Tag: #BJUI

Posts

Editorial: The impact of the surgical correction of Peyronie’s disease – a patient’s perspective

May 20, 2015/by David Ralph

Peyronie’s disease (PD) is an acquired benign connective tissue disorder of the tunica albuginea of the penis that leads to the formation of fibrous inelastic plaques. As a result of pain, worsening quality of erections, penile shortening and deformity, the quality of life of both the patient and their partner may be significantly affected, and this may lead to depression, low self-esteem and relationship difficulties [1].

At present, surgery represents the ‘gold standard’ treatment when PD is stable, and should be offered to guarantee a penis straight and rigid enough to allow penetrative intercourse.

The flow chart in the 2010 guidelines on PD indicates the type of surgery that should be offered according to the preoperative quality of the erection, degree of deformity and penile length, but patient perception of preoperative penile shortening is not taken into consideration [2]. Penile shortening does play an important part, however, with regard to postoperative patient satisfaction, as confirmed by Akin-Olugbade et al. [3], whose series of patients with PD reported the lowest satisfaction rates after penile prosthesis implantation.

According to the present series by Kueronya et al. [4], in which patient-perceived pre- and postoperative penile length loss in patients with PD was evaluated, 79.1% of patients perceived a degree of length loss attributable to PD, and a subjective loss of length of >2.5 cm translated into reduced ability with regard to sexual intercourse. In particular, patients who underwent penile prosthesis implantation reported more significant perceived shortening. This is not surprising, as patients with larger plaques, more severe forms of PD and fibrosis are more likely to have erectile dysfunction and ultimately to require a penile prosthesis implantation. Among patients who did not undergo penile prosthesis implantation, those requiring Nesbit plication reported less preoperative shortening than those requiring plaque incision and grafting, as the latter group presented with more severe deformities.

Further penile length loss caused by the surgical correction leads to bother to the patients, irrespective of the magnitude of the loss. The message from the present series by Kueronya et al. is that, to achieve higher postoperative satisfaction rates in this unfortunate cohort of patients, the choice of the type of surgery should take into consideration patient’s perceived preoperative penile shortening and not be based solely on the 2010 PD guidelines algorithm, because ultimately patients wish to obtain full restoration of the shape and size of penis they had before the onset of PD [2].

As patient’s perceived penile length plays such an important role in a patient’s postoperative satisfaction and because patients undergoing penile prosthesis implantation are those who have lost more length, length restoration should be offered simultaneously with penile prosthesis implantation [5, 6].

Kueronya et al. should be congratulated for their work, which is the first series evaluating patient’s perceived penile shortening and may represent a significant step towards the restoration of an adequate sex life in patients with PD.

Read the full article

Giulio Garaffa and David J. Ralph

St Peter’s Andrology and the Institute of Urology, University College London Hospitals, London, UK

References

1 Rosen R,Catania J, Lue T et al. Impact of Peyronie’s disease on sexual and psychosocial functioning: qualitative ﬁndings in patients and controls. J Sex Med 2008; 5: 1977–84

2 Ralph D, Gonzalez-Cadavid N , Mirone V et al. The management of Peyronie’s Disease: evidence-based 2010 guidelines. J Sex Med 2010; 7: 2359–74

3 Akin-Olugbade O, Parker M, Guhring P, Mulhall J. Determinants of patient satisfaction following penile prosthesis surgery. J Sex Med 2006; 3: 743–8

4 Kueronya V, Miernik A, Stupar S et al. International multicenter psychometric evaluation of patient reported outcome data for the treatment of Peyronie’s Disease. BJU Int 2015; 115: 822–8

5 Sansalone S, Garaffa G, Djinovic R et al. Simultaneous penile lengthening and penile prosthesis implantation in patients with Peyronie’s Disease, refractory erectile dysfunction and severe penile shortening. J Sex Med 2012; 9: 316–21

6 Egydio PH, Kuehhas FE, Sansalone S. Penile girth and length restoration in severe Peyronie’s Disease using circular and longitudinal grafts. BJU Int 2013; 111 (4 Pt B): E213–9

The Drugs Don’t Work

May 19, 2015/12 Comments/by Matthew Bultitude

For those pop enthusiasts amongst you, “The drugs don’t work” – the year was 1997; The band: The Verve. For those more urologically minded, you will immediately be thinking of the recent publication in the Lancet reporting on the use of tamsulosin and nifedipine vs. placebo for the medical expulsive therapy (MET) of ureteric stones. Current national (BAUS) and international (EAU guidelines) recommend the use of MET, usually with an alpha blocker – and often tamsulosin, and it has certainly become common practice in most Emergency and urology departments certainly across the UK and likely worldwide.

