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BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T(50) value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T(50) value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T(50) value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T(50) value was changed from 116 minutes (interquartile range, 90–151) to 131 minutes (interquartile range, 102–176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98–174) to 166 minutes (interquartile range, 127–218) in the etelcalcetide group. The increase in T(50) value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T(50) value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156

Many studies have been made on ABO-compatible kidney transplants following hematopoietic stem cell transplantation. However, there have been few reports on ABO-incompatible kidney transplantation following hematopoietic stem cell transplantation (HSCT). We report on the case of a successful ABO-incompatible kidney transplantation with high titers after bone marrow transplantation experienced no infectious episodes. The patient was a 38-year-old man with end-stage kidney disease resulting from interstitial nephritis induced by drug toxicity or graft-vs-host disease (GVHD). He had received allogeneic bone marrow transplantation from a human leukocyte antigen-identical unrelated donor to treat chronic myelogenous leukemia. The patient with high anti-B antibody titers (IgM 1:1024 IgG 1:256) received a desensitization protocol consisting of 2 doses of rituximab and 5 courses of plasmapheresis. The patient had prolonged depletion of circulating B cells 2 years after the transplant and was infected with cytomegalovirus viremia, pneumocystis jiroveci pneumonia, and adenovirus urinary tract infection at 2, 3, and 17 months post-transplant, respectively. Currently, at 6 years after his transplant, the patient has had no rejection and is in good clinical condition with only mild renal insufficiency. Our results suggest that ABO-incompatible kidney transplantation may be an effective renal replacement therapy for patients with end-stage kidney disease after HSCT, but desensitization in combination with immunosuppressants could lead to a state of over-immunosuppression, causing various infections.

Myeloid-derived suppressor cells (MDSCs) are one of the key players that contribute to immune evasion. The purpose of the present study was to investigate whether MDSCs could be a novel target for the treatment of cisplatin-resistant bladder cancer. We established cisplatin-resistant bladder cancer cell lines (MB49R, MBT-2R, and T24R) and evaluated chemokine expression and MDSC expansion. We also assessed the antitumor effect by depleting MDSCs with or without a α-PD-L1 antibody using MB49R xenograft models. The chemokine expression of CXCL1, CXCL2, and CCL2 increased in cisplatin-resistant cells compared to those in their parent strains. Monocytic MDSCs (Mo-MDSCs) were observed more frequently compared to polymorphonuclear MDSCs (PMN-MDSCs) in MB49R tumors. The immunosuppressive genes arginase 1 and iNOS were comparably expressed in each MDSC subtype. In vivo, combination therapy targeting both PMN- and Mo-MDSCs using α-Gr1 and α-Ly6C antibodies significantly reduced tumor volume with increased infiltration of CD8 T cells in the tumor. Finally, co-targeting pan-MDSCs and PD-L1 remarkably reduced the tumor growth. These findings suggest that targeting MDSCs might enhance the therapeutic effect of immune checkpoint inhibitors in cisplatin-resistant bladder cancers.

INTRODUCTION AND OBJECTIVE:In Japan, combined androgen blockade (CAB) with bicalutamide is widely used against advanced hormone-sensitive prostate cancer. Flutamide was widely used in clinical prac...

Introduction: Splenectomy had been previously performed in ABO-incompatible kidney transplantation to reduce the B cell pool. However, studies have shown that patients undergoing splenectomy may have a lifelong susceptibility to infection and mortality. Splenectomy may affect the incidence of cytomegalovirus (CMV) disease even at a very late stage after transplantation in ABO-incompatible recipients. Patients and Methods: Seven patients received their graft from an ABO-incompatible living donor at our institution and underwent splenectomy for B cell reduction. Among them, 3 recipients experienced very late-onset CMV disease approximately 10 years after their transplant and were enrolled in this study. Results: Very late-onset CMV disease occurred at 9 years and 9 months, 15 years, and 13 years and 5 months after transplantation, respectively. Two recipients suffered from CMV retinitis, while one experienced colitis. The age of the patients at onset of CMV disease was 69 years, 42 years, and 71 years, respectively. Conclusion: This may be the first report on very late-onset CMV disease after splenectomy in ABO-incompatible kidney transplantation. We should be aware that these recipients can experience very late-onset CMV disease even approximately 10 years after their transplant.

Alternative anti-androgen therapy (AAT) with flutamide after combined androgen blockade (CAB) therapy with bicalutamide for metastatic prostate cancer is common. However, no studies have compared enzalutamide without AAT with enzalutamide after AAT with flutamide as treatment for castration-resistant prostate cancer (CRPC). We aimed to compare the efficacies of flutamide and enzalutamide for CRPC. In our hospital, 55 patients were diagnosed with CRPC after CAB therapy and administered flutamide or enzalutamide between May 2014 and December 2017. Patients with flutamide failure were administered enzalutamide. We evaluated the (1) prostate-specific antigen (PSA) best response with initial therapy, (2) PSA progression-free survival with initial therapy (PSA-PFS), (3) PSA best response with enzalutamide therapy, (4) PSA-PFS of enzalutamide therapy, and (5) overall survival (OS). As first-line therapy, patients were administered enzalutamide (n = 29) or flutamide (n = 26). In the flutamide group, 18 patients showed disease progression and were administered enzalutamide. PSA best response was statistically higher in the enzalutamide group. PSA-PFS was significantly longer in the enzalutamide group [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.19–0.92, p = 0.024]. However, there was no significant difference in PSA best response with enzalutamide therapy and PSA-PFS between the first- and second-line enzalutamide therapies (HR 0.80, 95% CI 0.33–1.94, p = 0.62). There was no significant difference in OS between enzalutamide and flutamide groups (HR 1.85, 95% CI 0.53–6.42, p = 0.33). AAT with subsequent flutamide after CAB therapy with bicalutamide may be suitable for some CRPC patients.

