Category: BJUI Blog

EAU14 – The Multifaceted Goals Of Andrology: Maintaining Quality Of Life

April 13, 2014/2 Comments/by John Davis

A famous version of a saying attributed to Benjamin Franklin states “…but in this world nothing can be said to be certain, except death and taxes.” As a urologic oncologist, I cannot help with the taxes, but strive to delay the latter when threatened by urologic cancers. Our colleagues in andrology, however, are charged with the task of being sure the life lived is of high quality, and I am impressed at the large number of problems they face including infertility, erectile dysfunction, andhypogonadism. The latter problem is quite comprehensive when you consider the associated risks of cardiovascular disease, type 2 diabetes, sexual dysfunction, reduced energy, reduced muscle mass, weight gain, and many more. With this challenge, the first plenary session at the 2014 EAU gave an update on andrology with significant cross-over appeal to the uro-oncologist.

Prof W.H-G. Weidner started the session with an overview of male factor infertility, which comprises 50% of the contribution to childless couples. The causes can be idiopathic but then include primary testicular failure,varicocele, genetic disorder, obstruction, male accessory gland infection, hypogonadism, germ cell malignancy, and ejaculatory dysfunction. The diagnosis requires a comprehensive andrological exam if two separate semenalyses are abnormal.

Figure 1 Prof. W.H-G. Weidner from Giessen (DE) gave the first plenary presentation at the 2014 EAU, Stockholm, Sweden

Varicocele repair is known to improve ejaculate quality, however the effect on pregnancy rates does not always follow—counseling for the couple is also effective. The other major surgical intervention involves various techniques of microscopic sperm retrieval with essentially 100% retrieval rates. All factors considered, this leads to an approximate 20% “baby take-home” rate when used with ICSI. An interesting new trend is pediatric oncologist requesting sperm retrieval and cryopreservation for pre-pubertal patients who need chemotherapy.

Prof. S. Arver from Stockholm (SE) then reviewed the topic of testosterone supplementation in the ageing male. As a uro-oncologst in the 4th largest city in the USA, this is an every day topic. On the way to work I heard radio advertisements for local “Low-T Centers” that aim to attract potential patients who may be tired, or having problems with their sex life. Once I get to work, I see the new patients with an elevated PSA discovered as a downstream event once they’ve started testosterone replacement and had subsequent screenings. What do we know about the diagnosis of testosterone insufficiency and risks/benefits of replacements?

First, the diagnosis of testosterone (T) insufficiency is a combination of symptoms and laboratory assessment. Total serum T should be measured as a morning sample between 7-10am and fasting. If an afternoon measurement is low, it should be repeated in the proper circumstance. If the level is > 12 nmol/L it is likely normal, while 8-12nmol/L is a “grey zone” and < 8 nmol/L is probably associated with symptoms that would respond to therapy. The grey zone implies that some men can be symptomatic in the lower end of a normal range. In addition, a serum LH > 9 supports deficiency as the internal thermostat is trying to compensate, whereas LH 2-9 is uncompensated and may be a transient state.

The symptoms of low T are quite a list and organized under the categories is Physical/metabolic (decreased bone mineral density, muscle strength, etc.), sexual symptoms (libido, ED), and psychological (energy, fatigue, mood, etc.). To make matters worse, hypogonadism has a high prevalence with chronic renal failure, rheumatic disease, HIV, COPD, cancer therapy, opioid use, steroids, and male infertility. Of course, the most significant long-term concerns would be cardiovascular risk and type II diabetes. You can infact try using SARMs rather than steroids which is lot more better than steroids as per research studies. You can visit ceasar-boston.org to know more about SARMs.

T replacement is associated with significant responses in properly diagnosed patients, but dosing may be different—older patients may not clear it as fast and need dose titrations.

Prof. G.R. Dohle, Rotterdam (NL) continued the presentation with an emphasis on guidelines. Overall, the incidence of hypogonadism is 6% of middle age men and increasing in older men. Testosterone replacement may help with symptoms, increase weight reduction, and improve diabetes and bone mineralization. The side effects to note include increasing hematocrit, fluid retention, BPH, prostate cancer, gynacomastia, and recently sleep apnea, Arizona sleep apnea care offers treatment for this last one.

Is TRT a “fuel” for prostate cancer? Based on level 2 evidence, TRT should not be used for locally advanced or metastatic PCa. For PCa risk itself, there is a lack of evidence of association. For patients with localized disease treated with radical prostatectomy, there are only observational studies, but no risk of tumor recurrence with limited follow-up. A saturation model has demonstrated that the androgen receptor is saturated just over the castration level and therefore additional T should not increase further growth. The guidelines recommend careful monitoring with hematology levels, cardiovascular assessment, and PSA monitoring (for age > 40). Specifically, hematocrit and hemoglobin and PSA should be checked at 3, 6, and 12 months and then annually. They recommend at least 1 year of biochemical NED follow-up.

Figure 2 Prof. G.R. Dohle from Rotterdam (NL) presents he EAU guidelines on testosterone replacement andprostate cancer. #EAU2014.

The session then switched into another gear with the presentation by Prof John P. Mulhall from New York (USA) with the focused question as to whether or not TRT causes an increased risk of cardiovascular events. This topic has been covered by the New York Times and the Wall Street Journal based upon a hand full of studies concluding that the risk exists. These reports, of course, have led to many patients wanting to stop therapy, and the U.S. legal system creating a new industry of tort claims. This was a “getting into the weeds” talk by an expert with impressively high words per minute speaking pace. The theme was all about methodology, and I could never re-create the whole talk in summary. The bottom line was that 3 high profile papers including Basaria et al NEJM 2010,Finkle WD PLOS ONE 2014, and Vigen R JAMA 2013 all had significant limitations in the methods, which ProfMulhall concluded led to erroneous conclusions. To quote: “Bad science can hurt people,” and “ The good thing about good science is that it is true whether or not you believe it (reference Neil deGrasse Tyson).”

