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Acute kidney injury (AKI) due to rhabdomyolysis occurs because of renal ischemia or acute tubular necrosis due to the deposition of myoglobin casts in the renal tubules. Donors with AKI due to rhabdomyolysis are not contraindication for transplantation. However, the dark red kidney raises concerns about renal hypofunction or primary nonfunction after transplantation. We report the case of a 34-year-old man with a 15-year history of hemodialysis for chronic renal failure due to congenital anomalies of the kidney and urinary tract. The patient received a renal allograft from a young woman who suffered cardiac death. The serum creatinine (sCre) level of the donor at the time of transport was 0.6 mg/dL, and renal ultrasonography revealed no abnormalities in renal morphology or blood flow. Her serum creatine kinase level increased to 57,000 IU/L 58 h after femoral artery cannulation, and sCre level worsened to 1.4 mg/dL, suggesting AKI due to rhabdomyolysis. However, since the urine output of the donor was maintained, the sCre elevation was thought to be nonproblematic. The allograft had a dark red appearance at the time of procurement. The perfusion of the isolated kidney was good, but the dark red color did not improve. A 0-h biopsy showed flattening of the renal tubular epithelium and absence of the brush border and myoglobin casts in 30% of the renal tubules. Rhabdomyolysis-related tubular damage was diagnosed. Hemodialysis was discontinued on postoperative day 14. Twenty-four days after the operation, the transplanted kidney function progressed favorably (sCre 1.18 mg/dL), and the patient was discharged. Protocol biopsy 1 month after transplantation showed disappearance of myoglobin casts and improvement in renal tubular epithelial damage. The patient’s sCre level was approximately 1.0 mg/dL 24 months after transplantation, and he is doing well without complications.

The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

INTRODUCTION: The aim of this study is to characterize health related quality of life (HRQOL) in Japanese patients after bladder cancer surgery and to perform cross-cultural comparison between Japanese and American patients. METHODS: Firstly, we cross-sectionally assessed HRQOL of 371 patients in Japan using the Bladder Cancer Index (BCI-Japanese). HRQOL of the four groups of patients (native bladder without intravesical therapy, native bladder with intravesical therapy, cystectomy with ileal conduit, and cystectomy with neobladder) were assessed. Secondly, we compared the Japanese with the American cohort (n = 315) from the original BCI paper. After adjusting for age and gender, the differences in each BCI subdomain score was analyzed. RESULTS: Among Japanese patients, the urinary domain function score was significantly lower among the cystectomy with neobladder group, compared to the cystectomy with ileal conduit group (p

Purpose To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients. Patients and methods The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group. Results The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, 50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses. Conclusions The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib.

Background: Radical prostatectomy for de novo prostate cancer (PCa) among kidney transplant (KT) recipients (KTRs) can be challenging because of the location of the renal allograft, which may make robot-assisted radical prostatectomy (RARP) difficult to perform. In this study, we present the first case of RARP in a patient with two renal allografts in both iliac fossae. Case Presentation: A 72-year-old KTR was found to have organ-confined PCa. He had a first KT (in the right iliac fossa) 20 years ago, which he lost because of chronic allograft nephropathy, followed by a second KT (in the left iliac fossa) 8 years ago, which is now functioning well. We performed RARP with a right-nerve sparing technique. The surgical duration was 208 minutes, with an estimated blood loss of 50 mL and no intraoperative complications. The postoperative course was unremarkable. During the 21-month follow-up period, there was no incontinence or biochemical recurrence and the allograft function remained normal. Conclusion: RARP is feasible and can be performed safely in KT patients with two renal allografts in the pelvis.

