Heterologous expression and characterization of salt-tolerant ß-glucosidase from xerophilic Aspergillus chevalieri for hydrolysis of marine biomass.

A salt-tolerant exo-ß-1,3-glucosidase (BGL_MK86) was cloned from the xerophilic mold Aspergillus chevalieri MK86 and heterologously expressed in A. oryzae. Phylogenetic analysis suggests that BGL_MK86 belongs to glycoside hydrolase family 5 (aryl-phospho-ß-D-glucosidase, BglC), and exhibits D-glucose tolerance. Recombinant BGL_MK86 (rBGL_MK86) exhibited 100-fold higher expression than native BGL_MK86. rBGL_MK86 was active over a wide range of NaCl concentrations [0%-18% (w/v)] and showed increased substrate affinity for p-nitrophenyl-ß-D-glucopyranoside (pNPBG) and turnover number (kcat) in the presence of NaCl. The enzyme was stable over a broad pH range (5.5-9.5). The optimum reaction pH and temperature for hydrolysis of pNPBG were 5.5 and 45 °C, respectively. rBGL_MK86 acted on the ß-1,3-linked glucose dimer laminaribiose, but not ß-1,4-linked or ß-1,6-linked glucose dimers (cellobiose or gentiobiose). It showed tenfold higher activity toward laminarin (a linear polymer of ß-1,3 glucan) from Laminaria digitata than laminarin (ß-1,3/ß-1,6 glucan) from Eisenia bicyclis, likely due to its inability to act on ß-1,6-linked glucose residues. The ß-glucosidase retained hydrolytic activity toward crude laminarin preparations from marine biomass in moderately high salt concentrations. These properties indicate wide potential applications of this enzyme in saccharification of salt-bearing marine biomass.

The inclusion of nuclear area improves the Paris system for reporting urinary cytology.

OBJECTIVE: The Paris System for Reporting Urinary Cytology (TPS) is a well-known urinary diagnostic model; however, occasional false-positives are a problem. To address this issue, we developed an improved algorithm (IA), based on additional cytological features, for TPS diagnosis. METHODS: Cytological features were evaluated in 29 hard-to-classify cases, including 22 malignant cases and seven benign cases, using image analysis. The optimal IA was determined using the area under the receiver operating characteristic curve as an index. Re-evaluation was performed by applying measured values to the TPS and IA algorithms. RESULTS: Using TPS, 12 of the 22 malignant cases were reassigned to a more appropriate category, and the remaining 10 malignant cases remained hard-to-classify. Two of the seven benign cases were classified as suspicious for high-grade urothelial carcinoma, and the remaining five benign cases remained in the original category. The IA, which included nuclear area as a parameter, showed the same diagnostic sensitivity as TPS, and three of the seven benign cases were reassessed as negative. Thus, the positive and negative predictive values of the IA were higher than those of TPS (84.6% and 100% vs 75.9% and 0%). CONCLUSIONS: The newly developed IA is a practical algorithm with which to address the limitations of TPS and thus may contribute to improved diagnostic accuracy.

Clinical features of polymyalgia rheumatica patients in Japan: Analysis of real-world data from 2015 to 2020.

OBJECTIVES: To assess clinical features in patients with polymyalgia rheumatica (PMR) in Japan by the International Classification of Disease (ICD)-10 code assignment. METHODS: Demographics, treatment patterns, and concomitant diseases (identified using ICD-10 code only) in patients who were assigned the PMR ICD-10 code M35.3 at least once between 1 January 2015 and 31 December 2020 were aggregated from a nationwide medical information database owned by the Health, Clinic, and Education Information Evaluation Institute. RESULTS: The cumulative number of patients with PMR was 6325 (mean [standard deviation] age, 74.3 [11.4] years; male:female, 1:1.3). Most patients were >50 years (96.5%) with >33% between 70 and 79 years. Glucocorticoids were prescribed in ∼54% of patients within 30 days of PMR code assignment. All other drug types were prescribed in <5% of patients. Hypertension, diabetes mellitus, rheumatoid arthritis, and osteoporosis were noted in >25% and giant cell arteritis in 1% of patients. During the study period, 4075 patients were newly assigned the PMR code and 62% were prescribed glucocorticoids within 30 days. CONCLUSIONS: This is the first retrospective real-world data analysis describing the clinical features of PMR in a large patient population from Japan. Further studies of prevalence, incidence, and clinical features are warranted in patients with PMR.

