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Background To investigate whether subgroups of prostate cancer patients, stratified by positive surgical margin locations, have different oncological outcomes following robot-assisted radical prostatectomy. Methods A retrospective multicenter cohort study in prostate cancer patients undergoing robot-assisted radical prostatectomy was conducted at 10 institutions in Japan. Pre- and post-operative outcomes were collected from enrolled patients. Biochemical recurrence and clinical and pathological variables were evaluated among subgroups with different positive surgical margin locations. Results A total of 3195 patients enrolled in this study. Data from 2667 patients (70.1% [N = 1869] with negative surgical margins and 29.9% [N = 798] with positive surgical margins based on robot-assisted radical prostatectomy specimens) were analyzed. The median follow-up period was 25.0 months. The numbers of patients with apex-only, middle-only, bladder-neck-only, seminal-vesicle-only and multifocal positive surgical margins were 401, 175, 159, 31 and 32, respectively. In the multivariate analysis, PSA level at surgery, pathological Gleason score based on robot-assisted radical prostatectomy specimens, pathological T stage, pathological N stage and surgical margin status were independent risk factors significantly associated with biochemical recurrence-free survival. Patients undergoing robot-assisted radical prostatectomy with multifocal positive surgical margins and seminal-vesicle-only positive surgical margins were associated with worse biochemical recurrence-free survival than those with apex-only, middle-only and bladder-neck-only positive surgical margins. Patients undergoing robot-assisted radical prostatectomy with apex-only positive surgical margins, the most frequent positive surgical margin location, were associated with more favorable biochemical recurrence-free survival that those with middle-only and bladder-neck-only positive surgical margins. The study limitations included the lack of central pathological specimen evaluation. Conclusions Although positive surgical margin at any locations is a biochemical recurrence risk factor after robot-assisted radical prostatectomy, positive surgical margin location status should be considered to accurately stratify the biochemical recurrence risk after robot-assisted radical prostatectomy.

The aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated.Fifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan-Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors.The median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0-103.2) and 69.0 (95% CI: 34.3-81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034).A high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification.

Programmed death (PD)-1/PD-ligand 1 (PD-L1) antibodies have shown an intense clinical effect in some patients with PD-L1

Kidney biopsy was performed in a 64-year-old woman with type 2 diabetes, less than 1 g of proteinuria, who rapidly progressed to end-stage renal failure within about 2 years. At biopsy, a renal cell carcinoma, 8 mm in size, was diagnosed; the tumor was not evident on computed tomography performed before biopsy. The non-cancerous area was characterized by a high degree of thrombotic microangiopathy (TMA)-like endothelial cell damage. The clinical course of the patient showed that renal function deteriorated progressively after the use of two dipeptidyl peptidase 4 (DPP-4) inhibitors. A TMA-like lesion associated with DPP4 inhibitor administration may have contributed to the rapid decline in renal function.

Background: Prostate cancer is one of the most heritable human cancers. Lynch syndrome is an autosomal dominant inheritance caused by germline mutations in DNA mismatch repair (MMR) genes, which are also associated with an increased incidence of prostate cancer. However, prostate cancer has not been defined as a Lynch syndrome-associated cancer. The proportion of Lynch syndrome patients in primary prostate cancers is unclear. In this study, we investigated MMR protein loss using universal immunohistochemical screening to determine the prevalence of Lynch syndrome in patients with localized prostate cancer who underwent radical prostatectomy. Methods: One hundred twenty-nine surgical specimens from radical prostatectomy performed at Toranomon Hospital between 2012 and 2015 were retrospectively tested using universal screening with immunohistochemistry staining for expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6. For all suspected MMR-deficient patients, germline genetic tests focusing on MMR genes were performed. Results: MMR protein loss was found in only one patient (0.8%) who showed dual MSH2/MSH6 loss. This patient showed a single nucleotide germline mutation from c.1129 C to T (p.Glc377*) at exon 7 in the MSH2 gene. He was diagnosed with a primary prostate cancer at 66 years of age. He had a documented history of Lynch syndrome (Muir–Torre syndrome) with previous colon cancer, sebaceous tumor, and keratoacanthoma as well as subsequent bladder cancer, all of which also showed dual MSH2/MSH6 loss. He also had a strong family history of colorectal and other Lynch syndrome-associated cancers. The pathological stage was pT3aN0M0, and the pathological grade was Gleason 7(4+3) with tertiary pattern 5. Conclusions: In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

