Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutations in BRCA1/2, have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of BRCA1/2 alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of BRCA1/2. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with BRCA1/2 mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with BRCA1/2 mutations (cohort A, C) and HRD positive uLMS without BRCA1/2 mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.

Objectives: Although sarcopenia is diagnosed using appendicular lean mass (ALM), only a few long-term studies on changes in both ALM and bone mineral density (BMD) have been reported. The purposes of this study are to evaluate the changes in the parameters of lean mass and bone mass over a 10-year interval and to estimate the effects of osteoporosis pharmacotherapy on muscle. Methods: A total of 175 postmenopausal women were evaluated at baseline and after 10 years for BMD, ALM, fat mass, height, and weight. Subjects were further divided into an osteoporosis treatment group (n = 60) and a control group (n = 67) according to whether they had received pharmacotherapy for > 5 years. This was followed by propensity score matching for age, height, weight, and body mass index (BMI), and estimated parameters were compared between groups. Results: Height, weight, ALM, and fat mass decreased significantly over 10 years (P < 0.05). However, lean mass index (LMI), derived as the ALM divided by the height squared, increased significantly (P < 0.001). BMD increased significantly with osteoporosis treatment (P < 0.05), while no significant differences were observed between the osteoporosis treatment and control groups in the changes to ALM or fat mass. Conclusions ALM was decreased, while LMI was significantly increased. This contradictory result seems to be affected by age-related height loss. Thus, the effect of height loss needs to be considered when sarcopenia is evaluated longitudinally using LMI.

Objectives: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. Methods: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4–71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann–Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. Results: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. Conclusions BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

Objectives: Although sarcopenia is diagnosed using appendicular lean mass (ALM), only a few long-term studies on changes in both ALM and bone mineral density (BMD) have been reported. The purposes of this study are to evaluate the changes in the parameters of lean mass and bone mass over a 10-year interval and to estimate the effects of osteoporosis pharmacotherapy on muscle. Methods: A total of 175 postmenopausal women were evaluated at baseline and after 10 years for BMD, ALM, fat mass, height, and weight. Subjects were further divided into an osteoporosis treatment group (n = 60) and a control group (n = 67) according to whether they had received pharmacotherapy for > 5 years. This was followed by propensity score matching for age, height, weight, and body mass index (BMI), and estimated parameters were compared between groups. Results: Height, weight, ALM, and fat mass decreased significantly over 10 years (P < 0.05). However, lean mass index (LMI), derived as the ALM divided by the height squared, increased significantly (P < 0.001). BMD increased significantly with osteoporosis treatment (P < 0.05), while no significant differences were observed between the osteoporosis treatment and control groups in the changes to ALM or fat mass. Conclusions ALM was decreased, while LMI was significantly increased. This contradictory result seems to be affected by age-related height loss. Thus, the effect of height loss needs to be considered when sarcopenia is evaluated longitudinally using LMI.

Objectives: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. Methods: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4–71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann–Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. Results: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. Conclusions BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

Objectives: The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. Methods: Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. Results: In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. Conclusions These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

Objectives: This study aimed to clarify the present system of palliative care at general hospitals, and to examine the factors contributing to the opioid consumption. Methods: We surveyed the palliative care system using a self-administered questionnaire, which was mailed to 37 general hospitals in Southern and Southwestern wards, Tokyo. Multiple regression analyses were used to identify the associations between explanatory variables and the opioid consumption. Results: Valid responses were obtained from 18 hospitals (response rate: 48.6%). 35% of the general hospitals didn’t have a palliative care team and most hospitals had no specialists. In multivariate analyses, factors associated with the opioid consumption were pharmacists with speciality of pharmaceutical palliative care, physicians joined the palliative care education program based on the Cancer Control Act of Japan, and the number of physicians’ correct answers of questions regarding palliative care. Conclusion: The survey showed that the higher consumption of opioids is significantly associated with the number of health care workers who have knowledge of palliative care. Our study suggested that the arrangement of palliative care experts might decrease the differences in the opioid consumption between general hospitals.