EUT Congress News - Sunday 17 March

European Urology Today

EUT Congress News

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33rd 32nd Annual Annual Congress Congress of of the the European European Association Association of of Urology Urology

Sunday, March 2018 Saturday,1825 March 2017 Hot topics in andrology

Copenhagen, 16-20 March 2018 London, 24-28 2017

Informed patients mean fewer legal woes Lawyer Bertie Leigh: ‘To avoid nightmares, communicate well with patients’

By Erika de Groot

By Joel Vega Does the environment contribute to male infertility?

What are the conception risks with regards advancing paternal age?

Chaired by Dr. Maarten Albersen (BE) and Prof. Jens Sønksen (DK), Plenary Session 1: Hot topics, evidence quality and advances in andrology examined these issues during a well-attended session yesterday.

As paternal age increases, it presents no absolute barrier to conception, but it does present greater risks and complications, stated Prof. Andrea Salonia (IT) in his lecture “Are European men delaying fatherhood? Epidemiology and the effects of advancing paternal age in fertility potential and the offspring.”

“The older the male patient, the higher the probability of comorbid conditions,” said Salonia.

With advancing paternal age, published data support a decrease in fertility, a decline in semen quality, and a lower success rate for Assisted Reproductive Technology (ART). There is an upsurge in male germline ageing, an increased risk of neurodevelopmental outcomes such as autism, spectrum disorders and schizophrenia/psychosis, and higher risk of childhood cancers.

According to Dr. Marij Dinkelman-Smit (NL), who presented on behalf of Prof. Gert Dohle (NL), Endocrine Disrupting Chemicals (EDCs) may be linked to testicular dysgenesis syndrome and decreased fecundity. In Western society, sperm count has declined and testicular cancer cases have increased.

EDCs mimic the female hormone oestrogen (pseudo-oestrogens) or antagonise androgens (anti-androgens). EDCs can pass through the placenta and influence testicular development during early pregnancy (the ‘window of vulnerability’). EDCs can be found in plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics and pesticides. Dinkelman-Smit said there are studies confirming the link between mothers’ exposure to EDCs and cryptorchidism in sons.

On surgical therapy for male infertility, Prof. Dr. Sabine Kliesch (DE) said testis varicocele cases, therapies include varicocelectomy / embolisation, and microsurgical varicocele surgery in idiopathic oligozoospermic men to improve natural conception.

Regarding obstructive azoospermia, microsurgical reconstruction or (micro-)surgical retrieval are two of the therapeutic options.

For Non-obstructive azoospermia (NOA), TESE after genetic testing and counselling is the recommended therapeutic option. Other recommendations include microsurgical TESE for severe NOA; superior multifocal TESE rather than conventional TESE; and the option of histological analysis to detect germ cell neoplasia in situ (GCNIS).

Masson-Lecomte (FR) and Hugh Mostafid (GB), who defended their surgical approaches.

Patients well informed by their doctors on the risks of complex surgical and medical treatments are less inclined to fight bitter legal battles with healthcare professionals, said a renowned litigation lawyer during yesterday’s Plenary Session 2 which took up problematic surgical cases in bladder cancer.

In the first case, where the patient filed a suit (after cystectomy) due to the absence of a tumour, Burger said bladder removal was still warranted since there is a high rate of recurrence. He characterized it as a potentially “vicious” case, saying: “If you don’t do it right, it can lead to aggressive disease. No tumour doesn’t necessarily mean cure.”

In a full-house “Nightmare Session” chaired by urologist Tim O’Brien (GB), expert medical litigation lawyer Bertie Leigh (GB) returned for a second time to drive home his point on weak patient-doctor communication, which he says is often the reason why complex medical cases end up in the courtroom.

Lawyer Bertie Leigh (on podium) drives home a point on effective doctor-patient communication during Plenary Session 2’s ‘Nightmare’ cases on bladder cancer.

“The underlying point… is patient education. Doctors often hide behind the perceived protection provided by a consented patient but often miss the more important point of informing the patient,” said Leigh, who has conducted prominent cases in clinical negligence and regulatory law over the past 30 years.

post-operative pT0 finding (no tumour); the second an elderly patient who suffered intra and post-operative complications; and the third involving severe complications following a first transurethral resection of bladder tumour (TURBT).

The session reviewed three cases: the first concerning a patient who had radical cystectomy despite a

Facing intense questioning by Leigh were Maximilian Burger (DE), Morgan Rouprêt (FR), Alexandra

However, Leigh said the issue was not so much about the strategy taken by the doctor, but the way the planned treatment was communicated to the patient.

“It would help if doctors were not always so nice to their patients. At some point you have to share your uncertainty with them and make them understand the risks or severity of the treatment,” said Leigh.

The second case examined issues such as the lack of consensus on intra-operative complications, patient education, and the role of recording complication rates.

Technology strikes back Day-long Live Surgery session examines new surgical techniques

By Joel Vega

problems during the operation. Questions from the audience also included resection techniques and whether the option to shift to a radical nephrectomy is considered by the lead surgeon. Surprisingly, during a hands-vote, many of the audience opted for a radical nephrectomy when asked if they would consider the option.

Under the watchful ‘3D eyes’ of hundreds of congress participants, more than a dozen live surgeries were presented yesterday via direct transmission from Herlev Hospital in Denmark, a complex programme that involved surgeons from various countries.

Organised by the EAU Section of Uro-technology (ESUT) in collaboration with the EAU Robotic Urology Section (ERUS) and the EAU Section of Urolithiasis (EULIS), a combination of live and pre-recorded videos showed a wide range of sophisticated techniques in laparoscopic prostatectomy, percutaneous nephrolithotripsy, robot-assisted prostatectomy, various stone removal techniques, robotic bladder resection, and radical nephrectomy among many others.

A panel of experts monitor and comment on the direct transmission of live surgeries from Herlev to Copenhagen.

During Siemer’s operation, moderator Breda commented on the vein thrombosis that Seiner encountered. They also discussed clamping techniques and the pre-operative strategy to anticipate potential

The second part of the session covered pre-recorded video of confocal and endomicroscopy technology in upper tract tumours, robotic intracorporeal neobladder using the Wiklund technique and presented by Prof.

Peter Wiklund (SE) himself. Former ESUT chairman Prof.

Jens Rassweiler (DE) was also scheduled to demonstrate a 4K laparoscopic extraperitoneal radical nephrectomy, to be followed by current ESUT chair Prof. Evangelos Liatsikos (GR) performing a prone percutaneous nephrolithotripsy.

The live and pre-recorded operations were presented in four parts during the day-long session titled “Technology Strikes Back,” which formed part of the annual tradition of the ESUT to share educational content and practical insights regarding some of the most cutting-edge techniques in urological surgery.

Four sets of moderators provided commentary and asked questions to the participating surgeons for them to explain the rationale of the surgical steps they have taken, or shed insights on the pre-operative planning.

Coordinating on the eURO Auditorium were Dr. Alberto Breda (ES) and Prof. Dr. Andreas Gross (DE).

The first set showed a 3D laparoscopic prostatectomy performed by Prof. Jens Stolzenburg (DE), followed by a mini-prone percutaneous nephrolithotripsy by Prof. Udo Nagele (AT). Nagele demonstrated the laser ‘hammering’ of stones, and his attempts to retrieve a bigger stone fragment.

Dinkelman-Smit examines male fertility issues.

Sunday, 18 March 2018

Following Nagele’s procedure was a flexible ureteroscopic lithotripsy by Dr. Guido Giusti (IT) and a single-use ureteroscopic lithotripsy by Assoc. Prof. Kim Andreassen (DK) and robotic partial nephrectomy by Prof. Stefan Siemer (DE).

EUT Congress News

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“Guidelines have to be criticised to be improved”

Today’s Industry Sessions

EAU Guidelines Controversies session justifies recommendations

Industry sessions, starting at 17:45 hrs

By Loek Keizer

Keeping it real - Adaptations, perceptions and expectations in patients with OAB ASTELLAS PHARMA EUROPE LTD. Green Area, Room 1 (Level 0)

“Guidelines have to be improved. To be improved, they have to be criticised. If they are well criticised, it’s an improvement.” These are the words of Prof.

Nicolas Mottet (FR), chairman of the EAU Guidelines panel for Prostate Cancer.

Changing paradigms of advanced prostate cancer: Reality or dream?

JANSSEN PHARMACEUTICA Red Area, Room 1 (Level 0) TOOKAD (padeliporfin) Vascular Targeted Photodynamic Therapy Marketing Authorization (EMA) granted by European Commission November 10 2017 STEBA BIOTECH Blue Area, Room 5 (Level 0) ®

Urothelial cancer and immune checkpoint inhibitors: Data update, and case reviews in urology practice MSD Red Area, Room 2 (Level 0)

Mottet hailed the EAU Guidelines Controversies specialty session held yesterday as a very positive development in the discussion of the EAU Guidelines.

The session was organised as four hour-long debates between a moderator, two opposing views, a third, independent view and much audience discussion and voting. It drew large crowds, particularly when combining systemic treatment of metastatic prostate cancer was discussed.

Mottet was referring to the presence of Dr. Laurence Collette (BE) in the debate on prostate cancer. Dr. Collette is the Chief Statistician for the EORTC. Following a debate between Prof. Noel Clarke (GB) and Mr. Philip Cornford (GB) on the merits of combining systemic treatments for every patient or only a small selection, Dr. Collette weighed in on the data that both discussants were citing: “How much does the subgroup contribute to the full picture? We should consider the percentage of events, rather than the patients.” In the example of the CHAARTED trial, low volume disease accounted for 35% of the patients, but only 25% of events in its latest update. Definitions of “high volume disease are also debatable, relying on bone scans alone, distinguishing aggressive vs. slow-growing disease, and so on.

Examining the Guidelines “It’s not always possible for us to detail all the arguments that support what we write in the EAU Guidelines,” Mottet explained. “It’s nice to have a session like this, where we can explain our position, particularly when they are hot topics, like bladder preservation vs. removal. It’s good to hear arguments in favour and against, and then somebody completely outside of that paradigm, particularly when they address methodology.”

Based on the audience’s votes before and after this particular debate, it seems Dr. Collette swayed many of those present. Before the debate, the audience was split almost evenly between four possible answers to a question about newly-diagnosed M1a disease (enlarged retroperitoneal nodes only): ADT combined with Abiraterone acetate, ADT combined with Docetaxel, either drug or ADT monotherapy. Following the debate, nearly half of the audience voted for the third option, a combination of ADT and either drug.

Dr. Laurence Collette, who participated on a debate on the statistics of the combination of systemic treatments in metastatic hormone-sensitive PCa.

Shades of grey Mottet reflected on the choice of topics when the session was over. “When something is not black or white, the guidelines need to say something, and we have to explain our recommendations. At some point we might realise that we made mistakes, and that’s OK. Through evidence, discussion and criticism, we ultimately improve our guidelines,” he said.

Some of these “grey” topics that were debated in Saturday’s session include muscle-invasive and metastatic bladder cancer and the prospects of organ preservation becoming the gold standard; mesh vs. non-mesh surgery for genital prolapse and urinary incontinence and testis cancer.

Information: Crucial in antibiotic stewardship ESAU-ESIU course highlights antimicrobial resistance

By Erika de Groot

European Urology Today Editor-in-Chief Prof. M. Wirth, Dresden (DE) Section Editors Prof. T. E. Bjerklund Johansen, Oslo (NO) Mr. Ph. Cornford, Liverpool (GB) Prof. O. Hakenberg, Rostock (DE) Prof. P. Meria, Paris (FR) Dr. G. Ploussard, Paris (FR) Prof. J. Rassweiler, Heilbronn (DE) Prof. O. Reich, Munich (DE) Dr. F. Sanguedolce, London (GB) Dr. Z. Zotter, Budapest (HU)

Antibiotics alternatives Ass. Prof. Björn Wullt (SE) enumerated various alternatives to antibiotics for treating acute urinary tract infection (UTI) which ranged from observation (“wait and see”), NSAIDs (Nonsteroidal AntiInflammatory Drugs) and increased fluid intake (although these require further studies) to Canephron®, a phytotherapeutic medicinal product for which study results will be published soon.

Editing and Coordination J. Vega Onsite Reporting and Editing E. de Groot L. Keizer J. Tidman J. Vega X. Zheng

In his lecture “Non-antibiotic treatment and prevention in uncomplicated cystitis”, Wullt also mentioned

Communications and Promotion J. Bloemberg M. van Gurp I. Moerkerken

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EUT Congress News

By Jen Tidman

Colophon

No part of European Urology Today (EUT) may be reproduced without written permission from the Communication Office of the European Association of Urology (EAU). The comments of the reviewers are their own and not necessarily endorsed by the EAU or the Editorial Board. The EAU does not accept liability for the consequences of inaccurate statements or data. Despite of utmost care the EAU and their Communication Office cannot accept responsibility for errors or omissions.

alternatives to antibiotics for treating prophylaxis of recurrent UTI such as asymptomatic bacteriuria (ABU).

He cited a study by Dr. Tommaso Cai (IT) that ABU should not be treated in young women affected by UTI, suggesting it may play a protective role in preventing symptomatic recurrence. Additional alternatives included E. coli 83972, E. coli extract OM-89, and local oestrogen hormone replacement therapy (HRT).

Be informed “The best prevention is adequate information,” stated Dr. José Medina-Polo (ES) in his lecture Collateral

Medina-Polo added that the prescription of antibiotics should be adequately indicated and justifiable in order to avoid the use of broadspectrum antibiotics. He said that perioperative antibiotics should not be routinely continued beyond the first 24 hours post-surgery unless an infection is present.

Mathematical modelling “We need to improve antibiotic selection. In this sense, mathematical modelling is a good instrument to deliver that,” said Prof. Zafer Tandoğdu (GB) in his lecture Which antibiotics in what indication: The role of mathematical modelling. “Surveillance studies are highly important to derive that information to summarise the dynamic process which will help us improve our decisions.”

Greece leads the competition to win top prize

Lay-Out/Printing D. Blom G. Smit

Disclaimer

Dr. J. Medina-Polo hears congratulations on becoming a father, yesterday.

EAU Guidelines Cup: A new multiple-choice quiz

Advertising R. A. Matser L. Schreuder

EUT Editorial Office PO Box 30016 6803 AA Arnhem The Netherlands T +31 (0)26 389 0680 communications@uroweb.org

Antibiotic alternatives, further education and mathematical modelling were some of the topics explored today during the antimicrobial stewardship course (ABS): “From cystitis to urosepsis: What is the best way to deal with antimicrobial resistance (ABS certificates)?”

The course is part of the Joint meeting of the EAU Section of Andrological Urology (ESAU) and the EAU Section of Infections in Urology (ESIU) “When Basic Science meets Clinical Practice” chaired by Prof.

Nikolaos Sofikitis (GR) and Prof. Dr. Florian Wagenlehner (DE).

Founding Editor Prof. F. Debruyne, Nijmegen (NL)

effects of antibiotic treatment and how to minimise them (C. difficile and multiresistant pathogens.

Training focused on multidrug-resistant organisms (MDRO), local microbial prevalence, resistance patterns, and prescription of antibiotics is imperative, as are antimicrobial stewardship programmes dedicated to improving antibiotics. These programmes have demonstrated a reduction in the incidence of infections as well as the isolation of MDRO bacteria and C. difficile infections.

Dr. Dimitrios Deligiannis (GR), supported by Team Greece, emerged victorious in the third and final round of the cup EAU Guidelines Cup, a new competition to determine which EAU member knows the EAU Guidelines the best.

The contest was hosted by the Young Urologists Office (YUO) and European Society of Residents in Urology (ESRU) as part of YUORDay18. Prior to the annual congress, the first and second rounds took place online through multiple-choice questions. 450 contestants were whittled down to 125, and then the final three.

Introduced to the sounds of “We Are The Champions”, Deligiannis took on Dr. Giorgi Tsabutashvili (GE) and Team Georgia and Dr. Filippo Maria Turri (IT) and Team Italy. The audience also joined the competition using anonymous voting pads.

The questions posed covered several topics of the EAU Guidelines, varying from Peyronie’s disease, urolithiasis, renal, testicular and penile cancer, and much more. The results and prizes were announced to a soundtrack of “Eye Of The Tiger.”

Turri, the third place winner, and Dr. Mária Rodriguez-Monsalve Herrero (ES), the audience member with the highest score, received full access to UROsource, the EAU learning library for urologists which is the largest knowledge base in the field of urology with over 60,000 items of quality scientific content.

Tsabutashvili, the second place winner, won a four-volume set of Campbell-Walsh Urology (11th edition) featuring 22 new chapters including an increased focus on robotic surgery and imageguided diagnostics as well as online access to 130 video clips. As champion, Deligiannis can choose free attendance at any masterclass from the huge selection offered by the European School of Urology.

Thomas Knoll (DE) and Maria Ribal (ES) acted as the members of the jury for the session. Juan Vásquez Mendoza (DK) who moderated the session told the contestants, “You are all winners; you beat a lot of competition to get here.” He told the audience to stay tuned for next year’s cup which he promised would be even more fun.

Winners of the Guidelines Cup

Sunday, 18 March 2018

Improved QoL among male-to-female transgender after surgery New German study shows surgery leads to better QoL perception Male-to-female transgenders have better quality of life perception and reported improved psychosocial conditions following surgery, according to a study conducted in Germany.

The researchers developed a transgender-specific questionnaire which confirms for the first time that gender surgery significantly improves quality of life for the majority of patients. The study showed that 80% of male-to-female patients perceived themselves as women post-surgery. However, the quality of life of transgender individuals is still significantly lower than the general population. Many transgender individuals request gender reassignment surgery, but until now there only existed information on general aspects of health related quality of life (QoL) and non-validated questionnaires about improvement of QoL. Led by Dr. Jochen Hess, the researchers surveyed 156 patients for an average of more than six years after surgery. They developed and validated the new Essen Transgender Quality of Life Inventory (ETLI), the first methodology to specifically consider transgender QoL. They found that there was a high overall level of satisfaction with the outcomes of surgery. When

comparing the QoL of the last four weeks with the QoL during the time of the coming-out there was a highly significant increase on all subscales of the ETLI as well as for the global score indicating a large improvement of QoL in the course of the transitioning process.

“The good news is that we found that around three-quarters of patients showed a better quality of life after surgery. 80% perceived themselves to be women, and another 16% felt that they were ‘rather female’. Three women in four were able to have orgasms after reassignment surgery,” said Hess.

“It’s very important that we have good data on Quality of Life in transgender people. They generally suffer from a worse QoL than non-transgender population, with higher rates of stress and mental illness, so it’s good that surgery can change this, but also that we can now show that it has a positive effect,” he added.

“Until now we have been using general methods to understand quality of life in transgender individuals, but this new method means that we can address well-being in greater depth”. Recent data estimates that 1.4 million adults in the USA identify as transgender, which is about 0.6% of the population.

Comparable European figures are not available, but there is wide variation between reported prevalence in individual European countries. Transgender individuals have seen greater visibility in recent years due to the openness of personalities such as Caitlin Jenner, Chelsea Manning, and Andreja Pejic.

The team noted limitations to the study: there was a high drop-out rate and the results are from the single centre. “Nevertheless, we now have the first specific validated tool for measuring QoL in transgender patients. We hope that this means that we can go forward to gather better information to help us improve treatment”, said Hess.

Prof. Professor Piet Hoebeke (Ghent University Hospital, BE) commented on the study: “As patients develop a better understanding and higher acceptance of transgender surgery, more will seek gender confirming surgery. Despite this observation many doctors are still not convinced that this is a medical condition for which surgery can be offered as a valuable treatment. We need studies like this one to convince the medical world that these patients can get a better QOL with treatment”.

Congress news. . . . . . . . . . . . . . . . . . . . . . . . 1 Congress highlights . . . . . . . . . . . . . . . . . . 2/3 Phenotyping overactive bladder. . . . . . . . . . . 4 MRI fusion biopsies: Usability and future prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Long-term outcomes in male genital reconstruction . . . . . . . . . . . . . . . . . . . . . . . . 7 Managing complications during laparoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Multiparametric MRI and MRI/TRUS fusion in PCa . . . . . . . . . . . . . . . . . . . . . . . . . 9 EAU Guidelines harnesses potential of social media. . . . . . . . . . . . . . . . . . . . . . . . . 10 Radiomic TRUS - A new era. . . . . . . . . . . . . . 11 European Active Surveillance of Renal Cell Carcinoma Study . . . . . . . . . . . . . . . . . . 12 End-stage renal disease and kidney transplantation. . . . . . . . . . . . . . . . . . . . . . . 13 Dealing with complications after renal transplantation. . . . . . . . . . . . . . . . . . . . . . . 14 Underactive bladder. . . . . . . . . . . . . . . . . . . 17 Possible ways to refine prostate biopsy . . . . 20

Award Gallery

EAU PI: Are we clear enough? . . . . . . . . . . . 21 Pre- and post-testing ensure course excellence. . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Can I still use mesh for POP repair? . . . . . . . 23 Prostate cancer molecular and genetic biomarkers. . . . . . . . . . . . . . . . . . . . . . . . . . 25 Anatrophic nephrolithotomy: Safe and effective treatment. . . . . . . . . . . . . . . . . . . . 26 Developing a urology nursing educational curriculum. . . . . . . . . . . . . . . . . . . . . . . . . . 27

Best Booth Award 2018: Janssen Oncology, Pharmaceutical Companies of Johnson & Johnson From left to right: Erik Holl, Ivo Winiger-Candolfi, Joana Lencart, Johannes Engels, Chris Chapple, Jack Harris

Our Secretary-General Prof. Chris Chapple opens the EAU18 Exhibition

Best Paper on Fundamental Research: L. Derré (Lausanne, Switzerland)

Best Paper on Clinical Research: R. Seiler (Berne, Switzerland)

First Prize Best Abstract (Oncology): A. Birtle (Preston, United Kingdom)

First Prize Best Abstract (Non-Oncology): A. Chebbi (Rouen, France)

Second Prize Best Abstract (Oncology) O. Wegelin, (Nieuwegein, The Netherlands)

Second Prize Best Abstract (Non-Oncology): N. Sopko (Baltimore, United States of America)

Third Prize Best Abstract (Oncology): I. Eder (Innsbruck, Austria)

Third Prize Best Abstract (Non-Oncology) B. Pradere (Tours, France)

Best Scientific Paper Fundamental Research in European Urology: Y. Li (Vancouver, Canada) (Not pictured) Represented and supported by ELSEVIER

Best Scientific Paper EurUrol Clinical Research B. Escudier (Villejuif, France) (Not pictured) Represented and sponsored by ELSEVIER

Best Scientific Paper in European Urology: F. Porpiglia (Turin, Italy) Sponsored by ELSEVIER

Best Scientific Paper on Robotic Surgery in European Urology: N. Van De Berg (Leiden, The Netherlands) Accepted by H. Van der Poel.

Sponsored by the VATTIKUTI FOUNDATION

Sunday, 18 March 2018

EUT Congress News

3

Phenotyping overactive bladder On the way to tailored treatment Benoit Peyronnet Department of Urology University Hospital of Rennes Rennes (FR)

Overactive bladder (OAB) has been formally defined in 2002 by the International Continence Society (ICS) as urgency, with or without urge incontinence, usually with frequency and nocturia1.

