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Clever surgeons and challenging study endpoints

CaptureIntraoperative in vivo tracking of a periprostatic nerve with multiphoton microscopy in rat model.

In the last 6 months, the BJUI editorial team has evaluated an average of 59 urological oncology papers per month with an average acceptance rate of 16%. We receive additional papers for our ‘Translational Science’ section. Studies with high-quality methods are given the highest priority. Other papers compete well if they are highly applicable to clinical practice (i.e. comparative, multicentre, multi-surgeon design) and/or show us new ideas in surgical technique, re-designed study endpoints, or explore new sources of data. For translational science, the best candidates are studies that look at new diagnostic tests in humans and beyond simple immunostaining techniques. We want to evaluate biomarkers likely to be validated and translated into a clinical test. Clinical impact will be even higher if a biomarker is linked to a therapy outcome rather than just a risk estimate. We want our papers to guide us to better outcomes for our patients, hopefully control healthcare costs, and, yes, be well-cited in the literature.

Our review process is tough but fair, and we congratulate and highlight three authorship groups for acceptance into this month’s issue of BJUI. The theme of ‘clever surgeons and challenging study endpoints’ is well illustrated by all three groups. Zargar et al. [1] report on an exclusive database of high-volume minimally invasive surgeons who have tackled the partial nephrectomy option for small renal masses. The comparison is simple in concept and retrospective in design, but what they have done is to significantly increase the outcome measures into a ‘trifecta’ concept in perioperative outcomes (previously reported) with an even more stringent ‘optimal outcome’ endpoint that includes renal function preservation. With a database of 1185 robotic and 646 laparoscopic cases, the robotic procedures showed superior trifecta results (70% vs 33%), complication rates (14.8% vs 20.9%), positive surgical margin rates (3.2% vs 9.7%), and warm ischaemia time (18 vs 26 min). The optimal outcome endpoint included a minimum 90% estimated GFR (eGFR) preservation and no chronic kidney disease upstaging. Only the robotic cohort had sufficient data available and the rate was 38.5%. The latter figure is an interesting challenge, as defining such a high threshold for success challenges surgical technique and allows more room to identify incremental advancement. This may be the largest study of its kind, but non-randomised and with limitations discussed in peer review such as the learning curve influence, use of eGFR as an endpoint with two kidneys, and incomplete data. The definitions used are of interest and the field could use some uniformity moving forward in measuring perioperative and long-term benchmarks of quality.

Durand et al. [2] give us a glimpse into the future of surgery, a science fiction world of prostate surgery where nerves and prostatic glands can be colour coded and seen at a microscopic level in real time. The pictures stand for themselves, especially Fig. 1. If such imaging can be integrated into technique decisions, and perhaps future instrument designs, then perhaps we will have a whole new wave of studies possible on linking surgical technique to improved functional and oncological outcomes after radical prostatectomy. The paper has a nice depth in detail, methods, results, as well as narratives in solving technical problems with novel technology.

This issue’s ‘Article of the Month’ by Gavin et al. [3] is a different look at the question of morbidity after localised prostate cancer treatments, specific to long-term care at >2 years from treatment. The database is from a cancer registry and they have an impressive 54% response rate from a population that is 2–18 years from diagnosis. Rather than Likert-like scales of symptom severity, they simply look at ‘current’ vs ‘ever had’ symptoms and look at the total burden including multiple/overlapping symptoms. Although this may not be as robust and validated as the Expanded Prostate Cancer Index Composite (EPIC) instrument, the simple phrasing of ‘current’ vs ‘ever had’ is probably capturing a very high proportion of symptoms rather than dismissing them if minor or in the past. Again, we see more erectile dysfunction after radical prostatectomy and radiation with hormonal therapy, and more bowel symptoms after radiation therapy. Hormone therapy patients have hot flashes and fatigue, and watchful-waiting patients have some advantages but are certainly not free of symptoms. The burden of symptoms is interesting, nine of 10 reported at least one of seven key symptoms at some point and three of four are current. Therefore, as the authors indicate, ≈75% of prostate cancer survivors will have ongoing symptoms needing follow-up care. This is a significant database resource adding to our understanding of long-term outcomes of patients with prostate cancer and supporting the significance of the Durand et al. [2] study that may show the way forward towards reducing such burdens of disease treatment.

