Platelet-derived growth factor receptor-α (PDGFRα)-positive interstitial cells (ICs) are widely distributed in various organs and may be involved in the motility of various tubular organs. We, for the first time, aimed to investigate the distribution, immunohistochemical characteristics, and ultrastructure of PDGFRα-positive ICs in murine vas deferens, using confocal laser scanning microscopy, transmission electron microscopy (TEM), and immuno-electron microscopy (immuno-EM). For immunofluorescence, we used antibodies against PDGFRα and other markers of ICs. PDGFRα-positive ICs were distributed widely in the lamina propria, smooth muscles, and serosal layers. Although most PDGFRα-positive ICs labeled CD34, they did not label CD34 in the subepithelial layers. Additionally, PDGFRα-positive ICs were in close proximity to each other, as also to the surrounding cells. TEM and immuno-EM findings revealed that PDGFRα-positive ICs established close physical interactions with adjacent ICs. Extracellular vesicles were also detected around the PDGFRα-positive ICs. Our morphological findings suggest that PDGFRα-positive ICs may have several subpopulations, which can play an important role in intercellular signaling via direct contact with the IC network and the extracellular vesicles in the murine vas deferens. Further investigation on PDGFRα-positive ICs in the vas deferens may lead to understanding the vas deferens mortility.

Abstract. The present study reports a case of hemorrhage from branches of the right obturator artery following laparoscopic radical prostatectomy. On post-operative day 9, the patient complained of lower abdominal pain, and the hemoglobin and hematocrit levels had decreased. Emergency computed tomography angiography showed a large pelvic hematoma suggesting active bleeding. Transarterial embolization (TAE) was performed using microcoils. There were no post-procedure complications. At 3 months post-surgery, using computed tomography, the pelvic hematoma was shown to have been absorbed. To the best of our knowledge, TAE for a hemorrhage from the obturator artery following laparoscopic prostatectomy has not previously been described. TAE is a safe and minimally invasive treatment compared with surgical intervention, and should be considered as a treatment for post-operative arterial hemorrhage. IntroductionProstate cancer is one of the most common malignancies of the urinary tract. Based on incidence and mortality data from several agencies, the American Cancer Society estimates that 233,000 new prostate cancer cases and 29,480 mortalities from prostate cancer are projected to occur in the United States in 2014 (1). Prostate cancer is a heterogeneous disease that varies in spectrum from tumors with a low risk of mortality to highly aggressive malignant disease (2). Newly diagnosed prostate cancer has been increasing in Japan, and is predicted to be the first or second most common cancer by 2020 (3). Although the age-adjusted mortality rate, which had rapidly increased up to ~2,000, began to reduce slightly in 2004, the crude mortality rate has continued to rise gradually due to the ageing population (4). Radical prostatectomy has commonly been performed using an open retropubic approach for localized prostate cancer. However, in the past decade, with the development of laparoscopic and robotic techniques, laparoscopic radical prostatectomy (LRP) or robotic-assisted LRP (RALRP) has been widely accepted with the advantages of less invasiveness, shorter recovery, reduced blood loss, and improved visualization of the operative region compared to open techniques (5-7) Severe hemorrhage following prostatectomy is relatively rare, but is one of the serious complications. The current study presents a case in which arteriography with transarterial embolization (TAE) was beneficial for the treatment of severe hemorrhage following LRP. Case reportIn May 2013, a 70-year-old man first presented with lower urinary tract symptoms to the outpatient clinic of Kurume University Hospital, Fukuoka, Japan and was demonstrated to have an elevated the prostate-specific antigen (PSA) of 9.3 ng/ml. In September 2013, subsequent transrectal ultrasound-guided biopsy of the prostate showed prostate adenocarcinoma, with Gleason Score 3+4=7 involving 30% of the bilateral lobes. According to the imaging and biopsy findings, the tumor was classified as cT2cN0M0. In December 2013, LRP and pelvic lymphadectomy were performed without nerve sparing b...

