EUT Congress News - Saturday 25 March by European Association of Urology (EAU)

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32nd Annual Congress of the European Association of Urology

Saturday, 25 March 2017

London, 24-28 March 2017

EAU17: Addressing the challenges in medicine Sir Bruce Keogh: ‘Professional links are crucial to counter challenges’ By Joel Vega and Erika de Groot

The Opening Ceremony also highlighted this year’s awardees with Prof. Paul Abrams (GB) taking the EAU’s top honour, the Willy Gregoir Medal 2017. Also recognized were Prof. Per-Anders Abrahamsson (SE) who received the Frans Debruyne Lifetime Achievement Award, Prof. Christian Gratzke winner of the Crystal Matula, Dr. Riccardo Autorino (US) who won the Hans Marberger Award, Mr. Richard Turner-Warwick (GB) awarded with the Innovators Urology Award, and Dr. Masaki Shiota (JP) who received the Prostate Cancer Research Award. Recipients of this year’s Honorary Member titles were Professors Shin Egawa (JP), Tomas Hanus (CZ), Vito Pansadoro (IT), Eduardo Solsona (ES) and Dr. Patrick Walsh (US).

To the beat of drums and the blare of trumpets played by a uniformed 20-plus-member marching band, London welcomed participants to the 32 nd EAU Annual Congress (EAU17), the second annual congress held in the United Kingdom since 2002. “Whatever happens, meetings like this are vitally important since it is at these occasions that knowledge and professional links are developed, and at these events ideas take seed and take hold: the important ideas that will later lead to significant work and progress in medicine,” said Prof. Sir Bruce Keogh, NHS England’s Medical Director and Commissioner of the Commission for Health Improvement (CHI). Keogh noted the manifold challenges healthcare systems around the world are facing as he threw the challenge that physicians need to do better by strengthening their links across disciplines. EAU Secretary General Prof. Chris Chapple reiterated Keogh’s statements when he mentioned that the EAU has recently earned a reference network status with the European Commission.

“A challenge for urology is to carry the quality of European urology to the developing countries, and the EAU is doing a great job in starting that process,” said Abrams. Asked what advice he would give to young urologists, he replied: “Decide on your sub-specialty and pursue it intently.” Gratzke, one of the youngest awardees, on the other hand, commented that young urologists should focus on topics “they’re truly interested in and not what others think is relevant.”

A fanfare, marching band wins smiles and photo clicks from the Opening Ceremony audience

Remember to set tonight your clock 1 hour forward

Active surveillance in PCa: A thorny issue Prostate Cancer Prevention Group tackles limits of active surveillance By Joel Vega

chaired the meeting with Profs. Manfred Wirth (DE) and Arnulf Stenzl (DE).

The question of which prostate cancer (PCa) patients are suitable for active surveillance (AS) remains a complex issue, and experts yesterday cautioned that doctors should exercise due restraint to avoid over-treatment. The special session organized by the Prostate Cancer Prevention Group looked into low-risk PCa and identifying patients qualified for active surveillance, such as genetic factors, dietary and lifestyle, the role of miRNA, tissue, blood and urine–based biomarkers, role of imaging, and management of low-risk disease, among others. The full-day session also presented update lectures and discussions of the three major studies on AS (ProtecT, ERSPC and PLCO).

Prof. Freddie Hamdy (GB) gave updates on the ProtecT study and said the risk of death from prostate cancer over an average of 10 years is very low (1%) and that most PSA-detected clinically localized prostate cancers grow slowly.

Speakers (l-r) F. Hamdy and J. Hugosson and session chair A. Stenzl

“There is a general acceptance that there is overtreatment and that the question of screening has exacerbated that,” said Prof. Jack Cuzick (GB) who

Improving information access By Erika de Groot Patients’ access to clear and accurate medical information is a key element in modern healthcare and achieving this may well require a closer collaboration between doctors and their patients, according to healthcare professionals. The Special Session “EAU Patient Information Project: Setting standards in cooperation and care”, chaired by Prof. Thorsten Bach (DE) highlighted the significance of facilitating access to patient information. The EAU’s Patient Information (PI) aims to help patients better understand their conditions via the multilingual website patients.uroweb.org and the resources it provides, and to encourage open communication between patients and healthcare providers.

underscored the importance of translating clinical guidelines for patients. “Involving patients can spark collaborations with patients in healthcare design, education, research, and clinical improvements,” he said. Mr. Andrew Winterbottom (GB), founder and director of Fight Bladder Cancer UK Charity, stressed the importance of “good and speedy communication” between doctor and patient for the latter to understand their diagnoses, treatments, side effects, and prognoses to help reduce anxiety in patients. Winterbottom suggested that doctors work with patient advocacy groups to gain insight on patient experience. “We believe in evidence-based medicine, but we also believe in medicine-based support.”

“Surgery and radiotherapy reduce the risk of cancer progression and spread, but cause bothersome urinary, sexual and bowel symptoms,” added Hamdy. He also noted that patients who stayed on active monitoring avoid treatment side-effects. “But there is an increased risk of cancer progression and spread, and some symptoms increase gradually over time,” said Hamdy.

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EAU Secretary General, Prof. Chris Chapple (GB) Saturday, 25 March 2017

Continued next page

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PCa in 2017

Today’s Industry Sessions

4th ESO Prostate Cancer Observatory

Industry sessions, all starting at 18:00 hrs

By Loek Keizer

What lurks behind the storage aspects of male LUTS? ASTELLAS - Room Copenhagen, North Hall (Level 1) Nocturia: What do we need to know in 2017? Identifying the cause and tailoring the treatment FERRING PHARMACEUTICALS - Room Vienna, North Hall (Level 1)

Prostate cancer specialists should be aware of several key developments: encouraging results on the use of PSMA-PET, upcoming genomic studies, and an evolving reassessment of Gleason pattern 4 which could change risk classification and has serious clinical implications.

Intravesical GAG therapy: Application and impact on patient and public health IBSA - Room Amsterdam, North Hall (Level 1)

At the same time, these new developments should always take into account the quality of life of prostate cancer patients.

Treating urological cancers: New twists and turns in the road IPSEN PHARMA - Room Stockholm, North Hall (Level 1)

These topics and more were presented yesterday at the 4th ESO Prostate Cancer Observatory. It was one of the first special sessions held at the 32nd Annual EAU Congress in London and it drew a large audience. Chaired by Dr. Riccardo Valdagni (IT), coordinator of the European School of Oncology’s Prostate Cancer Programme, and EAU Adjunct Secretary General for Education Prof. Hendrik Van Poppel (BE), the Observatory was held under the auspices of Europa Uomo, the European Prostate Cancer Coalition.

Redefining the approach to advanced prostate cancer JANSSEN PHARMACEUTICA NV - Room Milan, North Hall (Level 1) Managing patients with NMIBC: Making the best out of instillation therapies MEDAC GMBH - Room London, North Hall (Level 1) Role of the immune system in genitourinary cancers MSD - Room Munich, North Hall (Level 1) Dealing with complex OAB patient profiles - In or out of EAU guidelines? PIERRE FABRE MEDICAMENT - Room Berlin, North Hall (Level 1) BPH and obstructive uropathy: Role of alphablockers RECORDATI SPA - Room Paris, North Hall (Level 1)

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. S. Sarikaya, Ankara (TR)

By Loek Keizer The afternoon of the first day of EAU17 featured a further six Urology Beyond Europe Sessions, in addition to those held in the morning. The session was chaired on behalf of the Urological Society of India (USI) by its President, Prof. Prem Nath Dogra (IN) and on behalf of the EAU by Prof. David Manuel Castro Díaz (ES).

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

While the two and a half-hour session covered a wide variety of topics, the main focus was on the lower urinary tract. Topics included Peyronie’s disease, the etiopathogenesis of LUTS, minimally invasive therapy for BPH, radical cystectomy and the use of meshes for reconstructive urology.

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Lay-Out/Printing D. Blom G. Smit

Innovations in surgery Speaker Prof. Derya Tilki (DE) provided the urologist’s view on surgery and focused on how new imaging technologies will influence surgical treatment, specifically PSMA imaging and its impact on salvage lymph node dissection.

Derya Tilki speaking on PSMA imaging and surgery at the ESO PCa Observatory

of PCa, but prospective randomized trials are lacking,”said Tilki. “Identification of patients who will benefit from surgical treatment largely depends on imaging, which at the moment still may underestimate the load of metastases. PSMA-radio-guided surgery for detection of PCa recurrences may become more routinely used in the next 12 months.” “Although imaging is improving, it remains our task to evaluate the clinical implication. We do not know at present whether improved imaging leads to a survival benefit, or might just be another source of overdiagnosis and overtreatment,” Tilki cautioned.

“Elnagar’s study was chosen as it innovatively applies ultrasound based technology as a relatively simple, readily available and harmless imaging tool into clinical practice while avoiding unnecessary irradiation and unnecessary use of technical resources. This approach has great potential for urology in the future,” said ESUI Chairman Dr. Jochen Walz. The 7th award by the ESUI was won by Elnagar for his study titled “A Prospective Comparative Study of Color Doppler Ultrasound with Twinkling and Noncontrast Computerized Tomography for the Evaluation of Acute Renal Colic.” The article was published in the September 2016 issue of the Journal of Urology.

The patient It was precisely the issue of over-diagnosis and overtreatment that Prof. Louis Denis (BE) made a point of warning the audience about during his talk. Speaking from the patient’s perspective, Denis stressed three crucial points for good clinical PCa practice: first, to treat the patient first, and then his cancer; second, that there is no definite relationship between LUTS and curable PCa; and finally that the serendipity of focal, indolent PCa leads to both over-detection and over-treatment in 50% of patients.

The study examined the use of twinkling color Doppler ultrasound versus noncontrast computerized tomography in the diagnosis of renal colic in emergency room patients.

Areas for improvement in the next 12 months were characterized by Denis as optimizing performance of validated risk prevention tools and using big data to overcome multivariable aspects when deciding on best treatment. Decisions on survivorship, life goals and non-medical aspects should be shared between patients and physicians to ensure patient-centered management.

The award is supported by an unrestricted grant of €1,500 from the Invivo Corporation (producer of UroNav). Previous awardees are M. Ritter (2016), V. Pasoglou (2015), F. Cornelis (2014), F. Lecouvet (2013), F. Farag (2012) and A. Briganti (2011).

The study showed that color Doppler ultrasound successfully identified stones in 702 (97.1%) patients and failed in 21 (2.9%), whereas noncontrast computerized tomography confirmed stones in 720 (99.6%) patients and was negative in 3 (0.4%).

Joint EAU-Urological Society of India Session explores hot topics

Onsite Reporting and Editing E. de Groot L. Keizer T. Parkhill J. Vega

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.

“We ask these experts, who are highly specialized in their respective fields, for their forecast for the future of prostate cancer treatment. There are so many new drugs, new technologies, and emerging genetic information. We would like their opinion, not only evidence-based, but their personal views and perspectives on what will be changing for prostate cancer treatment in the near future.”

Dr. Mahmoud Abdel Gawad Elnagar of the Emirates International Hospital (Al Ain/United Arab Emirates) won this year’s Vision Award presented annually by the EAU Section of Urological M.A. Elnagar Imaging (ESUI) for the most innovative imaging study published in urology during the previous year.

Lower Urinary Tract: Resolving controversies

Editing and Coordination J. Vega

Disclaimer

Valdagni: “The Annual EAU Congress is the perfect venue for our Observatory. Our goal is always to talk about the true state of the art of that year.” The session featured the perspective of researchers, urologists, imaging specialists, pathologists and both radiation and medical oncologists.

“Emerging data suggests that surgery may represent an important therapeutic modality in the management of oligometastatic nodal recurrence after local therapy

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

EUT Editorial Office PO Box 30016 6803 AA Arnhem The Netherlands T +31 (0)26 389 0680 F +31 (0)26 389 0674 communications@uroweb.org

Vision Award for Elnagar

Each topic was covered by an Indian urologist, and then by a European colleague. This way, the audience could reflect on differences in approach. Dogra explained: “When composing the scientific programme for this session, we wanted topics with some controversy, topics that are perhaps not completely clear to all urologists. By combining an Indian speaker with a European one, some of these

issues can be explored, and the attending urologists can practice with a clear mind.” “In fact,” Díaz added, “there isn’t such a big difference in approaches between Europe and India, medically speaking. Of course there are large differences in population, available technology and budgets, but urologists on both continents have the same medical approaches.” One set of differences was summarised in Dr. Sarakanur Raghunath’s (IN) talk on the Indian approach to prostate cancer castration resistance. For instance, more than 75% of patients are not insured, and over 80% cannot afford all available CRPC treatment options. Raghunath: “More than 98% of CRPC patients are treated by medical oncologists only, with urologists only involved when surgical interventions are required.” Historic ties Nevertheless, the EAU Guidelines are also followed on the subcontinent. Dogra: “Historically, having been part of the British Empire, we follow Europe and the UK, particularly with medical guidelines. We apply the same in our practice. The USI endorses the EAU

Continued from page 1, Improving information access

nurse can be a primary contact person for the patient.

In general, patients confide more with nurses than with doctors, according to Ms. Corinne Tillier (NL) who said that “…doctors are disinterested about psychological matters.” To encourage better dialogue, doctors should explain in a way that patients understand. To help patients remember information, Tillier suggested that, when permitted, the patient records the conversation with the doctor. She added doctors and nurses should collaborate, and that the

Dr. Giulio Patruno (IT) said inadequate health literacy is a serious problem in Italy affecting more than half of the population. He said educating patients makes them more efficient at maintaining good health, prompts them to make better choices and increases their willingness to access and use information. Prof. Carlos Llorente (ES) said there is also limited knowledge of English in Spain and fortunately the EAU

David Manuel Castro Díaz speaking on mesh use at the Joint EAU-ISU Session, Friday afternoon.

Guidelines, this is part of our memorandum of understanding.” It was these same historic ties that presumably contributed to the large attendance at the EAU-USI Session. Dogra was very happy with the scope for interaction: “This meeting was very well attended, compared to some earlier meetings. This time it was much more interactive due to the high attendance. Of course there is a large contingent of Indian urologists living in the UK. But naturally the subjects that we chose were attractive and interesting for urologists of any background.”

Patient Information is translated into Spanish. “The EAU PI is based on the latest EAU Guidelines. It is patientcentric and relevant to patients living in different countries.” He described the process of translation, starting with urologists translating the existing English content under the supervision of the Spanish Association of Urology. This content is adapted to local circumstances, then proofread by a professional translator as an added quality measure, and reviewed and endorsed by a national society. At this moment, eight out of 10 topics are now translated in Spanish. Saturday, 25 March 2017

Biosensor chips identify effective antibiotic treatment New technique is up to 8x faster than current methods Scientists have piloted silicon biosensor chips which can rapidly identify the best antibiotics for treating bacterial infections. The system can direct clinicians to the best antibiotic treatment in around two to six hours, rather than upwards of two days which is typical of conventional tests.

silicon biosensor chips. Each chip contains thousands of nano wells, which are coated with a material which allows bacteria to stick to the chip. Once the bacteria have stuck to the well, technicians use reflected visual light to count the bacteria, and to see whether the colony is growing. They can then add a different antibiotic in various dilutions to each chip to see which best inhibits bacterial growth, giving results within two to six hours.

The new technology, which is still in development, is being presented at this congress. The scale of the problem this test addresses is huge. Bacterial infections are still a major cause of death in the Western world, and because of overtreatment and mistreatment, antibiotic-resistant bacteria strains are increasing every day. In the UK, it is estimated that 300,000 patients a year acquire infections in hospital, with over 9,000 dying from bacterial infections.

“So far we have used the system to rapidly identify antibiotics for a range of bacteria, such as E. Coli, which causes many urinary tract infections (UTIs),” said Segal. Prof. Sarel Halachmi (Bnai-Zion Medical centre, and the Faculty of Medicine, Haifa), said: “We are currently at initial testing stages using commercial bacteria solution and also human bacteria isolated from urine samples, however we are not yet at the stage where we can roll this out for routine clinical use. But the system is accurate, simple, economical, and significantly shortens the time to accurate treatment recommendation which will save lives in the future.”

In Europe generally, over four million people acquire a healthcare-associated infection every year, and in the US around 100,000 die each year from hospital acquired infections. Up to 40% of these are Urinary Tract Infections (UTIs). It is vitally important for doctors to be able to identify which antibiotic works as rapidly as possible, but typically they need 24 hours to confirm the presence of bacteria, and at least another 24 to 36 hours to identify the correct antibiotic to use. The team, led by Prof. Ester Segal (Technion Israeli Institute of Technology, Haifa), has developed special

“Of course, there is more work to do before the system is generally available. We envisage the costs of the system being pretty low, with each analysis costing between $5 and $25“, said Halachmi.’

Audience at the EAU17 sessions

Day 1 Awards Gallery Congress news. . . . . . . . . . . . . . . . . . . . . . . . 1 Congress highlights . . . . . . . . . . . . . . . . . . 2/3 Radial forearm phalloplasty. . . . . . . . . . . . . . 5 Predictive markers in kidney cancer. . . . . . . . 6 Congenital penile malformations: Dartos and androgens . . . . . . . . . . . . . . . . . . 7 Prof. Chapple awards Prof. Abrams with the EAU Willy Gregoir Medal

Prof. Abrahamsson receives the EAU Frans Debruyne Life Time Achievement Award from Prof. Chapple

Mr. Turner-Warwick receives the EAU Innovators in Urology Award from Prof. Chapple

Managing BPH patients with bothersome storage LUTS. . . . . . . . . . . . . . . . . . . . . . . . . . 8 Relevance of histopathological subtypes. . . . . 9 Management of stent-related problems. . . . . 11 Prognostic biomarkers in renal cell carcinoma. . . . . . . . . . . . . . . . . . . . . . . . . . . 12 EAU Guidelines Office successes. . . . . . . . . . 13 New 2016 WHO classification of penile. . . . . 14 Heterogeneity in renal cell carcinoma. . . . . . 15

Prof. Gratzke receives the EAU Crystal Matula Award from Prof. Chapple and Mr. Ellacott from LABORIE

Dr. Autorino accepts the EAU Hans Marberger Award from Prof. Chapple and Mr. Dourver from KARL STORZ

Prof. Shiota accepts the EAU Prostate Cancer Research Award from Prof. Chapple and Prof. Schröder from the FHS FOUNDATION

Scrotal pain: A challenging diagnostic and therapeutic entity. . . . . . . . . . . . . . . . . . 16 Urology Under the Swastika. . . . . . . . . . . . . 17 Sexual dysfunction in male cancer survivors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Miniaturisation of PCNL . . . . . . . . . . . . . . . . 19 Focal therapy for prostate cancer. . . . . . . . . 20 Managing LUTS. . . . . . . . . . . . . . . . . . . . . . 22 ESU: Learning by doing. . . . . . . . . . . . . . . . . 23

Prof. Chapple congratulates Prof. Egawa with his EAU Honorary Membership

Prof. Chapple congratulates Prof. Hanuš with his EAU Honorary Membership

Prof. Chapple congratulates Prof. Pansadoro with his EAU Honorary Membership

The patients’ perspective. . . . . . . . . . . . . . . 25 Patient-doctor partnership. . . . . . . . . . . . . . 26 Glans necrosis after penile prosthesis implantation. . . . . . . . . . . . . . . . . . . . . . . . . 27 Battlefield injuries . . . . . . . . . . . . . . . . . . . . 29 LUTS in CVA patients. . . . . . . . . . . . . . . . . . . 30 EAUN launches catheterisation guidelines summary. . . . . . . . . . . . . . . . . . . 31

Prof. Chapple congratulates Prof. Solsona with his EAU Honorary Membership

Saturday, 25 March 2017

Prof. Chapple congratulates Dr. Walsh with his EAU Honorary Membership

For a complete overview of all prize winners visit the Awards Gallery in the North Hall

EUT Congress News

N OW EN R O L L I N G Phase III Trials in Patients with: High Risk Non-Metastatic Castration Resistant Prostate Cancer (nmCRPC)

www.clinicaltrials.gov (NCT02200614)

Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

www.clinicaltrials.gov (NCT02799602)

For further information on these trials please contact:

clinical-trials-contact @ bayer.com

Trial Sponsors: Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA, UK Orion Corporation, Orionintie 1, FI-02200 Espoo, Finland Bayer and the Bayer cross are registered trademarks of Bayer. ÂŠ Bayer. February 2017. UKMED01170028

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Saturday, 25 March 2017

Radial forearm phalloplasty A plastic surgeon’s point of view Dr. Loren S. Schechter FACS University Plastic Surgery Morton Grove Illinois (USA)

Phalloplasty represents the most complete genitoperineal transformation for transmen. In the author’s opinion, the radial forearm free flap remains the gold standard for phallic reconstruction. This procedure transfers tissue, including the radial artery, vena comitantes, cephalic vein, and lateral and medial antebrachial cutaneous nerves, from the forearm to reconstruct the penis and urethra. This flap allows the single-stage reconstruction of a sensate phallus and glans penis. Preoperative electrolysis of the volar, ulnar surface of the donor forearm may be required for depilation of what will become the penile urethra. Effective hair removal can take several months and should be completed at least two weeks prior to surgery. Potential drawbacks of this technique include the visibility of the donor site on the forearm, and the need for microsurgical skills. The perineal reconstruction is performed with construction of the fixed portion of the urethra using the vaginal and vestibular lining, and the scrotal reconstruction is completed with labia majora flaps. Urethral complications, including both strictures and fistulae, are not uncommon, and additional, secondary procedures performed at a later date are required for placement of testicular implants and the erectile prosthesis. Radial forearm phalloplasty is typically performed with two surgical teams. One team performs the vaginectomy, colpocleisis, creation of the fixed portion of the urethra, scrotoplasty, and placement of a suprapubic tube, while the second team harvests and shapes the forearm flap, then closes the forearm donor site.

incisions extend intravaginally and communicate with the planned vaginal flap. The vaginal flap is elevated and left in-situ, in anticipation of approximation to the vestibular lining. The vestibular incisions allow access to and exposure of the lateral aspect of the corporal bodies. The dorsal surface of the corporal bodies is exposed through a circumcision incision. The labial skin is dissected to the pubic symphysis, and care is taken to preserve the dorsal clitoral neurovascular bundles. Following exposure of the corporal bodies, the glans clitoris is de-epithelialized. One of the dorsal clitoral neurovascular bundles is harvested and tagged for subsequent neurorrhaphy. The nerve bundle on the side opposite of the planned vascular anastomosis is chosen. Reconstruction of the fixed urethra is completed with tubularization of the vestibular lining over an 18 French urinary catheter.

Figure 8: Postop radial forearm phalloplasty and mons lift

Figure 6: Placement of inflatable penile prosthesis

Donor site The donor site incision, taking the shape of an “omega (Ω),” is designed overlying the pubic symphysis. A subcutaneous tunnel is then created between the donor site incision and the degloved clitoris. The clitoris is transposed subcutaneously and fixed to the pubic bone. Fixation of the clitoris aids with stabilization of the urethral construct. The perineal portion of the surgery proceeds with resection of the labia minora and scrotoplasty so as to eliminate the remaining vestiges of the female anatomy. The labia minora are resected in their entirety, and the scrotoplasty is performed with medial transposition of the labia majora. Incisions on the lateral border of the labia majora facilitate their mobilization to a position anterior to the legs. Pelvic floor reconstruction is completed by suture approximation of the superficial pelvic musculature and layered skin closure. Interrupted sutures are preplaced in the os of the reconstructed fixed urethra, now located at the level of the pubic symphysis. These sutures will be used in the distal anastomosis between the penile urethra of the forearm flap and the fixed urethra created from the tubularized vestibular lining. At this point, the patient is taken out of lithotomy, placed in the supine position, and reprepped.

The vaginectomy is performed by removal of the vaginal epithelium from the fibromuscular vaginal wall. A combination of sharp dissection with scissors and electrocautery is used to remove the epithelium laterally, up to the vaginal apex. Anterior dissection of the mid-proximal vagina is performed. The distal epithelium, including the hymenal tissue is removed up to the margin of the paraurethral sulci, bilaterally, and the urethral meatus anteriorly. If a vaginal flap will be used in creation of the proximal urethra, the corresponding portion of the vagina is left intact. Interrupted mattress sutures of 2-0 vicryl are then used to perform the colpocleisis.

Dissection of the recipient vessels begins with an incision, extended obliquely from the donor site incision, along the groin crease. The superficial femoral artery, great saphenous vein, superficial inferior epigastric vein, superficial circumflex iliac vein, and ilioinguinal nerve are exposed. Vessel loops are used to encircle the superficial femoral artery, and the great saphenous is clamped proximally and divided distally. The ilioinguinal nerve is identified exiting the superficial inguinal ring and travelling with the round ligament. The nerve is transected distally and tagged for later neurorrhaphy.

The fixed portion of the urethra is created by tubularization of the vestibular lining, located between the native urethral orifice and the virilized clitoris. Two parallel incisions are made from the native urethral orifice and extend to the clitoris. The distal, dorsal aspect of the vestibular lining is spatulated in order to enlarge the anastomosis between the fixed and penile urethrae. When a vaginal flap is needed for construction of the proximal urethra, the vestibular

Flap harvest on the forearm begins with performance of an Allen’s test. A cutdown is performed at the wrist, the radial artery is identified and occluded with a microvascular clamp, and a Doppler signal to the thumb is confirmed. Dissection begins in the proximal forearm where the cephalic and median antebrachial veins are identified, and the lateral and medial antebrachial cutaneous nerves are dissected. The nerves are transected proximally and tagged for later

Figure 1: Radial forearm markings

Figure 3: Radial forearm flap shaped in-situ on forearm

Figure 2: Donor site markings

Figure 4: Immediate post op radial forearm phalloplasty

Saturday, 25 March 2017

Figure 5: Scrotoplasty and perineiplasty

Figure 9: Radial forearm phalloplasty and scrotoplasty

forearm donor site, or, alternatively, a bilayer wound matrix may be placed. If a wound matrix is utilized, a skin graft is performed at a later date. Most often, negative pressure wound therapy in conjunction with a topical antimicrobial dressing is utilized to dress the forearm donor site. A light compression wrap is then applied. Postoperatively, patients are maintained on a variable duration of bedrest with both transurethral and suprapubic catheters. Both mechanical and chemoprophylaxis are utilized for venous coaptation to the ilioinguinal and dorsal clitoral nerves, thromboembolism prophylaxis, aspirin 81 mg is respectively. A “tube-within-a-tube” technique is used administered daily, and flap monitoring is performed with a handheld Doppler. Range of motion is initiated to create the neophallus. on the donor forearm on postoperative day one, and The urethra is created from tubularization of the ulnar the negative pressure dressing is changed on postoperative day four or five. The patient is typically border of the flap, and the skin of the penile shaft is discharged from the hospital on postoperative day created from the skin of the radial border of the flap. eight. An intervening strip of skin between the ulnar and radial portions of the flap is de-epithelialized in order If a wound matrix was used on the forearm donor site, to provide a layered closure overlying the penile the patient returns to the operating room after urethra. approximately two weeks for placement of a skin graft. Negative pressure wound therapy may be utilized to Most often, flap elevation occurs in the suprafascial dress the skin graft, and the initial dressing change is plane over the muscle bellies, and the paratenon performed on postoperative day three or four. After overlying the distal tendons is preserved. During approximately four to six weeks, compression dissection of the radial border of the flap, the sensory garments may be placed on the forearm to assist with branch of the radial nerve is identified and preserved. scar maturation. Urination through the penile urethra The radial artery is dissected to its takeoff from the brachial artery so as to allow maximum pedicle length may begin as early as three weeks following phalloplasty. for the arterial anastomosis. The venous dissection incorporates the perforating branch between the vena Secondary procedure comitantes and cephalic vein. Testicular implants and penile prostheses are placed at a secondary procedure. While the testicular implants Glansplasty may be placed as early as three months following Following flap harvest, the penile urethra is tubularized over an 18-20 French urinary catheter, and phalloplasty, the penile prosthesis is typically placed nine to twelve months after the phalloplasty. This the skin of the shaft is closed in a layered fashion. A allows the development of protective sensation, which glansplasty is performed by elevation of a distallyis important for retention of the erectile device. based flap located approximately 3 cm from the distal border of the forearm flap. The glans is further defined by construction of the coronal ridge, and placement of Prior to placement of the testicular implants, and depending upon the volume of the scrotal sac, remote a skin graft at the donor site of the distal flap harvest. fill tissue expanders may be placed as an interval procedure. This aids with expansion of the scrotal sac, The phallus is transferred to its position on the pubic symphysis, and the urethral anastomosis is performed if necessary, and allows placement of larger testicular implants. first. The preplaced urethral sutures, located in the distal os of the fixed urethra, are sutured to the penile The final stage of penile reconstruction involves urethra. placement of the erectile device. While both malleable and inflatable prostheses are available, neither device Prior to occlusion of the femoral artery, a heparin is specifically designed for placement in a flap bolus is administered. In addition, the patient is maintained on a heparin drip during the performance phalloplasty. As such, anchoring of the prosthesis can of the anastomoses, and a heparin solution consisting be a challenge, and often requires fixation to the pubic bone. This may be performed with suture fixation to of 500 units/milliliter is used for intraluminal the periosteum of the pubis, or, alternatively, bone irrigation. The arterial anastomosis is performed first, anchoring. In addition, the prostheses can be wrapped in an end-to-side fashion, between the radial artery with an acellular dermal matrix to help form a “pseudo and the superficial femoral artery. Typically two or corpora cavernosa.” three venous anastomoses are performed in an end-to-end fashion between the cephalic and greater Most often, a three-piece inflatable prosthesis is saphenous veins and the antebrachial vein(s) and superficial inferior epigastric and superficial circumflex utilized. The pump is placed on one side of the scrotal sac and serves the purpose of a testicular implant, and iliac veins. The neurorrhaphies are then completed the reservoir is placed in a retroperitoneal position. between the lateral antebrachial cutaneous and Depending upon the dimensions of the phallus, either ilioinguinal nerve and the medial antebrachial and a single or dual cylinder is selected. dorsal clitoral nerves. Placement of Penrose drains in each groin and layered closure of the skin completes Saturday 25 March the procedure. 13.45-13.55: Meeting of the EAU Section of Genito-Urinary Reconstructive Surgeons Closure of the forearm donor site is performed by (ESGURS) reapproximation of the muscle bellies over a closed suction drain. A skin graft may be applied to the

Figure 7: Intraoperative testing of inflatable penile prosthesis

EUT Congress News

Predictive markers in kidney cancer No validated biomarkers yet to predict response to TKI therapy in mRCC Asso. Prof Egbert Oosterwijk Radboud UMC Nijmegen (NL)

The clinical management of patients with metastatic Renal Cell Cancer (mRCC) has changed dramatically with the implementation of VEGF receptor and mTOR inhibitors.