Professor A.L. Burnett from Baltimore (USA) delivered the AUA lecture on sexual function after urologic surgery. This was more of a review talk and a very complete one given the short time. Of course I am biased in his favor as he highlighted one of my publications on sural nerve grafting (Davis et al Eur Urol 2009) which effectively diminished the previous trend in this procedure with the randomized cohorts showing no difference from unilateral nerve sparing alone. There are certainly numerous teachings and publications on nerve sparing surgery technique, but even high volume surgeons have demonstrated and published that technique alone does not seem to eliminate the risk of post-operative erectile dysfunction. Therefore much focus has shifted to post-operative management and novel techniques.

In the post-operative management area, the commonly used term is “penile rehabilitation.” The concept is straightforward: to stimulate blood, maintain tissue oxygenation, protect endothelial function, and reduce tissue damage/atrophy. While the data certainly suggests that PDE5 inhibitors, vacuum erection devices, and injections can improve erections after surgery, the data are still not conclusive that a scheduled, rehabilitation is superior to on demand use. There are papers suggesting a benefit, but reasonable to conclude that this is not “holy grail” in solving the problem. He then outlined the various other research and alternative pathways under evaluation from neurotropic factors, androgen replacement in select patients, treatment of ejaculatory dysfunction, and counseling—the latter of which seems to augment the standard treatments).

Figure 3: Professor A.L. Burnett, Baltimore (USA) at #EAU2014

Prof. M. Albersen of Leuven (BE) continued this theme with a review of bench research in erectile dysfunction and the progress of stem cell research. Early work shows potential benefits at the smooth muscle, fibrosis, and innervation endpoints. At least 6 trials are now registered at clinicaltrials.gov in this area, but many are still looking at the safety aspects first. Prof M.J.H. Van Griethuysen ofRotterdam (NL) concluded the session with a review of future research funding.

Congratulations to the organizers and speakers for a strong start to #EAU2014. Where you in the audience? What were your take home messages?

John W. Davis, MD, FACS

Houston, Texas

Associate Editor, Urologic Ongology, BJU International

A new treatment option for prostatitis/prostatodynia?

April 10, 2014/9 Comments/by Roger Kirby

The management of patients with chronic pelvic pain attributed to chronic prostatitis has long been rather unsatisfactory. Even prolonged treatment with an aminoquinolone, such as ciprofloxacin, and an anti-inflammatory agent, or, alternatively an alpha blocker, seldom results in rapid resolution of the symptoms, and is commonly completely ineffective.

We recently encountered a patient, effectively disabled by prostatodynia, unresponsive to standard treatment, who had been taking morphine to control the pain from 2001 – 2008. He was unable to tolerate non-steroidal anti-inflammatory analgesics. In 2008 he was prescribed initially 10 mgs, then 20 mgs daily, of the phosphodiesterase type 5 (PDE5) inhibitor tadalafil, with immediate marked improvement of his symptoms. On cessation of the medication on 4 separate occasions, his symptoms returned; recommencement of treatment each time, with 5 mgs tadalafil daily, has resulted in similar persisting improvement of his symptoms, and he has been able to discontinue treatment with morphine. As a direct consequence of the conversation with this individual we have prescribed tadalafil 5 mgs daily in several of our patients with prostatitis; so far with uniformly beneficial results. Of course, we should point out that this is an off-label indication for this medication.

However, in addition to the symptom of pelvic pain, many men suffering from chronic abacterial prostatitis/prostatodynia also complain of associated lower urinary tract symptoms and ejaculatory discomfort. Consequently treatment with tadalafil at a dose of 5 mgs per day for a period of time would seem logical. It could be surmised that many of its beneficial effects might stem from an improvement of blood flow to pelvic organs as a consequence of its anti-inflammatory and vasodilatory activity, as well as a relaxant effect on smooth muscle, as has been previously suggested in the case of lower urinary tract symptoms by Karl-Eric Andersson and others.

Clearly the hypothesis that daily treatment with a PDE5 inhibitor might be beneficial in men suffering from the prevalent condition of chronic abacterial prostatitis/prostatodynia needs to be formally tested in the context of a randomized controlled trial. If the results of such a study were to prove positive the quality of life of very many sufferers of this disorder might be significantly improved. One might also speculate that it could provide a concomitant benefit to the partners of these often very unhappy men.

Read the full BJUI article

Roger Kirby, The Prostate Centre
Culley Carson III, The University of North Carolina
Prokar Dasgupta, The Prostate Centre, Guy’s Hospital, King’s College London

Editorial: Nationwide prostatectomy practice

April 9, 2014/1 Comment/by Henk G. van der Poel

Surgical management of prostate cancer is one of the most frequently performed urological procedures [1]. Available data suggests that surgeons’ experience is correlated with both oncological and functional outcome [2]. These initial observations stress the importance of concentration of prostatectomy in high-volume institutes. This centralisation could improve documentation and monitoring of outcome. The data presented by Røder et al. [1] from Denmark show a rapid increase in registered prostatectomy procedures in recent years in six institutes. It remains to be studied whether this is caused by centralisation and better registration or the results of an increased overtreatment. For that, data on the incidence of low-risk disease over time in their series needs analysis.

