癌72例、外陰癌19例、腟癌11例、子宮肉腫55例、子宮腺肉腫3例、転移性腫瘍23例であった。治療数は10年の経過でみると全体で増加している。CIN3、AIS、AEHを除く子宮頸癌・体癌比率の年次推移を検討すると令和2年度では0.49:1で、平成17年度から引き続き子宮体癌数が子宮頸癌数を上回り、体癌の比率が増大している。CIN3・AISを含めた子宮頸癌総数では、平成23年度1,088例から1,954例と1.8倍に増加していた。CIN3とAISが1,419例であり、昨年同様頸癌の3/4を占めている。AEHを含めた子宮体癌総数は昨年度1,150例から1,258例と増加した。子宮体癌はI期が812例と65%を占めており、I期症例の増加が目立った。卵巣癌はI期症例とIII期症例が多い例年の傾向は変わらなかった。平成30年度におけるCIS、AIS、AEHと境界悪性腫瘍を含む症例で、全国統計と神奈川県統計との比較をした。子宮頸癌49〜52%、子宮体癌28〜29%、卵巣癌20〜22%であり、神奈川県も全国と同等の比率であった。平成30年度におけるCIS、AIS、AEHと境界悪性腫瘍を除く症例で、全国統計と神奈川県統計との比較をした。子宮頸癌は全国で29%、神奈川県は26%であった。子宮体癌は全国で44%。神奈川県は46%であった。神奈川県は全国に比べ子宮頸癌が少なく、子宮体癌が多い傾向にあった。卵巣癌は全国、神奈川県とも、27〜28%でありほぼ同様であった。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

【緒言】妊娠授乳関連骨粗鬆症状(PLO)に関しこれまでにわれわれは整形外科医を対象としたアンケートを実施し、PLOの認知が不十分であること、周産期の腰痛患者にPLOが含まれていることを報告した。今回は産婦人科医を対象とした調査を実施し、両科の比較を行うことで診療連携における検討課題の抽出を目的とした。【方法】対象は県内の分娩施設130件とし、調査方法は2017年11月～2018年1月の期間に郵送による質問紙法で行った。質問内容は、(1)PLOに伴う脊椎骨折の症例経験の有無、(2)治療法、(3)骨密度測定の有無、(4)疾患概念の認識の有無とした。先行研究として2016年1～5月に自施設で行った横浜市内の整形外科337施設を対象とした調査結果と比較した。【成績】アンケートの回収率は95%であった。症例経験ありの分娩施設は8.1%で、過去1年に2症例、分娩約30,000件中1例(0.003%)の経験であった。一方症例経験ありの整形外科は8.8%で、過去1年に8症例、分娩約3,250件中1例(0.03%)の経験であった。治療は、断乳が産婦人科で80%、整形外科で28%に行われた(p<0.01)。骨密度測定は22%の施設で行われ、疾患の認識率は産婦人科が46%、整形外科が36%であった(p<0.05)。【考察】両科の診療経験を比較すると、患者の多くが整形外科を受診していた。この理由は腰痛が主訴のため、または産婦人科終診後のため整形外科の受診が選択されたと考えられる。治療法は整形外科での断乳が少数にとどまっていたことから、産婦人科で断乳のサポート、整形外科でコルセット装着を行うなどの多職種連携をすることでより適切な治療が可能になると考える。疾患の認識率は両科とも50%未満で、認識率が上昇すれば発症頻度はさらに高まる可能性がある。【結論】PLOの適切な治療介入には、認識率の上昇と整形外科との連携が必要だ。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.lanwpc.2021.100327

PubMed

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本疫学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy  

DOI： 10.5180/jsgoe.38.2_235

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

症例は40歳(0妊0産)で、子宮筋腫による過多月経と貧血が進行し全腹腔鏡下子宮全摘出術、両側卵管切除術を行った。手術所見でダグラス窩腹膜に約1cmの青黒色の結節を認め周囲に大網が一部癒着しており、子宮内膜症所見はr-ASRM分類2点であった。病理診断で子宮筋層・漿膜、両側卵管は子宮内膜症所見はなく、子宮筋腫であった。術後、周期的な性器出血や腹痛、臍部の疼痛があり、腟断端の生検で腟断端子宮内膜症の診断を得た。臍部はポート孔に生じた子宮内膜症を疑い生検を行ったが診断は得られなかった。術後、腟断端と臍部に子宮内膜症が生じたと考えてジェノゲスト内服を行い、症状は改善している。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02563&link_issn=&doc_id=20230206480041&doc_link_id=%2Fcj7sanai%2F2022%2F003802%2F041%2F0235-0239%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcj7sanai%2F2022%2F003802%2F041%2F0235-0239%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

AIM: The aim of this study was to examine the relationship between breastfeeding and postpartum maternal weight change. METHOD: This study used data from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Participants were categorized into two groups: full breastfeeding (FB) and non-full breastfeeding (NFB) groups. Postpartum weight changes between the FB (n = 26,340) and NFB (n = 38,129) groups were compared. RESULTS: At 6 months postpartum, mean weight retention was significantly lower in the FB group than in the NFB group (0.2 vs 0.8 kg, respectively, p<0.001). Weight retention differed by pre-pregnancy body mass index (BMI), with postpartum weights of overweight (pre-pregnancy BMI 25.0-29.9) and obese (pre-pregnancy BMI ≥30.0) participants being lower than pre-pregnancy weight; this trend was more pronounced in the FB group than in the NFB group (overweight: -2.2 vs -0.7 kg, respectively; obese: -4.8 vs -3.4 kg, respectively). Factors affecting weight retention at 6 months postpartum were weight gain during pregnancy (β = 0.43; p<0.001), pre-pregnancy BMI (β = -0.147; p<0.001) and feeding method. FB resulted in lower weight retention than NFB (β = -0.107; p<0.001). CONCLUSION: Breastfeeding reduced maternal weight retention, which was greater in mothers who were obese before pregnancy. For obese women, active breastfeeding may improve their health.

DOI： 10.1371/journal.pone.0268046

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

46歳女。胆石発作の診断の際に撮影されたCTで骨盤内腫瘍を認められ、当科に紹介された。造影MRIで骨盤内に3.5cm大の紡錘形腫瘤を認めた。腫瘤は恥骨と膀胱の間隙に存在し、T1強調像では筋肉と等信号で内部は不均一な淡い造影効果を示し、T2強調像では内部は不均一な高信号を示した。拡散強調像・ADC mapでは不均一な高信号を示した。これらの所見から、レチウス腔のAggressive angiomyxoma(AAM)を疑った。手術アプローチは、腫瘍の占拠部位を考慮すると会陰部からの単独アプローチによる腫瘍摘出は困難と考えられ、腹腔鏡手術による摘出が可能と考えられたため実施した。内視鏡を用いて腹腔内からレチウス腔を展開し、腫瘍を摘出することができた。摘出標本の病理組織所見からAAMと確定診断した。

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Publishing type：Research paper (scientific journal)   Publisher：Medknow  

DOI： 10.4103/aja202152

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Language：English   Publishing type：Research paper (scientific journal)  

This study investigated the implementation status, attitudes, and practices regarding maternal pertussis vaccination in delivery facilities in Kanagawa, Japan. We conducted a questionnaire survey of pertussis vaccination during pregnancy at 125 delivery service facilities, excluding midwifery clinics, in Kanagawa Prefecture from June 18 to July 20, 2020. The questionnaire comprised multiple-choice items, with single or multiple answers depending on the question. Of the 125 facilities surveyed, valid responses were obtained from 72 facilities (58%). There were 41 primary clinics with birthing facilities (57%), 16 general hospitals (not designated perinatal centers) (22%), 10 regional perinatal centers (14%), and five tertiary perinatal centers (7%). None of the facilities administered pertussis vaccination during pregnancy. Forty facilities (56%) reported knowledge of the severity of neonatal and infant pertussis infections. Twenty-three facilities (32%) reported knowledge of the prevention of pertussis infection by vaccination during pregnancy. All facilities reported willingness to consider vaccination if included in the Japanese guidelines. In Japan, the pertussis vaccination during pregnancy is not highly practiced by obstetricians; thus, it is not as popular as in other countries. Further studies are needed to promote strategies to prevent pertussis infection in the neonatal and infant periods.

DOI： 10.1080/21645515.2021.1958609

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Language：English   Publishing type：Research paper (scientific journal)  

In Japan, government subsidies for human papillomavirus (HPV) vaccination of girls aged 13-16 commenced in 2010. By early 2013, vaccination had become a widely accepted national immunization program. However, in June of 2013, the Ministry of Health, Labor, and Welfare (MHLW), the government's lead agency, suspended its recommendation for vaccination in response to reports of adverse vaccine events. The rate of HPV vaccination quickly dropped from 70% to almost zero, where it has lingered for eight years. In 2020, a new 9-valent HPV vaccine was licensed in Japan. The momentum seemed to be building for the resumption of HPV vaccinations, yet Japanese mothers remain widely hesitant about vaccinating their daughters, despite the well-proven safety and efficacy of the HPV vaccines. The Japanese government and our educational and medical institutions must work harder as a team to inform our parents and their children about the life-saving benefits of the HPV vaccine, and at the same time, we must respond to all their concerns and questions. The vaccine hesitancy of unvaccinated women born in 2000 and thereafter is a natural consequence of the suspension of the government's recommendation. We must also take every possible measure to reduce the significant risk for cervical cancer these women have.

DOI： 10.3390/vaccines9111263

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.lanwpc.2021.100300

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The World Health Organization (WHO) has officially declared a global strategy regarding the Elimination of Cervical Cancer in November 2020, which focuses on preventing cervical cancer through HPV vaccination, screening precancerous lesions and managing and treating invasive cervical cancer [...]

DOI： 10.3390/vaccines9101199

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

DOI： 10.1002/cam4.4252

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The human papillomavirus (HPV) vaccination rate in Japan has fallen to nearly zero since the suspension of governmental proactive recommendations in 2013, owing to the development of purported adverse events. OBJECTIVE: This study aimed to evaluate the effects of a brief web-based educational intervention using the theory of behavioral insights on the willingness of adults to consider the HPV vaccine for their daughters and sons. METHODS: We recruited 1660 participants aged 20 years or older in March 2018 via a webpage and provided them with a 10-item questionnaire related to the following aspects: awareness regarding HPV infection and vaccination, willingness for immunization, and actions for prevention. We randomly stratified participants based on sex and age with or without a brief educational intervention involving scientific information presented in an easy-to-read format. RESULTS: Only 484 (29.2%) of the respondents were aware of the benefits of HPV vaccination. Although only 352 (21.2%) of the respondents displayed a willingness for immunization of their daughters, there were 40 (4.8%) more respondents in the intervention group with this willingness (adjusted odds ratio [aOR] 1.32, 95% CI 1.04-1.69). In a subanalysis, the willingness toward vaccination for daughters in men was significantly higher in the intervention group (aOR 1.46, 95% CI 1.05-2.02). However, such a difference was not observed among women (aOR 1.20, 95% CI 0.83-1.73). CONCLUSIONS: This study suggests that a brief web-based educational intervention increases the willingness of adults to consider the HPV vaccine for their children, especially among men. Thus, providing adequate information to men may be a useful strategy to improve the currently low rates of HPV vaccination. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000049745 (UMIN-CTR); https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049745.

