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5th International Neuro-Urology Meeting (INUM)

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The Annual Congress of the International Neuro-Urology Society (INUS), organized by the Swiss Continence Foundation (SCF)

Neurogenic urinary tract, sexual and bowel dysfunction is highly prevalent and affects the lives of millions of people worldwide. It has a major impact on quality of life and, besides the debilitating manifestations for patients, it also imposes a substantial economic burden on every healthcare system.

It was a great honour and pleasure to organize the 5th International Neuro-Urology Meeting (INUM), which took place from 25-28 January 2017, in Zürich, Switzerland. We are proud to announce that the International Neuro-Urology Meeting, organized under the umbrella of the Swiss Continence Foundation (www.swisscontinencefoundation.ch), has become the official annual congress of the International Neuro-Urology Society (INUS, www.neuro-uro.org), a charitable, non-profit organization aiming to promote all areas of Neuro-Urology at a global level and whose inauguration was inspired during the last INUMs.

The world’s leading experts in Neuro-Urology provided an overview on the latest advances in research and clinical practice of this rapidly developing and exciting discipline. This unique meeting combined state-of-the-art lectures, lively panel discussions, and hands-on workshops with emphasis placed on interactive components. There were many opportunities to exchange thoughts, experiences and ideas and also to make new friendship.

The Swiss Continence Foundation Award: To promote the next generation of outstanding young researchers and clinicians who represent the future of Neuro-Urology, the prestigious Swiss Continence Foundation Award of 10’000 Swiss francs was awarded to the best contribution from a young Neuro-Urology talent: Marc Schneider from Zürich, Switzerland, convinced the international jury with the presentation of his PhD project “Anti-Nogo-A antibodies as a potential causal treatment for neurogenic lower urinary tract dysfunction after spinal cord injury”. He demonstrated in an animal model that intrathecally applied antibodies against the central nervous system protein Nogo-A which inhibits nerve fibre growth had beneficial effects on lower urinary tract dysfunction in rats with incomplete spinal cord injury by re-establishing a physiological micturition and preventing detrusor sphincter dyssynergia. This effect presumably occurs due to neuronal re-wiring of descending micturition circuits facilitated by the anti-Nogo-A antibodies. Anti-Nogo-A immunotherapy enters currently clinical trials in humans and could become a unique causal treatment option for lower urinary tract dysfunction in patients with incomplete spinal cord injury.

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One of many other highlights was the joint presentation of the EAU Secretary General Christopher R. Chapple and the BJUI Editor-in-Chief Prokar Dasgupta on the challenging topic “What should the neuro-urologist learn from the onco-urologist and vice-versa?”

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Finally, we are delighted to announce the 6th International Neuro-Urology Meeting to be held in Zürich, 25 to 28 January 2018. Save the date! For details please visit: www.swisscontinencefoundation.ch. We are looking forward to seeing you in Zürich!

Thomas M. Kessler, SCF Chairman and INUS Vice-President

Ulrich Mehnert, SCF Vice-Chairman and INUS Treasurer

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January 2017 Editorial: Infographics

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‘A picture is worth a thousand words’ is an English idiom that has been in use for over a 100 years. Never has it been truer than in the age of social media, when fans are perhaps more interested in ‘selfies’ with their celebrity superstars than in their autographs!

With this in mind, we at the BJUI launched infographics last year for some of our very best papers. And what a success it has been based on the positive responses from our avid readers on Twitter. The titles of the articles that were selected for this format were:

  1. Oncological and functional outcomes 1 year after radical prostatectomy for very-low-risk prostate cancer: results from the prospective LAPPRO trial [1].
  2. Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit [2].
  3. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement [3].

All three featured amongst the list of the top 20 papers with most page views on www.bjui.org and the top 10 most downloaded articles from Wiley online library (WOL), reaching a figure of >2500. This compares well to our most downloaded ‘Guideline of Guidelines’on thromboprophylaxis [4] at 2264. The infographics lay out clear messages on important topics in a concise manner and have undeniable appeal to busy clinicians, who often have just a few valuable minutes to keep abreast with the latest highlights (Fig. 1).

Figure 1. Extract of infographics for the Fernando et al. [2] paper ‘Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit’. NSS, nephron-sparing surgery.

We also thought we would kick off the New Year with Guidelines on minimally invasive adrenalectomy from the International Consultation on Urological Diseases (ICUD) consultation [5]. And of course the ‘hot topic’ of enhanced recovery to try and reduce the length of stay for our cystectomy patients without increasing complications or readmission rates [6].