Background Selective plasma exchange (SePE) is a new simple plasma exchange (PE) modality that enables removal of small and medium-sized molecules without removing larger substances such as coagulation factors. In this study, we examined the efficacy of SePE for removal of isoagglutinins in pre-transplant desensitization for ABO-incompatible (ABOi) kidney transplantation. Materials and methods A case series study was performed in 15 ABOi kidney transplant recipients (KTRs) who underwent SePE alone (7 cases) and SePE in combination with double-filtration plasmapheresis or simple plasma exchange (8 cases). The target processed plasma volume (PV) was set at 2 PV, and 5% albumin solution was used as the substitution fluid in all SePE sessions. Changes in isoagglutinin titers (IgG and IgM) and serum IgG, IgM, and fibrinogen levels were examined. We also compared the decrease in isoagglutinin titers between SePE and conventional methods (PE and double-filtration plasmapheresis). Results A total of 29 sessions of SePE were performed in the 15 KTRs. Isoagglutinin titers were controlled to ≤ 1:16 in all patients except for 2 with high isoagglutinin titers, and there were no cases of antibody-mediated rejection. SePE led to a median twofold decrease in isoagglutinin titers (IgG and IgM), with median IgG, IgM, and fibrinogen removal rates of 64.2, 11.7, and 25.5%, respectively. Side effects occurred in only 4 of the 29 sessions. Neither titer decreased after SePE in 30% of the sessions. However, the reductions in isoagglutinin titers in patients undergoing SePE were significantly less than those in patients treated with conventional methods. Conclusion Because SePE is less efficient in removing isoagglutinins compared to conventional methods, the use of SePE alone should be limited to patients with low isoagglutinin titers, and SePE in combination with conventional methods should be used for patients with high isoagglutinin titers. SePE may be a useful treatment option, if applied in appropriate cases, due to its lower cost (about half the price of PE using fresh frozen plasma in Japan) and fewer side effects. However, care is required because about 25% of fibrinogen is removed during SePE.

Background: Diabetes nephropathy is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The data are clear that kidney transplantation is superior to remaining on dialysis for patients with diabetes. However, there have been no reports on ABO-incompatible kidney transplantation in patients with ESKD due to diabetes nephropathy. Patients and Methods: We conducted a retrospective, observational study to investigate the clinical outcomes of ABO-incompatible kidney transplantation for patients with pre-existing diabetes nephropathy at our institution from April 2011 to October 2017. A total of 14 recipients were enrolled in this study. Results: All 14 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 89.9, and 89.9% at 1, 3, and 5 years, respectively. One patient died 20 months after transplantation with a functioning graft due to pancreas cancer. Two of the 14 patients (14.3%) developed biopsy-proven acute cellular rejection during the follow-up period. The median observation period was 32.0 months (range 5–83 months). Conclusion: ABO-incompatible kidney transplantation may be an acceptable renal replacement therapy for ESKD patients with diabetes.

Background/Aims: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. Materials: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. Results: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). Conclusion: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

// Satoshi Tamada 1 , Taro Iguchi 1 , Minoru Kato 1 , Jumpei Asakawa 1 , Kazuaki Kita 1 , Sayaka Yasuda 1 , Takeshi Yamasaki 1 , Yudai Matsuoka 2 , Kazuyuki Yamaguchi 2 , Kentaro Matsumura 2 , Ishun Go 2 , Tetsuji Ohmachi 2 and Tatsuya Nakatani 1 1 Department of Urology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545–8585, Japan 2 Department of Urology, Bell Land General Hospital, Naka-ku, Sakai City, Osaka 599–8247, Japan Correspondence to: Satoshi Tamada, email: s-tamada@med.osaka-cu.ac.jp Keywords: castration-resistant prostate cancer; combined androgen blockade; hormone-sensitive prostate cancer; progression; survival Received: September 19, 2018 Accepted: November 26, 2018 Published: December 11, 2018 ABSTRACT Purpose: The aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses. Materials and Methods: We examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8. Results: The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached). Conclusions: The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.

Aim To investigate whether hyperbaric oxygen (HBO) is effective for the pathophysiological findings in an IC/PBS-like mouse model induced by intravesical hydrogen peroxide (H2 O2 ). Methods Six-week-old ICR female mice (N = 16) were divided into four experimental groups: (1) sham control with intravesical vehicle instillation twice, and without subsequent treatment (N = 4); (2) H2 O2 instillation twice, followed by HBO (100% O2 , 2 ATA, 30 min per session) (N = 4); (3) H2 O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2 O2 instillation twice, followed by no treatment (N = 4). Body weight, voiding frequency, tidal voiding volume, and individual bladder pain threshold using the von-Frey test were measured. Whole body uptake of an inflammation-specific fluorescent pan-cathepsin was assessed by an in vivo imaging. Immunohistochemical staining and the mRNA expression of several biomarkers associated with chronic inflammation in resected bladders were evaluated. Results The HBO-treated group showed significant improvement in voiding frequency, tidal voiding volume, and the individual bladder pain threshold. Moreover, HBO markedly suppressed H2 O2 -induced inflammation, edema, and fibrosis in bladder wall, concomitant with a significant decrease in mRNA expressions of inflammation biomarkers and a significant increase in endothelial nitric oxide synthase expression. HBO also inhibited the expression of transient receptor potential channels induced by H2 O2 instillation. Conclusion These results suggest that HBO contributes to elimination of H2 O2 -induced long-lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.

【概要】糖尿病前段階かつ肥満である人は腎臓に負担がかかっていることを明らかにしました。糖尿病の合併症の代表として網膜症、腎症、神経障害があげられます。糖尿病は慢性腎臓病を発症し、透析を導入している患者の原疾患の40％以上を占めています。このような合併症を引き起こさないためには、早期発見・早期治療が肝要です。これまで糖尿病性腎症の前段階であっても腎臓に負担がかかっている可能性は推測されていましたが、実際にヒトで検討することは困難とされていました。研究グループは、合併症や既往歴、内服歴のない54名の腎移植ドナーを対象にGomezの式を用いて肥満度、インスリン抵抗性、糸球体内圧、アルブミン尿の関連性について検討しました。その結果、糖尿病前段階であっても肥満である人は糸球体内圧が高く、腎症の判断基準となるアルブミン尿が多いことが明らかになりました。本研究成果により、糖尿病前段階であっても腎臓への負担を把握することで慢性腎臓病を引き起こす前に防ぐことが期待されます。, Objecive : Little is known about the relationships between insulin resistance, intrarenal hemodynamics, and urinary albumin excretion (UAE) in humans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). The aim of the present study was to examine intrarenal hemodynamic abnormalities, insulin resistance, and UAE, in subjects with IFG and/or IGT. We hypothesized that intrarenal hemodynamic abnormalities would be associated with insulin resistance. RESEARCH DESIGN AND METHODS : Fifty-four kidney donors underwent 75 g oral glucose tolerance, and inulin and para-aminohippuric acid clearance testing. Insulin sensitivity index (ISI) was evaluated by the Matsuda Index. Intrarenal hemodynamic parameters were calculated by Gomez's formulae....

