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J. of Medical Imaging and Radiation Oncology     Hybrid Journal   (Followers: 2, SJR: 0.378, h-index: 23)
J. of Medical Primatology     Hybrid Journal   (Followers: 1, SJR: 0.473, h-index: 28)
J. of Medical Radiation Sciences     Open Access   (Followers: 2)
J. of Medical Virology     Hybrid Journal   (Followers: 6, SJR: 0.936, h-index: 82)
J. of Metamorphic Geology     Hybrid Journal   (Followers: 6, SJR: 2.003, h-index: 72)
J. of Microscopy     Hybrid Journal   (Followers: 1, SJR: 0.655, h-index: 70)
J. of Midwifery & Women's Health     Hybrid Journal   (Followers: 20, SJR: 0.439, h-index: 32)
J. of Molecular Recognition     Hybrid Journal   (Followers: 1, SJR: 0.986, h-index: 56)
J. of Money, Credit and Banking     Hybrid Journal   (Followers: 17, SJR: 2.196, h-index: 55)
J. of Morphology     Hybrid Journal   (Followers: 3, SJR: 0.602, h-index: 44)
J. of Multi-Criteria Decision Analysis     Hybrid Journal   (Followers: 1)
J. of Multicultural Counseling and Development     Hybrid Journal   (Followers: 1, SJR: 0.314, h-index: 23)
J. of Muscle Foods     Hybrid Journal   (Followers: 2)
J. of Neurochemistry     Hybrid Journal   (SJR: 1.754, h-index: 162)
J. of Neuroendocrinology     Hybrid Journal   (Followers: 4, SJR: 1.038, h-index: 75)
J. of Neuroimaging     Hybrid Journal   (Followers: 1, SJR: 0.597, h-index: 39)
J. of Neuroscience Research     Hybrid Journal   (Followers: 6, SJR: 1.218, h-index: 113)
J. of Nursing and Healthcare of Chronic Illne Ss: An Intl. Interdisciplinary J.     Hybrid Journal   (Followers: 2)
J. of Nursing Management     Hybrid Journal   (Followers: 18, SJR: 1.028, h-index: 34)
J. of Nursing Scholarship     Hybrid Journal   (Followers: 2, SJR: 0.903, h-index: 45)
J. of Obstetric, Gynecologic, & Neonatal Nursing     Hybrid Journal   (Followers: 18, SJR: 0.499, h-index: 37)
J. of Obstetrics and Gynaecology Research     Hybrid Journal   (Followers: 13, SJR: 0.371, h-index: 30)
J. of Oral Pathology & Medicine     Hybrid Journal   (Followers: 3, SJR: 0.632, h-index: 51)
J. of Oral Rehabilitation     Hybrid Journal   (Followers: 2, SJR: 0.729, h-index: 51)
J. of Organizational Behavior     Hybrid Journal   (Followers: 20, SJR: 2.541, h-index: 83)
J. of Orthopaedic Research     Hybrid Journal   (Followers: 13, SJR: 1.246, h-index: 96)
J. of Paediatrics and Child Health     Hybrid Journal   (Followers: 14, SJR: 0.439, h-index: 46)
J. of Pathology     Hybrid Journal   (Followers: 8, SJR: 3.025, h-index: 122)
J. of Peptide Science     Hybrid Journal   (Followers: 14, SJR: 0.662, h-index: 42)
J. of Periodontal Research     Hybrid Journal   (SJR: 0.596, h-index: 53)
J. of Personality     Hybrid Journal   (Followers: 11, SJR: 1.803, h-index: 75)
J. of Petroleum Geology     Hybrid Journal   (Followers: 4, SJR: 0.471, h-index: 22)
J. of Pharmaceutical Sciences     Hybrid Journal   (Followers: 193, SJR: 1.206, h-index: 102)
J. of Philosophy of Education     Hybrid Journal   (Followers: 6, SJR: 0.491, h-index: 17)
J. of Phycology     Hybrid Journal   (Followers: 5, SJR: 0.864, h-index: 77)
J. of Physical Organic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.603, h-index: 45)
J. of Phytopathology     Hybrid Journal   (Followers: 2, SJR: 0.513, h-index: 33)
J. of Pineal Research     Hybrid Journal   (SJR: 1.435, h-index: 73)
J. of Plant Nutrition and Soil Science     Hybrid Journal   (Followers: 3, SJR: 0.732, h-index: 44)
J. of Policy Analysis and Management     Hybrid Journal   (Followers: 13, SJR: 1.297, h-index: 43)
J. of Policy and Practice In Intellectual Disabilities     Hybrid Journal   (Followers: 5, SJR: 0.684, h-index: 8)
J. of Political Philosophy     Hybrid Journal   (Followers: 29, SJR: 1.774, h-index: 26)
J. of Polymer Science Part A: Polymer Chemistry     Hybrid Journal   (Followers: 160, SJR: 1.281, h-index: 98)
J. of Polymer Science Part B: Polymer Physics     Hybrid Journal   (Followers: 22, SJR: 0.932, h-index: 87)
J. of Polymer Science Part C : Polymer Letters     Hybrid Journal   (Followers: 5)
J. of Popular Music Studies     Hybrid Journal   (Followers: 8, SJR: 0.142, h-index: 2)
J. of Product Innovation Management     Hybrid Journal   (Followers: 12, SJR: 2.157, h-index: 72)
J. of Prosthodontics     Hybrid Journal   (SJR: 0.358, h-index: 28)
J. of Psychiatric and Mental Health Nursing     Hybrid Journal   (Followers: 33, SJR: 0.473, h-index: 35)
J. of Psychological Issues in Organizational Culture     Hybrid Journal   (Followers: 1)
J. of Public Affairs     Hybrid Journal   (Followers: 2, SJR: 0.294, h-index: 5)
J. of Public Economic Theory     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 8)
J. of Public Health Dentistry     Hybrid Journal   (Followers: 1, SJR: 0.546, h-index: 38)
J. of Quaternary Science     Hybrid Journal   (Followers: 23, SJR: 1.543, h-index: 59)
J. of Raman Spectroscopy     Hybrid Journal   (Followers: 9, SJR: 1.138, h-index: 62)
J. of Rapid Methods and Automation In Microbiology     Hybrid Journal   (Followers: 2)
J. of Regional Science     Hybrid Journal   (Followers: 6, SJR: 1.961, h-index: 36)
J. of Religious Ethics     Hybrid Journal   (Followers: 5, SJR: 0.189, h-index: 8)
J. of Religious History     Hybrid Journal   (Followers: 18, SJR: 0.133, h-index: 7)
J. of Renal Care     Hybrid Journal   (Followers: 1, SJR: 0.32, h-index: 11)
J. of Research In Reading     Hybrid Journal   (Followers: 10, SJR: 0.81, h-index: 19)
J. of Research in Science Teaching     Hybrid Journal   (Followers: 11, SJR: 2.998, h-index: 62)
J. of Research in Special Educational Needs     Hybrid Journal   (Followers: 3, SJR: 0.349, h-index: 8)
J. of Research on Adolescence     Hybrid Journal   (Followers: 4, SJR: 1.634, h-index: 47)
J. of Risk & Insurance     Hybrid Journal   (Followers: 8, SJR: 1.138, h-index: 32)
J. of School Health     Hybrid Journal   (Followers: 7, SJR: 0.79, h-index: 47)
J. of Sensory Studies     Hybrid Journal   (Followers: 2, SJR: 0.65, h-index: 27)
J. of Separation Science     Hybrid Journal   (Followers: 7, SJR: 1.092, h-index: 55)
J. of Sexual Medicine     Hybrid Journal   (Followers: 6, SJR: 1.006, h-index: 57)
J. of Sleep Research     Hybrid Journal   (Followers: 8, SJR: 1.05, h-index: 67)
J. of Small Animal Practice     Hybrid Journal   (Followers: 8, SJR: 0.737, h-index: 39)
J. of Small Business Management     Hybrid Journal   (Followers: 10, SJR: 0.988, h-index: 42)
J. of Social Issues     Hybrid Journal   (Followers: 16, SJR: 1.532, h-index: 63)
J. of Social Philosophy     Hybrid Journal   (Followers: 16, SJR: 0.118, h-index: 3)
J. of Sociolinguistics     Hybrid Journal   (Followers: 12, SJR: 1.511, h-index: 18)
J. of Software : Evolution and Process     Hybrid Journal   (Followers: 2)
J. of Supreme Court History     Hybrid Journal   (Followers: 6)
J. of Surgical Oncology     Hybrid Journal   (Followers: 1, SJR: 1.024, h-index: 69)
J. of Synthetic Lubrication     Hybrid Journal  
J. of Systematics Evolution     Open Access   (Followers: 4, SJR: 0.933, h-index: 19)
J. of Texture Studies     Hybrid Journal   (Followers: 2, SJR: 0.601, h-index: 29)
J. of the American Association of Nurse Practitioners     Partially Free   (Followers: 3, SJR: 0.36, h-index: 23)
J. of the American Ceramic Society     Hybrid Journal   (Followers: 22, SJR: 1.167, h-index: 119)
J. of the American Geriatrics Society     Hybrid Journal   (Followers: 12, SJR: 1.673, h-index: 138)
J. of the American Society for Information Science and Technology     Hybrid Journal   (Followers: 149, SJR: 1.555, h-index: 74)
J. of the American Water Resources Association     Hybrid Journal   (Followers: 18, SJR: 0.817, h-index: 56)
J. of the Association for Information Science and Technology     Hybrid Journal   (Followers: 1)
J. of the CardioMetabolic Syndrome     Hybrid Journal  
J. of the European Academy of Dermatology and Venereology     Hybrid Journal   (Followers: 9, SJR: 1.211, h-index: 51)
J. of the Experimental Analysis of Behavior     Hybrid Journal   (Followers: 2, SJR: 0.535, h-index: 35)
J. of the History of the Behavioral Sciences     Hybrid Journal   (Followers: 1, SJR: 0.46, h-index: 13)
J. of the Institute of Brewing     Free   (SJR: 0.528, h-index: 25)
J. of the Peripheral Nervous System     Hybrid Journal   (Followers: 2, SJR: 0.935, h-index: 40)
J. of the Royal Anthropological Institute     Hybrid Journal   (Followers: 29, SJR: 1.128, h-index: 25)
J. of the Royal Statistical Society Series A (Statistics in Society)     Hybrid Journal   (Followers: 9, SJR: 1.258, h-index: 44)
J. of the Royal Statistical Society Series B (Statistical Methodology)     Hybrid Journal   (Followers: 20, SJR: 5.518, h-index: 75)
J. of the Royal Statistical Society Series C (Applied Statistics)     Hybrid Journal   (Followers: 13, SJR: 0.877, h-index: 47)
J. of the Science of Food and Agriculture     Hybrid Journal   (Followers: 20, SJR: 0.781, h-index: 80)
J. of the Society for Information Display     Hybrid Journal   (Followers: 1, SJR: 0.521, h-index: 30)
J. of the Society for the Anthropology of Europe     Hybrid Journal   (Followers: 8)

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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  [1603 journals]   [SJR: 1.381]   [H-I: 96]
  • Extent of lymph node dissection at nephrectomy affects
           cancer‐specific survival and metastatic progression in specific
           sub‐categories of patients with renal cell carcinoma (RCC)
    • Authors: Umberto Capitanio; Nazareno Suardi, Rayan Matloob, Marco Roscigno, Firas Abdollah, Ettore Di Trapani, Marco Moschini, Andrea Gallina, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Roberto Bertini
      Abstract: Objective To test whether the number of lymph nodes removed affects cancer‐specific survival (CSS) or metastatic progression‐free survival (MPFS) in different renal cell carcinoma (RCC) scenarios. Methods We used Cox regression analyses to analyse the effect of the number of lymph nodes removed on CSS and MPFS in 1983 patients with RCC treated with nephrectomy. To adjust for possible clinical and surgical selection bias, analyses were further adjusted for number of positive nodes, presence of metastases, age, performance status, T stage, tumour size and grade. Results The prevalence of lymph node invasion was 6.1%. The mean follow‐up period was 83.3 months. Multivariable analyses showed that the number of nodes removed had an independent, protective effect on CSS in patients with pT2a–pT2b or pT3c–pT4 RCC (hazard ratio [HR] 0.91, P = 0.008 and HR 0.89, P < 0.001, respectively), in patients with bulky tumours (tumour size >10 cm, HR 0.97, P = 0.03) or when sarcomatoid features were found (HR 0.81, P = 0.006). The removal of each additional lymph node was associated with a 3–19% increase in CSS. When considering MPFS as an endpoint, the number of nodes removed had an independent, protective effect in the same patient categories. Conclusions When clinically indicated, the number of nodes removed affects CSS and MPFS in specific sub‐categories of patients with RCC.
