External validation of hemoglobin and neutrophil levels as predictors of the effectiveness of ipilimumab plus nivolumab for treating renal cell carcinoma.

Introduction: Pretreatment hemoglobin and neutrophil levels were previously reported to be important indicators for predicting the effectiveness of ipilimumab plus nivolumab (IPI + NIVO) therapy for renal cell carcinoma (RCC). Therefore, we aimed to validate this in a large external cohort. Methods: In total, 172 patients with RCC who underwent IPI + NIVO treatment at a multicenter setting were divided into three groups according to their pretreatment hemoglobin and neutrophil levels (group 1: non-anemia; group 2: anemia and low-neutrophil; and group 3: anemia and high-neutrophil). Results: Group 1 showed better survival than groups 2 and 3 (overall survival: 52.3 vs. 21.4 vs. 9.4 months, respectively; progression-free survival: 12.1 vs. 7.0 vs. 3.4 months, respectively). Discussion: In this large cohort, we validated our earlier observation that hemoglobin and neutrophil levels can be reliable predictors of the effectiveness of IPI + NIVO in advanced RCC. Thus, our approach may aid in selecting the optimal first-line therapy for RCC.

Evaluation of the scrotal thermal environment and the testicular sizes in prepubertal hemiscrotal agenesis without cryptorchidism.

Introduction: Hemiscrotal agenesis is a rare scrotal developmental disorder. Orchiopexy on the opposite side of the scrotum with rugae or scrotoplasty combined with orchiopexy is usually performed as a surgical treatment for hemiscrotal agenesis with cryptorchidism. Till date, there are only eight published case studies of hemiscrotal agenesis. Case presentation: A 6-year-old boy, who had been previously treated for infantile hemangiomas, was referred by a pediatrician to our hospital for the follow-up of hemiscrotal agenesis without cryptorchidism. Thermography demonstrated that the temperature of the right scrotal skin with no rugae was higher than that of the left scrotal skin with rugae. The patient's parent declined scrotoplasty because the hemiscrotal agenesis was to be followed up without scrotoplasty and scrotal ultrasonography revealed no abnormal findings in both testes. Conclusion: High-temperature environment may not impair the testicular growth in prepubertal hemiscrotal agenesis without cryptorchidism.

Multicenter surveillance of the outcomes of and antimicrobial susceptibility to acute cystitis caused by Staphylococcussaprophyticus.

In this study, we aimed to investigate the antimicrobial susceptibility of Staphylococcus saprophyticus in Japan. Additionally, we evaluated the effectiveness of different therapeutic agents and compared the differences in their outcomes in treating S. saprophyticus-induced acute cystitis, considering that cephem antibiotics are standard treatments for acute cystitis in Japan. This retrospective study was conducted at ten hospitals housing urology departments, where urologists were dispatched from the Department of Nephro-Urology, Nagoya City University Graduate School of Medicine. Initially, we prepared a list of S. saprophyticus cases detected between January 2012 and December 2021, using the bacteriological testing system of each hospital. Subsequently, we reviewed the electronic medical records of the listed cases to investigate the causative diseases, treatments, and outcomes in patients with acute cystitis. The number of S. saprophyticus samples collected in this study was 289 from urine specimens, including 157 from women with acute cystitis. All antimicrobial agents demonstrated good therapeutic efficacy in all patients, except in those who did not return for follow-up visits (30 %). Furthermore, only one case of inadequate therapeutic efficacy was observed in a patient treated with a third-generation cephalosporin. All the other patients were cured. These findings revealed that the susceptibility of S. saprophyticus to different antimicrobials did not differ considerably between the specimens from patients with acute cystitis and those from other patients, suggesting a similar trend of therapeutic efficacies of the tested antimicrobials against S. saprophyticus-induced acute cystitis.

The first detailed annual record on the National Clinical Database Urology Division in Japan: A report on five surgical procedures.

