| 1. |
Natsuko Yokota 1, Reiko Inoue 2, Keiko Kawamura 3, Katsuko Egashira 4, Hiroyuki Kuma 5, Kiyoko Kato 6, The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients, Eur J Obstet Gynecol Reprod Biol, 2024.04, Objective: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker.
Study design: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P
Results: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies.
Conclusion: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.. |
| 2. |
Kenta Nitahara 1 2, Atsuki Kawamura 1, Yuka Kitamura 3, Kiyoko Kato 2, Satoshi H Namekawa 3, Masaaki Nishiyama 1, Chromatin remodeler CHD8 is required for spermatogonial proliferation and early meiotic progression, Nucleic Acids Res, 10.1093/nar/gkad1256, 16, gkad1256, 2024.01, Meiosis is a key step during germ cell differentiation, accompanied by the activation of thousands of genes through germline-specific chromatin reorganization. The chromatin remodeling mechanisms underpinning early meiotic stages remain poorly understood. Here we focus on the function of one of the major autism genes, CHD8, in spermatogenesis, based on the epidemiological association between autism and low fertility rates. Specific ablation of Chd8 in germ cells results in gradual depletion of undifferentiated spermatogonia and the failure of meiotic double-strand break (DSB) formation, leading to meiotic prophase I arrest and cell death. Transcriptional analyses demonstrate that CHD8 is required for extensive activation of spermatogenic genes in spermatogonia, necessary for spermatogonial proliferation and meiosis. CHD8 directly binds and regulates genes crucial for meiosis, including H3K4me3 histone methyltransferase genes, meiotic cohesin genes, HORMA domain-containing genes, synaptonemal complex genes, and DNA damage response genes. We infer that CHD8 contributes to meiotic DSB formation and subsequent meiotic progression through combined regulation of these meiosis-related genes. Our study uncovers an essential role of CHD8 in the proliferation of undifferentiated spermatogonia and the successful progression of meiotic prophase I.. |
| 3. |
Kei Kawana 1, Osamu Kobayashi 1, Yuji Ikeda 1, Hideaki Yahata 2, Takashi Iwata 3, Toyomi Satoh 4, Azusa Akiyama 4, Daichi Maeda 5, Yumiko Hori-Hirose 6, Yukari Uemura 7, Kaori Nakayama-Hosoya 8, Kanoko Katoh 1, Yuki Katoh 9, Takahiro Nakajima 1, Ayumi Taguchi 10, Atsushi Komatsu 1, Mikiko Asai-Sato 1, Naoko Tomita 1, Kiyoko Kato 2, Daisuke Aoki 3, Shizunobu Igimi 11, Ai Kawana-Tachikawa 8, Danny J Schust 12, Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3, JNCI Cancer Spectr, 10.1093/jncics/pkad101., 7, 6, 2024.03, Background: Although many human papillomavirus (HPV)-targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine.
Methods: In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16-positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety.
Results: In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7-specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner.
Conclusion: This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16-positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects.
Trial registration: jRCT2031190034.. |
| 4. |
Kimiyo Kikuchi 1,
Takehiro Michikawa 2,
Seiichi Morokuma 3 4,
Norio Hamada 5 6,
Yoshiko Suetsugu 1,
Subaru Ikeda 1,
Kazushige Nakahara 6,
Kiyoko Kato 5 6,
Masayuki Ochiai 5 7,
Eiji Shibata 8 9,
Mayumi Tsuji 8 10,
Masayuki Shimono 8 11,
Toshihiro Kawamoto 8,
Shouichi Ohga 5 7,
Koichi Kusuhara 8 11;
Japan Environment and Children’s Study Group, Sleep quality and temperament in association with autism spectrum disorder among infants in Japan, Commun Med (Lond), 10.1038/s43856-023-00314-9, 16;3, 1, 2023.06, Background: Sleep problems and irritable temperaments are common among infants with autism spectrum disorder (ASD). The prospective association between such sleep problems and irritable temperaments and ASDs needs to be determined for elucidating the mechanism and exploring the future intervention study. Thus, in this study, we investigated whether sleep quality and temperament in 1-month-old infants are associated with the onset of ASD in 3-year-old children. We also assessed its sex-stratified associations.
Methods: We conducted a longitudinal study using data from 69,751 mothers and infants from a large-cohort study, the Japan Environment and Children's Study. We examined the prospective association between infant sleep quality and temperament at 1 month of age and ASD diagnosis by 3 years of age.
Results: Here we show infants with longer daytime sleep have a higher risk of later ASD than those with shorter daytime sleep (risk ratio [RR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Infants who experienced intense crying have a higher risk of ASD than those who did not (RR: 1.31, 95% CI: 1.00-1.72). There is a difference in sex in the association between a bad mood and later ASD. In particular, female infants experiencing bad moods have a higher risk of ASD than others (RR: 3.59, 95% CI: 1.91-6.75).
Conclusions: The study findings provide important information for future intervention to reduce the risk of future ASD.. |
| 5. |
Yurika Mukai 1, Yoshiki Kudo 1, Takashi Sugiyama 2, Kiyoko Kato 3, Measures for pregnant women with coronavirus disease 2019 at the National University Hospital: 34th National University Perinatal Medical Center Conference, J Obstet Gynaecol Res, 10.1111/jog.15650, 49, 7, 1684-1688, 2024.03, As 2 years have passed since the outbreak of coronavirus disease 2019 (COVID-19), we had an examination of the measures taken at the perinatal medical and child centers during this period at 42 National University Hospital. The first questionnaire survey was conducted during March 17-25, 2022 and the second questionnaire survey was conducted during April 4-30, 2022. For the treatment of pregnant women with COVID-19, a public health center-coordinated triage system had been created and implemented in each region and prefecture. The issues related to the hospital management of pregnant women with COVID-19 include the hindrances to the normal functioning of the center, the limited number of hospital beds and medical care systems as the beds were dedicated to patients with COVID-19, and the problems associated with the mode of delivery. There were no set rules regarding the management of mothers and babies at delivery and thereafter. Initially, cesarean delivery was allowed in almost all cases to reduce the risk of exposure to medical staff. Furthermore, many institutions did not permit expressed breast milk feeding and direct breastfeeding during the quarantine period. The COVID-19 pandemic has been created a shortage of healthcare delivery systems. It is expected that the emergence of new infectious diseases and pandemics will cause the same pressure on systems providing healthcare in the future.. |
| 6. |
Riko Mishima 1, Masaru Tanaka 1, Rie Momoda 1, Masafumi Sanefuji 2, Seiichi Morokuma 3, Masanobu Ogawa 4, Kiyoko Kato 4, Jiro Nakayama 5, Longitudinal gut mycobiota changes in Japanese infants during first three years of life, J Biosci Bioeng, 10.1016/j.jbiosc.2023.01.007, 135, 4, 266-273, 2023.04, Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.. |
| 7. |
Midori Kimura 1, Sawako Matsuzaki 2, Kanako Ishii 3, Masanobu Ogawa 4, Kiyoko Kato 4, Individual experiences and issues in predictive genetic testing for untreatable hereditary neuromuscular diseases in Japan, Eur J Med Genet, 10.1016/j.ejmg.2022.104667, 66, 1, 2023.01, Predictive genetic testing (PT) for hereditary diseases that do not have effective treatment or prevention strategies places a psychological burden on parties and their families. There has been little research on the psychosocial aspects of PT in Japan, nor are there any guidelines. To address this gap, we conducted a questionnaire survey of parties at genetic risk for untreatable hereditary neuromuscular diseases, and the National Liaison Conference of Genetic Medicine Departments (GMDs). Of the 63 parties who responded to the survey, 10 (15.9%) had undergone PT. Of the 67 GMDs, only 18 facilities (26.9%) were conducting PT with written procedures. At least two of the six parties with such results felt that some follow-up would be helpful. One party had taken PT for preimplantation genetic testing for monogenic (PGT-M); four, who had no experience, provided free text responses indicating that PGT-M or prenatal genetic testing was chosen as a motivation. Eight were unaware of PT, and six were unaware of their blood relatives' diseases being "hereditary." The results highlighted the need to: 1) develop guidelines for PT in untreatable hereditary diseases; 2) provide access to PT information; and 3) share the "heritability" of diseases with family and relatives.. |
| 8. |
Mukai Y¹,Kudo Y¹,Sugiyama T²,Kato K³, Measures for pregnant women with coronavirus disease 2019 at the National University Hospital: 34th National University Perinatal Medical Center Conference, J Obstet Gynaecol Res, 10.1111/jog.15650, 49, 7, 1684-1688, JIF:1.6(2022)・JCI:0.61(2022), 2023.07, As 2 years have passed since the outbreak of coronavirus disease 2019 (COVID-19), we had an examination of the measures taken at the perinatal medical and child centers during this period at 42 National University Hospital. The first questionnaire survey was conducted during March 17-25, 2022 and the second questionnaire survey was conducted during April 4-30, 2022. For the treatment of pregnant women with COVID-19, a public health center-coordinated triage system had been created and implemented in each region and prefecture. The issues related to the hospital management of pregnant women with COVID-19 include the hindrances to the normal functioning of the center, the limited number of hospital beds and medical care systems as the beds were dedicated to patients with COVID-19, and the problems associated with the mode of delivery. There were no set rules regarding the management of mothers and babies at delivery and thereafter. Initially, cesarean delivery was allowed in almost all cases to reduce the risk of exposure to medical staff. Furthermore, many institutions did not permit expressed breast milk feeding and direct breastfeeding during the quarantine period. The COVID-19 pandemic has been created a shortage of healthcare delivery systems. It is expected that the emergence of new infectious diseases and pandemics will cause the same pressure on systems providing healthcare in the future.. |
| 9. |
Kikuchi K¹,Michikawa T²,Morokuma S³⁴,Hamada N⁵⁶,Suetsugu Y¹,Ikeda S¹, Nakahara K⁶,Kato K⁵⁶,Ochiai M⁵⁷,Shibata E⁸⁹,Tsuji M⁸¹⁰,Shimono M⁸¹¹,Kawamoto T⁸,Ohga S⁵⁷,Kusuhara K⁸¹¹;Japan Environment and Children’s Study Group
Collaborators;Japan Environment and Children’s Study Group: Kamijima M, Yamazaki s, Ohya Y, Kishi R, Yaegashi N, Hashimoto K, Mori C, Ito S, Yamagata Z, Inadera H, Nakayama T, Iso H, Shima M, Kurozawa Y, Suganuma N, Katoh T, Sleep quality and temperament in association with autism spectrum disorder among infants in Japan, Commun Med (Lond), 10.1038/s43856-023-00314-9, 3, 1, 82-82, 2023.06, Background: Sleep problems and irritable temperaments are common among infants with autism spectrum disorder (ASD). The prospective association between such sleep problems and irritable temperaments and ASDs needs to be determined for elucidating the mechanism and exploring the future intervention study. Thus, in this study, we investigated whether sleep quality and temperament in 1-month-old infants are associated with the onset of ASD in 3-year-old children. We also assessed its sex-stratified associations.
Methods: We conducted a longitudinal study using data from 69,751 mothers and infants from a large-cohort study, the Japan Environment and Children's Study. We examined the prospective association between infant sleep quality and temperament at 1 month of age and ASD diagnosis by 3 years of age.
Results: Here we show infants with longer daytime sleep have a higher risk of later ASD than those with shorter daytime sleep (risk ratio [RR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Infants who experienced intense crying have a higher risk of ASD than those who did not (RR: 1.31, 95% CI: 1.00-1.72). There is a difference in sex in the association between a bad mood and later ASD. In particular, female infants experiencing bad moods have a higher risk of ASD than others (RR: 3.59, 95% CI: 1.91-6.75).
Conclusions: The study findings provide important information for future intervention to reduce the risk of future ASD.. |
| 10. |
Mishima R¹,Tanaka M¹,Momoda R¹,Sanefuji M²,Morokuma S³,Ogawa M⁴,Kato K⁴,Nakayama J⁵, Longitudinal gut mycobiota changes in Japanese infants during first three years of life, J Biosci Bioeng, 10.1016/j.jbiosc.2023.01.007, 135, 4, 266-273, JIF:2.8(2022)・JCI:0.69(2022), 2023.04, Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.. |
| 11. |
Kimura M¹,Matsuzaki S²,Ishii K³,Ogawa M⁴,Kato K⁴, Individual experiences and issues in predictive genetic testing for untreatable hereditary neuromuscular diseases in Japan, Eur J Med Genet, 10.1016/j.ejmg.2022.104667, 66, 1, 104667-104667, JIF:1.9(2022)・JCI:0.53(2022), 2023.01, Predictive genetic testing (PT) for hereditary diseases that do not have effective treatment or prevention strategies places a psychological burden on parties and their families. There has been little research on the psychosocial aspects of PT in Japan, nor are there any guidelines. To address this gap, we conducted a questionnaire survey of parties at genetic risk for untreatable hereditary neuromuscular diseases, and the National Liaison Conference of Genetic Medicine Departments (GMDs). Of the 63 parties who responded to the survey, 10 (15.9%) had undergone PT. Of the 67 GMDs, only 18 facilities (26.9%) were conducting PT with written procedures. At least two of the six parties with such results felt that some follow-up would be helpful. One party had taken PT for preimplantation genetic testing for monogenic (PGT-M); four, who had no experience, provided free text responses indicating that PGT-M or prenatal genetic testing was chosen as a motivation. Eight were unaware of PT, and six were unaware of their blood relatives' diseases being "hereditary." The results highlighted the need to: 1) develop guidelines for PT in untreatable hereditary diseases; 2) provide access to PT information; and 3) share the "heritability" of diseases with family and relatives.. |
| 12. |
Kikuchi K¹,Islam R²,Sato Y¹,Nishikitani M²,Izukura R³,Jahan N⁴, Yokota F⁵,Ikeda S¹,Sultana N⁴,Nessa M⁶,Nasir M⁶,Ahmed A⁷, Kato K⁸,Morokuma S¹,Nakashima N², Telehealth Care for Mothers and Infants to Improve the Continuum of Care: Protocol for a Quasi-Experimental Study, JMIR Res Protoc, 10.2196/41586, 11, 12, e41586-e41586, JIF:1.7(2022)・JCI0.52(2022), 2022.12, Background: Ensuring an appropriate continuum of care in maternal, newborn, and child health, as well as providing nutrition care, is challenging in remote areas. To make care accessible for mothers and infants, we developed a telehealth care system called Portable Health Clinic for Maternal, Newborn, and Child Health.
Objective: Our study will examine the telehealth care system's effectiveness in improving women's and infants' care uptake and detecting their health problems.
Methods: A quasi-experimental study will be conducted in rural Bangladesh. Villages will be allocated to the intervention and control areas. Pregnant women (≥16 gestational weeks) will participate together with their infants and will be followed up 1 year after delivery or birth. The intervention will include regular health checkups via the Portable Health Clinic telehealth care system, which is equipped with a series of sensors and an information system that can triage participants' health levels based on the results of their checkups. Women and infants will receive care 4 times during the antenatal period, thrice during the postnatal period, and twice during the motherhood and childhood periods. The outcomes will be participants' health checkup coverage, gestational and neonatal complication rates, complementary feeding rates, and health-seeking behaviors. We will use a multilevel logistic regression and a generalized estimating equation to evaluate the intervention's effectiveness.
Results: Recruitment began in June 2020. As of June 2022, we have consented 295 mothers in the study. Data collection is expected to conclude in June 2024.
Conclusions: Our new trial will show the effectiveness and extent of using a telehealth care system to ensure an appropriate continuum of care in maternal, newborn, and child health (from the antenatal period to the motherhood and childhood periods) and improve women's and infants' health status.. |
| 13. |
Yoshida K¹,Kusama K²,Azumi M¹,Yoshie M¹,Kato K³,Tamura K⁴, Endoplasmic reticulum stress-regulated high temperature requirement A1 (HTRA1) modulates invasion and angiogenesis-related genes in human trophoblasts, J Pharmacol Sci, 10.1016/j.jphs.2022.10.003., 150, 4, 267-274, JIF:3.5(2022)・JCI:0.92(2022), 2022.12, The pathogenesis of hypertensive disorder of pregnancy (HDP), which affects about 10% of pregnant women, is still incompletely understood. Our previous study showed that endoplasmic reticulum (ER) stress influences high-temperature requirement A serine peptidase 1 (HTRA1) expression and trophoblast invasion. However, the involvement of ER stress in the regulation of HTRA subtype expression and pathophysiology of HDP has not been characterized in extravillous trophoblasts (EVTs). To investigate this, HTR8/SVneo EVTs cell line was treated with the ER stress inducers Thapsigargin (Thap) or Tunicamycin (Tuni). Treatment with either Thap or Tuni inhibited trophoblast invasion, reduced HTRA1 and HTRA3 expression, but did not alter HTRA2 or HTRA4 expression. Knockdown of HTRA1 or HTRA3 also inhibited trophoblast invasion. Furthermore, treatment with either ER stress inducer or HTRA1 silencing increased the ratio of soluble fms-like tyrosine kinase-1/placental growth factor (sFLT1/PlGF), which is a marker of HDP. Immunohistochemical analysis revealed that HTRA1 is localized to EVTs and the endometrial decidua in the placenta of patients with HDP. These results suggest that factors that cause ER stress could result in the inhibition of EVTs invasion via HTRA1.. |
| 14. |
Michikawa T¹,Morokuma S²,Yamazaki S³,Yoshino A⁴,Sugata S⁴,Takami A⁴, Nakahara K⁵,Saito S⁶,Hoshi J⁶, Kato K⁵,Nitta H³,Nishiwaki Y¹, Maternal Exposure to Fine Particulate Matter and Its Chemical Components Increasing the Occurrence of Gestational Diabetes Mellitus in Pregnant Japa-nese Women, JMA J, 10.31662/jmaj.2022-0141, 5, 4, 480-490, 2022.10, Introduction: PM2.5 exposure is a suspected risk factor for diabetes. It is hypothesized that maternal PM2.5 exposure contributes to the development of gestational diabetes mellitus (GDM). The association between PM2.5 exposure and GDM is controversial and limited evidence is available for the exposure to PM2.5 chemical components. We investigated the association between maternal exposure to total PM2.5 mass and its components, particularly over the first trimester (early placentation period), and GDM.
Methods: Data were obtained from the Japan Perinatal Registry Network database, which includes all live births and stillbirths after 22 weeks of gestation at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). At one fixed monitoring site, we performed daily filter sampling of fine particles and measured daily concentrations of carbon and ion components. The average concentrations of total PM2.5 and its components over the 3 months before pregnancy and the first (0-13 gestational weeks) and second (14-27 gestational weeks) trimesters were calculated and assigned to each woman. We estimated the odds ratios (ORs) of GDM in a multilevel logistic regression model.
Results: Among 82,773 women (mean age at delivery = 33.7 years) who delivered singleton births, 3,953 (4.8%) had GDM. In the multiexposure period model, an association between total PM2.5 exposure and GDM was observed for exposure over the first trimester (OR per interquartile range (IQR = 3.63 μg/m3) increase = 1.09; 95% confidence interval (CI) = 1.02-1.16), but not for the 3 months before pregnancy or the second trimester. For PM2.5 components, only organic carbon exposure over the first trimester was positively associated with GDM (OR per IQR (0.51 μg/m3) increase = 1.10; 1.00-1.21).
Conclusions: This is the first evidence that exposure to total PM2.5 and one of its components, organic carbon, over the first trimester increases GDM occurrence in Japan.. |
| 15. |
Magarifuchi N¹,Yamada Y¹,Oishi Y²,Kato K³,Taguchi K⁴,Oda Y⁵, Neuroectodermal Rosettes in Immature Teratomas Are Not the Counterpart of Embryonal Tumours With Multilayered Rosettes, Anticancer Res., 10.21873/anticanres.15934, 42, 9, 4337-4344, 2022.09, Background/aim: Immature teratomas (IMT) are malignant germ cell tumours composed of immature embryonal tissue, mostly neuroectodermal tubules and rosettes. Meanwhile, embryonal tumours with multilayered rosettes (ETMR) are aggressive central nervous system tumours composed of neurocyte proliferation with rosette formation. The histopathological appearance of rosette formation in ETMR is the same as that in IMT. Recently, 19q13.42 amplification was reported as a specific genetic marker of ETMR. The aim of this study was to compare ETMR with IMT from histological, immunohistochemical and genetic perspectives.
Materials and methods: We retrospectively analysed tumour samples from 48 patients with IMT and 1 patient with ETMR. We performed fluorescence in situ hybridization (FISH) analysis, which revealed amplification of the 19q13.42 locus in the ETMR case. In addition, immunohistochemical analyses of LIN28A, β-catenin and p53 were performed.
Results: In FISH analysis all 48 cases of IMT showed diploidy. By immunohistochemical analysis, LIN28A expression was observed in 54% of IMT cases (25/48 cases) and in the ETMR case. Nuclear staining of β-catenin was observed in 33% of IMT cases (16/48 cases). Meanwhile, aberrant expression of p53 was not identified in IMT nor ETMR cases.
Conclusion: Genetic changes associated with IMT differ from those in ETMR, but LIN28A protein immunohistochemical expression, which is specific for ETMR, can be a biomarker for the immature neuroepithelial component in IMT.. |
| 16. |
Kodama K¹, Tateishi C₂, Oda T², Cui L¹, ＃Kuramoto K¹, Yahata H¹, Okugawa K¹, Maenohara S¹, Yagi H¹, Yasunaga M¹, Onoyama I¹, Asanoma K¹, Mori T², Katayama Y², Kato K¹, Development of novel tracers for sentinel node identification in cervical cancer, Cancer Sci, 10.1111/cas.15927, 114, 11, 4216-4224, JIF：5.7(2022)・JCI：1.09(2022), 2023.11, Indocyanine green (ICG) with near-infrared (NIR) fluorescence imaging is used for lymphatic mapping. However, binding of ICG to blood proteins like serum albumin can shorten its retention time in sentinel lymph nodes (SLNs). Here, we investigated the efficacy and safety of a new fluorescence tracer comprising phytate and liposome (LP)-encapsulated ICG. Coadministration of phytate with LP containing phosphatidic acid promotes chelation mediated by Ca2+ in bodily fluids to enhance SLN retention. Uniformly sized LPs (100 nm) encapsulating ICG under conditions that minimized fluorescence self-quenching during storage were produced. We analyzed the behavior of the new tracer (ICG-phytate-LP) and control tracers (ICG and ICG-LP) in the lymphatic flow of mice in terms of lymph node retention time. We also tested lymphatic flow and safety in pigs that have a more human-like lymphatic system. LPs encapsulating stabilized ICG were successfully prepared. Mixing LP with phytate in the presence of Ca2+ increased both the particle size and negative surface charge. In mice, ICG-phytate-LP had the best lymph node retention, with a fluorescence intensity ratio that increased over 6 h and then decreased slowly over the next 24 h. In pigs, administration of ICG and ICG-phytate-LP resulted in no death or weight loss. There were no obvious differences between blood test results for the ICG and ICG-phytate-LP groups, and the overall safety was good. ICG-phytate-LP may be a useful new tracer for gynecological cancers that require time for lymph node identification due to a retroperitoneal approach.. |
| 17. |
Yasunaga M, Yahata H, Okugawa K, Hori E, Hachisuga K, Maenohara S, Kodama K, Yagi H, Ohgami T, Onoyama I, Asanoma K, Kato K, Decision-making for Subsequent Therapy for Patients With Recurrent or Advanced Endometrial Cancer Based on the Platinum-free Interval, Am J Clin Oncol, 10.1097/COC.0000000000001021, 46, 9, 387-391, JIF:2.6(2022)・JCI：0.47(2022), 2023.09, Objective: The aim of this study was to evaluate the progression-free survival (PFS) and overall response rate (ORR) of patients with recurrent endometrial cancer (REC) or advanced endometrial cancer (AEC) retreated with platinum-containing chemotherapy (PCC) based on the platinum-free interval (PFI). We compared our results with those reported in the KEYNOTE-775 study (that used pembrolizumab plus lenvatinib).
Methods: A retrospective analysis was conducted of 65 patients with REC or AEC retreated with PCC between 2005 and 2020 at our hospital. Various clinicopathologic variables were analyzed: (1) age, (2) performance status, (3) histology, (4) history of pelvic irradiation in the adjuvant setting, (5) PFI, (6) chemotherapy regimen, (7) PFS and overall survival after retreatment with PCC, and (8) best ORR. Survival analyses were performed using Kaplan-Meier curves and log-rank tests.
Results: The best ORR and PFS were 43.3% and 9.5 months, respectively, in patients with REC/AEC with a PFI ≥6 months. These results were comparable with those of patients treated with pembrolizumab and lenvatinib. The best ORR and PFS of patients with a PFI of Conclusions: Pembrolizumab plus lenvatinib seems to be a better treatment choice for patients with REC or AEC with a PFI of |
| 18. |
Tomonobe H¹, Ohishi Y¹², Hachisuga K³, Yahata H³, Kato K³, Oda Y¹, High-grade Serous Carcinoma can Show Squamoid Morphology Mimicking True Squamous Differentiation, Am J Surg Pathol, 10.1097/PAS.0000000000002089, 47, 9, 967-976, JIF：5.6(2022)・JCI：2.24(2022), 2023.09, Tubo-ovarian high-grade serous carcinoma (HG-SC) and ovarian endometrioid carcinoma (EC) can show overlapping morphologic features, such as glandular and solid patterns. The differential diagnosis of these subtypes is thus sometimes difficult. The existence of "squamous differentiation" tends to lead to a diagnosis of EC rather than HG-SC. We noticed that HG-SC can contain a "squamoid component," but its nature has been poorly investigated. This study was thus established to clarify the nature of this "squamoid component" in HG-SC by investigating its frequency and immunohistochemical features. We reviewed hematoxylin and eosin-stained slides of 237 primary untreated cases of tubo-ovarian HG-SC and identified 16 cases (6.7%) of HG-SC with "squamoid component." An immunohistochemical staining panel (CK5/6, CK14, CK903, p40, p63, WT1, ER, and PgR) was used to analyze all of these 16 cases. We also selected 14 cases of ovarian EC with "squamous differentiation" as a control. The "squamoid component" in HG-SC was completely p40-negative and showed significantly lower expression of CK5/6, CK14, CK903, and p63 than the "squamous differentiation" in EC. The immunophenotype of the "squamoid component" in HG-SC was concordant with the conventional HG-SC component (WT1-positive/ER-positive). Furthermore, all 16 tumors were confirmed to be truly "HG-SC" by the findings of aberrant p53 staining pattern and/or WT1/p16 positivity, and the lack of mismatch repair deficiency and POLE mutation. In conclusion, HG-SC can on rare occasions show a "squamoid component" mimicking "squamous differentiation." However, the "squamoid component" in HG-SC does not represent true "squamous differentiation." The "squamoid component" is one part of the morphologic spectrum of HG-SC, which should be interpreted carefully for the differential diagnosis of HG-SC and EC. An immunohistochemical panel including p40, p53, p16, and WT1 is a useful adjunct to achieve a correct diagnosis.. |
| 19. |
Okugawa K¹, Yahata H², Ohgami T², Yasunaga M², Asanoma K², Kobayashi H³, Kato K², An update of oncologic and obstetric outcomes after abdominal trachelectomy using the FIGO 2018 staging system for cervical cancer: a single-institution retrospective analysis, J Gynecol Oncol, 10.3802/jgo.2023.34.e41, 34, 3, e41-e41, 2023.05, Objective: To apply the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system to all patients who underwent trachelectomy in our previous study and to update the oncologic and obstetric results.
Methods: We retrospectively reviewed the medical records of patients in whom abdominal trachelectomy was attempted between June 2005 and September 2021. The FIGO 2018 staging system for cervical cancer was applied to all patients.
Results: Abdominal trachelectomy was attempted for 265 patients. Trachelectomy was converted to hysterectomy in 35 patients, and trachelectomy was completed successfully in 230 (conversion rate: 13%). Applying the FIGO 2018 staging system, 40% of the patients who underwent radical trachelectomy had stage IA tumors. Among 71 patients who had tumors measuring ≥2 cm, 8 patients were classified as stage IA1 and 14 as stage IA2. Overall recurrence and mortality rates were 2.2% and 1.3%, respectively. One hundred twelve patients attempted to conceive after trachelectomy; 69 pregnancies were achieved in 46 patients (pregnancy rate: 41%). Twenty-three pregnancies ended in first-trimester miscarriage, and 41 infants were delivered between gestational weeks 23 and 37; 16 were deliveries at term (39%) and 25 were premature deliveries (61%).
Conclusion: This study suggested that patients judged to be ineligible for trachelectomy and patients receiving overtreatment will continue to appear using the current standard eligibility criteria. With the revisions to the FIGO 2018 staging system, the preoperative eligibility criteria for trachelectomy, which were based on the FIGO 2009 staging system and tumor size, should be changed.
