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Background: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs., Methods: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%)., Results: Our findings show that approximately one-third of the costs was borne by the patients., Conclusion: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities., (© 2024. The Author(s).)

Background: Perinatal mental health, such as postpartum depression, is an important issue that can threaten the lives of women and children. It is essential to understand the risk factors in advance and intervene before they can lead to postnatal depression. The risk factors of postpartum depression are reported to vary considerably in Japan. This study aimed to evaluate the risk factors for women with high Edinburgh Postnatal Depression Scale (EPDS) scores and to find women who may need our intervention to prevent postpartum depression., Methods: This was a retrospective observational study conducted at a single center. At the one-month check-up after birth, the EPDS test was performed in 1625 women who gave birth at our hospital from 2008 to 2016. We evaluated maternal, birth, neonatal and social factors and the breastfeeding status from medical records. Thereafter, we examined the factors that contributed to a high EPDS score., Results: There were 284 women in the high-score group with an EPDS of ≥ 9, and 1341 women in the low-score group with an EPDS score ≤ of 8. Maternal mental disorders and neonatal transport were significantly associated with high EPDS scores. Conversely, exclusive breastfeeding was significantly associated with the low-score EPDS group., Conclusions: The principal factor for high EPDS scores was a mental disease. Based on this result, we suggest that early intervention in women at high risk for postpartum depression could prevent serious consequences such as abuse and suicide., (© 2024. The Author(s).)

Electroencephalographic studies of working memory have demonstrated cortical activity and oscillatory representations without clarifying how the stored information is retained in the brain. To address this gap, we measured scalp electroencephalography data, while participants performed a modified n-back working memory task. We calculated the current intensities from the estimated cortical currents by introducing a statistical map generated using Neurosynth as prior information. Group analysis of the cortical current level revealed that the current amplitudes and power spectra were significantly different between the modified n-back and delayed match-to-sample conditions. Additionally, we classified information on the working memory task conditions using the amplitudes and power spectra of the currents during the encoding and retention periods. Our results indicate that the representation of executive control over memory retention may be mediated through both persistent neural activity and oscillatory representations in the beta and gamma bands over multiple cortical regions that contribute to visual working memory functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yoshiiwa, Takano, Ido, Kawato and Morishige.)

Background: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation., Methods: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program., Results: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity., Conclusion: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: Fertility preservation (FP) is becoming increasingly common among child, adolescent, and young-adult (CAYA) patients with cancer. However, Japan has long lacked definite estimates of utilization rates for FP services among CAYA patients with cancer, and little is known about disease/FP outcomes among users. Therefore, the Japan Society for Fertility Preservation (JSFP) launched the Japan Oncofertility Registry (JOFR) in 2018 and started the online registration of information regarding primary disease, FP, and data on prognosis and pregnancy outcomes. This study reports the analytical results of FP data registered in the JOFR as of 2021. Methods: Data about patients' primary disease(s), treatment courses, cancer and pregnancy outcomes, and specific procedures were extracted from the JOFR and analyzed. Results: In 2021, 1244 patients received counseling or treatment related to FP (540 males, 704 females). While the numbers of males in each age group were approximately equal, most females were aged between 31 and 40 years. In total, 490 male and 540 female patients underwent FP procedures. Leukemia, testicular cancer, and malignant lymphoma accounted for the majority of male cases seeking treatment, whereas breast cancer was the primary disease in two-thirds of the females. Since 1999, 395 patients have accumulatively experienced subsequent pregnancy. Conclusions: As of January 2022, >7000 cases from >100 fertility facilities have been registered in the JOFR. In the future, maintaining JOFR to disseminate information on cancer prognoses, pregnancy rates, and other oncofertility outcomes is expected to drive further expansion of oncofertility services in Japan.

