This study aimed to examine the impact of histological differences on positive surgical margins (PSM) and postoperative renal function in patients with renal cell carcinoma (RCC) who underwent robot-assisted partial nephrectomy (RAPN). This multicenter retrospective cohort study included patients with RCC who underwent RAPN at eight Japanese facilities between March 2016 and November 2023. The enrolled patients who underwent RAPN were divided into those with clear cell RCC (ccRCC group) and those with other histological subtypes (non-ccRCC group). The primary endpoint was to determine the differences in PSM rates according to histological type among patients who underwent RAPN. Secondary endpoint was the chronological assessment of renal function in patients undergoing RAPN, which was categorized according to histological type. To ensure a balance between the two groups with respect to variables that may influence perioperative outcomes, 3:1 propensity score matching was performed using logistic regression. Following propensity score matching at a 3:1 ratio, the analysis included 735 ccRCC and 245 non-ccRCC patients. No significant association was identified between the histological subtypes and PSM in multivariate analysis. Despite a decline in renal function of approximately 10% in both groups postoperatively, no significant difference was observed between the groups in the chronological changes in renal function over time. There was no statistically significant differences in the incidence of PSM based on histological type among the study groups nor substantial variations in postoperative renal function.

INTRODUCTION:Although the prevalence of nocturnal polyuria (NP) increases with age, the mechanisms underlying age-related changes in voiding patterns and the daytime-nighttime distribution of urine volume remain unclear. Given that the severity of nocturia and bladder function may differ across age groups, age-specific voiding profiles require clarification to enable the development of appropriate management strategies. Therefore, in this multicenter cohort study, we aimed to analyze the urinary patterns and clinical factors associated with NP using a voiding diary. MATERIALS AND METHODS:This multicenter retrospective observational study included patients who presented at 17 Japanese institutions with nocturia as the primary complaint in 2018-2022. The enrolled patients documented at least 2 days of voiding diaries, and their daily voiding patterns were thoroughly analyzed. NP was defined as an NP index (NPi) exceeding 0.33 calculated from 24-h and nocturnal urine volumes. Patients were stratified into five age groups (<50, 50-59, 60-69, 70-79, and ≥80 years) for comparative analysis. The primary study endpoint was identifying the clinical factors associated with NP. RESULTS:A total of 875 patients were included in the analysis. NPi levels increased with age and were significantly higher in the ≥80 years group than that in the other groups (p < 0.05). The prevalence of NP increased with age. A review of voiding diaries revealed that patients aged ≥80 years had significantly lower 24-h and daytime urine volumes and a notably higher incidence of NP than the other age groups (p < 0.05). The patients diagnosed with NP were older and had a higher prevalence of overactive bladder (OAB) than those without NP. A multivariate analysis identified age, the presence of OAB, maximal urinary volume, and 24-h urine volume as independent predictors of NP. CONCLUSIONS:These findings suggest that nocturia in older adults is not exclusively attributable to impaired bladder function. This hypothesis suggests that the condition is multifactorial and involves urinary symptoms, such as OAB, changes in urine volume, and symptoms related to comorbidities.

INTRODUCTION:Urothelial carcinoma (UC) with clear cell subtype is a malignant neoplasm characterized by a distinctive morphological pattern featuring a glycogen-rich cytoplasm. Due to its extremely rare occurrence in the upper urinary tract, an optimal treatment has not yet been established. CASE PRESENTATION:This study reports the case of an 81-year-old woman diagnosed with upper tract urothelial carcinoma (UTUC) with clear cell subtype located in the right renal pelvis. The patient underwent laparoscopic radical nephroureterectomy, and pathological findings showed that clear-cell morphology accounted for more than 90% of the tumor. Gemcitabine and carboplatin were administered as adjuvant chemotherapy. However, 3 months after completing adjuvant chemotherapy, the patient developed severe pain, and imaging examinations revealed metastasis to the para-aortic lymph nodes and retroperitoneum. Subsequently, the patient underwent systemic therapy with enfortumab vedotin (EV) and pembrolizumab (EV-P). Following a single cycle of EV-P, the patient exhibited substantial improvement in symptoms, and metastatic lesions decreased notably. Immunohistochemical testing confirmed strong expression of Nectin-4 in the tumor tissue. CONCLUSIONS:This is the first report to demonstrate the efficacy of EV-P for recurrent UTUC with clear cell subtype. In tumors exhibiting rare histological variants, the identification of biomarkers such as nectin-4 suggests their potential to guide effective treatment selections.

This study investigated whether neutrophil-to-lymphocyte ratio (NLR) kinetics, including changes within the first week after the initiation of first-line combination immunotherapy, are associated with overall survival (OS) in patients with advanced renal cell carcinoma (aRCC). Consecutive patients with aRCC treated with first-line immune checkpoint inhibitor combination therapy at 12 Japanese institutions were included in this retrospective study. The NLR was assessed at baseline (BL), within 7 days (D7), and 1 month (M1) after treatment initiation. Patients were classified into three groups according to NLR at BL and at D7 as follows: BL NLR low (< 3), NLR high-low (BL NLR ≥ 3 and D7 NLR < 3), and NLR high-high (BL NLR ≥ 3 and D7 NLR ≥ 3) groups. In total, 198 patients were included in the study, with a median follow-up of 18.0 months. The median NLR changed during follow-up at BL, D7, and M1 (BL, 3.28; D7, 3.23; M1, 2.74). OS stratified by NLR at each time point was significant at BL and D7, but not at M1. Among patients with BL NLR ≥ 3 (55

Purpose : Postoperative ileus is a common complication following robot-assisted radical cystectomy with urinary diversion using the small intestine. Daikenchuto, an oral medication, has been identified as a potential agent to promote intestinal motility. However, its efficacy in preventing ileus after robot-assisted cystectomy with intracorporeal urinary diversion remains unclear. Methods : This study analyzed patients who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion using the small intestine at Gifu University between November 2018 and May 2025. Patients who received perioperative Daikenchuto (TU-100, 7.5 g/day) from the day of hospital admission until discharge were assigned to Group I, whereas those who did not receive TU-100 were assigned to Group II. Patient backgrounds were adjusted using propensity score matching, and comparative analysis was performed. Results : A total of 145 patients were included in the final analysis. Following propensity score matching, 42 cases were allocated to each group. No significant differences were observed between both groups regarding length of hospital stay, postoperative ileus incidence rate, or duration from ileus onset to recovery. Conclusion : The effectiveness of Daikenchuto may be constrained in patients who have undergone robot-assisted radical cystectomy with intracorporeal urinary diversion using the small intestine.

Bladder sarcomatoid carcinoma is a rare, aggressive tumor with epithelial and mesenchymal features. We report a 69-year-old man with muscle-invasive bladder neck urothelial carcinoma with giant cell subtype. After two cycles of gemcitabine and cisplatin, imaging revealed tumor shrinkage. Robot-assisted radical cystectomy with pelvic lymphadenectomy and intracorporeal ileal conduit was performed. Pathology confirmed sarcomatoid carcinoma with lymphovascular invasion but negative margins. The urothelial component responded to chemotherapy, whereas the sarcomatoid component did not. No recurrence was observed for 18 months follow-up. Prompt chemotherapy and robotic surgery achieved a favorable outcome in this rare bladder cancer.

ABSTRACT Background We thank the authors for their thoughtful comments on our multicenter cohort study examining the association between aging and nocturnal polyuria in patients with nocturia. Response We agree that fluid intake, sleep status, renal function, lower extremity edema, comorbidities, and concomitant medications are important factors in evaluating nocturnal polyuria, particularly in older adults. Although voiding diaries provide detailed information on voiding time and voided volume, these additional clinical parameters were not consistently available in our retrospective multicenter dataset. Future prospective studies using standardized data collection methods will be necessary to further clarify the mechanisms underlying nocturnal polyuria and improve individualized clinical assessment and management. Conclusion We appreciate these constructive comments and believe that future standardized prospective studies will help clarify the mechanisms of nocturnal polyuria and improve individualized management in older adults.

BACKGROUND:Pembrolizumab is indicated as adjuvant therapy after nephrectomy in patients with high-risk renal cell carcinoma (RCC). However, data regarding the occurrence of treatment-related adverse events (TRAEs) associated with pembrolizumab in real-world clinical settings in Japanese patients remain limited. In this study, we aimed to assess the clinical safety of adjuvant pembrolizumab therapy in Japan. METHODS:This multicenter, retrospective, observational study enrolled patients who received adjuvant pembrolizumab therapy for RCC at five facilities in Japan between August 2022 and March 2025. The primary endpoint was the occurrence of TRAEs, which were classified by grade according to the Common Terminology Criteria for Adverse Events version 5.0. Secondary endpoints focused on disease-free survival (DFS) and overall survival (OS). RESULTS:This study enrolled 35 patients and had a median follow-up period of 7.0 months (interquartile range: 2.0-14.0). TRAEs occurred in 13 patients (37.1%), including two (5.7%) with grade ≥ 3 events. Five patients (14.3%) discontinued pembrolizumab treatment because of TRAEs, and no treatment-related deaths were observed. Grade ≥ 3 TRAEs included one case each of erythema multiforme, myocarditis, gastrointestinal perforation, and myasthenia gravis. During follow-up, no disease recurrence or death was observed, and the median DFS and OS were not achieved. CONCLUSIONS:The safety profile of pembrolizumab as an adjuvant therapy was found to be acceptable in Japanese patients with high-risk RCC. Therefore, postoperative adjuvant pembrolizumab following surgical intervention may be recommended as a treatment option for eligible patients in clinical practice.

Low-dose-rate brachytherapy with iodine-125 (LDR-BT) is an established curative radiation treatment modality for localized prostate cancer (PCa). This study aimed to evaluate the long-term incidence of secondary primary tumors (SPTs) following LDR-BT in Japanese patients with localized PCa and identify predictive factors associated with SPTs. We retrospectively reviewed the clinical records of 478 consecutive patients with localized PCa who underwent LDR-BT at the Gifu University Hospital. This study’s primary endpoint was SPTs incidence, including bladder and rectal/anal cancers. The secondary endpoint was the identification of risk factors for LDR-BT that predicted SPTs development. After a median follow-up period of 105 months, SPTs developed in 13 patients (2.7

Background:Although cisplatin is essential for neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), good renal function is a prerequisite for those patients receiving NAC. However, patients with normal renal function may experience nephrotoxicity after cisplatin administration. We investigated the safety and efficacy of a split-dose regimen of gemcitabine and cisplatin (split-dose GC) in MIBC patients with normal renal function. Methods:This retrospective study included 45 patients with MIBC who received standard GC, split-dose GC, or gemcitabine and carboplatin (GCarbo) as a NAC and subsequently underwent robot-assisted radical cystectomy. The efficacy and safety of two cycles split-dose GC were compared with those of other regimens. Results:Among the 45 patients with MIBC, 14 received standard GC, 14 received split-dose GC, and 17 received GCarbo. Pathological complete response rates were 28.6%, 21.4%, and 29.4% for surgical specimens obtained post-treatment with standard GC, split-dose GC, and GCarbo, respectively (P=0.86). Renal function after NAC was significantly lower in the standard- and split-dose GC groups than in the GCarbo group (P<0.001). Conclusions:Although the split-dose GC regimen showed a significant reduction compared to pre-treatment renal function, the pathological response rate and incidence of adverse events were similar to those of the other two regimens.

This study aimed to evaluate the outcomes of patients with advanced renal cell carcinoma (aRCC) who were histologically diagnosed with non-clear cell carcinoma (nccRCC) and received combination immunotherapy. Oncological outcomes were compared between patients with non-clear cell RCC (nccRCC group) and those with clear cell RCC (cc-RCC group) who received either immune checkpoint inhibitor (ICI) + ICI combination therapy (ICI + ICI) or ICI + tyrosine kinase inhibitor (TKI) therapy (ICI + TKI). This retrospective study analyzed patients with aRCC who received combination immunotherapy as first-line treatment at 12 institutions between August 2018 and November 2023. The primary endpoint was the comparison of overall survival (OS) between the nccRCC and cc-RCC groups. The secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) in both groups. The median follow-up periods for the nccRCC and cc-RCC groups were 17.7 and 20.4 months, respectively. The median OS was significantly shorter in the nccRCC group compared to the cc-RCC group (27.8 months vs. 62.8 months; p < 0.001). The ORRs in the nccRCC and cc-RCC groups were 52.4% and 63.6%, respectively. Among patients treated with ICI + ICI, the median OS was significantly shorter in the nccRCC group compared to the cc-RCC group (23.5 months vs. 62.8 months; p < 0.001). In the current era of ICI treatment, patients with nccRCC exhibit poorer oncological outcomes than those with cc-RCC. Indications should be evaluated thoroughly before selecting ICI + ICI treatment combinations for these patients.

