Update on the oncologic and obstetric outcomes of medroxyprogesterone acetate treatment for atypical endometrial hyperplasia and endometrial cancer.

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan.

Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies. Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted. Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]). Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

Identifying the high-benefit population for weight management-based cardiovascular disease prevention in Japan.

Background: Cardiovascular-disease (CVD) is the leading cause of death, and the association between obesity and CVD is particularly significant among women. Given the evidence highlighting the significance of weight-gain velosity, we aimed to elucidate its influence on cardio-ankle vascular index (CAVI), a reliable surrogate marker of CVD, and identify the high-benefit population where this influence is most pronounced. Methods: This multicenter retrospective study used electronic data from annual health checkups for workers in Japan. Individuals who voluntarily measured CAVI in 2019 were included, and weight-gain velosity was defined as the mean BMI gain from 2015 to 2019. Our primary outcome was the relationship between weight-gain velosity and CAVI. Results: Among 459 individuals, 53 had CAVI ≥ 9. Random forest analysis revealed that age was the most important factor, followed by lipid metabolism, weight-gain velosity, and glucose metabolism, with sex being the least important. Non-linear regression analysis of the effect of age on CAVI ≥ 9 showed the effect was pronounced after age 60, and the trend was greater in women. Among individuals aged 60 or younger, the aOR of weight-gain velosity for CAVI ≥ 9 was significantly positive (aOR 11.95, 95 %CI 1.13-126.27), while it was not significant for those older than 60. The relationship between weight-gain velosity and CAVI provides a new perspective on CVD risk factors. The effects of age, especially after 60, and weight-gain velosity in early- to middle-adulthood on arterial stiffness are emphasized. Conclusions: These findings underscore the importance of weight management under age 60, especially in women.

Amniotic fluid-derived small extracellular vesicles for predicting postnatal severe outcome of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a life-threatening condition with high morbidity and mortality rates. The survival rate of neonates with severe CDH is reportedly only 10%-15%. However, prenatal prediction of severe cases is difficult, and the discovery of new predictive markers is an urgent issue. In this study, we focused on microRNAs (miRNAs) in amniotic fluid-derived small EVs (AF-sEVs). We identified four miRNAs (hsa-miR-127-3p, hsa-miR-363-3p, hsa-miR-493-5p, and hsa-miR-615-3p) with AUC > 0.8 to classify good prognosis group and poor prognosis group in human study. The AUC for hsa-miR-127-3p and hsa-miR-615-3p, for predicting the poor prognosis, were 0.93 and 0.91, respectively. In addition, in the in vivo study, the miRNA profiles of the lung tissues of CDH rats were different from those of control rats. Additionally, two elevated miRNAs (rno-miR-215-5p and rno-miR-148a-3p) in the lung tissues of CDH rats were increased in the AF-sEVs of CDH rats. Our results suggest that severe CDH neonates can be predicted prenatally with high accuracy using miRNAs contained in AF-sEVs. Furthermore, miRNA profile changes in AF-sEVs reflected the lung status in CDH. Our findings may contribute to the development of advanced perinatal care for patients with CDH.

Practical weight management to minimize pregnancy complications and promote women's health: the possibility of interpregnancy care.

Pregnancy is an excellent opportunity to provide medical interventions to women. It is also a stress test used to predict health. Numerous studies have demonstrated that the pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are critical factors for pregnancy complications such as hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), large or small gestational age infants, and spontaneous preterm birth (sPTB). These complications are associated with an increased risk of cardiovascular disease (CVD), which is a leading cause of mortality in women. In addition, complications adversely affect the short- and long-term prognoses of children. Optimal GWG to reduce complications is recommended based on pre-pregnancy BMI; however, racial differences should also be noted. The values in the Japanese guidelines are lower than those in the American Institute of Medicine guidelines. The Asian BMI thresholds for CVD risk are also lower than those in Europe. Therefore, weight management should be based on racial/genetic background. Interpregnancy weight gain or loss has also been reported to be associated with the risk of pregnancy complications; however, few studies have been conducted in Asian populations. Our previous reports suggested that avoiding an excess of 0.6 kg/m2/year of annual BMI gain may reduce the risk of HDP or GDM, and insufficient gain of < 0.25 kg/m2/year may increase sPTB recurrence. Annual BMI is useful for practical weight control during interpregnancy. Based on these findings, effective approaches should be established to improve the health of women and their offspring.

Educational results of the Japan Maternal Emergency Life-Saving (J-MELS) simulation training organized by Japan Council for the Implementation of the Maternal Emergency Life-Saving System (J-CIMELS): a 12-month longitudinal follow-up study in Japan.

