Tag Archive for: #BJUI

You are here: / #BJUI

Posts

Editorial: Accepting the positive results of unconventional methods

/1 Comment/by

It is sometimes difficult to accept the results of a study based on a concept that is unfamiliar, involves unknown physiological mechanisms, or shows results that defy rational explanation. Remote ischaemic preconditioning (RIPC) is probably not a familiar topic to most urologists and, admittedly, was not familiar to this reviewer until now. Yet the authors, based on animal models and clinical data from non-urological literature, conducted a prospective, surgeon and patient ‘blinded’, randomised controlled trial to evaluate the potential benefit of RIPC in minimising ischaemic damage. By most available factors affecting postoperative renal function (warm ischaemia time, tumour complexity as measured by Preoperative Aspects and Dimensions Used for an Anatomical [PADUA] scores, preoperative renal function, tumour stage, etc.), no difference existed between the control and study groups. The authors found that patients undergoing RIPC had a lower change in estimated GFR (eGFR) at 1 month and appeared to have less ischaemic damage based on urinary marker levels (retinol binding protein) and functional imaging parameters. Unfortunately, the short-term benefit of RIPC did not translate to improvements over a longer period, with no differences at 6 months or in absolute eGFR between the two groups.

The authors should be congratulated for conducting such an elegant trial, unfamiliar and unconventional as the concept may be. Strengths of this study include its randomised ‘blinded’ design, correlation with metabolite, urinary marker and imaging findings, 6-month follow-up, and due diligence for assessing most pre-analytic factors. Limitations include the absence of data on residual functioning renal parenchyma, which arguably is the single best predictor of function in an operated kidney; additionally, this population with outstandingly good renal function (≈120 mL/min/1.73 m2 in both groups) with very few comorbidities (<5–10% incidence of hypertension and diabetes) may not translate equally to the less healthy, more renally impaired Western population. The results may appear to be underwhelming, but I agree with the authors that further study is needed, and in particular for the Western population. The major impact from this reviewer’s perspective is for the patient with baseline renal compromise, whose risk for short- and long-term ischaemic renal injury is greater, and who could most benefit from a simple protective measure. Should we now enter unfamiliar territory and accept that the results of a randomised, ‘blinded’, prospective trial of a simple but unconventional method provide sufficient justification for testing this strategy in a higher risk population?

Surena F. Matin
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Read the full article

Editorial: Equivalent outcomes for monopolar and bipolar TURP; but are we overlooking the potential for improvement in sexual function after surgery?

/by

Both BPH and sexual function (SF) have a major impact on quality of life in older men. Sexual dysfunction is a complex process encompassing both erectile and ejaculatory dysfunction, as well as reduced libido and difficulty achieving orgasm. Whilst retrograde ejaculation is an almost inevitable consequence of TURP, the evidence that TURP causes erectile dysfunction is conflicting. This is probably attributable, at least in part, to a lack of high-quality historical data. Studies now show that LUTS is a risk factor for sexual dysfunction, and we are becoming increasingly aware of the relationship that exists between LUTS, depression and sexual dysfunction.

Given the favourable safety profile of bipolar TURP (b-TURP), it is perhaps a surprise that this latest study from Mamoukalis et al. has failed to demonstrate any difference in outcomes with regard to the deterioration in SF after surgery. The authors should be praised for their attempts to examine in fine detail (using the International Index of Erectile Function [IIEF]-15 in this case) any potential differences between b-TURP and monopolar TURP (m-TURP).

The design of the bipolar system is such that tissue is removed at a lower temperature and therefore the likelihood of damage to surrounding tissues and nerves is reduced. Several randomized trials have compared b-TURP with m-TURP, but only a small number have looked specifically at sexual variables in a randomized setting. This multicentre study by Mamoukalis et al. randomized 279 men to one of the two resection techniques, looking specifically at overall SF quantified by the IIEF-15. No differences were detected in any aspect of SF; erectile function (EF) improved in 26.4% of patients in the m-TURP group compared with 19.6% in the b-TURP group, and remained stable in 60.9 and 60.8% of patients, respectively. A deterioration in EF was apparent in 12.7% of the m-TURP group compared with 19.6% of the b-TURP group (P = 0.323). These results mirror those of a similar randomized study by Akman et al. comparing a quasi-bipolar system with m-TURP. They demonstrated equivalence for all measured variables except for operating time and a 1.4% incidence of TUR syndrome in the m-TURP group. In their study, the EF domain of the IIEF-15 was measured before and after surgery. EF worsened in 17% of men, improved in 28.2% and was unchanged in 54.8%. A comparative evaluation of EF was performed in a sub-group of 188 sexually active non-catheterized men of whom 18.2% developed de novo erectile dysfunction.

