High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

Effect of HLA Genotype on Anti-PD-1 Antibody Treatment for Advanced Renal Cell Carcinoma in the SNiP-RCC Study.

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.

Efficacy of Transvaginal Surgery Using an ORIHIME Mesh With Wider Arms and Adjusted Length.

INTRODUCTION: Transvaginal mesh surgery (TVM) is an effective treatment measure for pelvic organ prolapse (POP). However, the ORIHIME mesh (Kono Seisakusho, Japan, Tokyo), which has the disadvantage of poor adherence to tissues, is currently the only product available for this procedure. Our research team has previously developed a modified ORIHIME mesh with wider arms with the aim of minimizing the risk of POP recurrence. Additionally, the length of the mesh behind the anterior vaginal wall has been adjusted to prevent urinary incontinence. The current study aims to examine the efficacy of this modified mesh in minimizing postoperative complications in patients undergoing uphold-type TVM. METHODS: The data of 84 patients who underwent TVM using ORIHIME at our hospital since July 2019 were retrospectively analyzed. The patients were divided into three groups as follows: (a) normal arms (NA; arm width < 6 cm; n = 29 cases); (b) wide arms without length adjustment (WA and LA (-); arm width > 6 cm; n = 27 cases); and (c) wide arms with length adjustment (WA and LA (+); n = 28 cases). Data were collected using various questionnaires, and the residual urine volume was measured before and after surgery. Additionally, the 60-minute pad test was performed where possible, and the recurrence and complication rates were recorded. RESULTS: The incidence of mesh exposure and urinary incontinence in daily life tended to be lower in the WA and LA (+) groups, although this difference was not statistically significant. The one-year postoperative POP recurrence rate, residual urine volume, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score were significantly lower in the WA and LA (+) groups compared to the other groups. CONCLUSION: Uphold-type TVM using the modified ORIHIME mesh with wider arms and adjusted length was associated with better postoperative treatment outcomes compared to TVM using the traditional ORIHIME mesh.

Photoacoustic microscopy for real-time monitoring of near-infrared optical absorbers inside biological tissue.

Significance: We developed a high-speed optical-resolution photoacoustic microscopy (OR-PAM) system using a high-repetition-rate supercontinuum (SC) light source and a two-axes Galvano scanner. The OR-PAM system enabled real-time imaging of optical absorbers inside biological tissues with excellent excitation wavelength tunability. Aim: In the near-infrared (NIR) wavelength range, high-speed OR-PAM faces limitations due to the lack of wavelength-tunable light sources. Our study aimed to enable high-speed OR-PAM imaging of various optical absorbers, including NIR contrast agents, and validate the performance of high-speed OR-PAM in the detection of circulating tumor cells (CTCs). Approach: A high-repetition nanosecond pulsed SC light source was used for OR-PAM. The excitation wavelength was adjusted by bandpass filtering of broadband light pulses produced by an SC light source. Phantom and in vivo experiments were performed to detect tumor cells stained with an NIR contrast agent within flowing blood samples. Results: The newly developed high-speed OR-PAM successfully detected stained cells both in the phantom and in vivo. The phantom experiment confirmed the correlation between the tumor cell detection rate and tumor cell concentration in the blood sample. Conclusions: The high-speed OR-PAM effectively detected stained tumor cells. Combining high-speed OR-PAM with molecular probes that stain tumor cells in vivo enables in vivo CTC detection.

Urosymphyseal fistula development following treatment for radiation-induced urethral stenosis in three patients with prostate cancer.

Introduction: Urosymphyseal fistula is a rare and devastating complication that develops after radiation therapy for prostate cancer and is often triggered by the treatment of radiation-induced urethral stenosis. Here, we report our experience with urosymphyseal fistulas in three patients with prostate cancer. Case presentation: Three patients with prostate cancer developed urethral stenosis after radiotherapy. The management of urethral stenosis was suprapubic tube placement in case 1, direct vision internal urethrotomy in case 2, and excision with primary anastomosis in case 3. All patients presented with severe suprapubic or thigh pain or both. Urosymphyseal fistulas were detected on magnetic resonance imaging. Conservative treatment was unsuccessful, and all patients required debridement of the necrotic pubic symphysis and simple cystectomy. In cases 1 and 2, ileal conduit urinary diversion was performed. Conclusion: Urologists need to be aware that urosymphyseal fistulas can occur in irradiated patients with prostate cancer, especially after urethral stenosis treatment.

Favorable Postoperative Outcomes After Transvaginal Mesh Surgery Using a Wide-Arm ORIHIME® Mesh.

Introduction Transvaginal mesh surgery (TVM) is an effective treatment option for pelvic organ prolapse (POP). Although ORIHIME®, the only available mesh product, is thin, soft, and easy to handle, it has the disadvantages of sliding off or mildly adhering to the surrounding tissues. The current study compared the efficacy of using wide-arm ORIHIME (Kono Seisakusho, Japan, Tokyo), non-wide arm ORIHIME, Gynemesh PS (Johnson and Johnson, Japan, Tokyo), and Polyform (Boston Scientific Japan, Japan, Tokyo) meshes for TVM. Methods The study included 116 patients who underwent TVM (Prolift with Gynemesh PS (n = 14); Elevate with Polyform (n = 43); Uphold with non-wide-arm ORIHIME (n = 24); Uphold with wide-arm ORIHIME (n = 35)) at our hospital. Pre- and post-surgical changes in symptoms were measured using questionnaires and 60-minute pad weight testing and compared by mesh type and surgical methods used. Results The residual urine volume, 60-minute pad weight testing, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and international consultation on incontinence questionnaire-short form score (ICIQ-SF) significantly improved one year postoperatively in the TVM with the wide-arm ORIHIME group. Comparison of pre and one-year postoperative findings by mesh type and surgical methods used showed no significant differences in the 60-minute pad test, IPSS, Quality of Life (QOL), OABSS, and urinary incontinence in daily life scores, and improvement in residual urine volume, ICIQ-SF, and mesh exposure and POP recurrence rates in the TVM with the wide-arm ORIHIME group. Conclusion TVM with wide-arm ORIHIME had better postoperative outcomes compared to TVM with other mesh products.

