Publications by authors named "Akihito Horie"

41 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

Identifying Issues in Fertility Preservation for Childhood and Adolescent Patients with Cancer at Pediatric Oncology Hospitals in Japan.

J Adolesc Young Adult Oncol 2021 Jul 22. Epub 2021 Jul 22.

Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.

We conducted a questionnaire survey in 15 pediatric oncology hospitals in Japan to better understand the current status of fertility preservation in childhood and adolescents. The survey period was from September 2020 to December 2020. We mailed questionnaires to 64 departments involved in pediatric cancer treatments at the 15 hospitals. The primary outcomes were the timing of providing explanations on fertility preservation, presence of health care provider while providing explanations, cooperation between medical staff, and cooperation between hospitals. The response rate was 100% (64/64). Regarding the time at which this information was provided, 79.6% of patients (43/54) received it before cancer treatment; 5.6% (3/54), after remission; and 14.8% (8/54), both time points. Nurses were mostly in attendance (70%) when oncologists provided information to patients. Nine (60%) hospitals did not have a reproductive department. Among these, 28.6% of the respondents referred patients to a reproductive facility that performed fertility preservation. Providing information about fertility preservation was challenging owing to the shortage of specific explanatory materials (35.1%) and the lack of cooperation between pediatric oncologists and reproductive endocrinologists (24.6%). Based on this survey, educational activities regarding fertility preservation centered on pediatric oncologists and nurses are needed. Furthermore, a system for providing explanatory materials for fertility preservation and encouraging cooperation at the physician and hospital levels is also needed (IRB No. H2020-111).
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http://dx.doi.org/10.1089/jayao.2021.0088DOI Listing
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

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

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

[Promotion of Equal Access to Medical Services for Children, Adolescent and Young Adult(CAYA)Cancer Patients with Reproductive Problems-A Nationwide Expansion of the Regional Oncofertility Network in Japan].

Gan To Kagaku Ryoho 2020 Dec;47(12):1691-1696

Dept. of Obstetrics and Gynecology, Gifu University Graduate School of Medicine.

Objectives: Fertility preservation is important for Children, Adolescent and Young Adult(CAYA)cancer patients. Although a regional oncofertility network was established in Japan in 2012, regional inequality persists. This study was aimed at expanding the oncofertility network throughout Japan.

Methods: Oncologists, reproductive medicine specialists, and administrative officials from 24 regions, currently without a regional oncofertility network, conferred to discuss problems and strategies for network expansion.

Results: Regional oncofertility networks had already been established in 4 of 24 regions. Consultation and support and a collaboration system between facilities and individual doctors were found in 13 and 14 regions, respectively. Regarding which organization should lead the network operation, the regions(number)chose the prefecture (10), prefectural cancer centers(10), and OB/GYN department of hospitals specializing in cancer treatment(9). Obstacles to establishing a regional oncofertility network were the lack of manpower(21), budget(19), know-how(16), and specialists( 12).

Discussion: CAYA cancer patients need equal access to oncofertility networks, and a public support system is essential for preserving the fertility of cancer patients. We should organize a oncofertility network in association with prefectural administration. Medical staff training and supply of materials using the Oncofertility Consortium Japan system are required to promote the oncofertility network throughout Japan.
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December 2020

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

Nationwide survey of Japanese breast oncology and reproductive endocrinology departments about the impact of breast cancer treatment on fertility.

J Obstet Gynaecol Res 2020 Oct 15. Epub 2020 Oct 15.

Department of Obstetrics and Gynecology, Yoshinogawa Medical Center, Yoshinogawa, Japan.

The purpose of this study is to assess the impact of breast cancer treatment on the reproductive potential. We conducted a nationwide survey of breast oncology and reproductive endocrinology and infertility (REI) departments using a questionnaire designed to assess the impact of breast cancer treatment on fertility. We received responses from 312 breast oncology departments (response rate, 31.9%) and 541 REI departments (response rate, 50.9%). The most common method of achieving pregnancy reported by breast oncology departments was natural insemination (69.6%), followed by assisted reproductive technology ( 15.6%) and intrauterine insemination (IUI; 14.8%). The most common method of achieving pregnancy reported by REI departments was conventional in vitro fertilization and/or intracytoplasmic sperm injection (51.0%), followed by natural insemination with or without ovulation induction (40.0%) and IUI (8.0%). The overall pregnancy rate for patients who underwent treatment for infertility at REI departments after breast cancer treatment was 39.0%. Vast patients who experienced breast cancer treatments conceived mainly by natural insemination based on the data from breast oncology departments. On the other hand, 61.0% of the patients who visited REI departments presumably due to infertility by natural insemination did not conceive even by infertility treatments with exclusive knowledge in REI departments.
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http://dx.doi.org/10.1111/jog.14469DOI Listing
October 2020

