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Journal Cover BJU International
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   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1464-4096 - ISSN (Online) 1464-410X
   Published by John Wiley and Sons Homepage  [1598 journals]
  • Preliminary experience using a tunica vaginalis flap as the dorsal
           component of Bracka's urethroplasty
    • Authors: L. Harper; JL Michel, F Sauvat
      Abstract: Purpose To evaluate clinical use of tunica vaginalis flap as the dorsal component of a two‐stage urethroplasty in boys with cripple hypospadias. Patients and Method We performed the first stage of a Bracka two‐stage urethroplasty, using a tunica vaginalis flap as the dorsal component in 6 boys with cripple hypospadias. We analyzed their clinical characteristics and the results of this technique. Results The average age of the patients was 4 years and 9 months (range: 34‐120 months). The average number of previous procedures the children had undergone was 4 (range: 3‐5). At 6 months follow‐up, all children presented significant fibrosis of the dorsal graft rendering it unusable for tubularization. Conclusions Exposure to the external environment seems to induce retraction and fibrosis of the tunica vaginalis. We believe one should be very cautious about using tunica vaginalis as the dorsal component of a two‐stage urethroplasty, as significant fibrosis might well render the flap unusable. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-26T09:15:27.77803-05:0
      DOI: 10.1111/bju.13604
  • Accuracy of ultrasound for renal stone detection and size determination:
           is it good enough for management decisions?
    • Authors: V Ganesan; S De, D Greene, FCM Torricelli, M Monga
      Abstract: Objectives To determine the sensitivity and specificity of ultrasound (US) for detecting renal calculi and to assess the accuracy of US for determining size of calculi and how this can affect counselling decisions. Materials and methods We retrospectively identified all patients at our institution with a diagnosis of nephrolithiasis who had an US followed by a non‐contrast computed tomographic (CT) within 60‐days. Patient characteristics, stone size (maximum axial diameter), and stone location was collected. Sensitivity, specificity, and size accuracy of ultrasound was determined using CT as the standard. Results A total of 552 US and CT examinations met the inclusion criteria. Overall the sensitivity and specificity of US was 54% and 91% respectively. There was a significant association between sensitivity of US and stone size (p < 0.001) but not with stone location (p = 0.58). US significantly overestimated the size of stones in the 0‐10 mm range (p < 0.001). Assuming stones 0 mm – 4 mm will be observed and stones ≥5 mm could be counselled on the alternative of intervention, we found that in 14% (54/384) of cases where CT would suggest observation, US would recommend an intervention. On the other hand, when using CT would suggest an intervention, US would suggest observation in 39% (65/168) of cases. On average 22% (119/552) of patients could be inappropriately counselled. Stones classified as 5‐10 mm by US had the highest probability, 43% (41/96), of having recommendation changed when a CT was performed. The use of KUB and US increases sensitivity (78%) but still 37% (13/35) of patients may inappropriately be counselled to undergo observation. Conclusions Using US to guide clinical decision making for residual or asymptomatic calculi is limited by low sensitivity and inability to accurately size the stone. As a result, 1 in 5 patients may be inappropriately counselled when using US alone. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-26T09:10:27.045077-05:
      DOI: 10.1111/bju.13605
  • Active surveillance is suitable for intermediate term follow‐up of
           renal oncocytoma diagnosed by percutaneous core biopsy
    • Authors: Shuo Liu; Stephen Lee, Prem Rashid, Haider Bangash, Akhlil Hamid, Jason Lau, Ronald Cohen
      Abstract: Objectives To evaluate the intermediate outcome of conservative management in patients with biopsy‐proven oncocytoma. Patients and Methods Patients with oncocytoma diagnosed on percutaneous core biopsy between January 2000 to December 2014 were identified from the renal biopsy database of a large specialist urologic pathology laboratory. After review of patient clinical records, the study cohort comprised only of patients enrolled in active surveillance. Clinicopathological and follow‐up details were reviewed for each case, in particular: type and interval of surveillance imaging, tumour growth, definitive intervention and reason for intervention. Where possible, correlation was made between the final surgical and the initial biopsy specimens. Results Fifty three patients diagnosed with oncocytoma on core biopsy were initially placed on active surveillance with median follow‐up of 34 months (range 6–109). The median age at diagnosis was 65 years (range 20–85) and median tumour size was 30 mm (range 13–87). Mean average tumour growth was 1.4 mm per annum (median 0 mm/year) with the majority (36 of 53, 68%) exhibiting minimal growth (less than 2 mm per annum) or partial regression. Forty seven of the 53 patients remained on active surveillance with no significant progression. Six patients elected to undergo definitive intervention (five surgical excision, one ablation). Renal oncocytoma was confirmed in all five patients who underwent surgical excision of their lesions. Conclusions The majority of oncocytomas in this study showed minimal growth rate or regression. Patients with biopsy proven oncocytoma can be conservatively managed with active surveillance.
      PubDate: 2016-07-26T01:22:04.519225-05:
      DOI: 10.1111/bju.13538
  • The Impact Of United States Preventive Services Task Force (USPTSTF)
           Recommendations Against PSA Testing On PSA Testing In Australia
    • Authors: Homayoun Zargar; Roderick den Bergh, Daniel Moon, Nathan Lawrentschuk, Anthony Costello, Declan Murphy
      Abstract: Objective To assess the impact of USPTSTF recommendations on PSA testing, prostate biopsy and prostatectomy in Australian men based on the available Medicare data. Patients and Methods Events were identified using Medicare item numbers for PSA (66655,66659), prostate biopsy (37219), prostatectomy (37210) and prostatectomy with lymph node dissection (37211) The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000‐2015. For each item number reports were also generated for all Australian states. For PSA testing the data was stratified for the three age groups of 45‐54, 55‐64 and 65‐74 years old. For assessment of the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were summed up. Results Steady declines in per capita incidences of all five item numbers assessed were observed for the three consecutive financial years (2013‐2015) since the publication of USPTSTF recommendation statement. These declines were observed across all Australian states. When examining the rate of PSA testing for the three age brackets 45‐54, 55‐64 and 65‐74 years old similar trends were identified Conclusions Since the introduction of USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over diagnosis and over treatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-25T11:30:35.752465-05:
      DOI: 10.1111/bju.13602
  • The potential role of unregulated autonomous bladder micromotions in
           urinary storage and voiding dysfunction; overactive bladder and detrusor
    • Authors: M.J. Drake; A. Kanai, D.A. Bijos, Y. Ikeda, I. Zabbarova, B. Vahabi, C.H. Fry
      Abstract: The isolated bladder shows autonomous micromotions, which increase with bladder distension, generate sensory nerve activity, and are altered in models of urinary dysfunction. Intravesical pressure resulting from autonomous activity putatively reflects three key variables; the extent of micromotion initiation, distances over which micromotions propagate, and overall bladder tone. In vivo, these variables are subordinate to the efferent drive of the central nervous system. In the micturition cycle storage phase, efferent inhibition keeps autonomous activity generally at a low level, where it may signal “state of fullness” while maintaining compliance. In the voiding phase, mass efferent excitation elicits generalized contraction (global motility initiation). In lower urinary tract dysfunction, efferent control of the bladder can be impaired, for example due to peripheral “patchy” denervation. In this case, loss of efferent inhibition may enable unregulated micromotility, and afferent stimulation, predisposing to urinary urgency. If denervation is relatively slight, the detrimental impact on voiding may be low, as the adjacent innervated areas may be able to initiate micromotility synchronous with the efferent nerve drive, so that even denervated areas can contribute to the voiding contraction. This would become increasingly inefficient the more severe the denervation, such that ability of triggered micromotility to propagate sufficiently to engage the denervated areas in voiding declines, so the voiding contraction increasingly develops the characteristics of underactivity. In summary, reduced peripheral coverage by the dual efferent innervation (inhibitory and excitatory) impairs regulation of micromotility initiation and propagation, potentially allowing emergence of overactive bladder and, with progression, detrusor underactivity. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-22T07:15:22.320644-05:
      DOI: 10.1111/bju.13598
  • Comparative testing of reliability and audit utility of ordinal objective
           calculus complexity scores. Can we make an informed choice yet'
    • Authors: Jiten Jaipuria; Manav Suryavanshi, Tridib K. Sen
      Abstract: Objectives To assess reliability of Guy's, Seoul National University renal stone (S‐RESC) and S.T.O.N.E. scores in percutaneous nephrolithotomy (PCNL) and assess utility in discriminating outcomes [Stone free rate (SFR), complications, need for multiple PCNL sessions and auxiliary procedures] valid across parameters of experience of surgeon, independence from surgical approach, and variations in institution‐specific instrumentation. Patients and methods Prospectively maintained database of 2 tertiary institutions was analysed (606 cases). Institutes differed in instrumentation while overall surgical team comprised – two trainees (experience 1000 cases). Scores were assigned and reassigned after 4 months by one trainee and expert surgeon. Interrater and test‐retest agreement were analysed by Cohen's kappa and Intraclass correlation coefficient. Multivariate logistic regression models were created adjusting outcomes for the institution, comorbidity, amplatz size, access tract location, the number of punctures, the experience level of the surgeon, and individual scoring system, and receiver operating curves were analysed for comparison. Results Despite some areas of inconsistencies, individually all scores had excellent interrater and test‐retest concordance. On multivariable analyses while the experience of the surgeon and surgical approach characteristics (such as access tract location, amplatz size, and number of punctures) remained independently associated with different outcomes in varying combinations, calculus complexity scores were found consistently independently associated with all outcomes. S‐RESC score had a superior association with SFR, the need for multiple PCNL sessions and auxiliary procedures. Conclusion Individually all scoring systems performed well. On cross comparison, S‐RESC score consistently emerged more superiorly associated with all outcomes signifying the importance of the distributional complexity of calculus (which also indirectly amalgamates influence of stone number, size, and anatomic location) in discriminating outcomes. Our study proves the utility of scores in prognosticating multiple outcomes and also clarifies important aspects of their practical application including future roles such as benchmarking, audit, training and objective assessment of surgical technique modifications. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-22T06:55:43.623573-05:
      DOI: 10.1111/bju.13597
  • Randomized controlled study of the efficacy and safety of continuous
           saline bladder irrigation after transurethral resection for the treatment
           of non‐muscle invasive bladder cancer
    • Authors: Takehisa Onishi; Yusuke Sugino, Takuji Shibahara, Satoru Masui, Tadashi Yabana, Takeshi Sasaki
      Abstract: Objective To evaluate the efficacy and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumor (TURBT) in patients with low‐ to intermediate‐risk non‐muscle invasive bladder cancer (NMIBC). Patients and methods In this prospective randomized study, 250 patients with primary low‐to intermediate‐risk tumors were enrolled. Patients were randomly allocated to receive CSBI (2,000 ml/h for first 1 hour, then 1,000 ml/h for 2 hours, and then 500 ml/h for 15 hours) or a single immediate instillation of mitomycin C (MMC) after TURBT. Primary end point was recurrence‐free survival, and secondary end points were progression‐free survival and adverse events. Results A total of 227 patients (114 in CSBI group and 113 in MMC group) remained for analysis after exclusion. The median follow‐up period was 37 months. No significant differences for patients’ characteristics were observed between the groups. Five‐year recurrence‐free rates for CSBI and MMC were 62.6% (95% confidence interval [CI]: 0.49‐0.73) and 70.4% (95% CI: 0.59‐0.78), respectively. Kaplan‐Meire analysis of recurrence‐free survival did not show any significant differences between the groups (log rank test: P = 0.53). Furthermore, there were no significant differences between the groups in terms of tumor progression rate and the median time to first recurrence. The incidence of adverse events was significantly lower in CSBI group. Conclusions CSBI after TURBT may be a treatment option for patients with low‐ to intermediate –risk NMIBC in terms of its prophylactic effect and safety. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-22T06:55:33.361119-05:
      DOI: 10.1111/bju.13599
  • The use of portable video media (PVM) versus standard verbal communication
           (SVC) in the urological consent process: a multicentre, randomised
           controlled, crossover trial
    • Abstract: Background Informed consent is a crucial component of patient care. Portable video media is an emerging technology which may help improve the consent process. Objectives To determine if portable video media (PVM) improves patient's knowledge and satisfaction acquired during the consent process for cystoscopy and insertion of a ureteric stent compared to standard verbal communication (SVC). Design, Participants and Methods Multi‐centre randomised controlled crossover trial. Patients requiring cystoscopy and stent insertion were recruited from two major teaching hospitals in Australia over a 15‐month period (July 2014 – December 2015). Information delivery via PVM and SVC. PVM consisted of an audio‐visual presentation with cartoon animation presented on an iPad. Patient satisfaction was assessed using the validated Client Satisfaction Questionnaire‐8 (max score 32) and knowledge was tested using a true/false questionnaire (max score 28). Questionnaires were tested after first intervention and after crossover. Scores were analysed using independent samples t‐test and Wilcoxon signed‐rank test for crossover analysis. Results Eighty‐eight patients were recruited. A significant 3·1 point (15·5%) increase in understanding was demonstrable favouring the use of PVM (p
      PubDate: 2016-07-21T02:31:50.693417-05:
      DOI: 10.1111/bju.13595
  • The ProCare Trial: a phase II randomised controlled trial of shared care
           for follow‐up of men with prostate cancer
    • Authors: Jon D Emery; Michael Jefford, Madeleine King, Dickon Hayne, Andrew Martin, Juanita Doorey, Amelia Hyatt, Emily Habgood, Tee Lim, Cynthia Hawks, Marie Pirotta, Lyndal Trevena, Penelope Schofield
      Abstract: Objectives To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer. Patients and Methods Men who had completed treatment for low to moderate risk prostate cancer within the previous eight weeks were eligible. Participants were randomised to usual care or shared care. Shared care entailed substituting two hospital visits with three visits in primary care, a survivorship care plan, recall and reminders, and screening for distress and unmet needs. Outcome measures included psychological distress, prostate cancer‐specific quality of life (PCSQoL), satisfaction and preferences for care and health care resource use. Results 88 men were randomised (Shared Care n=45; Usual Care n=43). There were no clinically important or statistically significant differences between groups on distress, PCSQoL, or satisfaction with care. At the end of the trial men in the intervention group were significantly more likely to prefer a shared care model to hospital follow‐up than those in the control group Intervention 63% vs Control 24% p=0.0007). There was high compliance with PSA monitoring in both groups. The shared care model was cheaper than usual care (Shared care AUS$1,411; Usual Care AUS$1,728; difference AUS$323 (plausible range AUS$91‐554)). Conclusion Well‐structured shared care for men with low to moderate risk prostate cancer is feasible and appears to produce clinically comparable outcomes to standard care at lower cost. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-19T01:35:29.712123-05:
      DOI: 10.1111/bju.13593
  • Routinely reported ‘equivocal’ lymphovascular invasion in
           prostatectomy specimens is associated with adverse outcomes
    • Authors: Elena Galiabovitch; Christopher M. Hovens, Justin S. Peters, Anthony J. Costello, Shane Battye, Sam Norden, Andrew Ryan, Niall M. Corcoran
      Abstract: Objective To evaluate the significance of routinely reported ‘equivocal’ lymphovascular invasion in prostatectomy specimens of patients with clinically localised prostate cancer. Materials and Methods Prospectively collected data from men who underwent prostatectomy for clinically localised prostate cancer were retrospectively reviewed. Rates of adverse pathological features and biochemical recurrence were compared between tumours positive, negative or ‘equivocal’ for lymphovascular invasion. Multivariable Cox regression analysis was performed to identify independent predictors of biochemical recurrence. Results In 1310 consecutive cases, lymphovascular invasion was present definitively in 82 (6.3%) and equivocally in 43 (3.3%). Similar to definitive lymphovascular invasion, ‘equivocal’ lymphovascular invasion was significantly associated with other adverse pathological features, including advanced stage, higher Gleason grade, and surgical margin positivity. Biochemical recurrence occurred more frequently in patients with tumours ‘equivocal’ (61%) or positive for lymphovascular invasion (71%) than in negative patients (14.7%). In addition, patients with both definitive and equivocal lymphovascular invasion had a significantly shorter biochemical recurrence‐free survival compared to negative patients. Multivariable Cox regression analysis indicated that the presence of either definitive or ‘equivocal’ lymphovascular invasion were independent predictors of disease recurrence (HR 3.32, 95%CIs 2.3‐4.8, p
      PubDate: 2016-07-19T01:35:27.28618-05:0
      DOI: 10.1111/bju.13594
  • Comparison of spinal cord contusion and transection: functional and
           histological changes in the rat urinary bladder
    • Authors: Benjamin N. Breyer; Thomas M. Fandel, Amjad Alwaal, E. Charles Osterberg, Alan W. Shindel, Guiting Lin, Emil A. Tanagho, Tom F. Lue
      Abstract: Objective To compare the effect of complete transection (tSCI) and contusion injury (cSCI) on bladder function and bladder wall structure in rats. Materials and Methods 30 female Sprague‐Dawley rats were randomly divided into three equal groups: uninjured controls, cSCI, and tSCI. The cSCI group underwent spinal cord contusion, while the tSCI group underwent complete spinal cord transection. 24‐hour metabolic cage measurement and conscious cystometry were performed at 6 weeks post‐injury. Results Conscious cystometry analysis showed that cSCI and tSCI groups had significantly larger bladder capacities than the control group. The cSCI group had significantly more non‐voiding detrusor contractions than the tSCI group. Both injury groups displayed more non‐voiding contractions compared to the control group. Mean threshold pressure was significantly higher in the tSCI group than in control and cSCI groups. The number of voids in the tSCI group was less compared to the control group. Metabolic cage analysis showed that the tSCI group had larger maximum voiding volume as compared to control and cSCI. VAChT/smooth muscle immunoreactivity was higher in control than in cSCI or tSCI rats. The area of calcitonin gene‐related peptide (CGRP) staining was lower in tSCI as compared to control or cSCI. Conclusions Spinal cord transection and contusion produce different bladder phenotypes in rat models of SCI. Functional data suggest that the tSCI group has obstructive high‐pressure voiding pattern, while the cSCI group has more uninhibited detrusor contractions. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-19T01:31:07.895521-05:
      DOI: 10.1111/bju.13591
  • ICUD‐EAU International Consultation on Minimally Invasive Surgery in
           Urology: Laparoscopic and Robotic Adrenalectomy
    • Authors: Mark W. Ball; Ashok K. Hemal, Mohamad E. Allaf
      Abstract: Objective To provide an evidence‐based systematic review of the use of laparoscopic and robotic adrenalectomy in the treatment of adrenal disease as part of the International Consultation on Urologic Diseases and European Association of Urology consultation on Minimally Invasive Surgery in Urology. Methods A systematic literature search (January 204‐January 2014) was conducted to identify comparative studies assessing the safety and efficacy of minimally invasive adrenal surgery. Subtopics including the role of minimally invasive surgery for pheochromocytoma, adrenocortical carcinoma, and large adrenal tumors were examined. Additionally, the role of transperitoneal and retroperitoneal approaches, as well as laparoendoscopic single‐site (LESS) and robotic adrenalectomy were reviewed. Result The major findings are presented in an evidence‐based fashion. Large retrospective and prospective data were analyzed. A set of recommendations provided by the committee was produced. Conclusions Laparoscopic surgery should be considered first line therapy for benign adrenal masses requiring surgical resection. Laparoscopic surgery should be considered first line therapy for patients with pheochromocytoma. While a laparoscopic approach may be feasible for select cases of ACC without adjacent organ involvement, an open surgical approach remains the gold standard. Large adrenal tumors without preoperative or intraoperative concern for ACC may be safely resected via a laparoscopic approach. Both transperitoneal and retroperitoneal approaches to laparoscopic adrenalectomy is safe. The approach should be chosen based on surgeon training and experience. LESS adrenalectomy should be considered an an alternative to laparoscopic adrenalectomy but requires further study. Robotic adrenalectomy may be considered an alternative to laparoscopic adrenalectomy but requires further study . This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-19T01:31:01.933677-05:
      DOI: 10.1111/bju.13592
  • Liquid biopsy: ready to guide therapy in advanced prostate cancer?
