Tumor-Microenvironment Characterization of the MB49 Non-Muscle-Invasive Bladder-Cancer Orthotopic Model towards New Therapeutic Strategies.

Bacillus Calmette-Guérin (BCG) instillations for the treatment of non-muscle-invasive bladder cancer patients can result in significant side effects and treatment failure. Immune checkpoint blockade and/or decreasing tumor-infiltrating myeloid suppressor cells may be alternative or complementary treatments. Here, we have characterized immune cell infiltration and chemoattractant molecules in mouse orthotopic MB49 bladder tumors. Our data show a 100-fold increase in CD45+ immune cells from day 5 to day 9 tumors including T cells and mainly myeloid cells. Both monocytic myeloid-derived suppressor-cells (M-MDSC) and polymorphonuclear (PMN)-MDSC were strongly increased in day 9 tumors, with PMN-MDSC representing ca. 70% of the myeloid cells in day 12 tumors, while tumor associated macrophages (TAM) were only modestly increased. The kinetic of PD-L1 tumor expression correlated with published data from patients with PD-L1 expressing bladder tumors and with efficacy of anti-PD-1 treatment, further validating the orthotopic MB49 bladder-tumor model as suitable for designing novel therapeutic strategies. Comparison of chemoattractants expression during MB49 bladder tumors grow highlighted CCL8 and CCL12 (CCR2-ligands), CCL9 and CCL6 (CCR-1-ligands), CXCL2 and CXCL5 (CXCR2-ligands), CXCL12 (CXCR4-ligand) and antagonist of C5/C5a as potential targets to decrease myeloid suppressive cells. Data obtained with a single CCR2 inhibitor however showed that the complex chemokine crosstalk would require targeting multiple chemokines for anti-tumor efficacy.

Reduction and follow-up of hospital discharge letter delay using Little's law.

QUALITY PROBLEM: As discharge letters (DL) hold important information for healthcare professionals and especially for general practitioners, rapid and efficient finalization is required. We describe a project aiming to reduce DL submission within 8 days in our Urology Department (UD), as required by the local Hospital Board (HB). INITIAL ASSESSMENT AND CHOICE OF SOLUTION: A team was built in UD with staff members and one external expert to study the root causes of delayed DL creation and develop sustainable strategies to improve and monitor the process, including habits changing, training and application of Little's Law. IMPLEMENTATION AND EVALUATION: The study started on January 2015 and ended up on March 2016, involving 908 and 616 DL for old and new process, respectively. The new process decreased the average delay of DL completion from 24.88 days to 14.7 days. Standard deviation of total average delay for DL completion fell from 10.1 days to 7.5 days. We identified four steps needed to DL creation and allowed maximum 2 days for every step completion. No additional resources were employed. LESSONS LEARNED: We were able to improve the process of DL creation, by analysing its steps and reducing their variability. This can be easily transposed to other medical departments.

Spoilt for Choice: A Survey of Current Practices of Surgical Urinary Stone Treatment and Adherence to Evidence-Based Guidelines among Swiss Urologists.

INTRODUCTION: Urologists have to master a variety of techniques to be able to offer the most appropriate surgical stone treatment for each individual patient. Therefore, we performed a survey among board-certified Swiss urologists to assess the availability of the different surgical methods, the current practices of surgical treatment of urolithiasis and the adherence to evidence-based guideline recommendations in Switzerland. METHODS: A 14-question survey assessed the working environment, equipment, perioperative settings and decision trees for specific stone scenarios. Data was analyzed using descriptive statistics and chi-square tests to determine differences between frequencies of answers. RESULTS: Hundred and five members of Swiss Urology (38%) completed the survey. All treatment modalities are available for the majority of respondents. Ureterorenoscopy was found to have the highest availability (100%) and was the preferred choice in the majority of stone scenarios. A high adherence to the guidelines was found for the treatment of ureteral stones <10 mm (100% proximal and distal), and >10 mm (69% proximal, 94% distal). All respondents answered in accordance with the guidelines regarding the treatment of middle and upper pole stones <10 mm, 10-20 mm and lower pole stones 10-20 mm. Guideline adherence was 99% for lower pole stones <10 mm, 78% for lower pole stones >20 mm, and 63% for middle/upper pole stones >20 mm. CONCLUSION: This survey provides a detailed insight into current stone treatment practices in Switzerland. The full spectrum of urinary stone treatment options is available for the majority of Swiss urologists. The choice of treatment shows a high accordance with evidence-based guidelines and a preference for retrograde endoscopic surgery in the majority of stone scenarios.

