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

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 LFowler CJ. Intravesical capsaicin as a treatment for refractory detrusor hyperreexia: a dual center study with long-term followup. J Urol 1997; 158: 208792

 

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: 43641

 

 

 

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

#AUA15 bursts to life in New Orleans

CaptureCreole cuisine, bustling Bourbon street, beads and beignets and 16,000 urologists.  #AUA15 has just drawn to a close in the birthplace of Jazz; New Orleans, Louisiana #NOLA. With 2,598 abstracts being presented, over 2,500 speakers and representation from more than 100 countries it was undoubtedly an educational and action packed five days.

This was my first AUA and while I knew it was going to be a big conference I was stunned by the size of it all. There were urologists everywhere, so much so that jiving to jazz on Frenchman became a game of ‘spot the urologist’ by the signature urology dance moves and stylish….ish dress code!!!! The scientific programme was so extensive it was difficult to find the time to attend all the sessions I wanted to. However, the committee deserve huge credit for developing the AUA2015 app and Daily news snippets that were available throughout the centre which made it easy to optimise your time at the meeting.

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The French Quarter, NOLA

The conference got off to a heated beginning with the Crossfire: Controversies in Urology session sparking plenty of debate. Few topics have ignited as much argument as the question of focal ablation for prostate cancer and the discussion between Mark Emberton MD, UCL, London and Aaron E. Katz, MD,PhD, Winthrop University Hospital was no different. To call it a lively session is an understatement. The question of alpha blockers being sold over the counter for BPH was also discussed during this session. Although the drugs have proven safe over the last 25 years clinicians have concerns that the loss of patient contact as a result of this relabeling would causes a loss of control in the treatment of men with BPH.

Friday drew to a close with the urotwitterati enjoying the social media TweetUp encouraging newbie tweeters to get involved. It clearly worked because #AUA15 set a new record and almost trebled it’s tweeting volume since #AUA13.

Day two, Saturday saw the opening of the Science and Technology hall. A spectacle of testicular, penile devices and stalls I have never seen. I fear what one might have thought had they stumbled into the conference centre by accident!!

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The @BJUIJournal #SoMe awards took place on Saturday evening. @DrHWoo deservedly bagged The Social Media Award 2015 for #UROJC. A well chosen venue there were no issues with Wifi for tweeting!!! Read the #SoMe blog for all award details

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Enjoying the @BJUIjournal cult #SoMe awards

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A personal favourite of mine at the conference was the 4th annual Residents Bowl which took place over three days; with residents engaging in a battle of the brains! Northeastern claimed the trophy in the end and team members on the winning side included this year’s BAUS representative @DerekHennessey.

BAUS, BJUI and USANZ came together on Sunday afternoon for a stellar line-up of speakers and topics. The session was well attended and speakers outlined the most recent data but more importantly shared the experience of techniques and outcomes in their centres and countries. I think this combined society session is a fantastic arena for all to both learn and educate each other on what is working best, where and why? The superb line up included Dan Moon, Jeremy Grummet, Henry Woo, Declan Murphy, David Nicol, Damien Bolton, Stephen Boorjian and Philip D. Stricker who all shared their clinical expertise.
BJUI Guest speaker Ben Challacombe discussed the evidence base for management of RCC by partial nephrectomy. Lower intraoperative complications and WIT were observed at their centre at Guy’s Hospital London, which is similarly reflected by low complication rates in the BAUS mandatory UK national nephrectomy audit. Professor Prokar Dasgupta started his up and down journey for the evidence supporting robotic cystectomy for TCC bladder by reminiscing on where it all began; kite-flying in India as a young boy.

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Much anticipated CORAL trial found that 90 day complication rates and oncological control were comparable in ORC v LRC/RARC.

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Finally the session closed with the presentation of the Coffey-Krane award to Gopa Iyer; Phase III Study of  everolimus in metastatic urothelial cancer collected on Dr Gopa’s behalf by David Quinlan. This award is for trainees who are based in the Americas and judged by a panel as the best publication accepted to the BJUI.

 

Overall, some of the big points of the conference were the amendments to AUA guidelines including Castration-Resistant Prostate Cancer, which was updated from just last year. Perhaps, the most significant was the first ever draft of AUA Peyronie’s disease guidelines; outlining recommendations from medical therapy to surgery.