At least one-third of the population was treated since 2008. The relatively short follow-up and associated few events, and high number of low-risk patients (47% had biopsy Gleason ≤6) make outcome analysis of less value. It is therefore not surprising that in their analysis low- and intermediate-risk tumors had similar outcome. On the other hand, despite prostatectomy, one-third of deaths during follow-up were prostate cancer related in their population. Consistent with reported data at 15 years after prostatectomy more patients died from prostate cancer than from other causes [3]. But still a considerable number of men died from prostate cancer. This also seems the case in the group of men often soothed for having indolent, low-risk disease. At 15 years Røder et al., reported 8.9% of these men with low-risk disease still dying from prostate cancer in Denmark, despite prostatectomy. And although this percentage was lower than that of the prostatectomy group in the Scandinavian Prostate Cancer Group Study Number 4 (SCPG-4) study (14.6%) [4], most men will still find it disturbingly high and it is three-times higher than the 3% life-time risk of dying from prostate cancer for all men. In other words, it may be perceived that prostatectomy does only partly reverse the risk of dying from prostate cancer, even in men with low-risk disease.

The data from Røder et al. [1] can, with longer follow-up, set the standard for oncological outcome on a national level. Of interest is the observation that, although not significant in the multivariate analysis, variation among institutes for outcome seems to exist but not clearly dependent on institutes volume. Variations of case-mix and patient selection could be topics of further study. With the short follow-up available we are also looking forward to data on functional outcome and perioperative complications that may be more mature. Comparison with now also available registries in Belgium and the Netherlands would be of interest.

It always strikes me that prostate cancer seems to be a systemic disease from the start even in assumed ‘low-risk’ disease, yet surgical management is only focused at loco-regional control. Perhaps the mortality improvement shown in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial by prostatectomy is merely caused by disease delay provided by local control even in the presence of systemic disease. Initial encouraging data from an ongoing study evaluating the role of radiotherapy to the prostate in the presence of bone metastases seem supportive of this notion. Is prostatectomy a debulking management of a systemic disease at most, and an unneeded cure for many, or is there this sub-sub group of men that is eventually fully benefiting from the intervention reversing not only death but also the debilitating effects of androgen ablation.

Henk G. van der Poel

Department of Urology, Netherlands Cancer Institute, Amsterdam, the Netherlands

Read the full article

References

Røder MA, Brasso K, Christensen IB et al. Survival after radical prostatectomy for clinically localised prostate cancer: a population-based study. BJU Int 2014; 113: 541–547
Vickers A, Savage C, Bianco F et al. Cancer control and functional outcomes after radical prostatectomy as markers of surgical quality: analysis of heterogeneity between surgeons at a single cancer center. Eur Urol 2011; 59: 317–322
Shikanov S, Kocherginsky M, Shalhav AL, Eggener SE. Cause-specific mortality following radical prostatectomy. Prostate Cancer Prostatic Dis 2012; 15: 106–110
Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708–1717

Are you ready to go to prison on a manslaughter charge?

April 8, 2014/96 Comments/by Roger Kirby

Which of us fancies ending their career with a spell in the clink? Being a surgeon in the UK has just become a whole lot riskier. We all know that in our job success can add extra years to our patients lives, by contrast, failure, can result in significant harm, or, in the worst circumstances, death. We all do our best, but sometimes things don’t work out. The sentence of two and a half years in prison for Mr David Sellu, who was referred a patient who developed peritonitis after an orthopaedic operation and subsequently died, smacks of injustice, and sends a shiver down the spine of all of us surgeons, who work hard on behalf of our patients, but who cannot always guarantee success.

The case is reported in detail in the latest bulletin of the Royal College of Surgeons (Ann R Coll Surg Engl (Suppl) 2014; 96: 112-113). It appears that the main problem was a delay in taking the patient to theatre because of the difficulty in finding an anaesthetist; a problem that cannot be reasonably be blamed upon the surgeon himself. If prosecutions for manslaughter become more frequent in circumstances similar to the Sellu case, we may all have to develop new defensive strategies. Madison Branson Lawyers are experts in the area of Proceeds of Crime and Confiscation Law. The prospect of ending an otherwise unblemished career in a prison cell as a result of an unfortunate clinical mishap might deter many from entering the profession in the first place. How should we react to the very sad scenario?

Roger Kirby, The Prostate Centre, London

Editorial: Do live case demonstrations have a future in surgical education?

April 2, 2014/by Walter Artibani

The ever increasing desire for instant access to information is a reflection of our times facilitated by social networks and by video and information technology. Nowadays, sport events are dissected and quantified from every possible perspective. We know almost real-time any detail of a soccer match: how many miles each player runs, how many good or bad passages of play, how many faults and so on, including if needed the details of heart rate and weight loss. The same and even more is available for example in formula one racing. Theoretically the same could easily be applied to surgical performance and it is foreseeable it will be applied, as a self-performance improvement method and as a development of one of the most popular ‘scientific and educational’ activities during surgical meetings, live case demonstrations (LCDs). All this, together with simulation, could in the near future have a tremendous impact on surgical performance and training. Twitter and Instagram show the power of the immediate real-time diffusion of events, as condensed as possible, so that the tweet or the instantaneous image can be visible and digested without losing time. Video clips follow the same concept and certainly BJUI is pioneering the use of short surgical video clips that are easily accessible and usable at any spare time of a busy day.

The core issue about LCDs is that at present there is no solid scientific evidence of their educational value, and this is outlined in the paper by Elsamra et al. [1] published in this issue of BJUI, which commendably attempts to evaluate the educational benefit of LCDs in terms of perception, clearly not a very strong criterion.

