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Editorial: Enzalutamide withdrawal syndrome: is there a rationale?

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Enzalutamide is a second generation non-steroidal antiandrogen (AA), which significantly improved overall  survival (OS) and progression-free survival (PFS) after docetaxel (AFFIRM study), and OS and radiographic PFS before chemotherapy (PREVAIL study) in patients with metastatic castration-resistant prostate cancer (mCRPC) [1].

Being a potent androgen receptor (AR) antagonist, an enzalutamide withdrawal syndrome (EWS) appeared unlikely [2,3]. In contrast with this position, and considering the well-known AR structural alterations in CRPC, very recent preclinical and clinical data support the possibility of the existence of an EWS after the discontinuation of this drug, in a castration-resistant setting.

In patients with mCRPC progressing on androgen-deprivation therapy (ADT), the AAWS, due to the interruption of first generation AAs (flutamide, bicalutamide, nilutamide, cyproterone acetate and megestrol acetate), often pursues as a further hormonal manipulation, although no level one studies supported its efficacy. AAWS leads to a PSA reduction in 15–30% of patients, with concomitant symptomatic relief and radiographic responses in some cases, without impacting on survival [1]. The molecular mechanisms of the AAWS are still unclear. One of the possible mechanisms responsible for the AAWS is the mutation of the AR. In vitro models showed that bicalutamide may switch from antagonist to agonist in LNCaP-cxD cell lines, due to an additional AR mutation in codon 741 during bicalutamide treatment [4]. Similarly, preclinical in vitro and in vivo studies demonstrated that initially enzalutamide exerts its AR antagonist activity, but during the treatment enzalutamide potently induces an AR mutation, leading to the mutant ARF876L, which confers agonism to enzalutamide, and resistance to enzalutamide therapy [1]. In the clinical setting, the first evidence of possible EWS has begun to appear. Phillips [5] observed EWS in one patient, 40 days after enzalutamide discontinuation. Rodriguez-Vida et al. [1] showed EWS in three of 30 (10%) patients with mCRPC after the drug cessation, although none of the 17 factors examined were statistically significant predictors of PSA decline after enzalutamide interruption. Considering the clinical characteristics of the three patients showing EWS, interestingly all of them were aged <70 years, had Gleason score ≥7, had bone and/or lymph node metastases without visceral sites of disease, and had had previous treatments with bicalutamide and docetaxel. In all three patients, EWS seems to have no correlation with: prostate cancer staging at diagnosis (M0 vs M1), PSA value before enzalutamide, PSA decline on enzalutamide treatment, LHRH analogues and enzalutamide therapy duration. Similarly to bicalutamide WS, in all three patients no symptomatic improvement was recorded during EWS.
Focusing on patient 1, interestingly he displayed initially a PSA response during enzalutamide and later a further PSA decline plus radiological response after enzalutamide interruption (i.e. EWS), showing a sensitivity either to initial enzalutamide antagonism and to subsequent agonism, and exhibiting an EWS not preceded by a bicalutamide WS. This supports previous data concerning different AR mutations for the two different AAs, without subsequent clinical correlations between the two different AAWSs. A LHRH analogue duration treatment (5 months) shorter than a subsequent enzalutamide duration therapy (21.4 months) suggests different tumoral cells sensitivity to different ADTs, in different stages (hormone naïve and castration-resistant prostate cancer), likely related to several AR structural alterations collected along the disease. Intriguingly, patient 3 discontinued enzalutamide after only 1.2 months, maybe due to primary resistance [6]; nevertheless, he showed a PSA
response after enzalutamide interruption, suggesting that EWS, characterised by the switch from enzalutamide antagonism to agonism, could occur even in prostate cancer patients primary resistant to this drug. Limitations of the two first clinical reports related to EWS include a restricted sample size, a reduced number of EWS events and a short duration of follow-up after enzalutamide discontinuation. Furthermore, preclinical studies on EWS and published data concerning AAWS described more frequently early stage mCRPC, while the two papers considered heavily pretreated patients with mCRPC, in whom EWS incidence could be reduced due to several previous treatments, which probably produced various AR alterations.

In conclusion, the preclinical models have demonstrated one possible plausible mechanism responsible for EWS and enzalutamide resistance. First clinical reports suggest the possibility of EWS in a minority of patients after enzalutamide discontinuation in mCRPC. Further studies are needed to confirm and detail the EWS, before translating these data into clinical practice.