Introduction: The diagnosis of BK virus nephropathy is based on renal biopsy findings, and the diagnosis of presumptive BK virus nephropathy is made by sustained plasma BK virus DNA loads of > 4 log10 copies/ml. However, the BK virus plasma viral load cutoff of 4 log10 copies/ml may underestimate the diagnosis of BK virus nephropathy. In this study, we evaluated the clinical significance of BK viremia in kidney transplant recipients. Patients and Methods: From January 2010 to November 2015, we experienced 8 kidney transplant recipients who developed BK viremia. We retrospectively analyzed these recipients, focusing on the plasma BK viral load at onset of BK viremia, time to BK viremia after transplantation, frequency of BK virus nephropathy, and our treatment for BK viremia. Results: The median plasma BK virus polymerase chain reaction at the diagnosis of BK viremia was 1600 copies/ml (370–9400 copies/ml). The median time to BK viremia after transplantation was 10.9 months (1.4–67.9 months). Three patients were associated with BK virus nephropathy on biopsy. Clearance of BK viremia was observed in all of these cases after intervention. Conclusions: Our study demonstrated that intervention in BK viremia with a viral load of < 4 log10 copies/ml may be needed to prevent the development of graft dysfunction and BK virus nephropathy in kidney transplant recipients. Keywords: BK virus, BK viremia, Kideny transplantation, Mizoribine, Cyclosporine

Androgen signal has been recently suggested to be associated with the progression of bladder cancer. Steroid sulfatase (STS) is a steroid sulfate activation enzyme, considered to be one of the key enzymes in the androgen signaling pathway. However, the role of STS in bladder cancer has not been elucidated. The purpose of the present study was to determine the clinical and functional significance of STS in bladder cancer. Immunohistochemical analysis of surgical specimens obtained by radical cystectomy (n=114) demonstrated that overexpression of STS was associated with the invasion of bladder cancer, as evidenced by the incidence of STS-positive cancers (11.5 and 37.1% in non-muscle invasive and muscle invasive bladder cancers, respectively; P=0.003). STS-positive cancer demonstrated shorter recurrence-free survival and cancer-specific survival (P=0.0027 and 0.0030, respectively). Furthermore, knockdown of STS significantly reduced cell migration and invasion capacities of bladder cancer cells (P

// Satoshi Tamada 1 , Taro Iguchi 1 , Sayaka Yasuda 1 , Minoru Kato 1 , Takeshi Yamasaki 1 and Tatsuya Nakatani 1 1 Department of Urology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan Correspondence to: Satoshi Tamada, email: s-tamada@med.osaka-cu.ac.jp Keywords: molecular targeted therapy; renal cell carcinoma; Memorial Sloan Kettering Cancer Center criteria; metastasis; intermediate risk Received: April 23, 2018 Accepted: May 18, 2018 Published: June 12, 2018 ABSTRACT Objectives: To investigate the necessity of stratifying patients in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center (MSKCC) criteria in a real-world population of patients with metastatic renal cell carcinoma. Patients and Methods: We retrospectively analyzed 234 consecutively treated patients who had received molecular targeted drugs. We examined the difference between progression-free survival and overall survival among patients in the intermediate-risk group of MSKCC criteria. We divided the intermediate group into two subgroups as follows: patients positive for only one risk factor (Int-1) and those positive for two risk factors (Int-2) including performance status, serum hemoglobin level, time from diagnosis to treatment, and corrected calcium and lactate dehydrogenase levels. Next, we evaluated the association between the number of metastatic organs, the presence of pancreatic metastasis, Int-1 or Int-2 grouping, and overall survival. Results: The median overall survival was 41.2 months. The median overall survival of the favorable-, intermediate-, and poor-risk groups of the MSKCC criteria were 91.0, 33.6, and 15.2 months, respectively. Patient characteristics were similar between the Int-1 and Int-2 groups. Increased positivity for risk factors of MSKCC classification between the two groups was for performance status and serum hemoglobin level. Progression-free survival and overall survival of the Int-1 group were significantly higher than those of the Int-2 group. In Cox proportional stepwise multivariate analysis, the Int-1 and Int-2 classification was an independent risk factor for overall survival. Conclusion: Patients in the intermediate-risk group had different prognoses depending on the number of positive risk factors.

Background: Cancer-related fatigue is one of the most prevalent symptoms that patients with cancer experience, but the mechanisms underlying it are unknown. We aimed to quantify and mechanistically evaluate the improvement in fatigue related to administration of the Kampo medicine, Kamikihito. Materials and methods: Initially, we recruited outpatients with urological diseases and compared fatigue levels of 37 patients with cancer with a control group of 23 volunteers who had recovered completely from cancer or who were being treated for dysuria. Fatigue level was estimated using an autonomic function analyzer. Then, Kamikihito was administered to another 35 patients treated with hormone or antitumor therapy for prostate cancer and metastatic renal cell cancer. Subjective fatigue and other problems of the patients were assessed using the Chalder fatigue scale, the Center for Epidemiologic Studies Depression scale, and the Epworth sleepiness scale. Serum levels of derivatives of reactive oxygen species and biological antioxidant potential were also measured. Results: Patients in the cancer treatment group experienced more fatigue compared with the control patients when evaluated using an autonomic function analyzer. The group of 35 patients who were administered Kamikihito showed improved scores for fatigue, depression, and sleepiness. Autonomic nervous system balance was also improved with Kamikihito administration. The Kamikihito group also had significantly lower reactive oxygen species metabolite levels and significantly higher antioxidant potential. Conclusions: Fatigue was more serious in patients with cancer than in control patients. Kamikihito rescued this fatigue and improved anxiety and sleepiness. It restored autonomic nervous system balance and antioxidant function. Keywords: Autonomic nerve system, Cancer-related fatigue, Fatigue score, Japanese traditional herbal medicine, Oxidative stress

The aim of this study was to evaluate the efficacy and toxicities of second-line chemotherapy regimens with docetaxel and gemcitabine (GD), or paclitaxel and gemcitabine (GP) for advanced or metastatic urothelial carcinoma (UC) that did not respond to first-line platinum-based chemotherapy. From 2002 to 2017, 78 patients with metastatic UCs that progressed after platinum-based chemotherapy were treated with either GD (n = 41) or GP (n = 37). We compared these two different regimens by analyzing their efficacy and toxicities in a retrospective manner. Of the 78 patients enrolled in this study, it was possible to determine treatment efficacy in 70; the proportion of patients with objective response and disease control were 8.6 (9/70) and 54.3% (38/70), respectively. The median progression-free survival and overall survival in the total population (GP and GD) were 3.5 (95% CI 0.6–53.3) and 9.6 months (95% CI 1.2–53.3), respectively. There was no significant difference between the two regimens (GD or GP) regarding survival outcomes. Treatment-related adverse events were mostly manageable, but one patient died as a result of febrile neutropenia. The presence of liver metastasis and anemia (Hb

Objectives To report the treatment outcomes of patients with extrinsic ureteral obstruction treated with metallic stents and to identify the factors predicting stent failure. Methods A total of 52 patients with extrinsic ureteral obstruction as a result of malignancy (66 ureters) were treated with metallic stents (Resonance® ) and included in the study. The median observation period was 118 days. Results The median survival time of these patients was 210 days, and the stent patency rate was 86.0% at 6 months and 60.0% at 1 year. Eight (15.4%) patients underwent nephrostomy as a result of stent failure. The occlusion rate of bilateral ureteral obstructed cases was significantly higher than that of unilateral cases. There was no correlation between the preoperative serum creatinine level, causes of ureteral occlusions (compression by tumor, lymph node metastasis, peritoneal dissemination), obstructed site (upper, middle, lower ureter) and stent failure. Conclusions Metallic stents are excellent in maintaining patency compared with the conventional stents. Therefore, they can be used as first-line treatment of malignant ureteral obstructions.

