Tag: Botox

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The times they are a-changin’

February 15, 2017/2 Comments/by Prokar Dasgupta

The other day, as the New York Times was getting excited about Nobel Laureate Bob Dylan new album ‘Triplicate’, I had the opportunity of remembering one of his classic songs. Let me explain. I turned up at the School of Surgery in central London for an academic committee meeting early that morning only to find that it had been cancelled. Due to a IT problem the email with this information never reached me! Rather than brave the London tube again, I decided to walk back to my hospital, which took me past my old hospital which sadly no longer exists.

The old hospital in question was The Middlesex Hospital in Mortimer Street, London (Fig.1). The original institution was built in 1745 at Windmill Street and moved in 1757 to Mortimer Street. I arrived there over 20 years ago to train at the Institute of Urology/St. Peter’s Hospital, a highly desirable post amongst surgical residents.

The Middlesex Hospital was closed in 2005 and sold to developers. It now houses swanky apartments and businesses around a beautiful Pearson Square, named after John Loughborough Pearson, who designed the Fitzrovia Chapel (Fig. 2) in 1890 inside the hospital. The Chapel survived the redevelopment as it is a protected building. So did one of the walls of the old hospital along Nassau Street which housed the radiotherapy building (Fig. 3). That facade has been preserved beautifully although there are no patients housed behind it anymore (Fig. 4).

So why I am telling you all this? Nostalgia you may say. But in fact much more. The 3 mile walk that morning allowed me to reflect on my own contribution to science and that of two friends who although slightly ahead of me in the training program at The Middlesex Hospital are gentlemen that I greatly admire.

One is Mark Emberton, now Professor at UCL, who has, through the PROMIS study, established the use of MRI prior to prostate biopsies rather than random TRUS biopsies for patients with a raised PSA. The other is David Ralph, an acclaimed Andrologist, who has just published our Priapism Guidelines, a must read for everyone managing this emergency. There is no doubt that both have made significant contributions to British Urology and patient care in the last 20 years during which so many things have changed.

As for me, I headed to Queen Square from The Middlesex Hospital, where many years of basic research in a Medical Research Council (MRC) funded lab led to the description of the so called “Dasgupta technique” of injecting Botox into overactive bladders. I was pleasantly surprised to hear that it had made its way into a number of texts including Smith’s Textbook of Endourology.

There are however certain things that do not change much. Next to the Middlesex Hospital, on Cleveland Street was the legendary Ragam’s (Fig. 5), which many would regard as THE go to South Indian restaurant. The masala dosa (pancake with spicy potatoes and hot lentil soup) used to cost £3.95 in 1994; 20 years later the price has gone up by only £2 to £5.95 (Fig. 6), while the quality remains as outstanding as ever.

Prokar Dasgupta @prokarurol

Editor-in-Chief, BJUI

In search of the ROSETTA stone (again)?

October 31, 2016/2 Comments/by Prokar Dasgupta

We are having an amazing year of scientific discovery in our specialty. 2016 has already seen the results of the only randomised trial comparing open versus robotic radical prostatectomy from Australia and the ProtecT trial from UK discussed intensively on Blogs@BJUI. The PROMIS of MRI is expected to change the practice of prostate biopsies in response to a raised PSA. The teams completing these trials deserve our heartiest congratulations as it is well known how difficult randomised trials in surgery are to initiate and complete.

As if this was not enough, this month the randomised controlled trial comparing Botox (Onabotulinum toxin A) to Interstim (sacral neuromodulation) in patients with refractory overactive bladder has been reported in JAMA. It is otherwise known as the ROSETTA study (Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment).

This is an example of what collaboration between individuals and teams within a pelvic floor group can achieve. Cindy Amundsen, the lead author, presented the trial results at the #AUA16 late breaking abstract session in San Diego.

The CONSORT diagram is shown here

The primary outcome measure showing Botox winning over Interstim (narrowly) in reducing urgency urinary incontinence is demonstrated in this diagram.

The summary results are shown here

So what would you do for your patient with refractory overactive bladder who has failed Anticholinergics and Mirabegron?