AIMS: This study aimed to evaluate the long-term results of Japan Maternal Emergency Life-Saving (J-MELS) simulation training on obstetric healthcare providers, over a 12-month follow-up period. METHODS: A total of 273 trainees from 17 J-MELS Basic courses conducted between August 2021 and October 2023 were included. The trainees' responses to the pre- and post-tests, questionnaires, and self-reports on the usefulness of the J-MELS scenarios in actual clinical settings at 1, 6, and 12 months after the training were analyzed. Multivariate logistic regression analysis was also conducted to identify the factors influencing knowledge retention. RESULTS: We found an overall improvement in clinical knowledge acquisition after J-MELS training and a significant retention of this improvement at least until 12 months later. However, these scores gradually declined over. Trainees reported increased usefulness of J-MELS scenarios in actual clinical practice at 1, 6, and 12 months after training, particularly in managing obstetric emergencies such as atonic postpartum hemorrhage. Knowledge retention was influenced by several specific factors, such as years of clinical experience, affiliated institutions, qualifications, and especially pre-test scores. CONCLUSION: Our longitudinal follow-up study demonstrated, for the first time, the long-term results of J-MELS simulation training using post-tests and self-report data. Our findings provide valuable insight into the impact of J-MELS simulation training on maternal emergency care. By elucidating the factors influencing knowledge retention and practical utility, the findings offer actionable recommendations for optimizing training strategies and improving maternal outcomes in actual clinical practice.

Plasma Exchange in Postpartum Hemorrhage (PPH)-Associated Thrombotic Microangiopathy (TMA): A Case Report.

Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features akin to TMA during the peripartum period such as eclampsia, preeclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and antiphospholipid syndrome. A 28-year-old woman with no significant past medical history developed TMA following a massive hemorrhage after an emergency cesarean section at 41 weeks of gestation. This case was finally diagnosed as postpartum hemorrhage (PPH)-associated TMA. The patient fully recovered after plasma exchange therapy. We posit the value of accumulating case reports, given that the documentation on the efficacy of plasma exchange in PPH-associated TMA is limited.

Safety assessments and clinical features of PARP inhibitors from real-world data of Japanese patients with ovarian cancer.

Poly (ADP-ribose) polymerase inhibitors have been increasingly used in ovarian cancer treatment. However, the real-world safety data of these drugs in Japanese patients are limited. This retrospective study included 181 patients with ovarian cancer who received olaparib or niraparib at two independent hospitals in Japan between May 2018 and December 2022. Clinical information and blood sampling data were collected. Regarding patient backgrounds, the olaparib group had higher proportions of patients with serous carcinoma, BRCA positivity, homologous recombination deficiency, and those receiving maintenance therapy after recurrence treatment than the niraparib group. Regarding toxicity properties, the most common reasons for discontinuation in the olaparib group were anemia, fatigue, and nausea, while the reason in the niraparib was thrombocytopenia. Thrombocytopenia caused by niraparib treatment occurred earlier than anemia caused by olaparib treatment. Patients with a low body mass index or who had undergone several previous treatment regimens were more likely to discontinue treatment within the first 3 months. Although we analyzed blood collection data, predicting treatment interruptions due to blood toxicity was challenging. In this study, we revealed the characteristics of patients and the timing of interruptions for each drug, highlighting the importance of carefully managing adverse effects.

Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta.

Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.

Real-world data of poly (ADP-ribose) polymerase inhibitor response in Japanese patients with ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors have been increasingly used in the treatment of ovarian cancer, with BRCA positivity and homologous recombination deficiency (HRD) being common biomarkers used for predicting their efficacy. However, given the limitations of these biomarkers, new ones need to be explored. METHODS: This retrospective study included 181 ovarian cancer patients who received olaparib or niraparib at two independent hospitals in Japan between May 2018 and December 2022. Clinical information and blood sampling data were collected. Patient characteristics, treatment history, and predictability of treatment duration based on blood data before treatment initiation were examined. RESULTS: High-grade serous carcinoma, BRCA positivity, HRD, and maintenance therapy after recurrence treatment were observed more frequently in the olaparib group than in the niraparib group. The most common reasons for treatment interruption were anemia, fatigue, and nausea in the olaparib group and thrombocytopenia in the niraparib group. Regarding response to olaparib treatment, complete response to the most recent treatment, maintenance therapy after the first chemotherapy, high-grade serous carcinoma, and germline BRCA positivity were observed significantly more frequently among responders than among non-responders. Furthermore, neutrophil counts were significantly higher among responders than among non-responders. CONCLUSIONS: Inflammation-related blood data, such as neutrophil count, obtained at the initial pre-treatment visit might serve as potential predictors for prolonged olaparib treatment. While this study offers valuable insights into potential indicators for prolonged olaparib treatment, it underscores the need for more expansive research to strengthen our understanding of PARP inhibitors and optimize treatment strategies in ovarian cancer.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Spatial distribution of tumor-resident macrophages as predictive biomarkers in endometrial cancer.