CYP450 regulators, or drug efflux transporters) and pharmacodynamics (genes encoding VEGF or VEGF receptors and interleukins). Unfortunately, most studies presented non-validated findings from retrospective cohort studies with rather small effect sizes. Moreover, heterogeneity between studies was large, sample sizes were limited, and replication of these findings is mostly lacking. Whether individual dosing regimens of TKIs and/or drug choice can be guided by genetic profiling is unclear.

microRNAs and long non-coding RNAs have been identified that may predict TKI response. Again, validation of these results is required, particularly because the group size was limited. Various predictive biomarker studies have focused on phenotypic analysis of primary RCC, essentially focused on TKI targets. In general, associations between particular phenotypes and TKI treatment have been observed, but not consistently.

Until relatively recent, the genetic inactivation of Von Hippel Lindau (VHL) tumor suppressor gene was the only known prevalent oncogenic driver event in clear cell RCC (ccRCC). It is now clear that mutations in PBRM1, BAP1, SETD2, and KDM5C are also common and results of randomized controlled trials have suggested that individual mutations may have prognostic value.

Through advances in molecular biology Schematic overview of relevant pathways in clear cell renal cell carcinoma a wide array of possibilities has become (ccRCC) and targeted therapies. Photo: European Urology Archives available for circulating biomarkers: circulating tumorcells (CTCs), microRNA With the wide range of clinical outcomes and the (miRNA), circulating cell-freeDNA large number of inhibitors available, predictive (cfDNA), and protein are now all recognized as evaluated, the risks of false-positive findings and markers are necessary to guide treatment. This will valuable possibilities. CTCs have been successfully statistical overfitting must not be underestimated. reduce unnecessary toxicity (improving quality of life), applied in e.g. breast cancer patients, but CTCs have Whether composite biomarker scores are of value drug use and reduce health costs while at the same rarely been studied in kidney cancer. This is not remains to be confirmed, albeit that it is likely that time improving treatment outcome. Analysis of the RECORD-3 trial that compared first-line surprising since a minority of RCC express EpCAM, the single biomarkers are not going to be informative. everolimus followed by sunitinib with first-line epithelial cell surface protein used by CTC assays for This explains the large number of (predictive) sunitinib followed by everolimus has suggested that positive cell selection. In summary, there are no validated biomarkers yet biomarker studies in mRCC. Generally, these distinct molecular subtypes based on PBRM1, BAP1, that can predict response to TKI therapy in mRCC. biomarkers have been derived from tumor tissue and KDM5C mutations could be associated with better Alternative methods will need to be developed for CTC Despite great efforts in this field, none of the (DNA, RNA and protein), almost invariably obtained clinical outcomes with everolimus (PBRM1) and of RCC. Plasma levels of multiple proteins involved in predictive biomarkers for TKI efficacy have been from the primary lesion, circulating angiogenic factors sunitinib (KDM5C). Thus, these may serve as angiogenesis and TKI have been investigated as validated for the use in clinic so far. and/or cytokine factors, as well as from host single predictive biomarkers, but validation studies are possible predictive biomarkers. Unfortunately, despite nucleotide polymorphisms (SNPs). needed to substantiate this finding. substantial efforts, it has proven difficult to correlate Many biomarker discovery studies, including plasma levels with TKI sensitivity. predictive biomarker studies have been conducted Several genetic variants have been tested for their Intratumor heterogeneity is very prevalent in RCC and in only a small number of patients, and validation in possible association with the treatment outcome of this obviously complicates biomarker development as In the RECORD-3 trail 121 circulating biomarkers with large patient cohorts and in prospective studies is mRCC patients. In general these SNPs were selected generally a single biopsy is evaluated in tissue-based relevance to the molecular pathways of kidney cancer necessary before these potential predictive markers in genes-encoding enzymes or transporters related to studies. Moreover, in almost all studies primary RCC is were studied. In total 29 biomarkers predictive of can find their way to the clinic. Combination of pharmacokinetics (PK) and pharmacodynamics (PD) of studied, which is less relevant as the metastatic everolimus efficacy and nine predictive of sunitinib several markers in a panel might improve predictive tyrosine kinase inhibitors (TKIs) which have been subclone(s) are under-represented in the primary efficacy were found. By combining the five with the capacity. associated with toxicity and efficacy of TKIs. tumor. strongest association with progression-free survival (PFS) a composite biomarker score was created that Saturday 25 March In a recent systematic review, strictly focusing on the Nevertheless, transcriptome analysis revealed ccRCC identified patients with a better everolimus PFS. 12.00-12.10: Joint meeting of the EAU Section of predictive biomarkers, the most promising molecular subtypes that may be predictive of sunitinib Urological Pathology (ESUP) and the EAU Section biomarkers on predicting TKI outcome were related to response of mRCC patients, and this could be used for Similarly, a six-marker signature correlated with of Urological Research (ESUR) pharmacokinetics (genes encoding CYP450 enzymes, personalized mRCC treatment with TKIs. Moreover, sorafenib efficacy. However, with many biomarkers

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Saturday, 25 March 2017

Congenital penile malformations: Dartos and androgens Ghent University Hospital maintains database of children undergoing surgery for CPM Dr. Anne-Françoise Spinoit Pediatric and Reconstructive Urology Robotics Ghent University Hospital Ghent (BE)

Over the past decades, epidemiologic studies have shown increasing incidence of Congenital Penile Malformations (CPMs)1-3. Anomalies of the male external genitalia may be confined to the clinical appearance, or might be the first clue indicating further underlying disorders that require evaluation. Hypospadias is the most frequent congenital penile defect affecting the external male genitalia, with an incidence around one in 250 male newborns2,4. It is therefore the most studied CPM. Buried penis (BP) is another CPM frequently encountered in pediatric urology. Although the true incidence of BP is unknown because of an ongoing debate about its definition, BP is probably the most frequent penile pathology after hypospadias5,6. When BP is observed as a CPM, is also described as inconspicuous penis, hidden penis, cryptic penis, concealed penis, meagapreputium with concealed penis, all those terms covering one single pathologic finding: a normal penile shaft is entrapped in pubic fatty tissues, only leaving a redundant preputium visible6-9. Hypospadias and BP are the most frequent CPM. Many other CPM can however be observed, even if they are very infrequent: aphallia (absence of penis), diphallia (penile duplication), penile torsion, epispadias (associated with the bladder exstrophy complex or as a stand-alone condition), penoscrotal transposition, … Dartos Tissue and Congenital Penile Malformations Dartos tissue (DT) is considered a superficial fascia, located immediately under the genital skin, originating in Scarpa’s abdominal fascia, and in Colle’s perineal fascia. It is superficial to Buck’s fascia. The composition of fibromuscular DT along the penile shaft determines elasticity of the subcutaneous tissue and the skin mobility10. The skin of the penis is highly elastic, and has no hairy elements. This skin is relatively fat free, and mobile because of its loose attachments to the underlying DT. Distally, it folds over itself, thereby creating the preputium, or foreskin covering the glans. The basic observation, during penile surgery, that, in many of the CPM, the DT had a different aspect than the DT in the normal penis, led to the set-up of a research line. In distal hypospadias repair, release of the fibrotic DT often corrects the ventral curvature, indicating that this tissue plays a role in the pathophysiology of the penile curvature. In BP, it is observed that the penis is entrapped in a cocoon of fibrotic DT. With penile deglovement, and release of penis out of its cocoon, the penile entrapment is resolved, restoring normal penile length11. Androgens and Congenital Penile Malformations Male external genital development depends, among others, on the conversion of testosterone by the 5-alpha reductase, produced by the primitive testicle from the third week on, into the more active dihydrotestosterone. Some disturbances in male hormonal production or action might be involved in CPMs, as already observed in Disorders of Sexual Development (DSD). There is an ongoing debate on whether CPMs should be regarded as a minimal condition in the spectrum of DSD, or should be considered as a completely different pathologic entity. In some DSD conditions like the virilizing form of congenital adrenal hyperplasia, where a 46 XX girl shows male genitals because of androgenic influence, or like complete androgen insensitivity syndrome, where a 46 XY boy has female external genitals, the hormonal influence is clear and quite well understood. In CPM without DSD, the etiologies are not so clear nor understood.

Saturday, 25 March 2017

Human male and female genitalia originate from a common identical genital tubercle. Sexual differentiation into male or female starts around the 8th gestational week, under the influence of the Sex-determining Region Y (SRY) gene12,13. With progressive differentiation of the undifferentiated gonad into testicle, androgen production is started, along with Anti-Müllerian Hormone (AMH), allowing further differentiation into male genitalia. Initial differentiation of the bi-potential undifferentiated gonad is androgen-independent until a testicle is formed. Further development of the male genitalia is androgen dependent, while regression of female (Müllerian) primitive structures is dependent on AMH production. Under the influence of androgens, the genital tubercle grows into the penis14. One of the questions that arise is whether DT development is hormone-dependent. It is known that the development of the male external genitalia occurs under hormonal influence so it seems logical that disturbances in the hormonal mechanisms can have any influence on DT patterns. In adult urology, some pathologies are known to be under the direct influence of androgens, like for instance development of prostate cancer. There is a lot of research going on about androgen receptors in pathologic and healthy prostatic tissue, searching there for clues to eventually Regarding the DT, the pathologist, blinded for the obtain a better control of the disease. indication for surgery, could confirm the surgical impression of an underlying pathology of the DT in As the DT is a genital tissue, we would logically CPM. Furthermore, it was found that the level of DT expect androgen receptors. Larry Baskin’s team architecture disorganisation was strongly correlated (UCSF) has been producing leading research over the with the clinical severity of the malformation16. last decade about the possible influence of androgens and their receptors in genital development. They Age at surgery had no influence on the DT observed genital development in the spotted hyena, a architecture pattern, confirming the pattern was fascinating animal which has the particularity of established at birth, and did not evolve with age in having extreme masculinization of the female external maturation process. genitalia2-5. The spotted hyena is a mammal that mates and gives birth through a dangling penis-like Regarding androgens, AR expression was significantly clitoris. Their findings showed early penile higher in the children operated for non-medical development is androgen independent, like human reasons (controls) compared to children operated for primitive penile development is believed to be2.

CPM (cases). In the control population, the age at surgery presented a significant influence on the quantity of the androgen receptors. These initial findings open large research perspectives about CPM’s, with potential clinical implications at time of reconstructive surgery. Editorial Note: Due to space constraints the reference list has been omitted. Interested readers can email at EUT@uroweb.org for a complete listing. Sunday 26 March 10.30-10.45: Thematic Session 7, Pediatric Urology

Of course, whether those findings can be transposed in humans remains unclear. Few studies have been investigating the possible role of androgens or estrogens in humans8-10. Initial studies of the same team showed that androgen receptor is overexpressed in boys with severe hypospadias4. This was however observed in a fibroblast cell line derived from neonatal human foreskin in a small series of patient comparing mild hypospadias to severe hypospadias. There are, to our knowledge, no data available exploring the androgen or estrogen receptors in human penile skin, or any other penile tissue. As environmental pollutants are believed to act like endocrine disruptors that might be at the source of the increased incidence of CPM during the last decades, exploring penile tissues’ androgen and estrogen receptors might provide some clues to complete the CPM puzzle. Based on this concepts, a research line investigating the role of DT in CPM was created, with androgens influence on this tissue to be discovered. Setting up a prospective database of children undergoing surgery for CPM15 Starting in November 2011, a databank was prospectively created in Ghent University Hospital with tissue samples collected from children undergoing primary penile surgery (PPS) for CPM, with children undergoing circumcision for nonmedical reason as control16. This database is to date still prospectively maintained. Ethical approval was obtained. The collected samples consisted of the excessive preputial tissue resected with the underlying DT in case of non-medical circumcision. In hypospadias, the analyzed samples consisted of the hooded prepuce and the DT resected for chordee correction. In BP, the samples consisted of preputial tissue and resected subcutaneous DT as described in our technique based on the anchoring of the stretched penis at its base with residual DT11. CPM, Dartos Tissue and androgens At time of the analysis, tissue samples of more than 500 children were included. Indications for surgery were CPM in children: hypospadias primary repair, epispadias and BP. Children undergoing circumcision for non-medical reasons, served as control group. EUT Congress News

Managing BPH patients with bothersome storage LUTS Individualized treatment still requires further studies Tiago Antunes-Lopes Department of Urology Hospital de S. João Translational NeuroUrology Institute for Molecular and Cell Biology University of Porto Porto (PT) Co-Author: F.Cruz (PT) Benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) is an agerelated disease, that increases in prevalence and incidence, affecting nearly 80% of men 70 years of age and older.1 However, many men with BPH will never seek medical care, nor will need treatment for BPH, as this condition only becomes clinically relevant when LUTS are present and bothersome enough to negatively impact the quality of life (QoL).1,2 In most individuals, voiding and storage LUTS often co-exist,3 but storage symptoms, including overactive bladder (OAB), are typically more troublesome.4 The last decade in functional urology was marked by a critical shift of paradigm in the management of male LUTS, away from the simplistic view of treating BPH by relieving bladder outlet obstruction (BOO) and associated voiding symptoms.5 In men, LUTS have traditionally been linked to benign prostatic obstruction (BPO), often caused by benign prostatic enlargement (BPE) resulting from the histologic condition of BPH.6

treatment and follow-up of non-neurogenic male LUTS including BPO.9 Combination of α1-blockers and antimuscarinics Although OAB symptoms may be exacerbated by BPO, in general, men report that α1-blockers improve urinary flow and nocturia, but not urgency and frequency.10 If the α1-blocker failed to provide complete relief of bothersome storage symptoms, a post-void residual (PVR) assessment is recommended and combination of an α1-blocker with an antimuscarinic should be initiated, although with caution in men with a PVR volume above 150ml.6 Antimuscarinic agents primarily block the postjunctional muscarinic M3 receptor responsible for detrusor contractions, acting during both storage and voiding phases of the micturion cycle (Figure 1).11 During storage, these drugs decrease smooth muscle “micromotions” (autonomous bladder activity due to the leak of acetylcholine from postganglionic parasympathetic nerves) leading to inhibition of bladder afferent mechanisms, with subsequent increase of bladder capacity and reduction of detrusor overactivity and urgency sensation.12 However, during the voiding phase these drugs might also reduce the efficiency of voiding contractions, preventing normal complete bladder emptying.13 Current antimuscarinic agents approved are oxybutynin, tolterodine, solifenacin, darifenacin, trospium, propiverine and fesoterodine. These drugs have different affinities for the different muscarinic receptors,13 and experimental data have shown greater bladder selectivity for tolterodine, darifenacin and solifenacin, compared with oxybutynin.2

Given most patients in OAB trials are women, urologists have debated the utility of antimuscarinics in Nevertheless, the origin of LUTS does not only men, due to the potential risk of precipitating UR. The implicate the prostate, but is also related to different TIMES study included 879 men with symptoms of BPH causes of bladder dysfunction. This is true for all types and OAB, randomized to receive either tolterodine 4 of LUTS: voiding symptoms (that can be related not mg ER + tamsulosin, one of the two drugs alone or only to BOO, but also detrusor underactivity or hidden placebo.14 A PVR >200ml was an exclusion criterion. At 12 weeks, tolterodine monotherapy significantly neurological dysfunction), storage symptoms (which can be due to specific bladder dysfunction) and reduced urgency urinary incontinence episodes versus nocturia (with multiple possible causes).7 Hence, the placebo, but no other parameters were improved. pathophysiology of LUTS is multifactorial, including Comparatively, combination therapy reached significant reductions in OAB outcomes (bladder diary variables, both urological and non-urological causes,6 that the clinician must consider in the differential diagnosis of International Prostate Symptom Score – total and BPH and OAB (Table 1). storage sub-scores). The role of the prostate as the unique origin of male LUTS is currently under dispute, and the bladder has become the new target in pharmacological research.8 Over the last few years, several pharmacotherapies have emerged for the treatment of male storage LUTS that persist after a trial with α1-blockers, which remain a classical mainstay of LUTS/BPH therapy. Although the use of antimuscarinics in men with BPH and OAB symptoms was avoided due to the risk of urinary retention (UR), there is now strong evidence to support the efficacy and safety of these drugs. More recently, two new drug classes have been introduced into the therapeutic armamentarium for male storage LUTS: β3-adrenoceptor agonists and phosphodiesterase type 5 inhibitors (PDE5-I).2 Therefore, in the case of persisting storage symptoms despite α1-blocker therapy, adding antimuscarinics or β3-adrenoceptor agonists seems a rational approach to manage the whole LUTS spectrum properly. On the other hand, PDE5-I have not only beneficial effects on male sexual function, but also in voiding and storage LUTS, constituting an alternative for α1-blockers in a particular group of patients.8 A combination of the available drug classes is logical and appropriated, being already indicated in the European Association of Urology guidelines on the

Figure 1: Temporal action in micturition cycle of α1-adrenergic receptor antagonists (α1-AR antagonists) and antimuscarinic agents combination therapy for men with both voiding and storage lower urinary tract symptoms. Note that antimuscarinics act during storage and voiding phases.

EUT Congress News

In a systematic review of the evidence for antimuscarinics for the treatment of storage LUTS in men, Kaplan and colleagues reported a rate of UR < 3%, with no significant changes in PVR,15 but one must recall that antimuscarinic OAB trials typically exclude men traditionally thought most likely to develop UR (baseline PVR >200ml, clinically significant BOO). Likewise, average prostate size in studies in which ultrasound measurements were performed tended to be low. As such, antimuscarincis are generally not recommended in men with PVR > 200ml, a large prostate, Qmax <10ml/s or a previous history of UR. Although antimuscarinics alone are efficacious and safe, a combination of an antimuscarinic with an α1-blocker was found to lead to greater symptomatic improvements than antimuscarinics alone.2 The NEPTUNE study is particularly relevant because it included men with urodinamically proven BOO with both storage and voiding symptoms.16 The combination of solifenacin and tamsulosin was non-inferior to placebo for PdetQmax and Qmax in men with LUTS and BOO, and there was no clinical or statistical evidence of increased risk of UR.16 Moreover, in the evaluation of long-term (up to 52 weeks) safety and efficacy of this combination therapy, the

Figure 2: Temporal action in micturition cycle of α1-adrenergic receptor antagonists (α1-AR antagonists) and β3-adrenergic receptor agonist (mirabegron) combination therapy for men with both voiding and and storage lower urinary tract symptoms. Note that mirabegron only act during storage phase.

Table 1: Causes of lower urinary tract symptoms (LUTS): differential diagnosis, drugs, other risk factors Differential diagnosis Bladder cancer Prostate cancer Prostatitis Bladder stones Interstitial cystitis Radiation cystitis Urinary tract infection Urethral stricture Neurogenic bladder dysfunction Detrusor underactivity Primary bladder neck hypertrophy Nocturnal polyuria

Drugs Antidepressants Anticholinergics Diuretics Narcotics Antihistamines Bronchodilators

reductions in total IPSS and total urgency and frequency score (TUFS) maintained, with a very low incidence of AUR (1.1%).17 Combination of α1-blockers and β3-adrenoceptor agonists In the bladder, β3-adrenoceptor is the principal subtype among all β-adrenoceptors.18 Mirabegron, the first and only available β3-adrenoceptor agonist is thought to enhance relaxation of detrusor muscle in the storage phase without affecting the contractility during micturition (Figure 2).19 The exact mechanism is not yet established but may involve the cyclic adenosine pathway, leading to increase in intracellular cyclic adenosine monophosphate (cAMP).2,19 β3-adrenoceptor agonists have no effect on voiding contractions. In a critical phase 2 trial, Nitti and colleagues assessed different urodynamic parameters of men with BOO and LUTS.20 A total of 200 men, 45 years old or older with LUTS and BOO were randomized to receive once-daily mirabegron 50mg or 100mg, or placebo for 12 weeks. At three-month follow-up, it was found that mirabegron 50 or 100mg did not impair PdetQmax or Qmax relative to placebo. Both treatment arms showed a significant decrease in micturition frequency versus placebo, but the 50mg mirabegron group presented a statistically significant reduction of urgency episodes. The adverse event profile was similar in all groups. Several phase III studies, which enrolled more than 25% of male patients, confirmed the efficacy, safety and tolerability of the β3-agonist mirabegron in men with LUTS.2,18 In these clinical trials the incidence of UR did not increase with mirabegron and was lower than that of placebo and the active control.2,18 In a more recent study, Ichiara et al. investigated the add-on of mirabegron 50 mg to 0.2 mg tamsulosin versus tamsulosin alone in men with BPO and OAB.21 They found a significant benefit on urgency, daytime frequency and QoL index after two months of treatment. Although the increase in PVR was significantly higher in the add-on group, acute UR occurred in only one case. The authors concluded that combined tamsulosin and mirabegron treatment is effective and safe for patients with BPO who maintains bothersome storage LUTS after tamsulosin monotherapy. These findings point out a new alternative pathway in the individualized treatment of patients with BPH and OAB symptoms. Phosphodiesterase type 5 inhibitors In the aging men LUTS frequently coexist with erectile dysfunction (ED). Epidemiological and pathophysiological links between ED and BPH/LUTS have been demonstrated.22 It was postulated that both conditions may share common mechanisms. Several studies suggest the involvement of the nitric oxide/ cyclic guanosine monophosphate (NO/cGMP) signaling pathway in smooth muscle contractility in bladder neck, urethra and prostate. Moreover, nitrergic nerves are agglomerated in the bladder outlet promoting cGMP-mediated relaxation.23 Other possible shared mechanisms underlying ED and LUTS include atherosclerosis in the pelvic vasculature, autonomic hyperactivity and alterations in RhoA/Rho kinase signaling.2 Although randomized controlled trials on the efficacy of sildenafil, tadalafil and vardenafil have been published, only tadalafil (5mg once daily) is licensed for the treatment of male LUTS in Europe.9 Recently, Gacci and colleagues have published a critical meta-analysis that selected 12 articles, seven on PDE5-I versus placebo (including 3214 men), and five

Other risk factors Diabetes mellitus Obesity Hypertension Aging Smoking Alcohol consumption

on the combination of PDE5-I with α1-blockers versus α1-blockers alone (including 216 men).24 Despite the use of PDE5-I alone was associated with a significant improvement of the IPSS and of the International Index of Erectile Function (IIEF) scores, the Qmax did not change after PDE5-I administration. Moreover, the combination of PDE5-I and α1-blockers was superior to α1-blockers alone in improving IPSS and IIEF scores, and interestingly also the Qmax. In a more recent study, Chapple et al. conducted an integrated analysis of data from four placebocontrolled, 12-week studies of tadalafil (5mg once daily) in 1499 men with LUTS/BPH, to evaluate the relative contributions of storage and voiding IPSS sub-scores to total IPSS at baseline and in response to treatment with tadalafil.25 They concluded that the greatest effect on total IPSS was noted for a storage sub-score percentage contribution to total IPSS of 42.7%. This analysis shows that for men with BPH, improvements during treatment with tadalafil apply to both storage and voiding symptoms at a constant ratio. Also, the extent of storage dysfunction before treatment did not affect the response to treatment. In conclusion, tadalafil is an effective and well tolerated alternative for BPH-related LUTS, essentially when treating men with concomitant ED. At the moment a treatment algorithm cannot be established, as many questions remain without answer. An individualized treatment approach, outlining which agent should be used in which patient, and at what stage, will require further studies to evaluate comparative efficacy and safety, and to define specific responder characteristics. The multifactorial etiology of male LUTS, as well as the frequent overlap of voiding and storage symptoms, anticipate a more widespread use of multiple combination therapies in the near future. References 1. Egan KB. The Epidemiology of Benign Prostatic Hyperplasia Associated with Lower Urinary Tract Symptoms: Prevalence and Incident Rates. Urol Clin North Am 2016;43(3):289-97. 2. Osman N, Aldamanhori R, Mangera A, et al. Antimuscarinics, β-3 Agonists, and Phosphodiesterase Inhibitors in the Treatment of Male Lower Urinary Tract Symptoms: An Evolving Paradigm. Urol Clin North Am 2016;43(3):337-49. 3. Sexton CC, Coyne KS, Kopp ZS, et al. The overlap of storage, voiding and postmicturition symptoms and implications for treatment seeking in the USA, UK and Sweden: EpiLUTS. BJU Int 2009;103(3):12-23. 4. Coyne KS, Sexton CC, Kopp ZS, et al. The impact of overactive bladder on mental health, work productivity and health-related quality of life in the UK and Sweden: results from EpiLUTS. BJU Int 2011;108(9):1459-71. 5. Chapple CR, Roehrborn CG. A shifted paradigm for the further understanding, evaluation, and treatment of lower urinary tract symptoms in men: focus on the bladder. Eur Urol 2006;49(4):651-8. 6. Gratzke C, Bachmann A, Descazeaud A, et al. EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction. Eur Urol 2015;67(6):1099-109.

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. Friday, 24 March Urology Beyond Europe, Joint Session of the European Association of Urology (EAU) and the Maghreb Union Countries

Saturday, 25 March 2017

Relevance of histopathological subtypes Which are the bad guys?

TNM stage, histological tumor grading and correct histological tumor classification are accepted prognostic parameters of renal cell carcinomas. International agreement was reached on the histological classification of renal epithelial neoplasms with the new World Health Organization (WHO)-classification of the tumors of the urinary system and male genital organs. The new “Blue Book” of the 2016 World Health Organization (WHO) classification of urogenital tumors contains significant changes, which were discussed at the WHO Consensus Conference in March 2015 in Zurich, Switzerland1. New or rare distinctive kidney tumors have been described, including HLRCC-associated RCC, SDH-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC and clear cell papillary RCC. These entities have now been included in the new WHO classification of renal tumors.

emphasis on the von Hippel-Lindau gene and hypoxia-inducible factor pathway-related proteins. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2011;24:1207-20. 9. Zhou H, Zheng S, Truong LD, Ro JY, Ayala AG, Shen SS. Clear cell papillary renal cell carcinoma is the fourth most common histologic type of renal cell carcinoma in 290 consecutive nephrectomies for renal cell carcinoma. Human pathology. 2013. 10. Gill AJ, Hes O, Papathomas T, Sedivcova M, Tan PH, Agaimy A, et al. Succinate Dehydrogenase (SDH)deficient Renal Carcinoma: A Morphologically Distinct Entity: A Clinicopathologic Series of 36 Tumors From 27 Patients. The American journal of surgical pathology. 2014. 11. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D,

Saturday 25 March 11.40-11.50: Joint meeting of the EAU Section of Urological Pathology (ESUP) and the EAU Section of Urological Research (ESUR)

Cutting-edge Science at Europe’s largest Urology Congress

EAU members are kindly invited to the EAU Booth G50 to collect the following complimentary items:

Congress delegates are kindly invited to collect the following complementary items:

EAU Extended Guidelines The EAU Extended Urological Guidelines edition 2017.

EAU17 Abstracts CD A CD containing all Join us! presented abstracts during the 32nd Annual EAU Congress can be collected at booth F26.

EAU Pocket Guidelines The pocket edition of the EAU Guidelines edition 2017.

References

E t CM nten -A d co EUcredite

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.

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EUROPEAN UROLOGY

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De Historia Urologiae Europaeae Vol. 24 The EAU History Office is presenting a slightly heftier edition of the annual De Historia this year, due to the high volume of quality material from last year’s 6th Annual Congress on the History of Urology in Munich. Features a wide range of interesting topics from the history of urology. Urology Under the Swastika, edited by Dirk Schultheiss and Friedrich Moll The result of many years of research, this book examines how the German occupation of Europe affected urology and urologists in the 1930s and 40s. The book was inspired by a recent German-language publication by the DGU on Urology in the Third Reic. European Textbook on Kidney Transplantation, edited by A. Figuereido and E. Lledo-Garcia A comprehensive volume that covers all aspects of kidney transplantation, prepared on behalf of the EAU Section of Transplantation Urology (ESTU). The book features leaders of the field, who offer a compilation of the latest research as well as their personal insights.

T +31 (0)26 389 0680 F +31 (0)26 389 0674 guidelines@uroweb.org www.uroweb.org #eauguidelines

Historia Urologiae Europaeae series is addressed to all European urologists. Its aim is to make known the ideas and the work of our predecessors, and to help us understand the current trends in the development of our speciality. Unfortunately, the treatises written in Sanskrit, ancient Chinese, Greek and Latin are both difficult to find and difficult to understand, and should, therefore, be translated into English. The same applies to more recent books published in various languages.

European Association of Urology

Guidelines 2017 edition

Most of the treatises produced before the 17th century, even the legendary ones, have gaps, mistakes and inconsistencies. Modern scientific research allows us to re-evaluate this ancient knowledge and examine it from new perspectives. The History Office of the EAU in collaboration with internationally based urologists, historians, philologists and other experts, conducts research, accumulates and shares this fascinating information in their annual publication, Historia Urologiae Europaeae.

“Remember the days of old, consider the years of many generations, ask thy father, and he will shew thee; thy elders, and they will tell thee.” (Deuteronomy 32:7)

EAU17 ESU Courses DVD A DVD including all presentations and course materials of the ESU Join us! Courses given during the congress can be collected at booth D28.

Cutting-edge Science at Europe’s largest Urology Congress

MINIMAL SYSTEM REQUIREMENTS Windows PC * Windows Vista / 7 / 8 / 10 Macintosh * OS X 10.5 and newer (Intel) Installation of Adobe Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer. If the application does not start automatically, please open the Explorer or Finder, go to your Disc Drive and run the “ESUCOURSES2017” Application. Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended. Before prescribing the product always refer to the prescribing information available in your country. For more information: EAU Education Office PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680 esu@uroweb.org, www.uroweb.org

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EAU17 ESU Courses 32nd Annual EAU Congress

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EAU17 Posters DVD A DVD containing posters presented during the 32nd Join us! EAU17 Posters Annual EAU Congress. A copy of the EAU17 Posters DVD is distributed in the congress bag. MINIMAL SYSTEM REQUIREMENTS Windows PC * Windows Vista / 7 / 8 / 10 Macintosh * OS X 10.5 and newer (Intel) Installation of Adobe Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer. If the application does not start automatically, please open the Explorer or Finder, go to your Disc Drive and run the “POSTERS2017” Application.

Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended. Before prescribing the product always refer to the prescribing information available in your country. For more information: European Association of Urology PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680, F +31 (0)26 389 0674 eau@uroweb.org, www.uroweb.org

COPENHAGEN

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Don’t forget to collect them! Dirk Schultheiss Friedrich Moll The publication of the European Textbook on Kidney Transplantation is the result of a project that involved the entire community of European professionals working in renal transplant clinical programs. Urologists, nephrologists, pathologists, microbiologists, transplant coordinators, nurses: all are essential to make an activity as complex as renal transplantation possible.