Androgen deprivation therapy is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration‐resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR‐V7), one of the causes of CRPC, is correlated with resistance to a new‐generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full‐length AR (AR‐FL), but little is known about its effects against CRPC cells expressing AR‐V7. In this study, we investigated the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer cell line LNCaP95 that expresses AR‐V7, and explored the mechanism by which Hsp70 regulates AR‐FL and AR‐V7 expression. Quercetin and VER155008 decreased cell proliferation, increased the proportion of apoptotic cells, and decreased the protein levels of AR‐FL and AR‐V7. Furthermore, VER155008 decreased AR‐FL and AR‐V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry identified Y‐box binding protein 1 (YB‐1) as one of the molecules regulating AR‐FL and AR‐V7 at the transcription level through interaction with Hsp70. VER155008 decreased the phosphorylation of YB‐1 and its localization in the nucleus, indicating that the involvement of Hsp70 in AR regulation might be mediated through the activation and nuclear translocation of YB‐1. Collectively, these results suggest that Hsp70 inhibitors have potential anti‐tumor activity against CRPC by decreasing AR‐FL and AR‐V7 expression through YB‐1 suppression.

Hyperuricemia has been reported to affect renal hemodynamics. In a recent study, both low and high levels of serum uric acid (SUA) were found to be associated with loss of kidney function. The goal of this study was to evaluate the relationship between SUA levels and intrarenal hemodynamic parameters in healthy subjects, using plasma clearance of para-aminohippurate (CPAH) and inulin (Cin). Renal and glomerular hemodynamics were evaluated by simultaneous measurements of CPAHand Cinin 48 healthy subjects (54.6 ± 13.4 yr). Intrarenal hemodynamic parameters, including efferent and afferent (Ra) arteriolar resistance, were calculated using Gómez’s formulas. Relationships of SUA levels with these intrarenal hemodynamic parameters were examined. In quadratic regression analysis, SUA levels had a significant inverse U-shaped relationship with Cin( P < 0.0001, R2= 0.350) and CPAH( P = 0.0093, R2= 0.188) and a U-shaped relationship with Ra( P = 0.0011, R2= 0.262). In multiple regression analysis with normal (3.5–6.0 mg/dl) and mildly low or high (6.0 mg/dl) SUA levels entered as dummy variables of zero and one, respectively, mildly low or high SUA levels were significantly and independently associated with Ra(β = 0.230, P = 0.0403) after adjustment for several factors ( R2= 0.597, P < 0.0001). Both mild hyperuricemia and mild hypouricemia are significantly associated with increased Ra, although weakly. The increase in Rain subjects with mild hyperuricemia or hypouricemia may be related to renal hemodynamic abnormalities, possibly leading to a decline in renal function.

Rat bladder cancer is nearly always papillary non-invasive urothelial carcinoma (UC). To establish an animal model mimicking invasive UC that arises from papillary non-invasive UC in the bladder, male human c-Ha-ras proto-oncogene transgenic rats (Hras128) were treated with 0.05% N-butyl-N-(hydroxybutyl)nitrosameine (BBN) in their drinking water and/or 0.1% phenylethyl isothiocyanate (PEITC) in their diet as follows: BBN (8 weeks)→PEITC (8 weeks); PEITC (8 weeks)→BBN (8 weeks); BBN alone (16 weeks); PEITC alone (16 weeks); and no treatment. At the end of week 16, the highest incidence of invasive UC was observed in the BBN→PEITC group. Therefore, we used Hras128 rats treated with BBN followed by PEITC as a model of invasive bladder cancer to identify invasion-associated proteins. Proteome analysis was performed to compare the protein profiles of invasive and non-invasive UC in Hras128 rats. We identified 49 proteins that were either overexpressed or underexpressed in invasive UC but not in non-invasive UC. Immunohistochemical analysis of carbonic anhydrase 2 (CA2), an overexpressed protein, showed that the relative number of CA2-positive UC was significantly higher for invasive UC compared to non-invasive UC in rats. Moreover, the incidence of CA2-positive cancers was also significantly higher for human muscle-invasive bladder cancer (MIBC) compared to non-MIBC (NMIBC) and was positively associated with the progression of NMIBC. Our findings indicate that CA2 is an invasion-associated factor and suggest that it could serve as a potential therapeutic molecular target for bladder cancers.

We have performed selective plasma exchange (SePE) as apheresis before ABO-incompatible kidney transplantation since 2015. In this study, we divided the SePE sessions into two groups, those using albumin alone (Group A) and those partially using fresh frozen plasma (FFP) (Group F), and compared their clinical efficacies. A total of 58 sessions of SePE (Group A: n = 41, Group F: n = 17) were performed in 30 recipients of ABOi kidney transplantation during the study period and the decrease in isoagglutinin titers, changes in the levels of serum IgG and IgM as well as coagulation factors (fibrinogen, factor XIII), and incidence of side effects were retrospectively compared. There was a more significant decrease of isoagglutinin titers in Group F compared to Group A. Immunoglobulins and coagulants were replenished in Group F. Meanwhile, the incidence of side effects was significantly higher in Group F. SePE using FFP, which can effectively decrease isoagglutinins titers and replenish immunoglobulin and coagulation factors, may be a beneficial treatment modality as apheresis before ABO-incompatible kidney transplantation, in spite of a disadvantage that there are many side effects.

A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared. There was no recurrence at 2 years, and axitinib was discontinued.

Objectives To investigate the prevalence of frailty, and the relationship of frailty based on the Kihon Checklist criteria with dialysis duration before transplantation and time after transplantation in kidney transplant recipients. Methods This study was a single-center, cross-sectional investigation carried out on kidney transplant recipients. To examine the association between the total Kihon Checklist score with time after transplant and dialysis duration before transplant, the multivariable proportional odds logistic regression model was used with adjustment for age, sex, body mass index, estimated glomerular filtration rate and serum albumin levels. Results Out of 205 kidney transplant recipients enrolled in this study, frail, prefrail and robust recipients accounted for 11.2%, 26.8% and 62.0%, respectively. Dialysis duration before transplantation was associated with frailty, but time after transplant was not associated with frailty. Conclusions The prevalence of frailty in kidney transplant recipients is approximately 11%, and it is associated with the duration of pretransplant dialysis. These findings suggest that a shorter dialysis duration might be beneficial for preventing frailty in kidney transplant recipients.

