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Highlights from the 6th International Neuro-Urology Meeting

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The world’s leading experts in Neuro-Urology met in Zürich, Switzerland, from 25-28 January 2018 at the 6th International Neuro-Urology Meeting (INUM) and provided an overview on the latest advances in research and clinical practice of this rapidly developing and exciting discipline. The INUM, organized under the umbrella of the Swiss Continence Foundation (www.swisscontinencefoundation.ch), is the official annual congress of the International Neuro-Urology Society (INUS, www.neuro-uro.org), a charitable, non-profit organization aiming to promote all areas of Neuro-Urology at a global level. This unique meeting combines state-of-the-art lectures, lively panel discussions, and hands-on workshops with emphasis placed on interactive components. In addition, there are many opportunities to exchange thoughts, experiences and ideas and also to make new friendship.

An important aim of the Swiss Continence Foundation (www.swisscontinencefoundation.ch) and International Neuro-Urology Society (INUS, www.neuro-uro.org) is the promotion of the next generation of outstanding young researchers and clinicians who represent the future of Neuro-Urology. Therefore, the prestigious Swiss Continence Foundation Award of 10’000 Swiss francs was awarded for the 5th time to the best contribution from a young Neuro-Urology talent who presented the current yet unpublished research at the young talents session of the INUM on Saturday 27 January. This year, An-Sofie Goessaert from Ghent, Belgium, convinced the international jury with the presentation of her project entitled “Nocturnal polyuria in spinal cord injury patients and the effect of conservative measures on urine production” and reached the highest scoring. She demonstrated in a prospective study on patients with spinal cord injury that compressive stockings have an effect on nocturnal urine production, increasing diuresis during daytime and decreasing it during sleep to nearly normal bladder capacity, which might allow to have undisturbed sleep and higher quality of life.

Swiss Continence Foundation Award Winner 2018 An-Sofie Goessaert (middle), Chairman of the Foundation Board Thomas M. Kessler (left) and Vice-Chairman of the Foundation Board Ulrich Mehnert (right).

Three of many other highlights were the “Nightmare session”, the state-of-the-art lecture by Karel Everaert on “Nocturia and nocturnal polyuria” and the surgery in motion presentation by Urs E. Studer on “Cystectomy”.

The Icon of Swiss Urology, Urs E. Studer (middle) with the INUM organising committee Ulrich Mehnert (left) and Thomas M. Kessler (right).

Finally, we are delighted to announce the 7th International Neuro-Urology Meeting to be held in Zürich, 24-27 January 2019. Save the date! For details please visit: www.swisscontinencefoundation.ch. We are looking forward to seeing you in Zürich!

 

Ulrich Mehnert & Thomas M. Kessler

 

The challenge with systematic reviews of non-randomised studies in urology

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In this issue, BJU International has made the conscious decision to publish a systematic review (SR) and meta-analysis (MA) by Guo et al. [1]to inform the question of whether patients undergoing nephrouretectomy for upper tract urothelial carcinoma are at increased risk of worse oncological outcomes. This question was also the topic of a similar review by Marchioni et al. [2] published earlier this year in this journal. Both studies were submitted around the same time and underwent independent, parallel peer review that resulted in different editorial decisions. Given their similarity in methodological quality they both deserved similar consideration for publication, which the journal is hereby honouring.

At the same time, this provides the unique opportunity to reflect on methodological developments in the field and BJU International‘s efforts to raise the bar of the methodological quality of SRs, which include the provision of an Assessment of Multiple Systematic Reviews (AMSTAR) rating [3]. AMSTAR is a validated tool to assess the components of a SR on an 11-point scale (0–11), with higher scores reflecting higher methodological rigor. An updated version of this tool has recently been provided, which offers greater clarity in interpretation [4]. Another related instrument that has become available is the Risk of Bias in Systematic Reviews (ROBIS), which assesses the study limitations in SRs (i.e., the relevance of the review, concerns with the review process, and potential bias introduced during the review) [5]. Meanwhile, while it would be premature to claim success, it is our impression that BJU International’s initiative to provide AMSTAR ratings is making a valuable contribution in raising awareness for such methodological issues and improving the transparency of published reviews.