The explanation for the equivalent outcomes is unclear and further investigation is required. Does the failure of bipolar TURP to demonstrate a benefit with regard to SF leave the door open for the competing minimally invasive laser technologies? The overall impact of the holmium laser compared with that of TURP appears to be equivalent, with a mean of 7.5 and 7.7% of patients reporting decreased erectile function, and 7.1 and 6.2% of patients reporting increased function after each surgery. From the data available thus far, it would also appear that photoselective vaporization of the prostate similarly has no overall deleterious impact on SF when compared with TURP in a randomized trial. Further randomized data are pending and are of course of great importance if we are to understand better how the procedures we perform for symptomatic BPH affect our patients. As technological advances are made the hope is that the ‘damaging’ effects of BPH surgery on overall SF (particularly EF) will reduce further, but it may indeed be that we are searching for small margins when our attention might be better focused on maximizing the likelihood of a positive outcome, facilitated by considering the preoperative status (general health as well as urinary and sexual function), aided by the use of validated questionnaires. A better appreciation and understanding of the factors that may increase the risk of ED after surgery (age, diabetes, metabolic syndrome, obesity, cardiovascular disease and psychological factors) will enable us to manage expectations more effectively. A shorter hospital stay with minimal postoperative discomfort and an early return to normal activities, coupled with good symptomatic improvement in the longer term can only serve to be of benefit with regard to improving SF outcomes.

One recent study reporting both the short-, medium- and long-term effects of TURP on SF highlighted the high incidence of LUTS before treatment with 57% overall reporting ED before surgery. Those with severe LUTS were much more likely to have significant sexual dysfunction before surgery. This study also demonstrated a 15% improvement in pre-existing ED which was related to the improvement in LUTS after TURP.

On reflection, therefore, it would seem reasonable to conclude from the evidence presented that, although retrograde ejaculation frequently occurs after outflow surgery, erectile function is as likely to improve as it is to deteriorate. By focusing on the specific patient characteristics for each individual case before surgery it is possible we can improve the proportion of patients achieving a favourable outcome. When counselling patients before surgery regarding SF we should therefore remember to include the potential benefits as well as the risks. Furthermore, for those patients particularly anxious about the possibility of worsening SF, a ‘lesser’ surgical procedure, which might not achieve a transurethral resection-like cavity should perhaps be considered as a compromise. However, a surgical alternative which is not equivalent to TURP may indeed reduce the likelihood of improving erectile function, given the interrelationship that appears to exist between LUTS and SF.

Richard Hindley
Department of Urology, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK.

Read the full article

Urologists up in arms? ….Diclofenac no longer indicated in high risk groups

/3 Comments/by

This blog is an update form the originally published comment article in BJU International, 110: 607–608.
DOI: 10.1111/j.1464-410X.2012.11330.x

On the 23rd June 2013 the MHRA (The Medicines and Healthcare products Regulatory Agency) issued a press release stating that ‘patients with serious underlying heart conditions, such as heart failure, heart disease, circulatory problems or a previous heart attack or stroke should no longer use diclofenac’. The MHRA is responsible for regulating all medicines and medical devices in the United Kingdom (UK) by ensuring they work and are acceptably safe.

 

 

The new guidelines in the UK state:

  • Diclofenac is now contraindicated in patients with established:
    – ischaemic heart disease
    – peripheral arterial disease
    – cerebrovascular disease
    – congestive heart failure (New York Heart Association [NYHA] classification II–IV)

Patients with these conditions should be switched to an alternative treatment at their next routine appointment

  • Diclofenac treatment should only be initiated after careful consideration for patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Now for urologists in the UK this has wider implications. What else are we to use for acute renal colic, chronic pelvic pain, prostatitis, urethritis and any other type of..-itis?