Passenger lymphocyte syndrome is a rare but important disease in which the donor lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. It occurs in ABO blood group-mismatched solid-organ and/or bone marrow transplant. We report a case of passenger lymphocyte syndrome occurring after ABO-incompatible kidney transplant. The recipient received rituximab as a desensitization protocol. On posttransplant day 18, the recipient showed a fall in her hemoglobin levels without identifiable bleeding source and an elevation of total bilirubin. Although hemolytic anemia was suspected, schizocytes on the peripheral smear were not observed. Anti-B-type antibodies were detected, and a diagnosis of passenger lymphocyte syndrome was confirmed. The patient was successfully treated with steroid pulse therapy, an increase of mycophenolate mofetil to 2 g/day, and conversion from cyclosporine to tacrolimus. To our knowledge, this is the first demonstration of passenger lymphocyte syndrome in an ABO-incompatible kidney recipients receiving rituximab.

Malnutrition is an important risk factor for the development of sarcopenia. Recently, phase angle (PhA) obtained from the bioelectrical impedance analysis is increasingly becoming known as a nutritional status marker and may be considered a good indicator to identify elderly patients at risk of sarcopenia. In this study, we investigated the prevalence of sarcopenia and the relationship between sarcopenia and PhA or body mass index (BMI) as nutritional factors, and evaluated the discrimination performance of these nutritional factors for sarcopenia in 210 kidney transplant recipients. The median age was 55 years and 11.1% had sarcopenia. This prevalence of sarcopenia was lower than previous reports in kidney transplant recipients, maybe because of the differences in sarcopenia definitions and population demographics such as age, sex, race, and comorbidities. Both PhA and BMI were negatively correlated with sarcopenia after adjusting for age, sex, dialysis vintage, time after transplant, presence of diabetes mellitus, hemoglobin, estimated glomerular filtration rate, and the other nutritional factor. The discrimination performance for PhA and BMI had enough power to detect sarcopenia. These results suggest that PhA and BMI can be used in clinical practice to predict sarcopenia in kidney transplant patients.

This review summarizes the latest insights on ABO‐incompatible living‐donor renal transplantation. Desensitization protocols and clinical outcomes were investigated, and a comparison was made with kidney‐paired donation, which is not permitted in Japan for ethical reasons. Although renal transplantation is greatly beneficial for most patients with end‐stage kidney disease, many of these patients must remain on dialysis therapy for extended periods due to the scarcity of organs from deceased donors. ABO blood type incompatibility was once believed to be a contraindication to renal transplantation due to the increased risk for antibody‐mediated rejection and early graft loss attributable to isoagglutinins. Recently, pretransplant desensitization strategies, such as removal of isoagglutinins and antibody‐producing cells, have achieved successful outcomes, although it remains unclear whether graft survival and patient morbidity are equivalent to those for ABO‐compatible renal transplantation. The present review suggested that ABO‐incompatible living‐donor renal transplantation might be a favorable radical renal replacement therapy for patients with end‐stage kidney disease.

Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly unknown. Enrolled in this study were 94 kidney transplant recipients and 134 kidney transplant donors, as the healthy controls, who were treated at our institution. The 75 g-oral glucose tolerance test (OGTT) was performed in the recipients, and the healthy controls received an OGTT before donor nephrectomy. We assessed the prevalence of glucose intolerance including impaired fasting glucose and/or impaired glucose tolerance, as well as insulin secretion and insulin resistance using the homeostasis model assessment, and compared the results between the two groups. Multivariate analysis after adjustment for age, gender, body mass index, estimated glomerular filtration rate, and systolic blood pressure showed that the prevalence of glucose intolerance, insulin resistance, insulin secretion, and 2 h plasma glucose levels were significantly higher in the kidney transplant recipients compared to the healthy controls. Elevation of insulin secretion in kidney transplant recipients may be compensatory for increase of insulin resistance. Impaired compensatory pancreas &beta, cell function may lead to glucose intolerance and NODAT in the future.

Enzalutamide is an oral androgen receptor targeted agent that has been shown to improve survival in PREVAIL trials and has been approved for patients with chemo-naive metastatic castration-resistant prostate cancer (CRPC). Meanwhile, flutamide is a non-steroidal oral anti-androgen that was commonly used before the approval of bicalutamide. The objective of the OCUU-CRPC study is to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative anti-androgen therapy (AAT) after combined androgen blockade (CAB) therapy that included bicalutamide in patients with CRPC. A total of 100 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day, 4 × 40 mg capsules once daily) and flutamide (375 mg/day; 3 × 125 mg tablets thrice daily) groups. The primary endpoint for the drug efficacy is the response rate of prostate-specific antigen (PSA) (i.e., the ratio of patients whose PSA declined by ≥50% from baseline) at 3 months. Meanwhile, the secondary endpoints are PSA progression rate at 3 and 6 months, PSA response rate at 6 months, change in quality of life, PSA progression-free survival, and safety. The patient registration started in January 2015 and will end in March 2018, and the follow-up period is 6 months after the last patient registration. The main result will be reported in March 2019. In the OCUU-CRPC study, we compare the efficacy and safety of enzalutamide or alternative AAT with flutamide in participants with CRPC who were previously treated with a CAB therapy with bicalutamide. The expected results of this study will be that enzalutamide is superior to flutamide in terms of PSA response. A longer time to disease progression with enzalutamide over flutamide may translate to better overall survival. However, flutamide may be more accessible for patients owing to its lower cost than enzalutamide. The OCUU-CRPC study was prospectively registered at clinicaltrials.gov ( NCT02346578 , January 2015) and University Hospital Medical Information Network ( UMIN000016301 , January 2015).