In this multicenter retrospective cohort study, we aimed to evaluate whether pelvic lymph node dissection (PLND) improved biochemical recurrence (BCR) in patients with prostate cancer (PCa) who underwent robot-assisted radical prostatectomy (RARP) in Japan. A multicenter retrospective cohort study of 3195 PCa patients undergoing RARP at nine institutions in Japan was conducted. Enrolled patients were divided into two groups: those who underwent RARP without PLND (non-PLND group) and those who underwent PLND (PLND group). The primary endpoint was biochemical recurrence-free survival (BRFS) in PCa patients who underwent PLND. We developed a propensity score analysis to reduce the effects of selection bias and potential confounding factors. Propensity score matching resulted in 1210 patients being enrolled in the study. The 2-year BRFS rate was 95.0% for all patients, 95.8% for the non-PLND group, and 94.3% for the PLND group (p = 0.855). For the all-risk group according to the National Comprehensive Cancer Network risk stratification, there were no significant differences between patients who did and did not undergo PLND. Based on the results of the log-rank study, PLND may be unnecessary for patients with PCa undergoing RARP.

Background/aim Expression of human leukocyte antigen (HLA) class I and II and CD74, which functions as a chaperone of MHC class II, play essential roles in T-cell recognition. The aim of this study was to elucidate the association between the HLAs and CD74, and their correlation with the infiltrated immune cells in renal cell carcinoma (RCC). Materials and methods We retrospectively investigated the expression of HLA-A/B/C, HLA-DR, and CD74 in 38 patients with advanced RCC (T3/T4), and evaluated their correlations with CD4 and CD8-positive T-cell infiltration using immunohistochemistry. Results The expression of HLA-A/B/C, HLA-DR, and CD74 on cancer cells was observed in 37, 20, and 31 patients, respectively. The density of CD8- and CD4-positive T cells showed a positive correlation with HLA-DR expression. The density of CD4-positive lymphocytes was significantly associated with CD74 expression. Conclusion The expression of HLA-DR, rather than CD74, on cancer cells was potentially associated with the anti-cancer immune microenvironment.

BackgroundRhabdomyolysis is a potentially fatal disease, and elevated serum creatine kinase (CK) is one of the key laboratory findings suggestive of this disease. It is important to distinguish rhabdomyolysis from other diseases because CK elevation can occur in a variety of etiologies. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma, but the frequency of CK elevation with this drug is still unknown.MethodsTo investigate the frequency of serum CK elevation induced by cabozantinib, we retrospectively reviewed the electronic medical records of patients with advanced renal cell carcinoma who received cabozantinib at our institution from April 2020 to March 2021.ResultsSeven patients were included in the study; six experienced serum CK elevation, four were classified as grade 1, and the remaining two as grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. In five patients, the time from cabozantinib administration to CK elevation was 14 days. Hypothyroidism can be one of the causes of CK elevation; however, two patients who had hypothyroidism caused by previous treatment were in the euthyroid condition due to hormone replacement. One patient with grade 1 CK elevation developed late-onset immune-related adverse event (irAE) myositis comorbid with suspected myasthenia gravis. One patient with grade 3 CK elevation developed muscle weakness and rhabdomyolysis.ConclusionsCK elevation is a common adverse event induced by cabozantinib. Most patients are asymptomatic and may not be clinically ill. However, physicians should be careful with the rare occurrence of symptomatic serum CK elevation, indicating rhabdomyolysis and neuromuscular irAEs, especially in patients who receive immune checkpoint inhibitors (ICIs).