As BJU International takes a lead in promoting high-quality SRs in urology, the journal has seen a considerable increase in the number of submissions, including SRs of non-randomised studies (NRS). Whilst much of what we practice on a day-to-day basis is based on evidence from NRS, studies of those designs have infrequently been included in the Cochrane Library, which has pioneered much of the underlying methodology. This is for a few reasons: First, the ‘garbage in–garbage out’ phenomenon; if the underlying individual studies only provide very low-quality evidence, combining these studies will rarely enhance the confidence we place in their results. Second, the need for methodological advances in the assessment and analyses of NRS. Third, when high-quality evidence from randomised controlled trials (RCTs) is available, it may be inefficient to review the NRS literature.

However, progress is being made on the methodology front. Members of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group are credited with having developed an approach for rating the quality or certainty of evidence from randomised and NRS to inform decision making [6]. While a body of evidence from RCTs, which starts as high-quality evidence, may be downgraded for study limitations, a body of evidence from NRS, which starts as low-quality evidence, may be upgraded for one of three reasons, most commonly for large magnitude of effect [7]. The underlying assumption is that, whilst we have to assume that bias is likely to be present in these studies, it is unlikely to explain the entire observed effect.

It nevertheless remains critical to assess the risk of bias of NRS. While the Newcastle-Ottawa scale (as used in both of these SRs) is a widely used instrument to evaluate risk of bias in NRS, it has critical limitations that the recently developed Risk Of Bias In Non-randomised Studies – of Interventions (ROBINS-I) seeks to overcome [8]. ROBINS-I evaluates NRS by using a standardised comparison to an RCT (i.e. target trial) [9]. In this way, ROBINS-I captures the bias inherent to studies without proper randomisation or allocation concealment, namely the lack of a balance of known and unknown confounders and selection of participants. ROBINS-I allows users to fundamentally start all studies at the same quality level, providing the transparency requested by some SR authors conducting SRs of NRS.

While ureterorenoscopy before nephroureterectomy may indeed increase the risk of intravesical recurrence as the authors suggest, additional exploration would be needed to make a statement about the causality of the relationship. Guo et al. [1] conducted sensitivity analyses to describe the potential for bias introduced by confounders of previous bladder tumour history and bladder-cuff management, thereby increasing our confidence that the observed effect may be closer to the truth. It seems equally important to note that Guo et al. found no increased risk in cancer-specific, recurrence-free or overall survival, which are other outcomes of potentially greater patient importance.

Understanding the inherent limitations of NRS, and placing their findings into appropriate clinical context are critical to the conduct of SRs. Moving forward, BJU International will continue to seek out the highest quality reviews that make use of the best, up-to-date methodology. We hope that these efforts will both serve as a beacon for the research community, but more importantly, result in improved evidence-based care for our patients.

Philipp Dahm*, Jae Hung Jung† and Rebecca L. Morgan‡
*Department of Urology, Minneapolis VA Medical Center, University of Minnesota, Minneapolis, MN, USA, †Department of Urology, Yonsei University Wonju College of Medicine,
Wonju, Korea and ‡Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada

 

References

 

1 Guo RQ, Hong P, Xiong GY et al. Impact of ureteroscopy before radical nephroureterectomy for upper tract urothelial carcinomas on oncological outcomes: a meta-analysis. BJU Int 2018; 121: 184-93

 

2 Marchioni M, Primiceri G, Cindolo L et al. Impact of diagnostic ureteroscopy on intravesical recurrence in patients undergoing radical nephroureterectomy for upper tract urothelial cancer: a systematic review and meta-analysis. BJU Int 2017; 120: 313–9

 

3 Dahm P. Raising the bar for systematic reviews with Assessment of Multiple Systematic Reviews (AMSTAR). BJU Int 2017; 119: 193

 

4 Shea BJ, Reeves BC, Wells G et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017; 358: j4008

 

5 Whiting P, Savovic J, Higgins JP et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol 2016; 69: 225–34

 

6 Guyatt GH, Oxman AD, Vist GE et al. GRADE: what is “quality of evidence” and why is it important to clinicians? BMJ 2008; 336: 995–8

 

7 Guyatt GH, Oxman AD, Sultan S et al. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol 2011; 64: 1311–6

 