There have however always been doubts regarding the use of these with many small heterogenous studies with variable inclusion/exclusion criteria, various blinding protocols and suspicion of publication bias when only positive trials get published. Regardless, the clear outcome from the Hollingsworth meta-analysis was that both alpha blockers and calcium channel blockers are effective for helping stone passage and so they crept into routine clinical use. This trial should change all of that with headline results:

No change in spontaneous stone passage at 4 weeks for either drug vs. placebo or compared against each other
No difference when analysed by stone size or location
No difference in analgesic use or time to stone passage

Aren’t those all the reasons we prescribe them? The first question of course is whether this trial is accurate. It certainly is a large trial with 1167 patients, randomised to the three double-blind arms in 24 centres in the UK. The trial (like many modern studies) is described as pragmatic. This has pros and cons. The advantages are that it replicates real life clinical practice allowing for variations in decision making (e.g. follow-up imaging in this paper) thus making it generally applicable. The downside of course is the lack of precision that this can introduce with stone passage possibly being only patient reported, or based on ultrasound, plain x-ray, IVU or CT. I guess we have to decide which type of trial we prefer, although it would be very difficult to mandate CT follow-up, with concerns about radiation safety, in this trial if that isn’t part of routine practice. Thus maybe this study is actually applicable to the vast amount of units around the world.

Secondly did it include the right type of patient? Well the current guidelines suggest using MET for any stone measuring up to 1cm in any part of the ureter … and that is what this trial did. And this is thus a strength given that it didn’t just focus on the distal ureter. Thus the trial population seems reasonable. One possibility is that if MET only works in the distal ureter (as almost all the studies only look at this), this could this explain the negative findings. Sub-group analysis of this based on location or stone size seems to suggest not unless it was underpowered to show a difference for this cohort of patients.

Whilst the odds ratios (see table) seem clear, the Forest plot shows the breakdown of subgroup by sex, stone size and location. Whilst not statistically significant, this does suggest a trend towards favouring MET for lower ureteric stones.

Thirdly, is it possible this trial is wrong … a type II error ? Well of course anything is possible, and the trial may be criticised for the follow-up mentioned above. However it does seem to provide easily the best evidence to date. Thus why has the use of MET been allowed to become routine practice based on a number of small trials all introducing inherent bias which is then amplified when a meta-analysis is performed. I guess it was the best evidence around at the time although it makes you wonder how many other interventions there are that we currently use that are based on smallish trials, and would they actually stand up to the rigour of a well conducted big multicentre trial?

My last question is will this change practice again? Well it should, but with no alternative (except time, fluids and NSAID’s) to offer patients with ureteric stones and given that alpha blockers are usually well-tolerated, I wonder whether people will continue to prescribe MET for the foreseeable future. But if we believe in evidence based medicine, and we do, then surely we should no longer prescribe MET for ureteric stones which after all is an off-licence indication.

Finally congratulations must go to the NIHR and the research team for answering a very important clinical question. Was the whole ‘MET’ story a placebo effect all along … or to quote another less well known song title from The Verve, was it “All in the mind”? The conclusion from this excellent study has to be yes.

Conflict of interest: Acted as PI for Guy’s and St. Thomas’ Hospital for this trial recruiting patients although have no part of study design, data analysis or publication.

Matthew Bultitude

Consultant Urologist, Guy’s and St. Thomas’ Hospital

Associate Editor, BJUI

Editorial: Selecting the right α-blocker – is silodosin your best option?

May 13, 2015/by Hugo Lavigueur-Blouin

A significant proportion of aging men will have bothersome LUTS and will eventually seek help for this problem. Various medical therapies are available to help aleviate these symptoms. Amongst the various treatments, α-blockers are some of the most widely used drugs. Novara et al. [1] recently published a report on the efficacy and safety of silodosin in a pooled analysis of individual patient data from three registrational randomized controlled trials comparing silodosin and placebo in patients with LUTS. Their study contributes pertinent information to aid the clinician in determining which α-blocker is best suited for specific patients with LUTS.