Low-Grade Endometrial Stromal Sarcoma with a Nodule-in-Nodule Appearance in Preoperative Magnetic Resonance Images.

Case Rep Obstet Gynecol 2020 30;2020:8973262. Epub 2020 Jul 30.

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

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignant disease and demonstrates various patterns in preoperative imaging. Therefore, accurate diagnosis is important. Given its unique form, we report a case of LG-ESS with a nodule-in-nodule appearance on preoperative imaging. A 41-year-old woman was referred to our department for further examination of a 45 mm diameter uterine corpus mass. Preoperative magnetic resonance imaging (MRI) revealed several small nodules within a larger nodule. T2-weighted images showed moderate-to-high signal intensity with focal bands of low signal intensity in the small nodules. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathological findings of the small nodules showed densely concentrated endometrial stromal cells reminiscent of a proliferative phase endometrium with a concentric arrangement of small spiral arteriole-like vessels. The small nodules exhibited an expansile growth pattern and were surrounded by less densely concentrated endometrial stromal cells intermingled with the normal uterine myometrium. LG-ESS with smooth muscle differentiation and sex cord-like elements was partially observed. In summary, LG-ESS demonstrating a unique nodule-in-nodule appearance on preoperative imaging histopathologically comprised tumor cells of varying densities. Our current case suggests that preoperative diagnostic imaging with MRI may be useful.
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http://dx.doi.org/10.1155/2020/8973262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414370PMC
July 2020

UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study.

BMC Cancer 2020 Aug 5;20(1):729. Epub 2020 Aug 5.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8501, Japan.

Background: Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy.

Methods: We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival.

Results: The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1.

Conclusions: Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.
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http://dx.doi.org/10.1186/s12885-020-07225-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405427PMC
August 2020

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems.

Int J Mol Sci 2020 Mar 10;21(5). Epub 2020 Mar 10.

Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Urayasu 279-0021, Japan.

Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely accepted that maternal-embryo communications, including embryonic signals, improve the receptive ability of the sex steroid hormone-primed endometrium. The embryo may utilize repulsive forces produced by an Eph-ephrin system for its timely attachment to and subsequent invasion through the endometrial epithelial layer. Importantly, the embryonic signals are considered to act on maternal immune cells to induce immune tolerance. They also elicit local inflammation that promotes endometrial differentiation and maternal tissue remodeling during embryo implantation and placentation. Additional clarification of the immune control mechanisms by embryonic signals, such as human chorionic gonadotropin, pre-implantation factor, zona pellucida degradation products, and laeverin, will aid in the further development of immunotherapy to minimize implantation failure in the future.
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http://dx.doi.org/10.3390/ijms21051885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084435PMC
March 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

Primary signet ring cell carcinoma of uterine cervix and related disease: two case reports and a review.

Int Cancer Conf J 2019 Oct 17;8(4):157-163. Epub 2019 May 17.

1Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Primary signet ring cell carcinoma of uterine cervix (SRCCC) is extremely rare. We present two cases of primary SRCCC that were treated with robot-assisted laparoscopic radical hysterectomy (RALRH). Case 1 had stage IB2 cervical adenocarcinoma, in which signet ring cell (SRC) was predominant. As adjuvant chemotherapy was not successful, she twice underwent surgical excision of recurrent tumors in pararectal lymph node and periureteral space 11 months and 27 months after RALRH, respectively. There were only SRCs observed in recurrent tumors. Case 2 had stage IB1 cervical adenocarcinoma, in which SRCs were detected only in the biopsy specimen, and no relapse occurred at 15 months after RALRH. PET/CT was useful for tumor detection in both cases, and the amount of SRC components was associated with the prognostic outcome. Considering the high recurrence rate and few complications at secondary surgery, minimally invasive surgery would be preferred as the primary surgery for SRCCC.
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http://dx.doi.org/10.1007/s13691-019-00375-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744541PMC
October 2019

Magnetic resonance relaxometry improves the accuracy of conventional MRI in the diagnosis of endometriosis-associated ovarian cancer: A case report.

