Publications by authors named "Eiji Kondoh"

96 Publications

A Case of Torsion in an Otherwise-Normal Ovary with a Giant Hematosalpinx Larger than Enlarged Ovary: Utilization of Diagnostic Laparoscopy for the Accurate Diagnosis.

Case Rep Obstet Gynecol 2021 23;2021:1371611. Epub 2021 Aug 23.

Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto City, Kyoto, Japan 606-8507.

We report a case of torsion in an otherwise-normal ovary with a giant hematosalpinx. A 23-year-old woman presented with complaints of abdominal pain and nausea. At initial visit, there was few abnormal findings of imaging tests, and we made a diagnosis of ovarian hemorrhage. Three days later, she came back with increased symptoms, and we detected the mass of a complex solid cystic structure with a unilocular cyst much larger than solid component. A diagnostic laparoscopy was performed immediately, and we could make a diagnosis of torsion in an otherwise-normal ovary with a giant hematosalpinx. We performed a salpingectomy and could preserve her ovary. This is the first case of torsion in an otherwise-normal ovary with a giant hematosalpinx which enlarged to a greater extent than the ovary.
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http://dx.doi.org/10.1155/2021/1371611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408003PMC
August 2021

A 36 kg Giant Ovarian Fibroma with Meigs Syndrome: A Case Report and Literature Review of Extremely Giant Ovarian Tumor.

Case Rep Obstet Gynecol 2021 15;2021:1076855. Epub 2021 Aug 15.

Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto city, Kyoto, Japan 606-8507.

Ovarian tumors can get extremely giant to occupy the whole abdominal cavity. We report a case of 36 kg solid ovarian tumor, which was the largest ovarian solid tumor that have been ever reported. A 54-year-old woman presented to our hospital with a chief complaint of markedly distended abdominal wall. Preoperative imaging examinations revealed that most of the tumor was uniform and its density was like that of subcutaneous fat. Pleural effusion was detected in the right thoracic region. We organized a multidisciplinary team and successfully resected the right adnexa. The patient had an uneventful postoperative course, and she was discharged on the 7 postoperative day and diagnosed with a fibroma of the ovary with Meigs syndrome. A comprehensive literature search revealed 48 cases of extremely giant ovarian tumor in these 20 years. Six out of 48 cases are solid. Twelve out of 48 cases are malignant or borderline malignant, and patients' age and tumor size/weight were not related to the frequency of malignancy/borderline malignancy. As many as 4 out of 48 patients died before their first hospital visit or early after surgery. Clinicians should consider a considerable high mortality and frequency of severe surgical complications when planning the treatment strategy for extremely giant ovarian tumors.
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http://dx.doi.org/10.1155/2021/1076855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382553PMC
August 2021

Maternal near-miss attributable to haemorrhagic stroke in patients with hypertensive disorders of pregnancy in Japan: A national cohort study.

Pregnancy Hypertens 2021 Aug 23;25:240-243. Epub 2021 Jul 23.

Department of Gynaecology and Obstetrics, Kyoto University, Kyoto, Japan. Electronic address:

Objectives: To investigate the epidemiologic and clinical characteristics of maternal near-misses attributable to haemorrhagic stroke (HS) occurring in patients with hypertensive disorders of pregnancy (HDP), with a focus on severe neurological morbidity.

Methods: A national retrospective cohort study was conducted using the national database of health insurance claims for the period 2010 to 2017. The subjects were all insured women with a diagnosis of both HDP and HS. Severe neurological morbidity requiring rehabilitation, types of HDP, types of HS, and magnesium sulphate use were tabulated.

Results: The number of women with HDP who were diagnosed with HS was 3.4 per 100,000 deliveries between 2010 and 2017. Forty percent of HDP-related HS cases had neurological morbidities requiring rehabilitation (1.4 per 100,000 deliveries), and 4.4% were in a persistent vegetative state after HS. Of the HDP cases who developed HS, 69.2% were severe HDP, of which 55.6% were without eclampsia. The most common type of HS was intracerebral haemorrhage (2.5 per 100,000 deliveries), followed by subarachnoid haemorrhage due to cerebral aneurysm (1.2 per 100,000 deliveries). The frequency of magnesium sulphate use increased in all patients with HDP-related HS in the second half of the study period (2014-2017) compared with the first half (2010-2013) (p < 0.0001). This was more evident in cases of HDP-related HS with eclampsia (31.9% to 83.8%) compared to those without eclampsia (25.0% to 42.9%).

Conclusion: Of the maternal near-miss cases due to HDP-related HS, 40.0% were rehabilitated and 69.2% were HDP without either eclampsia or severe hypertension.
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http://dx.doi.org/10.1016/j.preghy.2021.07.244DOI Listing
August 2021

Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells.

Sci Rep 2021 Jul 8;11(1):14167. Epub 2021 Jul 8.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.
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http://dx.doi.org/10.1038/s41598-021-93766-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266876PMC
July 2021

Sebaceous carcinoma of the vulva treated with sentinel lymph node biopsy: a case report and literature review.

Int Cancer Conf J 2021 Jul 5;10(3):239-243. Epub 2021 May 5.

Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.

