Archive for category: BJUI Blog

AUA Blog – Highlight of Day 1 and 2

Greetings from San Diego, California! The annual meeting of the American Urological Association (AUA) is underway with over 15,000 attendees converging on this beautiful city from around the world. As I arrived at Pearson International Airport in Toronto on Friday and made my way through security I ran into roughly twenty of my colleagues from in and around Toronto getting ready to board the same plane. Canadians have attended this meeting in droves for as long as I can remember. Arriving in San Diego was easy with nice access to the city from the airport. After checking into hotel the first order of business was to register, which was also easy at least on Friday.

 

As I arrived on Friday it was clear that the meeting was already in full swing. A variety of research programs were underway including a Basic Science Symposium that explored the underlying role of inflammation and fibrosis in urological disorders.

 

Most noteworthy and newsworthy on Friday was the AUA news release of its new Guidelines on the Early Detection of Prostate Cancer. These will be sure to generate a lot of discussion. In summary:

 

  • Screening under age 40 is not recommended
  • Routine screening of men between age 40 and 54 at average risk is not recommended
  • For those aged 55-69, a shared decision to screen is advocated with a PSA drawn perhaps every two years.
  • Routine screening is not recommended after the age of 70.

 

These guidelines will be formally presented during Monday’s plenary session. The full document can be found here. It is clear to me that our challenge as urologists to properly council our patients in light of these new guidelines will only increase when you consider some of the headlines in the media. What do you think of these new Guidelines? Comments below please?

 

The first full day of scheduled activity was Saturday. A variety of sections and societies held meetings on this day.  A number of courses were offered that continue to be well attended. This year a course pass was adopted that allowed individuals to get into most things available – a popular addition for AUA delegates. Highlights from the first day included:

  • The Engineering in Urology Section of the Endourology Society, highlighting advances in imaging as well as new robotic prototypes being developed from around the world. It will be interesting to see if any of these strange devices make it into the OR.
  • The Society of Urological Oncology was extremely well attended as usual. Dr Urs Studer delivered the Dr. W Whitmore Memorial Lecture and suggested that after more than 25 years in the PSA era a major re-think of how we treat prostate cancer is required.

 

Another very popular event was the live surgery session, which ran all day on Saturday. Highlights including a virtuoso robotic radical cystectomy with orthotopic ileal neobladder formation performed by Dr Indy Gill.  

                 

 

The role of robotic surgery to treat a variety of urological conditions is clearly expanding. For those of us in Canada the time is now to figure out how we will obtain, deploy, credential and manage this technology in our own publically funded healthcare system

 

The first plenary sessions began on Sunday. With the weather turning a little (I thought it never rains in Southern California?!) it made it easier to go indoors and listen to the talks and lectures inside. Highlight from plenary session one included a State-of-the Art Lecture of Technology’s role in the Future Management of Erectile Dysfunction by Dr Run Wang. Mention was made of nanotechnology and tissue engineering but perhaps the most intriguing near-term advance may be the advent of a smart phone app for operation of penile prostheses (yes it’s true!). Drs. Allen Seftel and Serge Carrier debated the role of the urologist in screening men with erectile dysfunction for cardiac disease. There was agreement on the link to cardiac disease but debate remains as to how many urologists will requisition stress tests. The second plenary session included an AUA Health policy update by Dr. David Penson and review by Dr. Peggy Pearle of the recertification process for urologists for the American Board of Urology.

As always, tremendous scientific efforts were on display at multiple poster and podium sessions. Predictably there was far too much for any one individual to entirely see. The discussion on Twitter via #AUA13 did allow for some ‘reporting’ at sites that I could not attend. A tremendous amount of work focusing on screening and active surveillance was clearly evident as well as the increasing use of new imaging techniques for managing these patients were evident. An afternoon session on HIFU and focal therapy left many people scratching their heads as to the utility of these modalities. The 47 % positive biopsy rate for HIFU was particularly disappointing. The best (or at least most entertaining) editorial of this session can be found in the twitter feed of @daviesbj.

 

 

In the science and technology exhibition area a tremendous presence from industry was again noted. Again, as a Canadian I am a little unsure as to how we will manage to incorporate all of this new technology when our hospital system is already strained. The Second Annual Residents Bowl narrowed down the field to two finalists, from the Western and South-eastern Sections. They will faceoff Monday at 1230 for the final. Finally the first Chief Residents’ debate highlighted that the future of our great speciality is very bright under the stewardship of these incredible young people.

 

For me a significant change to this meeting from past meetings is the use of social media to network, distribute ideas and scale down what often is a very large meeting into something that seems more accessible and local. The use of these multiple platforms has transformed the way we attend meetings. The recent meetings of the European Association of Urology (#eau13) and Urological Society of Australia and New Zealand (#USANZ13) highlight what can be achieved when this technology is used. Those not attending can participate actively. This has created an international participation in meetings in a way I have never seen before. The live twitter boards that you see around the convention centre here in San Diego, which are helping to spread the word, got their inspiration from these recent meetings.

 

 

A few individuals such as @daviesb and @DrHWoo and @tdave deserve credit for insisting that these boards become of feature of the 2013 meeting. Well done to AUA for taking a proactive approach to social media this year and for listening to your members. The hashtag to follow is #AUA13. I would encourage all to participate in this community. You will be amazed at how easily you can find out about what’s really going on at this meeting and also check in at venues that you cannot otherwise physically attend. You can see who are the leading influencers on twitter at #aua13 by checking out updated metrics via Symplur.  You can see from this link that the chatter is building daily. I look forward to seeing a similar picture at #CUA13 when the Canadian Urological Association meets in June.

 

The use of Social Media will rapidly increase in scope and become a necessary part of communication within our Urological meetings. The AUA (@Americanurol) has recently established a committee to establish guidelines help grow its use for AUA members. Sign up for an account and dive in. It is highly engaging, somewhat addictive, very informative and always fun!

 

The BJUI hosted a great event, The BJUI Social Media Awards, for all of the early adopters of social media on Saturday evening. In particular this group has networked and communicated regularly over the last six months and ‘meet’ once a month to run a journal club on twitter using the hashtag #urojc. They self-identify as urotwitterati. The BJUI
arranged for many of us to meet for the first time by hosting the #BJUISoMeAwards. It was a great event and will be fully featured in a separate blog this week along with details of the well-attended BAUS/BJUI Session that took place on Sunday afternoon and included the awarding of the Coffey-Krane Prize.