Artesunate, an antimalarial drug, induces ferroptosis, but the mechanism is still unclear. In the present study, we investigated how Artesunate induces ferroptosis in ovarian serous carcinoma. Experiments were performed using the ovarian serous carcinoma cell lines CaOV3 and SKOV3ip1, and the sensitivity of CaOV3 to Artesunate was higher than that of SKOV3ip1. Ferroptosis inhibitors inhibited Artesunate-induced intracellular lipid peroxi-dation and cell death. However, unlike class 1 ferroptosis inducer erastin, Artesunate had no effect on intracellular glutathione-SH levels. We found that Artesunate-induced changes in lysosomal Fe‍ 2+ were parallel to the induction of ferroptosis. Therefore, ferritin, which oxidizes and binds intracellular Fe‍ 2+ , may have an inhibitory effect on ferroptosis. Knockdown of nuclear coactivator 4, a key molecule of ferritinophagy (ferritin-specific autophagy), suppressed Artesunate-induced cell death. Knockdown of ferritin heavy chain by siRNA greatly enhanced the sensitivity to Artesunate, and overexpression of ferritin heavy chain greatly reduced the sensitivity of ovarian cancer cell lines to Artesunate. These results can explain the differential sensitivity of CaOV3 and SKOV3ip1 to Artesunate. In conclusion, enhancement of ferritinophagy is an important step involved in the mechanism of Artesunate-induced ferroptosis, and ferritin heavy chain levels may contribute to the regulation of sensitivity in Artesunate-induced ferroptosis in ovarian serous carcinoma cells., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Objective: To assess the magnetic resonance imaging (MRI) findings of endometrial cancers and to reveal the differences between endometrioid carcinoma (EC), serous carcinoma (SC), and clear cell carcinoma (CCC)., Methods: In this study, 274 consecutive patients with histopathologically confirmed endometrial cancer (231 ECs, 25 SCs, and 18 CCCs) who underwent MRI before hysterectomy were enrolled. MRI images were retrospectively reviewed and compared between the three pathologies., Results: The maximum diameters (55.6 ± 34.7 vs. 39.3 ± 21.6 vs. 39.4 ± 26.8 mm) (p < 0.05) and apparent diffusion coefficient (ADC) values (1.11 ± 0.21 vs. 0.84 ± 0.17 vs. 0.86 ± 0.16 × 10 -3 mm 2 /s) (p < 0.01) were significantly greater in CCCs than in ECs and SCs, respectively. Infiltrative growth pattern (33% vs. 6%) (p < 0.01) was more frequent in CCCs than in ECs. Peritoneal dissemination (16% vs. 0%) (p < 0.01) and heterogeneous signal on diffusion-weighted (61% vs. 32%) (p < 0.05) images were more frequent in SCs than in ECs, respectively. Abnormal ascites (12% vs. 11% vs. 0%) and heterogeneous signal on T1-weighted (28% vs. 50% vs. 9%), T2-weighted (64% vs. 72% vs. 36%), and fat-suppressed gadolinium-enhanced T1-weighted (80% vs. 90% vs. 46%) images were more frequent in SCs and CCCs than in ECs, respectively (p < 0.05)., Conclusions: SCs frequently exhibited a heterogeneous signal with peritoneal dissemination and abnormal ascites. Alternatively, CCCs tended to have a larger tumor size and higher ADC values with an infiltrative growth pattern, heterogeneous signal, and abnormal ascites., Key Points: • SCs tend to have a heterogeneous signal intensity with peritoneal dissemination and abnormal ascites compared to ECs. • CCCs tend to have a heterogeneous signal intensity with an infiltrative growth pattern and abnormal ascites compared to ECs. • CCCs have a larger tumor size and higher ADC values compared to ECs and SCs., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background/aim: Nausea and vomiting are two of the most distressing adverse events of cancer radiotherapy. The aim of this study was to examine the control rate and risk factors associated with nausea and vomiting in patients with cervical cancer receiving radiotherapy., Patients and Methods: This retrospective study examined patients with cervical cancer who received radiotherapy alone or with concomitant cisplatin. Patients who received radiotherapy alone were not administered antiemetic premedication, while patients who received radiotherapy with concomitant weekly cisplatin (40 mg/m 2 ) were administered antiemetic therapy comprising granisetron and dexamethasone. Risk factors for non-complete response (CR) were identified using multivariate logistic regression analysis., Results: Multivariate analysis indicated that younger age and concomitant weekly cisplatin were significant factors associated with non-CR across 5 weeks of treatment in patients who received radiotherapy. The proportion achieving CR among younger patients (<65 years) who received radiotherapy alone or with concomitant cisplatin was significantly lower than that among older patients (≥65 years) (Concomitant cisplatin: 27% vs. 67%, p=0.049; Radiotherapy alone: 62% vs. 91%, p=0.166). However, the proportion of patients achieving CR across 5 weeks of treatment was insufficient in all groups except for those aged ≥ 65 years who received radiotherapy alone., Conclusion: Antiemetic prophylaxis should be considered for younger patients with cervical cancer undergoing radiotherapy alone. Further, neurokinin-1 receptor antagonist should be added to 5-hydroxytryptamine type-3 receptor antagonist and dexamethasone as antiemetic prophylactic therapy for patients with cervical cancer undergoing radiotherapy with concomitant weekly doses of 40 mg/m 2 cisplatin., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK 1 RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT 3 RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK 1 RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy., Methods: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK 1 RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK 1 RA (non-NK 1 RA group: 31 patients) and with NK 1 RA (NK 1 RA group: 31 patients). The patients were selected using propensity score matching., Results: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK 1 RA group and 96.8% in the NK 1 RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine., Conclusions: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT 3 RA, and DEX without NK 1 RA may be a treatment option for patients receiving carboplatin-based chemotherapy., (© 2022. The Author(s).)

