Tag Archive for: International Prostate Symptom Score

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Article of the week: The effect of the urinary and faecal microbiota on lower urinary tract symptoms measured by the International Prostate Symptom Score: analysis utilising next‐generation sequencing

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. 

The effect of the urinary and faecal microbiota on lower urinary tract symptoms measured by the International Prostate Symptom Score: analysis utilising next‐generation sequencing

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

Abstract

Objective

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.

Patients and Methods

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.

Results

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.

Conclusions

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.

Editorial: Exercise to prevent LUTS – myth and reality

The pathophysiology of LUTS is one of the most intriguing issues in urology and the conundrum remains unsolved. Their multifactorial origin imposes a differential diagnosis that is often quite straightforward but sometimes complicated and at times the enigma is cracked only ex adiuvantibus. Clinical trials and personal experience have showed us that patients rarely become asymptomatic albeit our therapeutic efforts, suggesting that part of the problem is in the ageing process. So the question comes as to whether we can halt or delay ageing. Clearly some people age without LUTS apart from a physiological decrease in urinary flow. What goes wrong in our patients that stay right in some other subjects? Most of us would like to have a pill that could fix every problem, an easy answer to swallow and remedy our troubles, but this is not always the case.

‘Lifestyle’ is one of the most frequently cited words with 1 330 000 000 on Google today, more than double the ‘hits’ for happiness (a mere 576 000 000). No doubt that behind the lifestyle mantra there is an industry that makes billions on lifestyle issues, but as there is usually ‘no smoke without fire’ there must be something to it. Who has never been advised to change his way of life? Probably none, but who actually takes up the challenge and changes their routine? Clinical trials on the therapeutic effect of lifestyle changes cannot be analysed with an intent‐to‐treat analysis because ‘there’s many a slip ‘twixt cup and lip’ and we need look at those who really undertake the challenge.

There is a growing body of evidence that a healthy lifestyle will not just help to prevent cancer and cardiovascular events or keep you ‘fit’, but will also reduce the risk of developing LUTS [12]. In this issue of the BJUI, a paper from South Korea [3] provides rather convincing evidence that sitting for ≥10 h/day will increase your risk of storage and voiding symptoms, whilst doing exercise will reduce it. But what if you are a manager and your job is to read an endless number of reports each day? You cannot read whilst walking or doing exercise; you work for a living and LUTS may be the price you pay for a wealthier life.

As a surgeon I have an obsession for fixing things and making my patients better. If my patients have a sedentary job can I suggest a change in their lifestyle (not a change of job) that can counterbalance long sitting hours? The answer from the Korean cohort seems to be negative, as multivariate analysis of a subject cohort with long sitting hours suggested an increased risk of developing LUTS notwithstanding some exercise. I never thought that sitting was that bad but ‘est modus in rebus’ as Horace put it and probably sitting for too long is bad. Actually, my watch keeps telling me to stand at regular intervals, although I think I stand for too long in theatre (it also reminds me to breathe properly but that is another story).

This is a long way to say that I would rather be told what I can do right than be told what I am doing wrong. Is my personal risk of a poor outcome reversible? I think we have enough evidence from observational studies that exercise will reduce the risk of developing LUTS, but the time has come to embark on large prospective trials of LUTS treatment with lifestyle changes including exercise.

I have a number of patients who adopted a healthier lifestyle upon retirement (more info here about how they are doing it), lost weight, lowered their arterial pressure and their glucose levels, and their LUTS improved dramatically. What I need to know is whether this is the exception or whether this is the rule. These are not easy studies but I would rather work to answer an important academic question with a difficult and long‐term trial rather than doing an easier study that will not change the way we live and the way we practise.