Hyperbaric oxygen therapy is a promising medical technology that delivers oxygen to targeted tissues at high pressure to increase the amount of dissolved oxygen in the blood. Over the past three decades, hyperbaric oxygen has been used in a variety of conditions, including radiation-induced tissue injuries, non-healing states with ischemia and malignant neoplasms. In the field of urology, hyperbaric oxygen has also been applied to some pathological conditions (e.g. radiation-induced hemorrhagic cystitis, Fournier gangrene, interstitial cystitis, male infertility, acute kidney injury and urological cancers). In normal and injured tissues, hyperoxia from hyperbaric oxygen therapy contributes to anti-inflammation, angiogenesis through endothelial proliferation, enhanced fibroblastic activity, increased lymphocyte and macrophage activity, and bactericidal effects with the aim of wound repair. In cancerous tissues, the enhanced supply of oxygen into the hypoxic cancer cells can exert inhibitory effects on factors that contribute to their aggressiveness (e.g. cell survival, escape from apoptosis, epithelial-to-mesenchymal transition and tumor immunotolerance), and sensitize the tumor to radiation therapy and chemotherapy. However, further research, including multicenter clinical studies, is essential for determining the role of hyperbaric oxygen therapy in refractory urological diseases that are resistant to conventional therapies.

Immunotherapy based on blockade of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has shown promising clinical activity for renal cell carcinoma (RCC) patients; however, the most effective use of these agents in combination with conventional targeted therapy remains to be resolved. Here we evaluated the therapeutic efficacy of the combination of the mTOR inhibitor everolimus (EVE) and anti-PD-L1 using an immunocompetent mouse model of RCC. We first assessed the in vitro effect of EVE on PD-L1 expression in the human 786-O and mouse RENCA RCC cell lines and found that EVE upregulated PD-L1 expression in these RCC cell lines. We then treated RENCA tumor-bearing mice with EVE and found that PD-L1 expression was also increased in tumor cells after EVE treatment. To determine the antitumor effects of EVE alone, anti-PD-L1 alone, and EVE in combination with anti-PD-L1, we evaluated their antitumor effects on RENCA tumor-bearing mice. A significant decrease in the tumor burden was observed in the EVE alone but not in the anti-PD-L1 alone treatment group compared with the control group. Importantly, the combination of EVE with anti-PD-L1 significantly reduced tumor burden compared with the EVE alone treatment, increasing tumor infiltrating lymphocytes (TILs) and the ratio of cytotoxic CD8+ T cells to TILs. The results of the present study demonstrated that anti-PD-L1 treatment enhanced the antitumor effect of EVE in a mouse model, supporting a direct translation of this combination strategy to the clinic for the treatment of RCC.

Background: Despite advances in immunosuppressant medications, improvement in long-term survival for kidney transplant recipients has been more difficult to achieve. In fact, the number of patients with failing grafts who must either return to dialysis or undergo a second transplant is increasing. Second transplantation is associated with reduced mortality rates compared to remaining on dialysis after an initial graft loss. Nowadays, excellent ABO-incompatible kidney transplant outcomes have been achieved. However, there have been no reports on ABO-incompatible kidney transplantation as a second transplant. Patients and Methods: Three patients who received their graft from an ABO-incompatible living donor at our institution as a second transplant were enrolled in this study. We focused on immunosuppressive therapy for second ABO-incompatible kidney transplantation, donor-specific antibody status before the second transplant, patient and graft survivals, and complications. Results: All 3 patients successfully underwent ABO-incompatible kidney transplantation as a second transplant with a follow-up period of 141, 39, and 24 months. Patient and graft survival rates were 100%. Conclusions: ABO-incompatible kidney transplantation may be an acceptable treatment for patients who need a second renal replacement therapy after their initial graft failure.

Background Peritoneal dialysis (PD) access is important for patients undergoing PD. However, one of the potential complications of peritoneal dialysis access is damage to the dialysis tubing. Although most dialysis tubing damage is due to human error, there have been reports of damages attributed to pets owned by the patients. Much of the damage caused by pets has been attributable to cat biting or scratching, whereas the present case is an extremely rare case of dialysis tubing damage caused by a pet cockatoo. Case presentation A 65-year-old male with end-stage renal disease due to diabetic nephropathy who had been undergoing continuous ambulatory peritoneal dialysis (CAPD) for 6 years was admitted to our hospital with the chief complaint of dialysis tubing damage. While the patient was playing with his pet cockatoo on his belly after taking it out of its cage, the bird bit into his dialysis tubing of his transfer set without him realizing it, thus damaging the tube. The patient noticed that his dialysis tubing was leaking and realized that it had been damaged. He folded the end of the damaged tube, secured it with a rubber band to prevent further leakage, and made an emergency visit to our hospital. Upon inspection, we found that the dialysis tubing was completely disconnected, 28 cm from the metal connector of the connection tube. After consultation, the damaged tube was replaced. As a preventive measure for peritonitis, antibiotics were administered orally for 1 week (oral levofloxacin, 250 mg every 48 h). The patient was instructed to be careful when handling his cockatoo, and his CAPD treatment has been continued without incident to date. Conclusion This is a rare case report of PD tubing damage caused by a cockatoo kept at home. It may be necessary to pay sufficient attention to PD equipment damage by birds in PD patients keeping large birds, such as cockatoos.

Background Successful pregnancy outcomes after in vitro fertilization in kidney transplant recipients have been reported, but few cases of successful pregnancy after ABO-incompatible kidney transplantation have been described. Herein, we report on a successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient with rituximab, focusing on the changes in immunity. Case presentation A 35-year-old woman with end-stage kidney disease caused by IgA nephropathy was referred for kidney transplantation and successfully underwent an ABO-incompatible living-donor kidney transplant using rituximab from her 66-year-old father at the age of 36. Because she and her husband desired childbearing, they received fertility treatments, and embryo cryopreservation was performed before transplantation. Two years after the transplant, she desired pregnancy. Although immunoglobulin levels such as IgG, IgA and IgM had recovered to almost normal range, the peripheral CD19+ cells and CD20+ cells remained depleted. At 6 months after conversion from mycophenolate mofetil to azathioprine, frozen embryo transfer was performed during the hormone replacement cycle. At 37 weeks and 4 days gestation, a healthy baby girl weighing 2220 g was delivered by cesarean section for arrest of labor. There were no complications in both the recipient and her baby during the perinatal period. At 5 years after the transplant, the recipient has had no major complications including rejection or infection. Conclusions It is possible for women receiving ABO-incompatible kidney transplantation with rituximab to successfully become pregnant and deliver a heathy baby after in vitro fertilization, if IgG levels recover to normal range despite depleted peripheral blood B cells.