Keywords: FIGO 2018 Staging System; Trachelectomy; Treatment Outcome; Uterine Cervical Neoplasms..  |
| 20. |
Murakami K¹², Hamazaki N¹, Hamada N¹², Nagamatsu G¹, Okamoto I³⁴, Ohta H³⁴, Nosaka Y³⁴, Ishikura Y³⁴, Kitajima TS⁵, Semba Y⁶, Kunisaki Y¹⁶, Arai F¹, Akashi K⁶, Saitou M³⁴⁷, Kato K², Hayashi K⁸⁹¹⁰¹¹, Generation of functional oocytes from male mice in vitro, Nature, 10.1038/s41586-023-05834-x, 615, 7954, 900-906, 2023.04, Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes(1-5). Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.. |
| 21. |
濱田律雄¹、加藤聖子², 生殖細胞の発生からみた再生, HORMONE FRONTIER IN GYNECOLOGY 特集 ヒトの再生をめぐる諸問題, 30, 1, 21-28, 2023.03, 哺乳類の生殖細胞は、雌では卵子、雄では精子へと分化する。卵子と精子は融合して受精卵となり新しい個体が誕生し、その遺伝情報およびエピジェネティック情報を次世代に伝える。近年、多能性幹細胞であるiPS細胞／ES細胞を用いて、対外培養で生殖細胞の発生を再現する研究が進んでいる。これらの研究は、生殖細胞発生のメカニズムをさらに解明するための基盤となる。今後、対外培養によるiPS細胞からの卵子形成過程の観察をヒトに応用して不妊症への病態解明に寄与することなど、生殖医療への応用が期待される。. |
| 22. |
Yahata H¹, Kato K¹, Shimokawa M², Kawamura K¹, Shimono N³, Kawana K⁴, Okamoto A⁵, Aoki D⁶, Kimura T⁷, Study of the effects of in-person attendance at academic conferences on the health of the attendees under COVID-19 pandemic, J Obstet Gynaecol Res, 10.1111/jog.15626, Online ahead of print, 2023.02, Objective: To analyze the effects of in-person attendance at an academic conference held during the Covid-19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid-19 virus.
Methods: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7.
Results: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in-person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167-0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229-0.690, p = 0.0010]).
Conclusion: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in-person attendance at the congress.
Keywords: Covid-19 virus; academic conference; health of the attendees.. |
| 23. |
Yagi H¹, Oyamada I², Asanoma K², Kawakami M², Maenohara S², Kodama K², Matsumura Y², Hamada N², Hori E², Hachisuga K², Yasunaga M², Ohgami T², Okugawa K², Yahata H², Kato K², Tumor-derived ARHGAP35 mutations enhance the Gα13-Rho signaling axis in human endometrial cancer, Cancer Gene Ther, 10.1038/s41417-022-00547-1, 30, 2, 313-323, JIF：5.854(2021)・JCI：1.28(2021), 2023.02, Dysregulated G protein-coupled receptor signaling is involved in the formation and progression of human cancers. The heterotrimeric G protein Gα13 is highly expressed in various cancers and regulates diverse cancer-related transcriptional networks and cellular functions by activating Rho. Herein, we demonstrate that increased expression of Gα13 promotes cell proliferation through activation of Rho and the transcription factor AP-1 in human endometrial cancer. Of interest, the RhoGTPase activating protein (RhoGAP), ARHGAP35 is frequently mutated in human endometrial cancers. Among the 509 endometrial cancer samples in The Cancer Genome Atlas database, 108 harbor 152 mutations at 126 different positions within ARHGAP35, representing a somatic mutation frequency of 20.2%. We evaluated the effect of 124 tumor-derived ARHGAP35 mutations on Gα13-mediated Rho and AP-1 activation. The RhoGAP activity of ARHGAP35 was impaired by 55 of 124 tumor-derived mutations, comprised of 23 nonsense, 15 frame-shift, 15 missense mutations, and two in-frame deletions. Considering that ARHGAP35 is mutated in >2% of all tumors, it ranks among the top 30 most significantly mutated genes in human cancer. Our data suggest potential roles of ARHGAP35 as an oncogenic driver gene, providing novel therapeutic opportunities for endometrial cancer.. |
| 24. |
Asanoma K¹, Yahata H¹, Okugawa K¹, Ohgami T¹, Yasunaga M¹, Kodama K¹, Onoyama I¹, Kenjo H¹, Shimokawa M², Kato K¹, Impact of obesity on robotic-assisted surgery in patients with stage IA endometrial cancer and a low risk of recurrence: An institutional study, JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 10.1111/jog.15434, 48, 12, 3226-3232, 2022.12, Aim Westernization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic-assisted surgery according to whether patients are obese, morbidly obese, or nonobese. Methods Sixty-three patients with endometrial cancer who underwent robotic-assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) = 30 and = 35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated. Results Conversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between-group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2-29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19-46). Conclusion Patients with endometrial cancer who are obese can be treated safely by robotic-assisted surgery with a low risk of complications and few relapses.. |
| 25. |
Yasunaga M¹, Yahata H², Okugawa K², Shimokawa M³, Maeda Y², Hori E², Kodama K², Yagi H², Ohgami T², Onoyama I², Asanoma K², Kato K², Prognostic impact of adding bevacizumab to carboplatin and paclitaxel for recurrent, persistent, or metastatic cervical cancer, TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY, 10.1016/j.tjog.2022.06.005, 61, 5, 818-822, JIF:1.944(2021)・JCI:0.61(2021), 2022.09, Objective: Recent randomized phase III trial has shown significant benefit in overall survival (OS) for patients with advanced cervical cancer by adding bevacizumab to conventional chemotherapy. The aim of this study was to evaluate the prognostic impact for Japanese recurrent, persistent, or metastatic cervical cancer patients where bevacizumab was added to paclitaxel plus carboplatin.
Materials and methods: A retrospective analysis was performed on 90 patients with recurrent, persistent, or metastatic cervical cancer mainly treated by paclitaxel plus carboplatin between 2005 and 2019 at our hospital. Data for the following clinicopathological variables were analyzed: (1) bevacizumab use; (2) histology; (3) disease presentation; (4) performance status; (5) prior chemotherapy containing platinum agent; (6) pelvic disease; (7) prior pelvic radiotherapy; (8) location of target lesions. Survival analysis was performed using Kaplan-Meier curves, log-rank tests, Wilcoxon tests, and Cox proportional hazards models combined with propensity score matching.
Results: Adding bevacizumab to paclitaxel plus carboplatin showed significantly increased complete response to compared with that of non-users. In a Cox regression hazard model, bevacizumab use tended to show better OS though without statistically significance. After propensity score matching, adding bevacizumab to paclitaxel plus carboplatin showed a significant better OS by univariate analysis using Wilcoxon test, not by log-rank test.
Conclusion: Adding bevacizumab to paclitaxel plus carboplatin showed a limited prognostic impact for recurrent, persistent or advanced cervical cancer patients in the real world. Further effective second-line treatments are needed to prolong OS of patients with recurrent, persistent or advanced cervical cancer.
Keywords: Bevacizumab; Carboplatin; Drug therapy; Prognosis; Uterine cervical neoplasms.. |
| 26. |
Yasutake N¹, Iwasaki T², Yamamoto H², Sonoda K³, Kodama K⁴, Okugawa K⁴, Asanoma K⁴, Yahata H⁴, Kato K⁴, Oda Y², Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma, PATHOLOGY RESEARCH AND PRACTICE, 10.1016/j.prp.2022.153920, 235, 記事番号：153920, 2022.07, Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7-30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p Keywords: CDK8; Leiomyosarcoma; MED12; Prognosis; Uterus.. |
| 27. |
Sawano T¹, Kondo T², Ebihara G¹, Nagata K², Inoue H³, Fujiyoshi J¹, Ochiai M¹, Kido S⁴, Fujita Y⁴, Sakai Y¹, Kato K⁴, Tajiri T², Ohga S¹, Lung to thorax transverse area ratio as a predictor of neurodevelopmental outcomes in fetuses with congenital diaphragmatic hernia, Early Human Development, 10.1016/j.earlhumdev.2022.105598, 170, 記事番号：105598, 2022.07, Introduction: Infants with congenital diaphragmatic hernia (CDH) are at risk of neurodevelopmental disabilities. This study aimed to investigate the association between lung to thorax transverse area ratio (LTR) and neurodevelopmental outcomes at 3 years of age in fetuses with CDH.
Methods: We performed a retrospective study of infants with prenatally diagnosed isolated left-sided CDH born in Kyushu University Hospital between 2008 and 2016. We examined the association between prenatal ultrasound findings including LTR and development quotient (DQ) at 36 to 42 months of chronological age.
Results: We identified 34 live-born fetuses with isolated left-sided CDH, of which 30 survived and four died before discharge. The median LTR in the survivors was higher than in the non-survivors (p Conclusion: In fetuses with isolated left-sided CDH, prenatal LTR predicts the mortality but not neurodevelopmental outcomes at 3 years of age.
Keywords: Congenital diaphragmatic hernia; Neurodevelopmental outcome; Predictive parameter; Prenatal diagnosis.. |
| 28. |
Okugawa K¹, Yahata H¹, Hachisuga K¹, Tomonobe H¹, Yasutake N¹, Kodama K¹, Kenjo H¹, Yagi H¹, Ohgami T¹, Yasunaga M¹, Onoyama I¹, Asanoma K¹, Hori E¹, Ohishi Y² ³, Oda Y², Kato K¹, Evaluation of Clinical Significance of Lymphovascular Space Invasion in Stage IA Endometrial Cancer, Oncology, 10.1159/000521382, 100, 4, 195-202, JIF：3.734(2021)・JCI：0.6(2021), 2022.04, Introduction: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer.
Methods: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports.
Results: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (p = 0.07 and p = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (p = 0.11 and p = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (p = 0.92 and p = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively.
Conclusion: LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer.
Keywords: Endometrial cancer; Lymphovascular space invasion; Prognostic factors; Treatment outcome.. |
| 29. |
Yahata H¹,Kodama K²,Okugawa K²,Hachisuga K²,Yasutake N²,Maenohara S²,Yagi H²,Yasunaga M²,Ohgami T²,Onoyama I²,Asanoma K²,Kobayashi H³,Sonoda K⁴,Baba S⁵,Ishigami K⁵,Ohishi Y⁶,Oda Y⁷,Kato K², Long-term follow up after sentinel node biopsy alone for early-stage cervical cancer, Gynecol Oncol, 10.1016/j.ygyno.2022.01.031, 165, 1, 149-154, 2022.04, Objective: Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy.
Methods: We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed.
Results: The median age of the patients was 34 years (range, 21-73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25-145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate.
Conclusions: SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate.
Keywords: Cervical cancer; Long-term follow up; Sentinel node biopsy.. |
| 30. |
Nakahara K¹, Michikawa T², Morokuma S³⁴, Hamada N1⁴, Ogawa M¹⁴, Kato K¹⁴, Sanefuji M⁴⁵, Shibata E⁶⁷, Tsuji M⁶⁸, Shimono M⁶⁹, Kawamoto T⁶, Ohga S⁴⁵, Kusuhara K⁶⁹, Japan Environment and Children’s Study Group, Association of physical activity and sleep habits during pregnancy with autistic spectrum disorder in 3-year-old infants, Commun Med (Lond), 10.1038/s43856-022-00101-y, 2, 35, eCollection 2022, 2022.04, Background: We hypothesized that maternal lifestyle factors, such as physical activity and sleep habits, may be associated with autism spectrum disorder (ASD) in infants. This study aimed to investigate the association between maternal physical activity and sleep before and during pregnancy with infant ASD diagnosed by the age of 3 years.
Methods: We used the data from the Japan Environment and Children's Study between 2011 and 2014. The study included 103,060 pregnant women, among which, 69,969 women were analyzed. Participants were asked about their physical activity and sleep before and during pregnancy using questionnaires during pregnancy. Maternal physical activity was estimated using the international physical activity questionnaire. Based on the levels of physical activity before or during pregnancy, the participants were divided into five groups. Maternal sleep was analyzed based on sleep duration and bedtime. The outcome was diagnosis of ASD in 3-year-old infants.
Results: In mothers with higher physical activity levels during pregnancy, the risk ratios (RR) for ASD in their 3-year-old infants were lower (RR = 0.61, 95% confidence interval (CI) = 0.42-0.90). In contrast, too short (10 h) sleep durations during pregnancy were associated with higher risk ratios for ASD than 7-8 h sleep duration (too short: RR = 1.87, 95% CI = 1.21-2.90; too long: RR = 1.56, 95% CI = 1.00-2.48). These associations were not observed before pregnancy.
Conclusion: Maternal physical activity and sleep duration during pregnancy may be associated with ASD in infants.
Keywords: Autism spectrum disorders; Epidemiology; Paediatric research.. |
| 31. |
Nakahara K¹, Morokuma S², Maehara K¹, Okawa H¹, Funabiki Y³ ⁴, Kato K¹, Association of fetal eye movement density with sleeping and developmental problems in 1.5-year-old infants, Sci Rep, 10.1038/s41598-022-12330-1, 12, 1, 8236-8236, 2022.03, Eye movement density (EMD) is an evaluation index of rapid eye movements observed during sleep. This study aimed to investigate the association of fetal EMD with sleeping and developmental problems in infancy. We observed 60 normal singleton pregnancies (gestational age 28-37 weeks) using ultrasonography for 1 h. Fetal eye movements were counted, and EMD was calculated. Participants answered questionnaires regarding their child's sleep and development 1.5 years after their delivery. The outcomes of an infant's sleep were night awakening (yes or no), bedtime (before or after 22:00), and nighttime sleep duration ( |
| 32. |
Kiyokoba R¹ ², Uchiumi T³ ⁴, Yagi M¹ ⁵, Toshima T¹, Tsukahara S¹, Fujita Y², Kato K², Kang D¹, Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction, Sci Rep, 10.1038/s41598-022-07893-y, 12, 1, 4056-4056, 2022.03, Fetal growth restriction (FGR) and pre-eclampsia with fetal growth restriction (PE/FGR) are high-risk perinatal diseases that may involve high levels of human chorionic gonadotropin (hCG) and mitochondrial dysfunction. However, little is known about how these factors affect placental function. We investigated how mitochondrial dysfunction and high hCG expression affected placental function in unexplained FGR and PE/FGR. We observed elevated expression of hCGβ and growth differentiation factor 15 mRNA and protein levels in the placenta with both diseases. Likewise, antiangiogenic factors, such as Ang2, IP10, sFlt1, IL8, IL1B, and TNFα, were also upregulated at the mRNA level. In addition, the expression of COXI and COXII which encoded by mitochondrial DNA were significantly decreased in both diseases, suggesting that mitochondrial translation was impaired. Treatment with hCG increased Ang2, IP10, IL8, and TNFα mRNA levels in a dose-dependent manner via the p38 and JNK pathways. Mitochondrial translation inhibitors increased hCGβ expression through stabilization of HIF1α, and increased IL8 and TNFα mRNA expression. These results revealed that high expression of hCG due to mitochondrial translational dysfunction plays an important role in the pathogenesis of FGR and PE/FGR.. |
| 33. |
Morisaki N¹,Nagata C²,Morokuma S³,Nakahara K⁴,Kato K⁴,Sanefuji M⁵ ⁶,Shibata E⁷ ⁸,Tsuji M⁸ ⁹, Shimono M⁸ ¹⁰,Kawamoto T⁸,Ohga S⁵ ⁶,Kusuhara K⁸ ¹⁰, Japan Environment, Children’s Study Group, Lack of catch-up in weight gain may intermediate between pregnancies with hyperemesis gravidarum and reduced fetal growth: the Japan Environment and Children's Study, BMC Pregnancy Childbirth, 10.1186/s12884-022-04542-0, 22, 1, 199, 2022.03, Background: Women with nausea and vomiting of pregnancy (NVP) have higher birth weight infants, while those with hyperemesis gravidarum, a severe manifestation of NVP, have lower birth weight infants. We aimed to investigate the associations between maternal weight loss (a consequence of hyperemesis gravidarum), NVP, and infant birth weight.
Methods: This study was a secondary analysis of a nationwide birth cohort in Japan. Singleton pregnancies delivered at 28-41 weeks of gestation were included in the analysis. Women were categorized based on their weight change in the 1st trimester (as a proportion to their pre-pregnancy weight: > + 3%, > 0 to + 3%, > -3 to 0%, > -5 to -3%, ≤ -5%) and severity of NVP (no nausea, only nausea, vomiting but able to eat, vomiting and unable to eat). The effects of weight change and severity of NVP on infant birth weight and small for gestational age (SGA) were assessed using regression models. We further examined how these effects could be modified by maternal weight gain up to the 2nd trimester.
Results: Among 91,313 women, 5,196 (5.7%) lost ≥ 5% of their pre-pregnancy weight and 9,983 (10.9%) experienced vomiting and were unable to eat in the 1st trimester. Women with weight loss ≥ 5% in the 1st trimester had infants 66 (95% CI: 53, 78) g lighter and higher odds of SGA (aOR: 1.29; 95% CI: 1.14, 1.47) than women who gained > 3% during the same period. However, when adjusting for weight gain up to the 2nd trimester, women with weight loss ≥ 5% in the 1st trimester had infants 150 (95% CI: 135, 165) g heavier and lower odds of SGA (aOR: 0.39; 95% CI: 0.33, 0.46) than those who gained > 3% during the same period. In contrast, women with more severe NVP tended to have infants with larger birth weight and lower odds of SGA compared to women without NVP. These trends were strengthened when adjusting for weight gain up to the 2nd trimester.
Conclusions: Our study suggests the possibility that reduced fetal growth in pregnancies with hyperemesis gravidarum may be caused by the lack of catch-up in gestational weight gain up to the 2nd trimester.
Keywords: Birth weight; Fetal growth; Gestational weight gain; Hyperemesis gravidarum; Morning sickness; Nausea and vomiting of pregnancy; Small for gestational age.. |
| 34. |
Nakahara K¹, Michikawa T², Morokuma S³ ⁴, Hamada N¹ ⁴, Ogawa M¹ ⁴, Kato K¹ ⁴, Sanefuji M⁴ ⁵, Shibata E⁶ ⁷, Tsuji M⁶ ⁸, Shimono M⁶ ⁹, Kawamoto T⁶, Ohga S⁴ ⁵, Kusuhara K⁶ ⁹, The Japan Environment and Children's Study Group, Association of maternal hemoglobin levels during pregnancy with sleep and developmental problems in 1-year-old infants: A cohort study, Health Sci Rep, 10.1002/hsr2.552, 5, 2, e552, 2022.03, Background and aims: Maternal hemoglobin concentration during pregnancy is reported to be associated with various perinatal outcomes and may also be associated with infant development. This study aims to investigate the association between maternal hemoglobin levels during early or mid-pregnancy and sleep and developmental problems in 1-year-old infants.
Methods: We used the data of 66,935 pregnant women who were participants of the Japan Environment and Children's Study, a nationwide cohort study in Japan, between 2011 and 2014. Maternal hemoglobin level was examined at recruitment (mean gestational age, 15.3 weeks; SD, 2.85 weeks; range, 6-22 weeks). Information on infant sleep and development at the age of 1 year was acquired using a questionnaire. Infant development was evaluated using the Ages and Stages Questionnaire (ASQ).
Results: The mean (SD) maternal hemoglobin level was 12.0 (1.0) g/dl. Maternal hemoglobin levels were not associated with the majority of infant sleep and developmental outcomes. In the group with maternal hemoglobin Conclusion: Our results suggest that a low level of maternal hemoglobin during pregnancy is associated with late bedtime and abnormal fine motor skills in 1-year-old infants. Conversely, a high level of maternal hemoglobin may also be associated with the infant's late bedtime.
Keywords: development; hemoglobin; infant; pregnancy; sleep.. |
| 35. |
Michikawa T¹, Morokuma S², Takeda Y¹, Yamazaki S³, Nakahara K⁴, Takami A⁵, Yoshino A⁵, Sugata S⁵, Saito S⁶, Hoshi J⁶, Kato K⁴, Nitta H³, Nishiwaki Y¹, Maternal exposure to fine particulate matter over the first trimester and umbilical cord insertion abnormalities, Int J Epidemiol, 10.1093/ije/dyab192, 51, 1, 191-201, 2022.02, Background: Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes.
Methods: From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0-13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion.
Results: Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) μg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06-1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion).
Conclusions: Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.
Keywords: Abnormal cord insertion; fine particle; implantation; nitrate; organic carbon; pregnancy.. |
| 36. |
城戸咲、嘉村駿佑、佐藤由佳、佐藤麻衣、原枝美子、藤田恭之、加藤聖子, 胎胞視認例に対する治療的頸管縫縮術の成否に関する所見, 九州連合産科婦人科学会雑誌, 72, 11-16, 2022.02, 妊娠第2三半期の頸管開大例に対する治療的頸管縫縮術は妊娠延長効果が期待でき、分娩までの期間（中央値）は待機群で3-20日に対し、縫縮群で41-117日までに延長すると報告されている。しかし胎盤突出例では術中破水や、数日内に流早産に至る症例も少なからず存在し、手術に際し、週数や母体侵襲のバランスに苦慮することもある。また細胞可視例でも一部は術後早期の分娩に至る例があり、経過予測に基づいた個別管理が必要になる。手術時点でどういった臨床・検査所見に着目すると十分な妊娠延長を期待できる症例と判断できるのか、また術後はどの所見に留意すればより慎重な管理が必要な症例をピックアップできるのか、これらを知ることは臨床診療の上で有用である。そこで本研究では胎胞視認例における治療的頸管縫縮術の成否に関わる因子について検討した。. |
| 37. |
Kamura S¹'², Sasaki A¹, Ogawa K¹, Kato K², Sago H¹, Periconceptional folic acid intake and disturbing factors: A single-center study in Japan, Congenit Anom (Kyoto), 10.1111/cga.12449, 62, 1, 42-46, 2022.01, We investigated folic acid (FA) intake and disturbing factors in pregnant women who visited our center in 2017. Among 1531 pregnant women, 45.1% of women initiated FA supplementation before pregnancy. The risk of failure of supplementation was significantly lower among women of ≥35 (adjusted odds ratio [aOR] 0.43) and 30-34 years of age (aOR: 0.59) in comparison to women of Keywords: folic acid; neural tube defect (NTD); preconceptional care; risk factors; supplementation.. |
| 38. |
Michikawa T¹, Morokuma S², Yamazaki S³, Takami A⁴, Sugata S⁴, Yoshino A⁴, Takeda Y⁵, Nakahara K⁶, Saito S⁷, Hoshi J⁷, Kato K⁶, Nitta H³, Nishiwaki Y⁵, Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study, J Expo Sci Environ Epidemiol, 10.1038/s41370-021-00299-4, 32, 1, 135-145, 2022.01, Background: Maternal exposure to fine particulate matter (PM2.5) was associated with pregnancy complications. However, we still lack comprehensive evidence regarding which specific chemical components of PM2.5 are more harmful for maternal and foetal health.
Objective: We focused on exposure over the first trimester (0-13 weeks of gestation), which includes the early placentation period, and investigated whether PM2.5 and its components were associated with placenta-mediated pregnancy complications (combined outcome of small for gestational age, preeclampsia, placental abruption, and stillbirth).
Methods: From 2013 to 2015, we obtained information, from the Japan Perinatal Registry Network database, on 83,454 women who delivered singleton infants within 23 Tokyo wards (≈627 km2). Using daily filter sampling of PM2.5 at one monitoring location, we analysed carbon and ion components, and assigned the first trimester average of the respective pollutant concentrations to each woman.
Results: The ORs of placenta-mediated pregnancy complications were 1.14 (95% CI = 1.08-1.22) per 0.51 μg/m3 (interquartile range) increase of organic carbon and 1.11 (1.03-1.18) per 0.06 μg/m3 increase of sodium. Organic carbon was also associated with four individual complications. There was no association between ozone and outcome.
Significance: There were specific components of PM2.5 that have adverse effects on maternal and foetal health.
Keywords: Chemical component; Particulate matter; Placenta-mediated pregnancy complications; Placentation.. |
| 39. |
Kato K¹, Terauchi M², Annual report of the Women's Healthcare Committee, Japan Society of Obstetrics and Gynecology, 2021, J Obstet Gynaecol Res, 10.1111/jog.14986, 48, 1, 38-48, 2022.01, Our committee was founded in 2010 with the goal of improving women's health. This academic year we focused on the following five activities for the second consecutive year: cooperation between the department of pediatric surgery and the department of obstetrics and gynecology for the treatment of persistent cloaca and Mayer-Rokitansky-Küster-Hauser syndrome in Japan; assessment of the educational training of women's healthcare advisers; increasing screening for breast and cervical cancer; conducting the Nationwide Survey of Prescribing Practices for the Treatment of Menopausal Symptoms; and preventing osteoporosis in survivors of gynecologic cancer. The activities of each subcommittee are detailed below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2021;73(6):684-699).
Keywords: Mayer-Rokitansky-Küster-Hauser syndrome; cancer screening; healthcare adviser; menopausal symptoms; osteoporosis; persistent cloaca.. |
| 40. |
Kikuchi K¹, Sato Y², Izukura R³, Nishikitani M⁴, Kato K⁵, Morokuma S², Nessa M⁶, Nohara Y⁷, Yokota F⁸, Ahmed A⁹, Islam-Maruf R⁴, Nakashima N⁴, Portable health clinic for sustainable care of mothers and newborns in rural Bangladesh, Comput Methods Programs Biomed, 10.1016/j.cmpb.2021.106156, 207, 106156, 2021.08, Background and objective: Regular health checkups are important for mothers and newborns to detect health problems at an early stage; however, this is often difficult in resource-limited settings. Therefore, the portable health clinic (PHC) for maternal and child health (MCH), a telemedicine health checkup system, was introduced as an intervention study in a rural area in Bangladesh. The aim of this research project was to report findings that we had observed at a mid-point of the intervention period.
Methods: This was an intervention study conducted in Shariatpur, Bangladesh. The study population included pregnant/parturient women aged 15-49 years and their newborns. With the help of the newly created PHC for MCH, health workers, with a set of sensor devices in an attaché case, visited mothers and newborns at home to examine their health status. Their health status was triaged into four categories using a data management application, and in cases of affected or emergent health status, they were placed on remote video consultation with a doctor.
Results: In total, 94 women were included in the PHC for MCH intervention. The rate of participants who received antenatal care at least four times or postnatal care at least once increased (from 29% to 51%, and from 27% to 78%, respectively) compared with before introducing PHC for MCH. Using the PHC for MCH, we detected health problems in pregnant/parturient women; a relatively high percentage had anemia (45-54%) and/or abnormal pulse rate (20-40%). Moreover, after introducing the PHC for MCH, more than 40% of women who received multiple antenatal care or postnatal care checkups improved their health status.
Conclusions: The PHC for MCH could be an effective system to improve the health of mothers and newborns by increasing the availability of care. In the future, this system is expected to be used as a primary resource for maternity healthcare, not only in rural areas but also in other social environments.
Keywords: Bangladesh; Global Health; Maternal–Child Health Services; Telemedicine.. |
| 41. |
渡邊壽美子¹、加来恒壽¹'⁵、西村和徳²、植村瑞紀²、上原俊貴²、杉島節夫¹、加藤聖子¹、小田義直⁴、岩坂剛⁶, 子宮頸部腺系病変における細胞像の数量的解析 ―AGC に注目して―, 日本臨床細胞学会九州連合会雑誌, 52, 11-17, 2021.07, 目的：異型腺細胞(atypical glandular cell:AGC)の数量的解析を行い組織型推定困難症例における上皮内腺癌(AIS)細胞の特徴を調べる。
方法：細胞診検査が実施され、病理組織的診断が確定している61症例の細胞診標本を、細胞診の細胞像から組織型推定困難群(A群19症例)と、組織型推定可能群(B群42症例)に分け、細胞所見と集塊所見をImage Jを用いて比較検討を行った。
成績：A群におけるAISに関して、①AISの核面積は子宮頸部上皮内腫瘍(CIN)1より小さく良性腫瘍(Benign)との間に有意差がない。②AISの核間距離はCIN1およびBenignより有意に小さく分業状頸管腺過形成(LEDH)との間に有意差がない。③A群の全ての組織型において核クロマチンは主に核偏在し判別困難、④AISとLEGHの”核面積と核間距離の相関”は低い、という結果がが得られた。
結論：組織型推定困難症例であったAISの細胞診像では核の大きさやクロマチンの分布が良性と差がなく、核所見が乏しいため組織型の推定が困難であったと思われた。よって、腺細胞の集塊において、核間距離に有意差がある不規則重積性の認識は、AIS鑑別の一助になる可能性が示唆された。
Key words：cervical cytology, morphometry atypical glandular cell, adenocarcinoma in situ, irregular nuclear intussusception. |
| 42. |
Morisaki N¹, Piedvache A¹, Nagata C², Michikawa T³, Morokuma S⁴, Kato K⁵, Sanefuji M⁶,Shibata E⁷, Tsuji M⁸, Shimono M⁷, Ohga S⁹, Kusuhara K¹⁰, Japan Environment and Children’s Study Group, Maternal blood count parameters of chronic inflammation by gestational age and their associations with risk of preterm delivery in the Japan Environment and Children's Study, Sci Rep, 10.1038/s41598-021-93101-2, 11, 1, 記事番号：15522, 2021.07, Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), are three reportedly predictive biomarkers that reflect subclinical chronic inflammatory burden. However, how these biomarkers change during pregnancy and its clinical utility among pregnant women have been rarely studied. Among 76,853 singleton pregnancies delivered at 28-41 weeks of gestation that were enrolled in the Japan Environment and Children's Study, we observed the distribution of maternal NLR, PLR, and LMR values from week 0 to week 36 using spline curves, as well as their predictive values for preterm delivery with and without hypertensive disorders in pregnancy, placental abruption and intrauterine growth restriction (collectively termed ischemic placental disease due to their shared pathological and pathophysiological features) for measurements at 8-11 weeks, 12-17 weeks, and 18-21 weeks. NLR and PLR increased, whereas LMR decreased, with increasing gestation. High LMR and low NLR observed at 18-21 weeks, but not at earlier gestations, were associated with higher risk of preterm delivery with IPD (odds ratio 1.80 [95% CI 1.02, 3.19] per log[LMR]; odds ratio 0.49 [95% CI 0.29, 0.82] per log[NLR]). All parameters were not predictive of preterm delivery without IPD. We provide a robust reference curve for maternal blood count parameters NLR, PLR, and LMR by gestational week.. |
| 43. |
Yasunaga M¹, Yahata H², Okugawa K¹, Hori E¹, Kodama K¹, Yagi H¹, Ohgami T¹, Onoyama I¹, Asanoma K¹, Kato K¹, Prognostic impact of the subclassification of Müllerian cancer stage IV in the FIGO 2014 staging system with a focus of extra-abdominal lymph node metastases, Int J Clin Oncol, 10.1007/s10147-021-01908-w, 26, 7, 1330-1335, 2021.07, Background: The International Federation of Gynecology and Obstetrics (FIGO) staging system for Müllerian cancer was changed in 2014. Our objective was to evaluate the prognostic impact of stage IV subclassification in this new staging system, especially focusing on extra-abdominal lymph node metastasis.
