Publications by authors named "Tomoaki Ikeda"

277 Publications

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

Primary cytomegalovirus infection during pregnancy and congenital infection: a population-based, mother-child, prospective cohort study.

J Perinatol 2021 Jul 20. Epub 2021 Jul 20.

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

Objective: This study assessed maternal cytomegalovirus antibodies, and the occurrence of primary and congenital cytomegalovirus infections, and risk factors of congenital infection after a maternal primary infection.

Study Design: We included 19,435 pregnant women in Japan, who were tested for serum cytomegalovirus antibodies before 20 gestational weeks. Immunoglobulin (Ig) G avidity was evaluated in women with both IgG and IgM antibodies; tests were repeated at ≥28 gestational weeks among women without IgG and IgM antibodies.

Result: Primary and congenital infections were 162 and 23 cases, respectively. The risk ratios for congenital infection were 8.18 (95% confidence interval: 2.44-27.40) in teenage versus older women, and 2.25 (95% confidence interval: 1.28-3.94) in parity ≥ 2 versus parity ≤ 1. Of 22 live birth congenital infection cases, three had abnormal neurological findings.

Conclusion: We demonstrated teenage and parity ≥ 2 pregnant women as risk factors of post-primary congenital infection.
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http://dx.doi.org/10.1038/s41372-021-01157-9DOI Listing
July 2021

Laparoscopic Versus Robotic Hysterectomy in Obese Patients With Early-stage Endometrial Cancer: A Single-centre Analysis.

Anticancer Res 2021 Aug;41(8):4163-4167

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Background/aim: To compare the surgical outcomes of robotic and laparoscopic hysterectomy with or without pelvic lymphadenectomy among obese patients [body mass index (BMI) >30 kg/m] with early-stage endometrial cancer.

Patients And Methods: We examined 42 obese patients with early-stage endometrial cancer who underwent laparoscopic (LH) or robotic hysterectomy (RH) between April 2014 and April 2020 in our institution. We analysed intraoperative and postoperative data for both procedures.

Results: Of the 42 women, 22 and 20 patients underwent RH and LH, respectively, with or without pelvic lymphadenectomy. The operation times, harvested lymph nodes, and BMI did not differ between the groups. In the subset of patients who underwent pelvic lymphadenectomy, those in the RH group had shorter hospital stays (p=0.001) and less intraoperative bleeding (p=0.006).

Conclusion: Obese patients with endometrial cancer who underwent robotic surgery had less blood loss and shorter hospital stays than those who underwent laparoscopic surgery.
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http://dx.doi.org/10.21873/anticanres.15220DOI Listing
August 2021

Prognostic Benefit of ≥6 Cycles of Neoadjuvant Chemotherapy for Advanced Ovarian, Tubal, and Peritoneal Cancers.

Anticancer Res 2021 Aug;41(8):4157-4161

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Background/aim: A higher number of neoadjuvant chemotherapy (NACT) cycles translate to a lower risk of morbidity and mortality, but few studies have analyzed the prognostic impact of >4 cycles of NACT.

Patients And Methods: Overall, 52 patients [31 patients, NACT plus interval debulking surgery (IDS); 21 patients, NACT alone owing to progressive disease] who underwent NACT between January 2008 and December 2014 were evaluated.

Results: In total, 6, 7-10, and 11-18 cycles of NACT were performed in 52.3%, 27.3%, and 20.5% of the patients, respectively. The median overall survival was 76.0 months (range=36.0-94.0 months), and the median progression-free survival was 26.0 months (range=18.0-54.0 months) in the NACT plus IDS group.

Conclusion: At least six cycles of NACT plus IDS are associated with a lower rate of multi-organ resection and a high rate of complete resection or optimal (<1 cm) following IDS.
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http://dx.doi.org/10.21873/anticanres.15219DOI Listing
August 2021

Effectiveness of Laparoscopic Combined Retroperitoneal and Transperitoneal Approach in Para-aortic Lymphadenectomy for Endometrial Cancer.

Anticancer Res 2021 Aug;41(8):4151-4155

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Background/aim: This study aimed to compare laparoscopy with laparotomy and evaluate the effectiveness of a laparoscopic combined retroperitoneal and transperitoneal approach for para-aortic lymphadenectomy in patients with endometrial cancer.

