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Background: Expression levels of voltage-dependent T-type calcium channel subunit alfa 1H (Cav3.2), big conductance calcium-activated potassium channel (BKCa), and anoctamin 1 in the skin, including in peripheral nerve endings were previously found to be significantly elevated in patients with chronic kidney disease (CKD)–associated pruritus (CKD-aP). On the other hand, the expression of transient receptor potential 1 was significantly reduced. Methods: We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative reverse transcriptional polymerase chain reaction (RT-PCR)to measure the skin expression levels of the following ion channels in the skin: voltage gated sodium channel 1.7 (Nav1.7), voltage gated potassium channel 7.2 (Kv7.2), TWIK-related K+ channel 1 (TREK1), hyperpolarization-activated cyclic nucleotide-gated channel type 2 (HCN2), tyrosine kinase receptor A (TrkA), and piezo-type mechano-sensitive ion channel component 2 (Piezo2). Results: RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. Conclusion: In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2. RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Introduction Chromophobe renal cell carcinoma presents in early pathological stages with a lower risk of metastasis. However, aggressive features and metastasis can occur. A rare case of rapidly progressive disease with histological changes is presented. Case presentation A 56-year-old woman had a right renal tumor with multiple lymph node metastases, and the pathological diagnosis of the biopsy specimens from the primary tumor was chromophobe renal cell carcinoma. After sunitinib treatment, the metastatic lymph node had decreased in size and the numbers of circulating tumor cells were decreased, consequently, cytoreductive nephrectomy was performed. However, rapid progression of lymph node metastases was observed. Histopathological examination showed that the renal tumor was diagnosed as spindle cell renal carcinoma. Conclusion It appears that the primary tumor underwent epithelial-mesenchymal transition; further tissue specimen collection and analysis might be needed.

Introduction Intraperitoneal urinary bladder perforation due to blunt trauma in intoxicated patients requires quick and accurate diagnosis. However, this is difficult to correctly diagnose in intoxicated patients because their symptoms can be masked. We describe a rare case of intraperitoneal urinary bladder perforation that occurred after blunt trauma. Case presentation A 66-year-old intoxicated man stumbled, tripped on a stone step and landed on his lower abdomen, but felt no pain at the time. Two days later, he was diagnosed with intraperitoneal urinary bladder perforation, which was repaired by open surgery. Conclusion Urinary bladder perforation should be considered when patients present with abdominal pain and decrease in urine volume following trauma.

// Kei Ishibashi 1, 2 , Tobias Haber 2 , Ines Breuksch 3 , Susanne Gebhard 3 , Takashi Sugino 4 , Hitoshi Kubo 5 , Junya Hata 1 , Tomoyuki Koguchi 1 , Michihiro Yabe 1 , Masao Kataoka 1 , Soichiro Ogawa 1 , Hiroyuki Hiraki 1 , Tomohiko Yanagida 1 , Nobuhiro Haga 1 , Joachim W. Thuroff 2 , Dirk Prawitt 6, * , Walburgis Brenner 2, 3, * and Yoshiyuki Kojima 1, * 1 Department of Urology, Fukushima Medical University, Fukushima, Japan 2 Department of Urology, Johannes Gutenberg University Medical Center, Mainz, Germany 3 Department of Gynecology and Obstetrics, Johannes Gutenberg University Medical Center, Mainz, Germany 4 Department of Pathology, Shizuoka Cancer Center, Shizuoka, Japan 5 Advanced Clinical Research Center, Fukushima Medical University, Fukushima, Japan 6 Center for Pediatrics and Adolescent Medicine, Johannes Gutenberg University Medical Center, Mainz, Germany * These authors contributed equally to this work Correspondence to: Walburgis Brenner, email: brenner@uni-mainz.de Kei Ishibashi, email: keikun@fmu.ac.jp Keywords: renal cell carcinoma, tyrosine kinase inhibitor, resistance, IL-6, tocilizumab Received: March 01, 2017 Accepted: July 12, 2017 Published: July 21, 2017 ABSTRACT Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens. Cell proliferation and signal transduction activity were then quantified after co-treatment with tocilizumab, an IL-6R inhibitor, in vitro and in vivo . 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. Using a mouse xenograft model we can show that a combination therapy with tocilizumab and low dosage of sorafenib suppresses 786-O tumor growth, reduces AKT-mTOR pathway and inhibits angiogenesis in vivo more efficient than sorafenib alone. Furthermore FDG-PET imaging detected early decrease of maximum standardized uptake values prior to extended central necrosis. Our findings suggest that a combination therapy of IL-6R inhibitors and TKIs may represent a novel therapeutic approach for RCC treatment.