We are looking forward to engaging with you with more infographics in 2017.

Prokar Dasgupta, BJUI Editor-in-Chief
King’s Health Partners, London, UK

 

 

References

  1. Carlsson S, Jaderling F, Wallerstedt A et al. Oncological and functional outcomes 1 year after radical prostatectomy for very-low-risk prostate cancer: results from the prospective LAPPRO trial. BJU Int 2016; 118: 205–12
  2. Fernando A, Fowler S, O’Brien T, British Association of Urological Surgeons (BAUS). Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit. BJU Int 2016; 117: 874–82
  3. Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int 2016; 117: 677–85
  4. Violette PD, Cartwright R, Briel M, Tikkinen KA, Guyatt GH. Guideline of guidelines: thromboprophylaxis for urological surgery. BJU Int 2016; 118: 351–8
  5. Ball MW, Hemal AK, Allaf ME. International Consultation on Urological Diseases and European Association of Urology International Consultation on Minimally Invasive Surgery in Urology: laparoscopic and robotic adrenalectomy. BJU Int 2017; 119: 13–21
  6. Baack Kukreja JE, Kiernan M, Schempp B et al. Quality improvement in cystectomy care with enhanced recovery (QUICCER study). BJU Int 2017; 119: 38–49
See more infographics

Randomised Controlled Trials in Robotic Surgery

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PDGSep16It has been nearly 15 years since one of the first ever randomised controlled trials (RCT) in robotic surgery was conducted in 2002. The STAR-TRAK compared telerobotic percutaneous nephrolithotomy (PCNL) to standard PCNL and showed that the robot was slower but more accurate than the human hand [1].

In the 24 h since the much anticipated RCT of open vs robot-assisted radical prostatectomy was published in The Lancet [2], our BJUI blog from @declangmurphy was viewed >2500 times, receiving >40 comments, making it one of our most read and interactive blogs ever. It is a negative trial showing no differences in early functional outcomes between the two approaches.

And it is not the only negative trial of its kind as a number of others have matured and reported recently. The RCT of open vs robot-assisted radical cystectomy and extracorporeal urinary diversion showed no differences in the two arms [3], and likewise a comparison of the two approaches to cystectomy as a prelude to the RAZOR (randomised open vs robotic cystectomy) trial showed no differences in quality of life at 3-monthly time points up to a year [4]. The only RCT comparing open, laparoscopic and robotic cystectomy, the CORAL, took a long time to recruit and yet again showed no differences in 90-day complication rates between the three techniques [5].

In all likelihood, despite the level 1 evidence provided in The Lancet paper showing no superiority of the robotic over the open approach, the Brisbane study may not change the current dominance of robotic prostatectomy in those countries who can afford this technology. Why is this? Apart from the inherent limitations that the BJUI blog identifies, there are other factors to consider. In particular, as observed previously in a memorable article ‘Why don’t Mercedes Benz publish randomised trials?’ [6], there may be reasons why surgical technique is not always suited to the RCT format.

A few additional reflections are perhaps appropriate at this time:

  1. Despite the best statistical input many of these and future studies are perhaps underpowered.
  2. Many have argued that the RCTs have shown robotics to be as good, although not better than open surgery, even in the hands of less experienced surgeons.
  3. Patient reported quality of life should perhaps become the primary outcome measure because that in the end that is what truly matters.
  4. Cost-effectiveness ratios should feature prominently, as otherwise there is much speculation by the lay press without any hard data.
  5. Industry has a role to play here in keeping costs manageable, so that these ratios can become more palatable to payers.
  6. Surgery is more of an art than a science. The best surgeons armed with the best technology that they are comfortable with will achieve the best outcomes for their patients.

While this debate will continue and influence national healthcare providers and decision makers, the message looks much clearer when it comes to training the next generation of robotic surgeons. A cognitive- and performance-based RCT using a device to simulate vesico-urethral anastomosis after robot-assisted radical prostatectomy (RARP) showed a clear advantage in favour of such structured training [7]. In this months’ issue of the BJUI, we present the first predictive validity of robotic simulation showing better clinical performance of RARP in patients [8]. This is a major step forward in patient safety and would reassure policy makers that investment in simulation of robotic technology rather than the traditional unstructured training is the way forward.