We experienced a case of fumarate hydratase (FH) -deficient renal cell carcinoma (RCC) suspected of hereditary leiomyomatosis renal cell carcinoma (HLRCC) and herein report our findings. A 42-year-old man with an unremarkable medical history was referred to our hospital with an initial impression of renal cancer, cT3aN2M0. He underwent a right radical nephrectomy with lymph node dissection and showed a pathological diagnosis of FH-deficient RCC, pT3aN2. Clinicopathologic features indicated the possibility of HLRCC; however,-associated RCC. genetic testing showed negative for pathogenic FH mutation.HLRCC is an autosomal dominant condition caused by an FH gene mutation on chromosome 1q43. It is also a syndrome that develops in the smooth muscles of the skin and uterus, and has a renal cancer risk of 10-16%. HLRCC-associated RCC tends to metastasize early and shows poor prognosis. In FH-deficient RCC, the possibility of HLRCC-related RCC should be considered; thus, if patients fulfill the clinical diagnostic criteria, genetic counseling and screening of HLRCC are needed. Even if genetic testing does not confirm HLRCC, FH-deficient RCC still has a poor prognosis and careful follow-up is required.

Background: Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. In contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. Materials and Methods: Plasma samples were collected prospectively from patients with advanced and metastatic renal cell carcinoma (RCC) prior to initiation of ICI treatment (baseline) and 2 or 3 weeks after the first cycle of ICI treatment (post-dose 1). Plasma cytokines and chemokines (GRO [CXCL1], IL-17A, IL-1β, IL-6, IL-8, IP-10 [CXCL10], MCP-1 [CCL2], TNFα) were measured by Luminex system, and plasma level of CXCL13 and anti-CD74 autoantibody levels were measured by ELISA. Their association with irAEs was analyzed. Results: In a discovery cohort of 13 patients, plasma levels of CXCL1, IL-17A, IL-1β, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (p=0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in a validation cohort of 43 RCC patients who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (p=0.0246 and 0.0137, respectively). We evaluated the relationship between plasma levels of CXCL10 and CXCL13, which we measured in a previous study, and the incidence of irAEs. At baseline, the plasma CXCL13 level was positively associated with the CXCL10 level (p=0.0007), but no significant association was observed post-dose 1 (p=0.2678). Plasma CXCL13 levels were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (p=0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. Conclusion: Plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs. Citation Format: Yuji Miura, Takanobu Motoshima, Toshiki Anami, Hiromu Yano, Remi Mito, Shinji Urakami, Keiichi Kinowaki, Hirotake Tsukamoto, Ryoma Kurahashi, Yoji Murakami, Junji Yatsuda, Yukio Fujiwara, Tomomi Kamba, Yoshihiro Komohara. Predictive value of CXCL10 for the occurrence of immune related adverse events in patient with renal cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4326.

A 69-year-old man underwent renal transplantation due to chronic renal failure of unknown cause in 1991. Furthermore, in 2012 he again underwent renal transplantation due to renal graft dysfunction with focal segmental glomerulosclerosis. After the second renal transplantation, his renal function has been stable. In 2019, he presented to the urology department with gross hematuria. Cystoscopy revealed a 2 cm vesical calculus at the dome of the bladder near the right lateral wall. Therefore, we performed transurethral lithotripsy using the holumium laser method. The vesical calculus was crushed, revealing a suture at the center, suggesting the suture as the cause. We tried to remove the suture during operation, however, it was impossible. Although the remaining suture posed a risk for calculus development, there has been no recurrence of a calculus for 6 months after the operation. This case reports a vesical calculus at the ureterovesical anastomotic site, wherein the core was an absorbable suture used during the initial renal transplantation. It should be taken into consideration that there is a possibility of anastomotic calculus occurrence with absorbable sutures, even long after renal transplantation.