Patients And Methods: In this single-center retrospective study, patients with endometrial cancer who underwent para-aortic lymphadenectomy between December 2016 and November 2019 were analyzed. The patient's clinical and pathologic data were procured from medical records. Statistical analyses were performed using Fisher's exact and the Mann-Whitney U-tests.

Results: A total of 37 and 28 patients were included in the laparoscopic and laparotomy groups, respectively. The laparoscopic group had similar operative time, similar number of resected para-aortic and pelvic lymph nodes, less intraoperative blood loss and complications, lower rate of blood transfusion, and shorter postoperative stay than the laparotomy group.

Conclusion: Laparoscopic combined retroperitoneal and transperitoneal approach for endometrial cancer is safe and effective compared to laparotomy.
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http://dx.doi.org/10.21873/anticanres.15218DOI Listing
August 2021

Laparoscopic repair of segmental obturator nerve injury defect using an artificial nerve conduit: A case report.

J Obstet Gynaecol Res 2021 Jul 14. Epub 2021 Jul 14.

Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Mie University, Tsu, Mie, Japan.

Obturator nerve injury is an uncommon complication frequently associated with pelvic gynecologic or urologic cancer surgery. It can lead to disability or adversely affect quality of life. Large segmental defects are particularly difficult to manage as the limited mobility of the nerve prevents tension-free direct end-to-end anastomosis. A 36-year-old woman with cervical cancer underwent sentinel lymph node biopsy, laparoscopic radical hysterectomy, and bilateral adnexectomy. During the procedure, the sentinel lymph node (right obturator node) adherent to the obturator nerve was resected together with the nerve segment leaving a 3 cm defect. Immediate laparoscopic obturator nerve repair was performed using an artificial nerve conduit leading to successful recovery. We report this unique case due to rarity of large segmental obturator nerve defects and present laparoscopic nerve repair with artificial nerve conduits as a useful treatment alternative of these important injuries, without nerve donor site morbidity.
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http://dx.doi.org/10.1111/jog.14920DOI Listing
July 2021

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan.

Taiwan J Obstet Gynecol 2021 Jul;60(4):621-627

Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Japan; Mie Association of Obstetricians and Gynecologists, Tsu, Japan.

Objective: Investigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection.

Materials And Methods: We retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection.

Results: Twenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00-12.00 titers and 100% with 1.21-3.99 IgM titers) (p = 0.048).

Conclusions: Nulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.
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http://dx.doi.org/10.1016/j.tjog.2021.05.008DOI Listing
July 2021

Carboxylated Poly-l-Lysine as a Macromolecular Cryoprotective Agent Enables the Development of Defined and Xeno-Free Human Sperm Cryopreservation Reagents.

Cells 2021 Jun 8;10(6). Epub 2021 Jun 8.

Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.

In human sperm cryopreservation, test yolk buffer and human serum albumin have been used as permeating macromolecular-weight cryoprotectants. In clinical reproductive medicine, human serum albumin is frequently used because of low risks of zoonoses and allergic reactions. However, the risk of allogeneic infectious diseases exists, and the supply may be unstable because human serum albumin is derived from human blood. Therefore, the development of xeno-free human sperm cryopreservative reagents that could overcome the aforementioned problems is warranted. We succeeded in developing a new xeno-free and defined sperm cryopreservation reagent containing glycerol, carboxylated poly-l-lysine, and raffinose. The cryopreservation reagent was not significantly different in terms of sperm motility, viability, and DNA fragmentation and was comparable in performance to a commercial cryopreservation reagent containing human serum albumin. Moreover, the addition of saccharides was essential for its long-term storage. These results may help elucidate the unknown function of macromolecular-weight permeating cryoprotective agents.
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http://dx.doi.org/10.3390/cells10061435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227581PMC
June 2021

The physical and mental burden on obstetricians and gynecologists during the COVID-19 pandemic: A September 2020 questionnaire study.

J Obstet Gynaecol Res 2021 Jun 16. Epub 2021 Jun 16.

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

Aim: The aim of this study was to clarify the physical and mental burden of the COIVD-19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress.

