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.

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.

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.

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.

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.

Novel quantitative software for automatically excluding red bone marrow on whole-body magnetic resonance imaging in patients with metastatic prostate cancer: A pilot study.

OBJECTIVES: To establish a novel quantitative method that automatically excludes the red bone marrow and accurately quantifies the tumor volume on whole-body magnetic resonance imaging using updated imaging software. To also evaluate the association between the quantified tumor volume and the prognosis of patients with metastatic prostate cancer. METHODS: This prospective analysis included patients diagnosed with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer between 2017 and 2022. We developed an imaging software (Attractive BD_Score) that analyzed whole-body diffusion-weighted and in-phase and opposed-phase T1-weighted images to automatically exclude the red bone marrow. The quantified tumor volume was compared with that quantified by traditional whole-body diffusion-weighted imaging without red bone marrow exclusion. Prostate-specific antigen progression-free survival, time-to-pain progression, and overall survival were evaluated to assess the prognostic value of the quantified tumor volume. RESULTS: The quantified tumor volume was significantly smaller than that quantified by the traditional method in metastatic hormone-sensitive (median: 81.0 ml vs. 149.4 ml) and metastatic castration-resistant (median: 29.4 ml vs. 63.5 ml) prostate cancer. A highly quantified tumor volume was associated with prostate-specific antigen progression-free survival (p = 0.030), time-to-pain progression (p = 0.003), and overall survival (p = 0.005) in patients with metastatic hormone-sensitive prostate cancer and with poor prostate-specific antigen progression-free survival (p = 0.001) and time-to-pain progression (p = 0.005) in patients with metastatic castration-resistant prostate cancer. CONCLUSIONS: Our imaging method could accurately quantify the tumor volume in patients with metastatic prostate cancer. The quantified tumor volume can be clinically applied as a new prognostic biomarker for metastatic prostate cancer.

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.

Importance of considering interest in sex when evaluating satisfaction after robot-assisted radical prostatectomy.

OBJECTIVES: To assess the impact of patients' interest in sex on the satisfaction after robot-assisted radical prostatectomy, longitudinal changes of urinary and sexual functions and bothers were evaluated. METHODS: A total of 101 patients underwent robot-assisted radical prostatectomy in our institution. Based on sexual interest, they were divided into the high-interest and low-interest groups. Overall satisfaction, urinary function, urinary bother, sexual function, and sexual bother were evaluated using the expanded prostate cancer index composite questionnaire preoperatively and at 1, 3, 6, and 12 months after robot-assisted radical prostatectomy. We investigated the associations between the overall satisfaction and urinary function/urinary bother/sexual function/sexual bother scores (with higher score indicating better function and less impairment). RESULTS: In the high-interest group (n = 45), satisfaction correlated with high urinary function and urinary bother scores early after robot-assisted radical prostatectomy (urinary function: 1 and 3 months, urinary bother: 3 months postoperatively; P < 0.05) and then with high sexual bother score thereafter (sexual bother at 6 and 12 months after surgery; P < 0.05). Sexual function score did not correlate with satisfaction. In the low-interest group (n = 56), satisfaction correlated with high urinary function and urinary bother scores over time (urinary function: 3 and 6 months, urinary bother: at 3, 6 and 12 months postoperatively; P < 0.05). Neither sexual function nor sexual bother correlated with satisfaction postoperatively in the low-interest group. CONCLUSIONS: The impact of urinary and sexual functions and bothers on patients' overall satisfaction differed between patients with high- and low-interest in sex. The patient's interest in sex should be considered when assessing satisfaction after robot-assisted radical prostatectomy.

Recurrence- and progression-free survival in intermediate-risk non-muscle-invasive bladder cancer: the impact of conditional evaluation and subclassification.

OBJECTIVES: To assess the change in rates of recurrence-free survival (RFS) and progression-free survival (PFS) based on the duration of survival without recurrence or progression among patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), and to examine the predictive factors for recurrence at different time points by assessing conditional RFS and PFS. PARTICIPANTS AND METHODS: A cohort of 602 patients treated with transurethral resection of bladder tumour and histopathologically diagnosed with IR NMIBC was included in this retrospective study. RESULTS: The conditional RFS rate at 1, 2, 3, 4 and 5 years improved with increased duration of RFS; however, the conditional PFS rate did not improve over time. Multivariable analyses showed that recurrent tumour, multiple tumours, tumour size (>3 cm), immediate postoperative instillation of chemotherapy, and administration of BCG were independent predictive factors for recurrence at baseline. The predictive ability of these factors disappeared with increasing recurrence-free survivorship. Subclassification of these patients with IR NMIBC into three groups using clinicopathological factors (recurrent tumour, multiple tumours, tumour size) demonstrated that the high IR group (two factors) had significantly worse RFS than the intermediate (one factor, P < 0.001) and low IR groups (no factor, P = 0.005) at baseline. This subclassification stratified conditional risk of RFS also at 1, 3 and 5 years, which provides the basis for distinct surveillance protocols among patients with IR NMIBC. CONCLUSION: Conditional survival analyses of patients with IR NMIBC demonstrate that RFS changes over time, while PFS does not change. These data support distinct surveillance protocols based on the subclassification of IR NMIBC.