Sebaceous carcinoma (SC) is a rare and aggressive cutaneous malignancy. It often occurs on the eyelid, where it is called periocular SC, while extraocular SC mainly occurs on the head and heck. Extraocular vulvar SC is extremely rare; only nine cases have been described in the literature, and the optimal treatment strategy is unknown. We herein report a case of vulvar SC that was successfully treated with local excision in combination with sentinel lymph node biopsy (SNB). A 66-year-old female presented with vulvar discomfort. An 8 mm ulcerated mass was palpable in her left labia minora. Skin biopsy suggested SC. Imaging showed no swelling of the pelvic and inguinal lymph nodes and no metastasis. Sentinel lymph node scintigraphy using technetium-99 m showed three sentinel lymph nodes. The patient underwent local excision with SNB; intraoperative frozen-section examination revealed no nodal metastasis, and no further inguinal lymphadenectomy was performed. The final diagnosis was SC of the vulva, FIGO stage IB (pT1bN0M0). At the 14-month follow-up, she remained asymptomatic and had no signs of recurrence. The scientific rationale for SNB in extraocular SC has not yet been established, although SNB can be considered for periocular SC. However, considering the insufficient data on the management of vulvar SC and the aggressive nature of both periocular and extraocular SCs, SNB can be a reasonable and useful method for avoiding inadequate treatment and reducing the complications caused by unnecessary inguinal lymphadenectomy.
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http://dx.doi.org/10.1007/s13691-021-00488-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206379PMC
July 2021

Chronic abruption-oligohydramnios sequence (CAOS) revisited: possible implication of premature rupture of membranes.

J Matern Fetal Neonatal Med 2021 May 20:1-7. Epub 2021 May 20.

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

Aim: The pathogenic mechanism of chronic abruption-oligohydramnios sequence (CAOS) remains unknown, and there are no objective standards for diagnosis on imaging or using pathological evidence. We aimed to reconsider and clarify the true pathology of CAOS by integrating clinical, magnetic resonance imaging (MRI) and histopathological findings of the placenta.

Material And Methods: This is a case series of patients with CAOS managed at our hospital between 2010 and 2020. The clinical data of the patients, including MRI findings and placental pathology, were reviewed retrospectively.

Results: A total of 18 patients were eligible. Preterm birth occurred in 17 (94%) cases; the median gestational age at delivery was 25. Three neonates (17%) died within two years, and 10 neonates (56%) developed chronic lung disease. MRI was performed in 13 cases and clearly showed intrauterine hematoma and hemorrhagic amniotic fluid. Pathologically, in all cases, retroplacental hematoma was not detected, and fetal membranes were extremely fragile and ragged. Shedding and necrosis of the amniotic epithelium was a characteristic finding, which was confirmed in 17 cases (94%). Diffuse chorionic hemosiderosis (DCH) was detected in all cases.

Conclusions: The fundamental cause of CAOS is repeated intrauterine hemorrhage and subsequent subchorionic hematoma, which induces hemorrhagic amniotic fluid and DCH. Consequently, these factors result in the necrosis and weakening of the amnion. Therefore, the true pathology of CAOS is believed to be premature rupture of membranes rather than chronic abruption.
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http://dx.doi.org/10.1080/14767058.2021.1929159DOI Listing
May 2021

Figla promotes secondary follicle growth in mature mice.

Sci Rep 2021 05 10;11(1):9842. Epub 2021 May 10.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo, Kyoto, 606-8507, Japan.

The in vitro growth (IVG) of human follicles is a potential fertility option for women for whom cryopreserved ovarian tissues cannot be transplanted due to the risk of cancer cell reintroduction; however, there is currently no established method. Furthermore, optimal IVG conditions may differ between the follicles of adult and pre-pubertal females due to molecular differences suggested by basic research. To systematically identify differences between the secondary follicles of adult and pre-pubertal females, a comparative transcriptomic study using mice was conducted herein. Among differentially expressed genes (DEGs), Figla was up-regulated in mature mice. We successfully down-regulated Figla expression in secondary follicle oocytes by a Figla siRNA microinjection, and the subsequent IVG of follicles showed that the diameter of these follicles was smaller than those of controls in mature mice, whereas no significant difference was observed in premature mice. The canonical pathways of DEGs between control and Figla-reduced secondary follicles suggest that Figla up-regulates VDR/RXR activation and down-regulates stem cell pluripotency as well as estrogen signaling. We demonstrated for the first time that folliculogenesis of the secondary follicles of premature and mature mice may be regulated by different factors, such as Figla with its possible target genes, providing insights into optimal IVG conditions for adult and pre-pubertal females, respectively.
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http://dx.doi.org/10.1038/s41598-021-89052-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110814PMC
May 2021

Capturing human trophoblast development with naive pluripotent stem cells in vitro.

Cell Stem Cell 2021 06 7;28(6):1023-1039.e13. Epub 2021 Apr 7.

Department of Life Science Frontiers, CiRA, Kyoto University, Kyoto 606-8507, Japan. Electronic address:

Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placenta-derived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.
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http://dx.doi.org/10.1016/j.stem.2021.03.013DOI Listing
June 2021

Oncofertility care in young women and the outcomes of pregnancy over the last 5 years.

Future Sci OA 2021 Feb 2;7(4):FSO680. Epub 2021 Feb 2.

Department of Gynecology & Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 6068507, Japan.

Aim: To ascertain the actual outcomes of oncofertility care in young women to provide more appropriate care.

Materials & Methods: We analyzed the data of 67 female patients under 43 years of age who underwent oncofertility care between January 2015 and September 2019.