    • Abstract: The identification of molecular markers associated with response to specific therapy is a key step for the implementation of personalized treatment strategies in patients with metastatic prostate cancer (PC). Only in a low proportion of patients, biopsies of metastatic tissue are performed. Circulating tumor cells (CTC), cell free‐DNA (cfDNA) and RNA offer the potential for non‐invasive characterization of disease and molecular stratification of patients. Furthermore, a “liquid biopsy” approach permits longitudinal assessments, allowing sequential monitoring of response and progression and the potential to alter therapy based on observed molecular changes. In PC, CTC enumeration using the CellSearch© platform correlates with survival. Recent studies on the presence of androgen receptor variants in CTC have shown that the such molecular characterization of CTC provides a potential for identifying patients with resistance to agents that inhibit the androgen signaling axis, such as abiraterone and enzalutamide. New developments in CTC isolation, as well as in‐vitro and in‐vivo analysis of CTC will further promote the use of CTC as a tool for retrieving molecular information from advanced tumors in order to identify mechanisms of therapy resistance. In addition to CTC, nucleic acids such as RNA and cell free DNA (cfDNA) released by tumor cells into the peripheral blood contains important information on transcriptomic and genomic alterations in the tumors. Initial studies have shown that genomic alterations of the androgen receptor and other genes detected in CTC or cfDNA of patients with castration resistant prostate cancer (CRPC) correlate with treatment outcomes to enzalutamide and abiraterone. Due to recent developments in high throughput analysis techniques, it is likely that CTC, cfDNA and RNA will be an important component of personalized treatment strategies in the future. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-19T01:25:58.470194-05:
      DOI: 10.1111/bju.13586
  • Raised pre‐operative INR identifies patients at high risk of
           peri‐operative death after simultaneous renal and cardiac surgery
           for tumours involving the peri‐diaphragmatic inferior vena cava
           (IVC) and right atrium
    • Authors: Tim O'Brien; Archie Fernando, Kay Thomas, Mieke Van Hemelrijck, Craig Bailey, Conal Austin
      Abstract: Background The ability to predict and therefore avoid surgery in those patients likely to die from simultaneous renal and cardiac surgery for urological tumours involving the peri‐diaphragmatic vena cava and right atrium would be valuable. Objective To identify pre‐operative factors that predict thirty‐day mortality (TDM) in patients undergoing this type of surgery. Design setting and participants Retrospective review of peri‐operative outcomes in patients managed between December 2007 and January 2016 by a single team. Outcome measurements and statistical analysis Relationships with outcome analysed using Fisher's Exact and Mann Whitney U tests. Results and Limitations 46 patients of whom 41/46 (89%) underwent surgery. 20 males; 21 females. Median age 65 yrs (range 17‐95). 37 renal cell cancer, 1 adrenal cancer, 2 primitive neuroectodermal tumours and 1 leiomyosarcoma. Overall TDM 3/41 patients (7%). INR, age and eGFR correlated significantly with TDM. Mortality if INR >1.5, 3/5 (60%) compared to 0/36 (0%) if INR 1.5 and age >70 years 3/3 (100%) INR correlated with serious complications (≥Clavien 3) (INR>1.5: 5/5 (100%) vs INR
      PubDate: 2016-07-19T01:25:44.444591-05:
      DOI: 10.1111/bju.13587
  • Nanotechnology combination therapy: Tyrosine kinase‐bound gold
           nanorod and laser thermal ablation produce a synergistic higher treatment
           response of renal cell carcinoma in animal model
    • Abstract: Objective To investigate tyrosine kinase inhibitors (TKI) and gold nanorod (AuNR) paired with photothermal ablation in a human metastatic clear cell renal cell carcinoma mouse model. Nanoparticles have been successful as platform for targeted drug delivery in the treatment of urologic cancers. Likewise, the use of nanoparticles in photothermal tumor ablation, though early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and gold nanorods and activated with photothermal ablation have demonstrated significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model. Materials and Methods Immunologically naïve nude mice (Athymic Nude‐Foxn1nu) were injected bilaterally on the flanks (n=36) with 2.5 x 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786‐O). Subcutaneous xenograft tumors developed 1 cm palpable nodules. Gold Nanorods encapsulated in Human Serum Albumin Protein nanoparticles were synthesized with or without a TKI and injected directly into the tumor nodule. Irradiation was administered with an 808 nm LED diode laser for six minutes. Animals were sacrificed 14 days post‐irradiation; tumors were excised, formalin fixed, paraffin embedded, and evaluated for size and percent necrosis by a GU pathologist. Untreated contralateral flank tumors were used as controls. Results In mice that did not receive irradiation, TKI alone yielded 4.2% tumor necrosis on the injected side and administration of HSA‐AuNR‐TKI alone yielded 11.1% necrosis. In laser ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA‐AuNR had 63.4% necrosis. The combination of laser irradiation and HSA‐AuNR‐TKI had cell kill of 100%. Conclusions In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticle produced moderate necrosis. Irradiation with and without gold particles alone also improves tumor necrosis. However, when irradiation is paired with gold particle and drug‐loaded nanoparticle, the combination therapy demonstrated the most significant and synergistic complete tumor necrosis of 100% (p
      PubDate: 2016-07-19T01:25:43.255177-05:
      DOI: 10.1111/bju.13590
  • A 22‐year Restrospective Study: Educational Update and New Referral
           Pattern of Age at Orchidopexy
    • Abstract: Objectives Research suggesting progressive deterioration in an undescended testis (UDT) has led to the reduction in the target age for orchidopexy to 6‐12 months of age. However, it is still unknown whether changing targets have altered practice. The objective was to determine the current age at orchidopexy in China and whether changing targets have altered practice. Materials and Methods The demographics of orchidopexies performed in Children's Hospital of Chongqing Medical University between 1993 and 2014 were reviewed. Survey of general publics’ cognition of undescended testes and survey of primary healthcare practitioners’ current opinion on age at orchidopexy and referral patterns were performed. Results A total of 3784 orchidopexies were performed over 22 years. The median age at orchidopexy fell between 1993 to 2014. There was an initial drop in the age for orchidopexy between 2000‐2010(3 years old)compared with the median age between 1993‐2000(4 years old).(P
      PubDate: 2016-07-19T01:25:35.090771-05:
      DOI: 10.1111/bju.13588
  • Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic
           clear‐cell renal cell carcinoma patients treated with sunitinib
    • Abstract: Objectives To validate vascular endothelial growth factor receptor‐1 (VEGFR1) single nucleotide polymorphism (SNP) rs9582036 as a potential predictive biomarker in metastatic clear‐cell renal cell carcinoma (m‐ccRCC) patients treated with sunitinib. Materials and methods m‐ccRCC patients receiving sunitinib as first‐line targeted therapy were included. We assessed response rate (RR), progression‐free survival (PFS), overall survival (OS), and clinical and biochemical parameters associated with outcome. We genotyped five VEGFR1 SNPs: rs9582036, rs7993418, rs9554320, rs9554316 and rs9513070. Association with outcome was studied by univariate analysis and by multivariate Cox regression. Additionally, we updated survival data of our discovery cohort as described previously. Results Sixty‐nine patients were included in the validation cohort. rs9582036 CC‐carriers had a poorer PFS (8 versus 12 months, p=0.02) and OS (11 versus 27 months, p=0.003) compared to AC/AA‐carriers. rs7993418 CC‐carriers had a poorer OS (8 versus 24 months, p=0.004) compared to TC/TT‐carriers. rs9554320 AA‐carriers had a poorer RR (0% versus 53%, p=0.009), PFS (5 versus 12 months, p=0.003) and OS (10 versus 25 months, p=0.004) compared to AC/CC‐carriers. When pooling patients from the discovery cohort, as described previously (n=88), and the validation cohort, in the total series of 157 patients, rs9582036 CC‐carriers had a poorer RR (8% versus 49%, p=0.004), PFS (8 versus 14 months, p=0.003) and OS (13 versus 30 months, p=0.0004) compared to AC/AA‐carriers. Unfavorable prognostic markers at start of sunitinib were well balanced between rs9582036 CC‐ and AC/AA‐carriers. Conclusion VEGFR1 rs9582036 is a candidate predictive biomarker in m‐ccRCC‐patients treated with sunitinib. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-15T03:15:30.284154-05:
      DOI: 10.1111/bju.13585
  • Patient‐reported outcomes in the ProtecT randomised trial of
           clinically localised prostate cancer treatments: design and baseline
           urinary, bowel and sexual function and quality of life
    • Authors: JA Lane; C Metcalfe, GJ Young, TJ Peters, J Blazeby, KNL Avery, D Dedman, L Down, MD Mason, DE Neal, FC Hamdy, JL Donovan,
      Abstract: Objectives To present the baseline patient‐reported outcome measures (PROMs) in the ProtecT (Prostate testing for cancer and Treatment) randomised trial comparing active monitoring, radical prostatectomy and external‐beam conformal radiotherapy for localised prostate cancer and to compare results with other populations. Materials and methods 1,643 randomised men aged 50‐69 years in nine UK cities diagnosed with clinically localised disease identified by prostate‐specific antigen (PSA) testing (1999‐2009). Validated PROMs for disease‐specific (urinary, bowel and sexual function) and condition‐specific quality of life impacts (EPIC: 2005 onwards, ICIQ‐UI: 2001 onwards, ICSmaleSF), anxiety and depression (HADS), generic mental and physical health (SF‐12, EQ‐5D‐3L) were completed at prostate biopsy clinics before randomisation. Descriptive statistics presented by treatment allocation and by men's age and at biopsy and PSA testing time points for selected measures. Results 1,438 participants completed biopsy questionnaires (88%) and between 77‐88% were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms (LUTS) were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65‐70 years), whilst urinary bother and physical health was somewhat worse than in younger men (49‐54 years, all p
      PubDate: 2016-07-14T09:35:30.688114-05:
      DOI: 10.1111/bju.13582
  • Robotic perineal radical prostatectomy and pelvic lymph node dissection
           using a purpose‐built single‐port robotic platform
    • Authors: Daniel Ramirez; Matthew J. Maurice, Jihad H. Kaouk
      Abstract: Objective To describe the features of the novel, purpose‐built da Vinci model SP1098 single‐port (SP) robotic platform and describe a step‐by‐step approach for perineal prostatectomy and pelvic lymph node dissection in a cadaver model. Methods 3 SP robotic radical perineal prostatectomies and 2 pelvic lymph node dissections were performed on 3 male cadavers in order to assess the feasibility of the SP1098 da Vinci robotic platform. The steps of the procedure included division of the rectourethralis muscle, splitting of the levator ani muscles bilaterally, opening of Denonvilliers fascia with dissection of the seminal vesicles, apical dissection and urethral division, anterior and lateral dissection with ligation of prostatic pedicles, bilateral pelvic lymph node dissection, and creation of the new vesicourethral anastomosis. The main outcomes assessed were operative time per step, total operative time, intraoperative complications and need for conversion to conventional or open techniques. Results No conversions were required. No intraoperative complications were seen. Median OR time for performing SP robotic radical perineal prostatectomy and pelvic lymph node dissection was 210 minutes (range 180‐240). Conclusions We demonstrate the feasibility and efficacy of a novel, purpose‐built robotic system in performing SP radical perineal prostatectomy and, for the first time, describe feasibility of robotic perineal lymph node dissection. This SP system will facilitate single port applications and allow surgeons to perform major urologic operations via a small, single incision while preserving triangulation and optics, and eliminating clashing between instruments. Future clinical studies are needed to support these encouraging outcomes. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-13T11:21:55.741357-05:
      DOI: 10.1111/bju.13581
  • Predicting Complications in Partial Nephrectomy for T1a Tumors: Does
           Approach Matter?
    • Authors: Daniel Ramirez; Matthew J. Maurice, Peter A. Caputo, Ryan J. Nelson, Onder Kara, Ercan Malkoc, Jihad H. Kaouk
      Abstract: Objectives Contemporary guidelines for treatment of localized renal masses suggest nephron‐sparing surgery (NSS) as an option for T1a tumors in appropriate patients. Large comparative series assessing the risk of complications between open and robotic approaches for partial nephrectomy are lacking. Our objective is to assess differences in complications following robotic (RPN) and open partial nephrectomy (OPN) among experienced surgeons. Patients and methods We identified patients in our IRB‐approved, prospectively maintained database who underwent OPN or RPN for management of unifocal, T1a renal tumors at our institution between January 2011 and August 2015. Our primary outcome measure was the rate of 30‐day overall postoperative complications. Baseline patient factors, tumor characteristics and perioperative factors, including approach, were evaluated to assess the risk of complication. Results Patients who underwent OPN were found to have a higher rate of overall complications (30.3% vs 18.2%, p=0.038) with wound complications accounting for the majority of these events (11.8% vs 1.8%, p
      PubDate: 2016-07-13T11:20:44.439266-05:
      DOI: 10.1111/bju.13583
  • Germline Genetic Variation in JAK2 as a Prognostic Marker in Castration
           Resistant Prostate Cancer
    • Authors: Ben Y. Zhang; Shaun M. Riska, Douglas W. Mahoney, Brian A. Costello, Rhea Kohli, J.F. Quevedo, James R. Cerhan, Manish Kohli
      Abstract: Objectives To evaluate the prognostic significance of germline variation in candidate genes in patients with castration‐resistant prostate cancer (CRPC). Methods Germline DNA was extracted from peripheral blood mononuclear cells of CRPC patients enrolled in a clinically annotated registry. Fourteen candidate genes implicated in either initiation or progression of prostate cancer were tagged using single nucleotide polymorphisms (SNPs) from HapMap with minor allele frequency of >5%. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. Principal component analysis was used for gene levels tests of significance. For SNP level results the per allele hazard ratios (HR) and 95% confidence intervals (CI) under the additive allele model were estimated using Cox regression adjusted for age at CRPC and Gleason score (GS). Results Two hundred and forty two CRPC patients were genotyped (14 genes; 84 SNPs). The median age of the cohort was 69 years (range 43‐93). The GS distribution was 55% with GS≥8, 32% with GS=7 and 13% with GS
      PubDate: 2016-07-13T11:20:34.961192-05:
      DOI: 10.1111/bju.13584
  • Impact of ischemia time on renal function after partial nephrectomy: a
           systematic review
    • Abstract: Objective To assess the impact of ischemia on renal function after partial nephrectomy. Materials and methods A literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) criteria. In January 2015, the Medline and Embase databases were systematically searched using the protocol (“warm ischemia”[mesh] OR “warm ischemia”[ti]) AND (“nephrectomy”[mesh] OR “partial nephrectomy”[ti]). An updated search was performed in December 2015. Only studies based on a solitary kidney model or on a two‐kidney model but with assessment of split renal function were included in this review. Results Of the 1119 studies identified, 969 abstracts were screened after duplicates were removed: 29 articles were finally included in this review, including 9 studies that focused on patients with a solitary kidney. None of the nine studies adjusting for the amount of preserved parenchyma found a negative impact of warm ischemia time on postoperative renal function, unless this was extended beyond a 25‐minute threshold. The quality and the quantity of preserved parenchyma appeared to be the main contributors to postoperative renal function. Conclusion Currently, no evidence supports that limited ischemia time (i.e. ≤25 min) has a higher risk of reducing renal function after PN compared to a “zero ischemia” technique. Several recent studies have suggested that prolonged warm ischemia (>25–30 min) could cause an irreversible ischemic insult to the surgically treated kidney. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-13T11:20:34.302067-05:
      DOI: 10.1111/bju.13580
  • Urethral diverticulectomy with Martius fat pad interposition improves
           symptom resolution and reduces recurrence
    • Authors: S Malde; N Sihra, S Naaseri, M Spilotros, E Solomon, M Pakzad, R Hamid, JL Ockrim, TJ Greenwell
      Abstract: Objective To assess the presenting features and medium‐term symptomatic outcomes in women having excision of urethral diverticulum with Martius fat pad interposition Patients and Methods We reviewed our prospective database of all female patients having excision of a symptomatic urethral diverticulum between 2007 and 2015. Data on demographics, presenting symptoms and clinical features were collected, as well as post‐operative outcomes. Results Seventy women with a mean age of 46.5 years (range 24‐77) underwent excision of urethral diverticulum with Martius fat pad interposition over this period. The commonest presenting symptoms were a urethral mass (69%), urethral pain (61%) and dysuria (57%). Pre‐existing SUI was present in 41% (29) of women. Following surgery at a mean 18.9 (SD 16.4) months follow‐up (median 14 months), complete excision of urethral diverticulum was achieved in 100%, with resolution of urethral mass, dysuria and dyspareunia in all patients, and urethral pain in 81%. Immediately following surgery 10 (24%) patients reported de‐novo SUI. This resolved with time and pelvic floor muscle training such that at 12 months only 5 (12%) reported continued SUI. There was 1 symptomatic diverticulum recurrence (1.4%). Conclusions The commonest presenting symptom of a female urethral diverticulum is urethral pain followed by dysuria and dyspareunia. Surgical excision with Martius fat pad interposition results in complete resolution of symptoms in the majority of women. The incidence of persistent de novo SUI in an expert high‐volume centre is 12%. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-13T11:20:32.977848-05:
      DOI: 10.1111/bju.13579
  • Testosterone treatment is not associated with increased risk of prostate
           cancer or worsening of lower urinary tract symptoms: Prostate health
           outcomes in the Registry of Hypogonadism in Men (RHYME)
    • Abstract: Objectives To evaluate the effects of testosterone replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in PSA levels and lower urinary tract symptoms (LUTS) over time. Materials and Methods The Registry of Hypogonadism in Men (RHYME) is a multi‐national patient registry of treated and untreated, newly‐diagnosed hypogonadal men (n=999). Follow‐up assessments were performed at 3‐6, 12, 24, and 36 months. Baseline and follow‐up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies were subjected to blinded, independent adjudication for presence and severity of prostate cancer (PCa), Prostate Specific Antigen (PSA), and Testosterone (T) levels measured via local and central laboratory assays, and LUTS severity via the International Prostate Symptom Score (IPSS). Incidence rates per 100,000 person‐years were calculated. Longitudinal mixed models were used to assess effects of T on PSA and IPSS. Results Of 999 patients with clinically‐diagnosed HG, 750 (75%) initiated TRT, contributing 23,900 person‐months of exposure. Mean T levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 nmol/L to 11.3 nmol/L in untreated men. Fifty‐five (55) biopsies were performed for suspected prostate cancer, and 12 non‐cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on T (37.5%) compared to those not on T (37.0%) over the course of the study. No differences were observed in PSA levels, total IPSS score, or IPSS obstructive sub‐scale score by testosterone treatment status. Lower IPSS irritative sub‐scale scores were reported in treated men compared to untreated men. Conclusions Results support prostate safety of TRT in newly diagnosed men with hypogonadism (HG). This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-13T11:15:33.045254-05:
      DOI: 10.1111/bju.13578
  • Socioeconomic factors and penile cancer risk and mortality; a
           population‐based study
    • Abstract: Objective To investigate possible associations between socioeconomic status (SES) and penile cancer risk, stage at diagnosis, and mortality. Patients/subjects and methods A population‐based register study including men in Sweden diagnosed with penile cancer between 2000 and 2012 (1676 men) and randomly chosen controls (9872 men). Data were retrieved from the National Penile Cancer Register (NPECR) and several other population‐based healthcare and sociodemographic registers. Educational level, disposable income, marital status, and number of individuals in the household, were assessed as indicators of SES. The risk of penile cancer and penile cancer death in relation to SES were estimated using logistic regression and proportional hazards models, respectively. Cumulative cause‐specific mortality (CSM) estimates by SES were calculated using the Kaplan–Meier method. Results A low educational level and low disposable income were associated with an increased risk of invasive penile cancer. Furthermore, low educational level was associated with more advanced primary tumour stage. Divorced and never married men had a generally increased risk of penile cancer and were diagnosed with more advanced primary tumour stages. However, neither educational level nor marital status was associated with lymph node or distant metastases. Also, men in single‐person households had an increased risk of both non‐invasive and invasive disease. In men with invasive penile cancer, there were no significant associations of indicators of SES and CSM. Conclusions Low educational level, low disposable income, being divorced or never married, and living in a single‐person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival.
      PubDate: 2016-07-04T02:50:40.003606-05:
      DOI: 10.1111/bju.13534
  • Prediction of Pathologic Stage Based on Clinical Stage, Serum PSA, and
           Biopsy Gleason Score: Partin Tables in the Contemporary Era
    • Authors: Jeffrey J. Tosoian; Meera Chappidi, Zhaoyong Feng, Elizabeth B. Humphreys, Misop Han, Christian P. Pavlovich, Jonathan I. Epstein, Alan W. Partin, Bruce J. Trock
      Abstract: Objective ‐To update the Partin Tables for prediction of pathological stage in the contemporary setting and examine trends in patients treated with radical prostatectomy (RP) over the past three decades. Patients and Methods ‐From January 2010 through October 2015, a total of 4459 men meeting inclusion criteria underwent RP and pelvic lymphadenectomy for histologically‐confirmed prostate cancer at the Johns Hopkins Hospital. ‐Preoperative clinical stage, serum prostate‐specific antigen (PSA) level, and biopsy Gleason score (i.e. prognostic Grade Group) were utilized in a polychotomous logistic regression model to predict the probability of pathological outcomes categorized as: organ‐confined (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+). ‐Preoperative characteristics and pathological findings in men treated with RP since 1983 were collected and clinical‐pathological trends were described. Results ‐Median age at surgery was 60 years (range 34‐77) and median PSA was 4.9 ng/ml (0.1‐125.0). ‐The observed probabilities of pathological outcomes were: OC disease in 74%, EPE in 20%, SV+ in 4%, and LN+ in 2%. ‐The probability of EPE increased substantially when biopsy Gleason score increased from 6 (Grade Group 1) to 3+4 (Grade Group 2), with smaller increases for higher grades. The probability of LN+ was substantially higher for biopsy Gleason score 9‐10 (Grade Group 5) as compared to lower Gleason scores. ‐Area under the receiver operating characteristic curves for binary logistic models predicting EPE, SV+, and LN+ versus OC were 0.724, 0.856, and 0.918, respectively. ‐The proportion of men treated with biopsy Gleason score ≤6 cancer (Grade Group 1) was 47%, representing a substantial decrease from 63% in the previous cohort and 77% in 2000‐2005. The proportion of men with organ‐confined cancer has remained similar during that time, equaling 73% to 74% overall. ‐The proportions of men with SV+ (4.1% from 3.4%) and LN+ (2.3% from 1.4%) increased relative to the preceding era for the first time since the Partin tables were introduced in 1993. Conclusions ‐The Partin Tables remain a straightforward and accurate approach for projecting pathological outcomes based on readily available clinical data. ‐Acknowledging these data are derived from a tertiary care referral center, the proportion of men with OC disease has remained stable since 2000, despite a substantial decline in the proportion of men with biopsy Gleason score 6 (Grade Group 1). This is consistent with the notion that many men with Gleason score 6 (Grade Group 1) disease were overtreated in previous eras. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-01T09:40:24.014302-05:
      DOI: 10.1111/bju.13573
  • Immune check point blockade ‐ a treatment for Urological
    • Authors: Oussama Elhage; Christine Galustian, Prokar Dasgupta
      Abstract: In the last few years there have been concerted attempts at using the power of the immune system as an effective treatment option for cancer. This has become possible since our understanding of the workings of the immune system improved. Tumours form because of failure of the organism to destroy a rogue, mutated cell in an appropriate way. This article is protected by copyright. All rights reserved.