Objective Programmed cell death-1 antibody therapy has demonstrated improved progression-free survival and overall survival in patients with metastatic renal cell carcinoma. However, there are limited studies on biomarkers that can predict the efficacy of immune checkpoint inhibitors. We examined the influence of peripheral inflammatory biomarkers on the clinical outcomes of patients with metastatic renal cell carcinoma treated with nivolumab. Methods Data of 38 patients with metastatic renal cell carcinoma, who were treated with nivolumab monotherapy after receiving at least one molecular targeted therapy from November 2016 to February 2021, were retrospectively reviewed and analyzed. Results Median progression-free survival and overall survival were significantly shorter in patients with low absolute lymphocyte count (<1300/μl) versus those with high absolute lymphocyte count (progression-free survival: P = 0.0102; overall survival: P = 0.0026). Median overall survival was shorter in patients with high neutrophil–lymphocyte ratio (≥3.0) versus those with low neutrophil–lymphocyte ratio (P = 0.0344). Multivariate analysis showed that absolute lymphocyte count was an independent factor for progression-free survival (hazard ratio = 2.332, 95% confidence interval = 1.012–5.375, P = 0.0468) and overall survival (hazard ratio = 4.153, 95% confidence interval = 1.108–15.570, P = 0.0347). Increased absolute lymphocyte count, 1 month after nivolumab initiation, was a positive predictive factor for progression-free survival (hazard ratio = 0.419, 95% confidence interval = 0.189–0.926, P = 0.0317) and overall survival (hazard ratio = 0.285, 95% confidence interval = 0.091–0.890, P = 0.0308). Conclusion Our study indicates that peripheral absolute lymphocyte count, before nivolumab initiation, is a predictor of poor response in metastatic renal cell carcinoma. Additionally, increased absolute lymphocyte count, 1 month post-nivolumab initiation, can be a predictor of the effects of nivolumab.

Background Immune checkpoint inhibitors cause various immune-related adverse events. The present study examined the association between the incidence of immune-related adverse events and survival outcomes in patients treated with nivolumab plus ipilimumab for patients with advanced renal cell carcinoma. In addition, we compared the effect of adverse event profiles on survival for patients receiving nivolumab plus ipilimumab. Methods A total of 35 patients with advanced renal cell carcinoma who were treated with nivolumab plus ipilimumab from August 2018 to August 2021 were retrospectively reviewed and analyzed. Cox proportional hazards models were used for univariate and multivariate analyses, and hazard ratio and 95% confidence intervals were calculated. Results Of the 35 patients, 22 (62.9%) experienced immune-related adverse events. The median progression-free survival (P = 0.0012) and overall survival (P = 0.0147) were significantly longer in patients with immune-related adverse events than in those without immune-related adverse events. Multivariate analysis showed that the incidence of immune-related adverse events was an independent factor for progression-free survival (hazard ratio = 4.940, 95% confidence interval: 1.558–15.664, P = 0.0067). Skin reaction was a positive predictive immune-related adverse events for progression-free survival (hazard ratio = 9.322, 95% confidence interval: 1.954–44.475, P = 0.0051). Conclusion Patients with advanced renal cell carcinoma with immune-related adverse events had superior clinical outcomes of nivolumab plus ipilimumab treatment than those without immune-related adverse events. Skin immune-related adverse events may be effective biomarkers in patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab.

The smooth muscle contraction of the vas deferens has the important function of transporting sperm. Interstitial cells (ICs) play a critical role in the pacing and modulation of various smooth muscle organs by interactions with nerves and smooth muscle. Elucidating the three-dimensional (3D) architecture of ICs is important for understanding their spatial relationship on the mesoscale between ICs, smooth muscle cells (SMCs), and nerves. In this study, the 3D ultrastructure of ICs in the smooth muscle layer of murine vas deferens and the spatial relationships between ICs, nerves, and smooth muscles were observed using confocal laser scanning microscopy and focused ion beam/scanning electron microscopy. ICs have sheet-like structures as demonstrated by 3D observation using modern analytical techniques. Sheet-like ICs have two types of 3D structures, one flattened and the other curled. Multiple extracellular vesicle (EV)-like structures were frequently observed in ICs. Various spatial relations were observed in areas between ICs, nerves, and SMCs, which formed a complex 3D network with each other. These results suggest that ICs in the smooth muscle layer of murine vas deferens may have two subtypes with different sheet-like structures and may be involved in neuromuscular signal transmission via physical interaction and EVs.