Results: There were 28 patients with breast cancer, 19 patients with hematologic cancer and 20 patients with other cancer diagnoses. Breast cancer patients tended to take longer than hematologic cancer patients to initiate oncofertility treatment. Despite undergoing oncofertility care, seven of nine pregnant patients did not choose assisted reproductive technology (ART).

Conclusion: As spontaneous pregnancies were more common than ART pregnancies in our study, pregnancy by not only ART but also non-ART method is a viable option for young cancer survivors.
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http://dx.doi.org/10.2144/fsoa-2020-0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015666PMC
February 2021

Histological distribution pattern of hemosiderin deposition on the chorionic plate and fetal membrane of diffuse chorioamniotic hemosiderosis related to chronic abruption oligohydramnios sequence.

Placenta 2021 02 20;105:1-6. Epub 2021 Jan 20.

Department of Diagnostic Pathology, Kyoto University Hospital, Japan.

Introduction: Chronic abruption oligohydramnios sequence (CAOS) is histologically characterized by diffuse chorioamniotic hemosiderosis (DCH). However, the criteria for the histological evaluation of the extent of CAOS-related hemosiderin deposition (HD) of the membranes and the difference in HD between the chorionic plate (CP) and fetal membrane (FM) are not well studied. This case control study compared the degree and distribution pattern of HD on CP and FM to present the histological features of DCH and the criteria for histological evaluation.

Methods: From the medical records of Kyoto University Hospital (2010-2019), we selected 20 CAOS cases that were clinically diagnosed by Elliot's criteria. Twenty non-CAOS cases matched to the CAOS group by gestational age were selected as controls. We compared the clinical data and pathological features in the two groups. We performed iron staining in all the cases and analyzed HD in CP and FM according to the histological score (H-Score: 0-12), which was determined as the density (0-3) multiplied by the extent of staining (0-4).

Results: HD was found in 100% (20/20) of CAOS and 15% (3/20) of control cases. In both the FM and CP, CAOS cases showed a significantly higher HS than control cases (CAOS, HS = 4-12; Control, HS = 0-1, p < 0.0001). Three CAOS patients presented HD alone in the CP. The HS of the CP was significantly higher than that of the FM (p = 0.0003).

Discussion: CAOS presented DCH with HS ≥ 4. This study showed that the CP might be more suitable for evaluating DCH than the FM.
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http://dx.doi.org/10.1016/j.placenta.2021.01.013DOI Listing
February 2021

Three cases of seromucinous carcinoma of the ovary arising in endometriotic cysts.

Int Cancer Conf J 2021 Jan 21;10(1):46-53. Epub 2020 Sep 21.

Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan.

Ovarian seromucinous carcinoma (SMC) is an uncommon neoplasia and is composed predominantly of serous and endocervical-type mucinous epithelium. Due to its low frequency and difficult diagnosis, the natural history, characteristic imaging findings, and pathological features of SMC have not been adequately described in the literature thus far. We herein report three cases of ovarian SMC along with magnetic resonance imaging (MRI) findings. The diagnosis of SMC was made after staging laparotomy in all cases, and systemic chemotherapy was performed in two cases. No recurrence was observed in any of the cases. The MRI findings in SMC were so varied that characteristic imaging features useful for diagnosis were not found. In two cases, MRI suggested endometriotic cysts, and endometriosis and seromucinous borderline tumors (SMBTs) were detected concurrently in all cases by histological examination. Thus, it was suggested that SMC develops in multiple stages via endometriosis and SMBT. The cooccurrence of endometriosis and SMBT could also make the diagnosis of SMC more convincing.
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http://dx.doi.org/10.1007/s13691-020-00447-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797404PMC
January 2021

A Novel Direct Approach to the Deep Uterine Vein in Laparoscopic Radical Hysterectomy.

J Minim Invasive Gynecol 2021 Aug 23;28(8):1444-1445. Epub 2020 Dec 23.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine (Drs. Horie, Sunada, Kitamura, Yamanoi, Horikawa, Yamaguchi, Hamanishi, Kondoh, and Mandai).

Study Objective: To describe a direct approach to the deep uterine vein in laparoscopic radical hysterectomy.

Design: Demonstration of the laparoscopic technique with narrated video footage.

Setting: Securing sufficient radicality is extremely important when performing a radical hysterectomy for cervical cancer, either by laparotomy or by minimally invasive surgery. The nerve-sparing Okabayashi radical hysterectomy (NS-RH) was originally aimed at achieving both radical resection and function preservation [1-3]. A key procedure when performing NS-RH is intraoperative identification of the relationship between the deep uterine vein and pelvic splanchnic nerve fibers [4]. With this in mind, a safe and easy method for identifying the crossing point of the deep uterine vein and pelvic splanchnic nerve in the initial phase of the surgery may greatly improve the safety and efficacy of functional preservation in NS-RH. Herein, we describe a minimally invasive "direct approach" to the deep uterine vein.

Interventions: Before undergoing the pelvic lymphadenectomy, all steps of laparoscopic radical hysterectomy were performed. First, we identified the ureter on the posterior peritoneum, and the peritoneum was dissected just above the ureter. By continuously exploring the pelvic cavity along the ureter, especially through the opening of the space below the ureter in a cranial to caudal direction, we could easily identify the deep uterine vein. This procedure also exposed the fibers of the hypogastric nerve, clarifying the relationship of these structures.