Methods: A web-based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020.

Results: A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID-19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID-19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID-19 infection.

Conclusions: Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.
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http://dx.doi.org/10.1111/jog.14878DOI Listing
June 2021

Psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 pandemic.

J Obstet Gynaecol Res 2021 Jun 16. Epub 2021 Jun 16.

Department of Obstetrics and Gynecology, Teine Keijinkai Hospital, Sapporo, Japan.

Aim: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model.

Results: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557).

Conclusions: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.
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http://dx.doi.org/10.1111/jog.14877DOI Listing
June 2021

The Successful Use of Nitroglycerin for Uterine Hyperstimulation with Fetal Heart Rate Abnormality Caused by a Controlled-Release Dinoprostone Vaginal Delivery System (PROPESS): A Case Report.

Medicina (Kaunas) 2021 May 12;57(5). Epub 2021 May 12.

Department of Obstetrics and Gynecology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

The PROPESS, a controlled-release dinoprostone vaginal delivery system, is a pharmacological cervical ripening intervention and promotes cervical change causing uterine contraction. During insertion of the PROPESS, uterine hyperstimulation could occur and result in fetal heart rate (FHR) abnormality. We report a case of uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS in a pregnant woman. Postural change, oxygenation, fluid infusion, and the immediate PROPESS removal were ineffective to address the adverse event, so we administered nitroglycerin for acute uterine relaxation. The nitroglycerin resulted in uterine relaxation, and the FHR abnormality was resolved immediately, thereby preventing an emergency cesarean section. Therefore, nitroglycerin could be considered an effective option for uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS.
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http://dx.doi.org/10.3390/medicina57050478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151635PMC
May 2021

Current status of community-acquired infection of COVID-19 in delivery facilities in Japan.

PLoS One 2021 20;16(5):e0251434. Epub 2021 May 20.

Seijyo Kinoshita Hospital, Tokyo, Japan.

A nationwide questionnaire survey about community-acquired infection of coronavirus disease 2019 (COVID-19) was conducted in July 2020 to identify the characteristics of and measures taken by Japanese medical facilities providing maternity services. A case-control study was conducted by including medical facilities with (Cases) and without (Control) community-acquired infection of COVID-19. Responses from 711 hospitals and 707 private clinics were assessed (72% of all hospital and 59% all private clinics provided maternity service in Japan). Seventy-five COVID-19-positive pregnant women were treated in 52 facilities. Community-acquired infection was reported in 4.1% of the facilities. Of these, 95% occurred in the hospital. Nine patients developed a community-acquired infection in the maternity ward or obstetric department. Variables that associated with community-acquired infection of COVID-19 (adjusted odds ratio [95% confidence interval]) were found to be state of emergency prefecture (4.93 [2.17-11.16]), PCR test for SARS-CoV-2 on admission (2.88 [1.59-5.24]), and facility that cannot treat COVID-19 positive patients (0.34 [0.14-0.82]). In conclusion, community-acquired infection is likely to occur in large hospitals that treat a higher number of patients than private clinics do, regardless of the preventive measures used.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251434PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136647PMC
June 2021

Nationwide survey (Japan) on spontaneous hemoperitoneum in pregnancy.

J Obstet Gynaecol Res 2021 May 4. Epub 2021 May 4.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Aim: The purpose of this study was to evaluate the current state and clinical characteristics of spontaneous hemoperitoneum in pregnancy (SHiP) in Japan by performing a comprehensive survey.

Methods: We reviewed data on pregnant women who developed SHiP during 2013-2017 (for 5 years), and were admitted to any of the perinatal centers in Japan. The survey assessed maternal background and maternal and neonatal prognosis. We divided the cases into two groups, favorable and poor prognosis groups, and made comparisons between the two groups.

