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Phenotype-specific association of the locus with nonsyndromic cryptorchidism

Based on a genome-wide association study (GWAS) of testicular dysgenesis syndrome (TDS) reporting possible association with TGFBR3, we analyzed GWAS data from a larger, phenotypically restricted cryptorchidism population for potential replication of this signal.
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Preoperative Predictors of Pathologic Lymph Node Metastasis in Patients with Renal Cell Carcinoma Undergoing RPLND

Patients with locally advanced renal cell carcinoma (RCC) represent a subset of patients who may benefit from retroperitoneal lymph node dissection (RPLND). We aimed to identify preoperative clinical predictors of positive lymph nodes in patients with RCC without distant metastasis who underwent RPLND.
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Clinical Outcomes of Castration-resistant Prostate Cancer Treatments Administered as Third or Fourth Line Following Failure of Docetaxel and Other Second-line Treatment: Results of an Italian Multicentre Study

Abstract Background

The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit.

Objective

To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA.

Design, setting, and participants

We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel.

Outcome measurements and statistical analysis

The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis.

Results and limitations

We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences.

Conclusions

We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy.

Patient summary

It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent.

Take Home Message

Clinical outcomes of third-line new agents (NAs) in metastatic castration-resistant prostate cancer are similar regardless of the previous NA therapy. Some factors can help identify patients who fail to receive a survival benefit from third-line treatment.

Keywords: Abiraterone acetate, Cabazitaxel, Castration-resistant prostate cancer, Enzalutamide, Fourth line, Prognostic factors, Third line.

Footnotes

a Medical Oncology Department, Santa Chiara Hospital, Trento, Italy

b Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

c Medical Oncology Department, National Cancer Institute, Aviano, Italy

d Department of Radiological, Oncological and Anatomopathological Sciences, La Sapienza, University of Rome, Rome, Italy

e Medical Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padua, Italy

f Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori “Fondazione G. Pascale” - IRCCS, Naples, Italy

g Medical Oncology Department, General Hospital, Parma, Italy

h Medical Oncology I - Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Italy

i Medical Oncology Department, University of Torino, San Luigi Hospital, Orbassano, Italy

j Medical Oncology Department, Villa Sofia Cervello Hospital, Palermo, Italy

k Medical Oncology Department, General Hospital, Lugo di Romagna, Italy

l Medical Oncology Department, Santa Maria degli Angeli Hospital, Pordenone, Italy

m Medical Oncology Department, Fondazione Istituto Nazionale Tumori, Milan, Italy

n Medical Oncology Division, Azienda Ospedaliero Universitaria, Policlinico di Modena, Modena, Italy

o Medical Oncology Department, General Hospital, Cremona, Italy

p Medical Oncology Department, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

q Medical Oncology Department, General Hospital, Mirano, Italy

r Department of Medical Oncology and Haematology, Humanitas Clinical and Research Center, Rozzano, Italy

s Medical Oncology Department, General Hospital, Faenza, Italy

t Medical Oncology Department, San Vincenzo Hospital, Taormina, Italy

u Division of Medical Oncology, San Giacomo Hospital, Castelfranco Veneto, Italy

v Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy

w Medical Oncology Department, University Campus bio-Medico, Rome, Italy

x Medical Oncology Department, General Hospital, Verona, Italy

y Medical Oncology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy

z Medical Oncology Department, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

aa Medical Oncology Department, General Hospital, Imola, Italy

bb Medical Oncology Department, Niguarda Cancer Centre, Ospedale Niguarda Ca’ Granda, Milan, Italy

cc Medical Oncology Department, Referral Cancer Centre of Basilicata-IRCCS, Rionero in Vulture, Italy

dd Medical Oncology Department, General Hospital, Carpi, Italy

ee Medical Oncology Department, Santa Maria della Misericordia University Hospital, Udine, Italy

Corresponding author. Medical Oncology Department, Santa Chiara Hospital, Largo Medaglie d’Oro, 38100 Trento, Italy. Tel. +39 0461 902478; Fax: +39 0461 903364.

Article information

PII: S0302-2838(14)01022-7
DOI: 10.1016/j.eururo.2014.10.014
© 2014 European Association of Urology, Published by Elsevier B.V.

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Novel Therapeutic Approach for Neurogenic Erectile Dysfunction: Effect of Neurotrophic Tyrosine Kinase Receptor Type 1 Monoclonal Antibody

Abstract Background

Erectile dysfunction (ED) is a major health issue in aged populations, and neurogenic ED is particularly difficult to treat. Novel therapeutic approaches are needed for treatment of neurogenic ED of peripheral origin.

Objective

To investigate the therapeutic effects of a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile function and sexual behavior in a rat model of cavernous nerve injury (CNI).

Design, setting, and participants

In one experiment, 84 male rats were randomly assigned to seven groups. The groups underwent either CNI or sham surgery, subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations immediately after surgery and then 1 wk later. Erectile function was assessed and histologic/molecular analyses were performed at 6 wk after surgery. In a second experiment, 36 male rats were randomly divided into three groups. The groups underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the performance of the rats in sexual behavior tests was videotaped.