Conclusion: Because the relationship between the deep uterine vein and nerve fibers is the most important guidepost of this surgery, their identification in the early phase of the surgery enables us to perform the subsequent procedure precisely and securely. This direct approach to the deep uterine vein can be easily and safely performed.
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http://dx.doi.org/10.1016/j.jmig.2020.12.018DOI Listing
August 2021

Rethinking uterine compression suture for atonic postpartum hemorrhage.

Acta Obstet Gynecol Scand 2021 01;100(1):5-6

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

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http://dx.doi.org/10.1111/aogs.14035DOI Listing
January 2021

Predictive factors for flares of established stable systemic lupus erythematosus without anti-phospholipid antibodies during pregnancy.

J Matern Fetal Neonatal Med 2020 Nov 3:1-6. Epub 2020 Nov 3.

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

Purpose: To identify predictors of systemic lupus erythematosus (SLE) flares during pregnancy in patients previously considered to be at low risk.

Materials And Methods: The retrospective cohort study included 54 singleton pregnancies, managed between 2005 and 2019, involving maternal diagnosed SLE at a low disease activity (SLE Disease Activity Index ≤4) for ≥12 months before conception and without anti-phospholipid antibodies. Pregnancy outcomes were compared between patients who had SLE exacerbations during pregnancy (flare group,  = 21) and patients that did not have a flare (non-flare group,  = 33).

Results: The flare group had shorter gestational durations ( = .01), lower birth weights ( = .02), and a higher risk of emergent cesarean section ( = .002) compared with the non-flare group. The flare group demonstrated higher doses of prednisone ( = .04) at the time of conception as well as an increased rate of low 50% hemolytic complement (CH50) activity ( = .03) in the first trimester compared to the non-flare group. A decision tree drawn using a prednisone dose ≥10.5 mg/day and a low CH50 predicted SLE flares with a net accuracy of 78%.

Conclusions: A prednisone dose ≥10.5 mg daily and CH50 hypocomplementemia in early pregnancy are useful in the early detection of patients at a high risk of SLE exacerbation.
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http://dx.doi.org/10.1080/14767058.2020.1843626DOI Listing
November 2020

Severe fetal anemia as a consequence of extra-abdominal umbilical vein varix: A case report and review of the literature.

Congenit Anom (Kyoto) 2021 Jan 5;61(1):4-8. Epub 2020 Nov 5.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Umbilical vein varix is associated with a high incidence of fetal anomalies and perinatal complications. There are two types of umbilical vein varix: fetal intra-abdominal and extra-abdominal. Herein, a case is reported of severe fetal anemia with extra-abdominal umbilical vein varix. A 33-year-old primigravida was referred to our hospital for fetal growth restriction, fetal cardiomegaly, and decreased fetal movements at 26 weeks' gestation. A Doppler assessment showed an elevated middle cerebral artery peak systolic velocity at 2.2 MoM, suggesting fetal anemia. Umbilical vein varix had caused intermittent turbulent flow, provoking hemolytic anemia. Intrauterine transfusion improved fetal circulatory failure and anemia and prolonged gestational period. At 33 weeks' gestation, the patient underwent cesarean delivery due to nonreassuring fetal status. Pathological analysis revealed focal loss of vascular smooth muscle of the umbilical vein. Extra-abdominal umbilical vein varix has been reported in 14 cases including this case. The antenatal diagnosis rate is reported to be 79%; fetal heartbeat abnormalities and fetal deaths were reported as 50% and 14%, respectively. Eighty-six percent of patients had intra-umbilical cord thrombosis, but currently this is the only case of hemolytic anemia. Furthermore, extra-abdominal umbilical vein varix may present as fetal hydrops with anemia. During ultrasound examination of fetal anemia, umbilical cord screening should be performed with caution.
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http://dx.doi.org/10.1111/cga.12397DOI Listing
January 2021

Targeting Dormant Ovarian Cancer Cells and in an Mouse Model of Platinum Resistance.

Mol Cancer Ther 2021 01 9;20(1):85-95. Epub 2020 Oct 9.

Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Duke University Medical Center, Durham, North Carolina.

Spheroids exhibit drug resistance and slow proliferation, suggesting involvement in cancer recurrence. The protein kinase C inhibitor UCN-01 (7-hydroxystaurosporine) has shown higher efficacy against slow proliferating and/or quiescent ovarian cancer cells. In this study, tumorigenic potential was assessed using anchorage-independent growth assays and spheroid-forming capacity, which was determined with ovarian cancer cell lines as well as primary ovarian cancers. Of 12 cell lines with increased anchorage-independent growth, 8 formed spheroids under serum-free culture conditions. Spheroids showed reduced proliferation ( < 0.0001) and Ki-67 immunostaining (8% vs. 87%) relative to monolayer cells. Spheroid formation was associated with increased expression of mitochondrial pathway genes ( ≤ 0.001) from Affymetrix HT U133A gene expression data. UCN-01, a kinase inhibitor/mitochondrial uncoupler that has been shown to lead to Puma-induced mitochondrial apoptosis as well as ATP synthase inhibitor oligomycin, demonstrated effectiveness against spheroids, whereas spheroids were refractory to cisplatin and paclitaxel. By live imaging, ovarian cancer xenograft tumors were reduced after primary treatment with carboplatin. Continued treatment with carboplatin was accompanied by an increase in tumor signal, whereas there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0119DOI Listing
January 2021

Conservative management for retained products of conception after less than 22 weeks of gestation.