Results: Of the 407 facilities in Japan, 267 (66%) facilities responded to our survey. Overall, 31 cases of SHiP were registered. Maternal death occurred in one case (3%) due to liver bleeding with an unknown cause. Of 23 cases with a SHiP onset during pregnancy, 12 (53%) had been misdiagnosed as placental abruption. The prognosis for the fetuses included miscarriage or stillbirth in three cases (10%) and asphyxia in 12 cases (42%). There was no significant correlation between the amount of intra-abdominal blood loss and neonatal prognosis based on umbilical artery pH. Incidences of preterm birth <32 gestational weeks (adjusted odds ratio, 35.75; 95% confidence interval, 3.46-368.82) were higher in the poor prognosis group than that in the favorable group. Endometriosis and artificial reproductive techniques were both associated with 19% of all cases of SHiP.

Conclusion: SHiP was associated with maternal death and poor fetal prognosis. Prematurity and persistent uterine contractions which might be misdiagnosed as placental abruption seem to contribute to poor fetal prognosis.
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http://dx.doi.org/10.1111/jog.14819DOI Listing
May 2021

Transient effects of forebrain ischemia on fetal heart rate variability in fetal sheep.

Am J Physiol Regul Integr Comp Physiol 2021 06 21;320(6):R916-R924. Epub 2021 Apr 21.

Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.

Fetal heart rate variability (FHRV) is a key index of antenatal and intrapartum fetal well-being. FHRV is well established to be mediated by both arms of the autonomic nervous system, but it remains unknown whether higher centers in the forebrain contribute to FHRV. We tested the hypothesis that selective forebrain ischemia would impair the generation of FHRV. Sixteen chronically instrumented near-term fetal sheep were subjected to either forebrain ischemia induced by bilateral carotid occlusion or sham-ischemia for 30 min. Time, frequency, and nonlinear measures of FHRV were assessed during and for seven days after ischemia. Ischemia was associated with profound suppression of electroencephalographic (EEG) power, which remained suppressed throughout the recovery period ( < 0.001). During the first 5 min of ischemia, multiple time and frequency domain measures were increased (all < 0.05) before returning back to sham levels. A delayed increase in sample entropy was observed during ischemia ( < 0.05). For the first 3 h after ischemia, there was moderate suppression of two measures of FHRV (very-low frequency power and the standard deviation of RR-intervals, both < 0.05) and increased sample entropy ( < 0.05). Thereafter, all measures of FHRV returned to control levels. In conclusion, profound forebrain ischemia sufficient to lead to severe neural injury had only transient effect on multiple measures of FHRV. These findings suggest that the forebrain makes a limited contribution to FHRV. FHRV therefore primarily originates in the hindbrain and is unlikely to provide meaningful information on forebrain neurodevelopment or metabolism.
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http://dx.doi.org/10.1152/ajpregu.00032.2021DOI Listing
June 2021

Pregnancy-associated hemorrhagic stroke: A nationwide survey in Japan.

J Obstet Gynaecol Res 2021 Jun 5;47(6):2066-2075. Epub 2021 Apr 5.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Tsu, Mie, Japan.

Aim: The number of maternal deaths due to pregnancy-associated hemorrhagic stroke has not decreased despite a gradual decrease of maternal death in Japan. This study aimed to clarify the risk factors of hypertensive disorders of pregnancy-associated hemorrhagic stroke.

Methods: This retrospective study analyzed pregnancy-associated hemorrhagic stroke patients with hypertensive disorders of pregnancy between 2013 and 2017 among 407 Japanese maternal and perinatal centers. Patients were divided into good or poor outcome groups and their maternal backgrounds and neonatal prognoses were compared.

Results: We analyzed 61 cases, including 41 survival and 20 death cases, obtained from a secondary survey. Among the 61 hemorrhagic stroke cases, 62% were related to hypertensive disorders. Hypertensive disorders of pregnancy were observed in 75% of death cases. Use of MgSO or antihypertensive medication did not differ between the poor and good outcomes groups. In cases with antepartum onset of hypertensive disorders of pregnancy, outcomes were poor in 12 and good in 6 cases. Nine patients with poor outcomes and one with a good outcome had hypertension at the outpatient department without systemic evaluation (p = 0.043). Six poor outcomes patients and one good outcome spent more than 1 day from diagnosis at an outpatient clinic. Neurosurgery was performed in 11 poor outcome patients.

