糠谷 拓尚

BACKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapy (ICI plus ICI [IO-IO] or ICI plus tyrosine kinase inhibitor [IO-TKI]) is the standard first-line treatment for metastatic renal cell carcinoma (mRCC), but its impact in patients undergoing maintenance hemodialysis (HD) relative to non-HD patients remains unclear. METHODS: We retrospectively compared patients with mRCC who received first-line IO-IO or IO-TKI therapy (2018-2025) according to HD status at treatment initiation. Oncologic outcomes (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) and safety were assessed in the crude cohort and after inverse probability of treatment weighting (IPTW) based on propensity scores. IO-IO and IO-TKI regimens were also compared within the HD cohort. RESULTS: Among 601 patients, 37 were receiving HD. In the crude cohort, HD patients had significantly worse PFS, OS, and ORR (37% vs. 57%) than non-HD patients. After IPTW, PFS remained significantly shorter in the HD group (hazard ratios [HR] 1.76, 95% confidence interval [CI] 1.21-2.57; P = 0.003), whereas OS (HR 1.49, 95% CI 0.89-2.50; P = 0.1) and ORR (odds ratios 0.58, 95% CI 0.22-1.54; P = 0.3) were no longer significant. Safety, including Grade ≥3 adverse events, was comparable. Among HD patients, PFS and OS did not differ between IO-IO and IO-TKI regimens. CONCLUSIONS: In mRCC patients undergoing HD, first-line ICI-based combination therapy was associated with significantly shorter PFS, whereas the worse crude OS and ORR were attenuated after adjustment, largely reflecting baseline prognostic differences rather than reduced efficacy. With a comparable safety profile, it may be a reasonable option in selected patients undergoing HD.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies, including immune checkpoint inhibitor plus immune checkpoint inhibitor (IO + IO) and immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO + TKI) regimens, have significantly improved outcomes in metastatic renal cell carcinoma (mRCC). However, the prognostic impact of host-related factors in patients receiving these therapies remains unclear. METHODS: We retrospectively analyzed 493 patients with mRCC treated with IO+IO (n = 205) or IO+TKI (n = 288) as first-line therapy. Survival outcomes and treatment responses were evaluated according to host-related factors using Cox proportional hazards models. RESULTS: In the IO+IO cohort, multiple host-related factors were independently associated with worse overall survival, including BMI < 25 kg/m2 (HR 2.280, p = 0.007), dyslipidemia (HR 2.079, p = 0.019), PPI use (HR 1.605, p = 0.039), and opioid use (HR 2.919, p = 0.008). In contrast, in the IO+TKI cohort, only IMDC poor risk (HR 4.169, p < 0.001) and opioid use (HR 3.328, p < 0.001) were significantly associated with overall survival. Host-related factors showed limited associations with objective response and disease control rates in both cohorts. CONCLUSION: The prognostic impact of host-related factors differs according to treatment regimen in mRCC. These findings suggest that host immune and metabolic conditions play a more prominent role in immune-driven IO+IO therapy, whereas tumor-related factors may predominate in IO+TKI therapy.

OBJECTIVES: To evaluate the incidence, antimicrobial prophylaxis patterns, and risk factors for perioperative infections after robot-assisted radical prostatectomy (RARP) in a large Japanese multicenter cohort. METHODS: We retrospectively analyzed 6660 patients who underwent RARP between 2009 and 2021 and received Japanese Urological Association guideline-recommended prophylaxis with cefazolin (CEZ), ampicillin/sulbactam (ABPC/SBT), or second-generation cephalosporins (2ndCPs). Surgical site infection (SSI), urinary tract infection (UTI), and remote infection (RI) within 30 postoperative days were assessed. Infection rates were compared according to antibiotic regimen and duration (≤ 24 vs. > 24 h), and risk factors were evaluated using logistic regression. RESULTS: CEZ, ABPC/SBT, and 2ndCPs were administered to 4321 (64.9%), 1501 (22.7%), and 838 (12.6%) patients, respectively. Overall incidences of SSI, UTI, and RI were 1.2%, 1.4%, and 0.3%, respectively. SSI was mainly superficial, whereas deep or organ/space SSI was rare. No significant differences in SSI incidence were observed between ≤ 24- and > 24-h administration within each regimen. Multivariate analysis identified bowel injury as an independent risk factor for SSI. For UTI, body mass index (BMI) ≥ 30 kg/m2, leakage at catheter removal, indwelling catheterization ≥ 8 days, and ABPC/SBT use were associated factors. CONCLUSIONS: Perioperative infection rates after RARP were low. Prophylaxis within 24 h, particularly with CEZ or 2ndCPs, may be sufficient. Prevention of bowel injury and appropriate catheter management may further reduce postoperative infections.

BACKGROUND/AIM: Existing prognostic models for metastatic renal cell carcinoma (mRCC) were developed using all-age cohorts, and their validity in non-elderly patients remains unclear. We aimed to develop and validate our prognostic model for patients aged ≤65 years with mRCC, including non-clear cell histologies, and to establish a practical risk stratification system. PATIENTS AND METHODS: We retrospectively analyzed 210 patients with mRCC from multiple Japanese institutions. The primary endpoint was overall survival (OS). Independent prognostic factors were identified using a multivariable Cox regression analysis. A simplified scoring system was constructed to stratify patients into risk groups. Model discrimination was evaluated using the concordance index (C-index), with internal validation by bootstrap resampling. Clinical utility was assessed by a decision curve analysis (DCA). A nomogram was constructed based on the identified independent prognostic factors. RESULTS: During a median follow-up of 57 months, 77 OS events occurred; median OS was 65.7 months. Histopathological type, liver metastasis, C-reactive protein, serum-corrected calcium, and time to systemic therapy were independently associated with worse OS. Our prognostic model stratified patients into favorable- (n=89), intermediate- (n=76), and poor- (n=45) risk groups, with median OS of 95.1, 37.7, and 9.6 months, respectively (p<0.001). The 5-year C-index was 0.74, exceeding that of the International Metastatic RCC Database Consortium (IMDC) model (0.70). In DCA, our prognostic model showed higher net benefit across threshold of 0.3-0.6, corresponding to an average reduction of 3.26 unnecessary treatment escalations per 100 patients. The nomogram showed time-dependent C-indices of 0.83, 0.84, and 0.87 at 1, 3, and 5 years. CONCLUSION: Our prognostic model provides superior discrimination to and higher clinical utility than the IMDC model for predicting OS in non-elderly patients with mRCC, supporting age-specific risk stratification in this population.