Methods: Eighty-two patients with stage IV Müllerian cancer treated between 2005 and 2016 at our hospital were retrospectively analyzed. Data for the following clinicopathological variables were analyzed: (1) FIGO stage; (2) tumor stage; (3) lymph node status; (4) histologic type; (5) neoadjuvant chemotherapy; (6) optimal surgery; and (7) bevacizumab use. Survival analysis was performed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models.
Results: In accordance with the new classification, 28 and 54 patients were classified as FIGO IVA and IVB, respectively. In the Cox proportional hazards model, early-stage tumors (T1b-3b) and optimal surgery were statistically significant favorable prognostic factors. However, the new FIGO system did not discriminate prognostically between stage IVA and IVB. Median overall survival of stage IVB patients diagnosed with extra-abdominal lymph node metastasis only was better than that of stage IVA and stage IVB patients diagnosed with solid organ metastasis.
Conclusions: In this analysis of the revised FIGO system of patients reclassified as FIGO stage IVA or IVB, no new prognostic information was obtained. There is a possibility that stage IVB patients diagnosed with extra-abdominal lymph node metastasis only can be classified as an earlier stage. Further modification of the FIGO staging system may be needed to improve the prediction of patient prognosis.
Keywords: Extra-abdominal lymph nodes; Müllerian cancer; Prognosis; Stage IV subclassification.. |
| 44. |
Nakahara K¹, Michikawa T², Morokuma S³ ⁴, Ogawa M⁵, Kato K¹ ⁵, Sanefuji M⁵ ⁶, Shibata E⁷ ⁸, Tsuji M⁷ ⁹, Shimono M⁷ ¹⁰, Kawamoto T⁷, Ohga S⁶, Kusuhara K⁷ ¹⁰, Japan Environment and Children’s Study Group, Association of maternal sleep before and during pregnancy with sleep and developmental problems in 1-year-old infants, Sci Rep, 10.1038/s41598-021-91271-7, 11, 1, 11834-11834, 2021.06, This study investigated the association of maternal sleep before and during pregnancy with sleeping and developmental problems in 1-year-old infants. We used data from the Japan Environment and Children's Study, which registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their sleep habits prior to and during pregnancy. Follow-up assessments were conducted to evaluate the sleep habits and developmental progress of their children at the age of 1 year. Development during infancy was evaluated using the Ages and Stages Questionnaire (ASQ). Maternal short sleep and late bedtime before and during pregnancy increased occurrence of offspring's sleeping disturbances. For example, infants whose mothers slept for less than 6 h prior to pregnancy tended to be awake for more than 1 h (risk ratio [RR] = 1.49, 95% confidence interval [CI] 1.34-1.66), sleep less than 8 h during the night (RR = 1.60, 95% CI 1.44-1.79), and fall asleep at 22:00 or later (RR = 1.33, 95% CI 1.26-1.40). Only subjective assessments of maternal sleep quality during pregnancy, such as very deep sleep and feeling very good when waking up, were inversely associated with abnormal ASQ scores in 1-year-old infants.. |
| 45. |
Hachisuga K¹, Ohishi Y¹ ², Tomonobe H³, Yahata H³, Kato K³, Oda Y¹, Endometrial endometrioid carcinoma, grade 1, is more aggressive in the elderly than in the young, Histopathology, 10.1111/his.14400, 79, 5, 708-719, 2021.05, Aims: The aim of this study was to characterise grade 1 (G1) endometrioid carcinoma in the elderly, by using clinicopathological features and immunohistochemical features of surrogate markers of molecular subtypes.
Methods and results: We retrospectively analysed tumour samples from 268 patients with G1 endometrioid carcinoma (Conclusions: G1 endometrioid carcinoma in the elderly is more aggressive than that in the young, and elderly status is an independent predictor of shorter progression-free survival in this condition. We propose that type 1 tumours can be subdivided into type 1a (young age at onset and indolent) and type 1b (old age at onset and relatively aggressive).
Keywords: G1 endometrioid carcinoma; elderly; p53 expression; shorter progression-free survival.. |
| 46. |
Nakahara K¹, Michikawa T², Morokuma S³⁴, Ogawa M⁵, Kato K¹⁵, Sanefuji M⁵⁶, Shibata E⁷⁸, Tsuji M⁷⁹, Shimono M⁷¹⁰, Kawamoto T⁷, Ohga S⁶, Kusuhara K⁷¹⁰, the Japan Envi-ronment and Children's Study Group, Influence of physical activity before and during pregnancy on infant's sleep and neurodevelopment at 1-year-old, Sci Rep, 10.1038/s41598-021-87612-1, 11, 1, Article number 8099, 2021.04, The aim of this study was to investigate the association between maternal physical activity (PA) before and during pregnancy and sleep and developmental problems in 1-year-old infants. We used data from a nationwide cohort study in Japan that registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their PA before and during pregnancy, and the sleep and development of their children at the age of 1 year. Maternal PA was estimated using the International Physical Activity Questionnaire and was expressed in METs per week. We defined scores below the cut-off points of the Ages and Stages Questionnaire (ASQ) as abnormal for infant development. Based on the levels of PA before or during pregnancy, the participants were divided into five groups. In mothers with higher PA levels, the risk ratio for bedtime after 22:00 or abnormal ASQ scores in their 1-years-old infants were lower. These associations were observed for PA before and during pregnancy. Higher levels of maternal PA, both before and during pregnancy, may reduce sleep and developmental problems in infants.. |
| 47. |
Yoshida K¹, Kusama K¹, Fukushima Y¹, Ohmaru-Nakanishi T², Kato K², Tamura K¹, Alpha-1 Antitrypsin-Induced Endoplasmic Reticulum Stress Promotes Invasion by Extravillous Trophoblasts, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 10.3390/ijms22073683, 22, 7, 記事番号：3683, 2021.04, Alpha-1 antitrypsin (A1AT) is a glycoprotein that has been shown to protect tissues from proteolytic damage under various inflammatory conditions. Several studies show that A1AT may be associated with pre-eclampsia. However, the role of A1AT expression in placental physiology is not fully understood. In the present study, we aim to characterize the expression and function of placental A1AT. A1AT knockdown is found to reduce the expression of the serine protease HTRA1 in a trophoblast cell line. In addition, A1AT overexpression (A1AT-OE) increases the expression of HTRA1, IL6, CXCL8, and several markers of endoplasmic reticulum (ER) stress. Treatment with tunicamycin or thapsigargin, which induces ER stress, increases HTRA1 expression. Furthermore, immunohistochemistry reveals that HTRA1 is expressed in trophoblasts and the endometrial decidual cells of human placentas. An invasion assay shows that A1AT and HTRA1 stimulate cell invasion, but treatment with the ER stress inhibitors reduces the expression of HTRA1 and ER stress markers and prevents cell invasion in A1AT-OE trophoblasts. These results suggest that endogenous A1AT regulates inflammatory cytokine expression and HTRA1-induced trophoblast invasion via the induction of ER stress. It is concluded that an imbalance in the functional link between A1AT and ER stress at the maternal-fetal interface might cause abnormal placental development.
Keywords: alpha-1 antitrypsin; cell invasion; endoplasmic reticulum stress; extravillous trophoblast; high-temperature requirement A serine peptidase 1.. |
| 48. |
Sato Y¹, Hidaka N², Sakai A³, Kido S⁴, Fujita Y⁵, Okugawa K⁶, Yahata H⁷, Kato K⁸, Evaluation of the efficacy of vaginal progesterone in preventing preterm birth after abdominal trachelectomy, Eur J Obstet Gynecol Reprod Biol, 10.1016/j.ejogrb.2021.02.009, 259, 119-124, 2021.04, Objective: To determine whether vaginal progesterone (VP) reduces the rate of preterm birth in pregnant women after abdominal trachelectomy (AT) for early-stage cervical cancer STUDY DESIGN: This is an interventional study with a historical cohort. For the interventional study participants who had singleton pregnancies after AT between October 2016 and September 2020, the administration of vaginal progesterone was started between 16+ and 19+6 weeks of gestation and discontinued at 34 weeks of gestation or at the time of delivery, rupture of membranes, or massive uterine bleeding. We investigated obstetric and neonatal outcomes among the study participants and compared them with outcomes of the historical control group participants, included women with singleton pregnancies after AT who were managed without VP at our institution between January 2007 and September 2016, using Fisher's exact test and the Mann-Whitney U test The main outcomes were the gestational age at delivery and incidence of preterm birth before 37 weeks and 34 weeks of gestation.
Result: Twelve pregnancies in ten women were included in the VP group. In contrast, 19 pregnancies in 17 women were included in the historical control group. The incidence of preterm birth at Conclusion: The administration of vaginal progesterone did not reduce the rate of preterm birth among pregnant women after AT.
Keywords: Abdominal trachelectomy; Preterm birth; Preterm premature membranes rupture; Vaginal progesterone.. |
| 49. |
Sonoda K¹ ², Ohgami T², Hachisuga M², Fujita Y², Okugawa K², Yahata H², Kato K², Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition, Mol Clin Oncol, 10.3892/mco.2021.2229, 14, 4, Article number 67, Pages 1-7, 2021.04, Due to the recent trend of women having children at an older age, the number of pregnancies complicated by cervical cancer has increased. In the present study, the clinical characteristics of patients with cervical cancer complicated by pregnancy were analyzed. The clinicopathological characteristics and prognosis of patients with cervical cancer during pregnancy who underwent treatment at Kyushu University Hospital from January 2008 to December 2017 were assessed retrospectively from their medical records. The medical information of patients diagnosed within 6 months after parturition was also evaluated as these patients were considered to be affected by cervical cancer during pregnancy. A total of 19 women were diagnosed with cervical cancer during pregnancy (median age, 33 years), three of whom were diagnosed as negative for intraepithelial lesion or malignancy at the initial visit to a previous clinic after pregnancy. The tumor stage was IA1 in one patient, IB1 in 16 patients, IB2 in one patient and IVB in one patient. The median gestational age at the time of cervical cancer diagnosis was 13 weeks. One patient died of cervical cancer during the follow-up period. An additional 12 patients were diagnosed within 6 months after parturition. The median age of these patients was 35.5 years. Cancer screening was performed in 10 patients during pregnancy, none of whom were diagnosed with cervical cancer, including three patients who were negative for intraepithelial lesion or malignancy. Of the 12 patients, one had tumor stage IA1, eight had IB1, two had IB2 and one had IIB. Three patients experienced recurrence, of whom one died of cervical cancer. Advanced cervical cancer was diagnosed both during pregnancy and within 6 months after parturition. Diagnosis of cervical cancer during pregnancy is difficult even at an advanced stage; however, rapid diagnosis and prompt multidisciplinary treatment are critical. Therefore, it is necessary to improve the accuracy of cervical cancer diagnosis, and to characterize tumor cells and their microenvironment, during pregnancy.
Keywords: diagnosis; parturition; pregnancy; prognosis; uterine cervical neoplasms.. |
| 50. |
Kodama K¹, Yahata H², Okugawa K¹, Tomonobe H¹, Yasutake N¹, Yoshida S¹, Yagi H¹, Yasunaga M¹, Ohgami T¹, Onoyama I¹, Asanoma K¹, Hori E¹, Shimokawa M³, Kato K¹, Prognostic outcomes and risk factors for recurrence after laser vaporization for cervical intraepithelial neoplasia: a single-center retrospective study, Int J Clin Oncol, 10.1007/s10147-020-01848-x, 26, 4, 770-776, 2021.04, Background: Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years.
Methods: Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes.
Results: The mean patient age was 34 years (range 18-64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio [HR], 1.028; 95% CI 1.005-1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008-1.098; P = 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353-2.846; P = 0.0004).
Conclusions: Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence.
Keywords: Cervical intraepithelial neoplasia; Laser vaporization; Recurrence-free interval.. |
| 51. |
Yamaguchi S¹, Yahata H¹, Okugawa K¹, Kodama K¹, Yagi H¹, Yasunaga M¹, Ohgami T¹, Onoyama I¹, Asanoma K¹, Kato K¹, Hypersensitivity reaction to pegylated liposomal doxorubicin administration for Mullerian carcinoma in Japanese women, J Obstet Gynaecol Res, 10.1111/jog.14680, 47, 4, 1544-1548, 2021.04, Aim: PEGylated liposomal doxorubicin (PLD) is a therapeutic agent for gynecological malignancy. Hypersensitivity reaction (HSR) is a major adverse effect that usually disappears after halting administration of PLD. Premedication is usually not necessary before administration of PLD to prevent HSR. Here, we evaluated the frequency of HSR during administration of PLD following premedication in Japanese women.
Methods: We performed PLD administration in 78 patients (386 cycles) between 2013 and 2018. Granisetron hydrochloride and dexamethasone sodium phosphate were administered 30 min before PLD administration. Then, PLD (40 or 30 mg/m2 combined usage with carboplatin) was administered. We retrospectively reviewed the medical records of 78 patients and examined the frequency of HSR.
Results: Seven of 78 (9%) patients showed HSR by PLD administration following premedication. One patient showed cardiopulmonary arrest in 13 min after PLD administration (grade 4). The other six patients showed grade 2 HSR. All patients developed HSR in the first course. The incidence of HSR was significantly higher in patients with allergic history than in patients without allergic history (p = 0.0151).
Conclusions: Clinicians should be aware of the potential for HSR in patients administered PLD, particularly those with allergic history and those receiving the first cycle of PLD, even following premedication.. |
| 52. |
江崎 景子、下村 実奈代、石迫 千里、古川 眞希、床島 晴菜、三池 優起子、加藤 聖子、山口 真一郎、貝沼 茂三郎, 大建中湯のより効果的な内服方法に関する試験, 産婦人科漢方研究のあゆみ, 37, 6-10, 2021.03, 【はじめに】婦人科疾患開腹手術後のイレウス予防として、術後から大建中湯(以下TJ-100)を処方されていたが、本試験前までは、ほとんどの患者は顆粒のまま水で内服し、内服する際に飲み込みにくいという声が聞かれた。TJ-100は「腹中寒」が主要な使用目的であり、白湯で溶解し温服することがより理にかなっているとされる。そこで、TJ-100を白湯で溶解し内服する群と顆粒の状態で内服する群とで比較し内服状況と術後経過の調査を行った。
【方法】婦人科疾患の良性腫瘍を除く開腹手術を施行した患者に対し、術後1日目より、毎食前にTJ-100 2包を白湯100mLに溶解し内服する群(A:溶解群)と顆粒の状態で内服する群(B:顆粒群)の計30症例のランダム化比較試験を行った。術式や麻酔時間、出血量(輸血の有無)、排便状況、食事量、TJ-100以外の薬剤使用頻度、イレウスの有無、内服状況のデータ収集とともに、腹痛・悪心・不眠をvisual analogue scale(VAS)スケールでデータを数値化し、患者へ内服後の変化(腹部症状の変化)ついてアンケート調査を行った。【結果と考察】溶解群に侵襲の大きな手術が偏ったが、術後の初回排便が有意に早く、効果的であった。両群ともに、VASスケールに有意差は認めなかった。その他の副次的な項目に関しては、内服による効果が認められた。その他、アンケート調査結果などについて述べ、それらについて考察する。. |
| 53. |
Takamatsu K¹, Ogawa M¹, Obayashi S², Takeda T³, Terauchi M⁴, Higuchi T⁵, Kato K⁶, Kubota T⁷, A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: The KOSMOS Study, Evid Based Complement Alternat Med
., 10.1155/2021/8856149, 2021, 8856149-8856149, 2021.02, Objective: The KOSMOS study, a multicenter, randomized, double-blind, placebo-controlled trial, investigated the effects and safety of kamishoyosan (TJ-24), a traditional Japanese medicine, in the treatment of climacteric disorder.
Methods: Japanese women with climacteric disorder were administered a placebo during a 4-week run-in period, after which they were classified as placebo responders (R group) if their score on the modified Questionnaire for the Assessment of Climacteric Symptoms in Japanese Women (m-QACS) with excitability and irritability as the primary outcome improved by ≥ 3 points and as placebo nonresponders (NR group) otherwise. Members of the NR group were randomly allocated to receive either TJ-24 or placebo. After 12 weeks, their m-QACS scores, anxiety and depression, sleep, and overall quality of life (QOL) were compared.
Results: The TJ-24 and placebo arms in the NR group included 20 patients each. The change in the m-QACS scores of members of the NR group for excitability and irritability at 12 weeks versus baseline was -3.1 ± 1.7 in the TJ-24 arm, a significant decrease, but compared with -2.7 ± 2.2 in the placebo arm, no significant difference was between two arms. However, the proportion of participants whose score improved by ≥3 points was significantly higher in the TJ-24 arm. In the subgroup analysis of premenopausal women, the changes in the score for excitability and irritability were significantly larger in the TJ-24 arm. The incidence of adverse drug reactions or adverse events did not differ between the two arms, and no serious events were reported.
Conclusion: Although no significant difference was identified for the primary outcome, a significantly higher proportion of patients who received TJ-24 displayed improvement. Its high level of safety and effects on excitability and irritability in premenopausal women suggest that TJ-24 may be a useful treatment.. |
| 54. |
Suzuki I¹ ²,Yoshida S², Tabu K³, Kusunoki¹S¹, Matsumura Y², Izumi H⁴, Asanoma K², Yagi H², Onoyama I², Sonoda K⁵, Kohno K⁶, Taga T³, Itakura A¹, Takeda S¹, Kato K⁷, YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer, Sci Rep, 10.1038/s41598-021-83200-5, 11, 1, 4220-4220, 2021.02, Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.. |
| 55. |
Kawamura T¹, Tomari H¹, Onoyama I¹, Araki H², Yasunaga M¹, Lin C¹, Kawamura K¹, Yokota N¹, Yoshida S¹, Yagi H¹, Asanoma K¹, Sonoda K¹, Egashira K¹, Ito T², Kato K¹, Identification of genes associated with endometrial cell ageing, Mol Hum Reprod, 10.1093/molehr/gaaa078, 27, 2, gaaa078-gaaa078, 2021.02, Ageing of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine ageing are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20s and 40s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40s were significantly higher than that for patients in their 20s, as detected by a Mann-hitney U test. These results suggest that these genes are candidate markers for endometrial ageing and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.
Keywords: CXCL12; CXCL14; IL17RB; endometrial cell ageing; infertility; quantitative immunohistochemistry.. |
| 56. |
Yoshida S¹, Asanoma K¹, Yagi H¹, Onoyama I¹, Hori E¹, Matsumura Y¹, Okugawa K¹, Yahata H¹, Kato K¹, Fibronectin mediates activation of stromal fibroblasts by SPARC in endometrial cancer cells, BMC Cancer, 10.1186/s12885-021-07875-9, 21, 1, 156-156, 2021.02, Background: Matricellular glycoprotein, SPARC is a secreted molecule, that mediates the interaction between cells and extracellular matrix. SPARC functions as a regulator of matrix organization and modulates cell behavior. In various kinds of cancer, strong SPARC expression was observed in stromal tissues as well as in cancer epithelial cells. The function of SPARC in cancer cells is somewhat controversial and its impact on peritumoral stromal cells remains to be resolved.
Methods: We investigated the effects of SPARC expression in endometrial cancer cells on the surrounding stromal fibroblasts using in vitro co-culture system. Changes in characteristics of fibroblasts were examined by analysis of fibroblast-specific markers and in vitro contraction assay.
Results: SPARC induced AKT phosphorylation and epithelial-to-mesenchymal transition, consistent with previous reports. Cancer-associated fibroblasts of endometrial cancer expressed higher levels of mesenchymal- and fibroblast-associated factors and had a stronger contraction ability. Unexpectedly, cancer-associated fibroblasts expressed comparable levels of SPARC compared with fibroblasts from normal endometrium. However, co-culture of normal fibroblasts with SPARC-expressing Ishikawa cells resulted in activation of the fibroblasts. Immunodepletion of SPARC did not affect the activation of fibroblasts.
Conclusions: Our data indicated that SPARC activated fibroblasts only in the presence of fibronectin, which was abundantly secreted from SPARC-expressing endometrial cancer cells. These results suggested that a SPARC-fibronectin-mediated activation of fibroblasts might be involved in enhanced mobility and invasion of cancer cells.. |
| 57. |
Okugawa K¹, Yahata H², Sonoda K³, Kodama K², Yagi H², Ohgami T², Yasunaga M², Onoyama I², Kaneki E², Asanoma K², Kobayashi H⁴, Kato K², Evaluation of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer: a single-institution experience, Int J Clin Oncol, 10.1007/s10147-020-01778-8, 26, 1, 216-224, 2021.01, Background: To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer.
Methods: Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively.
Results: Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12-146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered.
Conclusion: Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.. |
| 58. |
Kato K¹, Terauchi M², Annual report of the Women's Health Care Committee, Japan Society of Obstet-rics and Gynecology, 2020, J Obstet Gynaecol Res, 10.1111/jog.14417, 47, 1, 52-62, 2021.01, Our committee was founded in 2010 with the goal of improving women's health. This academic year, we focused on five activities: cooperation between the departments of pediatric surgery and obstetrics and gynecology for the treatment of persistent cloaca and Mayer-Rokitansky-Küster-Hauser syndrome in Japan; assessment of the educational training of women's health-care advisers; increasing screening for breast and cervical cancer; conducting the Nationwide Survey of Prescribing Practices for the Treatment of Menopausal Symptoms; and preventing osteoporosis in survivors of gynecologic cancer. The activities of each subcommittee are detailed below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2020;72(6):697-707).. |
| 59. |
Yahata H, Sonoda K, Inoue S, Yasutake N, Kodama K, Yagi H, Yasunaga M, Ohgami T, Onoyama I, Kaneki E, Okugawa K, Asanoma K, Kato K, Is Adjuvant Therapy Necessary for Patients with Intermediate-Risk Cervical Cancer after Open Radical Hysterectomy?, Oncology, 10.1159/000508569, 98, 12, 853-858, 2020.11, Introduction: Adjuvant therapy is usually recommended for patients with intermediate-risk cervical cancer (deep stromal invasion [DSI], lymphovascular space invasion [LVSI], and bulky tumor) after radical hysterectomy. However, we previously reported that DSI, LVSI, and bulky squamous cell carcinoma (SCC) were not correlated with prognosis in multivariate analysis; therefore, the indications we use for adjuvant therapy include complete stromal invasion, not DSI or LVSI or bulky SCC. The objective of this study was to evaluate the adequacy of our therapeutic strategy for cervical cancer after radical hysterectomy.
Methods: We performed 321 type III open radical hysterectomies for cervical cancer between 2001 and 2013. Eighty-two patients with DSI, LVSI, or bulky SCC did not receive adjuvant therapy after radical hysterectomy under informed consent. We retrospectively evaluated the prognosis of these 82 patients.
Results: Forty-two patients had >2/3 DSI and 35 patients had 1/3-2/3 DSI. Five patients had LVSI alone. The mean patient age was 43 years (range, 27-72). Six patients (7%) experienced recurrence during a median follow-up period of 84 months (range, 1-206). Two of the 6 patients with recurrence suffered cervical cancer-related deaths, but the remaining 4 cases are alive without evidence of disease after treatment during a follow-up period of 87-165 months. The 5-year disease-free survival rate was 92.6%, and the 5-year overall survival rate was 96.3%.