On the one hand, this definition has certainly been beneficial by raising awareness of the medical community about storage lower urinary tract symptoms and their impact on quality of life, by facilitating clinical research in the field, and have had even a bigger impact through regulatory authorities (drug licensing), companies market access attitudes, patient information websites content or scientific societies actions and research. However, on the other hand, this broad definition could now appear as being more misleading than anything else and it has been the main driver of standardized “plumb” treatment strategies2-3 where the symptoms, after the physicians has dismissed urological/neurological alternative causes through a minimal work-up, are classified as “idiopathic” OAB expecting the diagnosis would be confirmed through an ex-juvantibus management.

The high discontinuation rates of OAB medications (including Beta3-agonists) from the first months after treatment onset, that have been widely reported over the past few years4, is a meaningful telltale sign emphasizing the limitations of this “one-size fits all” approach to OAB management. There are multiples clues in available literature suggesting that several subtypes of OAB might be distinguished and that it is more likely a heterogeneous syndrome rather than a homogenous disease5 supporting a paradigm shift from OAB as an idiopathic melting pot to a spectrum of multiple non-neurogenic subtypes.

Upon the invitation of Prof. Jean-Nicolas Cornu (University of Rouen, France), we worked with a panel of experts, by reviewing the literature, to provide a comprehensive point of view of the pathophysiology of non-neurogenic OAB, highlighting that “idiopathic” OAB is everything but idiopathic. We proposed that OAB might be phenotyped according to either underlying mechanisms or pathophysiological cofactors (Figure 1).

Differents anatomical origins of urgency have been proposed with historically two hypotheses, the myogenic (urgency initiated from the detrusor muscle) and the neurogenic (urgency initiated from the central nervous system (CNS)). The increasing evidence regarding the role of urothelium/suburothelium and bladder afferent signaling has given birth to a third “urotheliogenic” hypothesis (urgency initiated from the urothelium/suburothelium)5,6. Despite less clearly established, a fourth anatomical generator of urgency, the urethra, has been patently evidenced with noticeable refinement of its understanding and possible implication over the past decades (“urethrogenic” hypothesis)7.

Finally, growing interest regarding underactive bladder and detrusor overactivity may argued for a fifth mixed anatomical mechanism, from both a detrusor muscle and urothelium/suburothelium dysfunctions, as underactive bladder symptoms commonly overlap those of OAB (“urothelio-myogenic” hypothesis)8. These various anatomical origins of OAB are displayed in Figure 2.

Several pathophysiological co-factors have been implied as possible important determinants in OAB

Figure 2: Various anatomical origins of urgency

pathogenesis. Increasing evidence over the past few years have shown that metabolic syndrome9, affective disorders10, sex hormones deficiency11, urinary microbiota12, gastrointestinal functional disorders13, subclinical autonomic nervous system dysfunction14 may favor OAB and that OAB could have its own specific pathophysiology in all of these frameworks.

A “Prism” spectrum approach (Figure 3) could help identify these various OAB pathophysiological features using thorough clinical examination, urodynamics and likely several additional testings in the near future such as urinary markers, functional brain imaging, autonomic nervous system testings, quantitative sensory testings, serum assessments of corticotropin-releasing factor, testosterone,….

There is probably not one “single” idiopathic OAB syndrome but rather numerous non-neurogenic OAB phenotypes based on underlying mechanisms and pathophysiological co-factors/co-morbidities supporting a paradigm shift in OAB towards treatment strategies tailored to individual patient characteristics. However, there seems to be currently a lack of consensual techniques for assessing the relevant pathophysiological features of OAB and future studies are needed in this field.

Likewise, we believe that forthcoming studies should assess the outcomes of the various OAB treatments available nowadays in each different OAB subpopulations because the outcomes of each treatment might rely mostly on disease features and patient’s profiles. Pharmacological companies may be less inclined to promote trials assessing the outcomes of drugs in subgroups of patients because it would divide the potential subsequent market without decreasing studies-related costs.

Hence, it behooves the urological community to promote such studies. Finally, from a public health standpoint, the cost-effectiveness of a tailored vs. a “one-size fits all” treatment approach is still elusive and should be taken into consideration.

References 1. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society.

Neurourol Urodyn. 2002; 21(2):167-78.

2. Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455-63.

3. Lucas MG, Bosch RJ, Burkhard FC, et al. EAU guidelines on assessment and nonsurgical management of urinary incontinence. Eur Urol. 2012; 62(6):1130-42.

4. Chapple CR, Nazir J, Hakimi Z, et al. Persistence and Adherence with Mirabegron versus Antimuscarinic Agents in Patients with Overactive Bladder: A Retrospective Observational Study in UK Clinical Practice. Eur Urol. 2017; 72(3):389-399.

Figure 3: The diagnosis “prism” approach of non-neurogenic OAB

5. Hanna-Mitchell AT, Kashyap M, Chan WV, Andersson KE, Tannenbaum C. Pathophysiology of idiopathic overactive bladder and the success of treatment: a systematic review from ICI-RS 2013. Neurourol Urodyn. 2014; 33(5):611-7.

6. Chapple C. Chapter 2: Pathophysiology of neurogenic detrusor overactivity and the symptom complex of “overactive bladder”. Neurourol Urodyn. 2014;33 Suppl 3:S6-13.

7. Kirschner-Hermanns R, Anding R, Rosier P, Birder L, Andersson KE, Djurhuus JC. Fundamentals and clinical perspective of urethral sphincter instability as a contributing factor in patients with lower urinary tract dysfunction--ICI-RS 2014. Neurourol Urodyn.

2016;35(2):318-23.

8. Uren AD, Cotterill N, Harding C, et al. Qualitative Exploration of the Patient Experience of Underactive Bladder. Eur Urol. 2017;72(3):402-407.

9. Bunn F, Kirby M, Pinkney E, et al.Is there a link between overactive bladder and the metabolic syndrome in women?

A systematic review of observational studies. Int J Clin Pract. 2015;69(2):199-217.

10. Vrijens D, Drossaerts J, van Koeveringe G, Van Kerrebroeck P, van Os J, Leue C. Affective symptoms and the overactive

bladder - a systematic review. J Psychosom Res. 2015;78(2):95-108.

11. Hanna-Mitchell AT, Robinson D, Cardozo L, Everaert K, Petkov GV. Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014.

Neurourol Urodyn. 2016; 35(2):299-303.

12. Aragón IM, Herrera-Imbroda B, Queipo-Ortuño MI, et al.The Urinary Tract Microbiome in Health and Disease. Eur Urol Focus. 2016 in press 13. Malykhina AP, Wyndaele JJ, Andersson KE, De Wachter S, Dmochowski RR. Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS 2011. Neurourol Urodyn. 2012; 31(3):352-8.

14. Hubeaux K, Deffieux X, Raibaut P, Le Breton F, Jousse M, Amarenco G. Evidence for autonomic nervous system dysfunction in females with idiopathic overactive bladder syndrome. Neurourol Urodyn. 2011; 30(8):1467-72.

Sunday 18 March 08.00-10.15: Plenary Session 4, Contemporary storage LUTS management

EAU 2018, COPENHAGEN, 16–20 MARCH 2018, IPSEN SATELLITE SYMPOSIUM

Optimising patient management in urogenital cancers Chaired by Dr Maria Ribal (Spain), on Saturday 17 March Dr Peter Busch Østergren (Denmark) The significance of testosterone and gonadotropin suppression in advanced prostate cancer treatment Achieving the lowest levels of testosterone possible, combined with androgen suppression, has been shown to delay disease progression and increase overall survival in men with advanced prostate cancer. Dr Østergren presented key data from a recent study, which demonstrated that androgen deprivation therapy (24-week triptorelin depot) resulted in significantly lower testosterone levels compared with subcapsular orchiectomy in advanced prostate cancer.

Professor Morgan Rouprêt (France) Predicting the future of PDD - blue skies or dark clouds Prof. Rouprêt provided an overview of the future of imaging modalities in non-muscle invasive bladder cancer (NMIBC). Enhanced imaging techniques, such as photodynamic diagnosis (PDD), can help to identify suspect lesions, which may result in increased tumour detection. In addition, new optical diagnostic tools can provide real-time information on tumour invasiveness and grade to help differentiate tumour types and guide treatment decisions.

Professor Petri Bono (Finland) Current strategies and future challenges in 2nd line therapy in advanced RCC Led by Prof. Bono, this interactive presentation focussed on two patients with advanced RCC who had progressed following 1st line vascular endothelial growth factor (VEGF)-targeted therapy. An overview of current treatment guidelines in this setting, alongside data from recent clinical trials of targeted therapies and immuno-oncology agents, were presented and discussed.

Please visit the Ipsen booth E15 CBZ-ALL-000561 13 February 2018

Figure 1: From idiopathic to non-neurogenic OAB

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Sunday, 18 March 2018

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Through numerous industry collaborations, we seek to explore the potential synergies of combining our immunotherapies with other immune-modulators.

BAVARIAN-NORDIC.COM Sunday, 18 March 2018

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MRI fusion biopsies: Usability and future prospects MRI/TRUS fusion offers benefits in targeted biopsies despite challenges in accuracy and costs Dr. Lars Boesen Dept. of Urology Herlev University Hospital Herlev (DK)

to increase targeting accuracy. There are now several commercial software platforms available (Table 1) that differ in both technology (image acquisition and tracking mechanism) and biopsy route (transrectal sidefire/endfire or transperineal). An MRI T2W sequence is most often used for prostate/target contouring during MRI/TRUS image fusion, due to its high anatomical resolution and lower risk of artefacts.

However, other mpMRI sequences can be used depending on preferences and fusion-software.

Cognitive TBx Multiparametric MRI (mpMRI) of the prostate allows Cognitive “fusion” is the simplest, cheapest and first for high quality lesion detection and characterization technique by which MRI/TRUS fusion TBx was done. of the entire prostate gland. It has been shown to A pre-biopsy MRI is used to localize the target and the improve the detection of significant prostate cancer TRUS-operator uses this knowledge to aim the biopsy (sPCa)1-3 with a more accurate Gleason score (GS) needle at this prostatic area/zone. The main grading. advantage is that cognitive TBxs are performed without any additional hardware or software.

Lesions identified on mpMRI can be stratified by However, it requires experience and training since the suspicion and targeted by selective MRI-guided operator has to visually match suspicious lesions on biopsies (TBx) for improved diagnostic accuracy3. With the MRI to the corresponding real-time 2D TRUS this ability to identify highly suspicious areas at image, and translate it all into a 3D representation of mpMRI, TBxs are increasingly accompanying or the prostate based on zonal anatomy and tissue replacing multiple random TRUSbx cores (Figure 1). landmarks. Cognitive TBx has been shown to be superior to standard TRUS8, but presents potential human errors in the extrapolation of targets from MRI Figure 1: The poor prostate cancer target identification to TRUS without an image-overlay. Furthermore, cognitive TBx does not enable allocation of biopsies of transrectal ultrasoundguided biopsy (TRUSbx) cores for re-evaluation. (blue cores) often leads to missed significant cancers and/or risk of missing the most aggressive part (dark area) leading to possible Gleason score undergrading. In addition, the limited length of the TRUSbx cores leads to inadequate sampling of the anterior part.

Targeted biopsies (red cores) can be guided by MRI for improved diagnostic accuracy.

MpMRI Clinical guidelines include a structured uniform Prostate Imaging Reporting and Data System (PIRADS)2,4 to standardize and promulgate uniform high-quality mpMRI acquisition, interpretation and reporting with accurate communication among all involved physicians. Although the mpMRI protocol may be optimized for different clinical scenarios, guidelines overall recommend the use of T2 weighted imaging (T2W), diffusion weighed imaging (DWI) with its corresponding ADC (apparent diffusion coefficient) map and dynamic contrast enhanced (DCE) imaging for optimal PCa detection and characterization.

In practice, all suspicious lesions are registered on a regional prostate diagram and scored using the PIRADS v2 classification4 from 1-5 according to their probability of being sPCa (1- very low, 2- low, 3– intermediate, 4- high and 5– very high).

MRI/TRUS fusion TBx Multiple approaches exists for TBx of mpMRI suspicious lesions5. Direct in-bore TBx within the MRI suite can accurately sample lesions of interest with direct confirmation, but at considerable costs and limited availability. Fusing mpMRI data with TRUS (MRI/TRUS fusion) combines the superior imaging of mpMRI coupled with the easier-to-use ultrasound guidance, which allows skilled operators to perform TBx in an outpatient clinic saving time and costs, while preserving adequate targeting accuracy6.

Furthermore, TBx can be combined with systematic biopsies, as still recommended in the EAU guideline7.

Fusion TBx can be done either “cognitively” (use your brain) or assisted by software that has been developed

Software-based TBx: MRI/TRUS image-fusion software platforms have been developed to increase targeting accuracy and a number of features are common to all. First, pre-biopsy MRI data is obtained, the prostate is segmented and the lesions are identified. Second, the MRI data is exported into the TRUS fusion platform before the biopsy session. During the biopsy session, real-time TRUS images are obtained to which the segmented MRI data is electronically fused for biopsy guidance. The MRI data is then translated into “live”-images that move correspondingly in the same way the TRUS probe/image moves.

Several platforms have the ability to track and record biopsy sites during the procedure. This allows the operator to return to prior biopsy sites for either re-sampling in men under active surveillance or identify prior biopsied areas in men with prior negative biopsies undergoing re-biopsy. However, all image-fusion platforms encompass some degree of mis-registration and there will be a margin of error despite careful efforts to align the MRI and TRUS images. The different methods of fusing images affect the accuracy of TBx. A main difference is that MRI and TRUS images are fused either “rigidly” or “nonrigidly/elastic”.

In rigid fusion, the MRI and TRUS images are overlaid without real-time adjustment for patient movement or prostate deformation during the biopsy procedure. A non-rigid fusion system, however, tries to compensate for this by fusing organ volumes and use 3D contouring with elastic deformation algorithms.

However, a recent meta-analysis by Venderink et al.9 did not identify any difference in PCa detection rates between the two fusion methods.

Another difference between MRI/TRUS fusion platforms is the way the images are tracked.

Electromagnetic tracking is a popular method that uses a small electromagnetic emitter and receiver that tracks the spatial location of the TRUS probe. This technique is rather fast and allows for great freedom of motion, but may suffer from electromagnetic interference and only tracks the TRUS probe and not

the prostate itself. Thus, mis-registration between the prostate contour and internal landmarks/targets may occur. To improve the registration and rigid overlay, some platforms have incorporated software sensors into either a robotic arm10 or the needle guide11 and included a 3D reference volume for segmentation and contouring. Still, real-time adjustment for patient movement or prostate deformation during the biopsy procedure is a challenge.

Organ-based image registration is a non-rigid platform that tracks the organ (prostate) itself12.

References It requires a specialized 3D TRUS probe that the 1. Ahmed HU, El-Shater Boaily A, Brown LC, et al. operator uses repeatedly, and at any time during the Diagnostic accuracy of multi-parametric MRI and TRUS procedure, to create a 3D-scan of the prostate that is biopsy in prostate cancer (PROMIS): a paired validating automatically registered and fused with the confirmatory study. Lancet (London, England). segmented MRI data to create a final overlay of 2017;389(10071):815-822. doi:10.1016/S0140matching TRUS and MRI volumes. MRI targets are then 6736(16)32401-1. overlaid on TRUS for TBx. This method is developed to 2. Barentsz JO, Richenberg J, Clements R, et al. ESUR try to account for patient movement and deformation prostate MR guidelines 2012. Eur Radiol. 2012;22(4):746during the procedure.

757. doi:10.1007/s00330-011-2377-y.

Limits and future perspectives It is important to recognise that not all cancers are visible on MRI and lesions may be misinterpreted.

Furthermore, there is a fairly consistent rate of sPCa that is detected by standard TRUSbx and missed by TBx13. Each step of the process from MRI acquisition, interpretation and reporting to segmentation, image-fusion technique and the biopsy approach itself presents its own risks of error. MpMRIs may be misinterpretated, TBx may miss PCa lesions due to targeting errors and unnecessary TBx may be conducted due to false-positive mpMRI readings.

Furthermore, it is difficult to confirm real-time accurate biopsy-deployment within the target.

Sampling errors may be reduced by spacing biopsies and obtain more targeting cores per lesion. However, if an unexpected biopsy result occur, it is important to re-evaluate each step of the procedure to identify any potential risks of error.

There is no doubt that the MRI/TRUS fusion platforms will continue to evolve and further improve the diagnosis of PCa. Future development in image fusion platforms with automatic segmentation and deformable co-registration with real-time motion correction combined with improvements in the biopsy procedure (e.g. improved US resolution and biopsy allocation) may further improve targeting accuracy.

However, the best strategy has yet to be proven.

Furthermore, improvements may also include the use of additional US techniques beyond grey scale (e.g. contrast or elastography) for MRI/TRUS image-fusion.

In addition, an area that goes beyond the biopsy technique, is the future possibility of replacing the biopsy-needle with a catheter for focal treatment. As MRI/TRUS image-fusion platforms improve, it may allow for focal treatments outside the MRI/operating suite in the future.

There is an ongoing debate whether or not systematic biopsies should accompany TBx, especially in a re-biopsy setting. However, due to the abovementioned limitations significant cancers may remain undetected in a “targeted-only” approach.

Moreover, the cost-effectiveness of a diagnostic mpMRI, the additional use of TBx including purchase of expensive MRI/TRUS image-fusion platforms and the long-term outcomes have not been fully explored.

Despite limitations, an image-based mpMRI-strategy seems to improve patient quality of life by reducing over-diagnosis and over-treatment at comparable costs as the currents standard TRUSbx approach14.

Table 1: MRI/TRUS fusion platforms presented at the Thematic Session 08 “Overview of fusion biopsy devices” (with reservations to non-complete descriptions) Trade name MIM-Symphony / bkFusion Biojet

TRUS image Semi-automatic contouring

BioBot

Manual sweep with fixed probe Real-time manual TRUS, no sweep/prostate contouring Automatic sweep

Urostation

3D automatic sweep

Artemis

Manual sweep with fixed axis

UroNav

Manual freehand sweep

Ascendus / HI-RVS

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Tracking Electromagnetic tracking with external generator Mechanical arm with encoders; fixed probe stepper Electromagnetic tracking with external generator Robotic mechanical arm, organbased 3D fusion biopsy planning Organ-based real time fusion, 3D navigation Mechanical arm with probe and encoders, 3D navigation Electromagnetic tracking with external generator, 3D navigation

Added advantage MRI/TRUS fusion allows skilled urologists to perform targeted biopsies in an outpatient clinic and gives the operator the advantage of adding TBx to the systematic standard biopsy scheme, which is still the recommended standard approach. There is no clear advantage of one MRI/TRUS fusion platform compared to others15. Costs, local preferences and usability should be guiding the choice of which fusion platform to use.

biopsy route Transrectal / transperineal Transrectal / transperineal Transrectal / transperineal

Comments Predictive fusion, free hand transrectal manipulation Rigid registration, manual contouring

Transrectal

Rigid registration, alignment using anatomical landmarks Elastic registration, manual contouring, Automatic needle positioning Elastic registration, virtual targeting

Transrectal

Stabilized probe

Transrectal / transperineal

Free hand transrectal manipulation

Transperineal

3. Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MGM. Magnetic Resonance Imaging–targeted Biopsy May Enhance the Diagnostic Accuracy of Significant Prostate Cancer Detection Compared to Standard Transrectal Ultrasound-guided Biopsy: A Systematic Review and Meta-analysis. Eur Urol. 2015;68(3):438-450. doi:10.1016/j.eururo.2014.11.037.

4. Weinreb JC, Barentsz JO, Choyke PL, et al. PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol. 2016;69(1):16-40. doi:10.1016/j. eururo.2015.08.052.

5. F F Wegelin DI, van Melick HH, Hooft L, et al. Comparing Three Different Techniques for Magnetic Resonance Imaging-targeted Prostate Biopsies: A Systematic Review of In-bore versus Magnetic Resonance Imagingtransrectal Ultrasound fusion versus Cognitive Registration. Is There a Preferred Technique? Platin Prior – Rev – Prostate Cancer Editor by Matthew R. 5(2):1-7. doi:10.1016/j.eururo.2016.07.041.

6. Valerio M, Donaldson I, Emberton M, et al. Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review. Eur Urol. 2015;68(1):8-19. doi:10.1016/j.eururo.2014.10.026.

7. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017;71(4):618-629. doi:10.1016/j.eururo.2016.08.003.

8. Moore CM, Robertson NL, Arsanious N, et al. Imageguided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol.

2013;63(1):125-140. doi:10.1016/j.eururo.2012.06.004.

9. Venderink W, de Rooij M, Sedelaar J. M, Huisman HJ, Fütterer JJ. Elastic Versus Rigid Image Registration in Magnetic Resonance Imaging–transrectal Ultrasound Fusion Prostate Biopsy: A Systematic Review and Meta-analysis. Eur Urol Focus. July 2016. doi:10.1016/j. euf.2016.07.003.

10. Bax J, Cool D, Gardi L, et al. Mechanically assisted 3D ultrasound guided prostate biopsy system. Med Phys.

2008;35(12):5397-5410. doi:10.1118/1.3002415.

11. Singh AK, Kruecker J, Xu S, et al. Initial clinical experience with real-time transrectal ultrasonographymagnetic resonance imaging fusion-guided prostate biopsy. BJU Int. 2008;101(7):841-845. doi:10.1111/j.1464-410X.2007.07348.x.

12. Mozer P, Baumann M, Chevreau G, et al. Mapping of transrectal ultrasonographic prostate biopsies: quality control and learning curve assessment by image processing. Ultrasound. 2009;28(4):455-460. http://arxiv. org/abs/0903.5201.

13. Moldovan PC, Van den Broeck T, Sylvester R, et al. What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Metaanalysis from the European Association of Urology Prostate Cancer Guidelines Panel. Eur Urol.

2017;72(2):250-266. doi:10.1016/j.eururo.2017.02.026.

14. de Rooij M, Crienen S, Witjes JA, Barentsz JO, Rovers MM, Grutters JPC. Cost-effectiveness of Magnetic Resonance (MR) Imaging and MR-guided Targeted Biopsy Versus Systematic Transrectal Ultrasound-Guided Biopsy in Diagnosing Prostate Cancer: A Modelling Study from a Health Care Perspective. Eur Urol. 2013;66:430436. doi:10.1016/j.eururo.2013.12.012.

15. Gayet M, Van Der Aa A, Beerlage HP, Schrier BP, Mulders PFA, Wijkstra H. The value of magnetic resonance imaging and ultrasonography (MRI/ US)-fusion biopsy platforms in prostate cancer detection: A systematic review. BJU Int. 2016;117(3):392400. doi:10.1111/bju.13247.