      PubDate: 2014-05-22T03:43:07.745286-05:
      DOI: 10.1111/bju.12508
  • The changing face of urinary continence surgery in England: a perspective
           from the Hospital Episode Statistics database
    • Authors: John Withington; Sadaf Hirji, Arun Sahai
      Abstract: Objective To quantify changes in surgical practice in the treatment of stress urinary incontinence (SUI), urge urinary incontinence (UUI) and post‐prostatectomy stress incontinence (PPI) in England, using the Hospital Episode Statistics (HES) database. Patients and Methods We used public domain information from the HES database, an administrative dataset recording all hospital admissions and procedures in England, to find evidence of change in the use of various surgical procedures for urinary incontinence from 2000 to 2012. Results For the treatment of SUI, a general increase in the use of synthetic mid‐urethral tapes, such as tension‐free vaginal tape (TVTO) and transobturator tape (TOT), was observed, while there was a significant decrease in colposuspension procedures over the same period. The number of procedures to remove TVT and TOT has also increased in recent years. In the treatment of overactive bladder and UUI, there has been a significant increase in the use of botulinum toxin A and neuromodulation in recent years. This coincided with a steady decline in the recorded use of clam ileocystoplasty. A steady increase was observed in the insertion of artificial urinary sphincter (AUS) devices in men, related to PPI. Conclusions Mid‐urethral synthetic tapes now represent the mainstream treatment of SUI in women, but tape‐related complications have led to an increase in procedures to remove these devices. The uptake of botulinum toxin A and sacral neuromodulation has led to fewer clam ileocystoplasty procedures being performed. The steady increase in insertions of AUSs in men is unsurprising and reflects the widespread uptake of radical prostatectomy in recent years. There are limitations to results sourced from the HES database, with potential inaccuracy of coding; however, these data support the trends observed by experts in this field.
      PubDate: 2014-05-22T03:16:52.448775-05:
      DOI: 10.1111/bju.12650
  • Low free testosterone levels predict disease reclassification in men with
           prostate cancer undergoing active surveillance
    • Authors: Ignacio F. San Francisco; Pablo A. Rojas, William C. DeWolf, Abraham Morgentaler
      Abstract: Objective To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). Patients and Methods Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t‐test and a chi‐squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. Results A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels
      PubDate: 2014-05-04T21:48:04.430901-05:
      DOI: 10.1111/bju.12682
  • Role of urinary cations in the aetiology of bladder symptoms and
           interstitial cystitis
    • Authors: C. Lowell Parsons; Timothy Shaw, Zoltan Berecz, Yongxuan Su, Paul Zupkas, Sulabha Argade
      Abstract: Objectives To identify and characterise urinary cationic metabolites, defined as toxic factors, in patients with interstitial cystitis (IC) and in control subjects. To evaluate the cytotoxicity of the urinary cationic metabolite fraction of patients with IC vs control subjects and of individual metabolites in cultured urothelial cells. Subjects and Methods Cationic fractions (CFs) were isolated from the urine specimens of 62 patients with IC and 33 control subjects by solid‐phase extraction. CF metabolites were profiled using C18 reverse‐phase high performance liquid chromatography (RP‐HPLC) with UV detection, quantified by area‐under‐the‐peaks using known standards, and normalized to creatinine. RP‐HPLC and liquid chromatography (LC)‐mass spectrometry (MS)/tandem MS (MS/MS) were used to identify major CF peaks. HTB‐4 urothelial cells were used to determine the cytotoxicity of CFs and of individual metabolites with and without Tamm–Horsfall protein (THP). Results RP‐HPLC analysis showed that metabolite quantity was twofold higher in patients with IC compared with control subjects. The mean (sem) for control subjects vs patients was 3.1 (0.2) vs 6.3 (0.5) mAU*min/μg creatinine (P < 0.001). LC‐MS identified 20 metabolites. Patients with IC had higher levels of modified nucleosides, amino acids and tryptophan derivatives compared with control subjects. The CF cytotoxicity was higher for patients with IC compared with control subjects. The mean (sem) for control subjects vs patients was −2.3 (2.0)% vs 36.7 (2.7)% (P < 0.001). A total of 17 individual metabolites were tested for their cytotoxicity. Cytotoxicity data for major metabolites were all significant (P < 0.001): 1‐methyladenosine (51%), 5‐methylcytidine (36%), 1‐methyl guanine (31%), N4‐acetylcytidine (24%), N7‐methylguanosine (20%) and L‐Tryptophan (16%). These metabolites were responsible for higher toxicity in patients with IC. The toxicity of all metabolites was significantly lower in the presence of control THP (P < 0.001). Conclusions Major urinary cationic metabolites were characterised and found to be present in higher amounts in patients with IC compared with control subjects. The cytotoxicity of cationic metabolites in patients with IC was significantly higher than in control subjects, and control THP effectively lowered the cytotoxicity of these metabolites. These data provide new insights into toxic factor composition as well as a framework in which to develop new therapeutic strategies to sequester their harmful activity, which may help relieve the bladder symptoms associated with IC.
      PubDate: 2014-04-16T22:25:25.708897-05:
      DOI: 10.1111/bju.12603
  • In vitro fragmentation efficiency of holmium:
           yttrium‐aluminum‐garnet (YAG) laser lithotripsy – a
           comprehensive study encompassing different frequencies, pulse energies,
           total power levels and laser fibre diameters
    • Authors: Peter Kronenberg; Olivier Traxer
      Pages: n/a - n/a
      Abstract: Objective To assess the fragmentation (ablation) efficiency of laser lithotripsy along a wide range of pulse energies, frequencies, power settings and different laser fibres, in particular to compare high‐ with low‐frequency lithotripsy using a dynamic and innovative testing procedure free from any human interaction bias. Materials and Methods An automated laser fragmentation testing system was developed. The unmoving laser fibres fired at the surface of an artificial stone while the stone was moved past at a constant velocity, thus creating a fissure. The lithotripter settings were 0.2–1.2 J pulse energies, 5–40 Hz frequencies, 4–20 W power levels, and 200 and 550 μm core laser fibres. Fissure width, depth, and volume were analysed and comparisons between laser settings, fibres and ablation rates were made. Results Low frequency‐high pulse energy (LoFr‐HiPE) settings were (up to six times) more efficient than high frequency‐low pulse energy (HiFr‐LoPE) at the same power levels (P < 0.001), as they produced deeper (P < 0.01) and wider (P < 0.001) fissures. There were linear correlations between pulse energy and fragmentation volume, fissure width, and fissure depth (all P < 0.001). Total power did not correlate with fragmentation measurements. Laser fibre diameter did not affect fragmentation volume (P = 0.81), except at very low pulse energies (0.2 J), where the large fibre was less efficient (P = 0.015). Conclusions At the same total power level, LoFr‐HiPE lithotripsy was most efficient. Pulse energy was the key variable that drove fragmentation efficiency. Attention must be paid to prevent the formation of time‐consuming bulky debris and adapt the lithotripter settings to one's needs. As fibre diameter did not affect fragmentation efficiency, small fibres are preferable due to better scope irrigation and manoeuvrability.
      PubDate: 2014-04-16T03:55:29.785349-05:
      DOI: 10.1111/bju.12567
  • Robot‐assisted laparoscopic ureteric reimplantation: extravesical
    • Abstract: Objectives To describe our standardised approach to performing robot‐assisted extravesical ureteric reimplantation. Patients and Methods A total of 29 children, with high grade (III–V) vesico‐ureteric reflux (VUR) underwent robot‐assisted extravesical ureteric reimplantation between September 2010 and September 2013. Follow‐up renal ultrasonography was performed at 1 month and 3 months and a voiding cysto‐urethrogram (VCUG) was obtained at 4 months to assess VUR resolution. Results The mean (range) patient age at the time of surgery was 5.38 (3.0–10.0) years. Postoperative VCUG showed complete resolution of VUR in 32/40 ureters (80%). Of the remaining refluxing ureters, downgrading of VUR on VCUG was shown in 7/8 ureters (87.5%). The mean (range) length of hospital stay was 1.8 (1–3) days. Conclusions In conclusion, robot‐assisted extravesical ureteric reimplantation is technically feasible with acceptable resolution of VUR.
  • Health‐related quality of life from a prospective randomised
           clinical trial of robot‐assisted laparoscopic vs open radical
    • Abstract: Objective To compare health‐related quality‐of‐life (HRQoL) outcomes for robot‐assisted laparoscopic radical cystectomy (RARC) with those of traditional open radical cystectomy (ORC) in a prospective randomised fashion. Patients and Methods This was a prospective randomised clinical trial evaluating the HRQoL for ORC vs RARC in consecutive patients from July 2009 to June 2011. We administered the Functional Assessment of Cancer Therapy–Vanderbilt Cystectomy Index questionnaire, validated to assess HRQoL, preoperatively and then at 3, 6, 9 and 12 months postoperatively. Scores for each domain and total scores were compared in terms of deviation from preoperative values for both the RARC and the ORC cohorts. Multivariate linear regression was used to assess the association between the type of radical cystectomy and HRQoL. Results At the time of the study, 47 patients had met the inclusion criteria, with 40 patients being randomised for analysis. The cohorts consisted of 20 patients undergoing ORC and 20 undergoing RARC, who were balanced with respect to baseline demographic and clinical features. Univariate analysis showed a return to baseline scores at 3 months postoperatively in all measured domains with no statistically significant difference among the various domains between the RARC and the ORC cohorts. Multivariate analysis showed no difference in HRQoL between the two approaches in any of the various domains, with the exception of a slightly higher physical well‐being score in the RARC group at 6 months. Conclusions There were no significant differences in the HRQoL outcomes between ORC and RARC, with a return of quality of life scores to baseline scores 3 months after radical cystectomy in both cohorts.
  • Diagnostic performance and safety of a three‐dimensional
           14‐core systematic biopsy method
    • Abstract: Objective To investigate the diagnostic performance and safety of a three‐dimensional 14‐core biopsy (3D14PBx) method, which is a combination of the transrectal six‐core and transperineal eight‐core biopsy methods. Patients and Methods Between December 2005 and August 2010, 1103 men underwent 3D14PBx at our institutions and were analysed prospectively. Biopsy criteria included a PSA level of 2.5–20 ng/mL or abnormal digital rectal examination (DRE) findings, or both. The primary endpoint of the study was diagnostic performance and the secondary endpoint was safety. We applied recursive partitioning to the entire study cohort to delineate the unique contribution of each sampling site to overall and clinically significant cancer detection. Results Prostate cancer was detected in 503 of the 1103 patients (45.6%). Age, family history of prostate cancer, DRE, PSA, percentage of free PSA and prostate volume were associated with the positive biopsy results significantly and independently. Of the 503 cancers detected, 39 (7.8%) were clinically locally advanced (≥cT3a), 348 (69%) had a biopsy Gleason score (GS) of ≥7, and 463 (92%) met the definition of biopsy‐based significant cancer. Recursive partitioning analysis showed that each sampling site contributed uniquely to both the overall and the biopsy‐based significant cancer detection rate of the 3D14PBx method. The overall cancer‐positive rate of each sampling site ranged from 14.5% in the transrectal far lateral base to 22.8% in the transrectal far lateral apex. As of August 2010, 210 patients (42%) had undergone radical prostatectomy, of whom 55 (26%) were found to have pathologically non‐organ‐confined disease, 174 (83%) had prostatectomy GS ≥7 and 185 (88%) met the definition of prostatectomy‐based significant cancer. Conclusions This is the first prospective analysis of the diagnostic performance of an extended biopsy method, which is a simplified version of the somewhat redundant super‐extended three‐dimensional 26‐core biopsy. As expected, each sampling site uniquely contributed not only to overall cancer detection, but also to significant cancer detection. 3D14PBx is a feasible systematic biopsy method in men with PSA
  • Clinical role of pathological downgrading after radical prostatectomy in
           patients with biopsy confirmed Gleason score 3 + 4 prostate cancer
    • Abstract: Objective To identify preoperative factors predicting Gleason score downgrading after radical prostatectomy (RP) in patients with biopsy Gleason score 3+4 prostate cancer and to determine if prediction of downgrading can identify potential candidates for active surveillance (AS). Patients and Methods We identified 1317 patients with biopsy Gleason score 3+4 prostate cancers who underwent RP at the Memorial Sloan‐Kettering Cancer Center between 2005 and 2013. Several preoperative and biopsy characteristics were evaluated by forward selection regression, and selected predictors of downgrading were analysed by multivariable logistic regression. Decision curve analysis was used to evaluate the clinical utility of the multivariate model. Results Gleason score was downgraded after RP in 115 patients (9%). We developed a multivariable model using age, prostate‐specific antigen density, percentage of positive cores with Gleason pattern 4 cancer out of all cores taken, and maximum percentage of cancer involvement within a positive core with Gleason pattern 4 cancer. The area under the curve for this model was 0.75 after 10‐fold cross validation. However, decision curve analysis revealed that the model was not clinically helpful in identifying patients who will downgrade at RP for the purpose of reassigning them to AS. Conclusion While patients with pathological Gleason score 3 + 3 with tertiary Gleason pattern ≤4 at RP in patients with biopsy Gleason score 3 + 4 prostate cancer may be potential candidates for AS, decision curve analysis showed limited utility of our model to identify such men. Future study is needed to identify new predictors to help identify potential candidates for AS among patients with biopsy confirmed Gleason score 3 + 4 prostate cancer.