Conclusions: Adjuvant therapy for DSI, LVSI, or bulky SCC after open radical hysterectomy might not be necessary. Further data collection is warranted to determine the standard of care for patients with intermediate-risk cervical -cancer.. |
| 60. |
Kato M¹ ², Onoyama I¹, Kawakami M¹, Yoshida S¹, Kawamura K¹, Kodama K¹, Hori E¹, Cui L¹, Matsumura Y¹, Yagi H¹, Asanoma K¹, Yahata H¹, Itakura A², Takeda S², Kato K¹, Downregulation of 5-hydroxymethylcytosine is associated with the progression of cervical intraepithelial neoplasia, PLoS One, 10.1371/journal.pone.0241482, 15, 11, e0241482-e0241482, 2020.10, Around the world, cervical cancer is one of the most common neoplastic diseases among women, and the prognosis of patients in an advanced stage remains poor. To reduce the mortality rate of cervical cancer, early diagnosis and treatment are essential. DNA methylation is an important aspect of gene regulation, and aberrant DNA methylation contributes to carcinogenesis and cancer progression in various cancers. Although 5-methylcytosine (5mC) has been analyzed intensively, the function of 5-hydroxymethylcytosine (5hmC) has not been clarified. The purpose of our study was to identify the molecular biomarkers for early diagnosis of cervical tumors due to epigenetic alterations. To assess the clinical relevance of DNA methylation, we used immunohistochemistry (IHC) to characterize the level of 5hmC in 102 archived human cervical intraepithelial neoplasia (CIN) samples and cervical cancer specimens. The level of 5hmC was significantly decreased between CIN2 and CIN3. The progression of cervical tumors is caused by a reduction of TP53 and RB1 because of HPV infection. We observed that Tp53 and Rb1 were knocked down in mouse embryonic fibroblasts (MEF), a model of normal cells. The level of 5hmC was reduced in Tp53-knockdown cells, and the expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven translocation methylcytosine dioxygenase 1 (TET1) were induced. In contrast, there was no significant change in Rb1-knockdown cells. Mechanistically, we focused on apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) 3B (A3B) as a cause of 5hmC reduction after TP53 knockdown. In the human cell line HHUA with a wild-type TP53 gene, A3B was induced in TP53-knockdown cells, and A3B knockdown recovered 5hmC levels in TP53-knockdown cells. These data indicate that TP53 suppression leads to 5hmC reduction in part through A3B induction. Moreover, IHC showed that expression levels of A3B in CIN3 were significantly higher than those in both normal epithelium and in CIN2. In conclusion, 5hmC levels are decreased between CIN2 and CIN3 through the TP53-A3B pathway. Since A3B could impair genome stability, 5hmC loss might increase the chances of accumulating mutations and of progressing from CIN3 to cervical cancer. Thus, these epigenetic changes could predict whether CINs are progressing to cancer or disappearing.. |
| 61. |
Kato M¹ ², Onoyama I¹, Yoshida S¹, Cui L¹, Kawamura K¹, Kodama K¹, Hori E¹, Matsumura Y¹, Yagi H¹, Asanoma K¹, Yahata H¹, Itakura A², Takeda S², Kato K¹, Dual-specificity Phosphatase 6 Plays a Critical Role in the Maintenance of a Can-cer Stem-Like Cell Phenotype in Human Endometrial Cancer, Int J Cancer, 10.1002/ijc.32965, 147, 7, 1987-1999, 2020.10, The prognosis of patients with high-grade or advanced-stage endometrial cancer remains poor. As cancer stem-like cells (CSCs) are thought to be associated with endometrial cancers, it is essential to investigate the molecular mechanisms that regulate endometrial CSCs. Dual-specificity phosphatase 6 (DUSP6) functions as a negative-feedback regulator of MAPK-ERK1/2 signaling, but its role in endometrial cancer remains unknown. We investigated whether DUSP6 is involved in cancer cell stemness using endometrial cancer cell lines and specimens from endometrial cancer patients. DUSP6 induced the expression of CSC-related genes including ALDH1, Nanog, SOX2 and Oct4A, increased the population of cells in the G0/G1 phase, and promoted sphere formation ability. DUSP6 knockdown resulted in reduced cell invasion and metastasis, whereas DUSP6 overexpression inhibited apoptosis under serum-free conditions. Moreover, DUSP6 decreased phosphorylated ERK1/2 and increased phosphorylated Akt levels, which potentially induces CSC features. In patients with endometrial cancers, DUSP6 expression was determined using immunohistochemistry, and based on the results, the patients were dichotomized into high- and low-DUSP6-expression groups. Progression-free survival and overall survival were significantly shorter in the high-DUSP6-expression group. These results suggest that DUSP6 has potential value as a biomarker of CSCs and as a target of therapies designed to eliminate CSCs in endometrial cancer.. |
| 62. |
Matsui T¹, Tamoto R², Iwasa A², Mimura M², Taniguchi S¹, Hasegawa T¹, Sudo T¹, Mizuno H¹, Kikuta J¹, Onoyama I³, Okugawa K³, Shiomi M⁴, Matsuzaki S⁴, Morii E⁵, Kimura T⁴, Kato K³, Kiyota Y², Ishii M⁶, Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers, Cancer Res, 10.1158/0008-5472.CAN-20-0348, 80, 17, 3745-3754, 2020.09, Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC ≥0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection. SIGNIFICANCE: This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.. |
| 63. |
Nakahara K¹, Michikawa T², Morokuma S³ ⁴, Ogawa M⁵, Kato K¹ ⁵, Sanefuji M⁵ ⁶, Shibata E⁷ ⁸, Tsuji M⁷ ⁹, Shimono M⁷ ¹⁰, Kawamoto T⁷, Ohga S⁶, Kusuhara K⁷ ¹⁰, Japan Environment and Children’s Study Group, Non-reassuring foetal status and sleep problems in 1-year-old infants in the Japan Environment and Children's Study: a cohort study, Sci Rep, 10.1038/s41598-020-67856-z, 10, 1, 11432-11432, 2020.07, Abnormal autonomic function may cause false-positive non-reassuring foetal status (fpNRFS) and may also cause sleeping problems after birth. However, an association between fpNRFS and sleeping problems in infants has not been reported. We previously showed an association of NRFS with temperament, including bad mood and frequent crying for long durations in 1-month-old infants. In the present study, we aimed to assess this association in 1-year-old infants. A total of 62,612 single pregnant women were included in the analysis. fpNRFS was identified from medical records. Sleep problems, such as short sleep duration or crying at night, were investigated in 1-year-old infants using a questionnaire for mothers. We used a log-binominal regression model to explore the association of fpNRFS with each sleep problem and to estimate risk ratios (RRs). The number of fpNRFS cases was 2,071, with a frequency of 3.3%. We observed an association of fpNRFS with shorter sleep duration of less than 8 h a night (RR 1.30, 95% confidence intervals [CI] 1.10-1.54), crying at night (RR 1.19, 95% CI 1.03-1.39), and bedtime after 22:00 (RR 1.09, 95% CI 1.00-1.18). fpNRFS may be associated with sleep problems in 1-year-old infants.. |
| 64. |
Nakahara K¹, Michikawa T², Morokuma S³ ⁴, Ogawa M⁵, Kato K¹ ⁵, Sanefuji M⁵ ⁶, Shibata E⁷ ⁸, Tsuji M⁷ ⁹, Shimono M⁷ ¹⁰, Kawamoto T⁷, Ohga S⁶, Kusuhara K⁷ ¹⁰, Japan Environment and Children’s Study Group, Association of maternal sleep before and during pregnancy with preterm birth and early infant sleep and temperament, Sci Rep, 10.1038/s41598-020-67852-3, 10, 1, 11084-11084, 2020.07, This study aimed to investigate the association of maternal sleep before and during pregnancy with preterm birth, infant sleep and temperament at 1 month of age. We used the data of the Japan Environment and Children's Study, a cohort study in Japan, which registered 103,099 pregnancies between 2011 and 2014. Participants were asked about their sleep before and during pregnancy, and the sleep and temperament of their newborns at 1 month of age. Preterm birth data were collected from medical records. Maternal sleep was not associated with preterm birth, but subjective sleep quality during pregnancy was associated with late preterm birth (birth at 34-36 weeks of gestation). For example, participants with extremely light subjective depth of sleep were more likely to experience preterm birth (RR = 1.19; 95% confidence interval [CI] = 1.04-1.35). Maternal sleep both before and during pregnancy seemed to be associated with infant sleep and temperament at 1 month of age. Infants, whose mothers slept for less than 6 hours before pregnancy, tended to cry intensely (RR = 1.15; 95% CI = 1.09-1.20). Maternal sleep problems before and during pregnancy were associated with preterm birth and child sleep problems and temperament.. |
| 65. |
Okugawa K¹, Yahata H¹, Sonoda K¹, Ohgami T¹, Yasunaga M¹, Kaneki E¹, Kato K¹, Safety evaluation of abdominal trachelectomy in patients with cervical tumors ≥2 cm: a single-institution, retrospective analysis, J Gynecol Oncol, 10.3802/jgo.2020.31.e41, 31, 4, e41-e41, 2020.07, Objective: For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm.
Methods: We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study.
Results: We attempted trachelectomy in 212 patients. Among the 135 patients with tumors Conclusions: Abdominal trachelectomy with intraoperative frozen sections of sentinel lymph nodes and cervical margins is oncologically safe, even in patients with tumors ≥2 cm.. |
| 66. |
Tomari H¹ ², Kawamura T¹, Asanoma K¹, Egashira K¹, Kawamura K¹, Honjo K², Nagata Y², Kato K¹, Contribution of Senescence in Human Endometrial Stromal Cells During Prolifer-ative Phase to Embryo Receptivity, Biol Reprod, 10.1093/biolre/ioaa044, 103, 1, 104-113, 2020.06, Successful assisted reproductive technology pregnancy depends on the viability of embryos and endometrial receptivity. However, the literature has neglected effects of the endometrial environment during the proliferative phase on implantation success or failure. Human endometrial stromal cells (hESCs) were isolated from endometrial tissues sampled at oocyte retrieval during the proliferative phase from women undergoing infertility treatment. Primary hESC cultures were used to investigate the relationship between stemness and senescence induction in this population and embryo receptivity. Patients were classified as receptive or non-receptive based on their pregnancy diagnosis after embryo transfer. Biomarkers of cellular senescence and somatic stem cells were compared between each sample. hESCs from non-receptive patients exhibited significantly higher (p |
| 67. |
Nitahara K¹, Hidaka N¹, Sakai A¹, Kido S¹, Kato K¹, The impact of general anesthesia on mother-infant bonding for puerperants who undergo emergency cesarean deliveries, J Perinat Med, 10.1515/jpm-2019-0412, 48, 5, 463-470, 2020.06, Background Mother-infant bonding is an emerging perinatal issue. While emergency cesarean deliveries are associated with a risk of bonding disorders, the mode of anesthesia used for emergency cesarean deliveries has never been studied in this context. We aimed to investigate the impact of administering general anesthesia and neuraxial anesthesia to women undergoing cesarean deliveries on mother-infant bonding. Methods This was a retrospective, propensity score-matched multivariable analysis of 457 patients who underwent emergency cesarean deliveries between February 2016 and January 2019 at a single teaching hospital in Japan. The Mother-Infant Bonding Scale (MIBS) scores at hospital discharge and the 1-month postpartum outpatient visit were evaluated in the general anesthesia and the neuraxial anesthesia groups. A high score on the MIBS indicates impaired mother-infant bonding. Results The primary outcome was the MIBS score at hospital discharge in propensity score-matched women. After propensity score matching, the median [interquartile range (IQR)] MIBS scores were significantly higher in the general anesthesia group than those in the neuraxial anesthesia group at hospital discharge [2 (1-4) vs. 2 (0-2); P = 0.015] and at the 1-month postpartum outpatient visit [1 (1-3) vs. 1 (0-2); P = 0.046]. In linear regression analysis of matched populations, general anesthesia showed a significant and positive association with the MIBS scores at hospital discharge [beta coefficient 0.867 (95% confidence interval [CI] 0.147-1.59); P = 0.019] but not at the 1-month postpartum outpatient visit [0.455 (-0.134 to 1.044); P = 0.129]. Conclusion General anesthesia for emergency cesarean delivery is an independent risk factor associated with impaired mother-infant bonding.. |
| 68. |
Maehara K¹, Morokuma S², Nakahara K¹, Okawa H¹, Kato K¹, A study on the association between eye movements and regular mouthing movements (RMMs) in normal fetuses between 24 to 39 weeks of gestation, PLoS One, 10.1371/journal.pone.0233909, 15, 5, e0233909-e0233909, 2020.05, Regular Mouthing Movements (RMMs) are movements in which lips and lower jaw movements occur regularly and can be observed in the fetus using transabdominal ultrasonic tomography. In near term infants, it is known that RMMs form clusters during the quiet sleep period. The notation of RMMs is not uniform, and is described as spontaneous sucking movement or non-nutritive sucking in newborns. Non-nutritive sucking is used to evaluate neurological function after birth, but there are no fetal indicators. The purpose of this study was to clarify the changes in the RMM clusters in fetuses at 24-39 weeks of gestation, and to investigate the relationship with the non-eye movement (NEM) period, which corresponds to the quiet sleep period after birth. Subjects included 83 normal single pregnancy cases. Fetal RMMs and eye movement (EM) were observed for 60 minutes using ultrasonic tomography and recorded as moving image files. We created time series data of eye movements and mouth movements from video recordings, and calculated RMM clusters per minute within effective observation time, RMM clusters per minute in EM period, RMM clusters per minute in NEM period, mouthing movements per cluster and ratio of number of RMM clusters per minute between NEM and EM periods and analyzed using linear regression analysis. As a result, critical points were detected in at two time points, at 32-33 weeks and 36-37 weeks of gestation, in RMM clusters per minute within the effective observation time and RMM clusters per minute in NEM period, respectively. RMM clusters in human fetuses increased from 32-33 to 36-37 weeks. This change is thought to represent fetal sleep development and central nervous system development.. |
| 69. |
Sonoda K¹ ², Nogami M⁴, Kodama K², Oda Y³, Kato K², Re-evaluation of preoperative endometrial smears for the cytodiagnosis of uterine leiomyosarcoma, Eur J Gynaecol Oncol, 10.31083/j.ejgo.2020.02.4950 Original Research, 41, 2, 167-170, 2020.04, Introduction: Uterine leiomyosarcoma (ULS) is a highly aggressive and lethal tumor. The absence of specific symptoms and diagnostic imaging findings makes the diagnosis of ULS challenging. Endometrial sampling reportedly has a significantly lower predictive value in diagnosing ULS compared with epithelial uterine malignancies. Materials and Methods: The authors retrospectively reviewed the preoperative endometrial cytology findings in seven of the 12 patients with ULS who were treated in this institution between 2008 and 2017. The other five patients did not have preoperative samples obtained for cytology. Results: Only one of the seven patients was originally diagnosed with a malignant tumor, with preoperative cytology showing rounded tumor cells with enlarged, irregular, hyperchromatic, and sometimes multiple nuclei, with conspicuous nucleoli in a necrotic background. After re-evaluation of the preoperative specimens, atypical cells were detected in four of the six patients who were initially deemed to have negative findings. A monomorphic population of spindle cells with slightly hyperchromatic, elongated nuclei was detected in two patients. Another two patients had rounded tumor cells with a moderate amount of basophilic cytoplasm and round or oval nuclei with minimal atypia. Conclusion: Novel diagnostic techniques are needed to accurately identify ULS in the preoperative period. Careful microscopic observation of the entire cytological specimen, together with detailed patient medical information, are essential to making a correct preoperative diagnosis of ULS.. |
| 70. |
Kodama K¹, Sonoda K¹, Kijima M¹, Yamaguchi S¹, Yagi H¹, Yasunaga M¹, Ohgami T¹, Onoyama I¹, Kaneki E¹, Okugawa K¹, Yahata H¹, Ohishi Y¹, Oda Y¹, Kato K¹, Retrospective Analysis of Treatment and Prognosis for Uterine Leiomyosarcoma: 10-year Experience of a Single Institute, Asia Pac J Clin Oncol, 10.1111/ajco.13286, 16, 2, e63-e67, 2020.04, AIM: Uterine leiomyosarcoma (ULMS) is a highly aggressive and lethal disease. This malignancy remains the most common type of uterine sarcoma, affecting approximately 0.4/100 000 women each year. Our aim was to assess the treatment and prognosis of ULMS patients.
METHODS: A total of 14 patients were treated at our institution between January 2008 and July 2017. We retrospectively analyzed their clinicopathological variables, treatment and prognosis.
RESULTS: The median patient age was 63 years (range, 35-83 years). The largest group of patients had stage IB disease (stage IB, n = 8; IIB, n = 2; IIIB, n = 1; IVB, n = 3) and the largest group by histological subtype was ordinary (ordinary, n = 11; myxoid, n = 2; epithelioid, n = 1). Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed for all patients, with additional surgical procedures (e.g., tumor resection, lymphadenectomy) performed if necessary. Twelve patients received adjuvant chemotherapy (ACT) consisting of gemcitabine and docetaxel. Ten patients experienced recurrence and received multidisciplinary therapies, including tumor resection, chemotherapy, radiation and targeted therapies. The median observation period was 17 months (range, 5-75 months), and 11 patients were alive (without disease, n = 5; with disease, n = 6). Intriguingly, five of eight stage IB patients who received postoperative ACT were alive without disease.
CONCLUSION: ULMS is rare but is associated with a poor prognosis, even if multidisciplinary therapies are administered. However, ACT appears to be effective in improving the prognosis of patients with stage IB disease.. |
| 71. |
Hamada N, Hamazaki N, Shimamoto S, Hikabe O, Nagamatsu G, Takada Y, Kato K, Hayashi K, Germ cell-intrinsic effects of sex chromosomes on early oocyte differentiation in mice, PLoS Genet, 10.1371/journal.pgen, 16, 3, e1008676-e1008676, 2020.03, A set of sex chromosomes is required for gametogenesis in both males and females, as represented by sex chromosome disorders causing agametic phenotypes. Although studies using model animals have investigated the functional requirement of sex chromosomes, involvement of these chromosomes in gametogenesis remains elusive. Here, we elicit a germ cell-intrinsic effect of sex chromosomes on oogenesis, using a novel culture system in which oocytes were induced from embryonic stem cells (ESCs) harboring XX, XO or XY. In the culture system, oogenesis using XO and XY ESCs was severely disturbed, with XY ESCs being more strongly affected. The culture system revealed multiple defects in the oogenesis of XO and XY ESCs, such as delayed meiotic entry and progression, and mispairing of the homologous chromosomes. Interestingly, Eif2s3y, a Y-linked gene that promotes proliferation of spermatogonia, had an inhibitory effect on oogenesis. This led us to the concept that male and female gametogenesis appear to be in mutual conflict at an early stage. This study provides a deeper understanding of oogenesis under a sex-reversal condition.. |
| 72. |
貴島 雅子¹, 堀 絵美子², 小玉 敬亮¹, 権丈 洋徳¹, 安永 昌史¹, 兼城 英輔¹, 矢幡 秀昭¹, 加藤 聖子¹, 子宮頸癌に対する腹腔鏡下広汎子宮全摘出術および腹式広汎子宮全摘出術症例の比較検討, 日本産科婦人科内視鏡学会雑誌, 35, 2, 209-214, 2019.12, Objective: We compared the clinical outcomes of total laparoscopic radical hysterectomy (LRH) with abdominal radical hysterectomy (ARH) performed in women with cervical cancer.
Methods: Between November 2015 and February 2018, 19 women with cervical cancer (Stage IB1 or IIA1) underwent LRH, and 40 women with cervical cancer (Stage IB1 or IIA1) underwent ARH in our department. Patients' background, surgical outcomes, perioperative complications, and postoperative course were retrospectively compared between the groups. Statistical analysis was performed using the Student's t-test, Wilcoxon test, and the Fisher exact test.
Results: The operative time was significantly longer (587 vs. 422 min, pConclusion: Although this study included a limited number of patients and was a short-term study, LRH was safely performed in women with cervical cancer. Notably, no intergroup difference was observed in short-term outcomes. We will continue observation to determine the long-term prognosis in these women. . |
| 73. |
矢幡 秀昭、権丈 洋徳、堀 絵美子、貴島 雅子、小玉 敬亮、磯邉 明子、八木 裕史、大神 達寛、安永 昌史、小野山 一郎、兼城 英輔、奥川 馨、淺野間 和夫、加藤 聖子, 鏡視下手術におけるRadioisotope法を用いた子宮頸癌センチネルリンパ節同定法の有用性の検討, 九州臨床外科医学会々誌, 4, 1, 11-16, 2019.11, 目的：鏡視下手術におけるRadioisotope法でのセンチネルリンパ節（Sentinel Lymph Node:SLN）同定法の有用性について検討する。
方法：2014年1月から2018年12月までに子宮頸癌の診断で腹腔鏡下あるいはロボット支援下に広汎子宮全摘出術およびSLN検査を行った16例を対象とした。
結果：腹腔鏡下手術12例、ロボット支援下手術4例で進行期はIA1期1例、IB1期14例、IIA1期1例であった。16例中15例で両側にSLNを同定でき、1例は片側のみ同定できた。同定できたSLNは計47個であり、1症例あたり2.9個であった。部位別では外腸骨節が30個で最も多く、次いで閉鎖節14個であった。16例中7症例ではSLN生検後に骨盤リンパ節のバックアップ郭清まで行った。3症例でリンパ節転移を認めたが、全てのSLNに転移を認めたため、感度は100％であった。
結語：子宮頸癌鏡視下手術におけるRI法を用いたSLN同定は同定率、感度、陰性的中率も高く、有用な方法であると考えられた。. |
| 74. |
Yagi H¹, Onoyama I¹, Asanoma K¹, Hori E¹, Yasunaga M¹, Kodama K¹, Kijima M¹, Ohgami T¹, Kaneki E¹, Okugawa K¹, Yahata H¹, Kato K¹, Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer., FASEB J, doi: 10.1096/fj.201901278R, 33, 12, 13683-13694, 2019.12, Gα13, a heterotrimeric G-protein of the Gα12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Gα13 induces epithelial-mesenchymal transition in ovarian cancer (OvCa) cells through down-regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G-protein revealed that Gα13-regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Gα13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.-Yagi, H., Onoyama, I., Asanoma, K., Hori, E., Yasunaga, M., Kodama, K., Kijima, M., Ohgami, T., Kaneki, E., Okugawa, K., Yahata, H., Kato, K. Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer.. |
| 75. |
Yahata H¹, Sonoda K¹, Okugawa K¹, Yagi H¹, Ohgami T¹, Yasunaga M¹, Onoyama I¹, Kaneki E¹, Asanoma K¹, Kato K¹, Survey of the desire to have children and engage in sexual activity after trachelectomy among young Japanese women with early-stage cervical cancer, J Obstet Gynaecol Res, 10.1111/jog.14099, 2019.08, AIM: To evaluate how the desire to have children and engage in sexual activity change after trachelectomy in Japanese women with early-stage cervical cancer who strongly desired to have children before surgery.
METHODS: Desire to have children, coital pain, fear of sexual intercourse, sexual activity frequency and libido were assessed in cervical cancer patients who received follow-up after trachelectomy. An anonymous questionnaire survey was conducted via informed consent.
RESULTS: Of the 151 patients who underwent trachelectomy at Kyushu University Hospital between 2005 and 2015, 46 patients were evaluated; the response rate was 30%. The desire to have children disappeared in 13 of 46 (28%) patients, and 14 (30%) patients experienced increased coital pain. Moreover, 19 (41%) patients experienced fear of sexual intercourse, and sexual frequency decreased in 24 (52%) patients.
CONCLUSION: Trachelectomy is an important fertility-sparing surgical method; however, this study revealed loss of the desire to have children and/or to engage in sexual activity in some patients after surgery. Counseling about these issues is important and should be addressed.. |
| 76. |
Yamaguchi Y¹’², Tayama C¹, Tomikawa J¹, Akaishi R³, Kamura H¹, Matsuoka K⁴’⁵, Wake N², Minakami H⁶, Kato K², Yamada T⁷, Nakabayashi K⁸, Hata K⁹, Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2, Clin Epigenetics, 10.1186/s13148-019-0712-3, 11, 1, 113-113, 2019.08, BACKGROUND: H19 and IGF2 genes are imprinted and involved in regulating fetal and placental growth. The H19 differentially methylated region (DMR) is paternally methylated and maternally unmethylated and regulates the imprinted expression of H19 and IGF2. Epimutation at the H19-DMR in humans results in congenital growth disorders, Beckwith-Wiedemann and Silver-Russell syndromes, when erroneously its maternal allele becomes methylated and its paternal allele becomes unmethylated, respectively. Although H19 and IGF2 have been assessed for their involvement in pregnancy complications including fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH)/hypertensive disorder of pregnancy (HDP) intensively in the last decade, it is still not established whether epimutation at the H19-DMR in the placenta results in pathogenic conditions in pregnancy. We aimed to assess the frequency of H19-DMR epimutation and its effects on the allelic expression patterns of H19 and IGF2 genes among normal and abnormal pregnancy cases.
RESULTS: We enrolled two independently collected sets of placenta samples from normal pregnancies as controls and common pregnancy complications, FGR and PIH (HDP). The first set consisted of 39 controls and 140 FGR and/or PIH cases, and the second set consisted of 29 controls and 62 cases. For these samples, we initially screened for DNA methylation changes at H19-DMR and IGF2-DMRs by combined bisulfite restriction analysis, and further analyzed cases with methylation changes for their allelic methylation and expression patterns. We identified one case each of FGR and PIH showing hypomethylation of H19-DMR and IGF2-DMRs only in the placenta, but not in cord blood, from the first case/control set. For the PIH case, we were able to determine the allelic expression pattern of H19 to be biallelically expressed and the H19/IGF2 expression ratio to be highly elevated compared to controls. We also identified a PIH case with hypomethylation at H19-DMR and IGF2-DMRs in the placenta from the second case/control set.
CONCLUSIONS: Placental epimutation at H19-DMR was observed among common pregnancy complication cases at the frequency of 1.5% (3 out of 202 cases examined), but not in 68 normal pregnancy cases examined. Alteration of H19/IGF2 expression patterns due to hypomethylation of H19-DMR may have been involved in the pathogenesis of pregnancy complications in these cases.. |
| 77. |
Ikeda Y¹, Uemura Y², Asai-Sato M¹, Nakao T¹, Nakajima T¹, Iwata T³, Akiyama A⁴, Satoh T⁴, Yahata H⁵, Kato K⁵, Maeda D⁶, Aoki D³, Kawana K¹, Safety and efficacy of mucosal immunotherapy using human papilliomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine for the treatment of high-grade squamous intraepithelial lesion (HSIL): the study protocol of a ran-domized placebo-controlled clinical trial (MILACLE study), Japanese Journal of Clinical Oncology, 10.1093/jico/hyz095, 2019,1-4, 2019.07, We developed an HPV16 E7-expressing Lactobacillus-based therapeutic vaccine, IGMKK16E7, to elicit mucosal E7-specific TH1 cellular immune responses. This study aims to examine the safety and clinical efficacy of IGMKK16E7 on HPV16-positive high-grade squamous intraepithelial lesion (HSIL). This is a multicenter, placebo-controlled, double-blind randomized phase I/II trial to test the safety and efficacy of IGMKK16E7 against HPV16-positive HSIL. The groups will include placebo, low-dose (0.5 g/day), middle-dose (1 g/day), and high-dose (1.5 g/day) IGMKK16E7. The target sample size will be 41 patients per group, and our data on our former agent, GLBL101c, were used to calculate sample size for 70% power and an α level = 0.05. The primary endpoint is IGMKK16E7 safety and pathological regression at week 16, and the secondary endpoints are cytological regression and HPV16 E7 immunological response. This study protocol has been approved by the Japanese Pharmaceuticals and Medical Devices Agency. Patient enrollment will begin in May 2019.. |
| 78. |
Asanoma K¹, Hori E¹, Yoshida S¹, Yagi H¹, Onoyama I¹, Kodama K¹, Yasunaga M¹, Ohgami T¹, Kaneki E¹, Okugawa K¹, Yahata H¹, Kato K¹, Mutual suppression between BHLHE40/BHLHE41 and the MIR301B-MIR130B cluster is involved in epithelial-to-mesenchymal transition of endometrial cancer cells, Oncotarget, 10.18632/oncotarget.27061, 45, 10, 4640-4654, 2019.07, BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors involved in multiple cell activities including epithelial-to-mesenchymal transition (EMT). However, the expression mechanism of BHLHE40/41 in EMT remains unclear. In the present study, we showed that the expression levels of BHLHE40/41 were negatively correlated with those of the microRNA (MIR) 130 family in endometrial cancer (EC) specimens. Our in vitro assays indicated that the expression of BHLHE40/41 was suppressed directly by the MIR130 family in a 3'-untranslated region-mediated manner. In EC cells, the MIR130 family promoted EMT and tumor cell invasion by suppressing the expression of BHLHE40/41. We identified the critical promoter region of the MIR301B-MIR130B cluster for its basal transcription by the transcription factor, SP1. We also found that BHLHE40/41 suppressed the expression of MIR301B and MIR130B, and we identified a binding site in the promoter region for BHLHE40/41. This study is the first to report that BHLHE40/41 and the MIR301B-MIR130B cluster suppressed each other to regulate EMT and invasion of EC cells. We propose that BHLHE40/41 and the MIR130 family are excellent markers to predict the progression of EC cases, and that molecular therapy targeting the MIR130 family-BHLHE40/41 axis may effectively control EC extension.. |
| 79. |
甲斐 翔太朗¹、坂井 淳彦¹、中野 嵩大¹、城戸 咲¹、蜂須賀 正紘¹、日高 庸博¹、加藤 聖子¹, Cesarean hysterectomyにおける両側総腸骨動脈バルーン閉塞術の有効性と合併症, 日本周産期・新生児医学会雑誌, 55, 1, 108-113, 2019.05, Cesarean hysterectomy(CH)時の出血量低減目的に総腸骨動脈バルーン閉塞術(CIABO)が行われるが, 有効性や合併症の頻度に関しては十分に明らかではない. CIABOの有効性と合併症を検討した. 対象は2011年4月から2018年3月の間に当科でCHを施行した症例で, CIABOを併使したCIABO群(7例)としなかった非CIABO群(7例)に分類した. 術中出血量, 輸血量, 合併症を主要評価項目とした. 術中出血量はCIABO群が2,200-6,758g(中央値3,300g), 非CIABO群が1,908-23,319g(4,650g)で, 前者で少ない傾向がみられたが有意差は認めず, 輸血量も同様であった. CIABO群の1例で右総腸骨動脈血栓症を発症し, ヘパリンで加療した. CIABOがCH時の出血量を減らす可能性がある一方, 動脈血栓症を来した症例はリスク対効果に疑問を呈した.. |
| 80. |
城戸 咲¹、日高 庸博¹、甲斐 翔太朗¹、中野 嵩大¹、蜂須賀 正紘¹、藤田 恭之¹、加藤 聖子¹, SLE女性における妊娠中の原疾患増悪および妊娠高血圧腎症の合併に関連する妊娠時所見の検討．, 日本周産期・新生児医学会雑誌, 55, 1, 92-97, 2019.05, 全身性エリテマトーデス(SLE)を有する女性において, 妊娠中の原疾患増悪および妊娠高血圧腎症(PE)に関連する妊娠時所見を抽出することを目的とした. 2008年から2017年に当院で管理したSLE合併妊娠を対象とし診療録より後方視的に検討した. 妊娠中に症状や検査所見の増悪により加療が強化された症例あるいはPE合併例を増悪群とし, 妊娠成立時の諸所見を非増悪群と比較した. 対象は48女性計59妊娠で, 19妊娠が増悪群に, 40妊娠が非増悪群に分類された. SLE関連臓器障害既往(p |
| 81. |
Inoue S¹,², Ito H¹, Hosono S¹, Hori M¹, Matsuda T¹, Mizuno M¹, Kato K², Matsuo K¹, Net Survival of Elderly Patients with Gynecological Cancer Aged Over 75 Years in 2006-2008, Asian Pacific journal of cancer prevention, 10.31557/APJCP.2019.20.2.437, 20, 2, 437-442, 2019.02, BACKGROUND: The number of elderly patients with gynecological cancer in Japan is increasing in line with the aging of society. However, little has been reported on the survival of elderly patients aged 75 or older with gynecological cancer in Japan.
METHODS: To clarify survival in women aged 75 years or older with gynecological cancer, we analyzed data of 4,089 gynecological cancer cases (cervical cancer, 1,309 cases; endometrial cancer, 1,319 cases; and ovarian cancer, 1,461 cases) in patients aged 75 or older from 21 population-based cancer registries in Japan, diagnosed in 2006-2008. We calculated the net survival (NS) of younger (75-79 years old), older (80-84 years old) and the oldest age group (85-99 years old). We also calculated NS stratified by extent of disease and histological type.
RESULTS:Five-year NS of cervical cancer patients was 54.5% in the younger age group, 40.8% in the older age group and 28.2% in the oldest age group. Five-year NS of endometrial cancer patients was 64.5%, 51.6% and 39.0% in the younger, older and oldest age groups, respectively. Five-year NS of ovarian cancer was 34.7%, 18.8% and 8.3%, respectively.
