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OBJECTIVE To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs). PATIENTS AND METHODS This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose (18 F-FDG), gallium-68-(68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy. EXPECTED RESULTS The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features. CONCLUSION This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC.

Purpose/Objective(s) Standard treatment options for localized prostate cancer include active surveillance, radical prostatectomy, or local radiotherapy. While the use of high-intensity focused ultrasound (HIFU) as a primary treatment remains investigational, it is sometimes offered to select patients. At the time of HIFU failure, there is a lack of data in salvage treatment approach. Available data includes only small retrospective series with short-term follow-up. We therefore sought to evaluate our institutional experience in a cohort of patients treated with salvage radiation therapy (SRT) after primary HIFU failure. Materials/Methods We conducted a retrospective analysis of patients who had local failure after HIFU. This cohort of patients received salvage external beam radiation therapy (EBRT) delivered via intensity modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) based on the 'Phoenix' definition of PSA nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Kaplan-Meier analysis was performed examining bFFS, MFS and OS. Genitourinary and erectile dysfunction adverse events were analyzed. Results From 2010 to 2018, 12 patients had local relapse post primary HIFU and received salvage EBRT with or without androgen-deprivation therapy, 75% and 25% respectively. The mean initial PSA prior to salvage EBRT was 8.2ug/L (2.9-14.4ug/L). The median time from HIFU to salvage EBRT was 13.5 months (6-42 months). EBRT was delivered as either conventional (76-78 Gy in 38-39 fractions, n = 11) or hypofractionation (66 Gy in 22 fractions, n = 1). Mean PSA nadir post RT was 1.2ug/L (0.1-2.6 ug/L). Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (P = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported in men receiving EBRT as their primary treatment for localized prostate cancer. At a median follow-up of 46 months, only one patient had biochemical recurrence and radiological progression. The 5-year bFFS and MFS were both 83.3%. There were no deaths at the time of this analysis (OS = 100%). Conclusion To our knowledge this is one of the largest series reporting on modern SRT post HIFU failure. Our analysis shows that salvage EBRT is feasible, effective and carries no additional acute and delayed toxicity.

A 66-year-old male, with an undiagnosed duplex system, underwent a Robotic-assisted Radical Prostatectomy that was complicated by an ectopic ureter injury. Given the incidence of less than 0.001%, management of ectopic ureters for patients undergoing a RARP is foreign to most urologists. The delayed presentation lead us to opt for selective angioembolisation of the hydronephrotic segment. Symptoms completely resolved and a follow up scan showed resolution of the hydronephrosis as well as hypovascularized parenchyma of the upper moiety. A literature review was done along with this example of non-surgical management of a rare RARP complication.

Acute compartment syndrome is a surgical emergency that, if unrecognised, leads to tissue and muscle ischaemia, necrosis, multi-organ failure and even death. Gluteal compartment syndrome is a rare type of compartment syndrome that typically occurs as a sequela of trauma, and its presentation may be difficult to recognise. We describe a case of a patient who developed gluteal compartment syndrome following a prolonged renal surgery in lateral decubitus position. Our case report aims to raise clinicians’ awareness to consideration of this rare syndrome in patients presenting with lower extremity or back pain after prolonged surgery.

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer.

Partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU) is currently under investigation for clinically significant prostate cancer (Cs-PCa). Our primary objective was to assess the role of systematic control biopsies following HIFU-PGA in a cohort of Cs-PCa patients.We studied a single-center retrospective cohort of 77 men treated with HIFU-PGA between October 2015 and December 2019. Patients with unilateral Cs-PCa, defined as Gleason grade group (GGG) ≥2, with visible lesion on multiparametric magnetic resonance imaging (mpMRI) and prostate specific antigen (PSA) ≤15 ng/ml were included. All patients underwent mpMRI with systematic and targeted biopsies before and after HIFU-PGA. The primary outcome was the rate of Cs-PCa at control biopsy within 1 year of treatment. Logistic regression was performed to identify predictive factors of our primary outcome.Median age was 67 years (IQR 61-71), median PSA was 7 ng/ml (IQR 5.5-8.9). Pre-treatment biopsies revealed 48 (62.3%) GGG2 lesions, 24 (31.2%) GGG3 and 5 (6.5%) GGG4 lesions. Cs-PCa was found in 24 (31.2%) patients at systematic control biopsy post-HIFU; Cs-PCa was in the treated lobe for 18 (27%) patients. No variables were identified as significant predictors of Cs-PCa at control biopsy, including PSA kinetics and control mpMRI. Median followup time was 17 months (95% CI 15-21). Median time to any retreatment was 32 months (95% CI 23-42).Systematic control biopsy within a year after PGA for Cs-PCa can identify the presence of residual Cs-PCa in up to a third of patients. From our early experience, control biopsy should be systematically offered patients regardless of PSA kinetics or control mpMRI results.

Introduction: Conventional imaging (CI) performs poorly to identify sites of disease in biochemically recurrent prostate cancer. 68Ga-PSMA-11 positron emission tomography/ computed tomography (PET/CT) is most studied but has a very short half-life. This study reports the diagnostic performance of the novel prostate-specific membrane antigen (PSMA) radiotracer 18F-DCFPyL using real-life data, and tumor board simulation to estimate the impact of 18F-DCFPyL PET on patient management. Methods: Ninety-three 18F-DCFPyL PET/CT scans performed for patients previously treated for prostate cancer with a rising prostate-specific antigen (PSA) were retrospectively compared to contemporary CI, and clinical, imaging and PSA followups. A chart review was performed to document prior imaging, pathology results, serial serum PSA measurements, and other pertinent clinical data. Clinical utility of 18F-DCFPyL PET was measured using a simulated tumor board formed by three physicians with extensive prostate cancer experience deciding on management with and without knowledge of PET/CT results. Results: At median PSA 2.27 (interquartile range [IQR] 5.27], 82% of 18F-DCFPyL PET/CT demonstrated at least one site of disease: non-regional lymph nodes (37% of scans), regional lymph node metastases (28%), local recurrence (27%), bone metastases (20%), with higher PET positivity at higher PSA. Compared to 18F-DCFPyL PET/CT, CI showed overall poor performance, with accuracy below 20% for all extent of disease. PET/CT changed management in 44% of cases. The most frequent scenario was a radical change from initiating androgen deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) of oligo-lesional disease. In univariate and multivariate analysis, no patient characteristic could predict change of management by PET/CT results. Conclusions: 18F-DCFPyL significantly outperforms CI in recurring prostate cancer and is likely to impact management.