Andrea Tubaro and Cosimo De Nunzio
Department of Urology, SantAndrea Hospital, Rome, Italy

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References

  1. De Nunzio C, Presicce F, Lombardo R et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int 2016117: E29–35
  2. Gacci M, Corona G, Sebastianelli A et al. Male lower urinary tract symptoms and cardiovascular events: a systematic review and meta‐analysis. Eur Urol 201670: 788–96
  3. Park HJ, Park CH, Chang Y, Ryu S. Sitting time, physical activity and the risk of lower urinary tract symptoms: a cohort studyBJU Int 2018122: 293–99

Article of the Week: Sitting time, physical activity and the risk of LUTS

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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Sitting time, physical activity and the risk of lower urinary tract symptoms: a cohort study

Heung Jae Park*, Chang Hoo Park, Yoosoo Chang§¶ and Seungho Ryu§¶

 

*Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea, Department of Urology, School of Medicine, Gangneung Asan Hospital, Ulsan University, Gangneung, South Korea, Centre for Cohort Studies, Total Healthcare Centre, §Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea, and Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea

 

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Abstract

Objectives

To examine the association of sitting time and physical activity level with the incidence of lower urinary tract symptoms (LUTS) in a large sample of Korean men.

Materials and Methods

A cohort study was performed in 69 795 Korean men, free of LUTS at baseline, who were followed up annually or biennially for a mean of 2.6 years. Physical activity level and sitting time were assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form. LUTS were assessed using the International Prostate Symptom Score (IPSS) and clinically significant LUTS were defined as an IPSS score ≥8.

Results

Over 175 810.4 person‐years, 9 217 people developed significant LUTS (incidence rate, 39.0 per 1 000 person‐years). In a multivariable‐adjusted model, both low physical activity level and prolonged sitting time were independently associated with the incidence of LUTS. The hazard ratios (95% confidence intervals [CIs]) for incident LUTS comparing minimally active and health‐enhancing physically active groups vs the inactive group were 0.94 (95% CI 0.89–0.99) and 0.93 (95% CI 0.87–0.99), respectively (P for trend 0.011). The hazard ratios (95% CIs) for LUTS comparing 5–9 and ≥10 h/day sitting time vs <5 h/day were 1.08 (95% CI 1.00–1.24) and 1.15 (95% CI 1.06–1.24), respectively (P for trend <0.001).

Conclusions

Prolonged sitting time and low physical activity levels were positively associated with the development of LUTS in a large sample of middle‐aged Korean men. This result supports the importance of both reducing sitting time and promoting physical activity for preventing LUTS.

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Article of the Week: eNOS G894T gene polymorphism and responsiveness to a selective α1-blocker in BPH/LUTS

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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

The association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms

Yung-Chin Lee*,, Yung-Shun Juan*,,, Chia-Chu Liu*,,§, Bo-Ying Bao,**,††, Chii-Jye
Wang*,, Wen-Jeng Wu*,, Chun-Nung Huang*,† and Shu-Pin Huang*,,‡‡
*Department of Urology, Department of Urology, Faculty of Medicine, Kaohsiung Medical University, Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, §Department of Health, Executive Yuan, Pingtung Hospital, Pingtung,

 

Department of Pharmacy, **Sex Hormone Research Center, China Medical University Hospital, ††Department of Nursing, Asia University, Taichung, and ‡‡Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

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Objective

To prospectively investigate the association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms (BPH/LUTS), as nitric oxide has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract.

Patients and Methods

In all, 136 men with BPH/LUTS were recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin gastrointestinal therapeutic system (GITS) 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and post-void residual urine volume (PVR) at 12 weeks of treatment. The ‘responders’ to doxazosin GITS were defined as those who had a total IPSS decrease of >4 points from baseline. eNOS G894T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method.

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Results

Patients had statistically significant improvements in total IPSS, quality of life score, and Qmax (P < 0.01) after a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that being a eNOS 894T allele carrier was an independent risk factor for being a drug non-responder (P = 0.03, odds ratio 4.19). Moreover, a decreased responder rate (P = 0.01), as well as the lower improvements in IPSS (P = 0.02) and Qmax (P = 0.03) were significantly associated with increment in the T allele number.

Conclusions

The presence of the eNOS 894T allele had a significantly negative impact on responsiveness to a selective α1-blocker in BPH/LUTS treatment, suggesting that eNOS G894T gene polymorphism may be a genetic susceptibility factor for α1-blocker efficacy in men with BPH/LUTS.

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Editorial: Responsiveness to Medical BPH Therapy – Is There a Genetic Factor?

In this issue, Lee et al. [1] from Taiwan demonstrate that the endothelial nitric oxide synthase (eNOS) G894T gene polymorphism predicts responsiveness to α1-blocker therapy in men with BPH/LUTS.

