Preoperative serum tissue factor pathway inhibitor­2 level as a prognostic marker for endometrial cancer.

Advanced endometrial cancer (EC) often recurs and has a poor prognosis. Various serum markers have been used for EC but their usefulness as biomarkers is still unclear; therefore, identifying new biomarkers is important. The present study aimed to investigate whether the tissue factor pathway inhibitor-2 (TFPI2) level was elevated in the preoperative serum of patients with EC and if it may be a prognostic factor. The present retrospective study included 207 patients who had a confirmed pathological diagnosis of EC and received surgical therapy as the initial treatment between January 2011 and December 2017. Survival analysis was performed using Kaplan-Meier analysis and the Cox proportional hazards regression model. The 5-year disease-free survival and overall survival (OS) rates were 73.3 and 83.7%, respectively. The cut-off value for predicting OS for TFPI2 level was 177 pg/ml as determined from the receiver operating characteristic curve. A TFPI2 value ≥177 pg/ml was significantly associated with age ≥65 years (P<0.001), diabetes (P=0.035), stage (P<0.001), myometrial invasion (P<0.001), lymphovascular invasion (P=0.004), lymph node metastasis (P=0.010), distant metastasis (P<0.001), cancer antigen (CA) 125 ≥36 U/ml (P<0.001) and CA 19-9 ≥38 U/ml (P<0.001). In multivariate analysis, high-grade carcinoma [hazard ratio (HR), 2.439; P=0.041], lymph node metastasis (HR, 2.116; P=0.038), distant metastasis (HR, 3.604; P=0.009) and TFPI2 level ≥177 pg/ml (HR, 2.42; P=0.043) were significant prognostic factors affecting OS in patients with EC. These results suggest that the preoperative serum TFPI2 level, along with its histological type, lymph node metastasis and distant metastasis, was a prognostic factor for OS in patients with endometrial cancer.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Association of online activities with obstetrics and gynecology specialty choice: a nationwide online survey.

Objectives: To investigate the association between online activities and the number of new obstetrics and gynecology senior residents. Methods: A nationwide web-based, self-administered anonymous survey was conducted to investigate recruitment and clerkship activities during the coronavirus disease 2019 pandemic. An online questionnaire was sent to 576 obstetrics and gynecology training institutions in Japan between December 21, 2020, and January 31, 2021. Overall, 334 institutions that gave valid responses were included (response rate: 58.0%). Multivariate logistic regression analysis examined the association between online activities, including recruitment and clerkship activities, and the number of new obstetrics and gynecology senior residents in 2021. The stratified analysis by implementing face-to-face activities was conducted to clarify the association. Results: The number of new senior residents increased in 187 facilities (56.0%) and decreased in 147 facilities (44.0%). The facilities that implemented face-to-face and online activities were 185 (55.4%) and 120 (35.9%), respectively. In multivariate logistic regression analysis, an increased number of new obstetrics and gynecology senior residents was significantly associated with face-to-face activities (adjusted odds ratio (AOR)=2.58, 95% confidence interval (CI): 1.11-5.97, p<.001) but not with online activities. In the stratified analysis, online activities were significantly associated with an increased number of new obstetrics and gynecology senior residents among the facilities without face-to-face activities (AOR=3.81, 95% CI: 1.40-10.32, p=.009) but not among those with face-to-face activities (AOR=0.87, 95% CI: 0.42-1.78). Conclusions: Online activities were associated with an increased number of new obstetrics and gynecology senior residents among the facilities that did not conduct face-to-face activities.

Tissue Factor Pathway Inhibitor 2: A Novel Biomarker for Predicting Asymptomatic Venous Thromboembolism in Patients with Epithelial Ovarian Cancer.

