Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma.

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

Three-dimensional computed tomography-based resection process map for robot-assisted partial nephrectomy: propensity score matching of a single-center retrospective study.

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.

Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy-epispadias complex.

Introduction: The bladder exstrophy-epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation: We report the case of a 44-year-old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy-epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion: This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy-epispadias complex.

Efficacy of Robot-Assisted Ureteroureterostomy in Patients with Complex Ureteral Stricture after Ureteroscopic Lithotripsy.

BACKGROUND: Ureteral stricture (US) postureteroscopic lithotripsy (URSL) has emerged as a severe complication with the widespread use of laser technology. Furthermore, managing a complex US is challenging. Therefore, this study evaluated the efficacy of robot-assisted ureteroureterostomy (RAUU) in addressing US post-URSL and analyzed the pathology of transected ureteral tissues to identify the risk factors for US. METHODS: we conducted a prospective cohort study on patients who underwent RAUU for URSL-induced US from April 2021 to May 2023. RESULTS: A total of 14 patients with a mean age of 49.8 years were included in this study. The mean stricture length on radiography was 22.66 ± 7.38 mm. Nine (64.2%) patients had experienced failure with previous interventions. The overall success rate was 92.9%, both clinically and radiographically, without major complications, at a mean follow-up of 12.8 months. The pathological findings revealed microcalcifications and a loss of ureteral mucosa in 57.1% and 28.6% of patients, respectively. CONCLUSIONS: The RAUU technique shows promise as a viable option for US post-URSL in appropriately selected patients despite severe pathological changes in the ureter. Therefore, the migration of microcalcifications to the site of ureteral perforation may be a significant factor contributing to US development.

Postoperative Bladder Neck to Pubic Symphysis Ratio Predictive for De Novo Overactive Bladder after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution. METHODS: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio. RESULTS: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group (p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio (p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1). CONCLUSION: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

Clinical characteristics of Raoultella ornithinolytica bacteremia and antimicrobial susceptibility of Raoultellaornithinolytica.

Raoultella ornithinolytica (R. ornithinolytica) is a gram-negative rod that was considered related to Klebsiella oxytoca and was classified as R. ornithinolytica in 2001. R. ornithinolytica is known as a histamine-producing bacterium that causes mackerel poisoning. Although only few clinical cases of R. ornithinolytica infection in humans have been reported, the number of diagnosed cases is expected to increase owing to the advancements in identification methods. In the present study, we performed a retrospective analysis of cases of R. ornithinolytica infection detected at our hospital. From September 2019 to July 2021, 62 specimens positive for R. ornithinolytica were obtained after removing duplicates. The clinical courses of these cases were investigated retrospectively based on electronic medical records. Of the 62 specimens, 24 were sputum, 19 were urine, three were stool, six were blood, four were bile, and six were other specimens. All the six blood culture specimens in which R. ornithinolytica was detected were from male patients, and the causative diseases were cholangitis in four cases and complicated pyelonephritis in two cases. Of these, two patients with cholangitis succumbed to death due to the worsening of underlying cancer. Identification of R. ornithinolytica is reportedly difficult, and some instruments may misidentify it as Klebsiella oxytoca. The prognosis of R. ornithinolytica infection has been reported to be good when susceptible drugs are used. However, high mortality rates were also reported despite the use of these drugs, suggesting the need for further investigation of clinical features of R. ornithinolytica infection.

Identification of active spermatogenesis using a multiphoton microscope.

