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May Editorial: The Current Hot Topics in Functional Urology

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BJUI-May-2015-cover_smallFor some time, the challenge represented by managing the overactive bladder (OAB) has been dominant in functional urology research. The introduction of new therapies has galvanised the area, with mirabegron showing strong promise for many patients as a monotherapy. In addition, the potential for combined therapy using mirabegron with established antimuscarinics has recently been reported for urgency urinary incontinence [1]. Now that the place of onabotulinum-A injections in refractory cases is firmly established, management options have clearly taken a step forward in recent years. However, there remain people for whom even the more comprehensive current options are inadequate or intolerable. The need for basic science research remains a priority, in the hope of translation into clinical options. In this month’s BJUI, Aizawa et al. [2] report responses in an animal model to an inhibitor of fatty acid amide hydrolase, showing how exploiting the endocannabinoid pathway might be a translational focus for entirely new approaches in OAB. They consider an issue that is very important in developing clinical options, which is that the systems regulating bladder function are also fundamental in other organs, such as the CNS. As the compound they studied does not cross the blood–brain barrier, the potential generation of CNS adverse effects is reduced, which would be important for its potential as a new therapy.

OAB is a symptom syndrome based on storage-type LUTS [3]. Increasingly the field of functional urology is recognising the large number of people who present with voiding and post-micturition LUTS yet do not have BOO. Currently, there are no satisfactory treatment options for affected people and the symptoms can have considerable impact. Frustratingly, current diagnostic methods rely on urodynamic testing to establish whether the presence of detrusor underactivity explains voiding LUTS in an individual patient. Recently, the profession has established a move towards using symptoms to categorise the clinical need in patients [4]. Accordingly, the International Continence Society has established a working group to generate terminology for underactive bladder (UAB), which will report this year, including a symptom-based definition. A symptomatic diagnosis would be very helpful to enable therapy development to proceed without the need for urodynamic testing. Also, in this month’s BJUI, Kajbafzadeh et al. [5] report a clinical trial in UAB using transcutaneous interferential electrical stimulation in children. The treatment was delivered in the context of the rather laborious process currently required for managing this difficult problem, namely diet and fluid manipulation, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation training. The electrical stimulation was demonstrably beneficial, and included responses for the highly troublesome symptom of nocturnal enuresis. The comparatively straightforward nature of this therapeutic approach potentially makes it a valuable tool for dealing with a notoriously difficult problem.

Marcus J. Drake, Senior Lecturer
School of Clinical Sciences, University of Bristol, Bristol, UK

 

References

 

1 Drake MJ, Chapple C, Esen AA et al. Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BESIDE). Eur Urol 2016; [Epub ahead of print]. DOI: 10.1016/j.eururo.2016.02.030

 

2 Aizawa N, Gandaglia G, Hedlund P et al. URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats. BJU Int 2016; 117: 821–8

 

3 Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub- committee of the International Continence Society. Neurourol Urodyn 2002; 21: 167–78

 

4 Chapple CR, Osman NI , Birder L et al. The underactive bladder: a new clinical concept? Eur Urol 2015; 68: 351–3

 

5 Kajbafzadeh AM, Sharifi-Rad L, Ladi-Seyedian SS, Mozafarpour S. Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial. BJU Int 2016; 117: 793–800

 

Functional urology in the BJUI

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Although urological oncology is by far our largest section, it has increasingly become evident to us that the most cited part of the BJUI is functional urology. While this may come as a surprise, it is a reflection of the high quality of submissions that appear in this section. For your reading pleasure here are three “functional” articles in this issue worthy of attention. The paper from David Ginsberg also appears on the web journal as an article of the week.

In the first of our functional urology articles this month, Sjostrom et al. once again confirm the value of PFMT for the treatment of questionnaire and interview diagnosed SUI. Further, they show that an Internet-based program, which is more detailed and requires more contact (see Table 2 in the article), is more effective than a postal-based program in this regard after 3 months of usage (follow up at 4 months). What does more effective mean? For the ICIQ-UI SF scores, minimal difference in mean score is seen in the group scoring 1–5 (slight) and 6–12 (moderate) at baseline, a difference of 8.1 to 11 seen in the group scoring 13–21 (severe and very severe) at baseline (Figure 2). I like the PGI-I as a subjective patient global assessment. The largest difference was in the “very much better” group with minimal differences elsewhere (Figure 3). It would be interesting to know whether the larger difference occurred primarily in the severe and very severe groups as well. My take away is that PFMT is effective for SUI management. One can quibble about the lack of a physical exam here, but I suspect there would have been little difference. The real question is how best to apply this concept, keeping in mind the balance between results and efficient use of healthcare resources. My hypothesis would be that of the 3 methods of post, Internet and face-to-face therapy, there would be a preferred grouping based on the level of incontinence severity and education with the confounding factors of ages, socioeconomic class and desire for treatment, the latter associated with QOL impairment. A follow up at 6 and 12 months after treatment cessation would be helpful, and I am sure this is planned by the authors.