8 Deeks JJ, Dinnes J, D’Amico R et al. Evaluating non-randomised intervention studies. Health Technol Assess 2003; 7: iii–x, 1–173

 

9 Sterne JA, Hernan MA, Reeves BC et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919

 

Editorial: Viewpoint – Rationing and Surgical Care

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Limitation in the provision of surgical care has many causes. In a nationalised healthcare system, this often reflects lack of funds, leading to rationing of clinical services. Rationing itself takes a number of forms. Deliberate exclusion of specific operations (usually elective) or specific patient groups (smokers, obese) are the most common examples, but strategic extension of waiting times by the removal of ‘target’ times can also be used as a rationing tool.

Many surgeons are dismayed by these decisions. They feel that the surgical patient is unfairly targeted as the clinical and cost-effectiveness of many planned surgical interventions have been well characterised. Surgeon and institutional outcomes are freely available – unlike the situation in many non-surgical specialties, so how can it be fair to pick on the surgical patient?

The idea that non-urgent elective surgery falls into neat categories where delay has no adverse consequences for the patient mystifies many surgeons. Whilst all would advocate a healthy diet, exercise, weight loss and smoking cessation, decisions to withhold surgery from the obese or those who smoke is rarely evidence-based. Rationing based on such prejudice soon becomes illogical. Why should the obese cancer patient receive an operation when the obese incontinent patient cannot?

In the long term, the absence of a substantial volume of ‘routine’ surgery damages training as exposure to such procedures is limited. Surgery has become the soft target for rationing clinical services. Surgeons should make their patients aware of how this process will affect them. Healthcare planners need to hear a public voice as well as that of the clinicians.

Just occasionally, an apparent limitation can be beneficial. In this issue of the BJUI, the National Institute for Health and Care Excellence (NICE) provides clear guidance on preoperative testing. This is based on sensible recommendations such as: avoiding routine urine dipstick testing, routine chest X-rays, and glycated haemoglobin (HbA1c) in non-diabetic patients. All surgeons irrespective of their specialty would benefit from paying close attention to these important guidelines [1].

Derek Alderson

President of the Royal College of Surgeons of England; Emeritus Professor of Surgery, University of Birmingham; Editor-in-chief of BJS Open.

Read the full article

Reference

1 National Institute of Health and Care Excellence (NICE). Routine preoperative tests for elective surgery: © NICE (2016) Routine preoperative tests for elective surgery. BJU Int 2018; 121: 12–6

 

Highlights from the 6th International Alliance of Urolithiasis annual meeting 2017

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There is absolutely no doubt that #urolithiasis is a truly global disease. It is extremely rare in medicine to have a single disease entity with enough breadth and variety to generate such immense interest across the world that it merits a 3 days meeting on its own.

The International Alliance of Urolithiasis (IAU) was founded by Professor Zhangqun Ye, Professor Guohua Zeng (both from China), and Professor Kemal Sarica (Turkey, current chair of #EULIS) in 2010. The aim of the association is to provide a platform for urologists across the world to exchange knowledge on urinary tract stone disease, and to establish professional links for research.

Famous for the fine yellow rice wine produced in the region, Shaoxing in Southeast China was chosen as the host city of this year’s 6th IAU annual conference. This was our first time attending the IAU, and we were both honoured to be invited to speak at the conference. We must congratulate the association and the organising committee in putting together a truly excellent program, which included many thought-stimulating and inspiring talks by eminent local and international stone experts, provocative debates, and many live surgeries demonstrating latest endoscopic techniques in the management of challenging stone diseases.

Professor Guohua Zeng and @WayneLam_Urol

#IAU17 Day 1

#IAU17 started off with the Young Urologists sessions. These sessions not only provided an opportunity for young urologists from all over the world to present their work, but also set a stage for debates on controversial stone topics and a platform to interact with experienced and established eminent stone surgeons.