Mol Clin Oncol 2019 Sep 1;11(3):296-300. Epub 2019 Jul 1.

Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan.

Endometriosis is a precancerous condition for endometriosis-associated ovarian cancer (EAOC). In the present study, conventional magnetic resonance imaging (MRI) and MR relaxometry were used to examine a case of clear cell carcinoma that arose in a pre-existing right-sided benign ovarian endometrioma (OE). The 42-year-old nulliparous woman suspected of EOAC, as assessed by conventional MRI, requested fertility-sparing surgery such as laparoscopic endometrioma cystectomy. Furthermore, the MR transverse relaxation rate (R2) was determined using a single-voxel, multi-echo MR sequence using a 3 Tesla-MR system. An R2 value <12.1 s was indicative of malignancy, as described in previous studies. In the present study, MR relaxometry identified an R2 value of 7.98 s in the right cyst, which suggested the malignant transformation of benign OE. Based on these findings, fertility-sparing surgery was contraindicated. In conclusion, MR relaxometry may represent a new clinical approach as an adjunctive modality for the diagnosis of EAOC. When patients exhibiting a pelvic mass suspected of EAOC desire fertility-sparing treatment options, MR relaxometry can facilitate the selection of conservative management.
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http://dx.doi.org/10.3892/mco.2019.1889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667887PMC
September 2019

Hysteroscopic morphological pattern reflects histological grade of endometrial cancer.

J Obstet Gynaecol Res 2019 Aug 9;45(8):1479-1487. Epub 2019 May 9.

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

Aim: To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high- and low-grade cancer and low-grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy.

Methods: In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low-grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high-grade cancer, including endometrioid carcinoma grade 3 and other high-grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated.

Results: The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%).

Conclusion: Hysteroscopic papillary and polypoid structures can help distinguish between high- and low-grade cancer. Hysteroscopic differentiation between AEH and low-grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies.
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http://dx.doi.org/10.1111/jog.13998DOI Listing
August 2019

Endovascular trophoblast expresses CD59 to evade complement-dependent cytotoxicity.

Mol Cell Endocrinol 2019 06 11;490:57-67. Epub 2019 Apr 11.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.

In the human placenta, extravillous trophoblasts (EVTs) invade maternal decidual tissues (interstitial trophoblasts) and maternal spiral arteries (endovascular trophoblasts). Although endovascular trophoblasts are directly exposed to maternal blood containing complement components, they are not eliminated by complement-dependent cytotoxicity (CDC). In this study, we investigated the expression and possible function of CD59, one of the membrane-bound complement regulators, in EVTs. Immunohistochemistry of early embryo implantation sites revealed that CD59 was hardly expressed on interstitial trophoblasts, whereas it was intensely expressed on endovascular trophoblasts. Using the human EVT-like cell line Swan71, we established CD59-silencing Swan71 cells (Sw_CD59sh) and non-silencing control Swan71 cells (Sw_CTRsh). In vitro cell apoptosis assay showed that Sw_CD59sh cells were significantly more susceptible to CDC as compared to Sw_CTRsh. Our results suggest that CD59 confers some protection against maternal complement attack to the endovascular trophoblasts.
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http://dx.doi.org/10.1016/j.mce.2019.04.006DOI Listing
June 2019

Solitary fibrous tumor arising from pelvic retroperitoneum: A report of two cases and a review of the literature.

J Obstet Gynaecol Res 2019 Jul 7;45(7):1391-1397. Epub 2019 Apr 7.