      PubDate: 2016-07-01T09:27:33.253204-05:
      DOI: 10.1111/bju.13571
  • Primary Gleason Pattern Upgrading in contemporary D'Amico low‐risk
           prostate cancer patients: Implications for future biomarkers and imaging
    • Abstract: Objective To retrospectively assess the rate of primary Gleason upgrading (HGPGU) to primary Gleason pattern 4 or 5 in a contemporary cohort of D'Amico low‐risk prostate cancer (PCa) and PRIAS active surveillance (AS) patients and to develop a tool for HGPGU prediction. HGPGU is a contraindication in most AS and focal therapy protocols. Methods 10,616 patients with localized PCa were treated at a high volume European tertiary care center from 2010 to 2015 with radical prostatectomy. Analyses were restricted to 1,819 D'Amico low‐risk patients (17.1%) with PSA
      PubDate: 2016-07-01T09:27:08.321457-05:
      DOI: 10.1111/bju.13570
  • Contemporary retroperitoneal lymph node dissection (RPLND) for testis
           cancer in the UK – a national study
    • Authors: H Wells; M C Hayes, T O'Brien, S Fowler,
      Abstract: Objectives To undertake a comprehensive prospective national study of the outcomes of RPLND for testis cancer over a one year period in the United Kingdom. Patients and Methods Data were submitted online using the BAUS Section of Oncology Data and Audit System. All new patients undergoing RPLND for testis cancer between March 2012 and February 2013 were studied prospectively. Data was analysed using Tableau software and case ascertainment compared with Hospital Episode Statistics (HES) data. Results 162 men underwent RPLND by 20 surgeons in 17 centres. Mean case volume per centre was 9 (range 2 – 32) per centre and median case volume per surgeon 6 (1 – 30). Indication was residual mass post‐chemotherapy (73%); primary treatment (6%); relapse (14%); salvage (7%). Median time to surgery post chemotherapy was 8 – 12 weeks (12 weeks). 91% of procedures utilised open surgery. Median operating time was 3 – 4 hours (6 hours). Nerve sparing was performed in 67% (19% bilateral; 48% unilateral). Dissection was template in 81% and lumpectomy in 16%. 25% required additional intra‐operative procedures including 11% synchronous planned nephrectomy. 157/160 (98%) of recorded RPLND operations were completed. One was terminated due to bleeding and in two the mass could not be removed. There were no deaths within 30 days of surgery. 75% of men did not require a blood transfusion, 15% required 1 – 2 units and 10% received more than two units. 10% of men had post‐operative complications (Clavien grade 1 = 7, grade 2 = 7, grade 3 = 1). Mean length of stay was 5.5 days (range 1‐59). Histology showed necrosis in 22%; teratoma differentiated in 42%; and residual cancer in 36%. Conclusion This prospective collaborative national study describes for the first time the surgical outcomes after RPLND across the UK. The quality of RPLND in the UK appears high. The study can act as a benchmark for this type of surgery across the world. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-29T06:46:31.819732-05:
      DOI: 10.1111/bju.13569
  • PI‐RADS 4 or more: Active Surveillance no more
    • Authors: Marlon Perera; Nik Katelaris, Declan Murphy, Shannon McGrath, Nathan Lawrentschuk
      Abstract: The introduction of multiparametric Magnetic Resonance Imaging (mpMRI) has improved the diagnosis and risk stratification of intermediate and high‐risk prostate cancer. In addition to diagnosis, mpMRI has increasing become a useful tool for monitoring prostate cancer risk of patients on active surveillance (AS) programs. A significant proportion of men on AS programs have suspicious lesions on mpMRI [1]. Accordingly, repeat mpMRI provides means of non‐invasive assessment with the potential for fusion biopsy and preferential sampling of prostate cancer tissue. In 2012, the Prostate Imaging Reporting and Data System (PI‐RADS) introduced standardized reporting of prostate mpMRI. PI‐RADS 4 and 5 lesions have been classified as “clinically significant cancer is likely to be present” and “clinically significant cancer is highly likely” respectively. PI‐RADS 4 and 5 lesions are being increasing correlated with intermediate and high‐grade prostate cancer. As recently discussed in: “Gleason Pattern 4: Active Surveillance no more” [2], patients with intermediate‐risk prostate cancer are not suitable for AS. In light of this, the presence of PI‐RADS 4 or 5 lesions on men enrolled to AS programs for prostate cancer warrants concern. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-22T09:15:58.511445-05:
      DOI: 10.1111/bju.13562
  • The contemporary landscape of occupational bladder cancer within the
           United Kingdom: A meta‐analysis of risks over the last 80 years
    • Authors: Marcus G Cumberbatch; Ben Windsor Shellard, James WF Catto
      Abstract: Importance Bladder cancer (BC) is a common malignancy that arises through occupational carcinogen exposure. Here we analyse trends in UK to better understand contemporary occupational BC. Objective To profile the contemporary risks of occupational BC in the UK. Materials and methods Systematic review using PubMed, Medline, Embase and Web of Science was performed in March 2016. We selected reports of British workers in which BC or occupation were the main focus, with sufficient cases or with confidence intervals (CI). We used the most recent data in populations with multiple reports. We combined odds ratios and risk ratios (RRs) to provide pooled RRs of incidence and disease specific mortality (DSM). We tested for heterogeneity and publication bias. We extracted BC mortality from Office of National Statistics death certificates. We compered across regions and with our meta‐analysis. Results We identified 25 articles reporting risks in 702,941 persons. Meta‐analysis revealed significantly increased incidence for 12/37 and DSM for 5/37 occupational classes. Three classes had reduced BC risks. The greatest risk of BC incidence occurred in chemical process (RR 1.87 (1.50‐2.34)), rubber (RR 1.82 (1.4‐2.38)) and dye workers (RR 1.8, (1.07‐3.04)). The greatest risk of DSM occurred in electrical (RR 1.49 (1.19‐1.87)) and chemical process workers (RR 1.35 (1.09‐1.68)). BC mortality was higher in the North of England, probably reflecting smoking patterns and certain industries. Limitations include the lack of sufficient robust data, missing occupational tasks and no adjustment for smoking. Conclusion Occupational BC occurs in many workplaces and the risks for incidence and DSM may differ. Regional differences may reflect changes in industry and smoking patterns. Relatively little is known about BC within British industry, suggesting official data underestimate the disease. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-22T09:10:59.217584-05:
      DOI: 10.1111/bju.13561
  • What is the outcome of paediatric gastrocystoplasty when the patients
           reach adulthood'
    • Abstract: Objective To document the long‐term outcomes of paediatric augmentation gastrocystoplasty (AGC) in terms of preservation of renal function and maintenance of dryness, and to analyse the rate of complications. Patients and methods The medical records of children who had undergone AGC between 1992 and 2000 (minimum time interval of 15 years) were reviewed retrospectively. The following data were collected: age at surgery, the cause of bladder dysfunction, functioning of the AGC, any complications and the long‐term outcome of the patients. All of the patients were recontacted by telephone. Results A total of 11 AGCs were carried out between 1992 and 2000, at a median age of 11 years (range from 6.5 to 14 years). The diagnosis of patients undergoing AGC included myelomeningocele (n=4), bladder exstrophy (n=4), posterior urethral valves (n=1), irradiated bladder (n=1) and Prune Belly syndrome (n=1). Median follow‐up was 17 years (15‐19.5, all patients). Renal function was preserved or improved in 63% of patients and 80% of patients were dry after AGC. Seven of the 11 (63%) patients reported symptoms linked to haematuria‐dysuria syndrome, which was resistant to treatment in one case and requiring excision of the gastric patch. Three of the 11 patients (23%) developed a tumour on the gastric graft after a median delay of 20 years (range 11‐22) after the initial procedure. All had gastric adenocarcinoma of which two were metastatic at the time of diagnosis requiring pelvectomy with pelvic lymph nodes dissection and adjuvant chemotherapy. Seven of the 11 (63%) patients underwent excision of the gastric patch after a median time of 11 years (range 8.5‐20.5). Conclusions Our long‐term data confirmed that the majority of patients undergoing AGC had preservation of their renal function and were continent. However, long‐term, AGC was associated with a significant risk of malignant transformation and a high rate of surgical re‐intervention involving removal of the gastric patch. These results question the use of this technique for bladder augmentation, irrespective of the indication. We highlighted the importance of strict endoscopic follow‐up of all patients already having undergone an AGC and the need to inform and educated patients about tumour‐related symptoms. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-20T09:31:08.134243-05:
      DOI: 10.1111/bju.13558
  • Treatment patterns, testicular loss, and disparities in inpatient surgical
           management of testicular torsion in boys: a population based study
    • Abstract: Objectives To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and identify risk‐factors for TL utilizing a large nationally representative pediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT,
      PubDate: 2016-06-20T09:20:23.663547-05:
      DOI: 10.1111/bju.13557
  • Preoperative nomogram to predict likelihood of complications following
           radical nephroureterectomy
    • Abstract: objectives To construct a nomogram based on preoperative variables to better predict the likelihood of a complication occurring within 30‐days of radical nephroureterectomy (RNU). patients and methods The charts of 731 patients undergoing RNU at 8 academic medical centers between 2002 and 2014 were reviewed. Preoperative clinical, demographic, and comorbidity indices were collected. Complications occurring within 30‐days of surgery were graded using the modified Clavien‐Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post‐RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. Results 408 men and 323 women with a median age of 70 years and BMI of 27 were included. 75% of the cohort was of white race, 18% had an ECOG performance status ≥ 2, 20% had a Charlson Comorbidity Index > 5, and 50% had baseline CKD stage III or greater. Overall, 279 patients (38%) experienced a complication including 61 (22%) with Clavien III or greater events. A multivariate model identified 5 variables associated with complications including patient age, race, ECOG performance status, CKD stage, and Charlson comorbidity index. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. conclusions Using standard preoperative variables from this multi‐institutional RNU experience, we constructed and validated a nomogram for predicting perioperative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis prior to major surgery. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-20T09:15:24.530153-05:
      DOI: 10.1111/bju.13556
  • De Ritis ratio (AST/ALT) as a significant prognostic factor after surgical
           treatment in patients with clear cell localized renal cell carcinoma: a
           propensity score matched study
    • Abstract: Objective Our objective was to evaluate the detailed association of preoperative De Ritis ratio (AST/ALT) with postoperative clinical outcomes after surgical treatment of localized RCC. Materials and Methods We retrospectively reviewed data from 2,965 patients surgically treated for non‐metastatic RCC. Propensity scores for high AST/ALT were calculated and 430 patients with high AST/ALT were matched to 1,117 patients with low AST/ALT. The association between AST/ALT and postoperative outcomes was tested. Multivariate Cox analyses were performed to identify the independent predictors of progression‐free, overall‐ and cancer specific survival. Results According to receiver operating curve of AST/ALT to cancer‐specific mortality, we stratified the patients into two groups by a cut‐off value of 1.5. Before matching, patients with high AST/ALT showed worse progression‐free, overall, and cancer specific survival (all p < 0.001). In propensity score matched cohort with 1,547 patients, patients with high AST/ALT showed inferior survival outcomes in progression‐free, overall and cancer specific survival (all p < 0.001). On multivariate analysis, high AST/ALT was revealed as an independent predictor of disease progression (HR 1.372, 95% CI 1.003 – 1.882; p = 0.048), overall mortality (HR 1.559, 95% CI 1.069 – 2.272; p = 0.021), and cancer specific mortality (HR 1.974, 95% CI 1.250 – 3.118; p = 0.004). From the subgroup analysis according to tumour histology, high AST/ALT showed significant relationship with postoperative survival in clear cell RCC, but not in non‐clear cell RCC. Conclusion Increased AST/ALT was significantly associated with worse postoperative survival in patients surgically treated for localized clear cell RCC. Further prospective studies are needed to understand the prognostic value of preoperative AST/ALT. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-16T23:40:29.406957-05:
      DOI: 10.1111/bju.13545
  • The Origins of Urinary Stone Disease: Upstream mineral formations initiate
           downstream Randall's plaque
    • Authors: Ryan S. Hsi; Krishna Ramaswamy, Sunita P Ho, Marshall L. Stoller
      Abstract: Objectives To describe a new hypothesis for the initial events leading to urinary stones. A biomechanical perspective on Randall's plaque formation through form and function relationships is applied to functional units within the kidney we have termed the “medullo‐papillary complex” – a dynamic relationship between intratubular and interstitial mineral aggregates. Materials and Methods A complete MEDLINE search was performed to examine the existing literature regarding the anatomical and physiological relationships in the renal medulla and papilla. Sectioned human renal medulla with papilla from radical nephrectomy specimens were imaged using a high resolution micro X‐ray computed tomography. The location, distribution, and density of mineral aggregates within the medullo‐papillary complex were identified. Results Mineral aggregates were observed proximally in all specimens within the outer medulla of medullary complex and were intratubular. Distal interstitial mineralization at the papillary tip corresponding to Randall's plaque was not observed until a threshold of proximal mineralization was observed. Mineral density measurements suggest varied chemical compositions between the proximal intratubular (330 mg/cc) and distal interstitial (270 mg/cc) deposits. A review of the literature revealed distinct anatomical compartments and gradients across the medullo‐papillary complex that supports the empirical observations that mineralization proximally triggers distal Randall's plaque formation. Conclusion The initial stone event is initiated by intratubular mineralization of the renal medullary tissue leading to the interstitial mineralization that is observed as Randall's plaque. We base this novel hypothesis on a multiscale biomechanics perspective involving form and function relationships, and empirical observations. Additional studies are needed to validate this hypothesis. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-16T03:30:30.104098-05:
      DOI: 10.1111/bju.13555
  • Robotic Assisted Partial Cystectomy (RAPC): perioperative outcomes and
           early oncologic efficacy
    • Authors: David M. Golombos; Padraic O'Malley, Patrick Lewicki, Benjamin V. Stone, Douglas S. Scherr
      Abstract: Objective To report on patients undergoing robotic‐assisted partial cystectomy (RAPC), focusing on perioperative outcomes over a range of clinical, anatomic and pathologic variables as well as the overall oncological efficacy of this approach. Patients and Methods We retrospectively reviewed all patients who underwent robotic assisted partial cystectomy (RAPC) by a single surgeon between 2005‐2015. We identified 29 patients who underwent surgery for definitive management of a primary bladder tumor. Clinicopathologic data and perioperative variables were recorded. Continuous variables were compared using student's t‐test. Prediction of perioperative outcomes for those undergoing RAPC for intradiverticular neoplasms was done using univariable logistic regression. Survival was estimated using the Kaplan‐Meier method. Results Median patient age was 75 years [IQR 65‐81], 18 patients (62.1%) had an ASA classification of 3 or higher, and 10 patients (34.5%) had a history of prior abdominal surgery. Median blood loss was 50 cc and median length of stay was 1 day. Two patients (6.9%) experienced a perioperative complication and five (17.9%) a post‐discharge 90 day complication, all which were minor. Positive surgical margin rate was 3.6%, and in those with muscle invasive disease a median of 12 lymph nodes were removed. Neither size of diverticulum or need for ureteral reimplant were predictive of length of stay, blood loss, or complication (p>0.05). We did not encounter any wound, port site, or unusual recurrence patterns to suggest the technical factors of a robotic approach influenced oncologic outcomes. Five‐year overall and recurrence‐free survival rates were 79% and 68% respectively. Conclusion RAPC confers the ability to achieve favorable outcomes with low morbidity and reduced hospital stays. Oncological efficacy compares favorably with published literature. For experienced surgeons, this may represent the optimal surgical approach for organ preserving bladder surgery. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-15T00:05:34.677575-05:
      DOI: 10.1111/bju.13535
  • Active surveillance for low‐risk Non‐Muscle Invasive Bladder
           Cancer (NMIBC): mid‐term results from a Bladder cancer Italian
           Active Surveillance (BIAS) project
    • Abstract: Objective To report the oncologic safety and the risk of progression for patients with NMIBC included in an active surveillance (AS) program after the diagnosis of recurrence. Subjects and methods This is a prospective study enrolling patients with history of pathologically confirmed LG pTa‐pT1a Non‐Muscle Invasive Bladder Cancer (NMIBC) and diagnosed with a tumour recurrence. Inclusion criteria consisted of negative urine cytology, presence of ≤ 5 NMIBCs with a diameter ≤ 10 mm, absence of carcinoma in situ (CIS) or persistent gross haematuria. The primary outcome of interest was adherence to AS. Need to proceed with treatment was defined as progression in number/dimension/positive cytology/symptoms (gross haematuria persistent) or any further intervention (resection or electro‐fulguration). Finally, we assessed the up‐grading and up‐staging when transurethral resection of bladder tumour (TURBT) was performed. Results The study population consisted of 55 patients with a previous diagnosis of NMIBC (70 active surveillance events) prospectively recruited since 2008. The mean patient age was 69.8 years. Median follow‐up was 53 months. The median time patients remained under AS was 12.5 months. A disease progression was observed in 28 patients (51%). No patient experienced progression to muscle‐invasive disease. Fifteen patients (27.3%) showed an increase in the number and/or size of the tumour, 9 (16,4%) suffered from hematuria and 4 (7.3%) had a positive cytology. Only 5 (9%) patients in the whole series experienced progression to a high‐ grade tumour (G3) or presented with associated CIS. The overall adherence to the follow‐up schedule was 95%. Conclusion Our data showed that an AS protocol for NMIBC could be a reasonable option in a selected group of patients with small, recurrent cancers. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-13T21:30:28.357332-05:
      DOI: 10.1111/bju.13536
  • Role of Prostate Artery Embolization (PAE) in the Management of Refractory
           Hematuria of Prostatic Origin
    • Authors: Keith Pereira; Joshua A. Halpern, Timothy D. McClure, Nicholas A. Lewis, Isaam Kably, Shivank Bhatia, Jim C. Hu
      Abstract: Prostatic hematuria is among the most common genitourinary complaints of emergency room visits, distressful and troublesome to men and a challenging clinical problem to the treating physician. The most common etiologies of prostatic hematuria include benign prostatic hyperplasia and prostate cancer. Prostatic hematuria usually resolves with conservative and medical methods; failure of these interventions results in refractory hematuria of prostatic origin (RHPO), a potentially life‐threatening scenario. Several different treatments have been described, with varying degrees of success. Patients with RHPO are often elderly and unfit for radical surgery. Prostate artery embolization (PAE) has evolved as a safe and effective technique in the management of RHPO. Use of a superselective approach optimizes clinical success while minimizing complications. This minimally invasive approach improves patients with hemodynamic instability, serves as a bridge to elective surgery, and is a highly effective treatment for RHPO. It may obviate the need for more invasive and morbid surgical therapies. The aim of this review is to describe the current management of RHPO, the technique of PAE and review its efficacy and morbidity. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-13T02:20:35.892154-05:
      DOI: 10.1111/bju.13524
  • Redo‐buccal mucosa graft urethroplasty: Success rate, oral morbidity
           and functional outcome
    • Authors: Clemens M. Rosenbaum; Marianne Schmid, Tim A. Ludwig, Luis A. Kluth, Roland Dahlem, Margit Fisch, Sascha Ahyai
      Abstract: Objectives To determine success rate, oral morbidity and functional outcome of Redo‐buccal mucosa graft urethroplasty (BMGU) for treatment of stricture recurrence after prior BMGU. Patients and methods We included 50 Patients who underwent Redo‐BMGU between February 2009 and September 2014. Patients’ charts and non‐validated questionnaires were reviewed. Primary endpoint consisted of success rate defined as stricture‐free survival. Stricture recurrence was defined as any postoperative claims of catheterization, dilatation, urethrotomy or repeat urethroplasty or when maximum flow rate was
      PubDate: 2016-06-11T05:20:27.558344-05:
      DOI: 10.1111/bju.13528
  • Robotic‐assisted vs. open adrenalectomy: evaluation of cost
           effectiveness and perioperative outcome
    • Abstract: Objectives To compare Robotic assisted laparoscopic adrenalectomy (RALA) and open adrenalectomy (OA) with regard to intraoperative complications, perioperative outcome and cost effectiveness. Subjects/Patients And Methods Functional and statistical data from OA and RALA patients between 2001 and 2015 was prospectively recorded including intra‐ and post‐operative outcomes. We also utilized per‐day costs from current census reports (€540/d and €1145/d for normal and intermediate care) to evaluate treatment costs. Additional costs for RALA (€2288) were assumed in accordance with current literature. Patients were matched by ASA‐score, age, side of surgery and gender for comparison of OA and RALA. 28 matched pairs were analyzed for patient characteristics, perioperative outcomes and cost effectiveness. Statistical significance of outcome parameters were determined by student‐t‐test and Pearson's chi‐squared test. Results Due to the matching process, patient groups did not differ in their main characteristics. Length of stay was shorter for RALA (11.1 ± 4.8 vs. 6.8 ± 1.2 days, p
      PubDate: 2016-06-10T01:11:46.152834-05:
      DOI: 10.1111/bju.13529
  • Getting Personal with Prostate Cancer: DNA‐Repair Defects and
           Olaparib in Metastatic Prostate Cancer
    • Authors: Nicholas Raison; Oussama Elhage, Prokar Dasgupta
      Abstract: Despite the progress that has been made in the treatment of advanced prostate cancer, many patients with metastatic prostate cancer still progress to hormone resistance. Development of new agents has greatly expanded the treatment options for metastatic castrate resistant prostate cancer (mCRPC), however their impact on survival outcomes have been limited. There remains an acute need for improvements in the prognostic assessment and targeted treatment of mCRPC. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-09T05:58:24.850933-05:
      DOI: 10.1111/bju.13522
  • Spectrum of genomic alterations in FGFR3: current appraisal of the
           potential role of FGFR3 in advanced urothelial carcinoma
    • Authors: N. Sethakorn; P. H. O'Donnell
      Abstract: Molecular analysis has identified subsets of urothelial carcinoma (UC) expressing distinct genetic signatures. Genomic alterations in the oncogenic fibroblast growth factor receptor 3 (FGFR3) pathway are among the most well‐described in UC and have led to extensive and ongoing investigation of FGFR3‐targeted therapies in this disease, although no new drugs have yet been approved. Given the unmet need for effective treatments in advanced and metastatic UC, a better understanding of the known molecular alterations of FGFR3 and of the prior and ongoing clinical investigations of this promising target in UC deserve attention. The objective of this review is to describe the landscape of alterations and biology of FGFR3 in UC, comprehensively summarize the current state of UC clinical trials of FGFR3 inhibitors, and discuss future therapeutic applications. Using the Pubmed and Clinicaltrials. gov databases, articles describing the spectrum and biological activity of FGFR3 genomic alterations and trials of FGFR3 inhibitors in UC were identified. Search terms included “FGFR3 genomic alterations” and “urothelial cancer” or “bladder cancer.” Genomic alterations including translocations and activating mutations are increasingly described in advanced and metastatic UC. The majority of clinical trials have been performed in unselected populations. However, recent studies have reported encouraging preliminary data. We argue that routine use of molecular genomic tumor analysis in UC may inform selection of patients for appropriate trials and further investigate the potential for FGFR3 as a meaningful clinical target for this difficult disease. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-07T10:05:45.180624-05:
      DOI: 10.1111/bju.13552
  • Evaluation and establishment of a ward‐based geriatric liaison
           service for older urological surgical patients: POPS‐Urology
           (Proactive Care of Older People Undergoing Surgery)