OBJECTIVES: Patients with asymptomatic venous thromboembolism (VTE) are associated with an increased risk of pulmonary thromboembolism events. However, due to low specificity and high false-positive rates, D-dimer testing cannot be used alone to diagnose VTE. Tissue factor pathway inhibitor 2 (TFPI2), a new serodiagnostic marker for ovarian cancer, plays a role in blood coagulation system regulation. We hypothesized that combining D-dimer and TFPI2 would improve its utility in diagnosing VTE. This study aimed to look into the clinical utility of serum D-dimer and TFPI2 levels in detecting asymptomatic VTE in patients with epithelial ovarian cancer (EOC). DESIGN: From January 2008 to December 2015, researchers at Nara Medical University Hospital's Department of Gynecology conducted a single-center retrospective study. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of preoperative D-dimer, TFPI2, and D-dimer combined with TFPI2 in distinguishing VTE patients from those who did not have VTE. PARTICIPANTS: This study included 122 patients with EOC who met the inclusion and exclusion criteria out of 223 admitted to the hospital with EOC. The patients were divided into two groups: VTE (n = 25) and non-VTE (n = 97). RESULTS: There were significant differences in D-dimer, TFPI2, and CA125 levels and residual tumor between the VTE and non-VTE groups. The D-dimer level was found to be significantly related to age, body mass index, VTE, massive ascites, residual tumor, histology, and Federation of Gynecology and Obstetrics stage, whereas the TFPI2 level was only related to VTE. Multivariate analysis revealed that D-dimer (the optimal cutoff value, 3.5 µg/mL) and TFPI2 (the optimal cutoff value, 400 pg/mL) are independent risk factors for preoperative VTE. ROC analysis revealed that the area under the curve was 0.8266 for D-dimer, 0.7963 for TFPI2, and 0.8495 for the combination of D-dimer and TFPI2. When compared to the D-dimer test alone, the combination of D-dimer and TFPI2 had higher specificity (77.3-96.9%) and positive predictive value (48.8-81.2%) for the diagnosis of VTE. LIMITATIONS: This is a single-center retrospective study. CONCLUSION: The combination of D-dimer and TFPI2 may be useful to safely exclude VTE and select patients at high risk of VTE.

The Comparison of Three Predictive Indexes to Discriminate Malignant Ovarian Tumors from Benign Ovarian Endometrioma: The Characteristics and Efficacy.

This study aimed to evaluate the prediction efficacy of malignant transformation of ovarian endometrioma (OE) using the Copenhagen Index (CPH-I), the risk of ovarian malignancy algorithm (ROMA), and the R2 predictive index. This retrospective study was conducted at the Department of Gynecology, Nara Medical University Hospital, from January 2008 to July 2021. A total of 171 patients were included in the study. In the current study, cases were divided into three cohorts: pre-menopausal, post-menopausal, and a combined cohort. Patients with benign ovarian tumor mainly received laparoscopic surgery, and patients with suspected malignant tumors underwent laparotomy. Information from a review chart of the patients' medical records was collected. In the combined cohort, a multivariate analysis confirmed that the ROMA index, the R2 predictive index, and tumor laterality were extracted as independent factors for predicting malignant tumors (hazard ratio (HR): 222.14, 95% confidence interval (CI): 22.27−2215.50, p < 0.001; HR: 9.80, 95% CI: 2.90−33.13, p < 0.001; HR: 0.15, 95% CI: 0.03−0.75, p = 0.021, respectively). In the pre-menopausal cohort, a multivariate analysis confirmed that the CPH index and the R2 predictive index were extracted as independent factors for predicting malignant tumors (HR: 6.45, 95% CI: 1.47−28.22, p = 0.013; HR: 31.19, 95% CI: 8.48−114.74, p < 0.001, respectively). Moreover, the R2 predictive index was only extracted as an independent factor for predicting borderline tumors (HR: 45.00, 95% CI: 7.43−272.52, p < 0.001) in the combined cohort. In pre-menopausal cases or borderline cases, the R2 predictive index is useful; while, in post-menopausal cases, the ROMA index is better than the other indexes.

Tissue factor pathway inhibitor 2 as a serum marker for diagnosing asymptomatic venous thromboembolism in patients with epithelial ovarian cancer and positive D-dimer results.