CONCLUSION:We estimated NS in elderly patients aged 75 years or older with gynecological cancers in Japan using data from population-based cancer registries.. |
| 82. |
Fujita Y¹, Nakanishi TO², Sugitani M², Kato K², Placental Elasticity as a New Non-invasive Predictive Marker of Pre-eclampsia., Ultrasound in Med. & Biol, 10.1016/j.ultrasmedbio.2018.09.007 , 45, 1, 93-97, 2019.01, Point shear wave elastography is an ultrasonography technique used to evaluate tissue elasticity. We examined whether placental elasticity is useful for predicting the onset of pre-eclampsia. Two hundred twenty-one participants were divided into two groups: one group at low risk (n = 185) and the other at high risk (n = 36) for pre-eclampsia. The two groups were compared with respect to shear wave velocity (SWV) of the placenta. Use of SWV as a predictor of pre-eclampsia was also investigated by creating a receiver operating characteristic (ROC) curve. The ROC curve was used to set a cutoff SWV value for predicting pre-eclampsia. The SWV of the high-risk group was significantly higher than that of the low-risk group (p |
| 83. |
Morisaki N¹, Nagata C², Yasuo S³, Morokuma S⁴, Kato K⁵, Sanefuji M⁴, Shibata E⁶, Tsuji M⁷, Senju A⁶, Kawamoto T⁷, Ohga S⁸, Kusuhara K⁹, Japan Environment and Children’s Study Group, Optimal protein intake during pregnancy for reducing the risk of fetal growth restriction: the Japan Environment and Children's Study, Br J Nutr, 10.1017/S000711451800291X, 120, 12, 1432-1440, 2018.12, Clinical trials show that protein supplement increases infant size in malnourished populations; however, epidemiological studies in high-income countries have reported mixed results. Although these findings suggest a non-linear relationship between maternal macronutrient intake and fetal growth, this relationship has not been closely examined. We assessed the association between maternal protein intake and fetal growth among 91 637 Japanese women with singletons in a nation-wide cohort study using validated FFQ. The respondents answered the FFQ twice, once during early pregnancy (FFQ1; 16·3 (sd 6·0) weeks), and second during mid-pregnancy (FFQ2, 28·1 (sd 4·1) weeks). Daily energy intake and percentage energy from protein, fats and carbohydrates were 7477 (sd 2577) kJ and 13·5 (sd 2·0), 29·5 (sd 6·5) and 55·3 (sd 7·8) %, respectively, for FFQ1, and 7184 (sd 2506) kJ and 13·6 (sd 2·1), 29·8 (sd 6·6) and 55·3 (sd 7·9) %, respectively, for FFQ2. The average birth weight was 3028 (sd 406) g, and 6350 infants (6·9 %) were small for gestational age (SGA). In both phases of the survey, birth weight was highest and the risk of SGA was lowest when the percentage energy from protein was 12 %, regardless of whether isoenergetic replacement was with fat or carbohydrates. Furthermore, when protein density in the maternal diet was held constant, birth weight was highest when 25 % of energy intake came from fat and 61 % came from carbohydrates during early pregnancy. We found maternal protein intake to have an inverse U-curve relationship with fetal growth. Our results strongly suggest that the effect of protein on birth weight is non-linear, and that a balanced diet fulfilling the minimum requirement for all macronutrients was ideal for avoiding fetal growth restriction.. |
| 84. |
Egashira K¹, Hiasa K¹, Yokota N¹, Kawamura T¹, Matsushita T¹, Okugawa K¹, Yahata H¹, Sonoda K¹, Kato K¹, Infertility after abdominal trachelectomy, Acta Obstet Gynecol Scand, doi: 10.1111/aogs.13429, 97, 11, 1358-1364, 2018.11, INTRODUCTION: Despite numerous reports on pregnancy outcomes after trachelectomy, there are few descriptions of fertility treatment after trachelectomy. Moreover, little is known about the differences in fertility outcomes between various radical trachelectomy procedures. The purpose of this report was to clarify the infertility problems that occur in patients who have previously undergone an abdominal trachelectomy.
MATERIAL AND METHODS: We retrospectively investigated the medical records of 37 patients who received fertility treatments or were evaluated for menstrual disorders after trachelectomies in our institution between 2012 and 2016.
RESULTS: Twenty-two of 37 patients had complications which affected fecundity. Six patients had cervical stenosis requiring surgical dilation, 4 had ovarian insufficiency, and 14 had Asherman's syndrome.
CONCLUSIONS: In spite of efforts to preserve fertility, some patients have severe complications after trachelectomy, such as Asherman's syndrome, resulting in infertility. Clinicians should pay careful attention to the status of the endometrial cavity after trachelectomy.. |
| 85. |
Sato Y¹, Hidaka N¹, Nakano T¹, Kido S¹, Hachisuga M¹, Fujita Y¹, Kato K¹, Efficacy of an Emergency Cervical Cerclage Using Absorbable Monofilament Su-tures, Journal of Pregnancy 2018:4049792, 10.1155/2018/4049792, 2018.11, Introduction: Although nonabsorbable woven tape has been widely used for cervical cerclage, technical difficulties that can occur with an effaced cervix because of the thickness of the tape, and the risks of local infection are two major concerns. This study investigated perinatal outcomes of pregnancies involving an emergency cervical cerclage using absorbable monofilament polydioxanone sutures, which is a narrow thread and protects against bacterial infection.
Materials and Methods: We performed a chart review of patients who underwent emergency McDonald cerclage with polydioxanone sutures at our institution between 2007 and 2015. Gestational age at delivery, duration between cerclage and delivery, and neonatal prognosis were evaluated as primary outcomes.
Results:Among the 23 patients (18 singleton and five twin pregnancies) evaluated, ultrasound-indicated (progressive cervical length shortening) were eight (35%) and physical examination-indicated (fetal membranes that prolapsed into the vagina or dilated cervix) were 15 patients (65%). The median gestational age at cerclage was 22+3 weeks (range, 17+5 to 25+3 weeks). Postoperative spontaneous abortion occurred in only one patient. The median gestational age at delivery was 32+5 weeks (range, 20+5 to 40+6 weeks). Extremely preterm delivery before 28 weeks of gestation occurred in four (17%) cases. Full-term delivery was achieved in 10 (42%) cases. The duration between cerclage and delivery ranged from 5 to 136 days (median, 77 days). Except for one case of spontaneous abortion, all newborns survived till hospital discharge.
Conclusions:Although our series included some patients at high risk for spontaneous abortion and preterm delivery, satisfactory prolongation and favorable neonatal outcomes were achieved for most patients by using absorbable monofilament sutures, thus suggesting the efficacy of this type of suture for emergency cervical cerclage.. |
| 86. |
Morokuma S¹’², Michikawa T³, Kato K⁴’⁵, Sanefuji M⁴’⁶, Shibata E⁷’⁸, Tsuji M⁹, Senju A⁷'¹⁰, Kawamoto T⁷’⁹, Ohga S⁴’⁶, Kusuhara K⁷’¹⁰, Non-reassuring foetal status and neonatal irritability in the Japan Environment and Children's Study: A cohort study., Sci Rep, 10.1038/s41598-018-34231-y, 8, 1, 15853-15853, 2018.10, The aim of this study was to investigate whether non-reassuring foetal status (NRFS) affected an infant's temperament, or if the temperament formed prenatally resulted in an excessive heart rate reaction that was diagnosed as NRFS. We examined the correlation between NRFS and difficulty in holding a baby, and the amount of crying in the one month after birth, which was considered an indicator of the newborn's temperament. We divided the cases with NRFS into positive NRFS and false positive NRFS. NRFS was associated with bad mood, frequent crying for a long duration, and intense crying. After adjustment for other covariates, NRFS was associated with bad mood (odds ratio, OR = 1.15, 95% confidence interval, CI = 1.00-1.33), and intense crying (1.12, 1.02-1.24). In the multi-variable model, positive and false positive NRFS were not clearly associated with neonatal irritability. When stratified by parity, NRFS and false positive NRFS were likely to be positively associated with neonatal irritability in parous women. The clear association between NRFS and intense crying was observed in parous women (multi-variable adjusted OR = 1.46, 95% CI = 1.16-1.83), but not in nulliparae (1.01, 0.91-1.12) (p for effect modification |
| 87. |
Okugawa K¹, Sonoda K¹, Ohgami T¹, Yasunaga M¹, Kaneki E¹, Yahata H¹, Kato K¹, Pelvic abscess：A late complication of abdominal trachelectomy for cervical cancer, J Obstet Gynaecol, 10.1111/jog.13814, 2018.09, AIM:Only a few reports of pelvic abscess as a late complication of trachelectomy have been published to date. To evaluate the cases of pelvic abscess as a late complication of abdominal trachelectomy for cervical cancer.
METHODS: In June 2005, we began a clinical trial of abdominal trachelectomy at our institution. Written informed consent was obtained from all patients. We retrospectively reviewed the medical records of patients who underwent trachelectomy and extracted the data of patients who experienced pelvic abscess as a late complication.
RESULTS: From June 2005 to September 2017, we performed 181 trachelectomies at our institution. In total, 15 pelvic abscesses occurred in 12 of these patients more than 1 month after trachelectomy. The median postoperative period before the onset of pelvic abscess was 51 months (range, 1-104 months). Among the 15 cases, abscess formed in the uterine adnexa in 12, in a pelvic lymphocyst in two, and in the uterus in one. Abscess drainage was performed in six cases. Three patients underwent laparotomy with salpingo-oophorectomy.
CONCLUSION: It is possible that not only surgical removal of the uterine cervix but also the use of nonabsorbable suture in cervical cerclage and placement of an intrauterine device triggered post-trachelectomy infection. Pelvic abscess can occur as a late complication of abdominal trachelectomy.. |
| 88. |
Kitawaki J¹, Kato K², Annual report of the Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2018., J Obstet Gynaecol Res, 10.1111/jog.13803, 2018.09, Since 2010, the Women's Health Care Committee has addressed important issues linked to women's quality of life. The five agendas this committee has engaged this academic year are: (i) clinical study of urinary complications in perinatal and postpartum women's health care; (ii) education on infectious diseases prophylaxis in obstetrics and gynecology in Japan; (iii) educational activities regarding management guidelines for a female athlete's health care; (iv) training program for women's healthcare advisers; and (v) pregnancy- and lactation-associated osteoporosis (PLOP). The detailed activities of the five subcommittees are described herein. This report is based on the Japanese version of our annual report (Acta Obst Gynaec Jpn 2018; 70: 1538-1546), which publicizes the activities of our committee.. |
| 89. |
Yahata H, Kobayashi H, Sonoda K, Kodama K, Yagi H, Yasunaga M, Ohgami T, Onoyama I, Kaneki E, Okugawa K, Baba S, Isoda T, Ohishi Y, Oda Y, Kato K, Prognostic outcome and complications of sentinel lymph node navigation surgery for early-stage cervical cancer., Int J Clin Oncol, 10.1007/s10147-018-1327-y, 2018.08, BACKGROUND: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy.
METHODS: A total of 139 patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group.
RESULTS: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group.
CONCLUSIONS: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted.. |
| 90. |
Fujita Y, Kiyokoba R, Yumoto Y, Kato K, Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Sub-stitute for Max dP/Dt., Ultrasound Med Biol, 10.1016/j.ultrasmedbio.2018.02.001, 44, 7, 1433-1438, 2018.07, Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults.. |
| 91. |
Morokuma S¹, Maehara K², Okawa H², Kato K², Mine Y³, Nakauchi S³, Simplified Wide-Range Ultrasonic Measurements Using the Sensor Three-Dimensional System, J Med Ultrasound, 10.4103/JMU.JMU_17_18, 26, 2, 100-102, 2018.06, We developed a simplified three-dimensional ultrasonic device that can scan a wide area and performed measurements in the scanned area. The system is more compact than magnetic resonance imaging (MRI) systems and can measure random cross sections by acquiring volume data over a wide range through freehand scanning with a magnetic sensor unit that detects the transducer position. The system was applied successfully to a case with a huge myoma. Our system, in ways similar to computed tomography or MRI systems, can support both the objective understanding of the pathology of huge tumors and follow-up determinations of tumor diameters at arbitrary cross sections in the volume data.. |
| 92. |
Yasutake N¹, Ohishi Y¹, Taguchi K², Hiraki Y³, Oya M³, Oshiro Y⁴, Mine M⁵, Iwasaki T¹, Yamamoto H¹, Kohashi K¹, Sonoda K⁶, Kato K⁶, Oda Y¹, Insulin-like growth factor II messenger RNA-binding protein-3 is an independ-ent prognostic factor in uterine leiomyosarcoma, Histopathology, 10.1111/his.13422, 72, 5, 739-748, 2018.04, AIMS: The aim of this study was to identify the prognostic factors of uterine leiomyosarcoma (ULMS).
METHODS AND RESULTS: We reviewed 60 cases of surgically resected ULMSs and investigated conventional clinicopathological factors, together with the expression of insulin-like growth factor II messenger RNA-binding protein-3 (IMP3), hormone receptors and cell cycle regulatory markers by immunohistochemistry. Mediator complex subunit 12 (MED12) mutation analysis was also performed. Univariate analyses revealed that advanced stage (P CONCLUSIONS: IMP3 expression in ULMS could be a marker of a poor prognosis.. |
| 93. |
Sakai A¹'², Matsuda T¹, Doi H¹, Nagaishi Y¹, Kato K², Nakashima K³, Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice, Proc Natl Acad Sci U S A, 10.1073/pnas.1716479115, 115, 16, 4270-4275, 2018.04, Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 (Cxcr4), consequently increasing the ectopic localization of newborn neurons in the hilus. We also found that voluntary exercise in a running wheel suppressed this ectopic neurogenesis and countered the enhanced seizure susceptibility caused by prenatal VPA exposure, probably by normalizing the VPA-disrupted expression of multiple genes including Cxcr4 in adult NS/PCs. Replenishing Cxcr4 expression alone in NS/PCs was sufficient to overcome the aberrant migration of newborn neurons and increased seizure susceptibility in VPA-exposed mice. Thus, prenatal exposure to an AED, VPA, has a long-term effect on the behavior of NS/PCs in offspring, but this effect can be counteracted by a simple physical activity. Our findings offer a step to developing strategies for managing detrimental effects in offspring exposed to VPA in utero.. |
| 94. |
Yahata H, Sonoda K, Yasunaga M, Ogami T, Kawano Y, Kaneki E, Okugawa K, Tsunehisa Kaku, Kato K, Surgical treatment and outcome of early invasive adenocarcinoma of the uterine cervix (FIGO stage IA1)., Asia Pac J Clin Oncol 2017, 10.1111/ajco.12691, 14, 2, e50-e53, 2018.04, AIM: To investigate the surgical outcome of FIGO stage IA1 cervical adenocarcinoma.
METHODS: Between 2005 and 2011, 12 patients from Kyushu University Hospital had cervical adenocarcinoma, with a tumor depth of less than 3 mm and a horizontal width of less than 7 mm (FIGO stage IA1), diagnosed by cervical conization. All patients underwent simple hysterectomy or simple trachelectomy with pelvic lymphadenectomy.
RESULTS: The mean patient age was 34 years (range, 26-70 years). The median follow-up period was 70.5 months (range, 26-99 months). No pelvic lymph-node metastasis was seen, and no patient experienced disease recurrence.
CONCLUSION:Early invasive cervical adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread of 7 mm or less has little potential for nodal metastasis or recurrence. Therefore, simple hysterectomy or trachelectomy, without lymphadenectomy, might be an alternative treatment option for stage IA1 cervical adenocarcinoma.. |
| 95. |
Ohmaru-Nakanishi T¹, Asanoma K², Fujikawa M¹, Fujita Y¹, Yagi H¹, Onoyama I¹, Hidaka N¹, Sonoda K¹, Kato K¹, Fibrosis in Preeclamptic Placentas Is Associated with Stromal Fibroblasts Acti-vated by the Transforming Growth Factor Beta 1 (TGFB1) Signaling Pathway., Am J Pathol, 10.1016/j.ajpath.2017.11.008, 188, 3, 683-695, 2018.03, Although fibrosis is one of the most prominent pathologic features of preeclamptic (PE) placentas, its mechanism remains largely unknown. Consistent with previous reports, we observed overexpression of collagen; actin, α2, smooth muscle, aorta; connective tissue growth factor; and fibronectin in PE placentas compared with control ones. To investigate the mechanism of fibrosis in PE placentas, placental fibroblasts were isolated from PE placentas or normal pregnancies at delivery. The expression of fibrosis-related factors in fibroblasts was evaluated by real-time RT-PCR, Western blotting, enzyme-linked immunosorbent assay, and gene microarrays. An in vitro collagen gel contraction assay was also performed. Fibroblasts isolated from PE placentas showed higher expression levels of fibrosis-related factors compared with those from control ones. Global gene expression profiling of PE fibroblasts was contrasted with that of control ones and indicated an intimate association with transforming growth factor-β1 (TGF-β1) signaling. Furthermore, the PE fibroblasts expressed abundant phosphorylated SMAD family member 2 and showed higher expression levels of target genes of TGF-β1 signaling compared with the control ones. The PE fibroblasts also had a greater ability to contract compared with the control ones. Contractility also depended on TGF-β1 signaling. Our results suggest that TGF-β1 signaling is activated in the fibroblasts in PE placentas and that these active fibroblasts contribute to fibrosis.. |
| 96. |
Muraoka M¹, Nagata H², Hirata Y¹, Uike K¹, Terashi E¹, Morihana E¹, Ochiai M¹, Fujita Y³,Kato K³, Yamamura K¹, Ohga S¹, High incidence of progressive stenosis in aberrant left subclavian artery with right aortic arch., Heart Vessels, 10.1007/s00380-017-1056-6, 33, 3, 309-315, 2018.03, Right aortic arch with aberrant left subclavian artery (RAA/aLSCA) is a rare aortic arch anomaly. The clinical association of aLSCA stenosis with RAA/aLSCA has not yet been fully elucidated. The aim of this study was to investigate the diagnosis, incidence, management and outcome of aLSCA stenosis in infants with prenatally diagnosed RAA/aLSCA. Ten fetuses who were diagnosed as having RAA/aLSCA in Kyushu University Hospital between January 2011 and December 2014 were enrolled. The maternal and child medical records were reviewed to investigate sex, gestational age at the fetal diagnosis, gestational age and body weight at birth, the findings of computed tomography (CT), Doppler ultrasonography of the vertebral artery and angiography, and the complications and outcomes of aLSCA stenosis. In 8 of 10 patients, aLSCA stenosis was identified on the first CT examination after birth. No patients had dysphagia or respiratory distress. The stenosis spontaneously resolved in 3 patients. In 4 of the 5 remaining patients, aLSCA stenosis progressed, including one case in which complete occlusion occurred-the case was associated with retrograde flow from the left vertebral artery supplying the distal LSCA. Balloon angioplasty was successfully used to treat stenosis in two cases. The subclavian steal phenomenon and developmental problems were not observed in any patients. aLSCA stenosis was identified in 80% of patients with RAA/aLSCA after birth. The early detection and elective treatment of stenotic lesions may be required to prevent complete occlusion during the development of the cardiovascular and cerebrovascular systems.. |
| 97. |
Hidaka N , Kido S, Sato Y, Murata M, Fujita Y, Kato K, Thoracoamniotic shunting for fetal pleural effusion with hydropic change using a double-basket catheter: An insight into the preoperative determinants of shunt-ing efficacy., Eur J Obstet Gynecol Reprod Biol, 10.1016/j.ejogrb.2017.12.008, 221, 34-39, 2018.02, OBJECTIVES: Although the efficacy of thoracoamniotic shunting (TAS) for fetal hydrothorax is well-recognized, the coexistence of hydrops fetalis is still a clinical challenge. The preoperative determinants of shunting efficacy are not fully understood. In this study, we aimed to investigate the perinatal and postnatal outcomes of hydrops fetalis with pleural effusion treated by TAS using a double-basket catheter, and to discuss the preoperative factors predictive of patients who will benefit from TAS.
STUDY DESIGN: We conducted a retrospective study in hydropic fetuses with pleural effusion treated by TAS between 2007 and 2015. We extracted information regarding postnatal survival and pretherapeutic sonographic findings, including skin-edema thickness, pleural-effusion pocket size, and Doppler readings.
RESULTS: Twelve subjects underwent TAS at a median gestational age of 29+5 weeks (range, 25+5-33+2 weeks). Skin edema disappeared or regressed in 7. Three experienced early neonatal death and the other 9 ultimately survived after a live birth at a median gestational age of 33+4 weeks (range, 29+1-38+2 weeks). All surviving children, except for 1, had a pretherapeutic pleural-effusion pocket greater than the precordial-edema thickness. All 3 children that died had precordial-edema thickness equal to or greater than the size of the pleural-effusion pocket.
CONCLUSIONS: We achieved a high survival rate (75%) using the double-basket technique. A greater pretherapeutic width of skin edema compared with the pleural-effusion pocket is possibly suggestive of a treatment-resistant condition and subsequent poor postnatal outcome.. |
| 98. |
Inoue S¹’², Hosono S³, Ito H¹’⁴, Oze I¹, Nishino Y⁵, Hattori M⁶, Matsuda T⁷, Miyashiro I⁸, Nakayama T⁸, Mizuno M⁹, Matsuo K¹’⁴, Kato K², Tanaka H³’¹⁰, Ito Y⁸, J-CANSIS Research Group, Improvement in 5-Year Relative Survival in Cancer of the Corpus Uteri From 1993-2000 to 2001-2006 in Japan., J Epidemiol, 10.2188/jea.JE20170008, 28, 2, 75-80, 2018.02, BACKGROUND: Medical circumstances in Japanese patients with cancer of the corpus uteri have greatly changed since the late 1990s, including the introduction of concomitant therapy with taxane and platinum. We evaluated changes in survival rates for this cancer following these advances by analyzing data from population-based cancer registries in Japan.
METHODS:Data were available for 8562 cases of cancer of the corpus uteri from six prefectural cancer registries. We defined the two periods of 1993-2000 (1st period) and 2001-2006 (2nd period). Relative survival (RS) in each period was calculated to assess changes using an excess mortality model, with adjustment for age group (15-54, 55-69, and 70-99 years), extent of disease (localized, regional, and distant), and histological subtype.
RESULTS: Overall 5-year RS improved from 77.7% in the 1st period to 80.2% in the 2nd period, with an excess hazard ratio (EHR) of 0.785 (95% confidence interval [CI], 0.705-0.873). Five-year RS significantly improved in the group aged 55-69 years, in all groups by extent of disease, and in the endometrioid adenocarcinoma group. In particular, 5-year RS significantly improved in patients with endometrioid adenocarcinoma, from 84.5% to 89.7%, with an EHR of 0.698 (95% CI, 0.560-0.870).
CONCLUSION:Overall 5-year RS for cancer of the corpus uteri in Japan improved from the 1990s to early 2000s. These improvements might have been aided by the comprehensive medical development of management for this cancer, including the spread of concomitant therapy with taxane and platinum as a standard adjuvant chemotherapy in the early 2000s.. |
| 99. |
Sonoda K¹, Yahata H, Okugawa K, Kaneki E, Ohgami T, Yasunaga M, Baba S, Oda Y, Honda H, Kato K, Value of Intraoperative Cytological and Pathological Sentinel Lymph Node Di-agnosis in Fertility-Sparing Trachelectomy for Early-Stage Cervical Cancer, Oncology, 10.1159/000484049, 94, 2, 92-98, 2018.02, BACKGROUND AND OBJECTIVES: Trachelectomy, a fertility-sparing surgery for early-stage cervical cancer, can be performed only when there is no extrauterine extension present. Therefore, identifying the sentinel lymph nodes (SLNs) and using them to obtain an intraoperative pathologic diagnosis can provide information on the feasibility and safety of trachelectomy. Our aim was to assess the value of an intraoperative SLN diagnosis.
METHODS: We retrospectively analyzed the accuracy of intraoperative imprint cytology and frozen-section examination in 201 patients at our institution in whom trachelectomy was planned.
RESULTS: All patients could be evaluated for SLNs; a total of 610 SLNs were analyzed. Although the specificity of both imprint cytology and frozen-section examination was 100.0%, the sensitivity was only 58.6 and 65.5%, respectively. The diagnostic sensitivity was higher in 2-mm slices along the short axis than on bisection along the longitudinal axis. Imprint cytology correctly diagnosed 2 patients who had false-negative results on frozen section. The nature of the metastatic foci that caused an intraoperative false-negative diagnosis was either micrometastasis or isolated tumor cells.
CONCLUSIONS: The accuracy of intraoperative SLN diagnosis requires improvement, especially when small metastatic foci are present.. |
| 100. |
杉山裕子、佐々木寛、小松京子、藤山淳三、藪下竜司、上野喜三郎、小田瑞穂、矢納研二、植田政嗣、田路英作、板持広明、大石徹郎、奥川馨、加藤聖子、藤田博正、田上稔、田勢享、飯原久仁子、上坊敏子、鈴木雅子、三宅真司、大塚重則、畠山重春、森谷卓也, 子宮頸部細胞診精度管理における自動スクリーニング支援システムの有用性について, 日本臨床細胞学会雑誌, 57, 1, 19-34, 2018.01, 子宮頸部細胞診による子宮頚がん検診は、老人保健法により1983年より全国で開始され、2002年より現在の健康増進法に引き継がれている。2012年に策定されたがん対策推進基本計画では、「5年以内に受診率50％以上」の目標値が掲げられているが、子宮頚がんの受診率は、2013年が32.7％で、欧米諸国の受診率80％以上と比較すると極端に低いのが問題である。健診受診率50％以上の目標達成を考えると、今後子宮頸部細胞診検体数が増加することは確実で、細胞診断に携わる細胞検査士や細胞診専門医の大幅な負担増加が予想される。その結果、偽陰性すなわち、見落とし例の増加が懸念される。
日本臨床細胞学会では、偽陰性を少なくするため、細胞診断に関する精度管理の内容を定め、細胞検査士により陰性と判定された標本の10％以上について、細胞診専門医もしくは細胞検査士によちダブルチェックによる再検査を推奨している。したがって現状では、細胞検査士により陰性と判定された標本の約90％が再検査されることなく、陰性と報告されている。わが国で用いているこの10％ランダム再検査に比較して自動スクリーニング支援システムを使用したほうがより効率的に偽陰性を発見できるという事実から、米国では自動スクリーニング支援システムを精度管理目的に使用することが1996年FDAで承認され、広く用いられている。
すでにわれわれは、多施設共同研究として、「子宮頸部細胞診精度管理における自動スクリーニング支援システムの有用性に関する検討」を施行し、細胞検査士により陰性と判断された標本を本システムで再検査した。その結果、偽陰性すなわち、見落とし例が117例（1.19％）検出でき、その内高度扁平上皮内病変以上と判定されたものが、40例（34.2％）も検出でき、精度管理上本システムが有用であることを報告した。
今後子宮頸部細胞診検体数が増加する現状を考えた場合、偽陰性を減少させる効率的なシステム作りが精度管理上喫緊の課題である。本報告では、児童スクリーニング支援システムの子宮頸部細胞診精度管理における有用性について概説し、多施設共同研究の追加研究結果と合わせて報告する。. |
| 101. |
Ohmura Y¹, Morokuma S²’³，, Kato K³, Kuniyoshi Y⁴, Species-specific Posture of Human Foetus in Late First Trimester, Sci Rep, 10.1038/s41598-017-18384-w, 8, 1, 27-27, 2018.01, The ontogeny associated with the arm-hanging posture, which is considered ape-specific, remains unknown. To examine its ontogeny, we measured foetal movements of 62 human foetuses aged 10-20 gestation weeks using four-dimensional sonography. We observed that the first-trimester foetuses show this particular species-specific posture. After 11 weeks of gestation, all foetuses showed the arm-hanging posture, and the posture was most frequently observed at 14-16 weeks of gestation. Moreover, this posture often involved extension of both arms and both legs, indicating that it is not myogenic but neurogenic. Furthermore, early ontogeny suggests that it originates because of subcortical activity. Such posture extension bias and persistence indicates that vestibulospinal tract maturation involves the ontogeny of arm-hanging posture during 14-16 weeks of gestation.. |
| 102. |
Hidaka N¹, Sato Y², Kido S², Fujita Y², Kato K², Ductus venosus Doppler and the postnatal outcomes of growth restricted fetuses with absent end-diastolic blood flow in the umbilical arteries., Taiwanese journal of obstetrics & gynecology, 10.1016/j.tjog.2017.08.012, 56, 5, 642-647, 2017.10, OBJECTIVE: We aimed to evaluate the outcomes of growth-restricted fetuses with absent end-diastolic velocity in the umbilical arteries (UA-AEDV), and investigate the relationship between Doppler flow velocity waveforms in the ductus venosus (DV) and the clinical features.
MATERIALS AND METHODS: This was a retrospective study of growth-restricted fetuses diagnosed with UA-AEDV delivered at our institution between 2013 and 2015. The time from diagnosis of UA-AEDV to delivery, postnatal survival, and developmental prognoses were the primary outcomes. The time lag between the occurrence of UA-AEDV and an abnormal increase in the DV pulsatility index (DV-PI) were investigated. We also examined the correlation between the DV-PI values immediately before birth and umbilical cord arterial pH at birth.
RESULTS: The median gestational age at birth among the 18 subjects was 28+2 (24+0-34+6) weeks, and the observation period between the first detection of UA-AEDV and delivery ranged from 0 to 35 days with a median of 8 days. Among the 18 infants, 15 (83%) survived, among whom 2 were diagnosed with a developmental disability. Gestational age at delivery was significantly lower in the poor outcome group. A positive correlation (correlation coefficient, 0.68) was observed between the umbilical artery pH and the last measured DV-PI.