Purpose: This study aimed to evaluate the utility of uterine extension determined via MRI for the differentiation of large subserosal leiomyomas from ovarian tumors., Methods: In total, 55 patients with subserosal leiomyomas and 127 patients with ovarian tumors were included in this study. These patients were selected from a cohort of female patients whose pelvic masses were larger than 10 cm and who underwent preoperative MRI. We retrospectively reviewed the MRI and compared the diagnostic ability of uterine extension measurements and bridging vascular signs for differentiating subserosal leiomyomas from ovarian tumors., Results: The vertical height of the uterus (107.2 ± 36.4 mm vs. 59.9 ± 24.9 mm, p < 0.01), the uterine length (114.4 ± 34.9 mm vs. 80.4 ± 23.8 mm, p < 0.01), and the frequency of the bridging vascular sign (78% vs. 6%, p < 0.01) were significantly higher in subserosal leiomyomas than in ovarian tumors. For diagnosing subserosal leiomyoma, the area under the curve, sensitivity, and specificity of vertical height of the uterus, using cutoff threshold > 81 mm, were 0.89, 89%, and 80% and those of the uterine length, using cutoff threshold > 84 mm, were 0.85, 69%, and 93%, respectively. Alternatively, the sensitivity and specificity of bridging vascular sign were 78% and 94%, respectively., Conclusion: Uterine extension determined via MRI is a useful parameter for differentiating large subserosal leiomyomas from ovarian tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, local governments in Japan have established a public financial support system for fertility preservation in pediatric, adolescent, and young adult cancer patients. Fertility preservation has become popular for patients with cancers included in the gonadal toxicity risk classification of the 2017 edition of the Guideline for Fertility Preservation in Children, Adolescents and Young Adult Cancer Patients from the Japan Society of Clinical Oncology. However, patients with cancer and non-cancer diseases that are not included in the Guideline's gonadal toxicity risk classification also often receive treatment that may affect fertility, but they are often denied the opportunity of fertility preservation because no public financial support is available for diseases not listed in the Guideline. The national research project proposes including these diseases in the indications and treatment for fertility preservation. Therefore, we cooperated with the Japan Society for Fertility Preservation and the Ministry of Health, Labour and Welfare research group to solicit opinions from experts in each therapeutic area and reviewed the literature and overseas guidelines. This paper summarizes the findings of the project. We believe that it will be an important source of information for clinicians treating patients who need fertility preservation but note that the appropriateness of fertility preservation for the disorders listed in this report needs to be continuously reviewed as medical care advances., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive)., (© 2021. The Author(s).)

Introduction and Hypothesis: Little is known about the prevalence of pelvic organ prolapse (POP). We aimed to evaluate the prevalence of POP and identify its risk factors in Japan., Methods: This was a single-centre, cross-sectional study. We recruited Japanese women seen for a Pap smear from July 2018 through May 2019. After providing their informed consent, subjects were asked to complete questionnaires. Pelvic organ support was assessed using the POP quantification (POP-Q) system by an examiner. Logistic regression analyses were conducted to identify risk factors for POP., Results: There were 1032 women aged 21 to 84 years. The distribution of POP-Q stage was stage 0, 38.0%; stage I, 45.0%; stage II, 16.4%; stage III, 0.6%; and stage IV, 0%. Rates (95% confidence interval [CI]) of stage II or greater in each age group were 6.6% (2.4-10.8) in 20 s-30 s; 17.6% (13.3-21.9) in 40 s; 17.1% (12.9-21.3) in 50 s; 18.0% (12.6-23.4) in 60 s; and 28.7% (19.6-37.9) in 70 s and over. Multivariate analysis revealed the following risk factors for POP, with odds ratio (95% CI): body mass index [BMI] ≥ 25 kg/m 2 , 1.63 (1.05-2.51); BMI < 18.5 kg/m 2 , 0.40 (0.17-0.94); hysterectomy, 4.09 (1.55-10.80); ≥ 3 vaginal deliveries, 2.26 (1.19-4.28); and ≥ 1 cup of coffee per day, 0.63 (0.43-0.92)., Conclusion: Among Japanese women undergoing routine gynaecological examinations, 17.1% (14.7-19.5) had POP-Q stage II or greater. Overweight, hysterectomy and ≥ 3 vaginal deliveries increased the risk for POP, whereas underweight and daily coffee consumption decreased it., (© 2021. The International Urogynecological Association.)

Objective: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy., Methods: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival., Results: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS., Conclusion: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS., (© 2021. Japan Society of Clinical Oncology.)

This study clarifies the association between postpartum depression (PPD) and satisfaction with social support after childbirth through an anonymous survey of 427 postpartum mothers. Mothers' PPD was found to be significantly associated with satisfaction levels regarding formal-instrumental support (OR: 0.32, 95% CI: 0.162-0.632), informal-instrumental support (OR: 0.547, 95% CI: 0.313-0.955), and informal-psychological support (OR: 0.591, 95% CI: 0.384-0.912) in a multivariate logistic regression analysis. To prevent PPD, specialists as formal support providers must provide qualified care based on comprehensive judgments, and families as informal support providers should help with childcare, housework, and mental support., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine., Methods: Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors., Results: Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist., Conclusions: The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy., (© 2021. The Author(s).)

Although humans can direct their attention to visual targets with or without eye movements, it remains unclear how different brain mechanisms control visual attention and eye movements together and/or separately. Here, we measured MEG and fMRI data during covert/overt visual pursuit tasks and estimated cortical currents using our previously developed extra-dipole, hierarchical Bayesian method. Then, we predicted the time series of target positions and velocities from the estimated cortical currents of each task using a sparse machine-learning algorithm. The predicted target positions/velocities had high temporal correlations with actual visual target kinetics. Additionally, we investigated the generalization ability of predictive models among three conditions: control, covert, and overt pursuit tasks. When training and testing data were the same tasks, the largest reconstructed accuracies were overt, followed by covert and control, in that order. When training and testing data were selected from different tasks, accuracies were in reverse order. These results are well explained by the assumption that predictive models consist of combinations of three computational brain functions: visual information-processing, maintenance of attention, and eye-movement control. Our results indicate that separate subsets of neurons in the same cortical regions control visual attention and eye movements differently.