BACKGROUND: In the era of immuno-oncology (IO) combination therapy, prognostic tools for elderly patients with metastatic clear cell renal cell carcinoma (ccRCC) are lacking. This study aimed to identify prognostic factors in elderly patients and evaluate a novel risk model using the restricted mean survival time (RMST) and a decision curve analysis (DCA). METHODS: We retrospectively analyzed 203 patients aged ≥70 years with metastatic ccRCC treated with first-line IO combination therapy. Independent prognostic factors for overall survival (OS) were identified. Beyond the hazard ratio, a RMST analysis with a 24-month truncation time quantified absolute survival differences between risk groups. Clinical utility was evaluated using DCA. RESULTS: A multivariable analysis identified low body mass index, low Karnofsky performance status, elevated lactate dehydrogenase, low serum albumin, and liver metastases as independent prognostic factors. In the RMST analysis at 24 months, significant survival disparities were quantified. The intermediate- and poor-risk groups showed mean survival reductions of 1.92 and 6.27 months, respectively, from OS in the favorable-risk group. The model demonstrated a higher net benefit through DCA than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) classification across a wide range of threshold probabilities for 24-month OS. The model's C-index (0.728) was higher than that of the IMDC classification (0.603). CONCLUSIONS: Our prognostic model for elderly patients provides a practical tool for clinical decision-making by visualizing time-based survival differences via RMST and demonstrating potential clinical utility in DCA.

OBJECTIVES: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive histological variant associated with a poor prognosis. While immune checkpoint inhibitor (ICI)-based combinations have become the standard of care, the optimal first-line regimen, specifically dual immunotherapy (IO-IO) vs. IO plus tyrosine kinase inhibitor (IO-TKI), remains controversial. We herein examined the real-world clinical outcomes of Japanese patients with sRCC. METHODS: We conducted a retrospective multicenter study on 46 patients with advanced or metastatic sRCC receiving first-line ICI-based combination therapy between January 2018 and December 2024 (IO-IO: n = 18; IO-TKI: n = 28). In a comparative survival analysis, three favorable-risk patients in the IO-TKI group were excluded to align risk profiles, focusing on intermediate/poor-risk groups (n = 43). The primary endpoint was overall survival (OS). RESULTS: In the entire cohort (n = 46), the objective response rate was numerically higher in the IO-TKI group (64.3%) than in the IO-IO group (50.0%) (p = 0.37). In the comparative analysis of intermediate/poor-risk patients (n = 43), progression-free survival (PFS) was slightly longer (p = 0.071), and OS was significantly longer (p = 0.016) in the IO-TKI group than in the IO-IO group. A multivariable analysis adjusted for IMDC risk categories showed favorable survival with the IO-TKI regimen (HR 0.37, p = 0.061). CONCLUSIONS: The present study indicates that first-line IO-TKI combination therapy represents a promising treatment option with a potential survival advantage over IO-IO therapy for Japanese patients with sRCC. However, due to the retrospective design and small sample size, reliably determining the comparative efficacy of these regimens remains challenging, and further validation is warranted.

BACKGROUND: Standard first-line treatment for patients with advanced renal cell carcinoma (aRCC) has commonly included combined immune-oncology (IO) agents (IO-IO) or combinations of a tyrosine kinase inhibitor (TKI) and an IO agent (IO-TKI); however, there are few head-to-head comparative real-world studies, especially involving Japanese cohorts. OBJECTIVE: To compare prognoses of patients treated with IO-IO or IO-TKI therapy in routine Japanese clinical practice. METHODS: This retrospective study included 416 International Metastatic RCC Database Consortium (IMDC) intermediate- and poor-risk patients with aRCC treated with either IO-IO or IO-TKI at four institutions from September 2018 to February 2026. Effectiveness and safety outcomes were comprehensively compared. Overall (OS) and progression-free survival (PFS) rates were estimated with the Kaplan-Meier method. RESULTS: We used propensity-score matching to compare 324 patients (IO-IO: 162; IO-TKI: 162). The IO-TKI cohort showed significantly higher objective response rates than the IO-IO cohort (66 versus 44%, respectively, p < 0.01), longer PFS (17.1 versus 8.4 months, respectively, HR = 0.56, p < 0.01), and longer OS (51.7 versus 31.5 months, respectively, HR = 0.70, p = 0.04), although OS did not reach significance in the IMDC risk-stratified subgroups. While all-grade adverse events (AEs) were more common in the IO-TKI group (94 versus 83%, respectively, p < 0.01), rates of immune-related AEs and corticosteroid administration were significantly higher in the IO-IO cohort. The study limitations include the retrospective design and treatment strategy solely decided by each physician. CONCLUSIONS: IO-TKI combinations were associated with higher rates of adverse events but survival benefits in IMDC intermediate- and poor-risk patients with aRCC.

The clinical significance of comprehensive genomic profiling (CGP) has been established in metastatic castration-resistant prostate cancer (PC). However, the role of genomic profiling in localized PC remains unclear. In this exploratory study, we evaluated somatic genomic alterations in localized PC using an in-house CGP platform to examine their associations with biochemical recurrence (BCR) and recurrence-free survival (RFS) after radical prostatectomy. DNA extracted from surgical specimens of 314 patients with localized PC was analyzed for alterations in 164 cancer-related genes. Six genes (PTEN, BRCA2, POLD1, ERBB3, MYC, and SETD2) were more frequently altered in patients who developed BCR in exploratory analyses. Patients harboring alterations in any of these genes (n = 96) showed higher pathological T stage, increased BCR rates (27.1% vs. 6.4%), and inferior RFS compared with alteration-negative patients (n = 218; p < 0.001). In multivariate analysis, the presence of these alterations was independently associated with worse RFS. Among individual genes, BRCA2 alteration, and particularly BRCA2-SETD2 co-alteration, were associated with unfavorable outcomes, although the latter finding was based on a limited number of cases. In patients who developed BCR, alterations were associated with shorter PSA doubling time and poorer outcomes after salvage radiotherapy, particularly in margin-negative cases; however, these subgroup analyses were based on small numbers and should be interpreted as hypothesis-generating. These findings suggest that somatic genomic alterations identified at prostatectomy are associated with early recurrence in localized PC. Further validation in independent cohorts is required to determine whether genomic profiling may contribute to future risk stratification and management strategies.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC. METHODS: This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching. RESULTS: Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5). CONCLUSIONS: Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations.