BACKGROUND: The sperm retrieval rate of microdissection testicular sperm extraction varies from 25% to 60%. Therefore, it is necessary to establish objective selection criteria for identifying seminiferous tubules with spermatozoa. OBJECTIVES: Our aim was to develop a method for identifying spermatogenesis without sectioning testicular tissues. MATERIALS AND METHODS: Testicular tissues of 10-week-old normal rats were fixed with 4% paraformaldehyde. Fluorescent labeling of seminiferous tubule nuclei and F-actin was performed, and the specimens were observed without sectioning using a multiphoton microscope. Cryptorchid rats were used as a model lacking elongated spermatids. Multiphoton images were compared with images of normal seminiferous tubules. In addition, seminiferous tubules of 10-week-old normal rats were labeled by testicular interstitial injection of fluorescent probes and observed by a multiphoton microscope without fixation. Terminal deoxynucleotidyl transferase dUTP nick end labeling-stained images of normal and probe-injected testes were compared. RESULTS: In fixed seminiferous tubules, elongated spermatids were identified. In addition, F-actin of apical ectoplasmic specialization was observed around elongated spermatids. Furthermore, spermatogenic stages were identified by an array of nuclei or F-actin. In cryptorchid testes, elongated spermatids and F-actin of the apical ectoplasmic specialization were not observed. In testes injected with fluorescent probes, F-actin of the apical ectoplasmic specialization was observed, and spermatogenic stages were identified without fixation. There was no significant difference in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells per seminiferous tubule between normal and probe-injected testes. CONCLUSIONS: Seminiferous epithelium could be observed without sectioning of tissues by fluorescent probes and a multiphoton microscope. Active spermatogenesis was observed by labeling F-actin with and without fixation. Moreover, the toxicity of fluorescent probes was limited. Our method has a potential for live imaging of testicular tissue.

Testicular seminoma arising from infertile testes 6 years after microdissection testicular sperm extraction.

INTRODUCTION: In Western countries, the risk of a testicular germ cell tumor in men with male factor infertility is greater than in the general population. However, Japanese data on this risk are lacking. Additionally, the clinical course for the pathogenesis involved has not been clearly characterized. CASE PRESENTATION: A 35-year-old Japanese male underwent a right orchiectomy because of a mass in his right scrotum. He had a previous history of microdissection testicular sperm extraction undertaken 6 years ago. The final diagnosis of the right scrotal mass was a stage I seminoma. However, a relapse occurred in the left inguinal lymph node 2 years after surgery and the patient was consequently treated with systemic chemotherapy. Pathological analysis of a microdissection testicular sperm extraction sample yielded a germ cell neoplasia in situ in the right testis. CONCLUSION: In Japan, men who seek an evaluation for infertility might be more likely to develop testicular germ cell tumor.

Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Müllerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism.

PURPOSE: In cryptorchidism, germ cell development failure presents from infancy and may be reflected by altered hormonal levels produced by Sertoli cells. Our object was to assess for associations between serum hormone levels and testicular histopathology in cryptorchidism with an infertility risk according to the pretreatment undescended testicular positions. MATERIALS AND METHODS: Prepubertal cryptorchid boys aged 7-91 (median 20) months who underwent orchidopexy between 2014 and 2019 were included (122 unilateral [median 19 months {range 7-91}], 23 bilateral [24 months {11-81}]). We evaluated the pretreatment testicular position and size; serum hormone levels; and the mean number of germ cells per tubule transverse section (G/T). We also performed a subgroup analysis of boys aged ≤24 months at orchidopexy. RESULTS: Serum inhibin B levels and G/T were significantly lower in bilateral than in unilateral cryptorchid boys (median 96 [range 46-197] pg/ml vs 125 [21-354] pg/ml, p=0.026; 0.20 [0-2.59] vs 0.65 [0-4.55], p <0.001, respectively). Inhibin B/follicle-stimulating hormones (FSH) and anti-Müllerian hormone (AMH)/FSH ratios were positively correlated with G/T in bilateral cryptorchid boys aged ≤24 months (12, p=0.008 and p=0.019, respectively). Low inhibin B/FSH and AMH/FSH ratios and high FSH were predictors of impaired G/T as per receiver operating characteristic curves (p=0.019, p=0.004 and p=0.004, respectively), whereas in unilateral cryptorchid boys aged ≤24 months, serum hormone levels and G/T did not differ with the pretreatment testicular positions. CONCLUSIONS: In bilateral cryptorchid boys aged ≤24 months at orchidopexy, low inhibin B/FSH and AMH/FSH ratios may reflect impaired G/T and future infertility risk.