[Urology in 2018]. / Urologie.

This article summarizes the milestones in urology in 2018 in the following areas : urinary tract infection, functional bladder disorders, oncology and renal colic treatment.

Cet article résume les faits marquants en urologie en 2018 dans les domaines suivants : infection urinaire, troubles fonctionnels de la vessie, oncologie et traitement de la colique néphrétique.

[Current surgical treatments for women with stress urinary incontinence]. / Actualité du traitement chirurgical de l'incontinence urinaire d'effort chez la femme.

Surgical treatments for female stress urinary incontinence is in perpetual evolution. This article reviews the current surgical treatments for stress urinary incontinence in female. Bulking agents, Burch colposuspension, autologous sling, midurethral slings, single incision slings, artificial urinary sphincter and adjustable continence therapy (ACT) are discussed.

Les traitements chirurgicaux de l'incontinence urinaire d'effort chez la femme sont en perpétuelle évolution. Cet article passe en revue les options actuelles de traitement chirurgical de l'incontinence urinaire d'effort chez la femme. Les injections péri-urétrales d'agents de comblement, la colposuspension selon Burch, la bandelette sous-urétrale aponévrotique, les bandelettes sous-urétrales synthétiques, les mini-bandelettes (single incision sling), le sphincter urinaire artificiel et les ballonnets péri-urétraux (ACT) y sont présentés.

[Management of urologic cancers in elderly people†: which implications†?] / Prise en charge de cancers urologiques chez la population âgée†: quels enjeux†?

Elderly patients with urologic cancer are often undertreated because of their age. Recently, many studies showed that advanced age is not an absolute contraindication to radical surgery for bladder and prostate cancer patients. For small renal cancers, instead, active surveillance with a close follow-up may be a valid alternative to surgery because of a low risk of progression. Patients' selection remains a crucial step to define the best treatment. This article summarizes the new tendencies of urologic cancer management in elderly patients.

Les personnes âgées avec un cancer urologique sont souvent traitées de façon sous-optimale en se basant uniquement sur leur âge avancé. Récemment, plusieurs chercheurs se sont intéressés à cette classe de la population et ont montré que l'âge avancé n'est pas forcément une contre-indication à réaliser une chirurgie majeure. Cependant, l'évaluation des bénéfices et des risques est déterminante car la grande majorité des néoplasies du rein et de la prostate ont une lente évolution et un faible risque de progression, raison pour laquelle, une surveillance active avec des examens réguliers peut donc être la meilleure alternative. La sélection du patient reste une étape cruciale afin de proposer la meilleure option thérapeutique. Cet article résume les nouvelles tendances de prise de charge des 3 pathologies onco-urologiques les plus fréquentes.

[Urology]. / Urologie.

This article points at recent developments in urology in the field of malignant diseases of the urinary system and the diagnostic and therapeutic management of benign conditions as well, that occur frequently in our ageing population.

Cet article vise à faire le point sur certains récents développements en urologie tant dans le domaine des affections malignes du système urinaire que des prises en charge diagnostique et thérapeutique des affections bénignes qui surviennent fort fréquemment dans notre population vieillissante.

[Improved rehabilitation after major urological surgery : what role for the general practitioner ?] / Réhabilitation améliorée après chirurgie urologique majeure : quel rôle pour le médecin généraliste ?

Enhanced recovery after surgery (ERAS) is a multimodal concept aiming to reduce surgical stress and prevent postoperative complications. Once adapted to urologic patients in 2013, this protocol evolves continuously and many international centers have now implemented it. This article resumes ERAS key principles for general practitioners as they can have a significant impact on patient's optimization before surgery.

Le protocole de réhabilitation améliorée après chirurgie est un concept de prise en charge multimodale visant à anticiper puis gérer de manière optimale le stress chirurgical inhérent à toute intervention. Adapté depuis 2013 à l'urologie, il évolue régulièrement et les centres internationaux qui appliquent ses principes sont toujours plus nombreux. Avant une chirurgie majeure, il existe un potentiel d'optimisation d'un patient auquel le généraliste peut participer activement. Cet article résume à l'attention d'un médecin généraliste les principaux points constituant cette démarche.