To compare the postoperative tissue damage and longitudinal changes in functional and patient-reported outcomes after vesicourethral anastomosis with barbed suture and nonbarbed suture in robot-assisted laparoscopic radical prostatectomy (RARP). This was a prospective cohort study involving 88 consecutive patients who underwent RARP. These patients were categorized into the barbed suture group (n = 50) and the nonbarbed suture group (n = 38). Urethral and periurethral damages determined by magnetic resonance imaging at nine months after RARP were compared using generalized linear models. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, uroflowmetry, and the 1-h pad test were measured at baseline and at 1, 3, 6, 9, and 12 months after RARP. The findings were analyzed using mixed-effects models. Confounding was adjusted for using propensity score covariate adjustment. The likelihood of having Grade 2/3 urethral and periurethral damages was greater in the barbed suture group than in the nonbarbed suture group (adjusted risk ratios: 2.98 and 3.85, respectively). IPSS, QOL index, and urinary leakage transiently increased at one month after RARP in both groups. QOL index was higher in the barbed suture group than in the nonbarbed suture group at 1, 9, and 12 months (P = 0.023, P = 0.025, and P = 0.011, respectively). The barbed suture group had significantly more cases of urinary incontinence than the nonbarbed suture group at 3 months (P = 0.041). Other outcomes were comparable between the two groups at all time points. This cohort study showed that, after RARP, barbed sutures during VUA induced more severe tissue damage as determined by MRI and greater transient aggravation of QOL and continence function than nonbarbed sutures. The present findings suggest that using nonbarbed sutures during VUA may facilitate earlier acquisition of urinary QOL and urinary continence.

OBJECTIVES To assess whether atherosclerosis is involved in the development of overactive bladder and the function of lower urinary tract after robot-assisted radical prostatectomy. METHODS The present cohort consisted of 80 consecutive participants. The preoperative cardio-ankle vascular index was used to evaluate the presence of atherosclerosis. The present cohort was split into two groups, the atherosclerotic group, whose cardio-ankle vascular index was ≥9.0, and the control group, whose index was

Bypass pyeloplasty (BP) is a simple, non-dismembered procedure that is a side-to-side anastomosis without dividing the ureteropelvic junction (UPJ). BP has been considered more suitable especially for novice surgeons than dismembered pyeloplasty via the laparoscopic approach, but not reported. However, the disadvantage of laparoscopic BP is that it is difficult to suture the side of the anastomosis that is far from the camera. To overcome this disadvantage, a modified technique was developed. This procedure and its initial results are reported. Twenty-six consecutive patients underwent laparoscopic modified BP. The patients’ median age at surgery was 10.5 years. Ten patients were adults and 16 were children. The key step of modified BP involves dividing the UPJ after ureteral spatulation and suture of the dependent portion. This provides both better visualization of the anastomosis portion and easy anastomosis. All procedures were completed by laparoscopic modified BP. The median operative time was 246 (range 170–357) min. The median time for ureteropelvic anastomosis was 205 (range 145–311) min. There were no significant differences in mean operative time and ureteropelvic anastomotic time between adults and children (adults/children = 243 ± 49 min:252 ± 58 min, p = 0.66, 192 ± 33 min:214 ± 48 min, p = 0.21, respectively). Successful resolution of UPJO was observed in 96 % of cases. Laparoscopic modified BP combines the advantages of non-dismembered and dismembered pyeloplasty. Because there were no differences in mean operative and anastomotic times between adults and children, laparoscopic modified BP might be an efficient procedure for all ages, especially children.