Most of our patients are knowledgeable, extensively research their options on ‘Dr Google’ and decide what is good for them. It is for this reason that many did not agree to randomisation in other robotic vs open surgery RCTs, like LopeRA (RCT of laparoscopic, open and robot assisted prostatectomy as treatment for organ-confined prostate cancer) and BOLERO (Bladder cancer: Open vs Lapararoscopic or RObotic cystectomy). Many of them continue to choose robotic surgery without necessarily paying heed to the best scientific evidence. Perhaps what patients will now do is select an experienced surgeon whom they can trust to use their best technology to deliver the best clinical outcomes.

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

@declangmurphy
Associate Editor BJUI

References

1 Challacombe B, Patriciu A, Glass J et al. A randomized controlled trial of human versus robotic and telerobotic access to the kidney as the first step in percutaneous nephrolithotomy. Comput Aided Surg 2005; 10: 165–71
2 Yaxley JW, Coughlin GD, Chambe rs SK et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet 2016 [Epub ahead of print]. doi: 10.1016/S0140-6736(16)30592-X
3 Bochner BH, Sjoberg DD, Laudone VP, Memorial Sloan Kettering Cancer Center Bladder Cancer Surgical Trials Group. A randomized trial of robot-assisted laparoscopic radical cystectomy. N Engl J Med 2014; 371:389–90

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Messer JC, Punnen S , Fitzgerald J et al. Health-related quality of life from a

prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy. BJU Int 2014; 114: 896–902

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Khan MS, Gan C, Ahmed K et al. A single-centre early phase randomised controlled three-arm trial of open, robotic, and laparoscopic radical cystectomy (CORAL). Eur Urol 2016; 69: 613–21

6 O’Brien T, Viney R , Doherty A, Thomas K. Why don’t Mercedes Benz publish
randomised trials? BJU Int 2010; 105 : 293–5
7 Chowriappa A, Raza SJ, Fazili A et al. Augmented-reality-based skills training for robot-assisted urethrovesical anastomosis: a multi- institutional randomised controlled trial. BJU Int 2015; 115: 336–45
8 Aghazadeh MA, Mercado MA, Pan MM , Miles BJ, Goh AC. Performance of
robotic simulated skills tasks is positively associated with clinical robotic surgical performance. BJU Int 2016; 118: 4 75 –81

 

The impact factor may be flawed but important

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It has been a nice summer for the BJUI. Our impact factor has gone up to 4.387, the highest ever in the history of the Journal and we made the Altmetrics Top 50 for the first time ever with a score of 1166, Nature being the numero uno. I wanted to thank our editorial team, readers, authors and reviewers for their dedication and commitment, which made this possible.

bju13563-fig-0001

 

The question is how did we do this? For a journal without official society guidelines, it was not easy. So we had to focus on original articles rather than reviews and guidelines. There were three essential steps:

  1. Publishing the highest quality, citable papers irrespective of geographical location [1] – for example, this month we have highlighted the importance of personalised medicine in BPH from Taiwan [2], whereby the authors show that an endothelial nitric oxide synthase (eNOS) genetic polymorphism has a negative impact on response to α-blockers.
  2. Reducing the number of papers published while selecting clinically relevant, large prospective studies and trials – an example of this is the LAParoscopic Prostatectomy Robot Open (LAPPRO) study from Sweden [3], showing that even in very-low-risk prostate cancer, upgrading after radical prostatectomy occurs in over a third of patients and that the functional outcomes are not as good as expected.
  3. Amplifying our content through social media – this means that we believe in interaction with a wider audience, immediacy of response, and are not afraid of the occasional controversy and debate. An example is the comment on clostridium histolyticum collagenase followed by a brief editorial on what may increasingly be seen as an important treatment option for Peyronie’s disease [4].

Many consider the impact factor of a journal as a ‘gaming’ exercise, flawed by its very nature. I was very pleased to receive a WhatsApp from one of my colleagues saying how pleased he was that at the BJUI we have always played ‘with a straight bat’. An important consideration is that Universities often count original papers in the best journals for measuring academic output, which in turn drives income from various sources. In the UK this is given the term ‘returnable’ when considered within a system called the Research Excellence Framework. I am really pleased that the BJUI is now ‘returnable’ with its new impact factor and is seen as a serious player within a highly demanding system. I am aware that this also true for other international institutions, which is in keeping with our global presence as a journal without boundaries.