DOI： 10.2196/28355

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Language：English  

Serous endometrial intraepithelial carcinoma is the precursor of invasive uterine serous carcinoma. Here, we present two cases of serous endometrial intraepithelial carcinoma with omental micrometastasis and discuss their clinical significance. Two menopausal patients with abnormal endometrial biopsy findings underwent hysterectomy and comprehensive surgical staging (bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy). Although gross examination failed to detect tumors, the pathological diagnosis was serous endometrial intraepithelial carcinoma. Both patients had omental micrometastasis; they were diagnosed with International Federation of Gynecology and Obstetrics stage IVB disease and received postoperative chemotherapy. One patient died of the carcinoma 9 months after the hysterectomy, and the other had a recurrence of carcinoma 17 months after the end of the initial therapy. The present cases and literature review highlight the importance of meticulous inspection for micrometastasis in the abdominal cavity, including the omentum and peritoneum, for predicting prognosis.

DOI： 10.1111/jog.15020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc  

Aim: During pregnancy, the ovarian endometrioma generally decreases in size and occasionally ruptures. We evaluated (1) whether and how ovarian-endometrioma size changes from the first trimester to the postdelivery period, and (2) the type of endometrioma more likely to rupture during pregnancy. Methods: During an 18-year period (2000–2018), ultrasound in the first trimester revealed ovarian endometrioma in 149 pregnant women at our tertiary institute. Among these, we subjected 138 endometriomas in 145 patients to expectant management (wait-and-watch approach during pregnancy). We compared the cyst sizes in the first trimester and the postdelivery period, and defined a &gt
1 cm diameter size-change as a significant increase/decrease. We analyzed four patients with rupture and characterized the predictors of rupture. Results: A comparison of cyst sizes in the first trimester and the postdelivery period revealed that the size of 94 (68%), 37 (27%), and 7 ovaries (5.0%), respectively, decreased, remained unchanged, and increased
in 56 ovaries (40%), apparent cysts were no longer present. Of the 145 patients, four (2.8%) required emergency surgery for cyst rupture. Adhesion to the surroundings, an increase in cyst size, large size (diameter of ≥6 cm), and compression due to the enlarged uterus in late pregnancy were factors clinically related to rupture. Conclusions: Approximately two-thirds of ovarian endometriomas decreased in size during pregnancy (40% disappeared), 27% remained unchanged, and only 5% increased in size. However, 2.8% of pregnant women with endometrial cysts experienced rupture. We characterized risk factors for rupture
however, clinical application requires further evaluation.

DOI： 10.1111/jog.14862

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: The aim of this study was to clarify the physical and mental burden of the COIVD-19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress. METHODS: A web-based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020. RESULTS: A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID-19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID-19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID-19 infection. CONCLUSIONS: Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.

DOI： 10.1111/jog.14878

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. RESULTS: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557). CONCLUSIONS: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.

DOI： 10.1111/jog.14877

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Language：Japanese   Publisher：神奈川産科婦人科学会  

腹腔鏡下手術の適応が広がるにつれて摘出子宮の大きさも増大傾向にある。当院では、摘出した子宮をより安全に腹腔外へ摘出するために、症例に応じて臍創部から子宮を回収する方法を試みている。経腟回収群(A群)と経腹回収群(B群)で、患者背景、子宮回収時間、手術時間、出血量、摘出子宮の重量及び周術期合併症について違いがあるか、診療録をもとに後方視的に比較検討した。対象は全腹腔鏡下子宮全摘術を施行した288例とし、A群251例、B群37例であった。子宮の回収方法は、診察所見とMRI画像所見から術者が術前に判断し決定した。患者背景では体重とBMIに有意差を認めなかったが、未経産の割合がB群で67.6%とA群の33.1%に比較し有意に多かった。また、B群で子宮重量が有意に重く(A群387g vs B群574g、P<0.0001)、術中出血量も多かった(A群80g vs B群100g、P=0.0336)。また、手術時間(A群146分vsB群179分、P<0.0001)・子宮回収時間(A群8分vsB群23分、P<0.0001)もB群で有意に長かった。回収方法によらず子宮重量が大きいほど回収時間が長くなる傾向にあったが、子宮重量648g以上ではA群でより時間が長くなる傾向にあった。今回の検討で子宮回収方法の選択判断には、出産経験の有無が影響していることが分かった。また、術前に子宮重量を推定し回収方法を選択することで回収時間、ひいては手術時間の短縮を図ることができ、より低侵襲な手術を提供できる可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：栄研化学(株)  

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: We aimed to conduct a fixed-point observation questionnaire survey of changes in young women's human papillomavirus (HPV) vaccination status over the course of 10 years. We also investigated the influence of suspension of governmental recommendation for HPV vaccination since June 2013. METHODS: During 2011-2020, we conducted a self-completed questionnaire survey among newly enrolled female medical school students in Yokohama, Japan. The questionnaire featured items regarding HPV vaccination status, age, previous sex education, and knowledge about cervical cancer and HPV vaccination. RESULTS: HPV vaccine uptake rates in 2011 (5.4%) and 2012 (13.5%), when vaccination was self-funded, increased after 2013 (48.7%), when vaccination fees were subsidized. The rate dropped drastically in 2019 (14.3%) and 2020 (5.1%), after suspension of recommendation by the government. Comparisons between new students in 2015/2016, who had high vaccination rates (65.2%), and new students in 2019/2020, who had low vaccination rates (9.8%), showed decreased levels of HPV vaccination awareness, with fewer students having covered cervical cancer prevention in sex education and with respondents having less knowledge about the details of HPV vaccination. CONCLUSIONS: After the suspension of proactive HPV vaccine recommendation, markedly fewer students have been vaccinated against HPV, even those at the vaccination target age. This situation has substantially influenced the lower awareness about cervical cancer prevention, even among medical school students. To protect young women from cervical cancer in Japan, it is crucial for the government to resume proactive recommendation of HPV vaccines as soon as possible.

DOI： 10.1111/jog.14949

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Language：English   Publishing type：Research paper (scientific journal)  

Cancer therapy has priority over fertility preservation. The time available for fertility preservation in patients with cancer is often very limited and depends on the condition of the underlying disease. This case report presents the results of two rounds of controlled ovarian stimulations (COSs) performed after an induced abortion. The patient had mixed phenotype acute leukemia diagnosed during early pregnancy and underwent a surgical abortion, followed by ovarian stimulation using urinary follicle-stimulating hormone (uFSH) and gonadotropin-releasing hormone (GnRH) agonists. Oocyte retrieval was subsequently performed for oocyte cryopreservation. Despite good hormonal and ultrasonic follicular growth, no oocytes were obtained. During a second COS performed at a low human chorionic gonadotropin (hCG) level (less than 100 IU/L), several mature oocytes were obtained, suggesting that higher hCG levels during COS induce the absence of mature oocytes during normal follicular growth. It is recommended to start COS post-abortion after confirming a low hCG level while considering the timing of cancer treatment.

DOI： 10.1080/09513590.2021.1950135

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Language：English   Publishing type：Research paper (scientific journal)  

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.

DOI： 10.1111/cas.15060

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Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

In 2009, the United States Institute of Medicine (IOM) reported the optimal gestational weight gain (GWG) during twin pregnancy based on the pre-pregnancy body mass index (BMI). However, there are ethnic variations in the relationship between GWG and pregnancy outcomes. We aimed to establish the criteria for optimal GWG during twin pregnancy in Japan. The study included cases of dichorionic diamniotic twin pregnancy registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System between 2013 and 2017. We analyzed data for cases wherein both babies were appropriate for gestational age and delivered at term. Cases were classified into four groups based on the pre-pregnancy BMI: underweight (BMI &lt;18.5 kg/m²), normal weight (18.5 kg/m² ≤BMI&lt; 25.0 kg/m²), overweight (25.0 kg/m² ≤BMI&lt; 30.0 kg/m²), and obese (BMI ≥30.0 kg/m²) and we calculated the 25^th–75^th percentile range for GWG for the cases. The 3,936 cases were included. The GWG ranges were 11.5–16.5 kg, 10.3–16.0 kg, 6.9–14.7 kg, and 2.2–11.7 kg in the underweight, normal weight, overweight, and obese groups, respectively. Thus, in the current study, the optimal GWG during twin pregnancy was lower than that specified by the IOM criteria. Factoring this in maternal management may improve the outcomes of twin pregnancies in Japan.

DOI： 10.1371/journal.pone.0253596

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: The purpose of this study was to classify patients with placental abruption (PA) into those with a history of PA (recurrence group) and those without a history (first-occurrence group), and compare the two groups to investigate whether perinatal outcomes differ between first-time PA and recurrent PA. MATERIALS AND METHODS: Subjects include 6475 patients diagnosed with PA from the Pregnancy Birth Registry System of the Japan Society of Obstetrics and Gynecology. Patients were classified into recurrence group and first-occurrence group. Perinatal outcomes were compared between 141 patients in the recurrence group and 705 patients in the first-occurrence group with 1:5 propensity score matching, adjusting for maternal age, history of smoking, pregnancy-induced hypertension, and premature rupture of membranes as covariates. RESULTS: There were no cases of maternal mortality in either groups, and the perinatal mortality rate did not exhibit a significant difference. Gestational age at delivery was significantly earlier in the recurrence group than in the first-occurrence group (35.3 vs 37.9 weeks, p < .001). The rate of preterm delivery at less than both 32 and 37 weeks of gestation was significantly higher in the recurrence group. The rate of UmApH < 7.1 and 5 min Apgar score < 7 were significantly higher in the recurrence group (21 vs 13%, p = .020, 20% vs 10%, p = .003, respectively). CONCLUSIONS: The results suggest that recurrent PA occurs at an earlier gestational age and follows a more severe course than the first occurrence of PA.