J Obstet Gynaecol Res 2020 Oct 5;46(10):1982-1987. Epub 2020 Aug 5.

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

Aim: The aim of the study was to investigate the efficacy of conservative treatment in cases of retained products of conception (RPOC) with a preceding pregnancy of less than 22 weeks and to assess whether serum beta-human chorionic gonadotropin (hCG) levels could be a useful index to monitor the progress of treatment.

Methods: This is a case series of patients with RPOC developed after less than 22 weeks of gestation and managed expectantly with serial serum hCG measurement between 2011 and 2017. The clinical data of subjects were reviewed retrospectively. Cases that did not require invasive treatment such as surgery were designated as conservative management success.

Results: A total of 19 cases were eligible: 14 miscarriages and 5 induced abortions. Eleven patients underwent dilatation and curettage. The diagnosis of RPOC was made 35 (8-80) days after abortion. All patients were successfully treated with conservative management. Serum hCG levels at diagnosis were 29.6 (3.2-1585) mIU/mL. Serial measurement of serum hCG was continued until the levels became lower than the cutoff value, and the mean duration to hCG disappearance was 67.5 (6-183) days. In all cases, RPOC vanished spontaneously 77 (27-184) days after diagnosis. The disappearance of RPOC in the uterine cavity was subsequent to a significant decrease in serum hCG. Once serum hCG levels reached the cutoff value, no bleeding episodes were observed.

Conclusion: Conservative management for RPOC might be acceptable and effective. Furthermore, serial serum hCG levels reflect the activity of RPOC, and hCG may be a reliable index to monitor the progress of treatment.
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http://dx.doi.org/10.1111/jog.14405DOI Listing
October 2020

New era of trophoblast research: integrating morphological and molecular approaches.

Hum Reprod Update 2020 09;26(5):611-633

Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Many pregnancy complications are the result of dysfunction in the placenta. The pathogenic mechanisms of placenta-mediated pregnancy complications, however, are unclear. Abnormal placental development in these conditions begins in the first trimester, but no symptoms are observed during this period. To elucidate effective preventative treatments, understanding the differentiation and development of human placenta is crucial. This review elucidates the uniqueness of the human placenta in early development from the aspect of structural characteristics and molecular markers. We summarise the morphogenesis of human placenta based on human specimens and then compile molecular markers that have been clarified by immunostaining and RNA-sequencing data across species. Relevant studies were identified using the PubMed database and Google Scholar search engines up to March 2020. All articles were independently screened for eligibility by the authors based on titles and abstracts. In particular, the authors carefully examined literature on human placentation. This review integrates the development of human placentation from morphological approaches in comparison with other species and provides new insights into trophoblast molecular markers. The morphological features of human early placentation are described in Carnegie stages (CS), from CS3 (floating blastocyst) to CS9 (emerging point of tertiary villi). Molecular markers are described for each type of trophoblast involved in human placental development. We summarise the character of human trophoblast cell lines and explain how long-term culture system of human cytotrophoblast, both monolayer and spheroid, established in recent studies allows for the generation of human trophoblast cell lines. Due to differences in developmental features among species, it is desirable to understand early placentation in humans. In addition, reliable molecular markers that reflect normal human trophoblast are needed to advance trophoblast research. In the clinical setting, these markers can be valuable means for morphologically and functionally assessing placenta-mediated pregnancy complications and provide early prediction and management of these diseases.
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http://dx.doi.org/10.1093/humupd/dmaa020DOI Listing
September 2020

Two Cases of Ectopic Pregnancy Mimicking Gestational Trophoblastic Disease.

Case Rep Obstet Gynecol 2020 16;2020:2417428. Epub 2020 Jun 16.

Department of Gynecology and Obstetrics, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo, Kyoto 606-8507, Japan.

A well-known typical feature of ectopic pregnancy is an evident gestational sac structure outside of the uterus. However, some cases show atypical appearance that is described as a heterogeneous hypervascular mass. We report two cases of ectopic pregnancy that presented heterogeneous findings mimicking gestational trophoblastic diseases but were correctly diagnosed as ectopic pregnancies on MRI. The first case was an interstitial pregnancy in which the patient underwent surgical treatment. The second case was a cesarean scar pregnancy that was treated conservatively but showed spurious enlargement of pregnancy-related lesions after the treatment. Both cases lacked myometrial invasion on MRI, and the patients were diagnosed with ectopic pregnancies. Invasive findings on MRI may discriminate ectopic pregnancy from trophoblastic tumors and avoid unnecessary hysterectomy.
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http://dx.doi.org/10.1155/2020/2417428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315310PMC
June 2020

Mechanisms of thrombin-Induced myometrial contractions: Potential targets of progesterone.

PLoS One 2020 4;15(5):e0231944. Epub 2020 May 4.

Department of Gynecology and Obstetrics, Kyoto University, Graduate School of Medicine, Kyoto, Japan.