Introduction We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. Methods The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. Results This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12–66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach’s alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = − 0.19). A missing value percentage of > 15% was associated with old age (p Conclusions Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

The present study aimed to evaluate the efficacy of the real‐world use of axitinib and to develop a prognostic model for stratifying patients who could derive long‐term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split‐sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model’s favorable risk group might derive a long‐term survival benefit from axitinib treatment., The accuracy of the overall survival predictions made after the initiation of axitinib treatment, area under the curve (AUC) values were calculated for each model. The adjusted AUC values at 12, 36, and 60 months after the initiation of axitinib were 0.77, 0.82, and 0.82, respectively, for the axitinib treatment prediction model, and 0.69, 0.67 and 0.56, respectively, for the International Metastatic Renal Cell Carcinoma Database Consortium model.

Objective To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. Methods Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan–Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. Results Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). Conclusions In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.

INTRODUCTION AND OBJECTIVE:Patients who are diagnosed with high grade Ta, T1, or any Tis are generally regarded as high-risk non-muscle invasive bladder cancer (HR-NMIBC) according to the several p...

Objectives: With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. Methods and materials: We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. Results: The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391). Conclusions: Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints. (C) 2021 The Authors. Published by Elsevier Inc.

In selected patients, long-term systemic chemotherapy could be performed with a 1–3-month drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the options for long-term disease control., Objective Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1–3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). Methods Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. Results The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1–29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. Conclusions In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Objectives: During the past 2 decades, in order to improve perioperative and ontological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. Materials and methods: A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. Results: A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/ 838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. Conclusions: Surgical complications related to RC still remain significant problems, despite the recent improvements in surgical techniques and perioperative care. NAC did not increase the complications. (C) 2021 The Authors. Published by Elsevier Inc.

We revealed prognostic factors in metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Performance status, C-reactive protein level and response to prior chemotherapy were prognostic indicators., Objectives The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Methods Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan–Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. Results The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. Conclusions The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

INTRODUCTION AND OBJECTIVES:High-risk non-muscle invasive bladder cancer (HR-NMIBC) (high grade Ta, T1, and any Tis in NCCN category) patients are at higher risk of both recurrence and progression ...

Objectives: This study investigated the relapse pattern and oncologic outcomes after laparoscopic nephroureterectomy with template-based lymph node dissection (LND) in patients with clinically node-negative (cN0) upper urinary tract urothelial carcinoma. The frequency of lymph node metastasis, including micrometastases, was also evaluated. Methods and materials: A total of 105 patients with cTa-3N0M0 upper urinary tract urothelial carcinoma were analyzed, all of whom underwent regional LND during laparoscopic nephroureterectomy. Of those patients, 96 (91%) underwent complete LND in accordance with an anatomical template-based rule. We collected patient characteristics, pathological data, and follow-up data from medical charts. Micrometastases were assessed by pan-cytokeratin immunohistochemistry. Nonurothelial recurrence-free survival and cancer-specific survival were estimated using the Kaplan-Meier method. Results: The median number of lymph nodes removed was 12 (range, 1-59). Lymph node metastasis was identified by routine pathological examination in 7 (7/105, 6.7%) patients. Pan-cytokeratin immunohistochemistry revealed micrometastases in 5 additional patients (pNmicro +: 5/105, 4.8%). Nonurothelial disease recurrence was observed in 21 (20%) patients at a median of 10 months (range: 1- 33) after surgery. Distant metastasis was dominant (15/105, 14.3%), followed by locoregional recurrence (5/105, 4.8%) and both (1/105, 0.95%). The 5-year nonurothelial recurrence-free survival rates were 84.8% for pN0, 53.3% for pNmicro+, and 19.1% for pN+ (3-sample log-rank test, P < 0.0001). The 5-year cancer-specific survival rates were 95.0% for pN0, 53.3% for pNmicro+, and 23.8% for pN+ (P < 0.0001). Conclusions: Our observation showed that template-based LND could contribute to precise disease staging and better local disease control probably by eliminating nodal disease, compared with previous studies. The survival impact and ideal management of pNmicro+ disease should be evaluated in a larger cohort. (C) 2020 The Authors. Published by Elsevier Inc.

INTRODUCTION AND OBJECTIVE:We developed a Japanese version of the Bladder Cancer Index (BCI) to measure HRQOL in Japanese patients treated with various surgical methods. In addition, we performed a...