Read the full article

Alessandra Mosca
Medical Oncology, ‘Maggiore della Carità’ University Hospital, Novara, Italy

References

1 Rodriguez-Vida A, Bianchini D, Van Hemelrijck M et al. Is there an antiandrogen withdrawal syndrome with enzalutamide? BJU Int 2015; 115: 373–80

2 von Klot CA, Kramer MW, Böker A et al. Is there an anti-androgen withdrawal syndrome for Enzalutamide? World J Urol 2014; 32: 1171–6

3 von Klot CA, Kuczyk MA, Merseburger AS. No androgen withdrawal syndrome for enzalutamide: a report of disease dynamics in the postchemotherapy setting. Eur Urol 2014; 65: 258–9

4 Hara T, Miyazaki J, Araki H, Yamaoka M, Kanzaki N, Kusaka M. Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. Cancer Res 2003; 63: 149–53

5 Phillips R. An enzalutamide antiandrogen withdrawal syndrome. Nat Rev Urol 2014; 11: 366

6 Efstathiou E, Titus M, Wen S et al. Molecular characterization of Enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol 2015; 67: 53–60

 

Racing ahead

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Murphy-2015-BJU_InternationalSince the new Editorial team assumed the reins here at the BJUI in January 2013, we have worked hard to embrace social media as the transformative communication technology it clearly is. While our priority is to only publish papers of the highest quality, we have also ensured that the reach and engagement of these papers are maximised using our social media platforms – Twitter, Facebook, YouTube, Instagram and Blogs@BJUI.

In this month’s BJUI, there are two intriguing papers that deal with this area but that deliver contrasting messages. The first from Nason et al. analyses the Twitter activity of all urology journals over a recent 6-month period. It is clear that the major journals have adopted Twitter as a preferred social media platform and it is gratifying to see how well the BJUI performs when assessed using the metrics in this paper. However, Fuoco and Leveridge report that most urologists in a Canadian survey believe that ‘social media integration into medical practice is impossible’ and attitudes towards the professional role of social media were ‘generally negative’.

Nevertheless, the power of social media in enhancing our personal and professional communication is undeniable and we at the BJUI expect more and more urologists to embrace social media in the coming years. We will continue to evolve our social media strategy to ensure the BJUI is a highly ‘social’ experience.

On another note, the BJUI is pleased to support an excellent conference taking place in Dublin in April in the memory of our previous Editor-in-Chief, Professor John Fitzpatrick, who passed away suddenly last year. The Inaugural John Fitzpatrick Irish Prostate Cancer Conference takes place from 23–24th April 2015 and has attracted an outstanding International Faculty of colleagues and friends who look forward to exploring the most challenging areas in prostate cancer in his memory. Details here https://www.globalteamwork.ie/prostate.html.

Declan G. Murphy – BJUI Associate Editor – Social Media 

Department of Urology, University of Melbourne, Melbourne, VIC, Australia

Twitter @declangmurphy

 

 

Am I normal? Review Analyzes Data on Flaccid and Erect Penis Lengths in Men

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Press Release

A new analysis provides insights on what’s considered “normal” for penis length and circumference in men. The findings in BJU International may be helpful when counseling men who are worried about their size, or when investigating the relationship between condom failure and penile dimensions.

Some men are concerned about their penis size, and those who are preoccupied and severely distressed with the size of their penis may even be diagnosed with Body Dysmorphic Disorder. There have been no formal systematic reviews of penile size measurements and no attempts to create a graphical diagram, or nomogram, that depicts the distribution of the size of a flaccid or erect penis. Here you will get best penile traction therapy, do visit us.  People who are experiencing a lack of desire and interest in lovemaking may find sex toys and games to be beneficial in resolving their problems. Using games for sexual stimulation or arousal is considerably cheaper and easier than using other drugs. You can vists site for the best sex toy for your sexual life.

Dr. David Veale, of King’s College London and the South London and Maudsley NHS Foundation Trust, and his colleague from King’s College Hospital NHS Foundation Trust, set out to create such a nomogram of male penis size measurements across all ages and races. A search of the medical literature revealed 17 studies with up to 15,521 males who underwent penis size measurements by health professionals using a standard procedure. The nomograms revealed that the average length of a flaccid penis was 9.16 cm, the average length of a flaccid stretched penis was 13.24 cm, and the average length of an erect penis was 13.12 cm. The average flaccid circumference was 9.31 cm, and the average erect circumference was 11.66 cm. There was a small correlation between erect length and height.