 

References

 

 

3 Gavin AT, Drummond FJ, Donnelly C, OLeary E, Sharp L, Kinnear HRPatient-reported ever had and current long-term physical symptoms after prostate cancer treatments. BJU Int 2015; 397406

John W. Davis, MD
Associate Editor, BJUI

#pass4prostate gears up for Rugby World Cup

Declan_theatre2Here is a fun campaign which should appeal to anyone interested in rugby or prostate cancer for that matter. The 2015 Rugby World Cup kicks off in England and Wales next month and as part of their warm up schedule, Australia are playing USA Rugby in a friendly match at Soldier Field in Chicago on the 5th of September. As part of their sponsorship of this fixture, Astellas are supporting a social media campaign called #pass4prostate which will directly raise funds for prostate cancer research in both the USA and Australia.

As part of their support, Astellas will donate $5 to prostate cancer research and advocacy organizations for every qualifying #pass4prostate submission posted to Twitter, Facebook, or Instagram, up to a maximum contribution of $125,000 in the USA and a further $40,000 in Australia. Therefore to make sure we maximize this commitment, we need to drive lots of traffic using the #pass4prostate hashtag! You can see examples of Australian and US rugby players supporting the campaign below by throwing around special blue rugby balls, but the campaign is encouraging people to make videos supporting the campaign and throwing anything blue around (in a rugby style of course!).

pass4prostate 1

The campaign will run up to the match on 5th September, and there be lots of activity at the 2nd Prostate Cancer World Congress which takes place in sunny Far North Queensland, Australia, from 17-21st August 2015. Follow #pcwc15 or #pass4prostate to get involved!


For full details, please visit the pass4prostate website.

 

Declan Murphy

Melbourne, Australia

@declangmurphy

 

That’s what’s wrong with you and your ‘Star Wars’ generation

NathanJust a few years ago whilst operating, I was curious to find out about one of our unit’s patients on the ward. We still had a bit of time to go in the current case, a retroperitoneal lymph node dissection. There was a chance the patient on the ward would require surgery and being at that time of the day an earlier ‘heads up’ is always best. One of the theatre staff kindly paged our resident. It was 5.05pm. No response. The other resident who was scrubbed directed them to get the resident’s mobile phone and call direct. This did not seem unreasonable – perhaps they were tied up. Maybe the phone could rouse him?  Ring ring… Finally an answer. It’s the urology team wanting an update from the ward. “Sorry I’m in the car”. Have you rounded yet? Sort of. Is there a handover? Silence. We’ll call you back later!’

I was astounded at two things – the resident having clearly left without giving a handover in person (or verbally) and the fact that they appeared to have left without the customary afternoon ward round being conducted. I grumbled and sent the other resident up to check on the patient. Was I becoming one of those ‘grumpy old surgeons ‘ whining at the ‘youth of today’? I didn’t think so as what was expected was probably the minimum expected.

Fast forward two weeks. Same time being 5.05pm and the same resident actually appears in person to give handover (were they learning?) I couldn’t miss the chance to poke at him “What a surprise – you’re still here and it’s after 5pm!” The scrub nurse and registrar and Anaesthetist all laughed having been there when he was in the car on the prior occasion. Clearly smarting he quipped “That’s what’s wrong with you and your ‘Star Wars’ generation”… “What do you mean? what’s wrong?” I quizzed. He thought… then responded: “You all think you are the only ones who have worked hard and that all Gen Y doctors are lazy… You guys shoe-box all of us… .”. I pointed out I was miffed that he had left without handover. He claimed all was fine with the ward and had no real excuse for not giving handover but no ill effects happened and the patient in question avoided theatre. “Only just” I added.

All the while the ‘Star Wars’ jibe had gotten under my skin. His blatant and underhand use of the name of a movie that was perhaps the “God amongst Gods” being a classic tale of good and evil that had delivered many new words and ideas and music to at least one generation…

I took my time. So wanting to get it out of my system I chose my words carefully: “So you say ‘I’m part of the ‘Star Wars’ generation’ so that must make you… part of the ‘Avatar’ generation?” He paused… “That’s right – you are exactly right”. This was potentially going to be fun.

OK. “So remind me, who were the lead characters on Avatar? The female lead Avatar?” Deafening silence…. “What about the actors’ names?” … Silence…… I then pointed out it was embarrassing given one was Australian and I couldn’t help but point out the other I quickly recalled being Sigourney Weaver!

Maybe I was being a bit hard – “OK, what was the mineral they were mining on their planet?” Silence …….”unobtainium!” I yelped… “Who could forget that? Alright give me a line from the movie, any line?” Silence …. “Alright hum me the ‘Theme to Avatar'”… Again, silence.

