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Yamamoto H.,King's College London | Yamamoto H.,Urology Center | Fara A.F.,King's College London | Dasgupta P.,King's College London | And 2 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2013

Complement is undeniably quintessential for innate immunity by detecting and eliminating infectious microorganisms. Recent work, however, highlights an equally profound impact of complement on the induction and regulation of a wide range of immune cells. In particular, the complement regulator CD46 emerges as a key sensor of immune activation and a vital modulator of adaptive immunity. In this review, we summarize the current knowledge of CD46-mediated signalling events and their functional consequences on immune-competent cells with a specific focus on those in CD4+ T cells. We will also discuss the promises and challenges that potential therapeutic modulation of CD46 may hold and pose. © 2013 Elsevier Ltd. All rights reserved.


Elhage O.,Urology Center | Elhage O.,King's College London | Challacombe B.,Urology Center | Shortland A.,Guys Hospital | And 2 more authors.
BJU International | Year: 2015

Objectives: To evaluate, in a simulated suturing task, individual surgeons' performance using three surgical approaches: open, laparoscopic and robot-assisted. Subjects and Methods: Six urological surgeons made an in vitro simulated vesico-urethral anastomosis. All surgeons performed the simulated suturing task using all three surgical approaches (open, laparoscopic and robot-assisted). The time taken to perform each task was recorded. Participants were evaluated for perceived discomfort using the self-reporting Borg scale. Errors made by surgeons were quantified by studying the video recording of the tasks. Anastomosis quality was quantified using scores for knot security, symmetry of suture, position of suture and apposition of anastomosis. Results: The time taken to complete the task by the laparoscopic approach was on average 221 s, compared with 55 s for the open approach and 116 s for the robot-assisted approach (anova, P < 0.005). The number of errors and the level of self-reported discomfort were highest for the laparoscopic approach (anova, P < 0.005). Limitations of the present study include the small sample size and variation in prior surgical experience of the participants. Conclusions: In an in vitro model of anastomosis surgery, robot-assisted surgery combines the accuracy of open surgery while causing lesser surgeon discomfort than laparoscopy and maintaining minimal access. © 2014 The Authors. BJU International © 2014 BJU International.


Khan M.S.,Urology Center | Elhage O.,Urology Center | Challacombe B.,Urology Center | Murphy D.,Urology Center | And 4 more authors.
European Urology | Year: 2013

Background: Long-term oncologic and functional outcomes after robot-assisted radical cystectomy (RARC) for bladder cancer (BCa) are lacking. Objective: To report oncologic and functional outcomes in a cohort of patients who have completed a minimum of 5 yr and a maximum of 8 yr of follow-up after RARC and extracorporeal urinary diversion. Design, setting, and participants: In this paper, we report on the experience from one of the first European urology centres to introduce RARC. Only patients between 2004 and 2006 were included to ensure follow-up of ≥5 yr. We report on an analysis of oncologic outcomes in 14 patients (11 males and 3 females) with muscle-invasive/high-grade non-muscle-invasive or bacillus Calmette-Guérin-refractory carcinoma in situ who opted to have RARC. Intervention: RARC with pelvic lymphadenectomy was performed using the three-arm standard da Vinci Surgical System (Intuitive Surgical, CA, USA). Urinary diversion, either ileal conduit (n = 12) or orthotopic neobladder (n = 2), was constructed extracorporeally. Outcome measurements: Parameters were recorded in a prospectively maintained database including assessment of renal function, overall survival, disease-specific survival, development of metastases, and functional outcomes. Statistical analysis: Results were analysed using descriptive statistical analysis. Survival data were analysed and presented using the Kaplan-Meier survival curve. Results and limitations: Five of the 14 patients have died. Three patients died of metastatic disease, and two died of unrelated causes. Two other patients are alive with metastases, and another has developed primary lung cancer. Six patients are alive and disease-free. These results show overall survival of 64%, disease-specific survival of 75%, and disease-free survival of 50%. None of the patients had deterioration of renal function necessitating renal replacement therapy. Three of four previously potent patients having nerve-sparing RARC recovered erectile function. The study is limited by the relatively small number of highly selected patients undergoing RARC, which was a novel technique 8 yr ago. The standard da Vinci Surgical System made extended lymphadenectomy difficult. Conclusions: Within limitations, in our experience RARC achieved excellent control of local disease, but the outcomes in patients with metastatic disease seem to be equivalent to the outcomes of open radical cystectomy. © 2013 European Association of Urology.