 

Lastly on Sunday,  by the security guards in Sacramento CA, we were treated to a spectacular Reception on board the USS Midway, a first opportunity for most of us to go on board a gigantic aircraft carrier and see some wonderful aircraft. The flight simulators were only for those who had not had a few beers already and who could tolerate the high G forces! Well done again to AUA for this excellent event.

 

 

Monday’s plenary session will include some very interesting debate around nephrolithiasis and I look forward to a Town Hall led by Dr. Ralph Clayman debating Robots as a possible harbinger of Surgeon Obsolescence. New guidelines on castration resistant prostate cancer will also be presented. Stay tuned for further updates from @Matthayn on Wednesday

  

Dr Rajiv Singal

Urological Cancer & Robotics Lead, Toronto East General Hospital, Canada

Follow him on Twitter at @DrRKSingal

 

Read Day 3 & 4 Highlights here

 

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The Perfect Storm: How Hurricane Sandy Took Down Manhattan

Nobody could have really predicted the impact of Hurricane Sandy, which struck Manhattan on October 29, 2012. If you told us a year ago that a hurricane would shut down all of New York City for weeks and that the hospital would be closed for months, we never would have believed it. Six months later, things still have not completely returned to normal.

It all began on what seemed like an ordinary Friday afternoon, as we hurried between clinical duties and research meetings to get some semblance of order before the Halloween weekend. In the midst of the daily hubbub, emails and texts began pouring in about Hurricane Sandy, a massive tropical storm that was projected to hit New York City directly. All 3 hospitals served by the New York University (NYU) are located right along the water in Manhattan and many of the employees live nearby, causing significant concern.

As the storm approached, the lines at the local grocery and convenience stores grew exponentially, wrapping around aisles and often out the door and down the street. Shoppers filled carts with everything from toilet paper and toothpaste, to bottled water and batteries. As soon as their inventory was sold out, shop owners locked their doors and boarded up their windows in preparation for the storm.

When the meteorologists’ worst predictions appeared to be imminent, a mandatory evacuation order was issued for parts of east and southeast Manhattan. The inhabitants of these neighborhoods, many of which included the faculty, staff, residents, and medical students of NYU, migrated to the homes of friends and family. Others, whose apartments were just outside the evacuation zone, hunkered down for what was going to be a long, dark, cold, and wet night.

A few hours after the storm began to hit Manhattan, a massive explosion rocked the electric plant that supplies power to the lower half of Manhattan. Suddenly the skyline was transformed as half of New York City went completely dark, from 39th Street all the way to the southern tip of Battery Park. Without power, there was no electricity, no heat, and no hot water. The winds howled, uprooting trees and tearing down street signs, all while the rain flew sideways. The streets lining the East River flooded early and slowly rescinded overnight, leaving a wake of debris. When morning came, the residents of Manhattan peered out their windows to investigate the damage of the storm, not knowing what to expect.

The New York University (NYU) Department of Urology covers 3 hospitals. The Manhattan VA Hospital was evacuated in advance of the storm, with all of the patients transferred to other veterans’ hospitals in neighboring cities. Bellevue Hospital and NYU Langone Medical Center initially continued to operate during the storm, but were ultimately evacuated when the emergency power supply failed. Many of you may have seen the dramatic TV footage of babies from the ICU being ventilated while carried by nurses down the dark staircases to evacuate the hospital. The efforts made by the clinical staff to ensure patient safety during that time were truly heroic.

In the first few days after the storm, the lower half of Manhattan was like a war zone. With all of the skyscrapers, many people had to walk up and down 10-30 flights of stairs in the dark to look for food or supplies. Some of the elderly people in our neighborhood were unable to do this, so they literally sat in a dark apartment for >10 days eating whatever food remained in the pantry. There was also intermittent internet and cell phone service in the area, leaving people with a very eerie and disconnected feeling. The streets were mostly desolate, with many stores closed and some of them looted. Sanitation was another issue. Without any running water, many people used small amounts of their precious bottled water to flush the toilet once a day. Bags of refuse were carried up and down the dark staircases for disposal. And this is New York, what some (New Yorkers at least) would consider the “center of the universe!” With the world usually at your fingertips, many New Yorkers have never had to think about survival skills. Of course, CNN and other TV news stations featured all kinds of seemingly helpful tips during Hurricane Sandy on how to manage without electricity or running water, but most people who desperately needed this information had no way to watch these segments. Instead makeshift cell phone charging stations were set up along the street for desperate residents hoping to reconnect.

Mass confusion ensued. Many people’s homes and cars were flooded or destroyed. Military vehicles began to appear around the city to help restore order. The hospitals remained closed and patients were dispersed. There was no way to access the electronic medical record to find out the names and contact information for patients on the upcoming schedule. Even the institutional email system was down, so employees didn’t know when, where or if they needed to report to work. Insurance companies had their work cutout for them. Some even went to the extent of reducing their rates on new insurances and provided the cheapest van insurance and car insurances to the new policy holders. Collision repair technicians fix the outer body of cars. These technicians can also be trained in repairing internal components of a damaged automobile. Formal training is not always required, as many repair shops train employees on the job, but obtaining a degree or certification can assist in employment prospects. For people who owns a car, getting an insurance for it is a matter to be given a deep thought. Everyone knows that car insurance costs high, yet, important. The idea behind this gives the reason why premiums are a very dear commodity. However, in this new age of car insurances, a new type of car policy is born! This is one of the short-term insure companies introduced and termed the car insurance for one week. A car only insured for a one-week period. with this short coverage, the user or buyer of this insurance is not being prompted with so much requirements, unlike the regular or normal car policy in which many documentary, unlike the regular or normal car policy in which many documentary requisites are being asked to be prepared. Click here to find more about the author.

Over time, the city gradually started to reopen. A limited bus service began working at no charge, but the lines were several blocks long and the crowding was extreme. Most of the subway stations were flooded and it took several weeks to months for the subway and train services to be restored. There were also gas shortages leading to rationing. People had to wait for 2+ hours in line at the gas station, resulting in crazy stories like this one where a man pulled out a gun to jump the line.