  • Silencing histone deacetylase 2 using small hairpin RNA induces regression
           of fibrotic plaque in a rat model of Peyronie's disease
    • Abstract: Objectives To examine the therapeutic effect of adenovirus encoding histone deacetylase 2 (HDAC2) small hairpin RNA (Ad‐HDAC2 shRNA) in a rat model of Peyronie's disease (PD) and to determine the mechanisms by which HDAC2 knockdown ameliorates fibrotic responses in primary fibroblasts derived from human PD plaque. Materials and Methods Rats were distributed into four groups (n = 6 per group): age‐matched controls without treatment; rats in which PD has been induced (PD rats) without treatment; PD rats receiving a single injection of control adenovirus encoding scrambled small hairpin RNA (Ad‐shRNA) (day 15; 1 × 108 pfu/0.1 mL phosphate‐buffered saline [PBS]); and PD rats receiving a single injection of Ad‐HDAC2 shRNA (day 15; 1 × 108 pfu/0.1 mL PBS) into the lesion. PD‐like plaque was induced by repeated intratunical injections of 100 μL each of human fibrin and thrombin solutions on days 0 and 5. On day 30, the penis was harvested for histological examination. Fibroblasts isolated from human PD plaque were pretreated with HDAC2 small interfering (si)RNA (100 pmoL) and then stimulated with transforming growth factor (TGF)‐β1 (10 ng/mL) to determine hydroxyproline levels, procollagen mRNA, apoptosis and protein expression of poly(ADP‐ribose) polymerase 1 (PARP1) and cyclin D1. Results We observed that Ad‐HDAC2 shRNA decreased inflammatory cell infiltration, reduced transnuclear expression of phospho‐Smad3 and regressed fibrotic plaque of the tunica albuginea in PD rats in vivo. siRNA‐mediated silencing of HDAC2 significantly decreased the TGF‐β1‐induced transdifferentiation of fibroblasts into myofibroblasts and collagen production, and induced apoptosis by downregulating the expression of PARP1, and decreased the expression of cyclin D1 (a positive cell‐cycle regulator) in primary cultured fibroblasts derived from human PD plaque in vitro. Conclusion Specific inhibition of HDAC2 with RNA interference may represent a novel targeted therapy for PD.
  • Development and internal validation of a nomogram for predicting
           stone‐free status after flexible ureteroscopy for renal stones
    • Abstract: Objective To develop and internally validate a preoperative nomogram for predicting stone‐free status (SF) after flexible ureteroscopy (fURS) for renal stones, as there is a need to predict the outcome of fURS for the treatment of renal stone disease. Patients and Methods We retrospectively analysed 310 fURS procedures for renal stone removal performed between December 2009 and April 2013. Final outcome of fURS was determined by computed tomography 3 months after the last fURS session. Assessed preoperative factors included stone volume and number, age, sex, presence of hydronephrosis and lower pole calculi, and ureteric stent placement. Multivariate logistic regression analysis with backward selection was used to model the relationship between preoperative factors and SF after fURS. Bootstrapping was used to internally validate the nomogram. Results Five independent predictors of SF after fURS were identified: stone volume (P < 0.001), presence of lower pole calculi (P = 0.001), operator with experience of >50 fURS (P = 0.026), stone number (P = 0.075), and presence of hydronephrosis (P = 0.047). We developed a nomogram to predict SF after fURS using these five preoperative characteristics. Total nomogram score (maximum 25) was derived from summing individual scores of each predictive variable; a high total score was predictive of successful fURS outcome, whereas a low total score was predictive of unsuccessful outcome. The area under the receiver operating characteristics for nomogram predictions was 0.87. Conclusion The nomogram can be used to reliably predict SF based on patient characteristics after fURS treatment of renal stone disease.
  • Outcomes of men with an elevated prostate‐specific antigen (PSA)
           level as their sole preoperative intermediate‐ or high‐risk
    • Abstract: Objective To investigate the post‐prostatectomy and long‐term outcomes of men presenting with an elevated pretreatment prostate‐specific antigen (PSA) level (>10 ng/mL), but otherwise low‐risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). Patients and Methods PSA‐incongruent intermediate‐risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low‐risk features, and PSA‐incongruent high‐risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low‐risk features. Our institutional radical prostatectomy database (1992–2012) was queried and the results were stratified into D’Amico low‐, intermediate‐ and high risk, PSA‐incongruent intermediate‐risk and PSA‐incongruent high‐risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Results Of the total cohort of 17 608 men, 1132 (6.4%) had PII‐risk disease and 183 (1.0%) had PIH‐risk disease. Compared with the low‐risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93–2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64–4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05–2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89–9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67–2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50–4.95, P < 0.001) for the PIH group. Compared with low‐risk disease, PII‐risk disease was associated with a 2.85‐, 2.99‐ and 3.32‐fold greater risk of biochemical recurrence (BCR), metastasis and PCa‐specific mortality, respectively, and PIH‐risk disease was associated with a 5.32‐, 6.14‐ and 7.07‐fold greater risk of BCR, metastasis and PCa‐specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD 10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low‐risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low‐risk group, and consideration of surveillance is appropriate in these cases.
  • Combined injection of three different lineages of
           early‐differentiating human amniotic fluid‐derived cells
           restores urethral sphincter function in urinary incontinence
    • Abstract: Objective To investigate whether a triple combination of early‐differentiated cells derived from human amniotic fluid stem cells (hAFSCs) would show synergistic effects in urethral sphincter regeneration. Materials and Methods We early‐differentiated hAFSCs into muscle, neuron and endothelial progenitor cells and then injected them into the urethral sphincter region of pudendal neurectomized ICR mice, as single‐cell, double‐cell or triple‐cell combinations. Urodynamic studies and histological, immunohistochemical and molecular analyses were performed. Results Urodynamic study showed significantly improved leak point pressure in the triple‐cell‐combination group compared with the single‐cell‐ or double‐cell‐combination groups. These functional results were confirmed by histological and immunohistochemical analyses, as evidenced by the formation of new striated muscle fibres and neuromuscular junctions at the cell injection site. Molecular analysis showed higher target marker expression in the retrieved urethral tissue of the triple‐cell‐combination group. The injection of early‐differentiated hAFSCs suppressed in vivo host CD8 lymphocyte aggregations and did not form teratoma. The nanoparticle‐labelled early‐differentiated hAFSCs could be tracked in vivo with optical imaging for up to 14 days after injection. Conclusion Our novel concept of triple‐combined early‐differentiated cell therapy for the damaged sphincter may provide a viable option for incontinence treatment.
  • Is radical nephrectomy a legitimate therapeutic option in patients with
           renal masses amenable to nephron‐sparing surgery'
    • Abstract: The decision to perform a radical nephrectomy (RN) or a partial nephrectomy (PN), not unlike most decisions in clinical practice, ultimately hinges on the balance of risk. Do the higher risks of a more complex surgery (PN) justify the theoretical benefits of kidney tissue preservation' Data suggest that for patients with an anatomically complex renal mass and a normal contralateral kidney, for whom additional surgical intensity may be risky, such as the elderly and comorbid, RN presents a robust treatment option. Nevertheless, PN, especially for small and anatomically simple renal masses in young patients without comorbidities should remain the surgical reference standard, as preservation of renal tissue can serve as an ‘insurance policy’ not only against future renal functional decline, but also against the possibility of tumour development in the contralateral kidney. In the present review, we outline the ongoing debate between the role of RN and PN in treatment of the enhancing renal mass.
  • Differences in 24‐h urine composition between nephrolithiasis
           patients with and without diabetes mellitus
    • Abstract: Objectives To examine the differences in 24‐h urine composition between nephrolithiasis patients with and without diabetes mellitus (DM) in a large cohort of stone‐formers and to examine differences in stone composition between patients with and without DM. Patients and Methods A retrospective review of 1117 patients with nephrolithiasis and a 24‐h urine analysis was completed. Univariable analysis of 24‐h urine profiles and multivariable linear regression models were performed, comparing patients with and without DM. A subanalysis of patients with stone analysis data available was performed, comparing the stone composition of patients with and without DM. Results Of the 1117 patients who comprised the study population, 181 (16%) had DM and 936 (84%) did not have DM at the time of urine analysis. Univariable analysis showed significantly higher total urine volume, citrate, uric acid (UA), sodium, potassium, sulphate, oxalate, chloride, and supersaturation (SS) of UA in individuals with DM (all P < 0.05). However, patients with DM had significantly lower SS of calcium phosphate and pH (all P < 0.05). Multivariable analysis showed that patients with DM had significantly lower urinary pH and SS of calcium phosphate, but significantly greater citrate, UA, sulphate, oxalate, chloride, SSUA, SS of calcium oxalate, and volume than patients without DM (all P < 0.05). Patients with DM had a significantly greater proportion of UA in their stones than patients without DM (50.2% vs 13.5%, P < 0.001). Conclusions DM was associated with multiple differences on 24‐h urine analysis compared with those without DM, including significantly higher UA and oxalate, and lower pH. Control of urinary UA and pH, as well as limiting intake of dietary oxalate may reduce stone formation in patients with DM.
  • External validation of the Briganti nomogram to estimate the probability
           of specimen‐confined disease in patients with high‐risk
           prostate cancer
    • Abstract: Objective To establish an external validation of the updated nomogram from Briganti et al., which provides estimates of the probability of specimen‐confined disease using the variables age, prostate‐specific antigen (PSA), clinical stage and biopsy Gleason score in preoperatively defined high‐risk prostate cancer (PCa). Patients and Methods The study included 523 patients with high‐risk PCa, as defined by d'Amico classification, undergoing radical prostatectomy (RP) and bilateral lymph node dissection in one of two academic centres between 1990 and 2013. Specimen‐confined disease was defined as pT2–pT3a node‐negative PCa with negative surgical margins. The receiver–operator characteristic (ROC) curve was obtained to quantify the overall accuracy (area under the curve [AUC]) of the model in predicting specimen‐confined disease. A calibration curve was then constructed to illustrate the relationship between the risk estimates obtained by the model (x‐axis) and the observed proportion of specimen‐confined disease (y‐axis). The Kaplan–Meier method was used to assess biochemical recurrence (BCR)‐free survival. Results Patients' median age and PSA level were 64 years and 21 ng/mL, respectively. The definition of high‐risk PCa was based on PSA level only in 38.3%, a biopsy Gleason score >7 in 34.5%, a clinical stage >T2b in 6.9%, or a combination of these two or three factors in 20.3% of patients. Positive surgical margins were observed in 43.6%, with a rate of 14.8% in pT2 cancers and lymph node metastasis in 12.1% of patients. pT stage was pT0 in 0.9%, pT2 in 28.9%, pT3a in 37.5% and pT3b–4 in 32.7% of patients. Overall, 44.4% of patients (N = 232) had specimen‐confined disease. PSA and cT stage were independently predictive of specimen‐confined disease. The median (range) 2‐, 5‐, and 8‐year BCR‐free survival rates were significantly higher in specimen‐confined disease as compared with non‐specimen‐confined disease: 80.87 (73.67–86.29) vs 37.55 (30.64–44.44)%, 63.53 (52.37–72.74) vs 26.93 (19.97–34.36)% and 55.08 (41.49–66.74) vs 19.52 (12.50–27.70)%, respectively (P < 0.001). The ROC curve analysis showed relevant accuracy of the model (AUC 0.6470, 95% CI 0.60–0.69) although the calibration plot suggested that, for risks ranging from 0.3 to 0.5, the odds of extracapsular extension were underestimated. Conclusions This external validation of the Briganti nomogram shows relevant accuracy, although the relative imprecision for intermediate risk may limit its clinical relevance. Our follow‐up findings confirm the large proportion of specimen‐confined PCa with good oncological outcomes in this heterogeneous subgroup of patients with high‐risk PCa.