I have spent the last week thinking about the trial results carefully and was asked exactly this question at the International Endourology Forum in China. There are a number of important aspects to consider. The dose of Botox used in the trial was 200 units while the licensed dose is 100 units for overactive bladder of non-neurogenic origin. We know that one size does not fit all and indeed some patients failing 100 units need higher doses of Botox. It remains unknown as to what would have happened if 100 units of Botox was compared to Interstim as the authors are quite guarded about their own conclusions about the benefits.

The side effects also need to be carefully discussed with the patient. The UTI rate in the Botox group is about three times that of the Interstim group. Most patients may accept a period of oral antibiotics to counter this. The risk of CISC dropped from 8% at 1 month to 2% at 6 months in the Botox group. This is lower than previously reported in Phase lll studies. The need for revision or removal in the Interstim patients was around 3% – small but not to be ignored.

Punchline
If I was the patient in question, I would have Botox initially, preserving Interstim for later. It is less invasive and can be repeated roughly once a year if needed. Call me “lilly livered” but I do not like the idea of having a little box, however tiny, inside my bum and occasionally having to sit on it! I look forward to the smarter new generation of minimally invasive or even non-invasive nerve stimulators. But then it would need another randomised trial, many years of unanswered questions, perhaps even wastage of a lot of grant money…………..yawn!!

In the meantime, I will take my chances with Botox and counsel my patients accordingly. Unlike the famous ROSETTA stone, the key to understanding the mystery behind hieroglyphs and the controversy as to whether it should at all be in the British museum, I fail to see any such controversy with this nice trial in JAMA.

My thoughts and message are clear. Are yours?

Highlights from #BAUS15

June 24, 2015/by Rebecca Tregunna

#BAUS15 started to gain momentum from as early as the 26^th June 2014 and by the time we entered the Manchester Central Convention Complex well over 100 tweets had been made. Of course it wasn’t just Twitter that started early with a group of keen urologists cycling 210 miles to conference in order to raise money for The Urology Foundation.

Monday 15^th June 2015

By the time the cyclists arrived conference was well under way with the andrology, FNUU and academic section meetings taking place on Monday morning:

The BJU International Prize for the Best Academic Paper was awarded to Richard Bryant from the University of Oxford for his work on epithelial-to-mesenchymal transition changes found within the extraprostatic extension component of locally invasive prostate cancers.
Donna Daly from the University of Sheffield received the BJUI John Blandy prize for her work on Botox, demonstrating reductions in afferent bladder signaling and urothelial ATP release.

Professor Reisman’s talk on ‘Porn, Paint and Piercing’ as expected drew in the crowds and due to a staggering 44% complication rate with genital piercings it is important for us to try to manage these without necessarily removing the offending article as this will only serve to prevent those in need from seeking medical attention.
With the worsening worldwide catastrophe of antibiotic resistance, the cycling of antibiotics for prevention of recurrent UTIs is no longer recommended. Instead, Tharani Nitkunan provided convincing evidence for the use of probiotics and D-Mannose.

The afternoon was dominated by the joint oncology and academic session with Professor Noel Clarke presenting the current data from the STAMPEDE trial. Zolendronic acid conferred no survival benefit over hormones alone and consequently has been removed from the trial (stampede 1). However, Docetaxal plus hormones has shown benefit, demonstrated significantly in M1 patients with disease-free survival of 65 months vs. 43 months on hormones alone (Hazard ratio 0.73) (stampede 2). This means that the control arm of M1 patients who are fit for chemotherapy will now need to be started on this treatment as the trial continues to recruit in enzalutamide, abiraterone and metformin arms.

The evening was rounded off with the annual BAUS football tournament won this year by team Manchester (obviously a rigged competition!), whilst some donned the

lycra and set out for a competition at the National Cycle Centre. For those of us not quite so energetic, it was fantastic to catch up with old friends at the welcome drinks reception.

Tuesday 16^th June 2015

Tuesday kicked off bright and early with Professor John Kelly presenting results from the BOXIT clinical trial, which has shown some benefit over standard treatment of non-muscle invasive bladder cancer, but with significant cardiovascular toxicity.

The new NICE bladder cancer guidelines were presented with concerns voiced by Professor Marek Babjuk over discharging low-risk bladder cancer at 12 months given a quoted 30-50% five-year recurrence risk. Accurate risk stratification, it would seem, is going to be key.