Intervention

CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA-mAb.

Outcome measurements and statistical analysis

The intracavernous pressure response to cavernous nerve electrostimulation was measured and midpenile cross-sections were histologically examined. Western blotting (WB) of cavernous tissue protein was performed. Rats were assessed for chasing, mounting, intromission, and ejaculation behaviors during sexual behavior tests. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramerttest.

Results and limitations

Recovery of erectile function of varying degrees was observed in the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine hydroxylase–positive nerve fibers in the corpus cavernosum and enhanced neuronal nitric oxide synthase–positive fibers in the dorsal nerve. The ratio of smooth muscle to collagen in the corpus cavernosum was significantly improved in TrkA-mAb treatment groups compared to PBS vehicle and IgG control groups. WB confirmed these biological changes. There was a nonsignificant increase in the average number of intromissions and ejaculations in the TrkA-mAb group. The study limitations include small sample size, variability in sexual behavior, lack of data on the neuromuscular mechanism involved, and lack of information of the role of neurotrophins or cytokines in regeneration.

Conclusions

TrkA-mAb successfully inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on ED and sexual behavior disorder in a rat model of CNI.

Patient summary

This report provides strong evidence that a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on erectile dysfunction and sexual behavior disorder in a rat model of cavernous nerve injury. The results raise the possibility that human patients with neurogenic erectile dysfunction may respond to TrkA-mAb in a manner that parallels the response seen in our rodent study.

Take Home Message

A monoclonal antibody to neurotrophic tyrosine kinase receptor type 1 (TrkAR) successfully inhibits TrkAR activity and leads to sympathetic nerve regeneration. The monoclonal antibody had therapeutic benefits for erectile dysfunction and sexual behavior disorder in a rat model of cavernous nerve injury (CNI) and prevented fibrosis of the corpus cavernosum following CNI.

Keywords: Cavernous nerve injury, Neurogenic erectile dysfunction of peripheral origin, Tyrosine kinase receptor type 1 monoclonal antibody, Nerve regeneration, Sexual behavior.

Footnotes

a Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA

b Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, P.R. China

c Department of Urology, School of Medicine, Capital Medical University, Beijing, P.R. China

d Eli Lilly and Company, Indianapolis, IN, USA

Corresponding author. Department of Urology, University of California, San Francisco, 400 Parnassus Ave., Ste A-630, San Francisco, CA 94143-0738, USA. Tel. +1 415 3537339; Fax: +1 415 4763803.

These authors contributed equally.

Article information

PII: S0302-2838(14)01021-5
DOI: 10.1016/j.eururo.2014.10.013
© 2014 Published by Elsevier B.V.

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The quality of biopsy is directly linked to survival in patients with bladder cancer

MedicalNewsToday - Thu, 2014-10-23 04:00
UCLA researchers have shown for the first time that the quality of diagnostic staging using biopsy in patients with bladder cancer is directly linked with survival, meaning those that don't get...
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Temporal Trends and Factors Associated With Receipt of Systemic Therapy Among Patients Undergoing Cytoreductive Nephrectomy: An Analysis of the National Cancer Database

We evaluated temporal trends in utilization of systemic therapy among patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) from a large national cancer registry, and assessed characteristics associated with receipt of systemic treatment.
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The effect of "Modified Z" Trendelenburg Positioning on Intra-ocular pressure, during Robotic Assisted Laparoscopic Radical Prostatectomy - A Randomized control study

Trendelenburg positioning (TP) has a dramatic effect on the circulation and consequently, increases cerebral and intra-ocular pressure (IOP). We evaluated whether modification in TP can minimize the elevation of IOP.
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Congenital penile pathology is associated with abnormal development of the dartos muscle: a prospective study in a large cohort of children undergoing primary penile surgery in a tertiary reference centre

Pathophysiological mechanisms leading to chordae in hypospadias and to the hidden state of buried penis (BP) in the prepubic fat remain unclear. Resection of dartos tissue (DT) usually makes the penis straight in hypospadias and unhides it in BP, suggesting a common pathophysiology related to DT.
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Hounsfield density of renal papillae in stone formers: analysis based on stone composition

In the current study we examine the Hounsfield density of the renal papilla of stone-formers of all common stone subtypes to further understand the pathophysiology of stone formation.
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Prognostic impact of synchronous second primary malignancies on the overall survival of patients with metastatic prostate cancer

To determine the prognostic impact of synchronous second primary malignancy (SPM) on the overall survival (OS) of patients with metastatic prostate cancer (mPCa), as identifying features that stratify the risk of OS is critical for judicious application of a definitive therapy.
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Systematic Review and Meta-analysis of the Clinical Effectiveness of Shock Wave Lithotripsy, Retrograde Intrarenal Surgery, and Percutaneous Nephrolithotomy for Lower-pole Renal Stones