“We believe these graphs will help doctors reassure the large majority of men that the size of their penis is in the normal range. We will also use the graphs to examine the discrepancy between what a man believes to be their position on the graph and their actual position or what they think they should be” said Dr. Veale.

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Article: “Am I normal? A systematic review and construction of nomograms for flaccid and erect penis length and circumference in up to 15,521 men.” David Veale, Sarah Miles, Sally Bramley, Gordon Muir, and John Hodsoll. BJU International; Published Online: March 3, 2015 (DOI: 10.1111/bju.13010).

 

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Editorial: Malignant medication? Testosterone and cancer

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Testosterone therapy (TTh) in men with hypogonadism is becoming more commonplace among urologists, endocrinologists and even primary practitioners. While the definition of hypogonadism remains a moving target, the literature reflects very clear benefits of TTh in appropriately selected patients. As with any drug, the adverse effect profile helps to dictate the risk:benefit ratio and, over the past several years, numerous, primarily retrospective, analyses have provided mixed insights into the impact of TTh on cardiovascular disease and cancer, specifically prostate cancer.

Eisenberg et al. [1] take a step back from the focus on prostate cancer and evaluate the impact of TTh on general cancer incidence in a cohort of men treated in a single, large-volume andrology practice over 20 years. The authors found no difference in either overall cancer incidence or in the prostate cancer incidence in men on TTh in comparison with men not on TTh. This finding is significant as it supports the hypothesis that testosterone does not harmfully affect either hormonally responsive (prostate cancer) or non-hormonally responsive malignancies. Interestingly, the authors also observe a lower rate of all cancers in men on testosterone therapy. While not statistically significant, this finding is consistent with that of at least one other study focused on prostate cancer, in which men with high-risk prostate cancer receiving exogenous testosterone had a lower recurrence rate than a matched control group [2]. If borne out in future studies, a protective relationship between TTh and cancer would indeed reflect a novel benefit of treatment.

Nevertheless, at this time the jury remains out on a definitive assessment of the effects of TTh on both cancer as well as cardiovascular disease, and will probably continue to do so until controlled, prospective studies are completed. Numerous, mostly retrospective studies have examined the effects of endogenous testosterone and of the administration of exogenous testosterone, primarily on prostate cancer. While the details of these studies are beyond the scope of the present editorial, their findings have varied with regard to whether testosterone does or does not have effects on cancer incidence, biopsy findings, grade, recurrence rates and margin status, preventing a clear perspective on the effects of testosterone on cancer. Similarly, studies evaluating the impact of TTh on cardiovascular disease have also widely varied in their conclusions [3, 4]. Several recent large retrospective studies have found a detrimental relationship between TTh and cardiovascular disease in specific male populations, but have come under withering criticism from the community, with significant doubts cast regarding the veracity of their findings [5, 6].

The growing popularity of TTh has subjected it to a level of scrutiny applied to few other medications, resulting in a slew of peer-reviewed publications of varying quality and conclusions. In the effort to safeguard patients, investigators have hurriedly carried out retrospective data evaluation, which, by design, limits compensation for confounding factors and unfortunately results in an overall murky understanding of long-term adverse events related to TTh. Nevertheless, the clinical benefits of TTh are clear, and many patients are satisfied with the results of treatment. While physicians should remain the stewards of patient care, informed consent and a patient’s acceptance of both the known as well as the unknown risks of testosterone treatment should continue to be an integral part of the initiation and continuation of TTh, until additional high-quality data from clinical trials become available in the coming years.

Read the full article
Alexander W. Pastuszak
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

 

References

 

1 Eisenberg ML, Li S, Betts P et al. Testosterone therapy and cancer risk. BJU Int 2015; 115: 317–21

 

2 Pastuszak AW, Pearlman AM, Lai WS et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190: 639–44

 

3 Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. NEnglJMed2010; 363: 109–22

 

4 Shores MM, Smith NL, Forsberg CW et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012; 97: 2050–8

 

5 Vigen R, O’Donnell CI, Baron AE et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013; 310: 1829–36

 

6 Finkle WD, Greenland S, Ridgeway GK et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014; 9: e85805

 

Editorial: How active should active surveillance be?

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 Many investigators, including those from Johns Hopkins University (JHU) and the Prostate cancer Research International: Active Surveillance project (PRIAS), have provided meaningful data to strongly support the increasing use of active surveillance (AS) across the world. There are a multitude of strategies to minimise excessive rates of prostate cancer over detection and overtreatment. After the diagnosis of prostate cancer, the single best is AS for appropriately selected men.