  • Prostate cancer mortality outcomes and patterns of primary treatment for
           Aboriginal men in New South Wales, Australia
    • Abstract: Objective To compare prostate cancer mortality for Aboriginal and non‐Aboriginal men and to describe prostate cancer treatments received by Aboriginal men. Subjects and methods We analysed cancer registry records for all men diagnosed with prostate cancer in New South Wales (NSW) in 2001‐2007 linked to hospital inpatient episodes and deaths. More detailed information on androgen deprivation therapy and radiotherapy was obtained from medical records for 87 NSW Aboriginal men diagnosed in 2000‐2011. The main outcomes were primary treatment for, and death from, prostate cancer. Analysis included Cox proportional hazards regression and logistic regression. Results There were 259 Aboriginal men among 35214 prostate cancer cases diagnosed in 2001‐2007. Age and spread of disease at diagnosis were similar for Aboriginal and non‐Aboriginal men. Prostate cancer mortality 5 years after diagnosis was higher for Aboriginal men (17.5%, 95% Confidence Interval (CI):12.4‐23.3) than non‐Aboriginal men (11.4%, 95% CI:11.0‐11.8). Aboriginal men were 49% more likely to die of prostate cancer (Hazard Ratio 1.49, 95% CI:1.07‐1.99) after adjusting for differences in demographic factors, stage at diagnosis, health access and comorbidities. Aboriginal men were less likely to have a prostatectomy for localised or regional cancer than non‐Aboriginal men (adjusted Odds Ratio 0.60 95% CI:0.40‐0.91). Of 87 Aboriginal men with full staging and treatment information 60% were diagnosed with localised disease. Of these 38% had a prostatectomy (+/‐ radiotherapy), 29% had radiotherapy only and 33% had neither. Conclusion More research is required to explain differences in treatment and mortality for Aboriginal men with prostate cancer compared to non‐Aboriginal men. In the meantime, ongoing monitoring and efforts are needed to ensure Aboriginal men have equitable access to best care.
  • Lymphatic drainage in renal cell carcinoma: back to the basics
    • Abstract: Lymphatic drainage in renal cell carcinoma (RCC) is unpredictable, however, basic patterns can be observed in cadaveric and sentinel lymph node mapping studies in patients with RCC. The existence of peripheral lymphovenous communications at the level of the renal vein has been shown in mammals but remains unknown in humans. The sentinel lymph node biopsy technique can be safely applied to map lymphatic drainage patterns in patients with RCC. Further standardisation of sentinel node biopsy techniques is required to improve the clinical significance of mapping studies. Understanding lymphatic drainage in RCC may lead to an evidence‐based consensus on the surgical management of retroperitoneal lymph nodes.
  • Propensity‐score matched analysis comparing robot‐assisted
           with laparoscopic partial nephrectomy
    • Abstract: Objectives To compare the peri‐operative and early renal functional outcomes of robot‐assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) for kidney tumours. Materials and Methods A total of 237 patients fulfilling the selection criteria were included, of whom 146 and 91 patients were treated with LPN and RAPN, respectively. To adjust for potential baseline confounders, propensity‐score matching was performed. A favourable outcome was defined as a warm ischaemia time (WIT) of ≤20 min, negative surgical margins, no surgical conversion, no Clavien ≥3 complications and no postoperative chronic kidney disease (CKD) upstaging. Descriptive statistics and multivariable logistic regression analyses were performed before and after propensity‐score matching. Results Within the propensity‐score‐matched cohort, the RAPN group was associated with significantly lower estimated blood loss (EBL; 156 vs 198 mL, mean difference [MD] = −42; P = 0.025), a shorter WIT (22.8 vs 31 min, MD = −8.2; P < 0.001) and a higher proportion of malignant lesions (88.4 vs 67.5%; odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.2–5.67; P = 0.023). With regard to early renal functional outcomes, the mean last estimated glomerular filtration rate was 95.8 and 89.4 mL/min per 1.73 m2 (MD = 6.4; P = 0.01), with a mean ± sd percentage change of −4.8 ± 17.9 and −12.2 ± 16.6 (MD = 7.4; P = 0.018) in the RAPN and LPN groups, respectively. The intra‐operative complication rate was significantly lower in the RAPN group (1.3 vs 11.7%; OR 0.1, 95% CI 0.01–0.81; P = 0.018). On multivariable analysis, surgical approach (RAPN vs LPN, OR 5.457, 95% CI 2.075–14.346; P = 0.001), Charlson Comorbidity Index (OR 0.223; 95% CI 0.062–0.811; P = 0.023), diameter‐axial‐polar score (OR 0.488, 95% CI 0.329–0.723; P < 0.001) and preoperative CKD stage (OR 3.189, 95% CI 1.204–8.446; P = 0.020) were found to be independent predictors of obtaining a favourable outcome. Conclusions After adjusting for potential treatment selection biases, RAPN was found to be superior to LPN for peri‐operative outcomes (EBL, WIT and intra‐operative complications) and early renal functional preservation.
  • Early unclamping technique during robot‐assisted laparoscopic
           partial nephrectomy can minimise warm ischaemia without increasing
    • Abstract: Objective To compare perioperative outcomes of early unclamping (EUC) vs standard unclamping (SUC) during robot‐assisted partial nephrectomy (RAPN), as early unclamping of the renal pedicle has been reported to decrease warm ischaemia time (WIT) during laparoscopic PN. Patients and Methods A retrospective multi‐institutional study was conducted at eight French academic centres between 2009 and 2013. Patients who underwent RAPN for a renal mass were included in the study. Patients without vascular clamping or for whom the decision to perform a radical nephrectomy was taken before unclamping were excluded. Perioperative outcomes were compared using the chi‐squared and Fisher's exact tests for discrete variables and the Mann–Whitney test for continuous variables. Predictors of WIT and estimated blood loss (EBL) were assessed using multiple linear regression analysis. Results In all, there were 430 patients: 222 in the EUC group and 208 in the SUC group. Tumours were larger (35.8 vs 32.3 mm, P = 0.02) and more complex (R.E.N.A.L. nephrometry score 6.9 vs 6.1, P < 0.001) in the EUC group but surgeons were more experienced (>50 procedures 12.2% vs 1.4%, P < 0.001). The mean WIT was shorter (16.7 vs 22.3 min, P < 0.001) and EBL was higher (369.5 vs 240 mL, P = 0.001) in the EUC group with no significant difference in complications or transfusion rates. The results remained the same when analysing subgroups of complex renal tumours (R.E.N.A.L. nephrometry score ≥7) or RAPN performed by less experienced surgeons (
  • Exploring the evidence for early unclamping during robot‐assisted
           partial nephrectomy: is it worth the time and effort'
  • Baseline characteristics predict risk of progression and response to
           combined medical therapy for benign prostatic hyperplasia (BPH)
    • Abstract: Objective To better risk stratify patients, using baseline characteristics, to help optimise decision‐making for men with moderate‐to‐severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. Patients and Methods After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre‐treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. Results In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post‐void residual urine volume, serum prostate‐specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. Conclusions Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient‐specific benefits against possible risks of adverse effects for a given patient.
  • Association of Androgen Deprivation Therapy with Excess
           Cardiac‐Specific Mortality in Men with Prostate Cancer
    • Abstract: Objectives To determine if androgen deprivation therapy (ADT) is associated with excess cardiac‐specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI). Subjects/patients and methods Five thousand seventy‐seven men (median age, 69.5 years) with cT1c‐T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration, four months) between 1997 and 2006. Fine and Gray's competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity. Results After a median follow‐up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at five years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39‐1.78; P=0.64; n=2653) or in men with diabetes mellitus, hypertension, or hypercholesterolemia (2.09% vs 1.97%, AHR, 1.33; 95% CI, 0.70‐2.53; P=0.39; n=2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01‐10.64; P=0.048; n=256). In this subgroup, the five‐year cumulative incidence of CSM was 7.01% (95% CI 2.82‐13.82%) for ADT vs 2.01% (95% CI 0.38‐6.45%) for no ADT. Conclusion ADT was associated with a five percent absolute excess risk of CSM at five years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death.
  • Exploring associations between LUTS and GI problems in women: a study in
           women with urological and GI problems versus a control population
    • Abstract: Objectives First, to study the prevalence of self‐reported LUTS in women consulting a Gastroenterology clinic with complaints of functional constipation (FC), fecal incontinence (FI) or both, compared to a female control population. Secondly, to study the influence of FC, FI, or both on self‐reported LUTS in women attending a Urology clinic. Patients and methods We present a retrospective study of data collected through a validated self‐administered bladder and bowel symptom questionnaire in a tertiary referral hospital from three different female populations: 104 controls, 159 gastroenterological patients and 410 urological patients. Based on the reported bowel symptoms, patients were classified as having FC, FI, a combination of both, or, no FC or FI. LUTS were compared between the control population and the gastroenterological patients, and between urological patients with and without concomitant gastroenterological complaints. Results were corrected for possible confounders through logistic regression analysis. Results The prevalence of LUTS in the control population was comparable to large population‐based studies. Nocturia was significantly more prevalent in gastroenterological patients with FI compared to the control population (OR 9.1). Female gastroenterological patients with FC more often reported straining to void (OR 10.3), intermittency (OR 5.5), need to immediately revoid (OR 3.7) and feeling of incomplete emptying (OR 10.5) compared to the control population. In urological patients, urgency (94%) and UUI (54% of UI) were reported more often by patients with FI than by patients without gastroenterological complaints (58% and 30% of UI respectively), whereas intermittency (OR 3.6), need to immediately revoid (OR 2.2) and feeling of incomplete emptying (OR 2.2) were reported more often by patients with FC than by patients without gastroenterological complaints. Conclusion As LUTS are reported significantly more often by female gastroenterological patients than by a control population, and as there is a difference in self‐reported LUTS between female urological patients with different concomitant gastroenterological complaints, we suggest that general practitioners, gastroenterologists and urologists should always include the assessment of symptoms of the other pelvic organ system in their patient evaluation. The clinical correlations between bowel and LUT symptoms may be explained by underlying neurological mechanisms.
  • Candidate selection for quadrant‐based focal ablation through a
           combination of diffusion‐weighted magnetic resonance imaging and
           prostate biopsy
    • Abstract: Objectives ● To identify prostatic quadrants that could be preserved without intervention, using diffusion‐weighted magnetic resonance imaging (DWI) and extended core biopsy, as a step toward implementation of quadrant‐based focal ablation with potential preservation of erectile and ejaculatory functions, based on comparisons with unilateral hemigland ablation. Patients and Methods ● We conducted a prebiopsy DWI study including 648 quadrants in 162 men who underwent 14‐core biopsy including anterior sampling and radical prostatectomy for localized cancer. ● Imaging and pathology were analyzed on a quadrant basis. Each quadrant was assessed through four‐core sampling. Predictive performance of DWI and biopsy regarding quadrant status was analyzed. Results ● On radical prostatectomy specimens, 170 anterior (52.5%) and 172 posterior quadrants (53.1%) harbored significant cancer (SC). ● Negative predictive values of DWI, biopsy, and their combination for SC were 79.7%, 70.6%, and 91.1%, respectively, in anterior quadrants, and 78.5%, 81.3%, and 91.7%, respectively, in posterior quadrants. ● DWI incrementally improved the negative predictive values of biopsy in anterior (p
  • Enzalutamide in European and North American men participating in the
           AFFIRM trial
    • Abstract: Objective ● To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311). Patients and Methods ● Phase III, double‐blind, placebo‐controlled, multinational AFFIRM trial in men with metastatic castration‐resistant prostate cancer (mCRPC) after docetaxel. ● Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. ● The primary end point was overall survival (OS) in a post hoc analysis. Results ● Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. ● The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide‐treated, 0.87%) and one NA patient (1/263 enzalutamide‐treated, 0.38%) experienced seizures. ● The difference in median OS was related in part to the timing of development of CRPC and baseline demographics on study entry. Conclusion ● This post hoc exploratory analysis of the AFFIRM trial demonstrated a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA‐ and EU‐treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.