Preoperative pelvic floor muscle exercise for early continence after holmium laser enucleation of the prostate: a randomized controlled study.

BACKGROUND: Transient postoperative urinary incontinence is a bothersome complication of holmium laser enucleation of the prostate (HoLEP). The effects of preoperative pelvic floor muscle exercise (PFME) for early recovery of continence after HoLEP have never been elucidated. The aim of this study was to determine the benefit of preoperatively started PFME for early recovery of continence after HoLEP. METHODS: We randomly assigned patients to start PFME preoperatively and continue postoperatively (group A) or start PFME no earlier than the postoperative period (group B). The primary outcome was time to complete urinary control, defined as no pad usage. The secondary outcome was measured using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Univariate and multivariate analyses were performed to identify parameters associated with recovery of continence after HoLEP. RESULTS: Seventy patients were randomized across groups A (n = 35) and B (n = 35). Patients' characteristics were not different between groups A and B. The postoperative urinary incontinence rate significantly decreased in group A compared with that in group B at 3 months postoperatively [3% vs. 26% (P = 0.01)]. However, there were no significant differences between groups A and B at 3 days [40% vs. 54% (P = 0.34)], 1 month [37% vs. 51% (P = 0.34)], and 6 months [0% vs. 3% (P = 1.00)] postoperatively, respectively. The postoperative ICIQ-SF score was not significantly different between groups A and B at any time point postoperatively. In univariate analysis, patients who performed preoperative PFME had a 0.56-fold lower risk of urinary incontinence 1 month after HoLEP and a 0.08-fold lower risk of urinary incontinence 3 months after HoLEP. CONCLUSIONS: Preoperatively started PFME appears to facilitate improvement of early urinary continence after HoLEP. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network Clinical Trials Registry in Japan (UMIN000034713); registration date: 31 October 2018. Retrospectively registered.

One-surgeon basketing technique for stone extraction during flexible ureteroscopy for urolithiasis: A comparison between novice and expert surgeons.

OBJECTIVE: To determine the safety and efficacy of the one-surgeon basketing technique for stone extraction during flexible ureteroscopy when carried out by novice surgeons under instructor guidance. METHODS: We retrospectively compared perioperative results, complications and the "stone-free" rate (defined as ≤2 mm fragments on kidney-ureter-bladder imaging 1 month after flexible ureteroscopy) between experienced (group A, n = 50) and novice (group B, n = 50) surgeons using the one-surgeon basketing technique. RESULTS: Baseline patients' characteristics were similar between the two groups. There were no significant differences between groups A and B in operative time (mean 76 min vs 85 min, P = 0.46), stone-free rate (98% vs 92%, P = 0.36), postoperative fever events (4% vs 4%, P = 1.00) and postoperative hospital stay (24 h vs 24 h, P = 1.00). Clavien-Dindo grade IIIa complications (ureter injury) were only observed in two cases (4%) in group B. CONCLUSIONS: The one-surgeon basketing technique for the extraction of stone fragments during flexible ureteroscopy might be safely and effectively carried out by surgeons with no prior experience under proper guidance.

The risk factors of urinary tract infection after transurethral resection of bladder tumors.