 For decades, the concept of not treating a prostate cancer in otherwise healthy men, even if low-grade and low-volume was typically considered nihilistic and heretical, particularly in the USA. Thankfully, data have largely made this line of thinking anachronistic. The era of sensibly applied AS is upon us, and single-institution series with intermediate-term follow-up are excellent, with exceedingly low rates of metastasis or cancer-related death. However, we await longer-term (>10 years) outcomes from the contemporary PSA screening era.

 The ‘success’ of AS is largely dependent on the entry criteria, follow-up strategies, and indications for curative intervention. Highly restrictive inclusion criteria, rigorous biopsy based follow-up and strict definitions of reclassification triggering treatment have produced superb outcomes. Critics appropriately argue these criteria exclude a significant proportion of men with a low rate of requiring treatment or having metastases, if allowed on AS. Conversely, other programmes with looser entry criteria, more lax follow-up, and relaxed indications for intervention will be more inclusive and have lower rates of immediate or delayed intervention but must be counterbalanced against the expected higher rate of metastases or death.

 The current study [1] evaluates two different AS follow-up strategies from JHU and PRIAS. In general, JHU uses annual biopsies with progression defined as a new PSA density >0.15 ng/mL/mL or increasing tumour volume or grade beyond a certain threshold, while PRIAS recommends less frequent biopsies (years 1, 4, and 7) while relying on serological (PSA doubling time, PSADT) alongside histological indicators for defining progression and recommending treatment.

 Not surprisingly, different strategies lead to varying expected outcomes. Among the JHU patients, 38% were reclassified at a median of 2.1 years. Nearly two-thirds of the reclassified would have been identified at the PRIAS year 1 or triennial biopsies with 16% identified between PRIAS biopsies at a median delay of 1.9 years. The unanswerable but incredibly important question is whether this delay is essentially a non-issue, perhaps a favourable attribute (more AS time without compromising cure rates), or clinically disastrous (patients no longer curable).

 PRIAS relies heavily on PSA kinetics, which can be a double-edged sword. Among men in the JHU programme with >5 years follow-up, 11% would have delayed reclassification compared with PRIAS at a median time of 4.7 years. Additionally, 12% would have undergone intervention due to PRIAS-defined PSADT but not progressed based on the JHU protocol. It is convenient and perhaps intuitive that PSA kinetics should predict progression and meaningful clinical events for men on AS; however, the data from multiple studies have simply not supported this concept [2, 3].

 The JHU programme has restrictive entry rules compared with most other programmes, a rigorous biopsy based follow-up protocol, and strict criteria to treat, which is exactly why no metastasis or death have been reported among 769 men, some with up to 15 years follow-up[4]. Guidelines are needed but should not be overly prescriptive or rigid. For example, a surveillance biopsy showing a single core of Gleason 6 encompassing 60% of the total core or three cores of Gleason 6 with total cancer length of 3 mm would lead to a recommendation of treatment according to published JHU criteria. Many of us would not be phased with these biopsy reports and comfortably recommend ongoing AS.

 Data from AS series are very encouraging but it is highly likely we can do even better. For example, 10-year cancer-specific survival is 97% in the Sunnybrook AS experience and all five cancer-related deaths occurred in patients that would not meet most contemporary AS entry criteria [5, 6]. I am hopeful and confident that emerging data incorporating MRI imaging, serum biomarkers (e.g. prostate health index), or tissue-based biomarkers (e.g. Prolaris, Oncotype Dx) will provide us with a more comprehensive understanding of these men’s cancer such that tailored, evidence-based recommendations can be even more accurate.

 There is much yet to be learned about AS and this study [1] adds to our knowledge. Surveillance for prostate cancer is definitely active, but it is also dynamic and evolving.

Read the full article
Scott Eggener
Associate Professor of Surgery, University of Chicago, Chicago, IL, USA

 

References

 

1 Kates M, Tosoian JJ, Trock BJ, Feng Z, Carter HB, Partin AW. Indications for intervention during active surveillance of prostate cancer:
a comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) protocols. BJU Int 2015; 115: 216–22

 

2 Whitson JM, Porten SP, Hilton JF et al. The relationship between prostate specific antigen change and biopsy progression in patients on active surveillance for prostate cancer. J Urol 2011; 185: 1656–60

 

3 Fall K, Garmo H, Andrén O et al. Prostate-specific antigen levels as a predictor of lethal prostate cancer. JNatlCancerInst2007; 99: 526–32

 

4 Tosoian JJ, Trock BJ, Landis P et al. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J Clin Oncol 2011; 29: 2185–90

 

5 Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126–31

 

6 Krakowsky Y, Loblaw A, Klotz L. Prostate cancer death of men treated with initial active surveillance: clinical and biochemical characteristics. J Urol 2010; 184: 131–5

 

The Death of the Junior Surgeon

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jnrdocheadstoneI think I attended a meeting recently at which I fear, after many years of being slowly deprived of oxygen by various organisations, a component of a profession which I love and to which I have devoted so much of my life, finally started to give up the fight and started to die.