Sunday 18 March 10.30-12.00: Thematic Session 8; Overview of fusion biopsy devices

Sunday, 18 March 2018

Long-term outcomes in male genital reconstruction Evidence lack in long-term genital reconstruction results still a challenge Prof. Dr. Piet Hoebeke Paediatric Urology Ghent University Hospital Gent (BE)

External genital reconstruction in paediatric urology is challenging. Hypospadias, epispadias with or without bladder exstrophy (Bladder Exstrophy Epispadias Complex BEEC) and disorders of sex development (DSD) are among the most difficult problems encountered by paediatric urologists that require a lot of experience and are best treated by a multidisciplinary approach1.

In this group of patients management is complex and there is much disparity in the surgical correction techniques. More than 300 different techniques with a wide variety of modifications have been introduced for the treatment of these anomalies1,2.

Concerning the tremendous effect of the genitourinary reconstruction on adult life, the evaluation of the long-term results of different techniques in genitoplasty in paediatric are of the utmost importance. The complications of these reconstructive techniques can take decades before becoming evident3,4. The pubertal growth can alter the final functional and cosmetic aspects of the corrected genitalia. Moreover, the psychosexual development is only completed after the puberty, so the psychological and sexual function of patients who have undergone genital reconstruction can only be evaluated after puberty1,5-7.

A summary of the available studies is given in Table 1.

For mild hypospadias cosmesis and quality of life score good, lower urinary tract function and psychosexual outcome score neutral. For more severe hypospadias results on lower urinary tract function, psychosexual functioning and quality of life score neutral while the outcomes on cosmesis score bad which is also related to penile length which in this group of patients scores lower than median. For both categories the quality of research done on long-term outcomes score bad.

BEEC From the selected studies only few are on long-term and report on psychosexual outcome. In general “dryness” can be achieved, however, at the price of intermittent catheterisation through a continent stoma in more than half of the patients. In general, sexual function is impaired mainly due to the penile length.

BEEC impacts self-esteem, sexuality, body image and relationships in up to 50% of men. Half of the patients miss experience of sexual intercourse either due to technical incapability or secondary to psychosexual problems. A summary of the available studies is given in Table 2.

Table 2: Overview of Outcomes in BEEC

Table 3: Overview of Outcomes in DSD

Lower urinary tract function and quality of life score neutral while cosmetic outcome and psychosexual outcome score bad. There is only exceptional qualitative research on outcome, so this scores bad.

DSD Very scarce studies have reported the long-term outcomes of genital reconstruction in DSD patients, but what can be noted in these studies is the low rate of satisfaction with their sexual function in adulthood.

The most frequent complaints among these patients is the short penile length in comparison with unaffected people. Fertility issues add negatively to this low satisfaction. A summary of the available studies is Considering the fact that as the patients grow up the given in Table 3. Lower urinary tract function and cosmetic aspect becomes equally if not more quality of life score neutral while cosmetic outcome important than function, more attention should be and psychosexual outcome score bad. There is no paid to the aesthetic results in the long-term8,9. Genital qualitative research on long-term outcome, so this and reproductive functions have a great effect on the scores bad. quality of life in adult patients with penile anomalies in childhood7. However, most published studies have Long-term studies needed reported only short-term results in pre-pubertal Regarding the presented data in this review patients with very few studies on the long-term results presentation, further controlled long-term studies are focusing on the cosmetic and psychosexual outcomes needed to select best techniques for these groups of of these surgeries in adulthood. patients and to provide better consultation of parents for the future of their children before advising any This article presents the available long-term surgeries. outcomes of genitoplasty in childhood specifically focusing on the cosmesis, psychosocial and More attention should be paid to the impact of functional results. These data are based on a first reconstructive techniques on psychosexual review published in 2013 to which recent relevant development and cosmetic aspect after puberty, as studies are added. There is paucity of data on these factors play a crucial role in later quality of long-term effect of different genital reconstruction life in these subgroups of patients. Most studies techniques during childhood due to lack of validated that have been reviewed for this presentation do measurement tools and validated questionnaires not report the mean number of follow-up years and high loss of patients during follow up. Very few after the reconstructive surgery and instead report studies have investigated the different outcomes of the mean age at the follow-up as an indication of these surgeries in long- term especially after puberty the post-pubertal and long-term evaluation. This and adulthood10. can be noted as a major critique to these studies and future studies need to pay attention to the Hypospadias present defect. One point should be emphasized The selected studies suggest that patients who that surgeons should describe the pre-operative underwent hypospadias surgery are less satisfied findings in more detail and also be more with their urinary function compared with controls structured while evaluating the post-operative and they usually experience spraying, post-void results in follow up visits. dribbling and urinary stream deviation that are more prominent in patients with a history of severe and Without long-term follow-up evaluation of genital proximal hypospadias. Dissatisfaction about the reconstructions in childhood with precise description sexual function and appearance of penis is more of pre and post-operative data, no technique can be prevalent in those patients than in controls in considered as the gold-standard in the management adulthood. of patients with penile anomalies during infancy.

Finally, the fact that there is no long-term evidence on outcome of genital reconstruction in childhood, is one of the factors adding to the increasing resistance against genital normalizing surgery in childhood as advocated by Human Rights Watch and by the council of Europe. [Ref: http://assembly.coe.int/nw/xml/XRef/ Xref-XML2HTML-en.asp?fileid=24232&lang=en]

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Sunday 18 March 10.30-12.00: Thematic Session 9, Pediatric Urology Update

Patient Information

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Table 1: Overview of outcomes in mild and severe hypospadias

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Animated series: • Cystectomy • Cystoscopy • Double J-stent placement • How to change your stoma bag • PNL

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Managing complications during laparoscopy Tips and tricks to prevent complications during laparoscopic surgery Dr. Skolarikos Andreas Associate Professor of Urology National and Kapodistrian University of Athens Athens (GR)

Laparoscopic surgery was introduced in urology in the early 1990s. It took almost a decade for urologists to be convinced and change their everyday practice from open surgery to laparoscopic approach.

The main reasons for this delay included “resistance” to innovation, lack of certified training centers capable of releasing the “first” highly trained generation of urologic laparoscopists who, in turn, would be responsible for the training of the younger trainees, steep surgical learning curve, the advent of “new” complications and the rising difficulty for a “mainly” open surgeon to deal with them.

“Modern era” of pure laparoscopy very quickly faced the advent of the robotic consoles that combined the already achieved laparoscopic experience with the 3D vision and the benefits of the seven-degrees’ “surgical” freedom that made reconstruction easier even for the novice laparoscopic surgeon.

Despite the aforementioned difficulties “pure laparoscopy” clinical and training programs still run all over the world and so surgeons are inevitably confronted with complications. The best way to deal with complications is to prevent them from occurring.

However, when they occur it is crucial to recognize them early, ideally intraoperative, and repair them immediately.

Reducing complication rates Proper training during residency and a dedicated postgraduate fellowship are of paramount importance to reduce complication rate. Even after proper training, mentoring during the first cases is also very important. In addition, the surgeon should be responsible in creating a dedicated operating team including the anesthesiologist and specially-trained nursing staff. Furthermore, the surgeon should be responsible for the proper operating room set up which again is crucial for the success of the operation.

Table 1: Check list prior to a laparoscopic operation The Laparoscopic Urologist Should: • Thoroughly inform and give ample time to the patient and family; • Provide details regarding the nature of the disease, the procedure, the laparoscopic approach, the existing alternatives, the risks and the likelihood of conversion; • Give reassurance that the patient safety comes first; • Feel confident with the selected approach; • “Know” the patient and the surgical problem; • Think in advance about the possibility of a complication related to the procedure; and • Ask himself whether he knows how to handle a complication should it occurs.

As in every type of surgery, the laparoscopic urologist needs to follow a checklist before starting an operation (Table 1). Starting the operation by checking the operating room set-up, the instrument’s availability and performance is mandatory. Proper patient positioning is crucial. Provide adequate padding and avoid extreme bending and/or stretching while fixing the patient over the operating table.

Selecting and preparing in advance the appropriate suture is also wise (Figure 1). Cut the suture to a length of a trocar is a simple rule that fits the majority of the reconstructive necessities.

Figure 1

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To avoid anesthetic complications, keep intraabdominal pressures below 15 mmHg, avoid the creation of subcutaneous emphysema and reduce the operation time. Very rarely, a carbon dioxide gas embolism occurs. The surgeon and the anesthetist should think about it when there is a decrease in end-tidal CO2 and end-tidal O2 along with a decrease in patient’s blood pressure intra-operatively. The surgeon should try to avoid this complication by reducing the intra-abdominal pressure and the operating time. Immediate desufflation is mandatory.

Place the patient in Durant’s position and ask the anesthetist to make the appropriate ventilator adjustments. Aspiration of CO2 through the superior vena cava may be needed in severe cases.

Access to the peritoneal cavity or to the retroperitoneal space can be performed either by the Veress needle or the Hasson technique. Vascular and bowel injuries have been reported during access.

Several factors may predispose to access related complications (Table 2). To prevent access-related complications avoid areas with previous scars, lift the abdomen (peritoneum) prior to Veress needle insertion, use the open technique to get access, use non-bladed trocars with endoscopic guided ports (Visiport), insert trocars without tension and under direct vision, and always inspect abdomen after Veress needle and trocars are positioned.

Table 2: Factor predisposing to access-related complications Patient parameters • Obesity • Previous Surgery Surgeon Experience Port design • Port size • Blunt/cutting/radially expanding edges

Avoid inserting trocars in the pararectus line (7-10cm lateral from the midline) to prevent an inferior epigastric artery injury (Figure 2). If the artery is torn leave the trocar in place and treat immediately.

Hemorrhage can be easily tamponaded with the cannula. If necessary, a Foley catheter can be passed through the port site and drawn back to tamponade the vessel. For more significant bleeding, a figureeight stitch with a 2/0 Vicryl 4-inces long suture, on a CT-1 needle should be placed above and below the trocar. To save time and ease the procedure you can use Weck or Lapra-Ty clips to lock your suture line instead of making knots. Remove the port to ensure hemostasis has been achieved. The port can be replaced through the same site.

Figure 3 Figure 7: Iliac vein Injury

Figure 4: Apply pressure to aorta to control a small leak.

Figure 8

Rarely, major vascular injury will occur. Whenever pulsatile blood is coming out from Veress needle, do not twist or further manipulate the needle because you will turn a puncture to a laceration. Laparotomy is required to identify and correct the problem. If the bleeding is minimal after compression you can leave it and proceed with the procedure (Figures 3,4).

Otherwise, use thermal (bipolar, ultrasonic, argon beam) or non-thermal (intracorporeal suturing and bolsters) measures to control bleeding (Figures 5,6).

In the case of uncontrollable bleeding from Santorini’s plexus during radical prostatectomy apply pressure to the veins by grasping the catheter and applying tension toward the pubic symphysis for five to 10 minutes to tamponade bleeding.

Figure 5: Intracorporeal suturing to control bleeding

Figure 2 Figure 6: Use of bolsters to control bleeding

Vascular injury Major vascular injury can happen in 1-3% of the cases during laparoscopic urologic surgery with 0.5-3% uncontrollable bleeding. Prevention and high level of vigilance is paramount. To avoid major vascular injury get familiar with the anatomy and anticipate the structures while dissecting the tissues, ensure proper entry to the abdominal cavity, respect the anatomy, mobilize and retract the tissues thoroughly and do not work through “holes”. Moreover, think about physiology. When you dissect the renal hilum and you have clipped the renal artery, check whether the renal vein looks “empty” or not. If not, this means that you have to search for another artery to ligate. Working on a difficult hilum, instead of “digging” around the renal vein to identify the renal artery, you can ligate “everything” behind the vein first or en block ligate the renal hilum with an endo-GIA stapler. When you choose the later approach make sure that you mobilize the hilum properly at its lower and upper parts before ligating it.

When a major vein injury occurs you have to decide on whether ligation or division of the vein is needed (Figure 7). Small vena cava lacerations stop with adequate pressure in 80-90% of the cases.

Free-hand suturing, small serial titanic clips or Weck/ Lapra-Ty clips on a 3/0 prolene suture can be used when bleeding does not stop. Suture a lumbar vessel with a 2/0 Vicryl stich on a CT-1 needle and a renal vein with a 5/0 prolene figure-eight suture. While ligating the dorsal venous complex, during radical prostatectomy, the use of a metallic (Benique) urethral probe may allow for better visualization of the precise site of the stitch and help with the orientation during needle passage.

Major arterial bleeding may require vascular surgeon consultation. The urologist should be familiar with basic vascular surgery principles (Figure 8).

As a rule of thumb if the patient needs transfusion (more than two units) by the time you would be able to repair the vessel injury, open conversion and a vascular surgeon consultation may be needed.

Vascular stapler malfunction can occur in 0.3-0.2% of laparoscopic cases. Prevent an abnormal jaw closure by avoiding deploying the device before use. Faulty deployment may be secondary to interfering clips and/or tissue. Treat by opening and replacing the device. Suspect misfire when you have a difficulty to activate the stapler and replace it. Do not force the device because the cartilage may empty and the device won’t fire. Do not override the lockout mechanism of the stapler as this will end with transection without ligation. On both aforementioned situations, the stapler should be replaced. When bleeding occurs while functioning the stapler, apply pressure, improve tissue and vessel exposure and apply a clip, suture or another stapler proximal to the previous one to seal the vessel. Laparotomy may also be required.

Bowel injury Overall, bowel injury is rare during urologic laparoscopy (Figure 9). However, more than two thirds are not recognized at the time of surgery.

One-third are secondary to Veress needle insertion and 50% of inappropriate electro cautery use. Fasting for several hours prior to surgery and the insertion of an oro- or nasogastric tube can minimize the risk of gastric or small bowel injury during access. The operating team and the staff surgeon should check the insulation of the monopolar and bipolar instruments before the procedure. Avoid bowel injury by applying smooth retraction away from the bowel and by using low dissipation thermal energy. Refract from grasping the bowel or using monopolar electro cautery in close proximity. Avoid rectal injuries by proper dissection and incision of the Denonvillier’s fascia.

To expose the Denonvillier’s fascia properly, retract the seminal vesicles and vas deference anteriorly and the sigmoid colon posteriorly and cephalad maximally. Make a small horizontal incision into the fascia 2-3mm directly posterior to the junction of the seminal vesicles. Recognize the right plane by visualization of the yellow perirectal fat. While exiting the abdomen the site of the trocars should be investigated for herniated structures or omentum.

Finally, while exiting the abdomen, close all the defects in children and those more than 10mm in adults. When non-bladed dilating trocars are used the actual defect on the fascia can be half the size of the trocar and be left unclosed.

Think about bowel injury when foul smelling gas (Veress/trocar) or greenish fluid emerges in the operating field. Suture the lesion in a double layer (Figure 10) and try to avoid colostomy even with rectal injuries. If you recognize the injury postoperatively a laparotomy will most likely be needed.

Continued on page 9

Sunday, 18 March 2018

Multiparametric MRI and MRI/TRUS fusion in PCa A subset of patients could benefit from pre-biopsy mpMRI to avoid unnecessary biopsies Dr. Alexander Peltier Dept. of Urology, Institut Jules Bordet Brussels (BE)

Dr. Fouad Aoun Dept. of Urology, Hotel Dieu de France Beyrouth (LB)

The last decade was marked by a widespread use of PSA-based prostate cancer detection and an exponential rise in the number of prostate biopsies, in terms of patients, biopsies per patient and cores per biopsies.

However, some of these biopsies were unnecessarily performed while others have missed significant prostate cancers. In addition, more men with low-risk prostate cancer had been diagnosed and some were also unnecessarily treated. The limited specificity of PSA and the low detection rate of prostate cancer on 2D TRUS-guided biopsy generated much of the controversy existing about early prostate cancer detection in clinical practice.

One of these promising strategies is multiparametric MRI (mpMRI) and an MRI guided or MRI/TRUS fusion biopsy. We had the privilege in our institution to implement such a technology in our routine practice.

Thus, we offered, since 2012, mpMRI for every patient presenting with a clinical suspicion of prostate cancer, and in the case of a suspected lesion, an MRI/TRUS fusion targeted biopsy using the Koelis system followed.

At the beginning of our experience, enthusiasm for such an approach was high, and we elected our approach to be the new gold standard for every patient presenting with a clinical suspicion of prostate cancer in part because of the following: First, we have noticed that mpMRI/TRUS fusion biopsy results in a better distribution of sampling with respect to patient prostate anatomy1. This allows biopsy cores to be distributed homogeneously and symmetrically in the 3D space of the prostate.

“...in our study, MRI/TRUS fusion biopsy protocol improved prostate cancer detection rate compared to 2D TRUS guided protocol and demonstrated higher detection rate of clinically significant disease...”

This better sampling is due to “organ tracking” -that is the visualization of the metallic biopsy needle indwelling in the real volume of the prostate and monitoring of each biopsy core as a reality- and not as a fictive representation of a cognitively, operatordependent, mental distribution under the 2D TRUS plane. This better sampling allowed, by itself, in our Furthermore, the poor sampling of cancers under 2D TRUS and the underestimation of Gleason score widely practice better detection rate of clinically significant opened the door for the development of more accurate prostate cancer compared to 2D TRUS guided biopsy in the primary setting. strategies for the diagnosis of prostate cancer.

Managing complications during laparoscopy...

Continued from page 8

Avoid injury of the liver or spleen by careful insertion of the initial trocar and by careful retraction and mobilization of these two organs. Compression alone can be enough to manage minor injuries of the liver and spleen. Whenever laceration emerges apply electro cautery or argon beam diathermy (120-150 Watts) and/or hemostatic and observe for 10-15 minutes. Reduce the intraabdominal pressure at the same time. In case of more severe bleeding you can suture the liver parenchyma or convert to handassisted laparoscopy to proceed with partial or radical splenectomy. General surgery consult may be required.

Diaphragmatic injuries are also rare. They may occur at initial trocar placement, when a large upper pole renal/adrenal tumor abutting the diaphragm is treated, or when dissecting renal hilum, as the crura may stop there. Think about this type of injury when you observe paradoxical movements of the diaphragm. If the patient is stable from the ventilation standpoint, defer repairing intraoperative pneumothorax until the end of the primary laparoscopic procedure. A small/moderate rent can be repaired by a 2/0 Vicryl figure-eight stitch on a CT-1 needle. Larger defects tailor the position of a Dacron graft.

Prior to tightening the final stitch insert a 12-14Fr red rubber catheter through the abdomen and the rent to the pleural space. Place the external extracorporeal tip under water to create a water seal. Reduce the pneumoperitoneum to 5mmHg and ask the

Figure 9: Bowel Injury

Sunday, 18 March 2018

anesthetist to give 10-15 large insufflations through the ventilator. Concomitantly, tie the stitch down and pull the catheter. When the pneumothorax is realized postoperatively, it occupies <30% of the pleural cavity and the patient is stable, the CO2 will be absorbed spontaneously without requiring any treatment. When the pneumothorax is >30% or the patient is unstable a chest tube is necessary.

Anticipating complications Most of the complications can be anticipated and potentially avoided. As in every surgery the following general principles to prevent complications also apply to laparoscopic surgery: • Check the anatomy • Provide optimal exposure (i.e. an additional trocar) • Use a wide dissection rather than a deep one • Provide good visualization Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Saturday 17 March 10.15-15.00:Joint meeting of the EAU Section of Oncological Urology (ESOU), the EAU Robotic Urology Section (ERUS), the EAU Section of Uro-Technology (ESUT) and with the ESSO, ESTRO, EUOG, EORTC GUCG and SUO; Complications in treatment of urological cancers

Figure 10: Bowel Injury suturing

Precise registration of biopsy site

Second, histologic information gained from 3D biopsies showed longer cancer core length than standard 2D TRUS biopsies. This results from the intention to oversample different areas of the prostate rather than to cluster all biopsies to posterolateral peripheral zones.

Risk stratification systems used nowadays are based on the number of positive cores or the proportion of a core involved with cancer, then a man with disease classified as low-risk on standard biopsy may have that same disease classified as intermediate- or higher-risk disease on a 3D biopsy.

Third, MRI/TRUS fusion biopsy had yielded in our series an overall cancer detection rate of 62.7%, that is higher than most of the studies reporting on standard biopsy2.

In addition, in our study, MRI/TRUS fusion biopsy protocol improved prostate cancer detection rate compared to 2D TRUS guided protocol and demonstrated higher detection rate of clinically significant disease with fewer tissue samples removed from lesions. The yield of targeted biopsies was significantly higher than standard biopsies with a ratio of 28.9% of cancer on targeted cores compared to 9.8% of cancer on standard cores.

Our data are even more encouraging when comparing clinically significant prostate cancer detection rate between the two protocols; 20 patients with clinically significant disease on targeted cores had either no cancer or clinically insignificant disease on standard cores, and 11 patients with no cancer on targeted protocol had clinically insignificant disease on standard cores.

In contrast, one patient with clinically significant disease on standard protocol had a negative biopsy from a low suspicious lesion on the targeted protocol, and five patients with no cancer on standard protocol had a clinically insignificant cancer on targeted protocol. Therefore, MRI followed by MRI-targeted biopsy had resulted in fewer but better biopsies in our center.

Additionally some of the suspected region of interest is very difficult to sample even with the most sophisticated technology that we have especially when the region of interest is small in an enlarged prostate or in a difficult location. The heterogeneity of the index lesion and the number of cores to be taken per index lesion remains to be elucidated.

Prostate whole mounted histology demonstrate clearly that prostate cancer is not a round structure such as demonstrated by radiological contouring and that mpMRI tends to underestimate prostate cancer volume.

Furthermore, it is non-negligible to have several index lesion with the smallest harboring the most aggressive disease. It is noteworthy to mention that the majority of published data have come from excellence center with extensive experience with mpMRI. These results may not be reproducible in less experienced centers. The availability of mpMRI is also another limitation.

The issue of costs and health care value should definitely be considered. Despite the standardization of the characterization of the index lesion in the PIRADS score, inter-observer variability is not uncommon in clinical practice. Furthermore, the long-term impact of such an approach is not well determined.

In 2018, we think that it is too early to make recommendation on the routine use of pre-biopsy mpMRI in biopsy-naïve patients. However, we do live in an era of evidence-based medicine where personalized approach is gaining popularity. That’s why a subset of patient could benefit from pre-biopsy mpMRI.

The aim of such an approach is to avoid unnecessary biopsies in some patients and to improve the detection yield of clinically-significant disease in others. Patients with enlarged prostate, prior negative biopsy or a low clinical suspicion of prostate cancer are good candidates for a pre-biopsy mpMRI. Patients suitable for active surveillance could also benefit from Fourth, in patients with an enlarged prostate (> 50 mL mpMRI. in our study), we demonstrated higher detection rate for clinically significant prostate cancer when using Patients with anterior lesion or small index lesion the MRI targeted approach compared to standard on mpMRI as well as patients with clinically biopsy3. indolent disease or prior negative biopsy should be preferably sampled by an MRI- targeted Patients with an anterior lesion on mpMRI could approach. also be better sampled using such an approach.

Meanwhile, the PROMIS trial had clearly References demonstrated that 25% of patients could be spared 1. Peltier A et al. 3D versus 2D Systematic Transrectal unnecessary biopsies and their complications if Ultrasound-Guided Prostate Biopsy: Higher Cancer Detection Rate in Clinical Practice. Prostate Cancer. mpMRI is ordered in the pre-biopsy setting4.