In the current study, patients were subdivided into groups in order to better understand which patient would benefit most from the use of silodosin [2]. In addition, the article examines the safety of silodosin in these same distinct patient groups. With regard to efficacy, silodosin was significantly more effective than placebo in improving all IPSS-related variables and maximum urinary flow rate, regardless of the patient’s age. When comparing the efficacy of silodosin in different age groups, no difference was observed for any of the IPSS variables, whereas patients aged <65 years had a statistically significantly greater maximum urinary flow rate.

With regard to safety, silodosin was associated with a significantly higher adverse event (AE) rate compared with placebo. When comparing the safety of silodosin in patients aged <65 years and >65 years, the overall AE rate, ejaculatory dysfunction and discontinuation rate attributable to AEs were all higher in the younger age group. Interestingly, in patients with concomitant use of antihypertensive drugs, the use of silodosin was not associated with a higher risk of either dizziness or orthostatic hypotension.

In a previous study by the same authors, no clinically relevant or statistically significant differences with regard to diastolic blood pressure, systolic blood pressure or heart rate in patients taking silodosin as compared to placebo were found [3]; however, a minor statistically significant difference vs placebo was observed with tamsulosin. The present study by Novara et al. [2] further supports the belief that silodosin is a safe drug from a cardiovascular standpoint.

From a sexual standpoint, silodosin does not seem to perform as well. In the present study, patients in the silodosin group had significantly more adverse events as compared with the placebo group. Retrograde ejaculation was by far the most common side effect affecting 32.8% of patients aged <65 years vs 0.9% in the placebo group. Similarly, in a study by Chapple et al. [3], as many as 14.2% of patients in the silodosin treatment group had ejaculatory dysfunction, compared with 2.1 and 1.1% of patients in the tamsulosin and placebo treatment groups, respectively. Although the percentage of patients who discontinued treatment because of treatment-emergent AEs in the present study was small and not significantly different among all treatment groups, one might hypothesize that over a longer follow-up period, such a prevalent side effect could be responsible for a higher discontinuation rate. Consequently, it should be kept in mind that for patients desiring to maintain antegrade ejaculation, or who are bothered by treatment-onset ejaculatory dysfunction, especially younger patients, silodosin might not be the best treatment option. Furthermore, it should be recognized that some patients would potentially accept a reduction in treatment efficacy to preserve ejaculation [4].

With regard to clinical outcomes, few published papers comparing tamsulosin with silodosin are available [5, 6]. One article found no clinically significant difference between the two α-blockers [5] whereas the other, which was a post hoc analysis, found a marginal clinical benefit for silodosin over tamsulosin [4]. Unfortunately, head-to-head trials are not forthcoming, so it will not be possible to determine if one α-blocker is clinically better than the other. Furthermore, the present study, because it lacked an active control arm, did not compare silodosin with tamsulosin, which leaves something to be desired.

In conclusion, careful consideration should be given to specific patient characteristics such as age and comorbidities, along with personal preferences towards sexual function when offering patients α-blockers for treatment of LUTS.

Read the full article

Hugo Lavigueur-Blouin and Naeem Bhojani

Department of Urology, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada

References

1 Novara G, Chapple CR, Montorsi F. A pooled analysis of individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). BJU Int 2014; 114: 427–33

2 Novara G, Chapple CR, Montorsi F. Individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH): subgroup analyses of efﬁcacy and safety data. BJU Int 2015; 115: 802–4

3 Chapple CR, Montorsi F, Tammela TL et al. Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol 2011; 59: 342–52

4 Sturch P, Woo HH, McNicholas T, Muir G. Ejaculatory dysfunction after treatment for lower urinary tract symptoms: retrograde ejaculation or retrograde thinking? BJU Int 2014. doi: 10.1111/bju.12868

5 Montorsi F. Proﬁle of Silodosin. Eur Urol Suppl 2010; 9: 491–5

6 Novara G, Tubaro A, Sanseverino R et al. Systematic review and meta-analysis of randomized controlled trials evaluating silodosin in the treatment of non-neurogenic male lower urinary tract symptoms suggestive of benign prostatic enlargement. World J Urol 2013; 31: 997–1008

RSM Bladder Day

May 12, 2015/by Rebecca Tregunna

The urology section of the RSM left Wimpole Street and travelled up to sunny Queen Elizabeth Hospital in Birmingham on the 24th April to be educated in the ‘Management of Non-Muscle invasive and Muscle Invasive Bladder Cancer’. This meeting was organised in collaboration with Nick James and Rik Bryan at the Birmingham Warwick Uro-Oncology unit as the RSM looks to add to its regional programme of teaching days.