UROLOGY

In twenty-six diverse and essential chapters, the past, the current state of the art and the possible future for the procedure is explored by experts in their respective fields. European Textbook on Kidney Transplantation is a volume that will help those who are already experts to improve in their areas of knowledge, and those who, even without experience, want a comprehensive introduction to the subject.

under the

S WA S T I K A

The book was published by the European Urology Association and coordinated and edited by doctors Arnaldo Figueiredo and Enrique Lledó-García. It is the intention of the editors that this book become the standard manual on kidney transplantation of the entire urological community in Europe.

DE HISTORIA

European Textbook on Kidney Transplantation

UROLOGIAE EUROPAEAE VOLUME

2017 edition

Supported by an educational grant from:

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DE HISTORIA UROLOGIAE EUROPAEAE 24

1. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. European urology. 2016;70:93-105. 2. Delahunt B, Eble J. Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol. 1997;10:537-44. 3. Jiang F, Richter J, Schraml P, Bubendorf L, Gasser T, Mihatsch M, et al. Chromosomal imbalances in papillary renal cell carcinoma: Genetic differences between histologic subtypes. Am J Pathol. 1998;153:1467-73. 4. Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, et al. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. The New England journal of medicine. 2015. 5. Lohse CM, Gupta S, Cheville JC. Outcome prediction for patients with renal cell carcinoma. Semin Diagn Pathol. 2015;32:172-83. 6. Amin MB, MacLennan GT, Gupta R, Grignon D, Paraf F, Vieillefond A, et al. Tubulocystic carcinoma of the kidney: clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma. The American journal of surgical pathology. 2009;33:384-92. 7. Tickoo SK, Deperalta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, et al. Spectrum of Epithelial Neoplasms in End-Stage Renal Disease: An Experience From 66 Tumor-Bearing Kidneys With Emphasis on Histologic Patterns Distinct From Those in Sporadic Adult Renal Neoplasia. Am J Surg Pathol. 2006;30:141-53. 8. Rohan SM, Xiao Y, Liang Y, Dudas ME, Al-Ahmadie HA, Fine SW, et al. Clear-cell papillary renal cell carcinoma: molecular and immunohistochemical analysis with

Latif F, et al. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008;100:1260-2. 12. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, et al. The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. The American journal of surgical pathology. 2013;37:1490-504. 13. Frew IJ, Moch H. A clearer view of the molecular complexity of clear cell renal cell carcinoma. Annu Rev Pathol Mech Dis 2015;10:263-89.

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European Association of Urology

Renal tumors with benign or low malignant behaviour 1. Multiple publications report no recurrence or metastasis in patients with multilocular cystic renal cell carcinoma. Multilocular cystic renal neoplasm of low malignant potential, therefore, is now the WHO-recommended term for this lesion, because the prognosis is excellent. 2. The entity of papillary renal cell carcinoma has traditionally been subdivided into two types: type 1 and type 2 papillary renal cell carcinomas2,3. Recent molecular studies suggest that type 2 papillary renal cell carcinomas may not constitute a single well-defined entity, but rather individual subgroups with a different molecular background4. Type 1 papillary renal carcinomas have a better outcome than type 2 papillary RCC, but some patients with type 1 papillary RCC show tumor recurrence or metastasis. 3. Papillary adenomas are benign tumors and have been defined until 2015 as tumors measuring ≤ 0,5 cm. The WHO 2016 classification defines papillary adenomas as unencapsulated tumors with papillary or tubular architecture, low WHO/ ISUP grade and a diameter ≤1.5 cm. The decision to increase the size cut-off was due to available data that unencapsulated grade 1-2 tumors have no capacity to metastasize5. 4. Mixed epithelial and stromal tumors (MEST) encompass a spectrum of tumors ranging from predominantly cystic tumors (adult cystic nephromas) to tumors that are more solid. Most of these tumors are benign, but rare examples are associated with aggressive behavior. 5. Tubulocystic RCC is a dominantly cystic renal epithelial neoplasm. Although the nuclei are enlarged with WHO/ISUP grade 3 nucleoli, only 4 of 70 reported cases showed metastasis to bone, liver and lymph nodes6. 6. Clear cell papillary RCC is a renal epithelial neoplasm composed of low grade clear epithelial cells arranged in tubules and papillae7. They account for up to 5% of all resected renal tumors and arise sporadically, in end-stage renal disease and von Hippel-Lindau syndrome8,9. According to current knowledge, these tumors have an indolent behaviour. 7. Succinate dehydrogenase (SDH)-deficient RCC is a new tumor entity10-11. It presents mainly in young adults and most patients have germline mutations in a SDH gene11. The majority of SDH-deficient RCC has a good prognosis. In cases with sarcomatoid differentiation and necrosis, the prognosis is less favourable. 8. Acquired cystic disease associated RCC occurs in the kidneys of end-stage renal disease and acquired cystic kidney disease7. Most of these tumors have an indolent behavior. 9. Mucinous tubular spindle cell carcinoma are low-grade polymorphic renal epithelial neoplasms

Renal tumors with aggressive behavior 1. Clear cell renal cell carcinomas: Tumor grade and stage are the most important prognostic parameters. The 4-tiered WHO/International Society of Urological Pathology grading system is now recommended by the WHO12. This grading system has been validated for clear cell RCC and papillary RCC. Grade 4 tumors with aggressive behavior are defined by the presence of pronounced nuclear pleomorphism, rhabdoid and/or sarcomatoid differentiation. The WHO/ ISUP grading system has not yet been validated for other tumor types and is not recommended for chromophobe RCC. Various molecular alterations influence the biological behavior in ccRCC. The chromosome 3p locus contains up to seven potential ccRCC tumor suppressor genes: VHL, PBRM1, BAP1, SETD2, RASSF1A, TU3A, and DLEC1. The elucidation of the effects of different combinations of mutations on the initiation and progression of ccRCC will be an important future area of research13. ccRCC with BAP1 alterations have a poor outcome. In contrast to other solid tumors (e.g. melanoma or lung cancer), there are at present no predictive molecular biomarkers suitable for routine use14. The use of such biomarker has to consider the considerable genetic intratumoral heterogeneity with the parallel evolution of multiple tumor clones15,16. 2. Most carcinoids of the kidney have a poor prognosis with frequent occurrence of metastasis after nephrectomy. “Renal carcinoids” should be newly designated as well differentiated neuroendocrine tumors of the kidney and simultaneously placed within the group of endocrine tumors encompassing also small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas. 3. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated RCC are rare tumors occurring in the setting of non-renal leiomyomatosis and demonstrate germline Fumarate hydratase (FH) mutations17. The prognosis of these tumors is poor18. 4. Primary renal synovial sarcomas, renal primitive neuroectodermal tumors (PNET), collecting duct carcinomas and MiT-family-associated translocation carcinomas19 in adults have a very aggressive behaviour.

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Outcome prediction for renal cell cancer (RCC) remains controversial and although many parameters have been tested for prognostic significance, only few have achieved widespread acceptance in clinical practice.

with mucinous tubular and spindle cell features. The prognosis seems to be favorable. 10. Chromophobe RCC has a favourable prognosis. Tumor stage, sarcomatoid change, necrosis, and small vessel invasionpredict poor outcome. The WHO/ISUP grading system is not recommended for chromophobe RCC.

EAU17 ESU Courses 1

Prof. Dr. Holger Moch Department of Pathology and Molecular Pathology University Hospital Zurich Zurich (CH)

European Association of Urology 2017

EDITED BY PHILIP VAN KERREBROECK AND DIRK SCHULTHEISS

2017

Edited by Arnaldo Figueiredo and Enrique Lledó-García

EUT Congress News

Symposium sponsored by PIERRE FABRE MEDICAMENT

Dealing with complex OAB* patient proﬁles - in or out of EAU guidelines? Saturday, March 25th 2017 - 6:00 pm – 7:30 pm Location: Room Berlin, North Hall (level 1)

Chairman: John Heesakkers, the Netherlands Management of women with OAB* Montserrat Espuña Pons, Spain How to deal with OAB* in patients at risk of cognitive impairment? Emmanuel Chartier-Kastler, France The issue of the elderly with OAB* Philip Toozs-Hobson, UK *OAB: Overactive bladder This symposium is fully sponsored and supported by Pierre Fabre Medicament S.A.S., including honoraria and production of materials. Date of Preparation: January 2017 - UK/TOV/1216/0026g

da Vinci

LIVE Surgery Please join our live surgeries on

Sunday, 26th March • 14:00 - 17:00 Room Copenhagen (Boulevard, Level 1)

LIVE da Vinci Si® Partial Nephrectomy Surgery Operating Surgeon Ben Challacombe • Guy’s Hospital, London

LIVE da Vinci Xi® Nephroureterectomy with Integrated Table Motion Operating Surgeon Christophe Vaessen • la Pitié -Salpêtrière Hospital, Paris

Moderators Peter Wiklund - Karolinska lnstitutet, Stockholm Prokar Dasgupta - Guy’s Hospital, London Jens-Uwe Stolzenburg - University of Leipzig, Leipzig

The da Vinci® Xi® Surgical System is a CE Marked medical device of class 2b (CE 0543) under the European Medical Devices Directive (93/42/EEC) manufactured by Intuitive Surgical, Inc. To obtain complete information, including the intended purpose of the device as well as cautions and warnings, please refer to the user manuals of the da Vinci Xi Surgical System, Table Motion user manual, instruments and accessories user manual and other product information. ©2017 Intuitive Surgical, Inc. All rights reserved. PN 1033104-EU Rev A 2/17

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Saturday, 25 March 2017

Management of stent-related problems Managing complications from prolonged stent use Dr. Alberto Trinchieri Urology Unit, Manzoni Hospital Lecco (IT)

In the last 50 years, double J ureteral stents are included in the urologists’ armamentarium to be employed for the relief of the ureteral obstruction, whether the cause is intrinsic or extrinsic, or for treatment or prevention of complications of various urological procedures. However this device may cause troublesome symptoms that cause patients to request its removal or complications that require surgical treatment.

antimicrobial properties have been tested: heparin, diamond-like carbon, Teflon, hydrophilic agents, silver, antimicrobials peptides. Recently, significant progress has been made for drug-eluting stents (DES) to be used in the urinary tract similarly to those that have been used widely for cardiovascular disease, although this technology is more frequently applied for permanent metal stents rather than for temporary stents. Several options of drug-eluting stents are available: triclosan, antimicrobials, ketorolac, paclitaxel, zotarolimus, indomethacin

Pharmacological treatment Another option to increase stent tolerance is the pharmacological treatment (Table 3). For this purpose, orally administered alpha blockers and antimuscarinic agents were employed with controversial results. Two recent meta-analyses confirmed that alpha-blockers reduced urinary symptoms and pain related to the presence of the stent, thus improving The presence of a ureteral stent implies the general health condition and sexual life. Both appearance of some symptoms up to 80% of cases. alfuzosin and tamsulosin were effective, although an The symptoms are predominantly voiding disturbances advantage for tamsulosin was observed. Topical (frequency, urgency, dysuria, incomplete voiding) and administration of non-steroidal anti-inflammatory pain (suprapubic and/or flank pain). Less frequently, drugs in the bladder at the time of insertion of the hematuria or incontinence can be associated to stent stent ensures a short-term reduction of symptoms. placement. The causes of these symptoms are related to the mechanical effect of the stent on the bladder Complications and to the movements of the stent along the ureter in Ureteral stenting is also associated with specific connection with physical activity. The symptoms can complications that may require endoscopic treatment. be aggravated by the coexistence of a urinary tract The obstruction of the inner lumen of the stent is infection and the presence of encrustations on the manifested by back pain and sometimes hyperpyrexia stent surface. Flank pain mainly depends on urine in combination with ultrasound detection of reflux along the stent in the presence of high hydronephrosis. The replacement of the stent allows pressures at emptying of the bladder. for quick resolution of disturbances, although sometimes prolonged antibiotic treatment could be necessary. The encrustation of the stent may lead to a troublesome treatment in case of heavy burden of encrustations that are typically located at both ends of the stent. Before any treatment, the conditions of the stent should be evaluated with an accurate radiological study to define the location and the Contour injection burden of incrustations. A grading system KUB was ureteral stent set, recently introduced to identify cases that may require Photo: extensive endoscopic treatment for successful removal Boston Scientific of the encrusted stent (Table 4). A total score >= 9 was associated with multiple surgeries, multimodal Finally, the dislocation of the stent end below the approach and operative time > 180 minutes. bladder neck may cause urgency and incontinence. The presence and severity of symptoms related to the In the presence of limited encrustations, shock wave presence of a ureteral stent can be measured with a lithotripsy (SWL) represents a good option provided score that is derived from the replies to a specific that the kidney is maintaining a good function to questionnaire investigating six domains. The ensure the spontaneous expulsion of the fragments. In symptoms related to the presence of the stent can be case of larger deposits, encrustation at the distal stent prevented with a careful selection of the stent length should be treated by ballistic and laser endoscopic depending on the patient’s bodily measurements lithotripsy and those at the proximal end in the renal (Table 1). Recently a predictive model for preoperative cavities by percutaneous nephrolithotomy (PCN). In evaluation of the length of the ureteral stent to place most severe cases a combined retrograde and in the ureter has been developed. percutaneous approach is mandatory. Stent characteristics Tolerance to the presence of the stent can be also influenced by the characteristics of the device. Factors that can be considered are the consistency of the material, its shape and external coating of the stent. Stents of different composition and hardness or with variable durometry (hard stem but soft distal end) have been tested. Three different types of polymers are currently used for self-retained ureteral stents: thermoplastic materials such as polyurethanes, and thermoset elastomers such as silicone and hydrogels. Polyurethane stents are easy to form and have high drainage capacity, whereas silicone shows the best biocompatibility but a lower drainage efficacy. Spiral-cut stents to increase the flexibility and stent with the bladder end without coil to increase tolerability have been designed. Different types of external coating have been proposed and experimentally and clinically investigated to increase the tolerance of the device by avoiding the formation of bacterial biofilm or encrustations (Table 2). Numerous compounds with anti-adhesive or

Spontaneous fracture of the stent or fracture caused by traction at the time of removal is a rare event often associated with a prolonged stay of the stent. Other factors favoring the possible stent fracture are the “hostility” of urine or an inadequate positioning with formation of kinking. Typically, the rupture takes place mostly at the level of the drainage holes along the stem of the stent. Removing of the proximal fragments of the stent can be anterograde (PCN) or retrograde (URS).

The “forgotten” stent One of the most frequent causes of stent-related complications is the prolonged stay of the device because the patient is not conscious of its placement or forgets that it must be removed. Medico-legal accountability for the removal resides with the

Formula 22 CM FOR PATIENTS HEIGHT RANGING 149.5-178.5 BODY WEIGHT x 0.125 + 0.5 CM VERTICAL DISTANCE FROM L2 VERTEBRA TO PUBIC SYMPHISIS – 2 CM CHILD AGE (YRS) + 10

Saturday, 25 March 2017

Surface coatings Heparin

Anti-adhesive coating Reduced encrustation (high negative charge) No resistance to bacteria adherence

In vitro Clinical study

Cauda et al 2008 Lange et al 2009

Diamond-like carbon

Anti-adhesive

Reduced encrustation and biofilm Reduced symptoms and complications

In vitro Clinical study

Laube et al 2006 Laube et al 2007

PTFE (Teflon)

Anti-adhesive

Increased patency of metallic Animal study ureteral stents

Chung et al 2008

Hydrophilic agents

Anti-adhesive

Reduction E.coli adherence (enhanced by coupled antibiotics)

Animal study In vitro study

Pechey et al 2009 John et al 2007

Silver

Antimicrobial activity

Silver-alloy reducing catheter-associated UTI No definitive conclusion

Systematic review of studies with urethral catheters

Davenport & Keeley 2005 Beattie & Taylor 2011

Antimicrobials Antimicrobial activity peptides in biofilms Drug-eluting stents (DES)

Reduced presence and survival of bacteria

In vitro Animal study

Cirioni et 2007 Minardi et al 2007

Triclosan

Bacteriostatic or bactericidal

Reduction of antibiotic usage Clinical trials and symptoms No difference in rate bacteriuria/ infection

Cadieux 2009 Mendez-Probst 2012

Clarithromycin

Antibiotic

Prevention of biofilm infection

Animal study

Cirioni et al 2011

Ketorolac

Anti-inflammatory

Less pain medication

Multicenter clinical trial

Krambeck et al 2010

Indomethacin

Anti-inflammatory

Use in biodegradable urethral stent

Animal study

Kotsar et al 2012

Paclitaxel

Anti-proliferative agent

Prevent hyperplastic reaction to metal mesh stents

Animal study

Liatsikos et al 2007

Zotarolimus

Anti-proliferative agent

Prevent hyperplastic reaction to metallic stents

Animal study

Kallidonis et al 2011

Table 3: Pharmacological treatment of stent-related discomfort Author

Drug

N° patients

Results

Beiko 2004

Intravesical Instillation Ketorolac vs lidocaine vs oxybutynin vs saline

42 pts with ureteral stenting after SWL

Reduction irritative symptoms at 1 hour by ketorolac

Deliveliotis 2006

Alfuzosin 10 mg/day vs placebo for 4 weeks

100 pts with ureteral stenting Alfuzosin decreased urinary symptoms index and preserved general health and sexual function

Park 2009

Alfuzosin 10 mg/say vs tolterodine ER 4 mg/day vs placebo for 6 weeks

52 pts

Alfuzosin and tolterodine improved pain and urinary symptom index score

Damiano 2008

Alfuzosin 10 mg/day for 1 week (uncontrolled)

75 pts with ureteral stenting

Decreased flank pain and urinary symptoms

Beddingfield 2009

Alfuzosin 10 mg/day vs placebo for 10 days

55 pts with ureteral stenting after URS

Alfuzosin improved sleep interruption, use of analgesic, pain interfering with life, flank pain during micturition

Wang 2009

Tamsulosin 0.4 mg/day vs placebo for 1 week

79 + 75 pts with ureteral stenting after URS

Lower urinary symptoms , body pain and general health in the tamsulosin group

Nazim 2012

Alfuzosin 10 mg/day for 1 week

65 + 65 pts with ureteral stenting after URS

Alfuzosin group showed less urinary symptoms, better QoL, less pain score

Dellis 2014

Alfuzosin 10 mg day vs Tamsulosin 0.4 mg/day vs placebo

100 + 50 pts with ureteral stenting after SWL/URS

Decreased scores for urinary symptoms, body pain, general health index, sexual life No difference alfuzosin/tamsulosin

Norris 2008

Oxybutynin 10 mg vs 60 pts with ureteral stenting pheanazopyridine 200 mg after URS for 3 weeks vs placebo for 3 weeks

No difference for pain, urinary symptoms, use of analgesic or hematuria

Lamb 2011

Metanalysis of 5 studies with alfuzosin 10 mg or tamsulosin 0.4 mg

Reduction of urinary symptom score – 8.4%, CI -11.1 to -5.6 Reduction of pain score – 7.2%, CI -11.8 to -2-5

Kwon 2015

Metanalysis of 7 studies with alfuzosin 10 mg or tamsulosin 0.4 mg

416 pts

Reduction of urinary symptom - 4.85%, CI -8.53 -1.33 alfuzosin - 8.84%, CI -13.08 – 4.31 tamsulosin Reduction of pain score - 5.71%, CI -11.32 – 0.52 alfuzosin - 7.77%, CI -13.68 – 2.14 tamsulosin

Table 4: Classification of the complexity of stent incrustation (KUB) (Arenas 2016) Finally, the stent may migrate downwards or upwards losing its anchor in the kidney or in the bladder, respectively. Proximal migration towards the kidney is typically associated with an insufficient length of the stent, while the distal migration towards the bladder is most often explained by the shape of the proximal end of the stent and with poor memory material.

Table 1: Formulas for determining the adequate length of the ureteral stent by body measurements Author Ho 2008 Hao 2008 Hao 2008 Palmer 2007

Table 2: Surface coatings of ureteral stents and drug-eluting stents

K – kidney

No calcification

Coil calcification < 5 mm

Coil calcification > 5 mm

Coil calcification < 5 mm + coil filled

Coil calcification > 5 mm + coil filled

U – ureter

No calcification

Single calcification Single calcification Multiple calcification < 5 mm > 5 mm < 50%

Multiple calcification > 50%

B - bladder

No calcification

Coil calcification < 5 mm

Coil calcification > 5 mm + coil filled

Coil calcification > 5 mm

surgeon responsible for its insertion who is liable to prosecution if complications develop due to prolonged permanence of the device. For this reason several preventive strategies were developed to prevent this event (stent-card based registries, registries incorporating a barcode system, electronic registries with built-in automated reminders, use of reminder messages by SMS or registered post, wrist bands with barcodes) although information and education of the patients remain crucial. In conclusion, the ureteral stent represents a very useful tool that nevertheless exposed to side effects and complications. Indications for their proper use

Coil calcification < 5 mm + coil filled

should be scrupulously respected to avoid excessive use that may expose the patient to unnecessary suffering or at the risk of having to undergo additional treatment to address possible complications. Editorial Note: Due to space constraints the reference list has been omitted. Interested readers can email at EUT@uroweb.org for a complete listing. Saturday 25 March 13.05-13.15: Meeting of the EAU Section of Urolithiasis (EULIS) in cooperation with the EAU Section of Uro-Technology (ESUT)

EUT Congress News

Prognostic biomarkers in renal cell carcinoma More therapeutic options highlight role of prognostic markers Prof. Dr. Kerstin Junker Clinic of Urology and Pediatric Urology Saarland University Homburg/Saar (DE)

Renal cell carcinomas (RCC) account for more than 90% of renal tumors. RCC are subdivided into histologically defined subtypes. The most common subtypes are clear cell RCC (70-75%), papillary RCC (10-15%) as well as chromophobe RCC (5%) and the benign oncocytomas. Genetic analyses have shown that these subtypes are characterized by different chromosomal alterations suggesting that each subtype represents a distinct tumor entity with different tumor biology. What does it mean for daily clinical routine? It has been demonstrated by many clinical investigations that the prognosis in patients with renal cell tumors depends on the subtype. Patients with clear cell RCC have the worst prognosis compared to other RCC subtypes based on high frequency of distant metastases. For a long time, prognostic markers in renal cell carcinomas (RCC) did not really play a role, but they are more and more requested during the last decade because several therapeutic options are available depending on clinical stage. So we need markers allowing the definition of metastatic potential to decide which patients need an aggressive therapy. This is also important in small renal masses in order to decide if it is really necessary to perform surgery, especially in older patients. Here, biomarkers can help to identify aggressive tumors in biopsies. Furthermore, biomarkers are necessary to select patients for adjuvant therapies.

Until now, risk stratification in localized tumors is based on T-category and grading. But it is known that also small tumors can metastasize in about 20% on one hand, and that not all T3 tumors have a metastatic potential on the other hand. Therefore, a more individual approach characterizing aggressive tumors is requested. This would be of great importance for adjuvant clinical trials. Many putative prognostic biomarkers have been published for clear cell RCC (ccRCC). But it is clear now, that we need molecular signatures but not single markers because metastasis is a complex process including several changes in the tumor cells and their microenvironment. During the last years, such molecular signatures have been identified on different levels which are really promising. So gene expression signatures have been described by Rini et al. (16 gene signature1) or by Brannon et al. (ccA vs. ccB)2. These signatures can distinguish aggressive subtypes in ccRCC, especially in localized disease. They can help define an individual risk of metastasis independent on tumor size. In addition, our group developed a signature of four copy number alterations in ccRCC which can identify primary tumors with high metastatic potential by using a simple FISH-test3. This so called total number of aberrations score (TNSA score) was validated in two independent cohorts. Non-coding RNAs including microRNAs (miRNAs) represent another very interesting type of markers. We and other groups have shown that miRNA signatures are very promising because a limited number of miRNAs compared to mRNAs are necessary to identify aggressive metastatic tumors in RCC4-6. Another advantage of miRNAs is the high stability and the possibility to also use routine formalin fixed and paraffin embedded (FFPE) samples. Only little is known for other subtypes like papillary or chromophobe RCC which are characterized by a lower frequency of metastatic disease.

Papillary RCC subtypes In papillary RCC we have to distinguish two subtypes: type 1 with good prognosis and type 2 which is much more aggressive with shorter survival. The molecular pathology especially of type 2 was almost unknown for many years. Recently, complex TCGA data on pRCC have been published showing that an aggressive type 2 subtype is based on hypermethylation, 9p alterations, specific miRNA changes and partially on FH mutations. Patients with these tumor characteristics are younger and have a very poor prognosis. Based on these results, it seems possible to identify aggressive renal cell carcinomas by analyzing tumor samples. We have to learn that histopathological subtypes have to be further subdivided into groups with different prognosis based on a specific molecular background. However, recently published data on tumor heterogeneity in RCC provokes questions about the usefulness of biomarkers analyzed in tumor tissue samples. Until now, the influence of heterogeneity in primary RCC was analyzed systematically only in one study showing a heterogeneous picture of the ccA and ccB prognostic signature at least in some cases7. In contrast, Rini et al. have not seen a high heterogeneity of the 16 gene prognostic signature in a small cohort1. Therefore, we have to evaluate the quality and accuracy of the published prognostic signatures depending on tumor size as critically discussed by Gerlinger8. In addition, we have to start prospective clinical trials to proof the clinical utility of putative molecular signatures including biopsy material. In addition, liquid biopsies including free nucleic acids as well as extracellular vesicles are promising biomarkers for prognostic evaluation because they can help overcome problems which are based on intratumoral heterogeneity. But we have to evaluate if liquid biopsies are suitable as prognostic markers in addition to their diagnostic potential.

Figure: FISH on tumor cell nuclei (blue) from clear cell RCC: loss of 9p21 (green; 1 signal), centromere 9 (red; 2 signals)

Editorial Note: The reference list has been shortened due to space constraints. For a full list, email at communications@uroweb.org References 1. Rini B, et al. (2015), A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation studies. The lancet oncology. 16, 676-85. 2. Brannon AR, et al. (2010), Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. Genes & cancer. 1, 152-163. 3. Sanjmyatav J, et al. (2014), Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH. British journal of cancer. 110, 2537-43.

Saturday 25 March 11.50-12.00: Joint Meeting of the EAU Section of Urological Pathology (ESUP) and the EAU Section of Urological Research (ESUR)

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Saturday, 25 March 2017

EAU Guidelines Office successes New topics in the 2017 EAU Guidelines Prof. Dr. James N’Dow Chairman, EAU Guidelines Office Dept. of Urology University of Aberdeen Aberdeen (GB)

The EAU Guidelines are the most comprehensive continuously updated guidelines, available for urologists and related specialities, produced by a dedicated Guidelines Office involving approximately 300 international experts.

development of its guideline and stating its intention to disseminate it broadly. This year the EAU Guidelines Office is delighted to announce the inclusion of two new topics in the 2017 EAU Guidelines, Renal Transplantation and Thromboprophylaxis. The 2017 EAU Renal Transplantation Guideline represents a complete update of the previously discontinued 2009 Guideline. It has been developed by an international multidisciplinary group of urological surgeons, a nephrologist and a pathologist, chaired by Dr. Alberto Breda. All new and relevant evidence was identified, collated and appraised through a broad and comprehensive literature search covering a 10-year period. A total of 2,601 unique records were identified, retrieved and screened for relevance, making this one of the most comprehensive evidence-based guidelines for renal transplantation available to urologists today. Topics covered include: organ retrieval and transplantation surgery; donor and recipient complications; matching of donors and recipients; immunosuppression after kidney transplantation; immunological complications and follow-up after transplantation.

A bird’s eye overview of changes and their relevance for clinical practice will be the main focus of both courses giving attendees a quick insight into how the different fields are progressing. In addition to the two exciting ESU courses, the Guidelines Office will also have a presence at the EAU17 exhibition. We would encourage everybody to please stop by the EAU booth and meet our dedicated staff, who will be more than happy to answer any questions you may have regarding the many activities of the Guidelines Office.

Most importantly, the yearly publication of the EAU Guidelines would not be possible without the unwavering support of the EAU Executive Committee and Management team, our highly valued Guidelines Panels and young Guidelines Associates, our EAU membership and every user of the Guidelines globally. On behalf of the EAU Guidelines Office Board, thank you for your support and inspiration. We hope you enjoy using the 2017 update of the EAU Guidelines!

TP 59 1.0 02/2017/A-E

The EAU Guidelines are recognised worldwide as an important resource to assist clinicians in their everyday practice, they are currently available in more than 30 languages and endorsed by more than 55 national and scientific societies throughout Europe and the world. In addition, the Guidelines Board is honoured that the American Society of Clinical Oncology (ASCO®) has formally endorsed the EAU Guidelines on Muscle-Invasive and Metastatic Bladder The 2017 EAU Thromboprophylaxis in Urological Cancer (MIBC). Surgery Guideline is the first of its kind. The Guideline aims to provide practical evidence-based guidance The ASCO® endorsement process involved an regarding post-surgery thromboprophylaxis and assessment of methodologic quality using the peri-operative management of antithrombotic agents Rigour of Development subscale of the Appraisal of in urology. The need for such a guideline arose Guidelines for Research and Evaluation II (AGREE because existing recommendations for II). As part of this process, the EAU MIBC guideline thromboprophylaxis have been limited by a lack of was extensively reviewed for developmental rigour urology-specific evidence and also due to substantial by methodologists whilst the ASCO® Endorsement practice variation in the use of thromboprophylaxis in Panel reviewed the content and recommendations. urology, both within and between countries. To Along with its endorsement, ASCO® have added develop the new guidelines a series of systematic qualifying statements, highlighting the use of reviews of the baseline risk of venous chemoradiotherapy for select patients with MIBC thromboembolism and bleeding in a wide variety of and recommending a preference for clinical trials in urological procedures were completed. These reviews the treatment of metastatic disease in the provided a stronger evidence base for urological second-line setting. Overall, the ASCO® thromboprophylaxis guidelines than has been Endorsement Panel commended the EAU on the previously available. The resultant guideline provides

Adherence to national and international clinical guidelines is sub-optimal throughout Europe; therefore, the development of clinical guidelines must fundamentally be supported by an effective dissemination and implementation strategy. Dissemination should be an active process in which tailor-made information is actively imparted to the Clinical practice guidelines not only play a pivotal role appropriate audience/users. The EAU Guidelines Social Media (SoMe) group has been tasked with in health care practice, but are also a vital resource promoting discussion and triggering feedback from for the advancement of medical education. The EAU guidelines users via Facebook and Twitter. From its Guidelines Office is committed to actively pursue official start in January 2015, a total of 343 tweets have effective collaborations both within the EAU and externally which help to further the medical education been sent by the EAU describing the key points of the EAU guidelines, with a total of 8,709 tweets using the of young clinicians. A key example of this is the EAU hashtag #eauguidelines resulting in upwards of nine Guidelines Office systematic review programme, the million impressions and leading to a 40% increase in success of which is measurable in the numerous the number of followers of the EAU Twitter account European Urology publications it has produced to @uroweb. Furthermore, the SoMe group carried out date. Other highly productive collaborations include 16 guidelines twitter polls on specific EAU Guidelines the hosting of multiple European School of Urology questions to estimate the approximate adherence of (ESU) courses on changes in the guidelines. This responders to EAU Guidelines recommendations. year’s EAU17 courses include: These polls demonstrated that median adherence with guidelines recommendations was 62% among • “What’s new in the 2017 EAU non-oncology poll participants. The SoMe group recognise that Guidelines”, Sunday 26th 12.00-14.00, will focus on the major changes in the recommendation and participants in these polls represent a highly selected population with potential biases who may not be text of the EAU Guidelines of Incontinence, Male representative of the urologic community at large. LUTS and Urological Infections. During the course of 2017 the EAU SoMe group will • “What’s new in the 2017 EAU Renal, Bladder and continue to actively drive these processes forward, Prostate Cancer Guidelines”, Monday 27th 08.30-11.30, will focus on the major changes in the allowing for the continued dissemination of the optimum use of urological healthcare resources recommendations and text of the EAU Guidelines ultimately, leading to improved patient outcomes. of these three foremost oncology topics. procedure and patient risk-specific guidance weighing the benefit of reduced venous thromboembolism against the harm of increased bleeding. Furthermore, it provides recommendations for numerous urologic procedures with a simple and practical patient risk stratification scheme.

