Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

Do cancer detection rates differ between transperineal and transrectal micro-ultrasound mpMRI-fusion-targeted prostate biopsies? A propensity score-matched study.

INTRODUCTION: High-resolution micro-ultrasound (micro-US) is a novel precise imaging modality that allows targeted prostate biopsies and multiparametric magnet resonance imaging (mpMRI) fusion. Its high resolution relying on a 29 MHz transducer allows real-time visualisation of prostate cancer lesions; this might overcome the inaccuracy of conventional MRI-US fusion biopsy strategies. We compared cancer detection rates in patients who underwent transrectal (TR-B) versus transperineal (TP-B) MR-micro-US fusion biopsy. MATERIALS AND METHODS: 1:2 propensity score matching was performed in 322 consecutive procedures: 56 TR-B and 266 TP-B. All prostate biopsies were performed using ExactVuTM micro-US system with mpMRI image fusion. Clinically significant disease was defined as grade group ≥2. The primary objective was to evaluate the detection of clinically significant disease according to access route. The secondary outcomes were to compare the respective detection rates of random and targeted biopsies stratified per access route and to evaluate micro-US for its potential added value. RESULTS: 47 men undergoing TR-B and 88 undergoing TP-B were matched for age, PSA, clinical stage, prostate volume, PIRADS score, number of mpMRI-visible lesions and indication to biopsy. The detection rates of clinically significant and of any prostate cancer did not differ between the two groups (45% TR-B vs 42% TP-B; p = 0.8, and 57% TR-B vs 59% TP-B; p = 0.9, respectively). Detection rates also did not differ significantly between random (p = 0.4) and targeted biopsies (p = 0.7) stratified per access route. Micro-US targeted biopsy detected 36 MRI-invisible lesions in 33 patients; 19% of these lesions were positive for clinically significant disease. Overall, micro-US targeted biopsies upgraded 2% of patients to clinically significant disease that would have been missed otherwise. CONCLUSIONS: MR-micro-US-fusion TR-B and TP-B have similar diagnostic yields in terms of detection rates of clinically significant prostate cancer. Micro-US targeted biopsy appears to have an additional diagnostic value over systematic and MRI-targeted biopsies.

What Is the Best Candidate to Replace the Tarsus? A Biomechanical, Histological, and Optical Study Comparing Five Grafts.

Purpose: Reconstruction of the posterior lamella after eyelid tumor removal is challenging and not consensual. Tarsus is the most suitable graft, but is only available in small amounts. Herein, we aim to determine the most appropriate way to replace the tarsus by comparing the biomechanical, histological, and optical properties of five commonly used grafts. Methods: This study was conducted at the University hospital of Nice between June 2019 and June 2020. Five posterior lamella grafts (tarsus, conchal cartilage, sclera, hard palate, and dermis) were harvested in five fresh frozen cadavers. Biomechanical properties were assessed by tractometry. Collagen and elastin fibers were analyzed by using histological analysis and optical characterization with the second harmonic generation imaging. Results: The mean Young's modulus was 8.92 MPa (range, 2.90-22.90 MPa), 1.05 MPa (range, 0.39-1.76 MPa), 8.72 MPa (range, 2.0-23.50 MPa), 2.57 MPa (range, 0.41-4.35 MPa), and 1.44 MPa (range, 0.71-2.30 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The mean tensile strength was 3 MPa (range, 1.70-6.88 MPa), 0.54 MPa (range, 0.13-0.79 MPa), 2.87 MPa (range, 1.23-5.40 MPa), 1.4 MPa (range, 0.21-2.40 MPa) and 1.0 MPa (range, 0.46-1.43 MPa) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. Hard palate mucosa was the closest to the tarsus regarding the ratio of elastin and collagen fibers. The average second harmonic generation intensity was 221 arbitrary units (a.u.) (range, 165-362 a.u.), 182 a.u. (range, 35-259 a.u.), 369 a.u. (range, 206-533 a.u.), 108 a.u. (range, 34-208 a.u.), and 244 a.u. (range, 195-388 a.u.) for the tarsus, the conchal cartilage, the sclera, the hard palate mucosa, and the dermis, respectively. The hard palate mucosa and the dermis were the closest to the tarsus regarding the collagen fiber size and orientation, respectively. Conclusions: By attributing 2 points for each characteristic (biomechanical, histological, and optical), the hard palate mucosa and the sclera seem to be the most suitable grafts to replace the tarsus. Translational Relevance: The aim of this article was to assess the biomechanical, histological and optical characteristics of five of the most commonly used tarsal grafts; this may be helpful in decisions for clinical practice.

Identification of Urine Biomarkers to Improve Eligibility for Prostate Biopsy and Detect High-Grade Prostate Cancer.