Tissue factor pathway inhibitor 2 (TFPI2) is a serodiagnostic marker for epithelial ovarian cancer (EOC) and is the primary inhibitor of the extrinsic coagulation pathway. The present study assessed the diagnostic performance of TFPI2 for detecting venous thromboembolism (VTE) in patients with EOC and positive D-dimer results (>1.0 µg/ml). First, the clinical data of 81 patients with EOC admitted to Nara Medical University Hospital between January 2008 and December 2015 were collected. Also, 25 patients with VTE and 56 patients without VTE were included. Receiver-operating characteristic (ROC) curve analyses were performed to determine the diagnostic efficacy of TFPI2 in discriminating patients with VTE from those without VTE. Serum TFPI2 levels in patients with VTE were significantly higher than in non-VTE patients (median, 472.2 vs. 279.1 pg/ml, P<0.001). Using the Youden index, the optimal cutoff value for the TFPI2 level was set at 398.9 pg/ml. Furthermore, the sensitivity, specificity, positive predictive value and negative predictive value of TFPI2 for diagnosing VTE were 64.0, 80.4, 59.3 and 83.3%, respectively. Additionally, 80.4% of patients with TFPI2 levels <398.9 pg/ml were VTE-negative. ROC analysis demonstrated that the area under the curve for TFPI2 was 0.729 (95% confidence interval, 0.614-0.844). Conclusively, TFPI2 may distinguish patients with VTE from those without VTE among patients with EOC and positive D-dimer results.

Preclinical Activity of Plitidepsin Against Clear Cell Carcinoma of the Ovary.

BACKGROUND/AIM: To evaluate the antitumor effects of Plitidepsin against clear cell carcinoma (CCC) of the ovary. MATERIALS AND METHODS: The expression of eEF1A2 in ovarian cancer was assessed by immunohistochemistry. Using ovarian CCC cell lines, the antitumor effect of Plitidepsin was assessed both in vitro and in vivo. By over-expressing or knocking down the eEF1A2 expression, we investigated the role of eEF1A2 in the sensitivity of CCC cells to Plitidepsin. RESULTS: Immunoreactivity to eEF1A2 was observed in 76.2% of CCC, which was significantly higher than other histological subtypes of ovarian cancer. Plitidepsin exhibited significant antitumor activity toward chemonaive and chemoresistant CCC cells both in vitro and in vivo. Ectopic expression of eEF1A2 in CCC cells resulted in increased sensitivity to Plitidepsin. In contrast, eEF1A2 knockdown decreased sensitivity of CCC cells to plitidepsin. CONCLUSION: Plitidepsin, a novel anti-cancer agent that targets eEF1A2, may be a promising agent for treating ovarian CCC.

A Novel Predictive Tool for Discriminating Endometriosis Associated Ovarian Cancer from Ovarian Endometrioma: The R2 Predictive Index.

BACKGROUND: Magnetic resonance (MR) relaxometry provides a noninvasive tool to discriminate between ovarian endometrioma (OE) and endometriosis-associated ovarian cancer (EAOC), with a sensitivity and specificity of 86% and 94%, respectively. MRI models that can measure R2 values are limited, and the R2 values differ between MRI models. This study aims to extract the factors contributing to the R2 value, and to make a formula for estimating the R2 values, and to assess whether the R2 predictive index calculated by the formula could discriminate EAOC from OE. METHODS: This retrospective study was conducted at our institution from November 2012 to February 2019. A total of 247 patients were included in this study. Patients with benign ovarian tumors mainly received laparoscopic surgery, and the patients suspected of having malignant tumors underwent laparotomy. Information from a chart review of the patients' medical records was collected. RESULTS: In the investigative cohort, among potential factors correlated with the R2 value, multiple regression analyses revealed that tumor diameter and CEA could predict the R2 value. In the validation cohort, multivariate analysis confirmed that age, CRP, and the R2 predictive index were the independent factors. CONCLUSIONS: The R2 predictive index is useful and valuable to the detection of the malignant transformation of endometrioma.

Congenital contractural arachnodactyly suspected by abnormally long extremities by fetal ultrasound.

Congenital contractural arachnodactyly (CCA) is a rare disease with the clinical features of limited extension of multiple joints, arachnodactyly, camptodactyly, thin and long extremities, and so on. In the point of long extremities, CCA resembles Marfan syndrome (MFS). CCA is easily differentiated from MFS after birth due to the flexion of multiple joints, including elbows, knees, hips and fingers. During the fetal period, observation of arachnodactyly and folded fingers by fetal ultrasound is the means of differential diagnosis between these two diseases. We report on a case of CCA diagnosed with prenatal symptoms of long extremities, and introduced physiotherapy in early childhood for a better physical prognosis.

Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.