CONCLUSION: The time interval from initial detection of UA-AEDV to delivery is highly variable, and it is reasonable to manage these growth-restricted fetuses with UA-AEDV expectantly with careful surveillance for fetal well-being. Specifically, Doppler DV analysis is clinically valuable for their evaluation.. |
| 103. |
Setoguchi K, Cui L, Hachisuka N, Obchoei S, Shinkai K, Hyodo F, Kato K, Wada F, Yamamoto T, Harada-Shiba M, Obika S, Nakano K, Antisense Oligonucleotides Targeting Y-Box Binding Protein-1 Inhibit Tumor Angiogenesis by Downregulating Bcl-xL-VEGFR2/-Tie Axes, Mol Ther Nucleic Acids, 10.1016/j.omtn, 9, 170-181, 2017.12, Y-box binding protein-1 (YB-1), involved in cancer progression and chemoradiation resistance, is overexpressed in not only cancer cells but also tumor blood vessels. In this study, we investigated the potential value of amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting YB-1 (YB-1 ASOA) as an antiangiogenic cancer therapy. YB-1 ASOA was superior to natural DNA-based ASO or locked nucleic acid (LNA)-modified YB-1 ASO in both knockdown efficiency and safety, the latter assessed by liver function. YB-1 ASOA administered i.v. significantly inhibited YB-1 expression in CD31-positive angiogenic endothelial cells, but not in cancer cells, in the tumors. With regard to the mechanism of its antiangiogenic effects, YB-1 ASOA downregulated both Bcl-xL/VEGFR2 and Bcl-xL/Tie signal axes, which are key regulators of angiogenesis, and induced apoptosis in vascular endothelial cells. In the xenograft tumor model that had low sensitivity to anti-VEGF antibody, YB-1 ASOA significantly suppressed tumor growth; not only VEGFR2 but also Tie2 expression was decreased in tumor vessels. In conclusion, YB-1/Bcl-xL/VEGFR2 and YB-1/Bcl-xL/Tie signal axes play pivotal roles in tumor angiogenesis, and YB-1 ASOA may be feasible as an antiangiogenic therapy for solid tumors.. |
| 104. |
高山 彩¹, 村田 将春¹, 佐藤 由佳¹, 近藤 有希子¹, 日高 庸博¹, 藤田 恭之¹, 加藤 聖子¹, 双胎妊娠における試験経腟分娩の不成功に関わる因子の検討, 日本周産期・新生児医学会雑誌, 53, 3, 807-811, 2017.09, 双胎妊娠における試験経腟分娩の不成功に関わる因子を明らかにすることを目的とした. 対象は2005年から2014年の10年間に, 当院で妊娠34週以降に試験経腟分娩を行った双胎妊娠である. 両児経腟分娩となった症例を成功例, それ以外を不成功例と定義し, 不成功例の頻度を評価項目, 様々な母体背景を検討因子として調整オッズ比(aOR)をロジスティック回帰分析により求めた. 解析対象は129例であり, 試験経腟分娩の不成功例が22例(18%)であった. ロジスティック回帰分析の結果, 双胎経腟分娩の不成功に対する独立した予測因子は初産婦(aOR: 5.11, 95%信頼区間: 1.65-19.88)と分娩週数(aOR: 1.86, 95%信頼区間: 1.04-3.55)であり, 初産婦であることと分娩週数が遅いことは双胎経腟分娩の不成功に関わる因子であると考えられた.. |
| 105. |
Hidaka N¹, Sato Y¹, Kido S¹, Fujita Y¹, Kato K¹, Expectant management of pregnancies complicated by fetal growth restriction without any evidence of placental dysfunction at term: Comparison with routine labor induction., The journal of obstetrics and gynaecology research, 10.1111/jog.13461, 44, 1, 93-101, 2017.09, AIM: To assess the feasibility and practicality of expectant management for pregnancies with fetal growth restriction (FGR) at term without evidence of placental dysfunction.
METHODS: We reviewed the records of pregnancies with an estimated fetal weight ≤ 1.5 SD below the mean at 37 weeks of gestation. We excluded elective cesarean deliveries and pregnancies that, at 37 weeks, were complicated by oligohydramnios, decreased fetal cerebroplacental ratio, or pregnancy-related hypertensive disorders. Prior to May 2013, we performed routine labor induction for FGR at term; after that time, we used routine expectant management. The rate of delivery by cesarean or instrumental assist and the rate of neonatal morbidity were compared between the groups.
RESULTS: The gestational age at delivery and the neonatal birthweight were higher in the expectant management policy group (39+4 vs 38+1 weeks; 2405 vs 2205 g). The cesarean rate (7/77 vs 7/73) and the instrumental delivery rate (5/77 vs 6/73) did not differ. Neonatal hypoglycemia and hyperbilirubinemia were significantly less frequent (10/77 vs 21/73; 7/77 vs 20/73) in the expectant management policy group. Seven patients in the expectant management policy group underwent emergency cesarean delivery; five of these (71%) had required labor induction because of progression to oligohydramnios.
CONCLUSIONS: Expectant management policy for FGR at term can reduce neonatal morbidity without increasing maternal risk or the cesarean rate. Caution should be used, however, during labor if oligohydramnios develops during expectant management.. |
| 106. |
Morokuma S, Michikawa T, Yamazaki S, Nitta H, Kato K, Association between exposure to air pollution during pregnancy and false posi-tives in fetal heart rate monitoring., Scientific reports, 10.1038/s41598-017-12663-2, 7, 1, 1-8, 2017.09, Fetal heart rate (FHR) monitoring is essential for fetal management during pregnancy and delivery but results in many false-positive diagnoses. Air pollution affects the uterine environment; thus, air pollution may change FHR reactivity. This study assessed the association between exposure to air pollution during pregnancy and FHR monitoring abnormalities using 2005-2010 data from the Japan Perinatal Registry Network database. Participants were 23,782 singleton pregnant women with FHR monitoring, without acidemia or fetal asphyxia. We assessed exposure to air pollutants, including particulate matter (PM), ozone, nitrogen dioxide (NO2), and sulfur dioxide (SO2). In a multi-trimester model, first-trimester PM exposure was associated with false positives in FHR monitoring (odds ratio [OR] per interquartile range (10.7 μg/m3) increase = 1.20; 95% CI: 1.05-1.37), but not second-trimester exposure (OR = 1.05; 95% CI: 0.91-1.21) and third-trimester exposure (OR = 1.06; 95% CI: 0.96-1.17). The association with first-trimester PM exposure persisted after adjustment for exposure to ozone, NO2, and SO2; however, ozone, NO2, and SO2 exposure was not associated with false positives in FHR monitoring. First-trimester PM exposure may alter fetal cardiac response and lead to false positives in FHR monitoring.. |
| 107. |
Kido S, Hidaka N, Sato Y, Fujita Y, Miyoshi K, Nagata K, Taguchi T, Kato K, Re-evaluation of lung to thorax transverse area ratio immediately before birth in predicting postnatal short-term outcomes of fetuses with isolated left-sided congenital diaphragmatic hernia: a single center analysis., Congenit Anom (Kyoto), 10.1111/cga.12243, 1-6, 2017.08, We aimed to investigate whether the lung-to-thorax transverse area ratio (LTR) immediately before birth is of diagnostic value for the prediction of postnatal short-term outcomes in cases of isolated left-sided congenital diaphragmatic hernia (CDH). We retrospectively reviewed the cases of fetal isolated left-sided CDH managed at our institution between April 2008 and July 2016. We divided the patients into two groups based on LTR immediately before birth, using a cut-off value of 0.08. We compared the proportions of subjects within the two groups who survived until discharge using Fisher's exact test. Further, using Spearman's rank correlation, we assessed whether LTR was correlated with length of stay, duration of mechanical ventilation, and supplemental oxygen. Twenty-nine subjects were included (five with LTR |
| 108. |
Morokuma S, Shimokawa M, Kato K, Sanefuji M, Shibata E, Tsuji M, Senju A, Kawamoto T, Kusuhara K, Maternal sleep and small for gestational age infants in the Japan Environment and Children's Study: a cohort study., BMC Res Notes, 10.1186/s13104-017-2675-9, 10, 1, 394-394, 2017.08, OBJECTIVES: Small for gestational age infants have an increased risk of immediate complications, short-term morbidity and mortality, and long-term neurologic and metabolic disorders in adulthood. Previous research has shown that reduced sleep duration is a risk factor for SGA birth. However, only a few studies have evaluated maternal sleep as a risk factor for SGA birth. In the present study, we investigated the relationship between the amount and quality of mothers' sleep and infants' birth weight.
RESULTS: This cohort study (n = 8631) used data from the Japan Environment and Children's Study, an ongoing cohort study that began in January 2011. Data on sleep status (sleep duration and one indicator of sleep quality) and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of small for gestational age birth, and the results were expressed as risk ratios and their respective 95% confidence interval. No significant results were observed for sleep duration or tiredness upon waking. Neither the amount nor the quality of mothers' sleep was associated with the risk of small for gestational age birth.. |
| 109. |
Okawa H, Morokuma S, Maehara K, Arata A, Ohmura Y, Horinouchi T, Konishi Y, Kato K, Eye movement activity in normal human fetuses between 24 and 39 weeks of gestation., PLos One, 10.1371/journal.pone.0178722, 12, 7, 1-12, 2017.07, Rapid eye movement (REM) sleep occurs throughout a relatively large proportion of early development, and normal REM activity appears to be required for healthy brain development. The eye movements (EMs) observed during REM sleep are the most distinctive characteristics of this state. EMs are used as an index of neurological function postnatally, but no specific indices of EM activity exist for fetuses. We aimed to identify and characterize EM activity, particularly EM bursts suggestive of REM periods, in fetuses with a gestational age between 24 and 39 weeks. This cross-sectional study included 84 normal singleton pregnancies. Fetal EMs were monitored using real-time ultrasonography for 60 min and recorded as videos. The videos were manually converted into a time series of EM events, which were then analyzed by piecewise linear regression for various EM characteristics, including EM density, EM burst density, density of EMs in EM bursts, and continuous EM burst time. Two critical points for EM density, EM burst density, and density of EMs in EM bursts were evident at gestation weeks 28-29 and 36-37. Overall EM activity in human fetuses increased until 28-29 weeks of gestation, then again from 36-37 to 38-39 weeks of gestation. These findings may be useful for creating indices of fetal neurological function for prognostic purposes.. |
| 110. |
Michikawa T, Morokuma S, Fukushima K, Kato K, Nitta H, Yamazaki S, Maternal exposure to air pollutants during the first trimester and foetal growth in Japanese term infants, Environ Pollut, 10.1016/j.envpol.2017.06.069, 230, 387-393, 2017.06, Evidence supporting an inverse association between maternal exposure to air pollutants and foetal growth has been accumulating. However, the findings from Asian populations are limited, and the question of critical windows of exposure remains unanswered. We examined whether maternal exposure to air pollutants, in particular exposure during the first trimester (an important period of placental development), was associated with foetal growth in Japanese term infants. From the Japan Perinatal Registry Network database, we received birth data for 29,177 term singleton births in western Japan (Kyushu-Okinawa Districts) between 2005 and 2010. Exposure was expressed in terms of average concentrations of air pollutants (ozone, suspended particulate matter, nitrogen dioxide, and sulphur dioxide), as measured at the nearest monitoring stations to the respective delivery hospitals of the pregnant women, during the entire pregnancy and each trimester. As proxy markers of foetal growth restriction, we used small for gestational age (SGA), and adverse birth weight (low birth weight in addition to SGA). For pollutant exposure during the entire pregnancy, we did not observe the association with SGA and adverse birth weight. In the single-trimester model for the first trimester, however, we found a positive association between ozone exposure, and SGA (odds ratio [OR] per 10 ppb increase = 1.07, 95% confidence interval [CI] = 1.01-1.12) and adverse birth weight (OR = 1.07; 95% CI = 1.01-1.14). This association persisted in the multi-trimester model, and no association for exposure during the second or third trimester was observed. Exposure to other pollutants during each trimester was not associated with these outcomes. In conclusion, maternal exposure to ozone during the first trimester was independently associated with an elevated risk of poor foetal growth.. |
| 111. |
Sonoda K, Yahata H, Okugawa K, Kaneki E, Ｎakatsuki K, Naka M, Terado N, Ookubo F, Oda Y, Tsunehisa Kaku, Kato K, Isthmic-vaginal cytological findings after a trachelectomy for early-stage cervical cancer. , Cytopathology, 10.1111/cyt.12379, 28, 3, 243-245, 2017.06. |
| 112. |
Michikawa T, Morokuma S, Nitta H, Kato K, Yamazaki S, Comparison between air pollution concentrations measured at the nearest monitoring station to the delivery hospital and those measured at stations nearest the residential postal code regions of pregnant women in Fukuoka, Environmental Health and Preventive Medicine 2017 22:55, 10.1186/s12199-017-0663-2, 1-7, 2017.06, Background：Numerous earlier studies examining the association of air pollution with maternal and foetal health estimated maternal exposure to air pollutants based on the women’s residential addresses. However, residential addresses, which are personally identifiable information, are not always obtainable. Since a majority of pregnant women reside near their delivery hospitals, the concentrations of air pollutants at the respective delivery hospitals may be surrogate markers of pollutant exposure at home. We compared air pollutant concentrations measured at the nearest monitoring station to Kyushu University Hospital with those measured at the closest monitoring stations to the respective residential postal code regions of pregnant women in Fukuoka.
Methods：Aggregated postal code data for the home addresses of pregnant women who delivered at Kyushu University Hospital in 2014 was obtained from Kyushu University Hospital. For each of the study’s 695 women who resided in Fukuoka Prefecture, we assigned pollutant concentrations measured at the nearest monitoring station to Kyushu University Hospital and pollutant concentrations measured at the nearest monitoring station to their respective residential postal code regions.
Results：Among the 695 women, 584 (84.0%) resided in the proximity of the nearest monitoring station to hospital or one of the four other stations (as the nearest stations to their respective residential postal code region) in Fukuoka city. Pearson’s correlation for daily mean concentrations among the monitoring stations in Fukuoka city was strong for fine particulate matter (PM2.5), suspended particulate matter (SPM), and photochemical oxidants (Ox) (coefficients ≥0.9), but moderate for coarse particulate matter (the result of subtracting the PM2.5 from the SPM concentrations), nitrogen dioxide, and sulphur dioxide. Hospital-based and residence-based concentrations of PM2.5, SPM, and Ox were comparable.
Conclusions：For PM2.5, SPM, and Ox, exposure estimation based on the delivery hospital is likely to approximate that based on the home of pregnant women.. |
| 113. |
Wada T, Ohishi Y, Kaku T, Aman M, Imamura H, Yasutake N, Sonoda K, Kato K, Oda, Y, Endocervical Adenocarcinoma With Morphologic Features of Both Usual and Gastric Types: Clinicopathologic and Immunohistochemical Analyses and High-risk HPV Detection by In Situ Hybridization., Am J Surg Pathol, 10.1097/PAS.0000000000000833, 41, 5, 696-705, 2017.05, The fourth edition of the World Health Organization classification set up new entities of endocervical adenocarcinoma (ECA), namely the "usual type" and "gastric type." These 2 types are considered to be distinct histogenetically because of their differing immunophenotypes, human papillomavirus (HPV) status, and prognoses. Usual-type ECAs (U-ECAs) are virtually always associated with high-risk human papillomavirus (HR-HPV) infection. Gastric-type ECAs (G-ECAs) are believed not to be associated with HR-HPV infection. Morphologically, U-ECA cells are characterized by mucin-poor and eosinophilic cytoplasm, resembling endometrioid carcinoma (a pseudoendometrioid feature). G-ECA cells are characterized by abundant clear or pale, mucinous cytoplasm and distinct cell borders. However, in routine practice we noticed that some ECAs contain morphologically usual type-like components and gastric type-like components in a single tumor; we have named these "G+U" ECAs. The histogenesis of such tumors has not been investigated. We conducted the present study to clarify the clinicopathologic and immunohistochemical features and HPV status of G+U ECAs, and to determine whether G+U ECAs are genuine G-ECAs mimicking U-ECAs or genuine U-ECAs with gastric type-like morphology. We retrospectively analyzed a series of 70 consecutive cases of ECA diagnosed as mucinous ECA, endocervical type, and we reclassified them on the basis of the latest World Health Organization classification. We identified 48 (69%) pure U-ECAs, 9 pure G-ECAs, and 13 G+U ECAs. Ten of the 13 G+U ECAs (77%) showed no HR-HPV infection by in situ hybridization (HPV-unrelated G+U ECAs) and showed frequent HIK1083 expression and aberrant p53 expression in both usual type-like and gastric type-like components. The other 3 G+U ECAs showed HR-HPV infection (HPV-related G+U EACs) and frequent p16+/p53-/HIK1083- immunophenotype in both usual type-like and gastric type-like components. The U-ECAs were characterized by HR-HPV infection detected by in situ hybridization and frequent p16+/p53-/HIK1083- immunophenotype, similar to that of the HPV-related G+U ECAs. In contrast, the pure G-ECAs were characterized by the absence of HPV infection and frequent HIK1083 expression and aberrant p53 expression, similar to that of HPV-unrelated G+U ECAs. G+U ECAs thus represent a heterogenous group composed of genuine G-ECAs and genuine U-ECAs. Most of the G+U ECAs we examined were genuine HPV-unrelated G-ECAs with usual type-like components showing mucin-poor, eosinophilic cytoplasm (pseudoendometrioid morphology). A small population of G+U ECAs was genuine HPV-related U-ECAs with gastric type-like components showing mucin-rich, voluminous cytoplasm. Thus, both types of ECAs can occasionally display patterns of differentiation suggesting a component of the other type but true mixed tumors do not appear to exist. Ancillary techniques (immunohistochemical analysis of p16, p53, and HPV DNA detection assays) should be used to assure proper classification of tumors with mixed morphologic features.. |
| 114. |
池之上 李都子, 日高 庸博, 佐藤 由佳, 村田 将春, 藤田 恭之, 加藤 聖子, 当院における鉗子分娩例の検討．, 日本周産期・新生児医学会雑誌. 53(1): 23-29, 53, 1, 23-29, 2017.05, 2013年から2015年までの鉗子分娩61例を対象として、その成功率や母体・申請時合併症につき、診療録から後方視的に検討した。また、同時期の吸引分娩137例とMann-Whitne U 検定及びFisher直接確率検定を用いて比較した。61例の内訳は高位鉗子17例、低位鉗子32例、出口部鉗子8例であった。後方後頭位の牽引が5例含まれ、60例で遂娩が成功し、1例で帝王切開に移行した。57例が1回のみの牽引で娩出に至り、膣壁裂傷。3度以上の会陰裂傷、外陰膣血腫が各々39例、7例、4例で生じた。骨折や帽状腱膜下血腫などの重篤な児外傷はなかった。吸引分娩と比較して、最終的な遂娩成功率には差がなかったが、1回の牽引での遂娩成功率は有意に高く（57/61 vs 88/137. p |
| 115. |
Yumoto Y, Jwa SC, Wada S, Takahashi Y, Ishii K, Kato K, Usui N, Sago H, The outcomes and prognostic factors of fetal hydrothorax associated with trisomy 21., Prenatal Diagnosis, 10.1002/pd.5066, 37, 1-7, 2017.05, OBJECTIVES: To determine the characteristics, outcomes, and prognostic factors of fetal hydrothorax (FHT) with trisomy 21.
METHODS: A nationwide survey was conducted on FHT fetuses with trisomy 21 delivered after 22 weeks' gestation between January 2007 and December 2011 at perinatal centers.
RESULTS: The 91 cases of FHT with trisomy 21 included 28 (30.8%) diagnosed in utero and 63 (69.2%) diagnosed after birth. The natural remission rate was 6.6% (6/91). Thoracoamniotic shunting was performed in 14.3% (13/91) of cases. The survival rates of the hydropic, nonhydropic, and total cases were 47.0% (31/66), 84.0% (21/25), and 57.1% (52/91), respectively. The crude odds ratio for death was 8.2 (p = 0.003) for fetuses diagnosed at 26-30 weeks of gestational age (vs ≥30 weeks), 5.9 (p = 0.003) for hydrops, 4.0 (p = 0.04) for bilateral pleural effusion, 0.68 (p = 0.42) for associated cardiovascular anomalies, and 2.1 (p = 0.26) for thoracoamniotic shunting (vs no fetal therapy).
CONCLUSIONS: The prognosis of FHT with trisomy 21 was not very poor, but it was still worse than that of primary FHT. Hydrops, an early gestational age at the diagnosis and bilateral effusion, but not associated anomalies, were risk factors for death. Fetal therapy showed no survival benefit for FHT with trisomy 21.. |
| 116. |
Aman M, Ohishi Y, Imamura H, Shinozaki T, Yasutake N, Kato K, Oda Y, Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse
prognosis in ovarian clear cell carcinoma., Human Pathology, 10.1016/j.humpath.2017.04.008, 64, 156-163, 2017.04, Recent studies demonstrated that Protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress upregulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of COX2 and iNOS were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-OHdG expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early FIGO stage cases but 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-OHdG is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC.. |
| 117. |
Okugawa K, Kobayashi H, Sonoda K, Kaneki E, Kawano Y, Hidaka N, Egashira K, Fujita Y, Yahata H, Kato K, Oncologic and obstetric outcomes and complications during pregnancy after fertility-sparing abdominal trachelectomy for cervical cancer:a retrospective review.
, Int J Oncol, 10.1007/s10147-016-1059-9, 22, 2, 340-346, 2017.04, BACKGROUND: Trachelectomy was developed as a fertility-sparing surgery for early-stage cervical cancer in patients of childbearing age. The purpose of this study is to evaluate oncologic and obstetric outcomes and complications after abdominal trachelectomy.
METHODS: We began to perform abdominal trachelectomy in 2005. Our institutional review board approved this clinical study, and fully informed consent was obtained from each patient. The medical records of patients who underwent trachelectomy were retrospectively reviewed.
RESULTS: We performed 151 abdominal trachelectomies (89 radical trachelectomies, 48 modified radical trachelectomies, and 14 simple trachelectomies). The median age of the patients was 33 years, and the median postoperative follow-up period was 61 months. Although one patient experienced recurrence at the preserved cervix, none died after treatment. A total of 61 patients attempted to conceive after trachelectomy, and 21 pregnancies were achieved in 15 women. Hence, the pregnancy rate among patients who attempted to conceive was 25%. Fifteen babies were delivered by cesarean section between gestational weeks 23 and 37. Six babies were delivered at term. Six cases of preterm premature rupture of the membranes occurred. Varices appeared around the uterovaginal anastomotic site in five patients.
CONCLUSIONS: Our data indicate that the oncologic outcome was excellent but infertility treatment was necessary to achieve the majority of conceptions. Additionally, preterm premature rupture of the membranes and premature delivery were frequently observed. An improved pregnancy rate and prevention of complications during pregnancy are issues that should be addressed in future studies.
. |
| 118. |
Morokuma S, Tsukimori K, Hori T, Kato K, Furue M, The Vernix Caseosa is the Main Site of Dioxin Excretion in the Human Foetus., Sci Rep, 10.1038/s41598-017-00863-9, 7, 1, 739-739, 2017.04, Dioxins are highly toxic to foetuses and prenatal exposure leads to adverse health effects; however, the metabolic pathways involved in dioxin excretion are poorly understood. We determined the dynamics of maternal-to-foetal dioxin transfer during normal pregnancy and how foetuses eliminate polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls. Dioxin levels in maternal blood, cord blood, placenta, vernix caseosa, meconium, and amniotic fluid were analysed by high-resolution gas chromatography/mass spectrometry. The average levels of total dioxins, expressed as picograms of toxic equivalency quantity per gram of lipid and in parentheses, dioxin fraction, with maternal blood levels arbitrarily set as 100%, were as follows: maternal blood, 15.8 (100%); placenta, 12.9 (81.5%); cord blood, 5.9 (37.2%); vernix caseosa, 8.4 (53.2%); meconium, 2.9 (18.2%); and amniotic fluid, 1.5 (9.2%). Similar proportions were observed for each dioxin congener. Thus, the highest content of foetal dioxins was observed in the vernix caseosa, indicating that this is the major site of dioxin excretion in human foetuses.. |
| 119. |
Michikawa T, Seiichi M, Yamazaki S, Fukushima K, Kato K, Nitta H, Air Pollutant Exposure Within a Few Days of Delivery and Placental Abruption in Japan., Epidemiology, 10.1097/EDE.0000000000000605, 28, 2, 190-196, 2017.03, BACKGROUND: Placental abruption is an emergency obstetric complication. Although the etiology of abruption is not fully understood, acute stimuli, such as ischemia and/or inflammation, are associated with rupture of the decidual artery, resulting in placental separation. Ischemia and inflammation are acute biologic effects of air pollution. Using a case-crossover design, we tested the hypothesis that a short-term increase in exposure to air pollutants is a potential trigger of placental abruption.
METHODS: We received data for western Japan (Kyushu-Okinawa Districts) from the Japan Perinatal Registry Network database. From 2005 to 2010, 821 singleton pregnant women with placental abruption were identified. We assigned daily concentrations of air pollutants, including nitrogen dioxide (NO2), suspended particulate matter, ozone, and sulfur dioxide (SO2), from the nearest monitoring station to the respective delivery hospital of each woman. Because information on the onset day of abruption was not obtained, we assumed the case day to be 1 day before the day of delivery.
RESULTS: Exposure to NO2 at 2 days' lag was associated with placental abruption (temperature adjusted odds ratio per 10 ppb increase = 1.4; 95% confidence interval = 1.1, 1.8). The association patterns were similar, when we restricted to participants who delivered by emergency cesarean (1.4, 1.1, 1.9), or who delivered after 35 weeks of gestation (1.4, 1.0, 2.0). There was no association with suspended particulate matter, ozone, or SO2.
CONCLUSIONS: We observed an association between NO2 exposure at 2 days before the day of delivery and placental abruption in pregnant Japanese women.. |
| 120. |
愛甲 碧, 日高 庸博, 佐藤 由佳, 原 枝美子, 近藤 有希子, 村田 将春, 藤田 恭之, 加藤 聖子, 吸引器を用いた急速羊水除去の安全性と有害事象に関する検討, 福岡産科婦人科学会雑誌, 40, 2, 9-14, 2017.01, 【緒言】羊水除去の至適除去速度に関するコンセンサスはない。急激な羊水内圧の減少が胎盤早期剥離を誘発するかもしれないという懸念から緩徐な除去が慣習化されてきたが、その証拠は実際にはほとんどなく、長時間の仰臥位姿勢に伴う患者の苦痛は軽くない。当科で行った急速羊水除去の安全性を検証した。
【方法】2013年5月から2016年2月の間に羊水過多症に対して羊水除去を行った20症例（計31回）を対象とし、術中術直後の合併症、分娩転帰などについて診療録より後方視的に検討した。羊水除去の穿刺には18G PTC針を用い、延長チューブで穿刺針とATOM吸引娩出器VP-400を接続し、除去速度がおよそ100ml/分になるよう吸引圧を調節した。
【成績】母体年齢の中央値は32歳（25～43歳）で、初産婦、経産婦の10例ずつであった。羊水過多の原因として母体妊娠糖尿病が1例、胎児疾患が18例、特発性が1例あった。2回の羊水除去を要したものが9例、3回要したものが1例あった。羊水除去施行週数の中央値は33⁺⁵週（28⁺⁵－37⁺²週）で、1回除去量、除去所要時間、除去速度の中央値はそれぞれ2,000ml、20分、90ml/分であった。1週間以内の前期破水となったものが3例のみあったが、いずれもlate pretermの症例であった。1例に羊膜分離を認めたが早産には至らず、胎盤早期剥離や用紙肝塞栓をきたした症例はなかった。
【考案】吸引器を用いた急速羊水除去は胎盤早期剥離などの重篤な合併症を発生させることなく、母児に対して安全に施行されていた。. |
| 121. |
Kitade S, Onoyama I, Kobayashi H, Yagi H, Kato M, Tsunematsu R, Asanoma K, Sonoda K, Wake N, Hata K, Nakayama K, Kato K, FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian Tumors., Cancer Sci, 10.1111/cas.13026., Epub ahead of print, 2016.08, FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c-Myc, cyclin E, Notch and
c-Jun. FBXW7 is a known tumor-suppressor gene, and mutations in FBXW7 have been reported in various
human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian
cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes.
We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was
negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression
levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors
(P histological subtypes. In addition, p53-mutated ovarian cancer samples showed significantly lower levels
of FBXW7 expression compared with p53 wild-type cancer samples (P and bisulfite PCR sequencing experiments revealed that 5'-upstream regions of FBXW7 gene in p53-mutated
samples were significantly higher methylated compared with those in p53 wild-type samples (P This data indicates that p53 mutations might suppress FBXW7 expression through DNA hypermethylation
of FBXW7 5'-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was
associated with p53 mutations and the DNA methylation status of the 5'-upstream regions of FBXW7.. |
| 122. |
Morokuma S, Shimokawa M, Kato K, Sanefuji M, Shibata E, Tsuji M, Senju A, Kawamoto T, Kusuhara K, Relationship between hyperemesis gravidarum and small-for-gestational-age in the Japanese population:
the Japan Environment and Children's Study (JECS)., BMC pregnancy and childbirth, 10.1186/s12884-016-1041-6., 16, 247-247, 2016.08, BACKGROUND: Small-for-gestational-age in infancy is a known risk factor not only for short-term prognosis
but also for several long-term outcomes, such as neurological and metabolic disorders in adulthood.
