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Rutgers Cancer Institute of New Jersey advances understanding of surgical treatment options for genitourinary cancers

MedicalNewsToday - Thu, 2015-02-26 04:00
Helping to advance scientific and clinical knowledge to combat cancers that affect the bladder, kidneys, urinary tract and male reproductive organs, physician scientists at Rutgers Cancer Institute...
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Sunitinib, sorafenib of no benefit in ECOG-ACRIN renal cell trial

MedicalNewsToday - Thu, 2015-02-26 02:00
Research results highlighted at the press conference of a major medical meeting report no benefit from the use of either Sutent® (sunitinib) or Nexavar® (sorafenib) among patients with...
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Adjuvant sorafenib and sunitinib do not improve outcomes in locally advanced kidney cancer

MedicalNewsToday - Thu, 2015-02-26 02:00
Findings from a federally funded study suggest that patients with locally advanced kidney cancer should not be treated with either adjuvant (post-surgery) sorafenib or sunitinib.
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Impact of Baseline Corticosteroids on Survival and Steroid Androgens in Metastatic Castration-resistant Prostate Cancer: Exploratory Analysis from COU-AA-301

Abstract Background

Corticosteroids have been used to mitigate mineralocorticoid-related effects and restore sensitivity to abiraterone acetate. Corticosteroids may also mediate glucocorticoid receptor or mutated androgen receptor activation and adversely influence outcome.

Objective

This post hoc exploratory analysis investigated whether baseline corticosteroids were an independent prognostic factor and its level of contribution in the presence of other prognostic factors for overall survival (OS) in study COU-AA-301.

Design, setting, and participants

COU-AA-301 was a randomised study of abiraterone plus prednisone versus prednisone in metastatic castration-resistant prostate cancer patients after docetaxel.

Intervention

Patients were randomised 2:1 to abiraterone 1000 mg plus prednisone 5 mg by mouth twice daily versus prednisone.

Outcome measurements and statistical analysis

Association of OS with baseline corticosteroids was determined by univariate and multivariate Cox models.

Results and limitations

At study entry, 33% of patients received corticosteroids, had worse disease characteristics (p < 0.05 except liver metastases), and were more likely to have testosterone levels below the median (odds ratio: 2.92; chi-squarep < 0.0001). Associations between prostate-specific antigen response as well as circulating tumour cell decline and higher baseline androgen levels were demonstrated. Patients taking baseline corticosteroids had inferior OS in univariate analysis (hazard ratio: 1.48;p < 0.0001); however, in multivariate stepwise selection modelling, baseline corticosteroids did not add substantially to the model. This analysis is limited as a retrospective analysis and restricted to patients after docetaxel.

Conclusions

In the COU-AA-301 study, baseline corticosteroids were associated with adverse prognostic features, inferior OS, and lower baseline androgen levels but did not add substantial information to the final prognostic model. Thus in these data from study COU-AA-301, concurrent baseline corticosteroids did not have an independent impact on OS.

Patient summary

Baseline corticosteroids did not adversely affect abiraterone clinical benefit in metastatic castration-resistant prostate cancer. Their use was associated with patients having worse disease characteristics.

Take Home Message

Baseline corticosteroids did not significantly contribute to adverse outcomes in this phase 3 trial of abiraterone acetate. Additional research is necessary to establish the relevance of glucocorticoid receptor and mutant androgen receptor in patients treated with abiraterone.

Keywords: Abiraterone, Corticosteroids, Prostate cancer, Survival, Testosterone.

Footnotes

a Department of Medicine, University of Washington, Seattle, WA, USA

b Janssen Research and Development, Los Angeles, CA, USA

c Janssen Research and Development, Menlo Park, CA, USA

d Janssen Research and Development, Raritan, NJ, USA

e Dana-Farber Cancer Institute, Boston, MA, USA

f Institut Gustave Roussy, Villejuif, France

g The University of Texas MD Anderson Cancer Center, Houston, TX, USA

h Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

i Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA

j The Institute of Cancer Research and the Royal Marsden Hospital, Sutton, UK

Corresponding author. 1959 NE Pacific, Box 356158, Seattle, WA 91895, USA. Tel. +1 206 598 0860; Fax: +1 206 598 6986.