The huge rise in social media at urology conferences was demonstrated again by record-breaking figures via @symplur showing that the use of Twitter among the urology community continues to grow:

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#AUA15 was both an educational and social experience. I had a blast, learned loads and also got to experience the culinary delights of Muffuletta and Gumbo, take the trolley up St. Charles to the Garden district and simply encounter the warmth and friendliness of both the Louisiana folk and the huge family of Urology. The AUA Scientific Committee deserve a huge congratulations on the success of a stimulating, enjoyable and extensive scientific programme. I know I heard echoes of ‘best AUA yet’ in my company.

Áine Goggins

Medical Student; Queens University Belfast, Ireland

@gogsains

 

The 3rd BJUI Social Media Awards – #AUA15 in New Orleans

Murphy-2015-BJU_InternationalWhat a fun destination we had for the 3rd Annual BJUI Awards! As you may know, we alternate the occasion of these awards between the annual congresses of the American Urological Association (AUA) and of the European Association of Urology (EAU). Our first awards ceremony took place at the AUA in San Diego in 2013, followed last year in Stockholm at the EAU. This year, we descended on New Orleans, Louisiana to join the 16,000 or so other delegates attending the AUA Annual Meeting and to enjoy all that the “Big Easy” had to offer. What a fun city; a true melting pot of food, music and culture all borne out of the eclectic French, American and African cultures on show. I think I met more key opinion leaders in the clubs on Frenchman Street than I did in some of the prostate cancer poster sessions!

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You can read more about all that in our #AUA15 Conference Highlights blog, so on now to the Awards. The AUA Annual Meeting plays host to intense social media activity and it is fitting that the BJUI Social Media Awards gets to acknowledge the rapidly growing number of Uro-Twitterati in attendance. Over 100 of the most prominent tweeters turned up to the Ritz-Carlton to enjoy the hospitality of the BJUI and to hear who would be recognised in the 2015 BJUI Social Media Awards. Individuals and organisations were recognised across 16 categories including the top gong, The BJUI Social Media Award 2015, awarded to an individual, organization or innovation who has made an outstanding contribution to social media in urology in the preceding year. The 2013 Award was won by the outstanding Urology Match portal, followed in 2014 by Dr Stacy Loeb for her outstanding contributions.  This year our Awards Committee consisted of members of the BJUI Editorial Board (Declan Murphy, Prokar Dasgupta, Matt Bultitude as well as BJUI Managing Editor Scott Millar whose team in London drive the content across our social platforms).

 

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The full list of awardees, along with some examples of “best practice” in the urology social media sphere can be found on this Prezi. The winners are also listed here:

 

  • Most Read [email protected] – “Are you ready to go to prison on a manslaughter charge?”. Accepted by Dr Ben Challacombe, on behalf of Prof Roger Kirby, London, UK
  • Most Commented [email protected] – “Prof John Fitzpatrick – Life in the Fast Lane”. Accepted by Dr Ben Challacombe, on behalf of Prof Roger Kirby, London, UK
  • Best Blog Comment – Dr Brian Stork, Michigan, USA
  • Best BJUI Tube Video – Hospital volume and conditional 90 day post-cystectomy mortality. – accepted by Dr Angie Smith on behalf of Dr Matt Neilsen, North Carolina, USA.
  • Best Urology Conference for Social Media – SIU Annual Congress, Glasgow 2014. Accepted by Dr Sanjay Kulkarni on behalf of the SIU
  • Best Social Media Campaign – Dr Ben Davies, Pittsburgh, USA, for highlighting industry issues around BCG shortage
  • “Did You Really Tweet That” Award – Ben Davies, Pittsburgh, USA (three years running!)
  • Best Urology App – The Rotterdam Prostate Cancer Risk Calculator. Accepted by Dr Stacy Loeb on behalf of Dr Monique Roobol, ERSPC, Rotterdam, The Netherlands
  • Innovation Award 2015 – #eauguidelines. Accepted by EAU Guidelines panellists Dr Stacy Loeb and Dr Morgan Roupret, on behalf of Dr James N’Dow, Dr Maria Ribal, and the EAU Guidelines Committee.
  • #UroJC Award – David Canes, Boston, USA
  • Best Selfie – Morgan Rouprêt, Paris, France
  • Best Urology Facebook Site – European Association of Urology. Accepted by Dr Alex Kutikov, Digital Media Editor, European Urology
  • Best Urology Journal for Social Media – Nature Reviews Urology. Accepted by Editor-in-Chief, Annette Fenner
  • Best Urology Organisation – American Urological Association. Accepted by Taylor Titus, AUA Communications Office
  • The BJUI Social Media Award 2015 – International Urology Journal Club #urojc. Accepted by Dr Henry Woo, Sydney, Australia.