Chin P.T.,Wollongong Hospital | Bolton D.M.,Austin Hospital | Jack G.,Austin Hospital | Rashid P.,Urology Center | And 4 more authors.
Urology | Year: 2012

To evaluate the effectiveness of the prostatic urethral lift in relieving lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. A total of 64 men, aged >55 years, with moderate to severe symptomatic benign prostatic hyperplasia were treated and followed up at 6 Australian institutions. The treatment consisted of transurethral delivery of small implants to secure the prostatic lobes in an open condition, thereby reducing obstruction of the urethral lumen. The effectiveness, including International Prostate Symptom Score, quality of life, benign prostatic hyperplasia Impact Index, and peak urethral flow rate were assessed at 2 weeks and 3, 6, 12, and 24 months. The effect of this treatment on erectile and ejaculatory function was assessed using the Sexual Health Inventory for Men and Male Sexual Health Questionnaire for Ejaculatory Dysfunction. The prostatic urethral lift improved LUTS symptoms rapidly and durably. The International Prostate Symptom Score was reduced 42% at 2 weeks, 49% at 6 months, and 42% at 2 years in evaluable patients. The peak flow rate improved by >30% (2.4 mL/s) at all intervals compared with baseline. No compromise in sexual function was observed after this treatment. The present study demonstrated that LUTS and flow improvements without compromising sexual function. Although this was an early study with a small cohort, this therapy shows promise as a new option for patients with LUTS. © 2012 Elsevier Inc.


Woo H.H.,University of Sydney | Bolton D.M.,Austin Hospital | Laborde E.,Ochsner Medical Center | Jack G.,Austin Hospital | And 4 more authors.
Journal of Sexual Medicine | Year: 2012

Introduction. We investigated the prostatic urethral lift, a novel, minimally invasive treatment for symptomatic lower urinary tract complaints presumed to be from benign prostatic hyperplasia (BPH), which aims to mechanically open the prostatic urethra without ablation or resection. We hypothesized that this novel approach would not degrade erectile or ejaculatory function. Aims. We sought to determine the effect of the prostatic urethral lift procedure on erectile and ejaculatory function. Methods. The procedure was performed on 64 men in Australia with an average age of 66.9years and an average duration of lower urinary tract symptom (LUTS) of 4.7years. Primary inclusion criteria included International Prostate Symptom Score (IPSS)>13, Qmax of 5-12mL/second, and prostate specific antigen (PSA)<10ng/mL. Baseline IPSS was 22.9±5.4 (N=64). There were no inclusion criteria for sexual function. Baseline Sexual Health Inventory for Men (SHIM) was 11.7±8.6 (N=58); baseline Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) function score was 9.0±3.7 (N=46); and lack of sexual activity or unwillingness to answer sexual function questionnaires accounted for the reduced sample size in the sexual function instruments. Implants were placed to separate encroaching lateral prostatic lobes. Main Outcome Measures. Patients were evaluated at 6weeks and 3, 6, and 12months postprocedure via the SHIM and MSHQ-EjD instruments. Results. There was no evidence of degradation in sexual function after treatment for LUTS with the prostatic urethral lift procedure. Erectile function, as measured by SHIM, was slightly increased at all time points as compared with baseline. No patient reported retrograde ejaculation at any follow-up visit. Conclusions. We demonstrated significant improvement in LUTS with no evidence of degradation in erectile or ejaculatory function after treatment with the prostatic urethral lift procedure. This procedure warrants further study as a new option for patients underserved by current treatments for LUTS/BPH. © 2011 International Society for Sexual Medicine.


Challacombe B.J.,Urology Center | Bochner B.H.,Sloan Kettering Cancer Center | Dasgupta P.,Guys Hospital | Gill I.,University of Southern California | And 6 more authors.
European Urology | Year: 2011

Context: Minimally invasive radical cystectomy (MIRC) techniques for the treatment of muscle-invasive bladder cancer (BCa) are being increasingly applied. MIRC offers the potential benefits of a minimally invasive approach in terms of reduced blood loss and analgesic requirements whilst striving to provide similar oncologic efficacy to open radical cystectomy (ORC). Whether quicker recovery, shorter hospital stay, and a reduction in complications are routinely achieved with MIRC remains to be proved in prospective comparisons. Objective: To explore both laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RRC), focusing specifically on the oncologic parameters and comorbidity of the procedures. Reported complications from major centres are identified and categorised via the Clavien system. Positive margins rates, local recurrence, and both cancer-specific survival (CSS) and overall survival rates are assessed. Evidence acquisition: A comprehensive electronic literature search was conducted in November 2010 using the Medline database to identify publications relating to laparoscopic, robotic, or minimally invasive radical cystectomy. Evidence synthesis: There are encouraging short- to medium-term results for both LRC and RRC in terms of postoperative morbidity and oncologic outcomes. It seems possible in experienced hands to perform a satisfactory minimally invasive lymphadenectomy regarding lymph node counts and levels of dissection. Positive soft-tissue margins are similar to large open series for T2/T3 disease but inferior for bulky T4 disease. Local recurrence rates and CSS rates seem equivalent to ORC at up to 3 yr of follow-up; however, mature outcome data still need to be presented before definitive comparisons can be made. Conclusions: Robotic and laparoscopic cystectomy has a growing role in the management of muscle-invasive BCa. Long-term oncologic results are awaited, and there are concerns over the ability of MIRC to treat bulky and locally advanced disease, making careful patient selection vital. Forthcoming randomised trials in this area will more fully address these issues. © 2011 European Association of Urology.