Metastatic castration-sensitive prostate cancer (mCSPC) is a biologically heterogeneous disease with a variable clinical course. Over the past decade, the treatment landscape for mCSPC has evolved significantly, shifting from androgen deprivation therapy (ADT) alone to combination approaches, including chemotherapy and novel androgen receptor pathway inhibitors. Landmark trials, such as CHAARTED, STAMPEDE, and LATITUDE, have demonstrated significant survival benefits with the addition of docetaxel or abiraterone to ADT, leading to changes in clinical guidelines and practice. More recently, triplet therapies combining ADT, docetaxel, and androgen receptor signaling inhibitors have shown further improvement in patient outcomes, although optimal patient selection remains unclear. Furthermore, advances in molecular profiling and imaging have enabled more precise stratification of patients, allowing for personalized treatment strategies. This review provides a comprehensive overview of the current evidence regarding treatment strategies for mCSPC, including key clinical trials, real-world data, and ongoing research. Additionally, we discuss emerging therapies and potential future directions, such as the integration of novel agents targeting DNA repair pathways or radiopharmaceuticals targeting prostate-specific membrane antigen. As the therapeutic landscape continues to expand, a more nuanced understanding of disease biology and patient characteristics is essential for guiding individualized care and improving long-term outcomes in men with mCSPC.

Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO-IO and IO-tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO-IO and IO-TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO-IO and IO-TKI. In bone metastases (n = 80), OS tended to favor IO-TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO-TKI (P = 0.011). IO-TKI may be a more appropriate first-line option than IO-IO for mRCC with bone or liver metastases, while efficacy is similar for other sites.

BASCKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). Proton-pump inhibitors (PPIs), frequently used to treat gastrointestinal conditions, have been implicated in modulating ICI efficacy, potentially through gut microbiome dysbiosis. However, the impact of PPIs on ICI-based therapies for mRCC remains unclear. METHODS: This multicenter retrospective cohort study analyzed 427 patients with mRCC classified as intermediate or poor risk according to the IMDC criteria treated with first-line IO-IO (ipilimumab plus nivolumab) or IO-TKI (ICI plus tyrosine kinase inhibitor) therapies. Patients were stratified by PPI use during the 30 days before and including the day of ICI initiation. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between PPI users and nonusers. RESULTS: PPI use was significantly associated with shorter OS in patients receiving IO-IO therapy (median OS, 23.34 months vs. not reached; P = .002), but not in those receiving IO-TKI therapy (P = .909). Multivariate analysis confirmed PPIs as an independent prognostic factor for OS in the IO-IO group (HR, 1.647; 95% CI, 1.007-2.693; P = .046). No significant differences in PFS or ORR were observed between PPI users and nonusers in either group, although the complete response rate was notably lower in PPI users treated with IO-IO (1.6% vs. 10.3%; P = .025). CONCLUSIONS: PPI use was associated with inferior survival in mRCC patients receiving IO-IO therapy, potentially through microbiome modulation and other immunologic or clinical mechanisms; however, these findings are based on retrospective data and should be regarded as hypothesis-generating. Caution is advised when prescribing PPIs to patients undergoing ICI-based therapy, particularly IO-IO regimens, and prospective studies are needed to confirm whether avoiding unnecessary PPI use can improve clinical outcomes.

INTRODUCTION: We aimed to evaluate the feasibility, safety, and perioperative outcomes of single-port (SP) robot-assisted partial nephrectomy (RAPN) via the supine low anterior access (LAA) compared with conventional multi-port (MP) RAPN. METHODS: We retrospectively reviewed 65 patients with cT1a renal tumors who underwent retroperitoneal RAPN between October 2023 and September 2025. Fifteen patients underwent SP-RAPN via the supine LAA, and 50 patients underwent MP-RAPN via the lateral flank access (LFA). Perioperative outcomes and postoperative outcomes, including warm ischemia time (WIT), estimated blood loss (EBL), complications, trifecta achievement, renal function, and length of hospital stay, were compared between the two groups. RESULTS: After adjusting patient variables by 1:2 propensity score matching (PSM), 13 and 26 patients were in the respective groups, and there were no significant differences in baseline characteristics between groups. SP-RAPN demonstrated longer WIT (17.4 ± 3.2 vs. 13.7 ± 3.7 min, p = 0.004). EBL (95 ± 86.1 vs. 63.1 ± 89.3 mL, p = 0.295) and complication rates were similar, with no conversions or positive surgical margins in either group. Length of hospital stay was shorter in the SP group (7.3 ± 0.9 vs. 8.5 ± 0.9 days, p = 0.001). Trifecta achievement was 100% in SP-RAPN vs. 96.2% in MP-RAPN (p = 1). Postoperative renal function was comparable between the two groups. CONCLUSION: SP-RAPN via the supine LAA is a safe alternative to MP-RAPN, offering comparable oncologic outcomes with reduced hospitalization. Despite longer WIT during the learning phase, the supine LAA and single-port access may provide ergonomic and recovery benefits. However, further studies are warranted to assess its clinical benefits, cost-effectiveness, and long-term oncologic outcomes.

OBJECTIVES: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy. METHODS: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment. RESULTS: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio. CONCLUSIONS: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies.

BACKGROUND: Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen. METHODS: A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab. Logistic regression analyses assessed associations between clinical factors and early PD. RESULTS: During a median follow-up of 17 months, patients had median overall (OS) and progression-free survival (PFS) of 35 and 14 months, respectively. Objective response and PD rates were 49.9% and 24.9%, respectively. Patients with early PD had significantly worse OS than those with non-early PD (10 vs. 42 months; P = 0.0002). Multivariate analyses identified bone metastasis and performance status (PS) as independent indicators of early PD (P = 0.03 and 0.01, respectively). Early PD rates varied by metastatic site (lung, 19.3%; bone, 31.2%; brain, 10%; and liver, 30%). Patients with clear-cell RCC had a median OS of 48 months and PFS of 22 months. The identified variables of early PD were consistent across all patient populations evaluated. CONCLUSIONS: Bone metastasis and PS predict early PD in patients with mRCC treated with ipilimumab plus nivolumab, with antitumor effect of the regimen varying by metastatic site. Clarifying the characteristics of early PD may guide clinical decision-making in treatment selection.

BACKGROUND: Acute uncomplicated cystitis (AUC) is a urinary tract infection and is generally treated using antimicrobial therapy. Escherichia coli is the main causative agent of AUC. Recently, the prevalence of fluoroquinolone (FQ)-resistant-E. coli has demonstrated a noticeable increase. In this study, we aimed to investigate the effectiveness of appropriate antimicrobial treatment in AUC caused by E. coli in real-world clinical settings. METHODS: This retrospective cohort study reviewed the records of patients with AUC treated at the urology department of Minami Cooperative Hospital between April 2016 and December 2020. Effectiveness was defined as clinical improvement. RESULTS: The study cohort of 730 patients had a median age of 65.5 years (interquartile range, 57-78 years) and 23.2% were aged <55 years. E. coli was detected in 73.4% of patients, of whom 26.7% had levofloxacin (LVFX)-resistant strains. LVFX-resistant E. coli was associated with age ≥55 years and recurrent cases. Effectiveness was determined in 75.1% of cases, of which 75% complied with the Japanese or other international guidelines. The overall treatment effectiveness was highest with β-lactam (BL)/β-lactamase inhibitor (BLI) combinations (94.7%). The effectiveness of first- and third-generation cephalosporins (CPs) was 81.1-83.3%, and that of FQs and sulfamethoxazole-trimethoprim (ST) was 82.6-83.8%. For LVFX-resistant E. coli, the treatment effectiveness was highest (100%) with BL/BLI combinations, intermediate (75-81%) with first- and third-generation CPs and ST, and lowest (50%) with FQs. CONCLUSIONS: BL/BLI combinations had the highest effectiveness for the treatment of AUC.

BACKGROUND/AIM: Immune-related adverse events (irAEs) are associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immuno-oncology therapy. However, various irAEs occur during such therapy. In this study, we analyzed the association between irAEs and prognosis of patients with mRCC treated with nivolumab and ipilimumab. PATIENTS AND METHODS: We retrospectively collected data from 193 patients with mRCC who were treated with nivolumab and ipilimumab as first-line treatment between September 2018 and February 2023 at multiple institutions. We performed Cox proportional hazards analysis for progression-free (PFS) and overall (OS) survival to identify specific irAEs associated with prognosis. RESULTS: Among the 153 eligible patients (median age=68 years; range=27-86 years, the median PFS was 7.8 months (95% confidence interval=6.0-12.5 months), and the median OS was 34.0 months (95% confidence interval=23.9 months - not reached). The most common irAEs were endocrine disorder (28.8%), rash (18.3%), pulmonary disorder (10.5%), and liver dysfunction (9.8%). In the multivariate analysis, endocrine disorder-related irAEs were identified as prognostic factors for significantly better PFS and OS. Additionally, rash-related irAEs were significant prognostic factors, specifically for better OS (p<0.05). CONCLUSION: Both rash and endocrine disorder-related irAEs were predictors of survival outcomes in patients with mRCC treated with nivolumab and ipilimumab. Optimal management of these irAEs is essential for improving prognosis.

Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23-4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39-5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.

The composition of the distal ileum microbiota and the impact of fecal exposure during intracorporeal urinary diversion (ICUD) on gastrointestinal (GI) complications remain unclear. This study included 146 patients with bladder cancer who underwent ICUD without bowel preparation and received only a single day of antibiotic prophylaxis. Fecal samples were collected directly from the distal ileum during surgery, and ascitic fluid was obtained postoperatively from abdominal drains. Among the patients, 129 (88.3%) had minimal microbial growth in ileal feces, while 17 (11.7%) showed significant colonization. The most commonly identified organisms were Streptococcus, Enterococcus, Enterobacter, Klebsiella, and Candida. The incidence of GI complications was significantly higher in patients with positive ileal fecal cultures compared to those with no detectable growth (39.4% vs. 7.7%, P < 0.001), and even more pronounced in patients with positive ascitic cultures (72.5% vs. 11.3%, P < 0.001). Multivariate analysis identified positive ascitic cultures as an independent predictor of GI complications. Additionally, frailty was significantly associated with the presence of microbial growth in ascitic fluid. These findings suggest that, although the distal ileal microbiota is largely suppressed under short-term antibiotic prophylaxis, the presence of intra-abdominal bacteria or fungi is strongly linked to postoperative GI complications, including ileus. Frailty may contribute to microbial dysbiosis and the persistence of intra-abdominal pathogens, particularly Enterococcus and Enterobacter species.

Recently, urological surgery has undergone remarkable technological advances and these new technologies are being adapted to a wide array of medical fields. Robotic-assisted laparoscopic procedures are not limited to radical prostatectomy, but include partial nephrectomy, pyeloplasty, radical cystectomy, and more. Perioperative infection control measures are not limited to the selection, method, and duration of antimicrobials, but include new evidence about smoking cessation, abstinence from alcohol, blood glucose control, and nutritional status assessment as well as time off just before operations. The new 2023 JUA guidelines for the prevention of perioperative infections in the urological field include general remarks and itemized discussion. We chose three standard treatments related to background questions and nine clinical questions. Although we have organized information to the best of our ability, there are still many areas where evidence is lacking. We anticipate that urology specialists will continue to report new findings and accumulate more evidence regarding unresolved areas for the next revision.

OBJECTIVE: This study aimed to establish a robust predictive model for biochemical recurrence (BCR) in patients with prostate cancer who underwent robot-Assisted Radical Prostatectomy. MATERIAL AND METHODS: A cohort of 1700 patients who underwent robot-assisted radical prostatectomy (RARP) for prostate cancer between August 2009 and December 2022 was included. BCR was defined as two consecutive PSA levels exceeding 0.2 ng/mL post-radical prostatectomy. Cox proportional hazards regression identified predictive variables for BCR. Subsequently, pathologic T stage, PSA level, positive surgical margin, extraprostatic extension, and seminal vesicle involvement were retained. A nomogram was constructed using R software to predict BCR. The model was evaluated using the C-index and calibration curves. RESULTS: A total of 161 instances of BCR were observed during a median follow-up of 61.0 months (range, 12-162 months). The 5-year BCR-free survival rate for the cohort was 25 %. Univariate analysis demonstrated significant associations between BCR and PSA, clinical T stage, biopsy Gleason score, D'Amico risk classification, pathologic T stage, pathologic Gleason score, extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Multivariate analysis identified high PSA ≥20 ng/mL (HR: 1.93; p = 0.034), pathologic T stage 3-4 (HR: 1.89; p < 0.001), pathologic Gleason score 8-10 (HR: 5.43; p < 0.001), extraprostatic extension (HR: 1.41; p < 0.001), seminal vesicle involvement (HR: 1.92; p = 0.018), and positive surgical margin (HR: 2.73; p < 0.001) as independent predictors of BCR. The new model exhibited a C-index of 0.743 (95 % confidence interval: 0.741-0.745). CONCLUSION: The developed nomogram accurately predicts the likelihood of BCR-free status within 3 years following RARP. This allows for tailored follow-up strategies, optimizing resource allocation, and holds significant clinical utility, warranting broader implementation and further research.

Prostate cancer (PCa) is one of the most common cancers among men worldwide, and robot-assisted radical prostatectomy (RARP) is a widely used treatment for localized PCa. Achieving pentafecta outcomes, which include continence, potency, cancer control, free surgical margins, and no major complications, is a critical measure of surgical success and long-term prognosis. However, predicting these outcomes remains challenging. In this retrospective, single-center study, we analyzed data from 1,752 patients who underwent RARP for localized prostate adenocarcinoma between August 2009 and April 2023. The pentafecta outcome was achieved in 290 patients (16.6%). Multivariate analysis revealed that bilateral nerve sparing significantly increased the likelihood of achieving the pentafecta outcome (odds ratio 10.36, 95% CI: 5.75-18.66; p < 0.001). Preoperative potency and bilateral nerve sparing were also identified as key predictors. Nomograms were developed using preoperative and postoperative variables, including age, PSA level, biopsy Gleason score, clinical stage, pathological tumor stage, tumor grade, nerve sparing, and preoperative potency. Internal validation of the nomograms was performed using bootstrapping methods, demonstrating robust predictive performance. These nomograms provide valuable tools for personalized surgical planning and patient counseling and may be applicable to broader populations, given the inclusion of universally recognized predictive factors and rigorous validation. This study presents the development and validation of nomograms to predict pentafecta outcomes before and after RARP. These nomograms provide valuable tools for clinicians to estimate the likelihood of achieving postoperative pentafecta outcomes. Incorporating these nomograms into clinical practice may improve patient counseling and shared decision-making.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have improved survival in metastatic renal cell carcinoma (mRCC), with nivolumab (NIVO) plus ipilimumab (IPI) showing benefits in intermediate- and poor-risk patients. Despite first-line efficacy, progression is common, requiring second-line therapies. Tyrosine kinase inhibitors (TKIs) are commonly administered after ICIs; however, the relationship between progression-free survival (PFS) in first- and second-line settings is not well defined. This study examined the correlation of PFS in patients with mRCC treated with ICIs followed by TKIs. PATIENTS AND METHODS: This retrospective multicenter study analyzed 66 patients with mRCC who received NIVO + IPI as first-line therapy and subsequent TKIs between September 2018 and February 2023. Patients were stratified according to the International Metastatic RCC Database Consortium (IMDC) risk classification. RESULTS: Median PFS for second-line TKIs was 6.9 months, and overall survival was 17.7 months. While no significant correlation was observed between first- and second-line PFS in the overall cohort or the IMDC intermediate-risk subgroup, a significant positive correlation was found in the poor-risk group (Spearman's rho=0.677, p=0.002). CONCLUSION: Treatment outcomes in poor-risk patients may exhibit a predictable response pattern across therapy lines, potentially informing personalized treatment strategies.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

OBJECTIVE: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high-grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD-to-neutrophil diameter ratio for detecting HGUC cells in urine cytology. METHODS: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD-to-neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide. RESULTS: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut-off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index. CONCLUSIONS: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells.

BACKGROUND: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. METHODS: We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. RESULTS: Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). CONCLUSIONS: There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.

BACKGROUND: Recently, various novel robotic systems have been put into clinical use. The aim of the present study was to assess the perioperative outcomes of robot-assisted radical prostatectomy (RARP) using the Hugo™ RAS system, one of brand-new robot-assisted surgical platforms. METHODS: We performed RARP with the Hugo™ RAS system in 13 cases of localized prostate cancer (PCa) between August 2023 and February 2024 at our hospital. The perioperative outcomes of these 13 patients were assessed. RESULTS: The median operative and console times were 197 (interquartile range [IQR], 187-228) and 134 min (IQR, 125-157), respectively. The median docking time was 7 min (IQR, 6-10), and the median estimated blood loss was 150 mL (IQR, 80-250). The vesical catheter was removed on postoperative day 6 in all cases. A positive surgical margin was observed in one patient (7.7%), and none experienced major perioperative complications, defined as Clavien-Dindo classification ≥3. The median postoperative length of stay was 8 days (IQR, 8-8.5). CONCLUSIONS: This was the first study to focus on RARP using the Hugo™ RAS system in Japan. Although further investigations should be conducted to assess the long-term oncological and functional outcomes, the Hugo™ RAS system could provide safe and favorable perioperative outcomes for patients with localized PCa undergoing RARP.

OBJECTIVES: The optimal indication and survival benefits of prophylactic urethrectomy (PU) during radical cystectomy remain unclear. Therefore, this study aims to evaluate the impact of urethra-preserving surgery (UPS) on oncological outcome including its recurrence patterns, and to establish an optimal urethral management strategy with a novel UPS technique in the robotic era. PATIENTS AND METHODS: We retrospectively analyzed 281 male patients with bladder cancer who received radical cystectomy (RC) (115 with and 166 without PU) at our institutions between 2010 and 2023. Subsequently, perioperative and oncological outcomes were assessed between propensity score-matched cohorts. RESULTS: Urethral recurrence (UR) occurred in 5 patients (5/166, 3.0%), all of whom underwent open-RC. Three among those (1.8%) with concomitant metastasis were died of cancer. There were no statistically significant differences between the PU and UPS groups in urethral-recurrence free survival (urethral-RFS) (P = .14), local-RFS (P = .59) and overall survival (OS) (P = .84) in the entire cohort. However, the UPS group showed significantly worse urethral-RFS (P = .008), local-RFS (P = .005) and OS (P = .03) in patients with high-risk of UR. Analysis of recurrence patterns revealed that UPS in high-risk patients significantly increased local recurrence (25.8% vs. 5.0%, P = .02). Conversely, a novel robotic-UPS technique demonstrated significantly favorable perioperative outcomes, comparable local-RFS (P = .79) and OS (P = .16) without UR (0/134, 0%) when compared to robotic-PU. Robotic-UPS also exhibited significantly better local-RFS (P =.007) and OS (P < .001) than open-UPS. CONCLUSIONS: UR-related death was rare and PU did not show a survival benefit for the entire cohort. However, inappropriate UPS in patients at high-risk of UR may increase local recurrence which might be responsible for poor survival after UPS rather than disease progression derived from UR. The robotic-UPS has the potential to reduce unnecessary PU, urethral and local recurrence without compromising survival.

INTRODUCTION: Urine cytology is an indispensable test for detecting high-grade urothelial carcinoma (HGUC); however, the distinction between HGUC cells and morphologically similar benign atypical cells poses clinical challenges. In this study, we performed double immunostaining for p53 and vimentin to establish a diagnostic method to accurately distinguish HGUC cells from benign atypical cells. METHODS: This study included 41 cases of HGUC, 11 of urolithiasis, and 22 of glomerular disease diagnosed histopathologically or clinically. After preparing urine cytology specimens from voided urine samples, p53 immunostaining was performed, and the p53-positive intensity and p53 positivity rate were calculated. Subsequently, vimentin immunostaining was performed on the same specimens to calculate the rate of vimentin positivity. RESULTS: The HGUC cell group had a mean p53-positive intensity of 2.40, a mean p53 positivity rate of 73.2%, and a mean vimentin positivity rate of 5.1%. In contrast, the mean p53-positive intensity, p53 positivity rate, and vimentin positivity rate were 1.63, 36.7%, and 66.2%, respectively, in the benign atypical cell group. There were significant differences between the two groups for each parameter. Moreover, two multiple logistic regression models combining the results of these three parameters exhibited higher sensitivity and specificity than solely assessing the p53-positive intensity, positivity rate, and vimentin positivity rate. CONCLUSION: Since double immunostaining with p53 and vimentin distinguishes HGUC cells from benign atypical cells, it could be to improve the diagnostic accuracy of urine cytology.

INTRODUCTION: Postoperative Legionella pneumonia is very rare. CASE PRESENTATION: A 71-year-old male patient with prostate cancer (cT2bN0M0) underwent a robotic-assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable. CONCLUSION: When bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

BACKGROUND: The interaction between lymph node dissection (LND) during radical cystectomy (RC) and neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the role of LND in patients undergoing RC after NAC. PATIENTS AND METHODS: We retrospectively analyzed 259 patients with muscle-invasive bladder cancer (MIBC) who underwent RC following NAC at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2010 and 2022. Baseline characteristics, pathological outcomes, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between propensity score (PS)-matched cohorts. RESULTS: PS matching analysis resulted in 94 matched pairs from the adequate (standard or extended template) and inadequate (limited template or unilateral- or no-LND) LND groups. The median number of dissected nodes was significantly higher in the adequate LND group than in the inadequate LND group (19 vs. 5, P < .001). Similarly, a higher pathological node-positive rate (ypN+) was observed in the adequate group than in the inadequate group (18.1% vs. 7.4%, P = .03). The adequate LND group identified more ypN+ with ≤ ypT1 cases than the inadequate group (4 vs. 1). There were no statistically significant differences between the adequate and inadequate groups in RFS (P = .94), CSS (P = .54), and OS (P = .65). Subgroup analysis also showed comparable survival rates, even in patients with ≥ pT3 or cN+ disease. ypN+ was an independent predictor of OS in the Cox regression analysis, while adequate LND and the number of lymph nodes removed (≥10 or ≥15) were not associated with survival. CONCLUSIONS: Although adequate LND did not show a significant therapeutic effect in RC after NAC, adequate LND may have an important diagnostic role in detecting ypN+, which is a robust predictor, and is a useful biomarker to perform appropriate adjuvant immunotherapy especially in ≤ ypT1 cases.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted radical cystectomy using an intracorporeal ileal conduit in older compared to younger patients. METHODS: We retrospectively analyzed 122 patients who underwent robot-assisted radical cystectomy with an intracorporeal ileal conduit at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2012 and 2022. Patients were categorized into two groups: older (age ≥ 75 years; n = 53) and younger (age < 75 years; n = 69). Perioperative outcomes, complications, recurrence-free survival, cancer-specific survival, and overall survival were compared between the cohorts. RESULTS: The groups had no significant differences in perioperative outcomes, such as estimated blood loss, operative time, and blood transfusion rate. However, hospital stay was longer in the older patients than in the younger group (19 vs. 16 days; p < 0.001). The 30-day minor and major complication rates were 33.3% and 13.0%, respectively, for the younger group and 50.9% and 9.4% for the older group (p = 0.11). Urinary tract infection and bowel ileus were the most common complications in both groups. No significant differences were observed in recurrence-free survival, cancer-specific survival, and overall survival between the groups (p = 0.58, p = 0.75, and p = 0.78), and subgroup analysis in ≥cT3 revealed the older group tended to have poorer cancer-specific survival and overall survival (p = 0.07 and p = 0.01). Multivariate analysis indicated that older age was not associated with high-grade complications and cancer-specific survival. CONCLUSIONS: Robot-assisted radical cystectomy with an intracorporeal ileal conduit is a safe and effective treatment option for older patients.

BACKGROUND: Immune checkpoint inhibitors can cause various immune-related adverse events (irAEs). This study aimed to evaluate the association between the incidence of irAEs and oncological outcomes of metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as first-line therapy. PATIENTS AND METHODS: We retrospectively analyzed data from 69 patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy between September 2018 and September 2021 at 4 institutions. Cox regression analyses were performed to investigate the important factors affecting overall survival (OS) in patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy. RESULTS: During observation with a median follow-up of 9.1 months, the median OS was not reached, while the median progression-free survival was 6.0 months. Patients with irAEs had significantly prolonged OS and progression-free survival than those without irAEs (p = .012 and .002, respectively). Multivariate analysis showed that 3 independent factors, including C-reactive protein (CRP), irAEs, and performance status (PS), were significantly associated with OS (p = .04, .02, and .01, respectively). The patients were subsequently divided into 3 groups as follows: group 1, 20 patients with all 3 independent OS predictors; group 2, 18 patients with irAE predictors alone or 2 positive independent OS predictors (irAEs + CRP or irAEs + PS); group 3, 31 patients with 3 negative independent S predictors. OS varied significantly among the 3 groups (p = .004). CONCLUSION: The appearance of irAEs could predict OS in patients with mRCC treated with nivolumab plus ipilimumab as the first-line therapy.

(Background) The purpose of this study was to investigate the current status of urologists regarding the prevention of perioperative infections in preparation for the revision of the Guidelines for the Prevention of Perioperative Infections in Urological Field (2015). (Methods) From January 26 to March 30, 2022, we administered questionnaires to members of the Japanese Urological Association on their adherence to the guidelines and administration methods of antimicrobial prophylaxis for perioperative infections. There were 362 respondents. (Results) The respondents reported adhering to the guidelines completely (15.5%), to some extent (55.5%), poorly (24.3%), and not at all (4.7%). Adherence rates also varied for surgical procedures, ranging from 73.8% in transurethral resection of bladder tumor to 32.9% in laparoscopic (robot-assisted) contaminated surgery. Excluding contaminated surgery and transurethral resection of prostate, where long-term administration is relatively acceptable, open clean-contaminated surgery had the highest rate of long-term administration (≥72 h) (27.2%) and transurethral resection of bladder tumor had the lowest rate (7.3%). Adherence rates for clean surgery and transurethral ureteral lithotripsy shortened to a single dose of antimicrobial agents were low. (Conclusion) The selected antimicrobial agents were generally in compliance with the guidelines. With the exception of contaminated surgery, they were administered long-term in clean-contaminated surgery where the urinary tract and genitalia were exposed. Surgical procedures in which a single prophylactic dose of antimicrobial agents was administered had a low compliance rate. After the revision of the guidelines, it is considered important to update the clinical paths at each facility.

For patients with testicular tumors who need the surgical management, open retroperitoneal lymph node dissection (O-RPLND) is considered the gold standard treatment. However, recently, robot-assisted RPLND (R-RPLND) has gained popularity as a minimally invasive therapy alternative to O-RPLND and laparoscopic RPLND. Here, we report the case of a 32-year-old man presenting with a left testicular teratoma with several enlarged left para-aortic lymph nodes. After the orchiectomy, the patient underwent R-RPLND with an operation time of 279 min, console time of 189 min, bleeding volume of 59 mL, and no significant complications, resulting in a successful outcome. To the best of our knowledge, this is the first reported case of R-RPLND in Japan. Based on our experience, R-RPLND may provide safe and effective outcomes; however, further research is required before the widespread implementation of this technique.

BACKGROUND: Recently, robot-assisted surgery has been widely used to treat several urological cancers. Robot-assisted radical nephrectomy (RARN) was approved by the health insurance system in April 2022; however, RARN with inferior vena cava tumor thrombectomy (IVCTT) is still challenging. Also, its safety and feasibility have not yet been established owing to lack of literature, especially in Japan. CASE DESCRIPTION: We performed RARN with IVCTT in four patients between April 2022 and March 2023 at Fujita Health University Hospital. To reduce the risk of tumor embolism and major hemorrhage, an "IVC-first, kidney-last" robotic technique was developed. The safety and feasibility of RARN with IVCTT were evaluated by assessing the perioperative outcomes. Three women and one man were enrolled in this study. The median age was 72 years, and the tumor was on the right side in all cases. According to the Mayo Clinic thrombus classification, two patients were classified as level I, and the others were classified as level II. The two patients at level I did not undergo presurgical treatments, whereas the others at level II underwent presurgical treatments, which were combinations of tyrosine kinase inhibitors and immune-checkpoint inhibitors. The median operation and console times were 341 and 247 min, respectively. The median bleeding volume was 577 mL, and no complications beyond grade III of the Clavien-Dindo classification were observed. The median length of postoperative hospital stay was 10 days. CONCLUSIONS: Although the sample size was relatively small, we demonstrated the safety and feasibility of RARN with IVCTT in the Japanese population.

Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levels > 0.2 ng/mL after RARP; 90-day Clavien-Dindo complications ≤ 3a; and a negative surgical pathologic margin. The median follow-up period was 61.3 months (IQR 6-159 months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51-6.9), p < 0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31-6.37, p < 0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14-13.36, p < 0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (p < 0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice.

OBJECTIVE: The Paris System for Reporting Urinary Cytology considered the nuclear-to-cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high-grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. METHODS: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. RESULTS: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. CONCLUSIONS: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology.

BACKGROUND: The significance of BRCA alterations has been implicated in the development of metastatic castration-resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in-house next-generation sequencer (NGS) system. METHODS: DNA was extracted from formalin-fixed paraffin-embedded tissues of surgical specimens from 126 patients with clinically localized PC who underwent radical prostatectomy. The mutation information of 164 cancer genes was analyzed using the PleSSision-Rapid test. Both copy number (CN) variation and loss of heterozygosity of various genes, such as BRCA1 and BRCA2, were estimated and reported. RESULTS: Next-generation sequencer analyses revealed that the BRCA2 CN was decreased in 17 patients (13.5%) and the BRCA1 CN in six (4.8%) patients. NGS-based CN values were shown to be highly correlated with droplet digital PCR-based CN values. Tissue-specific BRCA expression investigated using the Human Protein Atlas showed that the decreased CN of BRCA2, but not BRCA1, is responsible for the decreased BRCA activity in PC. Ten of the 22 patients with decreased BRCA2 CN were presumed to have somatic heterozygous deletion. There were no observed associations between the heterozygous deletion of BRCA2 and various clinicopathological parameters. Furthermore, three of 10 patients developed biochemical recurrence within 3 months after surgery. Multivariate analyses revealed that the initial prostate-specific antigen levels and BRCA2 CN were independent factors for biochemical recurrence. CONCLUSION: Our results suggest that a decrease in BRCA2 CN may be used as a biomarker for predicting recurrence after surgery in localized PC. Early screening for somatic alterations in BRCA2 using NGS may help to broadly predict the risk of PC progression.