Conclusion: Pregnant women who present with a hypertensive disorder at an outpatient clinic probably need to undergo blood tests and careful observation. Delayed systemic evaluation and intensive care for only a few days may result in the development of hemorrhage.
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http://dx.doi.org/10.1111/jog.14786DOI Listing
June 2021

Looking at the data in the right perspective.

Am J Obstet Gynecol 2021 07 22;225(1):106-107. Epub 2021 Feb 22.

The Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, Japan Council for Quality Health Care, Tokyo, Japan; Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Mie, Japan.

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http://dx.doi.org/10.1016/j.ajog.2021.02.025DOI Listing
July 2021

The validity of the subsequent pregnancy index score for fertility-sparing trachelectomy in early-stage cervical cancer.

Fertil Steril 2021 May 13;115(5):1250-1258. Epub 2021 Feb 13.

Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan. Electronic address:

Objective: To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy.

Design: Retrospective cohort.

Setting: Academic multicenter.

Patient(s): Women ages <45 years with clinical stage I-II cervical cancer were enrolled between 2009 and 2013 (n = 393).

Intervention(s): Planned fertility-sparing trachelectomy.

Main Outcome Measure(s): Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined.

Result(s): There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%).

Conclusion(s): The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.
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http://dx.doi.org/10.1016/j.fertnstert.2020.09.162DOI Listing
May 2021

Categorization of cerebral palsy cases: a different perspective.

Am J Obstet Gynecol 2021 Aug 7;225(2):211-212. Epub 2021 Feb 7.

The Recurrence Prevention Committee, Japan Obstetric Compensation System for Cerebral Palsy, Japan Council for Quality Health Care, Tokyo, Japan; Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Mie, Japan.

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http://dx.doi.org/10.1016/j.ajog.2021.02.008DOI Listing
August 2021

Pulmonary thromboembolism during pregnancy and puerperium: Comparison of survival and death cases.

J Obstet Gynaecol Res 2021 Apr 1;47(4):1312-1321. Epub 2021 Feb 1.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Aim: In Japan, the frequency of maternal deaths due to obstetric hemorrhage has been decreasing in the last decade, while that resulting from other causes such as pulmonary thromboembolism (PTE) was consistent. To help reduce maternal deaths due to PTE, we investigated PTE during pregnancy and puerperium and compared the survival and death cases, and aimed to find out life and death factors.

Methods: This study was a retrospective analysis based on a clinical chart review in 407 maternal and perinatal centers. We compared the survival and death cases of PTE during pregnancy and puerperium from 2013 to 2017.

Results: In PTE during pregnancy, the survival cases underwent significantly earlier diagnoses than the death cases, and thromboprophylaxis was performed in most of both the survival and death cases of PTE during puerperium according to the existing Japanese guidelines; however, only one fourth of the total cases underwent anticoagulation to prevent venous thromboembolism (VTE).

Conclusions: Early diagnosis of PTE in suspected cases was associated with better survival during pregnancy.
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http://dx.doi.org/10.1111/jog.14687DOI Listing
April 2021

Evaluation of placental oxygenation index using blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) during normal late pregnancy.

J Matern Fetal Neonatal Med 2021 Jan 24:1-13. Epub 2021 Jan 24.

Department of Obstetrics and Gynecology, Mie University Faculty Medicine, Mie, Japan.

Aim: Noninvasive blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has recently been used to evaluate placental oxygenation. However, this method still has unresolved problems, such as long testing times and lack of normal values set. In the present study, we used a shorter protocol in BOLD-MRI and established normal values for placental oxygenation in late pregnancy.

Methods: We recruited 18 healthy singleton pregnant women (>32 weeks of gestation) who had a normal body size before pregnancy and a normal course of pregnancy. They underwent BOLD-MRI with three consecutive 4-min periods of different oxygenation: normoxia (21% O), hyperoxia (10 L O/min), and then normoxia. Placental time-activity curves were presented as signal intensity change relative to baseline (ΔR2*). The time from starting maternal oxygen administration to peak ΔR2*. To assess the relationship between peak ΔR2* values and placenta-related parameters and fetal development, the correlation between peak ΔR2*, placental weight, and neonatal birth weight was evaluated using Spearman's rank correlation test.