DOI： 10.1080/14767058.2019.1660766

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)神奈川県医師会  

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: In 2010, the Japan Society of Obstetrics and Gynecology (JSOG) changed the diagnostic criteria for gestational diabetes mellitus (GDM) to follow the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. As a result, many pregnant women with mildly impaired glucose tolerance (IGT) were newly diagnosed with GDM. This study aimed to verify the effects of interventions in pregnant women with mild IGT who were newly diagnosed with GDM based on the present JSOG criteria. METHODS: We defined mild IGT as a degree of IGT that would be diagnosed as GDM according to the present but not the previous JSOG criteria. We compared pregnancy and delivery outcomes in women with mild IGT who delivered a singleton at 22 weeks of gestation or later, between 2000 and 2009 (untreated group, n = 503) versus between 2011 and 2017 (treated group, n = 781). RESULTS: The incidence of GDM-related composite complications such as macrosomia, shoulder dystocia, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome was comparable in the untreated and treated groups (10.1% vs. 11.9%, p = 0.11). The pregnancy outcomes were also comparable, except for infant birth weights, which were lower in the treated group than in the untreated group (3014 g vs. 3094 g; p = 0.02). CONCLUSIONS: Pregnancy outcomes were not affected by the interventions in pregnant women with mild IGT.

DOI： 10.1111/jog.14783

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: This study aimed to clarify how the COVID-19 pandemic impacts psychological stress levels in postpartum women in Yokohama, Japan. METHODS: We retrospectively compared the rates of positive screening tests for postpartum depression (Edinburgh Postnatal Depression Scale score of 9 or more or self-injury factors) and liaison/psychiatric intervention rates between pre-pandemic and pandemic groups of postpartum women who delivered a live birth at our tertiary perinatal center in Yokohama, Japan between January 2019 and May 2020. Those whose postpartum health screening was performed in 2019 (March-June 2019) were considered the pre-pandemic group, and those whose screening was performed between March and June 2020 were considered the pandemic group. Adjustments were made for maternal background, pregnancy, and delivery outcomes, including a history of psychiatric disorders, complications, preterm delivery, NICU admission, and maternal postpartum complications, and the data were analyzed using a logistic regression analysis. RESULTS: Postpartum health screenings were performed on 339 women before the pandemic and 279 women during the pandemic. Positive screening rates for postpartum depression did not change before and during the pandemic (adjusted odds ratio 1.48, 95% confidence interval 0.885-2.46). CONCLUSIONS: There was no apparent increase in maternal psychological stress due to the COVID-19 pandemic in Yokohama, Japan. Postpartum women responded differently in settings with varied levels of disease severity and social restrictions.

DOI： 10.1111/jog.14776

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Language：Japanese   Publisher：(一社)日本遺伝カウンセリング学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：Japanese   Publisher：(一社)日本周産期・新生児医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC. METHODS: Serum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared. RESULTS: A total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II-IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125. CONCLUSIONS: High specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

DOI： 10.1007/s10147-021-01914-y

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: In 2013, a cohort study aimed to clarify the positive and negative effects of introducing the human papillomavirus (HPV) testing for population-based cervical cancer screening has been launched in Japan. This study included four screenings during the subsequent 7-year follow-up period. We aim to describe the results of the first round of this study on cervical cancer screening here. METHODS: This study began in September 2013 with recruitment completed in March 2016. Women aged 30-49 years were divided into 2 groups: those who received uterine cervical cytology alone in the first year (control group), or those who received a combination of cytology and HPV testing (intervention group), based on their age. After first screening, women with positive result of cytology or positive HPV test required referral. We summarized the results of the first round of cervical cancer screening. RESULTS: Of the 25,074 women who were eligible for the study, 13,845 women (55.2%) were screened with cytology alone; 11,229 women (44.8%) received a combination of cytology and HPV testing. After screening, 407 women (2.9%) in the control group and 1,003 women (8.9%) in the intervention group required referral, respectively. Adding HPV testing increased referral rate significantly (p<0.001). CONCLUSION: After first screening, introduction of HPV testing appears to contribute to significantly higher referral rates, suggesting that the number of colposcopies as a detailed examination may increase. These preliminary findings suggest that if HPV testing is introduced into screening, medical institutions need to be prepared for an increasing number of follow-up examinations.

DOI： 10.3802/jgo.2021.32.e29

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Language：English   Publishing type：Research paper (scientific journal)  

The ductus arteriosus (DA) immediately starts closing after birth. This dynamic process involves DA-specific properties, including highly differentiated smooth muscle, sparse elastic fibers, and intimal thickening (IT). Although several studies have demonstrated DA-specific gene expressions using animal tissues and human fetuses, the transcriptional profiles of the closing DA and the patent DA remain largely unknown. We performed transcriptome analysis using four human DA samples. The three closing DA samples exhibited typical DA morphology, but the patent DA exhibited aorta-like elastic lamellae and poorly formed IT. A cluster analysis revealed that samples were clearly divided into two major clusters, the closing DA and patent DA clusters, and showed distinct gene expression profiles in IT and the tunica media of the closing DA samples. Cardiac neural crest-related genes such as JAG1 were highly expressed in the tunica media and IT of the closing DA samples compared to the patent DA sample. Abundant protein expressions of jagged 1 and the differentiated smooth muscle marker calponin were observed in the closing DA samples but not in the patent DA sample. Second heart field-related genes such as ISL1 were enriched in the patent DA sample. These data indicate that the patent DA may have different cell lineages compared to the closing DA.

DOI： 10.3390/jcdd8040045

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpregu.00024.2021

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: Dienogest (DNG) is highly effective for relieving pain caused by endometriosis and adenomyosis. However, women with severe uterine swelling due to adenomyosis who take DNG usually experience metrorrhagia. This study aimed to examine the safety of DNG usage in women with adenomyosis. METHODS: This study included 20 women who were prescribed DNG for adenomyosis in our hospital from January 2016 to December 2016. We retrospectively analyzed women's clinical background characteristics (age, the use of the gonadotropin-releasing hormone agonist as pre-treatment of DNG, the uterus size [major axis, minor axis, maximum thickness in the myometrium, and length of the uterine body] by transvaginal ultrasonography [TVUS], hemoglobin level, and the presence of metrorrhagia during treatment). These variables were compared between the DNG continuation and discontinuation groups using the Mann-Whitney U test. RESULTS: Thirteen women continued DNG, and seven discontinued DNG within 12 months because of metrorrhagia. The uterine size was significantly larger in the discontinuation group than in the continuation group. All uterine measurements had high Spearman rank correlation coefficients (ρ > 0.8, P < 0.05). In six of seven cases in the discontinuation group, adenomyosis was in the anterior wall. Measuring the uterus size and locating adenomyosis by TVUS are simple methods of predicting DNG discontinuation. CONCLUSION: We consider that DNG can be safely administered in women with adenomyosis if the uterine size is <6 cm in the minor axis and the main lesion of adenomyosis is located in the posterior uterine wall.

DOI： 10.1111/jog.14612

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Language：English  

In pregnant patients with a divided uterine cavity, the decidual tissue on the nonpregnant side may be discharged prior to the delivery of the fetus. The pregnancy can continue if the uterine contractions and vaginal bleeding are controlled and the fetus is not in distress.

DOI： 10.1002/ccr3.4042

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: In 2010, the International Association of Diabetes and Pregnancy Study Group (IADPSG) proposed new criteria indicating that gestational diabetes mellitus (GDM) can be diagnosed if the fasting threshold of ≤92 mg/dL, 1-h threshold of ≤180 mg/dL, or 2-h threshold of ≤153 mg/dL are exceeded during the 75-g 2-h oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation. The World Health Organization (WHO) recommends using the proposed diagnostic threshold values of the IADPSG to diagnose GDM; however, it does not limit the timing of the 75-g OGTT. Since 2010 in Japan, GDM has been diagnosed using the same criteria as that proposed by the WHO. However, neither the JSOG nor the WHO has provided any evidence that it is appropriate to use a threshold beyond the range recommended by the IADPSG. METHODS: This was a single-centre retrospective study based on the medical records and delivery registry database of our centre. We included women who underwent a 50-g glucose challenge test (GCT) with results < 140 mg/dL at 24-28 weeks of gestation and subsequently underwent a 75-g OGTT after 29 weeks of gestation with abnormal glucose tolerance suspected based on clinical findings. The reference values for the 75-g OGTT followed the IADPSG criteria. Subjects were classified into the normal glucose tolerance (NGT) group and the GDM group. The type of delivery and neonatal outcomes of the two groups were compared. A multivariable analysis was performed to match the backgrounds of both groups. RESULTS: In total, the NGT and GDM group comprised 189 and 49 women, respectively. Emergency caesarean delivery rates were similar in the GDM and NGT groups (10.6 and 12.2%, respectively; adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 0.43-3.64; p = 0.74); however, the elective caesarean delivery rate was higher in the GDM group than in the NGT group (16.3 and 5.3%, respectively, adjusted OR, 3.60; 95% CI, 1.27-10.19; p = 0.01). No significant differences were observed in other maternal and neonatal outcomes between both groups. CONCLUSION: Although a diagnosis of GDM during the third trimester does not improve pregnancy outcomes, it increases the elective caesarean delivery rate.

DOI： 10.1186/s12884-021-03730-8

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/ijgo.13470

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

肝移植後妊娠は,妊娠高血圧症候群などの合併症の発症率上昇や免疫抑制剤内服による母体感染症,急性拒絶反応,早産や低出生体重児のリスクがあり,慎重な管理を要すると報告されているが,双胎妊娠の報告は稀で,本邦での報告はこれまでにない.今回我々は,肝移植後の双胎妊娠の1例を経験したため報告する.症例は37歳,1妊0産,先天性胆道閉鎖症に対して,33歳時に生体肝移植術の既往がある.クロミフェンによる排卵誘発で妊娠成立し,妊娠7週時に二絨毛膜二羊膜双胎と診断した.妊娠15週より第二子に18トリソミーを疑う多発奇形や胎児発育不全を認めた.妊娠27週0日に切迫早産の診断で入院管理とした.妊娠36週1日に帝王切開術を施行した.手術直後に重症妊娠高血圧症候群を発症し,降圧薬と硫酸マグネシウムを投与した.経過中に移植片の拒絶反応や感染徴候は認めなかった.第一子は生後8日目に正常退院,第二子は18トリソミーの診断となった.今回,肝移植後の双胎妊娠に対する慎重な管理により生児を得られた.多職種連携を要するため管理可能な施設は限られ,新生児集中治療室の病床管理や緊急時の母体搬送先についても事前の検討を要する.肝移植後患者には妊娠時のリスクについても患者教育を十分に行うこと,不妊治療では多胎妊娠とならないよう配慮することが望ましい.(著者抄録)