The meeting was well attended by both experts as well as trainees and we kicked off with John McGrath and a review of the evidence behind current haematuria investigations as well as the new NICE guidelines. Professor Charles Hutchinson from the University of Warwick then gave a detailed talk on pre-operative imaging in bladder cancer and this led to an interesting debate on the necessity of performing a full TURBT in cases of known muscle invasive disease if the patient will ultimately require a cystectomy. No consensus was reached although if definitely proceeding to cystectomy it is unlikely to be beneficial. If radiotherapy is considered then debulking is important.

Eva Comperat from the Service d’Anatomie and Cytologie Pathologiques du Pr Capron presented a fascinating histopathological perspective of bladder cancer and it was interesting to see that even amongst eminent pathologists there can be challenges in distinguishing pTa from pT1 disease with only 44% in one large study showing full agreement. The importance in reporting histological variants such as micropapillary or plasmocytoid was discussed due to the aggressive nature of these types and the need for more radical treatment. This was also re-iterated by Peter Rimington while discussing early cystectomy which should be offered to all suitable patients at high risk of progression according to EORTC tables, especially in young patients and in tumours which are multifocal, difficult to resect, have deep lamina propria or prostatic involvement and those with associated CIS.

A highlight for me was Professor John Kelly’s talk on the treatment option of hyperthermic Mitomycin C. HYMN Trial.

Data from the HYMN trial which looked at hyperthermic MMC vs. standard treatment in BCG failures was disappointing in that there was no difference in terms of disease free survival at 24 months. Outcomes were found to be worse in patients with CIS, but in patients with papillary disease, hyperthermic MMC had far more favourable results. This has led to the HIVEC I and HIVEC II trials currently recruiting in the UK and Spain looking at standard MMC vs. hyperthermic MMC in intermediate risk disease. It was also interesting to see new immunotherapy drugs currently in phase III trials which will hopefully be available in the near future.

Rik Bryan’s presentation on the evolving role of bio markers explained that the Bladder Cancer Diagnostic Programme had found that contrary to our beliefs, patients trust, and would rather accept certainty over burden and thus would rather continue with cystoscopic surveillance over bio-markers, unless the sensitivity of these bio-markers was over 99%. No such bio-marker has yet been found to be that accurate but current research into odor-readers, urinary dipsticks and DNA all look promising in terms of potential for both diagnosis and prognosis.

Both Nick James and Hugh Mostafid highlighted current research trials with the CALIBER RCT on chemo resection in recurrent low risk bladder cancer as well as the PHOTO trial looking at both clinical and cost effectiveness of photo-dynamic cystoscopy leading the way in terms of surgical trials currently recruiting. Nick also caused a stir on Twitter as he presented data showing a median survival advantage of more than a year between surgeons performing low or high volume of cystectomies annually. Surely we do not need more convincing evidence to centralise such surgery?

Reviewing bladder cancer from the oncologist’s perspective, Syed Hussein from the University of Liverpool explained that although there is a 6% overall survival benefit with neo-adjuvant chemotherapy there have been no RCT on MVAC vs gemcitabine/cisplatin regimes. Nick James’ talk on bladder preserving treatment added to this that synchronous chemoradiotherapy could be complementary to neo-adjuvant treatment and the addition of synchronous chemotherapy has been shown to provide a significant improvement in terms of loco regional control.

Vijay Ramani presented his series on salvage cystectomy with no significant difference in terms of complications for salvage vs. primary surgery as long as certain techniques were adopted such as division of ureters outside of the pelvis and using bowel at least 15-20cm proximal from the ileocaecal valve.