We are treating an ever aging population and the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, will increase. NSAIDs have been the cornerstone of pain relief in patients with first presentation of renal and ureteric lithiasis. The British Association of Urological Surgeons (BAUS) and the European Association of Urology (EAU) guidelines for the acute management of renal and ureteric lithiasis state the first line analgesia is an NSAID e.g. diclofenac [1][2]. There have been a number of clinical trials which have clearly shown that NSAIDs provide effective relief in patients who have acute stone colic [3][4][5].

Controversies of NSAID use

Rofecoxib (trade name Vioxx ®), was approved by the Food and Drug Administration (FDA) in May 1999. The drug was heavily promoted by the global pharmaceutical and chemical company Merck as safer than older generation NSAIDs. The increased risk of stroke was highlighted in a large study, the Vioxx gastrointestinal outcomes research (VIGOR) study, published in the New England Journal of Medicine in 2000. Merck voluntarily took rofecoxib off of the market on 30 September 2004 after research showed that it almost doubled the risk of myocardial infarction and stroke when taken for 18 months or longer. In 2007 Merck paid $4.85bn to settle about 26 000 lawsuits in the United States relating to the drug in state and federal courts.

What are the alternatives suggested?

Naproxen and low-dose ibuprofen are considered to have the most favourable thrombotic cardiovascular safety profiles of all non-selective NSAIDs. There is limited evidence for the use of naproxen and low-dose ibuprofen in the management of acute renal colic. We do not know if the efficacy is equivalent to diclofenac. There are a lot of unanswered questions since the press release, but the key questions remain: Is this guidance applicable to us as urologists? And will this change my practice?

This topic is an important area for urologists to be aware of as NSAIDs are prescribed daily in urological practise to a wide range of patients. There is some caution that has to be exercised when reviewing the published data. In a recently published meta-analysis by the Coxib and traditional NSAID Trialists’ (CNT) Collaboration group their data provides further evidence that the vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs.

The majority of trials evaluating the cardiovascular risk of NSAIDs have looked at a group of patients with predominately arthritis or Alzheimer’s disease; not a typical urological cohort of patients. None of the studies in the meta-analysis looked at the short term use of NSAIDs, in particular diclofenac. Some may argue that absolute rates of events were low and clinically irrelevant as the event rates in the included trials are considerably lower than in routine clinical settings.

The options for the treatment of acute urological pain have not changed in the past 15 years. COX-2 selective inhibitors and diclofenac are associated with an increased risk of thrombotic events. Naproxen is associated with a lower thrombotic risk and low doses of ibuprofen (1.2 g daily or less) have not been associated with an increased risk of myocardial infarction. The lowest effective dose of NSAIDs should be prescribed for the shortest period of time to control the symptoms and the need for long term treatment should be reviewed periodically. As we treat an ever aging population with increasing medical co-morbidities the widespread use of NSAIDs has to be evaluated and urologists need to keep up to date with current prescribing guidelines and long term cardiovascular risk factors. 

 

Jonathan Makanjuola is a Urology Trainee, Innovator and techie based at King’s College Hospital, London, United Kingdom. @jonmakUrology

References

  1. EAU guidelines on urolithasis. European Association of Urology; 2011. https://www.uroweb.org/gls/pdf/18_Urolithiasis.pdf. Accessed 12 December 2011.
  2. Guidelines for acute management of first presentation of renal/ ureteric lithiasis (excluding pregnancy). British Association of Urological Surgeons; 2008. https://www.baus.org.uk/AboutBAUS/publications/stones-guidelines. Accessed 12 December 2011.
  3. Phillips E, Kieley S, Johnson EB, et al. Emergency room management of ureteral calculi: current practices. J Endourol 2009; 23: 1021–1024.
  4. Micali S, Grande M, Sighinolfi MC, et al. Medical therapy of urolithiasis. J Endourol 2006; 20: 841–847.
  5. Engeler DS, Schmid S, Schmid HP. The ideal analgesic treatment for acute renal colic–theory and practice. Scand J Urol Nephrol 2008; 42: 137–142.

 

 

Comments on this blog are now closed.