[Ambulatory surgery in urology]. / Chirurgie ambulatoire en urologie : il est temps d'en parler.

The volume of ambulatory surgery in urology increases every year. Successful ambulatory care is defined by low hospital (re)admission rates, insuring optimal oncologic and functional outcomes. New medical techniques such as minimally invasive surgical approaches and less side effects of anesthesia have helped the development of ambulatory surgery. Additionally, it is essential to lower the burden of healthcare systems financially, without compromising quality of care. Ambulatory surgery needs a multidisciplinary team involvement, where the general practitioner has a key role.

La pratique ambulatoire en urologie augmente chaque année. Les avancées médicochirurgicales ont permis de diminuer les gestes invasifs et les effets secondaires des anesthésiques. Sur le plan financier, il est essentiel de contrôler les dépenses de santé publique, tout en maintenant comme premier objectif la sécurité du patient. Les critères de succès d'une prise en charge ambulatoire se mesurent au faible taux d'hospitalisation et de réadmission, sans compromission quant aux résultats de la chirurgie. La prise en charge ambulatoire exige une équipe pluridisciplinaire et le médecin traitant joue un rôle essentiel dans l'itinéraire clinique de son patient.

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect.

OBJECTIVE: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance. PATIENTS AND METHODS: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate. RESULTS: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015). CONCLUSION: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

[Urology : therapeutics news in 2016]. / Urologie.

This article summarizes recent advances in the field of urinary infections, bladder function, minimal invasive surgery and genitourinary cancers.

Cet article résume les progrès récents dans le domaine des infections urinaires, de la fonction de la vessie, de la chirurgie mini­invasive et des cancers génito-urinaires.

[Immunotherapy : a revolution in the management of urothelial bladder cancer ?] / Immunothérapie : une révolution dans la prise en charge du cancer de la vessie ?

The treatment of urothelial bladder cancer has changed very little in recent years, with high rates of disease recurrence and progression, even in low aggressive urothelial bladder cancer. Immunotherapy has already proven its effectiveness as a treatment for several types of cancer and has been used in high-grade non-muscle-invasive bladder cancer for decades. Recent findings on immune checkpoints inhibitors have opened up a new chapter for treatment of bladder cancer, offering interesting therapeutic perspectives that could revolutionize the management.

Le traitement du cancer de la vessie a très peu évolué depuis plusieurs années avec des taux de récidives et de progression élevés, même dans les tumeurs peu invasives. L'immunothérapie a déjà fait ses preuves comme traitement de plusieurs types de cancer et est utilisée dans le cancer de la vessie non musculo-invasif de haut grade depuis des décennies. Les récentes découvertes sur les inhibiteurs de points de contrôle immunitaire (checkpoints inhibitors) ouvrent tout un nouveau chapitre sur le traitement des différents stades du cancer de la vessie, y compris les tumeurs musculo-invasives et métastatiques, offrant des perspectives thérapeutiques, capables de révolutionner la prise en charge.

[Local treatment in oligometastatic urological malignancies : evidence of wishful thinking ?] / Ablation du cancer primaire dans les néoplasies urologiques oligométastatiques : évidence ou vœux pieux ?

In the past, it was generally considered that the window of curability had been missed in metastatic solid cancers. At present, novel evidence suggests that oligometastatic cancer might be amenable to a multimodal curative treatment, including ablation of the primary tumour. In this article, we summarise the indications, the controversies and future perspectives of local treatment in oligometastatic urological malignancies.

Dans le passé, on considérait le plus souvent que la fenêtre de curabilité dans les cancers solides à un stade métastatique avait été manquée. De nouvelles évidences suggèrent à présent que la maladie à un stade oligométastatique est accessible, dans certains cas, à un traitement multimodal curatif, incluant l'ablation de la tumeur primaire. Dans cet article, nous résumons les indications, les controverses ainsi que les perspectives futures du traitement local dans les cancers oligométastatiques urologiques.

Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.

Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

[Novelties in Urology in 2015]. / Quoi de neuf en urologie?

This paper brings to the general practitioner some clarifications with regard to open questions - such as prostate cancer screening - and points at some disease management in different fields - such as urinary stones, overactive bladder and immunotherapy in bladder cancer.