    • Abstract: Objective To assess the impact of introducing and embedding a structured geriatric liaison service, POPS‐Urology, using comprehensive geriatric assessment methodology, on an inpatient urology ward. Patients and Methods A phased quality improvement project was undertaken using stepwise interventions. Phase 1 ‐ A before‐and‐after study with initiation of a daily board round, weekly multidisciplinary meeting, and targeted geriatrician‐led ward rounds for elective and emergency urology patients ≥65 years admitted over two one‐month periods. Outcomes were recorded from medical records and discharge documentation, including length of inpatient stay, medical and surgical complications, 30‐day readmission and 30‐day mortality. Phase 2 ‐ A quality improvement project involving Plan‐Do‐Study‐Act cycles and qualitative staff surveys in order to create a Geriatric Surgical Checklist (GSCL) to: standardise the intervention in Phase 1, improve equity of care by extending to all ages, improve team working, and streamline handovers for multidisciplinary staff. Results Phase 1 ‐ 112 patients in the control month and 130 in the intervention month. Length of inpatient stay was reduced by 19% (mean 4.9 vs. 4.0 days, p=0.01), total postoperative complications were lower (RR 0.24 (0.10, 0.54), p=0.001). A non‐significant trend was seen towards fewer cancellations of surgery (10% vs. 5%, p=0.12) and 30‐day readmissions (8% vs. 3%, p=0.07). Phase 2 ‐ The GSCL was created and incrementally improved. Questionnaires repeated at intervals revealed the GSCL helped staff to understand their role better in multidisciplinary meetings, improved their confidence to raise issues, reduced duplication of handovers, and standardised identification of geriatric issues. Equity of care was improved by providing the intervention to patients of all ages, despite which the time taken for the daily board round did not lengthen. Conclusion This is the first known paper describing benefits of daily proactive geriatric intervention in elective and emergency urological surgery. The results suggest that using a multidisciplinary team board round helps to facilitate collaborative working between surgical and geriatric medicine teams. The GSCL enables systematic identification of patients who require a focussed comprehensive geriatric assessment. There is potential to transfer the GSCL package to other surgical specialties and hospitals in order to improve postoperative outcomes. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-04T02:15:25.916229-05:
      DOI: 10.1111/bju.13526
  • Pre‐biopsy 3T MRI and targeted biopsy of the index prostate cancer
           – correlation with robot assisted radical prostatectomy
    • Authors: Uday Patel; Prokar Dasgupta, Ben Challacombe, Declan Cahill, Christian Brown, Roshnee Patel, Roger Kirby
      Abstract: Objective To study whether pre‐biopsy 3T prostate MRI with targeted biopsy allows for accurate anatomical and oncological characterisation of the index prostate tumour and if this translates into improved positive surgical margin (PSM) rates after radical prostatectomy. Patients and methods Retrospective analysis of all men (n=201) who underwent robot‐assisted radical prostatectomy (RARP) between July 2012‐Juy 2014 Patients were divided into a study group (n=63) who had undergone pre‐biopsy 3T MRI, followed by visual targeted and systematic prostate biopsy; and a control group (n=138) who had undergone systematic biopsy alone. The two groups were well matched regarding patient and cancer characteristics. The primary study objective was to assess the accuracy of pre‐biopsy MRI for localising the index tumour Secondary study objectives were to assess the accuracy of MRI for the maximal tumour diameter(MTD) of the index tumour focus; and accuracy of the targeted biopsy for the Gleason score and primary Gleason grade of the index tumour focus and whether PSMs were improved after RARP The reference standard was whole gland pathology of the resected prostate gland. Continuous variables and proportions were compared using the t‐test and Mann Whitney test; or contingency tables respectively. Pearson correlation coefficient and Bland Altman plots were used to compare measurement of MTD. Results MRI accurately located the index tumour focus in 73%. Accuracies stratified according to PI‐RADS category 5, 4 and 3 were 94%, 75% and 60% respectively. Accuracies stratified according to MTD of ≤ 0.7cm, ≤1cm and > 1cm were 50%, 57% and 79% respectively. There was a positive linear correlation between MRI and histological MTD [r =0.42 (95% CI: 0.16‐0.63),; p=0.002]; but MRI generally underestimated the MTD – mean (95%CI) MRI measured MTD was 1.51cm (1.29‐1.72cm) vs. pathological MTD of 2.15cm (1.86‐2.43cm) Targeted biopsy identified 37% more cancer per core than non‐targeted biopsy. Mean (95% CI) maximal core length was 8.9mm (7.8‐10mm) vs. 6.5mm (5.8‐7.2mm); study and control groups respectively (p=0.0002;non‐paired t test) Gleason scoring was significantly more predictive after targeted biopsies, with unchanged scores in 40/63 (63%) vs. 62/138 (45%) in study and control groups respectively (p = 0.001; Fisher's test). The odds of Gleason up grading were 2.5 (p=0.028) greater in the control group. The primary Gleason grade was not significantly different in the two groups [45/63 (71%) vs. 91/138 (66%); study vs. control group respectively (p =0.51, Fisher's test)]. Overall PSMs were non‐significantly lower in the study group (15.8% vs. 18.8%; p = 0.84, Fisher's test); and the MRI location of the index tumour focus correlated with the site of PSM in 70% of cases in the study group Conclusion Pre‐biopsy MRI can accurately identify the index prostate tumour, especially in those with higher PI‐RADS grades and tumour diameter. Targeted biopsy of this focus retrieves significantly more cancerous tissue per core, and is more accurate regarding Gleason scores, but not primary Gleason grade. MRI underestimates MTD and PSMs were not significantly improved in our study This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-03T10:05:33.998399-05:
      DOI: 10.1111/bju.13525
  • Quality Improvement in Cystectomy Care with Enhanced Recovery (QUICCER
    • Authors: Janet E. Baack Kukreja; Maureen Kiernan, Bethany Schempp, Aisha Siebert, Adriana Hontar, Benjamin Nelson, James Dolan, Katia Noyes, Ann Dozier, Ahmed Ghazi, Hani H. Rashid, Guan Wu, Edward M. Messing
      Abstract: Objectives To determine if patients managed with a cystectomy enhanced recovery pathway (CERP) have improved radical cystectomy (RC) quality of care (Quality Improvement in Cystectomy Care with Enhanced Recovery‐QUICCER) defined by a decrease in length of stay (LOS) without an increase in complications or readmissions compared to those not managed with CERP. Subjects and Methods QUICCER is a non‐randomized quasi‐experimental study. Data were collected from June 2011 to April 2015. The CERP was implemented in July 2013. The primary endpoint was LOS. Secondary endpoints were quality scores, complications and readmissions. Multivariable regression was performed. Propensity score matching was done to further simulate randomized clinical trial conditions. A CERP quality composite score was created and evaluated for adherence to CERP elements. Results There were 79 CERP and 121 non‐CERP patients included. After matching, there were 75 non‐CERP patients. The LOS was significantly different. The CERP and non‐CERP groups had a median LOS of 5 days and 8 days, respectively, p < 0.001. Multivariable linear regression revealed any complication was the most significant predictor of total hospital days at 90 days after RC. The higher the quality composite score the shorter the length of stay, p < 0.001. There was no association of the CERP and increased complications or readmissions. Conclusions Audited quality measures in the CERP are associated with a reduction of LOS without increasing readmissions or complications. The CERP is important in the future improvement of RC perioperative care and provides an opportunity to improve the quality of care provided. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-03T10:05:30.848432-05:
      DOI: 10.1111/bju.13521
  • Recent advances in immuno‐oncology and the application to urological
    • Authors: Jennifer M. Mataraza; Philip Gotwals
      Abstract: Recent advances in immuno‐oncology have the potential to transform the practice of medical oncology. Antibodies directed against negative regulators of T cell function (checkpoint inhibitors), engineered cell therapies, and innate immune stimulators such as oncolytic viruses are effective in a wide range of cancers. Immune‐based therapies have had a clinically meaningful impact on the treatment of advanced melanoma and the lessons regarding use of single agents and combinations in melanoma may be applicable to the treatment of urological cancers Checkpoint inhibitors, cytokine therapy and therapeutic vaccines are already showing promise in urothelial bladder cancer, renal cell carcinoma and prostate cancer. Critical areas of future immuno‐oncology research include the prospective identification of patients who will respond to current immune‐based cancer therapies, and the identification of new therapeutic agents that promote immune priming in tumors, and increase the rate of durable clinical responses. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-03T10:05:24.354366-05:
      DOI: 10.1111/bju.13518
  • Cost‐effectiveness of zoledronic acid and strontium‐89 as bone
           protecting treatments in addition to chemotherapy in patients with
           metastatic castrate‐refractory prostate cancer: results from the
           TRAPEZE trial (ISRCTN 12808747)
    • Authors: L Andronis; I Goranitis, S Pirrie, A Pope, D Barton, S Collins, A Daunton, D McLaren, J O'Sullivan, C Parker, E Porfiri, J Staffurth, A Stanley, J Wylie, S Beesley, A Birtle, J Brown, P Chakraborti, S Hussain, M Russell, L Billingham, N James
      Abstract: Objectives To evaluate the cost‐effectiveness of adding zoledronic acid (ZA) or strontium‐89 (Sr89) to standard docetaxel chemotherapy for patients with castrate‐refractory prostate cancer (CRPC). Patients and methods Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2x2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost‐effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium‐89 versus no strontium‐89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the NHS and included expenditures for trial treatments, concomitant medications and use of related hospital and primary care services. QALYs were calculated according to patients’ responses to the generic EuroQol EQ‐5D‐3L instrument. Results are expressed as incremental cost‐effectiveness ratios (ICER) and cost‐effectiveness acceptability curves. Results The per‐patient cost for ZA was £12,667, £251 higher than the equivalent cost in the no ZA group. Patients in the ZA group experienced on average 0.03 QALYs more than their counterparts in no ZA. The incremental cost‐effectiveness ratio (ICER) for this comparison was £8,005. Sr89 was associated with a cost of £13,230, £1,365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was £16,884. The probabilities of ZA and Sr89 being cost‐effective were 0.64 and 0.60, respectively. Conclusions The addition of bone‐targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost‐savings). ZA and Sr89 resulted in ICERs below conventional willingness‐to‐pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost‐effective use of resources This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-03T04:00:39.500191-05:
      DOI: 10.1111/bju.13549
  • Urethral fixation technique improves early urinary continence recovery in
           patients who underwent Retropubic Radical Prostatectomy
    • Authors: Vincenzo Ficarra; Alessandro Crestani, Marta Rossanese, Vito Palumbo, Mattia Calandriello, Giacomo Novara, Silvio Praturlon, Gianluca Giannarini
      Abstract: Objectives to describe step by step an original urethra‐vesical anastomosis technique (Urethral fixation) in patients who underwent retropubic radical prostatectomy (RRP) and compare the observed early urinary continence recovery rates with those reported in a control group receiving a standard anastomosis technique. Moreover, we identified the predictors of early urinary continence recovery. Patients and methods We compared 70 patients who underwent RRP with urethral fixation technique with a contemporary control group of 51 patients who received RRP with a standard urethra‐vesical anastomosis. In the study group, the urethra‐vesical anastomosis was performed using 8 single stitches. Specifically, to avoid retraction and/or deviations we fixed the urethral stump laterally to the medial portion of levator ani muscle. Moreover, to maintain the normal position in the context of pelvic floor we fixed the urethra sphincter deeper to the medial dorsal rafe using a 3‐0 PDS stitch at 6 o'clock before completing the incision of the urethral wall. Urinary continence recovery was evaluated 1 week, 1, 2 and 3 months after catheter removal. Patients self‐reporting no urine leak were considered continent. Univariable and multivariable analyses were used to identify predictors of urinary incontinence at different follow‐ups. Results The two evaluated groups resulted comparable for all the pre‐operative variables. One week after catheter removal, 32 (45.7%) patients in the study group and 10 (19.6%) in the control group were continents (p=0.01), respectively. Similarly, 1 month after catheter removal, 46 (65.7%) patients in the urethral fixation group and 16 (31.4%) declared to be continent (p=0.001), respectively. Two months after catheter removal, 59 (84.3%) patients in the study group and 21 (41.2%) in the control group were continents (p
      PubDate: 2016-06-02T10:27:27.978848-05:
      DOI: 10.1111/bju.13514
  • Magnetic Resonance Microscopy May Enable Distinction Between Normal
           Histomorphological Features and Prostate Cancer in the Resected Prostate
    • Authors: Matthieu Durand; Manu Jain, Brian Robinson, Eric Aronowitz, Youssef El Douahy, Robert Leung, Douglas S. Scherr, Amelia Ng, Dominique Donzeau, Jean Amiel, Pascal Spincemaille, Arnauld Villers, Douglas J. Ballon
      Abstract: Introduction In vivo high‐resolution magnetic resonance imaging (MRI) at a microscopic level for the identification of prostate cancer (PCa) has not yet been achieved. This may be accomplished using MRI with high spatial resolution for ex vivo examination of prostate specimens. The objective was to determine imaging protocol parameters for characterization of prostate tissue at histologic length scales. Material and Methods Rapid acquisition with relaxation enhancement (RARE), spin echo (SE) and gradient echo (GRE) fast low angle shot (FLASH) data were acquired using ex vivo 3 Tesla or 7 Tesla magnetic field strengths from fresh prostatectomy specimens (n=15) obtained from either organ donor or PCa patients under Institutional Review Board approval. To achieve the closest correspondence between histopathological components and MRI images in terms of resolution and sectioning planes, multiple high resolution imaging protocols (ranging from few minutes to overnight) were tested. Ductograms were generated as part of image post‐processing. Specimens were subsequently submitted for histopathological evaluation. Results and Limitations A total of 7 imaging protocols were tested. Ex vivo 7 Tesla MRI identified normal components of prostate glands including ducts, blood vessels, concretions, and stroma at a spatial resolution of 60 X 60 X 60 μm3 to 107 X 107 X 500 μm3. Malignant glands and nests of tumor cells identified at 60 X 60 X 90 μm3 were highly comparable to low magnification (x2) histopathology. Ductograms enhanced the differentiation between benign and malignant glands. The results of this study are encouraging, and further work is warranted with a higher sample size. Conclusion We demonstrated that critical histopathological features of the prostate gland can be identified with high resolution ex vivo MRI examination and offer promise that MR microscopy of PCa will ultimately be possible in vivo. This article is protected by copyright. All rights reserved.
      PubDate: 2016-06-01T22:55:39.085473-05:
      DOI: 10.1111/bju.13523
  • If the robot is there, why not use it' Why we should use the robot for
           laparoscopic nephrectomy
    • Authors: Wayne Lam; Mollika Chakravorty, Ben Challacombe
      Abstract: Robot‐assisted laparoscopic nephrectomy (RALN) was first described over 10 years ago [1]. However, with the wide availability of established and experienced laparoscopic surgeons, investigation into the role and potential benefits of RALN has been limited. Many consider RALN to bare no additional benefits over laparoscopic radical nephrectomy (LRN) but see it as merely expensive, and regard it as ‘technical overtreatment’. On the other hand, robotic surgery improves laparoscopic dexterity with a better range of movement, three‐dimensional vision, tremor filtration, and motion scaling leading to better eye‐hand coordination. It is a tool for complex laparoscopic surgery and is indeed a very good one, but is there a role for RALN' This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-29T21:55:26.622065-05:
      DOI: 10.1111/bju.13509
  • Testosterone Undecanoate improves Sexual Function in Men with Type 2
           diabetes and Severe Hypogonadism: Results from a 30 week randomized
           placebo controlled study
    • Authors: Geoffrey Hackett; Nigel Cole, Atif Saghir, Peter Jones, Richards C. Strange, Sudarshan Ramachandran
      Abstract: Objective To evaluate the Sexual Function response to 30 weeks treatment with Long Acting Testosterone Undecanoate (TU) or Placebo (P) 199 men with type 2 diabetes and either severe or mild hypogonadism. Patients and Methods Men with hypogonadism (HG) were identified from 7 primary care T2DM registers. A 30 week randomised placebo controlled study of TU was carried out in 199 of these men (P: 107, TU: 92). The patient reported outcome measure was the IIEF ‐15. Men completing the study (n=189) were stratified firstly, by baseline total testosterone (TT) / free testosterone (FT) into Mild HG (TT 8.1–12nmol/l or FT 0.18‐0.25nmol/l) and Severe HG groups (TT ≤8nmol/l and FT ≤0.18nmol/l) and secondly by intervention (P and TU) leading to 4 groups; Mild HG/P, Mild HG/TU, Severe HG/P and Severe HG/TU. Statistical Analysis Changes in sexual function score (a secondary outcome of the study) at each visit within group (cf. baseline) and between groups (TU vs P) at each assessment (6, 18 and 30 weeks) were compared using Wilcoxon signed‐rank and Wilcoxon rank sum tests respectively. Results Significant improvement in erectile function was evident only in the Severe HG group following TU after 30 weeks, this finding also present when TU was compared to P. Intercourse satisfaction and sexual desire scores were also improved in the Severe HG group following TU at 6, 18 and 30 weeks, this increase in scores also evident when compared to P. TU did not appear to significantly alter orgasmic function in any of the patient groups. Conclusions Our study suggests that benefit in sexual symptoms following TU was evident principally in patients with HG with TT ≤8nmol/l and FT ≤0.18nmol/l. We also suggest 30 weeks of treatment is necessary before evaluating improvement in erectile function. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-27T07:30:49.738261-05:
      DOI: 10.1111/bju.13516
  • Robot‐assisted Fallopian Tube Transection‐anastomosis using
           the New REVO‐I Robotic Surgical System: Feasibility in a Chronic
           Porcine study
    • Authors: Ali Abdel Raheem; Irela Soto Troya, Dae Keun Kim, Se hoon Kim, Park Dong Won, Park Sung Joon, Gim Soo Hyun, Koon Ho Rha
      Abstract: Objectives Fallopian tube anastomosis is used for basic robotic training (Intuitive Surgical) because it emphasizes the unique advantages of a robotic surgical system (fine motor movements required for intracorporeal suturing, 3D vision, motion scaling, and tremor control). Furthermore, fallopian tube anastomosis resembles robotic radical prostatectomy in regards to port placement, pelvic area approach, and urethrovesical anastomosis. The aim of our study was to evaluate the feasibility and safety of the new REVO‐I robotic platform by performing fallopian tube transection‐anastomosis in live porcine models. Material and Methods A prospective chronic animal study was carried out in four Crossbred female pigs. The primary outcome was assessment of the pigs’ 2‐week survival. The secondary outcomes were measurements of intraoperative parameters and the complications or difficulties when using the REVO‐I. Results Fallopian tube anastomosis was successfully performed in 4 porcine models. The mean operative time was 66 min (range: 46‐104 min), the mean docking time was 22.25 min (range: 14–53 min), and the mean console time was 18 min (range: 13–20 min). The REVO‐I robotic system functioned appropriately, with no technical problems or difficulties noted during the procedures. Both the surgeon and the bed‐side assistants reported ease of use and better performance with subsequent procedures. All pigs were alive 2 weeks after surgery, with no perioperative complications related to the use of the robot. Conclusions The current pre‐clinical chronic animal study revealed that the REVO‐I robotic surgical system is a feasible and safe robotic instrument that can be used by surgeons to perform skillful robotic procedures in porcine models. Our next objective is to demonstrate its safety in humans. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-26T19:45:41.212882-05:
      DOI: 10.1111/bju.13517
  • Mirabegron causes relaxation of human and rat corpus cavernosum: could it
           be a potential therapy for erectile dysfunction'
    • Authors: Serap Gur; Taylor Peak, Faysal A. Yafi, Philip J. Kadowitz, Suresh C. Sikka, Wayne J.G. Hellstrom
      Abstract: Objective To examine the effects of mirabegron, a selective β3‐AR agonist that has recently been approved for the treatment of overactive bladder, in rat and human erectile tissues with a focus on elucidating the mechanism of such an action. Stimulation of β3‐adregenic receptors (ARs) localized in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacologic action for the patient who has overactive bladder and erectile dysfunction (ED). Materials and Methods Corpus cavernosal (CC) specimens were obtained from patients with ED and Peyronie's disease undergoing penile prosthesis implantation. Erectile responses were also evaluated in vivo following intracavernosal injection (ICI) of mirabegron in anesthetized rats. Mirabegron‐elicited relaxation responses (10‐8‐10‐3 M) on phenylephrine (Phe)‐induced contraction were observed in human and rat CC strips in isolated organ bath studies. The effects of inhibitors namely L‐NAME [N(G)‐nitro‐L‐arginine methyl ester (a competitive inhibitor of NO synthase), 100μM), ODQ [1H‐(1,2,4) oxadiazolo(4,3‐α) quinoxalin‐1‐one (a nitric oxide‐sensitive guanylyl cyclase (GC) inhibitor, 30μM), methylene blue (a NOS and GC inhibitör, 20μM), SR59230A (β3‐AR blocker, 1 μM), and fasudil (Rho‐kinase (ROCK) inhibitor, 0.1 μM)] on mirabegron‐induced relaxation responses were evaluated. Responses to mirabegron were compared with responses to isoprenaline and nebivolol. Immunohistochemistry was used to localize β3‐AR and ROCK in CC smooth muscle cells. In vivo rat data were expressed as intracavernosal pressure (ICP)/mean arterial pressure and total ICP. Results Mirabegron resulted in a relaxation of Phe‐evoked CC contractions in a concentration‐dependent manner and SR59230A antagonized mirabegron‐induced relaxations in human and rat CC. Other inhibitors, L‐NAME, ODQ, and methylene blue, did not affect the mirabegron‐induced relaxation responses. Mirabegron relaxation responses at concentrations (between 0.1 and 10μM) were enhanced by fasudil (ROCK inhibitor) in rat but not in human CC strips. KCl‐induced contractions in human and rat CC were partially inhibited by mirabegron. In vivo ICI of mirabegron (doses of 0.1 – 1 mg/kg) had a minor effect on ICP when compared to vehicle administration. Immunohistochemistry data showed β3‐ARs localization into the smooth muscle cells of human and rat CC. Conclusions Mirabegron markedly relaxed isolated CC strips by activating β3‐ARs independently of the NO‐cGMP pathway. There is also evidence of the existence of a close functional link between β3‐ARs and the RhoA/ROCKpathway. These results may support further clinical studies using combinations of mirabegron with ROCK and phosphodiesterase‐5 inhibitors (PDE5i) for the treatment of ED, especially in patients who do not respond to PDE5i therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-26T19:45:36.786185-05:
      DOI: 10.1111/bju.13515
  • Trends in urological stone disease: a 5‐year update of Hospital
           Episode statistics
    • Authors: Hendrik Heers; Benjamin W. Turney
      Abstract: Objective To provide a 5‐year follow‐on update on the changes in prevalence and treatment of upper urinary tract stone disease in the UK. Methods Data from the Hospital Episode Statistics (HES) website (w w w hesonline . nhs . uk ) were extracted, summarized, analysed and presented. Results The total number of upper urinary tract stone hospital episodes increased slightly from 83,050 in 2009‐10 to 86,742 in 2014‐15 (4.4% increase). The use of shock wave lithotripsy (SWL) for treating all upper tract stones remained stable over the 5‐year study period following a significant increase in previous years. There was a 49.6% increase in the number of ureteroscopic stone treatments from 12,062 in 2009‐10 to 18,055 in 2014‐15. Increase in ureterorenoscopy (flexible ureteroscopy) demonstrated the most rapid increase from 3267 to 6631 cases in the 5‐year study period (103% increase). The gap between the total number of ureteroscopies and SWL treatments continues to narrow. Open stone surgery continued to decline with only 30 reported cases in 2014‐15. Due to the continued rapid increase in the number of ureteroscopies performed, treatment for stone disease has continued to increase significantly in comparison to other urological activity. Conclusion This study provides an update on the changing landscape of the management of urinary tract stones in the UK. It demonstrates a sustained high prevalence of stone disease in the UK commensurate with levels in other developed countries. This study reveals a trend in the last 5 years to surgically intervene on a higher proportion of patients with stones. As in other countries, there is a significant increase in the use of ureteroscopy (particularly intrarenal flexible ureteroscopy) in the UK. These data have important implications for work‐force planning, training, service delivery and research in the field of urolithiasis. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-26T02:20:38.603941-05:
      DOI: 10.1111/bju.13520
  • Outcomes of high complex renal tumor (PADUA ≥ 10) following
           robot‐assisted partial nephrectomy with a median 46 months
           follow‐up: A tertiary center experience
    • Authors: Ali Abdel Raheem; Atalla Alatawi, Dae K. Kim, Abulhasan Sheikh, Ibrahim Alabdulaali, Woong K. Han, Young D. Choi, Koon H. Rha
      Abstract: Objectives To compare peri‐operative trifecta achievement and long‐term oncological and functional outcomes between low (6‐7), intermediate (8‐9) and high (≥10) PADUA complex renal tumors and to determine predictors for trifecta achievement. Material and Methods A retrospective analysis of data from 295 patients, who underwent RPN between 2006 to 2015 at high‐volume tertiary center was performed. Trifecta achievement was the main primary outcome measurement. The perioperative parameters and long‐term oncological and functional outcomes were the secondary outcome measurements. Groups were compared using Kruskal‐Wallis H test or chi‐square. Univariable and multivariable binary logistic regression analyses were performed to determine the most important determinant variables associated with trifecta accomplishment. The Kaplan‐Meier method was used to estimate for overall survival (OS), cancer‐specific survival (CSS) and cancer‐free survival (CFS). Results Out of 295 patients, 121 (41%) had PADUA score ≥10. Patients in high complex PADUA group had a larger tumor size, higher clinical stage ≥T1b, an increased risk of malignancy, longer warm ischemia time (WIT) and increased estimated blood loss (EBL) compared to intermediate and low complex groups (p=