We aimed to examine the relationship between D'Amico intermediate-risk and pathological grade group 1 (pGG1) after robot-assisted radical prostatectomy (RARP).In this retrospective multicenter cohort study, D'Amico intermediate-risk prostate cancer patients who did not receive neoadjuvant therapy, and underwent RARP at 10 institutions in Japan were examined for preoperative factors associated with pGG1.In total, we enrolled 1161 D'Amico intermediate-risk prostate cancer patients. The pGG1 and pGG ≥2 groups comprised 73 (6.3%), and 1088 (93.7%) cases, respectively. Biochemical recurrence-free survival (BCRFS) of the pGG1 group was equivalent to that of the D'Amico low-risk patients. Among the 3 D'Amico intermediate-risk factors (IRF), the pGG1-rate was 24% with prostate-specific antigen (PSA) of 10 to 20 ng/mL alone, and 30% with cT2b alone. Both groups had significantly higher pGG1-rates than other groups. Down-grading from biopsy GG ≥2 to pGG1 was relatively rare (3.9%). Patients with pGG1 were further stratified by prostate volume (PV) (cutoff, 40 cc) among patients with one IRF and PSA of 10 to 20 ng/mL. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV40 cc had a relatively good BCRFS similar to that of the D'Amico low-risk group.Among intermediate-risk prostate cancer patients, those with pGG1 have a good prognosis. Downgrading from biopsy GG ≥2 is rare, and definitive treatment may be recommended for patients with biopsy GG ≥2. Patients with one IRF, PSA of 10 to 20 ng/mL, and PV40 cc who are eligible for RARP may be candidates for active surveillance.

We evaluated oncological outcomes of patients undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) and their perioperative complications in Japan. We investigated clinical and pathological covariates to predict biochemical recurrence (BCR) after RARP.A retrospective multicenter cohort study was conducted in RARP patients with PCa at 10 institutions in Japan. Pre- and postoperative covariates were collected from enrolled patients. The primary endpoint was defined as biochemical recurrence-free survival (BRFS). Additionally, the association between BCR and clinicopathological covariates was determined.We enrolled 2670 patients in this study. The median follow-up period was 26.0 months. RARP-related perioperative complications were identified in 198 patients (7.4%), including 69 patients (2.6%) with grade 3/4 complications according to the Clavien-Dindo classification. The 2-year BRFS was 88.0%. Using the Kaplan-Meier method, initial prostate-specific antigen (PSA) level of ≤7.6 ng/mL, biopsy and pathological Gleason score (GS) of ≤7, clinical and pathological T1/2, and low/intermediate risks according to the National Comprehensive Cancer Network risk classification, and negative surgical margin status had significant BRFS than their counterparts. In multivariate analysis, initial PSA, biopsy and pathological GS, clinical and pathological T stage, and surgical margin status significantly correlated with BCR after RARP.In this study, RARP achieved a lower incidence of perioperative complications than other studies.

Selective identification of men with clinically significant prostate cancer (sPC) is a pivotal issue. Development of a risk model for detecting sPC based on the prostate imaging reporting and data system (PI-RADS) for bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters in a Japanese cohort is expected to prove beneficial. We retrospectively analyzed clinical parameters and bpMRI findings from 773 biopsy-naïve patients between January 2011 and December 2016. A risk model was established using multivariate logistic regression analysis and presented on a nomogram. Discrimination of the risk model was compared using the area under the receiver operating characteristic curve. Statistical differences between the predictive model and clinical parameters were analyzed using DeLong test. sPC was detected in 343 men (44.3%). Multivariate logistic regression analysis to predict sPC revealed age (P = 0.002), log prostate-specific antigen (P P P P

A 76-year-old man presented with gross hematuria and reported the use of anticoagulant for deep vein thrombosis (DVT). Blood tests revealed eosinophilia and thrombocytopenia. Urine cytology revealed a class I specimen with a few eosinophils in the urine. We performed cystoscopy, which revealed bladder masses with friable mucosa diffusely throughout the bladder. Magnetic resonance imaging revealed possible invasion of the bladder muscle by the masses. We performed transurethral resection of the bladder masses, and histopathological examination revealed eosinophilic infiltration of the bladder wall stroma without cancerous tissue. Therefore, the patient was diagnosed with eosinophilic cystitis.Eosinophilia and thrombocytopenia promptly resolved, and the bladder masses disappeared following the administration of prednisolone for eosinophilic cystitis. DVT also improved without recurrence of eosinophilic cystitis.

