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The NERI Nocturia Advisory Conference 2012: focus on outcomes of therapy

 

 

 

 

The New England Research Institutes, Inc. (NERI) Nocturia Advisory Conference 2012: focus on outcomes of therapy

Jeffrey P. Weiss1,2, Jerry G. Blaivas1,2, Marco H. Blanker9, Donald L. Bliwise3, Roger R. Dmochowski4, Marcus Drake11, Catherine E. DuBeau5, Adonis Hijaz7, Raymond C. Rosen6, Philip E.V. Van Kerrebroeck10 and Alan J. Wein8

1Department of Urology, SUNY Downstate College of Medicine, Brooklyn, 2Weill Medical College of Cornell University, New York, NY, 3Emory University School of Medicine, Atlanta, GA, 4Department of Urologic Surgery, Vanderbilt University, Nashville, TN, 5Division of Geriatric Medicine, UMass Memorial Medical Center and UMass Medical School, Worcester, MA, 6New England Research Institutes, Watertown, MA, 7Urology Institute, University Hospitals Case Medical Center, Cleveland, OH, 8Division of Urology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 9Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, 10Department of Urology, Maastricht University Medical Center, Maastricht, The Netherlands, and 11University of Bristol, Bristol, UK

INTRODUCTION

Nocturia, awaking to void urine, is a common and sometimes bothersome symptom that may impose detrimental impacts on sleep-quality, mood, and overall health [1]. The multi-factorial aetiology of nocturia, coupled with the recent demonstration that this symptom is highly variable over time and often resolves spontaneously [2] , makes nocturia a challenging clinical entity. Although nocturia may have little health impact for some, for others it can be a highly bothersome, debilitating condition. Multiple studies have shown an association between nocturia and disturbed sleep, reduced well-being, and increased morbidity [3, 4, 5].

A consensus statement published in 2011 provided guidance to clinicians who are confronted with the wide range of clinical presentations of nocturia [1]. That paper focused primarily on a description of nocturia, its prevalence, its impact on health-related quality of life (QOL) and overall health, and an overview of available treatment options. The present paper extends and elaborates on the previous paper by examining the most recent research on diagnostic and treatment outcomes. Numerous papers have been published in the 2 years since the previous conference was organised, and the field, as a whole, has a large and dynamic research agenda. This paper summarises the findings resulting from a 2012 conference of key thought leaders in the field of nocturia who focused on updating outcome studies published since the previous conference was held.

 

Video: Androgen-ablation therapy (AAT) associated autophagy

 

 

 

 

Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells?

Haley L. Bennett, Jacqueline Stockley, Janis T. Fleming, Ranadip Mandal, Jim O’Prey*, Kevin M. Ryan*, Craig N. Robson and Hing Y. Leung

Urology Research Laboratory and *Tumour Cell Death Research Laboratory, Beatson Institute for Cancer Research, Glasgow, and Solid Tumour Target Discovery Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

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OBJECTIVE

• To study the cellular effects of the anti-androgen bicalutamide on autophagy and its potential impact on response to androgen-ablation therapy (AAT) alone or combined with docetaxel chemotherapy in human prostate cancer LNCaP cells.

MATERIALS AND METHODS

• LNCaP cells were treated with bicalutamide  docetaxel, and cellular effects were assayed: lipidated LC3 (a microtubule-associated protein) for autophagy and its trafficking to fuse with lysosome; flow cytometry using propidium iodide or caspase 3 for cell death; and sulforhodamine B assay for cell growth.

RESULTS

• Bicalutamide treatment enhanced autophagy in LNCaP cells with increased level of autophagosome coupled with an altered cellular morphology reminiscent of neuroendocrine differentiation.

• Consistent with the literature on the interaction between androgen receptor activation and taxane chemotherapy, bicalutamide diminished docetaxel mediated cytotoxicity.

• Significantly, pharmacological inhibition of autophagy with 3-methyladenine significantly enhanced the efficacy cell kill mediated by AAT  docetaxel.

CONCLUSION

• Autophagy associated with bicalutamide treatment in LNCaP cells may have a pro-survival effect and strategy to modulate autophagy may have a potential therapeutic
value.

The indwelling Foley Catheter; an anachronism

The Simon Foundation for Continence was founded in 1982 by Cheryle Gartley to bring the subject into the open, remove the stigma surrounding incontinence and provide help and hope to the individuals. their families and their healthcare professionals. As President, Cheryle invited Roger Feneley, Calvin Kunin and David Stickler to the Foundations’ third conference in the series entitled Innovating  for Continence: The Engineering Challenge in 2011, to talk about catheter drainage of the bladder.  Their presentations each carried the same message that the design of the indwelling Foley catheter violated the integrity of the sophisticated defence mechanisms that protect the bladder from bacterial infection.  The morbidity and mortality caused by the Foley catheter and their costs to health services are no longer acceptable.  Research and Development of antimicrobial coatings alone will not resolve the problems of long-term catheterisation.