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Tissue factor pathway inhibitor‑2 (TFPI‑2) is a promising candidate as a serum biomarker of ovarian clear cell carcinoma (OCCC), a lethal histological subtype of epithelial ovarian cancer (EOC). TFPI‑2 is a secreted serine protease inhibitor that suppresses cancer progression through the inhibition of matrix protease activities. Previous studies have also identified TFPI‑2 in the nucleus, and a possible function of nuclear TFPI‑2 as a transcriptional repressor of matrix metalloproteinase‑2 (MMP‑2) was recently demonstrated. We are currently establishing TFPI‑2 as a serum biomarker for OCCC patients; however, TFPI‑2 expression in OCCC tissues has not been previously investigated. In the present study, we examined TFPI‑2 expression and its localization in 11 OCCC cell lines by western blotting and enzyme‑linked immune assay. Four cell lines expressed TFPI‑2 in the nucleus, cytoplasm and culture plate-attached extracellular fraction, while four other cell lines expressed TFPI‑2 only in the extracellular fraction. In the remaining three cell lines, TFPI‑2 was not identified in any fraction. The amount of secreted soluble TFPI‑2 showed similar trends to that of the plate‑attached fraction. We next investigated the expression levels and distribution of TFPI‑2 in surgically resected EOC tissues by immunohistochemistry. In 52 of the 77 (67.5%) OCCC tumors, TFPI‑2 expression was detected in at least one of the nuclear, cytoplasmic and extracellular matrix fractions. In contrast, we did not identify TFPI‑2 in the other EOC subtypes (n=65). TFPI‑2‑positive expression distinguished CCC from the other EOC tissues with a sensitivity of 67.5% and specificity of 100%. Although the inherent tumor suppressor function, statistical analyses failed to demonstrate correlations between TFPI‑2 expression and clinical parameters, including 5‑year overall survival, except for the patient age. In conclusion, we identified TFPI‑2 expression in the nucleus, cytoplasm and extracellular matrix in OCCC tissues. The high specificity of TFPI‑2 may support its use for diagnosis of OCCC in combination with existing markers.

DOI： 10.3892/or.2021.7944

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

令和元年度神奈川県産科婦人科医会婦人科悪性腫瘍登録の集計結果を報告する。総施設数383に対して300施設(78.3%)から回答を得た。県下で治療された婦人科悪性腫瘍総数は4308例でCIS、AIS、AEHと境界悪性腫瘍を除くと2450例であった。子宮頸癌2086例(扁平上皮癌1871例、腺癌系215例)、子宮体癌1150例、卵巣癌826例、卵管癌19例 腹膜癌56例 外陰癌20例 腟癌8例、子宮肉腫55例 子宮腺肉腫7例 転移性腫瘍36例であった。治療数は10年の経過でみると全体で増加している。CIN3、AIS、AEHを除く子宮頸癌・体癌比率の年次推移を検討すると令和元年度では0.55:1で、平成17年度から引き続き子宮体癌数が子宮頸癌数を上回り、体癌の比率が増大している。CIN3・AISを含めた子宮頸癌総数では、平成22年度1059例から2086例と2.0倍に増加していた。CIN3とAISが1519例であり、昨年同様頸癌の3/4を占めている。AEHを含めた子宮体癌総数は昨年度1107例から1150例と増加した。子宮体癌はI期が746例と7割を占めており、I期症例の増加が目立った。卵巣癌はI期症例とIII期症例が多い例年の傾向は変わらなかった。全国統計との比較では全国、神奈川県とも、子宮頸癌50〜51%、子宮体癌26〜28%、卵巣癌21%とほぼ全国と同等の比率であった。(著者抄録)

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

肝移植後妊娠は,妊娠高血圧症候群などの合併症の発症率上昇や免疫抑制剤内服による母体感染症,急性拒絶反応,早産や低出生体重児のリスクがあり,慎重な管理を要すると報告されているが,双胎妊娠の報告は稀で,本邦での報告はこれまでにない.今回我々は,肝移植後の双胎妊娠の1例を経験したため報告する.症例は37歳,1妊0産,先天性胆道閉鎖症に対して,33歳時に生体肝移植術の既往がある.クロミフェンによる排卵誘発で妊娠成立し,妊娠7週時に二絨毛膜二羊膜双胎と診断した.妊娠15週より第二子に18トリソミーを疑う多発奇形や胎児発育不全を認めた.妊娠27週0日に切迫早産の診断で入院管理とした.妊娠36週1日に帝王切開術を施行した.手術直後に重症妊娠高血圧症候群を発症し,降圧薬と硫酸マグネシウムを投与した.経過中に移植片の拒絶反応や感染徴候は認めなかった.第一子は生後8日目に正常退院,第二子は18トリソミーの診断となった.今回,肝移植後の双胎妊娠に対する慎重な管理により生児を得られた.多職種連携を要するため管理可能な施設は限られ,新生児集中治療室の病床管理や緊急時の母体搬送先についても事前の検討を要する.肝移植後患者には妊娠時のリスクについても患者教育を十分に行うこと,不妊治療では多胎妊娠とならないよう配慮することが望ましい.(著者抄録)

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In Japan, recommendations for HPV vaccines were suspended in 2013 due to unfounded safety fears. Although vaccine opponents claim modifying sexual behavior can prevent cervical cancer, no comprehensive data exist on sexual behavior and the risk of high-grade cervical disease in a Japanese population. This study investigates sexual behavior and the risk of HPV infection and cervical disease in 3968 women aged 20-41 yrs undergoing cervical screening between April 2014 and March 2016. Mean age at first intercourse was 18.4 yrs ± 2.8 and 32% of women reported ≥ 6 lifetime sexual partners. In regression analyses, number of partners was a significant risk factor for HPV infection. However, for high-grade disease (CIN2+), when HPV genotype was adjusted for, number of partners was not statistically significant. The greatest risk factor was an HPV16/18 infection (adjusted odds ratio 113.7, 95% CI: 40.8-316.9). In conclusion, we found that having an HPV16/18 infection and not sexual behavior was the most significant risk factor for high grade cervical disease in young Japanese women. These infections can be prevented by a highly effective vaccine and we recommend that the Japanese government resume proactive recommendations for the HPV vaccine immediately.

DOI： 10.1038/s41598-021-82354-6

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Whole-exome sequencing (WES) can detect not only single-nucleotide variants in causal genes, but also pathogenic copy-number variations using several methods. However, there may be overlooked pathogenic variations in the out of target genome regions of WES analysis (e.g., promoters), leaving many patients undiagnosed. Whole-genome sequencing (WGS) can potentially analyze such regions. We applied long-read nanopore WGS and our recently developed analysis pipeline "dnarrange" to a patient who was undiagnosed by trio-based WES analysis, and identified a heterozygous 97-kb deletion partially involving 5'-untranslated exons of MBD5, which was outside the WES target regions. The phenotype of the patient, a 32-year-old male, was consistent with haploinsufficiency of MBD5. The transcript level of MBD5 in the patient's lymphoblastoid cells was reduced. We therefore concluded that the partial MBD5 deletion is the culprit for this patient. Furthermore, we found other rare structural variations (SVs) in this patient, i.e., a large inversion and a retrotransposon insertion, which were not seen in 33 controls. Although we considered that they are benign SVs, this finding suggests that our pipeline using long-read WGS is useful for investigating various types of potentially pathogenic SVs. In conclusion, we identified a 97-kb deletion, which causes haploinsufficiency of MBD5 in a patient with neurodevelopmental disorder, demonstrating that long-read WGS is a powerful technique to discover pathogenic SVs.

DOI： 10.1038/s10038-020-00893-8

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Recommendations for HPV vaccines were suspended in 2013 due to unfounded safety fears in Japan. We aimed to clarify the differences between vaccinated and unvaccinated females in their awareness, knowledge, and behaviors toward cervical cancer, HPV vaccination and sex. Questionnaires were administered online to women aged 16 to 20. We conducted investigations for the following: awareness, knowledge, and actions for cervical cancer, HPV vaccination, and sexual activity, as well as items related to participants' social background. The survey in 828 girls revealed three points. The first is that more than half of the surveyed Japanese girls had poor knowledge about cervical cancer screening, HPV, or HPV vaccines. The second is that those in the unvaccinated group had a particularly poor knowledge of the subject and tended to have higher sexual activity. The final is that only 0.5% of the girls experienced changes in awareness about sexual activity after vaccination. In conclusion, this is the first large-scale survey analyzing the association between HPV vaccination and sexual activity in Japanese girls. Not only do unvaccinated girls not benefit from vaccines, but they also tend to engage in high-risk sexual behavior, and thus it is even more important to provide information on the effectiveness of vaccines and the usefulness of cancer screening.

DOI： 10.3390/vaccines9020087

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We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.

DOI： 10.1002/humu.24130

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIMS: To investigate whether the Institute of Medicine (IOM) guidelines for optimal gestational weight gain (GWG) in twin pregnancies are applicable to Japanese women. METHODS: This was a retrospective study involving women who delivered full-term twins at our tertiary center diagnosed with a normal prepregnancy body mass index. The women were divided into two groups, according to the optimal GWG recommended by the IOM (16.8-24.5 kg): the adequate GWG (AGWG) group with GWG meeting the guidelines and the low GWG (LGWG) group with GWG below the guidelines. Next, the women were divided into two groups according to birthweight: a group with both twins born appropriate for gestational age (AGA group) and a group with one or both twins born small for gestational age (SGA group). Their GWG as well as their pregnancy outcomes were compared. RESULTS: A total of 265 women were included. The AGWG group had a significantly higher proportion of hypertensive disorders of pregnancy than the LGWG group. There was no significant difference in the proportion of women with both twins born AGA or the rate of admission to the neonatal intensive care unit. Meanwhile, the median GWG in the AGA group was 13.6 kg, which was significantly higher than 12.0 kg in the SGA group. And even the median GWG in the AGA group was below the lower limit of the IOM guidelines. CONCLUSION: The optimal GWG for Japanese women with twin pregnancies may be below the IOM guidelines.

DOI： 10.1111/jog.14529

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Language：Japanese   Publisher：(公社)日本婦人科腫瘍学会  

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Language：Japanese   Publisher：東京医科大学医学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00877&link_issn=&doc_id=20210924430058&doc_link_id=%2Fcr4tokyo%2F2021%2Fs07901%2F049%2F0112-0112%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcr4tokyo%2F2021%2Fs07901%2F049%2F0112-0112%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：English  

Degenerated leiomyomas can rupture during pregnancy, and leakage of the fluid causes peritonitis in rare cases. If peritonitis associated with a degenerated leiomyoma is observed, the occurrence of rupture of the leiomyoma should be considered.

DOI： 10.1002/ccr3.3564

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Because the anterior lower uterine segment is stretched, the incarcerated gravid uterus case with a history of cesarean section is a good candidate for manual reduction.