The significance of information and communication technology education via tablets in college of physical therapy.

[Purpose] This study aimed to clarify whether collaborative learning could be promoted via information and communication technology education using tablets at college of physical therapy. [Participants and Methods] An online survey was conducted to evaluate collaborative learning among 81 first-year students at the Department of Physical Therapy actively using tablets in classes (six specific categories). [Results] The Friedman test had significant results, and a significant primary effect was observed between each questionnaire item. Following this, the Bonferroni test was performed for multiple comparisons, with significant differences were observed among certain items. [Conclusion] We reported employing tablets in the classroom positively impacted collaborative learning. Here, among the evaluations of collaborative learning, the items with the best results corresponded mainly to communication activation between students.

Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH. METHODS: In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide. RESULTS: The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference -93.5 dyn·s·cm-5; 95% CI -156.8 to -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue. CONCLUSION: Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

The potential diagnostic significance of crypt differentiation in gastric dysplasia.

AIMS: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.

The relationship between children's somatotypes, motor examination results, and motor skills: assessing 6- to 10-year-olds.

[Purpose] Childhood motor disorders and obesity are major health problems and concerns in children today. We performed a physical examination to test the motor system and motor ability of elementary school children based on their body types. [Participants and Methods] The obesity levels of 161 elementary school students aged six to ten were calculated based on the gender, age, and standard weight for each height category to classify them into somatotype groups, and analyze the relationships among the results of four motor examination items, Physical Fitness Test, and body composition analysis for two groups. [Results] More obese children were unable to reach the floor while performing a standing forward bend compared to non-obese children. In addition, a significant difference was found in the assessment of motor performance while performing side-to-side jumping, and obese children showed better values. Many endomorphic children were also unable to touch the floor with their hands when performing the standing forward bend. Among the items from a physical fitness test, the side-to-side hops revealed significant differences. There were no somatotype-related differences in the results of the body composition analysis. [Conclusion] In children aged six to ten years, somatotype differences were not associated with motor skill or body composition.

Effects of pain-related catastrophic thinking, anxiety, and depression on pain intensity and quality of life in patients with knee and low back pain.

[Purpose] We aimed to examine the effects of pain-related catastrophic thoughts and anxiety/depression on pain intensity and quality of life (QOL), and how these effects (relationships) vary with pain location, in outpatients with chronic pain. [Participants and Methods] We recruited 14 participants with low back pain (2 males and 12 females) and 14 with knee joint pain (3 males and 11 females). We used the following evaluation tools: the visual analog scale (to evaluate pain intensity), pain catastrophizing scale (in which scores are categorized into helplessness, rumination, and magnification), Hospital Anxiety and Depression Scale (for psychodynamic evaluation), and a questionnaire for QOL evaluation. [Results] There was no difference in pain intensity between the groups. The "low back pain" group showed a positive correlation between pain intensity and anxiety, while the "knee pain" group showed a positive correlation between pain intensity and helplessness. The "low back pain" group showed a negative correlation between health in QOL assessment items and helplessness, and between health and magnification. However, in the "knee pain" group, there was a negative correlation between health and rumination, between health and anxiety, and between positive mental attitude and magnification. [Conclusion] Mental status varied depending on the pain location, regardless of the intensity of the pain. This suggests that a psychological approach dependent on pain location is needed during physical therapy.