OBJECTIVES: The National Clinical Database (NCD) Urology Division commenced registration in April 2018 in Japan. This is the first report to focus on five surgeries for which detailed information is registered. METHODS: We herein describe annual trends in and the complication grades of the following five surgeries: partial nephrectomy, radical nephrectomy, radical cystectomy, radical prostatectomy, and pyeloplasty, using the NCD. A total of 149 417 patients treated with the five types of surgeries based on NCD data were enrolled in this report. RESULTS: The number of patients was 55 630 for partial/radical nephrectomy from April 2018 to December 2021, 83 653 for radical prostatectomy from April 2018 to December 2021, and 9342 for radical cystectomy from January 2020 to December 2021. In 2021, partial nephrectomy was performed on 7416 cases, radical nephrectomy on 7739 cases, radical prostatectomy on 22 692 cases, radical cystectomy on 4677 cases, and pyeloplasty on 792 cases. CONCLUSIONS: The results obtained showed that a robot-assisted or laparoscopic procedure has replaced open surgery as the common approach for all five surgeries. An analysis of NCD data may be useful for understanding trends in surgical procedures across the major field of urology.

Prognostic factors for non­metastatic castration­resistant prostate cancer treated with androgen receptor signaling inhibitors.

The treatment paradigm for non-metastatic castration-resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first-line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first-line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow-up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression-free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate-specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first-line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first-line treatment.

Annual record on the number of general urological surgeries registered in the National Clinical Database system between April 2018 and December 2021 in Japan.

BACKGROUND: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018. METHODS: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021. RESULTS: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories. CONCLUSIONS: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan.

Cachexia Index Is a Prognostic Indicator in Patients With Metastatic Urothelial Carcinoma Treated With Systemic Chemotherapy.

Background/Aim: Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy. Patients and Methods: The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan-Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS). Results: At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05]. Conclusion: CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.

Using fosfomycin to prevent infection following ureterorenoscopy in response to shortage of cephalosporins: a retrospective preliminary study.

BACKGROUND: In 2019, the shortage of cefazolin led to the demand for cefotiam and cefmetazole exceeding the supply. The Department of Nephro-urology at Nagoya City University Hospital used fosfomycin as a substitute for perioperative prophylaxis. This retrospective preliminary study evaluated the efficacy of fosfomycin and cefotiam for preventing infections following ureterorenoscopy. METHODS: The study included 182 patients who underwent ureterorenoscopy between January 2018 and March 2021). Perioperative antibacterial treatment with fosfomycin (n = 108) or cefotiam (n = 74) was administered. We performed propensity score matching in both groups for age, sex, preoperative urinary catheter use, and preoperative antibiotic treatment. RESULTS: The fosfomycin and cefotiam groups (n = 69 per group) exhibited no significant differences in terms of patients' median age, operative duration, preoperative urine white blood cell count, preoperative urine bacterial count, and the rate of preoperative antibiotic treatment. In the fosfomycin and cefotiam groups, the median duration of postoperative hospital stay was 3 and 4 days, respectively; the median maximum postoperative temperature was 37.3 °C and 37.2 °C, respectively. The fosfomycin group had lower postoperative C-reactive protein levels and white blood cell count than the cefotiam group. However, the frequency of fever > 38 °C requiring additional antibiotic administration was similar. CONCLUSIONS: During cefotiam shortage, fosfomycin administration enabled surgeons to continue performing ureterorenoscopies without increasing the complication rate.

Original Training for Laparoscopic Surgery by Making an Origami Paper Crane.