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Saturday, 25 March 2017

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New 2016 WHO classification of penile cancer HPV infection’s critical role in lower genital tract cancers Dr. Maurizio Colecchia Department of Pathology Fondazione IRCCS, Istituto Nazionale dei Tumori Milan (IT)

A new morphological and molecular classification of the histologic types of penile cancer based on the presence of human papilloma virus (HPV) has been presented in the 2016 edition of the WHO classification of urological tumors1 (Figure 1). Figure 1: Malignant epithelial tumours of the penis 2016 WHO Classification

Non–HPV-related penile Squamous cell carcinomas Squamous cell carcinoma Usual carcinoma Pseudohyperplastic carcinoma Pseudoglandular carcinoma Verrucous carcinoma Carcinoma cuniculatum Papillary carcinoma, NOS Adenosquamous carcinoma Sarcomatoid carcinoma Mixed carcinoma

HPV-related penile SqCCs Basaloid carcinoma Papillary–basaloid carcinoma Warty carcinoma Warty–basaloid carcinoma Clear cell carcinoma Lymphoepithelioma-like carcinoma Other rare carcinomas

Similar to what has been described for vulvar lesions, a bimodal pathogenesis for HPV-related and non-HPV-related penile cancers has been proposed. The critical role of HPV infection in cancers of the lower genital tract has been delineated during the last several decades, and particularly the presence of high-risk HPV subtypes in a subset of around half of penile carcinomas is widely accepted: depending on the population examined, the technique used, and tumor morphology, the HPV detection rate has been estimated to range from 30 to 83% of cases, while the prevalence is thought to be around 50%. In the majority of these cases, high-risk HPV subtypes (HPV-16 and HPV-18) were integrated into the genome; the same integrated subtype was observed in both primary and metastatic tumors. HPV is most frequently associated with basaloid or warty carcinoma variants, where it has been reported in 75–100 % of cases, while the majority of usual/keratinizing and verrucous carcinomas are not HPV related. HPV-16 infection appears to influence p16 protein and Rb gene expression, with the virus typically presenting in the nucleus of tumor cells in an episomal or integrated form. It is the most common viral type in penile carcinoma, accounting for 60–70% of high-risk HPV-positive cancers. Two mechanisms of dysregulated cell cycle control and apoptosis have been reported in penile carcinoma: one is HPV mediated and targets the p16INK4a-cyclinD-Rb pathway, while the other is not HPV mediated, with p14 gene mutation, MDM amplification, and altered p53 expression. Both mechanisms bring about cell cycle arrest with altered apoptosis, while inactivation of the Rb gene results in loss of negative control of p16 with overexpression of p16 protein. The altered expression of p16 protein was first associated with HPV’s oncogenic potential in cervical and genital lesions. Integrated HPV produces the E7 oncoprotein, which induces inactivation of the Rb gene and overexpression of the p16 protein, as can be detected by immunohistochemical staining. In addition to p16 immunohistochemistry, the detection of HPV in clinical specimens is based on nucleic acid probe technology, using hybridization procedures (Southern blot, Northern blot, ISH, hybrid 14

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capture) and DNA/RNA detection by means of the more accurate and expensive real-time polymerase chain reaction (PCR). Other causative agents are reported as lichen sclerosus, that may represent a preneoplastic condition in particular for some non-HPV-related cancers, i.e., verrucous, usual-type, papillary, and pseudohyperplastic carcinomas. When we consider carcinomas affecting exclusively the foreskin, the association of lichen sclerosus with penile invasive carcinoma is much higher (69%). Several other risk factors have been associated with the development of this cancer, including phimosis, previous radiotherapy, smoking or chewing tobacco, chronic inflammation, balanitis, injuries to the penis, and poor hygiene. Squamous cell carcinoma The most common histologic subtype of penile cancer (50–60 % of cases) is the squamous cell carcinoma (SCC), usual type. It occurs with different patterns of growth (i.e.: vertical and superficial spreading patterns). Macroscopically, usual SCC presents as an ulcerative, white-gray nodule. Accurate gross examination allows the detection of linear prominences (1–2 mm in thickness) in the mucous membrane adjacent to the invasive tumor, which microscopically appear as squamous hyperplasia or well-differentiated PeIN. Usual SCC is an infiltrating carcinoma that can be classified with a 3-grade system: grade 1, well differentiated, grade 2, moderately differentiated and grade 3, poorly differentiated according to the level of keratinization, cellular pleomorphism, and the presence of regular nests or sheets of tumor cells. Sarcomatoid change is considered a separate category2, which often is combined with other tumor types and conveys a very poor prognosis. Unusual patterns such as pseudohyperplastic, acantholytic, clear-cell, small-cell, and other patterns may be focally present in mixed tumors. Warty carcinoma Another frequently observed variant of SCC is warty carcinoma (5%-10% of penile cancers). Warty carcinomas are slow-growing lesions that may originate years before their histologic assessment. They are similar to vulvar neoplasms presenting as a large, firm, cauliflower-like mass with a white-gray surface, sometimes affecting multiple anatomical compartments. It has been found to encompass the glans, coronal sulcus, and foreskin as a cobblestonelike, firm mass. The gross appearance can be quite similar to that of condyloma acuminatum, but the nodularity is asymmetrical and frequently confluent. The cut surface of the penectomy specimen shows a papillomatous growth with penetration into the corpus spongiosum (Figure 2). Microscopically, there are complex papillae with pointed tips, irregular fibrovascular cores, and parakeratosis . The nuclei are large and wrinkled, with frequent bi- or multinucleation and koilocytotic atypia. The tumor-stroma interface is usually irregular and infiltrative. The main differential diagnosis is with benign condyloma, which lacks the cellular pleomorphism seen in warty carcinoma. In benign lesions, the nuclear koilocytosis is confined to the superficial layers, while in warty carcinoma, it extends throughout the tumor. More challenging cases present as non-invasive, flat, papillary lesions in the glans. In this presentation the detection of high-risk HPV (usually subtype 16), which is typical of warty carcinoma, may be necessary to distinguish it from giant condyloma. The reported incidence of HPV in warty carcinoma varies. The variability may be explained by different factors, including (a) viral DNA degradation in the preanalytic phase, (b) different sensitivity of the techniques used for HPV detection, and (c) selection of warty carcinomas based on nonuniform histopathologic criteria. Verrucous and papillary carcinomas are low-grade verruciform neoplasms that are frequently misdiagnosed as warty carcinoma. The clinical behavior of warty carcinoma is intermediate between that of the other types of low-grade verruciform tumors (papillary, verrucous) and usual SCC. Local recurrence after penectomy has been reported in 10% of cases and lymph node metastasis in 17–18%.

spindle cells (>50 %). The gross appearance of most tumors is a large, polypoid, fungating, and frequently ulcerated mass affecting the glans, with a vertical pattern of growth deeply infiltrating the corpora cavernosa; also the foreskin is frequently infiltrated. The presence of corporal intrapenile metastasis (so-called satellitosis), an unusual type of cancer progression, has been identified in the corpora cavernosa and the skin. Poorly differentiated spindle cell proliferation arising from the epithelium of the distal penis most likely represents a sarcomatoid carcinoma, although the connection with the lining epithelium may be difficult to assess even after extensive sampling. For this reason, despite the lack of a connection with the epithelium of the glans or the absence of high-grade PeIN, a large spindle cell tumor ulcerating the distal penis represents in the majority of cases sarcomatoid differentiation in an SCC.

Figure 2a: Warty carcinoma. Figure 2b: Diagram of a. T tumor, CS corpus spongiosum, CC corpus cavernosum, A tunica albuginea, F foreskin, U urethra

The spindle cell component is frequently disposed in interlacing bundles or embedded in a loose myxoid stroma resembling fibrosarcoma or leiomyosarcoma. Other areas may have angiosarcomatoid features, while heterologous elements (cartilaginous tissue, bone, strap cells corresponding to striated muscle with rhabdomyomatous features) have rarely been reported. The differential diagnosis includes different kinds of sarcomas and melanomas, but penile sarcomas are located in the deep penile shaft, an uncommon site for penile carcinoma. Patients with sarcomatoid carcinomas have a poor prognosis, and the survival is usually short (less than one year). The lymph node metastasis rate is very high (75–89%) and local and systemic recurrence is common (67%). Another variant of penile carcinoma is the basaloid histotype: basaloid carcinoma (BC) is an aggressive tumor occurring as a large, ulcerated mass with endophytic, vertical growth deeply penetrating the corpora cavernosa. It is generally composed of a monotonous population of small-to-medium- sized cells with basophilic cytoplasm.

Hybrid carcinoma occasionally presents lymph node metastases, which explains the presence of metastatic cases otherwise never reported in true verrucous carcinoma. The mortality rate is low and the selection of treatment (conservative versus radical with or without groin dissection) requires careful histologic grading and assessment of perineural invasion. In the last ten years many unusual histotypes were described increasing the difficulty for detecting and reporting the unusual features of these rare variants: clear cell, lymphoepithelioma-like, cuniculatum, pseudoglandular, pseudohyperplastic, adenosquamous, papillary basaloid are some of the unusual epithelial penile tumors, each not exceeding 20 cases reported in the literature (less than 1% of all penile cancers )1,3. The morphologic features of these new entities of the 2016 WHO classification are accurately detailed in the WHO blue book1.

Penile intraepithelial neoplasia (PeIN) Finally, a new WHO classification of precursors lesions of invasive penile cancer reports two main groups: HPV-related and non–HPV-related intraepithelial carcinomas (PeIN). Differentiated PeIN is most The pattern of solid nests of small cells is commonly associated with usual and low- grade predominant, while focal basaloid features may be subtypes of squamous carcinoma (non–HPV-related seen in association with other penile tumor subtypes . variants), whereas warty PeIN and basaloid PeIN are associated with warty or basaloid invasive carcinoma The solid pattern of growth with small, poorly (HPV-related variants). differentiated cells with scant cytoplasm resembles basal cell carcinoma (BCC) of the vulva. The preferred This specific association further supports the concept site of origin of BC is the glans. In the majority of BC of a bimodal pathway of penile carcinogenesis . For cases, carcinoma in situ (CIS) is present adjacent to most cases, there is a good correlation between the invasive carcinoma . This neoplasm is usually HPV subtype of PeIN and the associated invasive related and immunoreactive to p16. carcinoma1 (Figure 3). HPV positivity has been reported in a high percentage of BCs, ranging from 71 to 80%. For its poor prognosis Figure 3: Pathological classification of penile intraepithelial neoplasia (PeIN) this histotype needs an accurate and early detection when it occurs as superficial intraepithelial tumor (basaloid HPV-related PeIN) in bioptical samples. 1. Non–HPV-related PeIN Differentiated Mixed penile tumors harbor more than one histologic (simplex) PeIN subtype and each of the subtypes should make up at least 20% of the tumor mass. Their frequency ranges 2. HPV-related PeIN Basaloid PeIN between 20 and 33% of all penile carcinomas. Warty PeIN Warty–basaloid PeIN Most of these tumors are located in the glans. The 3. Other rare patterns of PeIN Pleomorphic most common mixed carcinoma is the warty-basaloid Spindle ,Clear cell ,Pagetoid SCC histotype. This tumor has more than 10% of basaloid cells that are located in superficial papillae or the deep front of invasion or in both areas. The References same histologic type shows koilocytosis and other 1. Moch H, Humprey PA, Ulbright TM, Reuter VE. characteristic features of warty carcinoma in more WHO Classification of Tumours of the Urinary than 10% of the tumor mass, even in the System and Male Genital Organs. Fourth edition intraepithelial variant. Warty-basaloid carcinomas IARC Lyon, 2016.   show a higher rate of metastasis (52%) than warty 2. ICCR Carcinoma of the penis dataset: carcinomas (33%), as the clinical behavior is related see www.iccr-cancer.org to the histologic grade, tumor thickness, and presence 3. Pathology of Testicular and Penile Neoplasms. Maurizio of vascular or perineural invasion.

Another classical example of mixed SCC is verrucous carcinoma with higher-grade foci consisting of usual Sarcomatoid carcinomas SCC, so-called hybrid carcinoma. Other less frequent Sarcomatoid carcinomas account for approximately combinations include usual-warty, mixed usual4% of penile carcinomas. They are a high-grade, basaloid, and occasionally observed cases of most likely HPV-unrelated variant of SCC characterized pseudoglandular carcinoma adjacent to a wellby biphasic neoplasia predominantly composed of differentiated SCC.

Colecchia ed. Springer International Publishing Switzerland 2016

Saturday 25 March 12.40-12.50: Joint meeting of the EAU Section of Urological Pathology (ESUP) and the EAU Section of Urological Research (ESUR)

Saturday, 25 March 2017

Heterogeneity in renal cell carcinoma The urologist’s view Prof. Vincenzo Ficarra Urologic Unit, Academic Medical Centre Hospital Santa Maria della Misericordia Udine (IT)

Dr. Fabio Zattoni Urologic Unit, Academic Medical Centre Hospital Santa Maria della Misericordia Udine (IT)

In the last decades, urologists learned that renal cell carcinoma (RCC) was not a single tumor but rather a heterogeneous group of cancers arising from renal cells of different segments of kidney’s tubules. Several histologic subtypes were described and classified in the last years according to their different morphological, molecular and cytogenetic characteristics (Table 1)1. Interestingly, pathological variants of RCC differ not only in disease biology, but also in clinical behavior, prognosis, and response to systemic therapy2. Looking at the three main histologic subtypes, clinical data showed that papillary (pRCC) and chromophobe RCC (chRCC) have often favorable pathologic stages and lower nuclear grades, as well as a lower risk of metastases, compared with clear cell RCC (ccRCC). Accordingly, the five -year cancer-specific survival probabilities ranged from 43% to 83% in ccRCC, from 61% to 90% in pRCC, and from 80% to 100% in chRCC3. Moreover, metastatic non-clear cell subtypes are shown to be poorly responsive to immunotherapy and/or modern targeted therapies. Prognosis of ccRCC is strongly influenced by other traditional and well-studied histopathological factors such as pathological staging, nuclear grade, coagulative necrosis, microvascular invasion and sarcomatoid de-differentiation3. Conversely, no molecular or genetic biomarkers of progression have proven sufficiently robust to enter clinical practice4. To further complicate the assessment of prognostic behavior and the interpretation of response to the different medical therapies, several studies showed that some morphological, immunohistochemical and molecular features are sometimes heterogeneous across different areas of the same tumor5. Briefly, areas of sarcomatoid de-differentiation, coexisting areas of different nuclear grades and/or different cellular types in the context of the same tumor represent the most common morphological intratumor heterogeneities (ITH) observed in ccRCC subtype (Figure 1). Concerning immunohistochemical factors, some studies highlighted that CD10, CK7, CD13, Ki67, and COX2 biomarkers had a patchy immunostaining pattern in ccRCC5. More complex is to investigate molecular ITH, i.e. the presence of genetically distinct subpopulations of cells within geographically distinct regions of the same primary tumor. Molecular ITH is an important driver of tumor adaptation and progression with significant implications for drug discovery and biomarker validation6. Briefly, molecular ITH can be expression of two different patterns of development. The linear patter is characterized by the fact that the production of a specific cell clone does not start until the previous cell is fully developed. Conversely, in the branched pattern various cell subclones coexist within the same tumor and each of them follows its own pattern of evolution. ccRCCs are characterized by a branched pattern of evolution with various mutations coexisting in different areas of the tumor. Several somatic mutations, somatic copy number variations, and gene expression analysis have been evaluated in the setting of ccRCC prognosis. Molecular biomarkers In a recent systematic review of the Literature, Gulati et al evaluated the prognostic impact of 28 molecular biomarkers on cancer-specific survival. The ccB expression signature (subgroup classified using 110 Saturday, 25 March 2017

genes) was the only independent predictor of cancer-specific survival. The authors highlighted as multiregional assessment of the tumors may improve the precision of this marker7. Indeed, ITH could explain the variability of clinical outcomes even between patients with tumors of apparently the same histologic type, stage, and grade. Available studies on molecular ITH in ccRCC clearly demonstrated that expression patterns of both good and poor prognosis can be detectable in different regions of the same tumor4. Moreover, aggressive subclones can be present in very small area of the ccRCC tumors, raising important questions regarding how single tumor should be optimally sampled to avoid an irreversible loss of information potentially important for patients5,8. According to the recommended criteria for nephrectomy sampling, pathologists taking a sample for every cm of the tumor and, additionally from any area that looks different o suspicious to the naked eye9. The consequence is that only a small percentage of the entire tumor is really sampled for histological, immunohistochemical, and, eventually, molecular analyses. Moreover, recent studies showed that a significant part of the ITH lies hidden beneath areas of the tumor without easily visible differences. This is the case of small, homogeneous-appearing renal tumors removed during partial nephrectomies in which an ITH can be detected in the context of a homogenous yellowish cut surface. Therefore, some authors suggested performing a more comprehensive sampling approach to better define the morphological, immunohistochemical and molecular characteristics of the tumor and its ITH. In details, an extended sampling was associated with a higher probability to detect a significant proportion of nuclear grade, significant areas of sarcomatoid de-differentiation, presence of coagulative necrosis, and presence of rhabdoid and syncytial cells5. Similarly, recurrent mutations in the PBRM1, SETD2, BAP1, and KDM5C have been underestimated after conventional sampling of the primary tumor specimen or in single biopsies because of their frequent subclonal status4. If multiregional sampling of the tumor may improve the predictive ability of available biomarkers, what sampling is enough remains a key question waiting for the pathologist’s answer. Urologists should strongly support pathologists to better define the more appropriate methods for surgical specimen sampling to define appropriately the morphological, immunohistochemical, and molecular characteristics of ccRCCs independently by their ITH. This task could improve current and future clinical practice in terms of better definition of follow-up schedules, participation in adjuvant trials and management of patients with lymph node, adrenal or vena cava involvement. Theoretically, molecular profiling of these last disease components could anticipate the composition of future metastases and guide the next adjuvant therapy. Renal tumor biopsies Obviously, the risk of underestimating the morphological, molecular and genetic complexity of ccRCC due to ITH is significantly higher when these parameters are assigned from renal tumor biopsies (RTB). RTB reached a very high accuracy in identify malignancies and in histotyping (>90% for ccRCC and pRCC). However, accuracy in grade is still moderate10,11. Nuclear grade heterogeneity can influence negatively the current role of RTBs in the clinical practice. Today, RTBs are useful to guide treatment decisions for small renal masses (SRMs), especially in elderly patients with significant comorbidities. Briefly, patients with

Table 1: Different morphological, molecular and genetic characteristics of main histologic subtypes Tumor type

Microscopic appearance

Clear cell

Abundant clear cytoplasm due to deposition of lipid and glycogen

Papillary

Papillary or tubulopapillary architecture. Calcifications, necrosis, and foamy macrophage infiltration. Distinct cell borders and a voluminous cytoplasm, nuclear morphology with perinuclear halos, binucleation

Chromophobe

Type 1: thin, basophilic papillae with clear cytoplasm Type 2: heterogenous, thicker papillae and eosinophilic cytoplasm. Classic: pale cytoplasm TP53 Eosinophilic: large tumor cells with fine eosinophilic granules

low-risk SRMs characterized by low growth rate, absence of coagulative necrosis, sarcomatoid de-differentiation and ISUP grade ≤2 can be candidates to active surveillance program. Patients who underwent RTBs to personalize the therapeutic strategies for their SRM must be adequately informed that a tumor nuclear grade heterogeneity could be present in more than 80% of cases with 10% of low-grade cases showing a contemporary high-grade component in <50% of the sample. Considering the histologic subtypes, patients with bioptical diagnosis of benign oncocytoma should be informed that in around 18% of cases a component chRCC features (hybrid concocytic chromophobe tumor) could be present (and missed at biopsy) in the same mass12. Missing information could be significantly higher considering molecular ITH. Indeed, clinical data showed that two-thirds of the somatic mutations are not detected in single biopsy procedures. Therefore, using only two to three cores of different tumor regions could be not sufficient to achieve an appropriate evaluation of molecular and genetic ITH in ccRCC. Patients with a metastatic ccRCC represent another interesting category in which ITH could play an important clinical role. Indeed, primary and secondary/metastatic cancers of the kidney differed in nearly one-half of RCC patients. Usually only single, synchronous or metachronous metastasis, surgically resectable are sampled in the clinical practice. In the majority of patients with metastatic disease, medical treatments have been based on histological profile of the primary tumor obtained from biopsy or cytoreductive nephrectomy specimen. However, studies analyzing primary tumors and metastases showed that genotypes can be discordant, genetic alterations that drive disease progression and treatment resistance can arise de novo, or expand from a small subclone undetected on the primary tumor. Therefore, studies evaluating cohorts of primarymetastasis pairs could identify the origin of the metastatic subclone and its associated variants. Sampling of metastases and progressive disease sites could be very informative about clonal dynamics in response to treatment pressure. In other words, repeat sampling is important to identify emerging clones that acquire dominance. In details, trunk events like VHL and PBRM1 mutations represent attractive drugs targets. Conversely, branch events including SETD2, PTEN and KDM5C mutations may be more relevant to predict progression and treatment resistance. In this scenario, urologists and medical oncologists should be more and more prone to

Figure 1: Clear Cell Renal Cell Carcinoma showing three subclones (A-B-C) with different morphological characteristics (Photo Courtesy of Prof Giudo Martignoni, University of Verona, Italy).

Known somatic alterations VHL, PBRM1, SETD2, BAP1, JARID1A, mTOR, PI3K MET NRF2, CUL3

Cytogenetic alterations 3p (90%), 14q, 8p, and 9p and gains at 5q and 12q Gains of 7, 8q, 12q, 16p, 17, 20, and loss of 9p. Papillary type 2 with gains of 8q, loss of 1p and 9p. Loss of chromosomes 1, 2, 6, 10, 13, and 17

support biopsy of metastatic sites or postmortem sampling in patients not suitable for metastasectomy. ITH could have also several consequences in drug development for advanced ccRCC but this step seems still far from an immediate change in clinical practice as well as the attempts to personalize therapy through prognostic or predictive biomarkers8. A crucial role In conclusion, ITH could play an important role in every aspect of the management of RCC including diagnosis, prognosis, design of personalized treatment strategies and stratification of patients into clinical trials. Clinicians should assess ITH of ccRCC using serial, multiregional tissue sampling of primary tumor (biopsy or nephrectomy specimen) and metastatic sites (surgical specimen, biopsy or post-mortem sampling) to collect appropriate information on longitudinal changes in clonal dynamics especially in response to treatment pressure4. References 1. Moch H., Humphrey PA, Ulbright TM et al WHO Classification of tumours of the urinary system and male genital organs. Lyon: International Agency for Research on Cancer; 2016 2. Shuch B., Amin A., Armstrong AJ et al. Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 2015; 67: 85-97 3. Ficarra V, Brunelli M, Cheng L et al Prognostic and therapeutic impact of the histopathologic definition of parenchymal epithelial renal tumors. Eur Urol. 2010; 58:655-68. 4. Soultati A., Stares M., Swanton C et al. How should clinicians address intratumour heterogeneity in clear cell renal cell carcinoma ? Curr Op Urol 2015; 26: 358-366 5. Lopez JI. Intratumor heterogeneity in clear cell carcinoma: a review for the practicing pathologist. APMIS 2016; 124: 153-159 6. Swanton C. Intratumor heterogeneity: evolution through space and time. Cancer Res. 2012; 72: 4875-82 7. Gulati S, Martinez P, Joshi T. Systematic evaluation of the prognostic impact and intratumour heterogeneity of clear cell renal cell carcinoma biomarkers. Eur Urol. 2014;66(5):936-48. 8. Gerlinger M, Catto JW, Orntoft TF et al Intratumour heterogeneity in urologic cancers: from molecular evidence to clinical implications. Eur Urol. 2015;67:729-37. 9. Algaba F, Delahunt B, Berney DM et al Handling and reporting of nephrectomy specimens for adult renal tumours: a survey by the European Network of Uropathology. J Clin Pathol. 2012;65:106-13 10. Tsivian M, Rampersaud EN Jr, del Pilar Laguna Pes M. Small renal mass biopsy--how, what and when: report from an international consensus panel. BJU Int. 2014;113(6):854-63. 11. Marconi L, Dabestani S, Lam TB et al Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy. Eur Urol. 2016; 69:660-73. 12. Conti A., Santoni M., Sotte V et al. Small renal masses in the era of personalized medicine: tumor heterogeneity, growth kinetics, and risk of metastasis. Urol Oncol 2015; 33: 303-309.

Saturday 25 March 12.20-12.30: Joint meeting of the EAU Section of Urological Pathology (ESUP) and the EAU Section of Urological Research (ESUR)

EUT Congress News

Scrotal pain: A challenging diagnostic and therapeutic entity The optimal treatment algorithm Dr. Yacov Reisman Amstelland Hospital Amstelveen (NL)

Although we lack founded epidemiological data, scrotal pain is a common complaint in a urological practice. The diagnosis can be challenging in both acute and chronic forms and therefore needed to be carefully evaluated with full patient history and physical examination, which sometimes may be prevented because of the pain and oedema. Nevertheless, there are no available clinical guidelines concerning this challenging problem. Probably because majority of guidelines are disease and not symptom oriented. Therefore, in this article and during the presentation, the important issues concerning the diagnosis and the treatment approach will be symptom-oriented. In this respect, when dealing with scrotal pain we need to distinguish between two forms of scrotal pain, the acute and the chronic one.

Chronic scrotal pain syndrome (CSPS)/ orchidalgia: A frustrating issue for the clinician and the patient The term “hidden epidemic” has been used when discussing chronic scrotal pain. This debilitating condition is associated with anxiety and frustration and characterized by intermittent or constant uni- or bilateral scrotal pain, occurring for at least 3 months that has a significant negative impact on daily life. This condition certainly represents symptom complex with little in the way of evidence to support specific medical and surgical interventions. These patients are challenging to both the urologist and the GP, and managing patient expectations when a cure may not be feasible can be difficult. According to the EAU chronic pelvic pain guidelines, we don’t have any reliable estimation on incidence and prevalence of chronic scrotal/testicular pain. In The Netherlands, the incidence is estimated at 350–400 cases per 100,000 men per year. In the USA, it affects up to 100,000 men per year due to varying etiologies. In the United Kingdom, the incidence has been estimated around 1%.