I paused, then in a friendly way with a wry smile, I stated: “May the force be with you!” and gleefully hummed the well known Star Wars theme… as he ducked off….

So was this reinforcing the stereotypes that Gen Y is all flash and glamour with No Substance?

Probably not, but it teaches us that one generation is not that far from the next (the other resident a Gen Y knew more about Star Wars than I did!!). And subsequently I have had some of the best residents ever. So it is all about attitude and understanding what is required. The resident really lifted their game after this, which was excellent and they ended up with a great report – having taken on board the veiled but constructive “criticism”.

Honesty and communication is the best policy, sometimes laced with humour and by doing this “Help them, you will”.

 

Nathan Lawrentschuk @lawrentschuk

University of Melbourne, Department of Surgery and Ludwig Institute for Cancer Research, Austin Hospital and Peter MacCallum Cancer Centre, Department of Surgical Oncology, Melbourne, VIC, Australia

 

Here comes the sun

BJUI-on-the-beach

Sun, sea, sand and stones: BJUI on the beach.

Welcome to this month’s BJUI and whether you are relaxing on a sun-drenched beach or villa somewhere having a hard-earned break, or back at your hospital covering for everyone else having their time off, we hope you will enjoy another fantastic issue. After an action packed BAUS meeting with important trial results, innovation, social media and the BJUI fully to the fore, this is a great moment to update yourself on what is hot in urology. This is probably the time of year when most urologists have a little extra time to take the BJUI out of its cover or open up the iPad and dig a little deeper into the articles, and we do not think you will be disappointed with this issue, which certainly has something for everyone.

In the ‘Article of the Month’, we feature an important paper from Egypt [1] examining factors associated with effective delayed primary repair of pelvic fractures that are associated with a urethral injury. Do be careful whilst you are travelling around the world, as most of the injuries in this paper were due to road traffic accidents. They reported 76/86 successful outcomes over a 7-year period. When a range of preoperative variables was assessed, four had particular significance for successful treatment outcomes. The paper really highlights that in the current urological world of robotics, laparoscopy and endourology, in some conditions traditional open surgery with delicate and precise tissue handling and real attention to surgical detail are the key components of a successful outcome.

Whilst you are eating and drinking more than usual over the summer, we have some food for thought on surgery and metabolic syndrome with one of our ‘Articles of the Week’. This paper contains an important message for all those performing bladder outflow surgery. This paper by Gacci et al. [2] from an international group of consecutive patients clearly shows that men with a waist circumference of >102 cm had a far higher risk of persistent symptoms after TURP or open prostatectomy. This was particularly true for storage symptoms in this group of men and should influence the consenting practice of all urologists carrying out this common surgery.

Make sure you are staying well hydrated on your beach this August, as the summer months often lead to increased numbers of patients presenting to emergency departments with acute ureteric colic, so it seems timely to focus on this area. To this end I would like to highlight one of our important ‘Guideline of Guidelines’ series featuring kidney stones [3] to add to the earlier ones on prostate cancer screening [4]and prostate cancer imaging [5]. This series serve to assimilate all of the major national and international guidelines into one easily digestible format with specific reference to the strength of evidence for each recommendation. Specifically, we look at the initial evaluation, diagnostic imaging selection, symptomatic management, surgical treatment, medical therapy, and prevention of recurrence for both ureteric and renal stones. Quite how the recent surprising results of the SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial will impact on the use of medical expulsive therapy remains to be seen [6].

So whether you are sitting watching the sunset with a drink in your hand or quietly working in your home at night, please dig a little deeper into this month’s BJUI on paper, online or on tablet. It will not disappoint and might just change your future practice.

 

References

 

 

3 Ziemba JB, Matlaga BR. Guideline of guidelines: kidney stones. BJU Int 2015; 116: 1849

 

4 Loeb S. Guideline of guidelines: prostate cancer screening. BJU Int 2014; 114: 3235

 

5 Wollin DA, Makarov DV. Guideline of guidelines: prostate cancer imaging. BJU Int 2015; [Epub ahead of print]. DOI: 10.1111/bju.13104

 

 

Ben Challacombe
Associate Editor, BJUI 

 

Future Directions in Urological Oncology

bju13076-fig-0001The field of urological oncology is rapidly changing. For example, robotic surgery, targeted therapy, and ablation techniques are oncological options that were in their infancy 10 years ago and are now mainstream in many areas of the world. Additionally, immunotherapy has recently become a promising avenue in multiple urological cancers. As we move forward, expect to see a larger presence of urological oncology literature obtained via social media, which BJUI has initiated and subsequently set the standard for the field. Related to this, this month’s edition of BJUI includes four online ‘Articles of the Week’, with each focusing on urological oncology.

