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Aim: Endometrial changes in Japanese transgender men (TGM) on testosterone use remain elucidated. This study aims to present TGM with endometrial cancer and insights from a literature review of similar cases. Furthermore, we investigated the correlation between endometrial cancer and severe obesity in TGM who underwent gender-affirming surgery., Methods: Between July 2020 and April 2023, two groups were assessed: 2 TGM with endometrial cancer and 43 TGM without cancer who underwent gender-affirming surgery. A literature review for TGM with endometrial cancer was conducted. Clinical data were retrospectively collected, and histopathological evaluation of female genital organs was performed., Results: Two TGM with endometrial cancer and an additional four similar cases were identified through a literature search. These TGM had severe obesity (body mass index [BMI] ≥30 kg/m 2 ) and long-term testosterone use, indicating a possible link between endometrial cancer and these factors. Subsequently, we investigated the 43 TGM without cancer. We revealed 30% with obesity (BMI ≥25), only three cases of severe obesity (BMI ≥30), and a significant correlation between testosterone use duration and BMI in TGM without cancer. Histological examination revealed focal proliferative endometrium in 51% of cases and polycystic ovarian changes in 77%., Conclusions: Our observations suggest a potential link between severe obesity, prolonged testosterone use, and endometrial cancer in transgender men. Histological changes in the female genital tract highlighted frequent focal proliferative endometrium, even under testosterone therapy. Further research should focus on larger, multi-institutional studies to confirm these findings and establish endometrial cancer screening for Japanese TGM., (© 2024 Japan Society of Obstetrics and Gynecology.)

Objective: Owing to the potential benefits of minimally invasive hysterectomy for endometrial cancer, the practice pattern has recently shifted in Japan. This study examined the trends in minimally invasive surgery (MIS) in patients with endometrial cancer in Japan., Methods: This retrospective observational study examined the Japan Society of Obstetrics and Gynecology Tumor Registry database between 2015-2019. This study examined the time-specific proportion change and predictors of MIS use in initial endometrial cancer treatment in Japan, and compared it with the use of abdominal surgery. Additionally, the association between hospital surgical treatment volume and MIS use was examined., Results: A total of 14,059 patients (26.5%) underwent minimally invasive hysterectomy, and 39,070 patients (73.5%) underwent abdominal hysterectomy in the study period. Patients who underwent MIS were more likely to be treated at high-volume centers, younger, central, or western Japan residents, registered in recent years, and had a tumor with stage I disease, type 1 histology, and less myometrial invasion (all adjusted p<0.05). The proportion of MIS treatments increased from 19.1% in 2015 to 34.3% in 2019 (p<0.001). On multivariable analysis, treatment at high-volume centers was a contributing factor for MIS (adjusted odds ratio=3.85; 95% confidence interval=3.44-4.30). MIS at high-volume centers increased significantly from 24.8% to 41.0% (p<0.001) during the study period, whereas MIS at low-volume centers remained at median 8.8%., Conclusion: MIS has increased significantly in recent years, accounting for nearly 34% of surgical management of endometrial cancer in Japan. High-volume treatment centers take the lead in performing MIS., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Purpose: This study aimed to examine MRI features and staging of neuroendocrine carcinoma (NEC) of the endometrium and evaluate survival., Methods: Clinical data, pathological, and preoperative pelvic MRI findings in 22 patients with histologically surgery-proven endometrial NEC were retrospectively reviewed. Tumors were pure NEC (n = 10) or mixed histotype (n = 12), with 13 large and nine small cell type., Results: International Federation of Gynecology and Obstetrics (FIGO) staging was I, II, III, and IV in 6, 2, 12, and 2 patients, respectively. In 13 (76.4%) of 17 patients with pathological deep myometrial invasion, MRI showed abnormal diffusely infiltrative high T 2 signal intensity throughout the myometrium with loss of normal uterine architecture. All tumors had restricted diffusion (apparent diffusion coefficient map low signal intensity, diffusion weighted imaging high signal intensity). Accuracy of T staging by MRI for all cases was 81.8%, with reference to pathology staging, while patient-based sensitivity, specificity, and accuracy for detecting metastatic pelvic lymph nodes was 60.0%, 100%, and 77.8%, respectively. Two intrapelvic peritoneal dissemination cases were detected by MRI. During follow-up (mean 30.4, range 3.3-138.4 months), 16 patients (72.7%) experienced recurrence and 12 (54.5%) died of disease. Two-year disease-free and overall survival rates for FIGO I, II, III, and IV were 66.7% and 83.3%, 50% and 100%, 10% and 33.3%, and 0% and 0%, respectively., Conclusion: Abnormal diffusely infiltrative high T 2 signal intensity throughout the myometrium with normal uterine architecture loss and obvious restricted diffusion throughout the tumor are suggestive features of endometrial NEC. Pelvic MRI is reliable for intrapelvic staging of affected patients.