Trocar site hernia resulting in intestinal necrosis 48 hours after robot-assisted radical prostatectomy.

INTRODUCTION: Trocar site hernia is a potentially serious sequela of laparoscopic procedures that may lead to bowel incarceration and strangulation. We report a case of trocar site hernia secondary to robot-assisted radical prostatectomy. CASE PRESENTATION: A 71-year-old Japanese man underwent robot-assisted radical prostatectomy without any intraoperative events; however, a brief dislodgement of a 12-mm AIRSEAL® trocar occurred. Forty-eight hours after the procedure, the patient exhibited coffee ground vomitus. Computed tomography revealed an intestinal prolapse at the 12-mm AIRSEAL® trocar site. He was diagnosed with a strangulated bowel due to trocar site hernia. Following an emergency exploration, 25 cm of gangrenous intestine was resected, and a functional end-to-end anastomosis was performed. CONCLUSION: In this case, brief dislodgement of the AIRSEAL® trocar may have caused severe subcutaneous emphysema and intestinal sucking. In such situations, certain closure of both, the peritoneum and the fascia, is necessary.

Rare case of immunoglobulin G4-related disease arising in gonadal glands with long-term remission without steroid treatment: Discussion and literature review.

INTRODUCTION: Immunoglobulin G4-related disease embraces a wide range of extra-pancreatic manifestations. However, localized pathogenesis in gonadal glands, including testes or seminal vesicles, is rare. The clinical course and therapeutic strategy for this disease have not been clearly characterized. CASE PRESENTATION: A 61-year-old Asian male had a left orchiectomy and right seminal vesicle biopsy because of a mass in the left testis and right seminal vesicle. Histological findings showed an infiltration of immunoglobulin G4-positive plasma cells in the respective tissues and met immunoglobulin G4-related disease diagnostic criteria. No recurrence and exacerbation have been observed after 12 years' follow-up without any clinical intervention. To date, immunoglobulin G4-related disease in gonadal tissue is rare. This is the first case with mass-forming lesions in both the testis and seminal vesicle. CONCLUSION: Based on the clinical course of our case and the literature, for patients with accurately diagnosed inactive gonadal immunoglobulin G4-related disease, watchful waiting is a feasible clinical treatment option.

LigaSure versus the standard technique (Hem-o-lok clips) for robot-assisted radical prostatectomy: a propensity score-matched study.

The aim of the study is to compare the utility and efficacy of the LigaSure system and standard surgical clips for robot-assisted radical prostatectomy. The medical records of 473 patients who underwent robot-assisted radical prostatectomy between May 2011 and 2018 were retrospectively reviewed and analyzed. The patients were divided into the LigaSure (n = 125) and Hem-o-lok (n = 348) groups, based on the device used to ligate the vascular pedicle. Owing to differences in the patient characteristics, a 1:2 propensity score matching was performed. In the final matched cohort, 375 patients were included for analysis. The median initial prostate-specific antigen level was not significantly different between the two groups. The median surgical and console times were significantly shorter for the LigaSure group than for the Hem-o-lok group (p < 0.001 and 0.003, respectively). The number of specimens with positive surgical margins was significantly lower in the LigaSure group than in the Hem-o-lok group (24.8 vs 40.8%, p = 0.002). The number of specimens with positive surgical margins for pathological stage T2 cases was also significantly lower in the LigaSure group than in the Hem-o-lok group (17.0 vs 37.5%, p < 0.001). However, non-focal positive surgical margins and biochemical recurrence-free survival rates at 1 year postoperatively were not significantly different (11.2 vs 18.4%, p = 0.075 and 91.2 vs 92.8%, p = 0.565, respectively). The LigaSure system was associated with fewer positive surgical margins and shorter operation time, indicating that it could be a useful alternative to Hem-o-lok clips for controlling the prostatic pedicle in robot-assisted radical prostatectomy, despite its high costs.