DOI： 10.1002/ccr3.3524

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Language：English   Publishing type：Research paper (scientific journal)  

Following the 2018 rubella outbreak in Japan, this study aimed to assess rubella prevention measures based on the vaccination and immunization status of pregnant women in Japan. Our cohort study involved 3 local core hospitals in Yokohama City, and a total of 666 pregnant women were recruited between June 2018 and September 2019 to answer an online questionnaire. In total, 67.5% pregnant women had received rubella vaccination. The rate of rubella vaccination among pregnant women in the present survey was lower than that among age-matched female participants in a nationwide survey conducted in 2018. Overall, the study results showed that women in their 20s had a higher vaccination rate than those in their 40s, women who were nonsmokers before pregnancy had a higher vaccination rate than those who were smokers, and women who were aware that rubella may affect fetuses had a higher vaccination rate than those who were unaware of this. This survey elucidated multiple predictive factors for rubella vaccination among pregnant women in Japan. Our results confirm the recommendation that women considering pregnancy should be vaccinated for rubella.

DOI： 10.7883/yoken.JJID.2020.762

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BACKGROUND: Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury. METHODS: Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was <8 mmHg. Neuronal injury was assessed after 72 h recovery. RESULTS: Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1-3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death. CONCLUSION: Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment. IMPACT: It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep. Arginine vasopressin levels were elevated at 1-3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

DOI： 10.1038/s41390-020-0845-2

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Language：English   Publishing type：Research paper (scientific journal)  

Fetal heart rate variability (FHRV) is a widely used index of intrapartum well being. Both arms of the autonomic system regulate FHRV under normoxic conditions in the antenatal period. However, autonomic control of FHRV during labor when the fetus is exposed to repeated, brief hypoxemia during uterine contractions is poorly understood. We have previously shown that the sympathetic nervous system (SNS) does not regulate FHRV during labor-like hypoxia. We therefore investigated the hypothesis that the parasympathetic system is the main mediator of intrapartum FHRV. Twenty-six chronically instrumented fetal sheep at 0.85 of gestation received either bilateral cervical vagotomy (n = 7), atropine sulfate (n = 7), or sham treatment (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Parasympathetic blockade reduced three measures of FHRV before UCOs (all P < 0.01). Between UCOs, atropine and vagotomy were associated with marked tachycardia (both P < 0.005), suppressed measures of FHRV (all P < 0.01), and abolished FHRV on visual inspection compared with the control group. Tachycardia in the atropine and vagotomy groups resolved over the first 10 min after the final UCO, in association with evidence that the SNS contribution to FHRV progressively returned during this time. Our findings support that SNS control of FHRV is acutely suppressed for at least 4 min after a deep intrapartum deceleration and takes 5-10 min to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.

DOI： 10.1152/ajpregu.00186.2020

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：Japanese   Publisher：(一社)日本産科婦人科内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)  

KEY POINTS: The majority of intrapartum decelerations are widely believed to be mediated by the baroreflex secondary to brief umbilical cord occlusions (UCOs) but this remains unproven. We examined the responses to brief-UCOs in fetal sheep and compared these to a phenylephrine-stimulated baroreflex in a separate cohort. A further cohort was instrumented with near-infrared spectroscopy to measure cerebral oxygenation during UCO. The first 3-4 s of the brief-UCOs were consistent with a baroreflex, and associated with a minor fall in fetal heart rate (FHR). Thereafter, the remainder of the FHR decelerations were highly consistent with the peripheral chemoreflex. The baroreflex is not sufficient to produce deep, rapid decelerations characteristic of variable decelerations and it is therefore likely to be a minor contributor to intrapartum decelerations. ABSTRACT: Fetal heart rate (FHR) monitoring is widely used to assess fetal wellbeing during labour, yet the physiology underlying FHR patterns remains incompletely understood. The baroreflex is widely believed to mediate brief intrapartum decelerations, but evidence supporting this theory is lacking. We therefore investigated the physiological changes in near-term fetal sheep during brief repeated umbilical cord occlusions (brief-UCOs, n = 15). We compared this to separate cohorts that underwent a phenylephrine challenge to stimulate the baroreflex (n = 9) or were instrumented with near-infrared spectroscopy and underwent prolonged 15-min complete UCO (prolonged-UCO, n = 9). The first 3-4 s of brief-UCOs were associated with hypertension (P = 0.000), a fall in FHR by 9.7-16.9 bpm (P = 0.002). The FHR/MAP relationship during this time was consistent with that observed during a phenylephrine-induced baroreflex. At 4-5 s, the FHR/MAP relationship began to deviate from the phenylephrine baroreflex curve as FHR fell independently of MAP until its nadir in association with intense peripheral vasoconstriction (P = 0.000). During prolonged-UCO, cerebral oxygenation remained steady until 4 s after the start of prolonged-UCO, and then began to fall (P = 0.000). FHR and cerebral oxygenation then fell in parallel until the FHR nadir. In conclusion, the baroreflex has a minor role in mediating the first 3-4 s of FHR decelerations during complete UCO, but thereafter the peripheral chemoreflex is the dominant mediator. Overall, the baroreflex is neither necessary nor sufficient to produce deep, rapid decelerations characteristic of variable decelerations; it is therefore likely to be a minor contributor to intrapartum decelerations.

DOI： 10.1113/JP279573

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

AIM: To clarify the status of personal protective equipment (PPE) and coronavirus disease 2019 (COVID-19) tests for pregnant women, we conducted an urgent survey. METHODS: The survey was conducted online from April 27 to May 1, 2020. Questionnaires were sent to core facilities and affiliated hospitals of the obstetrics and gynecology training program and to hospitals of the national perinatal medical liaison council. RESULTS: A total of 296 institutions participated in our survey; however, 2 institutions were excluded. Full PPE was used by doctors in 7.1% of facilities and by midwives in 6.8%. Our study also determined that around 65.0% of facilities for doctors and 73.5% of facilities for midwives used PPE beyond the "standard gown or apron, surgical mask, goggles or face shield" during labor of asymptomatic women. N95 masks were running out of stock at 6.5% of the facilities and goggles and face shields at 2.7%. Disposable N95 masks and goggles or face shields were re-used after re-sterilization in 12% and 14% of facilities, respectively. Polymerase chain reaction (PCR) testing of asymptomatic patients was performed for 9% of vaginal deliveries, 14% of planned cesarean sections and 17% of emergency cesarean sections. The number of PCR tests for obstetrics and gynecology per a week ranged from zero to five in 92% of facilities. CONCLUSION: The shortage of PPE in Japan is alarming. Sufficient stockpiling of PPE is necessary to prevent unnecessary disruptions in medical care. Appropriate guidelines for PPE usage and COVID-19 testing of pregnant women at delivery are needed in Japan.

DOI： 10.1111/jog.14382

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：English   Publisher：日本癌学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(一社)日本女性医学学会  

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Language：English   Publishing type：Research paper (scientific journal)  

In 2013, recurrent reports of diverse symptoms occurring in girls after receiving HPV vaccination appeared in Japanese media. The Ministry of Health, Labor and Welfare quickly responded by announcing a temporary suspension of its recommendation for the vaccine. The HPV vaccination rate soon fell to almost zero. In the present study, we calculated the potential future numbers of cervical cancer incidence and death that will be increased by this policy decision. We have assumed that the number of yearly vaccinations is evenly distributed across a daily basis. Future incidence and death increased in females born in FY2000 are estimated to be 3651 and 904, respectively, 4566 and 1130 for those born in FY2001, 4645 and 1150 for those born in FY2002, and 4657 and 1153 for those born in FY2003. In FY2020, the large increase of risks to females born in FY2004 amounts to 12.0 females per day who will now be at a higher risk for acquiring of cervical cancer in their future, and 3.0 females per day newly at risk for future death from that disease in its progressive form. No one should be able to accept this situation. We sincerely ask the government to resume its recommendation for the vaccine as soon as possible.

DOI： 10.1038/s41598-020-73106-z

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The effects of the age at estrogen replacement therapy (ERT) initiation on bone quality in Turner syndrome were evaluated using trabecular bone score. Early puberty ERT positively correlated with increase in bone quality. Early initiation of ERT is necessary for the acquisition of bone quality as well as bone density. INTRODUCTION: Studies have reported associations between bone mineral density and estrogen replacement therapy (ERT) in Turner syndrome (TS) patients; however, few studies exist on the effect on bone quality. The aim of this study was to evaluate the effects of the age at ERT initiation on bone quality of Japanese TS patients, cross-sectionally and longitudinally. METHODS: Cross-sectionally, 95 TS patients were divided into three groups based on their age at initiation of ERT: A (12-14 years, 11 patients), B (15-17 years, 47 patients), and C (over 18 years, 37 patients). To assess bone quality, trabecular bone score (TBS) was used. The effects of age at initiation and duration of ERT on TBS were examined using multiple regression analysis. In the longitudinal study, 48 patients who underwent dual-energy X-ray absorptiometry multiple times were divided into three groups: D (12-14 years, 8 patients), E (15-17 years, 18 patients), and F (over 18 years, 22 patients). Each group was analyzed for the rate of change in TBS per year. RESULTS: Cross-sectionally, the TBS showed significant differences among the three groups (TBS A, 1.302; B, 1.299; C, 1.245) (p = 0.013); group C was significantly lower than B (p = 0.014); bone quality was degraded. Multiple regression analysis revealed that age at ERT initiation significantly affected the increase in TBS (p = 0.002). Longitudinally, the rate of change of TBS was not significantly different in the three groups (p = 0.73). CONCLUSION: Early initiation of ERT may have positive effects on bone quality in TS. Large prospective studies will be needed.

DOI： 10.1007/s00198-020-05652-1

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Language：English   Publishing type：Research paper (scientific journal)  

The trend for cervical cancer in younger women has been increasing recently in Japan. However, as a result of the suspension of governmental recommendation, Japan's HPV (human papillomavirus) vaccination rate for girls born since 2000 has dropped sharply. We conducted an internet survey in December of 2019, 76 months after the suspension of recommendation, to verify the intention of mothers to inoculate their daughter under current circumstances and compared with our previous surveys and leaflet intervention effect. The rates of mothers who replied that they would "inoculate" were significantly higher at 9 and 23 months, but by 32 months after the suspension the rate was significantly lower (p < 0.05, p < 0.05, p < 0.05, respectively). The rates of the mothers who replied they would not inoculate were significantly lower at 9 months and 23 months, but at 76 months was significantly higher (p < 0.05, p < 0.05, p < 0.05, respectively). We found that intervention with a leaflet that could be used under the current suspension of the governmental recommendation did not increase the mothers' intention to inoculate their daughters. A leaflet that actively encourages vaccination may increase the intent of vaccination. It is strongly recommended that the MHLW promptly resume its recommendations for HPV vaccination.