“Prostate whole mounted histology demonstrate clearly that prostate cancer is not a round structure such as demonstrated by radiological contouring and that mpMRI tends to underestimate prostate cancer volume.”

Limitations As our experience with mpMRI and MRI/TRUS fusion biopsy matures, we noticed several limitations. Several significant cancers detected by systematic sampling were sometimes missed by mpMRI in our center. Are these truly MRI invisible tumor or misreading?

2013;2013:783243.

2. Peltier A et al. MRI-targeted biopsies versus systematic transrectal ultrasound guided biopsies for the diagnosis of localized prostate cancer in biopsy naïve men. Biomed Res Int. 2015;2015:571708.

3. Peltier A et al. Results of a comparative analysis of magnetic resonance imaging-targeted versus three-dimensional transrectal ultrasound prostate biopsies: Size does matter. Scand J Urol. 2016 Jun;50(3):144-8.

4. Ahmed HU et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822.

Sunday 18 March 10.30-12.00: Thematic Session 8, Overview of fusion biopsy devices

EUT Congress News

9

EAU Guidelines harnesses potential of social media Prostate and bladder cancers: Most popular 2017 Guidelines tweets

By EAU Guidelines Office Dissemination Committee

https://t.co/x4dqFXfxUx https://t.co/GyyeuhFVoP - 9,663 impressions.

The European Association of Urology (EAU) was the 2. Bladder instillation of chemo is strongly advocated few days after nephroureterectomy to first scientific association to systematically convert decrease subsequent recurrence #UTUC their clinical guidelines into social media posts for dissemination through Twitter. #eauguidelines - 8,942 impressions.

3. Testosterone therapy suppresses spermatogenesis and should not be used for The goals of this project, led by the Guidelines Office Dissemination Committee, were to increase the treatment of male infertility #eauguidelines - 5483 impressions. dissemination of the guidelines, and to test adherence to guidelines recommendations through a series of Twitter-based polls.

Spanish language 1. #uroUTI Fosfomicina (3g dosis única) 1era elección tto de ITU aguda no complicada In the past nine months (April 2017 – December 2017) http://bit.ly/1eBK3vj #eauguidelines - 5,024 a total of 93 unique English language and 65 unique impressions.

Spanish language tweets have been sent by the EAU describing the key points of the EAU guidelines. The 2. #priapismo isquémico es una emergencia most popular tweets in terms of social media médica. Tratamiento inmediato previene la #erectiledysfunction #eauguidelines - 4,816 distribution were: impressions.

3. Incidencia de #litiasis está incrementando y los English language niños también merecen evaluación metabólica.

1. What are the key steps of conducting #systematic #reviews? Methodology of #eauguidelines #eauguidelines #pediatria - 3,992 impressions

Figure 2: 2017 Summary statistics showing engagement of Guidelines tweets

Figure 3: Sample of an EAU Guidelines poll tweet

The #EAUGuidelines hashtag was ultimately used by 1,521 other Twitter users in addition to the EAU’s own guidelines tweets. There were a total of 5,667 tweets using the #eauguidelines hashtag, with an average of 12 tweets per participant and a total reach of 11,225,000 impressions.

participants represent a highly selected population with potential biases who may not be representative of the urologic community as a whole. Nonetheless, this feedback was freely and rapidly obtained and has allowed the Guidelines panel to prioritise key areas to address in future educational initiatives.

The highly structured programme of social media engagement undertaken by the EAU Guidelines Offices demonstrates the effectiveness of Twitter as a platform for the dissemination and real-time evaluation of clinical guidelines. Although the Twitter messages disseminated were brief and were used to highlight key recommendations from each Guideline, links in the tweets provided an additional source of web traffic to the full Guidelines.

The Dissemination Committee, led by Prof. Dr. Maria Ribal, are currently working on a programme of additional activities, including visual abstracts, to further develop the dissemination of the EAU guidelines. For updates, be sure to follow #eauguidelines.

Don’t miss the upcoming Guidelines Office European School of Urology courses during EAU18:

TP 61 2.0 02/2018/A-E

Approximately 50% of all traffic to the EAU’s website, Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility is guidelines-related with 5% of S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularitywww.uroweb.org.

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Infertility, Male Sexual Dysfunction and nomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility Thromboprophylaxis) - Sunday 18 March S-Technologies Ergonomic Easy and intuitive PDD in Precision ModularityDuring Flexibility Ergonomic Easy and intuitive Flexibility S-Techthe secondS-Technologies phase of the project, 16 guidelines 12.00-14.00. ologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility Twitter S-Technologies Ergonomic Easy and intuitive PDD in Precision MODULApolls were issued with a median of 126 RITY Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility Ergonomic Easy and intuitive respondents per poll. The median adherence S-Technologies Updated Renal, Bladder and Prostate Cancer PDD in Precision Modularity Easy and intuitive Ergonomic Modularity Flexibility S-Technologies Ergonomic Easy and 2018: intuitive PDD -in Precision Mowith guidelines recommendations was 62% Guidelines What’s changed?

Monday 19 dularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Flexibility Modularity Flexibility Ergonomic PDD in among poll participants.

The Dissemination MarchS-Technologies 08.30-11.30.

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Stop Guessing. Start Knowing.

10

EUT Congress News

Sunday, 18 March 2018

Radiomic TRUS - A new era Prof. Tillmann Loch Department of Urology Diakonissenkrankenhaus Flensburg University Teaching Hospital of the Christian-AlbrechtsUniversität Kiel Flensburg (DE) Urologic transrectal ultrasound (TRUS) was the first imaging modality evaluating the prostate enabling lesion guided targeted biopsies1. TRUS-guided systematic biopsies (sBx) have been and are the standard in PSA-based prostate cancer detection2,3.

However, systematic biopsies, frequently called “TRUS biopsies” have nothing to do with modern TRUS real-time lesion targeted biopsies of the prostate (Figure 1).

similarities with known cancer patterns are targeted and subsequently biopsied. These computer generated targets are artificial intelligence (AI)trained and are not visible with the human eye4.

The system is also able to monitor image changes during patient follow-up by collection of serial sections (ANNA 2.0), otherwise called artificial Intelligent Ultrasound computed tomography (AI-US-CT), which allows “trend monitoring”12.

With the help of internal landmarks, sections of AI-US-CT can be correlated on a mm level even after years (Figure 4). As a consequence, an integrated solution that combines longitudinal PSA with longitudinal imaging can be offered in patient follow-up.

Figure 4: Serial TRUS images of US-CT from prostate apex to base at approx. 5-mm intervals. a July 2015. b April 2017 with. c AI-US-CT analysis. Calcifications as internal landmarks prove exact correlation

pre-biopsies, and 24, 8 and 4 had a history of 1, 2, and 3 systematic biopsy sessions, respectively. Eleven patients were not judged as suspicious and did not have a prostate biopsy during monitoring.

Additionally, 12, 13, 7, 6, 3 and 4 patients underwent 1 (6 cores), 2 (12 cores), 3 (18 cores), 4 (24 cores), 5 (30 cores) and 6 (36 cores) ANNA/C-TRUS biopsy sessions, respectively.

Fifteen patients were diagnosed with PCa during their monitoring process. Their median age is 75 years (62–82), median prostate volume is 38 cc (11–97), median PSA is 6.95 ng/mL (1.37–47.3) and median PSA increase during the monitoring period was 6.95 ng/ mL (1.37–47.3). Seven of them did not have a history of systematic pre-biopsies, and 5 and 3 had a history of one and two systematic biopsy sessions, respectively.

Three patients were diagnosed with PCa in the first (total 6 sores), 5 in the second (total 12 cores), 3 in the third (total 18 cores), and 4 in the fourth (total 24 cores) ANNA/CTRUS biopsy session. The median time to diagnosis was 6 years. Four patients were diagnosed in a monitoring period of 2–5 years, 5 patients in a monitoring period of 6–9 years, and 5 patients in a monitoring period of 12 and 13 years (Table 2, Figure 1). All but 1 underwent a radical prostatectomy as PCa treatment. Only 2 were finally diagnosed with highly aggressive tumors (Table 2).

The first patient presented a Gleason Score 8 tumor and underwent radiation therapy, and the second a Gleason score 6 tumor with a pT3b local staging10.

cancer was compared with AI-US-CT group by each PI-RADS category.

Figure 7: PCa detection rates of AI-US-CT vs. syBX vs. mpMRI group

Detection rate for prostate cancer in AI-US-CT group (56/113, 49.6%) significantly differ from systematic group (36/106, 34.0%, p = 0.021) or mpMRI group (39/109, 35.8%; p = 0.043) (Fig 7). The number of targeted biopsy cores and positivity rate for biopsy cores in AI-US-CT group significantly differed from systematic group and mpMRI group (p < 0.001).

AI-US-CT-targeted 6-core biopsy significantly improved prostate cancer detection rate compared to mpMRI assisted 12-core systematic biopsy especially when PI-RADS category were 2 (9/43. 20.9%, p = 0.001) and 3 (10/34, 29.4%, p = 0.049) (Fig. 8).

Figure 1: The myth of systematic biopsies

Today, quantitative computer analysis with artificial intelligence (ANNA) of modern high frequency (7-29 MHz) computer-tomographic ultrasound (US-CT) has opened a new way of objective image interpretation of the prostate6. These “Radiomic” approaches are based on big data analysis providing information that is unavailable by visual interpretation.

An additional advantage of ANNA/C-TRUS is its development to a network-compatible module allowing users to transmit images for C-TRUS analysis from any internet platform for investigation with no hardware or software investment. After analysis, the cancer-suspicious marked images are then retransmitted via internet. Targeted biopsies can then be performed at any urologists’ office remotely (Figure 5). In that way, the images are easily reproducible and accessible10.

Multimodal, multi-parametric ultrasound (mpUS) approaches have been introduced allowing interpretation with excellent results7-9. Individual US techniques provide better results than the individual parameters of mpMRI (Fig 2).

Figure 5: Online platform allows remote handling and processing of images in order to target biopsies

How can I prove true detection rates?

To obtain meaningful data about the true number of missed PCa (false negatives), a radical prostatectomy immediately performed after negative diagnostics would be the only way to find out; however, this, of Novel ultrasound based modalities at lower costs than course, is not acceptable. The only other option is to cross-sectional imaging offer reproducible imaging of follow-up for at least 10 years, which seems prudent high quality are emerging and available to the to identify a negative effect of a missed tumor. urologist. Some of those, such as sonoelastography and contrast-enhanced US are under investigation7-9.

12-Year follow-up study of ANNA/C-TRUS Nevertheless, there are only few data on long-term A subset of 71 ANNA/C-TRUS patients were preoutcomes associated with novel prostate imaging. enrolled starting in 2000. Inclusion criteria were a Recently ANNA/ C-TRUS (Artificial neural network PSA > 4 ng/ml and/or PSA increase of 0.75 ng/mL/ analysis/Computer-assisted TRUS) utilized as US-CT year, and/or abnormal DRE. Follow-up was (ultrasound computer-tomography) data has been performed at 6 months with PSA measurements, DRE published in a 12-year follow-up protocol and in a and imaging. If PSA returned < 4 ng/ ml, follow-up randomized controlled trial (RCT)10,11. was extended to 1 year. Criteria for re-biopsy included a continuous PSA rise, a suspicious DRE, or a prostate biopsy demonstrating ASAP and/or extensive HGPIN. Figure 2: Sensitivities and specificities of MpMRI sequences vs. virtual mpTRUS techniques

Figure 3: Left: high resolution TRUS. Right: Computer marks cancer suspicious areas red

What is ANNA/C-TRUS ANNA/C-TRUS utilizes prostate cancer (PCa)-specific biometric signal information derived from radical prostatectomy specimens to identify suspicious areas (Figure 3). More specifically, it compares the findings of unknown patients with the patterns that were found in patients with PCa and subsequently were operated by radical prostatectomy. Instead of performing systematic biopsies, areas of greatest Sunday, 18 March 2018

Biopsies were always performed utilizing the ANNA/C-TRUS transrectal targeted biopsy system.

During every biopsy session, only six probes were taken. Of the patients that were finally diagnosed with PCa, additional data such as the type of treatment, possible biochemical relapse, local or distant recurrence, and possible patient death were recorded.

With a median follow-up of 12 years (9–17), 44 of them had a history of negative systematic random biopsies (1 to 3 sessions). Their median current age is 75 years (62–85), median PSA during the whole monitoring period is 6.52 ng/mL (0.5–47.3) and the median prostate volume is 60 cc (11–255 cc).

Outcomes after 12 years Fifty-six patients remained free of tumor, and are still undergoing the monitoring process. Their median age is 75.5 years (62–85), median prostate volume is 65 cc (23–255), and median PSA value during monitoring is 6.36 ng/mL (0.5–31.51). Their median PSA increase during monitoring is 4.92 ng/mL. In this subgroup of patients, 20 did not have a history of systematic

What does that mean ?

After 12 years of follow-up 15 out of 71 patients were finally diagnosed with PCa. Of them, only 2 suffered from aggressive tumors which were radically treated.

All of the patients are alive up to this day and no clinical tumor recurrence has been recorded, making ANNA/C-TRUS a safe monitoring method.

Second, this paper proves that significant tumors can be detected, even after multiple sessions and by taking only six biopsy cores, nullifying the need for general anesthesia and minimizing complication rates. By utilizing conventional random biopsy protocols, some authors suggest that after a second biopsy indicates no tumor, there is no further need to proceed with further biopsy sessions . This cannot be corroborated by the outcomes of this study.

Third, with the use of ANNA/C-TRUS 50–75% of the usually performed biopsy cores (range 8–24) could be spared over 12 years. All patients were included and completed the monitoring process, being subjected only to 6 biopsy cores per session, even in cases with large prostate glands or pervious negative biopsies.

A significant reduction of psychological and physical stress for the patient and urologist10.

RCT results: 6-core AI-US-CT vs. 12-core sBx vs. 12core mpMRI assisted sBx ANNA/C-TRUS with artificial intelligence AI-US-CT PCA detection rate has recently been compared with transrectal ultrasound guided 12­core systematic biopsy (systematic group) and mpMRI assisted 12­core systematic biopsy (mpMRI group) in a randomized controlled trial (RCT).

Figure 8: PCa detection rates of AI-US-CT in PI-RADS 2 and PI-RADS 3 subgroups

The RCT revealed a better rate of prostate cancer detection in AI-US-CT-targeted 6-core biopsy compared to TRUS-guided 12-core systematic biopsy and mpMRI assisted 12-core systematic biopsy.

This data suggests that the 12-core systematic biopsy may be replaced by 6-core AI-US-CT targeted biopsy for detection of prostate cancer in the future11.

Figure 9: Serial ANNA/C-TRUS patient monitoring over 9 years (suspicious areas in red). With the help of internal landmarks, sections of US-CT can be correlated on a mm level even after years

Why is ultrasound enough?

Long-term follow-up data and the RCT trail provide strong evidence that radiomic TRUS based urologic ANNA/C-TRUS is a useful method for the diagnosis of PCa and monitoring patients suspicious for PCa. Especially with a very low number to screen two patients to detect one PCA offers a superior alternative to systematic random biopsies. Moreover, after 12 years of follow-up, 97% of the patients were either without evidence of a PCa or were diagnosed in time, to be sufficiently treated13.

Figure 6: Study design of RCT 3 armed computer-randomized prospective trial

The RCT included 328 patients with suspicious for prostate cancer, randomized to AI-US-CT group, systematic group, and mpMRI group between January 2015 and December 2017. In AI-US-CT group, AI-US-CT guided 6-core biopsy was performed. In mpMRI group, mpMRI suspicious lesions were targeted by Figure 10: Perspectives for IA-US-CT radiomic ANNA approach 2-core TRUS guided biopsy, followed by 10-core systematic biopsy. Otherwise, 12-core systematic Editorial Note: Due to space constraints, the biopsy was performed (Figure 6). reference list can be made available to interested readers upon request by sending an email to: Outcomes measurements and statistical analysis: communications@uroweb.org The detection rate of prostate cancer, positivity rate for biopsy cores, number of biopsy cores needed to Sunday 18 March detect one prostate cancer were compared in 10.30-12.00: Thematic Session 4, Recent AI-US-CT group against systematic group and mpMRI developments in imaging of the prostate group. In mpMRI group, the detection rate of prostate EUT Congress News

11

European Active Surveillance of Renal Cell Carcinoma Study EAU RF study to assess AS outcomes in biopsy-proven kidney cancer Prof. Alessandro Volpe Associate Professor of Urology University of Eastern Piedmont Chaiman, Division of Urology Maggiore della Carità Hospital Novara (IT) In collaboration with the EAU Research Foundation, a prospective registry has been recently started to collect data on patients with small, incidentally detected, histologically confirmed renal cell carcinomas (RCCs) who are managed with active surveillance (AS). This observational registry is called European Active Surveillance of Renal Cell Carcinoma (EASE) study.

At 1 pm today (Meeting Room 14, Hall B3, M1/2, Bella Center) an investigator meeting will be held here in Copenhagen to present the status of the study to urologists from the institutions that have already joined the project and to those who would like to participate.

Principal Investigator: Alessandro Volpe, email address: ale.volpe@me.com Associate Professor of Urology University of Eastern Piedmont Novara, Italy

Objectives The primary objective of EASE is to assess the overall survival of patients who are diagnosed with incidental, histologically (biopsy) confirmed, <4 cm RCC and are managed conservatively with AS and to demonstrate that overall survival in this population is not significantly different compared to the overall survival of the general population without RCC and with similar age and comorbidities.

RCC. Biopsies are carried out under local anaesthesia with ultrasound or CT guidance. At baseline, information is collected on demographics, medical history, tumour-related symptoms and performance status. A physical examination is performed and blood and urine are collected. Abdominal imaging is performed by contrast-enhanced CT scan and MRI or, in case of contrast allergy or abnormal serum creatinine, by ultrasound.

The secondary objectives are: • the growth rate and progression rate of small renal tumors in AS; • the cancer-specific and progression-free survival of renal tumors in AS; • the identification of clinical and pathological predictors of fast growth rate and progression for small RCCs; • the identification of serum, urine and tissue predictive markers of fast growth rate and progression of small RCCs.

All patients follow a standardized AS protocol.

Follow-up visits are scheduled three and six months after diagnosis, every six months up to three years and yearly thereafter. A follow-up visit is also carried out at the time of progression when it occurs. Follow-up visits include medical history, physical examination and assessment of performance status, serial abdominal imaging and quality of life and anxiety by dedicated questionnaires. Voided urine and blood samples are collected and stored at definite time points for future analysis of predictive biomarkers.

Patient population A total of 400 patients with small, incidentally detected, histologically confirmed RCCs will be included and data related to the oncological outcomes of the AS approach will be collected.

Electronic Case Report Form The web-based database management system Marvin is used for collection of patient data. The system is intuitive and easy to use.

Study procedures A percutaneous biopsy of the renal mass is performed in all cases to histologically confirm the diagnosis of

Protocol Committee: • Alessandro Volpe • Axel Bex • Anders Bjartell • Peter Mulders • Grant Stewart • Wim Witjes EAU Research Foundation • Wim Witjes, Scientific and Clinical Research Director • Christien Caris, Clinical Project Manager • Joke van Egmond, Clinical Data Manager

Austria, Iceland and Lithuania already obtained ethics approval and started recuiting patients.

Other countries will follow shortly. Please join us.

New sites are welcome!

If you are interested to participate, please contact the EAU Research Foundation on researchfoundation@ uroweb.org Sunday 18 March 13.00: EAU RF EASE Study Investigators Meeting Meeting Room 14, Hall B3, M1/2, Bella Center

Study status More than 50 institutions across Europe have shown interest to include patients in the EASE registry.

Eleven centers from Italy, the Netherlands, Spain,

URO 84 2.0 02/2018/A-E

Rationale of EASE study Active Surveillance (AS) is a reasonable strategy for the management of small renal tumors in patients with advanced age or significant comorbidities. The evidence on AS is mainly based on retrospective and single institutional studies with relatively short follow-up. Moreover, the assessment of the oncological outcomes in these series can be biased by the presence of benign tumors since histological confirmation of malignancy was obtained only in a proportion of cases. EASE is the first multicenter prospective study on AS that includes only patients with histologically-proven RCC by percutaneous biopsy at enrollment and has therefore the potential to clearly define the oncological outcomes and the clinical role of this conservative approach for small RCCs.

Study team

With the expansion of treatment options for small renal masses, it is also increasingly important to identify reliable biomarkers that can differentiate tumours with different aggressiveness and metastatic potential at diagnosis, thereby enabling the urologist to choose the most suitable conservative or active management approach for the individual patient.

EASE will contribute to reach this goal since serum, urine and tissue specimens will be stored at baseline and at the time of tumor progression for the assessment of genetic and molecular predictors of fast growth and progression of small renal tumors.

As Every Detail Counts – Visibly higher resolution with the new flexible uretero-renoscopes FLEX-XC and FLEX-X2S

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Sunday, 18 March 2018

End-stage renal disease and kidney transplantation Management of polycystic kidney disease Dr. Arnaldo José Figueiredo Guideline Panel Member, EAU Working Group on Renal Transplant Centro Hospitalar e Universitário de Coimbra Coimbra (PT) Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease and the fourth most common renal disease requiring renal replacement therapy for end stage renal disease (ESRD) in Europe1.

It affects an estimated 600 000 individuals in Europe and is characterized by progressive development of numerous cysts in the kidneys, eventually leading to end-stage renal failure in the vast majority of patients, typically by the fifth or sixth decade of life2.

Mutations in the genes PDK1 and PDK2 are the most common cause of the disease, leading to an unopposed proliferation of renal tubular cells with formation of cysts. Mutation in PDK1 gene accounts for 85% of the cases and is associated with earlier and more rapid progression of the disease.

The urologist is involved in the management of this condition, both in patients without end-stage renal failure, to deal with complications such as stones, infected cysts, hematuria or tumours, and in later stages, in the event of kidney transplantation3.

Etiology of chronic pain is multifactorial and its initial management is not specific to the disease. It concurs to the poor quality of life of many of these patients, being difficult to treat and manage. Treatment should start by conservative measures and a less nephrotoxic analgesics like acetaminophen should be elected initially. If pain persists despite conservative measures and the patient hasn´t developed ESRD, laparoscopic cyst decortications with or without renal denervation may be indicated; if the patient is on dialysis, nephrectomy should be considered, either before or at the time of transplantation8.

Indications for nephrectomy After beginning renal replacement therapy, indications for nephrectomy should be balanced against the loss of diuresis, which is usually maintained until late in the evolution of the disease and helps the hydroelectrolytic balance, especially of potassium and phosphorus. On the other hand, recent data suggests that nephrectomy is associated with a better control of hypertension11.

Nevertheless, in the absence of symptoms or complications, nephrectomy is seldom indicated. When volume is the main concern, arterial embolization has been tried as a minimally invasive alternative to nephrectomy, achieving a volume reduction of 25-50%. However, results are poorer in very large kidneys, the ones that would benefit the most12. The main complication of embolization is infection with the need of nephrectomy. History of infected cysts or the presences of multiple calculi are, along with suspicion of neoplasia, contraindications for this approach.