Purpose: The purpose of this study was to determine the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of ovarian mature teratoma in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E)., Materials and Methods: A total of 125 women (mean age, 40.9±17.8 [SD] years; age range: 12-85 years) with 146 histopathologically or radiologically proven ovarian mature teratomas who underwent preoperative CT and MRI examinations were retrospectively included. Eight patients with 11 teratomas had NMDAR-E, whereas 117 patients with 135 teratomas did not have NMDAR-E. CT and MRI examinations were retrospectively reviewed and teratomas in patients with NMDAR-E were compared to those in patients without NMDAR-E. Comparisons were performed using Mann-Whitney U test or Fisher exact test., Results: In patients with NMDAR-E, maximum diameter of teratomas (26.1±9.3 [SD] mm), prevalence of teeth/calcification (36%) and rate of occupation by fat components (26%) were lower than those in patients without NMDAR-E (67.0±37.6 [SD] mm [P<0.01]; 75% [P<0.05]; and 65%[P<0.01], respectively). More than 75% of space was occupied by fat components in 76/135 teratomas (56%) in patients without NMDAR-E, whereas this was not observed in any teratoma in patients without NMDAR-E., Conclusion: By comparison with teratomas in patients without NMDAR-E, teratomas in patients with NMDAR-E are smaller, have few teeth/calcification, and the amount of space occupied by fat components is smaller., (Copyright © 2021 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Acute funisitis, a granulocyte-related inflammation of the umbilical cord, is associated with chorioamnionitis and perinatal adverse events. However, there is no efficient procedure for detecting clinically relevant umbilical cord inflammation. The objective of this study was to identify such inflammation, based on immunohistochemical assessment of umbilical cord vasculitis patterns., Methods: Accordingly, 261 cases were retrieved from a single medical institute. Using the well-established granulocyte marker CD15, we developed a five-tier umbilical cord inflammation-scoring system. Additionally, previous morphological assessments from pathological reports were compared to the immunohistochemical findings., Results: Analysis of results based on our new scoring system revealed that severe umbilical phlebitis (score 3) was significantly associated with maternal inflammatory response and that severe umbilical arteriophlebitis (score 4) was correlated with low umbilical arterial blood pH, a feature linked to fetal mortality and morbidity. These results corresponded with and were validated by the morphology-based assessments. Additionally, immunohistochemical analysis revealed the clinical and pathological relevance of vitelline vasculitis, a recently proposed condition. We found that analyzing three umbilical cord sections enabled superior detection of severe umbilical vasculitis than analyzing two sections. However, whether these sections were sampled from multiple distant sites or a single localized site did not significantly affect the detection of clinically relevant inflammation., Discussion: CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Purpose: Our purpose was to determine if MRI could be used to distinguish ovarian mucinous carcinoma (MC) from mucinous borderline tumor (MBT)., Materials and Methods: This study included 63 consecutive patients with histopathologically proven ovarian mucinous neoplasms (11 MCs and 52 MBTs) who underwent preoperative contrast-enhanced MRI. MRI images were retrospectively reviewed and compared between the 2 pathologies., Results: The maximum tumor diameters (219.7 ± 80.8 mm vs. 177.4 ± 56.5 mm, p <  0.05) and maximum mural nodule (MN) diameters (41.7 ± 33.8 mm vs. 6.6 ± 8.9 mm, p <  0.01) were significantly larger in MCs than in MBTs. MNs larger than 5 mm (82 % vs. 29 %, p <  0.01) and abnormal ascites (45 % vs. 12 %, p <  0.05) were significantly more frequent in MCs than in MBTs. Apparent diffusion coefficient (ADC) values of MN were significantly lower in MCs than in MBTs (1.20 ± 0.25 × 10 -3 mm 2 /s vs. 1.61 ± 0.35 × 10 -3 mm 2 /s, p <  0.05). No significant difference was found in number of loculi, honeycomb sign, stained glass appearance, fluid-fluid level, thickened septa larger than 5 mm, peritoneal dissemination, or T2 hypointense microcysts between MCs and MBTs. T2 hypointense microcysts were observed only in 7 MBTs (13%)., Conclusion: MRI findings of these 2 pathologies overlapped considerably. Compared with MBTs, MCs exhibited larger tumor size, larger MN size, and lower ADC values of MN, and MCs more frequently had MNs larger than 5 mm and abnormal ascites. T2 hypointense microcysts might be a specific MRI finding in MBTs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To assess MR imaging findings of low-grade serous carcinoma (LGSC) of the ovary compared with those of serous borderline tumor (SBT)., Methods: Twenty-four patients with histopathologically proven 7 LGSCs and 25 SBTs who underwent preoperative MR imaging were included. We retrospectively reviewed MR images and compared MR findings between the two pathologies., Results: The predominantly solid lesions were marginally more frequent in LGSCs than in SBTs (43% vs. 8%, p = 0.057). All predominantly cystic LGSCs were multilocular cystic lesions with mural nodules. Predominantly solid LGSCs exhibited pure solid masses in 2 of 3 and solid masses with intratumoral cysts in 1 of 3. Papillary growth pattern with internal branching was observed only in 18 of 25 SBTs. Signal intensity ratio on T2-weighted images (4.48 ± 1.55 vs. 8.40 ± 3.53, p < 0.01) and apparent diffusion coefficient (ADC) values (1.12 ± 0.21 vs. 1.73 ± 0.27 × 10 -3 mm 2 /s, p < 0.01) of solid components was significantly lower in LGSCs than in SBTs., Conclusion: Compared with SBTs, lower signal intensity on T2-weighted images and lower ADC values were characteristic features of solid components in LGSCs. Papillary growth pattern with internal branching was not observed in LGSCs.