Introduction: We aimed to assess the transferability of basic robotic skills from the simulator to the operating room while performing robotic-assisted radical prostatectomy (RARP) prostatectomy). Methods: Fourteen urology residents were randomized to two groups: group A was required to practice three sessions (nine tasks each) on the simulator, whereas group B was required to practice (same nine tasks) until they reached competency. Both groups were recorded while practicing on the da Vinci Surgical Skills Simulator (da Vinci Simulator). Both groups were then recorded while performing bladder mobilization during RARP. Senior residents from both groups were also recorded while performing urethro-vesical anastomosis during RARP. Recordings were assessed blindly using the validated GEARS tool by C-SATS. Spearman’s correlation coefficient (rho) was used to assess correlation between GEARS scores from practice sessions on the da Vinci Simulator and the GEARS scores from bladder mobilization and urethro-vesical anastomosis during RARP. Results: There was no difference in total GEARS scores between the two groups in the operating room. Total GEARS scores for “ring and rail 2” and “suture sponge” tasks correlated with the total GEARS scores during urethro-vesical anastomosis (rho=0.86, p=0.007; rho=0.90, p=0.002, respectively). GEARS’ efficiency component during “energy and dissection” task on the da Vinci Simulator correlated with GEARS’ efficiency component during bladder mobilization (rho=0.62, p=0.03). GEARS’ force sensitivity component during “ring and rail 2” and “dots and needles” tasks on the da Vinci Simulator correlated with GEARS’ force sensitivity component during bladder mobilization (rho=0.58, p=0.047; rho =0.65, p=0.02, respectively). Conclusions: Objective assessments of urology residents on the da Vinci Surgical Skills Simulator tasks ring and rail 2 and suture sponge correlated with their objective assessments of bladder mobilization and urethro-vesical anastomosis. Therefore, basic robotic skills could be transferred from the simulator to the operating room.

Introduction: Partial nephrectomy remains the gold standard in the management of small renal masses. However, minimally invasive partial nephrectomy (MIPN) is associated with a steep learning curve, and optimal, standardized techniques for time-efficient hemostasis are poorly described. Given the relative lack of evidence, the goal was to describe a set of actionable guiding principles, through an expert working panel, for urologists to approach hemostasis without compromising warm ischemia or oncological outcomes. Methods: A three-step modified Delphi method was used to achieve expert agreement on the best practices for hemostasis in MIPN. Panelists were recruited from the Canadian Update on Surgical Procedures (CUSP) Urology Group, which represent all provinces, academic and community practices, and fellowship- and non-fellowship-trained surgeons. Thirty-two (round 1) and 46 (round 2) panellists participated in survey questionnaires, and 22 attended the in-person consensus meeting. Results: An initial literature search of 945 articles (230 abstracts) underwent screening and yielded 24 preliminary techniques. Through sequential survey assessment and in-person discussion, a total of 11 strategies were approved. These are temporally distributed prior to tumor resection (five principles), during tumor resection (two principles), and during renorrhaphy (four principles). Conclusions: Given the variability in tumor size, depth, location, and vascularity, coupled with limitations of laparoscopic equipment, achieving consistent hemostasis in MIPN may be challenging. Despite over two decades of MIPN experience, limited evidence exists to guide clinicians. Through a three-step Delphi method and rigorous iterative review with a panel of experts, we ascertained a guiding checklist of principles for newly beginning and practicing urologists to reference.

INTRODUCTION AND OBJECTIVE:Focal High Intensity Focused Ultrasound Therapy (fHIFU) represents an alternative to active surveillance in low-risk prostate cancer (PCa). Oncological outcomes of this m...

Objectifs La therapie focale, notamment par HIFU (Ultrasons Focalises de Haute Intensite), se developpe avec l’objectif de traiter certains cancers de prostate localises en diminuant la morbidite comparativement aux traitements radicaux. Nous partageons les resultats du traitement focal a l’aide du systeme FocalOne® realises par deux centres academiques. Methodes Il s’agit d’une etude descriptive et analytique, internationale multicentrique, avec un recueil retrospectif des donnees. Les patients selectionnes ont beneficie d’un traitement par HIFU avec le systeme FocalOne® entre novembre 2014 et decembre 2019. Les criteres d’exclusion etaient : un stade N+ ou M+, un antecedent de radiotherapie ou hormonotherapie, un traitement superieur a 50 % du volume prostatique, un ISUP > 3 sur les biopsies initiales, et un suivi inferieur a 12 mois. Le critere de jugement principal etait le taux de retraitement. Une etude analytique a ete realisee, recherchant des facteurs pronostiques de retraitement. Nous avons egalement etudie les resultats fonctionnels. Resultats La cohorte se composait de 137 patients. L’âge median etait de 63 ans, le PSA moyen de 6,99 ng/mL, le volume prostatique de 49cc, le stade T2a etait predominant (48,8 %) avec 8,8 % de T2c, le score ISUP2 egalement (45,3 %) avec 18,2 % d’ISUP3. 38,7 % des traitements consistaient en une hemi-ablation. 76,6 % des patients ont eu des biopsies systematiques dans l’annee post-traitement. 21,8 % des biopsies retrouvaient un cancer significatif (ISUP > 1). Le taux de retraitement etait de 37,9 % dont 31,4 % de traitements radicaux. Le suivi median etait de 24 mois. La survie sans retraitement a 24 mois etait de 74 %. L’analyse univariee n’a pas retrouve de facteur pre ou peroperatoire pronostique de retraitement, seulement une tendance (p = 0,13) pour les petits volumes traites. Le taux de complications de grade 3 etait de 9,4 % ( Fig. 1 , Tableau 1 ). Conclusion Dans cette etude, la survie sans retraitement a 24 mois etait de 74 %, traduisant l’heterogeneite des indications et modalites de traitement. Le suivi est trop court pour evaluer les resultats oncologiques a long terme. Inclure les patients dans des cohortes de suivi, des essais cliniques, permettrait de mieux preciser les indications du traitement focal du cancer localise de la prostate.