Abstract

The prevalence of urolithiasis is increasing. Lower-pole stones (LPS) are the most common renal calculi and the most likely to require treatment. A systematic review comparing shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) in the treatment of ≤20 mm LPS in adults was performed. Comprehensive searches revealed 2741 records; 7 randomised controlled trials (RCTs) recruiting 691 patients were included. Meta-analyses for stone-free rate (SFR) at ≤3 mo favoured PNL over SWL (risk ratio [RR]: 2.04; 95% confidence interval [CI], 1.50–2.77) and RIRS over SWL (RR: 1.31; 95% CI, 1.08–1.59). Stone size subgroup analyses revealed PNL and RIRS were considerably more effective than SWL for >10 mm stones, but the magnitude of benefit was markedly less for ≤10 mm stones. The quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]) for SFR was moderate for these comparisons. The median SFR from reported RCTs suggests PNL is more effective than RIRS. The findings regarding other outcomes were inconclusive because of limited and inconsistent data. Well-designed, prospective, comparative studies that measure these outcomes using standardised definitions are required, particularly for the direct comparison of PNL and RIRS. This systematic review, which used Cochrane methodology and GRADE quality-of-evidence assessment, provides the first level 1a evidence for the management of LPS.

Patient summary

We thoroughly examined the literature to compare the benefits and harms of the different ways of treating kidney stones located at the lower pole. PNL and RIRS were superior to SWL in clearing the stones within 3 mo, but we were unable to make any conclusions regarding other outcomes. More data is required from reliable studies before firm recommendations can be made.

Take Home Message

Percutaneous nephrolithotomy and retrograde intrarenal surgery are significantly more effective than shock wave lithotripsy in achieving stone clearance at ≤3 mo for ≤20 mm lower-pole renal stones. However, there is a lack of data regarding other important outcomes.

Keywords: Nephrolithiasis, Urolithiasis, Kidney stones, Lithotripsy, Shock wave lithotripsy, Extracorporeal shock wave lithotripsy, Ureterorenoscopy, Retrograde intrarenal surgery, Percutaneous nephrolithotomy.

Footnotes

a Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK

b Academic Urology Unit, University of Aberdeen, Aberdeen, UK

Corresponding author. Department of Urology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, UK. Tel. +44 1224 438133; Fax: +44 1224 438165.

Article information

PII: S0302-2838(14)01005-7
DOI: 10.1016/j.eururo.2014.09.054
© 2014 European Association of Urology, Published by Elsevier B.V.

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UCLA research could help improve bladder function among people with spinal cord injuries

MedicalNewsToday - Wed, 2014-10-22 02:00
People who have suffered spinal cord injuries are often susceptible to bladder infections, and those infections can cause kidney damage and even death.
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Quantification of Asymptomatic Kidney Stone Burden by Computed Tomography for Predicting Future Symptomatic Stone Events

Urology (Gold Journal) In Press - Tue, 2014-10-21 00:00
To find the optimal characterization of asymptomatic radiographic stone burden on computed tomography (CT) scans.
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Emergency aid for overdoses

MedicalNewsToday - Mon, 2014-10-20 04:00
Every minute counts in the event of an overdose. ETH professor Jean-Christophe Leroux and his team have developed an agent to filter out toxins from the body more quickly and efficiently.
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Ultrasensitive Prostate-Specific Antigen and its Role after Radical Prostatectomy: a Systematic Review

Prostate-specific antigen (PSA) is an important tool for monitoring of patients with prostate cancer (PCa) after radical prostatectomy (RP). Ultrasensitive PSA (uPSA) assays with a lower limit of detection (LLD) of as low as 0.001 ng/ml are being increasingly used. This systematic review examines current available uPSA technologies and the role of uPSA in monitoring patients after RP.
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Relationship between Chronic Non-Urological Associated Somatic Syndromes (NUAS) and Symptom Severity in Urological Chronic Pelvic Pain Syndromes: Baseline Evaluation of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Study

We report data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) network to: (1) identify participants having either (a) urologic chronic pelvic pain syndromes (UCPPS) only or (b) chronic functional non-urological associated somatic syndromes (NUAS) in addition to UCPPS, (2) characterize these two subgroups, and (3) explore these two subgroups using three criteria: (a) the MAPP eligibility criteria, (b) self-reported medical history, or (c) RAND interstitial cystitis epidemiologic (RICE) criteria.
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Re: Measuring Low-Value Care in Medicare

A. L. Schwartz, B. E. Landon, A. G. Elshaug, M. E. Chernew and J. M. McWilliams
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Re: Pre-Operative Urodynamics in Women with Stress Urinary Incontinence Increases Physician Confidence, but Does Not Improve Outcomes

P. Zimmern, H. Litman, C. Nager, L. Sirls, S. R. Kraus, K. Kenton, T. Wilson, G. Sutkin, N. Siddiqui, S. Vasavada and P. Norton; Urinary Incontinence Treatment Network
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