One of the first sessions were talks on #PCNL. All speakers agreed choice and accurate access is key to a successful and effective #PCNL. It is interesting to know that in China, the vast majority of punctures are performed by urologists. And with experience due to high prevalence of stone disease in particular in the southern part of the country, the practice of pure ultrasound-guided puncture has gained popularity in the past decade. Dr Zhiyong Chen and Dr Xiao Yu, both from China, provided some tips and tricks on pure ultrasound-guided puncture for access for #PCNL, in particular when treating patients with complex or staghorn stones. Both sagittal and coronal planes should be used to assess all major and minor calyces, and they also interestingly showed that the benefit of aiming stones with multiple branches as the most effective first puncture point in patients with complex or staghorn stones.

Position of #PCNL has been a regular debate in stone conferences, and few speakers in the young fellow sessions presented their findings and reviews on the topic. Both #supine and #prone positions have their pros and cons but all presenters agreed that surgeon’s preference to offer best chance of achieving best outcome is the most important determining factor.

Another eye-catching presentation of the day was a randomised study conducted in China comparing standard #PCNL against mini-PCNL in the management of 2-4cm renal stone. The study randomised 800 patients and demonstrated that mini-PCNL was superior in terms of reduced bleeding, post-operative pain, shorter hospital length of stay, and more patients were ‘tubeless’ after the procedure. It is a well-designed study that will add much-needed high-quality data to the argument on #PCNL sizing.

#Sepsis remains one of the most worrying complications during endoscopic surgery for urolithiasis. Optimal method of culture technique was discussed, with Dr Kremena Petkova of Bulgaria arguing that renal, pelvis, urine and stone cultures are more specific and sensitive in predicting post-op complications. Both are superior to #MSU, with higher concordance between pathogens and antibiotic sensitivities. However, their results are not often available pre-operatively, and it’s best to use them as guidance on choice of anti-bacterial treatment if sepsis develops post-operatively. However, in patients with high risk of post-operative sepsis despite peri-operative prophylaxis; renal, pelvis, urine and stone culture should be considered.

Another very interesting study was a randomised trial presented by Dr Wei Zhu from Guangzhou, China, on investigating dosage required for prophylactic antibiotics for patients undergoing retrograde intrarenal surgery for stones. Their study suggested that stone size is a determining factor of whether patients require prophylactic antibiotics, with risk of post-operative sepsis being low if <200 mm2.

In the stone prevention session chaired by Professor Hans-Goran Tiselius from Sweden, Dr Guohao Li from China presented a study on reduction of urinary oxalate. Diet in general contributes to urinary oxalate concentration, and they discovered the use of a mushroom powder is able to reduce oxalate contents by degradation in traditionally oxalate-rich things such as spinach and tea. Their study found that the mushroom product is able to reduce urinary oxalate in stone-formers by up to 33%!

@Mattbultitude, representing @BJUinternational, was invited to give a talk on tips for submitting manuscripts to the journal to maximise the chances of publication. An interesting fact was that China submitted more papers to @BJUinternational in 2016 than the UK, and came second only to the USA. There are now services from the Journal’s publisher,Wiley, to help improve fluency of manuscripts for papers written by authors whose first language isn’t English, and perhaps this may further increase acceptance rates from countries such as China in the future (https://wileyeditingservices.com/en/translation-service/).

Heavy weights in #urolithiasis closed the last session of the first day of #IAU17. Professor Pal from India, with over 30 years of experience in PCNL, offered tips to young urologists on a procedure not often talked about in textbooks. Short, straight puncture track through a papilla into the most peripheral calyx harbouring or leading to the stone is what we should be aiming for when performing the puncture, and he suggested that meticulous alignment of the C-arm is crucial to provide the spatial information to guide us to do that. This was followed by Professor Jean de la Rosette from the Netherlands, who gave a provocative but strong arguments on why he felt #MET should not be recommended. This discussion came as a heated debate has been going on with regards to the recent publication of a very large, multi-centre randomised controlled trial from China suggesting the use of MET is beneficial in patients with larger distal ureteric stones, and of course much debate was initiated after his talk amongst the audience and on social media (see The Drugs Don’t Work … Or Do They? https://www.bjuinternational.com/bjui-blog/drugs-dont-work/).

