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We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01)., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The quality of transurethral resection of bladder tumor (TURBT) markedly varies among surgeons and may have a considerable impact on treatment outcomes. The importance of a surgical checklist for TURBT has been suggested in order to standardize the procedure and improve surgical and oncological outcomes. In the present study, we verified the usefulness of a checklist for managing patients with non-muscle-invasive bladder cancer (NMIBC)., Methods: This retrospective study included 201 NMIBC patients diagnosed with Ta, T1, or Tis between October 2011 and February 2021. After September 2016, TURBT was performed with a checklist. We analyzed the intravesical recurrence-free survival (RFS) rate and the presence or absence of the detrusor muscle in resected specimens before and after the introduction of the checklist. Survival rates were compared using the Log-rank test. A multivariate analysis with Cox proportional hazards modeling was performed to verify risk factors for intravesical recurrence., Results: Ninety-nine patients who underwent TURBT with the checklist (checklist group) were compared with 102 patients who underwent TURBT without the checklist (non-checklist group). When the analysis was narrowed down to 9 critical items, we observed a mean number of 9 documented items per operative report (98.0% completion) after implementation of the checklist. Two-year intravesical RFS rates in the checklist and non-checklist groups were 76.7 and 69.5%, respectively (p = 0.1059). The Cox proportional multivariate analysis showed that the rate of intravesical recurrence was slightly lower in the checklist group (hazard ratio 0.7376, 95% CI 0.4064-1.3388, P = 0.3170)., Conclusion: The introduction of a checklist is recommended for the standardization of TURBT and increasing the quality of operative reporting, and it may also improve oncological outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We examined the outcomes of eight weekly bacillus Calmette-Guérin induction therapy after second transurethral resection, and investigated risk factors for intravesical recurrence or disease progression in high-risk non-muscle-invasive bladder cancer patients., Methods: This retrospective study included 146 high-risk non-muscle-invasive bladder cancer patients who received eight weekly bacillus Calmette-Guérin instillations without a maintenance schedule between 2000 and 2019. Intravesical recurrence-free and progression-free survival rates were evaluated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify risk factors., Results: Pathological T staging in the first transurethral resection was pTa in 56 patients (38.4%), pT1 in 75 (51.4%) and primary carcinoma in situ in 15 (10.2%). A total of 109 (83.2%) with pTa-1 disease underwent second transurethral resection before bacillus Calmette-Guérin induction therapy, and residual disease was detected in 54 (49.5%). The completion rate of eight instillations was 82.2%. The 2- and 5-year intravesical recurrence-free survival rates were 80.7% and 75.2%, whereas the 2- and 5-year progression-free survival rates were 85.7% and 82.0%. Recurrent tumors (hazard ratio 6.5830, P = 0.0007) and residual tumors at the second transurethral resection (hazard ratio 4.0337, P = 0.0021) were risk factors for intravesical recurrence. Multiple tumors (hazard ratio 5.8056, P = 0.0302), pT1 disease (hazard ratio 3.7351, P = 0.0447) and residual tumors at second transurethral resection (hazard ratio 3.2552, P = 0.0448) were associated with disease progression., Conclusions: Accurate disease staging and disease elimination by second transurethral resection followed by eight weekly bacillus Calmette-Guérin instillations achieved good disease control. Our protocol (without a maintenance schedule) after thorough surgical resection has potential as a treatment option in the current bacillus Calmette-Guérin shortage., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC)., Methods: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared., Results: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651)., Conclusions: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. However, whether TEC phenotypes are altered by anticancer drugs remains to be clarified. Here, we show that ABCB1 expression increases after chemotherapy in urothelial carcinoma cases. The ratio of ABCB1-positive TEC before and after first-line chemotherapy in urothelial carcinoma tissues ( n = 66) was analyzed by ABCB1 and CD31 immunostaining. In 42 cases (64%), this ratio increased after first-line chemotherapy. Chemotherapy elevated ABCB1 expression in endothelial cells by increasing tumor IL8 secretion. In clinical cases, ABCB1 expression in TEC correlated with IL8 expression in tumor cells after first-line chemotherapy, leading to poor prognosis. In vivo , the ABCB1 inhibitor combined with paclitaxel reduced tumor growth and metastasis compared with paclitaxel alone. Chemotherapy is suggested to cause inflammatory changes in tumors, inducing ABCB1 expression in TEC and conferring drug resistance. Overall, these findings indicate that TEC can survive during chemotherapy and provide a gateway for cancer metastasis. Targeting ABCB1 in TEC represents a novel strategy to overcome cancer drug resistance. SIGNIFICANCE: These findings show that inhibition of ABCB1 in tumor endothelial cells may improve clinical outcome, where ABCB1 expression contributes to drug resistance and metastasis following first-line chemotherapy., (©2020 American Association for Cancer Research.)