Previous research has shown that severe nausea and vomiting in early pregnancy (NVP) and hyperemesis
gravidarum, which is an extreme form of NVP, represent risk factors for small-for-gestational-age birth.
However, there is no clear consensus on this association. Thus, in the present study, we investigated the
correlation between hyperemesis gravidarum and NVP on the one hand, and infant birth weight on the other,
using data from the Japan Environment and Children's Study (JECS).
METHODS: The data utilized in the present study were obtained from the JECS, an ongoing cohort study
that began in January 2011. Our sample size was 8635 parent-child pairs. The presence or absence of severe
NVP, hyperemesis gravidarum, and potential confounding factors were noted. A multivariable regression
analysis was used to estimate risks for small-for-gestational-age birth, and the results were expressed as risk
ratios and 95 % confidence intervals.
RESULTS: The risk ratios of small-for-gestational-age birth (95 % confidence interval) for mothers with
severe NVP and those with hyperemesis gravidarum were 0.86 (0.62-1.19) and 0.81 (0.39-1.66),
respectively, which represents a non-significant result.
CONCLUSIONS: In our analysis of JECS data, neither severe NVP nor hyperemesis gravidarum was associated with increased risk for small-for-gestational-age birth.. |
| 123. |
古賀 李都子, 日高 庸博, 佐藤 由佳, 原 枝美子, 近藤 有希子, 村田 将春, 藤田 恭之, 加藤 聖子, 当院における鉗子分娩例の検討．, 日本周産期・新生児医学会雑誌, 52, 2, 661-661, 2016.06, 【目的】当院では器械分娩の方法として長らく吸引分娩単独で行ってきたが、2013年に牽引力のより強いとされる鉗子分娩を導入し、必要状況に合わせて選択しとしてきた。鉗子分娩の成功率や母体・新生児合併症を検討した。
【方法】2013年から2015年までに鉗子分娩を施行した単胎妊娠例を対象とし、鉗子分娩の種類、牽引時の回旋、牽引回数、墜娩の成否、外傷や黄疸などの新生児合併症、母体産道裂傷や血腫形成の有無などにつき、診療録から後方視的に検討した。また、同時期の吸引分娩137例とMann-Whitney U検定及びFisher直接確率検定を用いて比較した。
【結果】鉗子分娩61例の内訳は高位鉗子4例、中位鉗子17例、低位鉗子32例、出口部鉗子8例であった。後方後頭位の牽引が5例含まれ、全61例中60例で墜娩が成功し、1例で帝王切開に移行した。墜娩成功60例のうち57例が1回の牽引で娩出に至り、膣壁裂傷、3度以上の会陰裂傷、外陰膣血腫がそれぞれ39例、7例、4例で生じた。骨折や頭蓋内出欠、帽状腱膜下血腫などの児合併症はなく、9例で黄疸に対して光線治療が行われた。吸引分娩と比較して、最終的な墜娩成功率には差がなかったが、1回の牽引での墜娩成功率は有意に高く(57/61vs90/137,p【結論】鉗子分娩は少ない牽引回数で児娩出が可能な効果的な急速墜娩法であり、新生児合併症の頻度も高くないが、産道裂傷や血腫形成には留意を要する。. |
| 124. |
川上 穣, 日高 庸博, 原 枝美子, 佐藤 由佳, 近藤 有希子, 村田 将春, 藤田 恭之, 加藤 聖子, 母体CMV-IgMが陰性であった先天性サイトメガロウイルス感染症の1例．, 超音波医学, 10.3179/jjmu. JJMU.A.59, 43, 3, 505-508, 2016.06, 妊娠中のサイトメガロウイルス（CMV）感染は児に不良な予後をもたらしうる重大な感染症であり，診断には母体の血清CMV-IgMが
用いられることが多い．症例は29歳の初産婦．妊娠24週の超音波検査で胎児の発育不全，腹水，腸管高輝度像を認めた．
胎児中大脳動脈最高血流速度が2.5 MoMと高値であり臍帯穿刺を行ったが，臍帯血の血色素量は9.2 g/dlと貧血は軽度で，一方で
血小板数が2.8万/μlと著明低値であった．母体血清よりTORCHスクリーニングを行ったが，CMV-IgMをはじめ全て陰性であった．
しかし諸所見からCMV感染を強く疑い，羊水でのCMV-PCR検査を行ったところ，陽性であり先天感染の診断に至った．
妊娠26週に胎児機能不全と診断したが急速墜娩を選択されず，子宮内胎児死亡となった．死産後の胎盤病理検査で巨細胞封入体を認め，免疫染色で抗CMV抗体が陽性であった．先天性CMV感染は母体のCMV-IgMが陰性であることをもって必ずしも否定されず，
諸所見で感染を強く疑えば羊水PCR検査を考慮すべきである．. |
| 125. |
Yahata H, Kobayashi H, Sonoda K, Shimokawa M, Ogami T, Saito T, Ogawa S, Sakai K, Ichinoe A, Ueoka Y, Hasuo Y, Nishida M, Masuda S, Kato K, Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately
emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in
patients with gynecologic cancer receiving paclitaxel and carboplatin., Int J Clin Oncol, 10.1007/s10147-015-0928-y., 21, 3, 491-497, 2016.06, BACKGROUND: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model.
Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently,
may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against
vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in
patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.
METHODS: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese
patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant
or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy.
The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the
proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively.
RESULTS: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group)
were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not
significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %;
P response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo
group.
CONCLUSION: The administration of aprepitant did not have a prophylactic effect on the HSR but was
effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination
chemotherapy.. |
| 126. |
村上 健太, 日高 庸博, 村田 将春, 藤田 恭之, 加藤 聖子, 500g未満で出生した胎児発育不全例の出生前経過と生後予後, 日本周産期・新生児医学会雑誌, 52, 1, 64-70, 2016.05, 2006年1月から2015年2月までに当科で胎児発育不全と診断し妊娠22週以降に500g未満で出生となった単胎症例を対象とし, 診療録から後方視的に検討した. 形態異常児は除外した. 対象は17例で, 児出生体重の中央値は404g(267-496g), 分娩週数の中央値は妊娠26週2日(妊娠24週0日-妊娠29週2日)で, すべて帝王切開分娩となっていた. 7例(41%)が高血圧または妊娠高血圧症候群を合併し, 11例(64%)に羊水過少, 全例に血流再分配像, 14例(82%)に臍帯動脈の拡張期途絶逆流現象を認めていた. 児は11例(65%)が生存退院し, 1例が精神発達遅滞, 1例が脳性麻痺と診断されていた. 生存退院率は低くなく, 重篤な発達障害をきたしたものも少数であった. 24週, 300gというラインは相応の予後が見込める水準と考えられ, 早期発症の胎児発育不全を管理するにあたって, 児救命を目指した産科管理を適用することが原則になって良いと考えられた.. |
| 127. |
Michikawa T, Morokuma S, Yamazaki S, Fukushima K, Kato K, Nitta H, Exposure to air pollutants during the early weeks of pregnancy, and placenta praevia and pla-centa accreta in the western part of Japan., Environ Int, 10.1016/j.envint.2016.04.037, 92-93, 464-470, 2016.05, BACKGROUND: Placenta praevia is an obstetric complication involving placental implantation in the lower uterine segment. Given the suggested aetiology of placenta praevia, adverse biological effects of air pollutants, such as plasma viscosity increment, endothelial dysfunction, and systemic inflammation, have the potential to induce low implantation. We explored the association between exposure to air pollutants during the pregnancy period up to implantation, and placenta praevia, in pregnant Japanese women. The outcome also included placenta accreta, which often exists in combination with placenta praevia.
METHODS: From the Japan Perinatal Registry Network database, we obtained data on 40,573 singleton pregnant women in western Japan (Kyushu-Okinawa Districts) between 2005 and 2010. We assigned pollutant concentrations (suspended particulate matter [SPM], ozone, nitrogen dioxide [NO2], and sulphur dioxide [SO2]), measured at the nearest monitoring station to the respective delivery hospital of each woman. A logistic regression model was used to adjust for several covariates.
RESULTS: The odds ratios (ORs) of placenta praevia per 10 units increase were 1.12 (95% confidence interval (CI)=1.01-1.23) for SPM over 0-4weeks of gestation, and 1.08 (1.00-1.16) for ozone. The association between exposure to NO2 and SO2, and praevia, was in the direction of increased risk. SPM exposure during 0-4weeks was associated with placenta accreta without praevia (OR=1.33, 95% CI=1.07-1.66). We found no association with exposure to air pollutants during 5-12weeks and the second trimester.
CONCLUSIONS: Exposure to air pollutants through to implantation was positively associated with placenta praevia and accreta.
. |
| 128. |
Masuda A, Katoh N, Nakabayashi K, Kato K, Sonoda K, Kitade M, Takeda S, Hata K, Tomikawa J, An improved method for isolation of epithelial and stromal cells from the human endometrium., The Journal of reproduction and development, 10.1262/jrd.2015-137, 62, 2, 213-218, 2016.04, We aimed to improve the efficiency of isolating endometrial epithelial and stromal cells (EMECs and EMSCs) from the human endometrium. We revealed by immunohistochemical staining that the large tissue fragments remaining after collagenase treatment, which are usually discarded after the first filtration in the conventional protocol, consisted of glandular epithelial and stromal cells. Therefore, we established protease treatment and cell suspension conditions to dissociate single cells from the tissue fragments and isolated epithelial (EPCAM-positive) and stromal (CD13-positive) cells by fluorescence-activated cell sorting. Four independent experiments showed that, on average, 1.2 × 10(6) of EMECs and 2.8 × 10(6) EMSCs were isolated from one hysterectomy specimen. We confirmed that the isolated cells presented transcriptomic features highly similar to those of epithelial and stromal cells obtained by the conventional method. Our improved protocol facilitates future studies to better understand the molecular mechanisms underlying the dynamic changes of the endometrium during the menstrual cycle.. |
| 129. |
Toomine Yukie, Sumiko Watanabe, Setsuo Sugishima, Yoshihiro Ohishi et al., Tamiya Sadafumi, Kobayashi Hiroaki, Sonoda Kenzo, Oda Yoshinao, Kato Kiyoko, Kaku Tsunehisa, Diagnostic value of squamous cell change associated with endometrial carcinoma: A cytopathologic approach., Diagn Cytopathol, 10.1002/dc.23418, 44, 3, 187-194, 2016.03, BACKGROUND: To determine the frequency of squamous cell change associated with endometrial carcinoma, to evaluate the relationship between squamous cell change and clinicopathological features, and to assess cytological findings for squamous cells with and without nuclear atypia in endometrial smears.
METHODS: In 103 cases of endometrioid adenocarcinoma of the endometrium having both histological and cytological specimens, the frequencies and relationships between the presence and absence of squamous cell changes were evaluated, as were the clinicopathological features of such changes. In endometrial smears, squamous cells with and without nuclear atypia were clinicopathologically assessed.
RESULTS: Squamous cell changes were found in 58.3% of cases that had both histological and cytological preparations. There were no significant differences between the group with squamous cell changes and the group without in any of the clinicopathological features. In the cytological smears, 70.0% of the 60 cases that showed squamous cell changes in both preparations did not have nuclear atypia of squamous cells, while 30.0% of those cases had atypia. The group of cases with squamous cells without atypia tended to be better differentiated than the group with atypia. Vessels were permeated significantly more often in the group with atypia than in the group without.
CONCLUSIONS: Our data suggest the importance of observing squamous cells in endometrial cytology, especially concerning findings on nuclei with vs without atypia, when endometrial carcinoma is suspected.. |
| 130. |
Yagi H, Asanoma K, Ohgami T, Ichinoe A, Sonoda K, Kato K, GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer., Oncogene, 10.1038/onc.2015.505., 2016.01, G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Gα12 and Gα13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which Gα12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Gα12/13 in human ovarian cancer tissues. Gα12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, Gα12/13 activation promoted cell growth. We used a synthetic biology approach using chimeric G proteins and GPCRs activated solely by artificial ligands to selectively trigger signaling pathways downstream of specific G proteins. We found that Gα12/13 promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we reveal that inhibition of YAP by short hairpin RNA or a specific inhibitor prevented the growth of ovarian cancer cells. Therefore, YAP may be a suitable therapeutic target in ovarian cancer.Oncogene advance online publication, 25 January 2016; doi:10.1038/onc.2015.505.. |
| 131. |
Inagaki T, Kusunoki S, Tabu K, Okabe H, Yamada I, Taga T, Matsumoto A, Makino S, Takeda S, Kato K, Up-regulation of lymphocyte antigen 6 complex expression in side-population cells de-rived from a human trophoblast cell line HTR-8/SVneo., Human Cell, 10.1007/s13577-015-0121-7, 29, 1, 10-21, 2016.01, The continual proliferation and differentiation of trophoblasts are critical for the maintenance of pregnancy. It is well known that the tissue stem cells are associated with the development of tissues and pathologies. It has been demonstrated that side-population (SP) cells identified by fluorescence-activated cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo cells derived from human primary trophoblast cells were isolated by FACS. HTR-8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In contrast, NSP cell cultures produced NSP cells and failed to produce SP cells. These SP cells showed self-renewal capability by serial colony-forming assay. Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells revealed that SP cells overexpressed several stemness genes including caudal type homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6 complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP cells. LY6D gene reduced its expression in the course of a 7-day cultivation in differentiation medium. SP cells tended to reduce its fraction by treatment of LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR-SVneo-SP cells showed enhanced migration. This is the first report that LY6D was important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with the phenotype of these SP cells.. |
| 132. |
Ohishi Y, Imamura H, Aman M, Shida K, Kaku T, Kato K, Oda Y, Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?, Int J Gynecol Pathol, 10.1097/PGP.0000000000000211., 35, 1, 56-65, 2016.01, "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.. |
| 133. |
Miyata T, Sonoda K, Tomikawa J, Tayama C, Okamura K, Maehara K, Kobayashi H, Wake N, Kato K, Hata K, Nakabayashi K, Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels., Sarcoma 2015, 10.1155/2015/412068, 1-14, Epub 2015 Dec 28, 2015.12, Uterine leiomyosarcoma (LMS) is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM),
a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.. |
| 134. |
Naka M, Ohishi Y, Kaku T, Watanabe S, Tamiya S, Ookubo F, Kato K, Oda Y, Identification of Intranuclear Inclusions is Useful for the Cytological Diagnosis of Ovarian Clear Cell Carcinoma, DIAGNOSTIC CYTOPATHOLOGY, 10.1002/dc.23322, 43, 11, 879-884, 2015.11, OBJECTIVE: The aim of this study was to clarify the diagnostic significance of the presence of intranuclear inclusions in clear cell carcinoma (CCC).
MATERIALS AND METHODS: We analyzed 98 imprint specimens and 53 ascites specimens from 98 ovarian carcinoma cases [28 CCCs, 37 serous carcinomas (SCs), 22 endometrioid carcinomas (ECs), and 11 mucinous carcinomas (MCs)]. We examined (1) frequency of intranuclear inclusion-positive cases of each ovarian carcinoma subtype, using imprint specimens, (2) frequency of intranuclear inclusion-positive cells of each ovarian carcinoma subtype, using imprint specimens, (3) frequency of intranuclear inclusion-positive cases of each ovarian carcinoma subtype, using ascites specimens, and (4) sensitivity and specificity of the presence of intranuclear inclusions for the cytological diagnosis of CCC.
RESULTS: (1) The frequency of intranuclear inclusion-positive cases in CCC (96.4%) was significantly higher than in SC (13.5%), EC (13.6%), and MC (18.2%) (P
CONCLUSIONS: The identification of intranuclear inclusions, in particular a high frequency and multiple intranuclear inclusions in a single nucleus, is useful for the cytological diagnosis of CCC. Furthermore, these results may be applicable to ascites cytology. Diagn. Cytopathol. 2015;43:879-884. © 2015 Wiley Periodicals, Inc.. |
| 135. |
Matsueda S, Hidaka N, Kondo Y, Fujiwara A, Fukushima K, Kato K, External iliac artery thrombosis after common iliac artery balloon occlusion during cesarean hysterectomy for placenta accreta in cervico-isthmic pregnancy, JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 10.1111/jog.12777, 41, 11, 1826-1830, 2015.11, Although the role of interventional radiology in the field of obstetrical hemorrhage has been widely reported upon recently, the rate of procedure-related complications has not been fully determined. We present the case of a patient who developed an external iliac artery thrombosis, a rarely reported complication associated with prophylactic common iliac artery balloon occlusion (CIABO). After CIABO, we found that the dorsalis pedis artery of the right foot was weak and the foot was cold, despite the fact that the patient had no complaints. Computed tomography demonstrated a linear thrombus in the right external iliac artery. We managed the patient conservatively using a heparin drip without the need for thromboembolectomy. Our experience suggests that it is important to consider the risk of thrombosis formation after CIABO. Physical examination post-procedure is key to identifying this complication early.. |
| 136. |
Takako Yamane, KAZUO ASANOMA, Hiroaki Kobayashi, Liu Ge, Hiroshi Yagi, Tatsuhiro Ogami, AKIMASA ICHINOE, Kenzo Sonoda, Norio Wake, Kiyoko Kato, Identification of the Critical Site of Calponin 1 for Suppression of Ovarian Cancer Properties., Anticancer Res., 35, 11, 5993-5999, 2015.11, BACKGROUND: Although several studies have demonstrated the tumor suppressive function of CNN1 (calponin 1), no studies have performed a site-specific analysis of CNN1 on tumor cell activities.
MATERIALS AND METHODS: We herein studied the site-specific effects of CNN1 in ovarian cancer cells using full-length CNN1 (fCNN1), three CNN1 repeats (3CNRs), or the first CNN1 repeat (CNR1) expression vectors. Ovarian cancer cells stably expressing each construct were analyzed for in vitro proliferation, cell motility, invasion, and soft agar assays. An in vitro model of pleural dissemination was also established.
RESULTS: Cell proliferation, anchorage-independent colony formation, cell motility, and cell invasion were all suppressed in fCNN1, 3CNRs, and CNR1-stably-expressing cells. CNN1 expression in mesothelial cells suppressed cancer cell invasion into a monolayer of mesothelial cells.
CONCLUSION: CNR1 showed similar suppressive effects as fCNN1. Results suggest CNR1 as a potential small synthetic peptide candidate for therapeutic strategies against ovarian cancer.. |
| 137. |
Imamura H, Ohishi Y, Aman M, Shida K, Shinozaki T, Yasutake N, Sonoda K, Kato K, Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor, HUMAN PATHOLOGY, 10.1016/j.humpath.2015.06.002, 46, 10, 1455-1463, 2015.10, Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.. |
| 138. |
Michikawa T, Morokuma S, Fukushima K, Ueda K, Takeuchi A, Kato K, Nitta H, A register-based study of the association between air pollutants and hypertensive disorders in pregnancy among the Japanese population., Envionmental research, 10.1016/j.envres.2015.08.024., 142, 644-650, 2015.10, BACKGROUND:
Ambient air pollution is hypothesized to be a risk factor for hypertensive disorders in pregnancy, one of the major pregnancy complications. Past studies have reported the supporting evidence, however this mainly referred to the Western population, and results from trimester-specific analysis have been varied. In this study, we focused on exposure during the first trimester of pregnancy (placental development stage), and tested the hypothesis among the Japanese population.
METHODS:
We drew on data from the Japan Perinatal Registry Network database, and studied 36,620 singleton pregnant women without medical complications, in western Japan (Kyushu and Okinawa districts) between 2005 and 2010. In addition, data on ozone, suspended particulate matter (SPM), nitrogen dioxide (NO2), and sulfur dioxide (SO2) concentrations were obtained. The nearest monitoring station to the respective birthing hospital was used as a reference point for assigning average concentrations of each pollutant during the first trimester of pregnancy for each woman. The logistic regression model was applied to assess the association between quintiles of each pollutant and hypertensive disorders in pregnancy.
RESULTS:
Mean concentrations during the first trimester were 41.3ppb for ozone, 27.4μg/m(3) for SPM, 11.8ppb for NO2, and 3.2ppb for SO2. High exposure to ozone was associated with an increased risk of hypertensive disorders in pregnancy (for highest quintile vs. lowest: odds ratio=1.20, 95% confidence interval=1.01-1.42). With regard to SPM, NO2 and SO2, we did not obtain the results with constant directionality.
CONCLUSIONS:
Ozone exposure during early pregnancy may be a risk factor for hypertensive disorders in pregnancy.. |
| 139. |
柿添 絵里, 日高 庸博, 城戸 咲, 村田 将春, 藤原 ありさ, 藤田 恭之, 福嶋 恒太郎, 加藤 聖子, Joel-Cohen 変法による超緊急帝王切開術の検討． , 日本周産期・新生児医学会雑誌, 51, 3, 1018-1023, 2015.09, 「概要」可及的迅速な児娩出を要する場合に全身麻酔下の超緊急帝王切開が行われるが, 児娩出までの時間をいかに短縮するかは周産期医療施設の重要な課題である. また, 下腹部横切開は美容上の優位性に加えて, 創痛やヘルニア形成が少ない利点をもつ. 2013年より導入した Joel-Cohen 変法による超緊急帝王切開術を後方視的に検討した. 全12例の手術週数の範囲は28+5-41+1週で, 4例が早産期の手術であった. 手術開始から児娩出までの時間は1.7±0.9分で, 最長3分であった. 総手術時間は62.8±16.2分, 術中出血量は947±468mlであった. 輸血例はなく, 他臓器損傷などの術中合併症もなかった. Tukey-Kramer 検定を用いて2012年以降の Pfannenstiel 法による超緊急帝王切開18例, 下腹部縦切開法による17例と多重比較すると, 手術開始から児娩出までの時間が Joel-Cohen 変法で他法より有意に短く, 総手術時間や出血量には差がなかった. Joel-Cohen 変法は超緊急帝王切開において短時間に児を娩出できる有効かつ安全な開腹法である.. |
| 140. |
城戸 綾子, 日高 庸博, 城戸 咲, 藤原 ありさ, 藤田 恭之, 福嶋 恒太郎, 加藤 聖子, 妊娠中に発症した急性虫垂炎症例の検討．, 日本周産期・新生児医学会雑誌, 51, 3, 997-1002, 2015.09, 「概要」急性虫垂炎合併妊娠の臨床像と周産期経過を後方視的に検討した. 診断週数の中央値は27週5日(14週0日-32週6日)であった. 全例が腹痛を主訴とし, 3例が右下腹部, 1例が心窩部を最強点とした. 1例に反跳痛を認め, 筋性防御を示した例はなかった. 1例で超音波検査で, 他の3例はCT検査で診断し, 手術を施行した. 妊娠14週の症例1例で全身麻酔下に腹腔鏡手術を行い, その他の3例では開腹手術が行われた. 自然穿孔例はなかった. 3例で術後に子宮収縮抑制剤を要し, 平均投与期間は6日間であった. 4例中3例はその後の妊娠経過で産科合併症を認めないまま正期産経腟分娩に至った. 低出生体重児や asphyxia 例はなかった. 今回の検討で, 虫垂切除術後の分娩転帰, 母児の予後は良好であった. これは来院後速やかに画像診断と手術を行ったことによると考えられた. また, 妊娠週数によっては腹腔鏡手術が第一選択となりうると考えた. . |
| 141. |
Hachisuga M, Oki S, Kitajima K, Ikuta S, Sumi T, Kato K, Wake N, Meno C, Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 10.1073/pnas.1504529112, 112, 38, E5300-E5307, 2015.09, Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left-right axis in mouse embryos. Expression of Pitx2, which plays a key role in left-right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to express Nodal and Pitx2 in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left-right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left-right axis required for heart morphogenesis.. |
| 142. |
KAZUO ASANOMA, Liu Ge, Takako Yamane, Yoko Miyanari, Tomoka Takao, Hiroshi Yagi, Tatsuhiro Ogami, AKIMASA ICHINOE, Kenzo Sonoda, Norio Wake, Kiyoko Kato, Regulation Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells., Mol Cell Biol, 35, 24, 4096-4109, 2015.09, BHLHE40 and BHLHE41 are basic helix-loop-helix type transcription factors that play key roles in multiple cell behaviors. BHLHE40 and BHLHE41 (BHLHE40/41) were recently shown to be involved in epithelial-to-mesenchymal transition (EMT). However, the precise mechanism of EMT control by BHLHE40/41 remains unclear. In the present study, we demonstrated that BHLHE40/41 expression was controlled in a pathological stage-dependent manner in human endometrial cancer (HEC). Our in vitro assays showed that BHLHE40/41 suppressed tumor cell invasion. BHLHE40/41 also suppressed the transcription of the EMT effectors, SNAI1, SNAI2, and TWIST1. We identified the critical promoter regions of TWIST1 for its basal transcriptional activity. We elucidated that the transcription factor, SP1, was involved in the basal transcriptional activity of TWIST1 and that BHLHE40/41 competed with SP1 for DNA binding to regulate gene transcription. This study is the first to report the detailed functions of BHLHE40 and BHLHE41 in the suppression of EMT effectors in vitro. Our results suggest that BHLHE40/41 suppress tumor cell invasion by inhibiting EMT in tumor cells. We propose that BHLHE40/41 are promising markers to predict the aggressiveness of each HEC case, and that molecular targeting strategies involving BHLHE40/41 and SP1 may effectively regulate HEC progression.. |
| 143. |
Satoru Kyo, Kiyoko Kato, Endometrial Cancer Stem Cell as a Potential Therapeutic Target., Semin Reprod Med, 33, 5, 341-349, 2015.09, Adult stem cells have recently been identified in several types of mature tissue and it has been also suggested that stem-like cells exist in cancerous tissues. It is believed that many cancer stem cells (CSCs) upregulate the expression of drug transporters, allowing them to efficiently pump antitumor agents out of the cells. CSCs reside in a quiescent state, making them resistant to chemotherapeutic agents that target rapidly cycling cells. They are also endowed with a more invasive and metastatic phenotype. These results indicate the requirement to develop a new target treatment for CSCs. There are several methods for the identification of CSCs; for example, detection by CSC markers, such as CD133, CD44, CD117(c-kit), aldehyde dehydrogenase 1 (ALDH1), and isolation of side population (SP), which are identified based on their ability to remove intracellular Hoechst 33342, a fluorescent dye. Here, we review recent articles that show the presence of stem cells in endometrial cancer and introduce the results of our own recent studies using CD133 or CD117 positive cells and SP cells.. |
| 144. |
Ohmaru T, Fujita Y, Sugitani M, Shimokawa M, Fukushima K, Kato K, Placental elasticity evaluation using virtual touch tissue quantification during pregnancy, PLACENTA, 10.1016/j.placenta.2015.06.008, 36, 8, 915-920, 2015.08, INTRODUCTION: Virtual touch tissue quantification (VTTQ) has been developed to evaluate tissue elasticity. Our previous study using delivered placentas showed increased elasticity in fetal growth restriction (FGR). Therefore, we investigated changes in placental elasticity during pregnancy, including complicated pregnancies.
METHODS: Based on complications, 199 women were divided into 5 groups (normal, FGR, pregnancy induced hypertension (PIH), diabetes mellitus and collagen disease), and shear wave velocity (SWV) of the placenta, measured using VTTQ, was compared. A cross-sectional study was performed with the 143 normal cases to construct the reference range. The association between placental SWV and the expression ratio of collagen fibers in the placenta stained with Masson's trichrome was determined.
RESULTS:The SWV was safely measured for all participants. The correlation between SWV and gestational weeks was not significant. The mean ± SD SWVs in the normal, FGR, and PIH groups were 0.98 ± 0.21, 1.28 ± 0.39, and 1.60 ± 0.45 m/sec, respectively. The FGR and PIH groups had significantly higher SWVs than that of the normal group. SWV and the expression ratio of collagen fibers were significantly correlated.
DISCUSSION: Based on the present findings, changes in SWV during pregnancy were associated with placental fibrosis, and increased SWV in PIH and/or FGR cases might be influenced by infarction, ischemic changes, and inflammation, as well as fibrosis. In conclusion, the measurement of placental SWV is potentially useful to evaluate the condition of the placenta during pregnancy.. |
| 145. |
Kanako Okamoto, Ryosuke TSUNEMATSU, Tomoko Tahira, Kenzo Sonoda, KAZUO ASANOMA, Hiroshi Yagi, Tomoko Yoneda, Kenshi Hayashi, Norio Wake, Kiyoko Kato, SNP55, a new functional polymorphism of MDM2-P2 promoter, contributes to allele-specific expression of MDM2 in endometrial cancers, BMC MEDICAL GENETICS, 10.1186/s12881-015-0216-8, 16, 1, 67, 2015.08, BACKGROUND:
The functional single nucleotide polymorphism (SNP) in the MDM2 promoter region, SNP309, is known to be associated with various diseases, particularly cancer. Although many studies have been performed to demonstrate the mechanism of allele-specific expression (ASE) on SNP309, they have only utilized in vitro techniques. It is unknown whether ASE of MDM2 is ascribed solely to SNP309, in vivo.