PURPOSE: Few studies mention the necessity of antimicrobial prophylaxis (AMP) for transurethral resection of bladder tumor (TURBT) and the risk factors for postoperative urinary tract infections (UTIs) after TURBT. To evaluate the necessity of AMP and to detect the risk of UTIs, we examined the perioperative clinical factors. METHODS: 687 patients who underwent TURBT between 2006 and 2017 at Hiroshima Prefectural Hospital were examined retrospectively. We defined the postoperative UTIs as febrile UTIs (≥ 38 °C). The AMP for the TURBT that we used was mostly cephalosporin generation 1. The association between the perioperative clinical/pathological factors and postoperative UTIs was assessed by logistic regression retrospectively. RESULTS: 21 patients (3.1%) suffered from postoperative UTIs, and almost all of them were successfully treated with the immediate administration of antibiotics. Univariate analysis showed that past pelvic radiotherapy (p = 0.024, odds ratio (OR) 6.00), tumor size (≥ 2cm) (p = 0.008, OR 3.38), age (≥ 75 years) (p = 0.036, OR 2.65), preoperative hospital stay (≥ 5 days) (p = 0.017, OR 3.76), asymptomatic pyuria (p = 0.038, OR 2.54) and bacteriuria (p = 0.044, OR 2.97) were all associated with postoperative UTIs. CONCLUSIONS: We demonstrated that AMP was effective for patients who underwent TURBT, and history of pelvic radiotherapy, high age, preoperative hospital stay and a certain tumor size were the risk factors as well as pyuria and bacteriuria of postoperative UTIs.

The Impact of Glycosylation of Osteopontin on Urinary Stone Formation.

Osteopontin (OPN) is a matrix glycoprotein of urinary calculi. This study aims to identify the role of aberrant glycosylation of OPN in urolithiasis. We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN levels in 110 urolithiasis patients and 157 healthy volunteers and 21 patients were prospectively longitudinal follow-up during stone treatment. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/full-length-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p < 0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin analysis of urinary full-length-OPN showed that urinary full-length-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. In the prospective longitudinal follow-up study, 92.8% of the stone-free urolithiasis group had Gal3C-S-OPN/full-length-OPN levels below the cutoff value after ureteroscopic lithotripsy (URS), whereas 71.4% of the residual-stone urolithiasis group did not show decreased levels after URS. Therefore, Gal3C-S-OPN/full-length-OPN levels could be used as a urolithiasis biomarker.

Preoperative risk classification using neutrophil-lymphocyte ratio and hydronephrosis for upper tract urothelial carcinoma.

BACKGROUND: To improve the prediction of outcomes in patients who will undergo radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), we examined the preoperative prognostic factors and established a risk classification model. METHODS: A total of 148 patients who underwent RNU without history of neo-adjuvant chemotherapy between 1999 and 2016 in Hiroshima University Hospital were retrospectively reviewed. Associations between preoperative/clinicopathological factors and outcomes including cancer-specific survival (CSS) and recurrence-free survival (RFS) were assessed. We specifically looked at neutrophil-lymphocyte ratio (NLR) due to growing evidence on its predictive role in cancer prognosis prediction. RESULTS: Preoperative elevated neutrophil-lymphocyte ratio (pre-op NLR, ≥3.0) and hydronephrosis (≥grade 2) were associated with advanced pathological stage; and were identified as independent predictive factors of shorter CSS and RFS in univariate and multivariate analysis. We classified the patients in three groups using preoperative factors and found that the 5-year CSS was 94.5, 75.9 and 44.7% and the 5-year RFS was 74.3, 57.6 and 28.7% in the low-risk group (neither pre-op NLR nor hydronephrosis), intermediate-risk group (either pre-op NLR or hydronephrosis) and high-risk group (pre-op NLR and hydronephrosis), respectively. High-risk group had significantly worse CSS (P = 0.0172) and RFS (P = 0.0014) than intermediate-risk group and low-risk group (CSS (P < 0.0001) and RFS (P < 0.0001)). CONCLUSIONS: Elevated pre-op NLR and hydronephrosis were identified as independent prognostic factors in patients with UTUC. These simple preoperative factors can stratify three prognostic groups and may help urologists in clinical decision-making before RNU.

[A Case of Myxofibrosarcoma of the Retroperitoneum].

Myxofibrosarcoma(MFS)is one of the most common sarcomas in the extremities of elderly patients.We report a rare case of MFS originating in the retroperitoneum.A 65-year-old man presented to our hospital with an intraabdominal tumor, which was identified by abdominal CT during an investigation of an abdominal protuberance.Contrast -enhanced CT and MRI revealed a 18×12 cm mass in the left retroperitoneum.The patient underwent retroperitoneum tumor resection.Operative findings showed that there was an indistinct area between the left side of the tumor and the abdominal wall.There was no residual tumor macroscopically after the operation.The histopathological diagnosis was MFS arising from the retroperitoneum. Four months later, local recurrence and para-aortic lymph node metastasis were diagnosed.We performed tumor resection; however, the recurrent tumor had invaded the iliopsoas and iliac muscles.Additionally, there was peritoneal dissemination around the tumor.Five months after the initial surgery, a recurrence on the back was identified.He died 7 months after the first operation.According to previous reports, patients who undergo an operation with pathologically negative margins achieve better surgical outcomes.Therefore, it is important to perform expanded resection with enough surgical margin as possible.