Purpose: Decidualized endometriomas (DEs) and seromucinous borderline tumors (SMBTs) exhibit similar MR findings including markedly hyperintense mural nodules within endometriotic cysts on T2-weighted images. The present study aimed to assess the efficacy of MR imaging for differentiating between DEs and SMBTs of the ovary., Materials and Methods: MR images of 8 DEs and 14 SMBTs were retrospectively assessed and compared according to pathologies., Results: With regard to quantitative assessments of mural nodules, the number and signal intensity ratios (SIRs) on T1-weighted images were significantly greater in DEs than in SMBTs (11.0 ± 8.4 vs. 4.3 ± 4.1, p < 0.05 and 2.36 ± 0.56 vs. 1.49 ± 0.27, p < 0.01, respectively), whereas the height was significantly lower in DEs than in SMBTs (4.5 ± 1.4 mm vs. 21.9 ± 11.4 mm, p < 0.01). However, there were no significant differences between DEs and SMBTs in the SIRs on T2-weighted images, SIRs on diffusion-weighted images, and apparent diffusion coefficient values. With regard to qualitative assessments of mural nodules, the lobulated margin, pedunculated configuration, and T2 hypointense core were significantly more frequent in SMBTs than in DEs (71% vs. 0%, p < 0.01; 86% vs. 0%, p < 0.01; and 43% vs. 0%, p < 0.05, respectively)., Conclusion: The number, height, SIRs on T1-weighted images, lobulated margin, pedunculated configuration, and T2 hypointense core of mural nodules within endometriotic cysts were useful MR findings for differentiating DEs from SMBTs.

Purpose: The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK 1 RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT 3 RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer., Methods: We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK 1 RA, 5-HT 3 RA, and DEX. The primary end point was complete response (CR; no emesis and rescue therapy) during overall phase (120 h after the start of carboplatin administration)., Results: Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ., Conclusions: Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy., Competing Interests: Declaration of competing interest No conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

To assess if intravoxel incoherent motion (IVIM) imaging can be used to predict early response to chemoradiotherapy (CRT) in cervical cancer. IVIM imaging before and during CRT (at doses of 20 and 40 Gy) was performed in 17 patients with cervical squamous cell carcinoma. The percentage changes of IVIM parameters were significantly higher for complete remission (CR) than non-CR groups. IVIM may play a supplementary role for predicting early response to CRT in cervical cancer.

Aim: The survival rates of cancer patients have greatly improved owing to the advances in oncology. The preservation of fertility in cancer patients is an important task. To determine the reality of cryopreservation of embryos, oocytes and ovarian tissue in cancer patients, large-scale survey analysis was performed in Japan., Methods: We sent 613 Japan Society of Obstetrics and Gynecology-certified assisted reproductive technology institutions a questionnaire about their experience of performing cryopreservation for cancer patients between January 2011 and December 2015. Subsequently, the institutions that conducted cryopreservation for cancer patients were sent a second questionnaire., Results: We received replies from 481 (78.5%) institutions. Among them, 126 (26.2%) conducted cryopreservation for cancer patients. These 126 institutions were sent a second questionnaire. Of these, 108 (85.7%) institutions responded. At the 108 institutions, 1085 embryo or oocyte cryopreservation procedures and 122 ovarian tissue cryopreservation procedures were conducted for cancer patients. Cryopreservation was mainly performed for breast cancer patients (~70%), followed by patients with hematological malignancy. A total of 361 and 19 embryo transfer cycles were performed for patients whose embryos and oocytes were cryopreserved, respectively, and 42 and seven institutions reported pregnancy outcomes after embryo transfer in patients that underwent embryo and oocyte cryopreservation, respectively. However, pregnancy was not observed in the seven cases that underwent ovarian tissue transfer., Conclusion: Indications, age limits and ovarian stimulation protocols for cryopreservation widely varied between the institutions. A national registration system for oncofertility must be established to evaluate the safety and efficacy of the current system., (© 2019 Japan Society of Obstetrics and Gynecology.)

Although ovarian serous carcinoma is a well-studied human gynecologic malignancy, this high-grade tumor remains fatal. The main purpose of this review is to summarize the accumulated evidence on serous malignant tumors and to clarify the unresolved issues. We discuss the 8 dichotomies of serous carcinoma: high grade versus low grade, ovarian versus extraovarian primary, extrauterine versus uterine primary, sporadic versus hereditary, orthodox versus alternative histology, p53 overexpression versus complete absence of immunophenotype, TP53-mutated versus intact precursor, and therapy responsive versus refractory. In addition, we summarize the molecular classification of high-grade serous carcinoma. This review would lead readers to rapid and parallel developments in understanding high-grade serous carcinoma.