Data about the outcomes of live surgery operations are scant. Clearly patient’s safety is the first goal of any surgical activity, and this applies to LCDs. As mentioned in the paper, the European Association of Urology (EAU) Executive felt the urgent need to establish procedures and regulations in order to endorse live surgery events. The reader can find all related information on the EAU website. These regulations are meant to be in the best interest of patients, surgeons and organisers. Among others, one important innovation is the requisite of a ‘patient advocate’ present during the LCD, being an experienced medical doctor, independent from the organising committee of the educational event, in charge of advising in case of unexpected events, which can endanger patient’s safety.

Moreover, the EAU has established a prospective database of all endorsed live surgery events. This will hopefully allow in a few years an answer, with solid data, to the question of whether an intervention performed during a live surgery event has the same outcome compared with the same intervention executed by the same surgeon in his usual environment. The more challenging goal is to quantify the educational value of a live surgical event and the jump from perception to scientific evidence is far from being an easy task.

Walter Artibani
Urologia – Azienda Ospedaliero Universitaria Integrata di Verona, Verona, Italy

Read the full article

Reference

Elsamra SE, Fakhoury M, Motato H et al. The surgical spectacle: a survey of urologists viewing live case demonstrations. BJU Int 2014; 113: 674–678

Quality matters most where the BJUI and stone disease are concerned

April 1, 2014/1 Comment/by Daron Smith

Size (and shape) is important and sometimes strings should be attached, but quality matters most where the BJUI and stone disease are concerned …

The Editor-in-chief of the BJUI has consolidated the journal’s commitment to accepting only the highest quality papers, and this is certainly evident in the upper urinary tract section of this edition, where two studies demonstrate what it takes to be published in the journal nowadays.

In the first article, Kerri Barnes and colleagues from University of Iowa Department of Urology [1] have followed their own department’s earlier retrospective analysis of the benefit of “tethered stents” [2], by analysing the safety and effectiveness of this approach in a prospective, randomised controlled trial. It is often stated that randomised controlled trials are difficult in surgical disciplines, but this study affirms the proverb that “where there’s a will, there’s a way”. Although there was a substantial drop out in the number of patients that could have been included (three quarters of the patients approached for the study declined to be involved as they wished to determine the nature of the stent left in situ), statistical significance was not approached for any of the key concerns that leaving a stent on a string might cause for either the patient or their surgeon.

Furthermore, they have shown that that leaving the strings in place allowed patients to remove their stents significantly earlier (and in the convenience of their own home), than if they had to return to hospital for cystoscopic removal a week or so post-operatively. Despite the established knowledge that stents contribute to postoperative morbidity and can adversely affect quality of life, and the increasing evidence that stents are not required in “uncomplicated” ureteroscopy, it is clear that most urologists continue to leave a stent for a sense of security after performing ureteroscopic stone surgery. Shorter stent dwell times may help reduce the overall burden of stent related symptoms, and it is worth emphasising that none of the patients whose stent was removed at 7 days post operatively had any adverse consequences; neither did the 15% of this group whose stents fell out even earlier. As Fernando and Bultitude [3] comment in the associated editorial, the next question is: “If you are going to place a stent, how long does the stent need to stay for?” Perhaps, in order to emphasise that, where stent bother is concerned, shorter is better, this should be re-phrased as “how little time is enough time for a stent to stay in”…

In the second, Will Finch, from Norfolk and Norwich University Hospital, and his colleagues from Addenbrooke’s Hospital, Cambridge [4], have shown that stone size assessments from CT are most reliably calculated by a 3D-reconstructed stone volume. They have demonstrated that the maximum diameter of a stone tends to predict its overall shape such that a rugby ball-shaped stone (a “prolate ellipsoid”) has the polar diameter as the major axis, whereas a disc-shaped stone (an “oblate ellipsoid”) has the equatorial diameter as its major axis. Stones less than 9mm in diameter tended to be prolate, whilst those of 9–15 mm in diameter tended to be oblate; stones larger than 15 mm in diameter approach the more “random” shape of a scalene ellipsoid, for which the formula used to calculate stone volume (length (l) × width (w) × depth (d) × π × 0.167, which is often simplified to (l × w × d) / 2 in clinical practice) can be used.

However, if this is used for all stones regardless of their size and shape, rugby-ball and disc-like stones of less than 15mm in size are likely to have their volume over-estimated. Accordingly, the authors challenge the guidance of the EAU regarding stone volume calculations [5] to recommend that formulae based on the shape of the stone (π/6*a*a*c* for an oblate and π/6*a*b*b* for a prolate stone – see the paper itself to make sense of this) offer a more accurate assessment of stone volume.

Whilst these formulae are recommended for day-to-day calculations to guide treatment choices, they emphasise that 3D-reconstructed stone volumes should be used to report stone volume in research papers. In an age of stone surgery where CTKUB is so widely used in patients’ imaging assessment, and accepting that stone volume is the key determinant of achieving a stone free patient, this would allow the most accurate comparisons between the effectiveness of different surgical treatments.