There is a long-standing interest in the establishment of a genetic marker for BPH/LUTS predicting clinical status, the natural history and – ideally – also responsiveness to for example medical therapy. The high prevalence of disease, the socioeconomic impact of diagnosis, medical and surgical treatment, and the availability of drugs (5α-reductase inhibitors) that alter the natural course of the disease justify the intensive search for a genetic marker for BPH/LUTS.

The few familial and twin studies suggest a (moderate) genetic background for this disease to an extent similar to other chronic diseases such as hypertension or diabetes mellitus type II [2, 3]. However, BPH/LUTS is a complex disorder and it is very unlikely that the pathogenesis can be reduced to a single gene or gene defect. Most likely, genetic alterations – besides inflammation, endocrine, myogenic, neurogenic, and morphological factors – act as co-factors.

Within the past decade numerous polymorphisms in the steroid-metabolism pathway, in cytokine genes, in the vitamin D receptor gene, the α-adrenoceptor gene, in homeobox genes, in the angiotensin converting enzyme, the glutathione S-transferase gene, and in the nitric oxide system (just to mention the most frequently studied ones) have been correlated to several clinical parameters of BPH/LUTS, such as symptom status, prostate volume, maximum urinary flow rate and the natural history of the disease [4, 5]. None of these studies provided compelling evidence that one of these polymorphisms (or combinations thereof) could serve as a clinically relevant marker [4, 5]. As indicated by Cartwright et al. [5], many of these genetic studies are hampered by a small sample size, lack of genotyping quality control, inadequate adjustment for populations from heterogeneous descent groups, and poorly defined/inhomogeneous study endpoints.

There is increasing evidence that the nitric oxide (NO)/cGMP pathway plays an important role in controlling the smooth muscle tone of the lower urinary tract. Decreases in the NO/cGMP pathway with age would result in decreased levels of intracellular cGMP and calcium, leading to less smooth muscle relaxation of the bladder and the prostate, thus worsening LUTS. NO is synthesised by at least three isoenzymes of NOS, inducible NOS (iNOS), neuronal NOS (nNOS) and eNOS [1]. The close relationship between NOS/NO pathway and the pathophysiology of BPH/LUTS was the rationale for the study by Lee et al. [1]. Using multiple logistic regression analysis adjusted for age and IPSS, the data showed that the eNOS 894T allele carrier was an independent factor for drug non-responders [1]. However, responsiveness to α1-blocker therapy was also strongly dependent on diabetes mellitus and hypertension, suggesting that the metabolic syndrome plays an important role in the pathogenesis of BPH/LUTS [1]. This is indeed the first study showing that a genetic factor is predictive of the responsiveness to medical BPH/LUTS therapy, therefore this study is significant.

Further studies in populations with other genetic backgrounds (e.g. Caucasian) are required to confirm and to generalise these data. Phosphodiesterase type 5 inhibitors have been proposed to act in BPH/LUTS via the NO systems; therefore, it would be interesting to test this genetic marker also in men treated with tadalafil 5 mg/day. Finally, one has to be aware of the fact that the authors have tested α-blocker monotherapy. All major guidelines recommend a combination of α-blocker and 5α-reductase inhibitor for men with larger prostates (e.g. prostate volume >30–40 mL) [6]. The mean prostate volume in this cohort was 35 mL suggesting that, according to guideline recommendations, these men would have required combined therapy [6].

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Stephan Madersbacher, Professor and Chairman
Department of Urology, Kaiser-Franz-Josef Spital, Vienna, Austria

 

References

 

 

2 Partin AW, Page WF, Lee BR, Sanda MG, Miller RN, Walsh PCConcordance rates for benign prostatic disease among twins suggest hereditary inuence. Urology 1994; 44: 64650

 

3 Rohrmann S, Fallin MD, Page WF et al. Concordance rates and modiable risk factors for lower urinary tract symptoms in twins. Epidemiology 2006; 17: 41927

 

4 Konwar R, Chattopadhyay N, Bid HK. Genetic polymorphism and pathogenesis of benign prostatic hyperplasia. BJU Int 2008; 102: 53643

 

 

6 Gravas S, Bach T, Bachmann A et al. Treatment of Non-Neurogenic Male LUTS. Available at: www.uroweb.org. Accessed March 2016.

 

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