This retrospective study compared the outcomes of sequential therapy using sunitinib followed by axitinib or the mammalian target of rapamycin (mTOR) inhibitors (everolimus or temsirolimus). Among 234 patients treated with molecular-targeted drugs for metastatic renal cell carcinoma, we selected 137 patients treated with sunitinib as the first-line therapy. We then compared patients treated with axitinib (n = 52) or mTOR inhibitors (n = 31), as the second-line treatment, and investigated the progression-free survival (PFS) and overall survival (OS). The PFS of axitinib-treated patients (median 8.7 months) was superior to that of mTOR inhibitors-treated patients (median 3.4 months; P = 0.001). Additionally, the OS from baseline of axitinib-treated patients (median 69 months) was superior to that of mTOR inhibitors-treated patients (median 33.4 months; P = 0.034). A multivariate analysis was performed with the following factors: the drugs used for the second-line treatment, the Memorial Sloan Kettering Cancer Center risk classification during the initial treatment, whether the discontinuation of the first-line treatment was due to adverse events, and whether the duration of response of the first-line treatment was less than 6 or 12 months. Importantly, the drugs used for the second-line treatment and Memorial Sloan Kettering Cancer Center risk classification were independent factors. Our findings suggest that axitinib works better than mTOR inhibitors after the first-line treatment with sunitinib.

This minireview focuses on the current knowledge about the introduction of everolimus (EVL), a mammalian target of rapamycin inhibitor, with calcineurin inhibitor (CNI) elimination or minimization in kidney transplant recipients at a late posttransplant stage. Within, we have summarized two major clinical trials, ASCERTAIN and APOLLO, and seven other retrospective or nonrandomized studies. In the open-label multicenter ASCERTAIN study, the estimated glomerular filtration rate (eGFR) at 24 mo after conversion was not significantly different between three groups-EVL with CNI elimination, CNI minimization and continued CNI unchanged-at a mean of 5.4 years after transplantation. However, recipients with baseline creatinine clearance higher than 50 mL/min had a greater increase in measured GFR after CNI elimination. In the open-label multicenter APOLLO study, adjusted eGFR within the on-treatment population was significantly higher in the EVL continuation group than in the CNI continuation group at 12 mo after conversion at a mean of 7 years posttransplantation. Other studies on recipients without adverse events and already having satisfactory renal function showed favorable graft function by EVL late-induction with CNI elimination or reduction. These studies showed that chronic allograft nephropathy, CNI nephrotoxicity, CNI arteriolopathy, cancer and viral infection (especially cytomegalovirus infection) may be good indications for late conversion to EVL.

Background: The growth in the end-stage kidney disease (ESKD) population has been predominantly in the older adult population. In Japan, ABO-incompatible kidney transplantation has become an acceptable treatment option. However, few studies have been conducted on elderly ABO-incompatible kidney transplantation. Patients and Methods: Seventeen patients aged 60 years and older who received their grafts from ABO-incompatible living donors at our institution between December 2006 and September 2016 were enrolled in this study, and the outcome of these recipients was evaluated. Results: All 17 patients underwent successful kidney transplantation. Both overall patient and graft survival rates were 100, 100, and 83.3% at posttransplant 1, 3, and 5 years respectively. Six of the 17 patients (35.3%) had an episode of biopsy-proven acute cellular rejection. Two patients who developed steroid- and deoxyspergualin-resistant acute rejection required anti-human thymocyte immunoglobulin. Conclusion: ABO-incompatible kidney transplantation may be an effective radical renal replacement therapy for elderly patients with ESKD, although it could be a high-risk procedure.

Since the introduction of molecular targeted agents for the treatment of metastatic renal cell cancer (mRCC), several treatment outcomes, including those from our facilities, have been reported. However, the outcome of these drugs, classified by the metastatic organs, is not well known. The present study reported the treatment results of molecular-targeted agents as classified by the metastatic organ at Osaka City University Graduate School of Medicine. A total of 180 consecutively treated patients who had received molecular targeted agents for metastatic renal cancer for 3 or more months were retrospectively analyzed. The overall survival was calculated and compared according to the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, the number of metastatic organs, and metastatic lesions. The median overall survival of patients with mRCC treated by molecular targeted agents was 34 months. A significant difference in survival rate between groups was found according to the MSKCC criteria. Patients with single metastatic organ lived significantly longer compared with those with metastases in multiple organs. Patients with pancreatic metastasis had a good response to molecular targeted drugs. Pancreatic metastasis, the number of metastatic organs, and MSKCC criteria were independent risk factors for overall survival. Treatment of mRCC by molecularly targeted agents did not show any difference by metastatic organs except for the pancreas, although its efficacy depends on the number of metastatic organs and the MSKCC classification.

The aim of our retrospective study was to evaluate the 5-year survival and time to castration resistant prostate cancer in patients with hormone sensitive prostate cancer treated with the gonadotropin releasing hormone antagonist, degarelix. Another aim was to evaluate the effects of changing the treatment from degarelix to a gonadotropin releasing hormone agonist after achieving stable disease control, on the clinical and oncological outcomes.Our analysis was based on the data of 108 patients with prostate cancer who were treated with degarelix. Of these, the treatment was changed from degarelix to a gonadotropin releasing hormone agonist in 57 patients (changed group), and the treatment with degarelix was continued in the other 51 (continued group). The overall 5-year survival was statistically superior in the changed (96.6%) group than that in the continued (74.1%) group (Degarelix is effective in the treatment of prostate cancer. Degarelix therapy can also be safely changed to a gonadotropin releasing hormone agonist without any adverse clinical or oncological effects.L’objectif de notre étude rétrospective était d’évaluer la survie à 5 ans et le délai de transition du cancer de la prostate hormono-sensible au cancer de la prostate résistant à la castration chez des patients porteurs d’un cancer de la prostate hormono-sensible qui étaient traités par un antagoniste de la gonadolibérine, le dégarélix. Un autre objectif était d’évaluer les effets sur les résultats cliniques et oncologiques du remplacement du dégarélix par un agoniste de la gonadolibérine après obtention d’un état stable et contrôlé.Notre analyse repose sur les données de 108 patients atteints d’un cancer de la prostate traités par dégarélix. Parmi ceux-ci, le traitement par dégarélix a été remplacé par un agoniste de la gonadolibérine chez 57 (groupe modifié), et le traitement par dégarélix a été poursuivi chez les autres patients (groupe inchangé). La survie globale à 5 ans était statistiquement plus élevée pour le groupe modifié (96.6%) que pour le groupe inchangé (74,1%;Le dégarélix est. efficace dans le traitement du cancer de la prostate. Le traitement par dégarélix peut aussi être remplacé en toute sécurité par un agoniste de la gonadolibérine sans aucun effet clinique ou oncologique indésirable.Antagonistes et inhibiteurs de la gonadolibérine, Agoniste de la gonadolibérine, Cancer de la prostate, Dégarélix, Résistant à la castration.