DOI： 10.3390/vaccines8030502

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpregu.00208.2020

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Language：Japanese   Publisher：神奈川産科婦人科学会  

晩婚化・晩産化と子宮頸癌発症の低年齢化に伴い、本邦での子宮頸癌合併妊娠の頻度は増加傾向にある。さらにHPVワクチン勧奨の停止などの社会的背景も重なり、今後もその頻度は増加していく可能性が高い。今回我々は、妊娠16週で子宮頸癌IB1期の診断に至ったが、妊娠継続を選択し母児ともに救命し得た1例を経験した。症例は36歳、4妊1産。子宮頸部に2cm大の易出血性腫瘤を認め、妊娠14週での子宮頸部細胞診でASC-H、妊娠16週での子宮頸部組織診で腺扁平上皮癌であったことから、子宮頸癌IB1期(T1b1N0M0)合併妊娠と診断した。患者及び家族の妊娠継続希望が強く、欧州のガイドラインを参考に妊娠管理を行った。妊娠31週で前期破水となり、産科適応での帝王切開分娩により1534gの女児を得た。子宮頸癌根治術は産褥38日目(子宮頸癌の診断より144日目)に施行し、再発低リスク症例として術後経過観察とした。本邦ではIB・II期子宮頸癌合併妊娠として提示されている治療管理方針はグレードC1であり、今後増加が予想される子宮頸癌合併妊娠症例での治療方針決定に難渋することが予想される。妊娠継続の可否、適切な治療の施行に向けて、管理・治療指針の確立が望まれる。(著者抄録)

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Although intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard for nonsurgical management of non-muscle-invasive bladder cancer, a considerable number of patients exhibit resistance to the adjuvant treatment with unexplained mechanisms. This study aimed to investigate whether and how androgen receptor (AR) signals modulate BCG cytotoxicity in bladder cancer. AR knockdown or overexpression in bladder cancer lines resulted in induction or reduction, respectively, in intracellular BCG quantity and its cytotoxic activity. Microarray screening identified Rab27b, a small GTPase known to mediate bacterial exocytosis, which was upregulated in BCG-resistant cells and downregulated in AR-shRNA cells. Knockdown of Rab27b, or its effector SYTL3, or overexpression of Rab27b also induced or reduced, respectively, BCG quantity and cytotoxicity. In addition, treatment with GW4869, which was previously shown to inhibit Rab27b-dependent secretion, induced them and reduced Rab27b expression in bladder cancer cells. Meanwhile, AR expression was upregulated in BCG-resistant lines, compared with respective controls. In a mouse orthotopic xenograft model, Rab27b/SYTL3 knockdown or GW4869 treatment enhanced the amount of BCG within tumors and its suppressive effect on tumor growth. Moreover, in non-muscle-invasive bladder cancer specimens from patients subsequently undergoing BCG therapy, positivity of AR/Rab27b expression was associated with significantly higher risks of tumor recurrence. AR activation thus correlates with resistance to BCG treatment, presumably via upregulating Rab27b expression. Mechanistically, it is suggested that BCG elimination from urothelial cells is induced by Rab27b/SYTL3-mediated exocytosis. Accordingly, Rab27b inactivation, potentially via antiandrogenic drugs and/or exocytosis inhibition are anticipated to sensitize the efficacy of BCG therapy, especially in patients with BCG-refractory AR/Rab27b-positive bladder cancer.

DOI： 10.1158/1535-7163.MCT-20-0050

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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AIM: Reports on pregnancy and delivery in women with Turner syndrome (TS) in Japan are limited to case reports, and the current situation remains unclear. Therefore, this study aimed to clarify the current situation of pregnancy and delivery in women with TS in Japan. METHODS: Our study comprised primary and secondary surveys and we included perinatal centers approved by the Ministry of Health, Labor and Welfare. RESULTS: A total of 24 cases from 19 facilities were reported, and we obtained individual information for 20 cases from 16 facilities. Of these 20 patients, 13 (65%) had become pregnant via oocyte donation. Three of these patients had received oocyte donation in Japan, while the other 10 had received donations in foreign countries. The other seven patients became pregnant with their own oocyte, with spontaneous menarche. Live babies were delivered by 18 patients, while an induced abortion was required at 18 weeks of gestation in one patient and an intrauterine fetal death from an unknown cause was detected at 38 weeks of gestation in another patient. Cesarean section was performed in 14 patients, with the most frequent indication being cephalopelvic disproportion. The rate of implementation of screening for complications related to TS was low, suggesting insufficient cooperation between facilities responsible for TS treatment, infertility and pregnancy and delivery management. CONCLUSION: To improve pregnancy outcomes in women with TS, improved cooperation between facilities and laws regarding oocyte donation in Japan are needed.

DOI： 10.1111/jog.14352

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

子宮摘出を要する産褥出血の症例は循環動態が不安定であり、リスクの高い手術となる場合が多い。今回我々は大動脈内バルーン遮断(Intra-aortic balloon occlusion;IABO)を行い、子宮摘出術で救命できた産科危機的出血の一例を経験した。症例は31歳、3妊2産で妊娠経過は特に問題はなかった。妊娠37週2日に陣痛発来し前医へ入院した。子宮口開大8cmの時点から陣痛促進剤を使用し、30分後に正常経腟分娩に至った。分娩1時間後にShock Index(SI)1.54のため子宮収縮薬の使用及び多量輸液をしたが改善なく、分娩2時間半後に非凝固性の出血が出現し、SI1.84となったため当院へ搬送となった。来院時、意識障害と持続する非凝固性の性器出血を認めた。子宮腔内バルーンタンポナーデによる止血を試み、挿入するも固定できず滑脱し、さらに大量輸血を行うも循環動態が不安定な状態が継続したため、子宮全摘術の方針とした。救急救命医によりIABOを行い、輸血を継続したところ循環動態が安定したため手術を開始した。開腹すると不全子宮破裂の所見であり、子宮摘出術により止血が得られた。術後は経過良好であり、合併症なく、術後8日目に退院した。産後出血に対する子宮摘出術はIABOを行うことでより安全に行うことができ、産褥搬送に関わる診療科等との連携も重要である。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

単角子宮では不妊症を14%に認めるが単角子宮そのものが不妊症の原因となるかは議論が残る。非交通性副角子宮を伴う単角子宮を有し体外受精を反復するも妊娠に至らず、合併する内膜症性嚢胞と月経困難症悪化に伴い副角子宮切除後、初回の採卵で妊娠に至った症例を経験したため、当院での副角子宮手術6例の転帰と文献的考察を加えて報告する。症例は37歳女性、0妊0産。8年間の不妊、右内膜症性嚢胞3cm、右副角子宮の診断で当科を受診した。精査の結果、左卵管に疎通性なく右副角子宮には交通性を認められず、体外受精の方針となった。解剖学的位置より右卵巣は穿刺できず左からのみ3回採卵、胚移植を4回行うも妊娠に至らず。この間に内膜症性嚢胞の増大と月経困難症を認めるようになったため、当科初診1年9ヵ月後、腹腔鏡下右副角子宮切除、右卵巣嚢腫摘出、左卵管切除を施行した。術後は左右卵巣から採卵できるようになり、初回の採卵・胚移植後に妊娠が成立し、妊娠37週で妊娠高血圧症候群による緊急帝王切開で生児を得た。本症例以外にも当院では不妊を主訴とした副角子宮の切除後妊娠例を経験しており、副角子宮が不妊の原因となるかどうかは結論が未だ出ないが、挙児希望のある副角子宮患者においては手術を積極的に考えていくことが考慮される。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

今回我々はベバシズマブ投与中に血栓症の初発症状として皮膚症状が出現したが、その原因を臨床的抗リン脂質抗体症候群と診断し抗血小板薬を投与しながらベバシズマブ併用化学療法を継続できた症例を経験したので報告する。症例は73歳。3妊3産。食思不振と腹部膨満感で紹介、画像検査で12cm大の左卵巣腫瘍、多発腹膜播種、大量腹水貯留、肝臓には最大径6cmの腫瘍を認めた。腹式単純子宮全摘術、両側付属器切除術、大網部分切除術及び腹膜生検を施行し、卵巣癌IVB期と診断した。残存する肝転移に対してパクリタキセル、カルボプラチン、ベバシズマブの併用療法を開始したところ、4サイクル投与日に右第2指及び第3指に爪の黒色変化を生じた。パクリタキセルの有害事象と考え継続したが、投与3日後に指の皮膚末端の黒色壊死への増悪を認めた。5サイクル目の治療を延期とし、臨床所見及び血液検査で抗リン脂質抗体が陽性であったことから臨床的抗リン脂質抗体症候群と診断した。外用薬や抗血小板薬を使用して8週間程で皮膚症状は改善したため、抗血小板薬を投与しながらベバシズマブ併用化学療法を再開することができた。化学療法による重篤な有害事象を疑った場合にすぐにベバシズマブを中止するのではなく血栓の原因を精査することで、ベバシズマブ投与が継続できる可能性がある。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

産科危機的出血は母体の循環動態によって治療方法が異なる。一般的には循環動態が不安定な場合は開腹術が優先される。今回、我々は産科危機的出血に対して大動脈内遮断バルーンを用いて循環動態を安定させ動脈塞栓術で止血を得た症例を経験したため報告する。症例は28歳、1妊0産、自然妊娠され経過順調だったが、妊娠40週3日に続発性微弱陣痛の診断でオキシトシンの点滴による陣痛促進を行った。子宮口全開大、St+1まで進行したが基線細変動小減少及び持続する胎児徐脈を認めたため、吸引分娩で児を娩出した。新生児は男児、2946g、Apgar scoreは1分値1点、5分値6点、9分値10点、臍帯動脈血pHは7.221であった。産後、子宮収縮薬や多量輸血を行っても止血を得られず当院に産褥搬送され分娩後3時間で当院へ到着した。多量輸血を行ったが循環動態が短期間で増悪したため、大動脈内遮断バルーンを胸部下行大動脈内でインフレートしたところ循環動態が改善した。不全子宮破裂が疑われ、止血治療として経カテーテル動脈塞栓術を選択した。止血術開始30分後に両側子宮動脈を塞栓し、90分で完全に止血し得た。止血後の経過は良好で、搬送後8日目に退院した。循環動態が不安定な産科危機的出血に対し、大動脈内遮断バルーンの使用により治療の選択肢が広がり、より安全に止血処置を行うことができる。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

症例は35歳6妊1産、31歳時に子宮頸癌IB1期(組織型Glassy cell carcinoma)と診断され妊孕性温存を強く希望し、他院で広汎子宮頸部摘出術を施行した。その後のフォローアップでは再発の兆候はみられず、33歳時に体外受精-胚移植で妊娠し、妊娠36週に帝王切開術で分娩した。今回、自然妊娠し、妊娠・分娩の管理目的に妊娠15週2日に当院を紹介され受診した。当院初診時は性器出血や感染兆候を認めなかったため、外来管理の方針とし、出血や子宮収縮などの切迫早産の兆候がみられた場合には入院管理にする方針とした。妊娠の経過中には切迫早産の兆候を認めず、胎児発育は良好であり、帝王切開術施行前日まで外来で管理できた。妊娠37週6日に予定帝王切開術で2920gの女児を娩出した。術中腹腔内の癒着や血管叢の損傷はなく、特に問題なく終刀した。術後は母児ともに経過良好であり、術後1週間で退院した。広汎子宮頸部摘出術後妊娠は、残存頸管が短く自然の子宮頸管による感染の防御機構も破綻するため、早産のハイリスクであるが、子宮収縮や子宮内感染兆候など切迫兆候を認めなければ外来管理及び正期産での分娩が可能である。(著者抄録)

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Radical hysterectomy and immediate sacral colpopexy using autologous fascia lata could be considered a treatment option for cervical cancer complicated by severe and symptomatic pelvic organ prolapse.