Implementation of The Paris System for Reporting Urine Cytology improves diagnostic accuracy of selective upper urinary tract cytology.

BACKGROUND: The Paris System for Reporting Urine Cytology (TPS) recommends diagnostic criteria for urinary tract cytology, focusing primarily on the detection of high-grade urothelial carcinoma (HGUC) in the lower urinary tract. The second edition of TPS (TPS 2.0), published in 2022, extends these recommendations to the upper urinary tract (UUT); however, there is a lack of comprehensive data on this subject. METHODS: In total, 223 consecutive UUT cytology specimens from 137 patients were retrieved and reclassified according to TPS 2.0 criteria and were compared with the original diagnosis based on the conventional system (CS). Histologic follow-up within a 3-month period was conducted for 43 patients. RESULTS: Histologic follow-up revealed 30 HGUCs, five low-grade urothelial carcinomas (LGUCs), and eight nonneoplastic fibrotic tissues. The risk of high-grade malignancy for each TPS diagnostic category was 16.7% for nondiagnostic/unsatisfactory, 2.3% for negative for HGUC (NHGUC), 42.1% for atypical urothelial cells, 50.0% for suspicious for HGUC (SHGUC), and 81.8% for HGUC. In all five cases of histologically diagnosed LGUC, the cytologic diagnosis was NHGUC. When SHGUC/HGUC was considered positive, the diagnostic accuracy of TPS had 63% sensitivity, 95% specificity, a 90% negative predictive value, and a 79% positive predictive value, which were better than those of CS. In addition, the TPS indices did not differ significantly between the specimens obtained before and after the application of contrast reagents. CONCLUSIONS: TPS implementation improved the accuracy of UUT cytology in predicting histologic HGUC, which was unaffected by the application of contrast reagents. These data indicate the usefulness of TPS for UUT cytology in routine clinical settings.

Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.

OBJECTIVE: To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer. METHODS: One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups. RESULTS: pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup. CONCLUSIONS: GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.

Clinical factors for tumor response, progression, and survival in nivolumab for advanced renal cell carcinoma in the SNiP-RCC study.

BACKGROUND: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. METHODS: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). RESULTS: We included 222 patients. The median age was 69 years (interquartile range 62-74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. CONCLUSION: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.

T1a Renal Cell Carcinoma With Metastasis: Japanese Society of Renal Cancer Retrospective Multi-institute Results.

BACKGROUND/AIM: Small renal cell carcinomas (sRCC) have drastically increased in recent years. Considering that sRCC have heterogeneous biology, it would be clinically relevant if specific clinical or pathological parameters could predict sRCC metastasis. In the present study, we aimed to assess the clinicopathological factors of pathologic T1a RCC (pT1a RCC) with or without metastasis to explore factors predicting metastasis. PATIENTS AND METHODS: The present study included 198 patients with pT1a RCC who underwent radical or partial nephrectomy at fifteen institutions belonging to the Japanese Society of Renal Cancer, between1985 and 2017. Clinicopathological parameters, including age, sex, tumour size, tumour side, histological subtype, histological nuclear grade, lymphovascular invasion, and histological growth patterns, were analysed. RESULTS: Fuhrman grade 3 or 4 tumours and infiltrative tumour growth patterns were significantly higher in patients with metastasis than in those without. The most common site of synchronous metastasis was the bone in patients with pT1a RCC (65.4%), whereas for patients with post-surgery metachronous metastasis (46.2%), it was the lungs. CONCLUSION: Histological growth pattern and nuclear grade are vital for predicting metastasis in pT1a RCC, suggesting careful long-term follow-up for such patients.

Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.

α-Actinin4 (ACTN4), an isoform of non-muscular α-actinin, is involved in enhancing cell motility and promoting cancer infiltration and metastasis in various cancers. However, information remains limited regarding the pathological significance of ACTN4 expression in upper urinary tract urothelial carcinomas (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who were treated with nephroureterectomy or partial ureterectomy, and analyzed the expression of the ACTN4 protein and the amplification of ACTN4 using immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed ACTN4 protein overexpression and 25 (15%) showed copy number gain (≥4 copies per cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly correlated with ACTN4 protein overexpression and several adverse clinicopathological factors, including higher pathological T stage, lymphovascular invasion, lymph node metastasis, positive surgical margin, concomitant subtype histology, and non-papillary gross finding. Cox univariate regression analyses revealed that both copy number gain of ACTN4 and ACTN4 protein overexpression were significant risk factors for extraurothelial recurrence and death (each p < 0.0001), but multivariate analysis revealed that only copy number gain of ACTN4 was an independent risk factor for extraurothelial recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, respectively). This is the first study demonstrating the aberrant expression status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic indicator in patients with UUTUC.