The aim of the present study is to investigate the effect of pad use for postprostatectomy incontinence on urinary quality of life (QoL) after robot-assisted laparoscopic radical prostatectomy (RARP) in the early postoperative period.Ninety patients underwent RARP simultaneously completed International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and modified pad use questionnaire that evaluated pad use and urinary QoL and a 24-hour pad test. Pad use was also assessed by pad form, pad size, the number of pad exchanges per day, and the timing of pad exchanges (i.e., to what extent the pad was wet when the patients exchanged it.). The investigation involved patients visiting the outpatient clinic for the first time after RARP. The association between pad use and urinary QoL was investigated.The mean frequency of pad exchanges was 2±2/day. The mean 24-hour pad test was 139±193 g/day. Multivariate analyses revealed the timing of pad exchanges was significantly associated with QoL on the ICIQ-SF and the modified pad use questionnaire (P=0.007 and P0.001, respectively) and the number of pad exchanges per day was significantly associated with QoL on the ICIQ-SF (P=0.01); QoL worsened with pad wetness and increasing frequency of pad exchange. The other factors relating to pad use were not significantly associated with aggravation of QoL.In the early postoperative period after RARP, the timing of pad exchanges was the most important factor affecting QoL. Namely, patients with postprostatectomy incontinence should wear the appropriate size of pad according to the volume of urinary incontinence and exchange pads when the pad is not too wet. On the other hand, pad form, pad size, and volume of urinary incontinence were not associated with decreased QoL.

Aims The aim of the present study was to investigate whether atherosclerosis could be associated with lower urinary tract dysfunction in the early postoperative period after robot-assisted laparoscopic radical prostatectomy (RARP). Methods Eighty consecutive patients undergoing RARP were investigated. The severity of atherosclerosis was evaluated by the cardio-ankle vascular index (CAVI) before RARP. Patients were divided into two groups, the atherosclerotic group (CAVI ≥9.0) and the control group (CAVI

We report a rare case of giant prostatic hyperplasia treated by open surgery. A 70-year-old man was suffering from macrohematuria. Computed tomography revealed a markedly enlarged prostate measuring 580 mL. The serum prostate-specific antigen level was 9.430 ng/mL. Prostatic biopsy showed benign prostatic hyperplasia. We perfomed retropubic open prostatectomy, since macrohematuria continued and he was also suffering from lower urinary tract symptoms. The adenoma was completely enucleated in one piece. The removed specimen was 13 × 11 × 6 cm in size and weighed 475 g. Histological examination also demonstrated prostatic fibromuscular hyperplasia. This is the 15th-heaviest adenoma ever reported in English-language journals. Transurethral surgical techniques or other minimally invasive approaches are performed for patients with small to medium-sized prostates. However, open surgery is recommended for markedly enlarged prostatic hyperplasia.

Objectives To elucidate the effect of postoperative urinary incontinence on nocturia-related quality of life after robot-assisted radical prostatectomy. Methods A total of 100 consecutive patients who underwent robot-assisted radical prostatectomy completed a nocturia quality of life questionnaire score and a frequency-volume chart before and after surgery. These patients were divided into two groups by continence status (continent and incontinent) according to the number of pad exchanges per day and the 1-h pad test after surgery. Assessment was carried out before surgery, and then at 3 and 12 months after surgery. Results The Nocturia Quality of Life questionnaire total score and the Bother/Concern subscore were significantly lower in incontinent patients at 3 and 12 months after surgery (Nocturia Quality of Life questionnaire total score: Bother/Concern subscores P = 0.006: P = 0.04 at 3 months after surgery; and P = 0.04: P = 0.02 at 12 months). Both nocturnal maximum voided volume and nocturnal frequency were not significantly different between continent and incontinent patients. On multivariate analysis, nocturnal urinary frequency (P = 0.01) and urinary incontinence (P = 0.005) were significantly associated with nocturia-specific quality of life. Conclusions Although the number of nocturia episodes was not significantly different between the continent and incontinent patients after surgery, the Nocturia Quality of Life questionnaire score was significantly worse in incontinent patients. In these patients, other than the number of nocturia episodes, psychological stress might worsen the Nocturia Quality of Life questionnaire score. Therefore, prevention of post-prostatectomy incontinence might be important to avoid aggravating the Nocturia Quality of Life questionnaire score.