In about 25-50% of cases of chronic scrotal pain, no causes are found. The urologists should take into consideration causes of chronic scrotal pain like, diabetic neuropathy, spermatocele/hydrocele, chronic epididymitis, herniated lumbar disc, inguinal hernia, painful bladder syndrome, prostatitis and other referred pain causes from Acute scrotal/testicular pain: To operate or not to abdomen/pelvis. Often CSPS is not associated with operate is the question any specific pathology and the pain is perceived in The “acute scrotum” may be viewed as the urologist’s testes, epididymis or vas deference. Two special equivalent to the general surgeon’s “acute abdomen.” form can be distinguished. The post-vasectomy Both conditions are guided by similar management pain syndrome, with incidence of 2-20% and can principles: the patient history and physical appear in all vasectomy techniques used. Lower examination are keys to the diagnosis and often guide risk is described in the no-scalpel vasectomy. The decision-making regarding whether or not surgical other form is post-inguinal hernia repair. Incidence intervention is appropriate. Imaging studies should is higher in the laparoscopic in comparison with complement, but not replace, sound clinical open hernia repair. judgment. When making a decision for conservative care, the provider must balance the potential It should be noticed that as the scrotum is innervated morbidity of surgical exploration against the potential by the ilioinguinal, genitofemoral and pudendal cost of missing a surgical diagnosis. A small but real, nerves, any pathology at the origin and course of negative exploration rate is acceptable to minimize these nerves may results in perception of scrotal pain. the risk of missing a critical surgical diagnosis. The nerves in the spermatic cord play an important role in scrotal pain. Studies show that the commonest cause of acute scrotum is epididymo-orchitis, followed by torsion of The clinician must be cautious about assuming that appendages. The most common cause in boys of chronic scrotal pain is constitutive in the chronic pelvic preschool age are spermatic cord torsion. The low pain syndrome, and must be diligent in ruling out temperatures during winter may account for the specific etiologies for scrotal pain prior to managing it increased incidence of the torsion of both the as a non-specific chronic pain syndrome. spermatic cord torsion and the appendages. Other important causes to remember are incarcerated CSPS may be associated with LUTS or sexual inguinal hernia, trauma, gangrenous infections or dysfunction but also with negative cognitive, complications of testicular cancer (infarction or behavioral, sexual or emotional consequences. hemorrhage). Rare are inflammations like HenochPast emotional or physical abuse and adverse Schonlein purpura (HSP) and fat necrosis of scrotal life-events are common in some of the men with wall. Acute scrotal pain could also be a referred pain CSPS and the patient should be asked about it as due to, for example, ureter stone. well. There is no single feature in the history, examination or investigation (mainly Doppler ultrasound and urine studies) that is pathognomonic for the diagnosis, the triad together is pivotal for the evaluation. Doppler ultrasound can assess anatomy and blood flow as well as localization of fluid collection or hernia. In the table below some of the distinguishing conditions of acute scrotal pain in adults are given. According to the finding on the history, examination and investigation, treatment steps should follow. The presentation will focus on the treatment consideration according to the diagnostic steps. The urologist should remember that a full range of scrotal pathology must be considered in acute scrotum cases. Several conditions that result in acute scrotum (e.g. trauma and testicle torsion) require surgical exploration, making this a very time sensitive condition. When testicular torsion is highly suspected, surgical exploration should follow. When epididymoorchitis is obvious, exclude sexual transmitted infection and appropriate antibiotics should be prescribed. When the clinical diagnosis is in doubt, urine analysis and Doppler ultrasound should be performed and management should be according to the findings. Cause Testicular Torsion Epididymitis Fournier’s gangrene Appendicular Torsion 16

Pain location Testis Epididymis Diffuse Upper pole of testis

EUT Congress News

After profound history taking about pain, anxiety, depression, overall function, LUTS, sexual function and physical examination should be performed which serve to confirm or exclude specific diseases associated with scrotal pain. Pelvic floor examination should be included as for men with CSCP and a positive pelvic floor exam with DRE, a trial of pelvic floor physical therapy can be an effective and non-operative treatment modality. Scrotal ultrasound usually does not help in the diagnosis of CSPS, it is often used to exclude intra-scrotal or inguinal pathology. The desired goal of the treatment is to allow the patient to return to routine activity without use of significant analgesics. As with any chronic pain condition, an honest, frank discussion with the patient about reasonable expectations is critical. There are many possible treatment modalities available, for which no good clinical practice guidelines exist. These include medication (antibiotics, NSAIDs, Alpha-adrenergic antagonists, tricyclic antidepressants, gabapentin, carbamazepine), minimal invasive (transcutaneous nerve stimulation, spermatic cord blockade, pelvic plexus blockade under TRUS) and surgical

Cremaster reflex Negative Positive Positive Positive

Other findings Profound swelling & high riding testis Epididymis induration, positive urine test Edema of the skin, crepitus, fever, rigors Tenderness of the anterior side of testis

There are no available clinical guidelines on scrotal pain, which makes this condition a challenge to many urologists. Photo: Wikimedia Commons

interventions (microsurgical denervation of spermatic cord or testicles, orchiectomy). Orchiectomy is the last resort in treatment of CSPS and should only be done if other therapies have failed. For postvasectomy pain, vaso-vasostomy can be performed. A multidisciplinary approach is often required so that the patient can benefit from different treatment modalities available at present. In conclusion, due to multiple etiologies and variable treatment outcomes, scrotal pain in acute or chronic form has been and will continue to be a challenging

complaint to manage. Although treatment options are improving, further and better studies are warranted for better understanding of the cause and the long-term effects. Developing of guidelines or standard operating procedures based on presented symptoms could help the urologists in management of the patients. Saturday 25 March 08.45-9.00: Plenary Session 2, Hot topics in andrology

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www.urochm.rcsed.ac.uk Saturday, 25 March 2017

Urology Under the Swastika EAU History Office presents new research into urology’s ‘darkest days’ By Loek Keizer

Schultheiss: “Aside from the very personal tragedies, we can also draw some conclusions about the field of urology as a whole. Generally speaking, the outbreak of the Second World War and subsequent occupation severely limited research and scientific exchange between European countries. National and international medical congresses were postponed or cancelled.”

The rise of national socialism and fascism in Europe and the subsequent occupation of the continent during the Second World War dramatically influenced and ruined the careers of urologists and with it the development of urology as an emerging medical specialty. Prof. Dirk Schultheiss

Dr. Friedrich Moll

In 1933, in Germany alone around a third of urologists were Jewish or otherwise connected to the Jewish community. The 1930s and 1940s saw European urologists dealing with the rapidly changing political situation, including collaboration, forced exile and even death.

and historians in their respective countries to research the topic. We’ve managed to assemble experts through our own office members and other partners. The last group to join was the Israeli team, which joined last summer and did a great job in that brief time.” The EAU History Office is launching its latest book The chapters of the book cover most European Urology Under the Swastika at EAU17. It explores the countries individually, but also some countries where history of European urologists and urology in the (Jewish) urologists fled to such countries as the period of the Nazi rule in Germany and the countries it United Kingdom, the United States, Argentina and the subsequently occupied. We spoke to its editors, former aforementioned Israel. EAU History Office Chairman Prof. Dirk Schultheiss (Giessen, DE) and Dr. Friedrich Moll (Cologne, DE). Effects on urology A large percentage of urological surgeons and related Urology Under the Swastika documents the fates of professions in 1930s Europe were Jewish or of Jewish urologists in this period and explores the effects of the origin. As the Nazi party came to power in Germany Second World War on urology. The complicity and (and then Europe), their rights to practice medicine involvement of physicians and medical societies under were restricted and, eventually, revoked. the influence of national socialism and fascism is presented in a wide range of chapters that cover “Urology, like dermatology and pediatrics had the several European countries and other continents. The highest percentage of Jewish doctors in Germany and dynamics that changed urology, both similar and Austria,” Schultheiss explained. “Among them were vastly different across the continent are based on new several of the world’s most prominent researchers. research and previously unknown sources. Their elimination from active work and research caused a loss of expertise and weakened the newly Project’s origins emerging speciality of urology.” These important issues first received attention from urologists and medical historians in Germany and The doctors who did not immigrate to safer countries Austria through an earlier research project of the were ultimately killed in camps or in some cases German Society of Urology or Deutsche Gesellschaft received exemption as they treated soldiers or für Urologie (DGU), published in 2011. otherwise were of value to their respective country or army. Urology Under the Swastika explores the Prof. Schultheiss: “From the publication of the DGU individual stories of several notable surgeons, as well books on, I’ve been trying to motivate both urologists as the field as a whole.

In addition to urology, the book touches on topics like eugenics, sexology and forced sterilization: all issues that were seized by Nazi science and relied on urologists to assist them. The collusion with power that some urologists chose or were forced to choose sets an example for medical practitioners to this day: “As urologists we still have to be very sensitive when medical practice and the power of politics or economics come together. The extreme cases of the 1930s and 1940s as depicted in certain chapters of this book should keep us all vigilant,” Schultheiss reflected. Research and the divided continent Co-editor Dr. Moll placed this Europe-wide research project into some historical context: “the status of historic research into these events differs very much across our continent. In some cases, we can build on extensive research into medicine during the War, but in others we had to rely on personal research and first- or second-hand accounts of urologists’ experiences in this period.”

“You must also not overlook the devastating (global) economic crisis of the 1920s and ethnic conflicts within newly established countries when investigating the state of urology. The long-term consequences of the First World War were felt throughout the following decades, eventually leading to the start of the Second World War.” In stark contrast to today, the continent and its urologists were far from united at that time. Moll: “The effects on urology and urologists of the rapidly changing political situation differ vastly from country to country. We hope that Urology Under the Swastika reflects this huge diversity and will prompt our colleagues to reflect on this painful period in our field.” • Urology Under the Swastika is one of the membership benefits at EAU17 and can be collected at the EAU Booth (G50) in the Exhibition

From the chapter on urology during the Spanish Civil War and Franco’s Spain: the insignia of (from left) Franco’s Falange • Urology Under the Swastika will be presented political organisation, the National Socialist German Workers’ and discussed during the second part of the Party (NSDAP) or Nazi Party, and the Blue Division. The military Special Session of the History Office, today at symbols of the nationalist military volunteers’ Blue Division 8:30-11:30, Room 9, Capital Suite (Level 3). clearly share the aesthetics of the other two. vprobeQuarterAdEUTFinal_Layout 1 2/14/17 10:14 PM Page 1

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Saturday, 25 March 2017

EUT Congress News

Sexual dysfunction in male cancer survivors Early intervention and rehabilitation- crucial in reducing complications Prof. Ates Kadioglu Section of Andrology Department of Urology Istanbul University Istanbul (TR)

Co-Authors: M. Kadihasanoglu (TR), S. Bajramovic (BA) Cancer is a major health concern worldwide and has a negative quality of life (QoL) impact. The importance of treating cancer-related complications in sexual function of patients has become more important with higher survival rates1. Even cancers that do not directly involve sexual organs can result in sexual dysfunction including erectile dysfunction (ED), structural penile changes, orgasmic and ejaculatory dysfunction and hypogonadism as a consequence of the adverse effects of multi-modal treatment. The severity of sexual dysfunction is significantly associated with poorer overall quality of life (QoL) and higher levels of depression. Therefore, besides the treatment alternatives, preoperative functional status and depression should be discussed with the patient when counseling cancer patients regarding the long-term side effects of cancer treatment2. This article reviews the sexual dysfunction in patients with prostate, penile, testicular, colon and rectal cancers. Prostate cancer Prostate cancer (Pca) remains the most common solid organ non-dermatologic cancer in men in the world. Therefore, preservation of continence and erectile function (EF) is among the most significant interests of patients with local Pca. The rates of sexual dysfunction after treatment are quite high with 70% of men affected despite the development of minimally invasive technology, evolving surgical techniques and a greater understanding of the anatomy of the pelvis. The contemporary literature reports rates of ED after radical prostatectomy (RP) to be around 60-70%, with some robotic and laparoscopic reports citing rates as low as 5-10%3. ED after RP is most often attributed to neuronal and/or vascular injury to the cavernous neurovascular bundle at the time of surgery. ED can occur as a consequence of neuropraxia caused by traction, compression, and coagulation4,5. The neuropraxia causes Wallerian degeneration of the neural structures. It leads to the denervation of the corpora cavernosa and the consequent loss of nocturnal EF activity, with penile hypoxia and fibrosis that can finally result in venous leakage responsible for ED6. Moreover, it has been suggested that the primary mechanism responsible for arterogenic ED may be the transection of the accessory pudendal arteries, which could lead to penile hypoxia independently of the status of the cavernosal nerves7. A cumulative meta-analysis of studies reporting EF in preoperatively potent patients, demonstrated a range of potency rates after LRP vs. ORP vs. RALP at 48 months were 58-74% and 49-74% and 60- 100% respectively8. Moreover, RALP also seems to promote a more rapid EF recovery as compared with ORP and LRP9.

brachytherapy indicates that it may provide better preservation of EF compared with EBRT alone or in combination with hormone therapy14. Vascular comorbidities may have a significant role in ED after RT. Penile deformities (penile length loss and curvature) penile shortening (PS) and Peyronieâ&#x20AC;&#x2122;s disease (PD) has been reported after RP. Several studies have shown that penile length decreases after RP, however rates of PS varied between 0-55% depending on whether a subjective or objective method was used for evaluation and on what cutoff value is used to define PS15-18. The pathophysiology of PS is clearly unknown. A number of mechanisms have been proposed and include anatomic alterations, neural damage, sympathetic nervous system over activity and histological alterations such as apoptosis19. Non-nerve-sparing surgery and ED have repeatedly been shown to be associated with loss of penile length after RP. Contemporary theories place hypoxia and cavernosal smooth muscle apoptosis as the most culpable cause for this length and girth loss. Strategies to reduce length loss and preserve function attempt to mitigate the hypoxia largely through return of early erections with injection therapy or use of PDE-5 inhibitors (PDE5Is)20-22. As a result, NS and postoperative EF, strongly correlate with preservation of penile length. The incidence of penile PD among men with Pca is higher than the normal population and Tal et al. found that incidence of PD after RP was 16.7% in 1,161 patients23. The pathogenesis of PD is still not clear but some authors have suggested that repetitive micro-trauma of the penile tissue during sexual intercourse can induce PD24. The analysis of the pre- and postoperative sexual domains from three prospective studies of high intensity focused ultrasound (HIFU) therapy, in which a maximum of 60% of the prostate could be ablated with an ablation zone had to be at least 10 mm from a neurovascular bundle, has shown that men exposed to HIFU experienced a small reduction in sexual function at six months after treatment25. When the current literature for ED in HIFU ablating the whole prostate gland is reviewed, the range of reported ED ranges from 2% to over 77% in men with normal EF preoperatively25. When the focal therapy studies are reviewed only, the rate of ED ranges from 11% to 45%25. The removal of the prostate and the seminal vesicles may in itself impact orgasmic disturbances including altered perception of orgasm, anorgasmia, and orgasm-associated pain as normal ejaculation is no longer possible. In addition, the correlation between orgasmic function and postoperative potency, nerve sparing, and urinary control implies that nerve damage may play a role26. Age <65 years, higher levels of education, NS surgery, lack of comorbidities and good EF after surgery were positively correlated with the ability to reach orgasm27. Anejaculation after RT is infrequently reported, and the published data on this issue are scarce.

Bladder cancer Bladder cancer, the fifth most common cancer in men in the United States, typically presents as a superficial transitional cell carcinoma that is locally resectable and curable. However, in a small minority of men their cancer is muscle invasive requiring more aggressive treatment with a greater risk of sexual dysfunction. Therapeutic options for this population However, conflicting data exists on this topic and no include surgery, RT and chemotherapy, usually clear statement can be made at this time, clearly demonstrating that robotic compared to laparoscopic associated with radical cystectomy (RC) with urinary diversion28. The long-term prognosis for those who or open is truly superior with respect to erectile undergo RC continues to improve with advances in preservation at this time. Xylinas et al. showed that the robot-assisted intrafascial approach provided early technique and earlier diagnosis, regrettably rates of ED and sexual QoL loss remains high29. satisfactory functional results with respect to postoperative potency10. Consequently, preoperative The etiology of ED after RC is strongly correlated with EF appears to be the best independent predictor of the peroperative injury to neurovascular bundle. A postoperative EF, with age, nerve sparing (NS) large number of animal models exist, describing the technique, surgeon experience, cardiac risk factors type and extent of this injury which has been and diabetes mellitus also contributing to recovery classified as traction, percussive, thermal, transection prediction. and devascularization injury. The high prevalence of post-surgical ED has driven researchers to consider Radiotherapy (RT)-induced male sexual dysfunction whether NS cystectomy is a safe alternative in the including ED and orgasmic dysfunction is thought to result from neurovascular bundle injury and is related treatment of bladder cancer. Several studies have reported accepted rates of potency after NS RC that to the amount of radiation given to the total penile range from 42% to 71%30-32. Numerous studies structure11. Two recent prospective trials showed an incidence of ED in 30-40% of the patients treated with showed that age is an important predictive factor of ED after nerve-sparing RC. Prostate preservation external beam RT (EBRT). Prospective studies have during RC provides better postoperative EF. PR for ED reported an increase of ED between one and two after RC is identical to the Pca survivor rehabilitation; years after RT, whereas ED rates did not seem to PR should be started with PDE5Is as soon as possible change after three years12,13. Recent data on 18

EUT Congress News

Sites of action of androgens in male sexual function, Photo: European Urology

after surgery. Early intervention is associated with better sexual functions and satisfaction rates in the light of current literature33,34. Penile cancer Penile cancer is relatively rare (0.58/100,000 men) in the developed countries of the world. However, in some regions of Africa, South America and Asia the incidence of penile cancer can be up to five times higher35. Penile cancer and its treatment can negative effect sexual function and intimacy, body image, urinary function mental health and QoL. Maddineni et al. reported that penile cancer treatment negatively affected well-being in up to 40% of patients with decreased sexual function in up to 60%36. Kieffer et al. found that men treated with penile-sparing surgery scored significantly better than those who underwent partial penectomy on the orgasmic function scale37. Yang et al. compared sexual performance between partial penectomy and glans preserving surgery and found that patients treated with glans preserving surgery had better performance in all of the IIEF domains score. Recently, brachytherapy has been recommended for initial treatment of invasive T1, T2 and selected T3 penile cancers by consensus guideline38. Delaunay et al. investigated the effect of brachytherapy on sexual function in patients with penile cancer and reported that 58.8% of patients had adequate sexuality after treatment and 47.3% stated that brachytherapy had not affected their sexuality and 15.8% of them had mild changes. Consequently, most patients stated that brachytherapy had little or no influence on their sexual life39. Testicular cancer Most testicular cancers are diagnosed early and approximately 70% of patients are diagnosed at a localized stage. Typically, treatment of testicular cancer begins with inguinal orchiectomy. After inguinal orchiectomy, early stage seminomas are often treated with radiation (45%), however late-stage seminomas (65%) and non-seminomas germ cell tumors are generally treated with chemotherapy especially at high stages of disease. ED has been reported in 12-40% of men treated for testicular cancer, regardless of cancer treatment method40. The etiology of ED in these patients is multifactorial depends on how the patient were treated. Psychogenic ED may be attributable to changes in body image after orchiectomy, loss of sense of manhood after orchiectomy, reduced feelings of well-being and other psychosocial changes associated with cancer41. Tal et al. investigated the pathogenesis of ED 12 months after the completion of therapy in men with testicular cancer. They suggested that ED in testicular cancer survivors is primarily non-vasculogenic42. Anejaculation may be observed in post-chemotherapy patients who underwent RPLND. The anejaculation rate of 7% was reported following nerve-sparing RPLD43. Colon and rectal cancers Colorectal cancer is the third most frequent cancer type observed in men following prostate and lung cancers44. The sexual dysfunction is generally caused by rectum mobilization due to ureteral injury and autonomous nerve degeneration, which was secondary to nerve injury in the hypogastric plexus and autonomic nerves encountered during the dissection of Denonvilliers fascia44. Postoperative sexual dysfunction has been reported in 10-50% of men treated for colon and rectal cancer45,46. Duran et al. demonstrated that a 17.8% decrease in the sexual function of men compared with the preoperational period after abdominoperineal resection and low

anterior resection44. Both erection and ejaculation were impaired significantly. Celentano et al. showed that avoiding macroscopic damage to nerves peroperatively (nerve sparing) helps with preserving erectile function47. Unfortunately, nerve-sparing surgery is not applicable in every patient. Early intervention is crucial Sexual dysfunctions are common in male patients with cancer and have been shown to vary in intensity and frequency according to treatment modality, age, pre-existing sexual function and many other factors. The early intervention of rehabilitative strategies may prevent loss of penile length and increased EF score. Despite several preventive and therapeutic strategies being available, there is no evidenced-based specific recommendation on the optimal rehabilitation or treatment regimen at this time. 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. References 1. Sadovsky R, Basson R, Krychman M, Morales AM, Schover L, Wang R, et al. Cancer and sexual problems. The journal of sexual medicine. 2010 Jan;7(1 Pt 2):349-73. PubMed PMID: 20092444. Epub 2010/01/23. eng. 2. Gandaglia G, Lista G, Fossati N, Suardi N, Gallina A, Moschini M, et al. Non-surgically related causes of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Prostate cancer and prostatic diseases. 2016 Jun;19(2):185-90. PubMed PMID: 26857023. Epub 2016/02/10. eng. 3. Kadioglu A, Ortac M, Brock G. Pharmacologic and surgical therapies for sexual dysfunction in male cancer survivors. Translational andrology and urology. 2015 Apr;4(2):148-59. PubMed PMID: 26816821. Pubmed Central PMCID: PMC4708121. Epub 2016/01/28. eng. 4. Salonia A, Burnett AL, Graefen M, Hatzimouratidis K, Montorsi F, Mulhall JP, et al. Prevention and management of postprostatectomy sexual dysfunctions. Part 1: choosing the right patient at the right time for the right surgery. European urology. 2012 Aug;62(2):261-72. PubMed PMID: 22575909. Epub 2012/05/12. eng. 5. Salonia A, Zanni G, Gallina A, Sacca A, Sangalli M, Naspro R, et al. Baseline potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy. European urology. 2006 Aug;50(2):360-5. PubMed PMID: 16413666. Epub 2006/01/18. eng. 6. Weyne E, Mulhall J, Albersen M. Molecular pathophysiology of cavernous nerve injury and identification of strategies for nerve function recovery after radical prostatectomy. Current drug targets. 2015;16(5):459-73. PubMed PMID: 25777276. Epub 2015/03/18. eng. 7. Mulhall JP, Secin FP, Guillonneau B. Artery sparing radical prostatectomy--myth or reality? The Journal of urology. 2008 Mar;179(3):827-31. PubMed PMID: 18221962. Epub 2008/01/29. eng. 8. Kilminster S, Muller S, Menon M, Joseph JV, Ralph DJ, Patel HR. Predicting erectile function outcome in men after radical prostatectomy for prostate cancer. BJU international. 2012 Aug;110(3):422-6. PubMed PMID: 22182202. Epub 2011/12/21. eng. 9. Kim SC, Song C, Kim W, Kang T, Park J, Jeong IG, et al. Factors determining functional outcomes after radical prostatectomy: robot-assisted versus retropubic. European urology. 2011 Sep;60(3):413-9. PubMed PMID: 21612859. Epub 2011/05/27. eng.

Saturday 25 March 12.-12.15: Joint meeting of the EAU Section of Andrological Urology (ESAU) and the EAU Section of Infections in Urology (ESIU)

Saturday, 25 March 2017

Miniaturisation of PCNL How did it affect our approach to stones’ treatment?

Jackman et al was the first to use the term “Mini” PCNL in 1998. Since then several companies and researchers reported on different types and sizes of smaller size PCNL. Definitions Since the introduction of “Mini” PCNL, researchers and companies produced several smaller size systems giving them different names. This has led to some confusion about what is meant by “Mini” and what are the indications and limitations of such technology. For example, Storz uses MIP as for Mini Invasive PCNL. However, MIP can be small (S: 8/11Fr), or large (L: 24Fr), which is in fact one of the “standard” size PCNL. In the table below there are examples of currently available sizes. There is no agreed classification. Browsing the literatures, it seems that “standard” size PCNL is referred to when using access sheath of more than 20Fr, “Mini” if the sheath is between 14 and 20Fr, “Ultra-Mini” for sheaths 11-13Fr and “Micro” if it is 8Fr or smaller.

4. Stone free rate (SFR): Variable way of reporting SFR and what tests are used to confirm this, make it difficult to compare the published outcome. Early reports indicated that SRF is less with smaller size PCNL at about 77% (Giusti Eur Urol 2007). With better experience, most researchers claim to have very good clearance rate up to 97% with no significant difference when compared to standard PCNL (Abdelhafez Scan J Urol 2016, Lu World J Urol 2013, Zeng PLoS 2013). Some advocate that SFR is better for multiple calyceal Technology is improving rapidly with a large range of available stones using multiple “mini” punctures (Cheng J systems, Photo: S. Al-Hayek Endourol 2010, Zhong Urol Res 2011); 5. Stone size and indications: There is no agreed size limit to when one can use “smaller” size PCNL. In theory, the smaller working channel could restrict the use of standard stone destruction devices limiting them to smaller stones. Laser seems to be the main energy source for stone clearance. Studies reported performing smaller size PCNL for stones from 1 to 2.5 cm. most recommend not using it for stones over 2.5 cm (Zeng, Abdelhafez Urol 2013). Interestingly, smaller PCNLs were reported to be effective in treating staghorn stones especially in paediatric population (Desai J Endourol 2004); 6. Operative time: Some researchers admit that smaller sheaths require longer operative time to clear stones (Giusti Eur Urol 2007, Mishra BJUI 2011, Abdelhafez Scan J Urol 2016). This could be due to the smaller optics making vision suboptimal and the use of laser rather standard stone removal devices with smaller fragments that could be retrieved. Others did not notice significant difference compared to larger sheaths (Bilen J Urol 2007, Lu World J Urol 2013). This, of course, depends on the size, location and hardness of the stone in addition to the method used to break the stone; and

Advantages and disadvantages of miniaturisation of PCNL There are some advantages of smaller size PCNLs 7. Patient positioning: “Small” size PCNLs were done such as reduced trauma, bleeding and other in both prone and supine positions with no clear complications. These need to be weighed against effect on stone clearance or complication rate. some possible disadvantages such as longer operative The supine position was associated with shorter time, reduced visibility and the need for auxiliary operative time and ability to combine with procedures. There is conflicting evidence as flexible ureteroscopy (Zhan Urol Int 2013). highlighted in the next few points: PCNL replacing RIRS? Can “smaller” size PCNL replace retrograde intra-renal 1. Less trauma: Having a smaller tract is likely to surgery (RIRS) using flexible ureteroscopy (FURS)? cause less trauma to the kidney especially in children where the smaller sheath is believed to As known, FURS has revolutionised the way we deal split the parenchyma rather than compress it with the upper urinary tract not only to deal with (Desai J Endourol 2004, Billen J Urol 2007 and stones but also to diagnose, treat urothelial Zeren J Endourol 2002). This would also reduce blood loss. However, there does not seem to be a carcinomas and bleeding. Currently, we can treat difference in acute phase marker when looked at renal stones with no need for open or percutaneous surgery especially for small stones. With the by Li (Urol 2010); introduction of “smaller” PCNLs, some advocate that they have advantages compared to FURS. 2. Complications rate: The reported overall complications’ rate varies from as low as 11% and up to 36%. However, there is reasonable evidence “Mini” PCNLs have been reported to have a better SFR for renal stones 2-3 cm (Pan Urolithiasis 2013) and for that smaller tract reduces the complication rates impacted upper ureteric stone (Gu World J Urol 2014) mainly for the more severe types with rare or no Clavien IV or V. (Abdelhafez Scan J Urol 2016, Zeng with shorter operative time (Kirac Urolithiasis 2013) compared to FURS. Sabnis (BJUI 2013) compared BJUI 2016, Cheng J Urol 2010, Mishra BJUI 2011, Zeng Urol Research 2011). This seems to hold true “Micro” PCNL to FURS for smaller stones (<1.5cm). He reported no difference in stone clearance rate, even for bigger size stones; mean operative time and length of stay in hospital 3. Postoperative drainage and hospital stay: With less with less stent requirement with “micro” PCNL but higher haemoglobin (Hb) loss and more pain and trauma and smaller tract, surgeons are more confident in avoiding postoperative nephrostomy analgesic requirement. However, in a recent meta-analysis, De et al (Eur Urol. 2015) reported that insertion leaving only a ureteric stent (tubeless) or nothing (totally tubeless). This usually reduces RIRS can provide higher stone free rate with less the pain, analgesia requirement and hospital stay hospital stay when compared with minimally invasive percutaneous procedures, including “Mini” and “Micro” Name Year/Author Size and Company PCNLs. STANDARD PCNL “Smaller” size PCNLs could Maxi 1980 Alken Wolf/ Storz Amplatz 26-30/32Fr have advantages over RIRS in MIP L Storz 24Fr patients with difficult or no MINI retrograde access, for example, MIP M 2001 Nagale/ Lahme Storz 15.5-18.5Fr patients with ileal conduit, kidney transplant, ureteric Super Mini 2014 Zeng and Sarica 14Fr stricture, stones in calyceal ULTRA MINI diverticulum and in neurogenic Ultra Mini 2013 J Desai LUT 11/13Fr patients with difficulty in MIP S Storz 8/11Fr getting them into lithotomy MICRO position. Those who can’t Mini Micro 2013 Sabins 8Fr & Storz 7.5Fr tolerate ureteric stents or prefer single procedure might prefer Micro 2011 M Desai & Barder Polydiagnost 4.85Fr “smaller” PCNL than FURS. Saturday, 25 March 2017

EAU Guidelines 2016 There is little mentioned about miniaturized PCNL systems in the EAU Guidelines. They stated that there is high efficacy but longer operation time with the benefits compared to standard PCNL has yet to be demonstrated. The guidelines also mentioned that smaller tracts cause less bleeding and complications, but further studies are needed to clarify this. They warned that smaller instruments bear the risk of increasing intra-renal pelvic pressure. Having this cautious approach is probably because the evidence is still primitive to support the regular use of “smaller’ PCNL systems with no large scale randomised control trials. Miniaturisation in practice The European section of Urolithiasis (EULIS) explored the current use of “smaller” PCNL in daily practice (SP Zanetti, Archivio Italiano di Urologia e Andrologia 2016). A survey was sent to 360 EULIS members in 2015 with 88 (24%) responded. 19% were nonEuropean. 58% of the responders performed small size PCNL (< 20Fr). 88% of the others were interested in doing them but they did not have the equipment. This interest is stronger regarding “Ultra-Mini” (75%)

than “Micro” PCNL (61%). The majority (79%) of the responders believe it is important, in terms of invasiveness, to move from regular to smaller PCNL mainly for stones smaller than 2cm. Nearly half of the responders believe “Mini” and “Ultra-Mini” PCNLs can replace RIRS. These results are interesting giving insight to current practice. It is still not clear if the availability of smaller size PCNL systems has changed the indications of treating urinary tract stones. Are we now performing smaller size PCNL for those stones which we could have kept under observation and treated conservatively? Will the total number of PCNLs (including smaller size) increase? With reduced hospital stay and associated complications, can we perform more PCNLs in elderly co-morbid patients? Significant progress There have been significant advances in technology for percutaneous nephrolithotomy surgery over the recent years. At present, standard size PCNL is still routinely performed in most units but many are interested to implement the use of smaller sizes. There is some evidence that smaller tract is associated with less pain, trauma, major complications and reduced hospital stay. In some hands it takes longer. Indications are expanding as surgeons become more familiar and confident with good stone free rate. FURS has an important role in managing renal stones with comparable SFR and shorter length of stay compared to smaller size PCNLs. Technology is improving rapidly with large range of available systems. We should be flexible and customise our selection based on the patients and stones’ characteristics. There is no one system or size that can fit every stone. Saturday 25 March 14.30-14.40: Meeting of the EAU Section of Urolithiasis (EULIS) in cooperation with the EAU Section of Uro-Technology (ESUT)

LLITE T E S I UM O

S S YMP A

The possibility to extract a stone through a percutaneous access under fluoroscopy was first reported by Johanson and Fernström in 1976. Between 1981 and 1984 Alken, Wickham and Segura have described endoscopic percutaneous nephrolithotomy (PCNL).

(Knoell J Eno Urol 2010, Lu World J Urol 2013, Abdelhafez Scan J Urol 2016, Mishra BJUI 2011);

Saturdthay 7 5 201 March 2 :30 9 18:00 -to1ckholm Room S Hall North ) (Level 1

Treating Urological Cancers

New Twists and Turns In The Road Chaired by Professor Nicholas D. James, University of Birmingham (UK)

UK/DEC09547a February 2017

Mr. Samih Al-Hayek Consultant Urological Surgeon Associate Lecturer Cambridge University Hospitals Cambridge (GB)

18:00 – 18:05

Welcome and introduction

18:05 – 18:30

How far have we improved on prostate cancer management ?

18:30 – 18:55

Systemic therapy in RCC – current landscape and future directions

18:55 – 19:20

The future of non-muscle-invasive bladder cancer management

19:20 – 19:30

Questions and answers

Nicholas D. James (UK) Thomas H. Lynch (Ireland) Susanne Osanto (NL)

Shahrokh F. Shariat (Austria) All

The past century has witnessed many advances in the diagnosis and treatment of prostate cancer, and more recently we have seen an evolution in the role of hormone manipulation in therapeutic strategies for this disease. As cancer care aims to move still further towards individualised medicine, developments and remaining challenges in the fields of genetic profiling and robotic surgery will be a focus for future research. In advanced renal cell carcinoma (RCC), new agents have shown significant survival benefit following first-line therapies. This has resulted in an expansion of second-line options and changes to treatment guidelines. Visualisation techniques have revolutionised the management of non muscle-invasive bladder cancer (NMIBC). Such techniques can contribute to earlier and improved detection and resection of NMIBC, more accurate risk stratification, and less invasive, risk-stratified follow-up.