I am involved in training as a training programme director as well as being a local trainer. As a TPD I have had to watch the separation of the London and KSS training programmes. This has happened, despite sitting in a room of thirty to forty senior trainers who all voiced the opinion that this is detrimental to the future of urology training for our trainees. The trainees also voiced an opinion that this was wrong but still it went ahead.

Recently, I sat in a room where, again, a group of thoughtful intelligent doctors spoke about the future of junior doctor training. We are about to impose a change in the training of foundation year doctors imposed upon our excellent organisation from what for most of us is a faceless organisation with whom we will never interact directly. We will be moving them into community-based jobs that no senior doctor round the table believed was in their interests or in the interests of the future of Britain’s healthcare, but we will still oversee that process.

And what test is being applied to what our junior doctors should be doing to justify these changes? The question – do the jobs they are doing have to be done by a doctor?

I can’t imagine for a second that this question can be critically applied to the new foundation year jobs in community work and answered affirmatively.

Furthermore when the role of any of our jobs is deconstructed, how much of that role needs to be done by a doctor? We can give up prescribing to a pharmacist, blood taking to a phlebotomist, ward based care to a physician’s assistant, outpatient follow-up (assuming it will be permitted in the future) to a nurse specialist, diagnostic procedures to a radiographer, diagnostics to a nurse consultant, audit to a data manager, construction and development of the department to an administrator, training programme planning to deanery educationalists, perioperative support to a clinical psychologist, etc, etc, etc.

How much of the work of a junior doctor has ever had to be that of a doctor?  The job of the junior doctor has always been all of these, whilst learning from and being inspired by the beauty of a carefully constructed ward consultation by a senior clinician who understood the subtleties of human interaction and the tensions and uncertainties of the patient lying in the bed in front of him or her. The junior doctor didn’t mind devoting much of his or her young life and many hours of hard work, including performing some menial tasks, because the new recruit was intelligent enough and committed enough to realise that hours spent on the wards and in clinic would turn themselves, currently a piece of apparently formless clay, into a fine piece of highly polished china.  They would, yes with hard work, hours spent studying, and arguably obsessional attention to detail and a constant desire to improve, become a fantastic  diagnostician, a remarkable clinician and, in some cases, a technically brilliant surgeon and the most wonderful observer of the human condition.

Which of any of our jobs must be done by a doctor? That is not a reasonable question to apply to much of what any doctor, or indeed I suspect what any professional, does in their day to day work. It is the totality of what they do that defines their role, not the minutely dissected individual parts of their job.  When dismembered, no organism has the functional beauty of its form when complete, nor is it able to survive when it is disassembled.

I fear that that is true of our glorious profession. What would Bright, Hodgkin or Astley-Cooper say if they could guide us now?

I am no Luddite. I work in a branch of medicine that has thrived in the technological development of its specialty, in a department that has led the way in introducing new ways of working, new ways of thinking about how care should be provided with a better understanding of patient processing and what frustrates patients when they access healthcare. We as a group have demonstrated how we are willing to embrace change when we perceive it to be for the benefit of our patients.

I have sat and watched changes being introduced, as have many of us over the years, suspicious that not all changes are really in the interests of the future of medical care. However, I sat down after attending the meeting to which I referred earlier and found myself asking these questions.

In Judaism, at a burial and for a year after the death of a close relative, we recite kaddish, the memorial prayer. Is it now time to recite kaddish for the role of the junior surgical hospital doctor?

Jonathan Glass – Consultant Urologist, Guy’s & St Thomas’ NHS Foundation Trust

 

Editorial: Conventional laparoscopic surgery – more pain, no gain!