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

Solitary fibrous tumors (SFT) rarely arise in the pelvis. Here, we report two cases of SFT arising from the pelvic retroperitoneum. The first case involves a 64-year-old woman diagnosed with a 5-cm pelvic mass. Magnetic resonance imaging revealed a solid and cystic mass with marked enhancement, but limited water restriction. During surgery, intraligamental tumor arising near the round ligament was resected. Pathologically, the tumor comprised dilated vessels and spindle-shaped cells positive for STAT6 and CD34. The second case involves a 53-year-old woman diagnosed with a 4.5-cm pelvic mass through computed tomography. Magnetic resonance imaging demonstrated a solid mass with multiple cysts with strong enhancement and slight water restriction. During surgery, the tumor was found in the retroperitoneum. Pathologically, spindle-shaped tumor cells positive for STAT6 and CD34 had proliferated around the prominent hyalinized vessels. Although rare in the pelvis, SFT should be suspected when a mass with strong enhancement is found.
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http://dx.doi.org/10.1111/jog.13965DOI Listing
July 2019

Aggressive adult granulosa cell tumor of the ovary without a FOXL2 mutation: A case report.

J Obstet Gynaecol Res 2019 Jul 5;45(7):1404-1409. Epub 2019 Apr 5.

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

We report a case of aggressive adult granulosa cell tumor (AGCT) of the ovary. On presentation, the tumor was localized in the right ovary; a total abdominal hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy were performed. While some areas of the tumor represented typical AGCT, other areas showed enlarged and hyperchromatic nuclei with numerous mitoses (>10/high-power field) with marked necrosis. The results of immunohistochemical analysis were compatible with AGCT, except that, in the necrotic portion, p53 was strongly positive, and the Ki-67 index was high. Four months after laparotomy, recurrent tumors developed in the bones, liver, lungs and dura mater. The patient responded well to chemotherapy consisting of five cycles of paclitaxel and carboplatin, but later, the tumors rapidly proliferated, and the patient died of disease 11 months after laparotomy. FOXL2 examination demonstrated that both portions of the primary tumor did not have a point mutation (402C→G) specific to AGCT.
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http://dx.doi.org/10.1111/jog.13969DOI Listing
July 2019

Oocyte cryopreservation for a female cancer patient after reaching adulthood.

Pediatr Int 2019 Feb 11;61(2):207-208. Epub 2019 Feb 11.

Departments of Human Health Science, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.

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http://dx.doi.org/10.1111/ped.13752DOI Listing
February 2019

Human chorionic gonadotropin value and its change prior to methotrexate treatment can predict the prognosis in ectopic tubal pregnancies.

Reprod Med Biol 2019 Jan 11;18(1):51-56. Epub 2018 Oct 11.

Department of Gynecology and Obstetrics Kyoto University Kyoto Japan.

Purpose: To investigate the role of beta-human chorionic gonadotropin (HCG) level and its change prior to methotrexate (MTX) treatment as predictors of treatment success and to access the posttreatment observation period for ectopic tubal pregnancy.

Methods: Clinical data of 41 females treated with MTX for tubal pregnancies were reviewed and analyzed retrospectively.

Results: Among 41 patients, 34 achieved complete resolution without surgery. No statistically significant difference was observed in the presence of hemorrhagic ascites, serum progesterone levels, or diameters of adnexal mass between the MTX success and failure groups. Serum HCG levels on the day of MTX administration (day 1) were significantly lower in the MTX success group. Moreover, % HCG change per day, which represents the increment ratio of HCG prior to MTX treatment, was significantly lower in the MTX success group. Receiver operating characteristic (ROC) curves demonstrated that the treatment success was predicted by % HCG change per day less than +12.6% per day with a sensitivity of 87% and a specificity of 71%. The duration from treatment to complete recovery was strongly correlated with day 1 HCG levels.

Conclusions: Pretreatment HCG change is a significant predictor of therapeutic success of MTX treatment, and the treatment period may be predicted from initial HCG levels.
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http://dx.doi.org/10.1002/rmb2.12247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332740PMC
January 2019

Novel subtype of atonic postpartum hemorrhage: dynamic computed tomography evaluation of bleeding characteristics and the uterine cavity.

J Matern Fetal Neonatal Med 2020 Oct 31;33(19):3286-3292. Epub 2019 Jan 31.