METHODS:
We attempted to evaluate ASE of MDM2 in vivo using post-labeling followed by automated capillary electrophoresis under single-strand conformation polymorphism conditions. For measuring a quantitative difference, we utilized the SNPs on the exons of MDM2 as markers, the status of which was heterozygous in a large population. To address the cause of ASE beyond 20 %, we confirmed sequences of both MDM2-3'UTR and promoter regions. We assessed the SNP which might be the cause of ASE using biomolecular interaction analysis and luciferase assay.
RESULTS:
ASE beyond 20 % was detected in endometrial cancers, but not in cancer-free endometria samples only when an SNP rs1690916 was used as a marker. We suspected that this ASE in endometrial cancer was caused by the sequence heterogeneity in the MDM2-P2 promoter, and found a new functional polymorphism, which we labelled SNP55. There was no difference between cancer-free endometria and endometrial cancer samples neither for SNP55 genotype frequencies nor allele frequencies, and so, SNP55 alone does not affect endometrial cancer risk. The SNP55 status affected the DNA binding affinity of transcription factor Sp1 and nuclear factor kappa-B (NFκB). Transcriptional activity of the P2 promoter containing SNP55C was suppressed by NFκB p50 homodimers, but that of SNP55T was not. Only ASE-positive endometrial cancer samples displayed nuclear localization of NFκB p50.
CONCLUSIONS:
Our findings suggest that both the SNP55 status and the NFκB p50 activity are important in the transcriptional regulation of MDM2 in endometrial cancers.. |
| 146. |
Yuka Otera, Seiichi Morokuma, Kotaro Fukushima, Ai Anami, Yasuo Yumoto, Yushi Itoh, Masayuki Ochiai, KIMIAKI HASHIGUCHI, Norio Wake, Haruhiko Sago, Kiyoko Kato, Neurological outcomes in Chiari type II malformations and their correlation to morpho-logical findings and fetal heart rate patterns: a retrospective study., 10.1186/s13104-015-1014-2, 27, 8, 57-57, 2015.02, BACKGROUND: Correlations among Chiari type II malformation (CMII) morphological findings, the proportion of fetal heart rate patterns corresponding to the quiet phase (QP), and neurological outcomes have yet to be investigated.
FINDINGS: The correlations among the morphological findings (i.e., the degree of ventriculomegaly, myelomeningocele levels, and degree of cerebellar herniation), proportion of time spent in QP, and developmental quotients (DQs) were analyzed in 22 children. The proportion of time spent in QP was compared between children with poor neurological outcomes (n = 9) and those with good outcomes (n = 13). Pearson's correlations and the Mann-Whitney U-test were used to assess for statistical significance; P
CONCLUSIONS: The proportion of fetal heart rate patterns corresponding to the QP might be a useful predictor of neurological outcomes in 2-year-old children with CMII.. |
| 147. |
Liu Ge, KAZUO ASANOMA, Tomoka Takao, Tsukimori Kiyomi, Uchi Hiroshi, Masutaka Furue, Kiyoko Kato, Norio Wake, Aryl hydrocarbon receptor SNP -130 C/T associates with dioxins susceptibility through regulating its receptor activity and downstream effectors including interleukin 24., Toxicology Letters, 232, 2, 384-392, 2015.01, Dioxins are persistent environmental pollutants that cause multiple adverse health effects in humans, mainly through binding to the ligand-activated transcription factor, aryl hydrocarbon receptor (AhR). Genetic variation in AhR may modulate the susceptibility to dioxins. In this study, we aimed to evaluate the effects of the single nucleotide polymorphism (SNP) -130 C/T in the AhR promoter on dioxin-inducible gene transcription, and to investigate interleukin-24 (IL-24) and interleukin-1β (IL-1β) as proxies for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. Using primary human chorionic stromal cells, we found that cells with the TT genotype showed higher AhR mRNA and protein levels than did those of the CC genotype. Microarray was carried out to analyze the gene expression profiles of cells (CC and TT genotype) after exposing the cells to TCDD. Several genes associated with human disorders were more highly up-regulated in cells of the TT genotype. Higher up-regulation of IL-24 and IL-1β mRNA in cells with the TT genotype was observed. Furthermore, blood samples from 64 Yusho patients who were accidentally exposed to high concentrations of dioxins were analyzed for the genotype, dioxins concentrations and serum levels of IL-24 and IL-1β. We observed higher serum IL-24 levels and lower serum IL-1β levels in Yusho patients with the TT genotype than in those with the CC genotype. AhR SNP -130 C/T affects serum IL-24 and IL-1β levels, independently of serum dioxins concentrations in Yusho patients. Our observations demonstrate that SNP -130 C/T modulates AhR expression and expression levels of IL-24 and IL-1β, and suggest an association of AhR SNP -130 C/T with the susceptibility to dioxins. . |
| 148. |
中野 崇大, 日高 庸博, 藤田 恭之, 福嶋 恒太郎, 加藤 聖子, 乳癌合併妊娠の臨床的検討．, 日本周産期・新生児医学会雑誌, 50, 4, 1275-1280, 2015.01, 乳癌合併妊娠の臨床経過と周産期予後を明らかにすることを目的とし, 2007年から2013年までの7例につき, 後方視的に検討を行った. 6例が妊娠中初発例, 1例が再発例であった. 初発6例の診断週数の中央値は20週(11-29週)であった. 進行期はstage Iが3例, IIAが2例, IIIBが1例, IV期が1例であった. 1例で胎児の18トリソミーを理由とした人工妊娠中絶が選択され, それ以外の6例で妊娠を継続し生児を得た. 中絶1例を除いた6例の治療開始週数の中央値は29週(19-32週)で, 全例で外科手術が行われた. また1例で妊娠中に化学療法が行われた. 中絶例以外の分娩週数の中央値は36週(35-37週)であった. 乳癌治療中や分娩中のNRFS診断例はなかった. 出生体重と臍帯動脈血pHの中央値は2,540g(2,125-2,970g), 7.29(7.19-7.38)であった. 重篤な新生児合併症はなかった. 今回の結果により乳癌合併妊娠の良好な周産期予後が示され, これは妊娠中に化学療法を行った症例でも同様であり, 乳癌治療に人工早産を先行させる必要はないと考えられた. . |
| 149. |
Kenzo Sonoda, Hideaki Yahata, AKIMASA ICHINOE, Koru Okugawa, Eisuke Kaneki, Yoshiaki Kawano, Hironori Kenjo, Tatsuhiro Ogami, Hiroshi Yagi, Ohga Saiji, Kaori Asai, Katsumasa Nakamura, Hiroshi Honda, Kiyoko Kato, Retrospective Analysis of Concurrent Chemoradiation with Triweekly Cisplatin plus 5-Fluorouracil Versus Weekly Cisplatin in Cervical Cancer., 35, 6, 3447-3454, 2015.01, BACKGROUND/AIM: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. The purpose of the study was to compare the outcomes of triweekly cisplatin plus 5-fluorouracil and weekly cisplatin regimens.
PATIENTS AND METHODS: We retrospectively reviewed data from 91 patients with stage IB1-IVA cervical cancer.
RESULTS: Out of 91 patients, 48 received triweekly CCRT and 43 received weekly CCRT. For triweekly CCRT, patients received a median of two chemotherapy cycles and median total doses of cisplatin and 5-fluorouracil were 210 mg/body and 8,525 mg/body, respectively. For weekly CCRT, patients received a median of five chemotherapy cycles and the median total dose of cisplatin was 252 mg/body. No statistically significant differences in overall survival or progression-free survival were noted between the two groups.
CONCLUSION: Both triweekly CCRT and weekly CCRT appear to have similar efficacy for cervical cancer patients, but the toxicities were better tolerable in weekly CCRT.
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| 150. |
Kohei Miyata, Tomoko Miyata, Kazuhiko Nakabayashi, Kohji Okamura, Masashi Naito, Tomoko Kawai, Shuji Takada, Kiyoko Kato, Shingo Miyamoto, Kenichiro Hata, Hiroshi Asahara, DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of
muscle-related genes and its involvement in transcriptional down-regulation.
, 10.1093/hmg/ddu457, 24, 2, 410-423, 2015.01, Although DNA methylation is considered to play an important role during myogenic differentiation, chronological alterations in DNA methylation and gene expression patterns in this process have been poorly understood. Using the Infinium HumanMethylation450 BeadChip array, we obtained a chronological profile of the genome-wide DNA methylation status in a human myoblast differentiation model, where myoblasts were cultured in low-serum medium to stimulate myogenic differentiation. As the differentiation of the myoblasts proceeded, their global DNA methylation level increased and their methylation patterns became more distinct from those of mesenchymal stem cells. Gene ontology analysis revealed that genes whose promoter region was hypermethylated upon myoblast differentiation were highly significantly enriched with muscle-related terms such as 'muscle contraction' and 'muscle system process'. Sequence motif analysis identified 8-bp motifs somewhat similar to the binding motifs of ID4 and ZNF238 to be most significantly enriched in hypermethylated promoter regions. ID4 and ZNF238 have been shown to be critical transcriptional regulators of muscle-related genes during myogenic differentiation. An integrated analysis of DNA methylation and gene expression profiles revealed that de novo DNA methylation of non-CpG island (CGI) promoters was more often associated with transcriptional down-regulation than that of CGI promoters. These results strongly suggest the existence of an epigenetic mechanism in which DNA methylation modulates the functions of key transcriptional factors to coordinately regulate muscle-related genes during myogenic differentiation. . |
| 151. |
Kazuhisa Hachisuga, Nobuhiro Hidaka, Yasuyuki Fujita, Kotaro Fukushima, Kiyoko Kato, Can we predict neonatal thrombocytopenia in offspring of women with idiopathic thrombocytopenic purpura?, Blood Res, 49(4): 259-264, 2014.12, BACKGROUND: We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia.
METHODS: Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count RESULTS: Sixty-six neonates from 49 mothers were enrolled in the study. Thrombocytopenia was observed in 13 (19.7%) neonates. Maternal treatment for ITP such as splenectomy did not correlate with a risk of neonatal thrombocytopenia. Sibling thrombocytopenia was more frequently observed in neonates with thrombocytopenia than in those without (7/13 vs. 4/53, PCONCLUSION: Thrombocytopenia in neonates of women with ITP cannot be predicted by maternal treatment history or platelet count. However, the presence of an older sibling with neonatal thrombocytopenia is a reliable risk factor for neonatal thrombocytopenia in subsequent pregnancies.
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| 152. |
Kenzo Sonoda, Kiyoko Kato, A disintegrin and metalloproteinase 9 is involved in ectodomain shedding of receptor-binding cancer antigen expressed on Siso cells.
, Biomed Res Int, 10.1155/2014/482396, 1-13, 2014.10, In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. RCAS1 alters the tumor microenvironment by inducing peripheral lymphocyte apoptosis and angiogenesis, while reducing the vimentin-positive cell population. Although proteolytic processing, referred to as "ectodomain shedding," is pivotal for induction of apoptosis by RCAS1, the proteases involved in RCAS1-dependent shedding remain unclear. Here we investigated proteases involved in RCAS1 shedding and the association between tumor protease expression and serum RCAS1 concentration in uterine cancer patients. A disintegrin and metalloproteinase (ADAM) 9 was shown to be involved in the ectodomain shedding of RCAS1. Given the significant correlation between tumor ADAM9 expression and serum RCAS1 concentration in both cervical and endometrial cancer as well as the role for ADAM9 in RCAS1 shedding, further exploration of the regulatory mechanisms by which ADAM9 converts membrane-anchored RCAS1 into its soluble form should aid the development of novel RCAS1-targeting therapeutic strategies to treat human malignancies. . |
| 153. |
Hitomi Okabe, Shintaro Makino, Kiyoko Kato, Kikumi Matsuoka, Hioyuki Seki, Satoru Takeda, The effect of progesterone on genes involved in preterm labor. , J Reprod Immunol, 10.1016/j.jri.2014.03.008, 104-105, 80-91, 2014.10, The decidua is known to be a major source of intrauterine PGF2α during late gestation and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well as the genes, using microarray analysis. Senescence was induced in primary cultured human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4+IL-1β decreased the expression levels of all of these genes in comparison to treatment with IL-1β alone (p |
| 154. |
Nurismangul Yusuf, Tetsunori Inagaki, Soshi Kusunoki, Hitomi Okabe, Izumi Yamada, Akemi Matsumoto, Yasuhisa Terao, Satoru Takeda, Kiyoko Kato, SPARC was overexpressed in human endometrial cancer stem-like cells and promoted migration activity.
, Gynecologic Oncology, 134, 2, 356-363, 2014.08, Objectives
We previously demonstrated that side-population (SP) cells found in human endometrial cancer tissue have features of cancer stem cells (CSCs). Endometrial cancer SP cells show enhanced migration, the potential to differentiate into the mesenchymal cell lineage, and they are associated with the epithelial–mesenchymal transition (EMT). In this study, we analyzed the expression and function of a specific protein, SPARC (secreted protein acidic and rich in cysteine) which we found to be up-regulated in endometrial cancer.
Methods
We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP (NSP) cells. We used the MetaCore package to identify the Gene GO pathway MAPs associated with the up-regulated genes. Here, we investigated the expression and functions of SPARC, one of the genes up-regulated in endometrial CSCs.
We established SPARC-overexpressing cells by transfecting endometrial cancer cells (Ishikawa cells [IK-SPARC cells]). We characterized these cells' growth rate, tumorigenicity, migration and invasion activity. The levels and locations of SPARC protein expression in Hec1SP cells-derived tumors and endometrial cancer tissues were examined by immunohistochemistry.
Results
SPARC was detected by microarray expression analysis during screens for up-regulated genes in SP and NSP CSC. The level of SPARC expression was enhanced in Hec1 SP cells compared with that in Hec1 non-SP cells. SPARC enhanced fibronectin expression and promoted migration activity in IK cells. SPARC expression suppressed tumor growth but promoted formation of tumor stroma.
SPARC was expressed in endometrial cancer tissues, in particular, poorly differentiated endometrioid adenocarcinoma, clear and serous adenocarcinoma,but not in normal endometrial tissue.
Conclusion
This is the first report of overexpression of SPARC in endometrial cancer stem-like cells. SPARC expression is associated with cell migration and stroma formation.
Keywords
SPARC; Endometrial cancer; EMT; CSCs; Cell migration
. |
| 155. |
Arisa Fujiwara, Kotaro Fukushima, Hirosuke Inoue, Takeshi Takashima, Hiromasa Nakahara, Shoji Satoh, Masayuki Ochiai, Toshiro Hara, Mototsugu Shimokawa, Kiyoko Kato, Perinatal management of preterm premature ruptured membranes affects neonatal prognosis.
, Journal of Perinatal Medicine, Volume 0, Issue 0, 1-7, 2014.01, Abstract Aim: To determine the factors affecting neonatal prognosis in preterm premature rupture of membranes (PPROM). Method: We conducted a case-control study involving 92 women between the years 2000 and 2010 diagnosed with PPROM between 25 and 31 weeks' gestation, who received antenatal steroids, and delivered between 26 and 31 weeks' gestation; a retrospective cohort study was conducted based on the results. We used data from four tertiary centers and compared the frequencies of neonatal neurologic deficits and neonatal deaths. Results: There was a difference between the two groups; specifically, the ND group (n=18) consisted of patients whose infants had neurologic deficits and/or neonatal deaths and the neurologically normal (NN) group (n=74) included NN neonates amongst the patients who had expectant management (94% vs. 73%, respectively). Multivariable analysis revealed that expectant management was independently associated with an increased risk for neonatal neurologic deficits and neonatal deaths (odds ratio, 16.14). All neonates with poor prognosis in the expectant-management group delivered within 14 days after PPROM. Conclusions: Expectant management within 14 days after PPROM is associated with poor neonatal outcomes. Decisions regarding an expectant strategy should be made carefully. An immediate, planned delivery after steroid administration should be considered to improve neonatal prognosis in patients who have PPROM after 26 weeks' gestation.. |
| 156. |
Masayuki Ochiai, Kinjo Tadamune, Yasushi Takahata, Mariko Iwayama, Takeru Abe, KENJI IHARA, Shouichi Ohga, Kotaro Fukushima, Kiyoko Kato, tomoaki taguchi, Toshiro Hara, Survival and Neurodevelopmental Outcome of Preterm Infants Born at 22-24 Weeks of Gestational Age, NEONATOLOGY, 10.1159/000355818, 105, 2, 79-84, 2013.11. |
| 157. |
Seiichi Morokuma, Kotaro Fukushima, Kiyoko Kato, Relationship between arousal response in newborn infants before micturition and bed-wetting from 5 to 7 years of age, EARLY HUMAN DEVELOPMENT, 10.1016/j.earlhumdev.2013.08.020, 89, 12, 989-991, 2013.12. |
| 158. |
Yuka Otera, Seiichi Morokuma, Kotaro Fukushima, Norio Wake, Kiyoko Kato, Correlation between regular mouthing movements and heart rate patterns during non-rapid eye movement periods in normal human fetuses between 32 and 40 weeks of gestation, EARLY HUMAN DEVELOPMENT, 10.1016/j.earlhumdev.2012.12.007, 89, 6, 381-386, 2013.06. |
| 159. |
Maiko Sugitani, Yasuyuki Fujita, Kotaro Fukushima, Kiyoko Kato, A new method for measurement of placental elasticity: acoustic radiation force impulse imaging, Placenta, 34, 11, 1009-1013, 2013.11. |
| 160. |
Soshi Kusunoki, Kiyoko Kato, Kouichi Tabu, Tetsunori Inagaki, Hitomi Okabe, Hiroshi Kaneda, Shin Suga, Yasuhisa Terao, Tetsuya Taga, Satoru Takeda, The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells, GYNECOLOGIC ONCOLOGY, 10.1016/j.ygyno.2013.03.005, 129, 3, 598-605, 2013.06, Goals: We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and
the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed and the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells.
Method: We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and –non-SP(NSP) cells and used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin.
Results: We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells.
Conclusion: This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs.. |
| 161. |
Tadahisa Takeuchi, Yoshihiro Ohishi, Hiroko Imamura, Murasaki Aman, Kaai Shida, Hiroaki Kobayashi, Kiyoko Kato, Yoshinao Oda, Ovarian Transitional Cell Carcinoma Represents a Poorly Differentiated Form of High-grade Serous or Endometrioid Adenocarcinoma, AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 37, 7, 1091-1099, 2013.07. |
| 162. |
Tomoko Yoneda, Ayumi Kuboyama, Kiyoko Kato, Tatsuhiro Ogami, Kanako Okamoto, Toshiaki Saito, Norio Wake, Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer, ONCOLOGY REPORTS, 10.3892/or.2013.2433, 30, 1, 25-34, 2013.07. |
| 163. |
Takao T, Asanoma K, Tsunematsu R, Kato K, Wake N, The maternally expressed gene Tssc3 regulates the expression of Mash2 transcription factor in mouse trophoblast stem cells through thr Akt-Sp1 signaling pathway, J Biol Chem.287(51):42685-42694,2012, 2012.12. |
| 164. |
Takao T, Asanoma K, Tsunematsu R, Kato K, Wake N, The maternally expressed gene Tssc3 regulates the expression of Mash2 transcription factor in mouse trophoblast stem cells through thr Akt-Sp1 signaling pathway, J Biol Chem.287(51):42685-42694,2012, 2012.12. |
| 165. |
Kiyoko Kato, Kusunoki S, Inagaki T, Yusuf N, Suga S, Terao Y, Arima T, Tsukimori K, Takeda S, Side-population cells derived from non-tumorigenic rat endometrial cells are a candidate cell of origin for malignant endometrial tumors, J Stem Cell Res Ther. doi:10.4172/2157-7633.S7-003, 2012. |
| 166. |
Fukushima K, Tsukimori K, Li D, takao T, Morokuma S, Kato K, Seki H, Takeda S, matsumura S, Wake N, Effect of transient TCDD exposure on immortalized human trophoblast-derived cell lines., Hum Exp Toxicol. 31(6):550-556, 2012, 2012.05. |
| 167. |
Takao T, Asanoma K, Kato K, Fukushima K, Tsunematsu R, Hirakawa T, Matsumura S, Seki H, Takeda S, Wake N: ,
Isolation and Characterization of Human Trophoblast Side-Population (SP) Cells in Primary Villous Cytotrophoblasts and HTR-8/SVneo Cell Line.
, PLoS One. , 6, 7, e21990, 2011.07. |
| 168. |
Onoda A, Ueno T, Uchiyama S, Hayashi SI, Kato K, Wake N: ,
Effects of S-equol and natural S-equol supplement (SE5-OH) on the growth of MCF-7 in vitro and as tumors implanted into ovariectomized athymic mice.
, Food Chem Toxicol.
, 49, 9, 2279-2284, 2011.09. |
| 169. |
Kato K, Kuhara A, Yoneda T, Inoue T, Takao T, Ohgami T, Dan L, Kuboyama A, Kusunoki S, Takeda S, Wake N: , Sodium Butyrate inhibitis the Self-Renewal Capacity of Endometrial Tumor Side-Population Cells by Induction a DNA Damage Response.
, Mol Cancer Ther.
, 10, 8, 1-10, 2011.09. |
| 170. |
Kukita Y, Yahara K, Tahira T, Higasa K, Sonoda M, Yamamoto K, Kato K, Wake N, Hayashi K: ,
A definitive haplotype map as determined by genotyping duplicated haploid genomes finds a predominant haplotype preference at copy number variation events.
, Am J Hum Genet.
, 86, 6, 918-928, 2009.06. |
| 171. |
Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N: ,
Low-dose mithramycin exerts its anti-cancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers.
, Cancer Sci. , 101, 6, 1387-1395, 2010.06. |
| 172. |
Higuchi M, Yamayoshi A, Kato K, Kobori A, Wake N, Murakami A:,
Specific regulation of point-mutated K-ras-immortalized cell proliferation by a photodynamic antisense strategy.
, Oligonucleotides. , 20, 1, 37-44, 2010.01. |
| 173. |
Kato K, Takao T, Kuboyama A, Tanaka Y, Ohgami T, Yamaguchi S, Adachi S, Yoneda T, Ueoka Y, Kato K, Hayashi S, Asanoma K, Wake N: , Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage. , Am J Pathol., 176, 1, 381-392, 2010.01. |
| 174. |
Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, Ueoka Y, Yamaguchi S, Ohgami T, Wake N, Level of reactive oxygen species induced by p21Waf1/CIP1 is critical for the determination of cell fate. , Cancer Sci., 100, 7, 1275-1283, 2009.07. |
| 175. |
Takahashi A, Kato K, Kuboyama A, Inoue T, Tanaka Y, Kuhara A, Kinoshita K, Takeda S, Wake N, Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells. , Gynecol Oncol., 113, 2, 270-276, 2009.02. |
| 176. |
Higasa K, Kukita Y, Kato K, Wake N, Tahira T, Hayashi K, Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions. , PLoS Genet., 124, 11, e1000468, 2009.11. |
| 177. |
Tanaka Y, Wake N, Kato K, Letter to Editor, Menopause, in press, 2009.05. |
| 178. |
Fukushima K, Murata M, Hachisuga M, Tsukimori K, Seki H, Takeda S, Kato K, Wake N, Gene expression profiles by microarray analysis during matrigel-induced tube formation in a
human extravillous trophoblast cell line: comparison with endothelial cells
, Placenta, 29(10):898-904, 2008.10. |
| 179. |
Higasa K, Kukita Y, Kato K, Wake N, Tahira T, Hayashi K, Evaluation of haplotype inference using definitive haplotype data obtained from complete
hydatidiform moles, and its significance for the analyses of positively selected regions
, PLoS Genetics, in press, 2009.05. |
| 180. |
Takahashi A, Kato K, Kuboyama A, Inoue T, Tanaka Y, Kuhara A, Kinoshita K, Takeda S, Wake N, Induction of senescence by progesterone receptor –B activation in response to cAMP in ovarian cancer
cells
, Gynecol Oncol, 113:270-276, 2009.05. |
| 181. |
Inoue T, Kato K, Kato H, Asanoma K, Kuboyama A, Oogami T, Ueoka Y, Wake N, The level of reactive oxygen species induced by p21 WAF1/CIP1 is critical the determination of cell
fate
, Cancer Sci, in press, 2009.05. |
| 182. |
Yamaguchi S, Asanoma K, Takao T, Kato K, WakeN, Homeobox gene NECC1 is epigenetically
silenced in human uterine endometrial cancer and suppresses edtrogen-stimulated proliferation of
cancer cells by inhibiting serum response factor
, Int J Cancer, 124(11),2577-2588, 2009.01. |
| 183. |
Tanaka Y , Kato K , Mibu R , Uchida S , Asanoma K , Hashimoto K , Nozaki M , Wake N, Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell
cycle-related protein expression
, Menopause, 15:442-453, 2008.05. |
| 184. |
Matsushita I, Uchida S, Yamaguchi A, Tanaka Y, Ogawa S, Kato K, Tsukimori K, Wake N, Interstitial pregnancy in a woman with congenital afibrinogenemia, J Obstet Gynaecol Res, 34(5), 914-918, 2008.10. |
| 185. |
Asanoma K,Kato H,Yamaguchi S,Shin CH,Liu ZP,Kato K,Inoue T,Miyanari Y,Yoshikawa K,Sonoda K,Fukushima K,Wake N, HOP/NECC1,a novel regulator of mouse trophoblast differentiation , J Biol Chem, 17:24065-74, 2007.08. |
| 186. |
Yamayoshi A, Kato K, Suga S, Ichinose A, Arima T, Matsuda T, Kato H, Murakami A, Wake N. , Specific apotosis induction in HPV－positive cervical carcinoma cells by photodynamic antisense regulation, oligonucleotides, 17：66-79, 2007.05. |
| 187. |
加藤聖子、田中義弘、山本奈理、梅崎美奈、内田聡子、和氣徳夫, ビスフォスフォネート（アレンドロネート）の癌細胞への効果の検討, Osteoporosis Japan, 15:88-90, 2007.07. |
| 188. |
Kato K, Yoshimoto M, Kato K, Adachi S, Yamayoshi A, Arima T, Asanoma K, Kyo S, Nakahata T, Wake N, Characterization of side population cells (SP cells) in human normal endometrial cells
, Human Reproduction, 22:1214-23, 2007.04. |
| 189. |
Suga S, Kato K, Yamayoshi A, Adachi S, Asanoma K, Yamaguchi S, Arima T, Kinoshita K, Wake N, An inhibitory effect on cell proliferation by blockage of the MAPK / Estrogen Receptor / MDM2 signal pathway in gynecologic cancer, Gynecologic Oncology, 105：341-350, 2007.03. |
| 190. |
Arima T,Yamasaki K,John RM,Kato K,Sakumi K,Nakabeppu Y,Wake N,Kono T, The Human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice., Genomics, 88(5):650-8, 2006.08. |
| 191. |
Ogura T, Kobayashi H, Ueoka Y, Okurgawa K, Kato K, Hirakawa T, Hashimoto S,Taniguchi S, Wake N, Nakano H , Adenovirus-mediated calponin h1 gene therapy directed against peritoneal dissemination of ovarian cancer ： bifunctional therapeutic effects on peritoneal cell layer and cancer cells
, Clin Cancer Res, 12.5216-23, 2006.12. |
| 192. |
Kato HD,Kondoh H,Inoue T,Asanoma K,Matsuda T,Arima T,Kato K,Yoshikawa T,Wake N, Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis., GynecolOncol, 10.1016/j.ygyno.2004.07.050, 95, 2, 281-289, 95(2),281-9, 2004.11. |
| 193. |
Ninomiya Y, Kato K, Takahashi A, Ueoka K, Kamikihara T, Arima T, Matsuda T,Kato H, Nishida J, Wake N,, K-Ras and H-Ras activation promote distinct consequences on endometrial cell survival., Cancer Research, 10.1158/0008-5472.CAN-3487-2, 64, 8, 2759-2765, 64, 2759-2765, 2004.04. |
| 194. |
Kamikihara T, Arima T, Kato K, Matsuda T, Kato H, Douchi T, Nagata Y, Wake N, Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer., International Journal of Cancer., 10.1002/ijc.20971, 115, 5, 690-700, 115,690-700, 2005.03. |
| 195. |
Horiuchi S, Kato K, Suga S, Takahashi A, Ueoka Y, Arima T, Nishida JI, Hachisuga T, Kawarabayashi T, Wake N., Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells., Exp Cell Res, 10.1016/j.yexcr.2005.01.003, 305, 2, 233-243, 1;305(2):233-243., 2005.05. |
| 196. |
Arima T, Kato K, Hayashida T, Kamikihara T, Matsuda T, Kato H, Shirayoshi Y, Oshimura M, Soejima H, Mukai T, Wake N, Zac, LIT1 (KCNQ10T1) and p57KIP2 (CDKN1C) are in an imprinted gene network which may play a role in Beckwith-Wiedemann Syndrome., Nucleic Acids Research, 10.1093/nar/gki555, 33, 8, 2650-2660, 33, 8,2650-2660, 2005.01. |