BACKGROUND: To investigate the role of CD47 expression and its relationship with tumor-resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. METHODS: A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). RESULTS: The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H-score and the density of CD68-positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68-positive macrophages at the tumor margin but a low density of CD163-positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). CONCLUSIONS: The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Factors affecting the long-term prognosis of patients in the AYA generation with epithelial ovarian cancer: A multicenter propensity score matching analysis.

OBJECTIVE: Ovarian carcinoma (OvCa) is more common in the elderly, but also affects the adolescent and young adult (AYA) generation, which refers to those aged 15-39 years. Although the characteristics of OvCa may differ between AYAs and non-AYAs, limited information is currently available on differences in prognostic factors. Therefore, we herein investigated prognostic factors for and the prognosis of OvCa in AYAs. We also examined the prognostic impact of fertility-sparing surgery in a subgroup analysis. METHODS: We retrospectively collected data on 4897 patients with OvCa from the databases of multiple institutions and ultimately included 1161 patients with epithelial ovarian cancer (EOC). We performed a survival analysis to compare AYAs and non-AYAs with backgrounds that conformed to those of AYAs using the propensity score (PS) matching method. A Cox regression analysis was also conducted to evaluate each predictor of recurrence-free survival (RFS) and overall survival (OS) in the original population. As a subgroup analysis, a multivariate analysis stratified by the AYA and non-AYA generations was performed. RESULTS: In total, 119 AYA patients were included in this study. After PS adjustments, no significant differences were observed in RFS or OS between AYAs and non-AYAs. Prognostic factors differed between AYAs and non-AYAs, particularly in histology and cytology. A multivariate analysis stratified by the AYA and non-AYA generations described that uterine-preserving surgery (UPS) did not have a significant impact on the prognosis of AYAs or non-AYAs. In cases with recurrence, no significant differences were observed in RFS and recurrent sites in the two groups. CONCLUSION: Characteristic prognostic factors for EOC in AYAs were identified. The present results indicate the limited prognostic impact of UPS for EOC in AYAs.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Postpartum and interpregnancy care of women with a history of hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are common complications associated with maternal and neonatal morbidity and mortality worldwide. Insights gained from long-term cohort studies have revealed that women with a history of HDP are predisposed to recurrent HDP in subsequent pregnancies and face heightened risks for cardiovascular and metabolic diseases later in life. Pregnancy is a unique condition that overloads maternal cardiac and metabolic functions, and is recognized as a "maternal stress test" for future cardiovascular and metabolic diseases. Pregnancy and postpartum period provide a valuable opportunity for identifying women with underlying and unrecognized cardiovascular and metabolic risk factors. Establishing an effective postpartum healthcare program for women who have experienced HDP is crucial in reducing the future risk of health complications. Postpartum care consists of supportive care for both mothers and children, including not only the assessment of physical and psychological well-being but also long-term postpartum preventive health management. Interpregnancy care is a continuum from postpartum care and includes supportive care to prepare for future pregnancies. Various initiatives across nations have been initiated to establish follow-up programs for women with a history of HDP; however, sufficient evidence of the impact of such programs is not available. Substantial challenges persist in establishing an efficient postpartum follow-up program, including educational strategies, selection of effective lifestyle interventions, and collaboration among various healthcare providers. This review outlines the postpartum and interpregnancy care of women who have experienced HDP as well as the current status and challenges of related healthcare initiatives in Japan.

Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.

Epithelial ovarian cancer (EOC) is often diagnosed in advanced stage with peritoneal dissemination. Recent studies indicate that aberrant accumulation of collagen fibers in tumor stroma has a variety of effects on tumor progression. We refer to remodeled fibrous stroma with altered expression of collagen molecules, increased stiffness, and highly oriented collagen fibers as tumor-associated fibrosis (TAF). TAF contributes to EOC cell invasion and metastasis in the intraperitoneal cavity. However, an understanding of molecular events involved is only just beginning to emerge. Further development in this field will lead to new strategies to treat EOC. In this review, we focus on the recent findings on how the TAF contributes to EOC malignancy. Furthermore, we will review the recent initiatives and future therapeutic strategies for targeting TAF in EOC.