      PubDate: 2016-05-26T02:20:33.22828-05:0
      DOI: 10.1111/bju.13501
  • Characterizing the Safety of Clomiphene Citrate in Male Patients through
           PSA, Hematocrit, and Testosterone levels
    • Authors: Jason C. Chandrapal; Spencer Nielson, Darshan P. Patel, Chong Zhang, Angela P. Presson, William O. Brant, Jeremy B. Myers, James M. Hotaling
      Abstract: As Pharmaceutical companies increase direct marketing of testosterone products, more men are being tested for low testosterone and initiating testosterone supplementation. (1) From 2001‐2011, androgen use among men 40 years or older increased over three fold from 0.81% in 2001 to 2.91% in 2011. (2) The leading treatment for men with hypogonadism is exogenous testosterone; however it is not without risks. Though testosterone supplementation improves sexual desire and libido, it also has a negative effect on fertility. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-25T21:45:42.384792-05:
      DOI: 10.1111/bju.13546
  • Early MAG‐3 diuretic renography results after pyeloplasty
    • Authors: Alice Faure; Kevin London, Grahame H.H. Smith
      Abstract: Objectives To describe the drainage and functional outcome following paediatric pyeloplasty, one week after stent removal (seven to nine weeks after pyeloplasty) using diuretic renography. Patients and Methods Between 2009 and 2014, we assessed the functional and drainage outcomes on mercaptoacetyltriglycine (MAG‐3) diuretic renograms from 66 children (69 kidneys) who underwent modified dismembered Anderson‐Hynes pyeloplasty for UPJ obstruction. Stents were left in place for 6 to 8 weeks and postoperative renal units were evaluated with MAG‐3 renogram one week after stent removal. Surgical success was defined by improvement of drainage (T/2 less than 20 min), stable or improved function on the postoperative MAG‐3 renogram and by decreased pyelocaliceal dilatation on US at one year. Results Of the 69 kidneys with preoperative median T/2 of 33.4 min (range 7.6‐200 min), 87% (60/69) had improved drainage curves with a median T/2 of 6.9 min (range 1.6‐19 min). Thirteen percent (9/69) had persistent impaired drainage with a median T/2 of 36 min (range 24‐108 min). One girl was found with a persistent obstructive pattern (T/2= 30 min) associated with a decreased SRF (from 42 to 33%) and a persistent hydronephrosis (at 28mm). Redo‐pyeloplasty was performed 2 months after the initial procedure (and 18 days after stent removal) and renal function recovered to 47%. All other 8 patients were free of symptoms; hydronephrosis improved at 1 year (anteroposterior diameter decreased from 28 to 18.5 mm, p=1.94) and SRF remained stable (44.5% versus 48.5% after repair, p=ns). Of the 29% (20/69) that had preoperative impaired SRF, postoperative renal function improved in 75% (from 27.5 to 43%, p=0.0002), remained unchanged in 2% and one (0.2%) deteriorated. Median postoperative follow‐up was 18 months (range 12‐90 months). Discussion There is no agreement regarding the gold standard investigation to use following pyeloplasty for ureteroplevic junction (UPJ) obstruction. Improvement in hydronephrosis on ultrasound (US) is slow and often takes more than 12 months. Based on animal studies, it is possible that missed recurrent obstruction will cause irreversible loss of renal function after 6 weeks. Therefore early postoperative assessment is desirable but there have been few reports on urinary drainage changes with early diuretic renography after pyeloplasty. Conclusion Most of renal units have improved drainage on diuretic renography 7 weeks after pyeloplasty and 1 week after stent removal. An early diuretic renogram is a reliable method of documenting surgical success after pyeloplasty. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-25T08:00:26.497543-05:
      DOI: 10.1111/bju.13512
  • Estimating the risks and benefits of Active Surveillance protocols for
           Prostate Cancer: A microsimulation study
    • Authors: Tiago M. de Carvalho; Eveline A.M. Heijnsdijk, Harry J. de Koning
      Abstract: Objective To estimate the increase in prostate cancer mortality (PCM) and the reduction in overtreatment resulting from different Active Surveillance (AS) protocols, compared to treating men immediately. Subjects and Methods We use a microsimulation model (MISCAN‐Prostate), with natural history based on ERSPC data. We estimate probabilities of referral to radical treatment while on AS, depending on disease stage, with data from John Hopkins AS cohort. We sample 10 million men representative of the US population and we project the effects of applying AS protocols differing by time between biopsies, compared to treating men immediately. Results AS with yearly follow‐up biopsies for low‐risk patients (≤ T2a‐stage and Gleason 6) increases the probability of PCM to 2.6% (1% increase) and reduces overtreatment from 2.5% to 2.1% (18.4% reduction). With biopsies every three years after the first year, PCM increases by 2.3% and overtreatment reduces from 2.5% to 1.9% (30.3% reduction). Including intermediate‐risk men (> T2a‐stage or Gleason 3+4) in AS increases PCM by 2.7% and reduces overtreatment from 2.5% to 2.0% (23.1% reduction). These results may not apply to African‐American men. Conclusions Offering AS for low‐risk patients is relatively safe. Increasing the biopsy interval from yearly to up to every 3 years after the first year, will significantly reduce overtreatment among low‐risk men, with limited PCM risk. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-25T00:54:12.656075-05:
      DOI: 10.1111/bju.13542
  • Performance of Robotic Simulated Skills Tasks is Positively Associated
           with Clinical Robotic Surgical Performance
    • Authors: Monty A. Aghazadeh; Miguel A. Mercado, Michael M. Pan, Brian J. Miles, Alvin C. Goh
      Abstract: Objective To compare user performance of four Fundamental Inanimate Robotic Skills Tasks (FIRST) as well as eight da Vinci Skills Simulator (dVSS) virtual reality tasks to intraoperative performance (concurrent validity) during robotic prostatectomy (RP). Our group has previously demonstrated face, content, and construct validity of these simulated robotic skills tasks. As there is no data in the robotic environment showing a significant relationship between simulation and clinical performance, we aim to show that a positive correlation exists between simulation and intraoperative performance. Materials and Methods Twenty‐one urologic surgeons of varying robotic experience were enrolled. Demographics were captured using a standardized questionnaire. User performance was assessed concurrently in simulated (FIRST exercises and dVSS tasks) and clinical environments (endopelvic dissection during RP). Intraoperative robotic clinical performance was scored using the previously validated 6‐metric Global Evaluative Assessment of Robotic Skills (GEARS) tool. Relationship between simulator and clinical performance was evaluated using Spearman's rank correlation. Results Performance was assessed in 17 trainees and 4 expert robotic surgeons with a median (range) number of previous robotic cases (as primary surgeon) of 0 (0‐55) and 117 (58‐600), respectively (p=0.001). Collectively, the overall FIRST (ρ=0.833, p
      PubDate: 2016-05-24T10:10:26.836047-05:
      DOI: 10.1111/bju.13511
  • Evolution and oncological outcomes of a contemporary radical prostatectomy
           practice in a UK regional tertiary referral centre
    • Authors: Vincent J. Gnanapragasam; David Thurtle, Anandagopal Srinivasan, Dimitrios Volanis, Anne George, Artitaya Lophatananon, Sara Stearn, Anne Y. Warren, Alastair D. Lamb, Greg Shaw, Naomi Sharma, Ben C. Thomas, Maxine G. Tran, David E. Neal, Nimish C. Shah
      Abstract: Objective To investigate the clinical and pathological trends over a ten‐year period for robotic‐assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. Patients and Methods 1500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data was collected on clinic‐pathological details at presentation as well as surgical outcomes and compared over time. Results The median(range) age of patients throughout the period was 62(35‐78) years. The proportion of pre‐operative high‐grade cases (Gleason sum 8‐10) rose from 4.6% in 2005‐2008 to 18.2% in 2013‐2015 (p
      PubDate: 2016-05-24T07:10:23.116148-05:
      DOI: 10.1111/bju.13513
  • Toxicity and efficacy of salvage 11C‐Choline PET/CT‐guided
    • Authors: Andrei Fodor; Genoveffa Berardi, Claudio Fiorino, Maria Picchio, Elena Busnardo, Margarita Kirienko, Elena Incerti, Italo Dell'Oca, Cesare Cozzarini, Paola Mangili, Marcella Pasetti, Riccardo Calandrino, Luigi Gianolli, Nadia G Di Muzio
      Abstract: Objective To report the 3‐year toxicity and outcome results of 11C‐Choline positron emission tomography/computed tomography (11C‐Ch‐PET/CT)‐guided radiotherapy, delivered with helical tomotherapy (Tomotherapy® Hi‐Art II® Treatment System, Accuray Incorporated, USA) (HTT) of lymph‐nodal (LN) relapses in prostate cancer patients. Patients and methods From 01/2005 to 03/2013, 81 patients with biochemical recurrence – after surgery±adjuvant/salvage radiotherapy (RT) or radical RT and with evidence of LN 11C‐Ch‐PET/CT pathological uptake underwent HTT (median PSA: 2.59(0.61‐187) ng/ml). 72/81 patients were treated on pelvic and/or lumbar‐aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost (SIB) to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C‐Ch‐PET/CT. Nine patients were treated without SIB(50‐65.5 Gy, 25‐30 fr). Results With a median follow‐up of 36 (9‐116) months, 91.4% of the patients presented a PSA reduction 3 months after HTT. The 3 year overall, local‐relapse‐free and clinical‐relapse‐free survival were 80.0%, 89.8% and 61.8%, respectively. The 3‐year actuarial incidences of ≥G2 rectal and ≥G2 GU toxicity were 6.6% (± 2.9%) and 26.3% (±5.5%) respectively. A PSA nadir ≥0.26 ng/ml (HR:3.6; 95%CI 1.7‐7.7, p=0.001), extra‐pelvic 11C‐Ch‐PET/CT positive LN location (HR:2.4; 95%CI 0.9‐6.4, p=0.07), RT previous to HTT (HR:2.7; 95% CI 1.07‐6.9, p=0.04) and number of positive LN (HR:1.13; 95%CI 1.04‐1.22, p=0.003) were the main predictors of clinical relapse after HTT . Conclusions 11C‐Ch‐PET/CT‐guided HTT is safe and effective in the treatment of LN relapses of previously treated prostate cancer patients. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-24T02:40:35.961914-05:
      DOI: 10.1111/bju.13510
  • High PCA3 scores are associated to elevated Prostate Imaging Reporting and
           Data System (PI‐RADS) grade and biopsy Gleason Score, at MRI/US
           fusion software‐based targeted prostate biopsy after a previous
           negative standard biopsy
    • Authors: Stefano De Luca; Roberto Passera, Giovanni Cattaneo, Matteo Manfredi, Fabrizio Mele, Cristian Fiori, Enrico Bollito, Stefano Cirillo, Francesco Porpiglia
      Abstract: Objective to determine the association among PCA3 score, Prostate Imaging Reporting and Data System (PI‐RADS) and Gleason Score (GS), in a cohort of patients with elevated PSA, undergoing MRI/US fusion software‐based targeted prostate biopsy (TBx) after a previous negative randomized “standard” biopsy (SBx) Patients and Methods 282 patients, undergone to TBx after previous negative SBx and PCA3 urine assay, were enrolled. The associations PCA3 score/PI‐RADS and PCA3 score/GS were investigated by K‐means clustering, ROC analysis and binary logistic regression model Results PCA3 score difference for negative versus positive TBx cohorts was highly statistically significant. One unit of increase in PCA3 score was associated to a 2.4% increased risk to have a positive TBx result. PCA3 score>80 and PI‐RADS≥4 were independent predictors for a positive TBx. The association between PCA3 score and PI‐RADS was statistically significant (PCA3 score median value for PI‐RADS groups 3‐4‐5 was 58‐104‐146, respectively; p=0.006). A similar pattern was detected for the relationship between PCA3 score and GS; an increasing PCA3 score was associated to a worse GS (median PCA3 score equal to 62‐105‐132‐153‐203‐322 for GS 3+4, 4+3, 4+4, 4+5, 5+4, 5+5, respectively; p
      PubDate: 2016-05-24T02:40:30.047294-05:
      DOI: 10.1111/bju.13504
  • Comparison of prostate cancer survival in Germany and the United States:
           Can differences be attributed to differences in stage distributions'
    • Authors: Alexander Winter; Eunice Sirri, Lina Jansen, Friedhelm Wawroschek, Joachim Kieschke, Felipe A. Castro, Agne Krilaviciute, Bernd Holleczek, Katharina Emrich, Annika Waldmann, Hermann Brenner,
      Abstract: Objectives To better understand influence of prostate‐specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer (PCa), up‐to‐date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States (US). Patients and Methods Incidence and mortality rates for Germany and the US for the period 1999 to 2010 were obtained from the Center for Cancer Registry Data at the Robert Koch Institute and the US Surveillance Epidemiology and End Results (SEER) database. For analyses on stage and survival, data from 12 population‐based cancer registries in Germany and from the SEER‐13 database were analyzed. Patients (≥15 years) diagnosed with PCa (1997‐2010), with mortality follow‐up to December 2010 were included. 5‐ and 10‐year RS and survival trends (2002‐2010) were calculated using standard and model‐based period analysis. Results Between 1999 and 2010, PCa incidence decreased in the US but increased in Germany. Nevertheless incidence remained higher in the US throughout the study period (99.8 vs. 76.0 per 100,000 in 2010). The proportion of localized disease significantly increased from 51.9% (1998‐2000) to 69.6% (2007‐2010) in Germany and from 80.5% (1998‐2000) to 82.6% (2007‐2010) in the US. Mortality slightly decreased in both countries (1999‐2010). Overall, 5‐ and 10‐year RS was lower in Germany (93.3%; 90.7%) than in the US (99.4%; 99.6%) but comparable after adjustment for stage. The same patterns were observed in age‐specific analyses. Improvements observed in PCa survival between 2002‐2004 and 2008‐2010 (5‐year RS: 87.4; 91.2; +3.8% units) disappeared after adjustment for stage (p=0.8). Conclusion The survival increase in Germany and the survival advantage in the US might be explained by differences in incidence and stage distributions over time and across countries. Effects of early detection or a lead time bias due to the more widespread utilization and earlier introduction of PSA testing in the US are likely to explain the observed patterns. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-21T09:25:47.721342-05:
      DOI: 10.1111/bju.13537
  • Analysis of the sperm functional aspects and seminal plasma proteomic
           profile from male smokers
    • Authors: M. P. Antoniassi; P. Intasqui Lopes, M. Camargo, D. S. Zylbersztejn, V. M. Carvalho, K. H. M. Cardozo, R. P. Bertolla
      Abstract: Objective To evaluate the effect of smoking on sperm functional quality and seminal plasma proteomic profile. Patients And Methods Sperm functional tests were performed in 20 nonsmoking men with normal semen quality, according to the World Health Organization (2010) and in 20 smoking patients: evaluation of DNA fragmentation by alkaline Comet assay; analysis of mitochondrial activity using DAB staining; and acrosomal integrity evaluation by PNA binding. Remaining semen was centrifuged and seminal plasma was utilized for proteomic analysis (LC‐MS/MS). The quantified proteins were used in Cytoscape 3.2.1 software for Venn diagrams construction, using the PINA4MS plugin. Then, differentially expressed proteins were also used for functional enrichment analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes and Reactome, using the Cytoscape software and the ClueGO 2.2.0 plugin. Results Smokers presented higher percentage of sperm DNA damage (Comet classes III and IV, p
      PubDate: 2016-05-21T09:20:29.809823-05:
      DOI: 10.1111/bju.13539
  • A retrospective analysis of laparoscopic partial nephrectomy with
           segmental renal artery clamping and parameters that estimate postoperative
           renal function
    • Authors: Pu Li; Chao Qin, Qiang Cao, Jie Li, Qiang Lv, Xiaoxin Meng, Xiaobing Ju, Lijun Tang, Pengfei Shao
      Abstract: Objective To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyze the factors affecting postoperative renal function. Patients And Methods A retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (Group A, n = 152) or segmental artery clamping (Group B, n = 314) from September 2007 to July 2015 in our department. Blood loss, operative time, warm ischemia (WI) time, and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated glomerular filtration rate (eGFR) of a subset of 60 patients in Group B were compared with GFR to evaluate the correlation between these functional parameters in predicting preserved renal function after LPN. Results The novel technique slightly increased operative time, WI time and intraoperative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with conventional technique. The blocking method and tumor characteristics were independent factors affecting GFR reduction, while WI time was not independent factors. Correlation analysis showed that eGFR presented better correlation with GFR compared with kidney volume (R2 = 0.794 cf. R2 = 0.199) in predicting renal function after PN.. Conclusions LPN with segmental artery clamping minimizes WI injury and provides for better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-21T01:40:42.058569-05:
      DOI: 10.1111/bju.13541
  • Prospective Evaluation of 68Gallium‐PSMA Positron Emission
           Tomography/Computerized Tomography for Preoperative Lymph Node Staging in
           Prostate Cancer
    • Authors: Pim J. van Leeuwen; Louise Emmett, Bao Ho, Warick Delprado, Francis Ting, Quoc Nguyen, Phillip Stricker
      Abstract: Objectives Conventional imaging techniques are inadequate for lymph node staging in prostate cancer (PC). This study aims to assess the accuracy of 68Ga‐PSMA positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in intermediate and high‐risk PC. Materials and Methods From April to October 2015, 30 patients with intermediate (n=3) or high‐risk (n=27) PC were prospectively enrolled. Patients underwent preoperative 68Ga‐PSMA PET/CT. Both visual and semi quantitative analysis was undertaken. Subsequently, all patients underwent a radical prostatectomy with an extended pelvic lymph node dissection (eLND). Sensitivity, specificity, positive and negative predictive value (PPV and NPV) for LN status of 68Ga‐PSMA were calculated using histopathology as reference. Results Eleven patients (37%) had lymph node metastases (LNMs), 26 LNMs were identified in the 11 patients. On a patient analysis, 68Ga‐PSMA PET/CT has a sensitivity of 64% for the detection of LNMs, specificity was 95%, PPV was 88%, and NPV was 82%. In total, 180 LN fields were analyzed. For the LN‐region‐based analysis, the sensitivity of 68Ga‐PSMA PET/CT for detection of LNMs was 56%, specificity was 98%, PPV was 90% and NPV was 94%. Mean size of missed LNMs was 2.7mm. Receiver operating characteristic (ROC) analysis demonstrated high accuracy of SUV max for the detection of LNMs, AUC 0.915 (95%CI 0.847‐0.983); optimum SUV max was 2.0. Conclusions In patients with intermediate to high‐risk PC, 68Ga‐PSMA PET/CT has a high specificity and a moderate sensitivity for LNM detection. 68Ga‐PSMA PET/CT has the potential to replace current imaging for LN staging of patients with PC scheduled for radical prostatectomy. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-21T01:35:28.35308-05:0
      DOI: 10.1111/bju.13540
  • Correlation between stage shift and differences in mortality in the
           European Randomized study of Screening for Prostate Cancer (ERSPC)
    • Authors: Leonard P. Bokhorst; Marco Zappa, Sigrid V. Carlsson, Maciej Kwiatkowski, Louis Denis, Alvaro Paez, Jonas Hugosson, Sue Moss, Anssi Auvinen, Monique J. Roobol
      Abstract: A 21% prostate cancer (PCa) mortality reduction was observed in the European Randomized Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow‐up. A direct correlation between stage shift and changes in PCa‐mortality would support earlier detection through screening as the main reason for this reduction. In this study we empirically estimate how changes in the risk of being diagnosed with (advanced) PCa are related to the changes in PCa death in the ERSPC using a meta‐regression approach. In total 81% and 89% of the changes in PCa mortality could be explained by changes in PCa incidence. Although this analysis cannot show direct causal relations, results support the hypothesis that PSA screening reduced PCa mortality by detecting cancer at an earlier stage while still curable. These findings do however not open the way to unrestricted PSA based screening for PCa. A balance between harm and benefit needs to be found. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-20T22:05:28.058554-05:
      DOI: 10.1111/bju.13505
  • Detecting Positive Surgical Margins: Utilization of Light Reflectance
           Spectroscopy on ex vivo Prostate Specimens
    • Authors: Aaron H. Lay; Xinlong Wang, Monica S. C. Morgan, Payal Kapur, Hanli Liu, Claus G. Roehrborn, Jeffrey A. Cadeddu
      Abstract: Objective To assess the efficacy of Light reflectance spectroscopy (LRS) to detect positive surgical margins (PSM) on ex vivo radical prostatectomy specimens. Materials and Methods A prospective evaluation of ex vivo prostate specimens using LRS was performed at a single institution from June 2013 to September 2014. LRS measurements were performed on selected sites on prostate capsule, marked with ink, and correlated with pathologic analysis. Significant features on LRS curves differentiating malignant tissue from benign tissue were determined using a forward sequential selection algorithm. A logistic regression model was built and randomized cross‐validation was performed. The sensitivity, specificity, accuracy, NPV, PPV, and area under the receiver operating characteristic curve (AUC) for LRS predicting PSM were calculated. Results Fifty prostate specimens were evaluated using LRS. LRS sensitivity for Gleason ≥7 PSM was 91.3%, specificity 92.8%, accuracy 92.5%, PPV 73.2%, NPV 99.4%, and AUC = 0.960. LRS sensitivity for Gleason ≥6 PSM was 65.5%, specificity 88.1%, accuracy 83.3%, PPV 66.2%, NPV 90.7%, and AUC = 0.858. Conclusions LRS can reliably detect positive surgical margins for Gleason 7 or above prostate cancer in ex vivo radical prostate specimens This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-20T04:01:54.465028-05:
      DOI: 10.1111/bju.13503
  • Attitudes and Knowledge of Urethral Catheters: A Targeted Educational
    • Authors: Andrew Cohen; Charles Nottingham, Vignesh Packiam, Nora Jaskowiak, Mohan Gundeti
      Abstract: Objectives To assess the training of medical students and their confidence in urethral catheter placement, given growing evidence of unnecessary urology consults and iatrogenic injury. Methods A third‐year medical school class was queried regarding their attitudes and knowledge of catheter placement prior to and after the Clinical Biennium. The Clinical Biennium introduces hands on skills prior to clinical clerkships. Urethral catheterization is one of the skill stations that students rotate through, and urology residents provide a didactic session and supervised simulation. Confidence was self‐rated regarding catheter technique, knowledge, troubleshooting, and comfort with placement in same and opposite gender. Factual questions were posed regarding proper insertion and malfunctioning catheters. Results Ninety‐two students participated in the initial survey, 41% female and 59% male. 87% of students had never placed a catheter. Students desired high confidence in catheter skills (4.4/5). There were no significant differences in responses for those with desire to pursue urology vs. other specialties, or procedural fields compared to non‐procedural fields. Prior independent learning was reported by 38% of students and was a predictor for increased confidence across all domains (p
      PubDate: 2016-05-18T02:41:01.612208-05:
      DOI: 10.1111/bju.13506
  • Robotic assisted technique for boari flap ureteral reimplantation
           (RA‐BFUR): replicating the techniques of open surgery in robotics
    • Abstract: The video describes our approach of a Robotic assisted Boari Flap Ureteral Reimplantation (RA‐BFUR). The technique is based on the open surgical technique of Übelhör. The experience includes 11 cases with excellent results after a mean follow‐up period of more than 12 months. RA‐BFUR could be considered as a safe and effective method of ureteral reimplantation of long distal ureteral strictures. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-17T01:35:36.566988-05:
      DOI: 10.1111/bju.13502
  • Results of a randomized, double‐blind, active‐controlled
           clinical trial with propiverine ER 30 mg in patients with overactive
    • Authors: Jing Leng; Limin Liao, Ben Wan, Chuanjun Du, Wei Li, Keji Xie, Zhoujun Shen, Zhuoqun Xu, Shiliang Wu, Zujun Fang, Lulin Ma, Shaomei Han, Cornelia Feustel, Yong Yang, Helmut Madersbacher
      Abstract: Objective To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg extended release formulation of tolterodine tartrate in patients with overactive bladder in a non‐inferiority trial. Patients and methods Eligible patients aged between 18 and 75 years with symptoms of OAB were enrolled in this multicentre, randomized, double‐blind, parallel‐group, active‐controlled study. After a 2‐week screening period patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8‐weeks treatment period. The efficacy was assessed using a 3‐days voiding diary and patient's self‐reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post void residual urine, and electrocardiograms. Results A total of 324 patients (244 female, 80 male) were allocated into the study. Both active treatments improved the variables of the voiding diary and patient's self‐reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared to the tolterodine ER 4 mg group after 8 weeks of treatment (FAS; ‐4.6±4.1 vs. ‐3.8±5.1, p=0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (p=0.026) and 8 weeks (p=0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated with a comparable frequency of adverse drug reactions between propiverine ER 30 mg and tolterodine ER 4 mg (FAS; 40.7% vs. 39.5%, p=0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment due to adverse drug reactions compared to propiverine ER 30 mg (7.4% vs. 3.1%). Conclusions Propiverine ER 30 mg was confirmed to be an effective and well‐tolerated treatment option for patients suffering from overactive bladder symptoms. This first head‐to‐head study demonstrated non‐inferiority of propiverine ER 30 mg compared to tolterodine ER 4 mg. This article is protected by copyright. All rights reserved.