Objective To present a new grouping of male patients with lower urinary tract symptoms (LUTS) based on symptom patterns and clarify whether the therapeutic effect of α1-blocker differs among the groups. Methods We performed secondary analysis of anonymous data from 4815 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan. Data on 7 International Prostate Symptom Score (IPSS) items at the initial visit were used in the cluster analysis. IPSS and quality of life (QOL) scores before and after tamsulosin treatment for 12 weeks were assessed in each cluster. Partial correlation coefficients were also obtained for IPSS and QOL scores based on changes before and after treatment. Results Five symptom groups were identified by cluster analysis of IPSS. On their symptom profile, each cluster was labeled as minimal type (cluster 1), multiple severe type (cluster 2), weak stream type (cluster 3), storage type (cluster 4), and voiding type (cluster 5). Prevalence and the mean symptom score were significantly improved in almost all symptoms in all clusters by tamsulosin treatment. Nocturia and weak stream had the strongest effect on QOL in clusters 1, 2, and 4 and clusters 3 and 5, respectively. Conclusion The study clarified that 5 characteristic symptom patterns exist by cluster analysis of IPSS in male patients with LUTS. Tamsulosin improved various symptoms and QOL in each symptom group. The study reports many male patients with LUTS being satisfied with monotherapy using tamsulosin and suggests the usefulness of α1-blockers as a drug of first choice.

We investigated the effect of pelvic arterial occlusive disease on the RhoA/Rho-kinase pathway in a rat model of chronic bladder ischemia.Male adult Sprague Dawley® rats at age 16 weeks were divided into arterial endothelial injury and control groups. The injury group underwent balloon endothelial injury of the bilateral iliac arteries and received a 2% cholesterol diet to induce pelvic arterial occlusive disease. The control group received a regular diet. At 8 weeks cystometrograms were performed. Bladder tissue was harvested for pharmacological studies and Western blot.Cystometrograms showed significantly lower bladder capacity in the arterial endothelial injury group than in controls. Organ bath studies revealed significantly decreased phasic contractions induced by carbachol in bladder strips from the injury group than from controls. In controls bladder strip tonic contractions induced by carbachol were significantly decreased compared with phasic contractions. However, no significant difference was observed between phasic and tonic contractions in the injury group. The Rho-kinase inhibitor Y-27632 produced a concentration dependent decrease in tonic contractions, which was more pronounced in the injury group. Western blot showed significantly increased RhoA and Rho-kinase β expression in the injury group.Our results suggest that pelvic arterial occlusive disease can affect the RhoA/Rho-kinase pathway in the bladder. This pathway might possibly be involved in the maintenance of tonic contraction and contribute to the bladder hyperactivity caused by pelvic arterial occlusive disease.

Although open retropubic radical prostatectomy has been the most commonly used surgical technique for patients with localized prostate cancer for decades, robot-assisted radical prostatectomy (RARP) has recently become an alternative option and widely used in Japan as well as around the world. RARP has been shown to have higher postoperative continent rates than retropubic and laparoscopic radical prostatectomy; however, urinary incontinence has remained one of the most significant causes for concern among patients who seek surgical treatment for prostate cancer, even after the introduction of RARP. The literature has shown that certain technical modifications to improve urinary continence are advocated as potential aids to reduce the risk of urinary incontinence after RARP. These modifications might be divided into 3 categories to realize the improvement of early return of urinary continence after RARP: 1) preservation, 2) reconstruction, and 3) reinforcement of the anatomic structures in the pelvis, which will make a new supporting system after radical prostatectomy. In this review, we discuss the intraoperative techniques to improve outcomes for early return of urinary continence following RARP, and provide a critical summary of current knowledge on its outcome in the literature.