Both articles are simple, straightforward, and well conducted studies that apply to the every-day practice of stone surgery. High quality papers are, of course, only really of benefit if they change practice for the better. So why not speak to your radiologist today about adding stone volume assessments to CTKUB reports (and point them to Finch et al. for the evidence) or even do it yourself! And the next time you put in a stent, reassure yourself, and the patient,

that there is no harm, and many benefits, in having some strings attached …

Daron Smith
University College Hospital, London, United Kingdom

Read the April issue

References

Barnes KT, Bing MT, Tracy CR. Do ureteric stent extraction strings affect stent-related quality of life or complications after ureteroscopy for urolithiasis: a prospective randomised control trial. BJU Int 2014; 113: 605–609
Bockholt N, Wild T, Gupta A, Tracy CR. Ureteric stent placement with extraction strings: no strings attached? BJU Int 2012; 110 (11 Pt C): E1069–1073
Fernando A, Bultitude M. Tether your stents! BJU Int 2014; 113: 517–518
Finch W, Johnston R, Shaida N, Winderbottom A, Wiseman O. Measuring stone volume – three-dimensional software reconstruction or an ellipsoid algebra formula? BJU Int 2014; 113: 610–614
Tiselius HG, Alken P, Buck C et al. European Association of Urology 2008 Guidelines on Urolithiasis. Available at: https://www.uroweb.org/fileadmin/user_upload/Guidelines/Urolithiasis.pdf. Accessed 17 June 2012

Welcome to the world of digital audio recordings of your consultations

March 27, 2014/19 Comments/by Roger Kirby

Has anybody ever tried to record one of your consultations? Yesterday, a patient of mine took his smartphone out of his pocket, placed it on my desk and said: “you don’t mind if I record this consultation do you doctor?” I tried not to look too surprised, gave my consent, and proceeded to go through the treatment options to him for his early prostate cancer. As I did so, perhaps a little more thoroughly and carefully than usual, I vaguely wondered whether the recording would be admissible in court or in front of the GMC if things did not go according to plan later.

By coincidence, last night I read in the BMJ a case where a patient had asked her family doctor whether she could use her smartphone to record the encounter (BMJ 2014;348g2078). Her doctor was apparently taken aback and paused to gather his thoughts. He asked the patient to put her phone away, saying that it was not the policy of the practice to allow patients to take recordings. The mood of the meeting shifted, initially jovial, the doctor had become defensive. She complied and turned off her smartphone.

As soon as the phone was turned off, the doctor raised his voice and berated her for making the request, saying that the use of a recoding device would betray the fundamental trust that is the basis of a good patient-doctor relationship. The patient tried to reason, explaining that the recording would be useful to her and her family, but the doctor shouted at her asking her to leave immediately and find another doctor.

It later transpired that the patient could prove that this had happened because she had a digital recording of the encounter. Although she had turned off her smartphone, she had a second recording device in her pocket, turned on, that had recorded every word!

According to the MDU, patients do not need their doctors’ permission to tape a consultation, as the information they are recording is personal to them and therefore exempt from data protection principles. Section 36 of the UK Data Protection Act 1998 states: “Personal data processed by an individual only for the purposes of that individual’s personal, family or household affairs (including recreational purposes) are exempt from the data protection principles and the provisions of Parts II and III”. There have taken some time to look into some of the most popular Nintendo Switch headsets on the market in an effort to help you out. Yes, it is true that there are many options out there, and it can be a chore to have to go through all of them yourself. That’s where they step in…they have done the tough work for you, and now we can present the best products reviewed on Audio Direct.

If you suspect that a patient is covertly recording you, you may be upset by the intrusion but if you act in a professional manner at all times then it should not really pose a problem. Your duty of care also means you would not be justified in refusing to continue to treat the patient. If you did, it could easily rebound on you and further damage your relationship with the patient. And, as the case described above illustrates, your refusal to continue with the consultation could easily be recorded!

Roger Kirby, The Prostate Centre, London

Editorial: Radical cystectomy: how do blood transfusions affect oncological outcomes?

March 26, 2014/by Shamim Khan

Kluth et al. [1] have conducted a large retrospective study from several institutions in North America and Europe to assess the impact of blood transfusion on oncological outcomes after radical cystectomy (RC) for bladder cancer. The hypothesis for a negative impact of transfusion on oncological outcomes stems from the observation that renal allograft survival is prolonged after pre-transplant blood transfusions because of its immuno-modulatory effects [2]. This finding prompted Gantt [3] to express concern about the possible adverse effects of transfusions in patients being treated for cancer. Since then, there have been numerous publications addressing this issue in various surgical journals including those of urology with conflicting messages.

Sadeghi et al. [4] queried the Columbia University Urologic Oncology Database. This included 638 patients undergoing RC between 1989 and 2010. Of these, 209 (32.8%) received perioperative blood transfusions. On univariate analysis, the number of units transfused was inversely related to overall and cancer-specific survival. However, on multivariate analysis, it did not prove to be an independent predictor of cancer-specific survival.

As the authors highlighted in this paper, Linder et al. [5] reported a large series of patients from the Mayo Clinic, which included 2060 patients undergoing RC over 25 years. Of this large cohort, 1279 (62%) received perioperative blood transfusion with adverse outcomes, not only in terms of overall and cancer-specific mortality, but also postoperative tumour recurrence.

RC is one of the most major surgical procedures performed in urological surgery. The vast majority of patients with bladder cancer requiring RC are in their mid-sixties, overweight and have several co-morbidities. Some of these patients present late and are anaemic at presentation.

Blood loss during open RC varies depending upon surgeons’ experience, patients’ body mass index, disease stage and availability of modern equipment, e.g. LigaSure™ or stapling devices. Blood transfusion may be required because of pre-existing anaemia or excessive blood loss during surgery. Variations exist in thresholds of anaesthesiologists and the surgeons for transfusions. All of these factors account for variation in reported frequency of transfusion rates for this operation and this is well reflected in many large series of RC.

As there are many confounding factors that may influence overall and cancer-specific survival in patients undergoing RC including stage of the disease, histological nature of the tumour, lymph node status and competing co-morbidities, it is very challenging to control for these factors in retrospective series. Hence, prospective well-controlled multicentre studies are the only way forward to answer this question.