Objective:: This study aimed to assess the efficacy of MRI for differentiating between uterine submucosal polypoid adenomyomas (PAs) and endometrial polyps (EPs)., Methods:: MRI was used to examine 40 histopathologically confirmed benign polypoid endometrial tumors (8submucosal PAs and 32 EPs). Atypical PAs were excluded from this study. Quantitative measurements (maximum tumor diameter, maximum cyst diameter, number of cysts, and apparent diffusion coefficient values) and qualitative imaging findings (predominance of cystic or solid components as well as presence of cysts, hemorrhage, myometrial invasion, fluid-fluid level, and fibrous core) were correlated with the two pathologies., Results:: The predominance of cystic components (37% vs 6%; p < 0.05) was more frequently observed in PAs than in EPs. The frequency of cysts (88% vs 25%; p < 0.01), hemorrhage (50% vs 9%; p < 0.05), and myometrial invasion (25% vs 0%; p < 0.05) were significantly higher in PAs than in EPs. No significant differences were observed in terms of the maximum tumor diameter, maximum cyst diameter, number of cysts, apparent diffusion coefficient values, and presence of fluid-fluid level and fibrous core between PAs and EPs., Conclusion:: The differences of MR findings with emphasis on cystic components and hemorrhage may be useful for differentiating between PAs and EPs., Advances in Knowledge:: The predominance of cystic or solid components and the presence of cysts, hemorrhage, and myometrial invasion were useful MR findings for differentiating between PAs and EPs.

Background: High-grade serous carcinoma, a representative high-grade ovarian carcinoma, is believed to be closely associated with a TP53 mutation. Recently, this category of ovarian carcinoma has gained increasing attention owing to the recognition of morphological varieties of TP53-mutated high-grade ovarian carcinoma. Herein, we report the case of a patient with high-grade serous carcinoma with mucinous differentiation., Case Presentation: A 59-year-old postmenopausal woman was referred to the gynecologist because of abnormal vaginal bleeding. The radiological assessment revealed an intrapelvic multicystic mass, which was interpreted as an early right ovarian cancer and then removed by radical surgery. Histologically, the cancer cells were found in the bilateral ovaries and para-aortic lymph nodes. The cancer cells showed high-grade nuclear atypia and various morphologies, including the solid, pseudo-endometrioid, transitional cell-like (SET) pattern, and mucin-producing patterns. Benign and/or borderline mucin-producing epithelium, serous tubal intraepithelial carcinoma, and endometriosis-related lesions were not observed. In immunohistochemistry analyses, the cancer cells were diffuse positive for p53; block positive for p16; partial positive for WT1, ER, PgR, CDX2 and PAX8; and negative for p40, p63, GATA3, Napsin A, and vimentin. The Ki-67 labeling index of the cancer cells was 60-80%. Direct sequencing revealed that the cancer cells contained a missense mutation (c.730G>A) in the TP53 gene., Conclusion: Mucinous differentiation in high-grade serous carcinoma is a rare and unique ovarian tumor phenotype and it mimics the phenotypes of mucinous or seromucinous carcinoma. To avoid the misdiagnosis, extensive histological and immunohistochemical analyses should be performed when pathologists encounter high-grade mucin-producing ovarian carcinoma. The present case shows that the unusual histological characteristic of high-grade serous carcinoma, the "SET" feature, could be extended to the solid, transitional, endometrioid and mucinous-like (STEM) feature.

Purpose: This study evaluated the current status of reproductive disorders and provision of information on oncofertility to female adolescent and young adult (AYA) cancer patients in Japan., Methods: A national survey of AYA cancer survivors was conducted. Children were <15 years old, and AYAs were 15-39 years old. Results from the survivors of other than gynecological disease who underwent chemotherapy were analyzed., Results: Among the survivors, 41.4% were concerned about their reproductive function and infertility, and 36.2% were aware of menstrual cycle abnormalities. Among them, 15.5% (n = 20) of all and 21.2% (n = 17) of the AYA-onset survivors suffered infertility due to chemo- or radiotherapy and gave up childbearing. These rates were significantly higher than those of healthy AYAs. Although 80.8% of AYA-onset survivors answered that they had received information on reproductive function and infertility, only 55.8% had received information on fertility preservation methods. Furthermore, only 22.4% of all and 42.3% of AYA-onset survivors had received pretreatment information on fertility preservation methods., Conclusions: Not a few AYA cancer survivors reported reproductive dysfunction. These findings indicate that information provided on therapy-related problems before cancer treatment in Japan was insufficient and highlight the need to improve patient decision-making and support systems for fertility preservation.

Purpose: This study aimed to evaluate the current status of reproductive disorders as long-term complications in adolescent and young adult (AYA) cancer patients by comparing survivors of childhood-onset with those of AYA-onset cancer in Japan., Methods: We conducted a national survey of AYA cancer survivors and healthy AYAs and analyzed the results from survivors who underwent chemotherapy and reported fertility problems as their current concern., Results: Among all of the childhood-onset survivors, 27 (35.5%; nine males [28.1%] and 18 females [40.9%]) listed reproduction fertility problems as their current concern. Among all AYA-onset survivors, 25 (69.5%; 1/4 males [25.0%] and 24/32 females [75.0%]) listed these problems as a current concern. In contrast, 96.3% (26/27) of all childhood-onset cancer survivors and 68.0% (17/25) of all AYA-onset cancer survivors who received chemotherapy listed these problems as a current concern., Conclusions: A considerable number of both childhood-onset and AYA-onset cancer survivors, and especially those who had undergone chemotherapy, reported reproductive dysfunction as a delayed complication. It is vitally important to establish a supportive care system both for the patients whose fertility was abolished after the completion of cancer treatment and prophylactically for patients before they begin treatment.