427 Background: We developed a Japanese version of the Bladder Cancer Index (BCI) to measure HRQOL in Japanese patients treated with various surgical methods. In addition, we performed a cross-cultural comparison of sexual function and bother in bladder cancer patients between the United States and Japan. Methods: The Japanese version of the BCI was developed through a multistage process after a pilot study. Its reliability and validity were examined in Japanese bladder cancer patients via a cross-sectional analysis. The patients were enrolled from August 2016 to March 2018. They also completed the Japanese version of Short Form (SF)-12, the EuroQol five-dimension scale (EQ-5D), and the Functional Assessment of Cancer Therapy-Bladder (FACT-BL). We also compared the Japanese cohort with an American cohort; i.e., the validation cohort used to develop the original version of the English BCI. Results: In total, 371 patients with a median age of 72 years and a median disease duration of 29 months were enrolled. Of these patients, 221 underwent transurethral resection of the bladder tumor, and 150 underwent radical cystectomy. The internal consistency value was ≥0.7 for all subscales, except the bowel function subscale. Each BCI domain was poorly correlated with the SF-12 and EQ-5D, but moderately well correlated with the FACT-BL. The urinary function and bowel function scales exhibited minimal (2.1–9.7%) amounts of missing data, whereas relatively high (≥15%) levels of missing data were seen in items relating to urinary bother, bowel bother, sexual function, or sexual bother. A missing data value of ≥15% was correlated with higher age (p

We revealed the feasibility of lymph node dissection (LND) with a laparoscopic approach and the equivalent oncological outcome of laparoscopic nephroureterectomy compared with open nephroureterectomy when regional LND is performed., Objective To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. Methods We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan–Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Results A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan–Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. Conclusion Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.

Rhombohedral lithium titanium phosphate, LiTi 2 (PO 4 ) 3 , has been considered a suitable anode material for aqueous lithium-ion batteries. However, the electrochemical behaviors of pure lithium-rich polymorphs have not been described yet even Li-rich phase may show better electrochemical properties than conventional LiTi 2 (PO 4 ) 3 at the expense of somewhat lowered capacity. We have synthesized orthorhombic Li 1.5 Ti 2 (PO 4 ) 3 (OLTP) and rhombohedral LiTi 2 (PO 4 ) 3 (RLTP) via sol-gel reactions and studied their fundamental electrochemical properties using galvanostatic charge/discharge and cyclic voltammetry (CV). Their feasibility as anode materials in LiFePO 4 //Li x Ti 2 (PO 4 ) 3 configurations using aqueous electrolytes were also considered. The faster kinetics of the orthorhombic lithium titanium phosphate in this study were attributed to higher Li + diffusivity and electrical conductivity, making this material an attractive alternative for conventional rhombohedral LiTi 2 (PO 4 ) 3 .

To determine the appropriate template of regional lymph node dissection (LND) at the time of laparoscopic nephroureterectomy (LNU) for patients with clinically node- negative urothelial carcinoma of the upper urinary tract.This prospective study included 45 patients undergoing LND with LNU in accordance with our prospective rules regarding the area of LND. Perioperative, pathologic, and follow-up data were collected. Micrometastasis in lymph nodes (LNs) was later evaluated by immunohistochemistry (IHC). Recurrence-free survival (RFS) was calculated with the Kaplan-Meier method.The median number of LNs removed was 14 (range 1-33). One patient with pT3 disease had node metastasis based on routine pathologic examination, and IHC revealed micrometastases in two additional patients (pT2 in one and pT3 in one). Therefore, 15% (3/20) of patients with ≥pT2 disease had node disease. After surgery, six patients experienced minor complications (Grade 1 or 2), and Grade 5 gastrointestinal bleeding after aspiration pneumonia developed in one elderly male patient on the 45th postoperative day, which was not considered to be associated with LND. At the last follow-up, lung metastasis developed in four patients (pT1 in one, pT2 in one, and pT3 in two), and presacral lymph node metastasis developed in one patient with a lower ureteral tumor (pT2), which was not included in our prospective template for a lower ureteral tumor. LN recurrence within/ near the LND area was not observed in patients with pelvic/upper ureteral carcinoma. The 2-year nonurothelial RFS rate was 84%.We consider that the present template represents regional LNs for patients with clinically node-negative pelvic/upper ureteral carcinoma, while presacral LNs may be incorporated into the regional LND template for patients with clinically node-negative lower ureteral carcinoma.