Figure: Algorithm for native kidney nephrectomy in ESRD patients: If and When needed

4.

Timing of nephrectomy 5.

There is no consensus regarding the best timing and technique for nephrectomy in transplant candidates, It is unclear if the deterioration of renal function when indicated13. There are arguments for the different leading to end-stage renal failure depends on the 6. alternatives – before, concurrent or after transplant. formation of new cysts during the life of the Nephrectomy before transplantation avoids the extra individual, if it is secondary to the growth of existing cysts, or if both mechanisms concur4. In any case, the morbidity and increased ischemia time associated 7. progression of this condition to ESRD, once considered with simultaneous performance of nephrectomy and transplant. On the other hand, native nephrectomy insurmountable, has been shown to be amenable to during transplantation maximizes the use of their being slowed down. The most studied pathophysiological mechanism for progression of this remaining function while waiting for transplant and avoids an extra surgery. Not least because native condition is the one involving vasopressin.

Vasopressin is elevated in ADPKD as a consequence of kidneys volume decreases after transplantation14, nephrectomy after transplantation is usually reserved a urine-concentrating defect and it has been demonstrated that lowering the vasopressin effect on for cases where complications develop. the kidney can potentially modify the disease course.

Native kidney nephrectomy at the time of transplant This can be achieved via dietary factors including seems to be the most common option, according to increased water intake, or by medication with the published series. This strategy is associated with vasopressin receptor antagonists, like tolvaptan5. longer operative times and slight, but non-significant additional operative morbidity and does not Urological complications of ADPKD compromise long-term graft survival15-17. A recent Nephrolithiasis is a common complication of ADPKD, publication looked at the American Nationwide occurring in approximately 30% of the patients. This Inpatient Sample for peri-operative complications in increased risk is probably due to low urinary flow 19,302 kidney transplant surgeries in patients with (and stasis) in the tubules and calyces due to ADPKD (long-term results were not evaluated), and compression from growing renal cysts as well as found that simultaneous nephrectomy and transplant concurrent urinary metabolic abnormalities6.

(9% of the total) was associated with higher risk for Management of ADPKD patients with kidney stones blood transfusion, post-operative complications and should follow the same principles as for other critical care interventions18. The lack of randomized patients. Treatment options include shock wave studies comparing these options hinders any strong lithotripsy, retrograde endoscopic surgery and recommendation. percutaneous nephrolithotomy (PNL). Gaining access for PNL may be challenging, due to the multiple cysts that may interfere with the accurate localization of the Type of nephrectomy compressed calyces. Both ultrasound and fluoroscopic Open nephrectomy has been the standard choice in guidance are feasible, but fluoroscopy seems to have the majority of publications. Laparoscopy may be challenging due to the massive size of the big kidneys an edge for better accuracy and efficacy7. and its benefits are lessened by the need for a large Pain is a common complication in these patients, very incision for specimen extraction. Still, laparoscopy is often being the symptom that leads to diagnosis8. The gaining acceptance, and a recent systematic review and meta-analysis of seven studies including 195 cases most common location is the flank, followed by the (118 LN/77 ON) concluded that although LN was back and abdomen, and it may be acute or chronic. associated with longer operative time and smaller Management of acute pain should be directed to specimens, it carried the benefit of a shorter length of identification and treatment of the underlying cause, hospital stay and lower morbidity19. that include nephrolithiasis, cyst hemorrhage, pyelonephritis and cyst infection. Inflammation of the The relevance of the urologist in the management of kidney should be suspected in the presence of adult dominant polycystic kidney disease is as tenderness on palpation of the costovertebral angle. relevant today as it always has been.

An abrupt onset of the pain, with or without hematuria, may be due to a ruptured or hemorrhagic cyst, which usually resolves with analgesics and rest. References Renal colic by an obstructing calculus should be ruled out, its treatment being the same as in the general population. The presence of fever and leukocytosis should raise the suspicion of infection, mandating cultures and antibiotics. However, around 61% of the patients fail this initial treatment, requiring percutaneous cyst drainage or surgery, including nephrectomy in up to 25% of cases9.Drainage may be required in case of poor response. Ultrasound and CT scan are the most used imaging techniques, but PET may be used to identify an infected cyst10.

Sunday, 18 March 2018

autosomal dominant polycystic kidney disease care: European ADPKD Forum and Multispecialist Roundtable participants. Nephrol Dial Transplant. 2017 Dec 22. doi: 10.1093/ndt/gfx327. [Epub ahead of print] Grantham JJ1, Mulamalla S, Grantham CJ, et al: Detected renal cysts are tips of the iceberg in adults with ADPKD. Clin J Am Soc Nephrol. 2012 Jul;7(7):1087-93. doi: 10.2215/ CJN.00900112. Epub 2012 May 10. van Gastel MDA, Torres VE: Polycystic Kidney Disease and the Vasopressin Pathway. Ann Nutr Metab. 2017; 70 Suppl 1:43-50. doi: 10.1159/000463063.

Mufti UB1, Nalagatla SK: Nephrolithiasis in autosomal dominant polycystic kidney disease. J Endourol. 2010 Oct;24(10):1557-61. doi: 10.1089/end.2010.0093.

Sun H1, Zhang Z2, Huang G1, et al: Fluoroscopy versus ultrasonography guided mini-percutaneous nephrolithotomy in patients with autosomal dominant

polycystic kidney disease. J Urol. 2016 Jan;195(1):141-6. doi: 10.1016/j.juro.2015.07.114 8. Tellman MW, Bahler CD, Shumate AM, et al: Management of pain in autosomal dominant polycystic kidney disease and anatomy of renal innervation. J Urol.

2015;193(5):1470-8. doi: 10.1016/j.juro.2014.10.124.

Editorial Note: Due to space constraints the reference list has been shortened. Interested readers can email at communications@uroweb.org to request for the full list.

Sunday 18 March 10.30-12.00: Thematic Session 7; End-stage renal disease and kidney transplantation: What the urologist needs to know

Join us!

urologyweek.org

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*

1. Spithoven EM, Kramer A, Meijer E, et al: Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival--an analysis of data from the ERA-EDTA Registry.

Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv15-25. doi: 10.1093/ndt/gfu017.

2. Petzold K1, Gansevoort RT2, Ong AC et al: Building a network of ADPKD reference centres across Europe: the EuroCYST initiative. Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv26-32. doi: 10.1093/ndt/gfu091.

3. Harris T, Sandford R, de Coninck B, et al: European ADPKD Forum multidisciplinary position statement on

EUT Congress News

13

Dealing with complications after renal transplantation Kidney transplant complications mean lower graft survival and longer hospitalisation Prof. Enrique Lledó-Garcia Chairman EAU Section of Transplantation Urology (ESTU) Head, Andrology Unit Hospital General Universitario Gregorio Marañón Madrid (ES)

Co-Author: F.J. Burgos-Revilla, Exofficio ESTU Board member Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease.

Although the surgical procedure has been standardised for decades, and inmunosupressive or antibiotic treatments have been standardised and optimized, both surgical and medical complications may occur.

It is really well known that the use of suboptimal donors (age >55 years, or comorbidity such as diabetes or hypertension) is associated with higher incidence of medical (18.8% vs 6%) and surgical (34.5% vs 20%) complications compared with use of standard donors1. Also, age and comorbidity have become common in patients on the waiting list for KT, and are risk factors for all types of complications after the procedure2.

Peripheral vascular disease (PVD) relates to inferior allograft survival in comparison to normal patients. PVD correlates with all-cause mortality (6.2 vs 3%), cardiovascular death (4 vs 1.7%), fatal infection (2.2 vs 1.2%), delayed graft function (DGF) (21.6 vs 16.2%) and graft failure (15.6 vs 8.2%)3. Also cardiovascular morbidity is higher in KT patients afetr a long period of time on dyalisis.

Surgical technique is a crucial factor with significant impact on development of perioperative complications, speciallly in complex recipients4.

Extravesical ureterocistoneostomy techniques, routinary use of DJ stent or using a shorter ureter along with avoiding ligature of lower pole arteries are important to prevent ureteral necrosis5.

Changes in immunosuppressive schedules according to the recipient characteristics have also influence on complications. Avoidance of combined MMF and mTOR inhibitors or loading doses is essential. It is advisable to delay introduction of these antiproliferative agents until the postoperative period, or to adjust their doses in relation to other comorbidity (BMI >30 kg/m2, diabetes, or DGF) or old age6.

DGF has been reported as an independent risk factor for development of different surgical complications (SCs)7, as well as cytomegalovirus infection or acute rejection. All these have been related for ureteral necrosis and renal artery stenosis.

Delayed Graft function (DGF) DGF is often defined as a need for dialysis within the first week following transplantation7; however, this need is often subjective. Another commonly used definition refers to the rate of falling creatinine within the first week. At present there lacks a standardised definition of DGF which can cause difficulty interpreting and comparing trials. DGF is often used as an early surrogate marker for long-term outcomes and therefore a standardised definition is essential. DGF is most pronounced in cadaver donor KT, specially in expanded criteria donor kidneys (ECDK) and Non-Heart-Beating donor kidneys (NHBDK) are8. Cold and warm ischemia time are strong predictors of DGF. Preservation method (cold storage Vs hypothermic machine perfusion-HMP) has influence on the development of DGF: Use hypothermic machineperfusion in type III kidneys from donors after cardiac death, kidneys with prolonged simple cold storage and expanded criteria donor kidneys8.

0.9-2.5% for arterial and 0.6-2% for venous Table 1: SCs after KT. Gesquitra Registry (Spanish Surgical Group of Surgical Complications after Kidney thrombosis. Risk factors for VC includes atheromatosis Transplantation (In European Textbook on kidney transplantation. PP 377-392. ESTU-EAU, 2017) of the donor or recipient arteries, due either to the inclusion of older recipients in waiting list with Complication % significant vascular comorbidity (peripheral vascular disease, previous vascular surgeries) or the use of Vascular thrombosis 3% expanded criteria donor kidneys from donor with Arterial thrombosis 1% significant vascular comorbidity.

Venous thrombosis 2% Combination of both situations is really common in daily practice, and the necessity of vascular reconstruction during the KT procedure or the implantation of renal graft on a vascular by-pass is becoming frequent, introducing a really challenging situation for the surgical team8.

TRAS

3.7%

Perirenal haematoma

4.8%

Active bleeding

1.2%

Ureteral stenosis

5.8%

Multiple arteries of the graft, perioperative hypotension episodes or perirenal collections (hematoma, urinoma, lynphocele) as well as prolonged vascular anastomosis time relates to VC and graft loss9.

Urinary fistula

5.6%

Symptomatic lymphocele

5.7%

Perirenal abscess

1.3%

WHAEs - Non-infectious - Infectious

15.6% 10.8% 4.8%

Doppler ultrasound (US) is mandatory in the immediate postoperative follow-up of KT. The diagnostic sensitivity and specificity of US for vascular thrombosis are close to 100%. Occlusion of the main renal artery is observed by the absence of arterial flow within the kidney, along with the absence of venous flow10.

The use of contrast-enhanced US allows one to measure microvascular perfusion accurately, and detect local parenchymal infarction. In renal vein thrombosis, the two most pathognomonic findings are absence of venous colour signal and reverse diastolic flow within the renal artery.

Graft renal artery stenosis ranges from 1-23%.

Conventional angiography remains the gold standard for diagnosis and can provide image guidance to endovascular therapy. CT angiography with 3D reconstruction or magnetic resonance angiography have shown excellent correlation with conventional angiographic findings11.

In the acute VC patient, surgical exploration is recommended in cases of ultrasound absence of graft perfusion; surgical thrombectomy in cases of salvageable graft or allograft nephrectomy in cases of non-viable graft are the best options8. The endovascular approach is considered the treatment of choice for haemodynamically significant renal artery stenosis; open surgical approach are reserved for cases of failed endovascular treatment.

Ureteral Complications (UC) Incidence of UC ranges from 2-10%. Risk factors are ischaemic injury, surgical technique, donor and recipient advanced ages, time on dyalisis and vascular anastomosis time; also type of inmunosupression (mTOR inhibitors) and acute rejection have been related to UC. The systematic use of DJ stent has been reported as a beneficial factor to reduce UC7. Endourological treatment is effective in small fistulas (not large, where open surgery should be the first option, specially in immediate post-op) and ureterovesical stricture with variable results, worst in longer stenosis in comparison to shorter cases. Other alternatives as endoscopic sealing of fistulas with cyanocrilate12 or endoureterotomy with holmium laser or cold knife in cases of recurrence after ballon dilatation13 are options to be considered before proceeding to open surgery.

Lymphoceles Global incidence of lymphoceles (both symptomatic and asymptomatic) is around 34%6 but symptomatic cases represent between 0.6% and 18%. Peak incidence occur from two weeks to six months14. Main cause of lymphocele relate to extensive dissection of lymphatic around the iliac vessels14. Other causes are mTOR inhibitors use as a part of inmunosupressive therapy or delayed graft function15.

Surgical Complications The incidence of SCs after KT ranges from 7%-31.5%6

Diagnostic approach is made by clinical suspicion (lymphorrea, lymphedema, obstructive uropathy) and confirmed by ultrasonography and fine-needle percutaneous aspiration with biochemical confirmation16.

Vascular Complications (VC) Renal graft vascular thrombosis after transplant usually leads to graft loss. The incidence ranges from

In relation to treatment, only symptomatic cases need intervention. Recomendations are to perform percutaneous drainage placement as the first

14

EUT Congress News

treatment for large and symptomatic lymphocele, with or without sclerotherapy with different agents.

Laparoscpic marsupialisation into the peritoneal cavity is highly recomended when percutaneous treatments fail8.

Wound complications This is the most frequent surgical post-transplant complication (10-15%)6. Among other risk factors, probably the use of antiproliferative immunosupresive drugs is the most important nowadays, mTOR inhibitors (mTORi: sirolimus and everolimus), with a range of 36-53% of patients using these drugs as part of pharmacologic schedule18. The combination of micofenolate (MMF) and mTORi along with the early use of these drugs should be discouraged19.

Conclusion Complications of kidney transplant relate to a decrease in graft survival. Also hospitalisation period is significatively prolonged. Costs of procedure when complications ocurr are also higher. Early diagnosis and treatment are important to decrease the consequences.

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Sunday 18 March 10.30-12.00: Thematic Session 7, End-stage renal disease and kidney transplantation: What the urologist needs to know

UROLOGY CLEARLY DEFINED

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Sunday, 18 March 2018

t e all i s th h i V in n o i s t 7 i u ib 5 E h h Ex oot B

TOOKAD® (padeliporfin)

Vascular Targeted Photodynamic Therapy1 Marketing Authorization (EMA) granted by European Commission November 10th 20172

Together Created by Steba Biotech from ref. 5

Non Thermal Light3

SYMPOSIUM

padeliporfin4

Date & Time: Location:

Sunday March 18 17:45 – 19:15 Blue Area, Room 5 (Level 0)

Chairman: M. Wirth, Dresden (DE) M. Wirth, Dresden (DE) Welcome 17:45 - 17:50

F. Montorsi, Milan (IT) Clinical Results (Ph. III) 17:50 - 18:10

I.S. Gill, Los Angeles (US) Active surveillance & TOOKAD® 18:10 - 18:30

A. Scherz, Rehovot (IS) Focal Therapy & Non thermal light 18:30 - 18:50

A.R. Azzouzi, Angers (FR) Procedure & Practical training 18:50 - 19:10

M. Wirth, Dresden (DE) Conclusion 19:10 - 19:15

TOOKAD (padeliporfin) 183 mg or 366 mg powder for solu�on for injec�on Abbreviated prescribing informa�on – please consult the full summary of product characteris�cs before prescribing. ▼ This medicinal product is subject to addi�onal monitoring. This will allow quick iden�fica�on of new safety informa�on. Healthcare professionals are asked to report any suspected adverse reac�ons.

Therapeu�c indica�ons: TOOKAD is indicated as monotherapy for adult pa�ents with previously untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy ≥ 10 years and: Clinical stage T1c or T2a, - Gleason Score ≤ 6, based on high-resolu�on biopsy strategies, - PSA ≤ 10 ng/mL, - 3 posi�ve cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 posi�ve cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm3.

Posology and method of administra�on: TOOKAD is restricted to hospital use only. It should only be used by personnel trained in the Vascular-Targeted Photodynamic therapy (VTP) procedure. The recommended posology of TOOKAD is one single dose of 3.66 mg/kg of padeliporfin. TOOKAD is administered as part of focal VTP. The VTP procedure is performed under general anaesthe�c a�er rectal prepara�on. Prophylac�c an�bio�cs and alpha-blockers may be prescribed at the physician’s discre�on. Retreatment of the same lobe or sequen�al treatment of the contralateral lobe of the prostate are not recommended.

Special populations. In pa�ents with severe hepa�c impairment TOOKAD should be used with cau�on.

In pa�ents with renal impairment or in elderly pa�ents no dose adjustment is needed. This medicinal product contains potassium. Illumination for photoactivation of TOOKAD. The solu�on is administered by intravenous injec�on over 10 minutes. Then the prostate is illuminated immediately for 22 minutes 15 seconds by laser light at 753 nm delivered via inters��al op�cal fibres from a laser device at a power of 150 mW/cm of fibre, delivering an energy of 200 J/cm. Treatment should not be undertaken in pa�ents where a Light Density Index (LDI) ≥ 1 cannot be achieved. See the SmPC for further instruc�ons.

Contraindica�ons Hypersensi�vity to the ac�ve substance or to any of the excipients. Any previous prosta�c interven�ons where the internal urinary sphincter may have been damaged, including trans-urethral resec�on of the prostate (TURP) for benign prosta�c hypertrophy. Current or prior treatment for prostate cancer. Pa�ents who have been diagnosed with cholestasis. Current exacerba�on of rectal inflammatory bowel disease. Any medical condi�on that precludes the administra�on of a general anaesthe�c or invasive procedures.

Special warnings and precau�ons for use: Tumour localisation. Before treatment, the tumour must be accurately located and confirmed as unilateral using high-resolu�on biopsy strategies based on current best prac�ce, such as mul�-parametric MRI-based strategies or template-based biopsy procedures.

Simultaneous treatment of both prostate lobes was associated with an inferior outcome in clinical trials and should not be performed. Insufficient pa�ents underwent retreatment of the ipsilateral lobe or sequen�al treatment of the contralateral lobe to determine the efficacy and safety of a second TOOKAD-VTP procedure. Follow-up post TOOKAD-VTP. There is limited biopsy data beyond 2 years a�er TOOKAD treatment, so long-term efficacy has not been determined. Residual tumour has been found on follow-up biopsy of the treated lobe at 12 and 24 months, usually outside of the treated volume, but occasionally within the area of necrosis. There is limited data on long-term outcomes and on poten�al consequences of post-TOOKAD local scarring in case of disease progression. At present TOOKAD-VTP has been shown to defer the need for radical therapy and its associated toxicity. Longer follow-up will be required to determine whether TOOKAD-VTP will be cura�ve in a propor�on of pa�ents. Following TOOKAD VTP, pa�ents should undergo digital rectal examina�on (DRE) and have their serum PSA monitored, including an assessment of PSA dynamics (PSA doubling �me and PSA velocity). PSA should be tested every 3 months for first 2 years post VTP and every 6-months therea�er in order to assess PSA dynamics (PSA Doubling Time (DT), PSA velocity). Digital Rectal Examina�on (DRE) is recommended to be performed at least once a year and more o�en if clinically jus�fied. Rou�ne biopsy is recommended at 2-4 years and 7 years post VTP, with addi�onal biopsies based on clinical/ PSA assessment. Radical therapy post VTP procedure. Limited informa�on is available regarding the safety and efficacy of radical prostatectomy a�er TOOKAD-VTP. Photosensitivity. There is a risk of skin and eye photosensi�vity with exposure to light post TOOKAD-VTP. It is important that all pa�ents follow the light precau�ons for 48 hours post-procedure to minimize the risk of damage to the skin and eyes.

Pa�ents should avoid exposure to direct sunlight (including through windows) and all bright light sources, both indoors and outdoors. For specific instruc�ons on light protec�on measures, see the SmPC sect. 4.4. Erectile dysfunction. Erec�le dysfunc�on may occur even if radical prostatectomy is avoided. Some degree of erec�le dysfunc�on is possible soon a�er the procedure and may last for more than 6 months. Extra-prostatic necrosis. There may be extraprosta�c necrosis in the peri-prosta�c fat.

Excessive extraprosta�c necrosis occurred as a result of incorrect calibra�on of the laser or placement of the light fibres. In consequence there is a poten�al risk of damage to adjacent structures, such as the bladder and/or rectum, and development of a recto-urethral or external fistula. A urinary fistula has occurred in one case due to incorrect fibre placement. The equipment should be carefully calibrated and use the treatment guidance so�ware to reduce the risk of clinically significant extraprosta�c necrosis.

Urinary retention/urethral stricture. Pa�ents with a history of urethral stricture or with urinary flow problems may be at increased risk of poor flow and urinary reten�on post the TOOKAD-VTP procedure.

Urinary incontinence. The risk of sphincter damage can be minimised by careful planning of the fibre placement using the treatment guidance so�ware. The TOOKAD-VTP procedure is contraindicated in pa�ents with any previous prosta�c interven�ons where the internal urinary sphincter may have been damaged. Inflammatory bowel disease. TOOKAD-VTP should only be administered a�er careful clinical evalua�on, to pa�ents with a history of ac�ve rectal inflammatory bowel disease or any condi�on that may increase the risk of recto-urethral fistula forma�on. Use in patients with abnormal clotting.

Pa�ents with abnormal clo�ng may develop excessive bleeding due to the inser�on of the needles required to posi�on the light fibres.

Interac�ons: The use of medicinal products that are substrates of OATP1B1 or OATP1B3 (repaglinide, atorvasta�n, pitavasta�n, pravasta�n, rosuvasta�n, simvasta�n, bosentan, glyburide) for which concentra�on-dependent serious adverse events have been observed should be avoided on the day of TOOKAD infusion and for at least 24 hours a�er administra�on. Medicinal products which have poten�al photosensi�sing effects (such as tetracyclines, sulphonamides, quinolones, phenothiazines, sulfonylurea hypoglycaemic agents, thiazide diure�cs, griseofulvin or amiodarone) should be stopped at least 10 days before the procedure with TOOKAD and for at least 3 days a�er the procedure.

An�coagulant medicinal products and those that decrease platelet aggrega�on (e.g. acetylsalicylic acid) should be stopped at least 10 days before the procedure with TOOKAD. Medicinal products that prevent or reduce platelet aggrega�on should not be started for at least 3 days a�er the procedure.

Fer�lity, pregnancy and lacta�on: Contraception. If the pa�ent is sexually ac�ve with women who are capable of ge�ng pregnant, he and/or his partner should use an effec�ve form of birth control to prevent ge�ng pregnant during a period of 90 days a�er the VTP procedure. Pregnancy and breastfeeding. TOOKAD is not indicated for the treatment of women.