INTRODUCTION: The training box is an effective tool used by surgical trainees. Suturing training is the common method of practicing laparoscopic surgery; however, the cost of needles and threads for long-term practice remains a problem. In this study, we incorporated the original Japanese training for laparoscopic surgery by making an origami paper crane (laparoscopic origami training (LOT)) and evaluated its effect on the clinical results as a long-term practice. METHODS: LOT was performed using a single 7.5 × 7.5 cm origami paper in the training box of laparoscopic surgery. In the bench-top study, the total time required to make one paper crane was measured and evaluated, and a self-efficacy questionnaire was designed to analyze the efficacy of LOT. In clinical practice, we retrospectively compared two resident groups, one that had previously trained on LOT (trained group) and the other that did not (less-trained group), by analyzing the pneumoperitoneum time (PT) for 10 cases. RESULTS: After making paper cranes in approximately 100 cases, the making time was reduced to approximately 10 min. Long-term results analyzing up to 1500 cases revealed that in addition to shortening the time required to make a paper crane, the shape of the crane also improved. Consequently, the median PT was significantly shorter in the trained group than in the less-trained group (129.0 (62-287) versus 208.5 (127-343) min; p<0.001). CONCLUSION: LOT contributed to introducing safe laparoscopic surgery to residents and improved their laparoscopic outcomes. We believe that this is a useful practice methodology that can be recommended to general physicians who wish to practice laparoscopic surgeries.

Efficacy of mini-endoscopic combined intrarenal surgery for pediatric kidney calculi: a single center retrospective study.

Management of large pediatric kidney calculi (PKC) is challenging. This study aimed to evaluate the efficacy and safety of miniature endoscopic combined intrarenal surgery (mini-ECIRS) for PKC. We retrospectively analyzed mini-ECIRS in 16 pediatric patients undergoing kidney stone treatment between November 2014 and October 2023 to determine its safety, efficacy, and associated outcomes. The median age was 50.50 (interquartile range: 36.75, 84.75) months, and the mean stone size was 21.63 ± 11.65 mm. The stone-free rate was 81.25%. The median decrease in hemoglobin level on the day after surgery was 1.10 (0.80, 1.55), and no patient required a blood transfusion. The median number of general anesthesia procedures was 2.00 (2.00, 2.00). Postoperative complications included fever in two patients and difficulty in removing the ureteral stent in one patient. In this cohort, five patients underwent pre-stenting under general anesthesia before mini-ECIRS. Age was significantly lower in the pre-stenting group than in the non-pre-stenting (P < 0.01); however, there were no significant differences in operative time, stone-free rate, total number of general anesthesia procedures, hemoglobin loss, or postoperative hospital stay between the groups. Mini-ECIRS was found to be a safe and efficient treatment method with a high stone removal rate in pediatric patients.

Experience and Prognostic Analysis with Avelumab Switch Maintenance Treatment in Metastatic Urothelial Carcinoma.

INTRODUCTION: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients. METHODS: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated. RESULTS: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.

Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones.

Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common type of kidney stone. Calcium oxalate appears in two forms in kidney stones: the stable phase, monohydrate (COM), and the metastable phase, dihydrate (COD). Particularly, COM stones with concentric structures are hard and difficult to treat. However, the factor determining the growth of either COM or COD crystals in the urine, which is supersaturated for both phases, remains unclear. This study shows that calcium phosphate ingredients preferentially induce COM crystal nucleation and growth, by observing and analyzing kidney stones containing both COM and COD crystals. The forms of calcium phosphate are not limited to Randall's plaques (1-2 mm size aggregates, which contain calcium phosphate nanoparticles and proteins, and form in the renal papilla). For example, aggregates of strip-shaped calcium phosphate crystals and fields of dispersed calcium phosphate microcrystals (nano to micrometer order) also promote the growth of concentric COM structures. This suggests that patients who excrete urine with a higher quantity of calcium phosphate crystals may be more prone to forming hard and troublesome COM stones.

Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma.

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

Defining a learning curve for urology trainees to achieve renal access without complications in endoscopic combined intrarenal surgery.

OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.

C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study.

BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

Prognostic outcomes in Japanese patients with metastatic castration-sensitive prostate cancer: Comparative assessments between conventional androgen deprivation therapy (ADT) and ADT with novel androgen receptor signal inhibitor.

OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

The impact of crystal phase transition on the hardness and structure of kidney stones.

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.