This study aimed to assess the risks and benefits of selective clamping in robot-assisted partial nephrectomy (RAPN). We retrospectively analyzed 372 patients who had undergone RAPN at our hospital between July 2010 and March 2021. After propensity score matching between the full and selective clamping groups, perioperative outcomes and postoperative preservation ratio of the estimated glomerular filtration rate (eGFR) were compared at 6 and 12 months of follow-up. After propensity score matching, we evaluated 47 patients from each group. While no significant differences were observed in surgical time, warm ischemia time, or incidence rates of all grades of complications between the two cohorts, the estimated blood loss (EBL) was significantly lower in the full clamping group than in the selective clamping group (30 vs. 60, p = 0.046). However, no significant intergroup differences were observed in the postoperative preservation ratio of eGFR at 6 or 12 months of follow-up (full clamping 94.0% vs. selective clamping 92.7%, p = 0.509, and full clamping 92.0% vs. selective clamping 91.6%, p = 0.476, respectively). Selective clamping resulted in higher EBL rates than did full clamping in RAPN. However, selective clamping provided no renal functional advantage over full clamping in our propensity-score-matched cohort.

Alanine-serine-cysteine transporter 2 (ASCT2) has been associated with increased levels of metabolism in various malignant tumors. However, its biological significance in the proliferation of prostate cancer (PCa) cells remains under investigation. We used the cBioPortal database to assess the effect of ASCT2 expression on the oncological outcomes of 108 PCa patients. To evaluate the function of ASCT2 in castration-sensitive PCa (CSPC) and castration-resistant PCa (CRPC), LNCaP cells and the ARV7-positive PCa cell line, 22Rv1, were assessed using cell proliferation assays and Western blot analyses. The ASCT2 expression level was associated with biochemical recurrence-free survival after prostatectomy in patients with a Gleason score ≥ 7. In vitro experiments indicated that the growth of LNCaP cells after combination therapy of ASCT2 siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone (p < 0.01, 0.01, respectively). After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions (p < 0.01, 0.01, respectively). We demonstrated that ASCT2 inhibition significantly reduced the proliferation rates of both CSPC and CRPC cells in vitro.

OBJECTIVES: To evaluate the risk factors for postoperative ileus in patients who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. METHODS: We retrospectively analyzed 78 patients with bladder cancer who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion at Fujita Health University between 2011 and 2021. Baseline characteristics and perioperative outcomes were compared between the cohorts with and without ileus. Logistic regression analysis was used to identify the risk factors for postoperative ileus. RESULTS: Out of the 78 patients included in this study, 20 (25.6%) developed postoperative ileus. The ileus cohort was associated with a significantly lower Geriatric-8 score (P = 0.003) and a higher rate of previous abdominal/pelvic surgery (P = 0.04) compared with those of the nonileus cohort. Significantly longer intestinal tract reconstruction time, hospital stay, time to mobilization, fluid intake, solid intake, flatus, and stool were observed in the ileus cohort. According to the results of the logistic regression analysis, the Geriatric-8 sum (P = 0.009), time to mobilization (P = 0.03), and time to fluid intake (P = 0.004) were independent predictors of postoperative ileus. In the model predicting postoperative ileus, the area under the receiver operating characteristic curve was 0.716, and the cutoff value of the Geriatric-8 sum was 13. CONCLUSIONS: Early mobilization and fluid intake and low Geriatric-8 scores were significant risk factors for postoperative ileus. Preoperative Geriatric-8 evaluation is a useful tool for predicting postoperative ileus. Comprehensive enhanced recovery after surgery, including key components, may help bowel recovery and prevent subsequent ileus.

To assess the perioperative and short-term functional outcomes of robot-assisted partial nephrectomy (RAPN) with intraoperative navigation using an ultra-high-resolution computed tomography (UHR-CT) scanner, we retrospectively analyzed 323 patients who underwent RAPN using an UHR-CT or area-detector CT (ADCT). Perioperative outcomes and the postoperative preservation ratio of estimated glomerular filtration rate (eGFR) were compared. After the propensity score matching, we evaluated 99 patients in each group. Although the median warm ischemia time (WIT) was less than 25 min in both groups, it was significantly shorter in the UHR-CT group than in the ADCT group (15 min vs. 17 min, p = 0.032). Moreover, the estimated blood loss (EBL) was significantly lower in the UHR-CT group than in the ADCT group (33 mL vs. 50 mL, p = 0.028). However, there were no significant intergroup differences in the postoperative preservation ratio of eGFR at 3 or 6 months of follow-up (ADCT 91.8% vs. UHR-CT 93.5%, p = 0.195; and ADCT 91.7% vs. UHR-CT 94.0%, p = 0.160, respectively). Although no differences in short-term renal function were observed in intraoperative navigation for RAPN in this propensity score-matched cohort, this study is the first to demonstrate that UHR-CT resulted in a shorter WIT and lower EBL than ADCT.

OBJECTIVE: This study aimed to compare the perioperative and long-term functional outcomes between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) in Japanese patients. METHODS: We retrospectively analyzed 242 patients who underwent either RAPN or OPN between 2007 and 2017 at our hospital. Propensity score matching was carried out between the two groups at a ratio of 1:1. Perioperative outcomes and postoperative estimated glomerular filtration rates (eGFR) were compared at one and three years of follow-up. RESULTS: After propensity score matching, we evaluated 39 patients from each group. The ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). Moreover, the estimated blood loss (EBL) was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). However, there were no significant differences in the postoperative eGFR between the two groups at one or three years of follow-up (OPN 54.8 vs. RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively). CONCLUSION: RAPN resulted in shorter ischemia durations and lower rates of EBL than did OPN; however, no differences in long-term renal function were observed between RAPN and OPN in our propensity-score matched Japanese cohort.