[A Case of Metastatic Renal Cancer Responding to Sunitinib as the Eighth Line Therapy].

A 62-year-old male presenting with gross hematuria and right renal mass was referred to our Urology Department. Computed tomography revealed a right renal mass, with multiple pulmonary lesions. He underwent right nephrectomy for highly suspected renal cell carcinoma with pulmonary metastases (cT3aN0M1). The pathological diagnosis was clear cell renal cell carcinoma, pT1b. Following surgery, he was treated with multiple regimens of chemotherapy, ranging from interferon alpha, multiple tyrosine kinase inhibitors such as sorafenib, axitinib, pazopanib and cabozantinib, everolimus, and nivolumab, all of which were discontinued after its induction, either due to adverse events or progressive disease. He was finally administered Sunitinib as the 8th line "last-ditch" treatment, which resulted in significant tumor shrinkage. No disease progression has been observed 25 months after initiating sunitinib administration.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Sterile versus non-sterile gloves during cystoscopy: A randomized prospective single-blind study.

Objective: The objective of this study is to evaluate the need for sterile gloves during cystoscopy by comparing the incidence of UTI symptoms between patients in whom the procedure is performed with non-sterile gloves with those performed with non-sterile gloves. Patients and Methods: This study had a randomized, prospective, single-blind design and included patients aged >20 years who underwent cystoscopy in either of two outpatient clinics between September 2015 and November 2021. The patients were allocated to a sterile group or a non-sterile group. Only the urologists were aware of whether or not the gloves were sterile. The patients were instructed to report any symptoms suggestive of UTI after cystoscopy. Results: A total of 1258 patients were enrolled in the sterile group and 1376 in the non-sterile group. Symptoms of UTI were reported by six patients (0.48%) in the sterile group and six (0.44%) in the non-sterile group. The between-group difference was not statistically significant (p = 0.88). Conclusion: It is not necessary to use sterile gloves during routine cystoscopy.

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment.

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

Normative Influence of the Stars: The Relative Indirect Effects of Celebrity Exemplars on Vaping Norm Perceptions Through Liking, Parasocial Relationship Strength, and Wishful Identification.

Although the influence of celebrities on public health-related attitudes and behaviors is well established, the specific role that celebrity examples play in shaping health-related social norm perceptions is not well understood. To examine the effect of celebrities on social norm perceptions, young adults were randomly assigned to read news articles about vaping that either featured one of four film stars using a vape pen or did not contain any celebrity exemplar. The presence or absence of a celebrity exemplar did not affect readers' perceptions of vaping social norms. However, three types of audience involvement with the celebrities - liking, parasocial relationship strength, and wishful identification, were examined as mediators of the relative effects of the different celebrities on vaping norm perceptions. The results suggest that celebrities who people like more and those who they wishfully identify with less can wield a greater influence on social norms. PSR strength did not mediate indirect effects of celebrity on social norm perceptions. These findings indicate that celebrities can shape public perceptions of social norms through some types of involvement.

[The Effect of Naldemedine Tosylate on the Postoperative Course of Robot-Assisted Radical Cystectomy].

Radical cystectomy is an invasive procedure frequently followed by postoperative complications. Although the protocol of enhanced recovery after surgery (ERAS) is used in the postoperative course, several components of the ERAS protocol may increase the workload of medical workers. In this study, we added naldemedine tosylate only to routine postoperative management instead of using the ERAS protocol and evaluated the effect on the postoperative course of robot-assisted radical cystectomy (RARC). We retrospectively investigated 58 patients who underwent RARC from May 2015 to February 2022 at our hospital and evaluated the postoperative complications, such as ileus and urinary tract infections, and, length of hospital stay (LOS). We used naldemedine tosylate for the patients who underwent RARC after November 2019. As a result, naldemedine tosylate reduced 26.8% of postoperative complications within 30 days after the operation (p＝0.041) and shortened LOS 8 days (p＝0.018). Naldemesine tosylate improved the postoperative course of RARC.

Risk analyses of nocturia on incident poor sleep and vice versa: the Nagahama study.