  • Hypoalbuminemia is Associated with Mortality in Patients Undergoing
           Cytoreductive Nephrectomy
    • Abstract: Objective ● To evaluate whether poor nutrition is associated with mortality in patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). Patients and Methods ● A multi‐institutional review of prospective databases identified 246 patients meeting inclusion criteria who underwent CN for mRCC from 1993‐2012. ● Nutritional markers evaluated were: body mass index
  • Survival disparities between Māori and non‐Māori men with
           prostate cancer in New Zealand
    • Abstract: Objective To examine temporal trends and current survival differences between Māori and non‐Māori men with prostate cancer in New Zealand. Subjects/patients and methods A cohort of 37,529 men aged 40+ years diagnosed with prostate cancer between 1996 and 2010 was identified from the New Zealand Cancer Registry and followed until 25 May 2011. Cause of death was obtained from the Mortality Collection by data linkage. Survival for Māori compared with non‐Māori men was estimated using the Kaplan‐Meier method, and Cox proportional hazard regression models, adjusted for age, year of diagnosis, socioeconomic deprivation and rural/urban residence. Results The probability of surviving was significantly lower for Māori compared with non‐Māori men at one, five and 10 years post‐diagnosis. Māori men were more likely to die of any cause (adjusted hazard ratio (HR), 1.84 [95% CI, 1.72, 1.97]) and of prostate cancer (adjusted HR, 1.94 [95% CI, 1.76, 2.14]). The adjusted HR of prostate cancer death for Māori men diagnosed with regional extent was 2.62‐fold [95% CI; 1.60, 4.31]) compared with non‐Māori men. The survival gap between Māori and non‐Māori men has not changed throughout the study period. Conclusion Significantly poorer survival was observed for Māori men compared with non‐Māori, particularly when diagnosed with regional prostate cancer. Despite improvements in survival for all men diagnosed after 2000, the survival gap between Māori and non‐Māori men has not been reduced with time. Differences in prostate cancer detection and management, partly driven by higher socio‐economic deprivation in Māori men, were identified as the most likely contributors to ethnic survival disparities in New Zealand.
  • The conservative management of renal trauma: a literature review and
           practical clinical guideline from Australia and New Zealand
    • Abstract: Although the conservative management of renal trauma has gained in popularity since the middle of the last century, there remains a lack of specific guidance as to what this conservative approach should entail. The literature on the conservative management of renal trauma is reviewed within the framework of the American Association for the Surgery of Trauma (AAST) kidney injury severity scale. The decision on when to initiate conservative management is examined within the modern context of ureteric stenting, percutaneous drainage, and embolisation. Additionally, grade four injuries and intra‐operative consults are examined separately in view of the difficulties these groups cause in making appropriate treatment decisions. Graded recommendations are made by a multi‐disciplinary panel consisting of urologists, radiologists, and infectious disease physicians. Recommendations are made regarding several key topics including: imaging, inpatient monitoring, thromboprophylaxis, bed rest, antibiotics, discharge criteria, return to activity, and follow‐up. These recommendations have undergone formal review and debate at the Western Australian USANZ 2013 state conference, and were presented at the USANZ 2014 annual scientific meeting. It is hoped that these recommendations may help standardise the conservative management of renal trauma, as well as stimulate further debate and research.
  • Real‐time in vivo periprostatic nerve tracking using multiphoton
           microscopy in a rat survival surgery model: a promising pre‐clinical
           study for enhanced nerve‐sparing surgery
    • Abstract: Objectives To assess the ability of MPM to visualize, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real‐time imaging in humans during RP. To investigate the tissue toxicity and the reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study. Patients and methods In vivo prostatic rat imaging was carried out using a custom‐built bench‐top MPM system generating real‐time 3D histologic images, after performing survival surgery consisting of mini‐laparotomies under xylazine/ketamine anesthesia exteriorizing the right prostatic lobe. The acquisition time and the depth of anesthesia were adjusted for collecting multiple images in order to track the periprostatic nerves in real‐time. The rats were then monitored for 15 days before undergoing a new set of imaging under similar settings. After sacrificing the rats, their prostates were submitted for routine histology and correlation studies. Results In vivo MPM images distinguished periprostatic nerves within the capsule and the prostatic glands from fresh unprocessed prostatic tissue without the use of exogenous contrast agents nor biopsy sample Real time nerve tracking outlining the prostate was feasible and acquisition was not disturbed by motion artifacts No serious adverse event was reported during rat monitoring; no tissue damage due to laser was seen on the imaged lobe compared to the contralateral lobe (control) allowing comparison of their corresponding histology. Conclusions For the first time, we have demonstrated that in vivo tracking of periprostatic nerves using MPM is feasible in rat models. Development of a multiphoton endoscope for intraoperative use in humans is currently in progress and must be assessed.
  • The Genetic Diversity of Cystinuria in a UK Population of Patients
    • Abstract: Objectives To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation Patients and Methods DNA sequencing and MLPA were used to identify the mutations in 74 patients in a specialist cystinuria clinic in the UK. Patients with type A cystinuria were classified into two groups: group M patients had at least one missense mutation. Group N patients had two alleles of all other types of mutations including frameshift, splice site, nonsense, deletions and duplications. The levels of urinary dibasic amino acids, age of presentation of disease, number of stone episodes and interventions were compared between patients in the two groups using Mann‐Whitney U test. Results 41 patients had type A cystinuria including one patient with a variant of unknown significance. 23 patients had type B cystinuria, including 6 patients with variants of unknown significance. One patient had 3 sequence variants in SLC7A9 however 2 are of unknown significance. Three patients had type AB cystinuria. Three had a single mutation in SLC7A9. No identified mutations were found in three patients in either gene. There were a total of 88 mutations in SLC3A1 and 55 mutations in SLC7A9. There were 23 pathogenic mutations identified in our UK cohort of patients not previously reported in literature. In patients with type A cystinuria, the presence of a missense mutation correlated to lower levels of urinary lysine (611.9mM/MC SE22.65 vs 752.3mM/MC SE46.39, p=0.0171), arginine (194.8mM/MC SE24.83 vs 397.7mM/MC SE15.32, p=0.0008) and ornithine (109.2mM/MC SE7.403 vs 146.6mM/MC SE12.7, p=0.0211). There was no difference in the levels of urinary cystine (182.1mM/MC SE8.89 vs 207.2mM/MC SE19.23, p=0.2343). Conclusions We have characterised the genetic diversity of cystinuria in a UK population including 23 pathogenic mutations not previously described in literature. Patients with at least one missense mutation in SLC3A1 had significantly lower levels of lysine, arginine, ornithine but not cystine than patients with all other combinations of mutations.
  • Cardiopulmonary Reserve as Determined by Cardiopulmonary Exercise Testing
           Correlates with Length of Stay and Predicts Complications following
           Radical Cystectomy
    • Abstract: Objective To investigate whether poor pre‐operative cardiopulmonary reserve and comorbid state dictate high risk status and can predict complications in patients undergoing radical cystectomy. Subjects and Methods 105 consecutive patients with transitional cell carcinoma (stage T1‐T3) undergoing robotic (n=38) or open (n=67) radical cystectomy in a single UK centre underwent pre‐operative cardiopulmonary exercise testing (CPET). Outcome measures and statistical analysis Prospective primary outcome variables were all cause complications and post‐operative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman's Rank Correlation and group comparison, the Mann Whitney U‐test and Fishers exact test. Any relationships were confirmed using the Mantel‐Haenszel Common Odds Ratio Estimate, Kaplan‐Meier analysis and the Chi‐squared test. Results AT was negatively (r = ‐·206, p = ·035), and VE/VCO2 positively (r = ·324, p = ·001) correlated with complications and LOS. Logistic regression analysis identified low AT (50% of patients presenting for radical cystectomy had significant heart failure, whereas pre‐operatively only very few (2%) had this diagnosis. Analysis using the Mann Whitney test showed that VE/VCO2≥33 was the most significant determinant of LOS (p = ·004). Kaplan‐Meier analysis showed that patients in this group had an additional median stay of 4 days (p = ·008). Finally, patients with an ASA grade of 3 and those on long‐term β‐blocker therapy were found to be at particular risk of MI and death following radical cystectomy with Odds ratios of 4.0 (p = ·042, 95% CI [1·05 – 15·24]) and 6.3 (p = ·008, [1·60 – 24·84]). Conclusion Patients with poor cardiopulmonary reserve and hypertension are at higher risk of post‐operative complications and have increased LOS following radical cystectomy. Heart failure is known to be a significant determinant of peri‐operative death and is significantly under diagnosed in this patient group.
  • Perioperative and renal functional outcomes of elective
           robot‐assisted partial nephrectomy (RAPN) for renal tumours with
           high surgical complexity
    • Abstract: Objective To evaluate the perioperative, postoperative and functional outcomes of robot‐assisted partial nephrectomy (RAPN) for renal tumours with high surgical complexity at a large volume centre. Patients and Methods Perioperative and functional outcomes of RAPNs for renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 performed at our institution between September 2006 and December 2012 were collected in a prospectively maintained database and analysed. Surgical complications were graded according to the Clavien‐Dindo classification. Serum creatinine and estimated glomerular filtration rate (eGFR) were assessed at the third postoperative day and 3–6 months after RAPN. Results In all, 44 RAPNs for renal tumours with PADUA scores of ≥10 were included in the analysis; 23 tumours (52.3%) were cT1b. The median (interquartile range; range) operative time, estimated blood loss and warm ischaemia time (WIT) were 120 (94, 132; 60–230) min, 150 (80, 200; 25–1200) mL and 16 (13.8, 18; 5–35) min, respectively. Two intraoperative complications occurred (4.5%): one inferior vena caval injury and one bleed from the renal bed, which were both managed robotically. There were postoperative complications in 10 patients (22.7%), of whom four (9.1%) were high Clavien grade, including two bleeds that required percutaneous embolisation, one urinoma that resolved with ureteric stenting and one bowel occlusion managed with laparoscopic adhesiolysis. Two patients (4.5%) had positive surgical margins (PSMs) and were followed expectantly with no radiological recurrence at a mean follow‐up of 23 months. The mean serum creatinine levels were significantly increased after surgery (121.1 vs 89.3 μmol/L; P = 0.001), but decreased over time, with no significant differences from the preoperative values at the 6‐month follow‐up (96.4 vs 89.3 μmol/L; P = 0.09). The same trend was seen for eGFR. Conclusion In experienced hands RAPN for renal tumours with a PADUA score of ≥10 is feasible with short WIT, acceptable major complication rate and good long‐term renal functional outcomes. A slightly higher risk of PSMs can be expected due to the high surgical complexity of these lesions. The robotic technology allows a safe expansion of the indications of minimally invasive PN to anatomically very challenging renal lesions in referral centres.
  • Sexual function and health‐related quality of life in women with
           classic bladder exstrophy
    • Abstract: Objective To investigate sexual function and quality of life in adolescent and adult women with classic bladder exstrophy (BE). Materials and Methods A two‐part observational cross‐sectional study with a questionnaire arm and a retrospective case review arm was performed. The study was undertaken in a centre providing a tertiary referral gynaecology and urology service. Outcomes were sexual function and quality‐of‐life scores. Results A total of 44 patients with BE were identified from departmental databases and included in the study, of whom 28 (64%) completed postal questionnaires. Sexual function scores and quality‐of‐life visual analogue scales were significantly poorer compared with normative data. Conclusions Bladder exstrophy has a detrimental psychological impact on women. In future, methodical multidisciplinary paediatric follow‐up research will help to identify predictors of better and worse adolescent and adult outcomes. Development and evaluation of cost‐effective psychological interventions to target specific problems is also warranted.
  • Evolution of shockwave lithotripsy (SWL) technique: a 25‐year single
           centre experience of >5000 patients
    • Abstract: Objective To assess the impact of various treatment optimisation strategies in shockwave lithotripsy (SWL) used at a single centre over the last 25 years. Patients and Methods In all, 5017 patients treated between 1989 and 2013 were reviewed and divided into groups A, B, C and D for the treatment periods of 1989–1994 (1561 patients), 1995–2000 (1741), 2001–2006 (1039) and 2007–2013 (676), respectively. The Sonolith 3000 (A and B) and Dornier compact delta lithotripters (C and D) were used. Refinements included frequent re‐localisation, limiting maximum shocks and booster therapy in group B and Hounsfield unit estimation, power ramping and improved coupling in group D. Parameters reviewed were annual SWL utilisation, stone and treatment data, retreatment, auxiliary procedures, complications and stone‐free rate (SFR). Results The SFR with Dornier compact delta was significantly higher than that of the Sonolith 3000 (P < 0.001). The SFR improved significantly from 77.58%, 81.28%, 82.58% to 88.02% in groups A, B, C, and D, respectively (P < 0.001). There was a concomitant decrease in repeat SWL (re‐treatment rate: A, 48.7%; B, 33.4%; C, 15.8%; and D, 10.1%; P < 0.001) and complication rates (A, 8%; B, 6.4%; C, 4.9%; and D, 1.6%; P < 0.001). This led to a rise in the efficiency quotient (EQ) in groups A–D from 50.41, 58.94, 68.78 to 77.06 (P < 0.001).The auxiliary procedure rates were similar in all groups (P = 0.62). Conclusion In conclusion, improvement in the EQ together with a concomitant decrease in complication rate can be achieved with optimum patient selection and use of various treatment optimising strategies.