Meanwhile, as soon as the airports reopened many foreigners began arriving into the midst of this scene for the New York City Marathon, which was supposed to take place the following weekend. With half of New York City flooded and in the dark, a huge controversy erupted over diverting scarce resources to allow the marathon to proceed. The New York Post ran a cover story exposing how power generators were being used to prepare the media tents for the marathon, and the race was ultimately cancelled <48 hours beforehand – too late for the many foreign runners who wasted huge sums of money and time making their way to storm-ravaged NYC unnecessarily.

On the clinical side, many NYU physicians obtained emergency privileges to practice in New Jersey. Nevertheless, this involved a long commute (>1 hour) for both patients and physicians to unfamiliar surroundings. In addition, most of these hospitals already operate at capacity. Office space was not available for the “displaced physicians” and it was often difficult just to find a free computer to use. Imagine if the entire staff from another hospital was suddenly transferred to your hospital – where would you put them and how could you accommodate their patients? Many surgeries could only be booked on nights or weekends when the OR was not in use by the local physicians, and could be bumped at the last minute. On-call coverage had to be reorganized to provide care for our patients all over the tri-state area, which was particularly challenging without the regular train and bus services to these areas. Bellevue and NYU Hospital began to partially reopen at the end of December 2012, and the Manhattan VA remained completely closed until March 2013. Even now, some of the clinical services at these hospitals have not been completely restored as the long repair process continues.

From the research standpoint, the impact was huge. Loss of the emergency generators caused many precious research experiments to be lost. Imagine if you collected special samples from around the world for your laboratory, or if you had stored tissue from patients with 20 years of follow-up data. Then one day a big storm came and it all washed away. Some of these things simply cannot be replaced. The situation was similarly bleak for clinical research since the server was also destroyed, resulting in massive data losses. Imagine that you got a grant, hired research personnel, completed several years of data collection and analysis, and even saved an extra copy of your work on the backup server, but suddenly all of that was gone. You could apply for an extension on your grant or insurance money for what was lost in the natural disaster, but it could take years to get back to where you were and this type of intellectual property loss is difficult to even quantify. The original personnel may not be available to re-do the work, the idea may no longer be timely, and what you really want to do is move forward with your research not spend months to years repeating what was already done.

What can we learn from this? Unfortunately, natural disasters happen, and many of the issues that transpired are impossible to predict or prevent, particularly at the individual level. If there are warnings about a major storm, take it very seriously. Keep a section in the closet with some basic supplies like batteries, flashlights, a radio and an emergency list of contacts. Make sure that all electronic devices are fully charged and that your data are backed up as much as possible in different locations. And hope that nothing like this ever happens again.

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

Dr. Marc Bjurlin is a Fellow in Urologic Oncology at New York University.

Comments on this blog are now closed.

Editorial: Incorporating prognostic grade grouping into Gleason grades

The ‘Gleason Grading System’ first proposed by Donald Gleason in 1966 was a revolutionary system for its time. As it advocated the use of a sum score that combined the two most common patterns of prostate cancer seen in a radical prostatectomy specimen to predict the biological outcome of the tumour, rather than the worst pattern that was in common usage with other tumour types, it was truly innovative. Furthermore, although several other classification systems for prostate cancer have been proposed since then, none has stood the test of time as well as the Gleason system and certainly no other system is in widespread use internationally.

Gleason and Mellinger went on to make adjustments and modifications to this classification system in 1974 and 1977, as the series of cases examined was expanded from the original 270 patients to >1000 patients.

Since then, there have been further changes to the Gleason Grading System with the advent of immunocytochemistry and in terms of clarification of the size and spacing of individual acini that are seen in the various patterns originally illustrated by Gleason. A tertiary pattern of prostate cancer, mentioned in passing by Gleason, has also become more clearly identified in a proportion of cases.

Possibly the most important advance regarding the Gleason Grading System was the result of an International Consensus Conference of Urological Pathologists in 2005. This meeting, comprising >80 specialist pathologists from 20 countries, published the updated or ‘Modified Gleason Grading System’. These guidelines were based on the changes in practice that had taken place in the diagnosis and treatment of prostate cancer in the previous 40 years and included evidence for the confirmation that Gleason 1 and 2 patterns should not be assigned on prostatic needle biopsy specimens and that all cribriform areas of tumour were best regarded as Gleason pattern 4 rather than Gleason pattern 3.

Although these modifications have been useful for the surgeon and pathologist, they have not clarified the Gleason grading system for the patient. It is not easy to explain or to understand why a system that in theory could produce a range of Gleason sum scores from 2 to 10, is in practice actually limited on prostatic biopsy to Gleason sum score 6 to 10. Thus, rather confusingly, Gleason 6 is the most favourable category of prostatic carcinoma in terms of prognosis, rather than indicating a ‘middle-of-the-scale’ tumour.

The paper presented in this issue of BJUI, ‘Prognostic Gleason grade grouping: data based on the modified Gleason scoring system’, attempts to compensate for this by allowing the categorisation of prostatic carcinoma not only in terms of Gleason sum score, but also into prognostic groups I to V that correlate with the sum score and may be easier for the patient to appreciate.

This is an important next step in the development of the Gleason Grading System and hopefully one that will be embraced by surgeons and pathologists and more easily accepted by patients.

Alex Freeman
Department of Histopathology, University College London Hospital, London, UK

Read the full article

Editorial: Targeting the pro-survival side-effects of androgen-deprivation therapy in prostate cancer

In this paper, Bennett et al. [1] report the effects of an anti-androgen drug on autophagy and the subsequent impact on response to androgen-deprivation therapy alone or combined with exiting chemotherapeutic treatments.

With an estimated 238,590 newly diagnosed cases and 29,720 deaths for 2013 in the USA, prostate cancer is, after skin cancer, the second most common cancer in men. Although the disease initially responds well to therapy, the cancer recurs in most patients within 1–2 years of the initial response. Few therapeutic options exist for patients with recurring prostate cancer and docetaxel is considered the standard of care. But despite clinical benefits, its effect is mainly palliative and often short-lived, and all patients eventually develop progressive disease with a median survival of 1–12 months. In addition, the decision of when to initiate docetaxel-based chemotherapy is an important one that is not clearly addressed by current treatment guidelines.