PCa screening is based on the measurements of the serum prostate specific antigen (PSA) to select men with higher risks for tumors and, thus, eligible for prostate biopsy. However, PSA testing has a low specificity, leading to unnecessary biopsies in 50-75% of cases. Therefore, more specific screening opportunities are needed to reduce the number of biopsies performed on healthy men and patients with indolent tumors. Urine samples from 45 patients with elevated PSA were collected prior to prostate biopsy, a mass spectrometry (MS) screening was performed to identify novel biomarkers and the best candidates were validated by ELISA. The urine quantification of PEDF, HPX, CD99, CANX, FCER2, HRNR, and KRT13 showed superior performance compared to PSA. Additionally, the combination of two biomarkers and patient age resulted in an AUC of 0.8196 (PSA = 0.6020) and 0.7801 (PSA = 0.5690) in detecting healthy men and high-grade PCa, respectively. In this study, we identified and validated novel urine biomarkers for the screening of PCa, showing that an upfront urine test, based on quantitative biomarkers and patient age, is a feasible method to reduce the number of unnecessary prostate biopsies and detect both healthy men and clinically significant PCa.

[Urinary incontinence: a good diagnosis as a basis for treatment]. / Incontinence urinaire: un bon diagnostic comme base de traitement.

Urinary incontinence: a good diagnosis as a basis for treatment Abstract. Abtract: Everyone has experienced incontinence at an early age. However, it also affects approximately 200 million people worldwide at the adult age. This common condition is frequently underreported by patients but can dramatically limit their social life. Subject to appropriate differential diagnosis, urinary incontinence is a condition that can be treated with good results in the majority of patients. This article provides a review of the essential symptomatology and current treatments, so that clinicians confronted with the problem may adopt the appropriate management.

Résumé. Tout le monde a connu l'incontinence, dès le plus jeune âge. Elle affecterait cependant encore 200 millions de personnes dans le monde à l'âge adulte. Cette pathologie du quotidien est relativement peu rapportée des patient(e)s, mais limite la vie sociale de façon parfois dramatique. Sous réserve d'un sous-diagnostic pertinent, l'incontinence urinaire est une pathologie traitable avec des résultats élevés. Cet article propose une revue de la sémiologie essentielle ainsi que des traitements actuels afin que tout clinicien confronté au problème adopte une prise en charge adéquate.

[Emerging biomarkers of prostate cancer]. / Les biomarqueurs émergents du cancer de la prostate.

Despite recent innovation, the clinical pathway in prostate cancer is not perfect. The indication to first and control biopsy, as well as treatment choice and adjuvant treatment are clinical scenarios in which diagnostic and prognostic biomarkers might assist in clinical decision making. Some emerging biomarkers have been validated in specific clinical scenarios. Nevertheless, their utility and cost effectiveness in the current clinical pathway is yet to be proven. The aim of this article is to present the current available evidence on the novel biomarkers and discuss their role for each stage of prostate cancer care.

En dépit de nombreuses innovations, l'itinéraire clinique du cancer de la prostate reste à ce jour imparfait. Ainsi, l'indication à une première et une deuxième biopsie, le choix du traitement approprié et l'ajout d'un traitement adjuvant sont autant de situations où des biomarqueurs, diagnostiques comme pronostiques, pourraient améliorer des décisions parfois lourdes de conséquences. De nombreux biomarqueurs émergents, avec leurs caractéristiques propres, bénéficient déjà d'un certain degré de validation clinique dans des situations précises. Néanmoins, une évaluation prospective de leur performance et de leur intérêt médico-économique global reste essentielle. Nous proposons dans cet article un tour d'horizon de ces nouveaux outils, ce pour chaque étape dans la prise en charge d'un cancer de la prostate.

Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell-Mediated Tumor Regression in the MB49 Bladder Cancer Model.

Preclinical data show that intravesical instillation of Ty21a/Vivotif, a commercial vaccine against typhoid fever, is an effective alternative option to standard Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC). Here, we characterized the inflammatory effects of Ty21a on the bladder and investigated the immune mechanisms underlying tumor regression toward the use of this bacterial vaccine in NMIBC patients. MB49 bladder tumor-bearing mice had significantly improved survival after intravesical instillations of Ty21a doses of 106 to 108 colony-forming units. By IHC and morphology, both BCG and Ty21a instillations were associated with bladder inflammation, which was decreased with the use of low, but effective doses of Ty21a. Flow-cytometry analysis showed a significant infiltration of T cells, natural killer (NK) cells, and myeloid cells, compared with controls, after a single dose of Ty21a, whereas this was only observed after multiple doses of BCG. The induced myeloid cells were predominantly neutrophils and Ly6C+CD103+ dendritic cells (DC), the latter being significantly more numerous after instillation of Ty21a than BCG. Ex vivo infection of human leukocytes with Ty21a, but not BCG, similarly significantly increased DC frequency. CD4+ and CD8+ T cells, but not NK cells nor neutrophils, were required for effective bladder tumor regression upon Ty21a treatment. Thus, the generation of antitumor adaptive immunity was identified as a key process underlying Ty21a-mediated treatment efficacy. Altogether, these results demonstrate mechanisms behind intravesical Ty21a therapy and suggest its potential as a safe and effective treatment for NMIBC patients.

[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.

[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.