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

Uterine atony is the leading cause of severe postpartum hemorrhage (PPH); however, the underlying cause of intractable atonic PPH unresponsive to conventional treatments (such as uterotonics and intrauterine balloon tamponade) remains unclear. The aim of this study was to investigate whether intractable atonic PPH is associated with the type of bleeding (arterial or nonarterial) and its location, along with variations in the size and shape of the uterine cavity after delivery. This retrospective study included women who had undergone a dynamic computed tomography (CT) scan for the management of severe PPH at Kyoto University Hospital between April 2011 and March 2017. Patients' electronic medical records were reviewed, and relevant clinical information was collected. The presence of contrast extravasation (CE) on CT images in the early phase (40 s) was regarded as active arterial bleeding. Bleeding sites and size of the uterine cavity were evaluated using an coordinate system. The size of the uterine cavity was compared between groups with CE into the upper and lower parts of the uterine body. Of the 60 women assessed for eligibility, 30 were included in the current analysis. Contrast extravasation was detected in 19 women, with 14 showing CE in the early phase. The presence of CE in the early phase was significantly associated with the need for transarterial embolization (Fisher's exact test,  = .0017). The upper and lower parts of the uterine cavity were 97.4 ± 2.7 mm (mean ± standard error of the mean) and 87.2 ± 3.5 mm in length, respectively. The maximum anteroposterior diameters of the upper and lower parts of the uterine cavity were 23.1 ± 2.6 and 76.0 ± 3.0 mm, respectively, and the largest transverse diameters were 67.3 ± 1.9 and 81.1 ± 2.3 mm, respectively. The group that showed CE into the upper uterine cavity had significantly larger qualitative parameters of the upper uterine cavity compared to the group with CE into the lower uterine cavity. The gate from the lower uterine cavity toward the upper uterine cavity was narrow (anteroposterior diameter of 22.6 ± 2.0 mm, transverse diameter of 40.7 ± 3.3 mm), and the intrauterine balloon was always found in the lower uterine cavity on the CT scan. The upper uterine body was characterized by a flat oval-shaped cavity ( plane), thick uterine wall, and lack of uniformity among bleeding sites (  =  62.4 ± 14.8 mm). In contrast, the lower uterine cavity was a circular shape ( plane) with thin walls, and bleeding sites were located at lateral sides around the level of the internal os ( =  -18.8 ± 4.9 mm). Atonic PPH has a significant subtype, named "PRACE," which is characterized by PPH, resistance to treatment, and arterial CE. The need for embolization can be predicted by the presence of arterial bleeding and its location, along with the shape of the uterine cavity.
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http://dx.doi.org/10.1080/14767058.2019.1571033DOI Listing
October 2020

Metabolomic Profiles of Placenta in Preeclampsia.

Hypertension 2019 03;73(3):671-679

Department of Obstetrics and Gynaecology, National Hospital Organization Kyoto Medical Center, Japan (K.K., I.K.).

Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide. We have previously reported that magnesium sulfate therapy is effective for early-onset (EO) preeclampsia. To investigate the molecular mechanisms underlying this favorable effect, metabolomics analysis of magnesium sulfate-treated preeclamptic placentas was performed using capillary electrophoresis time of flight mass spectrometry. There were significant metabolic differences between EO-preeclamptic placentas (n=7) and other placentas (late-onset preeclampsia [n=3], normal pregnancies [n=10]). In EO-preeclamptic placentas, the glutathione metabolism pathway was markedly upregulated, whereas single-sample gene-set enrichment analysis using a publicly available microarray dataset (GSE75010) showed that the glutathione metabolism pathway was significantly downregulated in EO-preeclamptic placentas compared with nonpreeclamptic controls. Metabolomic profiles showed that magnesium sulfate significantly promoted glutathione production in an immortalized trophoblast cell line under oxidative stress conditions but not under normal conditions. Magnesium sulfate suppressed hydrogen peroxide-induced production of reactive oxygen species. Exploratory analysis revealed that urinary 8-isoprostane was decreased in all 5 women treated with magnesium sulfate for preeclampsia with severe features. These findings suggest that magnesium sulfate is effective for treating EO-preeclampsia partly because of its antioxidant effects on trophoblasts.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12389DOI Listing
March 2019

Invasive Paget's disease of the vulva treated with a combination of surgery and concurrent chemoradiotherapy: A case report.

Mol Clin Oncol 2018 Nov 17;9(5):489. Epub 2018 Sep 17.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Kyoto 606-8507, Japan.