Article information

PII: S0302-2838(14)00616-2
DOI: 10.1016/j.eururo.2014.06.042
© 2014 Published by Elsevier B.V.

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Revolutionary 'pregnancy tester' to help UK's 1 million undiagnosed kidney disease cases

MedicalNewsToday - Wed, 2015-02-25 04:00
A new medical device which combines nanotechnology with a pregnancy tester could help diagnose and treat the 1 million people in the UK who don't know they have kidney disease, a new report by the...
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The European Association Of Urology Robotic Training Curriculum: The Journey Has Only Just Begun

Refers to article:

Pilot Validation Study of the European Association of Urology Robotic Training Curriculum

Alessandro Volpe, Kamran Ahmed, Prokar Dasgupta, Vincenzo Ficarra, Giacomo Novara, Henk van der Poel and Alexandre Mottrie

Accepted 14 October 2014

Footnotes

a Department of Urology, University of Leipzig, Leipzig, Germany

b Southern General Hospital, Glasgow, UK

Corresponding author. Department of Urology, University of Leipzig, Liebigstraße 20, D-04103 Leipzig, Germany.

Article information

PII: S0302-2838(15)00159-1
DOI: 10.1016/j.eururo.2015.02.005
© 2015 European Association of Urology, Published by Elsevier B.V.

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Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models

Abstract

The phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt (PI3K/Akt) pathway is a key pathway activated in castrate-resistant prostate cancer (CRPC). This preclinical study evaluates targeting of Akt with AZD5363 alone and in combination with enzalutamide (ENZ) to prevent and delay resistance. Our results demonstrate AZD5363 has significant proapoptotic, antiproliferative activity as monotherapy in ENZ-resistant cell lines in vitro and significantly decreased tumour growth in ENZ-resistant xenograft. The combination of AZD5363 and ENZ showed synergistic decreases in cell proliferation and induced cell-cycle arrest and apoptosis in prostate cancer cell lines LNCaP and C4-2. Notably, the combination of AZD5363 and ENZ resulted in an impressive regression of castrate-resistant LNCaP xenograft tumours without any recurrence demonstrated, whereas progression occurred with both monotherapies. Serum prostate-specific antigen (PSA) levels were also continuously suppressed, and nadir PSA levels were lower in the combination arm compared to ENZ alone. Combination AZD5363 and ENZ at time of castration similarly resulted in significant regression of tumours, with greater relative suppression of PSA compared to when administered to castrate-resistant xenografts. In summary, combination AZD5363 and ENZ significantly delays the development of ENZ resistance in preclinical models through synergistic increases in apoptosis and cell cycle arrest. Our results also suggest greater efficacy may be seen with earlier combination treatment. This study provides preclinical data to support evaluation of combination targeting of the PI3K/Akt pathway and the androgen-receptor axis in the clinic using AZD5363 and ENZ, respectively.

Patient summary

Targeting of the Akt and androgen receptor pathways with AZD5363 and enzalutamide, respectively, significantly delayed the development of enzalutamide-resistant prostate cancer through increased apoptosis and cell cycle arrest. This preclinical synergy provides a strong rationale for clinical evaluation of this combination.

Take Home Message

Targeting of the Akt and androgen receptor pathways with AZD5363 and enzalutamide, respectively, significantly delayed the development of enzalutamide-resistant prostate cancer through increased apoptosis and cell cycle arrest. This preclinical synergy provides a strong rationale for clinical evaluation of this combination.

Keywords: Akt inhibitor, Apoptosis, Enzalutamide, Prostate cancer.

Footnotes

a The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada

b AstraZeneca, Alderley Park, Macclesfield, UK

Corresponding author. The Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.

Article information

PII: S0302-2838(14)00748-9
DOI: 10.1016/j.eururo.2014.08.006
© 2014 European Association of Urology, Published by Elsevier B.V.