Effects on ability to drive and use machines: TOOKAD has no influence on the ability to drive or use machines.

Undesirable effects: Very common (≥ 1/10): Urinary reten�on, haematuria, dysuria, micturi�on disorders, perineal pain, male sexual dysfunc�on. Common (≥ 1/100 to < 1/10): Genito-urinary tract infec�on, haematoma, hypertension, haemorrhoids, anorectal discomfort, abdominal pain, rectal haemorrhage, hepatotoxicity, ecchymosis, back pain, urethral stenosis, urinary incon�nence, prosta��s, genital pain, prosta�c pain, haematospermia, fa�gue, abnormal clo�ng, perineal injury. For undesirable effects with an incidence lower than 1/100, please refer to the SmPC. Overdose: Limited informa�on. A prolonga�on of photosensi�sa�on is possible and precau�ons against light exposure should be maintained for an addi�onal 24 hours. An overdose of the laser light may increase the risk of undesirable extraprosta�c necrosis.

Prescrip�on status: BEGR Packages: 183 mg, powder for solu�on for injec�on, 1 vial; 366 mg, powder for solu�on for injec�on, 1 vial. The price will be published at www.medicinpriser.dk, when the product is on the market.

The Prescribing Informa�on (FEB2018) has been rewri�en and/or abbreviated as compared to the European Medicines Agency approved SmPC (NOV2017), which can be requested free of charge from the Marke�ng Authoriza�on Holder: Steba Biotech S.A., 7 Place du Théâtre, L-2613 Luxembourg, Luxembourg. info@stebabiotech.com

Adverse events can be reported to steba@primevigilance.com

1 - SmPC TOOKAD®. European Medicines Agency November 2017 2 - Community register of medicinal products for human use: http://ec.europa.eu/health/documents/community-register/html/h1228.htm#EndOfPage 3 - Azzouzi et al. Lancet Oncol. 2017 Feb;18 (2): 181-191 4- WHO Drug Information, Vol. 20, No. 4, 2006 5 - Azzouzi et al. World J Urol. 2015; 33:937-944

Sunday, 18 March 2018

www.stebabiotech.com | Info@stebabiotech.com

EUT Congress News

15

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1. Data on file 2. Hamstra, DA et al. Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: Secondary analysis of a phase 3 trial. Practical Radiation Oncology, Volume 8, Issue 1, e7 - e15 3. Karsh, L et al. Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data. Urology, Published online: November 23, 2017 4. Hamstra, DA et al. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):976-985. © Augmenix, Inc. All rights reserved. Augmenix, SpaceOAR and SpaceOAR logo are registered trademarks of Augmenix, Inc.

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www.urochm.rcsed.ac.uk 16

EUT Congress News

Sunday, 18 March 2018

Underactive bladder Studies on the bladder’s afferent pathway are needed to understand reversible stages of underactive bladder Dr. Tiago AntunesLopes Hospital de S. João Faculty of Medicine University of Porto Porto (PT)

Co-Author: L. Vale, University of Porto (PT) In the last few years, detrusor underactivity (DUA) has been increasingly recognized as a common cause of bothersome lower urinary tract symptoms (LUTS) affecting both sexes.

DUA was defined by the International Continence Society (ICS) as “a contraction of reduced strength and/ or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span”1. The exact prevalence of DUA is unknown, due to the lack of a non-invasive tool for diagnosis2, but it is more prevalent with aging, affecting as much as 48% of older men and 45% of older women undergoing evaluation for LUTS3. In contrast to detrusor overactivity (DO) or bladder outlet obstruction (BOO), DUA is largely under-researched and up till now no effective treatment is available.

Drawing an analogy to DO (urodynamic diagnosis) and overactive bladder (symptom complex), and with the aim to facilitate further clinical and epidemiological research, underactive bladder (UAB) was lately defined by the International Consultation on Incontinence – Research Society, as “the perception of detrusor underactivity, characterized by symptoms of prolonged voiding, hesitancy, slow and/or intermittent stream, and/or sensation of incomplete emptying”4. Hence, UAB is a symptom complex suggestive of DUA, comprising a range of storage, voiding and postmicturition LUTS, overlapping with symptoms of overactive bladder and symptoms associated with BOO. The coordination between both components of the lower urinary tract, the bladder and urethral sphincter, is finely controlled by the nervous system, allowing normal storage and periodic elimination of urine5.

Bladder contraction is initiated upon activation of sensory mechanisms that detect a sudden increase in intravesical pressure. The parasympathetic innervation is then activated, providing excitatory input to the detrusor. At the same time, the sympathetic drive to the bladder neck and urethral sphincter is interrupted.

As a result, the sphincter relaxes preceding detrusor contraction, allowing micturition5. Moreover, supraspinal centres (pons, periaqueductal grey, brain frontal cortex) participate on the regulation of bladder function, providing another level of complexity to micturition control6. Therefore, disruption at any step in these neuromuscular pathways can lead to DUA.

the central neural integrative control mechanisms.

Despite conventional models focused mainly on either efferent nerve (motor nerve) or myogenic dysfunction, contemporary views highlight the importance of the neural control mechanisms, particularly the afferent system. To develop novel effective therapies, a better understanding of the etiology and pathophysiological mechanisms of DUA is required.

Etiological factors 1. Aging Symptoms frequently observed with aging, as urinary retention, hesitancy, and incontinence, have been attributed to UAB8. Gilpin et al. reported on agerelated morphological changes, especially decreased axonal density of the human detrusor muscle9.

Moreover, Lepor and colleagues demonstrated an increase in collagen deposition in human aged detrusor10, and Elbadawi et al. suggested that normal aging bladder was associated with a “dense band pattern”, which is believed to precede dedifferentiation of the detrusor, leading to impaired cellular processes and increased fatigability11.

More recently, Mansfield et al. showed that the expression of M3 muscarinic receptors were decreased with aging, affecting cholinergic neurotransmission12.

These age-related changes were recently confirmed by Ito and colleagues13,14.They demonstrated that aged rats showed weaker contractile responses to carbachol and electrical field stimulation related to decreased cholinergic mediated contraction, lower M3 muscarinic receptor mRNA expression, and higher collagen deposition in isolated detrusor strips. In addition, cystometric investigations of old rats showed greater post-void residual volume and lower voiding efficiency. The authors concluded that these changes constituted key factors for UAB. 2. Diabetes mellitus One of the most common complications of diabetes mellitus is bladder dysfunction, referred as diabetic cystopathy (DCP). The severity of DCP is determined by the severity of diabetes itself and its duration, as well as the control of the disease. This urinary dysfunction has been described as impaired bladder sensation, reduced contractility and increased post-void residual3.

The pathogenic mechanism that leads to a decline in bladder emptying ability is believed to have a concomitant myogenic and neurogenic basis7.

Hyperglycemia underlies autonomic neuropathy (axonal degeneration and segmental demyelination) through activation of the polyol pathway, the generation of free radicals, activation of protein kinase C and formation of advanced glycation end-products7.

There is increasing evidence that epithelial cells and smooth muscle cells have mechanosensitive systems, which allow them to change gene expression and protein synthesis in response to obstruction32.

Figure 1: Causes and pathophysiological mechanisms in underactive bladder (adapted from Investig Clin Urol 2017;58 Suppl 2:S82-89).

performance deteriorates and an imbalance between the power of bladder musculature and outflow resistance develops, leading to a decompensated stage, when bladder emptying becomes more difficult, and histologically the muscle shows evidence of increased connective tissue deposition and fibrosis7.

This sequence of events is supported by several studies in animals, where obstruction is usually induced by a clip, ring or suture placed around the urethra18-23.

The most supported explanation for bladder decompensation occurrence is based on cyclic ischemic and reperfusion injury. The barrier function of the urothelium and the contractile function of the detrusor depend on adequate blood perfusion and supply of oxygen and nutrients.

Therefore, the blood vessels in the bladder wall must be able to adapt to the spatial changes that occur during the filling/voiding cycle, without compromising the blood flow24. The vascularity among different layers of the bladder wall is not uniform. Despite having a more extensive capillary network, the suburothelium also has a metabolic rate three times higher than that of the detrusor, and is the region of the bladder wall most vulnerable to ischemia25.

In patients with BOO, the raised intravesical pressure during voiding, leads to increased bladder wall tension, compression of the blood vessels and reduction in blood flow, with subsequent tissue ischaemia26. Nerves are highly sensitive to ischemia and hypoxia, occurring a decrease in the autonomic innervation of the detrusor muscle in patients with BOO27, which seems to impair the neuromuscular control of the bladder.

The decrease in bladder blood flow is followed by a reperfusion phase, with a rise in oxygen tension after Moreover, streptozotocin-induced diabetic rats had voiding. This cyclic ischemia/reperfusion, that occurs decreased levels of nerve growth factor (NGF) in the on each micturition cycle, has multiple implications dorsal root ganglia, associated with raised post-void throughout diverse pathophysiological pathways, residuals15. On the other hand, DCP can also result from which are the subject of numerous studies (e.g. myocyte impairment due to abnormalities in hypoxic-inducible factor – HIF, TGF-β, reactive oxygen intercellular connections and excitability, intracellular species, epithelial-mesenchymal transition – EMT)24.

7 signaling, receptor density and distribution .

The ischemia of the urothelium/suburothelium may According to the DCP temporal theory16, osmotic A multifactorial condition compromise many functions of these layers. The diuresis resulting from hyperglycemia could cause urothelium releases numerous neurotransmitters, DUA is multifactorial and can result from a variety of bladder distension and increase intravesical pressure, which are expected to activate receptors present in pathological processes, essential for the generation leading to compensatory bladder hypertrophy. While of an efficient voiding contraction, that can be suburothelium sensory nerves and generate sensory this stage would be characterized by storage LUTS, categorized as idiopatic, neurogenic, myogenic, or inputs. Among them, ATP and purinergic (mainly P2X3) with disease progression, the accumulation of functional (Table 1)7. receptors play a crucial role to initiate the micturition oxidative stress toxic products leads to nerve and reflex28.Cho et al. investigated the changes in the levels Several contributing factors have been suggested in the myocyte injury, which clinically manifests as reduced of ATP and NO in the urothelium of men with detrusor bladder sensation, voiding symptoms and impaired pathophysiology of UAB, including myogenic failure, underactivity and benign prostatic hyperplasia and bladder emptying16. efferent and/or afferent dysfunctions, and central concluded that ATP in the urothelium was significantly nervous system dysfunction (Figure 1). Myogenic decreased in these patients; however, there was no 3. Bladder outlet obstruction factors affect detrusor myocytes or their surrounding significant change in NO29. matrix, while neurogenic causes may affect the efferent The effects of BOO on the detrusor function have been This indicates that ATP may have an important role in or the afferent limb of the micturition reflex, as well as the subject of numerous experimental studies. It is believed that BOO the pathophysiology of DUA and it should be significantly alters the considered a potential diagnostic biomarker and a Idiopathic Ageing bladder’s structure and treatment target for DUA. Jiang et al. studied male physiology and ultimately patients with BOO and stated that this condition leads Neurogenic Stroke leads to severe functional to urothelial dysfunction, suburothelial inflammation, Parkinson disease impairment. At first, the cellular apoptosis and alterations of sensory proteins30.

Multiple sclerosis Peripheral neuropathies (e.g. diabetes mellitus) bladder undergoes Spinal cord, cauda equina and peripheral nerves lesions compensatory changes to Patients from the DUA subgroup had a higher (e.g. spinal canal stenosis, pelvic fractures, and pelvic surgery) generate additional expression of β3-adrenoreceptors, indicating a pressure and overcome decreased bladder sensation. Recently, Jiang and Kuo Myogenic Bladder outlet obstruction the raised outlet investigated urothelial barrier deficits, suburothelial Diabetes mellitus resistance. The detrusor inflammation and sensory proteins expressed in the Functional Fowler’s syndrome becomes hypertrophic bladder mucosa of patients with DUA. These patients Dysfunctional voiding and hyperplastic, had lower expression of M2 and M3 muscarinic Pharmacotherapy Drugs with anticholinergic effects (e.g. antimuscarinics, ensuring urine expulsion receptors, P2X3 receptors and eNOS and higher antihistamines, antipsychotics, antiparkinson medications, – compensated stage17. expression of β3-adrenoceptor than controls31. This antispasmodics, tricyclic antidepressants) leads to the conclusion that these signal changes could Opioids After a variable period of account for the clinical presentation of hyposensitivity time, contractile Table 1: Etiological factors in detrusor underactivity. during storage in patients with DUA31.

Sunday, 18 March 2018

Gheinani et al. investigated the regulatory role of miRNAs in BOO-induced lower urinary tract dysfunction (LUTD)33. They performed an integrated analysis of miRNA and mRNA paired expression profiling in the bladder biopsies of human patients using comprehensive next-generation sequencing– derived (NGS-derived) transcriptome data33.They identified common and unique miRNAs and their mRNA targets characteristic of BOO-induced LUTD and specific for urodynamically defined states of the disease, allowing systematic examination of the association between bladder function and the underlying activated biological processes (pathways and networks)33. The authors concluded that molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states.

Figure 2: Detrusor underactivity (DU) caused by bladder outlet obstruction (BOO) is associated with an early impairment of the bladder sensory mechanism, with less available urothelial ATP to promote bladder contraction. ATP levels in saline voided from control, underactive and hyperactive female rats [from Eur Urol Suppl. 2018 (in press)].

Recent studies demonstrate that impaired bladder urothelial signalling and sensory transduction pathways have a major role in the development of DUA. In an experimental work presented at this congress, L. Vale and colleagues tested the hypothesis that DU occurring after BOO results from an early impairment of the bladder afferent signaling mechanism34. For that they created partial urethral obstruction in female rats and performed cystometries at three and 15 days. ATP was measured in voided saline. DUA bladders were then submitted to intravesical infusion of ATP and serosal application of acetylcholine or ATP. At three days after BOO, 63% (5/8) of rats had increased frequency of contractions, while 29% (2/8) had normal frequency, and 13% (1/8) had DU (voiding by overflow).

At 15 days, 67% (6/9) of rats had DUA, while the remaining 33% (3/9) had more voiding contractions than controls. ATP in saline was significantly higher in rats with more voiding contractions and was significantly lower in those with DU (Figure 2).

Finally, in DU bladders, serosal application of acetylcholine or ATP generated immediate expulsive detrusor contractions, indicating the integrity of the detrusor muscle. Intravesical application of ATP generated immediate vigorous expulsive detrusor contractions, denoting a low availability of urothelial ATP. These results suggest that BOO impairs the afferent pathway before impairing the detrusor, with urothelial ATP being less available to promote bladder contraction. This mechanism may open new therapeutic options to overcome DUA after BOO. Conclusion Underactive bladder is a frequent, aging-related, multifactorial condition35. Impaired detrusor contractility has been regarded as a major etiologic factor of UAB/ DUA. However, the study of the contribution of the afferent pathway of the bladder to UAB/DUA emerges as an unmet need to understand initial and reversible stages of UAB/DUA. Reliable markers of bladder function/dysfunction are urgently required in order to not surpass the “point of no return”, which leads to bladder decompensation and failure.

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Sunday 18 March 10.30-12.00: Thematic Session 1, Underactive bladder: Under-diagnosed and underrecognised

EUT Congress News

17

Today’s European Urology Events Surgery-in-Motion

Aims and objectives: Surgery-in-Motion School is a special educational video library. In this two hour video based course, different experts will share their specific technique on the key steps in nerve sparing RARP. They will also discuss why they do it their way. At the end of the course, special complex cases will be shown, and the presenters will explain how to manage these.

10:00 - 10:10 Welcome and introduction Jim Catto, Sheffield (GB)

March 18th 10.00 – 12.00 Green Area, Room 15 (Level 0)

10:10 - 10:30 Bladder neck Declan Murphy, Melbourne (AU) Alexander Mottrie, Aalst (BE) Peter Wiklund, Stockholm (SE) Discussion 10:30 - 10:50 Lateral dissection Markus Graefen, Hamburg (DE) Declan Murphy, Melbourne (AU) Peter Wiklund, Stockholm (SE) Discussion 10:50 - 11:10 Apical dissection Markus Graefen, Hamburg (DE) Alexander Mottrie, Aalst (BE) Declan Murphy, Melbourne (AU) Discussion

11:30 - 11:55 Special cases: The use of ICG for peri-prostatic artery identification Alexander Mottrie, Aalst (BE) Ureteral orifices close to bladder neck management Markus Graefen, Hamburg (DE) Post TUR-P or HOLEP Peter Wiklund, Stockholm (SE) Very large prostate Declan Murphy, Melbourne (AU) Median lobe Alexander Mottrie, Aalst (BE) 11:55 - 12:00 Closing remarks Jim Catto, Sheffield (GB)

11:10 - 11:30 Anastomosis Markus Graefen, Hamburg (DE) Declan Murphy, Melbourne (AU) Peter Wiklund, Stockholm (SE) Discussion

Platinum hour

March 17th - 18th 16.00 – 18.00 European Urology booth #C3-C29

We would like to invite you to attend the Platinum Hour drinks reception to meet and greet the editors, authors and reviewers of the European Urology family of three: European Urology, European Urology Focus and European Urology Oncology. Please join us to toast to the family’s new sister journal European Urology Oncology.

This new journal complements the family by delivering high quality research while pursuing the goal of a multi-disciplinary approach. Urology, Medical Oncology, Radiation Therapy, Imaging, Pathology and Basic Research working together with the same final aim: to improve patient care. If you’ve got practice changing, groundbreaking research in urological oncology, you can directly submit your original article via this link: ees.elsevier.com/euonco.

We look forward to answer any questions about the new journal, or another member of the European Urology family, during the drinks reception at our booth!

europeanurology.com eufocus.europeanurology.com europeanurology.com/euoncology

18

EUT Congress News

Sunday, 18 March 2018

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With one of the following leadership courses: • Leadership for Medical Professionals Course • Nurses in a leadership role: Cultivating your leadership When: Monday, 19 March Fee: € 50 excl VAT Sign up at the YUO booth (H69) on the EAU square at the Exhibition Hall.

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19

Possible ways to refine prostate biopsy New technical advances will further boost the accuracy of current targeted biopsy Dr. Massimo Valerio Dept. of Urology, CHUV Laussanne (CH)

The adoption of imaging to inform clinicians about the location of suspicious cancerous lesions is a revolution in prostate biopsy. This shift has allowed the transition from random to targeted sampling, from a strategy based on chance to one based on precision, from an organ-centred to a cancer-centred paradigm.

We probably do not fully appreciate the extent of such a change. The implications of this shift are not evident to all of us since the treatment algorithms have not fully evolved yet.

Level 1 evidence shows that MR-targeted biopsy detects more clinically significant cancers than extended random sampling1. Further, this strategy is more efficient and effective for patients and healthcare systems. Few needles are needed to target a given region of the prostate, and an image-based pathway is likely to have advantages from a cost-effectiveness perspective2. How can this be improved? There are many ways to further ameliorate the accuracy of targeted sampling, but the true revolution would be to make this strategy available to all our patients.

MR targeted biopsy is a complex procedure. This does not mean that the procedure is especially difficult, nor highly technically demanding. This means that the overall performance – measured for instance by the detection of clinically significant cancer per whichever unit of men – relies on a chain of interconnected steps, each one influencing the others.

The imaging phenotype, provided at present by multiparametric MRI, can be exploited with three different strategies: “in bore” targeted biopsy, cognitive MR-TRUS fusion with visual targeted biopsy, and software-based MR-TRUS fusion targeted biopsy.

In-bore MR targeted biopsy – biopsy performed directly in the MR suite – is probably the most direct and intuitive way to guide biopsy, although its role is confined to few centres in the world due to resources and cost constraints.

Cognitive MR-TRUS fusion targeted biopsy relies on a skilled and trained operator who is able to cognitively register the preoperative MR over the TRUS in order to guide his/ her needles towards the target/s. A difficult task, which only in few expert hands seems comparable to more sophisticated MR targeted strategies. Software-based MR-TRUS fusion targeted biopsy has been progressively adopted by many centres, and represents a mid-way between the two.

Modern advanced software allow the clinicians to fuse the two image sources – MR & TRUS – and to compensate the incongruity between the two with a margin of error of few millimetres. This will be the theme of Thematic Session 8, in which we will be able to picture the latest advancement in computerised image fusion employing modern platforms.

objective comparison of own results against established benchmarks of quality. The European School of Urology course on prostate biopsy, offered at the time of this meeting, is one of such opportunities.

To disseminate the procedure across the board is the major challenge today, but it is very likely that in the next few years we will witness novel innovation.

There are many ways to refine and optimise prostate biopsy. These changes are likely to necessitate a new generation of software-fusion devices which are likely to evolve into a versatile platform able to integrate different information generated by various sources (Figure 1). The amalgamation of this with concomitant registration over a cartography to depict spatial anatomy will allow personalised treatment and the new wave of tissue-preserving approaches.

Improving anatomical imaging First, multiparametric MRI imaging will be improved, especially for T2-weighed imaging. In order to overcome motion artefacts due to patients’ movement, peristalsis of bowel loop, or movements of the prostate itself, manufacturers are developing novel T2 sequences with the aim to substantially improve anatomical imaging3. Also, higher field magnet strength at 7 Tesla are being evaluated. This would open new avenues for prostate biomarkers which are out of reach with lower magnet strength, Figure 1: Example of a modern platform integrating the information generated from various sources of energy with a 3D model.

This allows targeted sampling as well as personalised tissue-preserving strategies albeit the adoption of this technology in clinical practice is still hindered by some technical limitations.

Further, novel hyperpolarised MR allowing molecular imaging are likely to play a role and increase the diagnostic accuracy of present scans. Finally, computer-aided detection (CAD) will support the democratisation of multiparametric MRI. CAD seems to have same diagnostic performance than expert uro-radiologists, and relies on quantitative measurable parameters.

Second, the source of the imaging phenotype itself might be implemented. 68 Gallium PSMA-PET/CT is becoming a recognised imaging tool for metastatic assessment of men with primary, and recurrent disease after treatment. There is early evidence showing that PET-TRUS fusion biopsy might be complementary to MR-TRUS targeted, and better in some cases. The specificity of the ligand for prostate cancer might represent an attractive alternative in selected cases.

EUT Congress News

model. These innovations push our field towards the adoption of precision medicine.

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Sunday 18 March 10.30-12.00: Thematic Session 8, Overview of fusion biopsy devices

Third, the ability of modern platforms to register spatial distribution, and to store the 3D reconstruction for subsequent resampling allows the operator to embrace tissue-preserving approaches with more confidence. This permits not only re-visiting areas of the prostate with high accuracy for pathologic assessment of volume and/or grade progression, but also permits more detailed evaluation investigating genetic and biological signatures4.

Fourth, the sampling route might definitely shift. The transrectal route has been traditionally preferred to the transperineal one as this approach can be performed in the outpatient clinic with local anaesthetic, and had limited cost and resources constraints. However, at present, it is evident that the transperineal approach has significant advantages, and the supposed disadvantages can be overcome.