Recently, LiVP2O7 has been investigated as a possible high-voltage substitute for Li2FeP2O7. However, its Na-equivalent, NaVP2O7, as an economic replacement for Li2FeP2O7 has not yet been well understood. Here, for the first time, we report the feasibility of NaVP2O7 as a 3.4 V cathode material for Na-ion batteries. Having a theoretical capacity of 108 mA h g−1, it shows an initial discharge capacity of 38.4 mA h g−1 at 1/20C (1C = 108 mA g−1) in the voltage range of 2.5–4.0 V. Our study suggests that part of the sodium ions in the lattice structure exist as structural stabilizers and bring lattice distortion upon desodiation. This study also shows that the title compound, NaVP2O7, suffers from high intrinsic internal resistance, which limits the phase transition kinetics between pristine NaVP2O7 and desodiated Na1−xVP2O7.

Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high-volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90-day mortality rate = 2%), which were compatible with reports from Western high-volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy. Objective To determine the type, incidence and severity of 90-day morbidity after radical cystectomy in our institution and our affiliated hospitals in accordance with a standard reporting methodology. At present, most studies on complications associated with open radical cystectomy are derived from Western academic high-volume centres and data from Japan and other Asian countries remain very limited. Patients and Methods The study comprised a retrospective multi-institutional study. The records were reviewed of 928 patients who underwent open radical cystectomy between 1997 and 2010. All complications within 90 days of surgery were categorized into 11 specific categories and graded in accordance with the modified Clavien system. Multivariate regression models were used to determine predictors of complications. Results At least one complication was observed in 635 (68%) patients and a major (grade 3–5) complication was observed in 156 (17%) patients. The most common complication categories were infectious (30%), gastrointestinal (26%), wound-related (21%) and genitourinary (15%). The 30-day mortality rate was 0.8% and the 90-day mortality rate was 2%. A multivariate regression model showed that previous cardiovascular comorbidity and type of urinary diversion (i.e. ileal conduit or neobladder) were significant factors for any and major complications. Conclusions Surgical complication-related radical cystectomy is significant and both previous cardiovascular comorbidity and the type of urinary diversion were found to be significant factors for any and major complications. The 90-day mortality rate was 2%, which is compatible with reports from Western high-volume centres.

Objectives: To evaluate the prognostic role of different clinico-pathological parameters in node-positive patients treated by radical cystectomy. Methods: A retrospective multi-institutional study of 435 patients who underwent radical cystectomy between 1990 and 2005 was carried out. Of them, pathological lymph node (LN) metastases were found in 83 patients. Sixty of these 83 patients, whose clinical information and follow-up data were available, were included in the analysis. Twenty-five patients had undergone adjuvant chemotherapy, whereas 35 had not. A Cox proportional hazards model was used to determine the impact of the following clinico-pathological parameters on patient survival: number of resected LNs, number of positive LNs, LN density (defined as the ratio of the number of positive LNs divided by the total number of resected LNs) and adjuvant chemotherapy. Results: Median follow-up for surviving patients was 41 months (range 4–138) after surgery. The median survival time for all patients was 22 months (95% confidence interval, 15–42 months). At multivariate analysis, LN density of 25% or less, adjuvant chemotherapy and pure urothelial carcinoma were independently significant predictors of survival. Conclusions: Lymph node density predicts survival in patients with node-positive bladder cancer.