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Radical Prostatectomy Findings in Men on Active Surveillance: Variable Findings Dependent on Reason for Surgery and Entry Criteria

To study adverse findings in radical prostatectomy of men on an active surveillance program with different entry and exit criteria.
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Diet high in red meat may make kidney disease worse

MedicalNewsToday - Tue, 2015-02-24 04:00
An estimated 26 million people in the United States have chronic kidney disease, which can lead to complete kidney failure.
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Survey shows postmenopausal women with vaginal atrophy report improved satisfaction with VagiCap

MedicalNewsToday - Tue, 2015-02-24 03:00
Patient experience data presented at International Society for the Study of Women's Sexual Health Annual MeetingNewly released patient satisfaction survey results from a study of a novel...
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Science: Chromosome 'bumper repair' gene predicts cancer patient outcomes

MedicalNewsToday - Mon, 2015-02-23 02:00
Like a car's front and back bumpers, your cell's chromosomes are capped by "telomeres" that protect this genetic material against deterioration.
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Why are kidney patients starting dialysis sooner?

MedicalNewsToday - Mon, 2015-02-23 02:00
Doctors are likely embracing higher levels of kidney function as being appropriate for dialysis initiationHighlights: In VA medical centers, patients started dialysis progressively...
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Most patients with chronic kidney disease may experience long-term pain

MedicalNewsToday - Mon, 2015-02-23 02:00
Study uncovers concerns about drug-related problems in patientsHighlights: In a study of patients with pre-dialysis chronic kidney disease, most patients reported chronic pain.
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Active surveillance 'may be appropriate' for intermediate-risk prostate cancer

MedicalNewsToday - Sun, 2015-02-22 02:00
Comparable rates of mortality following radiotherapy mean that active surveillance may be apt for both low-risk and favorable intermediate-risk prostate cancer, a study suggests.
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Prognostic and Prediction Tools in Bladder Cancer: A Comprehensive Review of the Literature

Abstract Context

This review focuses on risk assessment and prediction tools for bladder cancer (BCa).

Objective

To review the current knowledge on risk assessment and prediction tools to enhance clinical decision making and counseling of patients with BCa.

Evidence acquisition

A literature search in English was performed using PubMed in July 2013. Relevant risk assessment and prediction tools for BCa were selected. More than 1600 publications were retrieved. Special attention was given to studies that investigated the clinical benefit of a prediction tool.

Evidence synthesis

Most prediction tools for BCa focus on the prediction of disease recurrence and progression in non–muscle-invasive bladder cancer or disease recurrence and survival after radical cystectomy. Although these tools are helpful, recent prediction tools aim to address a specific clinical problem, such as the prediction of organ-confined disease and lymph node metastasis to help identify patients who might benefit from neoadjuvant chemotherapy. Although a large number of prediction tools have been reported in recent years, many of them lack external validation. Few studies have investigated the clinical utility of any given model as measured by its ability to improve clinical decision making. There is a need for novel biomarkers to improve the accuracy and utility of prediction tools for BCa.

Conclusions

Decision tools hold the promise of facilitating the shared decision process, potentially improving clinical outcomes for BCa patients. Prediction models need external validation and assessment of clinical utility before they can be incorporated into routine clinical care.

Patient summary

We looked at models that aim to predict outcomes for patients with bladder cancer (BCa). We found a large number of prediction models that hold the promise of facilitating treatment decisions for patients with BCa. However, many models are missing confirmation in a different patient cohort, and only a few studies have tested the clinical utility of any given model as measured by its ability to improve clinical decision making.

Take Home Message

We reviewed the current knowledge on prognostic and prediction tools in bladder cancer, addressing specific clinical problems and assessing their clinical benefit.

Keywords: Bladder cancer, Radical cystectomy, Outcome, Disease recurrence, Survival, Prediction tool, Prognostic tool, Nomogram, Prediction, Prognosis.

Footnotes

a Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

b Department of Urology, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany

c Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada

d Department of Urology, Memorial Sloan-Kettering Cancer Center, Kimmel Center for Prostate and Urologic Tumors, New York, NY, USA

e Academic Urology Unit, University of Sheffield, Sheffield, UK

f Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

g Department of Urology, Eberhard-Karls University, Tuebingen, Germany

h EORTC Headquarters, Brussels, Belgium

i Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

j Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France

k Department of Urology, Medical University of Vienna, Vienna, Austria

l Department of Urology, UT Southwestern, Dallas, TX, USA

m Division of Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

Corresponding author. Department of Urology, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18–20, 1090 Vienna, Austria. Tel. +43 1 404 00 2616; Fax: +43 1 404 002332.

