In this podcast, Mr Feroz Ali Khan, Urology Registrar, Northampton General Hospital, talks about the BJUI Knowledge module “Who can we predict is going to have progression of BPH/LUTS”.
You can visit BJUI Knowledge here
bjuiknowledge.bjuinternational.com/
Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
Please use the comment buttons below if you would like to join the conversation.
If you only have time to read one article this week, we recommend this one.
Bradley Holland*, Mallory Karr*, Kristin Delfino*, Danuta Dynda†, Ahmed El-Zawahry‡, Andrea Braundmeier-Fleming*, Kevin McVary§ and Shaheen Alanee¶
*Southern Illinois University School of Medicine, †Center for Clinical Research, Southern Illinois University School of Medicine, Springfield, IL, USA, ‡Urology, University of Toledo, Toledo, OH, §Loyola University Chicago, Chicago, IL, and ¶Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA
To examine the correlation between urinary and faecal microbial profiles and the different aspects of lower urinary tract symptoms (LUTS) in men, as there is accumulating evidence that variations in the human microbiota may promote different benign disease conditions.
We extracted total DNA from urine and faecal samples of a group of men, under an Institutional Review Board‐approved protocol. At the same time, International Prostate Symptom Score (IPSS) data were collected. We then amplified the extracted DNA and sequenced it using bacterial 16S ribosomal RNA gene high‐throughput next‐generation sequencing platform, and analysed the microbial profiles for taxonomy to examine the correlation between the different operational taxonomy units (OTUs) and LUTS represented by the total IPSS, the different symptom levels of the IPSS (mild, moderate, and severe) and its subcomponents of storage, nocturia, voiding, and bother.
We included 30 patients (60 samples; one urine and one faecal per patient). In all, 48 faecal OTUs showed a significant correlation with one or more of the IPSS components; 27 with nocturia, 19 with bother, 16 with storage symptoms, and nine with voiding symptoms. The most substantial negative (protective) correlation was between Lachnospiraceae Blautia , a bacteria that increases the availability of gut anxiolytic and antidepressant short‐chain fatty acids, and bother (correlation coefficient 0.702; P = 0.001). The abundance of L. Blautia continued to have a protective correlation against LUTS when looking at the different levels of IPSS severity (moderate and severe vs mild, correlation coefficient 0.6132; P = 0.002). Ten unique urinary OTUs showed significant correlation with LUTS; eight with nocturia, one with bother, three with storage, and one with voiding, but no faecal OUT had more than a low correlation with the outcomes of interest in this study.
Our prospective work finds a plausible correlation between L. Blautia and LUTS. Additional studies are needed to determine if the correlations found in the present research are applicable to the general population of patients affected by LUTS.
Nikita Bhatt is a Specialist Trainee in Urology in the East of England Deanery and a BURST Committee member @BURSTUrology
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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
We invite you to use the comment tools at the bottom of each post to join the conversation.
If you only have time to read one article this week, it should be this one.
Mihir Desai*, Mo Bidair†, Kevin C. Zorn‡, Andrew Trainer§, Andrew Arther§, Eugene Kramolowsky¶, Leo Doumanian*, Dean Elterman**, Ronald P. Kaufman Jr.††, James Lingeman‡‡, Amy Krambeck‡‡, Gregg Eure§§, Gopal Badlani¶¶, Mark Plante***, Edward Uchio†††, Greg Gin†††, Larry Goldenberg‡‡‡, Ryan Paterson‡‡‡, Alan So‡‡‡, Mitch Humphreys§§§, Claus Roehrborn¶¶¶, Steven Kaplan****, Jay Motola**** and Naeem Bhojani‡
*Institute of Urology, University of Southern California, Los Angeles, †San Diego Clinical Trials, San Diego, CA, USA, ‡University of Montreal Hospital Center, Université de Montréal, Montréal, QC, Canada, §Adult Pediatric Urology and Urogynecology, P.C., Omaha, NE, ¶Virginia Urology, Richmond, VA, USA, **University of Toronto – University HealthNetwork, Toronto, ON, Canada, ††Albany Medical College, Albany, NY, ‡‡Indiana University Health Physicians, Indianapolis, IN, §§Urology of Virginia, Virginia Beach, VA, ¶¶Wake Forest School of Medicine, Winston-Salem, NC, ***University of Vermont Medical Center, Burlington, VT, †††VA Long Beach Healthcare System, Long Beach, CA, USA, ‡‡‡University of British Columbia, Vancouver, BC, Canada, §§§Mayo Clinic Arizona, Scottsdale, AZ, ¶¶¶UT Southwestern Medical Center, Department of Urology, University of Texas Southwestern, Dallas, TX, and ****Icahn School of Medicine at Mount Sinai, New York, NY, USA
To present 6‐month safety and effectiveness data from a multicentre prospective study of aquablation in men with lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH) with prostate volumes between 80 and 150 mL.