To complete the diverse and stimulating programme, Professor Peter Wiklund from the Karolinska University Hospital, Stockholm, presented a state of the art lecture on “Reconstruction rules! The robot has taken over?”. With discussion and impressive videos demonstrating intra-corporeal robotic neobladder reconstruction it was difficult not to be in awe of such an impressive series, with a 90% continence rate in males.

Overall it was fantastic to have the RSM in the West Midlands. Roger Plail has done much to reach out to those of us outside of London and I look forward to the Geoffrey Chisholm Prize Meeting and AGM on the 22nd May in Hastings. RSM President’s Day.

Rebecca Tregunna, Speciality Trainee, Burton Hospitals NHS Foundation Trust, West Midlands Deanery @RebeccaTregunna

What’s the Diagnosis?

May 8, 2015/by admin Z.9

Test yourself against our experts with our weekly quiz. You can type your answers here if you want to compare with our answers.

This image is taken from a recent BJUI paper (Bach et al, BJUI 2014).

No such quiz/survey/poll

Editorial: TRP channel – a reality that still requires many years of scientific efforts

May 6, 2015/by Francisco Cruz

Seventeen years have elapsed since the capsaicin receptor was first cloned by Caterina et al. [1] and the excellent review with an unusual provocative title by Deruyver et al. [2] was written. The capsaicin channel, re-named transient receptor potential (TRP) vanilloid receptor subtype 1 (TRPV1), is now commonly referred to as the founding member of the TRP family, as it currently includes 28 related channels, a number difficult to foresee in those early years [3].

TRP channels have been extensively studied in the lower urinary tract (LUT) with the aim of clarifying their role in micturition control and in the generation of LUTS. It is well accepted that TRP receptors have neuronal and non-neuronal expression [3, 4]. TRPV1 is fundamental to bladder hyperactivity and pain associated with LUT inflammation [3], while TRPV4 may participate in the generation of the normal sensation to void [5]. Another group of TRP receptors may even participate in bladder oncogenesis, which seems to be a role of TRPV2 [3]. The main substance of all this information is not a myth; rather it represents a large body of very solid scientific data.

There are certainly still many obscure areas. The distribution of TRP receptors in the bladder is certainly one of them. However, I disagree that a substantial part of available technical and financial resources have been allocated to study this matter. One should not forget that other matters, like the role of many TRP channels for bladder function, remain elusive. Broadly speaking, in my opinion, future key studies should tackle three very relevant but still unclear points. The importance of most TRP channels for bladder function is difficult to predict at the moment [3]. Just as an example, TRPA1 and TRPM8, which are sensitive to cold temperatures, are expressed in the bladder. However, the bladder, as all internal organs, is conserved at very constant physiological temperatures, making it difficult to understand the relevance of cold receptors to its function. Then, we need to find what the endogenous agonists for TRP receptors are in the LUT. Anandamide has been largely explored as an endogenous agonist for TRPV1 in the bladder [6], a fruitful observation as drugs able to manipulate endogenous levels of anandamide are currently being explored in clinical trials. The same holds true for the other members of the TRP family. TRPA1 may respond to infections due to its capacity to react to hydrogen sulphide [3]. But for the large majority of the TRP family endogenous agonists remain unknown. Finally, TRP antagonists that are simultaneously effective and safe must be generated. Most available TRPV1 antagonists, produced to date, although able to control bladder dysfunction in models of cystitis and spinal cord injury [3], cause hyperthermia and have been associated with an enlargement of ischaemic areas of the heart after coronary artery obstruction [3]. TRPV4 antagonists look very promising for controlling frequency but a compound safe for human use is still eagerly awaited [2]. Eventually the combination of antagonists for more than one of these receptors may prove effective at very low doses, so low that they do not generate serious adverse effects [7].

In conclusion, TRP receptors are a reality that still needs an enormous amount of work and dedication before becoming therapeutically useful. And that may take more time than we anticipate at the moment.