Article information

PII: S0302-2838(15)00075-5
DOI: 10.1016/j.eururo.2015.01.032
© 2015 European Association of Urology, Published by Elsevier B.V.

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Recurrence Patterns After Open and Robot-assisted Radical Cystectomy for Bladder Cancer

Abstract Background

Concerns remain whether robot-assisted radical cystectomy (RARC) compromises survival because of inadequate oncologic resection or alteration of recurrence patterns.

Objective

To describe recurrence patterns following open radical cystectomy (ORC) and RARC.

Design, setting, and participants

Retrospective review of 383 consecutive patients who underwent ORC (n = 120) or RARC (n = 263) at an academic institution from July 2001 to February 2014.

Intervention

ORC and RARC.

Outcome measurements and statistical analysis

Recurrence-free survival estimates were illustrated using the Kaplan-Meier method. Recurrence patterns (local vs distant and anatomic locations) within 2 yr of surgery were tabulated. Cox regression models were built to evaluate the effect of surgical technique on the risk of recurrence.

Results and limitations

The median follow-up time for patients without recurrence was 30 mo (interquartile range [IQR] 5–72) for ORC and 23 mo (IQR 9–48) for RARC (p = 0.6). Within 2 yr of surgery, there was no large difference in the number of local recurrences between ORC and RARC patients (15/65 [23%] vs 24/136 [18%]), and the distribution of local recurrences was similar between the two groups. Similarly, the number of distant recurrences did not differ between the groups (26/73 [36%] vs 43/147 [29%]). However, there were distinct patterns of distant recurrence. Extrapelvic lymph node locations were more frequent for RARC than ORC (10/43 [23%] vs 4/26 [15%]). Furthermore, peritoneal carcinomatosis was found in 9/43 (21%) RARC patients compared to 2/26 (8%) ORC patients. In multivariable analyses, RARC was not a predictor of recurrence. Limitations of the study include selection bias and a limited sample size.

Conclusions

Within limitations, we found that RARC is not an independent predictor of recurrence after surgery. Interestingly, extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in RARC than in ORC patients. Further validation is warranted to better understand the oncologic implications of RARC.

Patient summary

In this study, the locations of bladder cancer recurrences following conventional and robotic techniques for removal of the bladder are described. Although the numbers are small, the results show that the distribution of distant recurrences differs between the two techniques.

Take Home Message

Within limitations, among patients undergoing open or robot-assisted radical cystectomy, the latter was not a predictor of recurrence. However, there are distinct patterns of recurrence, as extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in robotically treated patients.

Keywords: Bladder cancer, Open radical cystectomy, Robot-assisted radical cystectomy, Recurrence, Local, Distant.

Footnotes

a Department of Urology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA

b Department of Urology, Bern University Hospital, Bern, Switzerland

c Department of Healthcare Policy and Research, Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY, USA

d Department of Medicine, Division of Hematology/Medical Oncology, Weill Cornell Medical College-New York Presbyterian Hospital, New York, NY, USA

Corresponding author. Department of Urology, Weill Cornell Medical College, 525 E 68th St, New York, NY 10021, USA. Tel. +1 646 6331322; Fax: +1 212 7468941.

Article information

PII: S0302-2838(15)00157-8
DOI: 10.1016/j.eururo.2015.02.003
© 2015 European Association of Urology, Published by Elsevier B.V.

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Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer

Abstract Context

Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment.

Objectives

A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment.

Evidence acquisition

A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported.

Evidence synthesis

The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5–7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24 981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7–11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies.

Conclusions

The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required.

Patient summary

We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment.

Take Home Message

We identified 26 studies including 7627 men on active surveillance. There were few prostate cancer deaths. Programs with a scheduled rebiopsy and including only men with Gleason 3 + 3 scores had the highest rates of change to radical treatment.

Keywords: Active monitoring, Active surveillance, Conservative management, Deferred treatment, Expectant management, Localized prostate cancer, Meta-analysis, Prostatic neoplasms, Systematic review, Watchful waiting.

Footnotes

a School of Social and Community Medicine, University of Bristol, Bristol, UK

b NIHR Bristol Nutrition Biomedical Research Unit, University of Bristol, Bristol, UK

c Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

d Guy's Hospital, London, UK

e Cancer Research UK, Cambridge Research Institute, Cambridge, UK

Corresponding author. School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Clifton, Bristol BS8 2PS, UK. Tel. +44 117 3314520; Fax: +44 117 9287325.