Cross-sectional relationships between nocturia and sleep problems have been well evaluated but the risk association for each incidence is scarcely reported. This analysis included 8076 participants of the Nagahama study in Japan (median age 57, 31.0% male) and associations between nocturia and self-reported, sleep-related problems (poor sleep) were evaluated cross-sectionally. Causal effects on each new-onset case were analyzed longitudinally after 5 years. Three models were applied: univariable analysis, adjustment for basic variables (i.e., demographic and lifestyle variables) and full adjustment for basic and clinical variables. The overall prevalences of poor sleep and nocturia were 18.6% and 15.5%, while poor sleep was positively associated with nocturia (OR = 1.85, p < 0.001) and vice versa (OR = 1.90, p < 0.001). Among 6579 good sleep participants, 18.5% developed poor sleep. Baseline nocturia was positively associated with this incident poor sleep (OR = 1.49, p < 0.001, full adjustment). Among 6824 non-nocturia participants, the nocturia incidence was 11.3%. Baseline poor sleep was positively associated with this incident nocturia (OR = 1.26, p = 0.026); such associations were significant only in women (OR = 1.44, p = 0.004) and under-50-year-old groups (OR = 2.82, p < 0.001), after full adjustment. Nocturia and poor sleep associate with each other. Baseline nocturia can induce new-onset poor sleep while baseline poor sleep may induce new-onset nocturia only in women.

[Risk Factors of Antiresorptive Agent-Related Osteonecrosis of the Jaw in Prostate Cancer Patients with Bone Metastases].

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a severe adverse event associated with use of bone resorption inhibitors (BRIs), such as zoledronic acid and denosumab. Based on the results of phase 3 clinical trials for BRIs, the frequency of ARONJ is reported to be 1 to 2%, but the actual frequency could be higher. We investigated 173 patients with prostate cancer with bone metastases who were treated either with zoledronic acid or denosumab at our hospital between July 2006 and June 2020. ARONJ occurred in 13 patients (8%); i.e., ten out of 159 patients (6%) who were treated with zoledronic acid, and three out of 14 patients (21%) who were treated with denosumab. Multivariate analysis showed that longer duration of BRI exposure and dental treatment before the initiation of BRI are associated with risk of ARONJ. ARONJ is associated with decreased mortality but the association is not significant. Generally, the occurrence of ARONJ may be underestimated; therefore, further studies are warranted to determine the actual frequency of ARONJ.

[Intraoperative Evaluation of Ureteral Blood Flow Using Indocyanine Green Fluorescence imaging on Living-Donor Kidney Transplantation].

Ureteral stenosis occurs in 2-10% after kidney transplantation. Most are caused by ischemia of the distal ureter and are difficult to manage. There is no standard method for evaluating ureteral blood flow during surgery, and it is left to the judgement of the operator. Indocyanine green (ICG) is used not only for a liver or cardiac function test but also for an assessment of tissue perfusion. We evaluated the intraoperative ureteral blood flow under a surgical light and by ICG fluorescence imaging in 10 living-donor kidney transplant patients between April 2021 and March 2022. No ureteral ischemia was detected under the surgical light, but ICG fluorescence imaging revealed/decreased blood flow in 4 of the 10 patients (40%). Further resection was performed in these 4 patients to increase the blood flow, and the median resection length was 1.0cm (0.3-2.0). The postoperative course was uneventful in all 10 patients, and no ureter-related complications were observed. ICG fluorescence imaging is a useful method for evaluating ureteral blood flow and is expected to help reduce complications caused by ureteral ischemia.

[Challenging Case of Primary Renal Castleman's Disease Accompanied with Bacterial Pyelonephritis].

Castleman's disease is a rare lymphoproliferative disease, mostly found in the mediastinum. The number of Castleman's disease cases involving the kidneys is still limited. We report a case of primary renal Castleman's disease sporadically detected during a regular health check-up as pyelonephritis with ureteral stones. In addition, computed tomography showed renal pelvic and ureteral wall thickening with paraaortic lymphadenopathy. A lymph node biopsy was performed, but it did not confirm either malignancy or Castleman's disease. The patient underwent open nephroureterectomy for diagnostic and therapeutic purposes. The pathological diagnosis was renal and retroperitoneal lymph node Castleman's disease with pyelonephritis.

Evaluation of sexual function after dutasteride treatment in patients with once-negative prostate biopsy and benign prostate hyperplasia.