Autophagy is a lysosomal catabolic pathway that promotes cell survival in response to starvation or other cellular stresses by degrading and recycling macromolecules and organelles. In recent years, this cellular process has been implicated in the aetiology of cancer; the roles it plays, however, in the development and maintenance of cancer appear conflicting [2–6]. Indeed, tumour cells appear to disable autophagy at an early stage, thereby facilitating the onset of tumorigenesis, whereas in existing malignancies autophagy is activated as a means of stress adaptation, resulting in metastatic dissemination [7–9]. Autophagy is also induced by nearly every anti-cancer treatment as an adaptive pro-survival mechanism against cytotoxic agents and may therefore favour radio- and chemo-resistance [10–12].

Bennett et al. [1] are the first to show the induction of autophagy due to suppression of androgen function in the absence of other cellular stresses in an androgen-sensitive cell line. The authors showed that anti-androgen treatment induced autophagy in LNCaP prostate cancer cells, resulting in a pro-survival effect that was abolished by pharmacological inhibition of autophagy, a response that is similar to that seen in tamoxifen-resistant breast cancer cells. Their study highlights the potential of combining anti-androgen therapy with autophagy inhibition in the treatment of prostate cancer. The mechanism by which anti-androgen therapy activates autophagy is unclear, but this study suggests that modulation of mammalian target of rapamycin (mTOR) signalling, a major cellular metabolism switch, may underlie this effect. Thus, agents that inhibit the pathway combined with inducers of metabolic stress or chemotherapeutic agents could enhance anti-cancer therapy by inhibiting stress adaptation and increasing cell damage. The search for novel inhibitors of the pathway is crucial in the fight against cancer.

Clearly, to this day, there are no simple rules for the outcome of targeting autophagy as a cancer therapy. The apparent conflicting effects of activating or inhibiting autophagy at various stages of the disease are likely to be dictated by the genetic background as well as the environmental cues tumour cells are exposed to. One of the main challenges in prostate cancer therapy is to determine the precise timing of drug application. Therefore, the identification of a ‘fingerprint’, including the aforementioned parameters, in prostate cancer is crucial for the selection of an effective treatment. The present study opens up potential new avenues in the treatment of prostate cancer but further in vitro and in vivo studies will be necessary for efficiently translating this knowledge into the clinic.

Vincent Zecchini and David E. Neal
Department of Uro-Oncology, University of Cambridge, Cambridge, UK

Read the full article

REFERENCES

  1. Bennett HL, Stockley J, Fleming JT et al. Does androgen-ablation therapy (AAT) associated autophagy have a pro-survival effect in LNCaP human prostate cancer cells? BJU Int 2013; 111: 672–82
  2. Oh SH, Lim SC. Endoplasmic reticulum stress-mediated autophagy/apoptosis induced by capsaicin (8-methyl-N-vanillyl-6-nonenamide) and dihydrocapsaicin is regulated by the extent of c-Jun NH2-terminal kinase/extracellular signal-regulated kinase activation in WI38 lung epithelial fibroblast cells. J Pharmacol Exp Ther 2009; 329: 112–22
  3. Qu X, Yu J, Bhagat G, Furuya N et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest 2003; 112: 1809–20
  4. White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res 2009; 15: 5308–16
  5. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 2003; 100: 15077–82
  6. Liang XH, Jackson S, Seaman M et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672–6
  7. Chiarugi P, Giannoni E. Anoikis: a necessary death program for anchorage-dependent cells. Biochem Pharmacol 2008; 76: 1352–64
  8. Douma S, Van Laar T, Zevenhoven J et al. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 2004; 430: 1034–9
  9. Yap KL, Zhou MM. Keeping it in the family: diverse histone recognition by conserved structural folds. Crit Rev Biochem Mol Biol 2010; 45: 488–505
  10. Chen S, Rehman SK, Zhang W et al. Autophagy is a therapeutic target in anticancer drug resistance. Biochim Biophys Acta 2010; 1806: 220–9
  11. Liu L, Yang M, Kang R et al. HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells. Leukemia 2011; 25: 23–31
  12. Lomonaco SL, Finniss S, Xiang C et al. The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells. Int J Cancer 2009; 125: 717–22

Bringing science closer to urologists

The BJUI has always promoted the best in basic science through its ‘Investigative Urology’ section. However, the new editorial team noticed a small problem – these articles were rarely cited, probably because they were rarely read. As we started speaking to our readers, the truth became rapidly obvious. Most urologists, being clinicians, could not understand the scientific content of these articles. Here was a major challenge. How were we going to attract our surgical readership to science?

Whilst maintaining our commitment to quality, we took three bold steps in discussion with our readership:

  1. Rename the section ‘Translational Science’, so as to highlight the potential clinical relevance of the best basic science papers.
  2. Assemble an editorial team of the best clinician-scientists, not just from molecular and cellular biology but other diverse fields, such as immunology, imaging, engineering and computational sciences.
  3. Precede original science papers with ‘Science made Simple’ articles. These were inspired by the highly successful For Dummies series from Wiley.

The idea behind For Dummies is making everything easier. With >250 million books in print and >1800 titles, For Dummies is the most widely recognised and highly regarded reference series in the world. Since 1991, For Dummies has helped millions make everything easier. Now, Dummies.com is bringing the ‘how-to’ brand online, where readers find proven experts presenting even the most complex subjects in plain English. Whether that means directions on how to hook up a home network, carve a turkey, knit your first scarf, or load your new iPod, you can trust Dummies.com to tell it like it is, without all the technical jargon. For Dummies is a simple, yet powerful concept. It relates to the anxiety and frustration that people feel about technology by poking fun at it with books that are insightful and educational and make difficult material interesting and easy.

Thus we originally thought of publishing articles entitled ‘Science for Dummies’.

Thankfully during a Visiting Professorship in Detroit, one of our science colleagues politely pointed out that urologists are anything but dummies. We have to thank her for suggesting a change of name to ‘Science made Simple’. The format is straightforward – simple language, to the point, along with a simple diagram.