OBJECTIVES To determine the role of lymph-node (LN) dissection in patients undergoing surgery for upper urinary tract (UUT) cancer. PATIENTS AND METHODS We reviewed the clinicopathological data from 312 patients with UUT cancer treated predominantly by nephroureterectomy. The relationship between clinical characteristics and cancer-specific survival (CSS) was analysed, focusing on node-related information. RESULTS In all, 166 patients had LN dissection while 146 did not (pNx). Multivariate analysis showed that T stage, grade and pN status were significant variables for CSS. The difference in survival between the pN0 and pNx groups remained significant in a multivariate analysis. The median (range) number of LNs removed was 6 (1–65). There was no significant difference in CSS between the 72 patients with fewer than six LNs removed and the 78 with six or more removed. CONCLUSIONS LN dissection is important for postoperative stratification of patients with UUT cancer because node-positive disease was one of the variables with a significant adverse effect on survival. In addition, the significant difference in survival between the pN0 and pNx groups might indicate a therapeutic benefit of LN dissection, although removing more LNs did not uniformly increase the probability of CSS.

If Th1 or Th2 polarization could be artificially manipulated, effective immune responses would be generated depending on nature of the targets. In this study we attempted to regulate CD40 expressions on dendritic cells (DCs) in order to modify the T cell response. It was found that reducing agents selectively inhibited surface expression of CD40 on DCs. This finding may provide a new strategy of DC-mediated modulation of the Th1/Th2 balance. It was also shown that NKT-produced Th1/Th2 cytokine balance was under control of negative feedback loop through DCs. Th1 cytokine-pretreated DCs mainly induced Th2 cytokine production, whereas Th2 cytokine-pretreated DCs induced Th1 cytokine production by alpha-galactosylceramide-stimulated NKT cells. The negative feedback regulation system could be applicable to therapeutics of various diseases based on immunological disorders.

Introduction The aims of this study were to show the 10-year results of voided urine cytology (VUC) performed using liquid-based cytology (LBC) with CytoRich Red and to discuss the factors that influence the sensitivity of low-grade urothelial neoplasia (LGUN) of the urinary bladder. Materials and method We calculated the sensitivity of VUC in 421 histologically confirmed cases included in the pathology database of Hokkaido Cancer Center in Japan and studied various factors influencing sensitivity. Results The cumulative sensitivity of VUC was 95.8% in 143 cases of primary high-grade urothelial carcinomas, compared with 59.5% in 74 cases of LGUN. These findings were only slightly different from the previous results of Koss et al. The sensitivity in LGUN, however, showed lower values in some conditions, including in secondary cases, with a lower frequency of examinations and smaller tumor volumes. LBC preparations allowed us to observe a greater number of tumor cells and cell clusters than conventional methods in LGUN cases. Conclusions The sensitivity of VUC can be improved by increasing the frequency of examinations and adopting a valid preparation method in order to augment the number of cells and cell clusters on individual glass slides. LBC preparations may allow cytopathologists to obtain a better sense for and understanding of the cytologic findings of LGUN.