Microvasculature of carotid atheromatous plaques: hemorrhagic plaques have dense microvessels with fenestrations to the arterial lumen.

BACKGROUND: Microvessels in atheromatous plaques are well known to play a role in plaque vulnerability associated with intraplaque hemorrhage, but their architecture remains unclear. The morphometry of the microvasculature and hemorrhage of human carotid atheromatous plaques (CAPs) were evaluated, and 3-dimensional (3D) reconstruction of the microvessels was performed. METHODS: CAPs were obtained by endarterectomy in 42 patients. The specimens were analyzed using light microscopy. Plaque hemorrhage was defined as an area-containing red blood cells (>1 mm2). To determine the histopathologic features of plaque hemorrhage, the plaque area was divided into 4 regions: cap, shoulder, lipid/necrotic core, and media. Then, the density of microvessels and macrophages in each region was quantified. Two representative lesions with either hemorrhagic or nonhemorrhagic plaque were cut into 90 serial sections. The sections were double stained with anti-CD34 and anti-α smooth muscle actin antibodies, scanned using a digital microscope, and reconstructed using TRI-SRF2 software. RESULTS: The hemorrhagic plaques showed a higher density of microvessels than nonhemorrhagic plaques in the shoulder, cap, and lipid/necrotic core (P=.03, .009, and .001, respectively), and there was positive correlations between its density and macrophages in each regions (P<.001, .001, and .019, respectively). 3D imaging also revealed dense microvessels with a network structure in the cap and shoulder regions of hemorrhagic plaques, and some of the vessels were fenestrated to the arterial lumen. CONCLUSIONS: The microvasculature of plaques with intraplaque hemorrhage was dense, some of which fenestrated to the arterial lumen. The pathologic 3D imaging revealed precise architecture of microvasculature of plaques.

Long-term Recurrence Rates of Low-risk Non-muscle-invasive Bladder Cancer-How Long Is Cystoscopic Surveillance Necessary?

BACKGROUND: While low-risk non-muscle-invasive bladder cancer (LR-NMIBC) has a low propensity to progress, the risk of recurrence remains high (50% within 4 yr). Guidelines recommend cystoscopic surveillance after resection, but the necessary duration of follow-up is debated. OBJECTIVE: To determine the risk of recurrence beyond 5 yr after diagnosis in patients with LR-NMIBC, and to identify risk factors of recurrence. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective observational study, patients who received their first transurethral bladder tumor resection before 2016 for LR-NMIBC were included. Low risk was defined as a primary, solitary, low grade, Ta bladder tumor measuring <3 cm. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was determination of the recurrence rates at 1, 2, and 5 yr. The secondary endpoints included overall recurrence-free survival (RFS) and high-risk RFS. A univariate analysis and multivariable logistic regression were performed to assess the risk factors for recurrence over the study period. RESULTS AND LIMITATIONS: The median age of the 577 patients was 70.9 yr, and 126 (21.8%) patients were female. The median follow-up was 69.6 (interquartile range: 58.4) mo, and recurrence was observed in 236 (40.9%) patients. The 1-, 2-, and 5-yr RFS rates were 81.6% (95% confidence interval 78.4-84.9), 72.4% (68.7-76.3), and 59.2% (55-63.8), respectively. Recurrence after 5 yr was observed in 13.1% (28/213). High-risk recurrence, defined as the first recurrence of a high-grade and/or ≥T1 tumor, occurred in 6.2% (36/579) overall and 2.8% (6/213) after 5 yr. The lack of a single postoperative dose of chemotherapy and tumor size >2 cm were prognostic factors of recurrence. CONCLUSIONS: The risk of recurrence in patients with LR-NMIBC decreases progressively after the 1st year and remains low beyond 5 yr. Discontinuation of endoscopic surveillance after 5 yr in patients with LR-NMIBC can be discussed. Treatment with postoperative chemotherapy and tumor size <2 cm may be relevant variables to identify patients who will benefit from cystoscopic follow-up as short as 12 mo. PATIENT SUMMARY: In this study, we observed that 13% of patients who did not have a recurrence during the first 5 yr following the diagnosis of low-risk non-muscle-invasive bladder cancer will recur after this time point. Discontinuation of cystoscopic surveillance can be discussed after 5 yr in these patients.

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.

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.