INTRODUCTION: Patients with benign prostatic hyperplasia are usually treated with 5α-reduced inhibitors (5ARIs) such as finasteride and dutasteride. However, studies on the influence of 5ARIs on sexual function have been controversial. In this study, we evaluated the impact of dutasteride treatment for erectile function in patients with once-negative prostate biopsy and benign prostate hyperplasia. PATIENTS AND METHODS: 81 patients with benign prostate hyperplasia were enrolled in a one-armed prospective study. They were administrated 0.5 mg/day of dutasteride for 12 months. Patient characteristics and changes of International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF)-15 scores at baseline and 12 months after dutasteride administration were examined. RESULTS: The mean ± standard deviation (SD) age of the patients was 69.4 ± 4.9 years and the prostate volume was 56.6 ± 21.3 mL, respectively. The mean ± SD prostate volume and PSA levels were decreased 25.0 and 50.9%, respectively, after 12 months of dutasteride administration. IPSS total, voiding subscore, storage subscore, and quality of life score significantly improved after 12 months of dutasteride administration. No statistically significant change in IIEF-total score from 16.3 ± 13.5 to 18.8 ± 16.0 (p = 0.14), IIEF-EF score from 5.1 ± 6.9 to 6.4 ± 8.3 (p = 0.13) were observed. There was no decrease in erectile function severity. CONCLUSION: Twelve months administration of dutasteride for patients with BPH improved urinary function and did not increase the risk of sexual dysfunction.

High-sensitivity low-noise photodetector using a large-area silicon photomultiplier.

The application of silicon photomultiplier (SiPM) technology for weak-light detection at a single photon level has expanded thanks to its better photon detection efficiency in comparison to a conventional photomultiplier tube (PMT). SiPMs with large detection area have recently become commercially available, enabling applications where the photon flux is low both temporarily and spatially. On the other hand, several drawbacks exist in the usage of SiPMs such as a higher dark count rate, many readout channels, slow response time, and optical crosstalk; therefore, users need to carefully consider the trade-offs. This work presents a SiPM-embedded compact large-area photon detection module. Various techniques are adopted to overcome the disadvantages of SiPMs so that it can be generally utilized as an upgrade from a PMT. A simple cooling component and recently developed optical crosstalk suppression method are adopted to reduce the noise which is more serious for larger-area SiPMs. A dedicated readout circuit increases the response frequency and reduces the number of readout channels. We favorably compare this design with a conventional PMT and obtain both higher photon detection efficiency and larger-area acceptance.

The Influence of Group Identification with Student Subgroups on Perceptions of Bystander Intervention to Prevent Sexual Assault.

College students can use bystander intervention tactics to prevent sexual assault within their communities. One's group memberships and group identification-conceptualized within social identity theory-could influence attitudes and behaviors related to bystander intervention. College students (n = 1,170) participated in an online survey measuring group membership with student subgroups, identification, and bystander intervention perceptions. Subgroups in this study included fraternities/sororities, student organizations, National Collegiate Athletic Association athletes, club/intramural sports, and spiritual/faith-based organizations. For various student subgroups, group identification was significantly correlated with individuals' perceived willingness and likelihood to engage in bystander intervention and their perceptions about the helpfulness of bystander intervention tactics.

Prostate cancer recurring as small-cell carcinoma with a BRCA2 somatic mutation.

Introduction: Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear. Case presentation: A 68-year-old man with prostate cancer was referred to our hospital. He was treated with combined androgen blockade (bicalutamide and degarelix acetate). The disease progressed to castration-resistant prostate cancer, but with additional treatment, prostate-specific antigen levels remained below 0.02 ng/mL. However, computed tomography revealed enlarged right inguinal lymph nodes; moreover, his neuron-specific enolase levels were elevated. Histopathologic analysis of a biopsied lymph node confirmed small-cell carcinoma. After administering cytotoxic chemotherapy (etoposide plus cisplatin and amrubicin), the patient temporarily improved before relapsing. After genetic testing of the biopsy specimen revealed a BRCA2 deletion, we administered the oral PARP-2 inhibitor olaparib, which has achieved partial remission for 8 months. Conclusion: PARP-2 inhibition may improve the survival of patients with BRCA2-positive small-cell carcinoma of the prostate.

Triple combination therapy for clinically nonmetastatic super-high-risk prostate cancer.

Introduction: Patients with nonmetastatic but exceptionally high-risk prostate cancer are liable to have biochemical failure and may even die. Triple combination therapy, which consists of surgery, radiotherapy, and androgen-deprivation therapy, as first-line treatment, may control the disease for a long period. Case presentation: We treated a patient with super-high-risk, nonmetastatic prostate cancer, with triple combination therapy. He was biochemical relapse free at 60 months after the initiation of treatment. Conclusion: Triple combination therapy may be an option for super-high-risk, nonmetastatic prostate cancer.