Intrauterine bleeding during pregnancy is a major risk factor for preterm birth. Thrombin, the most abundant coagulation factor in blood, is associated with uterine myometrial contraction. Here, we investigated the molecular mechanism and signaling of thrombin-induced myometrial contraction. First, histologic studies of placental abruption, as a representative intrauterine bleeding, revealed that thrombin was expressed within the infiltrating hemorrhage and that thrombin receptor (protease-activated receptor 1, PAR1) was highly expressed in myometrial cells surrounding the hemorrhage. Treatment of human myometrial cells with thrombin resulted in augmented contraction via PAR1. Thrombin-induced signaling to myosin was then mediated by activation of myosin light chain kinase- and Rho-induced phosphorylation of myosin light chain-2. In addition, thrombin increased prostaglandin-endoperoxidase synthase-2 (PTGS2 or COX2) mRNA and prostaglandin E2 and F2α synthesis in human myometrial cells. Thrombin significantly increased the mRNA level of interleukine-1β, whereas it decreased the expressions of prostaglandin EP3 and F2α receptors. Progesterone partially blocked thrombin-induced myometrial contractions, which was accompanied by suppression of the thrombin-induced increase of PTGS2 and IL1B mRNA expressions as well as suppression of PAR1 expression. Collectively, thrombin induces myometrial contractions by two mechanisms, including direct activation of myosin and indirect increases in prostaglandin synthesis. The results suggest a therapeutic potential of progesterone for preterm labor complicated by intrauterine bleeding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231944PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197857PMC
July 2020

Trial of labor after cesarean delivery (TOLAC) in Japan: rates and complications.

Arch Gynecol Obstet 2020 04 17;301(4):995-1001. Epub 2020 Mar 17.

Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe-Cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Purpose: To determine the rates of trial of labor after cesarean delivery (TOLAC) and complications in Japan.

Methods: We conducted a descriptive study of pregnant women with one prior cesarean section registered between January 2013 and December 2015 in the perinatal database of the Japan Society of Obstetrics and Gynecology. This database is a nationwide institution-based registry in Japan. This study included women who had undergone one prior cesarean delivery and who delivered a singleton by cephalic presentation between 37 and 41 weeks of gestation. We collected data on delivery method, particularly with regard to the involvement of TOLAC or elective repeated cesarean deliveries (ERCD). Rates of TOLAC were investigated by facility type, and we calculated the rates of maternal and perinatal complications including uterine rupture in TOLAC.

Results: During the study period, 647,098 births were registered. Among the 34,460 women who met the inclusion criteria, 1730 (5.0%) and 32,730 (95.0%) underwent TOLAC and ERCD, respectively. In total, 76.4% of hospitals did not perform TOLAC at all. Generally in perinatal medical centers, which are better equipped with facilities, 58.7% women did not perform TOLAC. With regard to complications, we identified eight cases (0.46%) of uterine rupture with TOLAC. TOLAC births did not include maternal death and perinatal death. Among women attempting TOLAC, 1532 (88.6%) had successful vaginal births.

Conclusion: The TOLAC rate in Japan was considerably lower than that reported in other countries, despite comparable complication rates.
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http://dx.doi.org/10.1007/s00404-020-05492-8DOI Listing
April 2020

Placenta Accreta in a Woman with Childhood Uterine Irradiation: A Case Report and Literature Review.

Case Rep Obstet Gynecol 2019 5;2019:2452975. Epub 2019 Nov 5.

Department of Obstetrics and Gynecology, Kyoto University Hospital, Kyoto, Japan.

The pregnancies of childhood cancer survivors who have received uterine irradiation are associated with a high risk of several obstetrical complications, including placenta accreta. The present case was a 26-year-old pregnant woman with a history of myelodysplastic syndrome treated with umbilical cord blood transplantation following chemotherapy and total body irradiation at the age of 10. Despite every possible measure to prevent preterm labor, uterine contractions became uncontrollable and a female infant weighing 892 g was vaginally delivered at 27 weeks of gestation. Under the postpartum ultrasonographic diagnosis of placenta accreta, we selected to leave the placenta . Although emergency bilateral uterine artery embolization was required, complete resorption of the residual placenta was accomplished on the 115 day postpartum. Our experience highlighted the following points. (1) The expectant management of placenta accreta arising in an irradiated uterus may not only fulfill fertility preservation, but may also reduce possible risks associated with cesarean hysterectomy. (2) Due to extreme thinning of and a poor blood supply to the myometrium, reaching an antepartum diagnosis of placenta accreta in an irradiated uterus is difficult. (3) The recurrence of placenta accreta in subsequent pregnancies needs to be considered after successful preservation of the uterus.
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http://dx.doi.org/10.1155/2019/2452975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875035PMC
November 2019

Reply: The Kyoto balloon system for postpartum hemorrhage: A hard balloon shaft offers an easier and surer way to apply direct pressure on bleeding sites.

Acta Obstet Gynecol Scand 2020 02 10;99(2):292-293. Epub 2019 Nov 10.

Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

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http://dx.doi.org/10.1111/aogs.13742DOI Listing
February 2020

Prioritizing Features to Redesign in an EMR System.

Stud Health Technol Inform 2019 Aug;264:1213-1217

Department of Social Informatics, Graduate School of Informatics, Kyoto University, Kyoto, Japan.