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

References

1 Dasgupta P. Quality has no boundaries. BJU Int 2014; 113: 1

 

2 Lee Y-C, Juan Y-S, Liu C-C et al. The association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective a 1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms. BJU Int 2016; 118: 313–19

 

3 Carlsson S, Jaderling F, Wallerstedt A et al. Oncological and functional outcomes 1 year after radical prostatectomy for very low risk prostate cancer. Results from the prospective LAPPRO trial. BJU Int 2016; 118: 205–12

 

4 Poullis C, Shabbir M, Eardley I, Mulhall J, Minhas S. Clostridium histolyticum collagenase – Is this revolutionary medical treatment for Peyronie’s disease? BJU Int 2016; 118: 186–92

 

Consensus guidelines for reporting prostate cancer Gleason Grade

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Prokar_v2The International Society of Urologic Pathology (ISUP) has endorsed modifications to the Gleason grading system for prostate cancer [1]. Five Grade Groups have been defined with tumors of Grade Group 1 being the least aggressive and having the lowest likelihood of progression, whereas those of Grade Group 5 have the highest likelihood of early systemic spread. This new system provides clearer guidance for pathologists to classify cancers on the basis of gland morphology, and it aligns better with contemporary management including active surveillance.

The editors of the major uro-oncology journals believe this is a helpful change for clinicians, researchers, and patients alike and are eager to help this system establish itself in the reporting of pathologic grade. To that end we are now asking investigators to use the new system in the reporting of prostate cancers in their publications. As the Grade Groups correspond to current Gleason scores 6, 3+4, 4+3, 8, 9 and 10, the translation should be relatively simple. Over the next one to two years, side-by-side reporting of old and new histology may temporarily be necessary. We do recognize that some institutional and national databases are not set up to make the translation and exceptions will be granted in these cases.

Anthony Zietman, Editor-in-Chief*, Joseph Smith, Editor†, Eric Klein , Editor-in-Chief‡, Michael Droller, Editor-in-Chief§, Prokar Dasgupta, Editor-in-Chief¶ and James Catto, Editor-in-Chief**

 

*International Journal of Radiation Oncology Biology Physics, †Journal of Urology, ‡Urology, §Urologic Oncology, BJUI and **European Urology

Reference

1 Epstein JI, Egevad L, Amin MB et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference of Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2016; 40: 244–52

 

Scientific impact and beyond

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After a constant upward trajectory for 3 years, in 2015 the BJUI achieved an impact factor (IF) of 3.53, the highest ever in its history. Complacency is not in our DNA and we hope to achieve much more. We set out to become the most read surgical journal on the web and as part of that initiative have just launched our Android app in addition to the existing iPhone and iPad app. But our true impact beyond the IF, lies perhaps in the Altmetric score.

Altmetric is a score of the impact of (or perhaps better, the attention attained by) articles, based on mentions over a period of time in online channels such as news outlets, science blogs, Twitter, Facebook, Sina Weibo and Wikipedia, amongst others. The automated algorithm’s calculation of an article’s score applies weighting to the sources, such that a mention on a news outlet is weighted 8, or in a science blog 5, whereas a Twitter mention is only weighted 1, and a Facebook mention 0.25. News outlet scores are also tiered by their reach, re-tweets score less than original tweets, and bias is accounted for, e.g. tweets by independent researchers count more than a tweet by the journal that published the article.

am-i-normal-altmet-smThe results are visualized as the ‘Altmetric donut’ with the calculated score in the centre. In the donut the different colours represent the different channels; so, for example Twitter is cyan, Facebook is dark blue, Blogs (including Weibo) are orange, News outlets red, Google+ is magenta, Video is pale green, Reddit is pale blue and Wikipedia is dark grey. The proportion of the donut that is shown in each colour generally reflects how much of the score was contributed to by that channel, but when many channels need to be represented then each is given a segment as is seen in the rainbow donut for our ‘Am I Normal’ article [Veale et al].

To give some context to the phenomenal level of interest in the ‘Am I Normal’ article, which at the time of writing boasts a score of 1034, most articles attain a score of 3 or under, and a score of 9 is sufficient to put an article in the top 10% of all 4,386,073 that Altmetric has scored. ‘Am I Normal’ is, perhaps unsurprisingly, in the top 1% of all articles scored.

Our other highly citable innovation is the BJUI Guideline of Guidelines (GOGs), which have made access to, and the understanding of, often conflicting urological guidelines a lot easier. Along with our other guidelines on chronic prostatitis [Rees et al] and continence [Tse et al], they will all be available in early 2016 as a virtual issue of GOGs [Loeb; Ziemba & Matlaga; Wollin & Makarov; Syan & Brucker] in a single repository on our web journal. Completely free, of course!