  • Factors influencing disease progression of prostate cancer under active
           surveillance: a McGill University Health Center cohort
    • Abstract: Objective To evaluate the clinical and pathological factors influencing the risk of disease progression in a cohort of patients with low–intermediate risk prostate cancer under active surveillance (AS). Patients and Methods We studied 300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with favourable parameters or who refused treatment and were managed with AS. Of those, 155 patients with at least one repeat biopsy and no progression criteria at the time of the diagnosis were included for statistical analyses. Patients were followed every 3–6 months for prostate‐specific antigen (PSA) measurement and physical examination. Patients were offered repeat prostatic biopsy every year. Disease progression was defined as the presence of one or more of the following criteria: ≥3 positive cores, >50% of cancer in at least one core, and a predominant Gleason pattern of 4. Results For the 155 patients, the mean (sd) age at diagnosis was 67 (7) years; the median (interquartile range) follow‐up was 5.4 (3.6–9.5) years. Of these, 67, 25, six, and two patients had two, three, four, and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score of ≤6. In all, 50 (32.3%) patients had disease progression on repeat biopsies, with a median progression‐free survival time of 7 years. The rate of disease progression decreased after the second repeat biopsy. The 5‐year overall survival rate was 100%. Having a PSA density (PSAD) of >0.15 ng/mL/mL, >1 positive core, and Gleason score >6 at the time of the diagnosis was associated with a significantly higher rate of disease progression on univariate analysis (P < 0.05), while a maximum percentage of cancer in any core of >10% showed a trend toward significance for a higher progression rate (P = 0.054). On multivariate analysis, only the presence of a PSAD of >0.15 ng/mL/mL remained significant for a higher progression rate (P < 0.05). Of the 155 patients, five (3.2%) subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13 (8.4%) underwent radical prostatectomy. Conclusion AS is a suitable management option for patients with clinically low‐risk prostate cancer. A PSAD of >0.15 ng/mL/mL is an important predictor for disease progression.
  • γEpithelial Na+ Channel and the Acid‐Sensing Ion Channel 1
           expression in the urothelium of patients with neurogenic detrusor
    • Abstract: Objective To investigate the expression of two types of cation channels such as the γEpithelial Na+ Channel (γENaC) and the Acid‐Sensing Ion Channel1 (ASIC1) in the urothelium of controls and in patients affected by neurogenic detrusor overactivity (NDO). In parallel, the urodynamic parameters were collected and correlated to the immunohistochemical (IHC) results. Subjects and Methods Four controls and 12 patients with a clinical diagnosis of NDO and suprasacral spinal cord lesion underwent to urodynamic measurements and cystoscopy. Cold cup biopsies were frozen and processed for immunohistochemistry and western blots. Spearman's correlation coefficient between morphological and urodynamic data was applied. One‐way ANOVA followed by Newman–Keuls multiple comparison post‐hoc test was applied for western blot results. Results In the controls, γENaC and ASIC1 were expressed in the urothelium with differences in their cell distribution and intensity. In NDO patients, both markers showed consistent changes either in cell distribution and labeling intensity compared to controls. A significant correlation between the higher intensity of the γENaC expression in urothelium of NDO patients and the lower values of bladder compliance was detected. Conclusion The present findings show important changes in the expression of γENaC and ASIC1 in NDO human urothelium. Of note, while the changes in γENaC might impair the mechanosensory function of urothelium, the increase of the ASIC1 might represent an attempt to compensate excess in local sensitivity.
  • An evaluation of the ‘weekend effect’ in patients admitted
           with metastatic prostate cancer
    • Abstract: Objectives To investigate whether mortality is increased for patients with metastatic prostate cancer (mCaP) admitted over the weekend. Patients and methods Using the Nationwide Inpatient Sample (NIS) between 1998‐2009, admitted patients with a diagnosis of prostate cancer and concomitant metastases were identified. Rates of in‐hospital mortality, complications, utilization of imaging and procedures were assessed. Adjusted logistic regression models examined associations of mortality and complications. Results A weighted sample of 534,011 patients with mCaP was identified, including 81.7% weekday and 18.3% weekend admissions. Of these, 8.6% died following a weekday vs. 10.9% after a weekend admission (p
  • Oncologic outcomes after partial versus radical nephrectomy in renal cell
           carcinomas smaller than 7 cm with presumed renal sinus fat invasion on
           preoperative imaging
    • Abstract: Objectives To compare oncological outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) for renal tumors ≤7 cm which preoperative imaging reveals potential renal sinus fat invasion (cT3a), as RN is preferred for these tumors due to concerns regarding high tumor stage. Materials and Methods Among 1,137 nephrectomies performed for renal tumors ≤7 cm from January 2005 to August 2012, 401 solitary cT3a renal cell carcinomas (RCCs) without metastases were analyzed. Classification as cT3a included only renal sinus fat invasion, as there were no tumors with suspected perinephric fat invasion. Multivariate models were used to evaluate predictors of recurrence‐free survival (RFS) and cancer‐specific survival (CSS). Results There were 34 RCCs (8.5%) with unexpected perinephric fat invasion, but only 77 RCCs (19.2%) were staged as pT3a. During the median follow‐up of 43.0 months, recurrence occurred in seven (6.7%) PN cases and 25 (8.4%) RN cases. Six recurred PN cases had positive surgical margins (PSMs). The two cohorts showed equal oncologic outcomes with respect to 5‐year RFS and CSS. Multivariate analyses revealed PSM, pathologic T stage, sarcomatoid dedifferentiation, and type of surgery as significant predictors of recurrence. Older age, pathologic T stage, and sarcomatoid dedifferentiation were significant predictors of cancer‐specific mortality. Conclusions Renal tumors ≤7 cm with presumed renal sinus fat invasion were mostly pT1. PN conferred equivalent oncologic outcomes to RN. If clear surgical margins can be obtained, PN should be considered for these tumors, as patients may benefit from renal function preservation.
  • Defining the Learning Curve for multi‐parametric MRI of the prostate
           using MRI‐TRUS fusion guided transperineal prostate biopsies as a
           validation tool
    • Abstract: Objectives To determine the accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) during the learning curve of radiologists using MRI targeted, transrectal ultrasound guided transperineal fusion biopsy (MTTP) for validation. Material And Methods Prospective data on 340 men who underwent mpMRI (T2 weighted and DW‐MRI) followed by MTTP prostate biopsy, was collected according to Ginsburg and STARD standards. MRI were reported by two experienced radiologists and scored on a Likert scale. Biopsies were performed by consultant urologists blinded to the MRI result and men had both targeted and systematic sector biopsies which were reviewed by a dedicated uropathologist. The cohorts were divided into groups representing five consecutive time intervals in the study. Sensitivity and specificity of positive MRI reports, Prostate cancer (CaP) detection by positive MRI, distribution of significant Gleason score and negative MRI with false negative for CaP were calculated. Data were sequentially analyzed and the learning curve was determined by comparing the first and last group. Results We detected a positive mpMRI in 64 patients from group A (91%) and 52 patients from group E (74%). CaP detection rate on mpMRI increased from 42% (27/64) in group A to 81% (42/52) in group E (p value
  • Minimum five‐year follow‐up of 1,138 consecutive laparoscopic
           radical prostatectomies
    • Abstract: Objectives To investigate the long‐term outcomes of laparoscopic radical prostatectomy (LRP). Methods A total of 1,138 patients underwent LRP during a 163 month period from 2000‐2008 of which 51.5%, 30.3% and 18.2% were in d'Amico's low‐, intermediate‐ and high‐risk groups [d'Amico, 1998], respectively. All intermediate‐ and high‐risk patients were staged by pre‐operative MRI or CT and isotope bone scanning and had a pelvic lymph node dissection (PLND), which was extended after April 2008. Median patient age (with range) = 62 (40‐78) yr; BMI = 26 (19‐44) kg/m2; PSA = 7.0 (1‐50) ng/ml and Gleason = 6 (6‐10). NVB preservation was done in 55.3% (bilateral = 45.5%; unilateral = 9.8%) of patients. Results Median gland weight = 52 (14‐214) g; operating time = 177 (78‐600) minutes; PLND in 299 (26.3%) of which 54 (18.0%) were extended; blood loss = 200 (10‐1300) ml; post‐op. Hospital stay = 3 (2‐14) nights; catheterization time = 14 (1‐35) days; complication rate = 5.2%; node count = 12 (4‐26); lymph node positivity = 0.8%; node involvement = 2 (1‐2); margin positivity = 13.9%; up‐grading = 29.3%; down‐grading = 5.3%; up‐staging from T1/2 to T3 = 11.4%; down‐staging from T3 to T2 = 37.1%. One case (0.09%) was converted to open surgery and 6 patients were transfused (0.5%). At a mean follow‐up of 88.6 (60‐120) months 85.4% of patients were free of biochemical recurrence, 93.8% were continent and 76.6% of previously‐potent non‐diabetic men
  • Number of positive pre‐operative biopsy cores is a predictor of
           positive surgical margins in small prostates after robot‐assisted
           radical prostatectomy
    • Abstract: Objective To determine the impact of prostate size on positive surgical margin (PSM) rates after RARP and the pre‐operative factors associated with PSM. Materials And Methods A total of 1,229 men underwent RARP by a single surgeon, from 2005 to August of 2013. Excluded were patients who had trans‐urethral resection of the prostate, neo‐adjuvant therapy, clinically‐advanced cancer, and the first 200 performed cases, to reduce the effect of learning curve. Included were 815 patients who were then divided into three groups: 45 g (group3). Multivariate analysis determined predictors of PSM and BCR. Results Console time and blood loss increased with increasing prostate size. There were more high‐grade tumors in group one (group1 vs. group2 and group3, 33.9% vs. 25.1 and 25.6%, p=0.003 and p=0.005). PSM were increased in 20 ng/dl, Gleason score >7, T3 tumor, and >3 positive biopsy cores. In group one, pre‐operative stage T3 (OR=3.94, p=0.020) and >3 positive biopsy core (OR=2.52, p=0.043) were predictive of PSM while a PSA >20ng/dl predicted the occurrence of BCR (OR=5.34, p=0.021). No pre‐operative factors predicted PSM or BCR for groups two and three. Conclusion A pre‐operative biopsy with >3 positive cores in men with small prostates predicts PSM after RARP. In small prostates with PSM, a PSA >20 ng/dl is a predictor of BCR. These factors should guide the choice of therapy and indicate the need for closer post‐operative follow‐up.
  • Perioperative Outcomes of Cytoreductive Nephrectomy in the UK in 2012
    • Abstract: Objectives To define the perioperative morbidity and 30‐day mortality of cytoreductive nephrectomy (CN) using the BAUS nephrectomy dataset for 2012, the first year of public reporting of individual surgeon outcomes in the United Kingdom. Patients & Methods All nephrectomies recorded in the database in 2012 were analysed, and cytoreductive cases identified. Outcome measures were: blood loss greater than 1000mls, transfusion requirement, intra‐ and post‐operative complications assessed by Clavien‐Dindo score, and 30‐day mortality (including failure‐to‐rescue rate). Univariate and multivariate logistic regression analysis was used to assess predictors of adverse outcomes. Results 279 cases were undertaken by 141 surgeons in 90 centres. WHO Performance Status was 0 or 1 in 72.4% (n = 202). Open nephrectomy was performed in 59% (n = 163), with the remainder laparoscopic. Conversion rate for laparoscopy was 14% (n=16). 40 patients underwent pre‐operative tyrosine‐kinase inhibitor treatment. No significant differences in outcome were observed for this group. 30‐day mortality was 1.79%. Intraoperative complications occurred in 11.9%, post‐operative complications in 20.8%. Complications of Clavien‐Dindo grade III or above occurred in 8%. Blood loss of greater than one litre occurred in 15.4% of cases and 24.1% of patients required a perioperative transfusion. Tumour size >10cm was an independent risk factor for blood loss >1 litre (p=0.021) and intraoperative complications (p=0.021). The number of metastatic sites was an independent predictor of blood loss >1 litre (p=0.001) and transfusion requirement (p=0.026). Performance status of two or more was also independently associated with intraoperative complication risk (p=0.021). Conclusions CN in contemporary UK practice appears to have excellent perioperative outcomes overall. Risk factors for adverse perioperative outcomes include tumour size over 10cm, number of metastatic sites and PS ≥ 2. The balance of risk and benefit for CN should be carefully considered for patients with poor performance status or extensive metastases.