Redesigning Electronic Medical Record (EMR) systems is needed to improve their usefulness and usability. For user-centered redesign, designers should consider which EMR features are the most important to the users. However, prioritizing the EMR features is complicated because: (i) EMR systems involve multiple users with different, and sometimes conflicting, priorities and (ii) targeting one feature will affect other features of the EMR system. In this work, we propose a method for prioritizing the features to target when redesigning an EMR system. The method takes into consideration the different priorities of the users and the relationships between the different features. We illustrate the method through a case study on redesigning EMR systems in Japanese antenatal care settings. Our results show the importance of considering the different types of EMR users and the relationships between different EMR features. Designers could use the proposed method as a decision-aid tool in EMR redesign projects.
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http://dx.doi.org/10.3233/SHTI190419DOI Listing
August 2019

Novel intrauterine balloon tamponade systems for postpartum hemorrhage.

Acta Obstet Gynecol Scand 2019 12 12;98(12):1612-1617. Epub 2019 Sep 12.

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

Introduction: Postpartum hemorrhage is the most common cause of maternal death worldwide. Although intrauterine balloon tamponade has been widely used as an effective procedure to control atonic postpartum hemorrhage, intrauterine balloon tamponade fails to control postpartum hemorrhage in approximately one-fifth of cases. The aim of this study was to evaluate the efficacy of novel intrauterine balloon tamponade systems for postpartum hemorrhage.

Material And Methods: We have developed two novel intrauterine balloon tamponade systems to maintain proper balloon placement. One was a shaft cover with its fixture system and the other was "the Kyoto balloon system" designed to provide direct pressure onto the upper uterine cavity. The efficacy of the intrauterine balloon tamponade systems was evaluated using a silicone three-dimensionally printed postpartum uterine cavity model.

Results: Measurements of balloon displacement during inflation showed that the shaft cover significantly prevented the Bakri balloon from being displaced. The residual fluid volume in the upper uterine cavity was significantly less with the Kyoto balloon system than with the Bakri balloon system, indicating the effectiveness of the Kyoto balloon for upper uterine cavity tamponade.

Conclusions: These innovative intrauterine balloon tamponade systems were effective for prevention of balloon displacement and for balloon tamponade of the upper uterine cavity in a 3D-printed postpartum-specific uterine cavity model.
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http://dx.doi.org/10.1111/aogs.13692DOI Listing
December 2019

Understanding the Situated Roles of Electronic Medical Record Systems to Enable Redesign: Mixed Methods Study.

JMIR Hum Factors 2019 Jul 9;6(3):e13812. Epub 2019 Jul 9.

Division of Medical Information Technology and Administration Planning, Kyoto University Hospital, Kyoto, Japan.

Background: Redesigning electronic medical record (EMR) systems is needed to improve their usability and usefulness. Similar to other artifacts, EMR systems can evolve with time and exhibit situated roles. Situated roles refer to the ways in which a system is appropriated by its users, that is, the unintended ways the users engage with, relate to, and perceive the system in its context of use. These situated roles are usually unknown to the designers as they emerge and evolve as a response by the users to a contextual need or constraint. Understanding the system's situated roles can expose the unarticulated needs of the users and enable redesign opportunities.

Objective: This study aimed to find EMR redesign opportunities by understanding the situated roles of EMR systems in prenatal care settings.

Methods: We conducted a field-based observational study at a Japanese prenatal care clinic. We observed 3 obstetricians and 6 midwives providing prenatal care to 37 pregnant women. We looked at how the EMR system is used during the checkups. We analyzed the observational data following a thematic analysis approach and identified the situated roles of the EMR system. Finally, we administered a survey to 5 obstetricians and 10 midwives to validate our results and understand the attitudes of the prenatal care staff regarding the situated roles of the EMR system.

Results: We identified 10 distinct situated roles that EMR systems play in prenatal care settings. Among them, 4 roles were regarded as favorable as most users wanted to experience them more frequently, and 4 roles were regarded as unfavorable as most users wanted to experience them less frequently; 2 ambivalent roles highlighted the providers' reluctance to document sensitive psychosocial information in the EMR and their use of the EMR system as an accomplice to pause communication during the checkups. To improve the usability and usefulness of EMR systems, designers can amplify the favorable roles and minimize the unfavorable roles. Our results also showed that obstetricians and midwives may have different experiences, wants, and priorities regarding the use of the EMR system.

Conclusions: Currently, EMR systems are mainly viewed as tools that support the clinical workflow. Redesigning EMR systems is needed to amplify their roles as communication support tools. Our results provided multiple EMR redesign opportunities to improve the usability and usefulness of EMR systems in prenatal care. Designers can use the results to guide their EMR redesign activities and align them with the users' wants and priorities. The biggest challenge is to redesign EMR systems in a way that amplifies their favorable roles for all the stakeholders concurrently.
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http://dx.doi.org/10.2196/13812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647759PMC
July 2019

Intracervical elastomeric sealant in an model.

J Matern Fetal Neonatal Med 2021 Apr 19;34(7):1109-1111. Epub 2019 Jun 19.

Department of Gynecology and Obstetrics, Kyoto University, Kyoto, Japan.

Background: Premature rupture of membranes occurring in previable midtrimester patients is associated with perinatal mortality, and optimal therapeutic methods are yet to be established.

Objective: This study's objective was to investigate whether an elastomeric sealant, which has been used as a hemostatic agent for arterial anastomosis, could plug the uterine endocervical canal to prevent leakage of intrauterine fluid in an model.

Methods: The elastomeric sealant or fibrin glue was applied to the cervix of uteri removed for benign gynecological disease ( = 4). Normal saline was administered into the uterine cavity through a catheter using a pressure infusion bag. Intrauterine pressure was measured using a digital pressure gauge, and the pressure at which normal saline started leaking out of the uterine cervix was compared between both the sealants.