Between September and December 2017, 101 men with LUTS attributable to BPH were prospectively enrolled at 16 centers in Canada and the USA.
The mean prostate volume was 107 mL. The mean length of hospital stay after the aquablation procedure was 1.6 days (range: same day to 6 days). The primary safety endpoint (Clavien–Dindo grade 2 or higher or any grade 1 event resulting in persistent disability) at 3 months occurred in 45.5% of men, which met the study design goal of < 65% (P < 0.001). At 6 months, 22% of the patients had experienced a Clavien–Dindo grade 2, 14% a grade 3 and 5% a grade 4 adverse event. Bleeding complications requiring intervention and/or transfusion were recorded in eight patients prior to discharge and in six patients after discharge. The mean International Prostate Symptom Score improved from 23.2 ± 6.3 at baseline to 6.7 ± 5.1 at 3 months, meeting the study’s primary efficacy endpoint goal (P < 0.001). The maximum urinary flow rate increased from 8.7 to 18.8 mL/s (P < 0.001) and post‐void residual urine volume decreased from 131 at baseline to 47 at 6 months (P < 0.0001). At 6 months, prostate‐specific antigen concentration reduced from 7.1 ± 5.9 ng/mL at baseline to 4.0 ± 3.9 ng/mL, a 44% reduction.
Aquablation is safe and effective in treating men with larger prostates (80–150 mL), without significant increase in procedure or resection time.
Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an editorial written by a prominent member of the urological community and the authors have also kindly produced a video describing their work. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.
If you only have time to read one article this week, it should be this one.
To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.
The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses (You can reduce aging under eye masks).
Fig. 1. Association between 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end product (AGE) levels. 8‐OHdG levels were significantly associated with AGE levels (R2 = 0.023, P < 0.001, Spearman’s rank correlation coefficient). However, the R2 value was too small to indicate strong correlation and the significant P value of this correlation does not reflect the strength of the relationship between the two biomarkers.
This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.
We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.
Oxidative stress has been defined as ‘an imbalance between oxidants and anti-oxidants in favour of the oxidants, leading to a disruption of redox signalling and control and/or molecular damage’ [1]. Reactive oxygen and nitrogen species (ROS/RNS) produced under oxidative stress are known to damage all cellular biomolecules (lipids, sugars, proteins and polynucleotides). ROS/RNS is often used as a generic term but it has been emphasized that all ROS/RNS molecules are not the same [2] and the term encompasses a diverse range of species, including, for example, superoxide, hydrogen peroxide, nitric oxide and peroxynitrite. The biological impacts of ROS/RNS depend critically on the particular molecule(s) involved, and on the microenvironment and physiological or pathological context in which it is being generated [2]. It should be emphasized that ROS are not only harmful agents that cause oxidative damage in pathologies but they also have important roles as regulatory agents in a range of biological phenomena. They are normally generated as by-products of oxygen metabolism; however, environmental stressors (ultraviolet radiation, ionizing radiations, pollutants, heavy metal and xenobiotics) contribute to greatly increase ROS/RNS production.
It is difficult to measure ROS/RNS, therefore, biomarkers are often used as a surrogate; however, many of the biomarkers are insufficiently validated and it is often difficult to draw general conclusions on their significance [3]. 8-OHdG, one of the major products of DNA oxidation, is one of the most commonly used biomarkers of oxidative stress. Advanced glycation end-products (AGEs) are a group of heterogeneous molecules that arise from the non-enzymatic reaction of reducing sugars with amino groups of lipids, DNA and especially long-lived proteins. This process occurs during normal metabolism but is even more pronounced under oxidative stress conditions. AGEs may be harmful and include modified proteins and/or lipids with damaging potential. Using 8-OHdG, AGEs and other biomarkers, several attempts have been made to link oxidative stress, either as a cause or contributor, or both, to a variety of diseases, including LUTS. As pointed out by Ghezzi et al. [4] ‘Today it is a challenge to find a disease for which a role of oxidative stress has not been postulated.’
Matsumoto et al. [5] investigated the possible relationship between some markers of oxidative stress and LUTS in a population of community-living subjects participating in a health promotion project. As markers of oxidative stress, they used 8-OHdG (urine) and AGEs (skin autofluorescence), while structured questionnaires were used to assess LUTS. In their study, despite univariate analyses revealing several significant associations, multivariate analyses showed that the only statistically significant finding was that AGEs were associated with moderate to severe nocturia. This association is thought-provoking but, without functional studies, difficult to evaluate. LUTS are multifactorial and reflect a number of different comorbidities/pathophysiologies. It cannot be excluded that this may contribute to the lack of associations between oxidative stress markers and symptoms.