The sepsis rate after transperineal biopsy is close to 0%; this compares to 1-4% rate when performing transrectal biopsy, according to the number of Interdependent steps previous biopsy sessions. In the era of re-sampling, Why software-based MR-TRUS fusion-targeted biopsy and considering that every previous biopsy session increases the risk of subsequent sepsis, this is a big has to be considered a complex procedure? It relies change. Further, the accuracy of targeted sampling on interdependent steps, namely: imaging acquisition, imaging reporting, transfer of information through the perineum is likely to be greater than through the rectum, although no high level evidence between radiologist and urologist, real-time TRUS acquisition, software-based fusion, and finally is available yet. While some areas of the prostate are easily accessible though the rectum, there are some clinician’s ability to sample a given target. The learning curve for each of these steps is unknown and which are difficult to sample, namely the apical region, the anterior portion of the prostate, and the needs to be determined, and as many opportunities as possible for training need to be offered in order to base, especially in men with large prostate. disseminate this complex procedure.

Transperineal targeted biopsy have ideal accessibility to all areas of the prostate with few exceptions.

Spatial location is therefore not a feature that hinders Uro-radiologists are actively facing these issues. The standardisation of the PIRADS score version 2, and the the accuracy and reliability of transperineal biopsy. proposal to ensure international standards by verification of outcomes through independent Finally, traditional limitations can be overcome. assessment of results are concrete examples of this Transperineal biopsy can be performed in the outpatient clinic under local anaesthetic and achieve process. We have to do the same with the high detection rate of clinically significant prostate development of multiple opportunities for training within national and international societies, the cancer5. standardization and implementation over time of the technique, the availability of direct and distant There a number of ways to refine prostate biopsy. resources for self-assessment, and the possibility of While MR targeted biopsy are being disseminated 20

across our profession through our societies, the technology is moving forward. Novel technical advancement will further ameliorate the accuracy of current targeted biopsy, but some will not. It is up to our scientific community to scrupulously evaluate these in order to reject or adopt them. The availability of novel sources of information that need to be integrated in the decision-making process with patients is a reality. Modern platforms are able to sustain this process by registering not only the preoperative MR over real-time TRUS, but also integrating all the available information within a 3D

REGISTER NOW Join us in the spectacular city of Paris, France, for the 36th World Congress of Endourology, the world’s foremost meeting dedicated to minimally invasive urologic surgery. Assembling today’s global leaders in endourology, WCE 2018 will provide unparalleled opportunities to expand your education, enhance your skills and exchange ideas.

Abstracts Now Open!

Learn more and submit your abstract at

www.WCE2018.com

Sunday, 18 March 2018

EAU PI: Are we clear enough?

A more animated website helps inform patients on various urology procedures Dr. Juan Luis Vásquez Member, EAU Patient Information Chairman, ESRU Herlev Gentofte Hospital Herlev (DK)

Urological diseases are common: they often cause a lot of discomfort and some can be life-threatening.

Plenty of urological information can be found online.

Unfortunately, we all know the problem of internetbased patient information.

In many cases, the information may be driven by financial interests and may cause more confusion than help. Moreover, much of the available information is not scientifically proven, and it may mislead some patients who might be desperate to try everything.

There is also the industry trying to sell their products. This type of information must be perceived as biased and needs to be put in perspective. On the other hand, if patients find unbiased and scientifically proven materials, the information may be difficult to understand if you don’t have a medical background.

The mission of the EAU is to raise the level of urological care. For many years we have mainly focussed on the urologist, but since 2016, the EAU decided to reach patients directly as well. So, the EAU Patient information Working Group (EAU PI) was created as a truly European collaboration for the benefit of patients and their families.

Our belief is, that well-informed patients are better equipped to talk about issues that worry them, and share more easily their concern about the way they experience their condition and treatments; encouraging a meaningful dialogue between the doctor and the patient, thus leading to better care.

The purpose of the EAU PI is to provide reliable, clear, unbiased and comprehensive information about urological diseases and their treatment, independently of the language patients speak or the country they come from. This enables patients and family to advance from a completely dependent individual, to an educated partner who is able to discuss the condition, leading to improving the understanding of what happens before, during and after treatment.

For this, EAU PI has dedicated an online platform with patient information regarding most urological conditions. All materials offered on this platform take into account the latest existing scientific evidence from the EAU Guidelines, the experience of medical experts and nurse practitioners, together with the view of patients.

EAU PI have achieved collaborative partnerships with different patient groups, such as Europa Uomo, Fighting Bladder Cancer UK, ECPC and the IKCC. Together, they formed a taskforce for the development of a patient information session during this year’s annual congress in Copenhagen. Patient group partnerships lets EAU PI engage in a dialogue with patient representatives regarding patient needs, which will help to prioritise and determine areas of interest.

HONcode certification As an additional honor and certificate of excellence, the EAU PI online platform received the HONcode certification. The HONcode is the most widely accepted reference for online health and medical publishers. Currently the HONcode is used by over 7,300 certified websites, more than 10 million pages, covering 102 countries.

HON is a non-governmental organisation that has been granted consultative status with the Economic and Social Council of the United Nations (ECOSOC).

The mission of the foundation is to guide the growing community of healthcare consumers and providers on the Internet to sound, reliable medical information and expertise. In this way, HON seeks to contribute to improved health care through patient empowerment and better-informed health professionals.

Sunday, 18 March 2018

To date, EAU PI has issued leaflets for almost all urological topics, both benign urology and urological cancers. These leaflets have been translated to several languages. But is this enough? Are we clear enough?

We know, that educating patients on scheduled treatments is crucial to ensure compliance.

Research has long shown that adequately prepared patients benefits in terms of adhering to necessary regimens, reduced anxiety, enhanced self-esteem, increased satisfaction with care and improved quality of life.

On the other hand, it is vitally important that patients understand what medical procedures they face, so that they can cope better with the procedure, and can give fully informed consent with regards treatment.

It is essential, therefore, to provide information that is clearly structured and easy to understand. An Australian study by Winter et al1 published in BJUI in 2016 shows that the use of portable video media improves patient’s knowledge and satisfaction acquired during the consent process for cystoscopy and insertion of a ureteric stent, compared to standard verbal communication.

Moreover, patients reported their preference towards receiving information using the portable video media. For this reason, in addition to the written leaflets, EAU PI has started to develop educative animated videos, where diverse urological treatments are explained in a very clear and comprehensive way.

One of the first animated videos introduced by EAU PI was about ureteroscopy (URS). Using this animated video, we conducted a pilot study to assess the level of understanding among patients who were about to undergo this surgical procedure. The animated video along with written information about the procedure was shown to patients scheduled for URS prior to any contact with the hospital staff.

Patients were presented an eleven-item questionnaire in order to evaluate patients’ rating followed by two questions testing the level of understanding of the provided information. For this pilot study, the information source and the questionnaire were translated into German, Turkish and Chinese, for multilingual evaluation.

A total of 120 questionnaires were evaluated: Germany (N:52), Turkey (N:51) and China (N=17). Of all participants, 60% were male and 40% were female.

35% of the patients were in the age group between 19 and 39 years, 45% between 40 and 59 years and 20% older than 59.

Satisfaction with the presented information was very high, reaching 90% favorable comments over all items, with less than 2% of patients that found the educational material unfavorable. 99% of the patients considered the information favorable in terms of preparing for the procedure.

Between nationalities, no significant differences in evaluation of the items could be identified, except the need for voice-over and subtitles for Chinese patients (82.4% preferred), as compared to only voice-over preferred in Turkey (70%) and Germany (73.5%).

Medical aspects like the need for anesthesia or secondary stent placement showed lower levels of understanding and may support the need for adjustment of the information. Both test questions have been answered correctly by 80.0% of the patients, suggesting a high level of comprehension; however, 5% of the patients did not give a correct answer, again, supporting the need for adjustment of details.

Animated videos This approach to patient information, using a cartoon animation narrated in lay language, allows each individual patient as much time as needed to understand the proposed procedure. This pilot study confirms that animated videos raise the level of understanding and improve patient confidence prior to treatment in 96.7% of participants. However, it should not replace a face-to-face discussion with the physician.

As we observed, a small number of patients did not understand the information delivered to them, but they may meet the physician already informed

The EAU Patient Information website showing the page with animated videos of various urological procedures such as ureteroscopy and cystoscopy, among others

and prepared, thus benefiting both the physician and the patient.

So far, EAU PI has prepared animated videos for the drug treatment of overactive bladder, placement of JJ stents, ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), shock-wave lithotripsy (ESWL), cystoscopy, urodynamics, cystectomy, care of stoma bag and transurethral resection of bladder tumors (TURBT). More are on the way, so stay tuned.

Reference 1. Winter M, et al. The use of portable video media vs standard verbal communication in the urological consent process: a multicentre, randomised controlled, crossover trial. BJUI 2016;118:823-828

Sunday 18 March 11.30-14.35: Special Session, EAU Patient Information Session

ENUCLEATION OF THE PROSTATE using Hemera Pulsed Thulium laser with updated settings

Dr J.B Roche

Groupe Urologie Saint- Augustin - Bordeaux (Fr) In this video, we will present a laser prostate enucleation using updated settings, along with a modified en bloc dissection. At last year’s ESUT session, we showed an original approach to enucleation using a pulsed Thulium laser.

For better performance, we changed settings to achieve a better bubble effect, thus achieving a clearer enucleation plane.

We will show how the thulium laser used in a pulsed mode can be combined with a minimally invasive endoscopic technique to treat large prostatic adenomas.

Pre-recorded video

March, 17th 16:54

eUro Auditorium (Level 0)

Procedure performed with 200 W Hemera ® Thulium Rocamed Laser

EUT Congress News

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Pre- and post-testing ensure course excellence Should evaluation tests be standardised?

Prof. Dr. J.M. Nijman UMC Groningen Chairman, EU-ACME Groningen (NL)

The quality and calibre of the courses organised by the European School of Urology (ESU) are its bedrock.

To ensure the excellence these courses are known for, pre- and post-tests were created.

Do I think these tests should be standardised?

Absolutely. I am a firm believer in this way of education. Read on to understand why.

What are pre- and post-tests?

Pre- and post-tests are tools to gauge the participants’ knowledge. How much do they know about the topics before they take the ESU courses? How much did they learn afterwards? Comprised of multiple-choice questions, the results of these tests will also determine which of the course topics need priority and emphasis.

Through these tests, the faculty can also evaluate if their delivery and teaching methods are effective, and which areas need fine-tuning. These tests are also good indicators of the quality of the course materials.

courses. If proven successful, these tests will continue in future congresses and be more prominent with stand-alone ESU Courses scheduled throughout the year. Educational activities are increasing and industry, one of the main providers and promoters, want to see that attendees are really improving their knowledge and it is worthwhile, from the teaching point of view, to invest.

Goal of the pre-test The pre-tests are designed to prompt the participants to prepare before attending the courses. One of the aims is for participants to answer questions via a digital platform two to three weeks before a course. The faculty will have ample time to adapt those answers and incorporate them into the programme and their presentations during the courses.

After participants take the pre-test, their results are used by the faculty as the basis to calibrate the courses and to improve them. And since most courses cover a variety of topics in a compact timeframe, topics will be streamlined by focusing on those that are not as familiar to participants and those that need more emphasis.

Post-test relevance After the completion of each course, participants will be asked to answer the same questions from the pre-test two to four weeks later. They can even do this at home. Their answers will provide significant

Pre- and post-tests were also created to satisfy the regulatory bodies of the Continuing Medical Education (CME) in several European countries and the Union Européenne des Médecins Spécialistes (UEMS). In some countries, it is even mandatory to organise these tests to qualify for CME credits.

During the Annual EAU Congress here in Copenhagen, the pre- and post-tests will accompany 10 selected

Some ESU courses accompanied by pre- and post-tests

How strong is your team?

Earlier version of the post-testing

insights that can assist the faculty. This feedback can also be used to improve the ESU courses in the following year.

Benefits for participants The pre-test will give participants an overview of specific topics that are important per course. The post-test will provide feedback to participants regarding their performance. Since the post-test is implemented weeks following the course, a higher score compared to the pre-test score indicates an increase in knowledge. A higher score also means the participants were able to retain their newly-acquired knowledge.

How the tests help the faculty Through the pre-test, the faculty will have a better understanding and overview of the participants’ current level of knowledge (or lack thereof). Their collective test results will give the faculty an indication which course topics require additional focus and progression, and which topics to skip.

The post-course test will also provide feedback on the faculty’s quality of

Sample overview of test results

teaching, their methods and delivery. The test may prompt them to revise presentations for the following year, encourage them to retain what works and/or change their teaching approach.

Improved through the years In the initial stages of the tests, questions were asked at the beginning of a course and the same questions were asked at the end of that course. The purpose was to see if the percentage of correctly answered questions would be higher after following a course. It was an immediate way to measure the impact of a course on the knowledge of the participants.

Last year, three courses were selected for a new way of testing wherein the faculty were asked to make the multiple-choice questions themselves based on the content of their courses.

To reiterate, if the pre- and post-tests are proven successful the aim is to include these tests in all courses during Annual EAU Congresses and, eventually, all stand-alone ESU courses. Although this has actually been done in the recent past, the wider aim is for consistent implementation in order to support both faculty and participants.

Education Online Improve your skills: e-learning at your own convenience

Our society is ageing at a rapid pace

Leading to an increased demand for urological services

We need to optimise patient care

Ensure an extended role of nursing colleagues

Invest in your clinical staff to optimise your multidisciplinary team

Your team is only as good as the weakest link

Your team is good - make it great!

Check out the new Guidelines E-course on Thromboprophylaxis Coming soon: • Sexual dysfunction, Infertility & Hypogonadism and LUTS (Lower Urinary Tract Symptoms) • NMIBC (Non-Muscle Invasive Bladder Cancer)

High standard, up-to-date courses

Free access with MyEAU account

Guidelines and topic-specific courses

Visit the EAUN counter (at the EAU booth (H69) in the Exhibition) to learn more about evidence-based nursing education and our membership offer: register 3 members of nursing staff, pay for only 2.

www.eaun.uroweb.org 22

EUT Congress News

All information is in line with the EAU Clinical Guidelines Prepared by urologists from all over Europe All accredited courses comply with the EU-ACME and UEMS/EACCME guidelines for e-learning

uroweb.org/education/online-education/ Sunday, 18 March 2018

Can I still use mesh for POP repair?

Mesh controversy prompts the need for better communication and consensus on quality standards Dr. Tufan Tarcan Professor of Urology Marmara University School of Medicine Istanbul (TR)

Despite the significant efforts of the scientific community to produce clear guidelines, the mesh controversy continues, affecting, in particular, national regulatory organizations and patient associations.

Indeed, the SCENIHR and European Urology Association (EAU) and European Urogynaecological Association (EUGA) statements have brought important insights to the controversy1,2. Both reports have investigated the current evidence and established a multidisciplinary consensus statement that included clear guidelines on the use of implanted materials for treating pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Meanwhile, patient associations have joined the debate and are putting more pressure on legal authorities to ban surgical meshes used in pelvic surgery.

Although, the number of patients participating in the lawsuits is relatively low compared to the number of patients with mesh repair, the impact of these unfortunate and disastrous cases is certainly very high and creates a significant public health problem that needs further attention. On the other hand, the national regulatory authorities are conducting their own assessments and taking legal actions, such as banning the use of transvaginal surgical mesh for the repair of POP or even banning mini slings for the repair of SUI in some countries3-5.

Unfortunately, the media-driven public hypersensitivity on surgical meshes is now being directed on mid-urethral synthetic sling (MUSS), although no current scientific evidence supports this perception. Under the light of these developments, urologists and urogynecologists would like to know whether they can still use synthetic meshes in pelvic surgery.

Has there been any change in the scientific evidence since the 2017 EAU/EUGA consensus statement?

The answer to this question is simply “No”, and the recently published statement should still be the primary guideline for the use of meshes in pelvic surgery. Briefly, the EAU/EUGA consensus statement has indicated that there is no clear advantage of transvaginal mesh in primary POP repair over native tissue, but mesh repair is associated with a higher complication and re-operation rate2. The risk of a mesh increases with its surface area and, thereby, its increasing density. In this context, a clear distinction should be drawn between the tape used for a MUSS and the larger amount of mesh used to treat POP2.

Accordingly, the efficacy and use of implanted tapes for SUI is evident and they can be recommended for use in clinical practice. In contrary, vaginallyimplanted mesh for POP is associated with increased risks. Therefore, its use should be restricted to expert individuals working in specialized departments and to complicated secondary cases. Whilst the risk associated with the trans-abdominal insertion of mesh for POP is considered more acceptable, its use should also be restricted to specialist practice2.

Supporting the aforementioned statement on transvaginal meshes, a recent randomized trial comparing the seven-year outcome of trocar-guided vaginal mesh with native tissue in recurrent POP has found similar composite success rates for mesh and native tissue. Repeat surgery rates were similar for both groups6. Mesh did not reduce long-term repeat surgery rates due to de novo POP in non-meshtreated vaginal compartments. Mesh exposure rates were high, but significant differences in pain and dyspareunia were not detected6.

The strong need for phenotyping patients exposed to synthetic meshes during pelvic surgery.

According to current evidence, three different risk groups have been identified by the consensus statement of the EAU/EUGA for the use of synthetic meshes: Sunday, 18 March 2018

1. Synthetic meshes for treatment of SUI (may be further sub-classified to MUSS and mini-slings); 2. Trans-abdominal synthetic meshes for the treatment of POP; and 3. Trans-vaginal synthetic meshes for the treatment of POP According to EAU/EUGA consensus, whilst the risk associated with the transabdominal insertion of mesh for POP is considered more acceptable, its use should also be restricted to specialist practice2. On the other hand, the use of MUSS for surgical treatment of SUI in both male and female patients is associated with good efficacy and acceptable morbidity2.

in pelvic surgery. The use of synthetic mesh in the treatment of POP should be restricted to expert individuals working in specialized departments and to complicated or secondary cases, preferably as a part of prospective research. It should also be clearly emphasized that MUSS have proven their long-term efficacy and safety and should not be sacrificed by an overreaction to synthetic slings. On the other hand, the efforts to find a better material for pelvic support must continue and be supported by government funds to find a permanent solution for this public health problem.

Recently, the Therapeutic Goods Administration (TGA) in Australia has decided to remove the use of mesh References products in the treatment of POP and single incision 1) SCENIHR, 2015. Final opinion on the safety mini-slings to treat SUI from the Australian Register of of surgical meshes used in Therapeutic Goods (ARTG)3. This decision was based urogynecological surgery, Available at: on their review which revealed that “the benefits do Shrinking of mesh on anterior vaginal wall (Photo: EUT Archives) http://ec.europa.eu/health/scientific_ not outweigh the risks these products pose to committees/emerging/docs/scenihr_o_049.pdf. patients”. The TGA has further noted that mini-slings 2) Chapple CR, Cruz F, Deffieux X, et al. Consensus are different devices compared with MUSS, and Statement of the European Urology Association and the vaginal-transvaginal-tvt-sling-the-mesh-scandal-nicetherefore MUSS were not removed from the ARTG. European Urogynaecological Association on the Use of guidelines-health-watchdog-nhs-suiHowever, this distinction between meshes used for POP repair and MUSS has not been always considered by the national regulatory organizations, and may even be more difficult to understand by our patients. Thus, there is a growing pressure coming from patient groups and media to ban the use of mesh completely from pelvic surgery4. For example, a “Sling the Mesh” campaign group now has more than 3,000 members and strongly advocates the prohibition of all kind of meshes used in pelvic surgery. Following the TGA decision in Australia, New Zealand has banned in January 2018 the use of all surgical mesh products whose sole use is the treatment of POP via transvaginal implantation and one product, a single incision mini-sling for the treatment of SUI (5). Although, not officially released yet, there has been news on the media about a draft guideline by NICE in UK that will recommend that mesh should be banned as a routine treatment for POP, and mesh implants for POP repair should only be used for research purposes7.

The recommendations of regulatory organizations on transvaginal meshes for POP repair are actually in parallel to the EAU/EUGA consensus which already stated that synthetic meshes for treating POP should be used only in complex secondary cases in specialist referral centers or as a part of research trial2.

Therefore, one can comment that more or less an overall consensus has been reached on vaginal meshes in POP repair.

It is strongly recommended that urologists and uro-gynecologists should follow the instructions of EAU/EUGA consensus until they are updated or changed with the new evidence2. However, the situation is becoming more complicated and blurry for transabdominal mesh-augmented POP repairs and even for MUSS. Although, synthetic slings are recommended to be safe in the surgical treatment of SUI in both male and female patients, this distinction draws little attention from the media and patient organizations2.

The 2011 US Food and Drug Administration (FDA) updated notification about the use of mesh in the treatment of POP was a milestone in POP repair history but also created a hypersensitivity not only for mesh augmented POP repairs but also for MUSS8. A recent study has investigated the news in the media about surgical meshes following this notification and found that only 40% of articles that first reported the announcement accurately specified that it applies to mesh for POP, not incontinence9. This misinformation has certainly affected the perception of the patients about surgical meshes and increased the level of anxiety on any kind of synthetic mesh indication. For example, a recent study has reported that patients in New Zealand have now developed a fear of mesh abdominal wall hernia repair due to inaccurate media reporting9.

Implanted Materials for Treating Pelvic Organ Prolapse and Stress Urinary Incontinence. Eur Urol. 2017; 72(3):424-431.

3) The alert of The Therapeutic Goods Administration, Department of Health, Australian Government https:// www.tga.gov.au/alert/tga-actions-after-reviewurogynaecological-surgical-mesh-implants. 22 December 2017.

4) https://news.sky.com/story/vaginal-mesh-use-shouldbe-restricted-to-research-only-says-healthwatchdog-11171079.

5) http://www.medsafe.govt.nz/hot/alerts/ UrogynaecologicaSurgicalMeshImplants.asp 6) Milani AL, Damoiseaux A, IntHout J, Kluivers KB, Withagen MIJ. Long-term outcome of vaginal mesh or n ative tissue in recurrent prolapse: a randomized controlled trial. Int Urogynecol J. 2017 Nov 22. doi: 10.1007/s00192-017-3512-3. [Epub ahead of print] 7) http://www.independent.co.uk/news/uk/home-news/

incontinence-a8111721.html 8) US FDA 2011. Urogynecologic Surgical Mesh: Update on the Safety and Effectiveness of Transvaginal Placement for Pelvic Organ Prolapse; 13 July 2011. http://www.fda. gov/downloads/MedicalDevices/Safety/AlertsandNotices/ UCM262760.pdf (accessed January 2017) 9) Koo K, Gormley EA. Transvaginal mesh in the media following the 2011 US food and drug administration public health notification update. Neurourol Urodyn. 2017 Feb;36(2):329-332.

10) Kelly S. Mesh abdominal wall hernia surgery is safe and effective- the harm New Zealand media has done. N Z Med J. 2017 6;130(1463):54-57.