Background: Although p53 signature, benign-appearing epithelial cells with p53 diffuse expression, is frequently found in the fallopian tubes, the clinical and pathological significance of this lesion in the case of high-grade serous carcinoma (HGSC) patients still remains unclear., Case Presentation: A 56-year-old woman was referred to the gynecologist on account of abdominal distention. Since radiological and serological workup suggested that her illness was due to advanced ovarian cancer (FIGO Stage IVB), she received neoadjuvant chemotherapy, and the clinical evaluation of the chemotherapeutic response was a partial response. She underwent total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and intra-pelvic and para-aortic lymphadenectomy. Histologically, the cancer cells showed high-grade nuclear atypia and spread into the bilateral ovaries, omentum, uterine serosa, and left fallopian tube. The cancer cells showed complete absence of p53 but overexpressed p16, whereas some of benign-appearing tubal epithelial cells overexpressed p53 but lacked p16 expression. The results of direct sequence analysis revealed that the ovarian cancer contains a 1 bp deletion in exon 8 of TP53. Finally, the histological diagnosis of HGSC with discordant p53 signature was made. Interestingly, nuclear expression of γ-H2AX, a well-known marker of DNA damage, was not only observed in both p53 aberrantly-expressing lesions but also the benign-appearing tubal epithelium without p53 overexpression. After the histological confirmation, she received adjuvant chemotherapy and has been in disease-free condition without any detectable tumor for 5 months., Conclusion: Recent evidence suggests that p53 signature is the putative precursor of p53 overexpression-type HGSC. Because the putative precursors of the other p53 immunophenotypical HGSC are not proposed, we presume γ-H2AX-expressing cells without p53 overexpression may be a potent candidate of null-type TP53-mutated tubal cells, which are named "γ-H2AX responsive foci."

Objective: Hyperintense area on T 1  weighted images (T 1 HIA) have been reported as suggestive features of uterine leiomyosarcoma (LMS), but differentiating LMS from leiomyoma (LM) is often difficult. This study aimed to evaluate the differences between uterine LMS and LM demonstrating intratumoral T 1 HIA., Methods: MRI was performed in 509 patients with 1137 uterine smooth muscle tumours [14 LMSs, 5 smooth muscle tumours of uncertain malignant potential , and 1118 LMs] which exceeded 3 cm in diameter. LM with red degeneration and lipoleiomyoma were excluded from the study. We retrospectively reviewed the images and assessed T 1 HIA within tumours. Results T 1 HIAs were observed in 11/14 (78.6%) LMSs, 0/5 (0%) smooth muscle tumours of uncertain malignant potential, and 15/1118 (1.3%) LMs. T 1 HIAs were more homogenous (53 vs 0%, p < 0.01) and more well-demarcated (60 vs 9%, p < 0.05) in LMs than in LMSs. T 2 hypointense rim within T 1 HIA (53 vs 9%, p < 0.05) was more frequently observed in LMs than in LMSs. The occupying rate of T 1 HIA (0.20 ± 0.24 vs 0.42 ± 0.27, p < 0.05) was smaller in LMs than in LMSs. The signal intensity ratio of T 1 HIA (1.83 ± 0.36 vs 1.38 ± 0.23, p < 0.01) was greater in LMs than in LMSs., Conclusion: T 1 HIA within LM showed more homogeneity, better demarcation, smaller occupying rate, and higher signal intensity than T 1 HIA within LMS. Advances in knowledge: The differences in T 1 HIA within tumours may be useful for differentiating between LMS and LM.

Objective: To examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy., Methods: This is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB-IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence., Results: There were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%., Conclusion: Surgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer., Competing Interests: CONFLICTS OF INTEREST All authors have no potential conflicts of interest to disclose.

Ovarian endometrial cysts cause some kinds of ovarian cancer, and iron is considered as one factor of carcinogenesis. In contrast, hypoxia is associated with progression, angiogenesis, metastasis, and resistance to therapy in cancer. We investigated hypoxia-induced perturbation of iron homeostasis in terms of labile iron, iron deposition, and iron regulatory protein (IRP) in ovarian endometrial cysts. Iron deposition, expression of IRPs, and a protein marker of hypoxia in human ovarian endometrial cysts were analyzed histologically. The concentration of free iron and the pO 2 level of the cyst fluid of human ovarian cysts (n = 9) were measured. The expression of IRP2 under hypoxia was investigated in vitro by using Ishikawa cells as a model of endometrial cells. Iron deposition and the expression of IRP2 and Carbonic anhydrase 9 (CA9) were strong in endometrial stromal cells in the human ovarian endometrial cysts. The average concentration of free iron in the cyst fluid was 8.1 ± 2.9 mg/L, and the pO 2 was 22.4 ± 5.2 mmHg. A cell-based study using Ishikawa cells revealed that IRP2 expression was decreased by an overload of Fe(II) under normoxia but remained unchanged under hypoxia even in the presence of excess Fe(II). An increase in the expression of IRP2 caused upregulation of intracellular iron as a result of the response to iron deficiency, whereas the protein was degraded under iron-rich conditions. We found that iron-rich regions existed in ovarian endometrial cysts concomitantly with the high level of IRP2 expression, which should generally be decomposed upon an overload of iron. We revealed that an insufficient level of oxygen in the cysts is the main factor for the unusual stabilization of IRP2 against iron-mediated degradation, which provides aberrant uptake of iron in ovarian endometrial stromal cells and can potentially lead to carcinogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion., Implications: Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR., (©2016 American Association for Cancer Research.)