      PubDate: 2016-05-13T03:45:45.284904-05:
      DOI: 10.1111/bju.13500
  • Chromogranin A and neuron‐specific enolase serum levels as
           predictors of treatment outcome in metastatic castration‐resistant
           prostate cancer patients under abiraterone therapy
    • Abstract: Objective To determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration‐resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post‐chemotherapy setting. Patients and Methods Chromogranin A (CGa) and neuron‐specific enolase (NSE) were determined in serum drawn before treatment with abiraterone of 45 mCRPC patients. Outcome measures were overall survival (OS), prostate‐specific antigen (PSA) response defined by PSA decline ≥50%, PSA progression‐free survival (PSA‐PFS) and clinical or radiographic PFS. Results CGa and NSE serum levels did not correlate (p=0.6). Patients were stratified in a low (n=9), intermediate (n=18) or high (n=18) risk group according to elevation of none, one or both neuroendocrine markers. Risk groups correlated with decreasing median OS (median OS not reached vs. 15.3 vs. 6.6 months; p
      PubDate: 2016-03-31T09:45:47.016166-05:
      DOI: 10.1111/bju.13493
  • Interpretation of conventional survival analysis and competing risk
           analysis: An example of hypertension and prostate cancer
    • Abstract: Most clinical studies use conventional methods for survival analysis and calculate the risk of the event of interest, however, it is important to understand that the study population is also at risk of competing events, for example death from other causes. Moreover, the risk of competing events may be dependent on the participants’ characteristics. Whether competing risks are taken into account or not, is of major importance when interpreting study results.Here, we use a practical example to elucidate the interpretational differences of absolute risk estimates obtained with both conventional methods for survival analysis and competing risk analysis. This article is protected by copyright. All rights reserved.
      PubDate: 2016-03-31T09:45:31.154284-05:
      DOI: 10.1111/bju.13494
  • Guidelines of Guidelines: Thromboprophylaxis for Urologic Surgery
    • Authors: Philippe D. Violette; Rufus Cartwright, Matthias Briel, Kari A.O. Tikkinen, Gordon H. Guyatt
      Abstract: The risks and benefits of thromboprophylaxis for urologic surgery depend on both patient specific and procedure specific factors [1,2]. Clinicians and patients must trade off a reduction in venous thromboembolism (VTE) against a potential increase in bleeding. Although investigators have not addressed the issue specifically for urological procedures, high quality evidence from randomized trials has demonstrated that pharmacological prophylaxis, with for example low molecular weight heparins (LMWH), decreases the risk of VTE in patients having abdominal or pelvic surgery by approximately 50% [1]. Best estimates for LMWH also suggest, however, an increase in the risk of post‐operative major bleeding by approximately 50% [1]. Although these relative risks are likely to be somewhat consistent across patients and procedures, the balance of benefits and harms varies with the absolute risk of VTE and bleeding. In patients with a high risk of VTE and a low risk of major bleeding, a 50% reduction in VTE represents a substantial benefit (for instance, from a baseline risk of 12% to 6%) and a 50% increase in bleeding represents a minimal increase in harm (for instance, from 0.2% to 0.3%). Patients whose risk of VTE without anticoagulation is low and whose bleeding risk is high face an opposite situation. This article is protected by copyright. All rights reserved.
      PubDate: 2016-03-31T09:31:56.923376-05:
      DOI: 10.1111/bju.13496
  • Change in Platelet Count as a Prognostic Indicator for Response to Primary
           Tyrosine Kinase Inhibitor Therapy in Metastatic Renal Cell Carcinoma
    • Authors: Zachary Hamilton; Hak J. Lee, Juan Himenez, Brian R. Lane, Song Wang, Alp T. Beksac, Kyle Gillis, Amy Alagh, Conrad Tobert, J. Michael Randall, Christopher J. Kane, Frederick Millard, Steven C. Campbell, Ithaar H. Derweesh
      Abstract: Objective To evaluate change in platelet count (ΔPlt) as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC). Patients and Methods Multi‐center retrospective analysis of mRCC patients undergoing primary TKI from 5/2005‐8/2014. ΔPlt was defined as post‐treatment platelet count after first cycle minus pre‐treatment platelet count. RECIST criteria were used to define partial response (PR), stable disease (SD), and progressive disease (PD). Analysis was conducted between subgroups with stable/increased (+ΔPlt) and decreased (‐ΔPlt) counts. Primary outcome was overall survival (OS) by Kaplan‐Meier analysis. Multivariable analysis (MVA) was conducted for risk factors associated with PD. Results 115 mRCC patients were analyzed, +ΔPlt 19 (16.6%) and –ΔPlt 96 (83%). More patients with +ΔPlt had Karnofsky score 2 metastases (78.9% vs. 51%, p=0.041). More patients with +ΔPlt had PD (89.4% vs. –ΔPlt 19.1%, p
      PubDate: 2016-03-24T05:00:31.954762-05:
      DOI: 10.1111/bju.13490
  • Safety, reliability and accuracy of small renal tumor biopsies: Results of
           a multi‐institution registry
    • Abstract: Objective To validate the safety, accuracy and reliability of RTB and its role in decreasing unnecessary treatment in a multi‐institution review. Materials and methods This was a multi‐institution retrospective study of patients who underwent RTB to characterize a SRM between 2011 and May 2015. Subjects were identified using the prospectively maintained Canadian Kidney Cancer information system (CKCis). Diagnostic and concordance rates were presented using proportions whereas factors associated with a diagnostic RTB were identified using a logistic regression model. Results Of the 373 biopsied SRMs, the initial biopsy was diagnostic in 87% of cases. Of the 47 nondiagnostic biopsies, 15 had a repeat biopsy of which, 80% were diagnostic. Therefore, when both were combined, a diagnosis was obtained in 91% of SRMs. Of these, 18% were benign. Size was the only factor found to be associated with achieving a diagnostic biopsy. RTB histology and nuclear grade (high or low) were found to be highly concordant with surgical pathology (86% and 81%, respectively). Of the discordant tumors (n=16), all were upgraded from low to high grade on surgical pathology. Adverse events were rare (
  • PADUA and RENAL nephrometry scores correlates with perioperative outcomes
           after robot‐assisted partial nephrectomy: analysis of the Vattikuti
           Global Quality Initiative in Robotic Urologic Surgery (GQI‐RUS)
    • Abstract: Objectives To evaluate and compare the correlations between PADUA and RENAL scores and perioperative outcomes and postoperative complications in a multicenter, international series of patients undergoing Robot‐assisted partial nephrectomy (RAPN) for masses suspicious of RCC. Patients and methods We retrospectively evaluated the clinical records of patients who underwent RAPN between 2010 and 2013 for clinical N0M0 renal tumours in four international Centers that completed all the data required for the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI‐RUS) database. All patients underwent pre‐operative computed tomography or magnetic resonance imaging to define the clinical stage and anatomic characteristics of the tumors. PADUA and RENAL scores were retrospectively assessed in each Center. Univariate and multivariate analyses were performed to evaluate the correlations between age, gender, Charlson comorbidity index, clinical tumor size, PADUA and RENAL complexity group categories and warm ischemia time >20 minutes, urinary calyceal system closure and grade of postoperative complications. Results Overall, 277 patients have been evaluated. The median tumor size was 33.0 millimeters (22.0‐43.0). The median PADUA and RENAL score were 8 and 7 respectively; 112 (40.4%), 86 (31.0%) and 79 (28.5%) patients were classified in the low, intermediate or high‐complexity group according to PADUA score, while 118 (42.5%), 139 (50.1%) and 20 (7.2%) were classified in the low, intermediate or high‐complexity group according to RENAL score, respectively. Both nephrometric tools significantly correlated with perioperative outcomes at univariate and multivariate analyses.. Conclusion A precise stratification of patients before partial nephrectomy is recommended, allowing to balance the potential threats and benefits of nephron‐sparing surgery. In our analysis, both PADUA and RENAL were significantly associated with prolonged WIT and high‐grade postoperative complications after RAPN. This article is protected by copyright. All rights reserved.
  • Perioperative and short‐term outcomes after Retzius‐sparing
           robot‐assisted radical prostatectomy stratified by gland size
    • Abstract: Objective o investigate the impact of preoperative prostate volume (PV) on the perioperative, continence and early oncological outcomes among patients treated with Retzius sparing robot assisted laparoscopic prostatectomy (RS‐RALP). Materials and Methods This is a retrospective analysis of 294 patients with organ‐confined prostate cancer (PCa) treated with RS‐RALP in a high volume center from November 2012 to February 2015. Patients were divided into three groups based on their TRUS volume as follows: group 1, (n=231, 60cc). Perioperative, oncological, and continence outcomes were compared between the three groups. Results The median prostate volumes for each group were; 26.1cc (22‐ 40 31), 45.9cc (41‐50) and 70cc (68‐85). Blood loss was higher in group 3 compared to group 2 and group 1; 475cc (312‐575), 200cc (150‐400) and 250cc (150‐400), respectively (p=0.001) Intraoperative transfusion rate was higher in group 3 patients (p=0.004) while complication rate did not differ (p=0.05). Console time was slightly higher but was not statistically significant in group 3 compared to groups 2 and 1; 100±35minutes, 92±34.4minutes and 93±24.8 minutes, respectively (p=0.70). BCR and continence rate did not differ between the three groups (p=0.89, p=0.25, respectively). Conclusion RS‐RALP is oncologically and functionally equivalent for all prostate sizes but technically demanding for larger prostate. We therefore recommend for surgeons to start at smaller sized prostate in the commencement of application of RS‐RALP technique. This article is protected by copyright. All rights reserved.
  • Phenotypic diversity of circulating tumour cells in patients with
           metastatic castration‐resistant prostate cancer
    • Abstract: Objectives To utilize a non‐biased assay of circulating tumour cells (CTCs) in prostate cancer (PCa) patients in order to identify non‐traditional CTC phenotypes potentially excluded by conventional detection methods reliant upon antigen and/or sized based enrichment. Patients and Methods 41 metastatic castration resistant prostate cancer (mCRPC) patients and 20 healthy volunteers were analysed on the Epic CTC Platform, via high throughput imaging of DAPI expression and CD45/cytokeratin (CK) immunofluorescence (IF) in all circulating nucleated cells plated on glass slides. IF for androgen receptor [AR] expression, and FISH for PTEN and ERG confirmed PCa origin of CTCs. Results Traditional (t) CTCs (CD45‐/CK+/morphologically distinct) were identified in 100% mCRPC patients. Using the above markers, we identified non‐traditional CTCs in mCRPC patients, including CK‐ and apoptotic CTCs. Small CTCs (≤WBC size) were identified in 98% of mCRPC patients. Total, traditional and non‐traditional CTCs were significantly increased in deceased vs. living patients at 18 months; however only non‐traditional CTCs associated with overall survival. Traditional and total CTC counts by the Epic platform in the mCRPC cohort were also significantly correlated with CTC counts by the CellSearch system. Conclusions Heterogeneous non‐traditional CTC populations that may be missed by other approaches are frequent in mCRPC; characterization of non‐traditional CTCs may provide additional prognostic or predictive information. This article is protected by copyright. All rights reserved.
  • Admissions to hospital due to fracture in England in patients with
           prostate cancer treated with androgen‐deprivation therapy – do
           we have to worry about the hormones'
    • Abstract: Objective To investigate the association between androgen‐deprivation therapy (ADT) and fracture risk in men with prostate cancer in England. Patients and Methods Using the Hospital Episodes Statistics database, which contains all the information about National Health Service (NHS) and NHS‐funded hospital admissions in England, for the years 2004–2008, 8 902 patients were found to have had prostate cancer and an admission to hospital with a fracture. Of these patients, 3 372 (37.8%) were identified as being treated with ADT, whilst 5 530 (62.2%) were not. There was a total of 228 852 admissions in the background population. Results The risk of a fracture requiring hospitalisation increased from 1.12 to 1.41 per 100 person‐years in a man with prostate cancer treated with ADT compared with those without ADT, an absolute increase of only 0.29 per 100 person‐years. When compared with the background population, there was an increase from 0.58 to 1.41 per 100 person‐years, a relative rate ratio increase of 2.4 (P < 0.01) with an absolute increase of 0.83 per 100 person‐years. Conclusion In England there was a small but statistically significant increased risk of fracture in men who had been treated with ADT. Men with prostate cancer, with or without ADT, were at an increased risk of fracture compared with the background population. We therefore suggest that if bone health is to be taken seriously in men with prostate cancer that all these men should be risk assessed (FRAX® or Qfracture® tools, as National Institute for Health and Care Excellence advised), as all men with prostate cancer have an increased risk of fracture, with those on ADT having slightly higher risk.
  • Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and
           mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with
           locally advanced or metastatic transitional cell carcinoma
    • Abstract: Objective To assess, in a multicentre phase II trial, the safety and efficacy of BEZ235, an oral pan‐class I phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) complex1/2 inhibitor, in locally advanced or metastatic transitional cell carcinoma (TCC) after failure of platinum‐based therapy. Patients and Methods Patients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All patients received BEZ235 until progressive disease or unacceptable toxicity. The primary endpoint was the progression‐free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely because BEZ235 was withdrawn from further development. Results A total of 20 patients (18 without and two with PI3K/Akt/mTOR alterations) were enrolled and received BEZ235. One partial response (5%) and two cases of stable disease (10%) were observed, all in patients without PI3K/mTOR pathway alterations. The PFS rate at 8 and 16 weeks was 15 and 10%, respectively; the median (range) PFS was 62 (38–588) days (95% confidence interval [CI] 53–110); and the median (range) overall survival was 127 (41–734) days (95% CI 58–309). Among the 90% of patients who experienced drug‐related adverse events of any grade, 50% experienced grade 3–4 adverse events, including stomatitis (15%), fatigue (5%), nausea (5%), diarrhoea (5%), renal failure (5%), cutaneous rash (5%), hepatotoxicity (5%) and hypertension (5%). Conclusion BEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Furthermore, this study showed that molecular stratification of patients for personalized medicine before treatment is feasible.
  • Extreme obesity does not predict poor cancer outcomes after surgery for
           renal cell cancer
    • Abstract: Objective To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m2) is associated with peri‐operative outcomes, overall survival (OS), cancer‐specific survival (CSS), or recurrence‐free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). Patients and Methods After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan–Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. Results In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m2 and 743 patients (88.1%) with a BMI < 40 kg/m2 who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587–1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3–6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30‐day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m2 was not a predictor of major complications (OR 0.58, 95% CI 0.227–1.47; P = 0.251) or 90‐day mortality (P = 0.4067). BMI ≥ 40 kg/m2 was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m2 was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5‐year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m2 and BMI ≥ 40 kg/m2, respectively (P = 0.69). The 5‐year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m2 and BMI ≥ 40 kg/m2, respectively. The 5‐year RFS rates for BMI < 40 kg/m2 and BMI ≥ 40 kg/m2 were 84.1 and 90.6%, respectively (P = 0.48). Conclusions Extreme obesity is not associated with worse peri‐operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.
  • Risk of thromboembolic disease in men with prostate cancer undergoing
           androgen deprivation therapy
    • Abstract: Objectives To investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT), while accounting for known TED risk factors. Materials and Methods We assessed TED risk for 42 263 men with PCa who were receiving ADT compared with a matched cohort of 190 930 without PCa. The associations between ADT and deep vein thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models, while accounting for previous PCa‐related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy. Results Between 1997 and 2013, 11 242 men with PCa received anti‐androgen monotherapy, 26 959 men received gonadotropin‐releasing hormone (GnRH) agonists, 1 091 men received combined androgen blockade and 3 789 men underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men had a higher risk of TED than the comparison cohort: hazard ratios (HRs) 1.67 (95% confidence interval [CI] 1.40–1.98) and 1.61 (95% CI 1.15–2.28), respectively. Men on anti‐androgen monotherapy had a lower risk: HR for DVT 0.49 (95% CI 0.33–0.74). TED risk was highest among those who switched from anti‐androgen to GnRH agonists: HR for PE 2.55 (95% CI 1.76–3.70). This increased from 2.52 (95% CI 1.54–4.12) in year 1, to 4.05 (95% CI 2.51–6.55) in year 2. Conclusion The incidence of TED among men on ADT increased with the duration of therapy and the risk was highest for those who switched regimen, suggesting that disease progression as well as ADT contribute to the propagation of TED risk. Nonetheless, these findings support the hypothesis that only men with a relevant indication should receive systemic ADT.