[Efficacy of Combination Chemotherapy of Gemcitabine and Nedaplatin for Squamous Cell Carcinoma of the Urinary Tract : Experience of Four Cases].

We report the use of combination chemotherapy of gemcitabine (800 mg/m² on day1 and 8) and nedaplatin (60 mg/m² on day 1), including neoadjuvant therapy in four cases of squamous cell carcinoma of the urinary tract. In each case, the dose was reduced after assessing the performance status and renal function of the patient. Among the four cases, the best overall outcome was complete response in one case, partial response in two cases, and stable disease in one case. The main adverse event observed was thrombocytopenia; however, no serious adverse events were observed, and this regimen was safely administered. Therefore, we believe that this regimen could be an effective treatment option for progressive squamous cell carcinoma originating from the urinary tract.

Development and validation of prediction model for incident overactive bladder: The Nagahama study.

OBJECTIVES: We aimed to develop models to predict new-onset overactive bladder in 5 years using a large prospective cohort of the general population. METHODS: This is a secondary analysis of a longitudinal cohort study in Japan. The baseline characteristics were measured between 2008 and 2010, with follow-ups every 5 years. We included subjects without overactive bladder at baseline and with follow-up data 5 years later. Overactive bladder was assessed using the overactive bladder symptom score. Baseline characteristics (demographics, health behaviors, comorbidities, and overactive bladder symptom scores) and blood test data were included as predictors. We developed two competing prediction models for each sex based on logistic regression with penalized likelihood (LASSO). We chose the best model separately for men and women after evaluating models' performance in terms of discrimination and calibration using an internal validation via 200 bootstrap resamples and a temporal validation. RESULTS: We analyzed 7218 participants (male: 2238, female: 4980). The median age was 60 and 55 years, and the number of new-onset overactive bladder was 223 (10.0%) and 288 (5.8%) per 5 years in males and females, respectively. The in-sample estimates for C-statistic, calibration intercept, and slope for the best performing models were 0.77 (95% confidence interval 0.74-0.80), 0.28 and 1.15 for males, and 0.77 (95% confidence interval 0.74-0.80), 0.20 and 1.08 for females. Internal and temporal validation gave broadly similar estimates of performance, indicating low optimism. CONCLUSION: We developed risk prediction models for new-onset overactive bladder among men and women with good predictive ability.

Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer.

PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.

Suppression of the optical crosstalk in a multi-channel silicon photomultiplier array.

We propose and study a method of optical crosstalk suppression for silicon photomultipliers (SiPMs) using optical filters. We demonstrate that attaching absorptive visible bandpass filters to the SiPM can substantially reduce the optical crosstalk. Measurements suggest that the absorption of near infrared light is important to achieve this suppression. The proposed technique can be easily applied to suppress the optical crosstalk in SiPMs in cases where filtering near infrared light is compatible with the application.

Protocol for development and validation of a prediction model for 5-year risk of incident overactive bladder in the general population: the Nagahama study.

BACKGROUND: An accurate prediction model could identify high-risk subjects of incident Overactive bladder (OAB) among the general population and enable early prevention which may save on the related medical costs. However, no efficient model has been developed for predicting incident OAB. In this study, we will develop a model for predicting the onset of OAB at 5-year in the general population setting. METHODS: Data will be obtained from the Nagahama Cohort Project, a longitudinal, general population cohort study. The baseline characteristics were measured between Nov 28, 2008 and Nov 28, 2010, and follow-up was performed every 5 years. From the total of 9,764 participants (male: 3,208, female: 6,556) at baseline, we will exclude participants who could not attend the follow-up assessment and those who were defined as having OAB at baseline. The outcome will be incident OAB defined using the Overactive Bladder Symptom Score (OABSS) at follow-up assessment. Baseline questionnaires (demographic, health behavior, comorbidities and OABSS) and blood test data will be included as predictors. We will develop a logistic regression model utilizing shrinkage methods (LASSO penalization method). Model performance will be evaluated by discrimination and calibration. Net benefit will be evaluated by decision curve analysis. We will perform an internal validation and a temporal validation of the model. We will develop a web-based application to visualize the prediction model and facilitate its use in clinical practice. DISCUSSION: This will be the first study to develop a model to predict the incidence of OAB.