INTRODUCTION AND OBJECTIVES: Surgeonand hospitalcase volume are identified as factors related with outcomes of surgical procedures. Radical cystectomy (RC), due to its major impact on the patient, might substantially benefit from centralization if this assumption were true. We aim to test this hypothesis in Spain, a country in which no lower limit nor centralization for radical cystectomy exists. METHODS: We performed a retrospective cohort review of patients undergoing RC in Spain during 2011 and 2012, accessing data from inpatient discharge forms (CMBD) of every patient operated on of radical cystectomy. CMBD is a mandatory file that is submitted to the Ministry of Health and provides information on patient’s demographics as well as morbidity and cause of discharge including death. Hospitals were stratified into volume quartiles depending on their 2-year cumulative cystectomy volume (very lowvolume 58). Hospitals were also categorized according to their size in beds and teaching facilities. A comparison with data in the literature was made. RESULTS: We analyzed 5,594 RCs in 266 centers of Spain during 2011 and 2012 (2,701 RCs in 2011 and 2,893 RCs in 2012). Mean age was 66.5 9.8 years and 84.7% were males. Mean hospital stay was 20.7 16.6 days. Mortality rate at 30, 60 and 90 days was 2.8%, 4.7% and 5.9%, respectively. 90-day mortality rate for very-low, low, medium and high-volume centers was 5.9%, 5.9%, 7% and 5.1%, respectively (p1⁄40.2). Hospital size and teaching facilities were not associated with mortality. A statistically significant difference was noted in the complications and readmission rate. These results compare favorably with reported multicenter series in the literature with 90-day mortality rate ranging from 4.2 to 7.9%. CONCLUSIONS: Our data do not support an urgent need for regionalization of radical cystectomy in our country. However, initiatives to improve surgical outcomes of radical cystectomy within individual national setting should be explored.

Objective: To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. Methods: A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed byopen surgery (n= 23) or laparoscopically (n=37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan–Meier method. Results: The median number of lymph nodes removed was 29 (range: 10–103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routinepathological examination. Afterexcluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n= 2, adenocarcinoma: n= 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P

The ability of extracellular stimuli to modulate dendritic cell (DC) activation of natural killer T (NKT) cells was not well understood. We investigated the effects of the T helper type 1 (Th1)/Th2-cytokine environment on DC induction of NKT cell-mediated cytokine production in mice. Pretreatment of myeloid DCs with Th1 or Th2 cytokines, interleukin (IL)-4 or interferon (IFN)-γ, led to the enhanced production of reciprocal cytokines by NKT cells (eg, IL-4 pretreatment led to the enhanced production of Th1 cytokines) in vitro and in vivo. Thus, the recognition of Th1 or Th2 cytokines by DCs acts as a negative feedback loop to maintain Th1/Th2-cytokine balance via NKT cell functions. Using these data, we manipulated cytokine levels and innate cytolytic activity in vivo to increase an antitumor response. This is the first description of a novel regulation system governing Th1/Th2 cytokine balance involving DCs and NKT cells. (Blood. 2005;106:1685-1693)

Aim To clarify prognostic factors of metatstatic urothelial carcinoma treated by systemic chemotherapy in real-world clinical practice in the Japanese population. Materials and methods A total of 228 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 were included in the present multi-institutional study. The gemcitabine plus cisplatin regimen was administered as first-line chemotherapy to 131 patients, whereas methotrexate, vinblastine, doxorubicin, and cisplatin or its modified regimen was given to 71 patients. Of the 228 patients, 119 received at least 2 different regimens and 22 underwent resection of metastases (metastasectomy). Multivariate survival analysis was performed using the Cox proportional hazards model. The characteristics included were age, sex, Eastern Cooperative Oncology Group performance status (PS), primary site, pathology of primary site, hemoglobin levels, lactate dehydrogenase levels, C-reactive protein levels, corrected calcium levels, estimated glomerular filtration rate levels, history of prior chemotherapy, metastatic sites, resection of primary site, number of metastatic organs, and metastasectomy. Results The median overall survival (OS) time was 17 months. On multivariate analysis, female sex, good Eastern Cooperative Oncology Group PS at presentation, hemoglobin level≥10 g/dl, and single organ metastasis were significant independent predictors of prolonged OS. For the survival effect of metastasectomy, the median OS time of the 22 patients with metastasectomy was 53 months, which was significantly longer when compared with patients not undergoing metastasectomy (15 mo). After adjustment for the 4 aforementioned prognostic factors, metastasectomy still remained significant (hazard ratio: 0.364, P = 0.0008). Conclusions Female sex, more favorable PS at presentation, hemoglobin level>10 g/dl, and single organ metastasis were favorable prognostic factors. In addition, metastasectomy was associated with long-term disease control.