Preoperative nutritional status is independently associated with wound healing in patients undergoing open surgery for ischemic tissue loss.

OBJECTIVES: The aim of this study was to determine the relationship between preoperative nutritional status and wound healing in patients undergoing surgical reconstruction for ischemic tissue loss. METHODS: The preoperative nutritional status of patients who underwent surgical reconstruction for ischemic tissue loss for the years 2011-2018 was retrospectively estimated using the Controlling Nutritional Status (CONUT) score. Patients were allocated to two groups: Group I, normal nutrition or mild malnutrition (CONUT score ≤4), and Group II, moderate-to-severe malnutrition (CONUT score ≥5). Wound healing was set as the primary endpoint and major amputation and death as the secondary endpoints. The wound healing, limb salvage, and overall survival rates were calculated after two years using the Kaplan-Meier method, and Cox proportional hazards regression analysis was performed to determine which variables were independently associated with these outcomes. RESULTS: Forty-eight patients with missing values for the CONUT score were excluded. A total of 174 limbs in 147 patients were studied (Group I: 115 limbs in 100 patients; Group II: 59 limbs in 47 patients). The mean duration of the study was 519 ± 270 days. The Kaplan-Meier curves showed that wound healing in Group I was superior to that in Group II (Group I vs. II: two-year wound healing, 97% vs. 79%; time to 50% wound healing, 83 vs. 150 days, p < 0.001), and multivariate analysis showed that the CONUT score was an independent predictor of wound healing (hazard ratio, 0.63; 95% confidence interval, 0.41-0.98; p = 0.038). CONCLUSIONS: Patients with better preoperative nutritional status are more likely to experience wound healing earlier than those with excessive malnutrition.

Restricted mean survival time as a summary measure of time-to-event outcome.

Many clinical research studies evaluate a time-to-event outcome, illustrate survival functions, and conventionally report estimated hazard ratios to express the magnitude of the treatment effect when comparing between groups. However, it may not be straightforward to interpret the hazard ratio clinically and statistically when the proportional hazards assumption is invalid. In some recent papers published in clinical journals, the use of restricted mean survival time (RMST) or τ-year mean survival time is discussed as one of the alternative summary measures for the time-to-event outcome. The RMST is defined as the expected value of time to event limited to a specific time point corresponding to the area under the survival curve up to the specific time point. This article summarizes the necessary information to conduct statistical analysis using the RMST, including the definition and statistical properties of the RMST, adjusted analysis methods, sample size calculation, information fraction for the RMST difference, and clinical and statistical meaning and interpretation. Additionally, we discuss how to set the specific time point to define the RMST from two main points of view. We also provide developed SAS codes to determine the sample size required to detect an expected RMST difference with appropriate power and reconstruct individual survival data to estimate an RMST reference value from a reported survival curve.

Development of a Surgical Sponge Counting System Using Radiographic Images.

Background. Retention of surgical sponges in patients is a relatively frequent medical malpractice. To prevent it, the surgical sites are scanned using X-ray. However, using radiography in the operation room induces X-ray exposure for both patients and staff. To prevent such issues, a novel sponge counting system was developed. Each surgical sponge used in common hospitals is composed of single radiopaque fibers. Methods. The proposed system scans surgical sponges to estimate their fiber length (EFL) and returns the number of it. In this study, an optimal image acquisition protocol was determined that allows an accurate count of sponges. X-ray doses and multi-angle image procedures were tested. Results. Measurement trials were performed and compared for both dry and blood-soaked sponges. As a result, the X-ray dose of 50 kV and 600 µA and the acquisition of 180 images per sample yielded an accurate EFL. The 180-image protocol achieved good performance in this study and allowed counting of one package of 10 sponges in 226 seconds. For these settings, a significant correlation was found between the actual number of sponges and the estimated fiber lengths. Additionally, the performance of the system was similar for either dry or blood-soaked items. Conclusion. The proposed system could accurately count surgical sponges and is a promising option in preventing the accidental retention of surgical sponges.