[Assessment and treatment of genitourinary infections]. / Bilan et traitements des infections urogénitales.

Antibiotics are most commonly prescribed for urinary bacterial infections. The purpose of this article is to review the most common infections of the genitourinary tract and to guide the choice of the most appropriate treatment. This choice depends also on the patients general state, local associated conditions and can range from observation to an emergency hospitalisation. Primary care physicians remain in the first line to take care of these patients but the urologists or the infectious disease specialists can provide some help in complex situations.

Les infections urinaires bactériennes sont l'une des principales indications à la prescription d'antibiotiques. Le but de cet article est d'aider le praticien à reconnaître les diverses infections du tractus urogénital et à les traiter en utilisant les antibiotiques de façon appropriée. Le choix du traitement dépend aussi de l'état général du patient, de conditions locales associées et peut aller de l'abstention thérapeutique à l'hospitalisation en urgence. Le médecin de famille est en première ligne dans la prise en charge de ces pathologies fréquentes et l'urologue ou l'infectiologue peuvent apporter leur contribution dans les situations complexes.

[Common medications and prostate cancer : what is the association ?] / Médicaments usuels en médecine de premier recours et cancer de la prostate : quelle relation ?

A possible association between prostate cancer and metabolic syndrome has recently been observed. Further, multiple experimental and epidemiologic studies have recently reported a probable association between common medications and prostate cancer. In this article, we summarize the results of those studies that explore the role of aspirin, oral antidiabetic medication and statins.

Une possible association entre le cancer de la prostate et le syndrome métabolique a récemment été mise en évidence. Plusieurs récentes études expérimentales et épidémiologiques ont suggéré un rôle protecteur de plusieurs médicaments largement utilisés en médecine de premier recours dans le cancer de la prostate. Nous résumons ici les résultats de ces études, en particulier pour l'aspirine, les antidiabétiques oraux et les statines.

[Management of genitourinary trauma]. / Prise en charge des traumatismes urogénitaux.

Urogenital trauma often occurs in the context of polytrauma patients. In this article, aimed at primary care practitioners and emergency physicians, we summarise the epidemiology and aetiology of these traumas as well as their management. The goal is to allow primary healthcare professionals to become acquainted with diagnostic and therapeutic strategies in genitourinary trauma patients.

Les traumatismes des organes génitaux externes et du système urinaire chez l'adulte se rencontrent souvent dans le contexte de patients polytraumatisés. Dans cet article, qui s'adresse aux médecins de premiers recours ainsi qu'aux membres des services d'urgences, nous résumons les caractéristiques épidémiologiques et étiologiques de ces lésions ainsi que les dernières recommandations concernant leur prise en charge. Le but est de permettre aux différents intervenants de se familiariser avec les stratégies diagnostiques et thérapeutiques face à un patient présentant un traumatisme urogénital.

Technical solutions to improve the management of non-muscle-invasive transitional cell carcinoma: summary of a European Association of Urology Section for Uro-Technology (ESUT) and Section for Uro-Oncology (ESOU) expert meeting and current and future perspectives.

The aim of the present review was to compare state-of-the-art care and future perspectives for the detection and treatment of non-muscle-invasive transitional cell carcinoma (TCC) of the bladder. We provide a summary of the third expert meeting on 'Optimising the management of non-muscle-invasive bladder cancer, organized by the European Association of Urology Section for Uro-Technology (ESUT) in collaboration with the Section for Uro-Oncology (ESOU), including a systematic literature review. The article includes a detailed discussion on the current and future perspectives for TCC, including photodynamic diagnosis, optical coherence tomography, narrow band imaging, the Storz Professional Image Enhancement system, magnification and high definition techniques. We also provide a detailed discussion of future surgical treatment options, including en bloc resection and tumour enucleation. Intensive research has been conducted to improve tumour detection and there are promising future perspectives, that require proven clinical efficacy. En bloc resection of bladder tumours may be advantageous, but is currently considered to be experimental.

[Second and third-lines therapy for the management of erectile dysfunction]. / Thérapie de deuxième et troisième lignes pour la prise en charge de la dysfonction erectile.

In this article, we summarize second and third lines therapeutic strategies for the management of erectile dysfunction. We also highlight common errors that can hinder the effectiveness of first-line treatment. Second-line strategies can also be considered upfront in patients with contraindications to PDE5 inhibitors.