A 59-year-old female experienced gross hematuria and right back pain, and she visited our hospital in March 2015. Abdominal computed tomography (CT) showed bilateral renal pelvic calculi; the right stone was 15 mm and the left stone was 18 mm in diameter. She had ulcerative colitis and had been taking salazosulfapyridine (SASP) for about 30 years. Urinalysis showed aciduria and deposition of urate crystals. An abdominal X-ray picture did not show a calculus shadow. We suspected uric acid calculus and started treatment with urinary alkalizer and uric acid production inhibitor.Three months later, abdominal CT showed enlargement of the bilateral renal pelvic calculi; the right stone was 25 mm and the left stone was 24 mm in diameter. She also complained of worse right back pain and underwent transurethral ureterolithotripsy for the right renal pelvic stone. The stone was orange, comparatively soft, and chipped down until it was approximately half of its original size. The stone analysis suggested suspected drug-induced urolithiasis, but not uric acid calculus. Thus, we investigated the stone and SASP using infrared spectroscopy, and the infrared absorption pattern was similar in both. The stone analysis demonstrated drug-induced urolithiasis induced by SASP.The patient's ulcerative colitis therapy was switched to mesalazine, and the amount of urinary alkalizer was increased. Abdominal CT 3 months thereafter showed dissipation of bilateral renal pelvic calculi. The patient did not take any preventative medication, and there was no recurrence of urolithiasis.

Background:To selectively identify men with clinically significant prostate cancer (sPC) is pivotal issue. To develop a risk model for detecting sPC based on Prostate Imaging Reporting and Data System (PI-RADS) for bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters in a Japanese cohort is expected beneficial.MethodsBetween January 2011 and December 2016, we retrospectively analyzed clinical parameters and bpMRI findings from 773 biopsy-naïve patients. A risk model was established using multivariate logistic regression analysis and was presented on a nomogram. Discrimination of the risk model was compared using the area under the receiver operating characteristic curve. Statistical differences between the predictive model and clinical parameters were analyzed using DeLong’s test.ResultssPC was detected in 343 men (44.3%). In the multivariate logistic regression analysis to predict sPC, age (P=0.002), log prostate-specific antigen (PPPP

Two patients with late recurrence of renal cell carcinoma were observed long term without treatment. Case 1 is an 83-year-old woman who underwent right nephrectomy at 57 years of age following a renal tumor diagnosis. Histopathological results revealed clear cell renal cell carcinoma, G2, pT1aN0M0. Pancreatic metastasis developed at age 71, and pancreatic tail excision was performed. A metastatic lesion appeared again at the head of the pancreas at age 74. The patient has been followed by observation only for 9 years without any new lesions. Tumor doubling time calculated from abdominal ultrasonography was 13.3 months.Case 2 is a 91-year-old male. At 78 years of age, right nephrectomy and inferior vena cava tumor embolectomy were performed for renal tumor. Histopathological results revealed clear cell renal cell carcinoma, G2, pT3bN0M0. Left adrenal metastasis appeared at age 84, and the patient has been followed for 7 years without new lesions. Tumor doubling time calculated from abdominal computed tomography (CT) images was 14.1 months.In both patients, no symptoms due to tumor recurrence ever appeared, and their activities of daily living (ADL) were maintained fairly well. In the case of solitary late recurrence in elderly renal cancer patients, observation may be a treatment option that avoids adverse effects and complications caused by treatment. In addition, it appears possible to predict the need for subsequent treatment by calculating the doubling time using several sequential CT images obtained after recurrence. If a new recurrent metastatic lesion appears or if the doubling time during a 2-to 3-year follow-up period is relatively short, however, new treatment should be considered without delay.

Factor XIII (FXIII) deficiency is a rare inherited coagulopathy. Standard perioperative management in those with FXIII deficiency requiring surgical procedures has not been elucidated. Herein, we report the case of a patient with FXIII deficiency who successfully underwent transurethral lithotripsy. Recombinant FXIII was used effectively in perioperative management and safely without any bleeding complications. This is the first report of a patient with FXIII deficiency in the field of urology.