Studies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles., (© 2021. The Author(s).)

Study Objective: To examine the diagnostic accuracy of hysteroscopic photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) in patients with endometrial cancer and premalignant atypical endometrial hyperplasia., Design: A single-center, open-label, exploratory intervention study., Setting: University Hospital in Japan., Patients: Thirty-four patients who underwent hysteroscopic resection in the Department of Obstetrics and Gynecology at Keio University Hospital., Interventions: Patients were given 5ALA orally approximately 3 hours before surgery and underwent observation of the uterine cavity and endometrial biopsy using 5ALA-PDD during hysteroscopic resection. Specimens were diagnosed histopathologically and the diagnostic sensitivity and specificity of hysteroscopic 5ALA-PDD for malignancy in the uterine cavity was determined. Red (R), blue (B), and green (G) intensity values were determined from PDD images, and the relationships of histopathological diagnosis with these values were used to develop a model for objective diagnosis of uterine malignancy., Measurements and Main Results: Three patients were excluded from the study because of failure of the endoscope system. A total of 113 specimens were collected endoscopically. The sensitivity and specificity of 5ALA-PDD for diagnosis of malignancy in the uterine cavity were 93.8% and 51.9%, respectively. The R/B ratio in imaging analysis was highest in malignant lesions, followed by benign lesions and normal uterine tissue, with significant differences among these groups (p <.05). The R/B and G/B ratios were used in a formula for prediction of malignancy based on logistic regression and the area under the receiver operating characteristic curve for this formula was 0.838. At a formula cutoff value of 0.220, the sensitivity and specificity for diagnosis of malignant disease were 90.6% and 65.4%, respectively., Conclusion: To our knowledge, this is the first study of the diagnostic accuracy of 5ALA-PDD for malignancies in the uterine cavity. Hysteroscopic 5ALA-PDD had higher sensitivity and identifiability of lesions. These findings suggest that hysteroscopic 5ALA-PDD may be useful for diagnosis of minute lesions., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach., Methods: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics., Results: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant., Conclusions: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale., (© 2018 John Wiley & Sons Ltd.)

Heat stress compromises fertility during summer in dairy and beef cows by causing nutritional, physiological and reproductive damages. To examine the difference in endometrial conditions in cows between summer and autumn, gene expression profiles were compared using a 15 K bovine oligo DNA microarray. The trial was conducted in the summer (early in September) and autumn (mid-November) seasons of two consecutive years (2013-2014) in Morioka, Japan. Endometrial samples were collected from the cows using a biopsy technique. The expressions of 268 genes were significantly higher in the endometrium collected in summer than those collected in autumn, whereas the expressions of 369 genes were lower (P<0.05 or lower). Messenger RNA expressions of glycoprotein 2 (GP2), neurotensin (NTS),E-cadherin (CDH1) and heat shock 105kDa/110kDa protein 1 (HSPH1) were validated by quantitative real-time PCR. Transcripts of GP2 and NTS were more abundant in the endometrium from summer than in the endometrium from autumn (P < 0.05). In contrast, the mRNA expressions of CDH1 were lower (P < 0.05) and those of HSPH1 tended to be low (P = 0.09) in the endometrium from summer. Immunohistochemical staining showed that GP2, NTS and HSPH1 were expressed in the endometrial epithelial or glandular epithelial cells. The serum concentrations of NTS collected from the cows in summer were higher than those collected from cows in autumn (P < 0.05). Collectively, the different gene expression profiles may contribute to functional differences in the endometrium between summer and autumn, and the increases in GP2 and NTS may have a relationship with the endometrial deficiency that causes infertility of cows in summer.