Read the full article

Francisco Cruz

Department of Urology, Al. Hernani Monteiro, Porto, Portugal

References

1 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389: 816–24

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

3 Avelino A, Charrua A, Frias B et al. Transient receptor potential channels in bladder function. Acta Physiol (Oxf) 2013; 207: 110–122

4 Birder LA, Kanai AJ, de Groat WC et al. Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci U S A 2001; 98: 13396–401

5 Gevaert T, Vriens J, Segal A et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 2007; 117: 3453–62

6 Dinis P, Charrua A, Avelino A et al. Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreﬂexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 2004; 24: 11253–63

7 Charrua A, Cruz C, Jansen K, Rozenberg B, Heesakkers J, Cruz F. Co- administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiates the effect of each drug in a rat model of cystitis. BJU Int 2014; [Epub ahead of print] doi: 10.1111/bju.12861

What’s the diagnosis?

May 1, 2015/by admin Z.9

Test yourself against our experts with our weekly quiz. You can type your answers here if you want to compare with our answers.

This image is taken from a recent BJUI paper (Huang et al BJUI 2015).

No such quiz/survey/poll

Is maintenance BCG an unnecessary evil? Summary of the April 2015 #urojc

May 1, 2015/by Sophia Cashman

The current BCG shortage, and the effect this is having on our bladder cancer patients, is an issue that continues to weigh heavily on many urologists. With no immediate solution in sight, and limited availability, a variety of tactics are being advocated to optimally use the current supply.

The April 2015 International Urology Journal Club #urojc debate focused on the timely paper by Martínez-Piñeiro et al¹. This paper reported the results of a randomised trial evaluating the outcomes of BCG induction followed by a modified three year maintenance regimen versus standard BCG induction alone in patients with high-risk non-muscle-invasive bladder cancer. The investigators concluded there was no observed decrease in recurrence and progression rates in those receiving just induction compared to induction and maintenance regimen.

This very topical debate kicked off on Sunday 12^th April.

Coinciding with the USANZ Annual Scientific Meeting, this month’s debate gave both those who were live tweeting at the conference, and those learning about the benefits of social media as a new concept, the opportunity to see the #urojc debate in action.

One of the first points of discussion raised was the difference between the maintenance protocol used in the study, consisting of one BCG installation every three months for three years, and the standard SWOG schedule.

The lack of difference in outcome between the two groups raised the question as to whether this indicated that their modified maintenance protocol is less effective that the current strategies.

The theme of alternative maintenance schedules continued, with some variation in practice noted.

Some of the variability in maintenance may be due to the tolerability and side effects experienced.

Although there may be a degree of acceptance amongst patients if there is thought to be a chance of improvement in risks of disease recurrence or progression.

The reason for the variability of response to BCG therapy between patients remains unclear.

For the patient, the lack of understanding of why this is the case may be a cause of distress, especially when faced with adverse effects and toxicity.

Inevitably it was not long until the key on-going issue of the lack of available BCG was raised.

This issue continues to cause a lot of angst for both patients and their treating urologists, with no immediate solution evident. There may however be light at the end of a somewhat long tunnel with the restarting of production by Sanofi.

In the mean time, the downstream effects of the production delay continues to compromise the treatment options for bladder cancer patients.

As the availability remains largely outside of clinicians’ hands, perhaps our focus at present needs to be on other factors we can control in order to improve the outcomes for our bladder cancer patients.

This debate surrounding this paper has raised a number of key points that, in the face of the BCG shortage, are worth considering. Until the supply is re-established, the BCG we have needs to be optimally used – however perhaps the most effective maintenance schedule needs further investigation. Or perhaps, due to the variation in tolerability and effectiveness between individuals, maintenance therapy needs to remain a more fluid concept.

As always, the #urojc debate involved healthy international discussions. This gives the unique ability to understand the global viewpoints on the study findings, and the current BCG crisis. Analytics of the debate using the #urojc hash tag from the website www.symplur.com again demonstrated the excellent involvement from participants, with over 180,000 unique impressions.

Thanks to all of those who participated this month. We look forward to the #urojc May debate – I am sure it will be as lively as ever.

1. Martínez-Piñeiro L, Portillo JA, Fernández JM, et al. Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013. European Urology March 2015 (Article In Press)

Editorial: Cardiopulmonary exercise testing: fortune-teller or guardian angel?

April 29, 2015/by John McGrath

In this month’s issue of BJUI, Tolchard et al. [1] describe their experience with the use of cardiopulmonary exercise testing (CPET) in patients undergoing radical cystectomy. In particular, they assess the value of cardiopulmonary reserve in predicting complications and the length of stay in hospital after surgery.