The President’s address followed along with the presentation of the St. Peter’s medal for notable contribution to the advancement of urology, which was presented to Pat Malone from Southampton General Hospital. Other medal winners included Adrian Joyce who received the BAUS Gold Medal, and the St. Paul’s medal went to Mark Soloway.

A plethora of other sessions ensued but with the help of the new ‘native’ BAUS app my programme was already conveniently arranged in advance:

‘Heartsink Conditions’ included pelvic and testicular pain and a fascinating talk by Dr Gareth Greenslade highlighted the importance of early and motivational referral to pain management services once no cause has been established and our treatments have been exhausted. The patient’s recovery will only start once we have said no to further tests: ‘Fix the thinking’

Poster sessions are now presented as ‘e-posters’, abolishing the need to fiddle with those little pieces of Velcro and allowing for an interactive review of the posters.

Pravisha Ravindra from Nottingham demonstrated that compliance with periodic imaging of patients with asymptomatic small renal calculi (n=147) in primary care is poor, and indeed, these patients may be better managed with symptomatic imaging and re-referral as no patients required intervention based on radiograph changes alone.

Archana Fernando from Guy’s presented a prospective study demonstrating the value of CTPET in the diagnosis of malignancy in patients with retroperitoneal fibrosis (n=35), as well as demonstrating that those with positive PET are twice as likely to respond to steroids.

Wednesday 17^th June 2015

Another new addition to the programme this year was the Section of Endourology ‘as live surgery’ sessions. This was extremely well received and allowed delegates to benefit from observing operating sessions from experts in the field whilst removing the stressful environment and potential for risk to patient associated with live surgery. This also meant that the surgeon was present in the room to answer questions and talk through various steps of the operation allowing for a truly interactive session.
Wednesday saw multiple international speakers dominating the Exchange Auditorium:

The BJU International guest lecture was given by Professor Hendrik Van Poppel: a heartfelt presentation describing what he believes to be the superiority of surgery over radiotherapy for high-risk localised prostate cancer.
The Urology Foundation presented the Research Scholar Medal to Ashwin Sachdeva from Freeman Hospital, Newcastle for his work on the ‘Role of mitochondrial DNA mutations in prostate carcinogenesis’. This was followed by an inspiring guest lecture by Inderbir Gill on ‘Robotic Urologic Oncology: the best is yet to come’ with the tag line ‘the only thing that should be open in 2015 is our minds’
Robotic Surgery in UK Urology: Clinical & Commissioning Priorities was a real highlight in the programme with talks from Jim Adshead and Professor Jens-Uwe Stolzenburg focussing on the fact that only 40% of T1a tumours in the UK were treated with partial (as opposed to radical) nephrectomy, and that the robot really is the ‘game-changer’ for this procedure. Inderbir Gill again took to the stage to stress that all current randomised trials into open vs. robotic cystectomy have used extracorporeal reconstruction and so do not reflect the true benefits of the robotic procedure as the dominant driver of complications is in the open reconstruction.

These lectures were heard by James Palmer, Clinical Director of Specialised Commissioning for NHS England who then discussed difficulties in making decisions to provide new technologies, controlling roll out and removing them if they show no benefit. Clinical commissioning policies are currently being drafted for robotic surgery in kidney and bladder cancer. This led to a lively debate with Professor Alan McNeill having the last word as he pointed out that what urologists spend on the robot to potentially cure cancer is a drop in the ocean compared with what the oncologists spend to palliate!

Thursday 18^th June 2015

The BJU International session on evidence-based urology highlighted the need for high-quality evidence, especially in convincing commissioners to spend in a cash-strapped NHS. Professor Philipp Dahm presented a recent review in the Journal of Urology indicated that the quality of systematic reviews in four major urological journals was sub-standard. Assistant Professor Alessandro Volpe then reviewed the current evidence behind partial nephrectomy and different approaches to this procedure.

Another fantastic technology, which BAUS adopted this year, was the BOD-POD which allowed delegates to catch-up on sessions in the two main auditoria that they may have missed due to perhaps being in one of the 21 well designed teaching courses that were available this year. Many of these will soon be live on the BAUS website for members to view.