Objective: Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system., Methods: Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival., Results: The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]., Conclusions: Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy., (© The Author(s) 2020. Published by Oxford University Press.)

Radical cystectomy (RC) is the gold standard for managing muscle-invasive and high-risknon-muscleinvasive bladder cancer, but is accompanied by non-negligible operative risk. The aim of this study is to identify preoperative variables to predict major perioperative complications after RC and to develop a nomogram using the cohort from multiple institutions in Japan. We retrospectively reviewed 668 patients who underwent open RC with ileal conduit or neobladder at Hokkaido University hospital and 20 affiliated institutions between 1997 and 2010. Complications occurring within 90 days of surgery were graded using modified Clavien classification system. We defined modified Clavien grade 3 or more as major complications and performed univariate and multivariate logistic regression analyses. Predictive accuracy of the nomogram was evaluated with the area under the receiver operating characteristics curve (AUC). A total of 528 men and 140 women were included in this study. There were a total of 160/668 patients (24%) with major perioperative complications. A multivariate model identified gender (OR : 1. 63, p=0. 04), cardiovascular comorbidity (OR : 1.48, p=0.03) and simultaneous nephroureterectomy (OR : 2.81, p=0. 01) as independent predictors. Using these 3 variables, a nomogram was developed with the AUC of 0.58. Predictive performance of our nomogram showed only fair performance ; but at least, we identified male, cardiovascular comorbidity and simultaneous nephroureterectomy as independent predictors of perioperative major complications.

Objective: To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians., Methods: A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between ≥80-year (n = 86) and <80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications., Results: American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the ≥80-year group compared with <80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (≥80-year group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively). The ≥80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications., Conclusions: In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory., (© The Author 2017. Published by Oxford University Press.)

Background: Current adaptive and dose escalating radiotherapy for muscle invasive bladder cancer requires knowledge of both inter-fractional and intra-fractional motion of the bladder wall involved. The purpose of this study is to characterize inter- and intra-fractional movement of the partial bladder wall using implanted fiducial markers and a real-time tumor-tracking radiotherapy system., Methods: Two hundred fifty one sessions with 29 patients were analysed. After maximal transurethral bladder tumor resection and 40 Gy of whole bladder irradiation, up to six gold markers were implanted transurethrally into the bladder wall around the tumor bed and used for positional registration. We compared the systematic and random uncertainty of positions between cranial vs. caudal, left vs. right, and anterior vs. posterior tumor groups. The variance in intrafractional movement and the percentage of sessions where 3 mm and 5 mm or more of intrafractional wall movement occurring at 2, 4, 6, 8, 10, and at more than 10 min until the end of a session were determined., Results: The cranial and anterior tumor group showed larger interfractional uncertainties in the position than the opposite side tumor group in the CC and AP directions respectively, but these differences did not reach significance. Among the intrafractional uncertainty of position, the cranial and anterior tumor group showed significantly larger systematic uncertainty of position than the groups on the opposite side in the CC direction. The variance of intrafractional movement increased over time; the percentage of sessions where intrafractional wall movement was larger than 3 mm within 2 min of the start of a radiation session or larger than 5 mm within 10 min was less than 5%, but this percentage was increasing further during the session, especially in the cranial and anterior tumor group., Conclusions: More attention for intrafractional uncertainty of position is required in the treatment of cranial and anterior bladder tumors especially in the CC direction. The optimal internal margins in each direction should be chosen or a precise intrafractional target localization system is required depending on the tumor location and treatment delivery time in the setting of partial bladder radiotherapy.

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 by open 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 routine pathological examination. After excluding 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 < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up., Conclusions: We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique., Methods: Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated., Results: Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%., Conclusions: Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.