  • Transperineal template prostate‐mapping biopsies: an evaluation of
           different protocols in the detection of clinically significant prostate
    • Abstract: Objectives To determine whether modified transperineal template prostate‐mapping (TTPM) biopsy protocols, altering the template or the biopsy density, have sensitivity and negative predictive value (NPV) equal to full 5‐mm TTPM. Patients and Methods Retrospective analysis of an institutional registry including treatment‐naïve men undergoing 5‐mm TTPM biopsy analysed in a 20‐zone fashion. The value of three modified strategies was assessed by comparing the information provided by selected zones against full 5‐mm TTPM. Strategy 1, did not consider the findings of anterior areas; strategies 2 and 3 simulated a reduced biopsy density by excluding intervening zones. A bootstrapping technique was used to calculate reliable estimates of sensitivity and NPV of these three strategies for the detection of clinically significant disease (maximum cancer core length ≥4 mm and/or Gleason score ≥3 + 4). Results In all, 391 men with a median (interquartile range, IQR) age of 62 (58–67) years were included. The median (IQR) PSA level and PSA density were 6.9 (4.8–10) ng/mL and 0.17 (IQR 0.12–0.25) ng/mL/mL, respectively. A median (IQR) of 6 (2–9) cores out of 48 (33–63) taken per man were positive for prostate cancer. No cancer was detected in 67 men (17%), whilst low‐, intermediate‐ and high‐risk disease was identified in 78 (20%), 80 (21%), and 166 (42%), respectively. Strategy 1, 2 and 3 had sensitivities of 78% [95% confidence interval (CI) 73–84%], 85% (95% CI 80–90%) and 84% (95% CI 79–89%), respectively. The NPVs of the three strategies were 73% (95% CI 67–80%), 80% (95% CI 74–86%) and 79% (95% CI 72–84%), respectively. Conclusion Altering the template or decreasing sampling density has a substantial negative impact on the ability of TTPM biopsy to exclude clinically significant disease. This should be considered when modified TTPM biopsy strategies are used to select men for tissue‐preserving approaches, and when modified TTPM are used to validate new diagnostic tests.
  • Evaluation of pT0 prostate cancer in patients undergoing radical
    • Abstract: Objective To evaluate the incidence, predictors and oncological outcomes of pT0 prostate cancer (PCa). Methods We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy (RP) for PCa at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow‐up PSA >0.4 ng/mL or biopsy‐proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT0 and non‐pT0 groups were carried out using chi‐squared tests. Recurrence‐free survival was estimated using the Kaplan–Meier method and compared using the log‐rank test. Results A total of 62 patients (0.3%) had pT0 disease according to the RP specimen. In univariable analysis, pT0 disease was significantly associated with older age (P = 0.045), lower prostate‐specific antigen (PSA; P = 0.002), lower clinical stage (P < 0.001), lower biopsy Gleason score (P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed disease recurrence over a median follow‐up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of
  • Complications after prostate biopsies in men on active surveillance and
           its effects on receiving further biopsies in the Prostate cancer Research
           International: Active Surveillance (PRIAS) study
    • Abstract: Objective To study the risk of serial prostate biopsies on complications in men on active surveillance (AS) and determine the effect of complications on receiving further biopsies. Patients and methods In the global Prostate cancer Research International: Active Surveillance (PRIAS) study, men are prospectively followed on AS and repeat prostate biopsies are scheduled at 1, 4, and 7 years after the diagnostic biopsy, or once yearly if prostate‐specific antigen‐doubling time is
  • Symptom burden and information needs in prostate cancer survivors: a case
           for tailored long‐term survivorship care
    • Abstract: Objectives To determine the relationship between long‐term prostate cancer survivors’ symptom burden and information needs. Patients and Methods We used population‐based data from the Michigan Prostate Cancer Survivor Study (2499 men). We examined unadjusted differences in long‐term information needs according to symptom burden and performed multivariable logistic regression to examine symptom burden and information needs adjusting for patient characteristics. Results High symptom burden was reported across all domains (sexual 44.4%, urinary 14.4%, vitality 12.7%, bowel 8.4%, emotional 7.6%) with over half of respondents (56%) reporting they needed more information. Top information needs involved recurrence, relationships, and long‐term effects. Prostate cancer survivors with high symptom burden more often searched for information regardless of domain (P < 0.05). High sexual burden was associated with greater need for information about relationships [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.54–2.72] and long‐term effects (OR 1.60, 95% CI 1.23–2.07). High bowel burden was associated with greater information need for long‐term effects (OR 2.28, 95% CI 1.43–3.63). Conclusions Long‐term prostate cancer survivors with high symptom burden need more supportive information. Tailoring information to these needs may be an efficient approach to support the growing population of long‐term prostate cancer survivors.
  • Issue Information ‐ TOC
  • Issue Information ‐ JEB
  • Issue Information ‐ Jnl info
  • Randomised controlled trials in robotic surgery
  • Optimal thromboprophylaxis remains a challenge
  • Active surveillance for prostate cancer: is it too active'
  • Tailored prostate cancer survivorship: one size does not fit all
  • Robotic simulation: are we ready to go'
  • Accurately determining patients who underwent robot‐assisted
           surgery: limitations of administrative databases
  • Optimum management of non‐muscle‐invasive micropapillary
           variant urothelial carcinoma: possibility for missed chance of cure'
  • Laparoscopic retroperitoneal partial nephrectomy using an ergonomic chair
           – demonstration of technique and matched‐pair analysis
    • Abstract: Objectives To present technique and long‐term results of retroperitoneal laparoscopic partial nephrectomy (LPN) focussing on the impact of an ergonomic platform. Patients and Methods Between January 2000 and May 2016, 287 patients (193 male, 94 female) underwent LPN by four surgeons. Median age was 59 (19‐85) years. Mean tumour size was 3.1 (1‐9) cm. Mean PADUA‐score was 7.3 (6‐12). Access was retroperitoneal in 235 (82%) cases. Since October 2010, we used ETHOSTM‐chair during excision of the tumour in 130 (45.3%) patients. 51 (17.7%) tumours were excised without ischemia and 226 (78.7%) tumours under warm ischemia with clamping of renal artery using an enucleo‐resection technique. We suture the resection bed and perform renorrhaphy using a barbed‐suture pre‐loaded with absorbable LAPRA‐TYTM‐clip. The impact of ETHOS‐chair was examined using a matched‐pair analysis (66 ETHOS vs. 67 Non‐ETHOS‐chair). Results Median operating time was 146 (60‐325) minutes. Median estimated blood loss was 99 (10 ‐ 3000) cc, mean warm ischemia time was 17.1 (7‐47) minutes. Histology showed 240 (83.6%) renal cell carcinomas and 46 (15.9%) benign tumours. Cumulative overall disease‐free survival rate after a median follow‐up of 84 (3‐155) months was 100 % for 203 pT1 renal cell tumours, local recurrence was observed in one patient (0.4%), who was managed by radical nephrectomy. There were two conversions (0.7%) to open surgery respectively to hand‐assisted laparoscopy. Perirenal hematoma was observed in 13 (4.5%) patients. 20 (6.9%) patients required transfusions (2‐11 units). We observed 5 urine leaks (1.7%) requiring prolonged drainage. Median hospital stay was 5 (3‐24) days. Three patients developed a‐v‐fistulas successfully occluded by super‐selective embolization (1.0%). Use of ETHOSTM‐chair resulted in shorter OR‐time (134.7 vs. 168.5 min., p = 0.04) including warm ischemia time (13.1 vs. 15.9 min., p=0.01) less complications (15% vs. 29.8%, p = 0.02). Limitation of the analysis is the fact that it is not prospective randomized trial. Conclusions LPN is technically difficult but oncologic effective. Standardization and simplification of endoscopic suturing using ETHOS‐chair significantly improved the outcome of the surgical procedure. This article is protected by copyright. All rights reserved.
  • Increasing age is not associated with toxicity leading to discontinuation
           of treatment in patients with urothelial non‐muscle‐invasive
           bladder cancer randomised to receive 3 years of maintenance bacille
           Calmette–Guérin: results from European Organisation for
           Research and Treatment of Cancer Genito‐Urinary Group study 30911
    • Abstract: Objective To determine the relationship of age to side‐effects leading to discontinuation of treatment in patients with stage Ta–T1 non‐muscle‐invasive bladder cancer (NMIBC) treated with maintenance bacille Calmette–Guérin (BCG). Patients and Methods We evaluated toxicity for 487 eligible patients with intermediate‐ or high‐risk Ta–T1 (without carcinoma in situ) NMIBC randomised to receive 3 years of maintenance BCG therapy (247 BCG alone and 240 BCG + isoniazid) in European Organisation for Research and Treatment of Cancer Genito‐Urinary Group trial 30911. The percentage of patients who stopped for toxicity and the number of treatment cycles that they received were compared in four age groups, ≤60, 61–70, 71–75 and >75 years, using the Mantel–Haenszel chi‐square test for trend. Results The percentage of patients stopping BCG for toxicity was 17.9% in patients aged ≤60 years, 21.9% in patients aged 61–70 years, 22.9% in patients aged 71–75 years, and 16.4% in patients aged >75 years (P = 0.90). For both systemic and local side‐effects, there was likewise no significant difference. Conclusion In patients with intermediate‐ and high‐risk Ta–T1 NMIBC treated with BCG, no differences in toxicity as a reason for stopping treatment were detected based on patient age.
  • Technical mentorship during robot‐assisted surgery: a cognitive
    • Abstract: Objective To investigate cognitive and mental workload assessments, which may play a critical role in defining successful mentorship. Materials and Methods The ‘Mind Maps’ project aimed at evaluating cognitive function with regard to surgeon's expertise and trainee's skills. The study included electroencephalogram (EEG) recordings of a mentor observing trainee surgeons in 20 procedures involving extended lymph node dissection (eLND) or urethrovesical anastomosis (UVA), with simultaneous assessment of trainees using the National Aeronautics and Space Administration Task Load index (NASA‐TLX) questionnaire. We also compared the brain activity of the mentor during this study with his own brain activity while actually performing the same surgical steps from previous procedures populated in the ‘Mind Maps’ project. Results During eLND and UVA, when the mentor thought the trainee's mental demand and effort were low based on his NASA‐TLX questionnaire (not satisfied with his performance), his EEG‐based mental workload increased (reflecting more concern and attention). The mentor was mentally engaged and concerned while he was engrossed in observing the surgery. This was further supported by the finding that there was no significant difference in the mental demands and workload between observing and operating for the expert surgeon. Conclusions This study objectively evaluated the cognitive engagement of a surgical mentor teaching technical skills during surgery. The study provides a deeper understanding of how surgical teaching actually works and opens new horizons for assessment and teaching of surgery. Further research is needed to study the feasibility of this novel concept in assessment and guidance of surgical performance.
  • The safety of robot‐assisted cystectomy in patients with previous
           history of pelvic irradiation
    • Abstract: Objective To determine the safety of robot‐assisted cystectomy (RAC) in patients with an irradiated pelvis, by comparing perioperative complication outcomes after RAC in patients with and without a history of pelvic irradiation. Patients and Methods In all, 252 consecutive patients underwent RAC at a tertiary referral centre from 2002 to 2013. Of all patients, 46 (18%) had a history of pelvic irradiation. Complications occurring at ≤30 days and ≤90 days of RAC were graded using the modified Clavien–Dindo classification system and additionally categorised by organ system. Baseline variables and outcomes of irradiated and non‐irradiated patients were compared using descriptive statistics. Multivariable logistic regression models were generated to test the effect of previous pelvic irradiation on complications. Results The indications for RAC in patients with a history of pelvic irradiation were: bladder cancer (30 patients, 65%), prostate cancer (two, 4%), fistulae (five, 11%), and intractable symptoms from radiation cystitis (nine, 20%). In all, 25 (54%) irradiated and 112 (54%) non‐irradiated patients had complications at ≤90 days (P > 0.9), of which 11 (24%) and 43 (21%) respectively had major complications (P = 0.7). One (2%) patient with and two (1%) patients without a history of irradiation died from surgical complications (P = 0.5). Infectious, bleeding, and gastrointestinal complications were the most common events in both groups. In multivariable analyses, a history of pelvic irradiation was not associated with a higher risk of complications. Conclusion RAC performed by an experienced surgeon is a reasonable option in selected patients with a history of pelvic irradiation, as complication rates do not significantly differ compared with non‐irradiated patients.
  • Conservative management of staghorn calculi: a single‐centre
    • Abstract: Objective To evaluate the outcomes of conservatively managed staghorn calculi, specifically looking at morbidity and mortality, incidence of infections and progressive changes in renal function. Patients and Methods A total of 22 patients with unilateral or bilateral staghorn calculi, who were treated conservatively, were included in the study. Patients were reviewed yearly with symptom assessment, urine culture and measurement of estimated glomerular filtration rate. Results The presentations to the urology department of staghorn calculi were incidental (41%), haematuria (36%), abdominal discomfort (5%) and recurrent urinary tract infections (UTIs; 18%). The reasons for conservative management in the cohort were comorbidities (59%), patient choice (36%) or poor access/anatomy (5%). In the whole cohort the rate of recurrent UTIs was 50%, the progressive renal failure rate was 14%, the disease‐specific mortality rate was 9%, the dialysis dependence rate was 9% and the rate of hospital attendances attributable to stone‐related morbidity was 27%. Comparison of outcome measures between the unilateral and bilateral staghorn stones showed statistically significant differences in disease‐specific mortality (0 vs 40%) and morbidity (12 vs 80%) in favour of the unilateral group. Although there was a lower incidence of UTIs (41 vs 80%), renal deterioration (6 vs 40%) and dialysis requirement (6 vs 20%) in the unilateral group, these findings were not statistically significant. Conclusions From the results, we conclude that conservative management of staghorn calculi is not as unsafe as previously thought. Careful patient selection to include unilateral asymptomatic stones with minimal infection, and thorough counselling with regard to the risks, could make conservative management a suitable option for specific patient groups.
  • Hypospadias repair with onlay preputial graft: a 25‐year experience
           with long‐term follow‐up
    • Abstract: Objective To evaluate the long‐term outcomes of hypospadias repair using an onlay preputial graft. Patients and Methods Patient records from 1989 to 2013 were retrospectively reviewed. One surgeon performed all cases and surgical technique was the same for all patients. Results There were 62 patients in the cohort, with a mean (range) follow‐up of 47.4 (1–185) months. The meatal location was separated into distal (one patient), midshaft (19) and proximal (42). In all, 22 (35.5%) patients had complications. There were three main types of complications, including meatal stenosis in three (4.8%), stricture in three (4.8%), and fistula in 21 (33.9%). The mean (range) timing of presentation with a complication after surgery was 24.9 (1–127) months. In all, 54.5% of the patients with complications presented at ≥1 year after the initial surgery and 31.8% presented at ≥3 years. On univariable analysis age at the time of surgery, length of the graft, presence of chordee or meatal location (proximal or midshaft) did not predict a complication. The width of the graft was associated with a complication, with each 1 mm increase in width decreasing the odds of a complication by 56%. On multivariable analysis width remained statistically significant (odds ratio 0.44, 95% confidence interval 0.230–0.840; P = 0.013) for predicting a complication. Conclusion Hypospadias repair with onlay preputial graft is an option for single‐stage repair, especially in cases of proximal hypospadias or where the urethral plate width and/or the glanular groove is insufficient for other types of repair. Compared with flaps, the use of grafts may decrease the risk of penile torsion and prevent less bulk around the urethra, improving skin and glans closure.
  • Mid‐term outcomes after AdVanceXP male sling implantation
    • Abstract: Objective To describe efficacy and safety of the AdVanceXP (Boston Scientific, Marlborough, MA, USA) retrourethral transobturator male sling after a mean follow‐up of almost 3 years. Patients and Methods A total of 41 patients underwent AdVanceXP implantation between July 2010 and March 2012 by a single surgeon. Patients were prospectively evaluated at baseline, after a mean follow‐up of 12months and after an individual maximum follow‐up. Efficacy was evaluated by daily pad usage, 24‐h pad testing, and validated questionnaires (International Consultation on Incontinence questionnaire [ICIQ]). Patient satisfaction was determined using the Patient's Global Impression of Improvement score; quality of life was evaluated using the International Quality of Life (IQOL) score. Patients needing 0 or 1 safety pad with a daily urine loss
  • Consensus guidelines for reporting prostate cancer Gleason Grade
  • Value of 3‐T multiparametric magnetic resonance imaging and targeted
           biopsy for improved risk stratification in patients considered for active
    • Abstract: Objective To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) of the prostate and transrectal guided biopsy (TRUS‐Bx) with visual estimation in early risk stratification of patients on active surveillance. Patients and methods patients with low‐risk, low‐grade, localized prostate cancer (PCa) were prospectively enrolled and submitted to a 3T 16‐channel cardiac surface coil mpMRI of the prostate and confirmatory biopsy (CB), which included a standard biopsy (SB) and visual estimation‐guided TRUS‐Bx. Cancer‐suspicious regions (CSRs) were defined using Prostate Imaging Reporting and Data System (PI‐RADS) scores. Reclassification occurred if CB confirmed the presence of a Gleason score ≥7, greater than three positive fragments, or ≥50% involvement of any core. The performance of mpMRI for the prediction of CB results was assessed. Univariate and multivariate logistic regressions were performed to study relationships between age, PSA, PSA density (PSAd), number of positive cores in the initial biopsy, and mpMRI grade on CB reclassification. Our report is consistent with START guidelines. Results a total of 105 patients were available for analysis in the study. From this cohort, 42 (40%) had PI‐RADS 1, 2, or 3 lesions and 63 (60%) had only grade 4 or 5 lesions. Overall, 87 patients underwent visual estimation TRUS‐Bx. Reclassification among patients with PI‐RADS 1, 2, 3, 4, and 5 was 0%, 23.1%, 9.1%, 74.5%, and 100%, respectively. Overall, mpMRI sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for disease reclassification were 92.5%, 76%, 81%, and 90.5%, respectively. In the multivariate analysis, only PSAd and mpMRI remained significant for reclassification (p
  • Serum levels of enclomiphene and zuclomiphene in hypogonadal men on
           long‐term clomiphene citrate treatment
    • Abstract: Objectives To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in hypogonadal men (HM) on long‐term clomiphene citrate (CC) therapy. To determine whether patient age, body mass index, or duration of therapy were predictive of relative concentrations of ENC and ZUC. Patients and Methods Men already on CC 25 mg daily therapy for secondary hypogonadism for a minimum of six weeks were recruited to have their ENC and ZUC levels assessed. Total testosterone (T), free testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) prior to initiation of and while on CC therapy were recorded for all patients. Patient demographics including age, body mass index, and medical comorbidites were recorded. Serum samples were obtained at the time of enrollment to determine ENC and ZUC concentrations. Results A total of 15 men were enrolled from June 2015 to August 2015. Median patient age was 36 (range 22‐70) years, median body mass index 32.0 (range 21.1‐40.3)kg/m2, and median duration of treatment 25.9 (range 1.7‐86.6) months. Baseline median total T, estradiol, and LH were 205.0 ng/dL, 17.0 pg/mL, and 4.0 mlU/mL, respectively. Post‐treatment median total T, estradiol, and LH increased to 488.0 ng/dL 34.0 pg/mL, and 6.1 mIU/mL, respectively (all p
  • The actual lowering effect of metabolic syndrome on serum
           prostate‐specific antigen levels is partly concealed by enlarged
           prostate: results from a large‐scale population‐based study
    • Abstract: Objectives To clarify the actual lowering effect of metabolic syndrome (MetS) on serum prostate‐specific antigen (PSA) levels in a Chinese‐screened population. Materials and Methods A total of 45,540 ostensibly healthy men aged 55‐69 years of old who underwent routine health check‐ups at Beijing Shijitan Hospital from 2008 to 2015 were included in this study. All subjects underwent detailed clinical evaluations. PSA mass density was calculated (serum PSA level × plasma volume ÷ prostate volume) for simultaneously adjusting plasma volume and prostate volume. According to the modified NCEP‐ATP III criteria, subjects were dichotomized by the presence of MetS, and the differences in PSA density and PSA mass density were compared between groups. Linear regression analysis was used to evaluate the effect of MetS on serum PSA levels. Results When larger prostate volume in men with MetS was adjusted, both the PSA density and PSA mass density in subjects with MetS were significantly lower than that in subjects without MetS, and the estimated difference in mean serum PSA level between subjects with and without MetS was greater than that before prostate volume was adjusted. In multivariate regression model, the presence of MetS was independently associated with an 11.3% decline in serum PSA levels compared with subjects without MetS. In addition, the increasing number of positive MetS components was significantly and linearly associated with the declining in serum PSA levels. Conclusion The actual lowering effect of MetS on serum PSA levels was partly concealed by the enlarged prostate in men with MetS, and the presence of MetS was independently associated with lower serum PSA levels. Urologists need to be aware of the effect of MetS on serum PSA levels and discuss this subject with their patients. This article is protected by copyright. All rights reserved.