Pelvic Anatomical Features After Retzius-Sparing Robot-Assisted Radical Prostatectomy Intended for Early Recovery of Urinary Symptoms.

Purpose: To elucidate factors contributing to early urinary continence recovery after retzius-sparing robot-assisted radical prostatectomy (RS-RARP) by evaluating postoperative pelvic anatomical features between RS-RARP and conventional RARP (CON-RARP). Materials and Methods: We retrospectively examined 50 men who underwent RS-RARP (n = 25; the RS-RARP group) and CON-RARP (n = 25; the CON-RARP group) between October 2017 and June 2018. Perioperative outcomes and postoperative urinary continence were assessed in both groups. Anatomical features including the bladder neck-to-pubic symphysis ratio (determined from cystograms) and membranous urethral length (MUL) (determined from magnetic resonance imaging) were evaluated. Result: The daily urinary incontinence rate at discharge was significantly lower in the RS-RARP group than in the CON-RARP group (0.046 [range: 0.014-0.160] vs 0.357 [range: 0.139-0.616], p < 0.001). Postoperative urinary continence at 1, 3, 6, and 12 months was 80%, 92%, 96%, and 96% in the RS-RARP group and 24%, 40%, 68%, and 84% in the CON-RARP group, respectively (p < 0.001). The urgency scores in the international prostate symptom score (IPSS) questionnaire at 1 and 3 months were significantly lower in the RS-RARP than in the CON-RARP group (p = 0.028 and 0.033, respectively). The quality of life (QOL) indices were more significantly improved in the RS-RARP group than in the CON-RARP group 1 month (p = 0.027) and 3 months (p = 0.045) postoperatively. Receiver operating characteristic analysis revealed that a postoperative MUL of 12.1 mm (area under the curve: 0.852) was the optimal cutoff value predictive of continence recovery after 1 month. Multivariate analysis demonstrated that RS-RARP (odds ratio [OR]: 23.6; p < 0.001) and prostate volume (OR: 0.926; p = 0.049) were the independent factors of a longer MUL. Conclusions: RS-RARP results in an early continence recovery and a better urgency score in the IPSS by suppressing the descent of the bladder and maintaining a long MUL. RS-RARP may contribute to a better QOL recovery after RARP.

Selective lysine-specific demethylase 1 inhibitor, NCL1, could cause testicular toxicity via the regulation of apoptosis.

BACKGROUND: Recent studies have shown that epigenetic alterations, such as those involving lysine-specific demethylase 1 (LSD1), lead to oncogenic activation and highlight such alterations as therapeutic targets. However, studies evaluating the effect of LSD1 inhibitors on male fertility are lacking. OBJECTIVES: We analyzed the potential toxicity of a new selective LSD1 inhibitor, N-[(1S)-3-[3-(trans-2-aminocyclopropyl)phenoxy]-1-(benzylcarbamoyl)propyl] benzamide (NCL1), in testes. MATERIALS AND METHODS: Human testicular samples were immunohistochemically analyzed. Six-week-old male C57BL/6J mice were injected intraperitoneally with dimethyl sulfoxide vehicle (n = 15), or 1.0 (n = 15) or 3.0 (n = 15) mg/kg NCL1 biweekly. After five weeks, toxicity and gene expression were analyzed in testicular samples by ingenuity pathway analysis (IPA) using RNA sequence data and quantitative reverse transcriptase (qRT)-PCR; hormonal damage was analyzed in blood samples. NCL1 treated GC-1, TM3, and TM4 cell lines were analyzed by cell viability, chromatin immunoprecipitation, flow cytometry, and Western blot assays. RESULTS: LSD1 was mainly expressed in human Sertoli and germ cells, with LSD1 levels significantly decreased in a progressive meiosis-dependent manner; germ cells showed similar expression patterns in normal spermatogenesis and early/late maturation arrest. Histological examination revealed significantly increased levels of abnormal seminiferous tubules in 3.0 mg/kg NCL1-treated mice compared to control, with increased cellular detachment, sloughing, vacuolization, eosinophilic changes, and TUNEL-positive cells. IPA and qRT-PCR revealed NCL1 treatment down-regulated LSD1 activity. NCL1 also reduced total serum testosterone levels. Western blots of mouse testicular samples revealed NCL1 induced a marked elevation in cleaved caspases 3, 7, and 8, and connexin 43 proteins. NCL1 treatment significantly reduced GC-1, but not TM3 and TM4, cell viability in a dose-dependent manner. In flow cytometry analysis, NCL1 induced apoptosis in GC-1 cells. CONCLUSIONS: High-dose NCL1 treatment targeting LSD1 caused dysfunctional spermatogenesis and induced caspase-dependent apoptosis. This suggests the LSD1 inhibitor may cause testicular toxicity via the regulation of apoptosis.