TOPIC OF THE YEAR 2017

* The Innovators in Bladder Cancer “Bladder Cancer Topic of the Year” will be voted on and results announced, at the end of this presentation.

This meeting is initiated and funded by Ipsen and will include reference to Ipsen medicines relevant to the agenda topics.

Please visit the Ipsen booth E16

Exib. Halls S7-S10 Level 1

EUT Congress News

Focal therapy for prostate cancer Is it ready for prime time? Dr. Rafael SanchezSalas L’Institut Mutualiste Montsouris Paris (FR)

available technology in a team-work fashion and its presentation was smartly featured (Stickiness Factor) and third, the previous elements found solid support on both improvements in technology and a strong desire to define a middle ground option between Active Surveillance and more radical options (The Power of Context).

A multi-focal disease The focal therapy researchers knew that their idea had hit the big time when major criticism rose towards the novel approach. As we know, PCa is a The prostate cancer (PCa) therapeutic pathway has multi-focal disease in 60 to 90% of patients. Within shifted dramatically over the past decade. With the the lesions it has been described an index or advent of highly refined imaging, PCa care has dominant lesion, which is the largest tumor nodule become more than a detailed analysis of preoperative that often correlates with the highest Gleason score patient and disease variables aiming to define the among the lesions, thus with the patient’s prognosis5. treatment. In the contemporary era, we are able to clearly depict prostatic lesions and reasonably predict The secondary or satellite lesions are usually small the grade of suspicion for malignancy1. and low-grade, meaning clinically insignificant. The most essential challenge in FT was to assume that by Primary treatment for localized prostate cancer has a treating the index lesion one would be providing rather complex landscape, which offers adequate adequate cancer control treatment for a disease cancer control and also aims to effectively preserve clearly recognized as multi-focal. Available evidence quality of life. Today, urologists have an array of allow us to state that the treatment of the index lesion choices to choose from for the treatment of localized is feasible, oncologically safe and with adequate prostate cancer. However, irrespective of the final functional results.6,7 therapeutic decision, we are highly dependent on Today, not only the broadcast of FT information has imaging for cancer visualization, prostate biopsy become more available in urological meetings but the approaches, patient selection and post-treatment control2. actual application of its concepts and techniques is probably at its peak. Focal therapy (FT) represents a potential shift in clinical practice featuring a tissue-sparing approach Beyond the actual potential of the technique and our personal enthusiasm, one should clearly understand to (PCa) armamentarium. It stands as a middle ground option between active surveillance and more there is a great deal more effort to be done to further radical options like radical prostatectomy or develop this field. Natarajan et al8 have recently radiotherapy. This approach can be summarized as added a well-conceived experience to support FT in follows: (1)define a clinical cohort of patients whose PCa. A phase I study on the safety of transrectal tumors harbor low to intermediate risk characteristics magnetic ultrasound imaging guided focal laser without indication for surveillance and lower than ablation in intermediary risk PCa. those bounded for radical therapy, (2)deploy a powerful imaging tool like multiparametric MRI to The authors clearly present how the technique is to be select target within the prostate in combination with implemented for both imaging and treatment. A total ultrasound, (3)select energies suitable to treat and of eight patients were treated; oncological and safety accomplish an oncologically safe organ-sparing outcomes were adequate with detailed information ablation with minimum toxicity, (4)match patients to on complications, quality of life and follow-up also energies, based on tumors characteristics and provided. The study features comprehensive cancer location, (5)post-treatment surveillance strategies control assessment including PSA (decreased in seven (PSA, MRI, Biopsy) to monitor treatment, with patients), imaging (7.7% of prostate volume) and prostatic biopsies as the most objective way to control biopsies (over 60% of negative biopsies in treated those treatments. area) without changes on urinary and sexual function at six-month follow-up. Through this experience, one More than eight years ago, Linder et al3 presented a understands the importance of detailed organization timely experience on FT for PCa ablation; this for focal therapy (FT) protocols. manuscript defined the three pillars of planning, treatment and control for FT. This manuscript Randomized controlled trial showed not only the necessary technological Of utmost importance, this year FT has been tested interaction in FT but the idea of imaging as an with the standard method for “rational therapeutic” in Medicine. Azzouzi et al9, compared Vascularessential part of the intervention in all of its phases. FT for PCa is today a “catching subject” in urological targeted photodynamic therapy (VTP) versus active oncology. As described by Malcolm Gladwell in his surveillance in men with low-risk prostate cancer in best-seller “The Tipping Point”4: First, some clever phase 3 randomized controlled trial. Two hundred and people thought of a novel therapeutical option for six patients were treated with vascular-targeted PCa able to offer cancer control with limited photodynamic therapy (VTP) and 207 patients morbidity (The Law of the Few). Second, the idea of underwent active surveillance. With a median FT for PCa was well developed integrating different follow-up at 24 months they verified a cancer progression rate of 28% vs 58% for the VTP and AS group, respectively. Moreover, there was no difference in terms of IPSS and IIEF scores and slightly higher Grade 2 complications in VTP group. This timely trial consolidates FT as a safe and effective treatment for low-risk PCa. Comparative study In this year’s EAU meeting, Garcia-Barreras (AM17-1444) et al from our institution present an interesting comparison of 1458 men (1222 robotic assisted radical prostatectomies and 236 FT) according to the NCCN PCa risk classification: 402(27.5%),388(26.6%) and 668(45.8%) very low risk, low risk and intermediate risk, respectively. Oncologic outcomes were analyzed in terms of biochemical recurrence (BCR) free survival and the need Figure 1C: Coronal view; Ultrasound images Figure 1C2: Coronal view; Ultrasound for further treatment. At a during ablation treatment. High intensity images during ablation treatment. Yellow median follow-up of 45.4 mo focused ultrasound* lines delineates the region of interest (ROI)* biochemical recurrence-free Figure 1A: Coronal view; T2 weighted magnetic resonance images (MRI). Red circle indicates tumor outlines.

EUT Congress News

Figure 1B: Coronal view; Diffusion-weighted MRI. Red circle indicates region of interest (ROI) for ablation.

Figure 1D: Coronal view; Real time contrast enhanced ultrasound during high intensity focused ultrasound treatment. Red circle delineates hypoechoic devascularized ablated zone.*

Figure 1E1: Coronal view; T2 weighted postoperative imaging. Red arrow shows the ablated zone.

survival was comparable among RARP and FT (89.4% for RARP vs 91% FT at 20 mo; p 0.69) and no differences were found in overall survival, neither mestastases-free survival between the two treatments; (p 0.85 and p 0.142, respectively). Although FT was associated with higher risk of further treatments (HR 5.21; 95% CI 3.7-7.35; p <0.001), a significant difference was found in terms of complications between treatments, having FT superior rates (15.3% vs 9% for RARP; HR 1.82 ; 95% CI 1.21-2.73; p 0.004). For selected patients with organ confined PCa, RARP and FT offered comparable oncological control with FT requiring higher additional treatments. Potency and continence appears to be better preserved in patients treated with FT. FT is definitively on the spotlight today and it has a great audience. Having said that, we are still at the point of diffusion of a technological interactive approach, which aims to consolidate a particularized, effective and less aggressive treatment for PCa. References 1. Muller BG, van den Bos W, Pinto PA, de la Rosette JJ. Imaging modalities in focal therapy: patient selection,

Figure 1E2: Sagital view; T2 weighted postoperative imaging. Red arrow shows the ablated zone.

*(Focal One HIFU, EDAP-TMS; Vaulx-en-Velin, France)

treatment guidance, and follow-up. Curr Opin Urol. 2014 May;24(3):218-24. 2. Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Magnetic Resonance-Guided Thermal Therapy for Localized and Recurrent Prostate Cancer. Magn Reson Imaging Clin N Am. 2015 Nov;23(4):607-19. 3. Lindner U, Weersink RA, Haider MA, Gertner MR, Davidson SR, Atri M, Wilson BC, Fenster A, Trachtenberg J. Image guided photothermal focal therapy for localized prostate cancer: phase I trial. J Urol. 2009 Oct;182(4):13717. 4. Gladwell, Malcolm. The tipping point – How little things can make a difference. Ed. Little, Brown and Company (2000).

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. Friday 24 March Urology beyond Europe, Joint Session of the European Association of Urology (EAU) and the Confederación Americana de Urología (CAU)

NOW

THERE’S

OPDIVO delivers superior OS vs. everolimus in adult patients with advanced RCC after prior therapy OPDIVO as monotherapy is indicated for the treatment of patients with advanced RCC after prior therapy in adults

Visit BMS at Booth No K12 to learn more OS – overall survival; RCC – renal cell carcinoma Information about this product, including adverse reactions, precautions, contra-indications and method of use can be found at: https://www.medicines.org.uk/emc/medicine/30476. Prescribers are recommended to consult the summary of product characteristics before prescribing. Legal classification: POM Marketing Authorisation holder: Bristol-Myers Squibb Pharma EEIG, Uxbridge Business Park, Sanderson Road, Uxbridge UB8 1DH, United Kingdom. Tel: 0800-731-1736. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Bristol-Myers Squibb Medical Information on 0800 731 1736 or medical.information@bms.com.

106172 EAU London OPDIVO RCC Advert v2.0 2017.02.14.indd 1

14/02/2017 16:18

Saturday, 25 March 2017

ADVERTORIAL This article is written and funded by

Meta-analysis re-reviews the current body of evidence 1

New insights and recommendations on decreasing the risk of progression in bladder cancer Blue-light cystoscopy (BLC) has shown promise in improving detection of bladder tumours and is increasingly becoming a standard in clinical practice.1 Just recently, the first meta-analysis showing the impact of hexaminolevulinate-guided bladder cancer Transurethral Resection of the Bladder (TURB) on reducing progression rates was published.1 At the same time, the new 2016 French National Guidelines2 (AFU) for the management of bladder cancer (BC) have been presented, in which blue-light cystoscopy is recommended for the first TURB in the majority of the BC patients. Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumours compared with standard white-light cystoscopy (WLC), resulting in more efficacious treatment.3 A meta-analysis of raw data had previously revealed an increase in the detection rate of carcinoma in situ (CIS) by 40%, and there were almost 25% patients with at least one additional Ta/T1 tumour seen with BL only (p < 0.001).4 Despite improved detectability of bladder cancer with BLC, literature has not reported a beneficial impact on progression in non-muscle-invasive bladder cancer (NMIBC). However, progression is one of the most important clinical outcomes in non-muscle-invasive bladder cancer as it indicates a worsening of disease.5 A working group compared the results of HAL- vs. white-light guided TURB and found out that rate of progression was significantly lower in patients in whom a TURB was performed with BLC versus WLC alone.1 This recently published meta-analysis by Gakis et al. included NMIBC studies published between 2000 and 2016 reporting on progression after HALand WL-based TURB. Eligible studies were identified via PubMed search and a manual search of publications in journals not listed in PubMed. The selection excluded non-English articles, non-original articles (i.e. review articles with or without systematic review or meta-analysis), editorials or case reports, studies on 5-aminolevulinic acid (ALA)-based TURB, and repeated publications on the same cohort to avoid publication bias. Overall more than 1,300 patients studied The review covered a total of 294 studies, of which five were considered for final analysis (Figure 1). Of the 1,301 patients in these five studies, 49.5% (n=644) underwent BL TURB and 50.5% (n=657) had a WL TURB. Progression was found in 6.8% of BL patients, (44/644) and 10.7% of WL patients (70/657), which was statistically significant (median odds ratio: 1.64, 1.10–2.45 for HAL vs. WL; p = 0.01). Progressionfree survival was reported in a single study and was longer after BL TURB and showed a trend towards improved survival (p = 0.05). The primary objective of the analysis was the rate of progression due to the fact that a beneficial impact of HAL-guided TURB on progression of NMIBC has not been confirmed in meta-analyses until now1. One reason may be that so far, clinical trials have used varying definitions or have failed to define disease progression altogether.5 Therefore, the International Bladder Cancer Group (IBCG) suggests a new definition that goes beyond the commonly used increase in stage from non-muscle-invasive to

UKHEX00164 February 2017

Saturday, 25 March 2017

muscle-invasive bladder cancer.5 The largest and most recent publication included in the review re-analysed the dataset of a phase III randomised trial on HAL- vs. WL-TURB with regard to progression using the new IBCG definition.5 “This is the first meta-analysis which shows a significant beneficial impact of NMIBC detection and resection with HAL-guided TURB on progression. Patients should therefore receive hexaminolevulinaterather than white-light-guided TURB [alone] at their first resection as this might allow more patients at risk of progression to be treated timely and adequately.” Professor Gakis from the Department of Urology, University Hospital Tuebingen, Germany, summarised the result of the review1. Diagnoses with BLC was also associated with decreased risk of recurrence of non-muscle-invasive bladder cancer versus WLC in another recently References published meta-analysis.6 This publication included 1. Gakis G, Fahmy O Systematic review and meta-analysis stratified analyses by use of 5-ALA and HAL. Findings on the impact of hexaminolevulinate- versus white-light were similar when looking at short-term, guided transurethral bladder tumour resection on intermediate-term and long-term recurrence risk. progression in non-muscle invasive bladder cancer. Effects on short-term and long-term recurrence were Bladder Cancer 2016;2:293–300. DOI: 10.3233/BLC-160060 statistically significant in trials that used HAL, and were 2. Rouprêt M et al. CCAFU French National Guidelines not statistically significant in trials that used 5-ALA.6 Diagnostic with Blue-light cystoscopy for the first resection Today, BLC is mentioned and recommended in the majority of Guidelines (Figure 2), including the recently updated American Urological Association (AUA), Association Française d’Urologie (AFU) and Deutsche Gesellschaft für Urologie (DGU) Guidelines from 2016. On November 17th, 2016, during the national meeting of the Association of French Urologists (AFU) in Paris, France, the new 2016 French National Guidelines for the management of Bladder Cancer were presented.7 The purpose of the Comité de Cancérologie de l’AFU (CCAFU) was to propose updated French Guidelines for non-muscle-invasive and muscle-invasive (MIBC) bladder cancers. In order to evaluate references and their levels of evidence, a Medline search had been conducted covering diagnosis, treatment and follow-up of bladder cancer between 2013 and 2016.

2016-2018 on bladder cancer. Prog Urol 2016;27 (Suppl 1):S673–S91. DOI: 10.1016/S11663–7087(16)307043–7. 3. Di Stasi SM et al. Hexaminolevulinate hydrochloride in the detection of non muscle invasive cancer of the bladder. Ther Adv Urol 2015;7(6):3393–50. DOI: 10.1177/ 1756287215603274 4. Burger M et al. Photodynamic diagnosis of non-muscleinvasive bladder cancer with hexaminolevulinate cystoscopy: A meta-analysis of detection and recurrence based on raw data. European Urology 2013;64(5):846–54.

DOI:10.1016/j.eururo.2013.03.059 5. Kamat A et al. The impact of blue light cystoscopy with hexaminolevulinate (HAL) on progression of bladder cancer – a new analysis. Bladder Cancer 2016;2(2):2733– 278. DOI: 10.3233/BLC-160048 6. Chou R et al., Comparative effectiveness of fluorescent versus white light cystoscopy for initial diagnosis or surveillance of bladder cancer on clinical outcomes: systematic review and meta-analysis. J Urol. Article in press. DOI: http://dx.doi.org/10.1016/j.juro.2016.10.061 7. Rouprêt et al. CCAFU French National Guidelines 2016-2018 on bladder cancer. Prog Urol 2016;27 (Suppl 1):S673–S91. DOI: 10.1016/S11663–7087(16)307043–7 8. Rouprêt et al. Cost effectiveness of TURBT of the bladder with blue light in patients with non-muscle invasive bladder cancer in France. Progres en urologie (2015) 25, 2563–264.

Prescribing Information Hexvix® (hexaminolevulinate) Presentation: Hexvix 85mg, powder and solvent for solution for intravesical use. Pack of one 10mL glass vial containing 85mg of hexaminolevulinate as 100mg hexaminolevulinate hydrochloride as a powder and one 50mL polypropylene or glass vial containing solvent. After reconstitution in 50mL of solvent, 1mL of the solution contains 1.7mg hexaminolevulinate which corresponds to an 8mmol/L solution of hexaminolevulinate. Indications: This medicinal product is for diagnostic use only. Hexvix blue light fluorescence cystoscopy is indicated as an adjunct to standard white light cystoscopy to contribute to the diagnosis and management of bladder cancer, in patients with known or high suspicion of bladder cancer. Dosage and Method of Administration: Hexvix cystoscopy should only be performed by healthcare professionals trained specifically in Hexvix cystoscopy. The bladder should be drained before the instillation. Adults (including the elderly): 50mL of 8mmol/L reconstituted solution is instilled into the bladder through a catheter. The patient should retain the fluid for approximately 60 minutes. Following evacuation of the bladder, the cystoscopic examination in blue light The new French Guidelines recommend blue-light should start within approximately 60 minutes. The cystoscopic examination should not be performed more than 3 cystoscopy for the first bladder cancer resection in the hours after Hexvix is instilled in the bladder. Also if the retention time in the bladder is considerably shorter than majority of patients and for consecutive TURBs in one hour, the examination should start no earlier than after 60 minutes. No minimum retention time has been many patients. This facilitates the most correct staging identified making examination non-informative. For optimal visualisation it is recommended to examine and map the entire bladder under both white and blue light before any surgical measures are initiated. Biopsies of all and grading, which is crucial for the optimal follow-up and management of the patient. In contrast mapped lesions should normally be taken under white light and complete resection should be verified by switching to blue light. Only CE marked cystoscopic equipment should be used, equipped with necessary filters to allow both to the former version of the Guideline the update standard white light cystoscopy and blue light (wavelength 380-450nm fluorescence cystoscopy). Children and includes the situations in which diagnosis with BLC adolescents: There is no experience of treating patients below the age of 18 years. Contraindications: Hypersensitivity can reduce the risk of recurrence. A cost-effectiveness to the active substance or to any of the excipients. Porphyria. Warnings and Precautions: The possibility of study applied to the French system revealed a QALY hypersensitivity including serious anaphylactic/anaphylactoid reactions should always be considered. Advanced gain (an economic indicator aiming to estimate the life support facilities should be readily available. Post-marketing experience with repeated use of Hexvix does not value of life) for the use of fluorescence guided TURB indicate that it represents a risk when used in follow-up in patients with bladder cancer however no specific with HAL starting with the first TURB of any NMIBC7,8. studies have been conducted. Hexaminolevulinate should not be used in patients at high- risk of bladder According to Morgan Rouprêt, Professor of Urology at inflammation, e.g. after BCG therapy, or in moderate to severe leukocyturia. Widespread inflammation of the bladder should be excluded by cystoscopy before the product is administered. Inflammation may lead to increased the Pitié-Salpétrière Hospital, University Paris, and porphyrin build up and increased risk of local toxicity upon illumination, and false fluorescence. If a widespread one of the authors of the Guidelines, “the strong level inflammation in the bladder becomes evident during white light inspection, the blue light inspection should be of evidence associated with the newest data incorporated avoided. There is an increased risk of false fluorescence in the resection area in patients who recently have into the European Guidelines for the use of blue light undergone surgical procedures of the bladder. Interactions: No specific interaction studies have been performed with hexaminolevulinate. Pregnancy and Lactation: There are no or limited data on the use of hexaminolevulinate cystoscopy should result in an increased level of in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to the reproductive urological care for the management of patients with toxicity. As a precautionary measure, it is preferable to avoid the use of Hexvix during pregnancy. It is unknown bladder cancer in France.” whether hexaminolevulinate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast- feeding should be discontinued during the treatment with Hexvix. Animal studies do not indicate effects on female fertility. Male fertility has not been investigated in animals. Undesirable effects: Most of the reported adverse reactions were transient and mild or moderate in intensity. The most frequently reported adverse reactions from clinical studies were bladder spasm (2.4%), dysuria (1.8%), bladder pain (1.7%) and haematuria (1.7%). Other commonly (>1/100 to <1/10) reported adverse reactions are: headache, nausea, vomiting, constipation, diarrhoea, urinary retention, pyrexia and post-procedural pain. Prescribers should consult the SPC in relation to other side effects. The adverse reactions that were observed were expected, based on previous experience with standard cystoscopy and transurethral resection of the bladder (TURB) procedures. Overdosage: No case of overdose has been reported. No adverse events have been reported with prolonged instillation times exceeding 180 minutes (three times the recommended instillation time), in one case 343 minutes. No adverse events have been reported in the dose-finding studies using twice the recommended concentration of hexaminolevulinate. There is no experience of higher light intensity than recommended or prolonged light exposure. Pharmaceutical Precautions: This medicinal product must not be mixed with other medicinal products. For single use only. Hexaminolevulinate may cause sensitisation by skin contact. The product should be reconstituted under aseptic conditions using sterile equipment. Any unused product should be discarded. Legal Category: POM. Basic NHS cost: Hexvix 85mg £375 per vial. UK Marketing Authorisation Number: Hexvix 85mg: PL34926/0017. UK Marketing Authorisation Holder: Ipsen Ltd., 190 Bath Road, Slough, Berkshire, SL1 3XE, UK. Tel: 01753 627777. Date of preparation of PI: October 2015. Ref: UK/HEX00036(1) Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard Adverse events should also be reported to the Ipsen Medical Information Department on 01753 627777 or medical. information.uk@ipsen.com Hexvix® is the property of Photocure. EUT Congress News

Managing LUTS Alpha-blockers: A relief for benign prostatic obstruction or only for LUTS improvement? Prof. Yasuhiko Igawa Department of Continence Medicine University of Tokyo Graduate School of Medicine Tokyo (JP)

In men with benign prostatic obstruction (BPO) lower urinary tract symptoms (LUTS) are caused by mechanical bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE) and/or by functional obstruction due to increased tension of prostatic smooth muscle mediated by sympathetic nerves. Because prostatic smooth muscle contraction is caused by sympathetic α1-adrenoceptor (α1-AR) stimulation, sympathetic α1-AR antagonists, α1-blockers, are widely used as the first-line drug therapy for LUTS associated with BPO. In fact, the EAU guideline for the Treatment of Non-neurogenic Male LUTS recommends offering α1-blockers to men with moderate-to- severe LUTS with Grade A recommendation1. The objective effects of α1-blockers on lower urinary tract function and particularly the beneficial effects on BPO require evaluation by urodynamic testing. Pressure flow study (PFS) is particularly useful to objectively evaluate bladder contractile function and the degree of BPO. Although it is expected that α1-blockers inhibit the effect of endogenously released noradrenaline on smooth muscle cells in the prostate and thereby reduce prostate tone and BOO, a review accumulating early reports published until 2002 suggested that α1-blockers led to a small reduction in BOO and an improvement in urodynamic parameters of up to 50%2. However, several more recently published studies have confirmed the positive effect of α1-blockers, including silodosin3,4, naftopidil5,6 and tamsulosin6,7, to improve BOO (Table 1). Especially regarding silodosin two recent studies demonstrated its significant effect to reduce BOO index (BOOI) as well as detrusor pressure at maximum flow (Pdet Qmax)3,4. Investigation of the ratio of mRNA expression to α1-AR subtypes in human prostate tissue showed that α1A-AR upregulation occurs in patients with BPH, in whom mRNA expression of the α1A-AR subtype is about nine-fold higher than in normal individuals8. Therefore, α1A-ARs are considered important factors in functional BOO in BPH. As silodosin is a highly selective antagonist for α1A-ARsubtype, with an affinity for the α1A-AR that is 583- and 55.5-fold higher than that for the α1B- and α1D-ARs, respectively9, this selectivity may contribute to its beneficial effect on BPO. Interestingly, a recently reported randomized head-to-head comparative study of silodosin and naftopidil, an α1D>α1A-AR antagonist, for efficacy in the treatment of BPE complicated by overactive bladder (OAB) demonstrated that silodosin (8 mg/ day) had greater improvement in OAB symptoms along with the maximum flow rate compared to naftopidil (75 mg/day) after 12 weeks-treatment, suggesting the importance of α1A-AR selectivity for the treatment of LUTS associated with BPO10. Limiting factors of α1-blockers’ efficacy What are the factors contributing to failure in improvement of subjective symptoms following

treatment with α1-blockers in patients with BPO? Hirayama et al.7 evaluated the efficacy of tamsulosin in men with LUTS and a prostate volume ≤ 20 mL (non-enlarged prostate) and compared to that in men with a prostate volume > 20 mL. They found that in the non-enlarged prostate group, both the pretreatment BOOI and bladder contractility index (BCI) correlated with the efficacy of treatment in improving maximum flow rate (Qmax). In contrast, BOOI and BCI did not correlate with Qmax in the enlarged prostate group. When Qmax was improved by ≥3.5 mL/s, the positive predictive value for both pretreatment BOOI >40 and BCI >100 was 100% in the non-enlarged prostate group. These findings suggest that the efficacy of tamsulosin more clearly correlated with BOO in men with a non-enlarged prostate rather than those with an enlarged prostate, suggesting its major action at functional BOO and limited efficacy against mechanical BOO. Supporting this view, Yamanishi et al.11 reported, based on their six-year follow up of silodosin monotherapy for the treatment of LUTS suggestive of BPH, that the withdrawal rate was higher in patients with a larger prostate, although the effects of silodosin to improve LUTS was immediate and stable up to 72 months. In addition to the mechanical aspect of BOO, the limited efficacy of α1-blockers may be explained by non-adrenergic mediators of prostate smooth muscle contraction, which contribute to smooth muscle tone and thereby functional BOO in parallel with α1-ARs12. Functional BOO should not depend solely on sympathetic activation of α1-ARs, since the tone of the prostatic smooth muscle in BPH is modulated by mechanisms other than stimulation of α1-ARs, e.g. thromboxane A213 and endothelins and by cooperative regulation of different intracellular effectors (MAPK, Akt, transcription factors) by by α1-ARs12. This is a new concept proposed by Hennenberg et al.12 on the regulation of prostate smooth muscle tone that α1-ARs in the prostate are not exclusively coupled to G proteins, but additionally interact with accessory binding partners (β-arrestin-2, clathrins) after GRK2-mediated phosphorylation. α1-Adrenergic contractility in the prostate does not only dependent on receptor expression levels, but also on regulation of α1-ARs by interaction with binding partners12. In addition to these intracellular changes of the prostate smooth muscle cells, it has been reported that treatment with silodosin for one year significantly increased serum testosterone level in patients with BPH, and a significant positive correlation was observed between the change in testosterone level and improvement in the BOOI, suggesting that hormonal changes may modify the beneficial effect of silodosin on BOO14. Changes in bladder function associated with BPO should modify LUTS comprising voiding and storage symptoms. Treatment-associated improvement of LUTS is correlated only poorly with BOO in men with BPH7,15. Thus, other mechanisms of action may be relevant. α1-ARs located outside the prostate (e.g. urinary bladder and/or spinal cord) and α1-AR subtypes (α1B- or α1D-ARs) may play a role as mediators of effects. α1-ARs in blood vessels, other non-prostatic smooth muscle cells, and the central nervous system may mediate adverse events1. In fact, a recent study evaluating the efficacy of silodosin with PFS revealed that insufficient improvement in storage function is a contributing factor to the failure in improvement of subjective symptoms after silodosin treatment in patients with BPH16.