Using data from the pro-PSA Multicentric European Study (PROMEtheuS) project, Abrate et al. [1] evaluated the utility of the Prostate Health Index (PHI) in 142 obese (body mass index BMI >30 kg/m2) men who underwent a prostate biopsy for an abnormal DRE or elevated PSA level. Among the 142 patients, 65 (45.8%) were found to harbour prostate cancer. Using the PHI threshold of 35.7, the authors determined that 46 (32.4%) negative biopsies could have been avoided while six (9.2%) cancers would have been missed. Related to this, Salami et al. [2] compared the cancer detection rates of MRI fusion biopsy vs standard 12-core TRUS-guided biopsy in 140 men with a previous negative prostate biopsy and a lesion appreciated on a multiparametric MRI. While the cancer detection rates were similar overall, the MRI fusion biopsy was more likely to detect clinically significant prostate cancer (48% vs 31%), defined as Gleason ≥7 or Gleason 6 with a lesion volume of >0.2 mL on MRI. In an era where over-diagnosis of prostate cancer is commonplace, data to better stratify patients who need (or do not need) a prostate biopsy and enhanced ways to identify clinically significant prostate cancers are of paramount importance.

Soares et al. [3] report their results among 1 138 contemporary laparoscopic radical prostatectomy patients who had at least 5 years of follow-up. Only one case required an open conversion and the transfusion rate was merely 0.5%. At last follow-up, 85% of patients had an undetectable PSA level, 94% of patients were continent, and 77% of non-diabetic men aged <70 years retained potency. These impressive single-surgeon results further suggest that the morbidity of prostate cancer surgery has diminished with increasing time and experience.

Additionally, Tolchard et al. [4] prospectively evaluated 105 patients with bladder cancer with preoperative cardiopulmonary exercise testing prior to radical cystectomy. Patients who received neoadjuvant chemotherapy were excluded and there was a 6% perioperative death rate with 90 days of follow-up. The results suggest that patients with poor cardiopulmonary reserve along with hypertension are at higher risk of perioperative complications and prolonged hospital stay; median length of stay was 22 and 9 days for patients with and without a complication. Furthermore, while only 2% of patients had a preoperative diagnosis of heart failure, there were a significant proportion of patients (50% in this study) found to have moderate-to-severe heart failure based on preoperative cardiopulmonary exercise testing. These provocative results suggest that the urological community should further investigate the utility of routine cardiopulmonary exercise testing in patients undergoing radical cystectomy along with the optimal incorporation of such testing in patients receiving neoadjuvant chemotherapy.

References

 

 

 

3 Soares R, Di BenedettoA, Dovey Z, Bott S, McGregor RG, Eden CGMinimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies. BJU Int 2015;115:54653.

 

 

R. Houston Thompson BJUI Consulting Editor (Oncology)
Mayo Clinic, Rochester, MN, USA

 

 

The X-Factor, Reality TV, and Live Surgery Demonstration

Declan theatreMy first suggestion to my wife was that I enter Pop Idol with my modified, radiation-bashing rendition of American Pie (chorus “bye bye brachytherapy seeds“). She quickly retorted “DIVORCE! YOU CANT SING!” I begrudgingly agreed. Then Britain’s Got Talent came along and I saw an overweight Greek father and son duo, Stavros Flatley, prance around the stage bare-chested, dancing to some traditional Greek music and I thought “YES! There is hope!” I put on Riverdance, grabbed my then three-year-old son and started teaching him the basics of an Irish jig. I pleaded with my wife to allow us enter the X Factor (or whatever reality TV show was auditioning at that time), but she again screamed “DIVORCE!”. It appeared my hopes of finding fame on reality TV were dashed forever (although I expect Masterchef might be interested in my prowess on the BBQ – Murphy’s Marvellous Marinade on a whole eye fillet deserves a wider audience).