Invasive Paget's disease of the vulva (IP) is rare among patients with vulvar cancer. Radiation therapy and chemotherapy are not considered as radical, whereas surgical resection of the tumor with abdominal lymphadenectomy is highly invasive. Thus, more effective and less invasive treatments for IP are required. The present study reports a case of a 64-year-old woman with IP, who was treated with a combination of surgery and concurrent chemoradiotherapy (CCRT). The patient was diagnosed with IP with suspected lymph node metastases to the inguinal and pelvic lymph nodes, after having suffered from pruritus vulvae for 7 years. Following mapping biopsy, wide local excision, bilateral inguinal lymph node resection and laparoscopic pelvic lymphadenectomy were successfully performed. The vulva was reconstructed with a local fat flap. Postoperative pathological examination revealed metastases to the bilateral superficial inguinal and the left obturator and lateral suprainguinal lymph nodes. Adjuvant CCRT (whole pelvic irradiation, 50.4 Gy with weekly cisplatin, 40 mg/m) was completed without notable complications. Therefore, laparoscopic pelvic lymphadenectomy may be useful in determining the irradiation field for adjuvant CCRT in patients with advanced IP.
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http://dx.doi.org/10.3892/mco.2018.1719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200998PMC
November 2018

Versican V1 in human endometrial epithelial cells promotes BeWo spheroid adhesion in vitro.

Reproduction 2019 01;157(1):53-64

Department of Obstetrics and Gynecology, Otsu Red Cross Hospital, Otsu, Japan.

The endometrium extracellular matrix (ECM) is essential for embryo implantation. Versican, a large chondroitin sulfate proteoglycan that binds hyaluronan and forms large ECM aggregates, can influence fundamental physiological phenomena, such as cell proliferation, adhesion and migration. The present study investigated the possible role of versican in human embryo implantation. Versican V1 expression and secretion in human endometrial epithelial cells (EECs) was most prominent in the mid-secretory phase. Versican expression in EECs significantly increased after treatment with estrogen and progesterone, but not by estrogen alone. We also established versican V1-overexpressing Ishikawa (endometrial cancer cell line) cells (ISKW-V1), versican V3-overexpressing (ISKW-V3) and control GFP-overexpressing (ISKW-GFP) Ishikawa cells. By the in vitro implantation model, the attachment ratio of BeWo (choriocarcinoma cell line) spheroids to the monolayer of ISKW-V1, but not of ISKW-V3, was found significantly enhanced compared with attachment to the ISKW-GFP monolayer. The conditioned medium derived from ISKW-V1 (V1-CM) also promoted the attachment of BeWo spheroids to the ISKW monolayer. However, this attachment-promoting effect was abolished when V1-CM was pretreated with chondroitinase ABC, which degrades chondroitin sulfate. Therefore, out of the ECM components, versican V1 may facilitate human embryo implantation.
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http://dx.doi.org/10.1530/REP-18-0333DOI Listing
January 2019

Factors Regulating Human Extravillous Trophoblast Invasion: Chemokine-peptidase and CD9-integrin Systems.

Curr Pharm Biotechnol 2018 ;19(10):764-770

Institute for Environmental and Gender-specific Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

The invasion of an extravillous trophoblast (EVT) into maternal decidual tissues, especially towards maternal spiral arteries, is an essential process in the human placental formation and subsequent normal fetal development. However, the precise regulatory mechanisms to induce EVT invasion towards arteries and/or to protect EVT from further invasion are not well understood. We found that a chemokine receptor, CCR1, was specifically expressed on EVT migrating towards maternal arteries. Using EVT isolated from a primary villous explant culture, RANTES, which is one of the ligands for CCR1, was shown to enhance EVT invasion. Furthermore, we observed that the platelets were deposited among intravascular EVT and platelet-derived soluble factors, which contained RANTES, enhanced EVT invasion. On the one hand, dipeptidyl peptidase IV (DPPIV), which can metabolize RANTES on the cell surface, was expressed on non-invading EVT and was demonstrated to suppress EVT invasion. In contrast, laeverin/aminopeptidase Q, which is specifically expressed on EVT, was shown to induce EVT invasion. Also, CD9 which is a cell surface marker of platelets and a regulator of integrin function was expressed on EVT and gene knockdown of the CD9 molecule enhanced EVT invasion. These findings suggest that the chemokine-chemokine receptor, chemokine-peptidase, and CD9-integrin systems play important roles in the regulation of EVT invasion during early human placental formation.
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http://dx.doi.org/10.2174/1389201019666181029164906DOI Listing
February 2019
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