DOI： 10.1002/ccr3.2883

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BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

DOI： 10.1136/jmedgenet-2020-106896

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Organized human papillomavirus vaccination (OHPV) in Japan was introduced in 2010 for girls aged 12-16 years who were born in 1994 or later. The rate of OHPV coverage was 70-80%. However, after suspension of the government vaccination recommendation, the coverage dramatically decreased. We aim to investigate the change in prevalence of HPV infection after the initiation of HPV vaccination. We recruited females aged 20-21 years attending public cervical cancer screening from 2014 to 2017 fiscal years (April 2014 to March 2018). Residual Pap test specimens were collected for HPV testing. We compared the prevalence of HPV type-specific infection between women registered in 2014 (born in 1993-1994, including the pre-OHPV generation) and registered in 2015-2017 (born in 1994-1997, the OHPV generation). We collected 2379 specimens. The vaccination coverage figures were 30.7%, 86.6%, 88.4% and 93.7% (p < 0.01) from 2014 to 2017, respectively. The prevalence of HPV16/18 infection significantly decreased from 1.3% in 2014 to 0% in 2017 (p = 0.02). The three most prevalent types were HPV52, 16 and 56 in 2014, and HPV52, 58 and 56 in 2015-2017, respectively. HPV16 and 33 infection rates decreased. On the other hand, the HPV58 infection rate was obviously increased after OHPV from 0.3% to 2.1%. Our study demonstrates that the prevalence of HPV16/18 infection dramatically decreased and the profile of type-specific HPV infection was changed after OHPV.

DOI： 10.3390/vaccines8030425

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: The Japanese government suspended proactive recommendations for the HPV vaccine in June 2013. The suspension is now in its seventh year, despite all the data pointing to the safety of the HPV vaccine. We reported a high vaccine effectiveness in the group of women vaccinated before their first intercourse (93.9%). The prevalence of cross-protected types of HPV 31/45/52 was also lower in the vaccinated group, and the vaccine effectiveness was 67.7%. Furthermore, prevalence of HPV16, 31 and 52 infection rates in the vaccinated group were obviously lower than that in the unvaccinated group, and no one had HPV18 or 45 infection in the vaccinated group. The addition of a cross-protective effect toward HPV types 31/45/52 to HPV types 16/18, which is the direct target of the bivalent HPV vaccine, may possibly prevent around 82% of invasive cervical cancer cases in Japan. With regard to the preventive effect of histological abnormalities, we also reported significant reduction in incidence of cervical intraepithelial neoplasia (CIN)3 or worse. Thus, the efficacy of the vaccine has been demonstrated for precancerous disease, and the diverse symptoms after HPV vaccination are likely functional somatic. For the future of Japanese girls, there is a need to resume the proactive recommendation of HPV vaccination and for immediate action to be taken by the Japanese government.

DOI： 10.3390/vaccines8030362

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Fetal heart rate (FHR) variability (FHRV) and ST segment morphology are potential clinical indices of fetal well-being during labor. β-Adrenergic stimulation by circulating catecholamines has been hypothesized to contribute to both FHRV and ST segment morphology during labor, but this has not been tested during brief repeated fetal hypoxemia that is characteristic of labor. Near-term fetal sheep (0.85 gestation) received propranolol (β-adrenergic blockade; n = 10) or saline (n = 7) 30 min before being exposed to three 2-min complete umbilical cord occlusions (UCOs) separated by 3-min reperfusions. T/QRS ratio was calculated throughout UCOs and reperfusion periods, and measures of FHRV (RMSSD, SDNN, and STV) were calculated between UCOs. During the baseline period, before the start of UCOs, propranolol was associated with reduced FHR, SDNN, and STV but did not affect RMSSD or T/QRS ratio. UCOs were associated with rapid FHR decelerations and increased T/QRS ratio; propranolol significantly reduced FHR during UCOs and was associated with a slower rise in T/QRS ratio during the first UCOs, without affecting the maximal rise or T/QRS ratio during the second and third UCO. Between UCOs propranolol reduced FHR and T/QRS ratio but did not affect any measure of FHRV. These data demonstrate that circulating catecholamines do not contribute to FHRV during labor-like hypoxemia. Furthermore, circulating catecholamines did not contribute to the major rise in T/QRS ratio during labor-like hypoxemia but may regulate T/QRS ratio between brief hypoxemia.

DOI： 10.1152/ajpregu.00026.2020

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AIMS/INTRODUCTION: This study aimed to investigate the effects of the introduction of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosing gestational diabetes mellitus (GDM) on maternal and neonatal outcomes in Japan. MATERIALS AND METHODS: This was a retrospective study carried out at a tertiary center in Japan. Previously in Japan, GDM was diagnosed if two or more of the following Japan Society of Obstetrics and Gynecology (JSOG) criteria were met: fasting plasma glucose ≥100 mg/dL, 1-h value ≥180 mg/dL or 2-h value ≥150 mg/dL on the 75-g oral glucose tolerance. Since 2010, GDM has been diagnosed if one or more of the following IADPSG criteria are met: fasting plasma glucose ≥92 mg/dL, 1-h value ≥180 mg/dL or 2-h value ≥153 mg/dL on the 75-g oral glucose tolerance. We compared the pregnancy outcomes of all pregnant women with singleton pregnancies after 22 weeks' gestation at our hospital before (JSOG period) and after (IADPSG period) the IADPSG criteria were adopted. RESULTS: There were 3,912 women in the JSOG period and 4,772 in the IADPSG period. GDM prevalence increased from 2.9% in the JSOG period to 13% in the IADPSG period (P < 0.001). No significant differences between the groups were found in rates of macrosomia, or large for gestational age, and no significant differences were found in birthweight. The neonatal hypoglycemia rate and neonatal intensive care unit admission rate were significantly lower in the IADPSG period (adjusted odds ratio 0.51 and 0.78, respectively). CONCLUSIONS: Introduction of the IADPSG criteria for diagnosing GDM increased GDM diagnosis frequency fourfold, but reduced neonatal intensive care unit admission and neonatal hypoglycemia rates significantly.

DOI： 10.1111/jdi.13223

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Language：Japanese   Publisher：東京医科大学医学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00877&link_issn=&doc_id=20201113360054&doc_link_id=%2Fcr4tokyo%2F2020%2Fs07803%2F046%2F0301-0301%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcr4tokyo%2F2020%2Fs07803%2F046%2F0301-0301%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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OBJECTIVES: Currently, no unified set of criteria to classify preeclampsia (PE) exists. Further, no consensus has been reached whether fetal growth restriction (FGR) should be included in diagnostic criteria for PE. We examined the adequacy of including FGR in diagnostic criteria for PE. STUDY DESIGN: Singleton pregnancy patients who developed PE before 34 weeks of gestation managed at a tertiary center between 2010 and 2016 were included. Patients were divided into two groups according to cause for PE diagnosis. In addition, those diagnosed with PE because of gestational hypertension (GH) and FGR were divided into two groups according to presence of proteinuria or organ dysfunction during the expectant management. MAIN OUTCOME MEASURES: Pregnancy prolongation from PE diagnosis. RESULTS: Of 69 PE patients, 18 (28.1%) were diagnosed as PE with GH and only FGR (F group). Pregnancy prolongation between PE diagnosis to delivery was longer in the F group than in PE cases with primary organ dysfunction (P group) (21 vs 10 days, P = 0.049). Of 18 patients in the F group, 12 (66.7%) subsequently had proteinuria or organ dysfunction (S group). The remaining 6 patients (33.3%) had no subsequent proteinuria or organ dysfunction (N group). There were no significant differences in prolongation of pregnancy from organ dysfunction onset to delivery between the S and P groups (10 vs 10 days, P = 0.36). CONCLUSIONS: Organ dysfunction onset may reflect PE progression more accurately than FGR onset. Further investigations on whether to include FGR into the diagnostic criteria for PE are needed.

DOI： 10.1016/j.preghy.2020.05.002

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INTRODUCTION: This study aimed to assess the validity of applying the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) at any time during pregnancy. RESEARCH DESIGN AND METHODS: This multicenter cohort study was conducted at five Japanese facilities from January 2018 to April 2019. The study cohort included women at a high risk of GDM who met one or more of the following IADPSG criteria during early pregnancy: fasting plasma glucose (FPG) ≥92 mg/dL and 75 g oral glucose tolerance test (OGTT) value of ≥180 mg/dL at 1 hour, or ≥153 mg/dL at 2 hour (hereafter early-onset GDM). Women diagnosed with early-onset GDM were followed up without therapeutic intervention and underwent the 75 g OGTT again during 24-28 weeks of gestation. Those exhibiting the GDM patterns on the second 75 g OGTT were diagnosed with true GDM and treated, whereas those exhibiting the normal patterns were diagnosed with false positive early GDM and received no therapeutic intervention. RESULTS: Of the 146 women diagnosed with early-onset GDM, 69 (47%) had normal 75 g OGTT values at 24-28 weeks of gestation, indicating a false-positive result. FPG levels were significantly higher in the first 75 g-OGTT test than in the second 75 g-OGTT test (93 mg/dL and 87.5 mg/dL, respectively; p<0.001). FPG levels were high in 86 (59%) women with early-onset GDM during early pregnancy but in only 39 (27%) women during mid-pregnancy. Compared with false positive early GDM, true GDM was more frequently associated with adverse pregnancy outcomes. CONCLUSIONS: Although women with early-onset GDM were followed up without treatment, the results of repeated 75 g OGTT during mid-pregnancy were normal in about 50%. Our data did not support the adoption of IADPSG thresholds for the diagnosis of GDM prior to 20 weeks of gestation.