Prokar Dasgupta, Editor-in-Chief, BJUI
Scott Millar, Managing Editor, BJUI
Jo Wixon, Publisher, John Wiley and Sons Ltd

 

 

The BJUI at the Lindau Nobel Laureates meeting

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Christina Sakellariou (BJUI Lindau Scholar), 64th Lindau Nobel Laureates Meeting, 2014.

Every year, Lindau, a south-eastern town and island of Germany, concentrates the greatest minds of science, representing the past, the present and the future. Nobel Laureates and young scientists from different disciplines, countries and backgrounds meet to ‘Educate, Inspire and Connect’ during talks and discussions given by the Laureates, social gatherings and an unforgettable boat trip to the garden-island of Mainau.

Last year, the BJUI became, to our knowledge, the first surgical journal to support one of the 600 young scientists to participate in the Lindau Physiology and Medicine meeting, and interact with 37 Nobel Laureates. It was the first time in the history of the meeting that the percentage of women participants was higher than that of the men!

Lindau is oriented to reach out to the future; the 5 days of the meeting were full of constructive and fruitful discussions between the Nobel Laureates and young scientists, sharing of experiences, knowledge and dreams, and inspirational and motivational moments, particularly those coming from the Laureates’ lectures. Drs Peter Agre and Roger Tsien shared some very personal moments and life experiences, while Oliver Smithies showed photographs of his 65-year-old laboratory book, leaving lasting impressions on the next generation.

As was highlighted in the opening ceremony, ‘what Brazil was for football, Lindau was for the Nobel Laureates and young scientists’. That week in Lindau provided our BJUI scholar the required strength, inspiration and motivation to continue answering questions through the highest quality of scientific research. This month the BJUI continues its Nobel theme with a fascinating paper on ‘tiny bubbles’ from Ramaswamy et al. [1], which the Editor-in-Chief first encountered at a meeting of the American Association of Genitourinary Surgeons (AAGUS).

The authors include Robert Grubbs who received the Nobel Prize for Chemistry in 2005. They have developed a minimally invasive technology to replace generated bubbles for shockwave lithotripsy (SWL) that can cavitate and fracture stones. Tagged microbubbles were self-assembled with a phospholipid surface and a perfluoronated carbon gas centre. These stable, short-lived microbubbles, were synthesised with bisphosphonate surface tags to facilitate selective attachment to the surface of stones. Ex vivo cavitation of microbubble-coated calcium urinary stones demonstrated excellent stone fragmentation. As the popularity of extracorporeal SWL diminishes, retrograde injection of ex vivo generated microbubbles may represent the next exciting frontier in minimally invasive stone surgery.

References

1 Ramaswamy K, Marx V, Laser D et al. Targeted microbubbles: a novel application for the treatment of kidney stones. BJU Int 2015; 116: 9–16

 

Prokar Dasgupta @prokarurol 
Editor-in-Chief, BJUI 

 

Christina Sakellariou
BJUI Lindau Scholar

 

 

Learning from The Lancet

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The Lancet, established in 1823, is one of the most respected medical journals in the world. It has an impact factor of 39, and therefore attracts and publishes only the very best papers. Like most journals that have evolved with modern times, it has an active web and social media presence, particularly based around Twitter.

On a Monday morning, last autumn, the Editor of the BJUI had a meeting with the Web Editor of The Lancet at Guy’s Hospital. There was a mutual interest in surgical technology, particularly as Naomi Lee had been a urology trainee before joining The Lancet full-time. The topic of discussion was robot-assisted radical cystectomy with the emergence of randomised trials showing little difference between open and robotic surgery, despite the minimally invasive nature of the latter [1, 2]. Thereafter, The Lancet kindly invited the BJUI team to visit its offices in London. The location is rather bohemian with a mural of John Lennon on the wall across the street! Here is a summary of what we learnt that day.

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1. Democracy – what gets published in The Lancet after peer review is decided at a team meeting, where editors of the main journal and its sister publications gather around a table to discuss individual articles. Most work full-time for The Lancet, unlike surgical journals that are led by working clinicians. No wonder that >80% of papers are immediately rejected and the final acceptance rate is ≈6%. Interesting case reports are still published and often highly cited because of the wider readership.

2. Quality has no boundaries – it does not matter where the article comes from as long as it has an important message. The BJUI recently published an excellent paper on circumcision in HIV-positive men from Africa [3]; the original randomised controlled trial had appeared some 7 years earlier in The Lancet [4].