 

Most of the Award winners were present to collect their awards themselves, including the omnipresent Dr Henry Woo who received our top gong for his work on the very successful International Urology Journal Club #urojc. The #urojc now has over 3000 followers and its monthly, asynchronous 48hr global journal club has become a huge event. Many other specialties and #FOAMed resources have recognised #urojc and BJUI are delighted to publish a blog summarising each month’s discussions. Well done to Henry, Mike Leveridge and others in setting and maintaining this outstanding example of social media adding real value.

A special thanks to our outstanding BJUI team at BJUI in London, Scott Millar and Max Cobb, who manage our social media and website activity as well as the day-to-day running of our busy journal.

See you all in Munich for #EAU16 where we will present the 4th BJUI Social Media Awards ceremony!

Declan Murphy

Associate Editor for Social Media at BJUI. Urologist in Melbourne, Australia

Follow Declan on Twitter @declangmurphy and BJUI @BJUIjournal

 

Future Directions in Urological Oncology

bju13076-fig-0001The field of urological oncology is rapidly changing. For example, robotic surgery, targeted therapy, and ablation techniques are oncological options that were in their infancy 10 years ago and are now mainstream in many areas of the world. Additionally, immunotherapy has recently become a promising avenue in multiple urological cancers. As we move forward, expect to see a larger presence of urological oncology literature obtained via social media, which BJUI has initiated and subsequently set the standard for the field. Related to this, this month’s edition of BJUI includes four online ‘Articles of the Week’, with each focusing on urological oncology.

Using data from the pro-PSA Multicentric European Study (PROMEtheuS) project, Abrate et al. [1] evaluated the utility of the Prostate Health Index (PHI) in 142 obese (body mass index BMI >30 kg/m2) men who underwent a prostate biopsy for an abnormal DRE or elevated PSA level. Among the 142 patients, 65 (45.8%) were found to harbour prostate cancer. Using the PHI threshold of 35.7, the authors determined that 46 (32.4%) negative biopsies could have been avoided while six (9.2%) cancers would have been missed. Related to this, Salami et al. [2] compared the cancer detection rates of MRI fusion biopsy vs standard 12-core TRUS-guided biopsy in 140 men with a previous negative prostate biopsy and a lesion appreciated on a multiparametric MRI. While the cancer detection rates were similar overall, the MRI fusion biopsy was more likely to detect clinically significant prostate cancer (48% vs 31%), defined as Gleason ≥7 or Gleason 6 with a lesion volume of >0.2 mL on MRI. In an era where over-diagnosis of prostate cancer is commonplace, data to better stratify patients who need (or do not need) a prostate biopsy and enhanced ways to identify clinically significant prostate cancers are of paramount importance.

Soares et al. [3] report their results among 1 138 contemporary laparoscopic radical prostatectomy patients who had at least 5 years of follow-up. Only one case required an open conversion and the transfusion rate was merely 0.5%. At last follow-up, 85% of patients had an undetectable PSA level, 94% of patients were continent, and 77% of non-diabetic men aged <70 years retained potency. These impressive single-surgeon results further suggest that the morbidity of prostate cancer surgery has diminished with increasing time and experience.