This meeting led to their publication ‘An indwelling catheter for the 21st Century’ in the BJUI.  In an era witnessing outstanding technological advances in medical implants the simple task of draining urine from the bladder should be performed without producing infection and a range of associated complications. The cyclical filling and emptying of the bladder is crucial to the bladder’s defence against bacterial infection but the design of the Foley catheter with the drainage eyes in its protruding tip distal to the self-retaining balloon not only prevents the bladder from emptying completely but can seriously damage the integrity of the protective urothelial lining.  Medical device manufacturers need to take up the challenge of producing a device which restores the function of the debilitated lower urinary tract without threatening its health.

 

This video explains the problem further.

 

The Simon Foundation’s 4th international conference, Innovating for Continence: The Engineering Challenge takes place this week in Chicago, IL

 

Dr David Stickler became interested in the problem of catheter-associated urinary tract infections in paraplegic patients at the Irish National Spinal Unit during his time as a lecturer in Trinity College Dublin in the early 1970s. Over the years as a reader in medical microbiology in Cardiff University he worked on many aspects of the problem from the fundamental biology of the bacterial biofilms that develop on catheters to the practical management of biofilm-induced catheter encrustation and blockage. Currently he is an honorary senior research fellow in the Cardiff University School of Biosciences.  

Dr. Kunin received his MD from Cornell University College of Medicine in 1953. He is Emeritus Professor of Medicine at the Ohio State University and Clinical Professor of Medicine at the University of Arizona. He has a distinguished background in infectious diseases, antimicrobial pharmacology, hospital infection control, urinary tract infections and promotion of appropriate use of antibiotics. He has published over 350 scientific articles and a book on urinary tract infections. He is a past president of the Infectious Diseases Society of American, served on NIH and FDA advisory committees and is an honorary academic consultant to the National Health Research Institute in Taiwan.

Mr Roger Feneley is an Emeritus Consultant Urologist to the North Bristol NHS Trust and Visiting Professor in the Faculty of Applied Science at the University of the West of England (UWE).  In 1998 he founded the BioMed Centre within the Bristol Urological Institute with the objective to improve the care of patients with intractable urinary incontinence.  In 2009, he founded Alternative Urological Catheter Systems Ltd to develop new urine collection systems.

 

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Video: Genetic predisposition to early recurrence in clinically localized prostate cancer

 

 

Genetic predisposition to early recurrence in clinically localized prostate cancer

Ángel Borque, Jokin del Amo, Luis M. Esteban*, Elisabet Ars§, Carlos Hernández**, Jacques Planas, Antonio Arruza††, Roberto Llarena, Joan Palou§, Felipe Herranz**, Carles X. Raventós, Diego Tejedor, Marta Artieda, Laureano Simon, Antonio Martínez, Elena Carceller, Miguel Suárez, Marta Allué, Gerardo Sanz* and Juan Morote

‘Miguel Servet’ University Hospital, *University of Zaragoza, Zaragoza, Spain, Progenika Biopharma S.A., University Hospital of Cruces, Bilbao, §Puigvert Foundation, ‘Vall d’Hebron’ University Hospital, Barcelona, **‘Gregorio Marañón’ University Hospital, Madrid, and ††Hospital of Txagorritxu, Vitoria, Spain

Read the full article

• To evaluate genetic susceptibility to early biochemical recurrence (EBCR) after radical prostatectomy (RP), as a prognostic factor for early systemic dissemination.

• To build a preoperative nomogram to predict EBCR combining genetic and clinicopathological factors.

PATIENTS AND METHODS

• We evaluated 670 patients from six University Hospitals who underwent RP for clinically localized prostate cancer (PCa), and were followed-up for at least 5 years or until biochemical recurrence.

• EBCR was defined as a level prostate-specific antigen >0.4 ng/mL within 1 year of RP; preoperative variables studied were: age, prostate-specific antigen, clinical stage, biopsy Gleason score, and the genotype of 83 PCa-related single nucleotide polymorphisms (SNPs).

• Univariate allele association tests and multivariate logistic regression were used to generate predictive models for EBCR, with clinicopathological factors and adding SNPs.

• We internally validated the models by bootstrapping and compared their accuracy using the area under the curve (AUC), net reclassification improvement, integrated discrimination improvement, calibration plots and Vickers’ decision curves.

RESULTS

• Four common SNPs at KLK3, KLK2, SULT1A1 and BGLAP genes were independently associated with EBCR.

• A significant increase in AUC was observed when SNPs were added to the model: AUC (95% confidence interval) 0.728 (0.674–0.784) vs 0.763 (0.708–0.817).

• Net reclassification improvement showed a significant increase in probability for events of 60.7% and a decrease for non-events of 63.5%.

• Integrated discrimination improvement and decision curves confirmed the superiority of the new model.