While we await robust evidence on the influence of perioperative transfusion on oncological outcomes, several potential options could be explored to avoid homologous blood transfusion. These include preoperative optimisation of haemoglobin levels through iron infusions, administration of erythropoietin where appropriate, and preoperative autologous-banking. Intraoperatively meticulous surgical technique, use of modern devices, e.g. LigaSure/stapler and Cell Savers, could be used to avoid homologous blood transfusion.

Fortunately, these studies aimed at raising awareness of potential risks of transfusions are appearing in the urological literature at a time when urologists are moving away from open to minimally invasive oncological surgery with a steady decline in the need for perioperative blood transfusion. This is one of the important steps in the right direction and will have a major impact on the need for blood transfusion in foreseeable future.

Muhammed S. Khan
Department of Urology, Guy’s Hospital and King’s College London School of Medicine, London, UK

Read the full article

References

Kluth LA, Xylinas E, Rieken M et al. Impact of perioperative blood transfusion on the outcome of patients undergoing radical cystectomy for urothelial carcinoma of the bladder. BJU Int 2014; 113: 393–398
Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973; 5: 253–259
Gantt CL. Red blood cells for cancer patients. Lancet 1981; 2: 363
Sadeghi N, Badalato GM, Hruby G, Kates M, McKiernan JM. The impact of perioperative blood transfusion on survival following radical cystectomy for urothelial carcinoma. Can J Urol 2012; 19: 6443–6449
Linder BJ, Frank I, Cheville JC et al. The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013; 63: 839–845

Future Proofing Urology – Conference Highlights from the USANZ ASM 2014

March 24, 2014/1 Comment/by Marnique Basto

Dr Marnique Basto (@DrMarniqueB)

Delegates of #USANZ14 received a sunny welcome at this year’s 67th annual scientific meeting in Brisbane, affectionately coined by Aussies as ‘Bris-vegas’ attributed to a love of Elvis and the city’s growing live music scene. The reins were passed from Professor Damien Bolton and A/Professor Nathan Lawrentschuk (@lawrentschuk) who convened last year’s ASM in Melbourne to Greg Malone (@DrGregJMal) and Eric Chung. @BJUIjournal Editor-in-chief Prokar Dasgupta (@prokarurol) praised the USANZ organising committee for their tremendous hospitality.

A star studded international faculty made the long-haul down under including Shahrokh Shariat, Alan Partin, Gerry Andriole, James Eastham, Rainy Umbas, Per-Anders Abrahamsson, Monique Roobol, Hein Van Poppel, Jean de la Rosette, Gerald Brock, Brad Leibovich, Gary Lemack, Tom Lue, Jonathan Coleman, Michael Jewett, Oliver Traxer, Eric Small, Adrian Joyce, Roger Kirby, Gopal Badlani, Sunil Shroff, Eila Skinner, Jaspreet Sandhu, Matthew Rettig, Pilar Laguna, Jaime Landman, Irwin Goldstein, Todd Morgan and Gregor Goldner.

The hype around #USANZ14, however, had kicked off well before conference doors opened with @USANZUrology mounting the largest pre-conference social media (SoMe) campaign of any Urology conference internationally to date. Over 200 tweets were generated in the five-day lead-up from the @Urologymeeting account, doubling last year’s efforts of the social media team at the Prostate Cancer World Congress in Melbourne. It’s fair to say Australia is setting a blazing pace in the use of SoMe to amplify the Urology conference experience and generate international engagement and global reach.

“Future proofing urology” was the conference theme this year to promote and foster multidisciplinary collegiality and evidenced urological practice. The theme was entwined throughout the four-day conference with the final day showcasing a multidisciplinary forum with international experts discussing complex cases. Additionally the Australian and New Zealand Urological Trials (@ANZUPtrials) session highlighted the interplay between urology, radiation and medical oncology and the current trials underway.

USANZ president David Winkle officially opened conference proceedings and we had the honour of Scottish-born Australian Scientist Professor Ian Frazer AC, the mastermind behind the Human Papilloma Virus vaccine and the fight against cervical cancer, deliver the Harry Harris oration. Professor Frazer’s ongoing dedication to implementing vaccination programs in low GDP countries such as Vanuatu and Butan was truly inspirational. Harry Harris was the first full time Urology specialist in Australia, and suitably the award of the seven newest fellows of the USANZ collegiate followed. Congratulations to all.

A lively point-counterpoint debate on the viability of prostate cancer prevention then ensued between Shahrokh Shariat (@DrShariat) on the negative and Gerald Andriole (@uropro) on the affirmative. Interestingly both parties used the same sets of data to reach opposite conclusions. The ability to use the opposition’s prior publications against them became the clincher in several of the debates throughout the conference; however, it was the ‘no show’ of hands from the audience when asked “who currently uses chemoprevention?” that reinforced the inevitable conclusion.

The BJUI session was then underway and A/Prof Nathan Lawrentschuk, Associate Editor of the BJUI USANZ supplement, outlined his vision for the journal going forward. The winner of the BJUI Global Prize awarded to a trainee who significantly contributed to the best international article went to Dr. Ghalip Lidawi for his paper titled ‘High detection rate of significant prostate tumours in anterior zones using transperineal template saturation biopsy’. In an Oscar-style award ceremony Dr Lidawi was broadcast from Tel Aviv. Professor Alan Partin (@alan_partin) went on to deliver a brilliant and balanced rationale behind why Gleason 6 IS prostate cancer and potentially coined the alternative name PENIS (‘Prostatic epithelial neoplasm of indeterminate significance’). News of ‘PENIS of the prostate’ hit social media channels instantly with Urologists chiming in from the US to give their opinion within minutes and before Dr Partin had even stepped down from the podium.

