The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial.

BACKGROUND: Uterine leiomyomas are common for reproductive-aged women and affect women's quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i.e., to reduce blood loss or surgical duration). Recently, relugolix (40 mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However, long-term administration should not be permitted liable to for climacteric disorder or osteoporosis, and evidence is lacking on the actual efficacy and extent of adverse effects of the every-other-day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety (i.e., reduction of adverse effects) by every-other-day administration after 2 months of everyday administration compared to daily administration throughout the duration. METHODS: A minimization adaptive randomized control trial (RCT) will be conducted. Patients (over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every-other-day administration for 16 weeks after 8 weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume reduction, and the secondary endpoints are the reduction of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration. DISCUSSION: This study aims to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects while maintaining the effect of leiomyoma reduction. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051230078. Registered on 26 July 2023.

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.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Energy redistribution analysis of dynamic mechanisms of multi-body, multi-joint kinetic chain movement during soccer instep kicks.

The purpose of this study is to develop a model to analyze energy redistribution mechanisms of a multi-joint limb system and to examine the mechanisms underlying the production of the mechanical energy of the system during instep kicking. Kicking movements of 11 collegiate soccer players were recorded using a motion capture system, and ground reaction force during kicks was measured. Using the experimental data and the state-space power analysis developed in the current study, the kinetic energy change of the modeled segments was decomposed into causal components due to various dynamic factors (muscular and non-muscular interactive moments). The results showed that the increase of the kinetic energy of the kicking limb resulted from the energy transfer mechanisms between the decelerated segment (a proximal segment) and accelerated segment (a distal segment), induced by a non-muscular interactive moment due to the external joint force or the centrifugal force. The proximal (thigh) to distal (shank) sequential motion pattern observed was due to the energy transfer mechanism induced by the centrifugal effect acting to accelerate the shank and decelerate the thigh. The fact suggests that effective use of that mechanism may be advantageous to enhance the kinetic energy of the kicking shank. In conclusion, energy transfer mechanisms likely play a greater role in dynamic kicking than muscle power output, and better coordination to exchange kinetic energy among segments makes kicking more efficient.

Multijoint kinetic chain analysis of knee extension during the soccer instep kick.

Although previous studies have shown that motion-dependent interactions between adjacent segments play an important role in producing knee extension during the soccer instep kick, detailed knowledge about the mechanisms underlying those interactions is lacking. The present study aimed to develop a 3-D dynamical model for the multijoint kinetic chain of the instep kick in order to quantify the contributions of the causal dynamical factors to the production of maximum angular velocity during knee extension. Nine collegiate soccer players volunteered to participate in the experiment and performed instep kicking movements while 3-D positional data and the ground reaction force were measured. A dynamical model was developed in the form of a linked system containing 8 segments and 18 joint rotations, and the knee extension/flexion motion was decomposed into causal factors related to muscular moment, gyroscopic moment, centrifugal force, Coriolis force, gravity, proximal endpoint linear acceleration, and external force-dependent terms. The rapid knee extension during instep kicking was found to result almost entirely from kicking leg centrifugal force, trunk rotation muscular moment, kicking leg Coriolis force, and trunk rotation gyroscopic-dependent components. Based on the finding that rapid knee extension during instep kicking stems from multiple dynamical factors, it is suggested that the multijoint kinetic chain analysis used in the present study is more useful for achieving a detailed understanding of the cause of rapid kicking leg movement than the previously used 2-D, two-segment kinetic chain model. The present results also indicated that the centrifugal effect due to the kicking hip flexion angular velocity contributed substantially to the generation of a rapid knee extension, suggesting that the adjustment between the kicking hip flexion angular velocity and the leg configuration (knee flexion angle) is more important for effective instep kicking than other joint kinematics.