[Quality Control of Medical Instruments and Cleaning Water].

PURPOSE: Herein we aimed to investigate the degradation of surgical instruments in our hospital and how water quality affects the rate of metal corrosion. MATERIALS AND METHODS: We observed 279 stainless steel instruments, and determined the presence of damage like metal corrosion or scale formation. We also measured the concentrations of chloride(Cl-)and silicate(SiO44-)ions in the water used for cleaning in our operating rooms, including tap water from the city water supply and reverse-osmosis(RO)filtered water. RESULT: Pitting corrosion was observed on 71% of the instruments we investigated. The concentration of Cl- was 0.7mg/L in tap water and 0.1mg/L in RO water, while the concentration of SiO44- was 0.3mg/L in both the tap and RO water. DISCUSSION: Of the dissolved ions Cl- and SiO44-, Cl- is more of a concern, as it causes pitting corrosion over time, while SiO44- causes scale formation. Considering the typical water quality in the operating-room environment, degradation must be monitored for the general maintenance of metal surgical instruments.

Prognostic factor of the two-year mortality after revascularization in patients with critical limb ischemia.

Purposes The aim of this study was to evaluate the risk factors for the two-year survival after revascularization of critical limb ischemia. Methods Between 2008 and 2012, 142 patients underwent revascularization. A retrospective analysis was performed to measure the risk factor. Results A total 85 patients underwent surgical revascularization, 31 patients underwent endovascular therapy while 26 patients underwent hybrid therapy. By multivariate analysis, the following variables were considered to be risk factors: ejection fraction <50 % (HR, 3.14; 95% CI, 1.22-7.95; P = 0.02), serum albumin level <2.5 g/dL (HR, 3.45; 95% CI, 1.01-11.7; P = 0.04) and nonambulatory status (HR, 4.11; 95% CI, 1.79-9.70; P < 0.01). The two-year survival rate of the patients with no risk factors was 85.5%, while the patients with at least one risk factor had an unfavorable prognosis (one; 56.7%, two; 45.4%). Conclusions The nonambulatory status, serum albumin level <2.5 g/dL and ejection fraction <50% were the risk factors for the two-year mortality after revascularization in critical limb ischemia patients. These risk factors may be useful for the treatment strategy of critical limb ischemia patients.

Radial forces of stents used in thoracic endovascular aortic repair and bare self-expanding nitinol stents measured ex vivo - Rapid rescue for obstruction of the innominate artery using bare self-expanding nitinol stents.

Purpose Our objective was to compare the radial forces of several stents ex vivo to identify stents suitable for rescue of the unexpected coverage of aortic arch branches in thoracic endovascular aortic repair. Methods We measured the radial forces of two types of self-expanding bare nitinol stents (E-luminexx and Epic) used singly or as double-walled pairs, and of three endoprostheses used in thoracic endovascular aortic repair (TEVAR, Gore c-TAG, Relay, and Valiant) by compressing the stent using an MTS Instron universal testing machine (model #5582). We also examined the compressive effects of the TEVAR endoprostheses and the bare nitinol stents on each other. Results The radial force was greater in the center than at the edge of each stent. In all stents tested, the radial force decreased incrementally with increasing stent diameter. The radial force at the center was two times greater when using two stents than with a single stent. In the compression test, only E-luminexx used as a pair was not compressed after compressing a Relay endoprosthesis by 12 mm. Conclusion Two E-luminexx stents are appropriate to restore the blood flow if a TEVAR endoprosthesis covers the innominate artery following innominate-carotid-left subclavian arterial bypass.

Rho-Kinase Inhibition During Early Cardiac Development Causes Arrhythmogenic Right Ventricular Cardiomyopathy in Mice.