Storage dysfunction in BPH The pathophysiology of storage dysfunction in BPH is complex, not only due to relief of BOO. Therapeutic effect of α1-blockers on storage symptoms at least partly occur independent of prostatic relaxation, perhaps involving direct effects on blood vessels, urothelium, afferent nerves, and/ or smooth muscle of the urinary bladder17. In animal models, where BOO is simulated by partial urethral obstruction and a prostate-dependent contribution can be excluded, α1-blockers effectively improved storage symptoms18. One of the factors involved in storage dysfunction following BOO may be chronic ischemia of the bladder. Bladder ischemia and repeated ischemia/ reperfusion during a micturition cycle may produce oxidative stress, leading to denervation of the bladder and the expression of tissue damaging molecules in the bladder wall. This may be responsible for the development of detrusor overactivity and OAB symptoms19. Pinggera et al.20 reported that α1-AR antagonists improved bladder blood flow and symptoms in patients with LUTS, and suggested that these drugs might ameliorate LUTS by increasing bladder blood flow. Supporting this view, chronic treatment with silodisin ameliorated bladder hyperactivity and bladder blood flow in a rat model of bladder chronic ischemia21. Moreover, it has been reported that both α1A- and α1D-ARs in the rat bladder are involved in the activation of the bladder mechano-sensitive Aδ fibres during bladder filling in normal rats22. Furthermore, another study demonstrated that in rats with BOO, bladder mechano-sensitive Aδ- fiber afferent activities were reduced, but both Aδ- and C-fiber afferent activities were intermittently enhanced by propagation of microcontractions during bladder filling when evaluated at Day 10 after induction of BOO23. Continuous treatment with silodosin starting at Day 4 inhibited the exaggerated Aδ- and C-fiber afferent responses related with microcontractions24. These studies suggested that enhanced bladder microcontractions and its related afferent activities may contribute to the development of storage dysfunctions in rats with BOO, and α1A-ARs are involved in the exaggerated afferent responses related with microcontractions. If it is true also in humans, α1-blockers could improve OAB symptoms at least partly through the inhibition of exaggerated mechanosensitive afferent activities related with microcontractions in men with BPO. References 1. EAU guideline for the Treatment of Non-neurogenic Male LUTS http://uroweb.org/guideline/treatment-of-nonneurogenic-male-luts/ 2. Kortmann BB, et al. Urodynamic effects of alphaadrenoceptor blockers: a review of clinical trials. Urology. 2003;62:1-9. 3. Matsukawa Y, et al. Efficacy of silodosin for relieving benign prostatic obstruction: prospective pressure flow study. J Urol. 2009;182:2831-5. 4. Yamanishi T, et al. Urodynamic effects of silodosin, a new alpha 1A-adrenoceptor selective antagonist, for the treatment of benign prostatic hyperplasia. Neurourol. Urodyn. 2010; 29: 558–62. 5. Yamanishi T, et al. Single-blind, randomized controlled study of the clinical and urodynamic effects of an alpha-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment of benign prostatic hyperplasia. Int J Urol. 2004;11:501-9. 6. Nishino Y, et al. Comparison of two alpha1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover

study. BJU Int. 2006;97:747-51. 7. Hirayama A, et al. Alpha-blocker test: alternative to pressure-flow study of bladder outlet obstruction and detrusor contractility in patients without an enlarged prostate. Int J Urol. 2004;11:20-5. 8. Nasu K, et al. Quantification and distribution of alpha1-adrenoceptor subtype mRNAs in human proximal urethra. Br J Pharmacol. 1998;123:1289-93. 9. Shibata K, et al. KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. Mol Pharmacol. 1995;48:250-8. 10. Matsukawa Y, et al. Comparison of Silodosin and Naftopidil for Efficacy in the Treatment of Benign Prostatic Enlargement Complicated by Overactive Bladder: A Randomized,Prospective Study (SNIPER Study). J Urol. 2016 Sep 8. [Epub ahead of print]. 11. Yamanishi T, et al. Six-year follow up of silodosin monotherapy for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: What are the factors for continuation or withdrawal? Int J Urol. 2015;22:1143-8. 12. Hennenberg M, et al. Prostatic α1-adrenoceptors: new concepts of function, regulation, and intracellular signaling. Neurourol Urodyn. 2014;33:1074-85. 13. Hennenberg M, et al. The receptor antagonist picotamide inhibits adrenergic and thromboxaneinduced contraction of hyperplastic human prostate smooth muscle. Am J Physiol Renal Physiol. 2013:305:F1383-90. 14. Matsukawa Y, et al. The Change of Testosterone Secretion During the Treatment of Alpha-1 Blocker in Patients with Benign Prostatic Hyperplasia. Urology. 2016;88:149-54. 15. Barendrecht MM, et al. Do alpha1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance? Neurourol Urodyn. 2008;27:226-30. 16. Matsukawa Y, et al. What are the factors contributing to failure in improvement of subjective symptoms following silodosin administration in patients with benign prostatic hyperplasia? Investigation using a pressure-flow study. Neurourol Urodyn. 2013;32:266-70. 17. Michel MC. The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: Alpha-blockers in the treatment of male voiding dysfunction—How do they work and why do they differ in tolerability? J Pharmacol Sci 2010;112:151–7. 18. Gu B, et al. Effects of alpha 1-adrenergic receptor subtype selective antagonists on lower urinary tract function in rats with bladder outlet obstruction. J Urol 2004;172:758–62. 19. Yamaguchi O, et al. Functional consequences of chronic bladder ischemia. Neurourol Urodyn. 2014;33:54-8. 20. Pinggera GM, et al. alpha-Blockers improve chronic ischaemia of the lower urinary tract in patients with lower urinary tract symptoms. BJU Int. 2008;101:319-24. 21. Goi Y, et al. Effects of silodosin, a selective α1Aadrenoceptor antagonist, on bladder blood flow and bladder function in a rat model of atherosclerosis induced chronic bladder ischemia without bladder outlet obstruction. J Urol. 2013;190:1116-22. 22. Aizawa N, et al. Functional roles of bladder α1adrenoceptors in the activation of single-unit primary bladder afferent activity in rats. BJU Int 2016; 117: 993-1001. 23. Sugiyama R, et al. Characterization of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction. ICS 2015 Abstract No. 516 24. Aizawa N, et al. Effects of silodosin and imidafenacin on the bladder mechanosensitive afferent activities of Aδ- and C-fibers related with microcontractions in male rats with bladder outlet obstruction. ICS 2016 Abstract no. 160

Saturday 25 March 13.00-13.15: Meeting of the EAU Section of Female and Functional Urology (ESFFU)

Table 1: Urodynamic effects of a1-blockers during the voiding phase in men with LUTS References [ reference no.]

Drug (dose/day)

No. of Men

follow-up

Matsukawa et al., 2009 [3] Yamanishi et al., 2010 [4] Yamanishi et al., 2004 [5] Nishino et al., 2006 [6] Nishino et al., 2006 [6] Hirayama et al., 2004 [7] Hirayama et al., 2004 [7]

Silodosin (8 mg/day) Silodisin (8 mg/day) Naftopidil (50 - 75 mg/day) Naftopidil (50 mg/day) Tamsulosin (0.2 mg/day) Tamsulosin (0.2 mg/day) Tamsulosin (0.2 mg/day)

57 29 31 34 34 35 (PV ≤ 20 mL) 26 (PV > 20 mL)

4 weeks 3 months 4 - 6 weeks 4 weeks 4 weeks 4 weeks 4 weeks

Mean Qmax (ml/sec) before Tx after Tx 5.9 ± 2.8 8.8 ± 3.0**** 6.7 ± 3.0 8.4 ± 3.5** 9.8 ± 4.4 13.5 ± 5.8*** 9.9 ± 0.6 13.5 ± 1.5*** 9.9 ± 0.6 13.2 ± 1.6*** 8.5 ± 2.8 10.5 ± 3.5* 8.9 ± 3.2 10.9 ± 5.1*

Mean PdetQmax (cmH2O) before Tx after Tx 72.5 ± 26.6 51.4 ± 17.9**** 80.6 ± 37.8 48.6 ± 25.3**** 82.9 ± 24.0 74.0 ± 24.4 74.9 ± 8.9 64.3 ± 9.7*** 74.9 ± 8.9 61.2 ± 8.0*** ND ND ND ND

Mean BOOI before Tx 60.6 ± 28.9 70.2 ± 38.1 64.2 ± 26.2 ND ND 49 ± 23 63 ± 26

after Tx 33.8 ± 20.4**** 32.6 ± 29.2**** 49.6 ± 33.2* ND ND 33 ± 16** 42 ± 24**

*: P < 0.05, **: P < 0.01, ***: P < 0.001 , ****: P < 0.0001 campared to before treatment ND: not determined PV: prostate volume 22

EUT Congress News

Saturday, 25 March 2017

ESU: Learning by doing How HOT courses cultivate knowledge through the years New HOT course on non-technical skills “Up to 80% of the crucial surgical skills are nontechnical skills. Alarmingly enough, one of the major causes of surgical error is underdeveloped nontechnical skills,” said Mr. Kamran Ahmed of King’s College London.

Dr. Ben Van Cleynenbreugel ESU, Coordinator HOT Courses Dept. of Urology UZ Leuven Leuven (BE)

The ESU aims to raise awareness of the many benefits of non-technical skills through the HOT course “Non-Technical Skills in Urology” which is the first of its kind. “The course will focus on communication, teamwork, decision-making, leadership and management skills,” said Ahmed.

Co-Author: K. Ahmed (London, GB) The European School of Urology (ESU) has developed the Hands-on Training (HOT) courses to educate doctors, nurses, technicians, clinical scientists, and residents in training by getting their hands ‘dirty’ working with instruments, educational devices and virtual trainers. When the European Urology Residents Education Programme (EUREP) began purely as a theoretical course, the HOT courses were initially offered as its complementary feature. “During its inception in 2007, the HOT courses were simply add-ons to attract people to do something with their hands. After all, surgeons need to work with their hands,” said Dr. Ben Van Cleynenbreugel of UZ Leuven, Coordinator of the ESU HOT courses. “We started with one HOT course which was a basic course in laparoscopy and six stations. At present, we offer about 100 HOT courses annually and we have 15 laparoscopy stations and eight endourology stations. The procedures demonstrated in the HOT courses are not only therapeutic but also diagnostic, e.g. ultrasound, urodynamics, to name a few. In addition, the standardisation of training pathways are being developed and evaluated during the courses. When you establish a curriculum, you need to test and fine-tune it,” added Van Cleynenbreugel.

Participants will experience full immersion in a simulated environment in a mobile operating theatre called the “Igloo”, which was developed by Prof. Roger Kneebone of the Imperial College London and his team. The ESU team will be led by Ahmed (Course Director), Prof. Prokar Dasgupta and Prof. Muhammad Shamim Khan of Guy’s & St Thomas’ Hospital. The other must-attend HOT courses at EAU17 ESU/ERUS Hands-on Training in Robotic Surgery (Intro and advanced virtual robotic procedural training courses) These courses aim to improve the participants’ control skills, hand-eye-coordination, and console performance in robot-assisted procedures. The following areas are covered: endowrist manipulation, camera control, 3rd arm control, needle placement and driving, suturing and knot-tying. ESU/ESUT Hands-on Training in Basic Laparoscopic Skills This HOT course focuses on the development of psychomotor skills essential in laparoscopy and suturing such as depth perception and bi-manual dexterity. Experienced tutors will train participants to master instrument handling, pattern cutting and intracorporeal suturing.

Basic laparoscopy (E-BLUS exam) The European training in basic laparoscopic urological skills (E-BLUS) is a programme which includes HOT courses of different levels; a set of training-box exercises developed and validated by the Dutch project Training in Urology (TiU) to train basic skills needed in urological laparoscopy; E-BLUS examination and certification; and an online theoretical course. ESU Hands-on Training in Urodynamics This HOT course offers an interactive environment with emphasis on equipment used, interpretation of traces, quality control and troubleshooting to improve skills in urodynamics.

A simulated environment is provided with mobile operating theatre called “Igloo,” Photo courtesy of © Imperial College London

ESU/ESUT Hands-on Training in Thulium Laser Prostate Vaporesection This course introduces participants to the laser tissue interaction of the Thulium 2 micron continuous wave laser with the use of two different training stations.

ESU/ESUT/ESUI Hands-on Training in MRI Fusion Biopsy The course delivers an overview on MRI reading, technical basics and different prostate biopsy approaches. Technical considerations, the transrectal or transperineal approaches are critically reviewed and discussed.

ESU/ESUT/EULIS Hands-on Training in Ureterorenoscopy Participants will be able to perform Semirigid and Flexible ureteroscopy, navigate through the pelvicalyceal system, and execute stone manipulation and extraction.

ESU Hands-on Training in OnabotulinumtoxinA Administration for OAB This procedure-focused course teaches participants the practicalities of OnabotulinumtoxinA administration through short lectures, videos and hands-on demonstrations using bladder models.

Innovation in Education Experience cutting-edge technology at the ESU’s “Innovation in Education” area. 3D animations, the newest laparoscopic tools, medical 3D printing, virtual reality, and the latest endoscopic simulators await participants, courtesy of 3DSystems, EFI, Health Animation, Materialise, Mimic, VirtaMed and X-Medical.

ESU/ESFFU Hands-on Training in Sacral Neuromodulation Procedure Standardisation Participants will practice the different steps of performing sacral neuromodulation (SNM) such as primary percutaneous nerve evaluation, tined lead and battery implantation and programming and also troubleshooting. ESU/ESUT Hands-on Training in Transurethral Therapy of LUTS – Bipolar TURP Participants will be taken through a sequential programme of Bipolar TURP (transurethral resection of the prostate) using normal endoscopic instruments in different models.

Live Biopsy and MRI Guided Focal Therapy

“It all started with a theoretical course with the HOT courses on the side. And now there are numerous sessions dedicated to the HOT courses with theory as the supplement. This is a reflection of how much these courses are appreciated. The courses were and still are a huge success. Our plans include global standardisation of surgical training and advanced simulation training,” said Van Cleynenbreugel. Saturday to Monday (25-27 March) Daily at 10.00 – 12.00 and 14.00 – 16.00: ESU Hands-on Training Course in Non-technical skills

DEMOS by the Experts

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11AM & 2PM

EDAP TMS Booth G26

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Treatment Planning Validation of Treated Area Elastic Fusion MRI/Biopsies + Contrast Imaging

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Saturday, 25 March 2017

EUT Congress News

Platinum Picture Perfect Please come to the European Urology booth #B02 and have your Platinum Postcard created and posted online. Daily from 10.00 to 18.00

europeanurology.com

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EUT Congress News

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Saturday, 25 March 2017

The patients’ perspective What a patient fears and needs Andrew Winterbottom Founder and Director Fight Bladder Cancer UK Charity and Patient Advocacy Group Chinnor (GB)

I have spent the last 10 years living this subject personally as it was about that time when I had my first brush with the fear and the needs of a cancer diagnosis. So I’m going to write about this subject in relation to being a cancer patient and, in particular, a bladder cancer patient, as well as from my role as founder and director of the charity Fight Bladder Cancer where we have supported thousands of patients and carers over the last seven-plus years and listened to their stories. Let’s start with FEARS. That moment you hear the word cancer, you go cold, your brain stops working and time stops completely. Things just hang there. The word cannot be taken back. Your life with cancer has begun and it will never end. Never. We run a Confidential Forum at Fight Bladder Cancer that, at any one time, has close to 3,000 members at different stages of their bladder cancer journey. It is a place where they can be honest in all its brutality. You don’t have to worry about upsetting your family. You don’t have to worry about asking a question and thinking that you must be stupid not to know something. You can ask the questions you are afraid to ask your doctor. You can explain the reality of the disease and the treatment is really affecting you. After all, we don’t want to worry our doctors or our families. So if you are wondering about what fears, anxiety or panic your patients are having, here is a brief snapshot in no particular order: Anger, “why me?”, pain, passing it on to children, having to tell family/friends, tiredness, cancer growing whilst waiting for tests, death, treatment and results, hair loss, operations, diet problems, diet worries, hospital stays, taking drugs, complications, side effects, job loss, pain control, sickness, time taken for recovery, financial problems, cost of treatment, travel and parking costs, emotional problems, sadness, depression, relationship problems, sex, recurrence, spread, mets, it getting worse, the unknown, treatment failure, drug shortages, treatment being stopped, becoming terminal. And death. These fears occur at different times, to a greater or lesser extent, for the rest of your life. For some, these fears never go away. As it was shown in a study from Georgia Regents University in March 2015, when compared with the general population, overall suicide risk was 2.7 times higher for bladder cancer patients, rates were 1.86 times higher in kidney cancer patients, 1.27 times higher in prostate cancer and 1.23 times higher in testicular cancer. An “All Clear” or a “NED” is great to hear, but we all fear the high recurrence rate so we know we have only a temporary reprieve before the next round of tests and the subsequent wait to hear the results. We know this is forever. So why do we have so much fear, anxiety and panic in our lives? As patients and carers we have a simplistic and limited knowledge about our condition. A knowledge that starts from the global fear of the word “cancer” that is fueled every day with media stories, some heartwarming, some desperately sad. But we all know the fundamental mantra that exists out there these days that one in two of us will get cancer at some point in our lives. Patients then go in two different ways. We either start researching madly for every last scrap of information we can find about the cancer or we decide that we just don’t want to know- what will be, will be. Both reactions are understandable but neither are particularly healthy. Dr. Google is a very careless physician. He tells you everything and nothing. Should you believe everything or should you believe nothing you read? Which are the correct facts and which are not? When you get five minutes just type “cancer cure” into Saturday, 25 March 2017

Google and see what comes up. When doing this, try and read without your professional head on. As newly diagnosed patients we have no idea what is right or wrong, what is a good source of information and what isn’t. If we are brave, we might then start to tell our family and friends. This then unleashes a cavalcade of advice based on anecdotes. Advice from how you need to start eating certain herbs and spices, stop drinking coffee, keep well away from sugar, don’t worry “its not a cancer you die from”, chemotherapy is worse than the cancer through to “there is a cure you know, its just that big pharma can’t make money out of it so that’s why they won’t let you have it”. Then there are the friends who simply disappear. Then there are the spouses that disappear soon after a cancer diagnosis. Then there are your friends and families who really do mean well but just don’t understand and unfortunately make you feel worse, more afraid, more alone. Hidden away, there is also domestic abuse and violence. Happily this is quite rare but, as professionals, you do need to know that this happens following a cancer diagnosis. The fear and the anger can come out in bad ways. For patients, timely and clear communication is as important as the quality of treatment

Hopefully, as you have read the first part of this article, you have been thinking “Yes, I know that. We do that to help that. Yes, we understand and we have protocols in place to help.”

The Waiting Room As bladder cancer patients we spend a good deal of our lives in what we call “the waiting room”. Good. All sorted then. This isn’t just the physical room at the hospital or at the doctor’s office. This is the psychological Yes, we see some fantastic exemplars of good practice waiting room. Waiting for an appointment, out there in helping patients with their fears but waiting for results, waiting for the results to be being honest, there is a really wide variation in explained, waiting to know what treatment we quality. I’m not talking about the treatments are going to need, waiting to see the new themselves as I know that, as a profession, you will specialist, waiting for the treatment to start, always strive to improve outcomes. waiting for the next phase of the treatment, waiting for the next check-up, waiting for the Patient’s needs results of the check-up. Waiting for the letter, Let’s move on to the patient needs. From over the waiting for that phone call. Waiting to hear if it years of hearing patients talk honestly about their has come back. Waiting. needs, we can get a snapshot of the most commonly defined needs. Again in no particular order: Information, understanding, knowing what to ask, explanations “that I can understand”, support, counseling, signposting where to get support, signposting where to get good information, being provided with a patient “buddy”, getting results quickly, getting treatment quickly, better guidance on side effects, explanations for any delays in results or treatments, being able to contact my medical team whenever I need help/reassurance. One word sums this all up. Communication. Good and speedy communication of what you know will provide most of these patient needs. Indeed, at Fight Bladder Cancer, we have a campaign for a new Quality Standard for Communication to be developed. At times you are all brilliant at this. We know because the patients tell us. But at too many times it is easy to fall below the quality that you can achieve because of the pressures of the real world. But for us patients, this communication is as important as the quality of our treatment. In fact, probably more important. We know that treatment doesn’t bring a guarantee of success. When the detail of treatments, side effects and prognosis is explained to us at diagnosis and during treatment, we understand that you are explaining what the evidence-based research says. We’d love you to be 100% sure of it all but we know you can’t. But we do need to understand and we need your help to ensure that we do understand and that we are not suffering in silence. We can be scared of talking to you, scared of asking you to repeat something because we didn’t understand what you just said. We will think of that question that is really important to us a 2 a.m. when we can’t sleep. Diagnosis, treatment and aftercare is a team game. If you are the captain of that team, make sure that the whole team understands the patient fears and needs. Put protocols in place to ensure that your practices are robust for the benefit of your patients and their carers. Make sure you measure how good you are in your measures to support the patient fears and needs. Talk to you patients about Quality of Life issues at every encounter. Work with patient advocacy groups like Fight Bladder Cancer to ensure that you hear the reality of the patient experience. Offer to help your nearest patient advocacy group.

Waiting too long to hear what you fear makes it worse. If you take anything from this article, remember to tell your patient what they need or want to hear as soon as possible. Take it from me, that extra day’s wait is hell. Sheer hell. Finally, don’t be scared of talking honestly with us patients, it will help us talk honestly with you and together we will get this right. Friday 24 March 12.40-12.50: Special Session Patient Information, EAU Patient Information Project: Setting standards in cooperation and care

Prostate enucleation using low energy pulsed Thulium laser with preservation of ejaculation Dr J.B Roche Groupe Urologie Saint-Augustin – Bordeaux (Fr) In this session, consultant urological surgeon Jean-Baptiste Roche enucleates a 130g prostate using the 200W Hemera® Laser from Rocamed. Harnessing the latest in laser technology, this low-energy pulsed device provides excellent results in terms of post-operative urinary function, minimizing the risk of incontinence, pelvic discomfort, and storage-related symptoms. When combined with an anatomically precise application, this type of dissection affords the maximum level of protection to the patient’s ejaculatory function, and greatly reduces the risk of recurrence. The presentation gives a clear, accessible, step-by-step insight into laser-based prostate enucleation, showing all phases of the procedure, from dissecting the apex of the prostate through to nal morcellation.

Pre-recorded video Session

March, 25th 16:55 eURO Auditorium (Level 0) Procedure performed with 200W Hemera® Thulium Rocamed Laser

Visit Us Booth I26 EUT Congress News

Patient-doctor partnership Co-designing innovation in healthcare through Patient Information (PI) Prof. Thorsten Bach Chairman EAU Patient Information Urology Centre Hamburg Asklepios Klinikum Harburg Hamburg (DE)

There is massive potential in patient-doctor partnership in improving healthcare. The collaboration can spark innovative solutions in health policies, education, clinical care, and medical research. Patient involvement gives health providers valuable insight on what matters most to patients, their families and caregivers. Patient engagement also means challenging the conventional thinking in disease treatment and management. According to the article “The Blockbuster Drug of the Century: An Engaged Patient” by Leonard Kish (Principal and Co-Founder at VivaPhi), “Medicine and the people it treats are complex adaptive systems; we need a complex adaptive-systems approach to medicine because each person reacts differently. We can only treat the population for so long and get great results; we need to use data and engagement to continuously learn how to improve care for each individual.” Patient involvement broadens the focus of medical research and improves personalised care. It identifies new patient-reported outcome measures, and enables researchers to use more patient-relevant outcomes in clinical trials. But what stands in the way of the patient-doctor collaboration? How does EAU’s Patient Information (PI) address this? What is PI’s role in cultivating said partnership? Misdiagnosis When patients seek help online regarding their conditions, they put their health at great risk. A vast amount of medical information may be available on the internet; but unfortunately, some websites contain inaccurate and outdated data. The misleading data might cause a patient to undermine his condition. He then avoids pursuing the treatment he needs. Or he becomes anxious as the online diagnosis balloons up his symptoms to an array of serious illnesses. For example, he Googles his flu-like symptoms. He then receives varied diagnoses from heart attack to early stages of an HIV infection. Rapid development in the medical and surgical treatments can also cause confusion in patients. Although the amount of information grows, it is neither checked, monitored nor regulated. Searching for answers via the internet may be easy and may feel non-invasive to a patient, but it is not a substitute for professional medical advice, diagnosis or treatment. Patient voice Some patients resort to consulting the internet for advice for a variety of reasons. They might be reluctant in expressing their concerns to their doctors. They might feel discomfort or embarrassment during medical consultations. Or they might think that they are not getting the empathy and understanding they

seek which makes it difficult for them to communicate to their doctors. These are what EAU’s PI aims to change. PI recognises that patient empowerment comes from knowing trustworthy information. Educating patients boosts their confidence and most importantly, helps them understand their conditions better. The PI website at www.patients.uroweb.org contains evidence-based information. It is the go-to platform to access reliable information. PI’s stakeholders – urology patients and their families, the general public, urologists, national societies, and patient organizations – are rest assured they will not be misinformed. When patients feel confident and at ease, they find it easier to talk to their doctors. And an open patientdoctor dialogue is highly encouraged by PI. Patients as educators PI aspires to have the patients to be both participants and educators in events. Their experience in having and coping with their conditions make them experts. Why not tap their knowledge to co-create better patient-centred treatments and procedures? Why not use their experience to identify what clinical trials to pursue? In the article “4 Trends Shaping The Future Of Medical Events”, Dr. Bertalan Meskó, PhD (healthcare speaker, author and consultant, aka The Medical Futurist) stated, “The most important stakeholders of healthcare have been ignored by most events for decades. I do not attend medical events that do not include patients either in the organising committee or among the speakers anymore. The future of medicine will put patients in the centre – how can we discuss it without involving them? Data show that patient satisfaction and outcomes skyrocket when we involve them in designing medicine.” When patients are involved, they see that they do have a say in treatments. They see that they are valuable contributors in the advancement and customisation of treatments. PI has presented the special session “EAU Patient Information Project: Setting standards in cooperation and care” yesterday, 24 March from 12:15 - 13:30. It was PI’s first of many sessions encouraging patientdoctor collaboration. The special session has included informative lectures such as “The society’s perspective – What can EAU Patient Information do for you, why do we need to translate GL for patients?” by Prof. C.R. Chapple, Sheffield (GB); “The patients’ perspective: What a patient fears and needs” by Mr. A. Winterbottom (co-founder of patient organization Fight Bladder Cancer); and “The nurses perspective: Things patients do not ask or do not dare to ask their doctors” by Mrs. C.N. Tillier, Amsterdam (NL), to name a few. Medical conferences that included patients Dr. Larry Chu (Professor of Anesthesiology, Perioperative and Pain Medicine and Director of the Stanford Anesthesia Informatics and Media) and his colleagues cited eight examples of medical conferences that have included patients in their paper “‘Nothing about us without us’ – patient partnership in medical conferences” (BMJ 2016;354:i3883 doi: 10.1136/ bmj.i3883) published in September last year.

Esther Robijn (Patient Information Coordinator) at the Patient Information booth in Munich

It stated that “Conference organisers should work towards patient involvement not only to foster the patient voice in academic medicine but to also realise true partnership and collaboration with patients as a means to drive truly meaningful innovation in healthcare.” PI website PI offers accurate and straightforward content to urology patients. This is to guarantee understanding of their conditions. The current topics on the PI website include: • Benign prostatic enlargement • Bladder cancer • Erectile dysfunction • Kidney cancer • Kidney stones • Nocturia • Overactive bladder • Prostate cancer • Urinary incontinence The topics mentioned above have been translated to more than 18 languages (and counting!) such as Spanish, German, Portuguese, Croatian, and Chinese to name a few. PI content continuously grows and improves to ensure that the patients receive updated, quality information. The new topics that are under development are as follows: • Cryptorchidism • Hypogonadism • Neurourology • Penile cancer • Penile curvature • Phimosis • Priapism • Primary urethral carcinoma • Signs and symptoms • Testicular cancer • Urachal cancer • Urine biomarkers

EAU Patient Information Working Group meeting in Hamburg. From left to right: Prof. Dr. T. Bach (DE), Dr. G. Patruno (IT), Dr. H. Reis (DE), Dr. J.P. Jessen (DE), Dr. M. Behrendt (CH), Ms F. Geese, MScN, RN (CH), Dr. Y. Tanidir (TR), Dr. F. Esperto (UK), Dr. R. Pereira e Silva (PT), Dr. M. Innocenzi (IT), Dr. S. Ottenhof (NL), Drs. J. Oosterman (NL), Ms E. Robijn (NL)

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User-friendly PI website navigation is intuitive and easy to use. All texts and illustrations are legible whether viewed via PC or mobile. Online readers may have short attention spans, but the website’s minimalist, uncluttered design keeps them interested.

Information found in the Library section of the website is available for download in PDF form, and medical terms are explained under the Glossary section. Your Treatment webpage Web-based information can be difficult to understand at times. This is especially true for patients who are unfamiliar with medical terms. Therefore, aside from straightforward text and multiple translations, PI will also present the information through the Your Treatment webpage. Your Treatment is one of the new PI products currently under development. It will contain the overview information about a procedure, how to prepare for the operation, and an animated video on how the procedure is performed. These videos will include procedures such as Percutaneous Nephrolithotomy (PNL) and Ureteroscopy (URS), which will have voice-overs and subtitles in English, Spanish, and Chinese (additional languages to follow). In Your Treatment, patients will also find information on what to expect after the procedure and what happens during follow-up. More essential feedback To further gain deeper understanding of patients’ needs, the PI website has a built-in survey functionality found in the surgical procedure page. PI also enlists the help of patient organisations to conduct surveys. Patient involvement The medical community has a lot to gain from patient involvement. Engaging patients widens research agendas, identifies new patient-centred domains, and help advance personalised care. PI fosters this patient-doctor collaboration through evidence-based information, event participation, and sustenance of an open patient-doctor dialogue. For more information, please visit the EAU PI website www.patients.uroweb.org. The EAU Patient Information desk is located on the Exhibition floor, adjacent to the EAU Booth. Friday 24 March Special Session Patient Information, EAU Patient Information Project: Setting standards in cooperation and care

Saturday, 25 March 2017

Glans necrosis after penile prosthesis implantation Recognising risk factors is crucial before taking surgical interventions Dr. Ahmad Shamsodini Takhtei Hamad Medical Corporation Dept. of Urology Doha â&#x20AC;&#x201C; Waab (QA)

Penile prosthesis (PP) implantation represents an excellent treatment option for patients with severe erectile dysfunction (ED) that is non-responsive to less invasive therapies and it has been accepted worldwide as a treatment for ED for more than 20 years. There are several common complications regarded to penile prosthesis, including infection, mechanical device malfunction, erosion, and pump and reservoir complications. Most of them are well-documented and therefore include a standardized treatment. However, the development of ischemic gangrene after PP implantation is very uncommon and very few cases have been reported, making it difficult to establish the real incidence of the issue. We perceived that glans ischemia and necrosis was an underreported complication. Penile glans necrosis, defined as ischemia to the glans due to compromised blood flow, with devastating consequences to both the patient and the physician. As very few cases have been reported, no established treatment protocol has been recognized yet. The blood supply to the glans penis consists of the dorsal arteries and the corpus spongiosum muscle surrounding the urethra. Obviously for glans ischemia to occur both blood supplies must be severely compromised. Our aim is to describe our experience with a case of ischemic gangrene of the distal penis after implantation of a PP. Our patient, a 59-year-old male refereed to our clinic, complained of erectile dysfunction of several years which did not respond to oral treatment and had dorsal penile curvature. On examination, he had a hard-dorsal penile plaque of more than 1 cm with short penis. His past medical history included being an ex-smoker for 30 years (he stopped recently) and noninsulin- dependent diabetes mellitus for 14 years. Although blood glucose was within normal limits in preoperative tests, his previous glycosylated haemoglobin was 9.5%. His penile Doppler study showed severe bilateral arterial insufficiency and hourglass deformity of mid-shaft of penis and hinge effect with poor rigidity to vasodilating agent.The surgical option and complications were discussed with the patient. The patient signed an informed consent and understood the risk of surgery. He underwent non-touch technique with circumferential subcoronal incision and classic de-gloving of the penile skin and mobilization of neurovascular bundle starting from the lateral aspect towards the midline that encountered severe fibrosis and calcified plaque. Further, the corpus spongiosum was mobilized to explore the hourglass deformity (Figure 1). Corporotomy done at penoscrotal region and dilatation of the corpora was carried out. Multiple transverse incision dorsally and grafting of the tunica was done ventrally to correct the bending and the hourglass deformity (Figure 2) and penile prosthesis was implanted in classic fashion. Immediately postoperatively the patient had more than normal oozing from the glans at the site of needle insertion. In the first postoperative day, the patient had more

Figure 7: Debridement of superficial helmet necrosis

Figure 2: Grafting of corpora ventrally

Figure 6: Infected prosthesis

Figure 3: congested glans

Figure 4: Dusky glans

than usual penile pain and congestion of the glans penis. (Figure 3). On the follow-up, the patient developed retention of urine that needed insertion of Folyâ&#x20AC;&#x2122;s catheter and glans started to be dusky (Figure 4). Day by day changes of the color of glans penis were noticed and showed black demarcation distal to the circumferential sub-coronal incision line including all the glans (Figure 5). On the seventh postoperative day decision of removal of implant was taken due to worsening of the pain and clear demarcation of necrosis of the glans penis through the peno-scrotal incision that revealed pus discharge, infected penile prosthesis (Figure 6). All the component of the implant was removed and washing of the corpora with copious amount of mixture of normal saline and hydrogen peroxide and two types of antibiotics were carried out. The patient did not show any clear signs of infection neither locally nor systematically, except for penile pain.

as it occurred in the present case. However, to date, nobody has related an increased level of glycosylated haemoglobin to a higher incidence of dry gangrene. We believe that these poorly-controlled patients with altered glycaemia were a determining factor in the initial ischemia and the subsequent worsening of the condition, which finally developed superinfection. Patients who are at risk for compromised blood flow to the glans should avoid high-risk concomitant surgical maneuvers during penile prosthesis surgery. There is a concern that the required extensive mobilization of the neurovascular bundle and the urethra may compromise distal penile circulation from both the dorsal penile arteries and corpus spongiosum muscle. Furthermore, when presented with a swollen, dusky, edematous, or discolored glans penis in the early post-operative period following penile prosthesis implantation, immediate removal of intracorporal

Figure 8: Excised tissue

components is mandatory. Less aggressive management is likely to lead to significant glandular loss with resultant penile disfiguration and considerable morbidity. Editorial Note: Due to space constraints the reference list has been omitted. Interested readers can email at EUT@uroweb.org for a complete listing. Saturday 25 March 14.15-14.25: Meeting of the EAU Section of Genito-Urinary Reconstructive Surgeons (ESGURS)

Call for Abstracts Submit your abstract by 28 April 2017 at www.WCE2017.com

Excision of helmet-like necrosis of the glans penis was performed two days after the extraction of the implant (Figure 7 and 8). Unfortunately, the glans penis did not improve due to uncontrolled blood sugar in spite of receiving hyperbaric chamber treatment. The superinfection and wet gangrene followed by tissue destruction and necrosis was further extended to the corpora and to distal corpus spongiosum that needed distal penectomy and spatulation of the urethra. Lessons learned Some lessons learned from this rare case is to recognize the risk factor for glans necrosis like patientâ&#x20AC;&#x2122;s comorbidities and the extent of surgical intervention that was carried out. Diabetes mellitus is the only risk factor associated with all cases reported,

Figure 1: Mobilization of corpus spongiosum and neurovascular bundle. Hourglass appearance of corpora.