Introduction: Patients aged 60 years and older stand for the fastest growing group of patients with end-stage renal disease worldwide, and the need for kidney transplants among this population is rising. In Japan, living donor kidney transplantation is mainly performed to deal with the severe shortage of deceased donors, and the number of spousal transplants is currently increasing. Patients and Methods: A total of 164 patients with ESRD underwent living donor kidney transplantation at our institution, of whom 21 patients aged 60 years and older had spousal kidney transplantation. ABO-incompatible kidney transplantation was performed in 5 of the 21 cases. We analyzed these recipients. Results: Patient and graft survival rates were 100%. The incidence of acute rejection was 23.8%. Eight patients experienced cytomegalovirus viremia, two patients experienced Pneumocystis jiroveci infection, and one experienced bacterial pneumonia. Two patients developed cancers and underwent curative operation after transplantation. Conclusions: Elderly kidney transplantation from spousal donors is associated with age-related immune dysfunction, which may develop infections and malignancies and could be immunologically high risk due to the high rate of ABO-incompatibility and poor histocompatibility. An effort to minimize the adverse effect of immunosuppression and to reduce the risk of acute rejection may be needed for an excellent long-term outcome.

BACKGROUND Rituximab induces long-lasting B cell depletion in the peripheral blood and increases the levels of proinflammatory cytokines associated with regulatory B cell depletion. Previous reports showed that B cell-related cytokine release after administration of rituximab may induce acute cellular rejection (ACR) and delayed-onset neutropenia. The present study was conducted to investigate the correlation between acute rejection and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. MATERIAL AND METHODS From June 2006 to July 2015, 47 patients with chronic renal failure received ABO-incompatible renal transplant with rituximab induction at Osaka City University Hospital. All 47 patients underwent plasmapheresis due to removal of anti-A/B antibodies and administration of rituximab, and their transplants were carried out successfully. We investigated the correlation between ACR and delayed-onset neutropenia in ABO-incompatible renal transplant recipients who underwent administration of rituximab for 1 year after transplantation. RESULTS Fourteen patients (29.8%) experienced ACR (group A), and 33 recipients did not develop ACR (group B). The frequency of delayed-onset neutropenia was higher in group A than in group B (p=0.0503). Multivariate logistic regression analysis revealed that the frequency of ACR correlated significantly with the prevalence of delayed-onset neutropenia. CONCLUSIONS Our results indicated that ACR in ABO-incompatible renal transplant recipients receiving rituximab was associated with delayed-onset neutropenia.

Objectives To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1-blocker naftopidil. Methods A total of 177 male patients with nocturia were included in the present study and randomized to morning or evening dosing of naftopidil. The International Prostate Symptom Score, quality of life index and nocturia quality of life index were compared between the two study groups at 12 weeks. Results A total of 143 patients (morning group: n = 70, evening group: n = 73) were analyzed as a result of the dropout of 34 patients because of failure to give consent, adverse events and failure to attend. Nocturia, quality of life index and nocturia quality of life index at 12 weeks were significantly better in the evening group compared with the morning group. In a multivariate model, both the dosing time of naftopidil and the initial nocturia quality of life index were significantly associated with change in nocturia quality of life index. Conclusions Evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms.

Objective: In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxelbased chemotherapy. Methods: Men (aged � 20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: � 5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with � 1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a � 50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. Results: Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by � 1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (.20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. Conclusions: Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical trial registration no: NCT01795703.

Purpose To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. Materials and methods This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. Results and limitations Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, −0.6 ± 0.9 in IM twice/day, and −0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. Conclusions A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

Aims The renin–angiotensin system (RAS) plays an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to investigate intrarenal RAS activity in patients with type 2 diabetes (T2DM). Methods We measured urinary angiotensinogen, a reliable biomarker of intrarenal RAS activity, in 14 controls without T2DM, 25 T2DM patients without nephropathy, 11 chronic kidney disease (CKD) patients without T2DM and 46 CKD patients with T2DM. Associations between urinary angiotensinogen and clinical parameters were examined. Results Compared with the controls, urinary [angiotensinogen:creatinine] were significantly higher in T2DM patients without nephropathy (4.70±2.22 vs. 8.31±5.27μg/g, p =0.037). Age, hemoglobin A1c (HbA1c) and fasting plasma glucose correlated significantly and positively with the log{urinary [angiotensinogen:creatinine]} ( r =0.632, p =0.007; r =0.405, p =0.027; r =0.583, p =0.003, respectively) in T2DM patients without nephropathy. In contrast, the urinary [angiotensinogen:creatinine] were not significantly different between CKD patients with and without T2DM (22.7±27.8 vs. 33.5±40.8μg/g, p =0.740); although they were significantly higher when compared with non-CKD patients. In the CKD patients with T2DM systolic blood pressure, serum creatinine, estimated glomerular filtration rate and urinary [albumin:creatinine] correlated significantly with the log{urinary [angiotensinogen:creatinine]} ( r =0.412, p =0.004; r =0.308, p =0.037; r =−0.382, p =0.001; r =0.648, p Conclusions Our findings indicate that poor glycemic control is significantly associated with intrarenal RAS activity in T2DM patients without nephropathy, and that decreased renal function is significantly associated with intrarenal RAS activity in CKD patients with T2DM.

BACKGROUND NEDD9 is one of the Crk-associated substrate (Cas) family proteins that mediate downstream signaling processes including cytoskeletal organization, cell-cycle and tumorigenesis. While NEDD9 plays a crucial role in epithelial–mesenchymal transition (EMT), the functional mechanism underlying NEDD9-mediated EMT in prostate cancer (PCa) remains uncertain. METHODS The expression levels of NEDD9 and its downstream molecules in PC-3, LNCaP, and VCaP cells exposed to transforming growth factor-β (TGF-β) were determined by western blotting. The invasion of these cells with ectopic overexpression of NEDD9 or silencing of NEDD9 expression was measured by transwell invasion assay. Human tissue samples comprising 45 PCa specimens and ten specimens of normal prostatic tissue were used for immunohistochemical (IHC) analysis of NEDD9 expression. RESULTS Both NEDD9 and its downstream signaling molecules associated with EMT were strongly induced by TGF-β in PCa cells. PC-3 cells with stable overexpression of NEDD9 had a mesenchymal phenotype and significantly enhanced cell invasion, despite their decreased cell proliferation. Knockdown of endogenous NEDD9 expression completely diminished TGF-β-triggered tumor invasion in several PCa cell lines. The IHC data revealed a significant positive correlation between the NEDD9 staining score and tumor aggressiveness (e.g., Gleason grade, serum PSA level). The NEDD9 staining score in primary PCa with bone metastasis was significantly higher than that in PCa without metastasis. CONCLUSIONS NEDD9 may be a key mediator involved in TGF-β-mediated EMT and cell motility in PCa cells and a novel target in the treatment of metastatic PCa and prevention of spread of localized PCa cells to other organs. Prostate 74:901–910, 2014. © 2014 Wiley Periodicals, Inc.