DOI： 10.1136/bmjdrc-2020-001234

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：(一社)関東連合産科婦人科学会  

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Language：Japanese   Publisher：日本遺伝カウンセリング学会  

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Language：Japanese   Publisher：日本遺伝カウンセリング学会  

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Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to clarify the risk factors for chlamydial infection and determine whether infection during pregnancy is associated with preterm birth in Japanese women. The subjects were women who underwent Chlamydia trachomatis polymerase chain reaction testing during a singleton pregnancy and delivered after the 22nd week of gestation at a tertiary care center between January 1, 2000 and December 31, 2016. We compared Chlamydia-positive (n = 259) and Chlamydianegative (n = 1,974) groups and evaluated the pregnancy outcomes. The Chlamydia-positive group had a higher rate of public assistance coverage, smoking during pregnancy, nulliparity, lack of a partner, presence of other sexually transmitted infections, high-risk social status, and younger age (P < 0.01). The incidence of preterm births was not different between the groups, with an odds ratio of 0.95 (95% confidence interval: 0.62-1.46). The incidences of low birth weight deliveries, premature rupture of membranes, and preterm premature rupture of membranes prior to the 37th week were also comparable between the groups. Chlamydial infection during pregnancy had no effect on preterm birth, even after adjustment for confounding factors.

DOI： 10.7883/yoken.JJID.2019.116

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本臨床細胞学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：(公社)日本産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

本邦では梅毒感染者の増加が報告され、梅毒合併妊娠及び先天梅毒の報告も増加している。今回、妊娠初期に梅毒血清反応陰性であったが妊娠中に梅毒感染をきたした梅毒合併妊娠の一例を報告する。症例は34歳2妊1産、自然妊娠後、初期より妊婦健診を受診し、妊娠初期検査では梅毒血清反応陰性であった。妊娠32週に手掌及び足部に皮疹が出現し、梅毒血清抗体価が陽性であったため妊娠36週0日に当科紹介となった。胎児は超音波、胎児心拍モニターともに明らかな異常は認めず、ペニシリンGの点滴で治療を開始し分娩まで継続した。妊娠37週6日に陣痛発来し自然経腟分娩に至り、新生児に先天梅毒を疑わせる症状は認めなかったが、同日より予防的にペニシリンGの点滴を開始した。その後、血清反応と髄液抗体反応の陰性を確認し治療を終了した。母体は治療を計4週間継続し、皮疹、血清抗体価ともに改善した。梅毒合併妊娠は、流死産、早産などのリスクを上昇させるため、診断後に早急に治療を要する。治療未完遂の際は先天梅毒を考慮し、新生児の血液検査、髄液検査を行う必要があり、検査、治療のために高次医療施設での管理が必要とされる。梅毒の臨床症状は多岐にわたるが、手掌、足底の皮疹は特徴的な所見であり、妊娠初期検査が陰性であっても症状や問診から梅毒が疑わしい場合には、早急に検査し治療につなげ、新生児先天梅毒の予防に努めるべきである。(著者抄録)

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

ターナー症候群の患者は、卵巣機能低下が背景にあるため自然妊娠率は低い。今回卵子提供から妊娠、分娩に至ったターナー症候群合併妊娠の一例を経験したので報告する。症例は36歳、13歳で低身長を契機にターナー症候群と診断され、成長ホルモン、エストロゲンの補充を開始し、以後Kauffman療法を継続していた。結婚後、不妊治療を行うも妊娠せず、卵子提供の方針とした。卵子提供で2度妊娠するも、初期自然流産及び妊娠38週時原因不明の子宮内胎児死亡という転帰であった。今回新たに3度目の卵子提供で妊娠し、妊娠12週までホルモン補充を行った。自宅血圧は異常なく、妊娠初期に妊娠糖尿病の診断に至るが、食事療法で血糖コントロールは良好であった。妊娠20週、30週の母体心エコーで異常はなかった。原因不明の子宮内胎児死亡の既往のため、妊娠34週より管理入院とした。妊娠36週6日に頸管拡張を行い、同日陣痛発来し、翌日妊娠37週0日に自然経腟分娩となった。児は2882g、女児、Apgar scoreは8点(1分後)/9点(5分後)だった。ターナー症候群合併妊娠は耐糖能異常や甲状腺機能低下症いった内科的合併症や妊娠中の妊娠高血圧症候群や妊娠糖尿病などの合併症の発生頻度が高いハイリスク妊娠であり、高い帝王切開率の報告がある。そのため、ターナー症候群合併妊娠では、妊娠前から分娩に至るまで適切な評価・診療が重要である。(著者抄録)

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：Japanese   Publisher：神奈川産科婦人科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

To estimate pregnancy complications in women newly diagnosed with gestational diabetes mellitus (GDM) according to the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria and verify the validity of introducing the IADPSG criteria in Japan. This retrospective study included data from women with singleton delivery at 22 weeks or later at a tertiary hospital during 2000-2009. We compared pregnancy outcomes between women who would now be diagnosed with GDM according to the IADPSG criteria but not by the old JSOG criteria (IGT group, n = 503) and women with normal glucose tolerance according to both the criteria (NGT group, n = 2,789). Multivariate analysis was performed and adjusted for background factors. Maternal age at delivery and pre-pregnancy BMI were significantly higher in the IGT group than in the NGT group, while gestational weeks at delivery did not differ between the groups. No difference was observed in the rates of GDM-related composite complications (defined as cases with at least one of the following: macrosomia, shoulder dystocia, neonatal hypoglycemia, neonatal hyperbilirubinemia, or neonatal respiratory distress syndrome) at 11.9% and 8.8% (adjusted odds ratio (OR) 1.30, 95% confidence interval (CI) 0.90-1.87, p = 0.16). Pregnancy outcomes did not differ significantly between the IGT and NGT groups, except for frequencies of total neonatal admissions at 10.5% and 7.1%, respectively (adjusted OR 1.55, 95% CI 1.12-2.13, p < 0.01).

DOI： 10.1507/endocrj.EJ19-0279

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Language：English   Publishing type：Research paper (scientific journal)  

Vitamin D deficiency is observed worldwide and represents a health hazard for mothers, infants and elderly persons. We know that many young Japanese women experience vitamin D insufficiency; however, there is a lack of knowledge regarding the serum 25-hydroxyvitamin D [25(OH)D] profile of pregnant Japanese women and of the association between maternal 25(OH)D level and maternal bone mass during pregnancy and lactation. In this longitudinal study, 160 pregnant Japanese women were enrolled; of them, 68 have been followed-up from the first trimester through at least 1 year of breast-feeding. We estimated serum 25(OH)D levels, intact PTH levels, calcaneus quantitative ultrasound (QUS: T score) scores, bone mineral density at the distal one-third of the radius, dietary intakes according to the Food Frequency Questionnaire, and sunlight exposure times. We found that Vitamin D deficiency is prevalent in Japanese women, irrespective of pregnancy or lactation, and our analysis suggested that 25(OH)D levels and BMI in the first trimester were related to the lactating women's bone mass from after delivery to 1 year after delivery.

DOI： 10.1007/s00774-019-01032-w

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：Japanese   Publisher：神奈川県医師会  

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Language：English   Publishing type：Research paper (scientific journal)  

We aimed to investigate the optimal range of gestational weight gain (GWG) for Japanese underweight (body mass index <18.5 kg/m2) women using the Japanese Birth Registry System. The study subjects included underweight women who were divided into groups according to the GWG recommendations of the Ministry of Health, Labour and Welfare (MHLW) (9-12 kg): <9.0 kg, group A; 9-12 kg, group B; and >12 kg, group C. The subjects were then classified according to the recommendations of the Institute of Medicine (IOM) (12.7-18.1 kg): <12.7 kg, group D; 12.7-18.1 kg, group E; and >18.1 kg, group F. In total, 148,135 cases were analysed. The frequencies of small for gestational age, preterm delivery, and caesarean delivery were as follows: 19.3%, 22.7%, and 28.5% for group A; 11.7%, 8.7%, and 22.8% for group B; 8.0%, 4.9%, and 21.5% for group C; 15.0%, 14.7%, and 25.2% for group D; 8.0%, 5.3%, and 21.5% for group E; and 7.0%, 5.5%, and 25.0% for group F, respectively. These results indicated that groups C and E had the best outcomes. Therefore, the IOM guidelines seem more appropriate than the MHLW guidelines. Therefore, the MHLW recommended GWG guidelines require revision.

DOI： 10.1038/s41598-019-54550-y

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Language：English   Publishing type：Research paper (scientific journal)  

KEY POINTS: •Therapeutic hypothermia needs to be started as early as possible in the first 6 h after acute injury caused by hypoxia-ischaemia (HI), but the severity and timing of HI are often unclear. In this study we evaluated whether measures of heart rate variability (HRV) might provide early biomarkers of HI. •The duration but not magnitude of suppression of HRV power and conversely increased sample entropy of the heart rate were associated with severity of HI, such that changes in the first 3 h did not discriminate between groups. •Relative changes in HRV power bands showed different patterns between groups and therefore may have the potential to evaluate the severity of HI. •Aberrant fetal heart rate patterns and increased arginine vasopressin levels in the first hour after moderate and severe HI were correlated with loss of EEG power after 3 days' recovery, suggesting potential utility as early biomarkers of outcome. ABSTRACT: Therapeutic hypothermia is partially neuroprotective after acute injury caused by hypoxia-ischaemia (HI), likely because the timing and severity of HI are often unclear, making timely recruitment for treatment challenging. We evaluated the utility of changes in heart rate variability (HRV) after HI as biomarkers of the timing and severity of acute HI. Chronically instrumented fetal sheep at 0.85 gestational age were exposed to different durations of umbilical cord occlusion to produce mild (n = 6), moderate (n = 8) or severe HI (n = 8) or to sham occlusion (n = 5). Heart rate (HR) and HRV indices were assessed until 72 h after HI. All HI groups showed suppressed very low frequency HRV power and elevated sample entropy for the first 3 h; more prolonged changes were associated with greater severity of HI. Analysis of relative changes in spectral power showed that the moderate and severe groups showed a shift towards higher HRV frequencies, which was most marked after severe HI. This shift was associated with abnormal rhythmic HR patterns including sinusoidal patterns in the first hour after HI, and with elevated plasma levels of arginine vasopressin, which were correlated with subsequent loss of EEG power by day 3. In conclusion, absolute changes in HRV power in the first 3 h after acute HI were not significantly related to the severity of HI. The intriguing relative shift in spectral power towards higher frequencies likely reflects greater autonomic dysfunction after severe HI. However, sinusoidal HR patterns and elevated vasopressin levels may have utility as biomarkers of severe HI.

DOI： 10.1113/JP278523

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