This month we feature an original article on gene fusions in prostate cancer in particular TMPRSS2:ERG. This is made simple by a For Dummies style explanation from Deloar Hossain and David Bostwick. You only have to see the vividly simple diagram to understand how a genetic deletion or translocation can make the joining of two genes possible. Important discoveries of the future will occur if top scientists wherever they maybe, work more closely with their clinical counterparts. We are keen to attract the best science to the BJUI by providing an attractive publishing platform to our best scientists. We also hope that you, our readers will enjoy this new format, engage with quality science in the BJUI, cite these important papers and ultimately relate to their clinical relevance for the benefit of your patients.

Dirk De Ridder, Associate Editor BJUI
Jo Wixon, Publisher BJUI
Prokar Dasgupta, Editor-in-Chief BJUI and King’s Health Partners

 

Blog report from USANZ ASM, Melbourne

Dr Marni Basto & Dr Sarah Wilkinson

G’day from the Annual Scientific Meeting of the Urological Society of Australia & New Zealand, easily identified globally this week using its hashtag, #USANZ13. This year’s meeting has taken place in Melbourne – the city of lane-way lattes, sport, lifestyle and culinary delights!  It has certainly been a jam-packed four days of academic content led by a stellar International Faculty – 23 key opinion leaders from every corner of the globe covering every aspect of urology. Almost 1000 delegates were registered and were joined by an additional 250 delegates from the Asia Pacific Prostate Society who convened their 3rd Annual Scientific Meeting as a conjoined event. There were a lot of urologists in Melbourne!

This year’s Annual Scientific Meeting convened by Professor Damien Bolton and Associate Professor Nathan Lawrentschuk (@Lawrentschuk) kicked off with an emotional Oration by Moira Kelley discussing her inspiring work with Mother Teresa and flying sick children to Western countries to undergo lifesaving medical treatment.  Tears were soon dried however as USANZ acknowledged Professor Anthony Mundy with an honorary membership for his profound achievements and long association with USANZ. The welcome reception provided a great opportunity for delegates to mingle and try the rich assortment of wines Australia has to offer.

Visiting American Professor James Eastham was full of praise for the manner in which approximately 1 in 6 men in Australia and New Zealand are managed by active surveillance compared to around 10% of eligible patients in the US.  Professor Eastham from Memorial Sloan Kettering Cancer Centre in New York went to press saying “Australia and New Zealand are among the best places in the world to be diagnosed with prostate cancer”.

Certainly active surveillance, focal therapy and the use of MRI in prostate cancer were hot topics of debate throughout the meet.  Prof Eastham’s was not alone in his reservations for focal therapy stating his view that “it should be considered experimental”.  Others on the International faculty such as Professor Mark Emberton argued in its defence in the appropriate setting. Dr Emberton also delivered the BJUI Lecture on “Best practice in prostate cancer imaging”. Other BJUI highlights included Editor-in-Chief Prof Prokar Dasgupta who delivered a wonderful overview of the “Scientific Advances in Robotic Surgery” as well as delivering some excellent tips for how to get published during the Surgical Authorship session. This very well attended session also featured Dr Annette Fenner, Editor-in-Chief of Nature Reviews Urology (and a prolific tweeter), who gave a masterful overview of how to write a review paper. BJUI Chairman Dr David Quinlan, challenged our assumptions by asking “Are men pursuing sexual function following radical prostatectomy”. Professor Dasgupta also announced the inaugural BJUI Global Prize Winner, accepted by Dr Yen-Chuan Ou.

The @BJUIJournal and its editors @prokarurol, @declangmurphy & @drhwoo were once again leading influencers throughout this year’s meeting showing form consistent with #EAU13 depicted by the metrics supplied by Symplur (@healthhashtags).  Around 135 participants got involved in the #USANZ13 discussion including many from around the world who joined the conversation.

A special mention to Toronto’s Dr Rajiv Singal (@drrksingal) who even made the list of top 10 influencers! And to our many other Twitter-mates who joined the conversation from all over the world.

It is safe to say social media, or what the Urology twitterati refer to as ‘SoMe’, has now cemented a definitive and purposeful place in engaging and reaching out to the International Urology community.  @Urologymeeting was the official handle with tweets also coming from the primary @USANZUrology official account.  The #USANZ13 hashtag was an obvious option and it appears despite last year’s AUA meeting hashtag controversy with the use of #Uro12 instead of #AUA12, we have now firmly set the hashtags for Urology meets around the world; #EAU13, #USANZ13, #AUA13, #BAUS13, #ERUS13, #ACU13 etc.

A select group of our young talented research and clinical registrars were challenged at the podium battling for the prestigious Keith Kirkland and Villis Marshall prizes.  These were awarded to Dr Isaac Thyer and Dr Sandra Elmer respectively at the Gala evening.  Located at the elegant Grand Ball Room at the Regent Theatre, the Gala evening was certainly an event to behold.  Professor Stephen Ruthven, current President of USANZ handed over the reins to Dr David Winkle who will hold the post for the next two years.

For the first time a dedicated “Social Media & Education” session was chaired by @declangmurphy and @drhwoo with presentations from some of the well known Aussie Uro-twitterati; @isaacthagasamy, and @wilko3040. The SoMe session saw our session chairs with their heads deep in their computers, ipads and iphones creating traffic Internationally with the USA, Canada, the UK and mainland Europe, while monitoring the Tweetchat stream. This traffic generated the largest peak of the conference as seen in the tweet activity graph with close to 400 tweets in the hour.

BJUI Associate Editor Declan Murphy wowed the crowd by abandoning Powerpoint in favour of Prezi to showcase the social media landscape. By way of emphasis, he demonstrated the utility of social media by Tweeting a link to his Prezi which at the time of writing had been viewed by well over 200 people (most from outside Australia). Social media revolution!

We are already looking forward to USANZ 2014 which will take place in Brisbane from 16-19th March 2014. Put the date in your diary – fun to follow on social media but much better in real life!