Aim: Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC., Methods: Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest., Results: For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002)., Conclusion: Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Aim: Although overexpression of p53 is usually found in uterine serous carcinoma (USC), it is also found in some uterine endometrioid adenocarcinomas (UEA). This report describes the clinicopathological features of the UEA with overexpression of p53 with special reference to a prognostic significance of nuclear grade., Material and Methods: Immunohistochemical expression of p53 was examined in 322 UEA and 34 USC. Greater than 50% staining was defined as the overexpression for p53. Cox's univariate and multivariate analyses for UEA were made., Results: There were 57 UEA (20.7%) showing overexpression of p53 and 31 USC (91.2%). The cancer-specific survival rate of patients with UEA without overexpression of p53, UEA with overexpression of p53 and USC was 88.2%, 76.3% and 45.7%, respectively. Univariate analyses showed overexpression of p53 to be a significant prognostic indicator in patients with UEA (P < 0.02). However, multivariate analyses for UEA showed that age, surgical stage, nuclear grade, myometrial invasion and lymphovascular space invasion were independent prognostic factors, while the significances of p53 immunoreactivity and architectural grade disappeared. In correlation between overexpression of p53 and nuclear grade, the patients with nuclear grade 1 and 2 UEA had a good prognosis, regardless of overexpression of p53. The cancer-specific survival rates of patients with nuclear grade 3 UEA with overexpression of p53 was 52.7% and was not significantly different from that of patients with nuclear grade 3 UEA without overexpression of p53 (66.7%) and USC., Conclusions: The prognostic significance of p53 immunostaining could not show in nuclear grade 3 UEA., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

Objectives: Although the expression of estrogen receptor (ER) is usually found in uterine endometrioid adenocarcinomas, it has recently been reported to be found in some uterine serous carcinomas (USCs). This report describes the clinicopathologic features of USC with an expression of ER-α, with special reference to the prognostic significance of ER-α., Methods: The immunohistochemical expression of ER-α was examined in 33 USCs. Greater than 10% staining was defined as an overexpression of ER-α. Cox univariate and multivariate analyses for USCs were performed., Results: A total of 7 USCs (21.2%) exhibited an expression of ER-α. All tumors were pure-type USCs and strongly demonstrated an overexpression of p53. The cancer-specific 5-year survival rates of patients with USC without an expression of ER-α and USC with an expression of ER-α were 54.5% and 0.0%, respectively (P = 0.04). The univariate analyses showed an expression of ER-α to be a significant prognostic indicator in patients with USC (P < 0.05). However, multivariate analyses for USCs showed that the surgical stage was an independent prognostic factor, whereas the significance of ER immunoreactivity disappeared., Conclusions: Uterine serous carcinoma with an expression of ER-α was associated with advanced-staged tumors and a significantly worse prognosis than that without an expression of ER-α. When an endometrial biopsy specimen reveals USC with an expression of ER-α and an overexpression of p53, the presence of an extrauterine lesion is suggested.

A high incidence (about 70%) of alteration in endometrial epidermal growth factor (EGF) profile, i.e., loss of 2 peaks on days 2-4 and 13-14, has been linked to a reduced fertility in multiparous repeat breeder Holstein cows. However, the EGF profile in Holstein heifers and other breeds (types) of cattle has not been investigated. In study 1, EGF concentrations were determined using endometrial tissues obtained by biopsy on days 3, 7 and 14 from 84 fertile Holstein heifers to obtain a normal range and 53 repeat breeder Holstein heifers to estimate incidence of alterations in the EGF profile. In repeat breeder heifers, EGF concentrations were similar to fertile controls on 3 days and five animals (9.4%) had an altered EGF profile with EGF concentrations below the normal range on days 3 and 14. In study 2, EGF concentrations on day 3 were repeatedly examined from the nulliparous period to the third postpartum period in 28 Holstein (dairy) and 47 Japanese Black (beef) cattle. The effect of parity on EGF concentrations on day 3 was different between Holstein and Japanese Black cattle. In Japanese Black cows, the EGF concentrations were consistently high throughout the study period, while in Holstein cows, the EGF concentrations decreased after the second calving. In conclusion, unlike multiparous repeat breeder Holstein cows, an altered EGF profile may not be a major cause of repeat breeding in Holstein heifers, and the peak EGF concentrations around day 3 may decrease even in fertile populations of multiparous dairy cows, but not in beef cows.

Objective: To investigate a new role of interleukin (IL)-17A in endometriosis., Design: Laboratory study., Setting: University hospital., Patient(s): Patients with ovarian endometrioma undergoing laparoscopy or laparotomy., Intervention(s): Primary culture of endometrioma stromal cells (EoSCs) was stimulated with IL-17A. Sections of endometrioma tissue were immunostained with antibodies for IL-17A, growth-regulated oncogene-α (Gro-α), and elastase, a marker of neutrophils. They were also examined with immunofluorescent double staining for IL-17A and myeloperoxidase, another marker of neutrophils., Main Outcome Measure(s): Concentration of Gro-α was measured using a specific ELISA. Neutrophil chemotaxis was measured with Boyden chamber method. Immunostained sections were examined under microscope., Result(s): Interleukin-17A increased the secretion of Gro-α from EoSCs dose-dependently. The conditioned medium of EoSCs stimulated with IL-17A attracted more neutrophils than that of EoSCs stimulated with vehicle, and the increase was inhibited by the addition of Gro-α-neutralizing antibody. On immunostaining, IL-17A and Gro-α were detected in similar areas of the stroma beneath the epithelium, where Gro-α was detected in cells with a stromal cell appearance whereas IL-17A was detected in neutrophils as determined by detection of elastase. Fluorescent immunostaining corroborated that myeloperoxidase-positive neutrophils were also positive for IL-17A., Conclusion(s): It is suggested that IL-17A produced by neutrophils stimulates Gro-α secretion from EoSCs, thereby recruiting more neutrophils and inducing perpetuating inflammation in endometriosis., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Magnetic resonance imaging was used to measure the endometrial T2 relaxation times of patients with infertility with fibroma. Although the location of fibromas did not influence the T2 relaxation times, we did observe a significant decrease in endometrial T2 relaxation times after myomectomy., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Out of 2,138 pregnant Japanese serows (Capricornis crispus), one case of the maceration of fetus was found in the winter of 1991, and examined pathologically. Because the fetus was covered with the hairs in the head and the neck regions, the fetus seemed to be implanted in the last breeding season and retained. The endometrium lacked the placentomes completely and showed metaplasia to the keratinized or non-keratinized squamous epithelium. In the non-keratinized region, the accumulation of neutrophils, eosinophils, lymphocytes, plasma cells and foreign giant cells was prominent in the subepithelial connective tissue.

We reviewed endometrial tissue from 166 cases of endometrial adenocarcinoma and hyperplasia--91 seen at Kyushu University, Fukuoka, Japan, and 75 at George Washington University, Washington, D.C., U.S.A.--to compare the prevalence of epithelial metaplastic changes in the two populations. Metaplasias were more common in the benign endometrium associated with carcinoma at George Washington University (78%) than at Kyushu University (54%). They were associated with carcinomas of lower grade and accompanied by hyperplasia at both institutions. These results indicate that endometrial metaplasias, like endometrial hyperplasias, tend to be associated with less virulent endometrial carcinomas and to be more common in American women (who represent a high-risk population for endometrial carcinoma) than in Japanese women (in whom the risk is low but rising.

A study was made of the 128 cases of primary tubal cancer reported to date in Japan, especially of the 61 cases with a preoperative cytologic examination, which was positive for malignancy in 28 cases (45.9%). A positive cytologic diagnosis was made on the cervicovaginal smear in 37.9% of the 58 cases so examined and on the endometrial smear in 80.0% of the 15 cases so examined. Of the 12 cases with positive endocervical smear cytologies, 11 were without endometrial invasion and 4 had no cancer cells in the cervicovaginal smear. Histologic examination of endometrial curettage specimens was positive for cancer in 8 (23.5%) of 34 cases so examined. Endometrial invasion by cancer cells was seen in 11.1% of the surgically extirpated endometrial specimens. The results of this study suggest that cytologic diagnosis is one of the most reliable methods for detecting primary tubal cancer before a surgical operation is undertaken. Its efficacy might be improved by more careful sampling and study in patients suspected of having primary tubal cancer.