The IBUS and BAUS joint session included a lecture from Manoj Monga from The Cleveland Clinic, which led to the question being posed on Twitter: ‘Are you a duster or a basketer?’The audience was also advised to always stent a patient after using an access sheath unless the patient was pre-stented.

The updates session is always valuable especially for those studying for the FRCS (Urol) exam with far too many headlines to completely cover:

Endourology: The SUSPEND trial published earlier this year was a large multi-centre RCT that showed no difference in terms of rates of spontaneous passage of ureteric stone, time to stone passage or analgesic use between placebo, tamsulosin and nifedipine. There was a hot debate on this: should we be waiting for the meta-analysis or should a trial of this size and design be enough to change practice?
Oncology-Prostate: The Klotz et al., paper showed active surveillance can avoid over treatment, with 98% prostate cancer survival at 10 years.
Oncology-Kidney: Ellimah Mensah’s team from Imperial College London (presented at BAUS earlier in the week) demonstrated that over a 14-year period there were a higher number of cardiovascular-related admissions to hospital in patients who have had T1 renal tumours resected than the general population, but no difference between those who have had partial or radical nephrectomy.
Oncology-Bladder: Arends’s team presented at EAU in March on the favourable results of hyperthermic mitomycin C vs. BCG in the treatment of intermediate- and high-risk bladder cancer.
Female and BPH: The BESIDE study has demonstrated increased efficacy with combination solifenacin and mirabegron.
Andrology: Currently recruiting in the UK is the MASTER RCT to evaluate synthetic sling vs. artificial sphincter in men with post-prostatectomy urinary incontinence.

Overall BAUS yet again put on a varied and enjoyable meeting. The atmosphere was fantastic and the organisers should be proud of the new additions in terms of allowing delegates to engage with new technologies, making for a memorable week. See you all in Liverpool!

Rebecca Tregunna, Urological Trainee, West Midlands Deanery @rebeccatregunna

Dominic Hodgson, Consultant Urologist, Portsmouth @hodgson_dominic

Article of the week: Botulinum toxins are not interchangeable for overactive bladder

July 10, 2013/2 Comments/by admin Z.9

Every week the Editor-in-Chief selects the 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Miss Ravindra and colleagues discussing their article.

If you only have time to read one article this week, it should be this one.

Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?

Pravisha Ravindra, Benjamin L. Jackson and Richard J. Parkinson

Nottingham Urology Centre, Nottingham University Hospitals, NHS Trust, Nottingham, UK

Read the full article

OBJECTIVE

• To compare the clinical effects of two different commercially available botulinum toxin type A products, onabotulinumtoxinA (Botox^®; Allergan Inc., Irvine, CA, USA) and abobotulinumtoxinA (Dysport^®; Ipsen Ltd, Slough, UK), on non-neurogenic overactive bladder (OAB).

PATIENTS AND METHODS

• We included 207 patients, who underwent treatment with botulinum toxin type A for non-neurogenic OAB from January 2009 to June 2012 at our institution, in a prospective database that recorded details of their presentation, treatment and outcomes.

• In December 2009, our institution switched from using onabotulinumtoxinA to using abobotulinumtoxinA.

RESULTS

• Results from the onabotulinumtoxinA cohort (n = 101) and the abobotulinumtoxinA cohort (n = 106) were compared.

• Similar reductions in daytime frequency, nocturia and incontinence episodes were observed after treatment, with no difference in duration of effect.

• The abobotulinumtoxinA cohort had almost twice the rate of symptomatic urinary retention (23 vs 42%) requiring intermittent self-catheterisation (ISC).

CONCLUSIONS

• AbobotulinumtoxinA use was complicated by a significantly higher risk of requiring ISC.

• The study suggests that these two toxins are not interchangeable at the doses used.