Introduction: Magnetic resonance imaging (MRI) is being more widely used in the detection of prostate cancer (PCa), particularly after an initial negative biopsy. In this study, we compared 12-core systematic biopsy (SYS), MRI-targeted biopsy (TAR), and the association of systematic and MRI-targeted (SYS+TAR) prostate biopsy in patients with previous biopsy and those who were biopsy-naive to evaluate the differences in terms of cancer detection and clinically significant cancer detection between the three modalities.Methods: Overall, 203 consecutive patients with suspicion of PCa were analyzed; 48.2% were biopsy-naive and 51.7% had at least one previous negative prostate biopsy. The median age was 66 years, median prostate-specific antigen (PSA) level was 7.9 ng/mL and median prostate volume was 46 mL. 38.9% had SYS, 19.2% TAR only, and 41.8% had SYS+TAR biopsy.Results: Overall, the PCa detection (PCaDR) was 63%. The SYS+TAR biopsy detected significantly more cancer than SYS and TAR only biopsies (72.9% vs. 56.9% and 53.8% respectively; p=0.03). Detection rate of clinically significant cancer (csPCaDR) was 50.7% overall; 65.8% in the SYS+TAR biopsy vs. 39.2% in the SYS and 48.7% in the TAR groups (p=0.002). In the biopsy-naive group, PCaDR and csPCaDR were significantly higher in the SYS+TAR group than in the SYS and TAR groups (p=0.01). In the repeat biopsy group, PCaDR and csPCaDR were equivalent in the TAR and SYS+TAR groups and higher than in the SYS group (p=0.001).Conclusions: TAR biopsy, when added to SYS biopsy, was associated with a higher detection rate of csPCa in biopsy-naive patients when compared to TAR and SYS only biopsies. In patients after previous negative biopsy, detection rates of csPCa were equivalent for SYS+TAR and TAR only biopsies, but higher than SYS.

Purpose Partial nephrectomy (PN) represents the treatment of choice for localized renal tumor

Introduction: We sought to evaluate the diagnostic performance of 18F-fluorocholine positron emission tomography-computed tomography (18F-FCH PET/CT) for initial staging of patients with high-risk prostate cancer. Secondary objectives were to compare the value of 18F-FCH PET/CT to conventional imaging modalities and to evaluate its clinical impact. Methods: We conducted a retrospective study of 76 patients who underwent 18F-FCH PET/CT for initial staging of high-risk prostate cancer. Using pre-established validation criteria, sensitivity and specificity were determined for metastatic disease. Results were compared to findings on magnetic resonance imaging (MRI), computed tomography (CT), and bone scan (BS) when available. Results: Twenty-two (29%) PET/CT scans were positive, 49 (64%) negative, and five (7%) equivocal for nodal or metastatic disease. Of the positive scans, 17 showed regional lymph node involvement, 12 distant nodes, five bone metastases, and three lung metastases. Overall per-patient sensitivity, specificity, positive and negative predictive values for metastatic disease were 65%, 100%, 100%, and 78%, respectively. Sensitivity, specificity, and positive and negative predictive values were 64%, 100%, 100%, and 80%, respectively, for nodal involvement and 86%, 100%, 100%, and 98%, respectively, for bone and other metastases. Conventional imaging was negative for the lesion(s) found on PET/CT in five patients. PET/CT changed the clinical management in nine patients (12%). Conclusions: Although 18F-FCH PET/CT offers some benefits over conventional imaging and demonstrates a high specificity, it remains limited by its sensitivity in the context of high-risk prostate cancer staging. PET with novel urea-based small molecule prostate-specific membrane antigen (PSMA) inhibitors may overcome some of these limitations. However, the interpretation of the study result is limited by the lack of available histological gold standard, the inclusion of several patients who received androgen-deprivation therapy (ADT) prior to PET/CT, our retrospective design, and a relatively small sample size.

Objectifs La tomographie par emission de positron (TEP) au « prostate specific membrane antigen » (PSMA) croit en popularite compte tenu de son role dans l’evaluation du cancer de la prostate. Le radiotraceur original, 68Ga-PSMA-11, a fait ses preuves quant a son utilite pour detecter le cancer precocement lors d’une recidive biochimique ; Nous presentons ici la detectabilite d’un autre traceur, le 18F-DCFPyL. Methodes Les dossiers cliniques, les images et les rapports d’imagerie des TEP/TDM au 18F-DCFPyL ont ete retrospectivement revus pour tous les hommes, en recidive biochimique ou connus metastatiques, afin de retracer les performances cliniques reelles des etudes TEP/TDM, effectuees sur un scanner hybride (Discovery ST, General Electric Medical Systems, Waukesha, WI, Etats-Unis) muni d’une TDM 16 barrettes. Les resultats de la TEP/TDM sont consideres « positifs » si au moins un site de maladie a ete rapporte ; « negatifs » quand aucun site n’a ete identifie. Resultats Nous avons retenu 93 patients avec TEP au 18F-DCFPyL apres au moins une ligne de traitement pour le cancer de la prostate. L’âge moyen etait de 70,6 ans. L’antigene prostatique specifique (APS) moyen au moment de la TEP etait 4,57 nmol/L (min 0,07 nmol/L ; max 51,09 nmol/L). Le score de Gleason median etait 7 (min 5 ; max 10). Les traitements anterieurs etaient : une prostatectomie chez 62 patients, radiotherapie chez 59 patients (34 avaient eu les deux) ; les autres patients avaient ete traites par ultrasons focalises de haute intensite (HIFU) (2), cryotherapie (1), hormonotherapie (1) ou suivis sans traitement (2). Les resultats de detection a la TEP par palier d’APS sont : 0,0–0,3 (1/5, 20 %) ; 0,3–0,5 (5/8, 63 %) ; 0,5–0,1 (7/8, 88 %) ; 1,0–2,0 (17/19, 89 %) ; > 2,0 (48/53, 91 %) ( Fig. 1 ). Conclusion Le 18F-DCFPyL a un taux de detection excellent pour la recidive biochimique du cancer de la prostate, ce taux augmente avec celui de l’APS dans le sang. Les avancements technologiques recents effectues sur les nouveaux appareils TEP promettent d’ameliorer ces taux de detection, surtout lorsque le volume de la maladie est tres petit.