Saturday, 25 March 2017

Figure 5: Glans necrosis

EUT Congress News

Today’s European Urology Events How to write the Introduction and Methods

ESU Writing Course Part 1

March 25th 11.00 – 13.00 Room 10, Capital suite (level 3)

ESU Writing Course Part 2

March 25th 14.30 – 16.30 Room 10, Capital suite (level 3)

Aims and objectives: To understand how to construct a well written Introduction and Methods section to your manuscript. To work through examples of good and bad practice, and to understand key points when writing. To get insight from editors about what they expect to see and what they look for. 1. Welcome Jim Catto, Sheffield (GB) 2. How to write an introduction Giacomo Novara, Padova (IT) 3. Group working I: Introduction. • Examples of good and bad introductions. • Where to get the introduction data from

How to write Results and Discussion Aims and objectives: To understand how to write the Results and Discussion sections of a scientific paper. To understand how to present your data to its best potential. To work through examples of good and bad practice. To to understand key points when writing. To get insight from editors about what they expect to see and what they look for. 1. Welcome - Jim Catto, Sheffield (GB) 2. How to write the results chapter Stephen Boorjian, Rochester (US) 3. Choosing and presenting your statistical analyses Melissa Assel, New York (US)

• Suggestions for own papers & draft own introduction • Present findings to audience 4. How to write the methods section Christian Gratzke, Munich (DE) 5. Key features for a systematic review Marcus Cumberbatch, Sheffield (GB) 6. What to look for in the statistics section Christian Gratzke, Munich (DE) 7. Group working II: Methods • Examples of good and bad methods. • Suggestions for own papers • Create own methods and tables • Present findings to audience 8. Questions and answers All faculty

4. Group working I: Results • Examples of good and bad Results. • Suggestions for own papers • Examples of graphs – which are appropriate and best • Present findings to audience 5. Writing the discussion section Jean-Nicolas Cornu, Rouen (FR) 6. What the editor looks when reviewing the results and discussion Stephen Boorjian, Rochester (US) 7. Group working II: Discussion • Examples of good and bad Discussions. • How to interpret the literature • Suggestions for own papers • What next? 8. Questions and answers All faculty

Come and see the Residents Corner Award winners accept their prize:

Residents’ Corner Awards

March 25th

Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel–Lindau Gene Mutation Status Yosra Messai, Sophie Gad, Muhammad Zaeem Noman, Gwenael Le Teuff, Sophie Couve, Bassam Janji, Solenne Florence Kammerer, Nathalie Rioux-Leclerc, Meriem Hasmim, Sophie Ferlicot, Véronique Baud, Arnaud Mejean, David Robert Mole, Stéphane Richard, Alexander M.M. Eggermont, Laurence Albiges, Fathia Mami-Chouaib, Bernard Escudier and Salem Chouaib European Urology, Volume 70 Issue 4, October 2016, Pages 623-632 Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non–Muscle-invasive Bladder Cancer Tom J.H. Arends, Ofer Nativ, Massimo Maffezzini, Ottavio de Cobelli, Giorgio Canepa, Fabrizio Verweij, Boaz Moskovitz, Antoine G. van der Heijden and J. Alfred Witjes European Urology, Volume 69 Issue 6, June 2016, Pages 1046-1052 To be held at 17.00 at the end of the Residents Session in Room Milan (Boulevard, level 1)

europeanurology.com 28

EUT Congress News

Saturday, 25 March 2017

Battlefield injuries Reconstruction of the blast-injured perineum Paul CB Anderson Dudley, West Midlands (UK) Honorary Consultant Urologist, Royal Centre for Defence Medicine Queen Elizabeth Hospital Birmingham (UK) Recent military operations in Afghanistan and Iraq have resulted in a small but significant number of servicemen suffering devastating perineal injuries, usually as the result of Improvised Explosive Devices (IEDs). These weapons also cause proximal lower limb amputation, pelvic fracture and anorectal injury alongside the genitourinary injuries and this combination became recognized as the ‘signature injury’ of the conflict (Figure 1). After initial stabilization and damage control surgery, wounded UK service personnel are transferred to the Royal Centre for Defence Medicine (RCDM), Queen Elizabeth Hospital, Birmingham, within 48 hours of their injury. At this acute stage a supra pubic catheter is normally all that is required whilst life threatening injuries and sepsis are dealt with. Although the genito-urethral injuries are severe they are often among the last series of operations to be undertaken (along side trimming of heterotopic ossification which affects the ability to wear prosthetic limbs) as more pressing problems are dealt with. As such, these men are only fully assessed once they are out-patients. This is perhaps unfortunate as time and time again when men were woken up on the Intensive Care Unit their first action was to feel between their legs to see whether they still had genitalia. They coped much better psychologically with the loss of limbs than genitalia and when seen in clinic to specifically address genito-urinary concerns they invariably stated they had frustratingly failed to get answers to any of their questions regarding future genital reconstruction. It therefore became necessary to see patients early on and discuss future reconstruction where it was identified that despondency over genitourethral injury was hampering recovery.

“These patients need more than surgeons alone to help them with their new lives, and although the conflict is over... there is still work to be done among this patient population.”

The suprapubic catheter, although the safest way to manage urine drainage, is understandably unpopular in this patient group who, due to their catabolic state and immobility, are hypercalciuric. This leads to recurrent bladder stone formation and blocked, encrusted catheters that are painful to remove with cystolitholapaxy, a regular hazard until reconstruction renders them catheter-free. When planning Genito-Urethral Reconstructive Surgery (GURS) it is important to determine the patient’s priorities to decide on timing – does he want the colostomy reversing first or the pelvic fractureFigure 3: A healed perineum and stumps are required before related urethral injury dealing with, to be free of the urethroplasty suprapubic catheter? Or perhaps they are in the middle of a complex multistage hand reconstruction that will allow them to use their electric wheelchair. It is important to not interfere with another surgeon’s planned procedures.

“The key to success is working within a highly skilled multidisciplinary team”

However, an enthusiastic plastic surgeon is essential to overcome the difficulties with loss of soft tissue, such as a complete lack of skin to cover a urethral reconstruction (Figure 4) or the creation of phallus when the normal options do not exist (Figure 5). Reconstructing these servicemen is technically difficult (often far more difficult than my civilian patient population) and it is always safest to stage repairs – vascularity of penile skin cannot be guaranteed when the penile shaft/remnant is completely skin-grafted for example. Although the patients are hard work, in that they represent complex surgery and multiple operations, they have a remarkable “can do” attitude - regarding their injuries as simply another challenge to be overcome. It is very humbling to deal with them and to listen to how matter of fact they are about how they cope with their new life, or even to hear them recount the stories of how they got their injuries.

As the number of men with severe genitourinary trauma increased it became very apparent that they needed a multidisciplinary approach - not simply a reconstructive urologist and a plastic surgeon (Mr Demetrius Evriviades) - and in February 2010 a mixed military and civilian Genitourinary Trauma Group was established with urology, plastic surgery, orthopaedics, general surgery, endocrinology, reproductive medicine, rehabilitation, mental health and scientists involved in the development of personal ballistic protection all represented.

GURS after blast injury can wait and, as stated before, it will often be one of the last series of operations they undergo. It is essential to work in a multidisciplinary team that can deal with anything from problems with ill-fitting prostheses to psychosexual issues to fertility. These patients need more than surgeons alone to help them with their new lives, and although the conflict is over (new conflicts unfortunately loom) there is still work to be done among this patient population.

Explaining realistic outcomes It is absolutely crucial that realistic outcomes are explained. It is not possible to create their old penis for them nor restore normal function after devastating injury. This is particularly hard to accept when you are only 19 years old. Not only can IED injuries can create a wide diastasis, they are associated with extensive soft tissue injury (Figure 2) not seen with civilian pelvic fracture related urethral injuries. The perineum and stumps need to heal (Figure 3) to allow a conventional (albeit more difficult than usual) bulbo prostatic anastamotic urethroplasty to proceed. Such surgery can be carried out by the urologist alone.

Figure 5: Neurotised anterolateral thigh flap to create phallus

References 1. L Uppal, PCB Anderson, D Evriviades. Complex lower genitourinary reconstruction following combat-related injury. Journal of the Royal Army Medical Corps. 2013;159 Suppl 1:i49-51. 2. DM Sharma, DM Bowley. Immediate surgical management of combat-related injury to the external genitalia. Journal of the Royal Army Medical Corps. 2013;159 Suppl 1:i18-20.

Figure 4: Two-stage urethral reconstruction covered by a tubed pedicled flap as all skin (and urethra) had been lost in the area of the penobulbar urethra

Saturday 25 March 12.25-12.35: Meeting of the EAU Section of Genito-Urinary Reconstructive Surgeons (ESGURS), Advancements in genito-urinary reconstruction

Come and meet with Peyronie’s experts TAKE THE CHANCE – TALK TO EXPERIENCED COLLAGENASE USERS Booth # H02 March 25, Saturday 10.00-10.30 15.30-16.00

Mr Amr Raheem Mr David Ralph

March 26, Sunday 13.00-13.30

Mr David Ralph

March 27, Monday 10.00-10.30

Mr Amr Raheem

XIAPEX® Abbreviated Prescribing Information (Peyronie’s Disease): (See XIAPEX Summary of Product Characteristics for full Prescribing Information). Presentation: Powder and solvent for solution for injection. The vial of powder contains 0.9 mg collagenase clostridium histolyticum. Indications: The treatment of adult men with Peyronie’s disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy. Dosage: Xiapex must be administered by a physician appropriately trained in the correct administration of the product and experienced in the diagnosis and treatment of male urological diseases. The recommended dose of Xiapex is 0.58 mg per injection administered into a Peyronie’s plaque. The volume of reconstituted Xiapex to be administered into the plaque is 0.25 ml. If more than one plaque is present, only the plaque causing the curvature deformity should be injected. A treatment course consists of a maximum of 4 treatment cycles. Each treatment cycle consists of two Xiapex injections and one penile modelling procedure. The second Xiapex injection is administered 1 to 3 days after the first injection. A penile modelling procedure is performed 1 to 3 days after the second injection of each treatment cycle. The interval between treatment cycles is approximately six weeks. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Treatment of Peyronie’s plaques that involve the penile urethra, due to potential risk to this structure. Warnings and Precautions: Allergic reactions – Following Xiapex injection, severe allergic reaction could occur, and patients should be observed for 30 minutes before leaving the clinic in order to monitor for any signs or symptoms of a serious allergic reaction Patients should be instructed to consult a doctor immediately if they experience any of these signs or symptoms. Emergency medication for treatment of potential allergic reactions should be available. Corporal rupture was reported as a serious adverse event after Xiapex injection in 5 out of 1044 patients (0.5%) in the controlled and uncontrolled clinical trials. In other Xiapex-treated patients (9 of 1044; 0.9%), a combination of penile ecchymoses or haematoma, sudden penile detumescence, and/or a penile “popping” sound or sensation was reported, and in these cases, a diagnosis of corporal rupture cannot be excluded. Severe penile haematoma was also reported as an adverse reaction in 39 of 1044 patients (3.7%). Signs or symptoms that may reflect serious injury to the penis should be promptly evaluated in order to assess for corporal rupture or severe penile haematoma. Use in patients with coagulation disorders – Xiapex must be used in caution in patients with coagulation disorders or those taking anticoagulants. See SmPC for details. Immunogenicity – As with any non-human protein medicinal product, patients may develop antibodies to the therapeutic protein. Special penile conditions/diseases not studied in clinical trials – Xiapex treatment in patients having a calcified plaque that could have interfered with the injection technique, chordee in the presence or absence of hypospadias, thrombosis of the dorsal penile artery and/or vein, infiltration by a benign or malignant mass resulting in penile curvature, infiltration by an infectious agent, such as in lymphogranuloma venereum, ventral curvature from any cause and isolated hourglass deformity of the penis has not been studied and treatment in these patients should be avoided. Long-term safety – Long-term safety of Xiapex is not fully characterised. The impact of treatment with Xiapex on subsequent surgery, if needed, is not known. Drug Interactions: Use of Xiapex in patients who have received tetracycline antibiotics e.g. doxycycline, within 14 days prior to receiving an injection of Xiapex is not recommended. Pregnancy & Lactation: Peyronie’s disease occurs exclusively in adult male patients and hence no relevant information for use in females. Driving and operating machinery: Minor influences on the ability to drive and use machines include dizziness, paresthesia, hypoesthesia, and headache. Patients must be instructed to avoid potentially hazardous tasks. Side Effects: Most adverse reactions were local events of the penis and groin and the majority of these events were of mild or moderate severity, and most (79%) resolved within 14 days of the injection. Very common (≥1/10): Penile haematoma, swelling, pain, ecchymosis. Common (≥1/100 to <1/10): Blood blister, Skin discolouration, Penile blister, Pruritus genital, Painful erection, Erectile dysfunction, Dyspareunia, Penile erythema. Injection site vesicles, pruritus, Localised oedema, Nodule Suprapubic pain, Procedural pain. For further information refer to summary of product characteristics. Legal Category: POM. Marketing Authorisation Holder: Swedish Orphan Biovitrum AB (publ), SE-112 76 Stockholm, Sweden. Package Quantities, Marketing Authorisation Numbers and UK Basic NHS Price: XIAPEX 0.9mg powder and solvent for solution for injection, EU/1/11/671/001, £650. Further information is available on request from: medical.info@sobi.com, Tel: +46 8 697 20 00. Date of Preparation: February 2017. Adverse events should be reported to your local regulatory authority and to Sobi at DrugSafety@sobi.com

Saturday, 25 March 2017

Figure 2A: IED blast producing very wide diastasis and Figure 2B: Concomitant soft tissue injury

SE-112 76 Stockholm Phone: +46 8 697 20 00 www.sobi.com

PP-2089

Figure 1: Signature injury of the early conflict: Note loss of both lower limbs, Colostomy for anorectal trauma, external fixator for pelvic fracture stabilization, suprapubic catheter and severe genitourethral injury.

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LUTS in CVA patients What do we need to know? Dr. Salvador Arlandis Functional and Reconstructive Urology Section HUP La Fe Valencia (ES)

stroke patients with UI and from 4% to 14% for stroke patients without UI. The resulting pooled HR was 5.1 (95% CI, 3.9â&#x20AC;&#x201C;6.7) and after adjusting for confounding variables the HR was of 2.2 (95% CI, 1.8â&#x20AC;&#x201C;2.7), and no differences were found among haemorrhagic and ischaemic stroke7.

A substantial part of this association is explained by the severity of the stroke, severity of disability, age and comorbid conditions associated to CVA. But UI itself increases risk of some other mortality factors as urinary infections (when high post-void residuals), Cerebrovascular accidents (CVA) is a prevalent falls and indwelling catheters. This stresses the disease in both developed and developing countries. importance of diagnosis and specific care for stroke In Spain, CVA is the second leading cause of mortality patients suffering from UI, two issues that are after heart ischemic disease. currently rarely met in clinical practice8.

symptomatic patients revealed various findings in 91% of them, including DO in 68%, detrusorsphincter dyssynergia (DSD) in 14% and uninhibited sphincter relaxation in 36%. Patients with urinary retention had destrusor acontractility and DSD. DO was noted in lesions of the frontal lobe as well as the basal ganglia, uninhibited sphincter relaxation in the frontal lobe, and DSD common in the basal ganglia.

Figure 2: Severe detrusor overactivity with voluntary contraction of external sphincter to avoid urinary incontinence, conditioning pseudo-dyssynergia in voiding phase

Above-mentioned findings seem to indicate that anteromedial frontal lobe and its descending pathway, and the basal ganglia seem to be mainly responsible for supranuclear types of pelvic and pudendal nerve dysfunction in patients with stroke10. Though this study could not find predominance of right side lesions for UI, some others found correlation of lesions located in the right brain hemisphere with UI14.

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Pelvic floor muscle exercises and bladder training are useful to restore continence in male and woman with good sphincteric voluntary control and mild functional impairment18-20. Rehabilitation therapies may be less effective in patients with worse functional status after Many several risk factors are associated with stroke: Continence, physical function and mental status severe stroke. Empirical treatment may be started age, diabetes, hypertension, tobacco, obesity, based on LUTS and evaluation of PVR. If empirical hypercholesterolemia, etc. Occlusive phenomena The presence of incontinence is an indicator of a more Another common finding in frontal lobe lesions is treatment is not effective, urodynamic studies are (embolic or thrombotic) and haemorrhagic lesions are severe stroke, so a worse overall outcome is expected uninhibited sphincter relaxation15. DSD is rare, only mandatory. According to guidelines, videothe main mechanism related to CVA. Stroke is the in those patients. Patients with impaired awareness frequently seen in patients with basal ganglia lesion. urodynamics is the gold standard, but if this is not first cause of disability in adults1. After a stroke, after stroke seems to have worse functional outcomes Brainstem lesions give a different profile from available, then a filling cystometry continuing into a one-third of the patients will die, another third will and lower continence rates at three months9. This hemispheric lesions, more frequently voiding LUTS. pressure flow study should be performed21. Generally, experiment disabilities and the rest will recover their impaired awareness seems to be related to video-urodynamics is rarely needed in the majority of Sakakibara et al reported findings from 39 patients previous level of function. With the increasing age of anosognosia (unawareness or denial of a neurological with acute brainstem stroke. Within three months from patients. population, the number of patients with post-stroke deficit). Decreased awareness or even neglect may onset, 49% had mixed LUTS, the most common being consequences is expected to increase in the future. develop an inability to recognize basic needs, like voiding difficulty and nocturnal urinary frequency in Anticholinergics are generally used for urgency and hygiene or need to void. New-onset post-stroke UI 28%, followed by urinary retention in 21%. UUI due to DO, but some issues about cognitive One of the more disabling consequences of CVA is with impaired awareness of bladder needs is a strong function arise and may be a limitation, especially in voiding dysfunction, mainly urinary incontinence (UI). and independent risk factor for poor outcome at three More recently, Lee et al reported findings in 20 patients with baseline cognitive impairment. Up to 64% of stroke survivors have lower urinary tract months. This probably reflects more serious brain patients with chronic brainstem stroke, and found that Mirabegron may be useful in these cases, but no symptoms (LUTS)2. Urologists must be aware about damage, affecting sustained attention and they had more frequent detrusor underactivity, and no clinical studies have been published about safety and consequences of CVA, mechanisms and factors information processing. overactivity, when compared to patients with upper efficacy in this population. In refractory DO patients, botulinum toxin may be useful, although there is only influencing treatment of voiding dysfunction. cervical SCI. Specifically, detrusor underactivity was Loss of bladder sensation is more frequent in patients mainly found when the central portion of the bilateral one published study showing lower efficacy in CVA with parietal lobe lesions, while those with frontal pons was involved. This finding was linked to lower patients (50%) compared to SCI patients (91.6%)22. Presentation lobe impairment show urgency UI and preserved Urinary retention may be the most frequent maximal detrusor pressure and higher compliance16. Some studies have reported good results with sacral presentation after a stroke. The exact mechanism of bladder sensation10. Turhan et al studied the influence neuromodulation. A systematic review shown 60% of action is not clearly known, but has been traditionally of UI in functional recovery after stroke. Presence of UI Urodynamic findings long term efficacy in CVA patients, but the number of named as â&#x20AC;&#x153;cerebral shockâ&#x20AC;?. Neurologic lesion is the on admission was a strong negative predictor of patients included was low23. When incontinence occurs after stroke, the most main explanation, but reduced consciousness, successful rehabilitation in the entire study group common urodynamic finding is DO with coordinated immobility and difficulties to communicate the need (OR=14.8, 95% CI: 6.5-33.9) as well as in subgroups of voiding. Figure 2 shows a severe DO with voluntary Voiding dysfunction may be due to anatomical to void may also play a role. Some studies show haemorrhagic and ischemic stroke patients (OR=25.0, contraction of external sphincter on EMG (patient is obstruction (usually BPH), functional obstruction (DSD CI: 3.9-160.5 and OR=13.9, CI: 5.4-35.5, respectively), higher incidence of retention in patients with larger or pseudodyssynergia), or detrusor hipo/acontractility. trying to avoid urinary incontinence). This voluntary neurologic lesions1. Retention tends to solve in the and in patients with cortical and subcortical lesion In case of anatomical obstruction secondary to control of external sphincter may be a good majority of patients after discharge1,3. locations (OR=30.2, CI: 7.2-126.7 and OR=9.3, CI: prostate enlargement, alpha-blockers are useful, but prognostic indicator of future social continence17. 2.7-31.4, respectively). Evidence of UI was a strong secondary effects (dizziness, hypothension) may be a problem during the rehabilitation period. If prostate There is an evolution from retention to an established negative predictor for stroke rehabilitation outcome in Detrusor acontractility is observed in patients with all age groups. Incidence of UI in patients aged over cerebellar lesions or in the acute phase of â&#x20AC;&#x153;cerebral voiding dysfunction, usually storage LUTS: urgency, surgery is needed, the urologist should refrain from 75 years was higher than in patients under 75 years11. shockâ&#x20AC;?. Another common urodynamic finding in performing transurethral prostatic resection for six to frequency, nocturia, nocturnal enuresis and urinary 12 months after a stroke because incontinence and incontinence. In general, 57-83% of neuro-urological Moreover, physical function is important for regaining patients with frontal lesions is uninhibited sphincter morbidity may be increased4. symptoms remain at one month post-stroke, and continence: patients with better physical scoring at relaxation with detrusor overactivity, then a severe 4 17 admission have higher probabilities of being incontinence with reduced awareness is seen . DSD is 71-80% recover spontaneously at six months . continent over time. rarely observed, only in those patients with basal Results of prostate surgery are variable, with Brittain et al. evaluated the prevalence and impact of ganglia lesions. Pseudodyssynergia is more frequently satisfactory results from only 50% to 92% of In the study of Edwards et al, UI after stroke was seen, as a consequence of a voluntary contraction of patients24,25. Only a small study has tried botulinum LUTS among stroke survivors in a community-based the external sphincter to avoid urine leakage (Figure 2). toxin injected in external sphincter for treatment of associated with greater dependence in basic and survey study. They found the prevalence of LUTS as instrumental activities of daily life, decreased follows: nocturia 49%, urinary incontinence 33%, pseudodyssyinergia, with good results (91% voiding urgency 19%, frequency 15%, straining 3.5% and pain participation and low life satisfaction12. Depression is Management improvement vs 40% control group). Detrusor 2.5%. All were found to be significantly more prevalent common after a stroke, and it seems to be related to hypocontractility or acontractility is usually managed During the acute phase (cerebral shock) in the stroke in the stroke than the non-stroke population2. disability level. Depression is a common complication unit, an indwelling catheter or suprapubic cystostomy by CIC, although sometimes may be challenging for after stroke. A recent multicenter study found is advisable for controlling diuresis and ensuring a patients with worse functional status. A proposed Incontinence and risk of death one-fifth of stroke survivors developed depression at good bladder emptying. Prophylaxis of urinary tract management algorithm can be found in Figure 3. Urinary incontinence is the most important voiding the 12-month follow-up, and complications at infection is necessary, specially in diabetic patients. Editorial Note: Due to space constraints the reference dysfunction after stroke and is usually secondary to discharge and urinary incontinence were significantly Bladder catheter must be removed as soon as detrusor overactivity (DO). UI affects about 39-79% of correlated with depression in multivariate analysis13. list has been omitted. Interested readers can email at possible, and empirical treatment based on LUTS patients within days after a new-onset stroke and Recovery of continence have positive effects on started. If reflex or spontaneous micturition is EUT@uroweb.org for a complete listing. 15-32% at one-year follow-up5,6. Occurrence of UI self-esteem and socialization, and should be a main initiated, post- void residual (PVR) measurement is after a stroke has been linked to worse functional objective in the management. mandatory, and if it is clinically significant, CIC should Saturday 25 March status, poorer quality of life, greater cost burden, be started if feasible. At the first stages of recovering 10.50-11.05: Meeting of the EAU Section of longer hospital stay, nursing home admission, heavier All of these factors (depression, functional outcome, period, palliative measures for incontinence are Female and Functional Urology (ESFFU) caregiver burden and death. UI is a major predictive quality of life, self-esteem, longer hospital stay, high advisable (pads or condoms). factor for both mortality and quality of life after CVA. family and caregiver burden, chance of institutionaliA recent review and meta-analysis search evidence on zation, etc.) are correlated and have influence on urinary incontinence outcomes after CVA (Figure 1). 24 studies included. The proportion of death at the end of the follow-up ranged from 34% to 61% for CVA topography and incontinence %& , #)$# Depending on the location of the cerebral lesion, ! & ( ( & & #'+& ( & !2'+%& %+ different urodynamic patterns and LUTS may be found. Cortical lesions often show detrusor

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Figure 1: Factors involved in post CVA urinary incontinence

EUT Congress News

Brain CT or MRI in symptomatic patients showed lesions of anterior and medial surface of the frontal lobe, anterior edge of the paraventricular white matter, genu of the internal capsule and large lesions of putamen or thalamus. Urodynamic studies of 22

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Figure 3: Proposed CVA management algorithm

Saturday, 25 March 2017

EAUN launches catheterisation guidelines summary Urethral intermittent catheterisation in adults Susanne Vahr, RN Chair-Elect EAUN University Hospital of Copenhagen Rigshospitalet Copenhagen (DK)

One of the goals for the EAUN is “To foster excellence in urological nursing throughout Europe” and writing guidelines is a way to achieve this. In 2009 EAUN published the first evidence-based guidelines and since then we have discussed the benefits of pocket guidelines to help nurses use the recommendations to guide their clinical practice. Thus, we are so happy that Wellspect gave us the opportunity to turn the recommendations from the full set of guidelines on intermittent catheterisation in adults into a pocket version. The EAUN believes there is a need to provide guidelines with recommendations that clearly state the level of evidence of each procedure, with the aim of improving current practices. The full set of guidelines1 on intermittent catheterisation is based on the best available evidence and aims to improve current practice through a standard and reliable protocol. This summary reflects all the main recommendations of the original guidelines. It was created by summarising into a concise form all the main guidance points and recommendations of the original. The chapter on urethral dilatation is not included in the edited summary. The release of this EAUN edited summary is a very important step in implementing the EAUN guidelines on “Catheterisation: Urethral Intermittent in Adults” in clinical practice. Knowledge dissemination is a crucial part of patient safety if evidence based knowledge is

not easily available in clinical practice, patients are at risk not to benefit from it. Knowledge management has been described as ‘getting the right knowledge to the right people, in the right place at the right time’2. One of the challenges in ensuring this is that nurses must realise what they do not know, to feel the need to consult guidelines, and they must be aware of the existence of the guidelines.

Evidence-based

Effective strategies to implement clinical guidelines therefore have multiple components: healthcare professionals, patients and stakeholders must be aware of the existence of the guideline, and the guideline must be easy to understand and easy to use. The usage report from The National Guideline Clearinghouse showed that last year the “Catheterisation: Urethral Intermittent in Adults” Guidelines was viewed 5,638 times. This means that quite a lot of nurses are aware of the existence of the guidelines, but far from everybody. To enhance the use of the guidelines, the EAUN hopes that an easy-to-carry around version like this pocket guideline will be a step in knowledge dissemination on intermittent catheterisation. The edited summary contains chapters on indications and contraindications, catheter material and types of catheter, procedures for intermittent catheterisation, principles of management of nursing interventions, complications, patient quality of life and methodology. The only appendix included in the pocket guideline is the step-by-step procedure on how to perform intermittent catheterisation as this is needed in daily practice. More appendices are available on-line. At the 18th EAUN meeting in London, 25-27 March, the edited summary will be launched and on Saturday 25 March at 15.30 -16.00 h. printed copies of the pocket guideline will be available for all delegates in the EAUN Booth on Level 3 and in the Exhibition hall (EAU Corner). If you would like to attend the session, please check the details below or in the EAU Events App.

guidelines for

B ES T P R A C T IC E IN U R O LO G IC A L H EA LT H C A R E An edited summa ry of the Europea n Association of Urology Nu rses evidence-ba sed guideline on

Intermittent Ure th Catheterisation ral in Adults

Supported by an unrestricted educat ional grant from Wellspect Health Care

EAUN Note: Wellspect HealthCare supported the edited summary with an unrestricted educational grant.

2. Kingston, J. Choosing a Knowledge Dissemination Approach. Knowledge and Process Management;19(3):160–170 (2012).

References 1. Vahr S, H. Cobussen-Boekhorst, J. Eikenboom, V. Geng, S. Holroyd, M. Lester, I. Pearce, C. Vandewinkel, Catheterisation-Urethral intermittent in adults.Dilatation, urethral intermittent in adults. Evidence-based Guidelines for Best Practice in Urological Health Care 2013. European Association of Urology Nurses.

Saturday 25 March 15.30 – 16.00: 18th International EAUN Meeting, State-of-the-art 1: Guidelines on urethral intermittent catheterisation in adults Location: Room 1

URO 57 4.0 08/2016/A-E

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Saturday, 25 March 2017

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Saturday, 25 March 2017