As we all know, 24-hour urine work-up is dreaded by most recurrent stone-formers.  It takes up a lot of the patient’s time and thus may result in incomplete collection or just simply be forgotten.  Professor Hans-Göran Tiselius described an abbreviated form of the 24-hour urine work-up that he uses in order to reduce patient inconvenience when collecting the urine samples. The first 16 hours are used to collect most of the common urine biochemistry of calcium, oxalate, citrate, etc while the last 8 hours are used to measure for urate and pH. Each portion is then extrapolated to achieve the final data. Through three examples, Professor Tiselius shows how it is easy to apply the results from the 24-hour urine to give specific dietary instructions and treatment to the patients in the prevention of stones.

One of the final talks of the day was presented by Professor Thomas Knoll from Germany on the use of miniaturised PCNL. Various high-quality comparative studies have demonstrated the benefit of miniaturised equipment for PCNL (in particular reduced morbidities), and interestingly the availability of miniaturised systems appeared to have increased the use of PCNL instead of using RIRS and ESWL for patients with renal stones.

This final session, with master stone surgeons sharing their experience and knowledge in the Young Urology Section, allowed the up-and-coming urologists a chance to pick the mind of the masters.  It set a great tone for the first day and created anticipation for the coming two days of the conference!

 

#IAU17 Day 2

Day 2 of the conference was full of exciting talks and live surgery, spanning over 12 hours from 07:50 in the morning to 20:00 in the evening!

This year @BJUinternational became an Affiliated journal of the IAU. To celebrate this, a virtual issue comprising the 10 best stone papers published in the journal over the past 2 years was published online (Best of Urolithiasis VI), and @mattbultitude, Consultant Urologist and head of stone unit at @guysurology, was invited to present these selected papers in the meeting.

Professor Alberto Trinchieri from Italy then provided an informative talk on the role of acid load in citrate excretion. Hypocitraturia is a common feature in up to 68% of calcium stone-formers. He argued that the acid load of the diet could decrease renal citrate excretion, and the LAKE score, could be a useful tool to be used as a food screener for acid load of diet.

The LAKE score by Professor Trinchieri.

He also argued that the use of oral alkaline citrate can potentially treat uric acid stones by dissolution and prevent calcium oxalate renal stones formation.

Dr Ravi Kulkani from the UK gave an interesting talk on the management of stones in the elderly population. He presented a study conducted at his institution of 60 patients with a median age of 84.6 years with low morbidity, post-op ITU stay and a median length of stay of only 1 day for the cohort. Complete stone clearance rate was still high in the elderly population studied. It is important to assess co-morbidity pre-operatively and optimise them before any surgical treatment, together with extensive anaesthetic input and assessment. Patient selection is crucial and a good outcome can still be achieved in the ever-growing geriatric population.

Following live surgery session demonstrating various tips and tricks of RIRS, the afternoon session on day 2 of #IAU continued to be comprehensive and informative. Professor Peter Alken from Germany gave a provocative talk on the underuse of chemolysis in treatment of patients with uric acid stones, of which most of the audience were in agreement. He argued that evidence suggests it is effective and should be recommended in the guidelines!

Professor Peter Alken from Germany on chemolysis for treatment of uric acid stone.

Professor Guohua Zeng, inventor of super-mini PCNL (SMP), gave a lecture on his experience using the second generation SMP. With the modified sheath enabling efficient irrigation-suction system, he found that the intrarenal pressure intraoperatively remained stably low, with shorter operative time and good stone clearance rate. Undoubtedly, SMP is useful in particular in the management of stones up to 3cm in size, and can be used as an adjunct to standard PCNL when multi-tracts are required. He has also presented his experience in using the technique in the paediatric population with good stone clearance rate and safe. (See The new generation super-mini percutaneous nephrolithotomy (SMP) system: a step-by-step guide)

 

Professor Guohua Zeng on the use of second generation SMP, with an improved
irrigation/suction system.

Another interesting study from Professor Gonghui Li revealed that post-endoscopic lithotripsy septic shock was heralded by a White Cell Count of <2.85 x 109/L at 2 hours post-operation, with sensitivity & specificity over 90%.  Stepping up the antibiotics and aggressive fluid resuscitation at this point could stave off significant hypotension or even mortality in his study.

Professor Gonghui Li of China on early detection of risk of septic shock post-surgery with White Cell Count at 2 hours post-op.