  • Identification of Binding Sites for C‐terminal proGRP‐derived
           peptides in Renal Cell Carcinoma: A Potential Target for Future Therapy
    • Abstract: Objective To determine the expression and biology of the neuroendocrine growth factor gastrin‐releasing peptide (GRP) and other proGRP‐derived peptides in renal cancer. Materials and methods Receptor binding studies, ELISA and radioimmunoassay were used to quantitate the presence of proGRP‐derived peptide receptors and their ligands in renal cancer cell lines and human renal cancers. Biological activity of proGRP peptides was confirmed with proliferation, migration, and ERK1/2 activation assays in vitro. In vivo, ACHN renal cancer xenografts were treated with proGRP‐derived peptides to assess tumour size and necrosis. HIF1α and VEGF expression was investigated with western blotting and ELISA respectively to determine the possible contribution of the proGRP peptides to tumour viability. Results In ACHN cells that express both proGRP‐ and GRP‐receptors, the expression of proGRP binding sites was 80 fold greater than the GRP‐receptor (GRPR). C‐terminal proGRP‐derived peptides stimulated the activation of ERK1/2, but with a different time course to GRP, consistent with the suggestion that these peptides may have unique cellular functions. Both GRP and proGRP47‐68 stimulated proliferation and migration of ACHN cells in vitro, but only GRP reduced the extent of tumor necrosis in ACHN xenografts. GRP, but not proGRP47‐68, was able to induce HIF1α and VEGF expression in ACHN cells. This may account in part for the reduction in necrosis following GRP treatment. C‐terminal proGRP‐derived peptides were present in all three renal cancer cell lines and a panel of human renal cancers, but mature amidated GRP was absent. Conclusion C‐terminal proGRP peptides are more abundant in renal cancers and their cell lines than the more extensively studied amidated peptide, GRP. These results suggest that C‐terminal proGRP‐derived peptides may be a better target for novel renal cancer treatments.
  • Prevalence of ciprofloxacin‐resistant Enterobacteriaceae in the
           intestinal flora of patients undergoing trans‐rectal prostate biopsy
           in Norwich, UK
    • Abstract: Objective To determine the efficacy of fluoroquinolone prophylaxis in patients undergoing trans‐rectal ultrasound scan (TRUS)‐guided biopsy of the prostate in the Norwich population, and its correlation with ciprofloxacin resistance in the faecal flora. We also aimed to determine the usefulness of a pre‐biopsy rectal screen for resistant bacteria in these patients. Patients and methods The incidence and microbiology of sepsis after TRUS‐guided prostate biopsies between 2007 and 2011 was audited retrospectively. Subsequently, in 2012, a prospective study was performed, collecting the same data but also culturing rectal swabs from all patients undergoing TRUS biopsy, with a post‐biopsy follow‐up period of 6 months. All patients were given prophylactic oral ciprofloxacin, as per Trust policy (750 mg 1 hour pre‐biopsy, followed by 250 mg q12h for 3 subsequent days). Results Between 2007 and 2011, 3600 patients underwent TRUS biopsy. Among these, 11 (0.3%) were admitted to hospital for post‐biopsy related sepsis but only 4 (0.1%) had ciprofloxacin‐resistant Escherichia coli confirmed from blood cultures: three had ciprofloxacin‐susceptible Enterobacteriaceae, and four had no ciprofloxacin susceptibility data. In 2012, 10 (3.7%) of 267 patients sampled pre‐biopsy had ciprofloxacin‐resistant E. coli recovered on rectal swab culture but none of these men presented with post‐biopsy sepsis; during the 6‐month follow‐up period, seven patients were diagnosed with urinary tract infections. Conclusion Ciprofloxacin‐resistant Enterobacteriaceae remains rare in the intestinal flora of the Norwich TRUS population, meaning that the drug remains adequate as prophylaxis. Pre‐biopsy rectal swabs may be useful for individual departments to periodically assess their own populations and to ensure their antibiotic policy remains valid. In populations where resistance is known to be highly prevalent, pre‐biopsy rectal swabs can help guide addition of further antibiotics to prevent post‐biopsy septicaemia.
  • Robotic retroperitoneal partial nephrectomy: a step‐by‐step
    • Abstract: Objective To describe a step‐by‐step guide for successful implementation of the retroperitoneal approach to robotic partial nephrectomy (RPN) Patients and Methods The patient is placed in the flank position and the table fully flexed to increase the space between the 12th rib and iliac crest. Access to the retroperitoneal space is obtained using a balloon‐dilating device. Ports include a 12‐mm camera port, two 8‐mm robotic ports and a 12‐mm assistant port placed in the anterior axillary line cephalad to the anterior superior iliac spine, and 7–8 cm caudal to the ipsilateral robotic port. Results Positioning and port placement strategies for successful technique include: (i) Docking robot directly over the patient's head parallel to the spine; (ii) incision for camera port ≈1.9 cm (1 fingerbreadth) above the iliac crest, lateral to the triangle of Petit; (iii) Seldinger technique insertion of kidney‐shaped balloon dilator into retroperitoneal space; (iv) Maximising distance between all ports; (v) Ensuring camera arm is placed in the outer part of the ‘sweet spot’. Conclusion The retroperitoneal approach to RPN permits direct access to the renal hilum, no need for bowel mobilisation and excellent visualisation of posteriorly located tumours.
  • Single nucleotide polymorphisms in fibroblast growth factor 23 gene,
           FGF23, are associated with prostate cancer risk
    • Abstract: Objective To determine whether sequence variants within the FGF23 gene are associated with the risk of developing prostate cancer in a Korean population. Patients and Methods Five common single nucleotide polymorphisms (SNPs) in the FGF23 gene were assessed in 272 patients with prostate cancer and 173 control subjects with benign prostatic hyperplasia. Single‐locus analyses were conducted using conditional logistic regression. In addition, we performed a haplotype analysis for the five FGF23 SNPs tested. Results Three SNPs in the FGF23 gene (rs11063118, rs13312789 and rs7955866) were associated with an increased risk of prostate cancer in our study population. Odds ratios for homozygous variants vs wild‐type variants ranged from 1.68 (95% confidence interval [CI]: 1.15–2.46) to 1.79 (95% CI: 1.16–2.75). Conclusion This is the first study showing that genetic variations in FGF23 increase prostate cancer susceptibility.
  • Science made simple: tissue microarrays (TMAs)
  • Prognostic and diagnostic implications of epithelial cell
           adhesion/activating molecule (EpCAM) expression in renal tumours: a
           retrospective clinicopathological study of 948 cases using tissue
    • Abstract: Objective To evaluate the expression and prognostic value of epithelial cell adhesion/activating molecule (EpCAM) in a large set of renal cell carcinomas (RCCs) using a tissue microarray (TMA) approach. Material and Methods We studied the immunohistochemical expression and overexpression of EpCAM on TMAs containing formalin‐fixed, paraffin‐embedded samples of 948 patients with documented renal tumours. EpCAM expression was defined as the presence of a specific membranous staining in >5% of the tumour cells. EpCAM overexpression was specified by calculating a total staining score (score range 0–12) as the product of a proportion score and an intensity score, and defined as a score >4. Results Of 948 cases, 927 (97.8%) were evaluable morphologically (haematoxylin and eosin stain). EpCAM expression was found in 233/642 (36.3%), 126/155 (81.3%), 54/68 (78.3%), 17/45 (37.8%), 13/30 (43.3%) of clear‐cell RCC, papillary RCC (pRCC), chromophobe RCC (cpRCC), oncocytomas and other unclassified tumour types, respectively. Log‐rank tests showed a significantly longer overall survival (OS [P = 0.047]) and a trend of EpCAM expression to be associated with a longer progression‐free survival (PFS) in all RCC entities (P = 0.065). EpCAM overexpression was significantly correlated with a better PFS in all RCC subtypes, cpRCC and pRCC (P = 0.011, 0.043 and 0.025, respectively). In multivariate analysis EpCAM overexpression was an independent marker for longer PFS in all RCC entities as well as in high grade RCC (P = 0.009 and P = 0.010, respectively). Conclusions The histological subtypes associated with a high rate of EpCAM expression were cpRCC and pRCC. This retrospective analysis demonstrated a trend towards longer OS and PFS for all major RCC subtypes. EpCAM expression had significant prognostic value in patients with cpRCC and pRCC. Furthermore, EpCAM overexpression in high grade RCC may be a helpful marker for prognostication.
  • A clinical evaluation of a sensor to detect blockage due to crystalline
           biofilm formation on indwelling urinary catheters
    • Abstract: Objective To test the performance and acceptability of an early warning sensor to predict encrustation and blockage of long‐term indwelling urinary catheters. Patients and Methods In all, 17 long‐term indwelling catheter users, 15 ‘blockers’ and two ‘non‐blockers’ (controls) were recruited; 11 participants were followed prospectively until catheter change, three withdrew early and three did not start. Two sensors were placed in series between the catheter and the urine bag at catheter change. The sensor nearest the bag was changed at the same time as the bag change (weekly); the sensor nearest the catheter remained in situ for the duration of the catheter's life. Bacteriology and pH determinations were performed on urine samples at each bag, sensor and catheter change. The colour of the sensors was recorded daily. On removal, each sensor and the catheter were examined for visible evidence of encrustation and blockage. Participants were asked to keep a daily diary to record colour change and any other relevant observations and to complete a psychosocial impact of assistive devices tool at the end of the study. Participants and carers/healthcare professionals (when involved in urine bag or catheter change) were asked to complete a questionnaire about the sensor. Results Urease‐producing bacteria were isolated from seven of the 14 patients (including early withdrawals; P. mirabilis in four, Morganella or Providencia in three). In six of the seven patients the sensors turned blue‐black; two of these were early withdrawals, two went to planned catheter change (one of these was recruited as a ‘non‐blocker’) and three had catheter blockage. The number of days of catheterisation before blockage was 22, 23 and 25 days, and the sensor changed colour within 24–48 h after insertion. The urine mean (range) pH of the sensors that turned blue‐black was 7.6 (5.5–9.0) and of the sensors that remained yellow 6.1 (5.1–7.5). The sensor was generally well‐received and was positive in the psychosocial assessment. Conclusions The sensor is a useful indicator of urine pH and of the conditions that lead to catheter blockage. It may be particularly useful for new indwelling catheter users. To be a universally acceptable predictor of catheter blockage, the time from sensor colour change to blockage needs to be reduced.
  • External validation of preoperative and postoperative nomograms for
           prediction of cancer‐specific survival, overall survival and
           recurrence after robot‐assisted radical cystectomy for urothelial
           carcinoma of the bladder
    • Abstract: Objective To externally validate currently available bladder cancer nomograms for prediction of all‐cause survival (ACS), cancer‐specific survival (CSS), other‐cause mortality (OCM) and progression‐free survival (PFS). Patients and Methods Retrospective analysis of a prospectively maintained database of 282 patients who underwent robot‐assisted radical cystectomy (RARC) at a single institution was performed. The Bladder Cancer Research Consortium (BCRC), International Bladder Cancer Nomogram Consortium (IBCNC) and Lughezzani nomograms were used for external validation, and evaluation for accuracy at predicting oncological outcomes. The 2‐ and 5‐year oncological outcomes were compared, and nomogram performance was evaluated through measurement of the concordance (c‐index) between nomogram‐derived predicted oncological outcomes and observed oncological outcomes. Results The median (range) patient age was 70 (36–90) years. At a mean follow‐up of 20 months, local or distant disease recurrence developed in 30% of patients. With an overall mortality rate of 33%, 17% died from bladder cancer. The actuarial 2‐ and 5‐year PFS after RARC was 62% (95% confidence interval [CI] 54–68) and 55% (95% CI 46–63), respectively. The actuarial 2‐ and 5‐year ACS was 66% (95% CI 59–72) and 47% (95% CI 37–55), respectively, and the 2‐ and 5‐year CSS was 81% (95% CI 74–86) and 67% (95% CI 57–76), respectively. The PFS c‐index for IBCNC was 0.70 at 5 years, and for BCRC was 0.77 at both the 2 and 5 years. The accuracy of ACS and CSS prediction was evaluated using the BCRC and Lughezzani nomograms. Using the BCRC nomogram, c‐indices of for 2‐ and 5‐year ACS were each 0.73 and c‐indices for 2‐ and 5‐year CSS were 0.70 each. The performance of Lughezzani nomogram for 5‐year ACS, cancer‐specific mortality and OCM were 0.73, 0.72 and 0.40, respectively. The BCRC nomogram prediction of advanced pathological stage and lymph node metastasis was modest, with c‐indices of 0.66 and 0.61, respectively. Conclusions Bladder cancer nomograms available from the current open RC literature adequately predict ACS, CSS and PFS after RARC. However, prediction of advanced tumour stage and lymph node metastasis was modest and the Lughezzani nomogram failed to predict OCM.