What's known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high-volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90-day mortality rate = 2%), which were compatible with reports from Western high-volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy.To determine the type, incidence and severity of 90-day morbidity after radical cystectomy in our institution and our affiliated hospitals in accordance with a standard reporting methodology. At present, most studies on complications associated with open radical cystectomy are derived from Western academic high-volume centres and data from Japan and other Asian countries remain very limited.The study comprised a retrospective multi-institutional study. The records were reviewed of 928 patients who underwent open radical cystectomy between 1997 and 2010. All complications within 90 days of surgery were categorized into 11 specific categories and graded in accordance with the modified Clavien system. Multivariate regression models were used to determine predictors of complications.At least one complication was observed in 635 (68%) patients and a major (grade 3-5) complication was observed in 156 (17%) patients. The most common complication categories were infectious (30%), gastrointestinal (26%), wound-related (21%) and genitourinary (15%). The 30-day mortality rate was 0.8% and the 90-day mortality rate was 2%. A multivariate regression model showed that previous cardiovascular comorbidity and type of urinary diversion (i.e. ileal conduit or neobladder) were significant factors for any and major complications.Surgical complication-related radical cystectomy is significant and both previous cardiovascular comorbidity and the type of urinary diversion were found to be significant factors for any and major complications. The 90-day mortality rate was 2%, which is compatible with reports from Western high-volume centres.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVES To determine the pathological features and clinical course of intravesical recurrence after nephroureterectomy (NU) for upper urinary tract (UUT) cancer. PATIENTS AND METHODS Among 325 patients undergoing NU with bladder cuff excision for UUT cancer, in this retrospective multi-institutional study we evaluated 113 who developed bladder tumour after NU. Excluding patients with (i) perioperative systemic chemotherapy or radiotherapy for UUT cancer; (ii) a history of previous or synchronous bladder cancer at the time of NU; (iii) distant metastasis at the time of NU; (iv) a follow-up of

To evaluate the prognostic role of different clinico-pathological parameters in node-positive patients treated by radical cystectomy.A retrospective multi-institutional study of 435 patients who underwent radical cystectomy between 1990 and 2005 was carried out. Of them, pathological lymph node (LN) metastases were found in 83 patients. Sixty of these 83 patients, whose clinical information and follow-up data were available, were included in the analysis. Twenty-five patients had undergone adjuvant chemotherapy, whereas 35 had not. A Cox proportional hazards model was used to determine the impact of the following clinico-pathological parameters on patient survival: number of resected LNs, number of positive LNs, LN density (defined as the ratio of the number of positive LNs divided by the total number of resected LNs) and adjuvant chemotherapy.Median follow-up for surviving patients was 41 months (range 4-138) after surgery. The median survival time for all patients was 22 months (95% confidence interval, 15-42 months). At multivariate analysis, LN density of 25% or less, adjuvant chemotherapy and pure urothelial carcinoma were independently significant predictors of survival.Lymph node density predicts survival in patients with node-positive bladder cancer.

Interleukin (IL)-21 shows pleiotropic effects on the proliferation, differentiation, and effector functions of leukocytes. However, the influence of IL-21 on dendritic cell (DC) activation of natural killer T (NKT) cells has not yet been elucidated. In the present study, we examined the effect of IL-21 on murine myeloid DC ability to induce NKT cell production of interferon-gamma (IFN-gamma) and IL-4. Pretreatment of DCs with IL-21 and alpha-galactosylceramide (alpha-GalCer), an NKT cell-specific ligand, resulted in the enhanced ability of the DCs to induce NKT cell production of IFN-gamma but not IL-4 in vitro compared to DCs pretreated with alpha-GalCer alone. A similar effect of IL-21 was observed when DCs pretreated with IL-21 and alpha-GalCer in vitro were transferred into naive mice. Direct administration of IL-21 to the mice also enhanced IFN-gamma production after injection of alpha-GalCer. Thus, IL-21 can modify DC ability to selectively enhance NKT cell production of IFN-gamma upon stimulation with alpha-GalCer.