Purpose: To evaluate postoperative renal function and risk factors for the loss of renal function in patients who had undergone radical cystectomy., Materials and Methods: A retrospective single institutional study evaluated 70 patients, including 54 men and 16 women who underwent radical cystectomy. The median follow-up period was 34.5 months (range, 12 to 228 months). In this cohort, four types of urinary diversions were studied, including ileal neobladder (n = 24), ileocecal neobladder (n = 12), ileal conduit (n = 25), and cutaneous ureterostomy (n = 9). Postoperative changes in renal function were reviewed, and the estimated serum creatinine-based glomerular filtration rate (eGFR) was calculated. The variables analyzed were age, a prior history of hypertension or diabetes mellitus, pre-operative renal function, type of urinary diversion, the postoperative occurrence of acute pyelonephritis, and the presence of chemotherapy., Results: The mean eGFR was 74.6 (range, 15.2 to 155.1) mL/min/1.73 m² before surgery and 63.6 (range, 8.7 to 111.5) mL/min/1.73 m² at the last follow-up. The 10-year renal deterioration-free interval was 63.8%. Multivariate analysis showed that a postoperative episode of acute pyelonephritis [Odds Ratio (OR), 3.21; 95% Confidence Interval (CI), 1.14 to 9.02; P = .03] and the presence of chemotherapy (OR, 3.27; 95% CI, 1.33 to 8.01; P = .01) were significant adverse factors., Conclusion: Twenty-four (34.2%) patients demonstrated reduced renal function during the follow-up period. Postoperative episodes of acute pyelonephritis and the presence of chemotherapy were found to be significant adverse factors.

Unlabelled: 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., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Objectives: To investigate the influence of baseline renal function and dose reduction of chemotherapeutic agents on the outcome of metastatic urothelial carcinoma patients with renal impairment., Methods: A total of 57 patients with metastatic urothelial carcinoma treated by systemic chemotherapy were included in the present study. The 24 h-creatinine clearance was measured before each cycle and dose reduction was carried out according to our guidelines. Patients were divided into two groups according to baseline 24 h-creatinine clearance: fit group (60 mL/min/1.48 m(2) ≤) and unfit group (60 mL/min/1.48 m(2) >). Clinical characteristics and final outcomes were compared between the two groups., Results: There was no significant difference in the total number of chemotherapy cycles of each patient between the two groups (fit group: median 5; unfit group: median 4; P=0.7466), although dose reduction was carried out significantly more often in the unfit group than in the fit group during treatment (fit group: median 0 cycles; unfit group: median 3.5 cycles; P=0.0016). Overall, the median survival was 16 months. There was a significant survival difference between the two groups (fit group: median 17 months; unfit group: median 10 months; P=0.0419). On multivariate analyses, impaired renal function at the baseline remained an adverse factor (HR 2.27, P=0.01)., Conclusions: "Unfit" was a poor prognostic factor for metastatic urothelial carcinoma. The dose reduction strategy contributed to continuous treatment in the unfit group. However, its contribution to the prognosis of unfit patients is uncertain., (© 2011 The Japanese Urological Association.)

Purpose: We determined whether diagnostic ureteroscopy for upper urinary tract cancer affects intravesical recurrence and cancer specific mortality., Materials and Methods: In a retrospective, multi-institutional study we evaluated 208 patients undergoing nephroureterectomy for upper urinary tract cancer who had no perioperative systemic chemotherapy, history of invasive bladder cancer, distant metastasis or incomplete followup data. Of these 208 patients 55 who composed the study group underwent diagnostic ureteroscopy before nephroureterectomy while 153 serving as controls did not. We analyzed intravesical recurrence and cancer specific survival using the Kaplan-Meier method with the log rank test used to assess significance., Results: There was no significant difference between the 2 groups in patient characteristics or upper urinary tract cancer stage and grade while followup, and the proportion of multiple tumors and lymphovascular invasion positive tumors were significantly greater in controls. The 2-year bladder recurrence-free survival rate was 60.0% in the study group and 58.7% in controls. There was no significant difference in the intravesical recurrence rate between the 2 groups (log rank test p = 0.972). Estimated Kaplan-Meier cancer specific survival was 88.3% and 78.1% at 5 years in the study and control groups, respectively (log rank test p = 0.0687)., Conclusions: Diagnostic ureteroscopy did not affect intravesical recurrence or cancer specific survival in patients with upper urinary tract cancer undergoing nephroureterectomy., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer., Methods: A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor beta1 (TGFbeta-1) was assessed using an immunohistochemical technique., Results: Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases., Conclusions: Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression.