Efficacy of robot-assisted partial nephrectomy compared to conventional laparoscopic partial nephrectomy for completely endophytic renal tumor: a multicenter, prospective study.

BACKGROUND: This study aimed to compare the efficacy of robot-assisted partial nephrectomy for completely endophytic renal tumors with the reported outcomes of conventional laparoscopic partial nephrectomy and investigate the transition of renal function after robot-assisted partial nephrectomy. METHODS: We conducted a prospective, multicenter, single-arm, open-label trial across 17 academic centers in Japan. Patients with endophytic renal tumors classified as cT1, cN0, cM0 were included and underwent robot-assisted partial nephrectomy. We defined two primary outcomes to assess functional and oncological aspects of the procedure, which were represented by the warm ischemic time and positive surgical margin, respectively. Comparisons were made using control values previously reported in laparoscopic partial nephrectomy studies. In the historical control group, the warm ischemia time was 25.2, and the positive surgical margin was 13%. RESULTS: Our per-protocol analysis included 98 participants. The mean warm ischemic time was 20.3 min (99% confidence interval 18.3-22.3; p < 0.0001 vs. 25.2). None of the 98 participants had a positive surgical margin (99% confidence interval 0-5.3%; p < 0.0001 vs. 13.0%). The renal function ratio of eGFR before and after protocol treatment multiplied by splits was 0.70 (95% confidence interval: 0.66-0.75). Factors such as preoperative eGFR, resected weight, and warm ischemic time influenced the functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSIONS: Robot-assisted partial nephrectomy for completely endophytic renal tumors offers a shorter warm ischemia time and comparable positive surgical margin rate compared with conventional laparoscopic partial nephrectomy.

Clinical characteristics and predictors of long-term postoperative urinary incontinence in patients treated with robot-assisted radical prostatectomy: A propensity-matched analysis.

OBJECTIVES: This study aimed to elucidate the clinical characteristics and predictors of long-term postoperative urinary incontinence (PUI) after robot-assisted radical prostatectomy (RARP). METHODS: This study included patients who underwent RARP at our institution and were stratified into PUI (≥1 pad/day) and continence (0 pad/day) groups at 60 months after RARP. A propensity score-matched analysis with multiple preoperative urinary status (Expanded Prostate Cancer Index Composite urinary subdomains, total International Prostate Symptom Score (IPSS), and IPSS-quality of life scores) was performed to match preoperative urinary status in these groups. Serial changes in urinary status and treatment satisfaction preoperatively and until 60 months after RARP were compared, and predictors of long-term PUI were assessed using multivariate logistic regression analysis. RESULTS: A total of 228 patients were included in the PUI and continence groups (114 patients each). Although no significant difference in preoperative urinary status was observed between the two groups, the postoperative urinary status significantly worsened overall in the PUI group than in the continence group. Treatment satisfaction was also significantly lower in the PUI group than in the continence group from 12 to 60 months postoperatively. Multivariate logistic regression analysis revealed that age (≥70 years) and biochemical recurrence (BCR) were significant predictors of the long-term PUI group (p < 0.05). CONCLUSIONS: Patients with long-term PUI had poor overall postoperative urinary status and lower treatment satisfaction than the continence group. Considering the age and risk of BCR is important for predicting long-term PUI when performing RARP.

Preoperative high serum total testosterone levels predict preserved postoperative sexual function in patients after nerve-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy. METHODS: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence. RESULTS: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008). CONCLUSIONS: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions.

Utility of the modified 5-item frailty index as a predictor of postoperative febrile urinary tract infection in patients who underwent ureteroscopy with laser lithotripsy.

PURPOSE: This study aimed to assess the effect of the modified 5-item frailty index on perioperative complications and surgical outcomes in patients who underwent ureteroscopy with laser lithotripsy for upper urinary tract stones. METHODS: Patients who underwent ureteroscopy with laser lithotripsy for upper urinary tract stones between 2019 and 2022 were reviewed retrospectively. Assessment was performed using the modified 5-item frailty index based on medical history (hypertension, diabetes, heart failure, chronic obstructive pulmonary disease) and functional status. Patients were categorized into the high (≥ 2) and low (≤ 1) modified 5-item frailty index groups based on the frailty score. We compared the perioperative complications and surgical outcomes between the two groups. RESULTS: Seventy-one (15.8%) and 393 (84.1%) of the 467 patients were classified into the high and low modified 5-item frailty index groups, respectively. The high modified 5-item frailty index group exhibited a significant association with increased febrile urinary tract infections compared to the low modified 5-item frailty index group [≥ 37.8 °C: 15 (20.3%) vs 13 (3.3%), p < 0.001; ≥ 38 °C: 9 (12.2%) vs 7 (1.8%), p < 0.001]. Surgical outcomes, including operative time and stone-free rate, did not differ significantly between the two groups. CONCLUSION: The modified 5-item frailty index is valuable for predicting postoperative complications, particularly febrile urinary tract infections, after ureteroscopy with laser lithotripsy for upper urinary tract stones. This index allows for practical preoperative risk assessment in patients who underwent ureteroscopy with laser lithotripsy.

Muscle-Invasive Bladder Cancer With Hydronephrosis Exhibits a High Frequency of Mutations in Fibroblast Growth Factor Receptor 3 Gene.

BACKGROUND/AIM: Recent studies have reported conflicting findings regarding the significance of hydronephrosis (HN) in muscle-invasive bladder cancer (MIBC). The molecular characteristics of MIBC with HN are unclear, therefore, we aimed to address the gaps in previous research and elucidate HN's molecular significance in patients with MIBC. MATERIALS AND METHODS: Clinical, genetic, and imaging information on bladder cancer patients enrolled in The Cancer Genome Atlas were obtained from public databases to analyze the association between the presence of hydronephrosis and genetic alterations and molecular subtyping. A total of 108 patients who underwent total cystectomy for MIBC at the Hiroshima University Hospital were enrolled in the study to verify the association between HN and renal function with patient prognosis. RESULTS: We observed a statistically significant difference in the distribution of molecular subtypes (p=0.0146). The proportion of patients with the luminal papillary subtype was approximately twice as high in patients with HN (48.8%) than in those without HN (25.0%). The mutation frequency of fibroblast growth factor receptor (FGFR) 3 was approximately three-fold higher in patients with HN (20.9%) than in those without HN (7.1%). Multivariate analysis, which considered HN and estimated glomerular filtration rate as confounding factors in our MIBC cohort, revealed that reduced renal function, but not HN, was an independent predictor for overall survival. CONCLUSION: MIBC presenting HN exhibits a high frequency of mutations in the FGFR3 gene. In addition, not HN itself, but reduced renal function due to HN may worsen the prognosis for MIBC.

Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Nesprin1 deficiency is associated with poor prognosis of renal cell carcinoma and resistance to sunitinib treatment.

INTRODUCTION: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). METHODS: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. RESULTS: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. CONCLUSIONS: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.

First reported human case of isolation of Vagococcus fluvialis from the urine of a former zoo clerk in Japan: a case report.

BACKGROUND: Vagococcal infections are extremely rare in humans. There are limited studies on the optimal methods for identification, antimicrobial susceptibility testing, and clinical manifestations of vagococcal infections. Herein, we report a patient with a urinary tract infection who had Vagococcus fluvialis in the urine. CASE PRESENTATION: An 84-year-old man presented to our urology department with a fever that had persisted for several days. He previously worked as a zoo clerk. The patient underwent a left nephroureterectomy for ureteral cancer 5 years ago, and total cystectomy and right cutaneous ureterostomy for muscle-invasive bladder cancer 1 year prior. He was empirically treated with 500 mg of levofloxacin intravenously every 24 h for the urinary tract infection. V. fluvialis was detected in his urine samples and Pseudomonas aeruginosa was detected in his urine and blood samples. Two bacterial species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. He was administered intravenous levofloxacin for approximately 1 week, followed by oral levofloxacin for another week, after which the infections were eradicated. CONCLUSIONS: To the best of our knowledge, this is the first report of V. fluvialis detected in human urine in Japan. Vagococcus spp. is commonly isolated from fish or animals, and based on the patient's work history, it is possible that the patient was a carrier because of transmission from animals.

First case report of robot-assisted radical cystectomy and intracorporeal urinary diversion using the hinotori Surgical Robot System.

Background: The field of robotic surgery is still continuously advancing, with several cutting-edge robotic systems currently under development. This study aimed to present the methodology and perioperative outcomes of robot-assisted radical cystectomy (RARC) and intracorporeal urinary diversion (ICUD) in patient with muscle invasive bladder cancer (MIBC) by utilizing the hinotori Surgical Robot System, a recently developed robot-assisted surgical platform. Case Description: A 79-year-old man with MIBC, cT2N0M0, received RARC and ICUD after two courses of neoadjuvant chemotherapy. We performed RARC and ICUD using hinotori, with a total operation time of 476 minutes. The insufflation time was 424 minutes, and the console time was 396 minutes. Total blood loss was 562 mL and no blood transfusion was necessary. During the perioperative period, a paralytic ileus occurred, although no severe adverse events were observed. The pathological examination showed ypT0N0M0, and no recurrence was observed by computed tomography scan up to 8 months postoperatively. Conclusions: This report demonstrates the successfully implementation of RARC and ICUD using the hinotori system, without perioperative adverse effects. While further exploration is required to assess the long-term and large-scale implications of RARC and ICUD using hinotori on oncologic and functional outcomes, these initial findings suggest that the hinotori Surgical Robot System holds promise as an application for RARC and ICUD in patients with MIBC.

Centrality angle is a novel nephrometry score to predict tumor complexity and perioperative outcomes for partial nephrectomy.

To propose the centrality angle (C-angle) as a novel simple nephrometry score for the evaluation of tumor complexity and prediction of perioperative outcomes in nephron-sparing surgery (NSS) for renal tumors. The analysis was based on 174 patients who underwent robot-assisted partial nephrectomy retrospectively. C-angle was defined as the angle occupied by the tumor from the center of the kidney in the coronal CT images. Other nephrometry scores were calculated and compared with C-angle. Associations between C-angle and perioperative outcomes were examined. Significant differences were found in C-angle between tumors greater and less than 4 cm, exophytic and endophytic tumors, and hilar and non-hilar tumors. C-angle was correlated with other nephrometry scores, including RENAL, PADUA, and C-index. Significant positive correlations with WIT, operation time, and EBL, and significant negative correlations with preserved eGFR. C-angle could predict perioperative complications. Patients with a C-angle > 45° had worse perioperative outcomes, including longer operative time, longer WIT, lower rate of preserved eGFR, and complications. C-angle can be used to evaluate the complexity of renal tumors and predict perioperative outcomes. C-angle can potentially be used for decision-making in the treatment of patients and to guide surgical planning of NSS.

Comprehensive genomic profiling testing in Japanese castration-resistant prostate cancer patients: results of a single-center retrospective cohort study.

OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.

Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

Prognostic Impact of the Modified 5-Item Frailty Index After Radical Nephroureterectomy in Patients With Upper Tract Urothelial Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: The modified 5-item frailty index can be used to evaluate frailty using 5 routinely encountered clinical variables. This study aimed to assess the impact of the modified 5-item frailty index in patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma. PATIENTS AND METHODS: In this multicenter retrospective study, we calculated the modified 5-item frailty index scores of patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma between 2010 and 2022. Patients were categorized into the high (≥2) and low (≤1) modified 5-item frailty index score groups. To assess the prognostic influence of the preoperative modified 5-item frailty index, we conducted Cox proportional regression analyses concerning progression-free, overall, and cancer-specific survival. RESULTS: Of 434 patients, 82, and 352 were classified into the high and low modified 5-item frailty index score groups, respectively. The high modified 5-item frailty index score group had significantly higher rates of severe surgical complications (P = .038) and ≥30 days of hospitalization (P = .049) and significantly worse progression-free (P = .012) and overall survival (P = .002) than the low modified 5-item frailty index score group. The multivariable Cox proportional hazard analysis revealed that a high modified 5-item frailty index score was independently associated with poor progression-free (P = .044), overall (P = .017), and cancer-specific survival (P = .005). CONCLUSION: The modified 5-item frailty index emerged as a significant predictive indicator of severe surgical complications and postoperative survival outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

Auraptene Enhances AMP-Activated Protein Kinase Phosphorylation and Thereby Inhibits the Proliferation, Migration and Expression of Androgen Receptors and Prostate-Specific Antigens in Prostate Cancer Cells.

Citrus hassaku extract reportedly activates AMPK. Because this extract contains an abundance of auraptene, we investigated whether pure auraptene activates AMPK and inhibits proliferation using prostate cancer cell lines. Indeed, auraptene inhibited the proliferation and migration of LNCaP cells and induced phosphorylation of AMPK or its downstream ACC in LNCaP, PC3, and HEK-293 cells, but not in DU145 cells not expressing LKB1. In addition, the mTOR-S6K pathway, located downstream from activated AMPK, was also markedly suppressed by auraptene treatment. Importantly, it was shown that auraptene reduced androgen receptor (AR) and prostate-specific antigen (PSA) expressions at both the protein and the mRNA level. This auraptene-induced downregulation of PSA was partially but significantly reversed by treatment with AMPK siRNA or the AMPK inhibitor compound C, suggesting AMPK activation to, at least partially, be causative. Finally, in DU145 cells lacking the LKB1 gene, exogenously induced LKB1 expression restored AMPK phosphorylation by auraptene, indicating the essential role of LKB1. In summary, auraptene is a potent AMPK activator that acts by elevating the AMP/ATP ratio, thereby potentially suppressing prostate cancer progression, via at least three molecular mechanisms, including suppression of the mTOR-S6K pathway, reduced lipid synthesis, and AR downregulation caused by AMPK activation.