These authors contributed equally.

Article information

PII: S0302-2838(15)00018-4
DOI: 10.1016/j.eururo.2015.01.004
© 2015 Published by Elsevier B.V.

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Dehydrated Human Amnion/Chorion Membrane Allograft Nerve Wrap Around the Prostatic Neurovascular Bundle Accelerates Early Return to Continence and Potency Following Robot-assisted Radical Prostatectomy: Propensity Score–matched Analysis

Abstract

We present a propensity-matched analysis of patients undergoing placement of dehydrated human amnion/chorion membrane (dHACM) around the neurovascular bundle (NVB) during nerve-sparing (NS) robot-assisted laparoscopic prostatectomy (RARP). From March 2013 to July 2014, 58 patients who were preoperatively potent (Sexual Health Inventory for Men [SHIM] score >19) and continent (no pads) underwent full NS RARP. Postoperative outcomes were analyzed between propensity-matched graft and no-graft groups, including time to return to continence, potency, and biochemical recurrence. dHACM use was not associated with increased operative time or blood loss or negative oncologic outcomes (p > 0.500). Continence at 8 wk returned in 81.0% of the dHACM group and 74.1% of the no-dHACM group (p = 0.373). Mean time to continence was enhanced in group 1 patients (1.21 mo) versus (1.83 mo;p = 0.033). Potency at 8 wk returned in 65.5% of the dHACM patients and 51.7% of the no-dHACM group (p = 0.132). Mean time to potency was enhanced in group 1, (1.34 mo), compared to group 2 (3.39 mo;p = 0.007). Graft placement enhanced mean time to continence and potency. Postoperative SHIM scores were higher in the dHACM group at maximal follow-up (mean score 16.2 vs 9.1). dHACM allograft use appears to hasten the early return of continence and potency in patients following RARP.

Take Home Message

In this feasibility study, dehydrated human amniotic membrane was placed around the neurovascular bundle of the prostate following full nerve-sparing robotic prostatectomy. A greater proportion of patients receiving the treatment returned to full continence and potency earlier compared to patients who did not receive the grafted tissue. Use of an allograft of dehydrated human amniotic membrane hastened the return of continence and potency in patients following robot-assisted radical prostatectomy.

Keywords: Biological dressings, Prostatic neoplasms, Robotics, Erectile dysfunction, Urinary incontinence, Convalescence.

Footnotes

a University of Central Florida School of Medicine & Global Robotics Institute, Florida Hospital-Celebration Health, Celebration, FL, USA

b Department of Urology, Fondazione Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

Corresponding author. Global Robotics Institute, Florida Hospital-Celebration Health, Urology, 410 Celebration Place, Suite 200, Celebration, FL 34744, USA. Tel. +1 407 3034673; Fax: +1 407 3034674.

Article information

PII: S0302-2838(15)00027-5
DOI: 10.1016/j.eururo.2015.01.012
© 2015 European Association of Urology, Published by Elsevier B.V.

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Prospective Randomized Trial Comparing 2 Flexible Digital Ureteroscopes: ACMI/Olympus Invisio DUR-D and Olympus URF-V

Urology (Gold Journal) In Press - Fri, 2015-02-20 18:00
To compare 2 digital flexible ureteroscopes in a randomized, prospective, clinical trial; the complementary metal oxide semiconductor–based Gyrus ACMI/Olympus Invisio DUR-D and the charged coupled device–based Olympus URF-V.
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A Systematic Review and Meta-analysis of Circumcision With Shang Ring vs Conventional Circumcision

Urology (Gold Journal) In Press - Fri, 2015-02-20 18:00
Herein, we conduct a systematic review and meta-analysis of the current evidence to compare the safety and efficacy of Shang Ring circumcision (SRC) with conventional circumcision (CC) for male patients. Articles were searched by 2 independent reviewers. Overall, 8 randomized controlled trials involving 3314 patients were included. Compared with the CC group, SRC is associated with shorter operative time, lower intraoperative pain score, higher satisfaction with penile appearances, less intraoperative blood loss, lower adverse event rate, and lower wound bleeding rate.
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