The finding of an association (or lack of it) between biomarkers of oxidative stress and LUTS does not reveal whether oxidative stress causes or contributes to LUTS. If ROS/RNS were causative/contributing factors to LUTS, it would be predicted that a positive response to antioxidant therapy and a decrease in ROS/RNS levels would not only support an involvement but would also be a promising treatment approach. In a prospective cohort study in the USA of 1670 men aged 65–100 years, Holton et al. [6] examined whether dietary antioxidants were associated with a reduced likelihood of LUTS progression or an increased likelihood of LUTS. They found that there were no significant associations between multiple dietary antioxidants and LUTS progression or remission over 7 years. Many other attempts to validate and exploit chronic antioxidant therapies have provided disappointing results, and still there is no antioxidant with sufficient efficacy to be approved by health authorities [4]. The question of whether antioxidant therapy may be harmful has not yet been answered. If the cause of LUTS is an increase of ROS/RNS in the bladder, it is questionable whether normalization of indicators of oxidative stress is safe, considering that the normal function of ROS/RNS in the rest of the body may be affected.
The clinical relevance of oxidative stress as a pathophysiological factor in lower urinary tract dysfunction or as a treatment target for various lower urinary tract disorders is still unclear. In addition, it has not been established that antioxidant therapy has any beneficial effect on LUTS.
by Karl-Erik Andersson
To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.
The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses.
This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.
We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.
In a recently published qualitative study, we found that urodynamic testing was acceptable to men with lower urinary tract symptoms (LUTS), despite some reporting apprehension, discomfort or embarrassment and, at times, inadequate provision of information. Men’s experiences of urodynamics highlight ways in which clinical practice can be improved, including better communication about what to expect during and after the test, minimising embarrassment by ensuring privacy, and timely discussion of test results in sufficient detail.
Ninety percent of men aged 50‐80 live with at least one LUTS, which can negatively impact quality of life. LUTS prevalence and severity increase with age, and with demographic aging the management of LUTS is an increasing priority. Urodynamics with invasive multichannel cystometry is widely used when medications haven’t successfully relieved symptoms and surgery for bladder outlet obstruction is being considered. But there is ongoing debate about the extent to which urodynamics should be used, reflecting lack of evidence regarding the effectiveness of urodynamics and how acceptable it is to patients.
What we did
The Urodynamics for Prostate Surgery: Randomised Evaluation of Assessment Methods (UPSTREAM) randomised controlled trial is a 4-year study funded by the National Institute of Health Research Health Technology Assessment Programme (UK). The trial randomised 820 men with LUTS from urology departments in 26 hospitals in England to either a care pathway consisting of non-invasive routine tests, or one of routine tests plus urodynamics. At 18-months after randomisation, UPSTREAM assessed the effect of urodynamics on symptoms and rates of surgery in men with bothersome LUTS seeking further treatment.
In a large qualitative study nested within the UPSTREAM trial, we explored men’s attitudes to and experiences of urodynamics, to provide in‐depth qualitative evidence to inform clinical practice. We interviewed a diverse group of 41 men with LUTS, including those who had had urodynamics and those who had not.
What we found
Recommendations
Based on men’s experiences, we recommend:
Acknowledgements
We acknowledge and thank the patients and clinicians involved in the UPSTREAM trial as well as the NHS trusts involved. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) program (project number 12/140/01). This study was designed and delivered in collaboration with the Bristol Randomised Trials Collaboration (BRTC), a UKCRC registered clinical trials unit which, as part of the Bristol Trials Centre, is in receipt of National Institute for Health Research CTU support funding. The views and opinions expressed are those of the authors and not necessarily those of the HTA program, NIHR, NHS, or the Department of Health and Social Care.
About the authors:
Dr Selman and Dr Horwood are Senior Research Fellows at University of Bristol, specialising in qualitative research in randomised trials. Twitter: @Lucy_Selman, @JPHorwood
Prof Drake is Professor of Physiological Urology at Bristol Urological Institute, North Bristol NHS Trust, and at Translational Health Sciences, Bristol Medical School, University of Bristol. Twitter: @MarcusDrakeUrol, @UroweESU
Dr Amanda Lewis is a Clinical Trial Manager at the University of Bristol, currently working in the area of Urology research. Twitter: @ALBrooks2015