  • Prostate cancer outcomes for men who present with symptoms at diagnosis
    • Abstract: Objective To compare clinical features, treatments and outcomes in men with non‐metastatic prostate cancer (PCa) according to whether they were referred for symptoms or elevated prostate specific antigen (PSA). Patients and methods This study used data from the South Australia Prostate Cancer Clinical Outcomes Collaborative database; a multi‐institutional clinical registry covering both the public and private sectors. Participants included all non‐metastatic cases from 1998‐2013 referred for urinary/prostatic symptoms or elevated PSA. Multivariate Poisson regression was used to identify characteristics associated with symptomatic presentation and compare treatments according to reason for referral. Outcomes (i.e. overall survival, PCa survival, metastatic‐free survival and disease‐free survival) were compared using multivariate Cox proportional hazards and competing risk regression. Results Our analytic cohort consisted of 4841 men with localised PCa. Symptomatic men had lower risk disease (IR= 0.70, CI 0.61‐0.81 for high vs low risk), fewer radical prostatectomies (IR=0.64 CI 0.56‐0.75) and less radiotherapy (IR=0.86, CI 0.77‐0.96) than men presenting with elevated PSA. All‐cause mortality (HR=1.31, CI 1.16‐1.47), disease‐specific mortality (HR=1.42, CI 1.13‐1.77) and risk of metastases (HR=1.36, CI 1.13‐1.64) were higher for men presenting with symptoms, after adjustment for other clinical characteristics. However, risk of disease progression did not differ (HR=0.90, CI 0.74‐1.07) amongst those treated curatively. Subgroup analyses indicated poorer PCa survival for symptomatic referral among men undergoing radical prostatectomy (HR=3.4, CI 1.3‐8.8), those over 70 years (HR=1.4, CI 1.0‐1.8), private patients (HR=2.1, CI 1.3‐3.3), those diagnosed via biopsy (HR=1.3, CI 1.0‐1.7) and those diagnosed before 2006 (HR=1.6, CI 1.1.2‐1.7). Conclusion Our results suggest that symptomatic presentation may be an independent negative prognostic indicator for PCa survival. More complete assessment of disease grade and extent, more definitive treatment and increased post‐treatment monitoring among symptomatic cases may improve outcomes. Further research to determine any pathophysiological basis for poor outcomes in symptomatic men is warranted. This article is protected by copyright. All rights reserved.
  • The influence of prostate‐specific antigen density on positive and
           negative predictive values of multiparametric magnetic resonance imaging
           to detect Gleason score 7‐10 prostate cancer in a repeat biopsy
    • Abstract: Objectives To evaluate the influence of PSA‐D on positive (PPV) and negative (NPV) predictive values of mpMRI to detect GS ≥7 cancer in a repeat biopsy setting. Patients and methods Retrospective study of 514 men with previous prostate biopsy showing no or GS 6 cancer. All had mpMRI, graded 1‐5 on a Likert scale for cancer suspicion, and subsequent targeted and 24‐core systematic image‐fusion guided transperineal biopsy in 2013‐2015. NPVs and PPVs of mpMRIs for detecting GS ≥7 cancer were calculated (±95% confidence intervals) for PSA‐D ≤0.1, 0.1‐0.2, ≤0.2 and >0.2 ng/ml/cm3, and compared by Chi‐square test for linear trend. Results GS ≥7 cancer was detected in 31% of the men. NPV of Likert 1‐2 mpMRI was 0.91 (±0.04) with PSA‐D ≤0.2 and 0.71 (±0.16) with >0.2 (p=0.003). For Likert 3 mpMRI, PPV was 0.09 (±0.06) with PSA‐D ≤0.2 and 0.44 (±0.19) with >0.2 (p=0.002). PSA‐D also significantly affected the PPV of Likert 4‐5 mpMRI lesions: the PPV was 0.47 (±0.08) with PSA‐D ≤0.2 and 0.66 (±0.10) with >0.2 (p=0.0001). Conclusion In a repeat biopsy setting, PSA‐D ≤0.2 is associated with low detection of GS ≥7 prostate cancer, not only in men with negative mpMRI, but also in men with equivocal imaging. Surveillance, rather than repeat biopsy, may be appropriate for these men. Conversely, biopsies are indicated in men with high PSA‐D, even if an mpMRI shows no suspicious lesion, and in men with an mpMRI suspicious for cancer, even if PSA‐D is low. This article is protected by copyright. All rights reserved.
  • Metastatic Potential to Regional Lymph Nodes with Gleason Score ≤7
           including Tertiary Pattern 5 at Radical Prostatectomy
    • Abstract: Objectives  To determine the risk of pelvic LN metastases at radical prostatectomy (RP) with GS ≤7: 3+3=6 (GG1); 3+4=7 (GG2); 3+4=7 (GG2) with tertiary pattern 5 (T5); 4+3=7 (GG3); 4+3=7 (GG3) with T5 using the 2014 Modified Gleason grading system and the novel Grade Group (GG) system. Materials and Methods  We searched our RP database between 2005 and 2014 for cases of GS ≤7 with simultaneous pelvic LN dissection (PLND). Since 2005, we have graded all glomeruloid and cribriform cancer as Gleason pattern 4 and graded mucinous adenocarcinoma based on the underlying architectural pattern consistent with the 2014 Modified Gleason grading system. All RPs were embedded in entirety, including the PLND. A total of 7442 cases were identified, of which 73 had at least 1 positive LN (+LN). Results  The incidence of regional LN metastases at RP for 3+3=6 (GG1); 3+4=7 (GG2); 3+4=7 (GG2) with T5; 4+3=7 (GG3); 4+3=7 (GG3) with T5 were 0%, 0.6%, 0.4%, 4.3% and 6.3% respectively. There was a statistically significant difference in risk of +LN at RP between the Grade Groups as defined by the novel Grade Group system. There was no statistically significant difference in risk of +LN at RP for men with 3+4 (GG2) vs. 3+4 (GG2) with T5 and for men with 4+3 (GG3) vs. 4+3 (GG3) with T5. Non‐pelvic LN involvement was identified in 0.2% of all RPs. Two patients with Gleason score 3+4=7 with
  • Renal fossa recurrence following nephrectomy for renal cell carcinoma:
           prognostic features and oncologic outcomes
    • Abstract: Objective To describe clinicopathologic features associated with increased risk of renal fossa recurrences (RFR) following radical nephrectomy (RN) and to describe prognostic features associated with cancer‐specific survival (CSS) among patients with RFR treated with primarily locally‐directed therapy, systemically directed therapy, or expectant management. Patients And Methods Records of 2502 patients treated with RN for unilateral, sporadic, localized RCC between 1970 and 2006 were reviewed. CSS following RFR was estimated using the Kaplan‐Meier method. Associations with the development of RFR and CSS following RFR were evaluated using Cox proportional hazards regression models. Results A total of 33 (1.3%) patients developed isolated RFR (iRFR) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases following RN (study cohort, N=63). Median follow‐up for the series was 9.0 years after RN and 6.0 years following RFR diagnosis. On multivariable analysis, advanced pathologic stage (pT2: HR 4.36, p=0.004; pT3/4: HR 4.39, p=0.003) and coagulative necrosis (HR 2.71, p=0.006) were independently associated with increased risk of iRFR. The median time to recurrence was 1.5 years post‐nephrectomy among the 33 patients with iRFR, and 1.4 years among all patients. Overall, median CSS was 2.5 years after iRFR diagnosis, 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. Following primary locally directed therapy (surgery, ablation, or radiation), systemic therapy, or expectant management, the 3‐year CSS rates among patients with iRFR were 63%, 50%, and 13% (p=0.001) and were 64%, 50%, and 28% (p=0.006) among all patients,respectively. On multivariable analysis, when compared to observation, locally directed therapies were associated with a significantly decreased risk of death from RCC (HR 0.26, p
  • Surgical quality of minimally invasive adrenalectomy for adrenocortical
           carcinoma: a contemporary analysis using the national cancer data base
    • Abstract: Objectives To compare quality outcomes between open (OA) and minimally invasive (MIA) adrenalectomy for adrenocortical carcinoma. Patients and Methods In the National Cancer Data Base, we identified 481 patients with non‐metastatic adrenocortical carcinoma who underwent adrenalectomy from 2010‐2013. OA and MIA were compared on positive‐surgical‐margin and lymphadenectomy rates (primary outcomes) and lymph node yield, length of stay, readmission, and overall survival (secondary outcomes). Using the intention‐to‐treat principle, minimally‐invasive‐converted‐to‐open cases were considered MIA. Logistic regression analysis was used to identify predictors of positive margins and lymphadenectomy. Associations between approach and the outcomes were further assessed by stage and tumor size. Results Overall, 161 patients (33.5%) underwent MIA. MIA was used more commonly in older, comorbid patients; for smaller, localized tumors; and at lower‐volume centers. In the intention‐to‐treat analysis, MIA independently predicted positive margins (OR 2.0, 95%CI 1.1‐3.6, p=.03) and no lymphadenectomy (OR 0.1, 95%CI 0.03‐0.6, p=.01). On subgroup analysis, the association between MIA and positive margins only held true for pT3 disease (48.7% vs. 26.7%, p=.01). A higher rate of margin positivity was observed for tumors ≥10 cm managed with MIA vs. OA, but this difference was not significant (28.2% vs. 18.5%, p=.16). Likewise, the association between MIA and no lymphadenectomy was only observed for male patients, tumors ≥10 cm, and cN0 disease. After excluding minimally‐invasive‐converted‐to‐open cases, the difference in margin positivity was less pronounced and non‐significant (OR 1.8, 95%CI 0.9‐3.4, p=.08). MIA was associated with significantly shorter median length of stay (3 vs. 6 days, p
  • Oncologic outcomes and complication rates after
           laparoscopic‐assisted cryoablation: a EuRECA
           multi‐institutional study
    • Abstract: Objective To assess complication rates and intermediate oncologic outcomes of laparoscopic‐assisted cryoablation (LCA) in patients with small renal masses (SRM). Patients and Methods A retrospective review of 808 patients treated with LCA for T1a renal masses from 2005 to 2015 at eight European institutions. Complications were analysed according to the Clavien‐Dindo classification. Kaplan‐Meier analyses were used to estimate 5 and 10‐year disease‐free survival (DFS) and overall survival (OS). Results Median age was 67 years (IQR: 58‐74). Median tumour size was 25mm (IQR: 19‐30). The transperitoneal approach was used in 77.7% of the patients. Median postoperative hospital stay was two days. A total of 514 patients with a biopsy‐confirmed RCC were available for survival analyses. Median follow‐up time for the RCC‐cohort was 36 months (IQR: 14‐56). A total of 32 patients (6.2%) were diagnosed with treatment failure. The 5/10‐year DFS was 90.4%/80.0% and 5/10‐year OS was 83.2%/64.4%, respectively. A total of 134 postoperative complications (16.6%) were reported, with severe complications (grade ≥ 3) in 26 patients (3.2%). An ASA score of three was associated with an increased risk of overall complications (OR: 2.85; 95%CI: 1.32‐6.20; p=0.005). Conclusions This large series of LCA demonstrates satisfactory long‐term oncologic outcomes for SRMs. However, although LCA is considered a minimally invasive procedure, risk of complications should be considered when counselling patients. This article is protected by copyright. All rights reserved.
  • Comparison of robot‐assisted and open partial nephrectomy for
           completely endophytic renal tumours: a single centre experience
    • Abstract: Objective To compare outcomes between robot‐assisted partial nephrectomy (RAPN) and open PN (OPN) for completely endophytic renal tumours. Patients and Methods We retrospectively reviewed 1 230 consecutive cases, consisting of 823 RAPNs and 407 OPNs, performed for renal mass at a single academic tertiary centre between 2011 and 2016. Of these, data on 87 RAPN and 56 OPN cases for completely endophytic renal tumours were analysed. Patient and tumour characteristics, operative, postoperative, functional, and oncological outcomes were compared between groups. Results Apart from a higher prevalence of solitary kidney among OPN cases (RAPN, 5.7% vs OPN, 21.4%; P = 0.005), demographic characteristics were similar between the groups. There were no statistically significant differences in tumour size (P = 0.07), tumour stage (P = 0.3), margin status (P = 0.48), malignant tumour subtypes (P = 0.51), and grades (P = 0.61) between the groups. Also, there were no statistically significant differences among the groups for warm ischaemia time (P = 0.15), cold ischaemia time (P = 0.28), and intraoperative (P = 0.75) or postoperative (Clavien–Dindo Grade I–V, P = 0.08; Clavien–Dindo Grade III–V, P = 0.85) complication rates. The patients in the RAPN group had a shorter length of stay (P < 0.001), less estimated blood loss (P < 0.001), and lower intraoperative transfusion rates (0% vs 7.1%, P = 0.02). No local recurrences occurred during a median (interquartile range) follow‐up of 15.2 (7–27.2) and 18.1 (8.2–30.9) months in the RAPN and OPN groups, respectively. There was no difference in estimated glomerular filtration rate preservation rates between groups for the early (P = 0.26) and latest (P = 0.22) functional follow‐up. Conclusion For completely endophytic renal tumours, both OPN and RAPN have excellent outcomes when performed by experienced surgeons at a high‐volume centre. For skilled robotic surgeons, RAPN is a safe and effective alternative to OPN with the advantages of shorter length of stay and less blood loss.
  • Management of Radiation Therapy Oncology Group (RTOG) grade 4 urinary
           adverse events (UAEs) from radiotherapy for prostate cancer
    • Abstract: Objective To describe the management of grade 4 Radiation Therapy Oncology Group (RTOG) urinary adverse events (UAEs) after radiotherapy (RT) for prostate cancer (PCa). We hypothesized grade 4 UAEs often require complex surgical management and subject patients to significant morbidity. Methods A single‐center retrospective review, over a 6‐year period (2010‐2015), identified men with RTOG grade 4 UAEs after RT for PCa. RT was classified as combined modality therapy (radical prostatectomy (RP) followed by external beam radiotherapy (EBRT), EBRT + low‐dose brachytherapy (LDR), EBRT + high‐dose brachytherapy (HDR), or other combinations of RT) or single modality RT. UAEs were classified as outlet (urethral stricture, bladder neck contracture, prostate necrosis, or recto‐urethral fistula) or bladder (contraction, necrosis, fistula, ureteral stricture, or hemorrhage). Results We identified 73 men with a mean age of 73 years. Forty‐four (60%) had combined modality therapy, consisting of RP + EBRT (19), high dose rate brachytherapy (HDR) + EBRT (19), low dose rate brachytherapy (LDR) + EBRT (5), and other combined modality RT (2). Twenty‐nine (40%) patients had single modality therapy consisting of EBRT (4), HDR (11), LDR (12), or proton beam (2). UAEs were isolated to the bladder in 6 (8%), the outlet in 52 (71%), and both in 15 (21%). UAE management included: conservative in 21 (29%), indwelling catheters in 12 (16%), reconstructive in 19 (26%), and urinary diversion in 23 (32%). Reconstruction included: ureteral (4), recto‐urethral fistula repair (2), and posterior urethroplasty (13), of which 14/16 (88%) surgeries with follow‐up >90 days were successful. Conclusions Although the incidence of RTOG grade 4 UAEs after PCa radiation treatment is not well defined, their morbidity is significant, and approximately one third of patients with these high‐grade complications require urinary diversion. Conversely only about a quarter of patients can be managed with conservative strategies or local surgeries. Reconstruction is successful in selected patients. This article is protected by copyright. All rights reserved.
  • The Role of Biobanking in Urology: A Review
    • Abstract: In the current era of individualized medicine, a biorepository of human samples is essential to support clinical and translational research. There have been limited efforts in this arena within the field of urology, as costs, logistical, and ethical issues represent significant deterrents to biobanking. The Johns Hopkins Brady Urological Institute (JHBUI) Biorepository was founded in 1994 as a resource to facilitate discovery. Since its inception, the biorepository has enabled numerous research endeavors including pivotal trials leading to the regulatory approval of four diagnostic tests for prostate cancer. In this review, we discuss the current state of biobanking within urology, outline the specific ethical and financial challenges of biobanking as well as solutions, and describe the operations of a successful urologic biorepository. This article is protected by copyright. All rights reserved.
  • Evolution of the Robotic Orthotopic Ileal Neobladder Formation: A Step by
           Step Update to The USC Technique
    • Abstract: Objective To describe, step‐by‐step, our updated, time‐efficient technique for intracorporeal neobladder formation. Patients and Methods There are five main surgical steps to forming the intracorporeal orthotopic ileal neobladder: isolation of the small bowel intestine; small bowel anastomosis; bowel detubularization and suture of the posterior wall of the neobladder; neobladder‐urethral anastomosis and folding the pouch; and ureteral‐chimney anastomosis. Improvements have been made during these steps to improve time efficiency without compromising neobladder formation. Results A total of 65 cm of small intestinal bowel is removed for neobladder formation. Our technical improvements have demonstrated an improvement in operative time from 450 minutes to 360 minutes. Conclusion We describe an updated step‐by‐step technique to our institution's robotic intracorporeal orthotopic ileal neobladder formation using a time‐efficient technique. This article is protected by copyright. All rights reserved.
  • Risk Prediction Tool for Grade Reclassification in Favorable‐Risk
           Men on Active Surveillance
    • Abstract: Objective To create a nomogram for men on active surveillance (AS) for prediction of grade reclassification (GR) above Gleason score 6 (Grade group >2) at surveillance biopsy. Materials and Methods From a cohort of men enrolled in an AS program, a multivariable model was used to identify clinical and pathologic parameters predictive of GR. Nomogram performance was assessed using receiver operating characteristic curves, calibration and decision curve analysis. Results Of 1374 men, 254 (18.50%) were reclassified to Gleason 7 or higher on surveillance prostate biopsy. Variables predictive of GR were earlier year of diagnosis (≤2004 vs. ≥2005; odds ratio [OR] = 2.16, P = < 0.0001), older age (OR = 1.05, P = 0.0004), higher prostate specific antigen density [PSAD] (OR = 1.19 [per 0.1 unit increase], P = 0.04), bilateral disease (OR = 2.86, P = < 0.0001), risk strata (low‐risk vs. very‐low‐risk, OR=1.79, P = 0.0009) and total number of biopsies without GR (OR = 0.68, P = < 0.0001). On internal validation, a nomogram created using the multivariable model demonstrated an area under the curve of 0.757 (95% CI = 0.730, 0.797) for predicting GR at the time of next surveillance biopsy. Conclusion The nomogram described is currently being used at each return visit to assess the need for a surveillance biopsy, and could increase retention in AS. This article is protected by copyright. All rights reserved.
  • COX‐2 Inhibition for Prostate Cancer Chemoprevention:
           Double‐Blind Randomized Study of Pre‐Prostatectomy Celecoxib
           or Placebo
    • Abstract: Objective To evaluate the biologic effects of selective cyclooxygenase‐2 inhibition on prostate tissue in men undergoing prostatectomy. Materials and Methods Patients with localized prostate cancer were randomized to receive either celecoxib 400 mg twice daily or placebo for four weeks prior to prostatectomy. Specimens were analyzed for levels of apoptosis, prostaglandins, and androgen receptor. Effects on serum prostate‐specific antigen (PSA) and post‐operative opioid use were also measured. Results Twenty‐eight of 44 anticipated patients enrolled and completed treatment. One patient on the celecoxib arm had a myocardial infarction post‐operatively. For this reason, and safety concerns in other studies, enrollment was halted. The apoptosis index in tumor cells was 0.29% (95% CI: 0.11‐0.47%) versus 0.39% (95% CI: 0.00‐0.84%) in the celecoxib and placebo arms, respectively (p=0.68). The apoptosis index in benign cells was 0.18% (95% CI: 0.03‐0.32%) versus 0.13% (95% CI: 0.00‐0.28%) in the celecoxib and placebo arms, respectively (p=0.67). PGE2 and androgen receptor levels were similar in cancer and benign tissues when comparing the two arms. Median baseline PSA was 6.0ng/ml and 6.2ng/ml for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in post‐operative opiate usage between arms. Conclusion Celecoxib had no effect on apoptosis, prostaglandins or androgen receptor levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents. This article is protected by copyright. All rights reserved.
  • Selective Arterial Clamping Does Not Improve Outcomes in Robotic Partial
           Nephrectomy; A Propensity Score Analysis Of Patients Without Impaired
           Renal Function
    • Abstract: Objectives To assess the benefit of selective arterial clamping (SAC) as an alternative to main renal artery clamping (MAC) during robotic partial nephrectomy (RPN) in patients without underlying chronic kidney disease. Subjects/Patients and Methods Our study cohort comprised 665 patients without impaired renal function undergoing MAC (n=589) and SAC (n=76) RPN respectively from four medical institutions from 2008‐2015. We compared complication rates, positive surgical margin (PSM) rates, and perioperative and intermediate term renal functional outcome between 132 MAC and 66 SAC patients after 2 to 1 nearest neighbor propensity score matching for age, sex, BMI, R.E.N.A.L. Nephrometry score, tumor size, baseline eGFR, ASA, Charlson Comorbidity Index (CCI), and warm ischemia time (WIT). Results In propensity matched patients, PSM (5.7% vs. 3.0%, p=.407) and complications (13.8% vs. 10.6%, p=.727) did not differ for MAC vs. SAC. Incidence of acute kidney injury in MAC vs. SAC (25.0% vs. 32.0%, p=.315) within the first 30 days was similar. At median follow‐up of 7.5 months, the percentage reduction in eGFR (‐9.3% vs. ‐10.4%, p=.518) and progression to CKD ≥ Stage 3 (7.2% vs. 8.5%, p=.792) showed no difference. Conclusions Our study findings show no difference in PSM, complications, nor intermediate term renal functional outcomes in patients with unimpaired renal function with SAC compared to MAC. When expected WIT is low, routine utilization of SAC may not be necessary. Further studies will need to determine the role of SAC in solitary kidney patients or in patients with significantly impaired renal function. This article is protected by copyright. All rights reserved.
  • Prostate size, nocturia, and the digital rectal exam: a cohort study of
           30,500 men
    • Abstract: Objectives To evaluate the utility of the digital rectal exam (DRE) in estimating prostate size and the association of DRE with nocturia in a population‐based cohort. Subjects and Methods We identified all men randomized to the screening arm of the PLCO trial for whom DRE results were available. Subjects were excluded with history of prostate surgery or incident prostate cancer. Prostate posterior surface area was derived from DRE sagittal and transverse estimates. Relationships between prostate posterior surface area, transrectal ultrasound (TRUS), PSA, and nocturia were analyzed using intraclass correlation coefficient (ICC), Spearman's rank correlation, and multivariable logistic regression. Results 30,500 men met inclusion criteria, with 103,275 screening visits containing paired DRE and PSA data. DRE posterior surface area estimates had an ICC of 0.547 (95% CI 0.541‐0.554) and were significantly yet modestly correlated with increased prostate‐specific antigen (rs=0.18, p
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Heriot-Watt University
Edinburgh, EH14 4AS, UK
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