Sunday 18 March 10.30-12.00: Thematic Session 5; Avoiding, managing and responding to pelvic floor surgical complications

28 - 31 August

Leading Continence Research and Education Call for Abstracts: 1 March - 3 April International Continence Society 48th Annual Meeting www.ics.org/2018

Alan J. Wein

Diane Newman

Roger R. Dmochowski

Lori Birder

Chairman

Scientific Co-Chair

Co-Chairman

Scientific Co-Chair

Impact of mesh controversy The mesh controversy is not over, but in contrary it is growing and affecting the practice of urologists and uro-gynecologists who treat POP and SUI. An effective communication is needed among medical associations, patient organizations and legal authorities to reach a consensus and improve the quality of medical help for our patients.

The 2017 EAU/EUGA consensus statement presents the rules for a good clinical practice for the use of mesh EUT Congress News

23

Introducing the newest member of our family of journals, European Urology Oncology.

The Editorial Team

We’re bringing together multiple disciplines — including urology, medical oncology and radiation oncology — to achieve one goal: to advance research in urological oncology.

Join our community of authors and reviewers collaborating for the benefit of patients in every corner of the world.

If you’ve got practice changing, groundbreaking research in urological oncology we hope to hear from you.

Submit your paper today: ees.elsevier.com/euonco

Alberto Briganti M.D., Ph.D. Editor in Chief Associate Professor of Urology, Vita-Salute University San Raffaele, Milan, Italy Laurence Albiges M.D., Ph.D. Associate Editor Medical Oncologist, Head of the Genitourinary Unit at Gustave Roussy Institute, Villejuif, France Gianluca Giannarini M.D. Associate Editor Urologist, Academic Medical Centre Santa Maria della Misericordia, Udine, Italy

Ashish M. Kamat M.D., M.B.B.S. Associate Editor Professor of Urologic Oncology & Cancer Research, The University of Texas, MD Anderson Cancer Center, Houston, US Paul Nguyen M.D. Associate Editor Associate Professor of Radiation Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, US

europeanurology.com/euoncology

Power. Flexibility. Usability.

Richard Wolf at EAU18

Hall C, Booth E 45 Developed to impress Multifunctional One laser for two procedures: Lithotripsy & Enucleation Powerful Power: 70 watts Energy: 5.0 joules Frequency: 60 hertz Unique Power Laser Fiber to maximize power output Intuitive Laser fibers can be identified within the aseptic package

Visit our website: megapulse70plus.richard-wolf.com

24

205_17_MegaPulse70plus_270_194_en_EAU18_day2.indd 1

EUT Congress News

70 W Holmium:YAG Laser System for Lithotripsy & Enucleation 05.02.2018 10:49:48

Sunday, 18 March 2018

Prostate cancer molecular and genetic biomarkers Biomarkers, imaging, and risk assessment tools continue to impact decision-making strategies

The ESUO’s second meeting once again demonstrated the growing need for an office urology perspective, in particular in the office management of the everprevalent prostate cancer.

ESUO addresses the core issues that impact the work and interests of urologists who provide comprehensive out-patient care in their own office environment. As opposed to a hospital’s out-patient department, office urologists single-handedly manage the full breadth of urological conditions on a daily basis, while collaborating closely with clinics on the one hand, and general practitioners on the other.

ESUO aims to provide support to office urologists, particularly with regards to scientific, clinical and professional information related to their specialty.

All about prostate biopsy in an office urology and outpatient setting The ESUO Section Meeting focused on practical office topics of biopsy and re-biopsy indications, the growing prostate cancer biomarker field, patient biopsy preparation, biopsy procedure, management of biopsy complications, the roles of TRUS and MRI biopsy guidance, as well as TRUS-MRI fusion biopsy.

It is impossible to overstate the relevance of these topics. Prostate biopsy is one of the most commonly performed office procedures in urology. Of the estimated 1.1 million men globally who are diagnosed with prostate cancer each year, about 225,000 are Europeans.

The last decades have seen a dramatic increase in prostate cancer incidence due to widespread PSA testing, increased male life expectancy, and an increase in the total number of men undergoing prostate biopsy. Prostate biopsy that is triggered solely by prostate-specific antigen (PSA) and digital rectal exam (DRE), carries the inherent risk of false-negative findings and leads to over-diagnosis of clinically indolent prostate cancer.

PSA has a positive predictive value for prostate cancer detection in the range of 25-40%, while it’s use to trigger prostate biopsy leads to negative biopsies in 65-70% of men presenting with a PSA in the range of 4-10ng/ml. Moreover, we have witnessed a shift away from the sensitivity to diagnose all cancers to more advanced diagnostic methods that improve the specificity to the discovery of the aggressive, high-grade prostate cancers.

During this period, the reputation of PSA was transformed from an initial “great” biomarker to “good” due to low-specificity, to “bad” as a trigger for over-diagnosis and over-treatment, to supposedly “harmful,” prompting the controversial US Preventive Services Task Force (USPSTF) recommendation against PSA screening in 2012. Five years later the USPSTF “scraped the congealed egg from its face with a dull knife” (quoting Prof. Benjamin Davies) and revised its position.

The current 2017 USPSTF guidelines recommend individualized screening of men aged 55-69, while conceding that screening does offer a small potential benefit of reducing the chance of dying from prostate cancer. The EAU Guidelines state: “Do not subject men to PSA testing without counselling them on the potential risks and benefits” (Level of Evidence 3, Recommendation Grade B), as well as “offer an individualised risk-adapted strategy for early detection to a well-informed man with a good performance status and a life-expectancy of at least 10 to 15 years” (Level of Evidence 3, Recommendation Grade B). The topic of prostate cancer screening (particularly with Sunday, 18 March 2018

Multiparametric prostate MRI, alongside biomarkers, has an EAU Guidelines designated role in the post-negative biopsy setting, while the National Comprehensive Cancer Network (NCCN) guidelines have gone further — providing a recommendation for biomarker and mpMRI use in the pre-biopsy setting.

Early use of biomarkers and mpMRI is inevitably the direction we are moving in.

During the ESUO meeting it was a privilege to discuss the dynamic topic of molecular and genetic biomarkers in the primary and secondary biopsy decision-making setting. At the dawn of the PSA-era, we are in the age of a growing need for liquid-biopsy biomarkers and risk stratification tools, for the non-invasive risk assessment of prostate-bearing men. By this time, we as urologists really need to know and use the available tools to avoid the pitfalls of PSA testing. At the same time, with so many options to choose from – highquality clinical validation is key, although often scarce.

ExoDx Prostate When you and your patient do make the informed decision to perform a prostate biopsy, make (Intelliscore) is unique in sure the quality of the sampling is maximal and in accordance with EAU Guidelines (Photo: S. that it has opened a new Czarniecki) category of urine-based biomarker tests – which need not be preceded by a conscientious DRE (as do Prostate cancer biomarkers, imaging, and risk PCA3 and SelectMDx). It is an exosome-based test – assessment tools will continue to transform the way we which means that the testing is performed on the urologists deal with prostate cancer detection at the protein and RNA content of cellular exosomes dawn of the PSA era. physiologically secreted from cells. The exosome content originating from cells of clinically significant Saturday 17 March prostate cancer is highly representative of their source.

10.15-14.00: Meeting of the EAU Section of A negative predictive value (NPV) of 97.5% should put Urologists in Office (ESUO) this new test in the scope of interest of urologists All about prostate biopsy in an office urology and seeking tools to decide whether it is justified to take a outpatient setting biopsy needle out of its sterile pouch.

What’s new and relevant in PCa biomarkers?

The EAU Guidelines recommendations have been well-defined and are readily available.

Blood-based biomarkers such as the 4K Score Test and prostate health index (PHI) have been recognized as the best studied. 4K Score has been shown to predict biopsy outcome more accurately than PSA and age alone, and with the addition of clinical information in the algorithm to have a solid diagnostic performance (AUC 0.82) in predicting clinically significant prostate cancer (Gleason Group Grade 4 and above) upon biopsy.

1.00

0.75

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0 0

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1 – Specificity

Official Scientific Journal Deutsche Gesellschaft für Urologie

The past year has seen the publication of a large meta-analysis which has shown evidence of 4K Score superiority over PHI in 11 of 12 clinical validation studies comprising of a total of 11,134 men as well as an interesting publication demonstrating near-equal clinical validity of 4K Score with or without DRE. Another multi-center prospective trial was also concluded demonstrating validity in a population with a large proportion of African-American men, bringing the total number of men involved in the 4K Score validation to an impressive >22,000.

Prostate Cancer Gene 3 (PCA3) is the other established EAU Guidelines recommended (post-DRE urine-based) prostate cancer biomarker. However, results of studies on the role of PCA3 in predicting clinical-pathological features of prostate cancer (Gleason Score, tumour volume, stage, extraprostatic extension) have been disappointingly contradictory. The three-gene urinary-panel (HOXC6, DLX1, TDRD1) developed at the same Nijmegen (NL) laboratory as PCA3 forms the basis of SelectMDx, which also includes clinical data, and can be used accurately to identify patients with clinically significant prostate cancer (AUC 0.78).

SelectMDx and mpMRI In the face of scarce head-to-head comparative biomarker studies, an interesting paper recently matched SelectMDx and mpMRI showing promising results regarding the correlation between the SelectMDx result and mpMRI standardized assessment.

SelectMDx outperformed PSA and PCA3 to predict mpMRI outcome (AUA ROC 0.83 vs. 0.66 and 0.65, respectively), with SelectMDx scores being significantly higher in men with PI-RADS 4-5 lesions on mpMRI.

Editorial Board Editors M.P. Wirth, Dresden O.W. Hakenberg, Rostock D. Castro-Diaz, Santa Cruz de Tenerife B. Wullich, Erlangen

Editorial Committee A. Briganti, Milan S. Egawa, Tokyo S. Madersbacher, Vienna M.S. Michel, Mannheim V. Mirone, Naples R. Mundy, London J. Nordling, Herlev M. Porena, Perugia J.J. Rassweiler, Heilbronn H. Rübben, Essen A. Stenzl, Tübingen J. Stolzenburg, Leipzig Y. Sun, Shanghai Language: English ISSN 0042–1138 (print) e-ISSN 1423–0399 (online)

Urologia Internationalis offers many benefits to authors: Cost-effective publishing No submission fee, free online color figures, no page limit, no publication fee for papers of 3 printed pages or less.

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The EAU Section of Urologists in Office (ESUO) held its inaugural meeting last year during the 32nd Annual European Association of Urology Congress (EAU17) in London. Here in Copenhagen for EAU18, the ESOU Section Meeting has “All about prostate biopsy in an office urology and outpatient setting” as its theme.

Unfortunately, promising tests such as the STHLM3 Model (Stockholm 3 Crucial implications model) and MiPS have The dramatic implications of the low specificity of PSA availability limited in for prostate cancer has led to an explosion of research Europe and the USA, into to the development and validation of tools to respectively. Their facilitate patient risk stratification and, particularly, to validation is also limited better guide prostate biopsy decision. The aim is, (as of this writing). frankly, to identify those men who truly harbor Interestingly, STHLM3 clinically significant disease, while leaving at peace is an example of a those with disease that will never impact their still evolving prostate life-expectancy, keeping away the biopsy needle. cancer biomarker, the algorithm was With that said, it is crucial to remember that the vast recently updated by majority of actual PSA testing occurs by order of the taking intact PSA out of general practitioners in most countries. This is the the formula and elephant in the room when urologists discuss PSA including HOXB13 instead screening.

- contributing to an improvement of AUC Novel tools that may aid the urologist include molecular from 0.74 from 0.75. and genetic biomarkers, which augment the specificity At the same time, it of prostate biopsy for clinically significant disease. continues to be studied Likewise, multiparametric prostate magnetic resonance within an exceptionally imaging (mpMRI) has allowed for the non-invasive homogenous Northern image-guided risk identification of clinically significant European population prostate cancer, as well as targeting. of men.

PSA and DRE as triggers for prostate biopsy) remains one of the most controversial topics in urology.

Sensitivity

Dr. Stefan W. Czarniecki HIFU CLINIC Prostate Cancer Center Warsaw (PL) @DrCzarniecki

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Anatrophic nephrolithotomy: Safe and effective treatment The lost art of open stone surgery for huge complex complete staghorn stone Dr. Toe Lwin Professor of Urology University of Medicine Yangon Yangon (MM)

Since the availability of ESWL and PCNL , the role of open surgery for renal stone has diminished.

Nevertheless, large complete complex stag horn stone C5 ( Rocco) remains a challenge for the noninvasive and minimally invasive procedures because of the requirements of additional or auxiliary procedures for stone clearance which lead to higher costs for the patients.

If PCNL alone is chosen for these stones, multiple access is unavoidable and that can cause more bleeding, necessitating blood transfusion. Complete complex stag horn stones are more commonly encountered in Asian countries for various reasons.

Cost effectiveness is a priority and majority of the hospitals cannot afford multiple treatment modalities for treatment of stones although tertiary hospitals can. We have tried laparoscopic surgery on large renal stones. We found out that single large stone, one or two stones in a single system or in the pelvis are suitable for laparoscopic surgery, but complex complete stag horn stones demand longer operation time hampering renal function.

Figure 6

Figure 3

Renal artery can be branched early and in these cases, both anterior and posterior branches need to be identified. Polar artery and lower pole aberrant artery should not be missed, if present. The key to success of further steps depends on successful identification and control of all arteries and arterial branches supplying the kidney. After identifying all arteries, these are ‘slinged’ individually. Our practice is using normal saline ice sludge to cool down the kidney for 10 minutes. (Figure 4)

Thus open surgery, anatrophic nephrolithotomy, is more commonly done for these cases. According to the literature, even in high-volume stone centers in developed countries, open surgery has to be done for these selected cases. Therefore, modern urological surgeons should be adept in the art of open stone surgery.

Figure 4

Preoperative antibiotics as dictated by urine C&S need to be given at the time of induction. Procedure is usually done under general anaethesia and patient placed in the lateral kidney position, flexed to widen the area between costal margin and ilaic crest.

Ten-minute immersion can cool down the core temperature of the kidney down to 15 degree centigrade and that state allows 30 minutes of warm ischemia time without impairing renal function.

The whole process must be finished in 20 to 30 minutes. Then, the arterial clamps are removed and bleeding from kidney incision or bleeding from inside the calyces, flowing down to pelvis and ureter needs to be checked. Some oozing from incision line can be stopped by compression with the swab for a few minutes. If there is persistent oozing or bleeding, test pressing the kidney from outside to control bleeding, and a new bite with Chromic or vicryl 20 on that particular site will stop the bleeding.

“Complete complex stag horn stones are more commonly encountered in Asian countries for various reasons. Cost effectiveness is a priority and majority of the hospitals cannot afford multiple treatment modalities...”

Figure 7

of renal function after surgery, post-operative functional study was done at one month. According to our study, we found out that renal function was improved in cases where there was reasonable parenchymal tissue and where there was significant obstruction.

In conclusion, open surgery anatrophic nephrolithotomy is a safe and effective treatment option for large complete complex stag horn stone, provided morbidity associated with large incision can be accepted.

Post-operative KUB is taken on the fourth day and discharge of the patient is usually on the fifth to the seventh day. In our 18-year study, Stone Free Rate(SFR) is 94.6%. SFR of initial four years is less than the latter part of the study. Due to the concern

Friday 16 March 09.15-12.15: Urology Beyond Europe, Joint Session of the European Association of Urology (EAU) and the Federation of ASEAN Urological Associations (FAUA)

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Live Demos by the Experts Figure 1

Incision is usually supra 12 (Figure 1) and in obese patients, through 12th rib incision may be necessary for better exposure. Usually, incision can be extended laterally about 1 to 2cm from the tip of 12th rib, but care must be taken not to open pleura that can be done by reflecting the diaphragm with the finger internally. Adequate exposure is essential to facilitate further steps. Gerota fascia is opened up and lower pole of the kidney is mobilised.

Figure 5

After that, the main renal artery or all arterial branches are temporarily clamped with bull-dog clamp/s. Incision is made along the Brodel’s line which is one third of the distance from cortical border to hilum. (Figure 5) If all renal artery branches are controlled, there is very minimal bleeding from the veins. All the stones are easily identified and removed. Those hidden in calyces can be detected by per-operative ultrasound and fluoroscopy and removed.

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When all stones are removed, infudibuloplasty is done to make the whole complex multiple calyceal systems into a single large calyceal system. (Figure 6) That can minimize the chance of recurrent stone formation as stasis can be reduced. Infundibuloplasty joins the sides of adjacent infundibula as shown in the figure. After that, the double J stent is inserted into ureter.

Figure 2

In doing so, we need to know that if there is extensive perinephric inflammation and adhesions, IVC can be very close and stuck to lower pole, and proper care is essential not to tear IVC accidentally. (Figure 2) In upper pole, adrenal can be separated easily in most cases. Then, mobilised kidney is raised up by a sling and renal artery is identified (Figure 3) 26

EUT Congress News

Thereafter, the opened-up kidney has to be closed back. The inner layer is approximated tidily by vicryl 30 with round needle 20mm or 26 mm in continuous fashion. The bites should not be deep into parenchyma tissue. Approximation of this inner layer must close up all calyceal system. Outer layer, that is cortical border, is closed with 20 Vicryl or Chromic with round needle 40 mm in vertical mattress fashion.

(Figure 7) Again, the bites should not be deep.

Sunday, 18 March 2018

Developing a urology nursing educational curriculum Challenge of curriculum development requires collective will and action Jerome Marley RN, MSc Member EAUN Scientific Congress Office Lecturer in Nursing Ulster University Belfast (NI) jt.marley@ ulster.ac.uk Around 475 BC, the philosopher Heraclitus wrote “The only thing that is constant is change”.

Our experience as urology nurses would surely support this view. Each day we wrestle with the seemingly ever-increasing demands of healthcare, set against the context of governments’ inability to fund such care to the extent it requires. And it could be argued that pressures on healthcare systems and professionals would not get better anytime soon.

In 2015, the United Nations published the DESA Report [Department of Economics and Social Affairs] which indicated that the current world population of 7.3 billion is expected to reach 8.5 billion by 2030 (12 years from now), 9.7 billion in 2050 (32 years from now) and 11.2 billion in 2100 (82 years from now). Set alongside these predictions, the UN also suggest that Europe will see a significant ageing of its population in the next several decades with an estimated 34% of the population projected to be over 60 years old by 2050. Of course, these are headline statistics, the accuracy of which needs further investigation.

However, if what is predicted is close to being true, then we will need to boost our creativity and prepare for the challenges ahead. The care offered by urology nurses will become even more vital in the years ahead and now is the time for us to consider how best we can increase our readiness to understand,

engage with and meet those challenges. What do we want our role to be and how are we to prepare ourselves and those who will follow us to do what is needed? These are big questions, very big questions indeed; they are easily asked, but more difficult to answer.

At this year’s EAUN Congress in Copenhagen, we will have an initial session where we join others to start the process of providing answers and to plan our educational future; we ask you to join us in this task.

We fully respect the determined and often unacknowledged efforts of individuals, organisations and institutions across the continent who work hard to offer educational provision in urology. However, notwithstanding their efforts, it remains that in Europe there are presently no agreed principles to guide our educational development.

Simply put, we do not have a curriculum, understood and agreed by all, that provides structure to how we educate ourselves to meet the urology nursing needs of tomorrow. What do we mean by a curriculum?

Broadly speaking, our understanding of a ‘curriculum’ is that it is similar to a roadmap that highlights the commonly agreed educational and practice landmarks that are important in the road ahead. Such a map could be used by individual countries to guide local education that enhances the role of urology nurses and the specific needs of the country itself. To assist us in this task, here in Copenhagen we will start by considering four key questions: 1. If we think of a curriculum as a ‘map’ that highlights key content for urology nursing; do we need such a map, and if ‘yes’, what should the content of the map include and why?

2. Across Europe we are not an all-graduate profession, we have considerable diversity in our educational preparation and practice, and no country has explicit routes or requirements for prescribed urology nurse education. So, at what level do we require our curriculum to be delivered?

4. If we succeed in writing a urological nursing curriculum, how should it be used?

Along with others, the EAUN also believes that now is the time for us to work to create a curriculum to ensure that urology nursing is increasingly fit for purpose, practice and award in the 21st century. We need you to help us do that.

During EAUN 2018, a ‘world café’ event will consider the fundamental issues mentioned above and your views will be vitally important. Rarely do we have the opportunity to participate so radically in a project that can fundamentally effect our collective future – but here in Copenhagen we will do just that.

be up to the task or we won’t. Urology nurses collectively have the experience, desire and ability to influence the future of urology healthcare across Europe, in an ever more positive, demonstrable and patient-centred way. It is this belief that drives our desire to develop a curriculum that will provide clear and agreed direction and recognition for urology nurse education to the benefit of all nurses in Europe, no matter where we practise. These are exciting times and we look forward to hear your views on what our tomorrow should be.

Reference United Nations (2015) World Population Prospects - The 2015 Revision. ttps://esa.un.org/unpd/wpp/publications/files/ key_findings_wpp_2015.pdf

If the only constant really is change, then it seems inevitable that more and more demands will be made of us in the years ahead, and rightly so. Either we will

Sunday 18 March 16.15 – 17.30: 19th International EAUN Meeting Specialty Session 3, Creating OUR Urology Nursing Curriculum – at the “no fairy-tale café” Green Area, Room 11 (Level 1)

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STEPS Sessions To Evaluate luate ProgresS Progres o in the management of urological cancers

3. Do we need to collaborate with others in writing a urological nursing curriculum, and if so, who should our collaborators be?

Learning from Experts in Onco-Urology Applications now open!

Visit Ipsen booth E15 during EAU18 to learn more

What is STEPS? STEPS, or “Sessions To Evaluate ProgresS in the management of urological cancers”, is a programme specifically designed for recently specialised onco-urologists who want to learn directly from worldleading experts in bladder, prostate, renal and testicular cancers.

The CME-accredited programme is a fundamental part of the EAU/ ESOU strategic partnership with Ipsen. It is founded on our shared commitment to the education of young urologists.

Bringing together a multinational group of medical professionals across several areas of expertise, and with different experiences, allows the fellows to see a variety of new treatment possibilities.

It can highlight the pitfalls and solutions provided by diverse approaches. It also opens the door to creating international ties among medical practitioners, and a networking opportunity that can prove invaluable for the careers of young clinicians.

“STEPS connects younger urologists from different countries – it’s very interactive with lots of new information and data discussed” STEPS fellow 2018

To date, 20 different internationally recognised experts, supported by the ESOU Board, have inspired 138 fellows from 29 countries – and our objective is to continue supporting STEPS to help improve the management of all patients with urological cancers.

Who should apply?

Recently specialised clinicians with a firm interest in the management of urological cancers, who: - Can demonstrate support from their Head of Department

Next event: Meet-the-Expert Session during the 16th Meeting of the EAU Section of Oncological Urology (ESOU) Saturday 19th January 2019 Prague, Czech Republic

- Are keen to participate in ESOU and EAU programs - Understand and speak English fluently “Within STEPS I really like the enthusiasm of the delegates and the interaction I can have with them as an expert” Peter Mulders, STEPS mentor 2018

Find out more about STEPS from the ESOU website: http://uroweb.org/section/esou/information/

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ESOU is an independent 3rd party meeting. Travel, accommodation, registration and subsistence costs are supported by Ipsen.

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