 

Marni Basto is  a Uro-Oncology Research Fellow at Peter MacCallum Cancer Centre, Melbourne, Australia

Twitter: @Dr MarniqueB

Sarah Wilkinson is a post-doctoral research fellow at Monash University, Melbourne. She is interested in how the prostate tumour microenvironment can be targeted as a therapeutic treatment for prostate cancer.

Twitter: @wilko3040

 

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Editorial: Think irritable bowel syndrome when treating overactive bladder

The bladder and bowel are functionally related organs; they lie in close proximity, have similar innervations and some structural similarities, albeit having different functional characteristics; they are both critical for the storage, collection and expulsion of waste products. Several previous clinical reports have suggested that LUTS, such as overactive bladder syndrome (OAB), can occur concurrently with disorders of the colon, such as irritable bowel syndrome (IBS).

In the study entitled ‘Relationship between overactive bladder and irritable bowel syndrome: a large-scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria’, Matsumoto et al. investigate the prevalence of OAB and IBS in Japan using a large scale internet based survey. In all, 10 000 randomly selected participants completed the surveys with equal numbers of men and women. Subjects were grouped according to age and gender and the prevalence and severity of OAB was assessed using the OAB symptom score (OABSS). The OABSS as an assessment tool combines OAB symptoms into a single score. Four main criteria were examined (daytime frequency, night-time frequency, urgency and urgency incontinence) and disease severity was assessed by overall score value (5, mild; 6–11, moderate; and >12 severe). Similar epidemiological studies have been conducted in the past; however, this is the first study to use the OABSS to assess OAB in a general population. IBS was assessed using the IBS module of the ROME III criteria.

The study found that in the population studied, the overall prevalence of OAB was 9.3% (with 9.7% of men and 8.9% of women affected) and increased with advancing age. Of those affected, 59% reported mild symptoms, 40% reported moderate symptoms and 1% reported sever symptoms. The prevalence of IBS was greater, with 21.2%  of people reporting symptoms (18.6% of men and 23.9% of women); however, conversely the incidence of IBS was reduced with age. Consistent with previous epidemiological studies conducted in Europe and the USA, 33.3% of participants reporting OAB symptoms also had concurrent IBS (32.0% men and 34.8% women), interestingly though, the prevalence of concurrent IBS and OAB was unaffected by age, suggesting that age is not a contributing factor to this relationship.

The exact aetiology of OAB and IBS, by virtue of the non-specific nature of both symptom syndromes, cannot be clearly defined. However, both disorders are characterised by at least increased frequency of visceral emptying due to increased sensation and in many cases motor hyperactivity. In the LUT this takes the form of urgency with associated detrusor overactivity in 40–90% of patients and in the bowel it manifests as pain and discomfort. Experimental studies in rodent models have shown that initiation of bladder overactivity using chemical agents, such as cyclophosphamide, can induce hypersensitivity of the colon and conversely induction of colitis can lead to altered bladder function resembling OAB (Bielefeldt K et al., Brumovsky PR et al., Pezzone MA et al.). The concurrence of these disorders suggests that there may be a common underlying pathology or dysfunction at least in a subset of patients.

One theory put forward to explain the concurrence of OAB and IBS is that of cross-organ sensitisation, whereby sensory innervation of the bladder and bowel interact. These interactions can occur at multiple levels. In the periphery, there is evidence for afferent fibres, which extensively branch and innervate multiple target structures. These dichotomising afferents converge at a single neurone in the dorsal root ganglion (DRG). Studies using retrograde tracers injected into the colon and bladder wall have identified specific DRGs neurones that receive projections from both organs, although the numbers or these neurones are low. Sensitisation of the endings in one organ by local inflammation damage or injury would probably impact on overall sensitivity after upregulation in excitability in all terminal receptive fields.

In addition to peripheral mechanisms, sensitisation of central pathways could also be a contributing factor in cross-organ sensitisation. Spinal neurones receiving afferent input from the bladder have been shown to respond to afferent input from other pelvic structures including the colon. Second-order neurones in the spinal cord therefore receive convergent input from various visceral structures, as well as somatic inputs. This theory provides an explanation for the phenomenon of referred pain, where sensations from the viscera are experienced in the associated somatic sensory fields. Such viscero-somatic convergence has been extensively investigated (the most common example of this is angina), but only recently has viscero-visceral referral received attention. Clearly much research is still required to understand these interactions; however; this study clearly highlights the concurrence of bladder and bowel disorders. Understanding the mechanism(s) involved could have important implications for future therapeutic interventions aimed at treating both OAB and IBS.

Donna Daly and Christopher Chapple*

Department of Biomedical Science, University of Sheffeld and *Department of Urology, The Royal Hallamshire Hospital, Sheffeld Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Midurethral tape surgery for incontinence; a possible victim of the vaginal mesh crisis?

Type 1 mesh is used in vaginal surgery for pelvic organ prolapse repair, along with the mid-urethral tapes for stress incontinence surgery. Tapes for incontinence surgery are well-established and systematic review shows that retropubic tape is probably more effective than colposuspension, risk of bladder perforation notwithstanding [1]. The various types of mid-urethral tape appear to have broadly equivalent efficacy, but the poor quality evidence-base is an issue. The real problem lies with the major complications that can occur, some of which are highlighted in the recent statement from the US Food & Drug Administration in response to concerns expressed by patients and other stakeholders. Mid-urethral tape itself is recognised to be at risk of important complications in the long term, and mesh exposure in the vagina is a major issue with considerable detrimental impact. Patient groups have become organised in recognition of this and they are setting up online dialogues and websites accordingly, for example “tvt-messed-up-mesh.org”. The surgical professions have to agree how best to manage the difficult problems, dealing with the exposed mesh and handling the further procedures needed to re-establish continence [2].

 

Litigation
These in themselves are serious issues, but another threat is looming; the potential that litigation arising in prolapse mesh surgery may extend to midurethral tapes. A huge number of court cases related to mesh prolapse repair has been established, affecting most of the major device manufacturers and key products, with such a volume of workload that multidistrict litigation has been established. A recent award to one claimant against Johnson & Johnson was more than $5 million. With the number of claimants running into thousands, many device companies are taking decisions on these products which will substantially affect their availability and use in the future. How this will affect mid-urethral tape is uncertain, but many companies will have strategic concerns in this area as well. Reporting of mesh-related adverse events has reasoned exponentially in the last few years [3], presumably resulting from increasing use and increasing awareness of potential problems. Self-reported complications to the FDA’s MAUDE database have risen for all forms of mesh including mid-urethral tapes. Particularly worrying is the potential that tape-related complications after tape placement can happen many years postoperatively [4].