  • Retzius‐sparing robot‐assisted laparoscopic radical
           prostatectomy: combining the best of retropubic and perineal approaches
    • Abstract: Objective To compare the early peri‐operative, oncological and continence outcomes of Retzius‐sparing robot‐assisted laparoscopic radical prostatectomy (RALP) with those of conventional RALP. Materials and Methods Data from 50 patients who underwent Retzius‐sparing RALP and who had at least 6 months of follow‐up were prospectively collected and compared with a database of patients who underwent conventional RALP. Propensity‐score matching was performed using seven preoperative variables, and postoperative variables were compared between the groups. Results A total of 581 patients who had undergone RALP were evaluated in the present study. Although preoperative characteristics were different before propensity‐score matching, these differences were resolved after matching. There were no significant differences in mean length of hospital stay, estimated blood loss, intra‐ and postoperative complication rates, pathological stage of disease, Gleason scores, tumour volumes and positive surgical margins between the conventional RALP and Retzius‐sparing RALP groups. Console time was shorter for Retzius‐sparing RALP. Recovery of early continence (defined as 0 pads used) at 4 weeks after RALP was significantly better in the Retzius‐sparing RALP group than in the conventional RALP group. Conclusions The present results suggest that Retzius‐sparing RALP, although technically more demanding, was as feasible and effective as conventional RALP, and also led to a shorter operating time and faster recovery of early continence. Retzius‐sparing RALP was also reproducible and achievable in all cases.
  • Lateral temperature spread of monopolar, bipolar and ultrasonic
           instruments for robot‐assisted laparoscopic surgery
    • Abstract: Objective To assess critical heat spread of cautery instruments used in robot‐assisted laparoscopic (RAL) surgery. Materials and Methods Thermal spread along bovine musculofascial tissues was examined by infrared camera, histology and enzyme assay. Currently used monopolar, bipolar and ultrasonic laparoscopic instruments were investigated at various power settings and application times. The efficacy of using an additional Maryland clamp as a heat sink was evaluated. A temperature of 45 °C was considered the threshold temperature for possible nerve damage. Results Monopolar instruments exhibited a mean (sem) critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s, the spread was >20 mm. For adjustable bipolar instruments the mean (sem) critical thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s. The PK and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8 (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm. Application of an additional Maryland clamp as a heat sink, significantly reduced the thermal spread. Histomorphometric analyses and enzyme assay supported these findings. Conclusions All coagulation devices used in RAL surgery have distinct thermal spreads depending on power setting and application time. Cautery may be of concern due to lateral temperature spread, causing potential damage to sensitive structures including nerves. Our results provide surgeons with a resource for educated decision‐making when using coagulation devices during robotic procedures.
  • Neoadjuvant chemotherapy for bladder cancer does not increase risk of
           perioperative morbidity
    • Abstract: Objective To determine whether neoadjuvant chemotherapy (NAC) is a predictor of postoperative complications, length of stay (LOS), or operating time after radical cystectomy (RC) for bladder cancer. Patients and Methods A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was performed to identify patients receiving NAC before RC from 2005 to 2011. Bivariable and multivariable analyses were used to determine whether NAC was associated with 30‐day perioperative outcomes, e.g. complications, LOS, and operating time. Results Of the 878 patients who underwent RC for bladder cancer in our study, 78 (8.9%) received NAC. Excluding those patients who were ineligible for NAC due to renal insufficiency, 78/642 (12.1%) received NAC. In all, 457 of the 878 patients (52.1%) undergoing RC had at least one complication ≤30 days of RC, including 43 of 78 patients (55.1%) who received NAC and 414 of 800 patients (51.8%) who did not (P = 0.58). On multivariable logistic regression, NAC was not a predictor of complications (P = 0.87), re‐operation (P = 0.16), wound infection (P = 0.32), or wound dehiscence (P = 0.32). Using multiple linear regression, NAC was not a predictor of increased operating time (P = 0.24), and patients undergoing NAC had a decreased LOS (P = 0.02). Conclusions Our study is the first large multi‐institutional analysis specifically comparing complications after RC with and without NAC. Using a nationally validated, prospectively maintained database specifically designed to measure perioperative outcomes, we found no increase in perioperative complications or surgical morbidity with NAC. Considering these findings and the well‐established overall survival benefit over surgery alone, efforts are needed to improve the uptake of NAC.
  • Nephron‐sparing management vs radical nephroureterectomy for
           low‐ or moderate‐grade, low‐stage upper tract urothelial
    • Abstract: Objective To compare overall and cancer‐specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron‐sparing measures (NSM) using a large population‐based dataset. Patients and Methods Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low‐ or moderate‐grade, localised non‐invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer‐specific mortality (CSM) and other‐cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all‐cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. Results Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low‐ or moderate‐grade, low‐stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well‐differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non‐cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26). Conclusions Patients with low‐ or moderate‐grade, low‐stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.
  • Impact of the type of ureteroileal anastomosis on renal function measured
           by diuretic scintigraphy: long‐term results of a prospective
           randomized study
    • Abstract: Objective To determine the long‐term effects of the direct refluxing‐type ureteroileal anastomosis technique with those of an antireflux technique on individual renal units, using diuretic scintigraphy in a prospectively randomized study. Patients and Methods Between 2002 and 2006, a prospective randomized study was conducted on 102 patients undergoing radical cystectomy and urinary diversion. In every patient, both ureters were randomized to be implanted using a direct refluxing technique or an antireflux, serous‐lined extramural tunnel (SLET) technique. Renal function (RF) was evaluated using 99mTc‐MAG‐3 diuretic scintigraphy. The serial changes in corrected glomerular filtration rate (cGFR) for each technique and for each side were compared. Results Over a median follow‐up of 6 years, the patients in both the direct refluxing and the SLET technique groups were found to have a significant reduction in mean (sd) cGFR between baseline and last follow‐up: cGFR decreased from 59.4 (12.4) to 45.6 (15.3) mL/min (P < 0.001) and from 54.3 (11.2) to 46.3 (12.8) mL/min (P = 0.002), respectively. Five patients (4.9%) in the SLET group developed obstruction (four left‐sided and one right‐sided) compared with one (0.9%) in the direct refluxing group (right‐sided). The onset of obstruction was noted 1–7 months after radical cystectomy. There was no significant difference between the groups in reductions in cGFR across the timepoints. Comparison of the two techniques according to the side of ureter implantation showed that the direct refluxing technique trended towards better functional outcomes on the left side. Conclusions There was no observed difference in the RF of individual renal units between the SLET and the direct refluxing groups in the long term. The need to incorporate an antireflux technique should be questioned and tailored according to the surgeon's experience and confidence.
  • Comparison of expected treatment outcomes, obtained using risk models and
           international guidelines, with observed treatment outcomes in a Dutch
           cohort of patients with non‐muscle‐invasive bladder cancer
           treated with intravesical chemotherapy
    • Abstract: Objective To compare the risks according to the American Urological Association (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncologico (CUETO) classifications with real outcomes in a cohort of patients in the Netherlands, and to confirm that patients who were undertreated according to these risk models have worse outcomes than adequately treated patients. Patients and Methods Patients treated with complete transurethral resection of bladder tumour and intravesical chemotherapy were included. Not all patients would have received intravesical chemotherapy had they been treated to current standards, and thus comparison of the observed outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables and CUETO scoring model was possible. The cohort was reclassified according to the definitions of five index patients (IPs), as defined by the AUA guidelines, and three risk groups, defined according to the EAU guidelines, to compare the outcomes of undertreated patients with those of adequately treated patients. Results A total of 1001 patients were available for comparison with the AUA definitions and 728 patients were available for comparison with the EORTC and CUETO models. There was a large overlap between the observed outcomes and expected recurrence and progression probabilities when comparison was made using the EORTC risk tables. The observed recurrence outcomes were in general higher than the expected probabilities according to the CUETO risk classification, especially in the long term. No differences in progression were found when comparing these two models to the Dutch cohort. Patients who were undertreated according to the guidelines showed, in general, a higher risk of developing recurrence and progression. Limitations are i.a. its retrospective nature and the differences in grading system. Conclusion Comparisons between the observed outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO risk models and the EORTC and AUA guidelines showed that lack of adherence to existing guidelines translates into worse outcomes.
  • Progression and predictors of physical activity levels after radical
    • Abstract: Objective To investigate the progression of all aspects (total, occupational, sports, household) of physical activity (PA) over time after radical prostatectomy (RP) and to find predictive factors for a decrease in PA. Patients and Methods In all, 240 men planned for open or robot‐assisted RP were analysed. All patients completed the Flemish Physical Activity Computerised Questionnaire before RP concerning PA over the past year and at 6 weeks, 3, 6 and 12 months after RP for the PA of the past month. A linear model for repeated measures was used to evaluate the progression of continuous variables over time and the effect of various predictors for the progression of patients over time. A logistic regression model for repeated measures was used to evaluate binary measures. Results Total, occupational, sports and household PA levels were significantly decreased at 6 weeks after RP, but recovered quickly to approximately baseline levels from that time. Predictive factors for decreased PA levels at 6 weeks after RP were a younger age (total PA level), being unskilled/semi‐skilled (occupational PA level) and being unemployed/retired (household PA level). RP type (open vs robot‐assisted) did not influence the different PA levels at 6 weeks, 3, 6 or 12 months after RP. The severity of first day incontinence and urine loss measured at 6 weeks and 3, 6 and 12 months after RP significantly affected total and/or household PA level at all time‐points. Conclusions This is the first study to investigate the progression of all aspects of PA (total, occupational, sports and household) after RP and to find predictive factors for a decrease in PA. All PA levels were significantly decreased at 6 weeks after RP and recovered quickly to approximately baseline levels from that time. Patients that had robot‐assisted RP did not have a faster recovery of PA than those that had open RP. Severity of first day incontinence and urine loss measured at 6 weeks and 3, 6 and 12 months after RP were significantly related to total and/or household PA level at all time‐points.
  • Malnourishment in bladder cancer and the role of immunonutrition at the
           time of cystectomy: an overview for urologists
    • Abstract: The ‘gold standard’ treatment for patients with carcinoma invading the bladder muscle is radical cystectomy (RC). Such patients are known to be at risk of malnutrition because of age and disease factors. Current evidence has established the nutritional and immunological benefits of immune‐enhancing nutritional supplements in upper gastrointestinal surgery. There are currently no guidelines for immunonutrition (IM) use in urology and bladder cancer specifically. We carried out a systematic review of the available literature in the MEDLINE/Embase database. We assessed the rates of malnutrition in RC cohorts and analysed the clinical impacts of nutritional deficiency. The impact of immune‐enhancing supplements was also investigated in RC cohorts with regard to postoperative outcomes. The prevalence of severe malnutrition was found to be 16–22%. There was a consistent association of malnourished patients with adverse postoperative outcomes in terms of mortality and morbidity. There is a paucity of data regarding IM in urological cohorts. Postoperative IM in RC was not found to have significant benefits beyond early return to a normal diet. There is not enough evidence in malnourished urological study cohorts to establish a consensus on IM. Until there are more well‐controlled comparative effective studies or randomized trials, the role of IM should be considered investigational in patients with bladder cancer.
  • Professor John M. Fitzpatrick 1948–2014: a life in the fast lane
  • Routine data expose a need for change
  • Pushing the robot‐assisted prostatectomy envelope – to the
           safety limits' Better outcomes
  • Upper tract urothelial carcinoma: do we really need to burn down the
  • Unveiling the surgical risk associated with neoadjuvant chemotherapy in
           bladder cancer
  • The importance of knowing testosterone levels in patients with prostate
  • Use of advanced treatment technologies among men at low risk of dying from
           prostate cancer
  • Recent insights into NF‐κB signalling pathways and the link
           between inflammation and prostate cancer
    • Abstract: Inflammation is involved in regulation of cellular events in prostate carcinogenesis through control of the tumour micro‐environment. A variety of bone marrow‐derived cells, including CD4+ lymphocytes, macrophages and myeloid‐derived suppressor cells, are integral components of the tumour micro‐environment. On activation by inflammatory cytokines, NF‐κB complexes are capable of promoting tumour cell survival through anti‐apoptotic signalling in prostate cancer (PCa). Positive feedback loops are able to maintain NF‐κB activation. NF‐κB activation is also associated with the metastatic phenotype and PCa progression to castration‐resistant prostate cancer (CRPC). A novel role for inhibitor of NF‐κB kinase (IKK)‐α in NF‐κB‐independent PCa progression to metastasis and CRPC has recently been uncovered, providing a new mechanistic link between inflammation and PCa. Expansion of PCa progenitors by IKK‐α may be involved in this process. In this review, we offer the latest evidence regarding the role of the NF‐κB pathway in PCa and discuss therapeutic attempts to target the NF‐κB pathways. We point out the need to further dissect inflammatory pathways in PCa in order to develop appropriate preventive measures and design novel therapeutic strategies.
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