Results: In all cases, the BOLD signal was elevated by maternal oxygen administration, with the peak resolving within 4 min after the end of oxygen administration. Peak ΔR2* and time to peak ΔR2* during oxygenation were 7.99 ± 2.58, and 458.1 ± 73.9 s, respectively. There was a significant correlation between peak ΔR2* and neonatal birth weight (percentile) ( = 0.537,  = .022), and between placental weight and neonatal birth weight ( = 0.769,  < .01).

Conclusions: In all cases, the BOLD signal increased with maternal hyperoxia using this protocol. So, 4 min observation following maternal oxygen administration is sufficient for peak ΔR2* evaluation. These reference values set in this study may be one of the indicators of BOLD signal changes in normal pregnancies after 32 weeks of gestation.
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http://dx.doi.org/10.1080/14767058.2021.1878140DOI Listing
January 2021

Aortic dissection during pregnancy and puerperium: A Japanese nationwide survey.

J Obstet Gynaecol Res 2021 Apr 21;47(4):1265-1271. Epub 2021 Jan 21.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Aim: This study aimed to characterize the incidence and clinical significance of pregnancy-related aortic dissection using a large-scale survey in Japan.

Methods: A questionnaire requesting the detailed information included in the clinical charts of pregnancy-related aortic dissection cases (without any personally identifying information) was designed between 2013 and 2017 and administered to 407 perinatal centers in Japan. The response rate was 70.5%. Seventeen cases of pregnancy-related aortic dissection were identified.

Results: Maternal death due to aortic dissection was observed in nine patients (56.2%) while seven survived (43.8%). Dissection occurred during the postpartum period in 10 cases (62.5%), the third trimester in 4 (25.0%), labor in 1 (6.2%), and the second trimester in 1 (6.2%). The most common underlying diseases were: Marfan syndrome (25.0%), Loeys-Dietz syndrome (6.2%), hypertension (6.2%), and Takayasu aortitis (6.2%). Stanford type A aortic dissection was associated with maternal death during both pregnancy and the postpartum period. However, deceased patients showed lower rates of pre-diagnosed connective tissue disease than did survivors.

Conclusions: The mortality rate of aortic dissection that occurred during pregnancy or postnatal periods was more than 50%. Aortic dissection occurred more frequently in the postnatal period than during pregnancy, and less frequently in women previously diagnosed with connective tissue disease than in women without any medical history of aortic disorders. If symptoms suggestive of aortic dissection, such as severe back pain, are observed, even after the end of pregnancy, exhaustive diagnostic examinations should be carried out.
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http://dx.doi.org/10.1111/jog.14657DOI Listing
April 2021

Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring.

Sci Rep 2021 01 13;11(1):1186. Epub 2021 Jan 13.

Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

We aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.
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http://dx.doi.org/10.1038/s41598-020-80643-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806616PMC
January 2021

Tadalafil Treatment Ameliorates Hypoxia and Alters Placental Expression of Proteins Downstream of mTOR Signaling in Fetal Growth Restriction.

Medicina (Kaunas) 2020 Dec 21;56(12). Epub 2020 Dec 21.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Edobashi, Tsu, Mie 8858507, Japan.

Fetal growth restriction (FGR) is associated with fetal mortality and is a risk factor for cerebral palsy and future lifestyle-related diseases. Despite extensive research, no effective treatment strategy is available for FGR. Mammalian target of rapamycin (mTOR) signaling is important for the growth of fetal organs and its dysregulation is associated with miscarriage. Here, we focused on mTOR signaling and investigated how the activities of phospho-ribosomal protein S6 (rps6) and phospho-eukaryotic translation initiation factor 4E (eIF-4E), which act downstream of mTOR signaling in the human placenta, change following treatment of FGR with tadalafil and aimed to elucidate the underlying mechanism of action. Placental hypoxia was investigated by immunostaining for hypoxia-inducible factor (HIF)-2α. Phosphor-rps6 and phosphor-eIF4E expression were examined by Western blotting and enzyme-linked immunosorbent assay, respectively. HIF-2α expression significantly increased in FGR placenta compared with that in the control placenta but decreased to control levels after tadalafil treatment. Levels of phospho-rps6 and phospho-eIF-4E were significantly higher in FGR placenta than in control placenta but decreased to control levels after tadalafil treatment. Tadalafil restored the levels of HIF-2α, phospho-rps6, and eIF-4E in FGR placenta to those observed in control placenta, suggesting that it could be a promising treatment strategy for FGR.
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http://dx.doi.org/10.3390/medicina56120722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767347PMC
December 2020

Nationwide study of mortality and survival in pregnancy-related streptococcal toxic shock syndrome.