In the evening, the conference became heated with various debates. Management of calyceal diverticulum stones has always been challenging. Mr Simon Choong from UCLH in London, UK, presented good arguments in the use of PCNL with high success rates, but Dr Yi Zhang also showed good clearance rate in experienced surgeons’ hands. And in selective cases, both minimally invasive and open surgery may have a role, presented by Dr Gang Zhu from China and Dr Zinelabidine Abouelfadel from Africa.

Debate on optimal management of 1-2cm lower pole renal stone has been a hot topic for years. Brian Eisner (@BEendourology) from the USA argued that with experience, RIRS stone clearance rate is approaching that of PCNL but with lesser morbidity. However, seeing a live surgery of clearing a >3 cm stone with a miniaturised PCNL technique on day 3 of the meeting, with the patient left completely tubeless post-operatively, may have changed his mind!

 

#IAU17 Day 3

The final day of the conference included 13 live #PCNL surgeries, demonstrating various puncture techniques, tips on how to improve accuracy for access, and advanced surgical techniques including various miniaturised #PCNL by local and international experts.

Professor Guohua Zeng from Guangzhou Medical University First Affiliated Hospital in China demonstrated the treatment of a 3.5cm lower pole renal stone using the second generation super-mini PCNL (SMP), which he invented. With its innovative sheath, which provides effective irrigation and controlled suction, he completed the surgery within 20 minutes. It was bloodless and tubeless, with visually complete stone clearance. Stones were completely extracted via its suction system for stone analysis.

Professor Qu Chen of China demonstrated the use of ultra-mini-PCNL, effectively clearing a medium sized renal stone in a matter of minutes. Interestingly, many surgeons in China prefers to use the ureteric catheter as inflow for irrigation, which generates a flow pressure to help flush stone fragments out – great tip!

13 live stone surgeries were broadcasted to the audience on day 2 of IAU2017

Mr Matt Bultitidue @mattbultitide (left) with Professor Guohua Zeng (middle) and
Dr Christian Seitz @SEITZ_C_C (right)

We must congratulate the #IAU17 organisers’ incredible effort in making the conference an inspiring and valuable learning experience to all who attended. The short duration (8-15mins) of presentations ensured that all the meaty details were packed in with very little fluff!  It was also a great opportunity to build bridges to network and collaborate research in #urolithiasis. We thoroughly enjoyed it and would definitely recommend any urologist with an interest in #urolithiasis to attend its future meetings, and we very much look forward to #IAU18 in Istanbul!

 

 

Dr Wayne Lam

Assistant Professor in Urology, Queen Mary Hospital, University of Hong Kong

Twitter: @WayneLam_Urol

 

 

 

Dr Brian Ho

Associate Consultant in Urology, Queen Mary Hospital, University of Hong Kong

 

A Lifetime of Giving – Donald S Coffey (1932-2017)

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For those who knew Donald Coffey (the “Chief’”), the inquisitive smile says it all. Don spent his professional life sharing his knowledge, wisdom, humor, and encouragement to everyone that he encountered and mentored –and the list is very, very long. It would be difficult to measure the impact Don had on the field of urology and cancer research, given the countless clinicians and scientists that he mentored and inspired to pursue academic careers.

Born in Bristol, VA in 1932, his life story is not in the least traditional including chemist, engineer, laboratory director, prostate cancer researcher, and cancer center director. During college, he worked as a chemist for the North American Rayon Company and after attending King College in Bristol, Tennessee and the University of East Tennessee, Don worked as an engineer at the Westinghouse Electronic Corporation. He eventually decided that he wanted to spend his life working on cancer, and ended up at Johns Hopkins on the advice of a mentor, where he spent more than 50 years giving to others.

Don spent his early years at Johns Hopkins in the Brady Urology Research labs washing glassware for graduate students and taking classes. In 1959 when the Brady Urological Institute was chaired by William Wallace Scott, Don was named the director of the Urological Research Laboratory for 1 year to fill the spot of Charles Tesar who was on sabbatical. He impressed Dr. Scott who encouraged him to obtain a graduate degree. A year later he entered the biochemistry graduate program at Johns Hopkins University School of Medicine. He earned his PhD in physiological chemistry in 1964, and was named the director of the Brady Laboratory for Reproductive Biology in 1969. In 1974, the lab merged with the Brady Research Laboratory and Donald Coffey was made director of the merged laboratories, a position he held until 2004. Together with Patrick C Walsh, Coffey built what would be considered by many as the premier training ground for surgeon scientists, many becoming distinguished academic leaders in urology.