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Advances in surgical technology have revolutionized the way surgery is performed today. Conventional laparoscopic surgery dominated the surgical paradigm for several decades, until robot-assisted surgery created the next giant leap. In the pressent article, Elhage et al. [1] compare and correlate physical stress and surgical performances among three modes of a standardized surgical step. Their study shows the obvious physical strain and technical limitations faced while performing conventional laparoscopic surgery, subsequently leading to compromised surgical outcomes. The physical impact of conventional laparoscopic surgery has been well documented through surgeon feedback as well as ergonomic assessment [2, 3]. Various studies have reported that higher physical stress, associated with ergonomic limitations, is experienced when performing conventional laparoscopy compared to the comfort and ease of robot-assisted surgery, as highlighted in the present study. Increased workload has also been associated with performance errors, with a steep learning curve needed to achieve surgical excellence during conventional laparoscopy [4].

Currently, the use of robot-assisted surgery is on the rise, as an alternative to both open and conventional laparoscopic surgery across the developed world, despite its obvious economic limitations. Better ergonomics during robot-assisted surgery will increase the comfort of the surgeon, but the future of surgery may easily be linked to the improvements experienced by all of us in the automobile industry. Developments, from manual gear-clutch control to automatic speed control and the luxury of adaptive cruise control today, make us safe drivers with minimal physical stress. The concept of adaptive cruise control, which adjusts the speed of a vehicle in relation to its surroundings, sounds similar to the leap from manual camera control during conventional laparoscopy to console-based control during camera navigation in robot-assisted surgery. With advances in the speed and size of computers, pneumatic-based joint mechanics and mindfulness meditation on the horizon, it will not be long before surgeons will sit back and watch the marvel of the machine. Surgeons just need to learn to hold on to their seats!

Read the full article
Syed J. Raza*, Khurshid A. Guru† and Robert P. Huben†
*Fellow, †Endowed Professor of Urologic Oncology, Department of Urology and A.T.L.A.S (Applied Technology Laboratory for Advanced Surgery) Program, Roswell Park Cancer Institute, Buffalo, NY, USA

 

References

 

1 Elhage O, Challacombe B, Shortland A, Dasgupta P. An assessment of the physical impact of complex surgical tasks on surgeon errors and discomfort: a comparison among robot-assisted, laparoscopic and open approaches. BJU Int 2015; 115: 274–281

2 Plerhoples TA, Hernandez-Boussard T, Wren SM. The aching surgeon: a survey of physical discomfort and symptoms following open, laparoscopic and robotic surgery.

J Robotic Surg 2012; 6: 65–723 Hubert N, Gilles M, Desbrosses K, Meyer JP, Felblinger J, Hubert J. Ergonomic assessment of the surgeon’s physical workload during standard and robotic assisted laparoscopic procedures. Int J Med Robot 2013; 9:142–147

4 Yurko YY, Scerbo MW, Prabhu AS, Acker CE, Stefanidis D. Higher mental workload is associated with poorer laparoscopic performance as measured by the NASA-TLX tool. Simul Healthc 2010; 5: 267–271

 

You may have heard it on the grapevine, but UroVine is now here

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UroVinePic3I was first introduced to Vine by my good friend Dr Fernando Gomez Sancha over a very enjoyable dinner in Milan during the European Association of Urology meeting in March 2013.  I thought that the concept was interesting and signed up on the spot.

Vine is a relatively new social media platform that allows users to create and share 6 second videos loops.  It brings out amazing creativity with the very restrictive maximum 6 second video duration. It is not dissimilar to the Twitter where users have to work within the content limits of the platform where one only has a 140 character to make a point. However, Twitter is probably a lot easier than trying to create 6 second video content.

Although signed up to a Vine account, I did not use it very much initially.  I was still a little unsure as to how I was going to be able make use of it either for personal or professional use.  Gradually over time, I started playing around and making some personal Vine clips, mainly at concerts or at sports events.  They were not particularly well thought out Vines and certainly of limited interest. I also tweeted a few of these Vines and I was impressed by the integration of Vine videos on the Twitter platform.  I should not have been surprised since Twitter owns Vine.

On Twitter, one can watch a Vine loop video without having to click a link out of the App or website as is the case for say YouTube. Additionally, the short Vine clips were a perfect match for Twitter users who wanted small bite sized content in this time poor world. I then became fascinated with Vine having this repetitious loop – it is almost captivating to the extent that you cannot help but to watch at least 3 or more loops. The first loop is like “what was that”, the second loop is like “I think it’s what I thought I saw” and third loop is like “I get it” and the fourth loop is because you could not work out exactly when the third loop ended and accidentally watched it for an additional time. Have a look some Vine clips and you will then understand what I mean.