Efficacy and safety of second-line cabozantinib after immuno-oncology combination therapy for advanced renal cell carcinoma: Japanese multicenter retrospective study.

Immuno-oncology (IO) combination therapy is utilized as a first-line systemic treatment for advanced renal cell carcinoma. However, evidence supporting the use of cabozantinib after IO combination therapy is lacking. We retrospectively analyzed patients who received second-line cabozantinib after IO combination therapy using the Japanese Urological Oncology Group (JUOG) database. In total, 254 patients were enrolled in the JUOG global study, and 118 patients who received second-line cabozantinib comprised the study cohort. The objective response rate, disease control rate, second-line cabozantinib progression-free survival (PFS), and overall survival from second-line for overall were 32%, 75%, 10.5 months, and not reached, respectively, for first-line IO-IO therapy were 37%, 77%, 11.1 months, and not reached, respectively, versus 24%, 71%, 8.3 months, and not reached, respectively, for first-line IO-tyrosine kinase inhibitor therapy. In univariate and multivariate analyses, discontinuation of first-line treatment because of progressive disease and liver metastasis were independent risk factors for PFS. All-grade adverse events occurred in 72% of patients, and grade 3 or higher adverse events occurred in 28% of patients. Second line-cabozantinib after first-line IO combination therapy for advanced renal cell carcinoma was expected to be effective after either IO-IO or IO-TKI treatment and feasible in real-world practice.

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

BACKGROUND: We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC). METHODS: We analyzed the expression and distribution of MCM4 in 124 upper tract urothelial carcinoma (UTUC) samples by IHC. Additionally, using 108 urine samples, we analyzed MCM4 Immunocytochemistry (ICC) expression in urine cytology. RESULTS: In normal urothelium, MCM4 expression was weak or absent. Meanwhile, the strong nuclear expression of MCM4 was observed in UTUC tissues, and it was detected in 77 (62%) of a total of 124 UTUC cases. MCM4-positive UTUC cases were associated with nodular/flat morphology, high grade, high T stage, and poor prognosis. Moreover, MCM4 expression was significantly higher in the invasive front than in the tumor surface. Similar results were also obtained in TCGA bladder cancer cohort. Additionally, MCM4 expression was associated with high expression of Ki-67, HER2, EGFR, and p53 in UTUC. Among representative cancer-related molecules, MCM4 had an independent predictive value for progression-free survival and high-grade UC. ICC for MCM4 was also performed on urine cytology slides and showed that the nuclear expression of MCM4 was more frequently found in UC cells than in non-neoplastic cells. The diagnostic accuracy of urine cytology was improved by combining MCM4 immunostaining with cytology. CONCLUSION: These results suggest that MCM4 might be a useful predictive biomarker for high-grade histology, tumor progression and poor prognosis in UC. Moreover, ICC for MCM4 might be helpful for UC detection as additional markers in the cytomorphology-based diagnosis.

The Efficacy of Neoadjuvant Gemcitabine and Cisplatin Chemotherapy for cT3N0M0 Upper Tract Urothelial Carcinoma: The Impact of Tumor Location.