The origin of CPET is in non-surgical specialties for the further investigation of patients with cardiac failure or unexplained breathlessness [2], but it subsequently gained utility in surgical fields, including the preoperative assessment of patients undergoing cardiac surgery [3].

In more recent times, it has been increasingly adopted within ‘high-risk’ preoperative assessment clinics for those patients undergoing a wide range of major elective, non-cardiac surgery; however, this enthusiastic uptake has often preceded more formal validation of the test’s ability to perform reliably in these new patient groups and their associated surgical procedures. The Bristol group [1] has therefore prospectively studied the role of CPET in 105 patients undergoing either robot-assisted or open radical cystectomy for TCC, using all-cause complications and length of stay as the primary outcome variables.

The researchers found that anaerobic threshold (AT), ventilatory equivalent for carbon dioxide (VE/VCO₂) and hypertension were independent predictors of postoperative complications. Using the criteria chosen by Older et al. [4] of an AT ≤ 11 mL/kg/min and or VE/VECO₂ ≥ 33, it was possible to define a high- and low-risk group. The high-risk group were 5.5 times more likely to experience a complication at 90 days compared with the low-risk group and, notably, all deaths and myocardial infarctions occurred in the high-risk group. As expected, they found that complications prolonged length of stay. Additionally, falling AT and or rising VE/VECO₂ also correlated with increasing length of stay. Their study therefore suggests that CPET may have a role in the preoperative risk stratification of patients undergoing radical cystectomy by an open or robot-assisted approach.

The authors acknowledge that the cohort size is small and from a single institution, thereby necessitating further validation work across multiple centres, as well as subgroup analysis of differing surgical approaches. Interestingly, their study excluded patients who had received neoadjuvant chemotherapy; for many UK cancer centres, this would exclude ∼70% of patients undergoing radical cystectomy. It would clearly be important in future studies to understand how CPET metrics perform in this wider cohort, where anaemia and impaired performance status are known to be more common.

On the assumption that further studies may validate the use of CPET as a preoperative risk-stratifying tool, the pertinent question is how do we translate this research finding into patient benefit? Interventions such as preoperative patient optimization, pre-habilitation exercise regimes or the planned escalation of postoperative care may confer benefits but, as yet, we do not know if they attenuate the increased risk of complications or the prolonged inpatient stay.

As further evaluation of CPET takes place, we should remain cautious about its use as a ‘rule-out’ investigation in those patients otherwise considered eligible for radical surgical treatment. To date, there have been no formal evaluations of patients’ quality of life or end-of-life care in ‘non-operated’ cases. Poor local control of pelvic malignancy remains one of the most challenging aspects of care for uro-oncologists and, at times, it may even outweigh the impact of postoperative surgical complications. Due consideration must be given to this aspect when advising individual patients about the predicted risks and benefits of therapeutic treatment options. The decision to operate should clearly be informed by the preoperative assessment, but it is imperative that it continues to involve the patient’s wider multidisciplinary team, whose responsibility it will be to provide lifelong care.

In conclusion, CPET offers an interesting opportunity to identify those patients at greatest risk of adverse outcomes after radical cystectomy; however, the full benefits will not be realized if it is simply the ‘bearer of bad news’. The key to its success will be the identification of modifiable behaviours, by both the patient and the clinical team, that lead to improved patient-related outcomes. These outcomes should not be restricted to overall or cancer-specific survival but also measures of return to good health and prior performance status. Such longer-term outcome data may then help us to more accurately delineate the point at which the risks of a surgical treatment can be confidently predicted to outweigh the alternative of non-operative care for individual patients.

Read the full article

John S. McGrath

Royal Devon and Exeter NHS Trust, Exeter, UK

References

1 Tolchard S, Angell J, Pyke M et al. Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications following radical cystectomy. BJU Int 2014; [Epub ahead of print]. doi: 10.1111/bju.12895

2 Szlachcic J, Massie BM, Kramer BL, Topic N, Tubau J. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 1985; 55: 1037–42

3 Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991;83: 778–86

4 Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116: 355–62

Editorial: A 3D window into the body?