This repetition had me thinking about how can we find a medical education application to this platform. The answer was really in Twitter. The best way was to use Twitter and Vine together. If a specific Twitter account were to be created to link to specific Vines, we could create a powerful medical education tool. The repetitious nature of the video loop enables us to reinforce a learning point.

On 3 February 2015, #UroVine was established using the account @UroVine. Vine clips have already been tweeted associated with key learning points. I would love to hear your feedback and to have your Vines submitted for tweeting.

UroVinePic1

Making a Vine is very simple. It does not have to be HD or have cinema ready professional production. The simplest thing to do is to take your mobile phone with the Vine App and to shoot selected video running off your laptop. More important is that there needs to be clear learning point that needs to reinforced.

UroVinePic2

The combined use of Twitter and Vine specifically for medical education has the potential to be a very powerful tool. With recent provision of Twitter Activity metrics for each tweet and Vine loop data, there is the potential for some interesting analysis. It is my belief that this is a first and once again a demonstration that Urology is leading the way with innovation in medical education and social media. I hope you will join us.

Henry Woo (@drhwoo) is Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney. He is the Editor in Chief of BJUI Knowledge, an innovative on-line CME portal that launches this year.

 

Social media makes global urology meetings truly global

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Loeb_photoThe use of social media continues to expand in urology and the BJUI is proud to be at the forefront of these efforts. All of the global urology meetings now have their own twitter feed, which is indexed using a ‘hashtag’ (e.g. #EAU14, #AUA14). Analogous to a Medical Subject Heading (MeSH) in PubMed, hashtags are used to categorise related tweets together in one place, providing a convenient way to follow conference proceedings.

Surrounding the 2014 European Association of Urology (EAU) Congress (9–16 April 2014), there were a record 5749 tweets from 761 unique contributors. The BJUI and its editorial team represented four of the top 10 social media influencers based on the number of times that they were mentioned in the #EAU14 conference twitter feed.

Social media engagement continued to grow to new heights at the 2014 AUA meeting. From 14–23 May 2014, there were a total of 10 364 tweets from 1199 unique contributors in the #AUA14 conference twitter feed. The BJUI and its editorial team represented six of the top 10 influencers based on the total number of mentions.

In addition to urology conferences, the BJUI continues to actively participate in social media throughout the year. We provide a variety of specialised content such as videos, picture quizzes, and polls, as well as free access to the ‘Article of the Week’. This provides a great way to stay up-to-date on the latest research in a dynamic, interactive setting.

Finally, I would like to call your attention to two ‘Articles of the Week’ featured in this issue of BJUI, both of which will be freely available and open to discussion on twitter. The first by Kates et al. [1] deals with the interesting question of the optimal follow-up protocol during active surveillance. Using yearly biopsy results from the Johns Hopkins active surveillance programme, they report what proportion of reclassification events would have been detected had the Prostate Cancer Research International Active Surveillance (PRIAS) protocol been used instead (including less frequent biopsies and PSA kinetics).

Another feature ‘Article of the Week’ by Eisenberg et al. [2] addresses the controversial link between testosterone therapy and prostate cancer risk. Among men undergoing hormonal testing at their institution, they used data from the Texas Cancer Registry to compare the rates of malignancy between those who were and were not using testosterone supplementation. We hope that these articles will stimulate an interesting discussion and encourage you to join us on twitter.

Dr. Stacy Loeb is an Assistant Professor of Urology and Population Health at New York University and is a Consulting Editor for BJUI. Follow her on Twitter @LoebStacy

 

Editorial: Opening the flood gates – HLE is superior to PVP for the treatment of CUR

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With the expansion in laser technology for treating symptomatic BPH, there are now two main techniques available to the budding urologist. Yet the management of chronic urinary retention (CUR) remains a significant challenge. In this issue of BJUI Jaeger et al. [1]present a retrospective study comparing holmium laser enucleation of the prostate (HoLEP) and photoselective vaporization of the prostate (PVP; using XPS 180 watt and HPS 120 watt systems) in the treatment of CUR.

Both HoLEP and PVP are now well-established treatment methods. Although PVP has seen a greater level of acceptance because of its shorter learning period, its use remains limited by prostate size and concerns about long-term durability. In contrast the favourable and enduring outcomes reported for HoLEP have meant that it is gaining recognition as the new ‘gold standard’ surgical treatment for BPH. Whilst PVP ablates the tissue laterally from the prostatic urethra, HoLEP involves an anatomical enucleation of all the prostatic adenoma before morcellation.