CONCLUSIONS

• Four SNPs associated with EBCR significantly improved the accuracy of clinicopathological factors.

• We present a nomogram for preoperative prediction of EBCR after RP.

Step-by-Step: Salvage robot-assisted radical prostatectomy

Salvage robot-assisted radical prostatectomy

Haidar Abdul-Muhsin, Srinivas Samavedi, Claudio Pereira, Kenneth Palmer and Vipul Patel
Global Robotics Institute, Celebration Health, Florida, USA

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Video: Commentary by Dr Arrabal-Polo on the calcium : citrate ratio.

Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis

Miguel Angel Arrabal-Polo*, Miguel Arrabal-Martin*,  Salvador Arias-Santiago**, Juan Garrido-Gomez, Antonio PoyatosAndujar§ and Armando Zuluaga-Gomez**

Department of Urology, San Cecilio University Hospital, **Department of Medicine, Baza Hospital, Department of  Medicine, University of Granada, and Departments of Traumatology and §Biochemistry, San Cecilio University Hospital, Granada, Spain

Read the full article
OBJECTIVE

• To analyse the importance of urinary citrate and the urinary calcium : citrate  ratio in patients with calcium renal lithiasis and severe lithogenesis compared with a control group of patients without lithiasis.

MATERIAL AND METHODS

• A cross-sectional study of 115 patients in eastern Andalusia, Spain was conducted.

• The patients were divided into two groups: Group A: 56 patients aged 25 – 60 years without calcium renal lithiasis; Group B: 59 patients aged 25 – 60 years, presenting with calcium renal lithiasis and severe lithogenesis.

• The citrate levels and the calcium : citrate ratio in the patients’ urine and the relationship of these two factors to lithiasic activity were analysed and compared.

RESULTS

• In Group B, 32.2% of the patients presented with hypocitraturia, compared with 14.3% of the patients in Group A (P = 0.02).

• The urinary citrate levels were lower in Group B than in Group A (P = 0.001) and the calcium : citrate ratio was higher in Group B than in Group A (P = 0.005).

• The results suggest that a patient urinary calcium : citrate ratio > 0.25 indicates severe lithogenesis (with a sensitivity of 89% and a specificity of 57%).

• After linear regression analysis, we found that the urinary citrate level is an independent factor associated with the changes in bone densitometry T-score values of patients.

CONCLUSIONS

• The patients with severe lithogenesis presented with hypocitraturia, which was associated with lower bone mineral density.

• The calcium : citrate ratio, which is linearly related to the bone resorption marker β-crosslaps, could be useful in evaluating the risk of severe lithogenesis when this ratio is > 0.25.

A Tale of Four Prostates

There was a time when doctors were reluctant to tell patients the truth about a diagnosis of cancer, and even more unwilling to discuss any illness from which they themselves suffered.  John Anderson broke the mould last year when he made a public announcement about his newly diagnosed liver metastases, which subsequently turned out to be the result of secondary spread of adenocarcinoma of the prostate.

John was President Elect of the British Association of Urological Surgeons (BAUS) at the time, so sadly had to resign his presidency (the best president we never had!) and subsequently his trusteeship of the Prostate Cancer UK charity. John’s energy and drive are legendary, he is a true surgeon’s surgeon. The stoicism and determination that he has displayed throughout a year in which he has received hormonal treatment, followed by chemotherapy, is awe-inspiring.

My admiration for John, in addition to my own recent diagnosis of localised prostate cancer, requiring robot-assisted radical prostatectomy (https://moreintelligentlife.co.uk/content/ideas/simon-garfield/prof-roger-kirby) led me to approach Sean Vesey and Damian Hanbury, whom I knew were similarly afflicted by a disease that carries a 1 in 9 lifetime risk. It occurred to me that there was a great deal to be gained from frank disclosure and discussion, as opposed to treating this problem as some dark, furtive secret. Women suffering from breast cancer are generally much more open about their problem and consequently receive much more support from friends, relatives and others who have been touched by the disease. This empowers them to make the difficult but smarter choices about their health by opting in to breast cancer treatment. Men need this kind of social encouragement and support so that we can be within reach to them as well.

The result was a publication entitled “a Tale of Four Prostates” in the upcoming issue of Trends in Urology and Men’s Health (www.trendsinurology.com) and a short accompanying video.

In this John, Damian and myself discuss the impact of our respective diagnoses and treatment. We sincerely hope that, by being frank, honest and transparent about our own situation, we can help other patients to help themselves by seeking advice and treatment earlier, and by sharing information about their diagnosis with others in order to mobilize support from their family and friends.

 

Sadly, John Anderson has since died. You can read an obituary by Roger Kirby here. 

 

 

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Best poster on learning curves: EAU 2013

 

Hamid Abboudi expains his poster on learning curves at EAU 2013 Congress, Milan

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