Burger M.,University of Würzburg | Betz D.,Urology Center | Hampel C.,Johannes Gutenberg University Mainz | Vogel M.,Astellas Pharma GmbH
World Journal of Urology | Year: 2014

Purpose: To evaluate the efficacy and safety of solifenacin for the treatment of OAB in men. Methods: This prospective observational study, reflective of actual practice patterns, was conducted in men older than 18 years who were prescribed solifenacin for the treatment of OAB symptoms. Men with suspected bladder outlet obstruction were excluded. The primary efficacy measure was change in OAB symptoms after 12 weeks of solifenacin. Also assessed were changes in severity of urinary urgency, IPSS, quality of life, cognitive function, and adverse events. Data were analyzed using descriptive methods. Results: A total of 799 men recruited at 251 centers, average age 67 years (range 27-92), received solifenacin 5 mg or 10 mg/day. Mean episodes of urinary urgency, frequency, and nocturia decreased by 4.4, 3.6, and 1.4 episodes/24 h, respectively. As per IPSS, severe urinary symptoms were reported by 20.4 % at baseline versus by 2.3 % at week 12. Both voiding and storage symptoms showed improvement. Patient-reported general health condition was excellent/good for 39 % at baseline increasing to 76 % at week 12. Adverse event rate was 5.5 %, and discontinuation of solifenacin due to an event was 1.6 %. No change in post-void residual urine volume was experienced in 80%, while an increase of ≥50 mL was observed in 2.2 %; no cases of acute urinary retention occurred. Baseline mean MMSE was 27.5 points versus 27.9 points at week 12. Conclusions: Solifenacin reduced all OAB symptoms, was well tolerated, and had no apparent effect on post-void residual urine volume. Cognitive function was unaltered in this population of older men with OAB. © 2013 Springer-Verlag Berlin Heidelberg.


Fleure L.,Urology Center
International Journal of Urological Nursing | Year: 2015

Long-term androgen deprivation therapy (ADT) for advanced prostate cancer can result in significant and distressing side effects and longer-term adverse metabolic effects. A seminar-based service improvement initiative was developed to provide information and strategies to understand ADT, to manage side effects and to provide lifestyle advice regarding cardiovascular and bone issues. The seminars were evaluated with patient questionnaires and were positively received. This approach has proven to be a valuable tool in the care of this patient group. © 2014 John Wiley & Sons Ltd. and BAUN.


Raison N.,Urology Center | Khan M.S.,Urology Center | Challacombe B.,Urology Center
Current Urology Reports | Year: 2015

Since the first telegraphic transmission of an electrocardiogram in 1906, technological developments have allowed telemedicine to flourish. It has become a multi-billion pound industry encompassing many areas of medical practice and education. Telemedicine is now widely used in surgery from performing operations to teaching and can be divided into three main components; telesurgery, telementoring and teleconsultation. Developments across these fields have led to remarkable achievements such as intercontinental telesurgery and telementoring. However, barriers to the further implementation of telemedicine remain. In this review, the developments and recent advances of telemedicine across the three domains are discussed together with the challenges and limitations that need to be overcome. © 2015, Springer Science+Business Media New York.


Wong K.A.,Urology Center | Mein R.,Guys Hospital | Wass M.,University of Kent | Flinter F.,Guys Hospital | And 3 more authors.
BJU International | Year: 2015

Objective To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation. Patients and Methods DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK. Patients with type A cystinuria were classified into two groups: Group M patients had at least one missense mutation and Group N patients had two alleles of all other types of mutations including frameshift, splice site, nonsense, deletions and duplications. The levels of urinary dibasic amino acids, age at presentation of disease, number of stone episodes and interventions were compared between patients in the two groups using the Mann-Whitney U-test. Results In all, 41 patients had type A cystinuria, including one patient with a variant of unknown significance and 23 patients had type B cystinuria, including six patients with variants of unknown significance. One patient had three sequence variants in SLC7A9; however, two are of unknown significance. Three patients had type AB cystinuria. Three had a single mutation in SLC7A9. No identified mutations were found in three patients in either gene. There were a total of 88 mutations in SLC3A1 and 55 mutations in SLC7A9. There were 23 pathogenic mutations identified in our UK cohort of patients not previously published. In patients with type A cystinuria, the presence of a missense mutation correlated to lower levels of urinary lysine (mean [se] 611.9 [22.65] vs 752.3 [46.39] millimoles per mole of creatinine [mm/MC]; P=0.02), arginine (194.8 [24.83] vs 397.7 [15.32] mm/MC; P<0.001) and ornithine (109.2 [7.40] vs 146.6 [12.7] mm/MC; P=0.02). There was no difference in the levels of urinary cystine (182.1 [8.89] vs 207.2 [19.23] mm/MC; P=0.23). Conclusions We have characterised the genetic diversity of cystinuria in a UK population including 23 pathogenic mutations not previously published. Patients with at least one missense mutation in SLC3A1 had significantly lower levels of lysine, arginine, and ornithine but not cystine than patients with all other combinations of mutations. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

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