During his tenure at Hopkins he became the Catherine Iola and J. Smith Michael Distinguished Professor of Urology, Professor of Oncology, Pharmacology, and Pathology; and a member of the professional staff of the Applied Physics Laboratory. He was chair of the Department of Pharmacology having never taken a course in pharmacology, and he helped found the Cancer Center without an MD degree. Don was fond of saying that he flunked out of college and never took a course in a department where he was a full professor. He told this to mentees not bragging, but as encouragement that anything is possible with passion –a trait that he embodied to the very end of his life. He simply seemed never to tire of teaching and mentoring students, inspiring in them his passion and love for discovery and life in general. He was one of the most positive forces I have ever met, and his infectious enthusiasm characterized both his professional and personal life. Don Coffey was one of Johns Hopkins greatest teachers and in recognition of this he was the recipient of the Dean’s Distinguished Mentoring Award.

Dr. Coffey had many interests, but primary among them were his curiosity and fascination on the origins of human creativity and homo sapiens’ place in the world. His annual St. Patrick’s Day lecture on this topic was legendary at Johns Hopkins and was delivered to many audiences beyond Hopkins. Don’s early research involved descriptions of a nuclear scaffolding or matrix that was the organizational structure for DNA regulating genetic function. His research focus involved changes in the nuclear structure and shape that he believed could explain the biology of prostate cancer and provide markers of lethal disease.

Don Coffey achieved much during his life that most of us would regard as epaulets; President of the American Association for Cancer Research (AACR), Fuller Award and Lifetime Achievement Award from the American Urological Association, an American Cancer Society Distinguished Service Award from the American Cancer Society, the AACR Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research. He minimized these accomplishments as natural fall out from pursuing his passion in life to “work on cancer.” But those who knew him well would agree that he would -without hesitation- say that his greatest award was witnessing the success of his colleagues and students.

Like all of his mentees and those fortunate enough to work with him, I spent countless hours with Don during a 2-year fellowship as an AUA Scholar. These sessions would go on for hours and could often devolve from science to the meaning of life, evolutionary biology, religion, relationships, etc; the one predictable was the unpredictable during an encounter with Don. They always ended the same way after hearing him say “and just one more thing and we are out of here”; have you eaten yet?” So off he would go with his student(s) in tow to enjoy a meal together and continue talking science.

It is difficult to capture in words the rich life that was Don Coffey over 85 years. Drs. Kenneth Pienta and Alan Partin probably said it best in written and spoken word; “For all of us who knew him and loved him, our grief is deep but our memories of the Chief bring joy that is boundless.”

To learn more about Donald Coffey’s life, take a look at the Donald Coffey story as told by his lovely and devoted wife Eula, his students, and himself (https://vimeo.com/122939259).

 

Bal Carter

Bernard L. Schwartz Distinguished Professor of Urologic Oncology, Johns Hopkins School of Medicine

 

The Drugs Don’t Work … Or Do They?

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The Verve made millions out of the hit single “The Drugs Don’t Work” … I doubt they would have made any money if they called it “The Drugs Don’t Work … Or Do They ?” but that is where we are in 2017 with medical expulsive therapy (MET) for ureteric stones.

In 2015, “The Drugs Don’t Work” was the most read blog of the year and for that won the “Best Blog of the Year” award at the BJUI Social Media awards. And it was all about SUSPEND. The trial that changed everything. We had been giving MET out like smarties. We loved it. Patients loved it. But many of us had doubts. The evidence was weak. “Large randomised trials are needed to confirm” the authors of small trials said. And so we did it in British Urology and it did change practice for many people. Doubts crept in around the world. More trials confirmed this. The Furyk study … MET doesn’t work in Australia (apart from a small advantage on small subgroup analysis). It doesn’t work in America either. Silodosin … promising but little benefit. But wait … the NIH are doing a trial. This will confirm once and for all. And as I was about to debate John Hollingsworth at the Rock Society at #AUA17 – thrown into the lion’s den of believers – it was released, a late breaking abstract – The STONE study and NO BENEFIT TO MET. Game over … MET is dead. Even non-believers were convinced in another debate with John in Vancouver at #WCE17.

