Masanori Ono

A case of Herlyn–Werner–Wunderlich syndrome with exacerbation of hematometra after adnexectomy

Abstract A 27‐year‐old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn–Werner–Wunderlich syndrome. Treatment must permit the outflow of menstrual blood.

Androgen-responsive FOXP4 is a target for endometrial carcinoma

AbstractAlthough low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Ptenff/PRcre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Ptenff/PRcre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.

Conception After Chemotherapy for Intraplacental Choriocarcinoma: Favorable 5-Year Follow-Up of the Mother and Child

BACKGROUND Intraplacental choriocarcinoma (IC) is a rare subtype of gestational choriocarcinoma that can be associated with placental hemorrhage and metastases to the mother and fetus. Chemotherapy can be effective in cases of placental localization and may not adversely affect fertility. This report describes a 32-year-old woman who conceived 10 months after chemotherapy for IC and achieved successful term delivery of that pregnancy. CASE REPORT A 32-year-old woman delivered her first child by vacuum extraction due to weak labor and fetal distress. The newborn presented with severe anemia, as well as elevated alpha-fetoprotein and fetal hemoglobin levels, suggesting fetomaternal hemorrhage. Placental histopathology revealed IC. Postpartum elevation of human chorionic gonadotropin levels prompted EMA-CO (etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine) chemotherapy; 7 treatment courses were completed without side effects or metastasis. Ten months after completion of chemotherapy, the patient spontaneously conceived. She subsequently delivered a healthy boy at 38+5 weeks of gestation; placental examination did not reveal malignancy. During the 5-year follow-up period, both children developed normally, and no maternal recurrence or metastasis was observed. CONCLUSIONS This report describes a case of postnatal diagnosis of IC via placental histopathology, followed by successful treatment and subsequent pregnancy within 1 year after chemotherapy completion. The findings highlight the importance of accurate diagnosis and appropriate management of IC; they support previous observations that chemotherapy does not preclude future successful pregnancies. Additionally, the report underscores the clinical challenges of IC, its implications for future pregnancies, and the need for long-term follow-up concerning both mother and child.

Novel Subtype Classification of Diffuse Uterine Leiomyomatosis Based on a Nationwide Survey in Japan

ABSTRACT Aim Diffuse uterine leiomyomatosis (DUL) is characterized by numerous uterine leiomyomas within and diffusely replacing the myometrium. However, because of its rarity, the prevalence, diagnostic criteria, and standard treatment for patients with DUL who wish to preserve their fertility remain unknown. This study aimed to clarify the current status of the diagnosis of DUL in Japan. Methods We conducted a web‐based survey targeting 1080 Obstetrics and Gynecology training institutions registered with the Japanese Medical Specialty Board. We asked them whether they had treated patients with DUL over the past 10 years (2013–2022). We obtained magnetic resonance imaging (MRI) scans from institutions that reported clinical experience with DUL, and conducted a central review to determine whether each case was consistent with DUL. We also investigated whether DUL could be classified into subtypes. Results Responses were obtained from 428 institutions, of which 128 reported clinical experience with DUL or DUL‐like multiple uterine leiomyomas, totaling 653 cases. MRI scans from 408 cases were centrally reviewed by a subcommittee, and 307 cases were confirmed as DUL. Based on the imaging characteristics, DUL was classified into three subtypes: total replacement, myometrial replacement, and submucosal‐dominant. Conclusions This survey revealed that 653 cases of DUL or DUL‐like multiple uterine leiomyomas were managed over a 10‐year period in Japan. Based on a central review of MRI scans, DUL can be classified into three distinct subtypes. Given the differences between these subtypes, treatment approaches for patients wishing to preserve fertility may vary, highlighting the need for further investigation.

BMAL1 Regulates Collagen Production in the Myometrium and Leiomyomas

Infertility and reproductive issues are commonly observed in animals with clock abnormalities. Substantial rodent data is available; however, relatively few studies have investigated the connection between fertility and clock abnormalities in humans. Therefore, this study aimed to analyze the expression of circadian clock genes and their impact on genes involved in collagen production in the human myometrium and leiomyomas (LM). The relationship between the expression of brain and muscle aryl-hydrocarbon-receptor-nuclear-translocator (Arnt)-like protein-1 (BMAL1) and the genes responsible for collagen synthesis in the human MM and LMs were investigated. Human MM and LM tissues were collected for analysis from patients who underwent hysterectomy analysis. Immunohistochemical analysis, cell culturing, immunofluorescence, small interfering RNA transfection, reverse transcription quantitative real-time polymerase chain reaction, scratch wound assays, and transwell assays were employed to gain a comprehensive understanding of the cellular and molecular processes. A correlation was found between BMAL1 expression and genes regulating collagen synthesis in primary cultures of human MM and LM cells. Moreover, the inhibition of BMAL1 differentially increased the migration and invasion of MM and LM cells. This work discloses the role of BMAL1 in collagen production in primary cultures of human MM and LM cells, offering insight into clock gene involvement in both normal and pathological uterine conditions. Furthermore, this study highlights the crucial role of BMAL1 in collagen synthesis in human MM and LM cells, underscoring the significance of BMAL1 in the regulation of reproductive physiology. These results suggest that BMAL1 might be a useful target molecule for anti-LM therapy.