Comparison of Real-Time Virtual Sonography Navigation Versus BioJet Navigation on Magnetic Resonance Imaging-Guided Prostate Needle Biopsy: A Single Institutional Analysis.

Objective: To analyze the effectiveness and complication rate of MRI-guided prostate needle biopsies by using real-time virtual sonography (RVS) vs BioJet navigation. Methods: We retrospectively reviewed 171 patients who underwent an MRI-guided prostate needle biopsy at our institution. Patients whose prostate-specific antigen level was >4.0 ng/mL and who had suspicious prostate cancer (PCa) lesions by multiparametric MRI (mpMRI) underwent 2-core MRI-guided targeted biopsy (TB) and for MRI-guided TB: RVS and BioJet. RVS navigation synchronized mpMRI images with transrectal ultrasound (TRUS) images. BioJet navigation used a software program that merged images from mpMRI and TRUS to produce a composite image. We retrospectively compared the detection rate of PCa and the frequency of severe adverse events (AEs) between these two navigation systems, focusing on patients. In addition, we compared the detection rate of MRI-guided TB cores of two navigation systems regarding anatomical position (transitional zone [TZ] or peripheral zone [PZ]). Results: Data from RVS and BioJet biopsy groups were from 65 and 106 patients, respectively. Of these, RVS-TB included 141 cores (PZ: 49 cores, TZ: 92 cores), and BioJet-TB included 276 cores (PZ: 73 cores, TZ: 203 cores). In detecting PCa, by conducting both systematic biopsy and TB, and AEs in patients, a significant difference was not noted between RVS and BioJet navigation systems. In addition, there was no significant difference in the total detection rate for PCa in TB cores between the two methods. However, in the TZ, BioJet navigation showed a significantly higher detection rate of PCa than RVS navigation (35.0% vs 17.4%, p = 0.0023) by analyzing the cores of MRI-guided TB. Conclusion: When targeting TZ lesions, BioJet navigation had a greater detection rate for PCa compared with that of RVS navigation.

Rare case of carcinoma in situ originated in right retrocaval ureter successfully managed with laparoscopic procedure.

INTRODUCTION: A retrocaval ureter is a rare congenital abnormality characterized by the persistence of the posterior subcardinal vein on the right, which causes the proximal ureter to deviate medially behind the inferior vena cava. The presence of retrocaval ureter is usually found because of the development of progressive hydronephrosis, but many cases are clinically silent. In addition, an urothelial malignancy associated with retrocaval ureter is very rare. CASE PRESENTATION: Herein we report a very rare case of a 57-year-old male with retrocaval ureter and carcinoma in situ diagnosed by ureteroscopy. In spite of strong adhesion in the area of the ureter behind the inferior vena cava, dissection was successfully managed by a laparoscopic procedure after cutting the ureter and separating it into two segments. CONCLUSION: Early histopathological diagnosis and radical laparoscopic surgery based on the results of ureteroscopy may lead to a good outcome, even in retrocaval ureter cases with a carcinoma in situ.