Dr. Ghalip Lidawi accepting his BJUI Global Prize via video message (photo courtesy of Imogen Patterson).

After the opening plenary each morning, the 950 delegates were treated to a range of concurrent sessions from the faculty, which included localised prostate cancer, endourology, andrology/prostheses, high risk prostate cancer, LUTS/BPH, prostate cancer multidisciplinary forum, urology general, bladder cancer, kidney cancer and abstract poster presentations. There was a concurrent nursing program also running during the USANZ schedule that proves year after year to be a huge success.

A stand out session of the meeting was on high-risk prostate cancer section on Monday afternoon. Professor James Eastham (who is rumoured to have just joined twitter!) discussed the role of pelvic lymph node dissection (PLND) for diagnostic and therapeutic purposes with reference to the Memorial Sloan Kettering (MSK) experience and the role of salvage PLND after radical prostatectomy for choline PET detected retroperitoneal or pelvic node recurrence. Professor Hein van Poppel went on to support the role of surgery in high-risk disease in this session, while Drs Shariat and Per Anders Abrahamsson discussed the latest in hormonal adjuvant therapy.

What makes USANZ special?

The abstract submissions this meeting far superseded last year in volume and quality requiring two concurrent poster presentation sessions running most of the conference. The use of transperineal template biopsy was a prominent theme again in the abstract series, as was active surveillance for low risk prostate cancer. Pleasingly we saw the development of large international collaborations involving Australia such as the Vattikuti Global Quality Initiative on Robotic Urologic Surgery where Mr Daniel Moon has collaborated with nine hospitals throughout Europe, North America and India on their growing robotic partial nephrectomy series.

Each year a select group of our young talented trainees compete for the prestigious Keith Kirkland (KK) clinical and Villis Marshall (VM) basic science prizes. This year Dr Kenny Rao (@DrKennyRao) was awarded the VM prize from a field of five candidates for his work titled ‘Zinc preconditioning protects the rat kidney against ischaemic injury’. Dr Helen Nicholson (@DrHLN) took out the KK prize over 10 other candidates for her work; ‘Does the timing of intraoperative non-steroidal anti-inflammatory analgesia affect pain outcomes in ureteroscopy? A prospective, single-blinded, randomised controlled trial’. These were awarded at the gala ball located at the Brisbane townhall, a venue soon to be filled by some of the most prominent in the world for the G20 summit. Other awards on the night included the Alban Gee for best poster to Shomik Sengupta (@shomik_s), the BAUS trophy (@BAUSUrology) to Michael Holmes and the Abbvie Platinum award to Niall Corcoran.

Unlike any other Urology meetings worldwide, the USANZ ASM is compulsory for all trainees from their third year on and is encouraged in the first two years. Trainees were treated to a breakfast meeting with Dr Shahrokh Shariat who imparted 14 career tips and then assisted @lawrentschuk in grilling trainees on difficult case studies in preparation for their fellowship exams. A brilliant learning opportunity! Trainees also got to meet one-on-one with international faculty members of their choice to facilitate potential future fellowships in somewhat of a staged ‘speed-dating’ affair – 10 minutes chat, then move on. To top off the trainee program, the @BJUIjournal delivered an extremely practical and useful workshop focussed on getting published in the digital and social media era where blogs are encouraged, tweets are citable and your CV now contains a social media section.

A SoMe session attracted a lot of attention from international delegates and twitter activity on the #USANZ14 hashtag skyrocketed as we were joined by Stacy Loeb (@LoebStacy) in Moscow, Alexander Kutikov (@uretericbud) in the US and Rajiv Singal (@DrRKSingal) in Canada. Declan Murphy (@declangmurphy), Henry Woo (@DrHWoo) and Todd Morgan (@wandering_gu) put on a masterful (and non-nauseating) prezi display with the audience taken on an e-health journey of novel gadgets and devices including one that measured tumescence and sends the file automatically to the physician records. The possibilities are endless! Twitter boards were back in force; a sign of a quality and successful conference according to @declangmurphy. The wifi at the conference venue could not be faulted!

Controversial areas of SoMe were also broached including the APRAH Advertising Guidelines that came into effect this week, Monday March 17. Australian Plastic surgeon Jill Tomlinson (@jilltomlinson) has actively opposed the guidelines that will see physicians responsible for all testimonials associated with them on the internet. The policy mandates this information be removed otherwise a fine of up to $5000 is possible, many feel this places an unreasonable burden on health practitioners to be responsible for content that they may potentially be unaware of. Read Jill Tomlinson’s letter to APRAH here.

The @BJUIJournal and its editors @prokarurol, @lawrentschuk, @declangmurphy and @alan_partin (left to right below) and off screen @drHwoo were prominent SoMe influencers of the meeting two years running. We were also delighted to have Mike Leveridge (@_theurologist) from Canada attending, one of the pioneering uro-twitterati. A mention goes out to fellow countryman @drrksingal who was again mistaken for being at the conference due to his strong SoMe presence from afar. The twitter activity for the conference period March 16 (00:00) to March 19 (23:59) generated nearly 1.4 million impressions and 2,326 tweets or approximately 344K impressions and 581 tweets per day. Based on the study conducted by our team examining metrics of all eight major urological conferences of 2013, #USANZ14 would comparatively rate second only to the AUA in the international engagement and global reach attained. Congratulations to @USANZUrology and @Urologymeeting for enhancing our conference experience and sending our message out to almost 1.4 million potential viewers in just a 4-day period.