A key aspect of the litigation relating to mesh use in vaginal prolapse surgery is the lack of premarketing testing of these devices and the weak evidence base [5]. Legal arguments involve the responsibility of the companies to demonstrate safety before marketing, and the urological profession has expressed the desirability of more stringent approaches to the development of surgical devices – especially given the highly stringent requirements for pharmaceutical companies in marketing new drugs. The professionals themselves are not blameless; preoperative counselling on risk, judicious selection of surgery according to the patients’ individual requirements, surgical training, careful follow-up and engagement where problems arise have caused difficulties in many cases previously. These points are expectations of professional practice, and the professions need to adhere to them – if necessary with input from governing bodies to ensure adherence is demonstrable. The area is rapidly changing and we can be sure that substantial dialogue and developments are predictable in the near future.
Approaches to management of tape complications
The management of mesh and tape-related complications is specialised and centralisation of management of these cases appears appropriate in order to have the best chance of acceptable outcome and to develop the necessary skills which would not be possible in centres handling only small numbers of cases. Potential complications include voiding dysfunction, mesh exposure, pain, LUTS, and persisting or recurrent incontinence. Voiding dysfunction is particularly likely if a woman already has a preoperative history of voiding symptoms, previous retropubic surgery, or if other reconstructive procedures are undertaken at the time of tape placement [6]. Voiding dysfunction can occur as a result of urethral compression by the tape – which will usually be palpable as an indentation of the urethra at its midpoint. Alternatively, voiding dysfunction arises from elevation of the endopelvic fascia – in which case, the urethra tends to be drawn upwards towards the retropubic space. In the first case, a tape incision can be effective, but in the latter case, an abdominal procedure to release the endopelvic fascia to its normal configuration might be needed. It is important to avoid instrumenting the urethra and levering the urethra downwards with an instrument placed into the urethra – this carries the risk of crushing the urethra against the tape, and is likely a major potential factor for subsequent erosion into the urethra.
The assessment of women with the tape complication needs to be comprehensive and fastidious. The considerations require awareness of tape exposure, incontinence, voiding dysfunction, proximity of adjacent structures, pain points and the state of the vagina/ labia/ pelvis. If mesh is exposed, it is essential to remove the unwanted material, though it may not be necessary to remove the entire tape. The excision of the material may leave a defect within the urethra, bladder or vagina, which needs to be closed- bearing in mind the principles for avoidance of subsequent fistula formation (i.e. watertight closure and interposition of healthy tissue between repaired structures). The woman will seek continence postoperatively and to deliver this, both the bladder outlet and the reservoir capacity of the bladder will need to be considered. If necessary, the woman may need to self-catheterise afterwards, and whether the patient will find this practical and acceptable must be confirmed preoperatively. The possibility that the planned operation may fail has to be considered, and accordingly steps taken to ensure that subsequent options are not excluded. For example, excision of mesh may best be achieved with placement of a flap of omentum into the area of the defect, to keep open the subsequent possibility of artificial urinary sphincter placement. It is very clear that extensive experience in all aspects of reconstructive urology are needed in order to get the best outcome in this context.
The looming threats
The immediate future sees several key challenges, including:
1. Training of surgeons in primary incontinence surgery to minimise risk of complications arising
2. Training of surgeons to manage complications
3. Regulatory arrangements as authorities come to grips with major complications occurring with significant incidence
4. Strategic concerns as device companies change their view of the merit of this indication for their profitability
5. The need for proper data on device use, outcomes and adverse consequences
6. The ongoing need to find new management options for improving efficacy and safety in surgical management of incontinence

Professional consensus and dialogue is clearly a high priority to ensure a good outcome for all.

 

Dr Marcus Drake is Consultant Surgeon at the Bristol Urological Institute, Bristol, UK, subspecialising in Female and Reconstructive Urology, Neurourology and Urodynamics He is Chairman of the International Continence Society’s Standardisation Steering Committee

References
1. Novara, G., et al., Updated systematic review and meta-analysis of the comparative data on colposuspensions, pubovaginal slings, and midurethral tapes in the surgical treatment of female stress urinary incontinence. Eur Urol, 2010. 58(2): p. 218-38.
2. Smith, A.R., W. Artibani, and M.J. Drake, Managing unsatisfactory outcome after mid-urethral tape insertion. Neurourol Urodyn, 2011. 30(5): p. 771-4.
3. Shah, H.N. and G.H. Badlani, Mesh complications in female pelvic floor reconstructive surgery and their management: A systematic review. Indian journal of urology : IJU : journal of the Urological Society of India, 2012. 28(2): p. 129-53.
4. Jones, R., et al., Risk of tape-related complications after TVT is at least 4%. Neurourol Urodyn, 2010. 29(1): p. 40-1.
5. Abrams, P., et al., Synthetic vaginal tapes for stress incontinence: proposals for improved regulation of new devices in Europe. Eur Urol, 2011. 60(6): p. 1207-11.
6. Molden, S., et al., Risk factors leading to midurethral sling revision: a multicenter case-control study. Int Urogynecol J Pelvic Floor Dysfunct, 2010. 21(10): p. 1253-9.

 

 

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The indwelling Foley Catheter; an anachronism

The Simon Foundation for Continence was founded in 1982 by Cheryle Gartley to bring the subject into the open, remove the stigma surrounding incontinence and provide help and hope to the individuals. their families and their healthcare professionals. As President, Cheryle invited Roger Feneley, Calvin Kunin and David Stickler to the Foundations’ third conference in the series entitled Innovating  for Continence: The Engineering Challenge in 2011, to talk about catheter drainage of the bladder.  Their presentations each carried the same message that the design of the indwelling Foley catheter violated the integrity of the sophisticated defence mechanisms that protect the bladder from bacterial infection.  The morbidity and mortality caused by the Foley catheter and their costs to health services are no longer acceptable.  Research and Development of antimicrobial coatings alone will not resolve the problems of long-term catheterisation.