 

 

Editorial: Impact of ERSPC study on PSA testing in the Netherlands

/2 Comments/by
General practitioner (GP)’s view on screening for prostate cancer in the Netherlands: the impact of a randomized trial

I am grateful to be given the opportunity to provide an editorial comment on a so-far unique publication investigating the impact of results of the European Randomized study of Screening for Prostate Cancer (ERSPC) on the attitude of Dutch GPs in requesting a serum determination of PSA in men aged >40 years. Access to data from one of the major health insurance companies and the structure and data acquisition of regional laboratories in the Netherlands provided an opportunity to carry out the project. This included the differentiation of age groups, of primary as opposed to repeat PSA testing and, in the case of the hospital database, of repeat PSA testing within 1 year, which provided the opportunity to address the primary goal of the study: the evaluation of the difference in primary PSA testing rates as well as follow-up testing before and after the 2009 publication of interim data from the ERSPC study. The fact that a Dutch translation of this publication and a recommendation by the Dutch Association of General Practitioners (Nederlands Huisartsen Genootschap, NHG) were mailed at the same time and the fact that GP guidelines had not been changed since 2005 in the Netherlands provided an important basis for the reported study.

Two different databases were used and PSA testing was evaluated 1 year before and 1 year after March 2009 (excluding the month March 2009). An overview of the data acquisition and results is given in Table 1. In brief, the data based on insurance claims show a significant decrease in PSA use before and after the 2009 publication. This decrease was less pronounced or not seen at all in men aged 70–80 or >80 years. The study selectively identified men in the ERSPC region of Rotterdam after exclusion of those assigned for re-testing in the screening arm. In line with earlier investigations, the PSA testing rate in the Rotterdam region was considerably higher then in the rest of the Netherlands. This effect was blamed on increased awareness and possibly on the motivation of men randomized into the control group of the study. The so-called ‘hospital database’ refers to a regional GP laboratory. It remains unexplained why only 2098 men of the total of 9766 men who were identified as having undergone primary PSA testing (Tables 1 and 2 in the study) were included in the analysis. These data show that there was no overall difference in testing before and after the ERSPC publication, but the proportion of re-testing decreased significantly between the two periods.

Table 1: Data acquisition and results.

Several comments can be made on this study. First, information provided on the insurance claims database allows an estimate of the proportion of men in whom PSA is evaluated (123 996/715 000 = 17.3%) and of those who undergo primary PSA testing for early diagnostic purposes (66 848/715 000 = 9.4%). The overall figure contrasts sharply with the results of a study by the Central Bureau of Statistics in the Netherlands, published in 2006. The study shows PSA use of 30–40% for the age groups 60–70 years or older.

Second, as the authors acknowledge, the differentiation between primary PSA tests for the purpose of early diagnosis and for other purposes may not be entirely reliable; however, the bias resulting from possibly incorrect assumptions is likely to be small.

Third, the sub-analysis of data coming from the Rotterdam region is likely to show the impact of greater awareness resulting from written informed consent before randomization and the effect of randomization into a control group. The data confirm an earlier evaluation of this subject (reference 7 in Van der Meer et al.) and at the same time provide a rough estimate of the level of contamination which may take place in the ERSPC study, Rotterdam region.

Fourth, it is interesting to see how age and previous PSA values influence the request for repeat PSA studies. It is counterintuitive (Table 3 in Van der Meer et al.) that even in the critical PSA range 4–10 ng/mL a significant decrease of PSA use within 1 year was seen. The multivariate analysis shows that study period before and after 2009, PSA categories and age groups are all significantly related to the decrease of PSA re-testing within 1 year.

Finally, as one of the initiators of the ERSPC study, I should like to refer to two important follow-up publications (Schröder et al., Heijnsdijk et al.) that point to the over-diagnosis and over-treatment of prostate cancer as the main reasons why the almost 30% reduction in prostate cancer mortality in screened men cannot (yet) be used for establishing population-based screening. For these reasons, the authors fully agree with the viewpoint of the Dutch GP Association and the recommendation against routine use of PSA-driven screening for prostate cancer; however, as pointed out in the last sentences of their paper instruments are now available to decrease over-diagnosis and the rate of unnecessary biopsies. In addition to that, it should be realized that men who are well informed and wish to be tested for prostate cancer cannot be refused PSA testing. To assist this process, the International Society of Urology (SIU) and the international movement ‘Movember’ have recently made available on their websites a validated decision aid for men who wish to be tested, their GPs and their treating urologists.