Read Previous Articles of the Week

Editorial: Botulinum toxin-A for overactive bladder: formulations, dosing and clean intermittent catheterisation

July 10, 2013/by Arun Sahai

The article by Ravindra et al., in this issue of the BJUI, tries to address an important question of comparing the 2 commonest types of botulinum toxin-A (BTX-A), Ona- and AbobotulinumtoxinA. In their institution they changed from OnbotulinumtoxinA to AbobotulinumtoxinA and thus compared results of their different case series for patients with overactive bladder syndrome. Very few studies have tried to address this issue for botulinum toxin-A use in the urinary tract and to my knowledge there are no head to head studies. The authors found the 2 types of BTX-A equivalent in terms of voiding diary parameters, ICIQ questionnaires, patient reported global satisfaction and duration of effect but noted a significant difference for clean intermittent self catheterisation (CISC) rates (23% OnabotulinutoxinA vs 42% AbobotulinumtoxinA). The dose used for OnabotuliumtoxinA was 200 IU and for AbobotulinumtoxinA was 500 IU initially and then later 300 IU. One must bear in mind some important considerations which limit the impact of the result. Namely the non-randomised, retrospective nature of the study and the fact that the study was not designed or powered to assess the BTX-A formulations in this way. The primary endpoint in this case was a patient reported satisfaction measure indicating that 85% had ‘better’ or ‘much better’ symptoms which I think is a fair reflection in my experience. Furthermore there were significant gaps in data acquisition particularly for voiding diary, PVR and ICIQ data which again is not that uncommon in retrospective studies. No urodynamic data was included which I think may also have been interesting to look at when assessing outcomes and CISC rates.

None the less the study generates some interesting discussion about the formulations, optimal dosing and the dosing equivalence. The study is one of the first to report on the use of AbobotulinumtoxinA at 300 IU as most studies utilised 500 IU. In view of the move to lower doses of OnabotulinumtoxinA to treat refractory OAB of 100–150 IU, this dose seems appropriate. Evidence from a large dose ranging RCT using OnabotulinumtoxinA suggests no further efficacy beyond doses of 150 IU but an increase in voiding dysfunction. Interestingly CISC rates are still high at 300 IU in this study. A recent systematic review tried to assess the 2 formulations in aspects of BTX-A use for various lower urinary tract dysfunction. Due to the heterogenousity of the studies, a lack of standardised or high quality data a direct comparison between the 2 was not formally possible. It was noted that OnabotulinumtoxinA has been studied more extensively compared to AbobotulinumtoxinA and with both formulations CISC rates could be high at the doses used in this study (OnabotulinumtoxinA 43%; AbobotulinumtoxinA 35%). Assessing the compound muscle action potential of the extensor digitorum brevis muscle in healthy volunteers has suggested an AbobotulinumtoxinA to OnabotulinumtoxinA ratio of 1.57:1 (95% confidence interval: 0.77–3.20 units) with the data indicating that a dose-equivalence ratio of 3:1 was just within statistical error limits but ratios over 3:1 were too high. The same author following a review of the literature in treatments outside the urinary tract suggest a ratio of 2–2.5:1 maybe the most appropriate. An animal model of spinal cord injury and neurogenic detrusor overactivity to compare the 2 formulations has recently been published. The minimal effective dose of Abo- and OnabotulinumtoxinA was found to be 10 IU and 7.5 IU, respectively, for significant changes in cystometry.

When should CISC be instigated? Practice seems to vary considerably and thus results difficult to compare. Many clinicians will base CISC decisions on a cut off, typically 100–200 mL or on whether patients are symptomatic with their PVR. Chapple has suggested >40% of the functional capacity as a significant PVR and this to me seems entirely logical. Future studies should consider this as an endpoint regarding CISC.

At present, the decision as to which formulation is used in clinical practice is often based on local pharmacy regulation and financial considerations. Licensing is undoubtedly going to have a significant influence on this practice. OnabotulinumtoxinA is now licensed for use in many parts of the world to treat neurogenic detrsuor overactivity and has recently been approved by the FDA in the USA to treat refractory OAB. At the time of writing this editorial, no formulation is currently approved for refractory OAB in the UK.

Arun Sahai
Consultant Urologist & Honorary Senior Lecturer, Department of Urology, Guy’s Hospital MRC Centre for Transplantation, King’s College London, King’s Health Partners

Read the full article

Video: botox course the preferred choice for non-neurogenic OAB

July 10, 2013/1 Comment/by admin Z.9

Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?

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Pravisha Ravindra, Benjamin L. Jackson and Richard J. Parkinson

Nottingham Urology Centre, Nottingham University Hospitals, NHS Trust, Nottingham, UK

Read the full article

OBJECTIVE