This meeting led to their publication ‘An indwelling catheter for the 21st Century’ in the BJUI.  In an era witnessing outstanding technological advances in medical implants the simple task of draining urine from the bladder should be performed without producing infection and a range of associated complications. The cyclical filling and emptying of the bladder is crucial to the bladder’s defence against bacterial infection but the design of the Foley catheter with the drainage eyes in its protruding tip distal to the self-retaining balloon not only prevents the bladder from emptying completely but can seriously damage the integrity of the protective urothelial lining.  Medical device manufacturers need to take up the challenge of producing a device which restores the function of the debilitated lower urinary tract without threatening its health.

 

This video explains the problem further.

 

The Simon Foundation’s 4th international conference, Innovating for Continence: The Engineering Challenge takes place this week in Chicago, IL

 

Dr David Stickler became interested in the problem of catheter-associated urinary tract infections in paraplegic patients at the Irish National Spinal Unit during his time as a lecturer in Trinity College Dublin in the early 1970s. Over the years as a reader in medical microbiology in Cardiff University he worked on many aspects of the problem from the fundamental biology of the bacterial biofilms that develop on catheters to the practical management of biofilm-induced catheter encrustation and blockage. Currently he is an honorary senior research fellow in the Cardiff University School of Biosciences.  

Dr. Kunin received his MD from Cornell University College of Medicine in 1953. He is Emeritus Professor of Medicine at the Ohio State University and Clinical Professor of Medicine at the University of Arizona. He has a distinguished background in infectious diseases, antimicrobial pharmacology, hospital infection control, urinary tract infections and promotion of appropriate use of antibiotics. He has published over 350 scientific articles and a book on urinary tract infections. He is a past president of the Infectious Diseases Society of American, served on NIH and FDA advisory committees and is an honorary academic consultant to the National Health Research Institute in Taiwan.

Mr Roger Feneley is an Emeritus Consultant Urologist to the North Bristol NHS Trust and Visiting Professor in the Faculty of Applied Science at the University of the West of England (UWE).  In 1998 he founded the BioMed Centre within the Bristol Urological Institute with the objective to improve the care of patients with intractable urinary incontinence.  In 2009, he founded Alternative Urological Catheter Systems Ltd to develop new urine collection systems.

 

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Editorial: Prostate cancer families – predicting disease before and after the radical

In this issue of BJUI, Borque et al. discuss a subject that is now very close to my heart. Aged 48 years, I am 6 weeks post radical prostatectomy for a Gleason 3 + 4 prostate adenocarcinoma measuring ~2 mL in volume, with a PSA level of 2.54 ng/mL. Histology reassures me it is organ confined and seminal vesicle negative. My father and his brother both died aged 63 years of Gleason 10 prostate cancer and my brother is awaiting his radical prostatectomy in a few weeks. I have two sons, one of whom has asked me when he should be tested. Any prognostic information is going to help me advise my family.

In all, 85% of prostate cancers appear to be sporadic. The incidence of all prostate cancers is 1 in 8500 under the age of 40 years, rising to 1 in 15 at 60–69 years and 1 in 8 after that. The lifetime risk in the UK for all men is 8–10%.

The genetics of prostate cancer are confused by case clustering; the family members of men with a prostate cancer diagnosis seek out early advice from their physician resulting in detection of some clinically questionable cancers and an apparent higher incidence in certain families. These families do not necessarily have genetically determined prostate cancer.

The lifetime risk is altered dramatically by having two or more first-degree relatives with a diagnosis of prostate cancer; if the disease in the relative is identified before the age of 65 years the risk is increased further. Bratt suggests the risk rises from 15 to 20% when a single first-degree relative is diagnosed aged < 60 years. Zeegers et al., in a meta-analysis, have shown that diagnosing prostate cancer in a relative aged < 65 years increases the relative risk of having prostate cancer by 3.3, and having two first-degree relatives increases the relative risk by a factor of 5.1.

Analysis of a huge database from Sweden including data on 182 000 fathers and 3700 sons with prostate cancer suggest a standardised incidence ratio of 9.4 in men with a father and brother diagnosed with prostate cancer, with further analysis also showing unsurprisingly that the risk increases as an individual ages. Some true ‘prostate cancer families’ have been identified. These families have three or more relatives with prostate cancer often associated with a diagnosis at a young age, possibly with an increased tendency to an aggressive
phenotype; my uncle was 18 months from diagnosis to death from his disease, my father 4 years. In these families, the relative risk in male family members is 3.39 in those where the diagnosis of identified sufferers was made aged > 65 years, and 7.33 where the diagnosis is in men aged < 65 years. These risks which effectively give a lifetime risk in the individual of 45–50% are associated with carriage of a gene identified as increasing the prostate cancer risk. The best identified of these genes is the BRCA2 (breast cancer type 2 susceptibility protein) gene, which is associated with an increased risk of other cancers including breast, ovarian, gallbladder and pancreatic cancer, as well as malignant melanoma. This gene, carried in 1% of
Ashkenazi Jewish families, is associated with prostate cancer families in this population.

Now my prostate has been removed, I need to determine my chance of treatment failure. It would be interesting to know whether my genes and my single nucleotide polymorphisms (SNPs), which have almost certainly been responsible for me developing prostate cancer, can also predict my chance of developing early biochemical recurrence (EBCR) and the possibility of needing further treatment. In the Borque et al. article, I would appear on the first model (Fig. 1) to have a chance of ECBR of between 1 and 5%. This risk, according to this study, could increase to up to 30%, if I was to have four SNPs associated with prostate cancer (Fig. 2). Furthermore, we need to know whether identification of SNPs is any better than other possible predictors of EBCR and disease progression, such as the identification of lymphovascular invasion and tumour volume in the final specimen and the presence of extraprostatic extension, data not included in this study. Incidentally, I had no evidence of lymphovascular invasion.

The authors identify that this study needs repeating, particularly in a more ethnically diverse group (this study included Caucasian origin as an entry criterion), and we await longer term data to see how SNPs predict metastasis and prostate cancer-related death.

Jonathan M. Glass
Department of Urology, Guys & St Thomas’ Hospital Trust, London, UK

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