So imagine the surprise as this month in European Urology, the largest study ever conducted was released. 3450 patients. A good quality double-blind placebo-controlled RCT. The headline … Overall MET does work (86% vs. 79%). And this was judged on a fairly hardcore follow-up schedule of CT scans weekly for 4 weeks – how many people do that in their practice? On subgroup analysis stones >5mm show greatest benefit (87 vs. 75% stone passage). Stones ≤ 5mm showed no benefit (88% vs 87%) although there is some advantages for time to passage (148 vs.249 hours), colic episodes (1.9 vs.9.4%) and analgesia requirements (89 vs.236mg). So what do we do now? Firstly I suspect this has just cemented the current position of the 2017 #EAUGuidelines which already states “the greatest benefit might be among those with large (distal) stones”. I do also feel this trial requires greater scrutiny – does this really change everything again?

Some facts: 3296 patients included in the analysis. Only 15 patients declined entry to the study – that is amazing! Recruited in 30 centres in China over 2 years which finished in 2013. The inclusion criteria was for distal ureteric stones from 4-7mm (interestingly a fact not expressed in the abstract). Not 3mm; not 8mm; 4-7mm only. So a narrow window which probably represents the potential target benefit for MET. There are lots of exclusion criteria – diabetes, previous stone on that side, previous ureteroscopy on that side and ‘severe hydronephrosis’. So if the emergency departments are to follow this study they need to select stones of 6 or 7mm in longest diameter, only in the distal ureter and without “severe hydronephrosis” whatever that means. I’m not sure I totally know and I’m a urologist. Good luck to the ED docs with that one!

I need to ask, why has it taken 4 years for this to be published? There is no long-term follow-up required in this study. Outcomes should be known within 28 days. With such international controversy surely this should have been a priority to publish? Only the authors can answer this question but such delayed publication suggests to me some issue with the data. This was a company sponsored trial – so why weren’t they pushing for publication? Only they know. Company involvement to me automatically introduces a degree of murkiness about the outcomes in any trial – just look at the problem with oncology trials. Even more so when they are “involved with preparation of the manuscript”. That gives them a controlling interest in the publication of the outcomes and that really concerns me. It probably shouldn’t … the results are the results … but it still concerns me. It’s one thing supplying the medications for a trial but having control of the manuscript? What data is missing? For example, how many people in each group complied with the imaging protocols? We don’t know. How many patients didn’t undergo any follow-up imaging at all? We don’t know. How many patients did not attend (DNA) for follow-up at each stipulated week (as DNA rates are often high for colic patients)? We don’t know. Any small differences between the groups might explain the differences in final outcome. How many returned the analgesia and pain questionnaires? We don’t know. What were the compliance rates with medication? We don’t know. Importantly, why were the side-effects the same in both groups in such a big sample? That worries me a lot. This trial is powered to show small differences and even the most ardent MET supporters will concede that MET comes with a tolerable increase in side-effects – other studies have clearly shown that. That concerns me. Is that actually a surrogate marker of quality for this study?

Don’t get me wrong, other studies definitely have their limitations as well. Furyk – underpowered for larger stones. STONE – confounded by small stones? SUSPEND – real-life follow-up without mandated imaging. There is no doubt this trial will shift the balance in the debate. I thought MET was dead but, as per the EAU guidelines, MET may confer benefit for stones >5mm but in reality only those measuring 6 or 7mm – an absolute benefit of 12% for that specific group. It definitely doesn’t help stone passage for ≤ 5mm stones. It is interesting that whilst SUSPEND was criticised for having such high stone passage rates of ~ 80% – that is exactly what is seen in this paper and in a more select larger stone group. That is curious. Placebo did very well again. It’s a shame we can’t prescribe that!

What will I do? I might use MET a bit more for the carefully selected and counselled “larger stone” – I did anyway – but I certainly don’t feel we are back to giving this out to everyone who walks through the door.

 

Matthew Bultitude

Consultant Urologist, Guy’s and St. Thomas’ Hospital

Associate Editor, BJUI

 

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