Over the past decade, there has been a shift towards medical management of BPH. Despite the resultant increase in numbers of men developing CUR, best practice for this challenging and clinically important group remains highly debated. The term CUR is used to describe a constellation of presentations, and current imprecise, even arbitrary, definitions make the interpretation of existing studies difficult. Historically, CUR has been almost universally excluded from trials because of the anticipation of poor outcomes and high complication rates, while the presence of detrusor hypotonia, particularly with low-pressure retention, has led to concerns of treatment failure following surgery. This dilemma for urologists has been aggravated by conflicting evidence in the published literature [2].

Jaeger et al. [1] assessed all patients with CUR who were treated in their institution either with HoLEP (72 patients) or PVP (31 patients). CUR was defined as a persistent post-void residual urine volume (PVR) >300 mL or urinary retention refractory to multiple voiding trials. While preoperative urodynamic studies were not routinely performed, those patients found to have low bladder contractility or acontractility were not excluded.

Both HoLEP and PVP produced similarly effective outcomes in terms of symptom score improvement, PVR reduction and Qmax increase in voiding patients. Complication rates were also similar in the two groups (15 and 26% for HoLEP and PVP, respectively, P = 0.27), but, importantly, HoLEP was shown to offer substantially better rates of spontaneous voiding than PVP, 99 vs 74% of patients, in spite of a lower median bladder contractility index in the HoLEP group (73 vs 90, P = 0.012).

Both PVP and HoLEP have previously been studied in isolation in treating patients with CUR. Whilst Woo et al. [3] demonstrated significant reductions in PVR after PVP (GreenLight HPS 120-W), the presence of detrusor under-activity was not established. Outcomes after PVP in patients with urodynamically proven detrusor hypotonia have been shown to be significantly worse than in patients with normal detrusor funtion [4].

The effectiveness of HoLEP has been shown in treating CUR secondary to BPH in a large study of 169 patients with symptom score improvements of 159% and spontaneous voiding in 98.25% [5]. Furthermore, even in patients with proven impaired bladder contractility, HoLEP led to spontaneous voiding in 95% [6] at least in the short term.

The findings from the present study further support the use of HoLEP specifically in CUR. Jaeger et al. are the first to compare the two technologies head on, albeit in a non-randomised study, in the treatment of CUR. Whilst both treatments showed reasonable efficacy despite low or absent bladder contractility in a number of patients, a significant advantage was seen with HoLEP, with the total removal of any obstructing tissue. These results were unaffected by the presence of preoperative impaired bladder on urodynamic studies. This study suggests that HoLEP is superior to PVP in the treatment of CUR, probably because of the larger prostatic channel that enucleation produces. Measurement of postoperative PSA readings would have been a useful addition to illustrate this. Nevertheless, the findings add to the growing body of evidence to support the use of HoLEP in treating CUR, irrespective of preoperative bladder function.

Read the full article

Nicholas Raison and Ben Challacombe

Urology Department, Guy’s and St Thomas’ NHS Trust, Guy’s Hospital, Great Maze Pond, London, UK

References

1 Jaeger CD, Mitchell CR, Mynderse LA, Krambeck AE. Holmium laser enucleation and photoselective vaporization of the prostate for patients with benign prostatic hyperplasia and chronic urinary retention. BJU Int 2015; 115: 295–9

2 Ghalayini IF, Al-Ghazo MA, Pickard RS. A prospective randomized trial comparing transurethral prostatic resection and clean intermittent self-catheterization in men with chronic urinary retention. BJU Int 2005; 96: 93–7

3 Woo H, Reich O, Bachmann A et al. Outcome of GreenLight HPS 120-W laser therapy in specific patient populations: those in retention, on anticoagulants, and with large prostates (≥ 80 ml). Eur Urol Suppl 2008; 7: 378–83

4 Monoski MA, Gonzalez RR, Sandhu JS, Reddy B, Te AE. Urodynamic predictors of outcomes with photoselective laser vaporization prostatectomy in patients with benign prostatic hyperplasia and preoperative retention. Urology 2006; 68: 312–7

5 Elzayat EA, Habib EI, Elhilali MM. Holmium laser enucleation of prostate for patients in urinary retention. Urology 2005; 66: 789–93

6 Mitchell CR, Mynderse LA, Lightner DJ, Husmann DA, Krambeck AE. Efficacy of holmium laser enucleation of the prostate in patients with non-neurogenic impaired bladder contractility: results of a prospective trial. Urology 2014; 83: 428–32

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