Objectifs La therapie par ultrasons focalises de haute intensite (HIFU) est une alternative a la surveillance active pour les cancers de prostate (CaP) de faible risque. Les resultats de cette therapie pour les CaP de risque intermediaire sont discutes. L’objectif de notre etude etait d’analyser les resultats oncologiques de l’HIFU chez les patients atteints d’un CaP de risque intermediaire. Methodes Il s’agit d’une etude retrospective monocentrique nord-americaine issue d’une cohorte prospective de patients avec CaP cliniquement significatif (CaPCS) traites par HIFU entre mai 2015 et octobre 2018. Les criteres d’inclusion etaient : lesion unilaterale de groupe anatomopathologique ISUP 2 et 3, lesion visible en IRM, PSA Resultats Soixante-sept patients ont ete inclus dont 56 % ISUP2 et 37 % ISUP3 avec suivi median de 19 mois IC95 % (15 ;30). Le PSA median etait de 6,2 ng/mL IQR (5,0 ;9,5). L’IRM retrouvait une lesion Pi-RADS ≥ 4 chez 90 % des patients. Le temps median de traitement etait de 69 min IQR (55 ;87) pour un volume median traite de 27 % IQR (20 % ;36 %) du volume total. A 6 mois, le taux de CaPCS dans la zone traitee etait de 12,5 %. L’IRM post-traitement montrait une lesion Pi-RADS ≥ 4 uniquement chez 25 % des patients avec CaPCS a la biopsie de controle. La dysfonction erectile et l’anejaculation etaient retrouvees respectivement chez 12,5 % et 7,5 % des patients. A 2 ans, la survie sans traitement complementaire etait de 76 % IC95 % (56 % ;88 %) et la survie sans traitement radical de 86 % IC95 % (67 % ;95 %). Un retraitement HIFU a ete possible chez 8 % des patients. Conclusion Le traitement des CaP de risque intermediaire par HIFU est faisable et est associe a des resultats oncologiques et fonctionnels acceptables. Ces resultats doivent etre confirmes avec une duree de suivi plus importante.

Objectifs La therapie par ultrasons focalises de haute intensite (HIFU) est une option therapeutique pour les cancers de prostate (CaP) cliniquement significatif (CaPCS). Une biopsie de controle a 6 mois (M6) apres traitement est recommandee. L’objectif de notre etude etait d’analyser les facteurs predictifs de presence d’un CaPCS a la biopsie de controle a M6 post-HIFU. Methodes Etude retrospective monocentrique nord-americaine issue d’une cohorte prospective de patients avec CaPCS defini par la presence de grade 4 de Gleason biopsique traites par HIFU entre mai 2015 et octobre 2018. Les criteres d’inclusion : lesion unilaterale de groupe anatomopathologique ISUP 2 et 3, lesion visible en IRM et PSA Resultats Soixante-sept patients inclus dont 56 % ISUP2 et 37 % ISUP3. Le PSA median etait de 6,2 ng/mL (IQR : 5,0 ; 9,5). Le volume median traite par HIFU etait de 27 % (IQR : 20 % ; 36 %) du volume total. A 6 mois, le taux de CaPCS dans la zone traitee etait de 12,5 % et de 21 % en glande entiere. Le pourcentage de volume traite etait plus faible chez les patients ayant un CaPCS a M6 23 % (IQR : 20 ; 26) vs 30 % (IQR : 26 ; 39) (p = 0,0011). L’âge, le PSA, le PSAd et le groupe ISUP au diagnostic, ainsi que le type de traitement (hyperfocal vs hemi-ablation), la decroissance de PSA ou l’IRM a M6 etaient comparable dans les deux groupes (p > 0,05). En analyse bivariee, aucun parametre n’etait predictif de la presence d’un CaPCS a la biopsie M6. Conclusion Les donnees oncologiques initiales et l’IRM de controle ne sont pas predictives de la presence de CaPCS apres HIFU. La biopsie de controle a 6 mois doit etre systematique. Ces donnees doivent etre validees par de plus larges cohortes.