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty changes of the right ventricle, ventricular arrhythmias, and sudden death. Though ARVC is currently regarded as a disease of the desmosome, desmosomal gene mutations have been identified only in half of ARVC patients, suggesting the involvement of other associated mechanisms. Rho-kinase signaling is involved in the regulation of intracellular transport and organizes cytoskeletal filaments, which supports desmosomal protein complex at the myocardial cell-cell junctions. Here, we explored whether inhibition of Rho-kinase signaling is involved in the pathogenesis of ARVC. APPROACH AND RESULTS: Using 2 novel mouse models with SM22α- or αMHC-restricted overexpression of dominant-negative Rho-kinase, we show that mice with Rho-kinase inhibition in the developing heart (SM22α-restricted) spontaneously develop cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, resulting in premature sudden death, phenotypes fulfilling the criteria of ARVC in humans. Rho-kinase inhibition in the developing heart results in the development of ARVC phenotypes in dominant-negative Rho-kinase mice through 3 mechanisms: (1) reduction of cardiac cell proliferation and ventricular wall thickness, (2) stimulation of the expression of the proadipogenic noncanonical Wnt ligand, Wnt5b, and the major adipogenic transcription factor, PPARγ (peroxisome proliferator activated receptor-γ), and inhibition of Wnt/ß-catenin signaling, and (3) development of desmosomal abnormalities. These mechanisms lead to the development of cardiac dilatation and dysfunction, myocardial fibrofatty changes, and ventricular arrhythmias, ultimately resulting in sudden premature death in this ARVC mouse model. CONCLUSIONS: This study demonstrates a novel crucial role of Rho-kinase inhibition during cardiac development in the pathogenesis of ARVC in mice.

Elective endovascular vs. open repair for abdominal aortic aneurysm in octogenarians.

PURPOSE: The purpose of this study was to investigate the operative mortality and short-term and midterm outcomes of treatment of abdominal aortic aneurysm in Japanese patients over 80 years of age. METHODS: Between January 2007 and December 2011, 207 patients underwent elective repair of infrarenal abdominal aortic aneurysms. Comorbidities, operative morbidity and mortality, midterm outcomes were analyzed retrospectively. RESULTS: The average age (endovascular aneurysm repair, 84.4 ± 0.3; open, 82.8 ± 0.3, P < 0.01) and the percentage of hostile abdomen (endovascular aneurysm repair, 22.2%; open repair, 11.1%, P < 0.05) were higher in the endovascular aneurysm repair group. Percentage of outside IFU was higher in open repair (endovascular aneurysm repair, 38.5%; open repair, 63.3%, P < 0.01). The cardiac complication (endovascular aneurysm repair, 0%; open repair, 5.6%, P < 0.01) and length of postoperative hospital stay (endovascular aneurysm repair, 10.3 ± 0.8 days; open, 18.6 ± 1.6 days, P < 0.05) were significantly lower in the endovascular aneurysm repair group. There were no differences in operative mortality (endovascular aneurysm repair, 0%; open, 1.1%, P = 0.43) and the aneurysm-related death was not observed. The rate of secondary interventions (EVAR, 5.1%; open repair, 0%, P < 0.01) and midterm mortality rate were much higher in the endovascular aneurysm repair group. CONCLUSIONS: Endovascular aneurysm repair is less invasive than open repair and useful for treating abdominal aortic aneurysm in octogenarians; however, open repair can be acceptable treatment in the inappropriate case treated by endovascular aneurysm repair.

Radial force measurement of endovascular stents: Influence of stent design and diameter.

BACKGROUND AND PURPOSE: Angioplasty and endovascular stent placement is used in case to rescue the coverage of main branches to supply blood to brain from aortic arch in thoracic endovascular aortic repair. This study assessed mechanical properties, especially differences in radial force, of different endovascular and thoracic stents. MATERIAL AND METHODS: We analyzed the radial force of three stent models (Epic, E-Luminexx and SMART) stents using radial force-tester method in single or overlapping conditions. We also analyzed radial force in three thoracic stents using Mylar film testing method: conformable Gore-TAG, Relay, and Valiant Thoracic Stent Graft. RESULTS: Overlapping SMART stents had greater radial force than overlapping Epic or Luminexx stents (P < 0.01). The radial force of the thoracic stents was greater than that of all three endovascular stents (P < 0.01). CONCLUSIONS: Differences in radial force depend on types of stents, site of deployment, and layer characteristics. In clinical settings, an understanding of the mechanical characteristics, including radial force, is important in choosing a stent for each patient.

Management of surgical instruments with radio frequency identification tags.

PURPOSE: To prevent malpractices, medical staff has adopted inventory time-outs and/or checklists. Accurate inventory and maintenance of surgical instruments decreases the risk of operating room miscounting and malfunction. In our previous study, an individual management of surgical instruments was accomplished using Radio Frequency Identification (RFID) tags. The purpose of this paper is to evaluate a new management method of RFID-tagged instruments. DESIGN/METHODOLOGY/APPROACH: The management system of RFID-tagged surgical instruments was used for 27 months in clinical areas. In total, 13 study participants assembled surgical trays in the central sterile supply department. FINDINGS: While using the management system, trays were assembled 94 times. During this period, no assembly errors occurred. An instrument malfunction had occurred after the 19th, 56th, and 73 th uses, no malfunction caused by the RFID tags, and usage history had been recorded. Additionally, the time it took to assemble surgical trays was recorded, and the long-term usability of the management system was evaluated. ORIGINALITY/VALUE: The system could record the number of uses and the defective history of each surgical instrument. In addition, the history of the frequency of instruments being transferred from one tray to another was recorded. The results suggest that our system can be used to manage instruments safely. Additionally, the management system was acquired of the learning effect and the usability on daily maintenance. This finding suggests that the management system examined here ensures surgical instrument and tray assembly quality.

[Efficacy and Prognostic Factors of Estracyt ® in Patients with Castration-Resistant Prostate Cancer (CRPC) : From the Data Analysis of Estracyt ® Special Drug Use Investigation].

Estracyt○R (estramustine phosphate) is a medical drug for prostate cancer with cytotoxic activity causing disruption of microtubule organization and indirect androgen production suppressing activity by its metabolite, estradiol. Based on the data obtained from the Estracyt○R Special Drug Use Investigation which surveyed the clinical efficacy and safety of Estracyt○R in patients with prostate cancer whose relapse of prostate cancer after combined androgen blockade (CAB) therapy was confirmed, we evaluated the progression-free survival, prognostic factor, decrease in prostate specific antigen (PSA) level and safety. This surveillance was conducted at 147 institutions nationwide between October, 2010 and September, 2013 and clinical efficacy was evaluated in 239 cases and safety in 329 cases. The median duration of progression-free survival, PSA progression-free survival and PSA response were 169 days (95%CI, 142-190), 197 days (95%CI, 169-267) and 385 days, respectively. The decrease in PSA level was observed in 125 cases (52.3%). Rate of PSA decline ＞50 and ＞25% were 18.4 and 43.1, respectively, and rate of PSA best response (PSA decline ＞ 50%) was 32.6%. Multivariate analysis demonstrated that long duration of prior CAB therapy, Estracyt○R - pretreatment PSA value and bone metastasis influenced progression-free survival significantly. Adverse events were observed in 127 cases (38.6%). The major adverse events were anorexia which was observed in 35 cases (10.9%), gastrointestinal disorders observed in 32 cases (9.7%), abnormal laboratory test values observed in 31 cases (9.4%) and gynecomastia observed in 16 cases (4.9%). These results suggest the clinical efficacy and safety of Estracyt○R for chemotherapy-naïve castration-resistant prostate cancer (CRPC), and Estracyt○R is regarded as one of the treatment options for patients with CRPC, especially for patients who had long duration of prior CAB therapy.