Objective To elucidate the etiology of lower urinary tract symptoms (LUTS) after radical prostatectomy, the present study investigated associations between postoperative urethral and vesical anatomic features on magnetic resonance imaging (MRI) and LUTS. Patients and Methods Fifty consecutive patients undergoing radical prostatectomy also underwent preoperative and postoperative MRI. Preoperative MRI only evaluated preoperative membranous urethral length (MUL). Postoperative MRI evaluated postoperative MUL, posterior-urethral vesical angle, depth of the urethrovesical junction (UVJ), and urinary pooling inside the urethra and bladder neck configuration. At the same time as postoperative MRI, International Prostate Symptom Score (IPSS), quality of life index, continence grade, and uroflowmetry parameters were investigated. Associations between preoperative or postoperative MRI variables and questionnaire results or uroflowmetry were analyzed to examine the relationships between the morphology of urethral and vesical anatomic features and LUTS. Results Preoperative and postoperative MRI variables were not significantly associated with IPSS total score or uroflowmetry results. Urinary pooling inside the urethra was significantly associated with urgency score in the IPSS ( P = .005). Postoperative MUL ( P P = .002), and urinary pooling inside the urethra ( P = .04) were significantly associated with continence grade. Conclusion Urinary pooling inside the urethra might induce urgency, and postoperative MUL and depth of UVJ were related to urinary incontinence. Avoiding damage to the nerves involved in continence to prevent inflow of urine into the urethra, preservation of MUL, and development of procedures to prevent descent of the bladder neck during surgery are therefore recommended.

Background The aim of the present study was to investigate the impact of the Great East Japan Earthquake on laboratory findings in chronic hemodialysis (HD) patients in Fukushima. Methods Changes in laboratory findings and cardiothoracic ratio (CTR) between before and after the earthquake were retrospectively analyzed in 90 adult HD patients with end-stage renal disease (ESRD). Two hospitals located within 80 km from the Fukushima Daiichi Nuclear Power Plant, where American government recommended to evacuate from the area, participated in the study. HD duration was shortened by 0.5-1 hour for 1 month after the earthquake. Multivariate analyses were performed to identify the factors contributing to change of measurement values. Results Blood urea nitrogen (BUN) value was significantly transiently decreased for 1-2 weeks after the earthquake (P=0.002). In multivariate analysis, age showed a tendency to be related to the decrease of BUN level (P=0.05). Hematocrit value was significantly elevated after two months compared with that at baseline (P=0.02), although the elevation was small. The other measured values and CTR were not significantly changed compared with those before the earthquake. Conclusions Laboratory findings and CTR did not worsen despite the shortening of HD duration. Hence, in this disaster, as far as chronic HD patients with ESRD were concerned, it was possible for the duration of HD treatment to be safely decreased.

Background When urine output increases, voided volume at each voiding also increases in normal subjects. This is generally understood as a vesical adaptation response to diuresis (VARD). Because lower urinary tract symptoms (LUTS) are supposed to be improved by the change in bladder function after robot-assisted laparoscopic radical prostatectomy (RARP), the aim of the present study was to investigate whether VARD is involved in the improvement of LUTS after RARP. Methods 100 consecutive patients who underwent RARP and had the International Prostate Symptom Score (IPSS), quality of life (QOL) index, a frequency-volume chart (FVC), uroflowmetry, and post-voided residual urine (PVR) available were evaluated before and after RARP. This cohort was divided into patients with and without preoperative LUTS according to the preoperative IPSS total score. VARD was defined as the presence of a significant correlation between the urine output rate and voided volume at each voiding (R2>0.2). Results In patients with preoperative LUTS, the IPSS total, storage, and voiding symptom scores were significantly improved after RARP (all P

Congenital partial absence of a fallopian tube has rarely been reported in the lit- erature. A 29-year-old nulligravida woman presented with a two-year history of infertility. Hysterosalpingography revealed an obstructed left fallopian tube with a normal uterine cavity and right fallopian tube. After several AIH treatments, diagnostic laparoscopy was per- formed, revealing segmental absence of the mid portion of the left fallopian tube. Only a 1-cm stump of the left fallopian tube remained, the majority of the isthmic portion was absent. A 3-cm distal ampullary portion with normal-appearing fimbria was attached to the left pelvic sidewall near the pelvic brim. No other abnormal findings were observed for the uterus, right fallopian tube, and ligaments surrounding the uterus. There are two possible etiologies of partial absence of the fallopian tube:congenital absence associated with developmental alterations of the Mullerian ducts or asymptomatic torsion followed by autoamputation and reabsorption.