To assess competency of urology post-graduate trainees (PGTs) in percutaneous renal access (PCA). Upon obtaining ethics approval and informed consents, PGTs between post-graduate years (PGY-3 to PGY-5) from all four urology programs in Quebec were recruited. PCA competency of each participant was assessed objectively by performing task 4 on the PERC Mentor™ simulator, where they had to correctly access and pop 7 balloons in 7 different renal calyces and subjectively by the validated Percutaneous Nephrolithotomy—Global Rating Scale (PCNL-GRS). A total of 26 PGTs with a mean age of 29.2 ± 0.7 years participated in this study. When compared with the 21 PGTs without practice, all 5 PGTs who had practiced on the simulator were competent (p = 0.03), performed the task with significantly shorter operative time (13.9 ± 0.7 vs. 4.4 ± 0.4 min; p

To assess determinants of performance on the Transfer Task of the Basic Laparoscopic Urologic Surgery (BLUS(©)) skills curriculum administered at Objective Structured Clinical Examinations (OSCEs).After obtaining Institutional Review Board approval and informed consent, urology trainees (Postgraduate Year [PGY]-3 to PGY-5) from four different training programs (A, B, C, D) were recruited for the study. Transfer Task Times (TTTs) were compared and correlated with previous laparoscopic experience, amount of endotrainer practice and scores obtained at practice sessions and other OSCE stations.A total of 37 trainees were evaluated on three successive semiannual OSCEs from May 2011 to May 2012, including 16 (43.2%) trainees from program A with a dedicated laparoscopic skills training program. Compared with trainees from programs B, C, and D, trainees from program A had significantly more practice per week (0 v 45 minutes, p=0.001) and significantly lower median TTTs at OSCEs (114 [68-209] v 74 [52-189] seconds, p=0.001) despite significantly lower number of laparoscopic cases assisted within the previous 6 months (13 [0-57] v 2 [0-35], p=0.001). For program A trainees, TTTs moderately correlated with median TTTs at practice sessions (r=0.57, p=0.001) and negatively correlated with amount of practice per week (r=-0.41, p=0.003). Thus, more training resulted in faster times at OSCEs. On multivariate analysis, amount of practice per week was the only significant predictor of TTTs at OSCEs (p=0.028).Performance on the transfer task of BLUS during OSCEs significantly correlated with the amount of practice rather than the number of laparoscopic cases assisted.

Purpose: To provide key evidence-based strategies to improve outcomes of radiofrequency ablation and limit recurrences of small renal tumors.Materials and Methods: The literature was searched via OvidSP MEDLINE from 1997 to current using MeSH terms. All levels of evidence and types of reports were reviewed.Results: We comprehensively reviewed technical issues, mechanisms, imaging criteria, ablative success, enhancement within one month, contraindications, oncological efficacy, morbidity rates, and follow-up strategies.Conclusion: The technique is safe and effective. Tumors < 2.5 cm are statistically most likely to remain disease-free. Anterior tumors are contraindicated. Strict follow-up is needed to detect failures, most of which occur within 3 months and can be easily salvaged with repeat radiofrequency ablation. Homogeneous enhancement within 1 month is not necessarily a failure, and tends to disappear after 4 to 6 weeks. Multi-disciplinary meetings must occur to discuss each case prior to treatment.

The aim of this study was to prospectively identify predictors of radiation exposure during ureteroscopy.Eighty-five consecutive patients who presented for ureteroscopies and laser lithotripsy were considered. Fluoroscopy time (FT) was obtained from radiology reports for each patient, and clinical data were obtained from chart review. Nine patients were excluded (three unconfirmed FTs, four staghorn calculi, one ectopic kidney, and one multiple ureteral strictures). Seventy-six patients were included in the study. Univariate and multivariate linear regression were used to identify factors that determined FT.The patient cohort was 65.8% male with a mean age of 52.7 years. Mean FT was 183 s, and mean surgical time was 68.4±29 minutes. Mean stone size was 10±5 mm in the greatest dimension. A large proportion of patients (50%) had renal stones, multiple stones were present in 31.6% of cases, and 22.3% of stones were radiolucent. Cases were equally distributed between surgeons A and B, and 46% of patients had preoperative stents. On multivariate analysis, increased FT was independently associated with surgeon A (104 additional seconds per case, P0.001), longer duration of surgery (14 s per 10 minutes, P0.001), and male patients (54 s per procedure, P=0.02). Age, stone characteristics, presence of ureteral stent, and stone-free status did not correlate with FT.Surgeon behavior, longer duration of surgery, and male gender were significant predictors of FT and, hence, radiation exposure during ureteroscopy. In the present study, stone characteristics were not found to be predictors of FT.

Objectives To calculate the efficiency quotient (EQ) of the latest mobile Storz Modulith SLX-F2 lithotripter and to identify the factors determining the stone-free rate. Methods A retrospective review of a prospectively collected database of the first consecutive 533 patients undergoing shock wave lithotripsy (SWL) from June 2009 to February 2010 was performed. A total of 16 patients with radiolucent stones and 43 patients with incomplete follow-up were excluded. The patients were followed up with plain radiography to assess the stone-free status. Univariate and multivariate analyses were performed to identify the factors determining the stone-free rates. Results Follow-up was complete for 474 patients, with a mean age of 54.2 ± 14.5 years. The success rate after a single SWL session was 82.7% (renal 82.2% and ureteral 83.3%; P = .81). The retreatment rate was 14.7% (renal 15.2% and ureteral 14.2%; P = .79). The stone-free rate was 77% (renal 74.1% and ureteral 80.9%; P = .10). Of the 474 patients, 43 had pre-SWL ureteral stents, and 13 required post-SWL ureteral stenting; 35 patients required post-SWL curative procedures. The EQ was 0.66, and the modified EQ was 0.62. On multivariate analysis, the stone-free patients had a smaller stone size (9.5 vs 10.3 mm, P = .02), younger age (53.1 vs 58.0 years, P = .002), right-sided stones (83.6% vs 71.0% P = .001), and the absence of a ureteral stent (78.7% vs 64.3%; P = .001). Conclusions The mobile Storz Modulith SLX-F2 lithotripter has an acceptable EQ of 0.66. In the present study, smaller stones (

Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy.Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week.No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate.The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia.