Background/Objectives: Abnormal glycan formation on the cancer cell surface plays a crucial role in regulating tumor functions in bladder cancer. In this study, we investigated the roles of glucosaminyl (N-acetyl) transferase 2 (GCNT2) in bladder cancer progression and immune evasion. GCNT2 synthesizes I-branched polylactosamine chains on cell surface glycoproteins. Understanding its functions will provide insights into tumor–immune interactions, facilitating the development of effective immunotherapeutic strategies. Methods: GCNT2 expression levels in bladder cancer cell lines and patient tumor samples were analyzed via quantitative polymerase chain reaction and immunohistochemistry. GCNT2 functions were assessed via overexpression and knockdown experiments. Its effect on natural killer (NK) cell-mediated cytotoxicity was evaluated via in vitro assay. Cytotoxic granule release from NK cells was measured via enzyme-linked immunosorbent assay. Results: GCNT2 expression was inversely correlated with bladder cancer aggressiveness in both cell lines and patient samples. Low GCNT2 levels were associated with advanced tumor stage and grade, suggesting the tumor-suppressive roles of GCNT2. Notably, GCNT2 overexpression enhanced the susceptibility of bladder cancer cells to NK cell-mediated killing, whereas its knockdown promoted immune evasion. GCNT2-overexpressing cells strongly induced the release of cytotoxic granules from NK cells, indicating enhanced immune recognition. Conclusions: Our findings suggest that aggressive bladder tumors evade NK cell immunity by decreasing the GCNT2 levels and that I-antigen glycans synthesized by GCNT2 are crucial for NK cell recognition by tumor cells. Our findings provide insights into the tumor–immune interactions in bladder cancer and GCNT2 and its associated pathways as potential targets for novel immunotherapeutic strategies.

To examine daytime voiding patterns in patients with nocturnal polyuria (NP) and identify a novel predictive indicator based on voiding frequency ratios. A retrospective analysis of 875 patients with nocturia from 17 Japanese institutions (January 2018–December 2022) was conducted. Patients were divided into two groups based on the nocturnal polyuria index (NPi) > 33

Background and Objective:Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced renal cell carcinoma (aRCC), leading to the adoption of combination regimens. Either dual ICI regimens or ICI plus tyrosine kinase inhibitor (TKI) are now established as the first-line standard treatment. While phase III trials have demonstrated significant survival benefits of ICI combination therapy over TKI monotherapy, real-world reports, particularly from Japan, have revealed variable outcomes influenced by patient and tumor characteristics. Treatment-related adverse events (TRAEs), including immune-related adverse events (irAEs), are increasingly recognized not only as safety concerns but also as potential predictive biomarkers. In this review, we aimed to compare the clinical trials and real-world outcomes of combination immunotherapy with a focus on Japanese patients, and to examine the prognostic significance of TRAEs. Methods:A narrative literature review was conducted using PubMed and Scopus for English-language studies published between April 2018 and August 2025. Search terms included the following MeSH terms: kidney neoplasm, carcinoma, renal cell, immunotherapy, nivolumab, ipilimumab, pembrolizumab, avelumab, axitinib, cabozantinib, lenvatinib, and biomarkers; and free-text terms: advanced, combination immunotherapy, irAEs, and TRAEs. Phase III trials and retrospective/prospective real-world studies were included, and abstracts and case reports were excluded. Key Content and Findings:Nivolumab plus ipilimumab (NIVO + IPI) and various ICI + TKI regimens (avelumab + axitinib, pembrolizumab + axitinib, nivolumab + cabozantinib, pembrolizumab + lenvatinib) have shown superior efficacy to sunitinib in pivotal trials. Real-world Japanese cohorts often include older patients with poor performance status and non-clear cell RCC (ncc-RCC), leading to shorter overall survival (OS) and progression-free survival (PFS), despite comparable objective response rates (ORRs) to trials. Several studies on patients treated with NIVO + IPI have demonstrated that TRAEs/irAEs are associated with improved ORR and OS, with multivariate analyses identifying them as independent, favorable prognostic factors. However, this correlation was less consistent in ICI + TKI regimens, in which toxicity may be derived from either component. Conclusions:Combination immunotherapy offers substantial benefits for aRCC; however, real-world outcomes can differ from trial data owing to patient heterogeneity. TRAEs show promise as prognostic markers in NIVO + IPI but require further validation in ICI + TKI. Prospective multicenter registries with standardized adverse event reporting, coupled with translational studies, are needed to refine regimen selection and personalized therapy.

Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an uncommon malignant neoplasm with few reported cases, particularly among male patients. Currently, only nine documented cases have been reported worldwide, including the present case. The present case report describes the incidental detection of PRMC in an 86-year-old male patient. Despite being offered surgical intervention, the patient initially opted against treatment. Consequently, follow-up imaging examinations were performed for 3 subsequent years. The tumor, initially measuring 31 × 32 × 31 mm, gradually increased to 58 × 60 × 59 mm. Subsequently, the patient underwent laparoscopic retroperitoneal tumor resection. Histopathological examination revealed adenocarcinoma characterized by intestinal differentiation. The patient has exhibited no evidence of disease for 1 year postoperatively. The present case is noteworthy, as this disease rarely occurs in men, thereby offering significant potential for educational and scientific contributions. Notably, the patient’s age, longitudinal observation of tumor progression through imaging over a period of 3 years, and complete surgical excision of the tumor are salient features of this case. These findings may prove useful in the diagnosis and treatment strategy for male patients with PRMC.

Kidney transplantation (KT) is a useful treatment option for patients with end-stage chronic kidney disease to avoid dialysis and achieve a good quality of life. In Japan, approximately 90

Randomized phase III trial results have demonstrated enfortumab vedotin (EV), an antibody–drug conjugate (ADC) consisting of an anti-Nectin-4 human IgG1 monoclonal antibody and monomethyl auristatin E, is a useful treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) that progressed after immune checkpoint inhibitor (ICI) therapies. This multicenter retrospective cohort study aimed to identify predictive factors for the efficacy of EV therapy and prolonged overall survival (OS) of patients in clinical practice. This study included patients with la/mUC who received ICI treatment. Patients who subsequently received EV treatment, those who received non-EV chemotherapy, and those who received no treatment were defined as EV, non-EV, and best supportive care (BSC) groups, respectively. The median OS was 20, 15, and 7 months in the EV, non-EV, and BSC groups, respectively (p < 0.001). Patients with la/mUC who had a complete or partial response after EV treatment had a significantly prolonged OS compared with those with stable or progressive disease. Univariate analysis showed age, neutrophil-to-lymphocyte ratio (NLR), dysgeusia, and rash as independent predictors of OS improvement. NLR and dysgeusia were independent predictors of OS after EV in multivariate analysis. Patients without these factors had a significantly prolonged OS compared to those with both factors. In real-world practice, EV therapy is an effective treatment for patients with la/mUC after ICI treatment.

Renorrhaphy is often performed after tumor resection during robotic-assisted laparoscopic partial nephrectomy (RAPN). This study aimed to investigate the association between renorrhaphy performance and inflammatory markers. A retrospective cohort study was conducted including patients with renal cell carcinoma who underwent RAPN at eight institutions in Japan between April 2016 and November 2023. The primary endpoint was the association between the renorrhaphy performance in RAPN and the postoperative inflammatory markers. The secondary endpoints were perioperative outcomes in patients with and without renorrhaphy. The patients were divided into two groups at the time of RAPN: those who underwent renorrhaphy (renorrhaphy group) and those who did not (omitted group). In total, 934 patients were enrolled in this study. After propensity score matching, the rate of change in C-reactive protein and neutrophil-lymphocyte ratio on postoperative day 28 were not significant difference between the two groups. In contrast, the rate of change in platelet-lymphocyte ratio (PLR) on postoperative day 28 was significantly higher in renorrhaphy group than omitted group. Regarding surgical outcomes, the renorrhaphy group had a significantly longer hospital stay, operative time, and warm ischemia time (P = 0.038, P = 0.022, and P = 0.009, respectively) than the omitted group did. Furthermore, the omitted group had a significantly higher rate of Trifecta achievement than the renorrhaphy group did. This study demonstrated that renorrhaphy performance in RAPN was significantly associated with the higher value of postoperative PLR.

The overall survival (OS) of patients with prostate cancer (PCa) who receive locally definitive therapy is generally better than that of patients who do not receive definitive therapy. There is no difference in the incidence of local recurrence or distant metastasis between treatment modalities. Because the prognosis of PCa is relatively good, many studies have focused on quality of life after treatment as an endpoint. However, a limited number of patients develop biochemical recurrence after definitive treatment for PCa and subsequently develop distant metastasis or die from PCa. Therefore, we believe that preventing local recurrence and distant metastasis and prolonging the OS should be emphasized when selecting a treatment modality for PCa. In this review, the significance and usefulness of radical prostatectomy and radiation therapy as the main modalities of definitive therapies for local PCa and locally advanced PCa were evaluated, as well as the outcomes of OS and PCa-specific mortality and the treatment options after biochemical recurrence to improve the oncological outcomes.

Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.