Background To assess the prophylactic efficacy of postoperative single intravesical instillation with pirarubicin (THP) and mitomycin C (MMC) for low-risk non-muscle-invasive bladder cancer (NMBC). Patients and methods A total of 103 clinically low-risk NMBC patients were preoperatively randomized into either THP (n=49) or MMC (n=54) groups. The primary endpoint was recurrence-free survival. Results The median follow-up periods of the THP and MMC groups were 955 and 1008 days, respectively (p=0.76). Twelve patients (24.5%) in the THP group and 7 (13%) in the MMC group had bladder cancer recurrences. The two-year recurrence-free survival of the THP group and the MMC group was 77.8% and 86.4%, respectively (p=0.20). Neither groups had severe toxicity. Conclusion In low-risk NMBC, the prophylactic effect against postoperative single intravesical instillation with THP was not superior to that with MMC.

Objective The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with α1 -adrenoceptor antagonists. Methods Patients with persistent storage symptoms refractory to α1 -adrenoceptor antagonists for benign prostatic hyperplasia were enrolled in the study. Patients were randomly assigned to either a 5 mg tadalafil or 5 mg solifenacin treatment group for 12 weeks. International Prostate Symptom Score, Overactive Bladder Symptom Score, urinary flow rates, residual urine volume, and blood pressure were measured prospectively before treatment and after 4 and 12 weeks of treatment. Changes from baseline were compared between groups. The rate of treatment discontinuation due to adverse effects was evaluated. Results Of the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups. Conclusions Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α1 -adrenoceptor antagonists.

Cytotoxic chemotherapy has been the mainstay of medical therapy for metastatic urothelial cancer. Currently, the gemcitabine/cisplatin regimen is widely used worldwide as the standard first-line medical treatment. Very recently, in 2017, pembrolizumab, a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1, was approved as a second-line treatment to be used after platina-based chemotherapy for metastatic urothelial cancer in Japan. Based on its promising anti-tumor efficacy and manageable safety profile as demonstrated in the phase III KEYNOTE-045 trial, pembrolizumab therapy is expected to be rapidly introduced for treating metastatic urothelial cancer in clinical practice. The paradigm of medical treatment for patients with metastatic UC is dramatically changing through the introduction of this and other immune-checkpoint inhibitors. In this article, we provide a brief overview of these immune-checkpoint inhibitors and a comprehensive summary of the use of cytotoxic chemotherapy for metastatic urothelial cancer, including ongoing clinical trials.

(Background) Multiple renal angiomyolipoma (AML) may develop concurrently with tuberous sclerosis complex (TSC) and lung lymphangioleiomyomatosis (LAM). In recent years, an increase in subjects undergoing chest computed tomography examinations, including medical examinations, has been accompanied by an increase in LAM cases that are diagnosed while still asymptomatic. Surgical treatment may also be performed for renal AML to prevent bleeding. We clarified the clinical features of AML that is complicated by LAM, and discussed the significance of screening for LAM. (Methods) Between January 1, 2006 and April 30, 2014 two groups, comprising 7 patients with LAM (LAM-AML group) and another 26 patients without LAM (sporadic AML group), were compared with regard to findings for renal AML such as imaging examinations, pathological features, and treatment course. Screening for LAM was chest CT scanning. (Results) In the LAM-AML group, there were younger and more female cases and tumors tended to be multiple, large and bilateral. 85.7% of cases underwent surgery. On the other hand, in the sporadic group 73.1% of cases were followed up without treatment. There was no preoperative lung screening except the one TSC case and all 5 LAM cases were diagnosed postoperatively. One LAM patient was symptomatic and eventually required lung transplantation, while all other LAM cases were handled by monitoring the course, without treatment. (Conclusion) Many cases of asymptomatic LAM are untreated. However, the poor prognosis, risk of a need for general anesthesia, and potential for renal sparing by selection of pharmacotherapy must be taken into account. In that light-especially in the case of young women-patients with multiple renal AML should undergo preoperative screening for LAM.