Study Type – Therapy (outcomes research) Level of Evidence 2c OBJECTIVE • To evaluate if two commonly used laparoscopic simulators could be adapted and used successfully for the robotics platform in a laparoscopic and roboticnaive medical student population. MATERIALS AND METHODS • We identified two widely validated laparoscopic simulation programs, LapSim® (Surgical Science Sweden AB), and ProMIS® (Haptica, Ireland)for inclusion in the study. The McGill Inanimate System for Training and Evaluation of Laparoscopic Skills® task set was used for ProMIS, and adapted for the DaVinci® console (Intuitive Surgical, Inc., Sunnyvale, CA, USA) robotic platform. • We then randomized 20 naive medical students to receive training on either LapSimor ProMIS, both or neither, and evaluated them beforeand aftertraining. RESULTS • When the groups were compared at baseline, there were no statistical differences in mean scores amongst the groups in univariate analysis (α= 0.05). • Whencomparing mean scores within groups before and after training sessions, statistically significant performance enhancement in all four robotic tasks were identified in the groups receiving dual training. CONCLUSION • We have shownthat the use of ProMIS hybrid and LapSimvirtual reality (VR) simulators in conjunction with each other can considerable improve robotic console performance in novice medical students compared with hybrid and VR simulation alone.

Percutaneous nephrolithotomy (PCNL) in the prone position is associated with a 0.1% risk of colon injury, yet there have not been any reported cases of colon injury with supine PCNL. The aim of the present study was to prospectively compare CT scans of patients performed in both supine and prone positions on bolsters.Sixteen consecutive patients (mean age 55, 12 men) with 19 renal units (3 bilateral) who presented for PCNL underwent preoperative supine (without bolsters) and prone (with bolsters) noninfused CT scans. Axial images through lower pole calices containing stones necessitating percutaneous access were then analyzed. Percutaneous access was planned based on both supine and prone CT scans. Skin-to-stone distance (cm), angle of the percutaneous tract to the anterior-posterior axis (degrees), and visceral organ-to-tract distance (cm) were measured.Visceral organ-to-tract distance was significantly shorter in the prone position when compared with the supine position (2.8 cm vs 3.5 cm, P=0.04). In three renal units, visceral organ-to-tract distance in the prone position was less than 0.4 cm. Furthermore, the prone position was associated with significantly shorter skin-to-stone distance (7.6 cm vs 9.0 cm, P=0.0005) and significantly wider angles (40 degrees vs 35 degrees, P=0.02). Small sample size and simulation of the percutaneous access tract are two limitations of the present study.When prone PCNL is contemplated, preoperative planning CT scans that are performed in the prone position with bolsters provide better preoperative assessment of colon-to-percutaneous renal tract distance.

Ureteral stricture is the most common urologic complication after renal transplantation. When endourologic management fails, open ureteral reconstruction remains the standard treatment. The complexity of some of these procedures makes it necessary to explore other means of repair. This study evaluated the intermediate-term outcome of subcutaneous pyelovesical bypass graft (SPBG) on renal transplant recipients. We reviewed 8 patients (6 male and 2 female; mean age 52 years) with refractory ureteral strictures postrenal transplantation, who received SPBG as salvage therapy. All patients failed endourologic management and half failed open management of their strictures. After a mean follow-up of 19.4 months, 7 out of 8 renal grafts have good function with mean GFR of 58.5 mL/min/1.73 m(2), without evidence of obstruction or infection. One patient lost his graft due to persistent infection of the SPBG and one patient developed a recurrent urinary tract infection managed with long-term antibiotics. SPBG offers a last resort in the treatment of ureteral stricture after renal transplantation refractory to conventional therapy.

We present the first randomized clinical study using BackStop, a novel reverse thermosensitive water-soluble polymer that is dispensed above the stone(s) and temporarily occludes the ureter to prevent retropulsion of stone fragments during ureteroscopic lithotripsy. After fragmentation is completed and concretions are extracted, conventional irrigation with saline dissolves the polymer, which is then flushed out.A total of 68 subjects with a single stone in the proximal ureter and an indication for ureteroscopic lithotripsy were enrolled in this prospective, randomized, single-blind, controlled, multisite clinical study. Each subject was randomly assigned to the BackStop group (34) or the control group (34 with no antiretropulsion device). For subjects in the experimental group BackStop was dispensed into the ureter above the stone using a 3Fr or 5Fr catheter. Ureteroscopic lithotripsy was performed in all subjects using pneumatic or laser energy. Measured end points included the retropulsion rate, the need for subsequent procedures, the stone-free rate at followup, the occurrence of adverse events and ureteral occlusion, if any, and post-stone fragmentation and extraction.Subjects randomized to the BackStop group experienced a statistically significant (p = 0.0002) lower rate of retropulsion (8.8%, 3 of 34) vs the control group (52.9%, 18/34). There were no adverse events in the BackStop group and BackStop was successfully dissolved in every subject, resulting in a patent ureter.BackStop appears to be a novel, safe and effective means of preventing stone fragment retropulsion during ureteroscopic lithotripsy for the management of ureteral stones.

Kidney transplantation is the therapeutic option of choice for patients with end-stage renal disease. With the advent of safer harvesting techniques and immunosuppression, both donor and recipient outcomes have markedly improved in recent years. Kidney donation from Living donors remains the single most important factor responsible for improving patient and graft survival. The laparoscopic donor nephrectomy has revolutionized renal transplantation, allowing expansion of the donor pool by diminishing surgical morbidity while maintaining equivalent recipient outcome. This technique is now becoming the gold-standard harvesting procedure in transplant centres worldwide, despite its technical challenge and ongoing procedural maturation, especially early in the learning curve. Previous contraindications to laparoscopic donor nephrectomy are no longer absolute. In the following analysis, the procedural aspects of the laparoscopic donor nephrectomy are detailed including pre-operative assessment, operative technique and a review of the current literature delineating aspects of both donor and recipient morbidity and mortality compared with open harvesting techniques.