The article by Volpe et al. shows that the same indications can be used for recommending outlet reduction via TURP in the post renal transplant as in the general population. The only issue not specified was whether the pre-TUR serum creatinine in the 5/32 patients requiring catheterization (measured before catheterization), was higher than the others and, if so, may have skewed the group results. Nevertheless, it is important to acknowledge that renal transplant patients have the same LUT issues as “normals” and, for these fragile men it may be especially important to be cognizant of LUT obstruction as a potential adverse but correctible factor for decreased renal function.

Regarding the article by Ginsberg et al. on the differences in efficacy and tolerability between 8 mg of fesoterodine, 4 mg of ER tolterodine and placebo in patients with OAB, the authors are to be commended, in my opinion, for publishing this article, which is bound to generate much controversy among those who carefully read it. It is true that this is probably the first large study to compare antimuscarinic efficacy separately in women and men. The article begins by pointing out the pharmacokinetic issues with the drug that the sponsor previously promoted as the gold standard of antimuscarinic therapy. It does show that the higher (double) dose of active agent produces a ‘better” efficacy result albeit with an increase in dry mouth frequency but not in other adverse events. A useful result of the article is to make one consider the questions of what constitutes a clinically significant result as opposed to a statistically significant one and what the mechanism is of the profound placebo effect, especially with reference to the objective parameters recorded (Fig 2). Almost 50% of women and 60% of men become diary dry on placebo. It would also be interesting to reconcile the greater (but not large) differences between the subjective or QOL measures and the objective ones. As a take home, if both drugs were similarly priced, or available through health care benefits, the choice would be obvious. If not, what would the difference be worth?

Alan J. Wein, MD, FACS, PhD(hon)
Associate Editor – Functional Urology
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA

 

Original publication of this editorial can be found at: doi: 10.1111/bju.12326. BJUI 2013; 112: 277. 

The Best of British

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We live in a world that is getting smaller mainly because of global friendship, the Internet and the ease of travel. The British contribution to this should be a matter of pride for every UK urologist. Many friends and colleagues say that the BJUI has gone global, a decision that was made during the editorship of Hugh Whitfield and promoted under John Fitzpatrick. It was the correct move and has allowed British urology to maintain its prominent position in the rapidly changing world of academic publishing.

During BAUS 2013 we wanted our readers to know that the B in BJUI remains vital to the journal. We continue to publish and promote the best papers from UK for the benefit our local and international audience.

So here is the “Best of British” virtual issue, a selection of the most cited papers from UK in the BJUI in 2012-13. There are articles from every part of the British Isles proving that geography is not a barrier to quality.

It came as a surprise to me that Functional urology is the most cited section of the BJUI. We have highlighted a controversial but real life follow-up of patients having Botulinum toxin A injections for overactive bladder (OAB), a multicentre trial of a mini-sling and the natural history of urinary symptoms amongst ketamine users.

This is complemented by a Translational Science paper on the inhibition of stretching-evoked ATP release from bladder mucosa by anticholinergic agents. High-quality basic research with rapid translation is becoming real, thanks to the growth of Biomedical Research Centres in UK and overseas. We want to publish the best science papers and make them relevant to surgeons through Science Made Simple, a section that explains why our readers should care about science in a “dummies” fashion. The term “autophagy” is set to become as important as apoptosis.

Urological oncology is the largest section of the BJUI. There is considerable interest in prostate biopsies through the transrectal and transperineal routes and attempts at better imaging through MRI and perhaps Histoscanning. The role of surgery in high-risk prostate cancer is of particular relevance to British urologists within multidisciplinary teams as a number of our patients have aggressive, palpable and locally advanced disease. It is becoming clear that robotics can achieve oncological outcomes as robust as open surgery even in these patients. The Robotics and laparoscopy section of the BJUI has some of our most cited papers. We have given it prominence by featuring beautiful illustrations of  these common and evolving procedures in a Step by Step fashion on the front cover of our paper journal. Finally, a randomised controlled study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy, has an important message.

While a number of new modalities of resection such as blue light and narrow band imaging are emerging, good quality white light resection by experienced endoscopists must not be ignored. It is not just about resection, however; adjuvant intravesical gemciabine found its way into a systematic review in patients with non-muscle invasive disease.

The Upper urinary tract often suffers at the hands of the bladder and prostate but is equally important. We have highlighted systematic reviews of ureteroscopic and percutaneous management of upper tract urothelial carcinoma, its surgical management by other modalities and the changing trends in stone disease that will be of interest to our endourological colleagues.

We have introduced a new Surgical Education section and bring to your attention the first results from the BAUS SIMULATE project, which combines technical and non-technical skills. This will be of great importance to every British trainee and indeed we are the international standard bearers in this field, thanks to your active participation.

We thoroughly enjoyed selecting this issue for your reading pleasure. A number of these articles have already been free downloads on www.bjui.org as articles of the week, and are now free to everyone as part of this virtual issue. They are further promoted internationally through our social media network and we are hoping to see a number of you at the BJUI SoMe course during BAUS.

Enjoy the highest quality, most cited articles from Britain. And be very proud, you deserve it!

The Best of British

Prof. Prokar Dasgupta, Editor in Chief, BJUI, Guy’s Hospital, King’s College London. @prokarurol

Scott Millar, Managing Editor, BJUI. @BJUIjournal

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