April 22, 2015/by Matthew Bultitude

If real-time tracking is accurate enough to tell you that Roger Federer’s serve was on the line or that David Beckham’s free kick was indeed over the goal line, then surely tracking systems could help us guide needles and wires into different parts of the body? In this month’s BJUI, Marien et al. give us an insight into the future of access for percutaneous procedures [1]. Currently, percutaneous access to the body for biopsy, renal access or treatment of malignancy is usually based on two-dimensional imaging, with the expertise of the operator compensating for the lack of real-time three-dimensional (3D) visualization of the surgical field. In this paper, the authors hypothesized that integrating virtual reality visualization with real-time position tracking of the needle/instrument would improve navigation. This improvement remains unproven and the study is a first step on that road.

The authors assess the feasibility of a novel method of percutaneous access (Translucent^TM Medical Inc.) using a freely movable tablet display to help guide the percutaneous puncture to its target (see Fig. 1). The success of such a system would rely on a high degree of accuracy and the authors set out to test this in a cadaveric model. Fiducial markers were placed in the kidneys and prostates of cadavers to mimic tumours. A CT scan was then performed to allow 3D model reconstruction. An electromagnetic field was generated around the body and magnetic sensors (fixed to the skin and in the urethral catheter) were used for localization. The software then allows real-time demonstration of the needle trajectory with a predicted line beyond the needle tip overlaid on the 3D model. The authors were able to quickly reach the target (mean time 43 s) with apparent good accuracy, which was calculated to be within 2.5 mm; however, further fiducial markers were deployed at the centre of the target to allow the accurate measurement of accuracy. The distance between the ‘target’ fiducial and the ‘treatment’ fiducial was 16.6 mm in the prostate and 12.0 mm in the kidney. This difference was probably attributable to either movement of the organ or deformation of it from the needle puncture itself. These errors were predominantly in the z-axis (i.e. depth), suggesting that they were caused by movement and deformation by the needle itself, which therefore poses the challenge of how the errors might be reduced, especially when a living human model may have more compliant tissues and of course be moving with respiration.

Figure 1. Tablet screen displaying real-time ‘three-dimensional window into the body’ with real and projected trajectory of needle

The present paper by Marien et al. is not the first report of using tracking for percutaneous access in urology. Using different technology, Rassweiler et al. [2] reported on the percutaneous puncture of the kidney for nephrolithotomy using an iPad with surface skin markers, which were visualized by the rear-facing camera of the iPad, and this information was processed to calculate the location of the tissues beneath based on a preoperative CT. This system, and I suspect all others, will rely on a CT being performed in the exact position of the surgery, which is another limiting step until this can be performed at the same time as the surgery.

There are of course concerns regarding use of this technology. The accuracy was limited when analysing the actual position of the ‘treatment’ fiducial because of movement of the tissues. This is likely to be worse in living tissue. There was no respiratory movement which would probably make accurate tracking difficult, although placement of markers to allow movement tracking may help overcome this. Rodrigues et al. [3] reported high accuracy of percutaneous nephrolithotomy puncture after deployment of an electromagnetic sensor in the target calyx with ureterorenoscopy in a porcine model but without a 3D model.

My major concern is that of false reassurance. A nice image is portrayed on the screen which is believed by the surgeon, while in fact there is a significant mismatch caused by patient/tissue movement, either since the preoperative planning CT scan or intra-operatively. The falsely reassured surgeon then inadvertently damages surrounding organs.

It is clear that this technology is work in progress, but it does offer promise that real-time tracking of a percutaneous needle is possible, with accurate representation on a 3D model reconstruction helping to guide the surgeon to the target.

Read the full article

Matthew Bultitude

Department of Urology, Guy’s and St. Thomas’ Hospital, London, UK

References

1 Marien A, De Castro Abreu AL, Desai M et al. Three-dimensional navigation system integrating position-tracking technology with movable tablet display for percutaneous targeting. BJU Int 2015; 115: 659–65

2 Rassweiler JJ, Muller M, Fangerau M et al. iPad-assisted percutaneous access to the kidney using marker-based navigation: initial clinical experience. Eur Urol 2012; 61: 628–31

3 Rodrigues PL, Vilaca JL, Oliveira C et al. Collecting system percutaneous access using real-time tracking sensors: ﬁrst pig model in vivo experience. J Urol 2013; 190: 1932–7