PURPOSE: Upper tract urothelial carcinoma (UTUC) can be divided into renal pelvis tumor (RPT) and ureteral tumor (UT) based on the tumor origin. This study aimed to evaluate the efficacy of neoadjuvant chemotherapy with gemcitabine and cisplatin (NAC-GC) in terms of the pathological outcomes and oncological prognoses in patients with UTUC. We also compared its efficacy between RPT and UT. MATERIALS AND METHODS: Patients who underwent radical nephroureterectomy for clinical T (cT)3N0M0 UTUC between 1999 and 2021 were included. Patients who underwent NAC-GC and those who did not were included in the NAC-GC and non-NAC-GC groups, respectively. Based on the tumor origin, we divided patients with UTUC into RPT and UT groups. Oncological prognosis was assessed using progression-free survival (PFS) and overall survival. RESULTS: Of 44 patients, 20 (45.5%) and 24 (54.5%) patients were in the NAC-GC and non-NAC-GC groups, respectively. The NAC-GC group had significantly lower pathological T stage and negative lymphovascular invasion (LVI), and a better PFS (p < .05) compared to those in the non-NAC-GC group. Among patients with RPT, the NAC-GC group had significantly negative LVI and better PFS than the non-NAC-GC group (p < .05). In contrast, in patients with UT, the NAC-GC group had no significant difference in pathological outcomes, and no significant difference in oncological prognosis was observed between the NAC-GC and non-NAC-GC groups. CONCLUSION: NAC-GC improves both pathological outcomes and oncological prognosis in patients with cT3N0M0 UTUC. With regard to tumor location, RPT has better pathological outcomes and oncological prognoses than UT.

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology.

ßIII-Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high-grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki-67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer-related molecules, TUBB3 was an independent predictor of progression-free survival and high-grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high-grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

Retrospective evaluation of the improvement in the urinary status-related quality of life after robot-assisted radical prostatectomy.

OBJECTIVES: This study aimed to investigate the characteristics of patients who report improvement in quality of life (QOL) related to urinary status after undergoing robot-assisted radical prostatectomy (RARP) for localized prostate cancer. METHODS: We retrospectively reviewed the patients who underwent RARP between May 2010 and May 2021 at our institution and were preoperatively unsatisfied with their urinary status. Patients were grouped as Group 1 (improved patients: "satisfied" with urinary status based on international prostate symptom score QOL [IPSS-QOL] = 0-2 at 12 months after RARP) and Group 2 (unimproved group: "unsatisfied"-IPSS-QOL 3-6). Additionally, the Expanded Prostate Cancer Index Composite (EPIC) urinary subdomains (urinary function, urinary bother [UB], urinary incontinence, and urinary irritation/obstruction [UIR]) and IPSS were evaluated preoperatively and till 12 months after RARP. RESULTS: Of the 237 patients, 72 (30.4%) were Group 1, and 165 (69.6%) were Group 2. Only UB and UIR improved at 12 months after RARP in Group 1, while other EPIC urinary subdomains remained unimproved at 12 months in both groups. On the other hand, IPSS improved at 12 months in both groups. Univariate and multivariate analysis revealed that the nerve-sparing, preoperative low IPSS (<11 vs. ≥11), and low IPSS-QOL (3 vs. 4-6) were associated with improvement in urinary status-related QOL (p < 0.05). CONCLUSIONS: Improvement in UB and UIR are important factors to ascertain improvement in urinary status-related QOL after RARP. Nerve-sparing and preoperative IPSS/IPSS-QOL values are useful predictors of this improvement.

Dual immunocytochemical staining of annexin A10 and p53 in low-grade and papillary urothelial carcinoma contributes to improvement of diagnostic accuracy in urine cytology.

BACKGROUND: Urothelial carcinoma (UC) is a common type of human cancer and, although urine cytology is a useful method for identifying high-grade UC (HGUC), its ability to diagnose low-grade UC (LGUC) is limited. The authors previously reported that annexin A10 (ANXA10) expression was strongly linked to both papillary and early stage LGUC and was inversely correlated with p53 expression in upper tract UC (UTUC) and bladder UC. However, it remains largely unknown whether ANXA10 is useful as a diagnostic marker for urine cytology. METHODS: In this study, the authors used 104 biopsy and 314 urine cytology samples to investigate the efficacy of ANXA10 and p53 expression by immunohistochemistry and immunocytochemistry. RESULTS: In immunohistochemistry analysis, expression levels of ANXA10 and p53 were either weak or absent in noncancerous tissues, whereas ANXA10 overexpression was observed patients with LGUC, and strong expression of p53 was identified in patients with HGUC. In immunocytochemistry analysis, sensitivity was not good for the detection of UC, especially UTUC, by cytology alone, but it was improved by combining cytology with ANXA10 and p53 to detect both bladder UC and UTUC. Receiver operating characteristic curve analysis also confirmed the diagnostic superiority of cytology combining ANXA10 and p53 for the detection of all UCs, including both HGUC and LGUC (area under the curve, 0.84). CONCLUSIONS: To the authors' knowledge, this is the first report that the combination of ANXA10 and p53 has potential application as a diagnostic immunomarker for improving the diagnostic accuracy of urine cytology.