3. Statisticians – the good ones are a rare breed and sometimes rather difficult to find. While we have two statistical editors at the BJUI, sometimes, it is difficult to approach the most qualified reviewer on a particular subject. The Lancet occasionally faces similar difficulties, which it almost always overcomes due to its’ team approach.

4. Meta-analysis and systematic reviews – they form a significant number of submissions to both journals. It is not always easy to judge their quality although a key starting point is to identify whether the topic is one of contemporary interest where there are significant existing data that can be analysed. Rare subjects usually fail to make the cut.

5. Paper not dead yet – this is certainly the case at The Lancet office, where its editors gather together with paper folders and hand-written notes. We are almost fully paperless at the BJUI offices, and are hoping to be completely electronic in the future. A recent live vote of our readership during the USANZ Annual Scientific Meeting in Adelaide, Australia, indicated that the majority would like us to go electronic in about 2–3 years’ time; however, ≈30% of our institutional subscribers still prefer the paper version and are reluctant to make the switch.

The BJUI and The Lancet are coming together to host a joint Social Media session at BAUS 2015, which will provide more opportunity to learn from one of the best journals ever. We hope to see many of you there.

References

 

1 Messer JC, Punnen S, Fitzgerald J, Svatek R, Parekh DJ. Health-related quality of life from a prospective randomised clinical trial of robot- assisted laparoscopic vs open radical cystectomy. BJU Int 2014; 114: 896–902

 

2 Lee N. Robotic surgery: where are we now? Lancet 2014; 384: 1417

 

3 Kigozi G, Musoke R, Kighoma N et al. Male circumcision wound healing in human immunodeficiency virus (HIV)-negative and HIV-positive men in Rakai, Uganda. BJU Int 2014; 113: 127–32

 

4 Gray RH, Kigozi G, Serwadda D et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369: 657–66

 

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

Scott Millar
Managing Editor, BJUI 

 

Naomi Lee
Web Editor, The Lancet

 

Capsaicin, resiniferatoxin and botulinum toxin-A – a trip down memory lane

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Over 20 years ago, I went to work at Queen Square, the Mecca of Neurology, as Medical Research Council fellow to Prof. Clare Fowler, an international expert in the neurogenic bladder. She has now retired leaving a lasting legacy, which features in this edition of the BJUI.

I clearly remember my first meeting with Vijay Ramani (now Consultant Urologist in Manchester) and Dirk De Ridder (Associate Editor, BJUI), which led to a collaborative paper on the effects of capsaicin in refractory neurogenic detrusor overactivity (NDO) [1]. While we were busy studying suburothelial nerves in NDO, with many hours of computerised image analysis, a seminal paper describing the ‘capsaicin receptor’ appeared in Nature [2]. This was my first encounter with transient receptor potential (TRP) channels. They continue to excite urologists and neurologists alike as potential therapeutic targets in overactive and painful bladders [3].

Just like semisynthetic capsaicin, derived from chillies, which acted through TRP receptors, TRPV1 antagonists are effective but have numerous side-effects including hyperthermia. No surprises here But there are other subtypes, such as TRPV4 and TRPM8, which are generating a lot of interest in the field of drug discovery.

Life, of course, moved on. Capsaicin never received a license for NDO and was followed by resiniferatoxin (RTX), which also made a rapid exit as it adhered to the plastic bags that it was dispensed in as a solution. Botulinum toxin-A turned out to be the game changer [4]. After extensive trials and safety studies, it has changed the lives of many millions with incontinence secondary to DO, who have failed most other first-line treatments. It has a licence for clinical use and the science behind its mechanism of action has led to many fascinating discoveries.

So, are TRP inhibitors the next big thing in functional urology? After 20 years of fundamental research, they certainly have the potential. As with most eureka moments in translational research, only time will tell.

 

References

 

1 De Ridder D, Chandiramani V, Dasgupta P, Van Poppel H, Baert L, Fowler CJ. Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J Urol 1997; 158: 2087–92

 

2 Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin- receptor homologue with a high threshold for noxious heat. Nature 1999; 398: 436–41

 

3 Deruyver Y, Voets T, De Ridder D, Everaerts W. Transient receptor potential channel modulators as pharmacological treatments for lower urinary tract symptoms (LUTS): myth or reality? BJU Int 2015; 115: 686–97

 

4 Sahai A, Dowson C, Khan MS, Dasgupta P. Improvement in quality of life after botulinum toxin-A injections for idiopathic detrusor overactivity: results from a randomized double-blind placebo-controlled trial. BJU Int 2009; 103: 1509–15

 

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

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