Fritz H. Schröder
Erasmus Medical Center, Rotterdam, The Netherlands.

Read the full article

Bladder Cancer: a stagnant foe?

/6 Comments/by

This month’s topic for the Twitter-based International Urology Journal Club #urojc was bladder cancer, with a paper titled ‘Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades’ by Zehnder et al, published online in July 2013. Open access to the paper was kindly provided by the BJUI.

 Zehnder and colleagues undertook a retrospective analysis of the University of Southern California cohort and identified 1488 patients with muscle invasive bladder cancer who underwent radical cystectomy and extended pelvic lymph node dissection between 1998 and 2005. They also included 190 patients from the University of Bern cohort to determine outcomes in patients with clinical N0 disease who were upstaged on pathology to node positive disease. Analysis, performed based on decade of intervention, showed no significant difference in overall survival (OS) or recurrence free survival (RFS) over the three decades. 10-year RFS was 78-80% for organ confined, lymph node negative, 53-60% in locally advanced, LN –ve and 30% in LN positive patients.

 

 

Firstly, it has certainly been suggested that the overall survival and cancer free survival outcomes are not as good in broader population based studies (Ontario Cancer Registry). Why?

 

 

 

 

Analysis of the SEER database has shown that cancer specific survival and overall mortality has not improved for any clinical stage of bladder cancer and in fact suggests that the incidence is increasing in the United States.

 

 

And of course, we must always look at the study design and determine whether the outcomes are reflective of the patient populations that we see in practice.

 


 

The roles of neo- and adjuvant chemotherapy were discussed at length. Only 6% of patients received neoadjuvant chemotherapy, with worse OS and RFS in multivariate analysis. The use of adjuvant chemotherapy actually almost doubled from the 80’s to 90’s, stable in the 00’s at 29%.

 

  

 

 

 

 

 

If neoadjuvant chemotherapy is so widely recommended, why has its use failed to take off?

 

 

 

 

 

 

 

Jim Catto suggested an excellent clinical pathway for the implementation of neoadjuvant chemotherapy.

If indeed bladder cancer is the poor cousin of prostate cancer, why has progress stagnated and what can we change?

 

 

 

 

 

 

 

 

 

 

So what are my humble take home messages from the discussion surrounding this month’s #urojc paper?

  1. Current data suggests that we have made no significant progress in bladder cancer outcomes over the past 30 years
  2. Early referral and diagnosis coupled with timely intervention key; be wary of progression in context of high grade NMIBC
  3. Both surgeon volume and hospital volume are thought to be independent predictors of overall survival. Patie nts do best at a high volume facility under the care of a high-volume Uro-oncologist in a multidisciplinary context
  4. Neoadjuvant chemotherapy, despite randomized controlled trial evidence in favour of its use, has poor uptake in a real world setting. Advances in dense dose regimens (MVAC and Phase III GC underway) with resultant improvement in progression free survival, lower toxicity profile and fewer dose delays make for an attractive partner to radical cystectomy and extended pelvic lymph node dissection.

To finish with the words of the self-proclaimed Urology King of Twitter, Dr Ben Davies:

 

 

 

Winner of the best tweet prize for July’s #urojc was Mike Leveridge from Queens University, Canada – he was certainly a little frustrated with the apparent lack of progress we have made. The July #urojc Best Tweet Prize was kindly supported by the Nature Journal “Prostate Cancer Prostatic Diseases” which is edited by Dr Stephen Freedland and will be a complimentary 12 month online access to the journal.

 

 

 

 

 

 

Do join us for the August #urojc which commences on Sunday 4th/Monday 5th depending on your time zone.

Dr Helen Nicholson is an Australian Urology Trainee, currently based at The Sydney Adventist Hospital, NSW. Tweeted initially under duress, now a voluntary convert @DrHLN

 

Comments on this blog are now closed.

 

 

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

/by

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
© 2024 BJU International. All Rights Reserved.