Background Balance control during standing is essential while performing surgery. The postural sway must be controlled to enhance movement accuracy. Postural control was compared between novices and experts during standardized laparoscopic tasks. Methods Seven novices with limited exposition to laparoscopy were compared with 7 expert surgeons. The subjects were requested to perform 4 laproscopic tasks on the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) and a quiet standing task while standing on 2 force platforms. An analysis of variance (ANOVA) with repeated measures was performed to compare groups and the different conditions. Significant level was set at P Results The technical requirements of the laparoscopic tasks impacted on postural sway in both anteroposterior and mediolateral directions. Furthermore, results indicate that the experts have a significantly better postural balance for all tasks compared to novices. Conclusion Postural sway increases with the technical requirements of minimally invasive surgery. This study showed that postural control performance while standing improves with laparoscopic expertise.

Background Clinical applicability of newly discovered reagents for molecular imaging is hampered by the lack of translational models. As the dog prostate cancer (DPC-1) model recapitulates in dogs the natural history of prostate cancer in man, we tested the feasibility of single-photon emission computed tomography (SPECT)/CT imaging in this model using an anti-prostate-specific membrane antigen (PSMA)/17G1 antibody as the radiotracer. Methods Immunoblots and immunohistochemistry (IHC) with 17G1 were performed on canine and human prostate cancer cell lines and tissues. Five dogs with DPC-1 tumors were enrolled for pelvic and, in some instances, thoracic SPECT/CT procedures, also repeated over time. Controls included 111indium (In)-17G1 prior to DPC-1 implantation and 111In-immunoglobulins (IgGs) prior to imaging with 111In-17G1 in dogs bearing prostatic DPC-1 tumors. Results 17G1 cross-reactivity with canine PSMA (and J591) was confirmed by protein analyses on DPC-1, LNCaP, and PC-3 cell lines and IHC of dog vs. human prostate tissue sections. 17G1 stained luminal cells and DPC-1 cancer cells in dog prostates similarly to human luminal and cancer cells of patients and LNCaP xenografts. SPECT/CT imaging revealed low uptake (≤2.1) of both 111In-17G1 in normal dog prostates and 111In-IgGs in growing DPC-1 prostate tumors comparatively to 111In-17G1 uptake of 3.6 increasing up to 6.5 values in prostate with DPC-1 lesions. Images showed a diffused pattern and, occasionally, a peripheral doughnut-shape-like pattern. Numerous sacro-iliac lymph nodes and lung lesions were detected with contrast ratios of 5.2 and 3.0, respectively. The highest values were observed in pelvic bones (11 and 19) of two dogs, next confirmed as PSMA-positive metastases. Conclusions This proof-of-concept PSMA-based SPECT/CT molecular imaging detecting primary prostate tumors and metastases in canines with high cancer burden speaks in favor of this large model’s utility to facilitate technology transfer to the clinic and accelerate applications of new tools and modalities for tumor staging in patients. Electronic supplementary material The online version of this article (doi:10.1186/s13550-015-0155-6) contains supplementary material, which is available to authorized users.

We report three cases of end-stage renal failure necessitating hemodialysis subsequent to BCG administration for the treatment of upper-urinary tract transitional-cell carcinoma in patients with a solitary kidney, one with normal renal function and two with chronic renal failure prior to BCG instillation. We discuss treatment-related issues with pertinent literature review.

Following laparoscopic donor nephrectomy (LDN), recovery has only been studied using traditional outcomes, subjective and confounded by comorbidity and psychosocial variables. The purpose of this study is to estimate surgical recovery following LDN using standardized, validated instruments and to compare this recovery profile to that obtained with traditional measures. This was a prospective study of patients undergoing LDN at a single institution between September 2001 and January 2004 (n = 35). At baseline and 4 weeks following surgery, functional exercise capacity was measured using the 6-min walk test (6MWT) and health-related quality of life was assessed with the Short Form-36 (SF-36) questionnaire, including physical component summary (PCS) and mental component summary (MCS) scores. Patients' self-assessment of recovery and time to resumption of regular activities was ascertained. At follow-up (median 29 days), patients' 6MWT was lower by a median of 30 m (p = 0.07) and PCS decreased from 57.1 to 42.3 (p = 0.0001), whereas MCS remained constant. Overall, length of stay, return to activities and patient-stated recovery were inadequate outcomes for classifying patient recovery using 6MWT and PCS as the reference standards. Four weeks following LLDN, patients have returned to baseline exercise capacity, but not baseline general physical health. Traditional measures of recovery are incomplete descriptors of recovery.

Patients undergoing laparoscopic live donor nephrectomy (LLDN) commonly receive large amounts of fluid intraoperatively to counter the negative effects of pneumoperitoneum on renal function. Our aim is to demonstrate that a low-volume fluid management strategy does not adversely affect donor or recipient outcomes.Fifty-two patients underwent LLDN between December 2000 and January 2004. Data were collected in prospective databases, and augmented with retrospective medical record review. Donors were divided into two groups: the fluid-load group (n = 24) received10 ml/kg/h of intravenous crystalloids intraoperatively, while the fluid-restriction group (n = 28) received10 m/kg/h.Donors in the fluid-restriction group had a lower intraoperative urine output. There were no differences in postoperative creatinine levels (117.5 micromol/L vs 121.5 micromol/L, p = 0.8) or complications (4.2% vs 7.1%, p = 0.9). In the recipients, there were no differences in postoperative creatinine levels up to 12 months, incidence of delayed graft function (18% vs 10%, p = 0.7) or acute rejection (9% vs 5%, p = 1.0) between groups.Lower volume fluid management strategies in LLDN do not appear to worsen recipient outcomes nor are they detrimental to the donors.

Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted.

Introduction: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL).Methods: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification system, we selected 5 independent, blinded expert robotic surgeons to classify 100 ligaments based on morphology into a 4-type system: parallel, V-shaped, inverted V-shape, and fused. One week later, a subset of 25 photographs was sent to the same experts and classified. Statistical analyses were performed to determine both the intra-rater and inter-rater reliability of the proposed system.Results: Inverted V-shaped ligaments were noted most frequently (29.97%), parallel and V-shaped ligaments were found at 19.19% and 11.11%, respectively and fused ligaments were noted less frequently (6.06%). There was good intra-rater agreement (κ = 0.66) and inter-rater agreement (κ = 0.67) for the classification system.Conclusions: This classification system provided standardized descriptions of ligament variations that could be adopted universally to help clinicians categorize the variants. The system, validated by several blinded expert surgeons, demonstrated that surgeons were able to learn and correctly classify the variants. The system may be useful in helping to predict peri- and postoperative outcomes; however, this will require further study.

We assessed whether a combination of the fibrin tissue adhesive Tisseel® (human fibrinogen and thrombin) plus the hemostatic matrix FloSeal® (bovine derived gelatin matrix/human thrombin) could safely replace the conventional deep medullary suture without compromising outcomes.Laparoscopic mid pole and one-third partial nephrectomy was performed on the right kidney of 12 female pigs. The only difference between the 2 groups of 6 pigs each was the use of a fibrin tissue adhesive plus hemostatic matrix combination in group 2 instead of the deep medullary running suture in control group 1. Renal scans and angiograms were performed at baseline and before sacrifice at 5-week followup. Retrograde in vivo pyelogram was also done.No significant difference was seen in operative parameters or postoperative course between the groups. Renal scans revealed a statistically insignificant trend toward greater uptake loss in group 1 and angiograms showed 3 major vessel occlusions in that group. No active bleeding was detected. Those 3 kidneys had significantly poorer postoperative uptake on renal scan than that of other kidneys (18.6% vs 39.4%, p = 0.013). Only 1 small asymptomatic pseudoaneurysm was noted in group 1. No urine leakage was found in either group. No major vessel occlusion, pseudoaneurysm or urinary complications developed in group 2.Even after deep one-third partial nephrectomy FloSeal with concurrent Tisseel appeared sufficient to control major medullary vascular injuries and replace the deep medullary conventional suture without compromising operative outcomes. The potential advantages seen during functional and vascular examinations by decreasing the risk of unnecessary segmental vessel occlusion need further clinical evaluation.

Background Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC-1. Methods Primary cultures were established from a canine poorly differentiated prostatic adenocarcinoma. Population doubling time was determined by counting nuclei after cell lysis. Tumorigenicity was assessed in nude mice and in one adult immunodeficient dog. Immunoscintigraphy was performed in both models using a monoclonal antibody (mAb) raised against the [44–62] sequence of human PSMA. Results DPC-1 cells have a rapid growth in vitro (doubling time, 27 hr) which is not stimulated by androgens. In addition, DPC-1 displays immunoreactivity to human PSA and PSMA. DPC-1 was found to be highly tumorigenic not only in nude mice but also for the first time after orthotopic seeding in an immunodeficient dog. This allograft mimicked, in a compressed form, the aggressive biological behavior of spontaneous dog prostate adenocarcinoma. Immunoscintigraphy using a 131Iodine-labeled PSMA mAb clearly visualized induced tumors in nude mice and in the dog allograft. Conclusions This study suggests that DPC-1 may constitute a powerful model for assessing new diagnostic and/or therapeutic tools in the management of prostate cancer. Prostate 46:2–10, 2001. © 2001 Wiley-Liss, Inc.

Objective To assess the rationale for virus-mediated gene transfer into the urethra in vivo and in vitro, using a rabbit model, as this is an attractive approach to prevent recurrence after the endoscopic management of urethral strictures. Materials and methods Primary cultures of rabbit urethral stromal cells were infected with adenoviral and retroviral solutions carrying a nucleus-targeted β-galactosidase (β-Gal) reporter gene (respectively 109 and 107 plaque-forming units/mL). In addition, to mimic the human clinical situation, a model was developed of thermally induced stricture in rabbit urethra which produced fibrotic stenosis within 15 days. Using a prototype channelled balloon catheter, these strictures were endoscopically dilated and then instilled with the β-Gal adenoviral or retroviral constructs. Results The application of recombinant adenovirus and retrovirus harbouring a nucleus-targeted β-Gal reporter gene to cultured rabbit urethral stromal cells resulted in a high transduction efficiency of up to 90% and 96%, respectively. Five days after infection, histochemical and immunohistochemical staining of the strictured urethrae showed a 3% rate of transfection targeted to stromal cells within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry, immunohistochemistry and PCR. Conclusion These results represent the first report of endoscopic adenovirus and retrovirus-mediated gene transfer to the urethra. Although at a low rate, transduction reached stromal cells transmurally within the induced strictures and was site-specific.

Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. Patients and methods Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. Results Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable ‘telomerase inhibitor’. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive. Conclusion These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.

Direct gene transfer to the ureter is an attractive approach to prevent restenosis after endourologic management of ureteral strictures. We therefore assessed the rationale for adenovirus-mediated gene transfer in the ureter in vitro and in vivo using a porcine model.Primary cultures of porcine ureteral epithelial and stromal cells were infected with an adenoviral solution carrying a nucleus-targeted beta-Galactosidase (beta-Gal) reporter gene (6.5 10(8) pfu/ml.). In addition, in order to mimic the human clinical situation, we have devised a model of thermally-induced stricture in porcine ureter which produced tight fibrotic stenosis within 8 days. Using a purposely designed channelled balloon catheter prototype, these strictures were endoscopically dilated and then instilled with the same beta-Gal adenoviral construction.Application of recombinant adenovirus harboring a nucleus-targeted beta-Gal reporter gene to cultured porcine urothelial and stromal cells resulted in high transduction efficiency of up to 99% and 84% respectively. Seven days after infection, X-Gal staining of the strictured ureters demonstrated transfection up to 2 mm. depth within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry (X-Gal staining) and PCR.This data represents the first report of adenovirus-mediated gene transfer to the ureter. It remained site specific by endourologic retrograde clinically applicable techniques.