Introduction To clarify the mechanisms responsible for running-induced asymptomatic gross hematuria. Case presentation We identified 12 patients who visited our outpatient clinic with hematuria after running as a chief complaint. In 9 of 12 patients (75%), cystoscopic findings revealed mucosal contusions at the center of the posterior wall. Our examination including cystoscopy and magnetic resonance imaging revealed that this bladder contusion development was caused by the repeated contact of the bladder posterior wall against the fixed bladder neck by vertical motion in the empty bladder lumen during running. All patients with bladder contusion were male because the bladder neck is more firmly fixed to the pelvic floor by the protruding prostate in men than women. Gross hematuria in all patients quickly resolved without treatment after running cessation. Conclusion This is the first report in which cystoscopic findings showed that running-induced macroscopic hematuria can be frequently caused by traumatic bladder contusion.

The aim of this study was to investigate the efficacy and safety of tadalafil add-on therapy with αPatients with persistent storage symptoms refractory to αOf the 75 patients recruited to the study, 38 and 37 were assigned to the tadalafil and solifenacin groups, respectively. There were no significant difference in baseline characteristics between the two groups. The change in the amount of residual urine volume was significantly larger in the solifenacin- than tadalafil-treated group; other parameters, including lower urinary tract symptoms and uroflowmetry measures, did not differ significantly between the two groups. Seven (18%) and 12 (32%) patients in the tadalafil and solifenacin groups, respectively, discontinued treatment because of adverse events. The main reasons for discontinuation in the tadalafil group were stomach discomfort or nausea and dizziness or vertigo; voiding difficulty and constipation were the main reasons for discontinuation in the solifenacin group. There was no significant difference in blood pressure fluctuations from baseline between the two groups.Tadalafil add-on therapy was not inferior to solifenacin add-on therapy in terms of effect and safety. Therefore, tadalafil could be an alternative add-on drug for patients with persistent lower urinary tract symptoms refractory to α

Objective: To determine the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis and its impact on patient management with upper tract urothelial carcinoma (UTUC). Patients and Methods: Consecutive patients with UTUC underwent 18F-FDG PET/CT after CT for initial staging (n = 47) and for restaging at recurrence (n = 9). Diagnostic accuracy for detecting metastases with PET/CT and CT was compared statistically. The impact of PET/CT on patient management was assessed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. Results: In the lesion-based analysis, 142 lesions were diagnosed as metastases. The sensitivity of PET/CT was significantly better than that of CT (85 vs. 50%, p = 0.0001). In the patient-based analysis, 22 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy of PET/CT tended to be superior to those of CT, but these values were not significantly different (95, 91, and 93% vs. 82, 85, and 84%; p = 0.25, 0.50, and 0.063, respectively). The clinicians changed their assessments of disease extent and management plans in 18 (32%) and 11 (20%) patients, respectively, based on the PET/CT results. Conclusions: The diagnostic accuracy of PET/CT for detecting metastasis was superior to that of CT. PET/CT provided additional information to the CT-based staging, which had an impact on patient management.

To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

Objective To assess the change in disease-specific health-related quality of life and to evaluate patient-perceived satisfaction after radical prostatectomy (RP) or intensity-modulated radiotherapy (IMRT) with androgen deprivation therapy (ADT) for patients with high-risk prostate cancer (PCA) that has been defined by the European Association of Urology guideline. Methods Between 2006 and 2010, 150 patients with high-risk PCA who underwent either RP (n = 97) or IMRT with ADT (n = 53) were enrolled in this prospective health-related quality of life study. Disease-specific health-related quality of life at baseline, 3, 6, 12, and 24 months and patient-perceived satisfaction at 12 and 24 months after these treatments were estimated using the Expanded Prostate Cancer Index Composite. Results Urinary bother and irritation and obstruction scores did not change significantly between both treatment groups throughout the 2-year follow-up. ADT greatly influenced sexual and hormonal functions and bothers in patients who received IMRT with ADT. The patient-perceived satisfaction at 12 months after the treatments was approximately 80% in both treatment groups, and there was no significant difference between the 2 groups. At 12 months after the treatments, urinary function ( P = .001) was identified as the most significant predictor of patient-perceived satisfaction, although it was not associated with the treatment type. Conclusion The majority of patients with high-risk PCA who received RP or IMRT with ADT reported high patient-perceived satisfaction after the treatments. This study showed that improvement in urinary function might contribute to patient-perceived satisfaction after the treatments.