J Obstet Gynaecol Res 2021 Mar 21;47(3):928-934. Epub 2020 Dec 21.

The Japan Maternal Death Exploratory Committee, Tokyo, Japan.

Aim: Streptococcal toxic shock syndrome is associated with the highest infection-related maternal mortality rates. We conducted a comparative analysis of the background factors and treatment course between survivors and nonsurvivors to improve our understanding concerning the optimal initial treatment approach for this fulminant disease.

Methods: This retrospective observational study was conducted based on clinical data collected from two national organizations. Clinical data of patients who died or survived (i.e. background information, clinical course and treatment administered) were collected.

Results: Records of 13 dead and 15 surviving patients were collected and analyzed. No statistically significant differences were found between the groups regarding age, parity, season, gestational age or the patients' location at the onset of symptoms. After the initial symptom onset, the survivors received antibiotics more systematically during their first visit to a clinic (P = 0.006). More survivors had received treatment within 1 h of onset of fulminant disease (P = 0.069). The number of fetal deaths was significantly higher in the mortality group (P = 0.003), while the fetal survival number was higher in the group of maternal survivors (P = 0.055). Maternal survivors with nonspecific initial symptoms received early intervention when there was a family history of group A streptococcal infection or a positive rapid antigen test result.

Conclusion: Intensive care, including systemic antibiotic administration, may contribute to maternal survival when administered immediately (within 1 h) after the fulminant streptococcal toxic shock syndrome onset. Eliciting a family history of streptococcal infection and conducting a rapid antigen test can identify the patients needing early intervention.
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http://dx.doi.org/10.1111/jog.14619DOI Listing
March 2021

sFlt-1 value predicts pregnancy prolongation periods from diagnosis in pregnant women diagnosed with early-onset preeclampsia.

J Matern Fetal Neonatal Med 2020 Nov 18:1-4. Epub 2020 Nov 18.

Department of Obstetrics and Gynecology, Mie University School of Medicine, Mie, Japan.

Purpose: The aim of this study is to analyze whether soluble fms-like tyrosine kinase-1 (sFlt-1) can be correlated with the severity of PE.

Materials And Methods: This study was conducted in a single hospital and is a prospective, observational study. sFlt-1 was measured at the diagnosis of preeclampsia. The period from diagnosis to pregnancy termination (pregnancy prolongation periods) was defined as the barometer for the severity of PE. The correlations between sFlt-1 level with pregnancy prolongation periods were then analyzed.

Results: Eighteen pregnant women diagnosed with early-onset preeclampsia were recruited. sFlit-1 value significantly negatively correlated with the pregnancy prolongation period from diagnosis ( = .003,  = 0.647).

Conclusion: sFlt-1 was correlated with the pregnancy prolongation periods after onset of PE. sFlt-1 in early-onset PE may reflect the severity of PE in pregnant women.
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http://dx.doi.org/10.1080/14767058.2020.1849093DOI Listing
November 2020

Cervical schwannoma in the early stage of pregnancy: a case report.

BMC Surg 2020 Oct 20;20(1):245. Epub 2020 Oct 20.

Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Background: Although spinal schwannomas generally grow very slowly, it has been reported that these clinical growths and their associated neurological symptoms accelerate during pregnancy. Because these cases are rare, surgical intervention for this tumor during pregnancy poses a significant challenge. The change of pregnancy-related hormones, such as estrogen and progesterone, is considered to have an effect on the clinical symptoms of spinal tumors. Expressions of the receptors for estrogen and progesterone in orbital and vestibular schwannomas have been reported; however, those expressions in spinal schwannomas have not been examined.

Case Presentation: A 36-year-old woman at 8 weeks' gestation suffered from developing neck pain and neurological symptoms in the right upper extremity. Magnetic resonance imaging (MRI) confirmed the presence of a cervical intradural extramedullary tumor. Under general anesthesia, using intraoperative neurophysiological monitoring of motor-evoked potentials (MEPs), spinal tumor resection following a hemi-laminoplasty was performed in a prone position at 12 weeks gestation. The pathological diagnosis following surgery was spinal schwannoma. Her neurological symptoms were significantly improved after surgery and she delivered a healthy baby in her 40th week of pregnancy. At a 12-month follow-up, no abnormalities were observed during medical examinations of both mother and child. An immunohistochemical study identified the expression of estrogen receptors, but not progesterone receptors, in the spinal schwannoma.

Conclusions: A cervical spinal schwannoma was successfully removed under general anesthesia at 12 weeks gestation by coordination between orthopaedic, obstetric and anesthesia teams. For the first time, an immunohistochemical analysis showed that the expression of estrogen receptors was identified in spinal schwannoma cells, suggesting the possibility that these hormone receptors in spinal schwannoma might contribute to the worsening of neurological symptoms during pregnancy.
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http://dx.doi.org/10.1186/s12893-020-00903-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576856PMC
October 2020

Effects of antenatal dexamethasone and hyperglycemia on cardiovascular adaptation to asphyxia in preterm fetal sheep.

Am J Physiol Regul Integr Comp Physiol 2020 12 14;319(6):R653-R665. Epub 2020 Oct 14.

The Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia ( < 0.001), increased arterial pressure ( < 0.001), and reduced femoral ( < 0.005) and carotid ( < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia ( < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.
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http://dx.doi.org/10.1152/ajpregu.00216.2020DOI Listing
December 2020

Early alteration in apparent diffusion coefficient and tumor volume in cervical cancer treated with chemoradiotherapy or radiotherapy: Incremental prognostic value over pretreatment assessments.

Radiother Oncol 2021 02 8;155:3-9. Epub 2020 Oct 8.

Department of Radiology, Mie University Hospital, Tsu, Japan.

Purpose: Our study aimed to evaluate a prognostic value of early changes in apparent diffusion coefficients (ADC) and tumor volume during treatment in patients with cervical cancer treated with chemoradiotherapy or radiotherapy, and to assess whether the early changes provided an incremental value to pre-treatment ADC and tumor volume in predicting disease recurrences.

Methods And Materials: A total of 103 patients with stage IB-IVA cervical cancer including 76 (74%) patients with stage ≥IIIA who underwent magnetic resonance imaging before and during (25 ± 4.6 days after start) the treatment were enrolled. Eighty-one patients received chemoradiotherapy and the remaining 22 had radiotherapy. Both a volumetric ADC and volume of a tumor before and during treatment were measured. %ADC increase and %Volume reduction were defined as changes in the ADCs and tumor volume before and during treatment, respectively.

Results: During a median follow-up of 2.7 years, 42 (41%) patients had disease recurrences. Univariate Cox regression analysis revealed that pre-treatment ADC (Hazard ratio [HR] = 2.8; p = 0.002), %ADC increase (HR = 6.8; p < 0.001), and %Volume reduction (HR = 2.7; p = 0.003) were significant predictors for disease recurrences. On multivariate analysis, %ADC increase was the only independent predictor (adjusted HR = 5.2; p < 0.001) for disease recurrences when adjusted for %Volume reduction and pre-treatment ADC. Global chi-square analysis demonstrated that %ADC increase and %Volume reduction had an additional prognostic value over pre-treatment ADC and tumor volume (p < 0.05). Kaplan-Meier curve analysis showed that both smaller %ADC increase and %Volume reduction were associated with worse prognosis in disease-free survival (log-rank, p < 0.001 and p = 0.002, respectively).

Conclusions: Among patients with cervical cancer treated with chemoradiotherapy or radiotherapy, early changes in tumor ADCs and tumor volume during treatment are associated with better prognosis. %ADC increase and %Volume reduction during the treatment have an additional prognostic value for predicting tumor recurrence to pre-treatment ADC and tumor volume.
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http://dx.doi.org/10.1016/j.radonc.2020.09.059DOI Listing
February 2021
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