Additionally, Tolchard et al. [4] prospectively evaluated 105 patients with bladder cancer with preoperative cardiopulmonary exercise testing prior to radical cystectomy. Patients who received neoadjuvant chemotherapy were excluded and there was a 6% perioperative death rate with 90 days of follow-up. The results suggest that patients with poor cardiopulmonary reserve along with hypertension are at higher risk of perioperative complications and prolonged hospital stay; median length of stay was 22 and 9 days for patients with and without a complication. Furthermore, while only 2% of patients had a preoperative diagnosis of heart failure, there were a significant proportion of patients (50% in this study) found to have moderate-to-severe heart failure based on preoperative cardiopulmonary exercise testing. These provocative results suggest that the urological community should further investigate the utility of routine cardiopulmonary exercise testing in patients undergoing radical cystectomy along with the optimal incorporation of such testing in patients receiving neoadjuvant chemotherapy.

References

 

 

 

3 Soares R, Di BenedettoA, Dovey Z, Bott S, McGregor RG, Eden CGMinimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies. BJU Int 2015;115:54653.

 

 

R. Houston Thompson BJUI Consulting Editor (Oncology)
Mayo Clinic, Rochester, MN, USA

 

 

Lessons learned from Asian Urology

Glasgow has been in the news a lot this year. The fantastic Commonwealth Games were followed by an excellent Société Internationale d’Urologie (SIU) meeting with its unique Scottish flavour. This month we move our attention to two other nations that have hosted the SIU – China and India. We present two large studies, which are well worth your reading pleasure, not just because of their sheer size but also for their messages and citability.

Since the initial discovery in 2007 of ketamine-associated cystitis by Shahani et al. [1] in Canada, scattered cases had also been reported in some European countries including the UK. However, the gravity of this ketamine problem was subsequently found to be far greater in Asian countries, particularly Hong Kong, Taiwan, Mainland China and Malaysia.

Although ketamine-associated uropathy is a medical problem, it takes root in much deeper social problems, and in turn perpetuates these problems and produces new issues. As the devastating effect of ketamine abuse on the society is unveiled, there are numerous collaborations between Hong Kong and Mainland China to combat it. Government and non-government organisations join hands in educating the public, youths in particular, on the irreversible damage that ketamine can cause to body and mind. More stringent laws have been enacted against drug traffickers, with high-profile enforcements. Abundant funds have also been set up to encourage research in this field.

With all these concerted efforts, according to official statistics in Hong Kong and Mainland China, the number of ketamine abusers is on the decline. However, this is no reason for complacency, as the numbers of abusers we capture probably represent only the ‘tip of the iceberg’. More and more evidence is indicating a substantial population of undiscovered ketamine abusers, who sniff ketamine stealthily at home for years without being noticed by their families.

Any effective solution to ketamine-associated uropathy [2] must involve identifying and extending help to this vast hidden group of abusers. The problem is daunting by its sheer magnitude. There are in addition, delicate issues of privacy, rights and self-esteem that require great sensitivity and patience. It is a job that requires experts from different specialties to cooperate. Urologists must work with social workers, teachers, paediatricians, psychiatrists, psychologists, nurses, occupational therapists and others. Last but not least, parental and family support is paramount in helping our youth to win this fight.

For those endourologists busily treating stone disease we highlight the evolution of shockwave lithotripsy (SWL) over 25 years in >5000 patients [3]. In many parts of the world, not just Asia, extracorporeal SWL (ESWL) has seen a drop in its popularity in parallel with an increase in the use of percutaneous nephrolithotomy (PCNL) and ureteroscopy. Patients seem to be more inclined to be stone-free with fewer interventions even if these are of an invasive nature.

For those readers more interested in immediacy through our web journal, the Best of China virtual supplement is the one not to miss. There have been many calls for a BJUI Android app from our friends in the East. We are almost there!

Read the full article

Peggy Sau-Kwan Chu and Prokar Dasgupta*

Division of Urology, Department of Surgery, Tuen Mun Hospital, Hong Kong *King’s College London, Guy’s Hospital, London, UK

References

1 Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology 2007; 69: 810–2

2 Tam YH, Ng CF, Pang KK et al. One-stop clinic for ketamine-associated uropathy: report on service delivery model, patients’ characteristics and non-invasive investigations at baseline by a cross-sectional study in a prospective cohort of 318 teenagers and young adults. BJU Int 2014; 114: 754–60

3 Jagtap J, Mishra S, Bhattu A, Ganpule A, Sabnis R, Desai M. Evolution of shockwave lithotripsy (SWL) technique: a 25-year single centre experience of >5000 patients. BJU Int 2014; 114: 748–53

 

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