At about that time, the vogue of having live surgery demonstrations featuring at clinical meetings was really gaining momentum. The World Robotic Symposium, European Robotic Urology Symposium, European Society for Urological Technology section meeting at the EAU, Challenges in Laparoscopy & Robotics and others, were all featuring live surgery demonstrations as a prominent part of their scientific program. These sessions feature enormous high-definition screens, 3D broadcast in some circumstances, parallel operating rooms, and live interaction with the surgical team, and have proved enormously popular with audiences and sponsors alike. In fact, without live surgery, some of these meetings would be quite dull –there is certainly a commercial value in featuring live surgery as part of the program as is demonstrated by the huge numbers attending these sessions. Whether it is the lure of seeing world-famous surgeons perform robotic prostatectomy, partial nephrectomy or various types of salvage surgery, or the ever-present possibility of seeing a complication and its management, there is a blood-lust which surgical audiences have for this type of entertainment, sorry – education, and which is being met by the organisers of urology conferences. A merry band of surgeon-entertainers roam the world turning up at these conferences with their entourage of assistants and scrub nurses, and turning on the charm for the huge audiences which the big names now attract.

However, some controversy surrounds the ethics and conduct of live surgery. We wrote in the BJUI previously about some concerns we had and questioning the absolute educational value of these demonstrations. Well known leaders such as Dr Arthur Smith have also voiced concerns about live surgery and in some specialties and some countries, live surgery demonstrations are banned. In response, it has been encouraging to see the European Robotic Urology Society (now an official Section of the EAU), whose annual meeting is a live surgery spectacular, work with others to generate guidelines and ethical standards for the conduct of live surgery at scientific meetings. These will be published in the coming months.

So when it dawned on me that the personal price to pay for fame on reality TV was too high, I resigned myself to a life away from the glamour and fame of reality TV. However, I was very interested when Alex Mottrie and Ben Challacombe invited me to do a live robotic radical prostatectomy for the European Robotic Urology Symposium in London a few months ago. I had only ever done live surgery demonstrations for quite small audiences previously (I had done my karaoke version of American Pie to bigger audiences), and I was somewhat daunted and excited by the prospect of doing live surgery for a big audience, especially one full of the “Gods of Robotic Surgery”. The reality TV star inside me was saying ‘YES! I AM GOING TO BE A STAR!!” So I said yes. And the nerves started soon after. By the time it got to the opening morning of ERUS (in stunning post-Olympics London), I was pretty anxious. The case was straight-forward and I had done hundreds already, so why was I nervous? Well the audience was big (>800), and they looked blood-thirsty – I could feel them licking their lips at the prospect of something going badly wrong. I knew that a few of the “good luck mate” wishes that I had received that morning could be interpreted as “I hope you don’t hurt your head when you fall off your pedestal”. And the big guys were all over the place. The live surgery roll included Vip Patel, Richard Gaston, Alex Mottrie, Prokar Dasgupta, James Porter, Ronney Abaza, Mike Stiefleman, Ashok Hemal and Peter Wiklund. Francesco Montorsi was in the operating room next door and we would be operating in parallel. It was somewhat daunting. Even the stars looked nervous before going live with their surgery, some were even quite temperamental as the stress builds, but when they go live to the convention centre, they put on their “TV-face” and the show begins – all sweetness and charm. Quite a show.

Before live surgery at Guy’s

In the “Green Room” before live surgery at Guy’s Hospital in London for ERUS 2012: Ken Palmer, Geoff Coughlin, Jim Porter, Vip Patel, Declan Murphy, Francesco Montorsi and Declan Cahill

For me, I figured out that the reason I was nervous was that I did not want to make a mess of it in front of a big audience. Human nature has a vain streak to it, and much as I am embarrassed to admit it, I realised that some of my anxiety was just that – I wanted to look and sound good on the big screens. There – I’ve said it! Something certainly added a different stress to the normal pressure of wanting to do an excellent job for your patient, and I expect that even the highly experienced live surgery stars who feature at these meetings do feel this extra pressure. Especially when things get a little sticky or you cause some bleeding and someone at the other end is asking “why did you do that?” Thankfully my case went nicely and my patient has done very well – details to be presented at next year’s ERUS as part of their new guidelines which will see feedback from all cases from the previous Symposium – an excellent initiative.

Doing robotic radical prostatectomy at ERUS 2012

Doing robotic radical prostatectomy at ERUS 2012

Doing robotic radical prostatectomy at ERUS 2012

So for now, the reality TV star in me has been sated and life goes on. Although I did hear there may be a new reality TV series in Australia for amateurs who fancy themselves as crocodile hunters. I wonder would she let me do that….

Declan Murphy
@declangmurphy

 

Declan Murphy is Honorary Clinical Associate Professor at the Department of Surgery, University of Melbourne, St Vincent’s Hospital and Director of Robotic Surgery at the Peter MacCallum Cancer Centre. He had previously been consultant urological surgeon at Guys & St Thomas’ NHS Foundation Trust in London.

 

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