The BJUI Workshop featured Editor-in-Chief Prokar Dasgupta and Associate Editors Nathan Lawrentschuk, Declan Murphy and Alan Partin.

In 2015 we take a trip to Adelaide for the 68^th Annual Scientific Meeting of USANZ with experts already confirmed including Steven Kaplan, Martin Koyle, Morgan Rupert, Matthew Cooperberg and Glenn Preminger. See you all there!

Dr Marnique Basto (@DrMarniqueB) is a USANZ trainee from Victoria who has recently completed a Masters of Surgery in the health economics of robotic surgery and has an interest in SoMe in Urology.

Check out the new BJUI Instagram feed for more photos from #usanz14 www.instagram.com/bjui_journal

Editorial: mTOR-related non-infectious pneumonitis: a potential biomarker of clinical benefit?

March 19, 2014/by Simon Chowdhury

The study by Atkinson et al. [1] published in the present issue of the BJUI is the largest study to date to address the role of non-infectious pneumonitis (NIP) as a predictive biomarker in patients with RCC who are treated with mammalian target of rapamycin (mTOR) inhibitors. It is also the first article to correlate mTOR-related NIP with improved overall survival (OS). Until now, only radiological response as measured by RECIST and progression-free survival (PFS) had been correlated to the onset of NIP in two small retrospective studies [2, 3], but the results obtained in those studies were contradictory and, therefore, this correlation remains controversial.

While the predictive relationship between NIP and OS needs to be further investigated in well-designed prospective clinical trials, the implications of such a relationship may be significant because no predictive biomarkers for mTOR inhibitors have been validated to date. In the era of targeted therapies, the detection of biomarkers of treatment efficacy is crucial to differentiate the subpopulations of patients who are most likely to benefit from treatment. Several biomarkers, such as the development of arterial hypertension and hypothyroidism, have been correlated with improved outcomes in patients with advanced RCC treated with vascular endothelial growth factor pathway inhibitors [1]; however, there are currently very limited data regarding the potential predictors of the clinical efficacy of mTOR inhibitors. A recent study by Lee et al. [4] showed that greater increases in serum cholesterol levels from baseline in patients with advanced RCC treated with temsirolimus were significantly associated with longer PFS and OS. Interestingly, temsirolimus-related hypertriglyceridemia and hyperglycaemia were not associated with improved clinical outcomes. Although NIP or hypercholesterolaemia must still be validated prospectively to ascertain whether they are true surrogate biomarkers of pharmacodynamic effect or just confounding epiphenomena, these promising findings may be the first steps in the identification of predictive biomarkers in mTOR inhibitor therapy.

Other important aspects addressed by Atkinson et al. [1] are the uncertainty of the pathogenesis of mTOR-related NIP and the lack of clinical predictive factors. Older age and treatment with everolimus were the only significant predictive factors of onset of NIP in their multivariate analysis. Similarly, a retrospective study by Dabydeen et al. [2] showed a statistically nonsignificant higher incidence of NIP in patients with RCC treated with everolimus compared to those treated with temsirolimus. Interestingly, in a randomized phase II study testing three different dose levels of temsirolimus (25,75 and 250 mg/week) in patients with advanced RCC, none of the six patients diagnosed with NIP were in the highest dose group of 250 mg/week [5], suggesting that mTOR-related NIP might have a non-dose-dependent pathogenesis. Similarly, a meta-analysis of 2233 patients affected by different tumours including RCC treated with an mTOR inhibitor failed to show any relationship between median treatment duration and incidence of NIP [6]. Finally, underlying respiratory conditions before treatment, such as the presence of lung metastases [6], chronic obstructive pulmonary disease or smoking habit [2], were not shown to be predictive factors of development of mTOR-related NIP. Another study by White et al. [3] showed that the development of pneumonitis in patients with RCC treated with everolimus was not associated with more impaired baseline pulmonary function tests, indicating that pulmonary function tests may not help identify patients with an increased risk of pneumonitis nor predict its severity. At present, there are therefore very few pretreatment clinical predictive factors to help clinicians identify patients at higher risk of developing mTOR-related NIP.

In conclusion, given the potential value of NIP as a predictive biomarker of survival in patients with RCC treated with mTOR inhibitors, Atkinson et al. [1] suggest that efforts should be made to avoid dose reductions and treatment discontinuation whenever possible. However, predictive factors of the severity of lung toxicity are needed to identify those patients at risk of developing life-threatening NIP as the maintenance of dose intensity may be crucial for maximizing clinical benefit.

Read the full article

Alejo Rodriguez-Vida, Noan-Minh Chau and Simon Chowdhury
Department of Medical Oncology, Guy’s Hospital, London, UK

References

Atkinson BJ, Pharm D, Cauley DH et al. mTOR inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: management, predictors, and outcomes. BJU Int 2014; 113: 376–382
Dabydeen DA, Jagannathan JP, Ramaiya N et al. Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: incidence, radiographic findings and correlation with clinical outcome. Eur J Cancer 2012; 48:1519–1524
White DA, Camus P, Endo M et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med 2010; 182: 396–403
Lee CK, Marschner IC, Simes RJ et al. Increase in cholesterol predicts survival advantage in renal cell carcinoma patients treated with temsirolimus. Clin Cancer Res 2012; 18: 3188–3196
Atkins MB, Hidalgo M, Stadler WM et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004; 22: 909–918
Iacovelli R, Palazzo A, Mezi S, Morano F, Naso G, Cortesi E. Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials. Acta Oncol 2012; 51: 873–879