Results: No fluid leakage was observed with the elastomeric sealant until the pressure exceeded 20 kPa (150 mmHg), while the leakage onset pressure with fibrin sealant was 6.6 ± 1.8 kPa (50 ± 14 mmHg). The threshold leak pressure where the onset of liquid flow was initiated was significantly different between both the sealants ( < .0001).

Conclusions: Intracervical elastomeric sealant exhibited powerful fluid leakage prevention in an model. The sealant would have potential to prevent the leakage of amniotic fluid in pregnancies with previable premature rupture of membranes.
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http://dx.doi.org/10.1080/14767058.2019.1626367DOI Listing
April 2021

Placental sonic hedgehog pathway regulates foetal growth via insulin-like growth factor axis in preeclampsia.

J Clin Endocrinol Metab 2019 May 23. Epub 2019 May 23.

Department of Obstetrics and Gynecology, Kyoto University, Kyoto, Japan.

Background: Placental dysfunction is the underlying cause of common major disorders of pregnancy, such as foetal growth restriction (FGR) and preeclampsia. However, the mechanisms of placental dysfunction are not entirely elucidated. We previously reported 10 reliable preeclampsia pathways based on multiple microarray data sets, among which was the sonic hedgehog (SHH) pathway. Here we describe the significant role of SHH signalling involved in placental development and foetal growth.

Methods: The placental expression levels of surrogate markers of the SHH pathway, patched homolog 1 (PTCH1) and glioma-associated oncogene homolog 2 (GLI2), were evaluated using quantitative real-time polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry. We investigated the underlying mechanisms of the SHH pathway in trophoblast syncytialization, a critical process for placental development and maturation, using primary cytotrophoblasts. Moreover, the potential roles of placental SHH signalling in the regulation of the insulin-like growth factor (IGF) axis were explored by pathway analysis of microarray data. Finally, the influence of SHH signalling on foetal growth was examined by placental administration of cyclopamine, an SHH pathway inhibitor, to pregnant mice.

Results: The SHH pathway was downregulated in preeclampsia placentas and its activation was highly correlated with birth weight. Trophoblast syncytialization was modulated by non-canonical SHH-adenylate cyclase (ADCY) signalling rather than canonical SHH-GLI signalling. The IGF1R pathway was regulated by both non-canonical SHH-ADCY signalling and canonical SHH-GLI signalling. Inhibition of placental SHH signalling significantly reduced foetal weight in mice.

Conclusion: Placental development and foetal growth were regulated through the SHH pathway via the IGF axis.
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http://dx.doi.org/10.1210/jc.2019-00335DOI Listing
May 2019

Risk of preterm birth after the excisional surgery for cervical lesions: a propensity-score matching study in Japan.

J Matern Fetal Neonatal Med 2021 Mar 30;34(6):845-851. Epub 2019 May 30.

Perinatology Committee of the Japan Society of Obstetrics and Gynecology, Kanagawa, Japan.

Introduction: There is a paucity of data on the risk of preterm birth subcategorized by gestational age in pregnancies after the pre-pregnancy excisional treatment for cervical lesions. In addition, little is known about the effect of prophylactic cerclage on the risk of preterm birth. The aim of this study was to investigate the risk of preterm birth stratified by gestational period and its reduction by the prophylactic cerclage in women with prior excisional surgery.

Materials And Methods: We retrospectively analyzed a cohort of singleton pregnancies in the Japan Perinatal Registry Network Database (2013-2014,  = 307,001). Cases included pregnancies after the surgery (i.e. conization and loop electrosurgical excision procedure). Controls comprised the propensity-score matched pregnancies without pre-pregnancy surgery. The main outcome was the occurrence of preterm birth. The effect of prophylactic cervical cerclage on the risk of preterm birth after the excisional surgery was also examined using cases.

Results: In the propensity-score matched population (cases,  = 1389; controls,  = 1389), cases exhibited a higher risk of preterm birth and preterm prelabor rupture of membranes (PROM), compared with controls (preterm birth: 25.3 versus 10.6%; preterm PROM: 14.0 versus 3.5%: both  < .0001). Odds ratios (OR; 95% confidence interval [CI]) for preterm birth at 22-27 weeks, 28-31 weeks, 32-33 weeks, and 34-36 weeks were 3.4 [1.8-6.5], 4.6 [2.7-7.7], 2.2 [1.4-3.5], and 2.1 [1.6-2.7], respectively. The association was stronger for preterm PROM at earlier gestational age (22-27 weeks, 28-31 weeks, 32-33 weeks, and 34-36 weeks: 5.2 [2.3-11.8], 7.1 [3.4-15.0], 3.8 [1.7-8.3], and 3.9 [1.8-4.6], respectively). In cases, 171 underwent the prophylactic cervical cerclage. The occurrence of preterm birth and preterm PROM was comparable between those with and without the cerclage (28.7 versus 24.2, and 12.9 versus 13.3%, respectively).

Conclusions: Pre-pregnancy excisional cervical surgery was associated with the increased risk of preterm birth, especially before 32 weeks of gestation. The prophylactic cerclage did not reduce the risk of preterm birth.
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http://dx.doi.org/10.1080/14767058.2019.1619687DOI Listing
March 2021
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