Purpose: To retrospectively compare the MR findings of histological subtypes of clear cell carcinomas (CCCs) of the ovary., Materials and Methods: This single-center retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. Between April 2005 and August 2015, we found 51 consecutive patients with histopathologically proven CCCs. Among them, 44 CCCs in 37 patients who underwent preoperative MR imaging were included. CCCs were pathologically divided into three subgroups: (1) four clear cell adenofibroma-associated CCCs, (2) 21 endometriosis-associated CCCs, and (3) 19 indeterminate CCCs. The statistical tests were used to compare the frequency of qualitative assessments and value of quantitative measurements among the histological subtypes., Results: On T2-weighted images, hypointense areas within solid components were more frequently observed in clear cell adenofibroma-associated CCCs [3/4 (75%)] than in the remaining CCCs [1/40 (3%)] (p < 0.01), and the signal intensity ratios (SIRs) of solid components were significantly lower in clear cell adenofibroma-associated CCCs (0.27 ± 0.13) than in the remaining CCCs (0.61 ± 0.18) (p < 0.01). On T1-weighted images, hyperintensities of cystic components were more frequently observed in the endometriosis-associated CCCs [17/21 (81%)] than in the remaining CCCs [5/20 (25%)] (p < 0.01), and the SIRs of cystic components were significantly higher in endometriosis-associated CCCs (2.99 ± 1.51) than in the remaining CCCs (1.82 ± 1.10) (p < 0.01)., Conclusion: MR features may help differentiate between adenofibroma-associated and endometriosis-associated CCC.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Purpose: We evaluated our 2-year experience of the regional oncofertility network in Gifu Prefecture (GPOFS) in order to establish a more sophisticated regional oncofertility networking model in Japan., Methods: Questionnaires were distributed twice in January 2013 to 57 departments in 35 hospitals that provide cancer treatment in Gifu Prefecture, before the establishment of the regional oncofertility network. The number and type of disease of the referred adolescent and young adult (AYA) cancer patients who visited the oncofertility clinic in Gifu University Hospital via the GPOFS were analyzed., Results: The majority of regional oncologists are aware of the need to provide information about oncofertility to their patients, but they cannot provide sufficient information due to their lack of knowledge about reproductive medicine. Eighty-one AYA patients were referred to our clinic for oncofertility counseling in the first 2 years after the establishment of the GPOFS., Conclusions: The GPOFS as the first regional oncofertility network in Japan has just started and may be working to help both AYA cancer patients and their oncologists. The nationwide establishment of the regional oncofertility network model could help both AYA cancer patients and oncologists., Competing Interests: Tatsuro Furui, Motoki Takenaka, Hiroshi Makino, Keiko Terazawa, Akio Yamamoto and Ken‐ichiro Morishige declare that they have no conflict of interest.

Purpose: The aim of the study was to evaluate the results of high-dose-rate interstitial brachytherapy (HDR-ISBT) for patients with advanced cervical carcinoma in which intracavitary radiation therapy may result in a suboptimal dose distribution., Methods and Materials: Between 1995 and 2005, 25 patients of median age 64 years were treated with external beam radiation therapy and HDR-ISBT. The International Federation of Gynecology and Obstetrics stages of the patients were I (4%), II (16%), III (68%), and IVA (12%). Whole pelvic irradiation of 30Gy/15 fractions was followed by HDR-ISBT of 30Gy/5 fractions/3 days. Subsequently, additional pelvic external beam radiation therapy of 20Gy/10 fractions was delivered with a midline block. The median followup period was 55 months., Results: The actuarial 5-year progression-free survival and overall survival rates for all cases were 42% and 54%, respectively. For the 17 patients with a Stage III tumor, the 5-year local control and overall survival rates were 73% and 51%, respectively. Two patients (8%) developed late toxicities of Grade 3., Conclusions: A high rate of pelvic control and survival with acceptable level of late toxicities were obtained for patients with advanced cervical carcinoma treated with HDR-ISBT.

Objective: The level of lysophosphatidic acid (LPA) is elevated in patients with ovarian cancer, and LPA has been reported to have a pivotal role in cancer dissemination. In the current study, the effect of LPA on the motility of ovarian cancer cells was investigated., Methods: We analyzed the effects of LPA on the migration activity, the focal adhesion formation, and the tyrosine phosphorylation of focal adhesion proteins in human ovarian cancer cell lines Caov-3 and OVCAR-3. Inhibitors of the small GTPase Rho, one of its downstream effectors (Rho-associated kinase (ROCK)), myosin light chain kinase (MLCK), and myosin light chain (MLC) phosphatase were used to examine the mechanism of LPA-induced cellular effects., Results: LPA enhanced the migration of ovarian cancer cells and facilitated their invasion. Rho and ROCK played essential roles in the migratory process, as evidenced by the inhibition of migration and focal adhesion formation of cancer cells by Clostridium botulinum C3 exoenzyme (C3), an inhibitor of Rho, or Y-27632, an inhibitor of ROCK. LPA also evoked the formation of focal adhesions and tyrosine phosphorylation of focal adhesion kinase and paxillin, all of which were inhibited by C3 or Y-27632., Conclusion: These results suggest that LPA induced the migration of ovarian cancer cells, at least in part, through accelerated formation of focal adhesions mediated by Rho/ROCK-induced actomyosin contractility. This study may provide the basis for new therapies to control the metastasis of ovarian cancer.